Abstracts on Xiao Chaihu Tang (Japanese: Sho-Saiko-To):

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Abstracts on Xiao Chaihu Tang (Japanese: Sho-Saiko-To):

 

Akase-T, Hamada-Y, Higashiyama-D, Akase-T, Tashiro-S, Sagawa-

K, Shimada-S.|(2002)|Trends in the prescriptions of Kampo

medicines over a six-year period.|Journal of Traditional Medicines;

vol 19; no 2; pp 58-75; ISSN: 1340-6302; Publisher: Medical and

Pharmaceutical Society for Wakan-Yaku; Sugitani; Japan; 18

ref.|Changes in the prescriptions of Kampo medicines (Sino-

Japanese traditional herbal medicines) issued at a university

hospital over a six-year period were investigated. Prescriptions

including a Kampo medicine (79,132 sheets) issued at Kitasato

University Hospital in Kanagawa Prefecture, Japan, over a 6-year

period from 1994 to 1999 were analyzed. We found that Kampo

medicines were mainly prescribed for patients of ages 30-39 yr and

50-59 yr, and were most frequently prescribed by the department of

Obstetrics & Gynecology, followed by Internal Medicine and

Dermatology. Ninety-six percent of the prescriptions were

combined with modern medicine, and the percentage of Kampo

medicines with instructions about its combination with western

medicines in the package insert was approximately 1%. Among

the prescriptions that combined a Kampo medicine with western

medicine, the most frequently prescribed combination was a

xanthine derivative and a Mao (Ephedrae herba, Ephedra sinica

Stapf)-containing Kampo medicine, especially theophylline and

Kakkon-to. Regarding such combinations, the monitoring of

adverse effects and a check of the prescription seemed to be

important. The use of Toki-shakuyaku-san and Dai-kenchu-to

rapidly increased and the use of Sho-saiko-to, Ninjin-yoei-to, Go-rei-

san, and Hochu-ekki-to decreased over the study period. From

these trends in the prescriptions, it is believed that the demand for

Kankyo, Zingiberis siccatum rhizoma, Zingiber officinale Roscoe,

Koi, Saccharum granorum, Sansho, Zanthoxyli Fructus,

Zanthoxylum piperitum De Candolle, Shakuyaku, Paeoniae Radix,

Paeonia lactiflora Pallas, and Botampi, Moutan cortex, Paeonia

suffruticosa Andrews, will increase rapidly in the future. It is

important to carry out similar investigations at a wide variety of

hospitals and clinics including emergency hospitals and sanatoria

to clarify the future balance of the supply and demand of Kampo

medicines and their constituent herbs.

 

Akase-T, Tashiro-S, Ishibashi-A, Akase-T, Kaneko-M, Komatsu-Y,

Sagawa-K, Shimada-S.|(2001)|Pharmacoepidemiological study of

the clinical efficacy of Sho-saiko-to (Xiao-Chai-Hu-Tang) in chronic

liver disease patients.|Journal of Traditional Medicines; vol 18; no 3;

pp 95-106; ISSN: 1340-6302; 14 ref.|The clinical effectiveness of

Sho-saiko-to based on 609 hepatitis out-patients at the Kitasato

University Hospital, Japan during September 1995-96 was studied

by pharmacoepidemiological methods. In the cases of the patients

who suddenly stopped the Sho-saiko-to therapy, the increases in

serum aminotransferase activities and other markers were

observed. The results showed the usefulness of Sho-saiko-to for

maintaining the hepatic functions.

 

Akbar-S-M-F, Yamamoto-K, Abe-M, Ninomiya-T, Tanimoto-K,

Masumoto-T, Michitaka-K, Horiike-N, Onji-M.|(1999)|Potent

synergistic effect of sho-saiko-to, a herbal medicine, during vaccine

therapy in a murine model of hepatitis B virus carrier.|European

Journal of Clinical Investigation; vol 29; no 9; pp 786-792; ISSN:

0014-2972; 23 ref.|Sho-saiko-to (TJ-9) is known to improve the

symptoms of hepatitis B (HBV). A recently developed vaccine

therapy is known to reduce viral replication in some chronic HBV-

carriers. The impact of a combination of vaccine therapy and sho-

saiko-to (TJ-9), and the mechanism underlying the therapeutic

effect of TJ-9, were investigated in HBV-transgenic mice (HBV-Tg)

expressing similar levels of HBV-related antigens and HBV DNA.

Mice received either a TJ-9-enriched diet or a monthly injection of

vaccine containing hepatitis B surface antigen (HBsAg), or both, for

12 consecutive months. Twelve months after starting the therapy,

9% (1 of 11), 61% (11 of 18) and 100% (10 of 10) of HBV-Tg

receiving only the TJ-9-treatment, only the monthly vaccine or both

the TJ-9 and vaccine, respectively, responded to therapy and

became completely negative for HBsAg. Spleen lymphocytes and

antigen presenting cells (APC) from TJ-9-treated HBV-Tg produced

significantly higher levels of IgM, IgG and antibodies to keyhole

limpet haemocyanin (KLH) and showed significantly higher

stimulatory capacity in allogenic mixed leukocyte reaction (MLR)

compared with the spleen cells and APC from HBV-Tg receiving

normal diet without TJ-9. These data confirm the therapeutic role of

TJ-9 during HBV infection and inspire optimism of a widespread

use of TJ-9 during immune therapies.

 

Amagaya-S, Hayakawa-M, Ogihara-Y, Ohta-Y, Fujiwara-K, Oka-H,

Oshio-H, Kishi-T.|(1989)|Treatment of chronic liver injury in mice by

oral administration of Xiao-Chai-Hu-Tang.|Journal of

Ethnopharmacology; vol 25; no 2; pp 181-187; ISSN: 0378-8741;

19 ref.|Oral administration of Xiao-Chai-Hu-Tang (XCHT) attenuated

the hepatic fibrosis which developed in mice after repeated doses

of carbon tetrachloride. XCHT is a boiling water extract made from

Bupleurum falcatum roots, Glycyrrhiza glabra roots, Panax ginseng

(P. pseudoginseng) roots, Pinellia ternata tubers, Scutellaria

baicalensis roots, Zingiber officinale rhizomes and Zizyphus

vulgaris (Ziziphus sativa) fruits in the ratio 7:2:3:5:3:1:3.

 

Amagaya-S, Ishige-A, Takeda-S, Shindo-S, Maemura-S, Kubo-M,

Komatsu-Y, Okada-M, Itoh-T, Terasawa-K.|(1998)|General

pharmacological properties of TJ-9 extract.|Phytomedicine; vol 5;

no 3; pp 165-175; 34 ref.|The general pharmacological properties of

TJ-9 extract (Shosaiko-to) were investigated in various experimental

animals. TJ-9 extract at 0.3, 1.0 and 3.0 g/kg showed no effect on

spontaneous locomotor activity, hexobarbital-induced sleeping

time, electroshock-, strychnine-, and pentylenetetrazol-induced

convulsions, frequency of acetic acid-induced writhing, body

temperature and skeletal muscle coordination in mice. In

anaesthetized dogs, TJ-9 extract at 0.3, 1.0 and 3.0 g/kg, had no

effect on the frequency of respiration, blood pressure, heart rate

and ECG. TJ-9 extract at 10-4, 10-5 and 10-6 g/ml also had no

effect on acetylcholine or barium chloride-induced contraction of

guineapig ileum. TJ-9 extract at 10-4 g/ml, however, increased

histamine-induced contractions and spontaneous motility of the

guineapig ileum. TJ-9 extract at 0.3, 1.0 and 3.0 g/kg had no effect

on blood coagulation and platelet aggregation in rats. TJ-9 extract

at the lowest dose of 0.3 g/kg inhibited the gastric juice secretion,

gastric pH and gastric acid output, and at 1.0 g/kg inhibited the

gastric acidity and bile secretion in rats. TJ-9 extract at 0.3, 1.0

and 3.0 g/kg, however, had no effect on the intestinal transport of

charcoal meal in rats. TJ-9 extract at 3.0 g/kg produced a decrease

of urine volume, but never decreased the urine electrolytes, Na+,

K+, and Cl- concentration. These results suggest that TJ-9 extract

exerts antiulcer properties by inhibiting the gastric secretion and

gastric acid output, but it showed no notable pharmacological

effects on the central nervous system, autonomic nervous system

or smooth muscle function, respiratory and cardiovascular system,

and blood coagulation and fibrinolysis function.

 

Borchers-A-T, Hackman-R-M, Keen-C-L, Stern-J-S, Gershwin-M-

E.|(1997)|Complementary medicine: a review of immunomodulatory

effects of Chinese herbal medicines.|American Journal of Clinical

Nutrition; vol 66; no 6; pp 1303-1312; ISSN: 0002-9165; 54 ref.|This

review presents some representative examples of in vitro and in vivo

studies examining the diverse effects of Chinese herbal medicines

(many of which are also used in traditional Japanese medicine) in

experimental animal models as well as in man and their proposed

modes of action. Medicines covered are: Juzen-taiho-to, Shosaiko-

to (Chinese name: Xiao-Chai-Hu-Tang), Saiboku-to, glycyrrhizin,

Shigyaku-to, Kakkon-to (Chinese name: Ge-Gen-Tang), Sho-seiryu-

to (Chinese name: Xian-Qing-Long-Tang), Ryo-kan-kyomi-sin-ge-nin-

to (Chinese name: Ling-Gan-Jiang-Wei-Xin-Xia-Ren Tang), Kanzo-

bushi-to, Ninjin-youei-to (Chinese name: Ren-Shen-Yang-Rong-

Tang) and Tripterygium wilfordii (Chinese name: Lei-Gong-Teng).

 

Borchers-A-T, Sakai-S, Henderson-G-L, Harkey-M-R, Keen-C-L,

Stern-J-S, Terasawa-K, Gershwin-M-E.|(2000)|Shosaiko-to and

other kampo (Japanese herbal) medicines: a review of their

immunomodulatory activities.|Journal of Ethnopharmacology; vol

73; no 1/2; pp 1-13; ISSN: 0378-8741; Many ref.|The use of

alternative medicine, including consumption of herbal products and

dietary supplements, has been increasing substantially both in the

United States and in Western Europe. One area that is gaining

increased attention is the use of Oriental Medicine including

Kampo, or Japanese herbal medicine. Herein, we review

representative examples of research available on the most common

use of Kampo medicinals, namely to improve the immune

response. We also provide an extensive background on the history

of Kampo. There are more than 210 different Kampo formulae used

in Japan and most uses of Kampo are to modulate the immune

response, i.e. to improve immunity. We have extracted data on

seven common Kampo medicinals (Shosaiko-to, Juzen-taiho-to,

Keishi-ni-eppi-ichi-to, Keishi-ni-eppi-ichi-to-ka-ryo-jutsubu, Keishi-

bushi-to, Toki-shakuyaku-san and Unsei-in) , and the data are

reviewed with respect to in vitro and in vivo activities for both

humans and experimental animals; the ingredients as well as the

problems with classification of these materials are presented.

Research suggests that Kampo herbals are biologically active and

may have therapeutic potential. While it is believed that Kampo

medicines have few side effects, there is a paucity of data on their

toxicity as well as a relative lack of knowledge of the bioactive

constituents and potential drug interactions of these agents.

 

Buimovici-Klein-E, Mohan-V, Lange-M, Fenamore-E, Inada-Y,

Cooper-L-Z.|(1990) |Inhibition of HIV replication in lymphocyte

cultures of virus-positive subjects in the presence of Sho-saiko-to,

and oriental plant extract.|Antiviral Research; vol 14; no 4/5; pp 279-

286; ISSN: 0166-3542.|

 

Egashira-T, Takayama-F, Yamanaka-Y, Komatsu-

Y.|(1999)|Monitoring of radical scavenging activity of peroral

administration of the Kampo medicine Sho-saiko-to in

rats.|Japanese Journal of Pharmacology; vol 80; no 4; pp 379-382;

ISSN: 0021-5198; 14 ref.|The Kampo medicine, Sho-saiko-to,

scavenged superoxide anion, hydroxyl and 1,1-diphenyl-2-

picrylhydrazyl (DPPH) radicals in a dose-dependent fashion in vitro.

The transition of free-radical-scavenging activity in plasma after oral

administration of Sho-saiko-to in rats was investigated. From the

response-time profile, kinetic parameters including values for Ka

(absorption rate constant), Tmax (peak concentration time), T1/2

(half life) and MRT (mean residence time) of radical scavenging

activity in plasma could be calculated for the different radicals.

These parameters, calculated from the dynamics of antioxidation,

are considered a very meaningful procedure to examine the effects

of Sho-saiko-to.

 

Food and free radicals: proceedings of the first symposium,

Yamagata, 16 June, 1994, Hiramatsu M Plenum Press, 1997 113-

117 (27 ref.) ISBN: 0-306-45493-9.|(1997)|Mixed natural

antioxidants.|Hiramatsu-M.|It has been suggested that specially

formulated mixtures of natural water- and lipid-soluble antioxidants

may be valuable prophylactics for diseases (such as cancer,

inflammation, diabetes, cardiovascular disease and neurological

diseases) that are related to free radical damage. In this chapter,

the composition and free-radical scavenging activity of mixed

natural antioxidants (Japanese) is described. The mixed natural

antioxidants that are described are Sho-saiko-to-go-

keishikashakuyaku, baicalein, Toki-shakuyaky-san, Ganoderma

Lucidum, Kanglaojianshenye, long-life SOD, and Fructus

Momordicae.

 

Fugh-Berman-A.|(2000)|Herb-drug interactions.|Lancet (British

edition); vol 355; no 9198; pp 134-138; ISSN: 0140-6736; 65

ref.|Concurrent use of herbs may mimic, magnify or oppose the

effect of drugs. Plausible cases of herb-drug interactions include:

bleeding when warfarin is combined with Ginkgo biloba, Allium

sativum, Angelica sinensis or Salvia miltiorrhiza; mild serotonin

syndrome in patients who mix Hypericum perforatum with serotonin-

reuptake inhibitors; decreased bioavailability of digoxin,

theophylline, cyclosporin and phenprocoumon when these drugs

are combined with H. perforatum; induction of mania in depressed

patients who mix antidepressants and Panax ginseng;

exacerbation of extrapyramidal effects with neuroleptic drugs and

Areca catechu; increased risk of hypertension when tricyclic

antidepressants are combined with Pausinystalia yohimbe (P.

jobimbe); potentiation of oral and topical corticosteroids by

Glycyrrhiza glabra; decreased blood concentrations of prednisolone

when taken with the Chinese herbal product xaio chai hu tang (sho-

saiko-to); and decreased concentrations of phenytoin when

combined with the Ayurvedic syrup shankhapushpi. Anthranoid-

containing plants (including Cassia senna and Rhamnus purshiana)

and soluble fibres (including guar gum and psyllium) can decrease

the absorption of drugs. Many reports of herb-drug interactions are

sketchy and lack laboratory analysis of suspect preparations.

Health-care practitioners should caution patients against mixing

herbs and pharmaceutical drugs.

 

Fujiwara-K, Mochida-S, Nagoshi-S, Iijima-O, Matsuzaki-Y, Takeda-

S, Aburada-M.|(1995)|Regulation of hepatic macrophage function

by oral administration of Xiao-Chai-Hu-Tang (Sho-saiko-to, TJ-9) in

rats.|Journal of Ethnopharmacology; vol 46; no 2; pp 107-114;

ISSN: 0378-8741; 19 ref.|The effect of Xiao-Chai-Hu-Tang (Sho-

saiko-to, TJ-9; used in traditional Chinese medicine to treat liver

diseases), the extract of a mixture of 7 herbs, on hepatic

macrophage function was studied using rats. Hepatic macrophages

were activated by i.v. injection of Corynebacterium parvum or 70%

partial hepatectomy. Oral administration of TJ-9 (1 g/kg) for 3

weeks prior to activation did not affect the ability of these

macrophages to produce superoxide anions (evaluated in situ by

liver perfusion with nitro blue tetrazolium and phorbol myristate

acetate). However, the administration of TJ-9 attenuated the

blocking effect produced by pretreatment with gum arabic, a high

MW polysaccharide, on macrophage activation after partial

hepatectomy. When gum arabic was added to the medium of rat

hepatic macrophage cultures containing normal rat sera, their

ability to produce superoxide anions was reduced in a dose-related

manner. This reduction was attenuated by replacing the sera with

sera obtained from rats given oral doses of TJ-9 for 3 weeks.

 

Hattori-Y, Kasai-K, Sekiguchi-Y, Hattori-S, Banba-N, Shimoda-S-

I.|(1995)|The herbal medicine Sho-Saiko-To induces nitric oxide

synthase in rat hepatocytes.|Life Sciences; vol 56; no 7; pp 143-

148; ISSN: 0024-3205; 19 ref.|The effects of Sho-Saiko-To (SST, a

Japanese herbal drug composed of 7 medicinal plant extracts) on

nitric oxide (NO) biosynthesis in rat hepatocytes were studied by

measuring the stable end-product nitrite and the mRNA of inducible

NO synthase (iNOS). Interferon- gamma (IFN) alone failed to

induce NO synthesis. SST did not elicit NO synthesis at

concentrations up to 300 micro g/ml (when administered alone),

but dose-dependently induced NO production in the presence of

IFN. The combined administration of SST and IFN also induced

iNOS mRNA in the cells. Also, SST increased NO synthesis

caused by interleukin-1 or bacterial lipopolysaccharide as a single

agent, or in combination with IFN. The ability of SST to induce NO

biosynthesis could be related to the hepatoprotective properties of

the drug.

 

Hiramatsu-M, Komatsu-M.|(1999)| Mixed Japanese herbs and age-

related neuronal functions.| Antioxidant food supplements in human

health, Packer L Academic Press, 1999 411-428 (43 ref.) ISBN: 0-

12-543590-8.|Diseases such as Parkinson's, Alzheimer's, brain

ischemia, amyotrophic lateral sclerosis, brain injury, and post-

traumatic epilepsy are associated with free radicals and are

involved in neuronal cell death. It has recently been suggested that

some plant extracts may have potential role in the treatment and

prevention of dementia. This chapter reviews studies of the effects

of mixed herb extracts of Sho-saiko-to-go-keishi-ka-shakuyaku-to

and Toki-shakuyaku-san on aged neuronal functions. The use of

Hachimi-jio-gan in the treatment of diabetes, prostatic hypertrophy,

urinary disturbance, sterility and kidney disturbances is mentioned.

The herbs were found to have free-radical-scavenging activity, could

enhance cholinergic function, and had oestrogen-like functions in

the acceleration of microcirculation and enhancement of energy

metabolism. Toki-shakuyaku-san may be suitable for the treatment

of dementia of Alzheimer's disease, vascular dementia, or senile

dementia. The structures of the main components of Sho-saiko-to-

go-keishi-ka- shakuyaku-to and Toki-shakuyaku-san are illustrated.

 

Hiramatsu-M, Liu-J, Hamada-H, Mori-A, Yoneda-T, Sakamoto-

M.|(1995)|Use of natural antioxidants as a prophylactic for

neurological disorders.|Nutrition, lipids, health and disease:

proceedings of the UNESCO conference, Penang, September

1994, Ong A.S.H AOCS Press, 1995 276-279 (19 ref.) ISBN: 0-

935315-64-0.|The efficacy of some natural antioxidants having free

radical scavenging activity was studied in iron-induced

epileptogenic rats (as a model for post-traumatic epilepsy) and rat

brain ischaemia. The active components of the following herbs were

identified and discussed: the Japanese herbal medicine Sho-saiko-

to-go- keishikashakuyaku-to (TJ-960) and one of its active

components bicalein, Kanglaojianshenye and Ganoderma lucidium

(Chinese slow-ageing preparations), and beta-catechin. A table is

presented that shows the changes in aged rat brains and their

recoveries by TJ-960 treatment. A daily mixture of natural

ingredients can protect against neurological diseases related to

free radicals associated with ageing.

 

Homma-M, Oka-K, Ikeshima-K, Takahashi-N, Niitsuma-T, Fukuda-

T, Itoh-H.|(1995)|Different effects of traditional Chinese medicines

containing similar herbal constituents on prednisolone

pharmacokinetics.|Journal of Pharmacy and Pharmacology; vol 47;

no 8; pp 687-692; ISSN: 0022-3573; 25 ref.|The 3 major traditional

Chinese medicines, Sho-Saiko-To, Saiboku-To and Sairei-To, have

similar herbal constituents (compositions tabulated) including

Glycyrrhiza glabra which contains glycyrrhizin, a strong inhibitor of

11 beta -hydroxysteroid dehydrogenase. Cross-over open trials

were performed in healthy subjects to clarify prednisolone

pharmacokinetics on co-administration of these preparations. All

subjects received a single oral dose of 10 mg prednisolone before

oral treatment with one of the test preparations. After a 2-week

wash-out interval, they received one of the test preparations for 3

days at daily doses of 7.5 or 9.0 g. On the third study day, 10 mg

prednisolone was administered orally in combination with the test

preparation. Area under the curves (AUC) of prednisolone before

and after the treatment decreased from 0.94 to 0.78 mg h litre-1 in

the Sho-Saiko-To group, increased from 0.92 to 1.06 mg h litre-1 in

the Saiboku-To group, and did not change in the Sairei-To group.

AUC ratios of prednisone and prednisolone, which reflect the 11

beta - hydroxysteroid dehydrogenase activity, increased in the Sho-

Saiko-To group, decreased in the Saiboku-To group and did not

change in the Sairei-To group after the treatments. Similar results

were observed in ratios of endogenous cortisone to cortisol.

Because of the equal glycyrrhizin content in all 3 preparations,

differences in the 11 beta -hydroxysteroid dehydrogenase effect

amongst the 3 groups were unexpected. These observations

suggest that some unknown metabolic enzyme modifiers,

promoters or inhibitors, may be involved in these traditional

treatments.

 

Horie-Y, Kajihara-M, Yamagishi-Y, Kimura-H, Tamai-H, Kato-S,

Ishii-H.|(2001)|A Japanese herbal medicine, Sho-saiko-to, prevents

gut ischemia /reperfusion-induced hepatic microvascular

dysfunction in rats.|Journal of Gastroenterology and Hepatology; vol

16; no 11; pp 1260-1266; ISSN: 0815-9319; 34 ref.|Background and

aim: We have reported that gut ischaemia/reperfusion (I /R) causes

hepatic microvascular dysfunction. Nitric oxide (NO) has been

found to be a modulator of the adhesive interactions between

leukocytes, platelets and endothelial cells. Sho-saiko-to (TJ-9), a

Japanese herbal medicine, is reported to have protective effects

against liver injury and to regulate NO production. The objective of

this study was to determine whether TJ-9 affects hepatic

microvascular dysfunction elicited by gut I/R, and to investigate the

role of NO. Methods: Male Wistar rats were exposed to 30 minutes

of gut ischaemia followed by 60 minutes of reperfusion. Intravital

microscopy was used to monitor leukocyte recruitment and the

number of non-perfused sinusoids (NPS). Plasma tumour necrosis

factor (TNF)- alpha and alanine aminotransferase (ALT) activities

were measured. In another set of experiments, TJ-9 (1 g/kg per day

intragastrically) was administered to rats for 7 days. In some

experiments, dexamethasone (ST) (2 mg/kg per day intravenously)

was administered. Results: In control rats, gut I/R elicited

increases in the number of stationary leukocytes, NPS and plasma

TNF- alpha and ALT activities, and these changes were mitigated

by the pretreatment with TJ-9. Pretreatment with an NO synthase

inhibitor diminished the protective effects of TJ-9 on the increase in

leukostasis in the pericentral region, NPS, and plasma TNF- alpha

levels, but not its effect on the increase in leukostasis in the

midzonal region, total number of stationary leukocytes, or plasma

ALT activities. Pretreatment with TJ-9 increased plasma

nitrite/nitrate levels. The responses caused by gut I/R were

attenuated by the pretreatment with ST. Pretreatment with an NO

synthase inhibitor did not affect the effect of ST. TJ-9 attenuated

the gut I/R-induced hepatic microvascular dysfunction and

inflammatory responses such as TNF-alpha production in the early

phase via enhancement of NO production, and sequential

hepatocellular damage via its antiinflammatory effect like

corticosteroid effect.

 

Huang-XianXi, Yamashiki-M, Nakatani-K, Nobori-T, Mase-

A.|(2001)|Semi-quantitative analysis of cytokine mRNA expression

induced by the herbal medicine Sho-saiko-to (TJ-9) using a Gel

Doc system.|Journal of Clinical Laboratory Analysis; vol 15; no 4;

pp 199-209; ISSN: 0887-8013; 36 ref.|The RT-PCR method was

employed to determine the cytokine mRNA expression of human

peripheral lymphocytes induced by the Japanese herbal medicine

Sho-saiko-to (TJ-9). The results showed that the mRNA expression

of IL-12, IL-1 beta , IL-10, TNF- alpha , G-CSF, and IFN-gamma

increased after 6 h in culture. This is the first reported finding that

TJ-9 is an IFN- gamma inducer. Next, cytokine mRNA expression

was semi-quantitatively measured using the Gel Doc system with a

CCD camera and then statistically analysed to determine which

component of TJ-9 was the true cytokine inducer. The results

showed that the scutellaria root is the main component inducing

the cytokines, while the glycyrrhiza root is the secondary

component. When the cytokine concentrations in the supernatants

of cell cultures were measured by ELISA, the levels of IL-12, IL-1

beta , IL-10, TNF- alpha , and G-CSF reflected mRNA expression

levels in the cell fraction. However, the level of IFN- gamma was

below the detectable limit. The effects of various reagents on many

different kinds of cytokine mRNA expression could be analysed

objectively in a short time using the Gel Doc system. Many

important findings could be demonstrated by this simple, easy,

sensitive, and cheap method. After the clinical significance of

cytokine analysis is confirmed, this method may become a useful

clinical examination tool.

 

Inoue-M, Shen-YiRong, Ogihara-Y.|(1996)|Restorative effect of

Shosaikoto (Kampo medicine) on diminution of nitric oxide

synthesis in murine peritoneal macrophages induced by

hypercholesterolemia.|Biological and Pharmaceutical Bulletin; vol

19; no 11; pp 1468-1473; ISSN: 0918-6158; 57 ref.|Shosaikoto is a

Kampo medicine containing Bupleurum roots, Pinellia tubers,

Scutellaria roots, Panax pseudoginseng roots, Zingiber rhizomes,

Ziziphus fruits and Glycyrrhiza roots. To clarify the mechanism by

which Shosaikoto shows antiatherosclerotic action, its effect on

macrophage function was studied. The production of nitric oxide

(NO), prostaglandin E2 and interleukin 1 by macrophages in mice

was reduced following feeding on a cholesterol-enriched diet. This

reduction was observed 1 week after the beginning of cholesterol

feeding. Reduced macrophage function and NO production

associated with hypercholesterolaemia was restored by

Shosaikoto (daily dose of 1.2 g /kg) treatment. When the content

of lysophosphatidylcholine (LPC) was measured, no difference was

observed between mice fed a cholesterol-enriched diet in the

presence or absence of Shosaikoto treatment, suggesting that the

restorative effect of Shosaikoto is not due to the inhibition of LPC

production or accumulation. Shosaikoto prevented the modification

of macrophage function induced by atherogenic factors which is

probably linked to its antiatherosclerotic action.

 

Inoue-M, Shen-YiRong, Ogihara-Y.|(1996)|Shosaikoto (Kampo

medicine) protects macrophage function from suppression by

hypercholesterolemia.|Biological and Pharmaceutical Bulletin; vol

19; no 4; pp 652-654; ISSN: 0918-6158; 21 ref.|The feeding of

cholesterol-enriched diet to mice for 2 weeks was enough to

reduce production of nitric oxide (NO), prostaglandin E2 (PGE2)

and interleukin-1 (IL-1) in thioglycollate-elicited murine

macrophages. Although not showing antihypercholesterolaemic

action against ICR mice, Shosaikoto, a Kampo medicine, partially

prevented the reduction of NO and IL-1 production induced by the

feeding of a cholesterol-enriched diet, and completely released the

reduction of PGE2 production. The malfunction of macrophage

induced by hypercholesterolaemia may contribute to early

atherogenesis and Shosaikoto retains macrophage function to

prevent the development of atherosclerosis, even though serum

cholesterol is markedly increased.

 

Ishizaki-T, Sasaki-F, Ameshima-S, Shiozaki-K, Takahashi-H, Abe-

Y, Ito-S, Kuriyama-M, Nakai-T, Kitagawa-M.|(1996)|Pneumonitis

during interferon and/or herbal drug therapy in patients with chronic

active hepatitis.|European Respiratory Journal; vol 9; no 12; pp

2691-2696; ISSN: 0903-1936; 31 ref.|Four cases of acute

pneumonitis are reported from Japan due either to interferon or a

herbal drug, Sho-saiko-to, or both in combination, in patients with

chronic active hepatitis. These cases shared common clinical

features: fever, dry cough, dyspnoea, hypoxaemia, diffuse infiltrates

both on chest radiography and chest computed tomography,

restrictive pulmonary functional impairment, and alveolitis on

examination of transbronchial lung biopsy, all of which suggest

acute interstitial pneumonia. Also, lymphocytosis was observed in

association with the dominant CD8+ T-cell subset in

bronchoalveolar lavage fluid. A lymphocyte stimulation test using

peripheral blood was positive to interferon in one case and to Sho-

saiko-to in another. All patients responded to oral prednisolone

therapy. Peripheral soluble interleukin-2 receptor levels decreased

in parallel with improvement in the clinical course. All patients were

free of symptoms with a follow-up of 1-3 yrs. Interferon- and/or Sho-

saiko-to-induced acute pneumonitis may be due to allergic-

immunological mechanisms rather than toxicity, and peripheral

levels of soluble interleukin-2 receptor appear to be good markers

of disease activity.

 

Itoh-S, Marutani-K, Nishijima-T, Matsuo-S, Itabashi-M.|(1995)|Liver

injuries induced by herbal medicine, Syo-saiko-to (xiao-chai-hu-

tang).|Digestive Diseases and Sciences; vol 40; no 8; pp 1845-

1848; ISSN: 0163-2116; 20 ref.|Syo-saiko-to (Sho-Saiko-To),

known as xiao-chai-hu-tang in Chinese, is a herbal medicine

consisting of 7 plants which is used to treat liver diseases,

including chronic viral hepatitis, fevers, fatigue, abdominal

discomfort and nausea. Four case reports (all women) on the

hepatotoxic effects of Syo-saiko-to are reported.

 

Kaneko-M, Kawakita-T, Tauchi-Y, Saito-Y, Suzuki-A, Nomoto-

K.|(1994)|Augmentation of NK activity after oral administration of a

traditional Chinese medicine, Xiao-Chai-Hu-Tang (Shosaiko-

to).|Immunopharmacology and Immunotoxicology; vol 16; no 1; pp

41-53; ISSN: 0892-3973; 23 ref.|Xiao-Chai-Hu-Tang (Japanese

name: Shosaiko-to) is composed of the hot water extract of 7

medicinal plants (Bupleurum sp., Scutellaria spp., Ziziphus sp.,

Panax sp., Glycyrrhiza sp, Zingiber sp. and Pinellia sp.). Oral

administration of Xiao-Chai-Hu-Tang (1000 mg/kg) to mice

significantly augmented natural killer (NK) cell activity in the liver

and peripheral blood, and stimulated NK cell-mediated cytotoxic

activity. The clinical efficacy of Shosaiko-to in patients with chronic

viral hepatitis is due to augmentation of NK activity in the liver.

 

Kase-Y, Yuzurihara-M, Iizuka-S, Ishige-A, Komatsu-Y.|(1997)|The

effects of Hange-shashin-to on gastric function in comparison with

Sho-saiko-to.|Biological and Pharmaceutical Bulletin; vol 20; no 11;

pp 1155-1159; ISSN: 0918-6158; 36 ref.|Hange-Shashin-To (TJ-14)

is used to treat acute and chronic gastrointestinal catarrh,

fermentative diarrhea and acute gastroenteritis, whereas Sho-Saiko-

To (TJ-9) is used to treat acute febrile disease, pneumonia,

bronchitis, the common cold, hepatic dysfunction and chronic

gastroenteric disease. The herbal contents are the same except for

the fact that TJ-14 contains Coptis rhizomes whereas TJ-9 contains

Bupleurum roots instead of Coptis. The effects of TJ-14 on gastric

function were examined in comparison with TJ-9. Oral treatment

with TJ-14 (125-500 mg/kg) in rats caused dose-dependent

suppression of ethanol-induced gastric injury, while it did not

suppress gastric lesions induced by water-immersion stress. TJ-9

(125-500 mg/kg, p.o.) suppressed both water-immersion stress-

induced gastric lesions and ethanol-induced gastric injury in a dose-

dependent manner. Intraduodenal administration of TJ-14 even at

500 mg/kg did not affect gastric juice secretion, while TJ-9 at 125

to 500 mg/kg dose-dependently suppressed gastric juice secretion.

TJ-14 (125-500 mg /kg, p.o.) accelerated gastric emptying in

normal rats and improved the delayed gastric emptying induced by

BaCl2 in a dose-dependent manner, whereas such effect was not

noted with TJ-9. Oral treatment with TJ-14 at 500 mg/kg

significantly suppressed apomorphine-induced vomiting, but it did

not affect copper sulfate-induced vomiting. TJ-14 had an anti-ulcer

action (probably based on its ability to protect the gastric mucosa),

improvement of gastric emptying and an anti-emetic action. TJ-9

also showed anti-ulcer effects, probably based on its ability to

suppress gastric secretion and to protect the gastric mucosa. This

experiment demonstrated the effectiveness of TJ-14 and TJ-9

against gastric disease, and provided basic data which explain the

differences in clinical application between these two kampo

medicines.

 

Kato-M, Liu-Wei, Yi-Hong, Asai-N, Hayakawa-A, Kozaki-K-I,

Takahashi-M, Nakashima-I.|(1998)|The herbal medicine Sho-saiko-

to inhibits growth and metastasis of malignant melanoma primarily

developed in ret-transgenic mice.|Journal of Investigative

Dermatology; vol 111; no 4; pp 640-644; ISSN: 0022-202X; 23

ref.|The antitumour and antimetastatic effects of Sho-saiko-to and

its chemically defined ingredients were investigated against primary

skin melanomas developed in a metallothionein-I (MT)/ret

transgenic mouse line and against a melanoma cell line (Mel-ret)

derived from a primary tumour developed in a MT/ret transgenic

mouse. In vitro, Sho-saiko-to suppressed the growth of Mel-ret

cells more strongly than any single ingredient of Sho-saiko-to,

although baicalin as one of several ingredients tested also

suppressed it significantly. In vivo, Sho- saiko-to: (i) significantly

delayed the onset of tumour development (1.5 months); (ii) retarded

the transition to malignancy; (iii) significantly decreased the

incidence of distant metastasis to brain, kidney and liver at the

malignant stage; and (iv) significantly prolonged life span (2.6

months). Moreover, Sho-saiko-to and baicalin down-regulated the

matrix metalloproteinase-2 and -9 expression levels, and

upregulated their inhibitor expression level in both primary tumours

and Mel-ret cells.

 

Kato-M, Marumoto-M, Hayashi-M, Maeda-T, Hayashi-

E.|(1984)|Pharmacological studies on Saiko prescriptions. IV.

Effect of Shosaiko-to on swelling of rat hind paws induced by

carrageenin. V. Mechanisms of actions of Shosaiko-to on swelling

of rat hind paws induced by carrageenin.|Yakugaku Zasshi; vol 104;

no 5; pp 509-515; 516-523; 15 ref.|The constituents of this

traditional Chinese drug with anti-inflammatory activity were

Bupleurum root, Scutellaria root, Zingiber rhizome and ginseng

(Panax ginseng) root. Of the remaining 3 constituents, Glycyrrhiza

root had only a minor effect, and Ziziphus fruit and Pinellia tuber

had no effects.

 

Kawakatsu-T, Nomura-S, Kido-H, Yamaguchi-K, Fukuroi-T, Suzuki-

M, Yanabu-M, Kokowa-T, Yasunaga-K.|(1994)|Effect of three

Japanese Kampo medicines on platelet activation by monoclonal

anti-platelet membrane glycoprotein antibodies.|American Journal

of ; vol 22; no 1; pp 71-76; ISSN: 0192-415X; 16

ref.|Idiopathic thrombocytopenic purpura is an autoimmune disease

caused by the interaction of IgG and other antibodies with the

surface of platelets or megakaryocytes. Thrombocytopenia is

thought to be caused by phagocytosis and destruction of antibody-

coated platelets; some antiplatelet antibodies also directly destroy

platelets. The effect of 3 Japanese Kampo medicines, Sho-Saiko-

To (contains 7 plants, also known as TJ-9), Juzen-Taiho-To

(contains 10 medicinal plants, also known as TJ-48), and Sairei-To

(contains 12 medicinal plants, also known as TJ-114), was

investigated on platelet activation by an anti CD9 monoclonal

antibody (NNKY1-19) and an antihuman Fc gamma -receptor II

monoclonal antibody (NNKY3-2). Sho-Saiko-To and Sairei-To

partially suppressed aggregation induced by NNKY1-19 and

suppressed collagen-induced aggregation, and Juzen-Taiho-To

suppressed aggregation induced by NNKY3-2. The 3 Kampo

medicines did not affect antibody binding to platelets. All 3

medicines inhibited platelet activation induced by antiplatelet

antibodies without altering the binding of these antibodies to the

platelets.

 

Kayano-K, Sakaida-I, Uchida-K, Iizuka-N, Miyamoto-K, Okita-

K.|(1998) |Inhibitory effects of Sho-saiko-to (TJ-9) on liver

fibrosis.|Journal of Traditional Medicines; vol 15; no 5; pp 432-433;

1 ref.|

 

Kayano-K, Sakaida-I, Uchida-K, Okita-K.|(1998)|Inhibitory effects of

the herbal medicine Sho-saiko-to (TJ-9) on cell proliferation and

procollagen gene expressions in cultured rat hepatic stellate

cells.|Journal of Hepatology; vol 29; no 4; pp 642-649; ISSN: 0168-

8278; 38 ref.|Hepatic stellate cells (Ito cells or lipocytes) were

isolated from male Wistar rats. Water-soluble constituents of Sho-

saiko-to were obtained at concentrations of 10, 100, 250, 500 and

1000 micro g/ml and added to the cell culture medium.

Morphological transformation of cells was observed under a phase-

contrast microscope. Flow cytometric analysis was performed on

day 4 of culture to evaluate the potential of the cells to proliferate

by analysing cell cycles. Northern blot analysis was carried out on

day 3 of culture to determine the expressions of type I and type III

procollagen mRNAs. Sho-saiko-to (500 and 1000 micro g/ml)

inhibited morphological transformation of the stellate cells to

myofibroblast-like cells. It resulted in accumulation of the cells in

the G0/G1 phase (118.8 plus or minus 0.7% and 119.2 plus or

minus 0.5%, respectively as compared with control) and

significantly decreased the number of cells in the G2/M phase

(47.5 plus or minus 8.1% and 48.9 plus or minus 2.0%,

respectively). At the same concentrations, it also significantly

suppressed type I procollagen mRNA expression to 51.5 plus or

minus 6.4% and 34.9 plus or minus 3.7%, respectively, and type III

to 51.3 plus or minus 12.3% and 46.7 plus or minus 11.4%,

respectively. Sho-saiko-to could be a potent inhibitor in the

pathogenesis of liver fibrosis.

 

Kojima-K, Mizukami-H, Tazawa-T, Nose-M, Inoue-M, Ogihara-

Y.|(1998)|Long-term administration of " sho-saiko-to " increases

cytochrome P-450 mRNA level in mouse liver.|Biological and

Pharmaceutical Bulletin; vol 21; no 4; pp 426-428; ISSN: 0918-

6158; 16 ref.|Simplified differential display of mRNA was applied to

isolate and identify the genes in mouse liver that are

transcriptionally regulated upon administration of sho-saiko-to

(used in Japan to treat hepatitis and other inflammatory diseases).

A cDNA fragment up-regulated by sho- saiko-to was isolated and

characterized. cDNA sequencing and subsequent database

analysis revealed that the fragment showed significant sequence

similarity to mouse testosterone 16-alpha-hydroxylase

(cytochrome P-45016 alpha ) cDNA. The increased level of m RNA

expression of cytochrome P-45016 alpha in association with sho-

saiko-to administration suggests a molecular mechanism for the

chemopreventive effect of sho-saiko-to. This result indicates the

usefulness of the mRNA differential display technique to investigate

the molecular mechanism of Kampo medicine.

 

Kusunose-M, Qiu-Bing, Cui-TaiLin, Hamada-A, Yoshioka-S, Ono-

M, Miyamura-M, Kyotani-S, Nishioka-Y.|(2002)|Effect of Sho-saiko-

to extract on hepatic inflammation and fibrosis in

dimethylnitrosamine induced liver injury rats.|Biological and

Pharmaceutical Bulletin; vol 25; no 11; pp 1417-1421; ISSN: 0918-

6158; Publisher: Pharmaceutical Society of Japan; Tokyo; Japan;

29 ref.|Sho-saiko-to extract, a Chinese herbal medicine, is widely

used for the treatment of chronic hepatitis in Japan. However, it is

not clear what conditions of hepatic inflammation and fibrosis are

improved by Sho-saiko-to. We therefore induced various stages of

liver injury in model male Wistar rats and administered Sho-saiko-

to extract. We then evaluated the liver inflammation and liver

fibrosis-improving effects of Sho-saiko-to extract. The liver injury

model rats were produced by administration of various doses of

dimethylnitrosamine (DMN) and Sho- saiko-to extract was

administered to these rats. Then the liver inflammation and fibrosis-

improving effects of Sho-saiko-to extract were evaluated according

to L-asparate aminotransferase (AST), L-alanine aminotransferase

(ALT), liver retinoid levels, levels of hydroxyproline, Transforming

Growth Factor- beta (TGF- beta ) and the liver fibrosis area. These

indicators depended on the total doses of DMN. The ability of Sho-

saiko-to extract to improve liver inflammation and fibrosis was

limited to the following levels of the respective parameters: AST

levels (234-264U/litre), ALT levels (208-232 U/litre), TGF- beta

levels (1102-1265 pg/g liver tissue), hydroxyproline levels (633-719

nmol/g liver tissue), and liver fibrosis area (9.7-10.6 times for

normal rat). These findings suggest that Sho-saiko-to extract is

effective in the treatment of liver inflammation and fibrosis up to a

certain degree of severity, but it produces no improvement in more

severe cases.

 

Kyo-R, Nakahata-N, Sakakibara-I, Kubo-M, Ohizumi-

Y.|(1998)|Effects of Sho-saiko-to, San'o-shashin-to and Scutellariae

Radix on intracellular Ca2+ mobilization in C6 rat glioma

cells.|Biological and Pharmaceutical Bulletin; vol 21; no 10; pp

1067-1071; ISSN: 0918-6158; 26 ref.|Glial cells are able to support

neurons physically and functionally. The effects of Kampo

medicines on glial cell function, especially Ca2+ mobilization, were

investigated. C6 rat glioma cells expressed neurotransmitter

receptors (H1-histamine-, muscarinic cholinergic and adrenergic

alpha 1-receptors), stimulation of which resulted in

phosphoinositide hydrolysis and increase in intracellular Ca2+

concentrations ((Ca2+)i). Aqueous extracts of Sho-saiko-to and

San'o-shashin-to, Kampo medicines which contain Ogon (i.e.

Scutellariae Radix, the root of Scutellaria baicalensis), inhibited the

increase in (Ca2+)i induced by histamine (100 micro M), in a

concentration-dependent manner. The water extract of Scutellariae

Radix potently decreased (Ca2+)i in a concentration-dependent

manner. Sho-saiko-to, San'o-shashin-to and Scutellariae Radix

significantly inhibited histamine-induced accumulation of total

(3H)inositol phosphates, consistent with their inhibition of the

increase in (Ca2+)i. These results suggest that Sho-saiko-to, San'o-

shashin-to and Scutellariae Radix inhibit Ca2+ mobilization, acting

by inhibiting the activation of phospholipase C by receptors. This

inhibitory effect may be important in interpreting the

pharmacological actions of these Kampo medicines.

 

Li-Chuan, Homma-M, Ohkura-N, Oka-K.|(1998)|Stereochemistry

and putative origins of flavanones found in post-administration urine

of the traditional Chinese remedies Shosaiko-to and Daisaiko-

to.|Chemical and Pharmaceutical Bulletin; vol 46; no 5; pp 807-811;

ISSN: 0009-2363; 17 ref.|The optically active flavanones

dihydrowogonin and dihydrooroxylin A were found in the urine of

healthy volunteers who orally received extracts of Scutellaria

baicalensis or the traditional Chinese remedies Shosaiko-to and

Daisaiko-to on separate occasions. These remedies, which

consisted of dried extracts of Scutellariae Radix, Bupleuri Radix,

Pinelliae Tuber, Zizyphi Fructus and other herbs, contained

metabolic precursors of these flavanones, but not the flavanones

themselves, in stoichiometrically sufficient amounts. Structures

and stereochemistry of the flavanones were elucidated by UV,

circular dichroism (CD), electron impact (EI)-MS and 1H-NMR

analyses, showing that the biotransformations from the

corresponding flavones (wogonin and oroxylin A) were

stereoselective with a preference for the S-enantiomers. The

putative origins of the flavanones were confirmed in terms of

pharmacokinetics. Renal excretion times of the flavanones and the

flavones suggested that the stereoselective transformations might

have occurred in the intestinal tract as a result of microfloral

metabolism before absorption.

 

Li-Chuan, Homma-M, Oka-K.|(1998)|Characteristics of delayed

excretion of flavonoids in human urine after administration of

Shosaiko-to, a herbal medicine.|Biological and Pharmaceutical

Bulletin; vol 21; no 12; pp 1251-1257; ISSN: 0918-6158; 21

ref.|Shosaiko-to (TJ-9) is a herbal medicine consisting of 7

medicinal plants. TJ-9 (5 g) was administered to 5 healthy

volunteers, and the types and amounts of compounds excreted in

the urine for the following 52 h were determined by HPLC analysis.

Excretion rate-time curves were analysed. Four flavonoids

(liquiritigenin, baicalein, wogonin and oroxylin A) were found in

urine samples and in TJ-9. Glycosides in TJ-9 were also

transformed by microflora. Davidigenin, which was not found in TJ-

9, was an intestinal metabolite of liquiritigenin. Two flavanones, S-

dihydrowogonin and S-dihydrooroxylin A, were identified as the

metabolites of wogonin and oroxylin A, respectively. Excretion rate-

time curves of the flavonoids were divided into 3 types of structure-

dependent absorption: (1) fast absorption of herbal-origin aglycons;

(2) moderately-delayed absorption of aglycons derived from herbal

glycosides; and (3) markedly-delayed absorption after the

molecular transformation of herbal compounds. Individual excretion

profiles seemed to depend on microflora activities. S-

dihydrowogonin and S-dihydrooroxylin A were found in half of the

volunteers, suggesting that there are rapid and poor metabolizers of

flavonoids.

 

Li-Chuan, Homma-M, Oka-K.|(1998)|Chiral resolution of four major

flavanones in post-administrative urine of Chinese herbal medicines

by HPLC on macroporous silica gel coated with cellulose tris(3,5-

dimethylphenylcarbamate).|Biomedical Chromatography; vol 12; no

4; pp 199-202; ISSN: 0269-3879; 18 ref.|Direct chiral resolution of 4

major flavanones, recovered from urine obtained after administration

of the traditional Chinese medicines Daisaiko-to and Shosaiko-to,

was achieved by HPLC on Chiralcel OD, a macroporous silica gel

coated with cellulose tris(3,5-dimethylphenylcarbamate).

Chromatographic conditions were optimized for satisfactory

enantiomeric resolution of the polysubstituted flavanones. Urinary

liquiritigenin and naringenin were mixtures of R and S-enantiomers,

while dihydrowogonin and dihydrooroxylin A were predominantly

excreted as S-enantiomers. Hence the described chiral HPLC

technique can be applied to evaluate the pharmacokinetics of chiral

flavanone enantiomers after oral administration of the herbal

medicines.

 

Liu-ChiNian, Chen-Ping, Editor: Liu-ChiNian, Chen-

Ping.|(1999)|Well-known formulas and modified applications.|Well-

known formulas and modified applications; xvi + 425 pp; ISBN: 7-

03-006553-0; Publisher: Science Press; Beijing; China.|This series

is intended for students and practitioners of traditional Chinese

medicine (TCM). This volume concerns the TCM formulas recorded

in the classic texts. Eighteen main formulas and 117 derivative

formulas are described in the 18 chapters. Each chapter is divided

into 3 sections giving a comment on the primary formula itself with

details of its ingredients, compatibility, administration and function;

the clinical applications of the formula for the treatment of particular

diseases; and finally the derivative formulas and their applications.

The formulas covered are as follows: Ma Huang Tang, Gui Zhi

Tang, Bai Hu Tang, Xiao Chai Hu Tang, Si Ni San, Ban Xia Xie Xin

Tang, Er Chen Tang, San Ao Tang, Wu Ling San, Si Jun Zi Tang,

Sheng Mai San, Liu Wei Di Huang Wan, Si Ni Tang, Ping Wei

San, Da Cheng Qi Tang, Li Zhong Wan, Si Wu Tang, and Wu Mei

Wan.

 

Liu-ZhenLi, Tanaka-S, Horigome-H, Hirano-T, Oka-

K.|(2002)|Induction of apoptosis in human lung fibroblasts and

peripheral lymphocytes in vitro by Shosaiko-to derived phenolic

metabolites.|Biological and Pharmaceutical Bulletin; vol 25; no 1;

pp 37-41; ISSN: 0918-6158; 27 notes and ref.|Shosaiko-to is a

Kampo medicine used for the treatment of chronic hepatitis in

Japan. Lately, over 200 cases of interstitial pneumonia have been

reported resulting from Shosaiko-to therapy, and the number of

cases increased when patients were administrated interferon (IFN)-

alpha at the same time. However, the mechanisms of this

Shosaiko-to implicated interstitial pneumonia are not fully

understood. In this study, we examined by flow cytometry analysis

the in vitro effects of 7 phenolic compounds (lignans and

flavonoids), which were detected from human urine after

administration of Shosaiko-to, and IFN- alpha on inducing

apoptosis in human lung fibroblasts and peripheral blood

mononuclear cells (PBMCs). Among the 7 compounds, baicalein

and medicarpin (10 micro g/ml) showed significant apoptosis-

inducing effects on human PBMCs. In human lung fibroblasts,

medicarpin exhibited a significantly higher activity to induce

apoptosis compared to the control, and the percentage of cells

undergoing apoptosis showed time- and dose-dependent

increases. Baicalein (0.1 and 1 micro g/ml, isolated from

Scutellaria baicalensis), liquiritigenin (10 micro g/ml, isolated from

Glycyrrhiza glabra) and davidigenin (10 micro g /ml) also showed

significant effects after 96 h treatment. Whereas, baicalin, oroxylin

A and wogonin did not show any effect on inducing apoptosis in

PBMCs and fibroblasts. Baicalein and medicarpin significantly

inhibited the growth and reduced the viability of lung fibroblasts. IFN-

alpha had no apoptosis-inducing effect, and it did not show

synergistic interaction with any of the compounds derived from

Shosaiko-to on inducing apoptosis in both human lung fibroblasts

and PBMCs. Phenolic compounds found in human post-

administrative urine of Shosaiko-to, especially baicalein and

medicarpin, exhibited a direct effect on human lung fibroblasts and

immune cells to induce apoptosis.

 

Matsumoto-T, Shibata-T.|(1998)|The ex vivo effect of the herbal

medicine Sho-saiko-to on histamine release from rat mast

cells.|European Archives of Oto-Rhino-Laryngology; vol 255; no 7;

pp 359-364; ISSN: 0937-4477; 33 ref.|The traditional Japanese

herbal medicine, Sho-saiko-to (SST), has been used orally to treat

several chronic diseases including allergic rhinitis and bronchial

asthma. The effect of SST on histamine release and the

intracellular Ca2+ response in mast cells ex vivo was investigated.

A single dose of 1.0 g SST/kg was administered orally to

immunized rats 2-12 h before death. Mast cells were then

separated from peritoneal lavages and stimulated with antigen.

Inhibition of histamine release was greatest at 3 h after oral

administration. This inhibitory effect was dose-dependent and was

weaker than that of tranilast. In contrast, at 3 h, SST had no effect

on the antigen-induced Ca2+ response of the mast cells and failed

to inhibit compound 48/80-induced histamine release. The findings

show that SST has an active anti-allergic effect. SST inhibited IgE

receptor-associated protein phosphorylation in the histamine

release pathway.

 

Matsumoto-Y, Kato-M, Tamada-Y, Mori-M, Ohashi-

M.|(1997)|Enhancement of interleukin-1 alpha mediated autocrine

growth of cultured human keratinocytes by Sho-saiko-to.|Japanese

Journal of Pharmacology; vol 73; no 4; pp 333-336; ISSN: 0021-

5198; 12 ref.|The effects of Sho-saiko-to, the most commonly used

herbal medicine in Japan, on the production of interleukin (IL)-1

alpha by cultured human epidermal keratinocytes was investigated.

IL-1 alpha production was significantly promoted by treatment with

Sho-saiko-to (100 or 500 micro g/ml) for 24 or 48 h. Expression of

IL-1 alpha receptors was upregulated after treatment with Sho-

saiko-to (500 micro g/ml for 24 h or 100 or 500 micro g/ml for 48 h);

these cells showed the characteristics of multilayered differentiated

keratinocytes. The presence of an anti-IL-1 alpha antibody during

treatment (500 micro g /ml for 24 or 48 h or 100 micro g/ml for 48

h) significantly down-regulated the synthesis by the keratinocytes

and induced damage in them. Keratinocytes treated with Sho-saiko-

to might produce IL-1 alpha and express IL-1 alpha receptors. IL-1

alpha may regulate the proliferation and differentiation of

keratinocytes after Sho-saiko-to treatment. Sho-saiko-to enhanced

autocrine growth mediated by IL-1 alpha .

 

Matsuta-M, Kosaka-N, Nakatsuji-S, Awata-N.|(1998)|The inhibitory

effect of Sho-saiko-to on porcine serum-induced hepatic fibrosis in

rats.|Journal of Traditional Medicines; vol 15; no 2; pp 135-140; 15

ref.|The effects of Sho-saiko-to (Xiao-Chai-Hu-Tang, SHO) on

porcine serum-induced hepatic fibrosis were investigated in rats.

Porcine serum (0.5 ml/head) was administered i.p. twice a week for

8 weeks. During the administration of porcine serum, rats were fed

ad libitum the powdered diet containing SHO extract at 1.5 or

4.5%. In porcine serum-treated control group, plasma GOT

(aspartate aminotransferase) and GPT (alanine aminotransferase)

levels were significantly increased, plasma prothrombin time was

prolonged and hydroxyproline content in the liver was dramatically

increased at the end of the experiment. These changes were

significantly inhibited by SHO treatment. Histologically and

morphometrically, hepatic fibrosis which appeared in control group

was apparently ameliorated in SHO-treated groups. These results

indicate that SHO inhibits porcine serum-induced hepatic fibrosis in

rats and may be useful in treatment of hepatic fibrosis in clinic.

 

Miura-T, Nakai-Y, Arai-I, Amagaya-S, Kubo-M, Komatsu-Y, Okada-

M.|(1998) |The studies of compounds contained in Sho-saiko-to on

the inhibition of NO production.|Journal of Traditional Medicines; vol

15; no 5; pp 442-443; 4 ref.|

 

Miyamoto-K, Lange-M, McKinley-G, Stavropoulos-C, Moriya-S,

Matsumoto-H, Inada-Y.|(1996)|Effects of Sho-saiko-to on

production of prostaglandin E2, (PGE2) leukotriene B4 (LTB4) and

superoxide from peripheral monocytes and polymorphonuclear

cells isolated from HIV infected individuals.|American Journal of

; vol 24; no 1; pp 1-10; ISSN: 0192-415X; 31

ref.|The effects of Sho-saiko-to (SST), a traditional Chinese

medicine consisting of 7 medicinal plants, on the production of

PGE2 by monocytes and LTB4 and superoxide by

polymorphonuclear cells (PMNC), isolated from healthy and HIV

(human immunodeficiency virus)-infected individuals, were studied.

SST inhibited the production of PGE2 from monocytes stimulated

by opsonized zymosan in all groups including the healthy control

group. SST also inhibited the production of superoxide by FMLP-

stimulated PMNC. SST enhanced the production of LTB4 from

A23187-stimulated PMNC. SST might be useful in the treatment of

HIV infection, since inhibition of PGE2 or superoxide production will

lead to indirect suppression of HIV, and enhancement of LTB4 will

contribute to the upregulation of the immune reaction in HIV-

infected individuals.

 

Miyamura-M, Ono-M, Kyotani-S, Nishioka-Y.|(1998)|Effects of sho-

saiko-to extract on fibrosis and regeneration of the liver in

rats.|Journal of Pharmacy and Pharmacology; vol 50; no 1; pp 97-

105; ISSN: 0022-3573; 19 ref.|Sho-saiko-to, one of the most widely

used Chinese herbal preparations (containing 7 herbs), has long

been used for the treatment of chronic liver diseases. Its effect in

retarding the process of liver fibrosis and accelerating liver

regeneration, especially its effect on Ito cells (which store fats,

mainly retinol palmitate) that are thought to be deeply involved with

liver fibrosis was investigated. Sho-saiko-to extract or its active

constituents (glycyrrhizin, baicalin and baicalein) were orally

administered (0.75, 1.5 or 3% in the food) for 14 days to rats with

dimethylnitrosamine-induced liver-injury. After treatment with sho-

saiko-to extract, hepatic function improved, histopathological

results confirmed repair of liver tissue, and retinoid levels

increased. However, when active constituents of sho- saiko-to

extract were administered alone, liver retinoid levels remained low,

implying that interaction among active constituents of the extract is

involved in the suppression of Ito cell activation. When sho-saiko-to

extract was administered to 70% hepatectomized normal and liver-

injured rats, liver weight, the number of S-phase-cells and retinoid

levels increased with time. However, these changes were different

for normal and liver-injured rats, suggesting that the site of action of

sho-saiko-to extract in regenerating liver is different for normal and

liver-injured rats. These results show that sho-saiko-to extract was

useful for suppressing the activation of Ito cells.

 

Mizushima-Y, Oosaki-R, Kobayashi-M.|(1997)|Clinical features of

pneumonitis induced by herbal drugs.|Phytotherapy Research; vol

11; no 4; pp 295-298; ISSN: 0951-418X; 21 ref.|Twenty-four cases

(22 patients) with herbal drug-induced pneumonitis were reviewed

based on the Japanese medical literature. Eight types of herbal

drugs were reported as causative agents, and 15 of the 24 cases

were due to Sho-Saiko-To. On chest X-ray films, one patient with

bronchial asthma showed a pattern of pulmonary infiltration with

eosinophilia (PIE syndrome) and the others a diffuse interstitial

pneumonitis. The duration of herbal drug intake was variable from a

period of one day to several months. Major clinical symptoms were

dyspnoea, cough and fever. The laboratory data showed

hypoxaemia and positive inflammatory reactions with increased

WBC and raised ESR and CRP. Results of bronchoalveolar lavage

showed an increased lymphocyte or neutrophil population and a

low OKT4/OKT8 ratio. The in vitro lymphocyte stimulation test was

positive in 74% (17/23) of cases and the in vivo challenge test

100% (10/10).

 

Nakahata-N, Kutsuwa-M, Kyo-R, Kubo-M, Hayashi-K, Ohizumi-

Y.|(1998)|Analysis of inhibitory effects of Scutellariae Radix and

baicalein on prostaglandin E2 production in rat C6 glioma

cells.|American Journal of ; vol 26; no 3/4; pp 311-

323; ISSN: 0192-415X; 34 ref.|Inhibitory mechanism of the water

extract of Scutellaria baicalensis on prostaglandin E2 (PGE2)

release was examined in C6 rat glioma cells. The extract reduced

Ca2+ ionophore A23187-induced PGE2 release by inhibiting

arachidonic acid (AA) liberation. Sho-saiko-to and San'o-shashin-

to, which contain S. baicalensis, also inhibited PGE2 release.

A23187 caused phosphorylation of mitogen-activated protein

kinase (MAPK), resulting in activation of cytosolic phospholipase

A2 (cPLA2). S. baicalensis extract and baicalein inhibited the

phosphorylation of MAPK. Baicalein, but not baicalin, inhibited

A23187-induced PGE2 release.

 

Nakayama-T, Sakamoto-S, Mori-T, Nagasawa-

H.|(1994)|Suppression of tumourigenesis and tumour growth of

mouse mammary glands by a traditional Chinese herbal medicine,

Sho-saiko-to.|Oncology Reports; vol 1; no 1; pp 75-78; 11

ref.|Hyperplastic alveolar nodule (HAN) is a representative

preneoplastic state in mammary glands of mice. The effect of Sho-

saiko-to (containing 7 medicinal plants) on the formation and

growth of HAN and mammary tumour growth in SHN virgin mice

was investigated. Chronic oral administration of Sho-saiko-to

reduced the number and the area of HAN and mammary

thymidylate synthetase activity, and reduced the concentration of

serum prolactin. In established mammary tumours, 20-day

administration of Sho-saiko-to reduced the activity of thymidylate

synthetase and thymidine kinase, and slightly reduced serum

prolactin concentration; a significant change of mammary-tumour

growth was not observed. Sho-saiko-to may prevent mammary

tumourigenesis by suppression of the de novo pathway of

pyrimidine nucleotide synthesis and mammary tumour growth by

suppression of the salvage pathway as well as the de novo

pathway in mice.

 

Nishimura-N, Naora-K, Hirano-H, Iwamoto-K.|(1998)|Effects of Sho-

saiko-to on the pharmacokinetics and pharmacodynamics of

tolbutamide in rats.|Journal of Pharmacy and Pharmacology; vol

50; no 2; pp 231-236; ISSN: 0022-3573; 15 ref.|Interactions

between Sho-saiko-to (Xiao Chai Hu Tang), a major Chinese

traditional medicine, and co-administered drugs were investigated.

The effects of Sho-saiko-to on the pharmacokinetics and glucose

responses of a sulfonylurea hypoglycaemic agent, tolbutamide,

after oral administration in rats were determined. Plasma

tolbutamide and glucose levels were periodically measured in male

Sprague-Dawley rats cannulated in the jugular vein after

administration of tolbutamide (50 mg/kg) with or without Sho-saiko-

to extract powder (300 mg/kg). Co-administration of both drugs

tended to elevate the plasma tolbutamide concentration in the

absorption phase. A 2-compartment lag-time model described the

plasma tolbutamide concentration-time data. The maximum

concentration of tolbutamide was significantly increased and time

to reach the maximum concentration was reduced to about 70%

following co-administration with Sho-saiko-to. There was no

significant change in area under the curve or in the elimination half-

life of tolbutamide. The extent of the lowering effect of tolbutamide

on plasma glucose levels was increased up to 0.75 h and

decreased after 5 h after co-administration with Sho-saiko-to. Sho-

saiko-to slightly promoted the gastrointestinal absorption of

tolbutamide. Elevation of gastrointestinal absorption rate by Sho-

saiko-to might potentiate the hypoglycaemic effect of tolbutamide

in the early period after oral administration.

 

Nishimura-N, Naora-K, Hirano-H, Iwamoto-K.|(1999)|A Chinese

traditional medicine, Sho-saiko-to (Xiao-Chaihu-Tang), reduces the

bioavailability of tolbutamide after oral administration in

rats.|American Journal of ; vol 27; no 3/4; pp 355-

363; ISSN: 0192-415X; 16 ref.|The effects of Sho-saiko-to on the

pharmacokinetics of tolbutamide were investigated in rats. After

intravenous administration of tolbutamide (5 mg/kg), no significant

change in the pharmacokinetics of tolbutamide was observed in

both groups of single and multiple (7 days) pre-administration of

Sho-saiko-to (500 mg/kg). In the study of single oral administration

of tolbutamide (50 mg/kg), co-administration of Sho-saiko-to tended

to accelerate the initial absorption rate of tolbutamide. The area

under the plasma concentration-time curve of tolbutamide after oral

administration was significantly reduced by Sho-saiko-to.

Subsequently, a significant decrease was observed in the oral

bioavailability of this drug when Sho-saiko-to was given

concomitantly. Sho-saiko-to reduced the bioavailability of

tolbutamide after oral administration in rats, and this change was

not related to hepatic metabolism.

 

Nishimura-N, Naora-K, Hirano-H, Iwamoto-K.|(2001)|Changes in the

dissolution of tolbutamide by a traditional Chinese medicine, Sho-

saiko-to (Xiao Chaihu Tang).|Biological and Pharmaceutical

Bulletin; vol 24; no 4; pp 409-413; ISSN: 0918-6158; 18

ref.|Dissolution rate is considered an important factor affecting

absorption and efficacy after the oral administration of tolbutamide.

Since in many cases traditional Chinese herbal medicines,

including Sho-saiko-to (TJ-9, Xiao Chaihu Tang), are taken with

other drugs, it is likely that the dissolution and absorption of

concomitant drugs in the gastrointestinal tract are influenced by

the presence of traditional Chinese herbal medicines. In this study,

the effects of TJ-9 on the in vitro dissolution of tolbutamide were

examined. We carried out the dissolution test of tolbutamide in the

absence or presence of traditional Chinese medicines (Kakkon-to,

TJ-1; Hachimi-jio-gan, TJ-7; Chorei-to, TJ-40; Shakuyaku-kanzo-to,

TJ-68; TJ-9; Glycyrrhizae Radix, GR; glycyrrhizin, GL) by using a

pH 1.2 dissolution medium. Tolbutamide was determined by HPLC

assay. The moment parameters, i.e., mean dissolution time (MDT),

and the dissolution rate constant up to 20 min (kd) were estimated

from the dissolution profiles on the basis of the first-order kinetics.

Preparations containing GR, namely TJ-1, TJ-9 and TJ-68,

significantly reduced the kd and increased the MDT of tolbutamide,

while TJ-7 and TJ-40 had no effect on the early dissolution profile of

tolbutamide. The extent of decrease in the kd in the presence of TJ-

1, TJ-9 and TJ-68 was dependent on their GR contents. Similar

inhibitory effects on the dissolution rate of tolbutamide were

observed when GR alone was added to the test medium. In

addition, GL, a major constituent of GR, induced a 50% increase in

MDT and a 30% decrease in kd. The above results indicate that

Chinese traditional preparations containing GR have an inhibitory

effect on the in vitro dissolution of tolbutamide, which is derived

from GL in the preparations.

 

Nishioka-Y, Kyotani-S, Miyamura-M, Kusunose-M.|(1992)

|Influence of time of administration of Shosaiko-to extract granule (a

Chinese drug) on (the) blood concentration (in men) of its active

constituents (glycyrrhizin, baicalin and baicalein, in 10

men).|Chemical and Pharmaceutical Bulletin; vol 40; no 5; pp 1335-

1337; ISSN: 0009-2363; 7 ref.|

 

Nose-M, Terawaki-K, Iwahashi-N, Oguri-K, Ogihara-

Y.|(2002)|Comparative study of the high molecular mass fraction

and low molecular mass fraction of Sho-saiko-to in a murine

immunologically induced liver injury model.|Biological and

Pharmaceutical Bulletin; vol 25; no 1; pp 64-67; ISSN: 0918-6158;

34 ref.|We compared the pharmacological actions of the high and

low molecular mass fractions of Sho-saiko-to using a murine (male

ICR mice) immunologically induced liver injury model to estimate

the roles of these fractions in the expression of the

pharmacological action. In a Bacillus Calmette-Guerin

(BCG)/lipopolysaccharide (LPS)-induced liver injury model, Sho-

saiko-to and both of its fractions significantly reduced the

increases in the aminotransferase levels in the serum. They also

reduced the increase in the nitric oxide (NOx) level in the serum.

On the other hand, Sho-saiko-to and its high molecular mass

fraction suppressed the increase in plasma NOx level in an LPS-

induced endotoxin shock model but its low molecular mass fraction

did not. These results suggest the possibility that both fractions

act hepatoprotectively in a different manner. We believe that these

results can help to elucidate the mechanism of action of

ingredients in Sho-saiko-to.

 

Nose-M, Terawaki-K, Ogihara-Y.|(1997)|The role of a crude

polysaccharide fraction in the macrophage activation by

" Shosaikoto " .|Phytomedicine; vol 4; no 1; pp 23-26; 19 ref.|Oral

administration of the traditional Japanese/Chinese herbal medicine

Shosaikoto (1.4 g/kg for 7 days), prepared from 7 medicinal herbs,

to male ICR mice, enhanced phagocytosis of casein-induced

peritoneal macrophages and nitric oxide (NO) production of

thioglycollate broth-induced murine peritoneal macrophages in vitro.

Ethanol-precipitation of the Shosaikoto extract was carried out to

produce 2 fractions: one of ethanol-precipitates (EP) and one

ethanol-soluble (ES). The EP fraction, which consisted of

polysaccharide, showed enhancement of phagocytosis and NO

production comparable to that of Shosaikoto. The ES fraction,

which consisted of low molecular compounds, did not affect

macrophage function. The results suggest that the crude

polysaccharide fraction plays an important role in macrophage

activation by Shosaikoto.

 

Ohnishi-N, Okada-K, Yoshioka-M, Kuroda-K, Nagasawa-K, Takara-

K, Yokoyama-T.|(2002)|Studies on interactions between traditional

herbal and western medicines. V. Effects of Sho-saiko-to (Xiao-Cai-

hu-Tang) on the pharmacokinetics of carbamazepine in

rats.|Biological and Pharmaceutical Bulletin; vol 25; no 11; pp 1461-

1466; ISSN: 0918-6158; Publisher: Pharmaceutical Society of

Japan; Tokyo; Japan; 23 ref.|The possibility of pharmacokinetic

interactions between Sho-saiko-to extract powder (TJ-9), the most

widely used traditional Chinese herbal (Kampo) medicine in Japan,

and carbamazepine (CBZ), an important anti-epileptic drug, was

examined in 9-week-old female Sprague Dawley rats. There was no

significant difference in the protein binding of CBZ in serum

obtained before and after the single oral administration of TJ-9. The

addition of TJ-9 to normal hepatic microsomes inhibited CBZ-10,11-

epoxylase activity in a concentration-dependent manner. Liver

weight, amounts of P450 and cytochrome b5 in hepatic

microsomes and the formation of carbamazepine-10,11-epoxide

(CBZ-E), an active metabolite of CBZ, by microsomes were not

influenced by 2-week repeated oral pretreatment with TJ-9 (1

g/kg/day), although pretreatments with phenobarbital (80 mg/kg/d,

i.p.) significantly increased these parameters. The simultaneous

oral administration of TJ-9 (1 g/kg) significantly decreased the peak

plasma concentration of CBZ and the area under the concentration-

time curve of CBZ-E, and lengthened the time to reach the peak

concentration of CBZ after oral administration of CBZ. Two-week

repeated oral pretreatment with TJ-9, however, did not affect the

plasma concentration-time profile or any pharmacokinetic

parameter of CBZ or CBZ-E. Also, a single oral administration of TJ-

9 (1 g/kg) significantly delayed gastric emptying. These results

indicated that the simultaneous oral administration of TJ-9 with

CBZ to rats decreased the gastrointestinal absorption of CBZ, at

least in part, by delaying gastric emptying, without affecting the

metabolism of CBZ.

 

Ohnishi-T, Yoneyama-H, Hamamoto-T, Ishida-T, Takahara-J,

Ichikawa-Y.|(1996)|Induction of cytochrome P-450-linked

monooxygenase system in rat liver microsomes by Xiao-Chaihu-

Tang.|American Journal of ; vol 24; no 2; pp 143-

151; ISSN: 0192-415X; 26 ref.|Xiao-Chaihu-Tang (Sho-Saiko-To), a

mixture of 7 medicinal plants, is used to treat chronic liver

diseases. Administration of Xiao-Chaihu- Tang to rats for 2 weeks

induced a 25% increase in the cytochrome P-450 content of female

rat liver microsomes; no changes were observed in male

microsomes. Using various xenobiotics (benzphetamine,

aminopyrine etc.) it was shown that Xiao-Chaihu-Tang stimulated

the activities of cytochrome P-450-linked monooxygenases in

female liver microsomes; little changes in enzyme activity were

observed in male microsomes. However, in control rats, male liver

microsomes had higher contents of cytochrome P-450 and higher

cytochrome P-450-linked monooxygenase activities than female

microsomes.

 

Ohtake-N, Nakai-Y, Yamamoto-M, Ishige-A, Sasaki-H, Fukuda-K,

Hayashi-S, Hayakawa-S.|(2002)|The herbal medicine Shosaiko-to

exerts different modulating effects on lung local immune responses

among mouse strains.|International Immunopharmacology; vol 2;

no 2/3; pp 357-366; ISSN: 1567-5769; 46 ref.|Shosaiko-to (SST), a

Chinese/Japanese traditional herbal medicine, has recently been

demonstrated to increase lung interleukin-6 (IL-6) levels and to

ameliorate pulmonary disorders in BALB/c mice (BALB). In the

present study, we examined the effects of SST on lung cytokine

levels and lipopolysaccharide (LPS)-induced lung injury in C57BL/6

mice (B6), which are known to show different immune responses

from BALB due to the difference in genetic backgrounds. In B6, in

contrast with BALB, SST decreased lung IL-6 levels and

exacerbated LPS-induced lung injury. Investigation of the active

components of SST suggested that multiple ingredients were

supposed to be responsible for IL-6-attenuating activity in vivo.

Further, we examined the effect of metabolites of major ingredients

of SST on IL-6 production from lung immune cells in vitro.

Saikogenin D and oroxylin A attenuated IL-6 production in LPS-

stimulated alveolar macrophages of B6 more than in that of BALB.

Liquiritigenin, which was previously reported to enhance IL-6

production in anti-CD3 monoclonal antibody-stimulated lung

mononuclear cells of BALB, showed no effect on that of B6. These

findings suggest that SST may have different, possibly even

opposite, effects on lung immunity in hosts with different genetic

backgrounds.

 

Ohtake-N, Suzuki-R, Daikuhara-H, Nakai-Y, Yamamoto-M,

Amagaya-S, Ishige-A, Sasaki-H, Komatsu-Y, Fukuda-K, Hayashi-

S.|(2000)|Modulation of lung local immune responses by oral

administration of a herbal medicine Sho-saiko-to.|International

Journal of Immunopharmacology; vol 22; no 6; pp 419-430; ISSN:

0192-0561; 73 ref.|Sho-saiko-to (SST), a Chinese/Japanese herbal

medicine (Kampo medicine) widely used to treat chronic hepatitis

in Japan, is known to modulate immune responses. We

administered SST to BALB/c mice orally and examined the lung

tissue levels of pro anti-inflammatory cytokines, interleukin-1 beta

(IL-1 beta ), tumour necrosis factor-alpha (TNF- alpha ) and

interleukin-6 (IL-6), and the effects of SST on acute lung injury

induced by instillation of lipopolysaccharide (LPS) or IL-1. Although

SST had no effect on lung TNF- alpha or IL-1 beta level, it

increased IL-6. Investigation of active fractions of SST suggested

that multiple ingredients were supposed to be responsible for IL-6-

inducing activity. Liquiritigenin, a metabolite of liquiritin which is

one of the major ingredients in SST, enhanced in vitro IL-6

production in anti-CD3 monoclonal antibody (anti-CD3 m Ab)-

stimulated lung mononuclear cells in a cell-type specific and dose-

dependent manner. SST suppressed LPS-induced lung injury at

the later phase when lung leak was evident while being ineffective

on initial neutrophil sequestration to the lung in these models.

These findings suggest that SST modulates lung inflammation by

regulating local immune response.

 

Ohta-Y, Nishida-K, Sasaki-E, Kongo-M, Hayashi-T, Nagata-M,

Ishiguro-I.|(1997)|Comparative study of oral and parenteral

administration of Sho-saiko- to (Xiao-Chaihu-Tang) extract on D-

galactosamine-induced liver injury in rats.|American Journal of

; vol 25; no 3/4; pp 333-342; ISSN: 0192-415X; 23

ref.|The preventive effect of Sho-saiko-to (Xiao-Chaihu-Tang) extract

(TJ-9), p.o. or i.p., on the progression of D-galactosamine (GalN)-

induced liver injury was examined in 5-week-old male Wistar rats.

Rats treated once with GalN (500 mg/kg, i.p.) received TJ-9 (1

g/kg) 2 h after GalN treatment. Both p.o. and i.p. administration of

TJ-9 prevented the progression of liver injury 24 h after GalN

injection to similar degrees. Although total protein and albumin

concentrations in serum and protein concentrations in the liver

decreased with the progression of GalN-induced liver injury, TJ-9-

treatment prevented these decreases. Decreases in serum and

liver triglyceride (triacylglycerols) concentration with the

progression of liver injury were not attenuated after p.o. or i.p.

administration of TJ-9. The activities of liver 5'-nucleotidase and

glucose-6-phosphatase, marker enzymes of liver plasma and

microsomal membranes, respectively, decreased during the

progression of liver injury. A similar preventive effect on the

decrease of both enzyme activities was found after administration

of TJ-9. The effects of TJ-9 against the progression of GalN-induced

liver injury could be related to improving impaired liver protein

synthesis and repairing disrupted liver plasma and microsomal

membranes.

 

Ohtsuka-M, Fukuda-K, Yano-H, Kojiro-M.|(1995)|Effects of nine

active ingredients in Chinese herbal medicine Sho- saiko-to on 2-(2-

furyl)-3-(5-nitro-2-furyl)acrylamide mutagenicity.|Japanese Journal of

Cancer Research; vol 86; no 12; pp 1131-1135; ISSN: 0910-5050;

23 ref.|The antimutagenic effects of 9 active compounds present in

Sho-saiko- to on mutagenesis induced by a direct-acting mutagen,

2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide (AF-2) were investigated in

Salmonella typhimurium, strain TA100. The active compounds

examined were classified into 2 major groups, saponins and

flavonoids, the former comprising glycyrrhizin, saikosaponins a, c

and d, and ginsenosides Rb1 and Rg1, and the latter, baicalin,

baicalein and wogonin. Saikosaponin a and ginsenoside Rb1

significantly reduced the mutagenicity of AF-2 when applied post-

AF-2-treatment. Ginsenoside Rb1 also decreased the mutagenic

activity of AF-2 in a simultaneous treatment protocol. The results

indicate that saikosaponin a and ginsenoside Rb1 may enhance

DNA repair, and ginsenoside Rb1 may also have the ability to

inactivate the mutagenic activity of AF-2 directly. Saikosaponin d

and baicalin showed a slight enhancing effect. None of the

compounds, except baicalein, showed any toxic effect on the test

strain.

 

Ohtsu-S, Izumi-S, Iwanaga-S, Ohno-N, Yadomae-

T.|(1997)|Analysis of mitogenic substances in Bupleurum chinense

by ESR spectroscopy.|Biological and Pharmaceutical Bulletin; vol

20; no 1; pp 97-100; ISSN: 0918-6158; 18 ref.|The polyphenolic

substance(s) in the hot water extract of B. chinense (PSF) showed

strong mitogenic activity. When analysed using ESR

spectroscopy, it was found that (i) PSF showed a strong ESR

signal on g = 2.005 which was similar to the commercially available

lignin; (ii) Sho-saiko-to, which contains an extract of B. chinense,

showed similar signals on ESR; and (iii) powdered B. chinense

showed similar signals on g = 2.005. Peroxidase activity, essential

for producing polyphenolic substances, was detected in the cold

water extract of B. chinense. In addition, the signal intensity of the

ESR spectrum of B. chinense was increased after boiling. The data

of the ESR spectra of the model reactions using lignin, arginine,

proline and maltose also strongly suggested that a certain

chemical modification proceeded during the hot water extraction to

increase the percentage of the stable free radical. The mitogenic

substance in B. chinense was a polyphenolic substance extracted

by hot water, and its structure was modified during extraction to

increase the stable free radical components.

 

Okada-K, Kazaki-H, Togo-K, Tomizawa-N, Hara-S, Kaneda-

Y.|(1995)|Effect of Chinese medicines (Kampo) on antihistamine

reactivity and mast-cell degranulation in dogs.|Journal of the Japan

Veterinary Medical Association; vol 48; no 9; pp 673-676; ISSN:

0446-6454; 13 ref.|33 healthy dogs were medicated with 1.50 g/day

of Sho-seiryu-to and 1.25 g/day of Sho-fu-san, Touki-inshi or Sho-

saiko-to for a week, and the inhibitory effects on reactivity to

histamine and mast-cell degranulation were evaluated by

measuring skin wheal size at the injection site after intradermal

injection with compound 48/80 or histamine phosphate. One week

after medication, significant declines in these skin wheal sizes

were observed with Touki-inshi (83.3%), Sho- saiko-to (77.4%) or

Sho-seiryu-to (79.0%) in reaction to compound 48 /80, and Sho-fu-

san (75.6%), Sho-saiko-to (72.8%) or Sho-seiryu-to (81.1%) in

reaction to histamine phosphate. Blood cortisol concentrations

were significantly higher after medication with Sho- saiko-to and

Sho-seiryu-to. The results were indicative of therapeutic effects of

the drugs in the treatment of canine allergic dermatitis and pruritus.

 

Ono-M, Miyamura-M, Kyotani-S, Saibara-T, Ohnishi-S, Nishioka-

Y.|(1999)|Effects of Sho-saiko-to extract on liver fibrosis in relation

to the changes in hydroxyproline and retinoid levels of the liver in

rats.|Journal of Pharmacy and Pharmacology; vol 51; no 9; pp 1079-

1084; ISSN: 0022-3573; 11 ref.|The effects of Sho-saiko-to extract

on liver fibrosis were investigated in rats with dimethylnitrosamine-

induced liver-injury. Hydroxyproline and retinoid levels in the liver

were measured as indicators of liver function. In liver-injured rats,

the hydroxyproline level (957 plus or minus 154 nmol/g) was about

4.16-times that found in control livers (230 plus or minus 11

nmol/g). Administration of Sho-saiko-to (0.75, 1.5 or 3%) reduced

the hydroxyproline level significantly (to 554 plus or minus 58, 356

plus or minus 51 and 374 plus or minus 66 nmol/g, respectively).

Single administration of the active constituents of Sho-saiko-to,

glycyrrhizin, baicalin or baicalein, decreased the hydroxyproline

level significantly compared with the control, but the decrease was

smaller than in the Sho-saiko-to group. Liver retinoid level was

higher in the Sho-saiko-to group than in the control; the value

increased dose-dependently. A significant negative correlation was

detected between the hydroxyproline level and retinoid level in the

liver of liver-injured rats. Significant negative correlations were

detected between the liver hydroxyproline level and the liver

concentrations of the active constituents (glycyrretic acid, baicalin

and baicalein) in liver-injured rats. Administration of Sho-saiko-to

inhibited collagen production while an increase in retinoid level

inhibited activation of Ito cells leading to inhibition and prevention of

liver fibrosis.

 

Ono-M, Miyamura-M, Kyotani-S, Saibara-T, Ohnishi-S, Nishioka-

Y.|(2000)|Effect of Sho-saiko-to extract on HGF and TGF- beta

levels of intraorgans in liver-injured rats after partial

hepatectomy.|Journal of Pharmacy and Pharmacology; vol 52; no

1; pp 111-118; ISSN: 0022-3573; 12 ref.|To examine the effects of

Sho-saiko-to extract on liver regeneration, Sho-saiko-to extract

(0.75%, 1.5% or 3%) was administered to 70% partial

hepatectomized rats with dimethyl-nitrosamine-induced liver-injury.

S phase cell number, liver retinoid levels, hepatocyte growth factor

(HGF) and transforming growth factor-beta (TGF- beta ) levels in

each intraorgan were measured as indicators of liver regeneration.

Three to 7 days after hepatectomy, HGF and TGF- beta levels of

the liver and spleen of the Sho-saiko-to extract groups were

significantly different from the levels of the ordinary food group.

HGF levels in the Sho-saiko-to extract groups were approximately

1.3-1.8 times higher in the liver and approximately 1.8-2.1 times

higher in the spleen compared with the levels found in the ordinary

food group. TGF-beta levels in the Sho-saiko-to extract groups

were approximately 0.38-0.47 times the level in the liver and 0.58-

0.77 times the level in the spleen of the ordinary food group. There

was no difference in HGF and TGF- beta levels of the kidney and

lung between the Sho-saiko- to extract group and the ordinary food

group. There was a significant and positive correlation between

HGF level and S phase cell number in the liver (r=0.826,). There

was a significant and negative correlation between TGF- beta level

and the retinoid level in the liver (r=-0.696) . In addition, the levels of

the active constituents of Sho-saiko-to extract (glycyrrhetic acid,

baicalin and baicalein) showed high values in the liver and spleen of

partial hepatectomized rats, and increased from the third day after

partial hepatectomy. These results show that Sho-saiko-to extract

induces liver regeneration by increasing the production of HGF and

suppressing the production of TGF- beta in the liver and spleen of

partial hepatectomized rats. It was considered that the increase in

the Sho-saiko-to extract active constituent levels in the liver and

spleen greatly influences this action.

 

Piras-G, Makino-M, Baba-M.|(1997)|Sho-saiko-to, a traditional

Kampo medicine, enhances the anti-HIV-1activity of lamivudine

(3TC) in vitro.|Microbiology and Immunology; vol 41; no 10; pp 835-

839; ISSN: 0385-5600; 24 ref.|Sho-saiko-to (SST) was examined

for its inhibitory effect on HIV-1replication in peripheral blood

mononuclear cells (PBMCs). SST alone moderately inhibited HIV-1

replication at a concentration of 25 micro g/ml. When SST was

combined with zidovudine (AZT), lamivudine (3TC) or AZT plus 3TC,

SST enhanced the anti-HIV-1 activity of 3TC. In contrast, SST

slightly enhanced the anti-HIV-1 activity of AZT plus 3TC but did

not enhance the activity of AZT alone. These results suggest that

the combination of SST and 3TC has potential as a

chemotherapeutic modality of HIV-1 infection.

 

Rossi-M, Meyer-R, Constantinou-P, Caruso-F, Castelbuono-D,

OBrien-M, Narasimhan-V.|(2001)|Molecular structure and activity

toward DNA of Baicalein, a flavone constituent of the Asian herbal

medicine " Sho-saiko-to " .|Journal of Natural Products; vol 64; no 1;

pp 26-31; ISSN: 0163-3864; 31 ref.|The molecular structure of

baicalein, a constituent of the herbal drug Sho-saiko-to, was

determined using X-ray diffraction. Its structure is discussed in

relation to conformation and hydrogen-bonding interactions.

 

Sakaguchi-S, Furusawa-S, Yokota-K, Sasaki-K, Takayanagi-M,

Takayanagi-Y.|(1996)|Effects of antitumor activity and protection of

shock symptoms by a traditional Chinese medicine (Sho-saiko-to)

in recombinant human tumor necrosis factor administered

mice.|Biological and Pharmaceutical Bulletin; vol 19; no 11; pp

1474-1478; ISSN: 0918-6158; 24 ref.|The effects of a traditional

Chinese medicine Sho-saiko-to (Kampo prescription) were

investigated on various metabolic disorders and antitumour activity

of recombinant human tumour necrosis factor (rh TNF)

administered to mice. The glycogen level in liver of rhTNF (5 x 104

units/mouse, i.v.)-injected mice was lower 4 h after intoxication

than that in the control. Administration of rhTNF to Sho-saiko-to

(daily dose of 500 mg/kg, p.o.)-pretreated mice resulted in a higher

level of glycogen than that in rhTNF-treated mice. In mice

pretreated with Sho-saiko-to, the level of fibrinogen 4 h after rhTNF

injection markedly increased compared with that in mice treated

with rhTNF alone. NO-2 in murine macrophage cell line J774A.1

was estimated using mice serum after administration of Sho-saiko-

to. J774A.1 cells stimulated with endotoxin (1 micro g/ml) and

rhTNF (1 x 104 units/ml) effectively produced nitric oxide (NO). The

suppressive effect of Sho- saiko-to-pretreated serum on NO

generation by endotoxin/TNF-activated J774A.1 cells was

ascertained. When cells were incubated with endotoxin/TNF and

Sho-saiko-to-pretreated serum (10-100 micro l), the NO level was

significantly lower than that in control serum incubated with

endotoxin/TNF alone. The effect of Sho-saiko-to (1 and 10 micro g

/ml) on in vitro cytotoxicity by rhTNF against Meth-A Sarcoma cells

was dose dependent. In addition, there was a remarkable

enhancement of antitumour activity of rhTNF by Sho-saiko-to

pretreatment in mice. Sho-saiko-to may protect mice from severe

shock syndrome caused by rhTNF, and may enhance rhTNF-

induced antitumour activity.

 

Sakaguchi-S, Furusawa-S, Yokota-K, Sasaki-K, Takayanagi-

Y.|(1995)|Depressive effect of a traditional Chinese medicine (Sho-

Saiko-To) on endotoxin-induced nitric oxide formation in activated

murine macrophage J774A.1 cells.|Biological and Pharmaceutical

Bulletin; vol 18; no 4; pp 621-623; ISSN: 0918-6158; 18 ref.|Sho-

Saiko-To, also called TJ-9, is a traditional Chinese crude drug

composed of 7 medicinal plants. An experiment was conducted on

the suppressive effect of TJ-9, obtained from a commercial source

in Japan, on nitric oxide (NO) generation by endotoxin-activated

J774A.1 cells. NO production was dose-dependently stimulated by

endotoxin (0.01-10 micro g/ml). When J774A.1 cells were

incubated with endotoxin (0.1 micro g/ml) and TJ-9 (10-20 micro

g/ml), NO production was slightly lower than that in cells treated

with endotoxin alone. Treatment with TJ-9 at 50-100 micro g/ml

significantly inhibited endotoxin-activated NO generation in J774A.1

cells, but TJ-9 at 10-100 micro g/ml alone was ineffective in

inducing NO formation and in inhibiting cell viability in the J774A.1

cells.

 

Sakaguchi-S, Tsutsumi-E, Yokota-K.|(1994)|Defense effects of a

traditional Chinese medicine (Sho-Saiko-To) against metabolic

disorders during endotoxemia; approached from the behavior of the

calcium ion.|Biological and Pharmaceutical Bulletin; vol 17; no 2;

pp 232-236; ISSN: 0918-6158; 28 ref.|A study on intracellular Ca2+

in mice was carried out as an approach to clarify the preventive

effects of the traditional Chinese medicine Sho-saiko-to (used to

treat chronic hepatitis) against various metabolic disorders during

endotoxaemia. Japanese Sho-saiko-to (Kampo prescription TJ-9)

contains extracts of 7 crude drugs: Bupleuri Radix, Pinelliae Tuber,

Scutellariae Radix, Zizyphi Fructus, Ginseng Radix, Glycyrrhizae

Radix and Zingiberis Rhizoma. The cytosolic-free Ca2+

concentration ((Ca2+)i) in single liver cells was estimated using a

photonic microscope system. At 18 h after intoxication by injection

with endotoxin (6 mg/kg, i.p.), the (Ca2+)i of a single liver cell was

elevated in comparison with the control, whereas pretreatment of

mice with TJ-9 (500 mg/kg daily, p.o.) before endotoxin resulted in

a markedly lower (Ca2+)i. In mice pretreated with TJ-9, the Ca2+-

ATPase activity in liver plasma membrane 18 h after endotoxin

injection was markedly higher (than without TJ-9). In contrast, the

Ca2+-ATPase activity in liver mitochondria was lower in

endotoxaemic mice pretreated with TJ-9 than in mice given

endotoxin alone. State 3 respiration and the respiratory control

index (RCI), which are the parameters of mitochondrial function,

were respectively 41% and 35% lower in the livers of mice given

endotoxin than in those of control mice. However, TJ-9

pretreatment led to markedly higher levels of state 3 respiration and

RCI in endotoxin-treated mice. These findings suggest that TJ-9

has a protective effect against the damage of liver mitochondrial

function in endotoxin-poisoned mice. Kampo prescription Sho-

saiko-to may protect against various metabolic disorders caused

by the change in Ca2+ mobility in the ischaemic state of tissues

during endotoxaemia.

 

Sakamoto-S, Furuichi-R, Matsuda-M, Kudo-H, Suzuki-S, Sugiura-

Y, Kuwa-K, Tajima-M, Matsubara-M, Namiki-H, Mori-T, Kawashima-

S, Nagasawa-H.|(1994)|Effects of Chinese herbal medicines on

DNA-synthesizing enzyme activities in mammary tumours of

mice.|American Journal of ; vol 22; no 1; pp 43-

50; ISSN: 0192-415X; 11 ref.|The aqueous extracts of 2 Kampo

medicines: Sho-saiko-to (containing 7 medicinal plants) and Juzen-

taiho-to (containing 10 medicinal plants), significantly reduced the

activity of thymidine kinase in mammary tumours of mice. The

extracts also reduced the activity of thymidylate synthetase, and

lowered the concentration of serum prolactin in the treated animals,

but these results were not statistically significant.

 

Sakamoto-S, Mori-T, Sawaki-K, Kawuchi-Y, Kuwa-K, Kudo-H,

Suzuki-S, Sugiura-Y, Kasahara-N, Nagasawa-H.|(1993)|Effects of

Kampo medicine " Sho-Saiko-To " on DNA-synthesizing enzyme

activity in 1,2-dimethylhydrazine-induced colonic carcinomas in

rats.|Planta Medica; vol 59; no 2; pp 152-154; ISSN: 0032-0943; 12

ref.|Sho-Saiko-To (SST) is a modified Japanese traditional herbal

medicine containing 7 medicinal plants. The effect of SST on the

activities of DNA-synthesizing enzymes in DMH-induced colonic

carcinomas in rats was investigated. Six-week administration of

SST prevented nearly 100% of the body weight loss and the final

number of colonic carcinomas compared with rats treated with

DMH alone. SST treatment suppressed the enhanced activities of

thymidylate synthetase and thymidine kinase which were involved

in the de novo and salvage pathways of pyrimidine synthesis,

respectively, in DMH-induced colonic carcinomas. These results

indicate that SST may show direct and/or indirect inhibition of the

development of colonic carcinomas.

 

Sakomoto-S, Muroi-N, Matsuda-M, Tajima-M, Kudo-H, Kasahara-

N, Suzuki-S, Sugiura-Y, Kuwa-K, Namiki-H, Mori-T, Kawashima-S,

Nagasawa-H.|(1993)|Suppression by kampo medicines in

preneoplastic mammary hyperplastic alveolar nodules of SHN virgin

mice.|Planta Medica; vol 59; no 5; pp 425-427; ISSN: 0032-0943;

14 ref.|Sho-saiko-to (SST), Keishi-bukuryo-gan (KBG), and

Shakuyaku-kanzo-to (SKT) are Japanese modified traditional

Chinese herbal medicines (Kampo medicines) consisting of 7, 5,

and 2 medicinal plants, respectively. The hyperplastic alveolar

nodule (HAN) is a representative preneoplastic state in the

mammary glands of mice. The effects of SST, KBG, and SKT were

investigated on the formation and growth of HAN in a high-

mammary-tumour strain of SHN virgin mice. Oral administration of

SST for 60 days (beginning at 90 days of age) reduced the number

and area of HAN, and reduced both mammary thymidylate

synthetase activity and the serum concentration of prolactin. These

results indicate that SST may have a preventative effect on

malignant mammary transformations.

 

Sako-T, Motiyoshi-S.|(1998) |Clinical application of TKD-9(sho-

saiko-to) in hepatopathy in dogs.|Journal of Veterinary Medicine,

Japan; vol 51; no 6; pp 449-453; ISSN: 0447-0192; 7 ref.|

 

Shen-YiRong, Inoue-M, Nagatsu-Y, Ogihara-Y, Aburada-

M.|(1996)|Anti-hyperlipidemic and anti-atherosclerotic actions of

Shosaikoto (Kampo medicine).|Biological and Pharmaceutical

Bulletin; vol 19; no 9; pp 1160-1165; ISSN: 0918-6158; 39

ref.|Shosaikoto, a Kampo medicine, was prepared using Bupleurum

roots, Pinellia tubers, Scutellaria roots, Panax pseudoginseng

roots, Zingiber rhizomes, Zizyphus (Ziziphus) roots and Glycyrrhiza

roots. The antiatherosclerotic action shown by Shosaikoto was

studied using hypercholesterolaemic mice. Oral administration of

Shosaikoto significantly suppressed the elevation of serum

cholesterol in C57BL/6 mice fed a 1.25% cholesterol-enriched diet

for 4 weeks and improved the T cell ratio in peripheral blood, which

decreased with the increase of serum cholesterol level. In addition,

Shosaikoto reduced the accumulation of cholesteryl oleate, which

alters macrophages into foam cells, after the treatment of

macrophages with oxidized or acetylated low density lipoprotein

(LDL). Enzymatic studies revealed that treatment of macrophages

with oxidized LDL enhanced acyl-coenzyme A:cholesterol

acyltransferase (ACAT) activity and markedly reduced neutral

cholesteryl ester hydrolase (NCEase) activity. Shosaikoto

treatment prevented this decrease in NCEase activity although it

slightly augmented ACAT activity. Thus, Shosaikoto, which is

known to modulate the immune system, improved macrophage and

lymphocyte functions diminished by hypercholesterolaemia,

resulting in an antiatherosclerotic action.

 

Shen-YiRong, Inoue-M, Ogihara-Y.|(1996)|Effect of Shosaikoto

(Kampo medicine) on the adherence of monocytes in

hypercholesterolemic rabbit.|Biological and Pharmaceutical

Bulletin; vol 19; no 1; pp 149-152; ISSN: 0918-6158; 19

ref.|Monocytes/macrophages are known to be involved in

atherogenesis, and the adherence of monocytes to the

endothelium is considered an earliest characteristic of

atherogenesis. Therefore, the mechanism was studied by which

Shosaikoto, a Kampo medicine, shows anti-atherosclerotic action,

which has been already shown in hypercholesterolaemic rabbits.

Hypercholesterolaemia in rabbits gradually reduced the monocyte

number in peripheral blood, whereas Shosaikoto treatment

suppressed this decrease in circulating monocytes. Also, although

monocytes from hypercholesterolaemic rabbits increased in

adherence to endothelial cells even without lipopolysaccharide

activation, Shosaikoto treatment reduced the enhanced adherence

observed in monocytes from hypercholesterolaemic rabbits. The

anti-atherosclerotic action shown by Shosaikoto resulted partly

from the suppression of the enhanced adherence characteristic of

hypercholesterolaemia.

 

Shimizu-I.|(2000)|Sho-saiko-to: Japanese herbal medicine for

protection against hepatic fibrosis and carcinoma.|Special issue:

selected reviews in gastroenterology and hepatology for the new

millennium; Journal of Gastroenterology and Hepatology; vol 15; no

Supplement; pp D84-D90; ISSN: 0815-9319; 85 ref.|The Chinese

herbal medicine, Sho-saiko-to (Xiao-Chai-Hu-Tang, Chinese name),

an officially approved prescription drug in Japan most commonly

administered to outpatients with chronic liver disease, chronic

hepatitis and liver cirrhosis, is described. Its effects on hepatic

fibrosis and hepatic carcinogenesis are reviewed. Sho-saiko-to is a

combination of seven herbs: Bupleurum root, Pinellia tuber,

Scutellaria root, jujube fruit, ginseng root, glycyrrhiza root and

ginger rhizomes. It contains the flavonoids baicalin, baicalein and

saikosaponin-a as its active components, which have the ability to

inhibit cell proliferation. A similarity of chemical structures was

observed between these flavonoids and those of silybinin and

quercetin. Silybinin and quercetin showed anti-fibrogenic properties

in vitro and in animal models of hepatic fibrosis. It is noted that Sho-

saiko-to may have beneficial effects not only on hepatic fibrosis but

also on hepatocellular carcinoma development in patients with liver

disease.

 

Shiraiwa-K.|(1999)|Efficacy of combined administration of

antibiotics, nonsteroidal anti-inflammatory drug and herbal

medicines on lung carcinogenesis by N-nitrosobis(2-

hydroxypropyl)amine in rats.|Journal of Nara Medical Association;

vol 50; no 4; pp 303-315; ISSN: 0469-5550; 44 ref.|The efficacy of

combined administration of antibiotics, nonsteroidal

antiinflammatory drug (NSAID) and herbal medicines against N-

nitrosobis(2-hydroxypropyl)amine (BHP)-induced lung

carcinogenesis was investigated in rats. BHP (2000 ppm in water)

was given to rats for 12 weeks, then the test compounds were

given to rats in the diet for 8 weeks. In one experiment, rats were

treated with 0.02% erythromycin (EM), 0.04% ampicillin (AMP),

1.5% sho-saiko-to, EM + sho-saiko-to or AMP + sho-saiko-to. The

incidences of adenocarcinoma (AC) and non-small cell carcinomas

including AC were completely inhibited in rats given AMP + sho-

saiko-to. The numbers of alveolar hyperplasia (AH) and total lung

lesions including AH, adenoma (Ad) and AC, squamous

metaplasia, squamous cell carcinoma (SqC) and adenosquamous

carcinoma (ASqC) were decreased in rats given AMP + sho-saiko-

to or EM + sho- saiko-to. In a second experiment, rats were

treated with 0.04% AMP, 0.006% piroxicam, AMP + piroxicam or

AMP + 0.75% ogon. The incidences and numbers of AC and non-

small cell carcinomas including AC were decreased in rats given

AMP + piroxicam or AMP + ogon. The inflammatory reactions in

lung lesions were reduced in rats given AMP + sho-saiko-to or

AMP + piroxicam. Combined administration of antibiotics and

NSAID or herbal medicines inhibited the progression of lung

carcinogenesis due to suppression of chronic inflammation.

 

Stickel-F, Brinkhaus-B, Krahmer-N, Seitz-H-K, Hahn-E-G,

Schuppan-D.|(2002)|Antifibrotic properties of botanicals in chronic

liver disease.|Hepato-Gastroenterology; vol 49; no 46; pp 1102-

1108; ISSN: 0172-6390; Publisher: H.G.E. Update Medical

Publishing S.A; Athens; Greece.|Cirrhosis of the liver is a major

complication of various chronic liver diseases and results from

excess production and decreased degradation of extracellular

matrix. Pro-inflammatory cytokines, toxic metabolites and certain

drugs can trigger enhanced fibrogenesis in hepatic stellate cells

and myofibroblasts, the major matrix-producing cells. Since

treatment of established cirrhosis is limited, therapeutic

interventions that inhibit or mitigate fibrogenesis are needed.

Numerous drugs have been investigated for their antifibrotic

potential and botanicals constitute a significant fraction of them.

Colchicine has been used to treat various chronic liver diseases

with controversial results. To date, there is a lack of studies in

appropriate animal models and well-controlled human trials to

demonstrate its antifibrotic properties. Silymarin has so far failed to

clearly show an antifibrotic effect in human studies, whereas

animal experiments suggest that this mixture of flavolignanes may

be beneficial in patients which have not yet developed cirrhosis.

Animal studies indicate an antifibrotic potential of Shosaiko-to, a

herbal combination frequently used in China and Japan for the

treatment of chronic viral hepatitis, but mechanisms of action need

to be further explored. Other botanicals include trans-resveratrol, a

flavonoid extracted from grapevine, and Salvia miltiorrhiza which

were shown to interfere with the process of hepatic stellate cell

activation. Herbal combinations, such as compound 861 and

LIV.52 were advocated as antifibrotics or hepatoprotectives, but

studies in humans have either been of questionable design or

resulted in cessation of the trial due to adverse outcomes.

 

Stickel-F, Egerer-G, Seitz-H-K.|(2000)|Hepatotoxicity of

botanicals.|Public Health Nutrition; vol 3; no 2; pp 113-124; 112

ref.|Many herbal preparations and other botanicals are believed to

be harmless and are commonly used for self-medication without

supervision. The aim of this paper is to examine the evidence for

hepatotoxicity of botanicals and draw conclusions regarding their

pathology, safety and applications. Current literature on the

hepatotoxicity of herbal drugs and other botanicals is reviewed

(published between 1965 and 1998). The aetiology, clinical picture

and treatment of Amanita poisoning are described. Hepatotoxic

effects have been reported for some Chinese herbal medicines (Jin

Bu Huan, Ma-Huang and Sho-saiko-to), pyrrolizidine alkaloid-

containing plants, Teucrium chamaedrys, Larrea tridentata,

Atractylis gummifera, Callilepsis laureola, and others. The

frequency with which botanicals cause hepatic damage is unclear.

There is a lack of controlled treatment trials and the few studies

published to date do not clarify the incidence of adverse effects.

Many plant products do not seem to lead to toxic effects in

everyone taking them, and they commonly lack a strict dose-

dependency. For some products, such as Sho-saiko-to, the picture

is confused further by demonstrations of hepatoprotective

properties for some components. Severe liver injury, including

acute and chronic abnormalities and even cirrhotic transformation

and liver failure, have been described after the ingestion of a wide

range of herbal products and other botanical ingredients. In certain

situations herbal products may be just as harmful as conventional

drugs.

 

Suzuki-H, Kumada-H, Sato-A, Shiraki-K, Honma-Y, Kogure-T,

Terasawa-K.|(2000)|Guidelines of Sho-saiko-to/Xiao-Chaihu-Tang

treatment in patients with chronic hepatitis C.|Journal of Traditional

Medicines; vol 17; no 3; pp 95-100; 30 ref.|In the last decade,

interstitial pneumonia (IP) presumably induced by Sho-saiko-

to/Xiao-Chaihu-Tang has emerged when treating patients with

chronic hepatitis C. Here, we present the guidelines for the safe

use of Sho-saiko-to. To reveal clinical features and

pathophysiological aspects, we inspected case reports and basic

studies of patients with IP probably induced by Sho-saiko-to. In

addition, the association between IP and chronic hepatitis C itself

was further analysed clinically and pathologically. It is desirable to

study further the pathogenesis of IP induced by Sho-saiko-to to

make the guidelines more suitable.

 

Tamura-M, Nose-M, Kojima-K, Mizukami-H, Ogihara-Y.|(1998)

|Scientific evaluation of Kampo (No.12). Effect of long term

administration of Sho-saiko-to on the induction of drug metabolic

enzyme (cytochrome P450).|Journal of Traditional Medicines; vol

15; no 5; pp 344-345.|

 

Terawaki-K, Nose-M, Ogihara-Y.|(1997)|The effects of crude

polysaccharide fractions of 4 kinds of Kampo-hozai administered

orally on nitric oxide

production by murine peritoneal macrophages.|Biological and Pharmaceutical

Bulletin; vol 20; no 7; pp 809-811; ISSN: 0918-6158; 16 ref.|The effects of

crude polysaccharide fractions of 4 kinds of Kampo-hozai, Shosaiko-To,

Daisaiko-To, Hachimi-Jio-Gan and Hochu-Ekki-To, were studied on nitric oxide

(NO) production by 3% thioglycollate-induced murine peritoneal macrophages.

Oral administration of these fractions to mice for 7 days augmented

lipopolysaccharide (0.1-10 micro g/ml)-induced NO production by peritoneal

macrophages. There is a possibility that a crude polysaccharide fraction

affects the macrophage function in most Kampo-hozai.

 

Terawaki-K, Nose-M, Ogihara-Y.|(1998)|The role of crude polysaccharide

fractions on the mitogenic activity by Shosaikoto.|Phytomedicine; vol 5; no 5;

pp 347-352; 16 ref.|Shosaikoto, which is a mixture of 7 traditional (Japanese

and Chinese) herbal medicines, has several immunomodulating activities.

Especially, Shosaikoto is a potent polyclonal B cell mitogen in vivo and in

vitro. In order to characterize the active substances for mitogenic activity,

Shosaikoto was fractionated by means of ethanol precipitation to give 2

fractions, called ethanol-precipitate (EP) fraction and ethanol-soluble (ES)

fraction. The EP fraction consisted mainly of polysaccharides and showed

significant mitogenic activity. The ES fraction consisted of low-MW compounds

and did not exhibit the activity in vitro. The EP fraction of hot water

extracts of Glycyrrhizae Radix and Bupleuri Radix showed mitogenic activity;

the ES fraction of a hot water extract of Glycyrrhizae Radix, and all fractions

of hot water extract of Scutellariae Radix, showed cytotoxicity. The crude

polysaccharide fractions could play an important role in the mitogenic activity

of Shosaikoto.

 

Tsuji-M, Yoshida-Y, Kodama-K, Okazaki-M, Oguchi-K.|(1994)|Protective effect of

Sho-saiko-to (Xiao-chai-hu-tang) on primary cultured rat

hepatocytes.|Phytotherapy Research; vol 8; no 2; pp 100-102; ISSN: 0951-418X; 7

ref.|The protective effects of the crude drug, and the complete and incomplete

prescriptions of a traditional Chinese medicine, Sho-Saiko- To (consisting of 7

medicinal plants), against CCl4-induced hepatotoxicity in primary cultured rat

hepatocytes were studied. The complete SST prescription showed the most potent

protective effect, whilst with the exception of Scutellaria root extract, other

components were ineffective. An incomplete prescription lacking Jujube

(Ziziphus) or Ginger (Zingiber officinale) exhibited a similar effect to that

of the SST in this system.

 

Watanabe-K, Jin-GuangBi, Nakada-T, Santa-K, Kato-H, Toriizuka-K,

Hanawa-T.|(1998)|Effect of Juzentaiho-to and Shosaiko-to on Th1/Th2

balance.|Journal of Traditional Medicines; vol 15; no 5; pp 284-285; 5

ref.|Three healthy men and 10 women were administered Sho-Saiko-To (SST 7.5

g/day) or Juzen-Taiho-To (JTT; 7.5 g/day) for 2 weeks. Both JTT and SST

increased secretion of IFN- gamma (interferon- gamma ) and IL-4 (interleukin-4)

from peripheral blood mononuclear cells. Only SST changed the Th1/Th2 (T helper

type 1/T helper type 2 lymphocyte) balance, since SST predominantly stimulated

IFN- gamma , whereas JTT stimulated IFN- gamma and IL-4 equally.

 

Watanabe-K, Tamaru-N, Takihara-H, Yoshida-M.|(1994)|Syosaiko-to and Saiboku-to

(Chinese-Japanese herbal medicine) suppress the release of arachidonic acid

metabolites from cultured porcine pulmonary artery endothelial cells.|Journal

of Ethnopharmacology; vol 43; no 3; pp 191-196; ISSN: 0378-8741; 20

ref.|Syosaiko-to (Sho-Saiko-To), used in Chinese-Japanese medicine to treat

chronic hepatitis, is the boiled extract of 7 herbs including Panax ginseng (P.

pseudoginseng) and Zingiber officinale, whereas Saiboku-to, prescribed for

bronchial asthma, is composed of Syosaiko-to plus Poria cocos (Macrohyporia

extensa), Magnolia obarata (M. hypoleuca) and Perillae frutescens (Perilla

frutescens). The effects of Syosaiko-to and Saiboku-to on the arachidonic acid

metabolism of porcine pulmonary artery endothelial cells (PPAEC) in culture

were investigated. 6-keto-PGF1 alpha , a stable end product of prostacyclin,

released by PPAEC during a 48-h incubation period with 1000 micro g/ml of

Syosaiko-to or Saiboku-to, was significantly decreased. Analysis of the

eicosanoid profile by HPLC revealed that release of cyclooxygenase and

lipoxygenase derivatives from PPAEC was decreased during 24-h incubation

periods with 500 micro g/ml of Syosaiko-to or Saiboku-to. The results may

explain the antiinflammatory effects of Syosaiko-to and Saiboku-to.

 

Watanabe-S, Kitade-Y, Masaki-T, Nishioka-M, Satoh-K, Nishino-H.|(2001)|Effects

of lycopene and Sho-saiko-to on hepatocarcinogenesis in a rat model of

spontaneous liver cancer.|Nutrition and Cancer; vol 39; no 1; pp 96-101; ISSN:

0163-5581; Publisher: Lawrence Erlbaum Associates Inc; Mahwah; USA.|The

Long-Evans Cinnamon (LEC) rat is a well-characterized model of spontaneous

hepatocarcinogenesis. It has been shown that dietary administration of lycopene

or the herbal medicine Sho-saiko-to (TJ-9) has anticarcinogenic activity,

although the mechanism by which these products protect against carcinogenesis

is not well known. We investigated the outcome of administration of lycopene

and TJ-9 on the occurrence of hepatic neoplasia in LEC rats. A diet containing

0.005% lycopene (originally the product of tomato oleoresin containing 13%

lycopene) and 1% TJ-9 (crude extracts of 7 herbs: bupleurum root, pinellia

tuber, scutellaria root, jujube fruit, ginseng root, glycyrrhiza root, and

ginger rhizome) was administered from 6 weeks of age until the rats were

sacrificed at 76 weeks of age, at which time most of the nontreated animals

were known to have hepatocellular carcinoma (HCC). Development of HCC in

treated groups was analyzed histologically by comparison with untreated

controls. Glutathione S-transferase placental form (GST-P) was analyzed by an

immunohistochemical method. Concentration of copper, iron, and zinc, which

appear to play a role in hepatocarcinogenesis in LEC rats, was analyzed. The

percent areas of HCC in the liver specimens of control, lycopene, and TJ-9

groups were 17.9 plus or minus 17.1%, 27.2 plus or minus 20.8%, and 27.6 plus

or minus 18.4%, respectively. These intergroup differences were not

significant. The percent area, number of areas, and mean size of area staining

positively for GST-P revealed no significant differences between the groups.

The number of GST-P-positive areas within the HCC lesions was greater in the

TJ-9 group than in the control or lycopene group (p=0.024 and p=0.012,

respectively). The study also demonstrated a lower concentration of iron in

livers of the lycopene group than the control group (p=0.019). There were no

differences in serum alpha -fetoprotein levels or the cumulative survival rates

between the groups. Long-term administration of lycopene or TJ-9 did not reduce

the risk of hepatocarcinogenesis in LEC rats.

 

Wu-X, Akatsu-H, Okada-H.|(1995)|Apoptosis of HIV-infected cells following

treatment with Sho-saiko-to and its components.|Japanese Journal of Medical

Science and Biology; vol 48; no 2; pp 79-87; ISSN: 0021-5112; 16 ref.|A high

dose of baicalin, a component of a traditional Chinese drug, Sho-saiko-to,

selectively induced apoptosis of HIV-infected CEM cells with a high

viral-releasing capacity and at a low dose to stimulate proliferation of

infected cells with a relatively lower capacity of HIV production. The drug and

another of its components, baicalein, produced similar results.

 

Yamaoka-Y, Kawakita-T, Kaneko-M, Nomoto-K.|(1996)|A polysaccharide fraction of

Zizyphi Fructus in augmenting natural killer activity by oral

administration.|Biological and Pharmaceutical Bulletin; vol 19; no 7; pp

936-939; ISSN: 0918-6158; 14 ref.|Shosaiko-to (Xiao-chai-hu-tang, SHO), a Kampo

medicine used in Japan to treat chronic hepatitis or distress and fullness in

chest and ribs, was prepared by decocting a prescription of 7 kinds of crude

drugs (Bupleurum chinense roots, Pinellia ternata tubers, Scutellaria

baicalensis roots, Zizyphus jujuba (Ziziphus sativa) fruits, Panax ginseng (P.

pseudoginseng) roots, Glycyrrhiza glabra roots and Zingiber officinale

rhizomes). The effects of extracts and various fractions of SHO were

investigated in mice following oral administration. The extracts of Ziziphus

jujuba, Zingiber officinale, S. baicalensis, G. glabra and P. ternata augmented

natural killer (NK) activity. The high MW fraction of Ziziphus jujuba was the

most effective in augmenting NK activity. An active polysaccharide fraction was

obtained from the high MW fraction of Ziziphus jujuba. This polysaccharide

fraction with a MW of approximately 43 000 contained 54.7% carbohydrate, 61.8%

uronic acid and 20.9% protein. The sugar moiety was composed of rhamnose,

arabinose, xylose, fucose, mannose, galactose, glucose and galacturonic acid in

molar ratios of 28:59:11:9:7:32:20:100.

 

Yamashiki-M, Nishimura-A, Nobori-T, Nakabayashi-S, Takagi-T, Inoue-K, Ito-M,

Matsushita-K, Ohtaki-H, Kosaka-Y.|(1997)|In vitro effects of Sho-saiko-to on

production of granulocyte colony-stimulating factor by mononuclear cells from

patients with chronic hepatitis C.|International Journal of Immunopharmacology;

vol 19; no 7; pp 381-385; ISSN: 0192-0561; 16 ref.|During the past 2 years,

drug-induced interstitial pneumonia was reported in 66 Japanese patients

(mainly among chronic hepatitis C patients) undergoing treatment with the

Japanese herbal medicine " Sho- saiko-to " (TJ-9, a combination of 7 herbal

ingredients). As interstitial pneumonia is also induced by granulocyte

colony-stimulating factor (G-CSF), the effects of TJ-9 on G-CSF production in

peripheral blood mononuclear cells were examined. In patients with hepatitis B

or C, G-CSF production in the absence of any stimulation was significantly

lower than in healthy controls (P<0.01). G-CSF production increased with

increase of TJ-9 levels; hence, TJ-9 could induce excessive production of G-CSF

in hepatitis C patients and be a cause of interstitial pneumonia.

 

Yamashiki-M, Nishimura-A, Nomoto-M, Nakano-T, Sato-T, Suzuki-H, Zheng-Q-X,

Klapproth-J-M, James-S-P, Kosaka-Y.|(1994)|Effects of Japanese herbal medicine

" Sho-Saiko-To " on in vitro production of tumor necrosis factor-alpha on (in)

peripheral blood mononuclear cells.|Drug Development Research; vol 31; no 3; pp

170-174; ISSN: 0272-4391; 26 ref.|Sho-Saiko-To (TJ-9) is a modified preparation

of the Chinese herbal medicine, Xiao-Chai-Hu-Tang. TJ-9 contains bupleurum

(Bupleurum sp.) root, pinellia (Pinellia sp.) tuber, scutellaria (Scutellaria

sp.) root, jujube (Ziziphus sp.) fruit, ginseng (Panax sp.) root, glycyrrhiza

(Glycyrrhiza sp.) root and ginger (Zingiber sp.) rhizome. Using peripheral

blood mononuclear cells obtained from 12 healthy volunteers, the effect of TJ-9

and 2 other herbal medicines, Dai- Saiko-To (TJ-8) and Saiko-Keishi-To (TJ-10),

on the production of tumour necrosis factor- alpha was investigated. All drugs

tested induced an increase in the levels of tumour necrosis factor- alpha ;

TJ-9 was the most active drug.

 

Yamashiki-M, Nishimura-A, Nomoto-M, Suzuki-H, Kosaka-Y.|(1996)|Herbal medicine

'Sho-saiko-to' induces tumour necrosis factor- alpha and granulocyte

colony-stimulating factor in vitro in peripheral blood mononuclear cells of

patients with hepatocellular carcinoma.|Journal of Gastroenterology and

Hepatology; vol 11; no 2; pp 137-142; ISSN: 0815-9319; 38 ref.|'Sho-saiko-to'

(TJ-9) is a Japanese herbal medicine commonly administered to patients with

chronic viral liver disease in order to improve their overall physical

condition and to prevent the development of liver cancer. The present in vitro

study demonstrated that addition of TJ-9 to cultures of peripheral mononuclear

cells from patients with hepatocellular carcinoma accompanied by liver

cirrhosis resulted in dose-dependent increases in production levels of the

cytokines, tumour necrosis factor- alpha (TNF- alpha ) and granulocyte

colony-stimulating factor (G-CSF). Increases in the production of TNF-alpha and

G-CSF in control cell cultures exposed to different herbal medicines were low,

indicating the specificity of the response to TJ-9. TNF- alpha and G-CSF are

known to play important roles in the biological defence mechanism.

Administration of TJ-9 may, therefore, be beneficial for patients afflicted

with intractable liver diseases because it could mildly induce these cytokines.

 

Yamashiki-M, Nishimura-A, Sakaguchi-S, Suzuki-H, Kosaka-Y.|(1996)|Effects of

the Japanese herbal medicine 'Sho-saiko-to' as a cytokine

inducer.|Environmental Toxicology and Pharmacology; vol 2; no 4; pp 301-306; 25

ref.|The herbal medicine, Sho-saiko-to (TJ-9), has been widely prescribed to

chronic viral liver disease patients in Japan. The induction of cytokines such

as interleukin-1 beta (IL-1 beta ), tumour necrosis factor- alpha (TNF- alpha )

and granulocyte-colony stimulating factor (G-CSF), on some fractions of human

peripheral blood mononuclear cells (PBMC) by TJ-9 and each of its 7 plant

components was studied. IL-1 beta , TNF- alpha , and G-CSF were highly induced

by Scutellaria root and Glycyrrhiza root acting on monocytes/macrophages. By

repeating the experiments using the same substances treated with taxol (an LPS

(lipopolysaccharide) antagonist), it was confirmed that these inductions were

not attributable to the presence of low levels of LPS in TJ-9 solution, and

that they were a specific effect of TJ-9.

 

Yen-M-H, Lin-C-C, Chuang-C-H, Liu-S-Y.|(1991)|Evaluation of root quality of

Bupleurum species by TLC scanner and the liver protective effects of

" Xiao-chai-hu-tang " prepared using three different Bupleurum species.|Journal

of Ethnopharmacology; vol 34; no 2-3; pp 155-165; ISSN: 0378-8741; 36 ref.|A

simple and rapid system, using a TLC scanner, is described for quantitative

analysis of saikosaponins a, c and d, the major bioactive principles of

Bupleurum species. Results with B. kaoi, native to Taiwan, showed that the

roots, rhizomes and leaves + stems contain greater amounts of saikosaponins

than those of the cultivated B. falcatum var. komarowi and the imported B.

chinense. The liver-protective effects of aqueous extracts of the Chinese

preparation Xiao-chai-hu-tang were evaluated using CCl4-induced toxicity in

rats. This medicine is a mixture of 7 crude drugs (listed) and was prepared

using roots of the 3 Bupleurum species and aerial parts of B. kaoi and B.

falcatum var. komarowi for comparison. When the roots of B. kaoi were included,

the acute increase in serum transaminase levels was greatly reduced and certain

histological changes induced by CCl4 also showed a reduction. When aerial parts

of B. kaoi or B. falcatum var. komarowi were used, there were similar though

less marked effects.

 

Yoshida-K, Mizukawa-H, Honmura-A, Uchiyama-Y, Nakajima-S, Haruki-E.|(1994)|The

effect of Sho-saiko-to on concentration of vitamin E in serum and on granuloma

formation in carrageenin cotton pellet-induced granuloma (in) rats.|American

Journal of ; vol 22; no 2; pp 183-189; ISSN: 0192-415X; 16

ref.|The effect of Sho-saiko-to (consisting of the extracts of 7 medicinal

plants) on the concentration of vitamin E in serum and on granuloma formation

induced by cotton pellets (containing carrageenin (carrageenan)), was

investigated in rats. Sho-saiko-to treatment (450 mg/kg) inhibited granuloma

formation, but increased the serum concentrations of vitamin E, cholesterol and

phospholipids. Despite the lipid-increasing action of Sho-saiko-to, the

concentration of serum lipid peroxide was significantly lower than in the

control group. Also, a significant negative correlation between the

concentration of vitamin E and granuloma weight was observed. Vitamin E plays

an important role in promoting the antiinflammatory effect of Sho-saiko-to.

 

Yoshino-M, Ito-M, Okajima-H, Haneda-M, Murakami-K.|(1997)|Role of baicalein

compounds as antioxidant in the traditional herbal medicine.|Biomedical

Research; vol 18; no 5; pp 349-352; 15 ref.|Antioxidant activity was determined

for commercial Sho-saiko-to (a traditional Sino-Japanese herbal medicine used

against hepatitis) and its main components, against enzymatic and non-enzymatic

iron-mediated lipid peroxidation in rat liver microsomes. Protective effects

were shown by Sho-saiko-to and wogon (extract of Scutellaria roots). Baicalein

and its glycoside baicalin (the main flavonoids in wogon, comprising e.g. 1%

and 14% of its dry solids) also inhibited microsomal lipid peroxidation, their

respective IC50 values being 0.5 and 6 micro M. The antioxidant action of

baicalein compounds in Scutellaria root extract can explain the protective

effect of Sho- saiko-to on liver function.

 

Zhang-KeJia.|(1999)|Control of animal viral diseases by traditional Chinese

medicine.|Chinese Journal of Veterinary Medicine; vol 25; no 12; pp

38-39; 14 ref.|Functions of traditional Chinese medicines to control

viral disease are mainly in antiviral activity, enhancement of

immune function, prevention of secondary infection, relieving

symptoms and reducing stress. Five classical and 8 modern

prescription are introduced for different purposes, including Ying

Qiao San (powder of Lonicera and Forsythia), Xiao Chaihu Tang

(minor decoction of Bupleurum), Qingkailin injection, Chai Lian

Tang etc., in addition, acupoint vaccination has been tried to

control and prevent various viral disease.

 

 

 

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