Recent Abstracts on Herbal Medicine

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_Author | _Title | _Journal | _Contact | _Abstract

 

Butters, D. E.; Whitehouse, M. W. | Treating inflammation: some

(needless) difficulties for gaining acceptance of effective natural

products and traditional medicines. | Inflammopharmacology 2003,

11 (1), 97-110, | Therapeutics Research Unit, Dept. of Medicine,

Univ of Queensland, Princess Alexandra Hospital, Woolloongabba,

Qld. 4102, Australia. | The quality of so-called 'natural medicines' is

extraordinarily variable. Lack of resolute pharmacological assays

contributes to this hiatus. More stringent evaluation of anti-

inflammatory and anti-pyretic activities in rats can help resolve

some of the uncertainties surrounding (a) preparations of some

herbal products including so-called 'nature's aspirin' (e.g.

willowbark, ginger), cat's claw, celery seed, etc., and (b) some

animal lipids (e.g. Lyprinol® (NZ Mussel), emu and fish oils).

These animal products can be a remarkable resource for

supplementing conventional/allopathic therapy for inflammatory

disease, e.g. providing lipoxygenase inhibitors. Beyond the

verifiable science, the healing professions and the general public

still need to examine more carefully criteria for QUALITY(S) in any

alternative medicine-to ensure the good (= both reputations and

products) are not destroyed by the bad-in essence counteracting

Gresham's Law which states: the bad tends to displace the good.

 

Cha, Y. Y.; Lee, E. O.; Lee, H. J.; Park, Y. D.; Ko, S. G.; Kim, D.

H.; Kim, H. M.; Kang, I. C.; Kim, S. H. | Methylene chloride

fraction of Scutellaria barbata induces apoptosis in human U937

leukemia cells via the mitochondrial signaling pathway. | Clin Chim

Acta 2004, 348 (1-2), 41-8. | Graduate School of East-West

Medical Science, KyungHee Univ, Yoingin 449-701, South Korea. |

BACKGROUND: Scutellaria barbata D.Don has been applied to

treat cancers, inflammation and urinary disease. However, its

antitumor mechanism still remains unclear. METHODS: With

methylene chloride fraction of Herba Scutellariae barbatae (MCSB),

apoptosis-related experiments were carried out on human U937

leukemia cells by (a) 2,3-bis 2-4-nitro-5-sulphophenyl 2H-

tetrazolium-5-carboxanilide (XTT) assay for cytotoxicity; (b)

terminal deoxynucleotidyl-transferase-mediated dUTP nick end

labeling (TUNEL) assay for morphological changes; © cell cycle

analysis; (d) Western blot analysis of poly(ADP-ribose) polymerase

(PARP), caspase-8, caspase-9, caspase-3 and Bax, Bcl-2 and

cytochrome c expressions for apoptosis signaling pathway.

RESULTS : MCSB inhibited the proliferation

of human U937 leukemia cells in a dose-dependent manner

(IC50 = approximately 10 ug/ml). MCSB dose-dependently

increased the sub-G1 DNA contents by cell cycle analysis.

DNA fragments indicating induction of apoptosis were observed

in MCSB-treated U937 cells by TUNEL assay. Caspase-9 and

caspase-3 were activated while caspase-8 was intact by

MCSB. Similarly, MCSB effectively cleaved PARP, increased

the ratio of Bax/Bcl-2 and released the cytochrome c from

mitochondria during apoptosis in U937 cells. CONCLUSIONS:

Our results suggest that MCSB can induce apoptosis via the

mitochondria-mediated signaling pathway.

 

Chakraborty, S.; Roy, M.; Taraphdar, A. K.; Bhattacharya, R.

K. | Cytotoxic effect of root extract of Tiliacora racemosa and

oil of Semecarpus anacardium nut in human tumour cells. |

Phytother Res 2004, 18 (8), 595-600. | Dept of Environmental

Carcinogenesis and Toxicology, Chittaranjan National Cancer

Institute, 37, S. P. Mukherjee Road, Kolkata 700 026, India. |

Tiliacora racemosa and Semecarpus anacardium, the two plants

frequently used in Ayurvedic medicine for the treatment of

cancerous diseases, have been selected to examine their action

in four human tumour cell lines: acute myeloblastic leukaemia

(HL-60), chronic myelogenic leukaemia (K-562), breast

adenocarcinoma (MCF-7) and cervical epithelial carcinoma

(HeLa). In cells grown in appropriate media the ethanol extract

of T. racemosa root, the total alkaloids isolated from this organ

and S. anacardium nut oil prepared according to the Ayurvedic

principle were found to have cytotoxic activity. The alkaloid

fraction from T. racemosa had maximum cytotoxicity and was

effective against all four cell lines. S. anacardium oil was

cytotoxic only in leukaemic cells. These herbal preparations

were not cytotoxic towards normal human lymphocytes,

suggesting their action is specific for tumour cells. On

microscopic examination the cells treated with these agents

exhibited characteristic morphological features of apoptosis,

such as cell shrinkage, and the formation of apoptotic bodies.

Fluorescent staining with propidium iodide revealed distinct

chromatin condensation and nuclear fragmentation. The

apoptotic index paralleled the cytotoxic parameters, and

fragmented DNA extracted free of genomic DNA from treated

cells displayed a typical ladder pattern on gel electrophoresis.

Apoptosis induced by alkaloids and phenolics, the active

principles present in T. racemosa and S. anacardium,

respectively, was found to be mediated by the activation of

caspases.; Copyright © 2004 John Wiley & Sons, Ltd.

 

Chen, Z. H.; Hurh, Y. J.; Na, H. K.; Kim, J. H.; Chun, Y. J.;

Kim, D. H.; Kang, K. S.; Cho, M. H.; Surh, Y. J. | Resveratrol

inhibits TCDD-induced expression of CYP1A1 and CYP1B1

and catechol estrogen-mediated oxidative DNA damage in

cultured human mammary epithelial cells. | Carcinogenesis 2004,

25 (10), 2005-13. | College of Pharmacy, Seoul National Univ,

Seoul 151-742, South Korea. | Resveratrol (3,5,4'-

trihydroxystilbene), a naturally occurring phytoalexin present in

grapes and other foods, has been reported to possess

chemopreventive effects as revealed by its striking inhibition of

diverse cellular events associated with tumor initiation,

promotion and progression. In our present study, 2,3,7,8-

tetrachlorodibenzo-p-dioxin (TCDD), when treated with the

cultured human mammary epithelial (MCF-10A) cells, induced

the expression of cytochrome P450 1A1 (CYP1A1) and 1B1

(CYP1B1) that are responsible for the oxidation of 17beta-

estradiol to produce catechol estrogens. Resveratrol strongly

inhibited the TCDD-induced aryl hydrocarbon receptor (AhR)

DNA binding activity, the expression of CYP1A1 and CYP1B1

and their catalytic activities in MCF-10A cells. It also reduced

the formation of 2-hydroxyestradiol and 4-hydroxyestradiol

from 17beta-estradiol by recombinant human CYP1A1 and

CYP1B1, respectively. Furthermore, resveratrol significantly

attenuated the intracellular reactive oxygen species (ROS)

formation and oxidative DNA damage as well as the cytotoxicity

induced by the catechol estrogens. Our data suggest that

CYP1A1- and CYP1B1-catalyzed catechol estrogen formation

might play a key role in TCDD-induced oxidative damage, and

resveratrol can act as a potential chemopreventive against dioxin-

induced human mammary carcinogenesis by blocking the

metabolic formation of the catechol estrogens and scavenging

the ROS generated during their redox cycling.

 

Corder, R.; Warburton, R. C.; Khan, N. Q.; Brown, R. E.;

Wood, E. G.; Lees, D. M. | The procyanidin-induced pseudo

laminar shear stress response: a new concept for the reversal of

endothelial dysfunction. | Clin Sci (Lond) 2004, 107 (5), 513-7.

| William Harvey Research Institute, Barts and the London,

Queen Mary's School of Medicine and Dentistry, Charterhouse

Square, London EC1M 6BQ, U.K. | Reduced endothelium-

dependent vasodilator responses with increased synthesis of ET-

1 (endothelin-1) are characteristics of endothelial dysfunction in

heart failure and are predictive of mortality Identification of

treatments that correct these abnormalities may have particular

benefit for patients who become refractory to current regimens.

Hawthorn preparations have a long history in the treatment of

heart failure Therefore we tested their inhibitory effects on ET-1

synthesis by cultured endothelial cells. These actions were

compared with that of GSE (grape seed extract), as the

vasoactive components of both these herbal remedies are mainly

oligomeric flavan-3-ols called procyanidins. This showed

extracts of hawthorn and grape seed were equipotent as

inhibitors of ET-1 synthesis. GSE also produced a potent

endothelium-dependent vasodilator response on preparations of

isolated aorta. Suppression of ET-1 synthesis at the same time

as induction of endothelium-dependent vasodilation is a similar

response to that triggered by laminar shear stress. Based on

these results and previous findings, we hypothesize that through

their pharmacological properties procyanidins stimulate a pseudo

laminar shear stress response in endothelial cells, which helps

restore endothelial function and underlies the benefit from

treatment with hawthorn extract in heart failure

 

Gali-Muhtasib, H.; Diab-Assaf, M.; Boltze, C.; Al-Hmaira, J.;

Hartig, R.; Roessner, A.; Schneider-Stock, R. | Thymoquinone

extracted from black seed triggers apoptotic cell death in human

colorectal cancer cells via a p53-dependent mechanism. | Int J

Oncol 2004, 25 (4), 857-66. | Dept of Biology, American Univ

of Beirut, Beirut, Lebanon. amro | For centuries,

the black seed (Nigella sativa) herb and oil have been used in

Asia, Middle East and Africa to promote health and fight

disease. Thymoquinone (TQ), the most abundant constituent

present in black seed, is a promising dietary chemopreventive

agent. We investigated the effects of thymoquinone (TQ) against

HCT-116 human colon cancer cells and attempted to identify its

potential molecular mechanisms of action. We report that TQ

inhibits the growth of colon cancer cells which was correlated

with G1 phase arrest of the cell cycle. Furthermore, TUNEL

staining and flow cytometry analysis indicate that TQ triggers

apoptosis in a dose- and time-dependent manner. Apoptosis

induction by TQ was associated with a 2.5-4.5-fold increase in

mRNA expression of p53 and the downstream p53 target gene,

p21WAF1. Simultaneously, we found a marked increase in p53

and p21WAF1 protein levels but a significant inhibition of anti-

apoptotic Bcl-2 protein. Co-incubation with pifithrin-alpha (PFT-

alpha), a specific inhibitor of p53, restored Bcl-2, p53 and

p21WAF1 levels to the untreated control and suppressed TQ-

induced cell cycle arrest and apoptosis. p53-null HCT-116 cells

were less sensitive to TQ-induced growth arrest and apoptosis.

These results indicate that TQ is antineoplastic and pro-

apoptotic against colon cancer cell line HCT116. The apoptotic

effects of TQ are modulated by Bcl-2 protein and are linked to

and dependent on p53. Our data support the potential for using

the agent TQ for the treatment of colon cancer.

 

Hioki, C.; Yoshimoto, K.; Yoshida, T. | Efficacy of bofu-tsusho-

san, an oriental herbal medicine, in obese Japanese women with

impaired glucose tolerance. | Clin Exp Pharmacol Physiol 2004,

31 (9), 614-9. | Dept of Endocrinology and Metabolism,

National Hospital Organization Kyoto Medical Center, Kyoto,

Japan. chioki | 1. In the present study, we

conducted the first randomized, double-blind, placebo-

controlled study of bofu-tsusho-san (BF), an oriental herbal

medicine (24 mg/day ephedrine in Ephedrae Herba and an

efficacy equivalent of 280 mg caffeine, judging from the

phosphodiesterase-inhibitory effect of Glycyrrhizae Rx,

Forsythiae Fructus and Schizonepetae Spica and another 14

crude drugs) in obese women with impaired glucose tolerance

(IGT). 2. The aim of the present study was to determine whether

BF was effective in decreasing visceral adiposity and insulin

resistance. Eighty-one Japanese women (body mass index

(BMI) 36.5 +/- 4.8 kg/m2) with IGT and insulin resistance (IR),

who had been treated with a low-calorie diet (5016 kj/day:

1200 kcal) and an exercise regimen (1254 kj/day: 300 kcal),

were randomized to receive either placebo (n=40) or BF

treatment (n=41) three times a day. 3. After 24 weeks

treatment, the BF group lost significantly (P 600.01) more

bodyweight and abdominal visceral fat without a decrease in the

adjusted resting metabolic rate (RMR), whereas the placebo

group lost bodyweight (P 600.05) and had no significant change

in abdominal visceral fat. The BF group had a lower fasting

serum insulin level (P 600.05), a lower insulin area under the

curve (P 600.05) and a lower level of the homeostasis model

assessment of insulin resistance (P 600.01) compared with

values before treatment 4. We conclude that BF could be a

useful herbal medicine in treating obesity with IGT.

 

Jagetia, G. C.; Baliga, M. S. | Polyherbal extract of septilin

protects mice against whole body lethal dose of gamma

radiation. | Phytother Res 2004, 18 (8), 619-23. | Dept of

Radiobiology, Kasturba Medical College, Manipal 576-104,

India. gc.jagetia | The effect of various doses

(5, 10, 20, 40, 60, 80, 100, 120, 140 and 160 mg/kg b. wt.) of

50% ethanolic extract of Septilin (a herbal preparation) was

studied on the radiation-induced mortality in mice exposed to 10

Gy of gamma-irradiation. Treatment of mice with different doses

of Septilin, consecutively for 5 days before irradiation, delayed

the onset of mortality and reduced the symptoms of radiation

sickness when compared with the non-drug treated irradiated

controls. All doses of Septilin provided protection against

gastrointestinal (GI) deaths ( death within 10 days of irradiation).

However, the best protection was observed at 100 mg/kg b. wt.

of Septilin, as the number of survivors after 30 days post-

irradiation was highest (58.33%) in this group when compared

with the other doses of Septilin. The number of survivors was

1.75 fold greater for 100 mg/kg Septilin when compared with

the 2-mercaptopropionylglycine (MPG, 33.33%) which was

used as a positive control. The LD(50) of Septilin was 1250

mg/kg as against the optimum protective dose of 100 mg/kg.

Our study demonstrates Septilin as a good radioprotective

agent.; Copyright © 2004 John Wiley & Sons, Ltd.

 

Jia, W.; Gao, W. Y.; Yan, Y. Q.; Wang, J.; Xu, Z. H.; Zheng,

W. J.; Xiao, P. G. | The rediscovery of ancient Chinese herbal

formulas. | Phytother Res 2004, 18 (8), 681-6. | School of

Pharmacy, Shanghai Jiao Tong Univ, Shanghai, China.

weijia@mail:sjtu.edu.cn | This review presents some recent

discoveries of ancient Chinese herbal formulas evolved through

thousands of years of clinical practice. It appears that many of

the ancient combination formulas have sound scientific basis

through modern pharmacological evaluation. Significant chemical

changes occurred during the preparation (decoction) process of

a prescribed herbal formula. For example, some toxic

ingredients were significantly reduced and new active

compounds generated due to the chemical interactions among

the ingredients. Many combination formulas showed significantly

better pharmacological results than individual herbal medicines

participated in the formula. These findings suggest that the

current drug screening and regulatory methodology will not be

appropriate for the development of a botanical drug containing a

group of phytochemicals, in which a synergistic interaction from

chemical ingredients plays a fundamental role to treat disease. If

we view a diseased state in a holistic and dynamic way, i.e. it

involves interactions among many biological systems in human

body and these interactions change as the disease improves or

worsens, the treatment of such disease with a single chemical

entity may not be logical or technically feasible. Combination

formulas may hold the potential to become the therapeutics of

choice in the future due to the synergistic effect and dynamic

adjustment achieved by the multiple ingredients that will restore

the balance of an imbalanced or diseased human body.;

Copyright © 2004 John Wiley & Sons, Ltd.

 

Jirong, Y.; Xiaoyan, Y.; Taixiang, W.; Defen, S.; Birong, D. |

Zhiling decoction for vascular dementia. | Cochrane Database

Syst Rev 2004, (4) CD004670 | Dept of Geriatrics, West China

Hospital, Sichuan Univ, 37 Guo Xue Xiang, Chengdu 610041,

CHINA. | BACKGROUND: Zhiling decoction has a fixed

composition of 15 Chinese herbs The properties of each of

these herbs and in combination provide the therapeutic rationale

for a possible action of Zhiling decoction in dilating cerebral

vessels and increasing cerebral blood flow, as well as reducing

serum cholesterol. Thus the aim of this review is to evaluate

efficacy and safety of Zhiling decoction for the treatment of

vascular dementia. OBJECTIVES: To assess the efficacy and

safety of Zhiling decoction for vascular dementia. SEARCH

STRATEGY: The Specialized Register of the Cochrane

Dementia and Cognitive Improvement Group was searched on 2

January 2004 using the term Zhiling. This Register contains

records from all major health care databases and many ongoing

trials databases and is updated regularly. In addition the

reviewers hand searched 83 Chinese Traditional Medicine

Journals (1993 to 2003). SELECTION CRITERIA:

Randomised trials comparing Zhiling decoction with placebo in

people with vascular dementia. DATA COLLECTION AND

ANALYSIS: Two reviewers independently assessed trial quality

and extracted data. Study authors were contacted for additional

information. Adverse effects information was collected from the

trials where possible. MAIN RESULTS : In the absence of any

suitable randomised placebo-controlled trials in this area, we

were unable to perform a meta-analysis. REVIEWERS'

CONCLUSIONS: The currently available evidence is

insufficient to assess the potential for Zhiling decoction to treat

vascular dementia. The little objective data concerning the

management of Zhiling decoction versus Naofukang suggests

that Zhiling decoction may be effective in treating vascular

dementia.There is no evidence for or against Zhiling as a

treatment for vascular dementia. Further randomised, double-

blind, placebo-controlled trials are urgently needed in order to

define the relative efficacy and acceptability of Zhiling in vascular

dementia.

 

Katagiri, F.; Inoue, S.; Sato, Y.; Itoh, H.; Takeyama, M. |

Comparison of the effects of Sho-hange-ka-bukuryo-to and

Nichin-to on human plasma adrenocorticotropic hormone and

cortisol levels with continual stress exposure. | Biol Pharm Bull

2004, 27 (10), 1679-82. | Dept of Clinical Pharmacy, Oita Univ

Hospital, Hasama-machi, Japan. FKATA |

Sho-hange-ka-bukuryo-to and Nichin-to, traditional Chinese

herbal (Kampo) medicines have been used to treat vomiting and

nausea. Traditional herbal medicines have frequently been used

in the empirical treatment Some patients who take these

medicines have no organic disease but have conditions classified

as non-ulcer dyspepsia (NUD). To determine the

pharmacological effects of Sho-hange-ka-bukuryo-to, Nichin-

to, and the two herbs (Pinelliae Tuber and Zingiberis Rz, both of

which are included in Sho-hange-ka-bukuryo-to and Nichin-to),

we examined the effects of these medicines on the plasma levels

of adrencorticotropic hormone (ACTH) and cortisol under

stress conditions by repetitive blood sampling. After a single

administration of Kampo medicine or a placebo, venous blood

samples were taken before and 20-240 min after administration.

A single administration of Sho-hange-ka-bukuryo-to caused

significant suppression of an increase in plasma ACTH-

immunoreactive substance (IS) levels at 120 to 180 min and

tended to suppress increases in plasma cortisol levels at 240

min, compared with the response to a placebo. A single

administration of Nichin-to caused significant suppression of

increases in plasma ACTH-IS levels at 120 min compared with

a placebo group, but had no effect on plasma cortisol levels.

Pinelliae Tuber had no significant effects in plasma ACTH-IS or

cortisol, but Zingiberis Rz significantly suppressed the increase of

ACTH-IS (120 min) and cortisol (180 min). These medicines

have a modulatory effect on the hypothalamo-pituitary-adrenal

(HPA) axis and autonomic nervous function. These effects might

be beneficial in stress-related disease and suggest that this

medicine has clinical pharmacological activity.

 

Katagiri, F.; Itoh, H.; Takeyama, M. | Effect of Sho-hange-ka-

bukuryo-to on gastrointestinal peptide concentrations in the

plasma of healthy human subjects. | Biol Pharm Bull 2004, 27,

(10), 1674-8. | Dept of Clinical Pharmacy, Oita Univ Hospital,

Hasama-machi, Japan. FKATA | Sho-hange-

ka-bukuryou-to, a traditional Chinese herbal (Kampo) medicine,

has been used to treat hyperemesis of pregnancy, nausea and

vomiting. Most traditional herbal medicines are prepared from

several herbs For example, Sho-hange-ka-bukuryo-to is

prepared from three herbs : Pinelliae Tuber, Zingiberis Rz and

Hoelen. Thus, to determine the precise mechanism of the

pharmacological effects of CHMs is too difficult. So we have

elucidated the effect of some CHMs by examining the change of

the plasma levels of brain-gut peptides. In this study, we

investigated the effects of Sho-hange-ka-bukuryo-to on the

plasma levels of gut-regulated peptides (gastrin, somatostatin,

motilin and vasoactive intestinal peptide (VIP)) and

gastrointestinal mucosa regulatory neuropeptides (calcitonin

gene-related peptide (CGRP) and substance P) in healthy

human subjects. A single oral administration of Sho-hange-ka-

bukuryo-to caused significant increases in plasma somatostatin-,

CGRP- and substance P-immunoreactive substance (IS) levels,

compared with a placebo group. Transient elevation of gastrin-

IS levels in the placebo group was inhibited by the administration

of Sho-hange-ka-bukuryo-to, but the medicine showed no

effects on plasma motilin- or VIP-IS levels. In conclusion, these

results might indicate that the pharmacological action of Sho-

hange-ka-bukuryo-to is closely related to changes in gastrin-,

somatostatin-, CGRP- and substance P-IS levels in human

plasma.

 

Kawashima, K.; Nomura, A.; Makino, T.; Saito, K.; Kano, Y. |

Pharmacological properties of traditional medicine (XXIX):

effect of Hange-shashin-to and the combinations of its herbal

constituents on rat experimental colitis. | Biol Pharm Bull 2004,

27 (10), 1599-603. | Dept of Kampo Medicinal Science,

Hokkaido College of Pharmacy, Katsuraoka-cho, Otaru, Japan.

kkawa38 | Hange-shashin-to (HST) has

been used as an herbal formula to treat inflammatory ulcerative

gut diseases complicated with psychoneurosis in Japanese

traditional Kampo medicine. The aim of the present study is to

clarify anti-colitic effect of HST using a model of colitis induced

by intracolonic instillation of 2,4,6-trinitrobenzene sulfonic acid

(TNBS) in rats, and to evaluate the pharmaceutical properties of

its herbal components. The colonic damage was elucidated by

macroscopic damage scores, colon wet weight and area of

mucosal necrosis. Orally administered HST significantly reduced

the colonic damage. Other rats were orally treated with single-

component berberine (BE), baicalin (BA), glycyrrhizin (GL) or

saponin fraction of ginsenosides (GS), or with the mixture (TL)

of BA, BE, GL and GS, or with the combinations of BA plus

BE (BA-BE), or that of GL plus GS (GL-GS). Oral treatment

of TL ameliorated colitis observations. However, no effects

were found to treat single-component BA, BE, GL or GS,

whereas the GL-GS combination ameliorated the colitis. These

results suggest that HST might suppress inflammatory bowel

disease (IBD) and imply that there will be a potential benefit in

the traditionally derived herbal combination.

 

Kelly, K. M. | Complementary and alternative medical therapies

for children with cancer. | Eur J Cancer 2004, 40 (14), 2041-6.

| Division of Pediatric Oncology, Dept of Pediatrics, College of

Physicians and Surgeons of Columbia Univ, 161 Fort

Washington Avenue, IP-7, New York, NY 10032, USA.

kk291 | Complementary and alternative medical

therapies (CAM) are treatments that generally fall outside of the

mainstream of conventional medicine. CAM therapies are used

by 31-84% of children with cancer, including many children

enrolled on clinical trials. CAM therapies are often used for the

treatment of side-effects of cancer or cancer therapy, and only

rarely as an alternative to conventional therapy Regulation of

CAM therapies varies worldwide, and many therapies have not

been subject to scientifically conducted analyses. Adverse

events have been described, especially from the contamination

of herbs Only rare reports of interactions of CAM therapies with

conventional anticancer treatments have been reported. Several

research studies of CAM in children with cancer are underway.

In the interim, non-pharmacological therapies such as mind-body

medicine, manipulative and body-based therapies and energy

therapies may be used for supportive therapy. Research is

needed before biologically based CAM therapies may be

recommended in conjunction with conventional therapy.

 

Kim, S. W.; Choi, S. C.; Choi, E. Y.; Kim, K. S.; Oh, J. M.;

Lee, H. J.; Oh, H. M.; Kim, S.; Oh, B. S.; Kimm, K. C.; Lee,

M. H.; Seo, G. S.; Kim, T. H.; Oh, H. C.; Woo, W. H.; Kim,

Y. S.; Pae, H. O.; Park, D. S.; Chung, H. T.; Jun, C. D. |

Catalposide, a compound isolated from catalpa ovata,

attenuates induction of intestinal epithelial proinflammatory gene

expression and reduces the severity of trinitrobenzene sulfonic

Acid-induced colitis in mice. | Inflamm Bowel Dis 2004, 10 (5),

564-72. | Digestive Disease Research Institute, Dept of

Microbiology and Immunology, Wonkwang Univ School of

Medicine, Iksan, Chonbuk 570-749, Seoul 122-701, Korea. |

Certain irinoid-producing plants have been used as herbal anti-

inflammatory remedies. Here we evaluated whether catalposide

(CATP), a single compound isolated from irinoid-producing

plant Catalpa ovata, has a potential for preventing or

ameliorating diseases characterized by mucosal inflammation.

Preliminary microarray-based gene expression test revealed that

CATP, which alone did not significantly affect expression of any

of the >8,000 genes analyzed, attenuated the expression of

tumor necrosis factor-alpha (TNF-alpha)-induced

proinflammatory genes including interleukin-8 (IL-8) in human

intestinal epithelial HT-29 cells. Down-regulation of IL-8 mRNA

accumulation was also reflected by the decreased IL-8 secretion

in CATP-treated HT-29 cells. The signal transduction study

revealed that CATP significantly attenuates TNF-alpha-

mediated p38 and extracellular signal-regulated kinase (ERK)

phosphorylation. Further, CATP reduced NF-kappaB-

mediated transcriptional activation as well as Ikappa-Balpha

degradation. To establish the in vivo relevance of these findings,

we examined whether CATP could affect intestinal inflammation

in vivo using the mouse model of trinitrobenzene sulfonic acid

(TNBS)-induced inflammatory colitis. Intrarectal administration

of CATP dramatically reduced the weight loss, colonic damage,

and mucosal ulceration that characterize TNBS colitis.

Moreover, CATP suppressed the expression of TNF-alpha,

interleukin-1beta, and intercellular adhesion molecule-1 along

with the inhibition of NF-kappa B p65 translocation into nucleus

in TNBS colitis. Collectively, current results demonstrate that

CATP may be an effective agent for the treatment of diseases

characterized by mucosal inflammation.; Copyright 2004

Lippincott Williams & Wilkins

 

Ko, S. G.; Koh, S. H.; Jun, C. Y.; Nam, C. G.; Bae, H. S.;

Shin, M. K. | Induction of apoptosis by Saussurea lappa and

Pharbitis nil on AGS gastric cancer cells. | Biol Pharm Bull

2004, 27 (10), 1604-10. | Dept of Tumor Biology, Cancer

Research Institute, College of Medicine, Seoul National Univ,

Yongon-dong, Chongno-gu, Korea. sgko9209 | We

performed this study to understand the molecular basis

underlying the antitumor effects of Saussurea lappa, Pharbitis nil,

Plantago asiatica and Taraxacum mongolicum, which have been

used for herbal medicinal treatments against cancers in East

Asia. We analyzed the effects of these medicinal herbs on

proliferation and on expression of cell growth/apoptosis related

molecules, with using an AGS gastric cancer cell line. The

treatments of Saussurea lappa and Pharbitis nil dramatically

reduced cell viabilities in a dose and time-dependent manner, but

Plantago asiatica and Taraxacum mongolicum didn't. FACS

analysis and Annexin V staining assay also showed that both

Saussurea lappa and Pharbitis nil induce apoptotic cell death of

AGS. Expression analyses via RT-PCR and Western blots

revealed that Saussurea lappa, but not Pharbitis nil, increased

expression of the p53 and its downstream effector p21Waf1,

and that the both increased expression of apoptosis related Bax

and cleavage of active caspase-3 protein. We also confirmed

the translocation of Bax to mitochondria. Collectively, our data

demonstrate that Saussurea lappa and Pharbitis nil induce

growth inhibition and apoptosis of human gastric cancer cells,

and these effects are correlated with down- and up-regulation of

growth-regulating apoptotic and tumor suppressor genes,

respectively.

 

Masuda, Y.; Shima, G.; Aiuchi, T.; Horie, M.; Hori, K.;

Nakajo, S.; Kajimoto, S.; Shibayama-Imazu, T.; Nakaya, K. |

Involvement of tumor necrosis factor receptor-associated

protein 1 (TRAP1) in apoptosis induced by beta-

hydroxyisovalerylshikonin. | J Biol Chem 2004, 279 (41),

42503-15. | Laboratory of Biological Chemistry, School of

Pharmaceutical Sciences, Showa Univ, Tokyo 142-8555,

Japan. masuda | beta-

Hydroxyisovalerylshikonin (beta-HIVS), a compound isolated

from the traditional oriental medicinal herb Lithospermum Rx, is

an ATP non-competitive inhibitor of protein-tyrosine kinases,

such as v-Src and EGFR, and it induces apoptosis in various

lines of human tumor cells. However, the way in which beta-

HIVS induces apoptosis remains to be clarified. In this study,

we performed cDNA array analysis and found that beta-HIVS

suppressed the expression of the gene for tumor necrosis factor

receptor-associated protein 1 (TRAP1), which is a member of

the heat-shock family of proteins. When human leukemia HL60

cells and human lung cancer DMS114 cells were treated with

beta-HIVS, the amount of TRAP1 in mitochondria decreased in

a time-dependent manner during apoptosis. A similar reduction

in the level of TRAP1 was also observed upon exposure of cells

to VP16. Treatment of DMS114 cells with TRAP1-specific

siRNA sensitized the cells to beta-HIVS-induced apoptosis.

Moreover, the reduction in the level of expression of TRAP1 by

TRAP1-specific siRNA enhanced the release of cytochrome c

from mitochondria when DMS114 cells were treated with either

beta-HIVS or VP16. The suppression of the level of TRAP1 by

either beta-HIVS or VP16 was blocked by N-acetyl-cysteine,

indicating the involvement of reactive oxygen species (ROS) in

the regulation of the expression of TRAP1. These results suggest

that suppression of the expression of TRAP1 in mitochondria

might play an important role in the induction of apoptosis caused

via formation of ROS.

 

Montbriand, M. J. | Herbs or natural products that increase

cancer growth or recurrence. Part 2 of a 4-part series. | Oncol

Nurs Forum 2004, 31 (5), E99-115 | College of Medicine, Univ

of Saskatchewan, Saskatoon, Canada.

montbriand | PURPOSE/OBJECTIVES: To

review 32 herbs and natural products that show potential to

increase cancer growth or recurrence or to interfere with cancer

treatments DATA SOURCES: Natural Medicines

Comprehensive Database and Lawrence Review of Natural

Products Monograph System. DATA SYNTHESIS: Early

evidence shows that patients who have or have had cancer

should avoid 32 herbs and natural products. Some herbs and

natural products have estrogenic effects that enable these

products to compete with hormone cancer therapies, whereas

others interfere with chemotherapy treatment or may induce

recurrence of cancer. CONCLUSIONS: Healthcare

professionals can be resources for patients who have cancer,

helping them to avoid or identify products that may induce

cancer growth or interfere with cancer treatment

IMPLICATIONS FOR NURSING: The information in this

article is designed to provide quick access for healthcare

professionals working in clinical oncology.

 

Nishikawa, M.; Ariyoshi, N.; Kotani, A.; Ishii, I.; Nakamura,

H.; Nakasa, H.; Ida, M.; Nakamura, H.; Kimura, N.; Kimura,

M.; Hasegawa, A.; Kusu, F.; Ohmori, S.; Nakazawa, K.;

Kitada, M. | Effects of continuous ingestion of green tea or

grape seed extracts on the pharmacokinetics of midazolam. |

Drug Metab Pharmacokinet 2004, 19 (4), 280-9. | Graduate

School of Pharmaceutical Sciences, Chiba Univ. | Limited

systematic data on herb-drug interaction are available, despite

many opportunities to concomitant use of herb with prescribed

drugs. We investigated the effects of 15 herbal extracts in

dietary supplements on CYP2C9, CYP2D6 and CYP3A4

activities in human liver microsomes. Strong inhibition of these

CYP activities was found by the addition of green tea extracts

(GTE) or grape seed extracts (GSE) in vitro. To examine the

effects of these extracts on CYP3A activities in vivo, the

pharmacokinetics of midazolam (MDZ) was analyzed in rats.

Although single treatments with these extracts had negligible

effects, 1 week of treatment with them resulted in a significant

increase in the ke of intravenously administered MDZ, indicating

the induction of CYP3A in the liver. In contrast, 1 week of

treatment with GTE, but not GSE, caused a significant increase

in the C(max) and AUC(0-infinity) of orally administered MDZ

without change in the t(1/2), suggesting a reduction in CYP3A

activity in the small intestines. These studies indicate that

subchronic ingestion of GTE or GSE may alter the

pharmacokinetics of MDZ, and the effects of GTE on CYP3A

activity appear opposite between liver and small intestine, which

could not be predicted from in vitro experiments.

 

Nong, Y. B.; Lin, Q.; Duan, W. H.; Yang, H. | Constructing a

Cox proportional hazard regression model of prognosis factors

of acute myocardial infarction by retrospective cohort study. |

Zhongguo Zhong Xi Yi Jie He Za Zhi 2004, 24 (9), 781-4. |

Affiliated Dongzhimen Hospital, Beijing Univ of Chinese

Medicine, Beijing (100700). nelumbo |

OBJECTIVE: To study the effects of the potential factors,

including Chinese herbal decoction, on the long-term prognosis

of acute myocardial infarction (AMI). METHODS: Previous

clinical data of 162 patients with AMI were collected, who were

followed-up to observe the important events for prognosis, as

death and cardio-cerebral episode, and the Cox proportional

hazards regression model was used to assess the relative factors.

RESULTS : The degree of cardiac function (by New York

grading) increased 1 grade when age increased for 10 years,

and the relative hazardous degree (RHD) raised to 1.983 and

3.169. After treatment with Chinese herbal decoction and

angiotensin converting enzyme inhibitor (ACEI), the RHD could

be reduced to 0.177 and 0.161 respectively. Taking the

important cardio-cerebral events, including death, as the

endpoint, when age increased for 10 years, the cardiac function

would increase for 1 grade and RHD of endpoint events

increased to 2.021 and 1.863, if patients had history of anterior

infarction, arrhythmia and diabetes mellitus, it increased to

2.903, 2.588 and 4.039 respectively. Chinese decoction and

ACEI treatment could reduce it to 0.093 and 0.141

respectively. CONCLUSION: Age, heart failure, anterior

infarction, arrhythmia and diabetes mellitus are the hazardous

factors of the long-term prognosis of AMI, Chinese herbal

decoction and ACEI are the protective factors.

 

Oberlies, N. H.; Kim, N. C.; Brine, D. R.; Collins, B. J.;

Handy, R. W.; Sparacino, C. M.; Wani, M. C.; Wall, M. E. |

Analysis of herbal teas made from the leaves of comfrey

(Symphytum officinale): reduction of N-oxides results in order of

magnitude increases in the measurable concentration of

pyrrolizidine alkaloids. | Public Health Nutr 2004, 7 (7), 919-

24. | Natural Products Laboratory, RTI International, Research

Triangle Park, NC 27709, USA. oberlies

CONTRACT/GRANT NUMBER- N01-ES-

55386.ES.NIEHS | OBJECTIVES: To determine the relative

quantities of two hepatotoxic pyrrolizidine alkaloids, symphytine

and echimidine, in teas prepared from comfrey leaves

(Symphytum officinale), and to determine the potential

contribution of the N-oxide forms of these alkaloids to levels of

the parent alkaloids. DESIGN: Comfrey leaves were purchased

from three commercial sources and used to prepare tea in a

manner consistent with the methods used by consumers. An

extraction scheme was devised for extraction of the alkaloids,

and a gas chromatographic method was developed to quantify

the two major alkaloids, symphytine and echimidine.

Recognising that the N-oxide derivatives of these alkaloids have

also been identified in comfrey preparations, chemical reduction

was applied to determine the total quantities of the alkaloids as

free bases and as N-oxide derivatives. RESULTS : The

concentration of symphytine and echimidine varied considerably

between teas prepared from leaves purchased from the different

vendors of plant material. Moreover, a much higher

concentration of symphytine was found in the tea when steps

were included to reduce N-oxides prior to analysis. The

treatment of pure symphytine with hot water did not generate the

N-oxide derivative de novo. CONCLUSIONS: Since the

pyrrolizidine alkaloids are known to be hepatotoxic,

consumption of herbal teas made from comfrey leaves may be ill-

advised. The concentration of pyrrolizidine alkaloids in such teas

may be underestimated substantially unless the concentration of

N-oxides is taken into consideration.

 

Ong, E. S.; Len, S. M.; Lee, A. C.; Chui, P.; Chooi, K. F. |

Proteomic analysis of mouse liver for the evaluation of effects of

Scutellariae Rx by liquid chromatography with tandem mass

spectrometry. | Rapid Commun Mass Spectrom 2004, 18 (21),

2522-30. | Centre for Analytical Science, Health Sciences

Authority, 11 Outram Road, Singapore 169078, Republic of

Singapore. | Scutellariae Rx or Scutellaria baicalensis is a

medicinal plant that contains major flavonoids such as baicalein,

baicalin, wogonin and wogonosides. The present work

describes the development of an approach using proteomic

analysis of mouse liver to study the effects of prolonged

exposure to substances present in chemically standardized

Scutellariae Rx extracts. Histopathological examination of the

mouse liver was compared with the proteome data. The

botanical extracts were prepared using pressurized liquid

extraction (PLE). A method without isotope labeling was

developed, using proteolytic digestion with one- and two-

dimensional liquid chromatography with tandem mass

spectrometry, and was used to characterize the extent of

differential protein expression in mouse liver in response to

external factors such as extracts from Scutellariae Rx. From the

histopathological examination and proteome data, significant

changes in the mouse livers were not observed for the low-dose

group. The Scutellariae Rx extracts at high dose were observed

to cause damage at the bile duct and expression change of a

number of proteins including some involved in catabolism of

triglyceride-rich particles, carbohydrate metabolism, regulators

of cell signaling processes, and enzymes involved in

biotransformation. Thus, proteomic analysis of liver samples

from mice treated with botanical extracts is a promising

approach to provide information on any potential toxicity effects

of the extracts. The present method also provides another means

for comparing proteomes in biological samples such as liver

lysates from mice subjected to different treatments Copyright ©

2004 John Wiley & Sons, Ltd.

 

Owen, A. J.; Roach, P. D.; Abbey, M. | Regulation of low-

density lipoprotein receptor activity by estrogens and

phytoestrogens in a HepG2 cell model. | Ann Nutr Metab 2004,

48, (4), 269-75. | Dept of Physiology, Univ of Adelaide,

Australia. alice, owen | BACKGROUND/AIMS:

Estrogen treatment is thought to lower low-density lipoprotein

(LDL) cholesterol levels by increasing clearance through hepatic

LDL receptors. This study aimed to determine the effect of

estrogens and phytoestrogens on LDL receptor activity in a

human hepatoma cell line, HepG2. METHODS: HepG2 cells in

culture were incubated for 24 h with estrogen or phytoestrogen

and LDL receptor activity was measured by examining the

cellular binding of colloidal gold-labelled LDL. RESULTS :

17Beta-estradiol significantly increased LDL receptor activity

whereas estriol had negligible effects Incubation with the

isoflavonoids, formononetin, biochanin A and daidzein, caused

significant elevations in receptor activity at concentrations above

40 uM. Coumestrol, a coumestan with a high level of estrogenic

activity, caused a 3-fold increase in receptor activity at a

concentration of 50 uM. Of the phytoestrogenic mammalian

lignans enterolactone and enterodiol, only enterolactone

displayed the ability to significantly upregulate LDL receptor

activity at 50 uM. CONCLUSION: This study suggests that the

LDL receptor-stimulating effect of natural estrogens is mainly

due to estradiol and that the cholesterol-lowering effect of diets

high in phytoestrogens may be due in part to their ability to

increase hepatic LDL receptor activity.; Copyright © 2004 S.

Karger AG, Basel.

 

Park, T. H.; Kim, D. H.; Kim, C. H.; Jung, H. A.; Choi, J. S.;

Lee, J. W.; Chung, H. Y. | Peroxynitrite scavenging mode of

alaternin isolated from Cassia tora. | J Pharm Pharmacol 2004,

56, (10), 1315-21. | College of Pharmacy, Aging Tissue Bank,

Pusan National Univ, Busan 609-735, Korea. | Peroxynitrite

(ONOO-), formed from the reaction of superoxide (.O2-) and

nitric oxide (NO), is a potent oxidant that contributes to the

oxidation of various cellular constituents, including lipids, amino

acids, sulfhydryls and nucleotides. It can cause cellular injury,

such as DNA fragmentation and apoptotic cell death ONOO-

toxicity is also reported to be involved in inflammatory and

neurodegenerative diseases, such as Alzheimer's disease,

Parkinson's disease and atherosclerosis. Moreover, the

necessity for a strong ONOO- scavenger is important because

of the lack of endogenous enzymes that protect against the

damage caused by ONOO-. The aim of this study was to

evaluate the ability of natural products to scavenge ONOO-.

We tested various plant extracts for their ONOO- scavenging

activity. Among them, extract from Cassia tora, which is well

known as an oriental herb in traditional medicine, showed potent

ONOO- scavenging activity. Further analysis identified the

phenolic active components, alaternin and nor-rubrofusarin

glucose, as potent ONOO- scavengers. Spectrophotometric

analysis demonstrated that alaternin and nor-rubrofusarin

glucose led to a decrease in the ONOO- -mediated nitration of

tyrosine through electron donation. In bovine serum albumin,

alaternin, but not nor-rubrofusarin glucose, showed significant

inhibition of ONOO- -mediated nitration in a dose-dependent

manner. We believe alaternin can be developed as an effective

ONOO- scavenger for the prevention of ONOO- -associated

diseases.

 

Peredery, O.; Persinger, M. A. | Herbal treatment following

post-seizure induction in rat by lithium pilocarpine: Scutellaria

lateriflora (Skullcap), Gelsemium sempervirens (Gelsemium) and

Datura stramonium (Jimson Weed) may prevent development of

spontaneous seizures. | Phytother Res 2004, 18 (9), 700-5. |

Laurentian Univ, Sudbury, Ontario, Canada. | About 1 week

after the induction of status epilepticus in male rats by a single

systemic injection of lithium (3 mEq/kg) and pilocarpine (30

g/kg), rats were continuously administered one of three herbal

treatments through the water supply for 30 days. A fourth group

received colloidal minerals and diluted food grade hydrogen

peroxide in tap water, while a fi fth group of rats received only

tap water (control). Herbal treatments were selected for their

historical antiseizure activities and sedative actions on the

nervous system. The numbers of spontaneous seizures per day

during a 15 min observation interval were recorded for each rat

during the treatment period and during an additional 30 days

when only tap water was given. Rats that received a weak

solution of the three herbal fl uid extracts of Scutellaria lateri fl

ora (Skullcap), Gelsemium sempervirens (Gelsemium) and

Datura stramonium (Jimson Weed) displayed no seizures during

treatment while all the other groups were not seizure-free.

However, when this treatment was removed, the rats in this

group displayed numbers of spontaneous seizures comparable to

the controls. Although there is no proof that herbal remedies can

control limbic or temporal lobe epilepsy, the results of this

experiment strongly suggest that the appropriate combination of

herbal compounds may be helpful as adjunctive interventions.

Copyright © 2004 John Wiley & Sons, Ltd.

 

Rasoanaivo, P.; Ramanitrahasimbola, D.; Rafatro, H.;

Rakotondramanana, D.; Robijaona, B.; Rakotozafy, A.;

Ratsimamanga-Urverg, S.; Labaoied, M.; Grellier, P.; Allorge,

L.; Mambu, L.; Frappier, F. | Screening extracts of Madagascan

plants in search of antiplasmodial compounds. | Phytother Res

2004, 18 (9), 742-7. | Institut Malgache de Recherches

Appliquoees, 101-Antananarivo, Madagascar. | 190 plants, of

which 51 are used to treat malaria in traditional medicine, were

collected in 5 different ecosystems of Madagascar for a

screening programme devoted to the search of naturally-

occurring antimalarial compounds. 39 plants, of which 12 are

used as herbal antimalarials, were found to display in vitro

activity against Plasmodium falciparum with a median inhibitory

concentration (IC(50)) lower than 5 ug/ml while 9 had an

IC(50) ranging from 5 to 7.5 ug/ml. Seventeen of them exhibited

cytotoxic effects on murine P388 leukemia cells with an IC(50)

60 10 ug/ml. The biological activities were mostly located in the

ethyl acetate fractions. Bioassay-directed fractionation is

underway to isolate the active constituents. Copyright © 2004

John Wiley & Sons, Ltd.

 

Scifo, C.; Cardile, V.; Russo, A.; Consoli, R.; Vancheri, C.;

Capasso, F.; Vanella, A.; Renis, M. | Resveratrol and propolis

as necrosis or apoptosis inducers in human prostate carcinoma

cells. | Oncol Res 2004,14 (9), 415-26. | Dept of Biological

Chemistry, Medicinal Chemistry and Molecular Biology, Univ of

Catania, Viale Andrea Doria, 6, 95125 Catania, Italy. |

Vegetables and fruit help the prevention and the therapy of

several kinds of cancer because they contain micronutrients, a

class of substances that have been shown to exhibit

chemopreventive and chemotherapeutic activities. In the present

study the effects of resveratrol (100 and 200 uM), a phytoalexin

found in grapes, and of the ethanolic extract of propolis (50 and

100 ug/ml), a natural honeybee hive product, were tested in

androgen-resistant prostate cancer cells (DU145), a cell line

resembling the last stage of prostate carcinoma. A comparison

between the activity of these micronutrients and vinorelbine

bitartrate (Navelbine), a semi-synthetic drug normally used in the

therapy of prostate cancer, was conducted. Several biochemical

parameters were tested, such as cell viability (MTT assay), cell

membrane integrity (lactate dehydrogenase release), cell redox

status (nitric oxide formation, reactive oxygen species

production, reduced glutathione levels), genomic DNA

fragmentation (COMET assay) with special attention on the

presence of apoptotic DNA damage (TUNEL test), and

possible mitochondrial transmembrane potential alteration

(deltapsi). Our results point out the anticancer activity of

resveratrol and propolis extract in human prostate cancer,

exerting their cytotoxicity through two different types of cell

death : necrosis and apoptosis, respectively. The data obtained

suggest the possible use of these micronutrients both in

alternative to classic chemotherapy, and in combination with

very low dosage of vinorelbine (5 uM).

 

Smith, P. C.; Santibaonez, J. F.; Morales, J. P.; Martinez, J. |

Epidermal growth factor stimulates urokinase-type plasminogen

activator expression in human gingival fibroblasts. Possible

modulation by genistein and curcumin. | J Periodontal Res 2004,

39 (6), 380-7. | Faculty of Odontology, Univ of Chile, Santiago,

Chile. | Regulation of the extracellular matrix turnover is a crucial

process in wound healing and the progress of periodontal

disease. It has been proposed that urokinase-type plasminogen

activator (uPA), under the control of growth factors or

cytokines, provides the proteolytic potential to the

accomplishment of these cellular events. Epidermal growth

factor (EGF) is one of the growth factors that has been shown to

be active in uPA regulation. Methods: In this study, we have

assessed the effect of EGF on uPA expression in primary

cultures of human gingival fibroblasts. We also studied the

signaling pathways involved in this process and the role of the

dietary phytoestrogens curcumin and genistein as potential

modulators of this response. Results : Human gingival fibroblasts

expressed a basal uPA activity, which was inhibited by genistein,

but not by curcumin. After treatment with 10 ng/ml EGF, uPA

production was strongly stimulated. Exposure to genistein and

curcumin inhibited EGF-stimulated urokinase production,

although only genistein showed a statistically significant inhibitory

response. Using more specific inhibitors, we found that the

mitogen-activated extracellular kinase and c-Jun N-terminal

kinase (JNK) inhibitors PD98059 and SP600125 also blocked

the EGF-dependent stimulatory effect On the other hand,

SB203580, inhibitor of the p38 member of mitogen-activated

protein kinase family, did not alter this response. In accordance

to these findings, EGF stimulated a potent activation of JNK and

a mild activation of extracellular signal-regulated kinases 1/2.

Finally, EGF stimulated the phosphorylation of its receptor and

tyrphostin (AG1478), curcumin and genistein were able to inhibit

this stimulatory effect Conclusions: These results indicate that

EGF constitutes a strong stimuli on uPA expression in human

gingival fibroblasts. EGF-stimulated uPA production involves the

activation of the extracellular signal-regulated kinases 1/2 and

JNK signaling pathways and might be modulated by the natural

phytoestrogens curcumin and genistein.

 

Tokiwa, T.; Harada, K.; Matsumura, T.; Tukiyama, T. | Oriental

medicinal herb, Periploca sepium, extract inhibits growth and IL-

6 production of human synovial fibroblast-like cells. | Biol Pharm

Bull 2004, 27 (10), 1691-3. | Kohno Clinical Medicine

Research Institute, Shinagawa-ku, Tokyo, Japan.

t.tokiwa | Periploca sepium (PS) has traditionally

been used in oriental medicine for treatment of rheumatoid

arthritis (RA). We investigated the aqueous extract of PS (PSE)

in its effects on human rheumatoid arthritis-derived fibroblast-

like cells. In cell culture studies, PSE inhibited the growth and IL-

6 production of the cells in dose dependent manners. The

extract of Glycyrrhiza glabra (GG), which has also been used to

treat RA and chosen as a reference here, slightly inhibited the

growth of RA cells. A study of PSE fractionation indicated that

the active material inhibiting IL-6 production is filterable by

ultrafiltration, suggesting that substances with low molecular

weight might be involved in an inhibition of IL-6 production.

These results support the view that PSE represents a rich source

of growth inhibition and anti-IL 6 production.

 

Tsuda, H.; Ohshima, Y.; Nomoto, H.; Fujita, K.; Matsuda, E.;

Iigo, M.; Takasuka, N.; Moore, M. A. | Cancer prevention by

natural compounds. | Drug Metab Pharmacokinet 2004, 19 (4),

245-63. | Dept of Molecular Toxicology, Nagoya City Univ

Graduate School of Medical Sciences. | Increasing attention is

being paid to the possibility of applying cancer chemopreventive

agents for individuals at high risk of neoplastic development. For

this purpose by natural compounds have practical advantages

with regard to availability, suitability for oral application,

regulatory approval and mechanisms of action. Candidate

substances such as phytochemicals present in foods and their

derivatives have been identified by a combination of

epidemiological and experimental studies. Plant constituents

include vitamin derivatives, phenolic and flavonoid agents,

organic sulfur compounds, isothiocyanates, curcumins, fatty

acids and d-limonene. Examples of compounds from animals are

unsaturated fatty acids and lactoferrin. Recent studies have

indicated that mechanisms underlying chemopreventive potential

may be combinations of anti-oxidant, anti-inflammatory, immune-

enhancing, and anti-hormone effects, with modification of drug-

metabolizing enzymes, influence on the cell cycle and cell

differentiation, induction of apoptosis and suppression of

proliferation and angiogenesis playing roles in the initiation and

secondary modification stages of neoplastic development.

Accordingly, natural agents are advantageous for application to

humans because of their combined mild mechanism. Here we

review naturally occurring compounds useful for cancer

chemprevention based on in vivo studies with reference to their

structures, sources and mechanisms of action.

 

Vaziri, N. D. | Oxidative stress in uremia: Nature, mechanisms,

and potential consequences. | Semin Nephrol 2004, 24 (5), 469-

73. | | Oxidative stress has emerged as a constant feature of

chronic renal failure (CRF). The presence of oxidative stress in

CRF is evidenced by an overabundance of lipid, carbohydrate,

and protein oxidation products in the plasma and tissues of

uremic patients and animals. We recently have shown that

oxidative stress in CRF animals is associated with and, in part,

owing to up-regulation of superoxide-producing enzyme,

nicotinamide-adenine dinucleotide phosphate (NAD(P)H)

oxidase, and down-regulation of superoxide dismutase (SOD).

The functional significance of these findings was confirmed by

favorable response to administration of the cell-permeable SOD-

mimetic agent, tempol, in CRF rats. Oxidative stress in CRF

plays an important role in the pathogenesis of the associated

hypertension (oxidation of NO and arachidonic acid and

vascular remodeling), cardiovascular disease (oxidation of

lipoproteins, atherogenesis), neurologic disorders (nitration of

brain proteins, oxidation of myelin), anemia (reduction of

erythrocyte lifespan), inflammation (nuclear factor kappa B

activation), fibrosis, apoptosis, and accelerated aging. The CRF-

induced oxidative stress is aggravated by diabetes, uncontrolled

hypertension, and autoimmune diseases, which independently

increase production of reactive oxygen intermediates, and

frequently are associated with CRF. In addition, dialysis

treatment (blood interaction with dialyzer membrane and

dialysate impurities), acute and chronic infections (blood access

infection, hepatitis, and so forth), and excessive parenteral iron

administration intensify CRF-associated oxidative stress and its

adverse consequences in patients with end-stage renal disease.

The problem is compounded by limited intake of fresh fruits and

vegetables (K + restriction), which contain numerous natural

phytochemicals and antioxidant vitamins.

 

Whitehouse, M. W.; Butters, D. E. | Combination anti-

inflammatory therapy:

synergism in rats of NSAIDs/corticosteroids with some herbal/animal products. |

Inflammopharmacology 2003, 11 (4), 453-64. | Therapeutics Research Unit, Dept

of Medicine, Univ of Queensland, Princess Alexandra Hospital, Woolloongabba,

Queensland 4102, Australia. | A useful function of any complementary medicine

is to supplement some of the benefits from other treatment modalities. In rats,

extracts from Indian celery seed and the NZ green-lipped mussel are powerful

nutraceuticals that (i) amplify the potency of salicylates and prednisone for

treating pre-established chronic inflammation (arthritis, fibrosis) and (ii)

reduce the steroid's gastrotoxic and lymphopenic side effects Such combinations

might also be useful for treating inflammatory components of (a) osteoarthritis

caused by microcrystalline hydroxyapatite (BCP) and (b) pseudo-gout, associated

with calcium pyrophosphate crystals; that are usually refractory to

monotherapy.

 

Wu, B.; Liu, M.; Zhang, S. | Danshen agents for acute ischaemic stroke. |

Cochrane Database Syst Rev 2004, (4), CD004295 | |

BACKGROUND: Based mainly on experimental data which indicates improvement to

the cerebral microcirculation, Danshen, a herbal medicine, is widely used to

treat acute ischaemic stroke in China. We aimed to assess the evidence from

RCT

s of their effects OBJECTIVES: To review the randomised or quasi-

RCT

s of Danshen agents for acute ischaemic stroke. The primary objective was to

determine whether Dan Shen agents improve functional outcome without causing

undue harm in patients with acute ischaemic stroke. Secondary objectives were

to assess the effect of Danshen agents on impairment and on quality of life.

SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (last

searched September 2003), the register of the Cochrane Complementary Field

(last searched September 2003) and the Chinese Stroke Trials Register (last

searched September 2003). In addition we searched the following bibliographic

databases: The Cochrane Central Register of Controlled Trials (The Cochrane

Library, Issue 4, 2002), MEDLINE (1996 to December 2002), EMBASE (1980 to

December 2002), CINAHL (1982 to December 2002), AMED (1985 to December 2002)

and China Biological Medicine Database (CBM-disc 1979 to December 2002). We

handsearched 10 Chinese journals, searched clinical trials and research

databases, scanned reference lists and contacted the pharmaceutical company

manufacturing Danshen. SELECTION CRITERIA:

RCT

s or quasi-randomised controlled clinical trials comparing Dan Shen agents with

placebo or open control (no placebo) in patients with acute ischaemic stroke.

DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials for

inclusion, assessed trial quality and extracted the data. MAIN RESULTS : Eight

potentially eligible trials were identified, of which three trials (304

patients) were included. Two trials were excluded and three trials are awaiting

assessment. Numbers of deaths and dependent patients at the end of follow-up of

at least three months were not reported in the three included trials. Only one

trial reported adverse events. Three trials measured the outcome " significant

improvement in neurological deficit at the end of treatment " . Compound Danshen

agents were associated with a significant increase in the number of patients

with the outcome (Peto Odds Ratio (OR) 2.72, 95% Confidence Interval (CI) 1.10

to 6.72). No deaths were reported within the first two weeks of treatment or

during the whole follow-up period (21 to 28 days). The trials did not include

any assessment of quality of life. REVIEWERS' CONCLUSIONS: There were too few

patients and outcome events to draw reliable conclusions from the present data.

The methodological qualities of all included studies were poor. Further

high-quality

RCT

s should be performed.

 

 

Xu, W.; Ziqing, L.; Yinrun, D.; Xiaoyan, W.; Jinglun, X. | Tripterygium

hypoglaucum (level) Hutch induces aneuploidy of chromosome 8 in mouse bone

marrow cells and sperm. | Mutagenesis 2004, 19 (5), 379-82. | State Key

Laboratory of Genetic Engineering, Institute of Genetics, School of Life

Sciences, Fudan Univ, Shanghai, 200433, People's Republic of China. |

Aneuploidy of mouse chromosome 8 induced by a Chinese medicinal herb,

Tripterygium hypoglaucum (level) Hutch (THH) was investigated by fluorescence

in situ hybridization (FISH) in vivo. Male mice were treated with THH (single

i.p. injection) at doses of 120, 240 and 480 mg/kg. Colchicine (COL, 1.5 mg/kg

i.p.) was used as a positive control. Bone marrow cells and epididymal sperm

were collected 24 h and 22 days after treatment, respectively. Chromosome 8

aneuploidies induced by THH in bone marrow cells and sperm were determined by

FISH with a biotin-16-dUTP labelled DNA probe corresponding to the centromeric

region of chromosome 8. The hybridized probe was detected with avidin-FITC. The

frequencies of trisomy 8 in bone marrow cells were 0.16% in the solvent control

group, 0.39% in the COL-treated group and 0.33, 0.41 and 0.41% in the

THH-treated groups, respectively. The frequencies of disomy 8 sperm were 0.11%

in the solvent control group, 0.27% in the COL-treated group and 0.23, 0.27 and

0.27% in the THH-treated groups, respectively. The experiment showed that

induced aneuploidy frequencies were higher in bone marrow cells than in sperm

with COL and the two higher doses of THH (P 60 0.05). All groups were

significantly different from the corresponding solvent controls (P 60

0.01-0.001), but there was no dose-related increase in either cell type.

Considering the present results together with our previous studies, it appears

that THH is a potent mammalian aneugen which may pose a genetic risk to human

patients.

 

Yanpallewar, S. U.; Rai, S.; Kumar, M.; Acharya, S. B. | Evaluation of

antioxidant and neuroprotective effect of Ocimum sanctum on transient cerebral

ischemia and long-term cerebral hypoperfusion. | Pharmacol Biochem Behav 2004,

79 (1), 155-64. | Dept of Pharmacology, Institute of Medical Sciences, Banaras

Hindu Univ, 221 005 Varanasi, India. | Free radicals are implicated in

causation of cerebral reperfusion injury and chronic cerebral hypoperfusion in

rats is associated with functional and histopathological disturbances. Ocimum

sanctum (OS), a plant widely used in Ayurveda, has been shown to possess

anti-inflammatory, antioxidant and cognition-enhancing properties. In the

present study, we investigated the effect of methanolic extract of OS leaves in

cerebral reperfusion injury as well as long-term hypoperfusion. Occlusion of

bilateral common carotid arteries (BCCA) for 30 min followed by 45 min

reperfusion caused increase in lipid peroxidation and up-regulation of

superoxide dismutase (SOD) activity accompanied by fall in tissue total

sulfhydryl groups (TSH) in rat forebrains. Ascorbic acid levels were unchanged,

however. OS pretreatment (200 mg/kg/day for 7 days) prevented this

reperfusion-induced rise in lipid peroxidation and SOD activity. OS

pretreatment also stabilized the levels of TSH during reperfusion. Long-term

cerebral hypoperfusion (a model of cerebrovascular insufficiency and dementia)

induced by permanent occlusion of BCCA for 15 days demonstrated altered

exploratory behavior in open-field testing and memory deficits as tested by

Morris' water maze. Histopathological examination of hypoperfused animals

revealed reactive changes, like cellular edema, gliosis and perivascular

inflammatory infiltrate. OS treatment (200 mg/kg/day for 15 days) significantly

prevented these hypoperfusion-induced functional and structural disturbances.

The results suggest that OS may be useful in treatment of cerebral reperfusion

injury and cerebrovascular insufficiency states.

 

Yuan, C. S.; Mehendale, S. R.; Wang, C. Z.; Aung, H. H.; Jiang, T.; Guan, X.;

Shoyama, Y. | Effects of Corydalis yanhusuo and Angelicae dahuricae on Cold

Pressor-Induced Pain in Humans: A Controlled Trial. | J Clin Pharmacol 2004, 44

(11), 1323-7. | Dept of Anesthesia & Critical Care, Univ of Chicago, 5841 S.

Maryland Avenue, MC 4028, Chicago, IL 60637. | Pain is considered the most

common complaint worldwide for which patients seek treatment Conventional

analgesic agents play an important role in modern pain therapy, but they cause

several adverse effects Therefore, newer and better analgesics continue to be

investigated. In this controlled clinical trial, the authors evaluated the

analgesic effects of 2 herbal medicines, Corydalis yanhusuo and Angelicae

dahuricae. They used the cold-pressor test-a simple, reliable, and

widely used model in humans-for induction of tonic pain. They

demonstrated that after a single, oral administration of the extracts

of C. yanhusuo and A. dahuricae, the pain intensity and pain

bothersomeness scores significantly decreased (both P 60 .01).

Dose-related analgesic effect was also observed. Results from this

study suggest that C. yanhusuo and A. dahuricae may have a

potential clinical value for treating mild to moderate pain.

 

Zhang, W.; Leonard, T.; Bath-Hextall, F.; Chambers, C.; Lee, C.;

Humphreys, R.; Williams, H. | Chinese herbal medicine for atopic

eczema. | Cochrane Database Syst Rev 2004, (4), CD002291 |

Academic Rheumatology, Univ of Nottingham, Clinical Sciences

Building, City Hospital, Nottingham, England, UK, NG5 1PB. |

BACKGROUND: Traditional Chinese herbal mixtures have been

used to treat atopic eczema for many years. Their efficacy has

attracted public attention and recently some clinical trials have

been undertaken. OBJECTIVES: To assess the effects of Chinese

herbal mixtures to treat atopic eczema. SEARCH STRATEGY: We

searched the Cochrane Central Register of Controlled Trials

(CENTRAL) (January 2004), the Cochrane Skin Group Specialised

Register (January 2004), MEDLINE (1966 to January 2004),

EMBASE (1980 to January 2004), CINHL (1980 to January 2004)

and a number of complementary medicine databases. In addition,

the cited references of all trials identified and key review articles

were searched. Pharmaceutical companies involved in oral

traditional Chinese herbs and experts in the field were contacted.

SELECTION CRITERIA: RCTs of Chinese herbal mixtures used to

treat atopic eczema. DATA COLLECTION AND ANALYSIS: Two

reviewers independently applied eligibility criteria, assessed the

quality of the trials and extracted data. Any discrepancies were

discussed to achieve consensus. MAIN RESULTS : Four RCTs,

with eight weeks for each phase, met the inclusion criteria. The

trials randomised 159 participants aged from 1 to 60 years. The

withdrawal rates ranged from 7.5% to 22.5% and no trial used

intention to treat analysis. Three trials were randomised placebo

controlled, two-phase cross-over designs assessing the same

Chinese herbal mixture, Zemaphyte. In two of these three trials the

reduction in erythema and surface damage was greater on

Zemaphyte than on placebo, and participants slept better and

itched less and expressed a preference for Zemaphyte. The fourth

trial was an open-label design comparing Zemaphyte in herbal form

with Zemaphyte as a freeze dried preparation. There was a

reduction in erythema and surface damage with both formulations,

but no comparison between the two formulations was reported.

Some adverse effects were reported in all four trials, but none were

regarded as serious. REVIEWERS'

CONCLUSIONS: Chinese herbal mixtures may be effective to treat

atopic eczema.

However, only four small poorly reported RCTs of the same

product, Zemaphyte, were found and the results were

heterogeneous. Further well-designed, larger scale trials are

required, but Zemaphyte is no longer being manufactured.

 

 

 

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