Recent herbal abstracts on Medline

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Menopause. 2005 Nov 1;12(6):734-740 [Epub ahead of print] Use of

dong quai (Angelica sinensis) to treat peri- or postmenopausal

symptoms in women with breast cancer: is it appropriate? Lau CB, Ho

TC, Chan TW, Kim SC. School of Pharmacy, The Chinese University of

Hong Kong, Shatin, NT, Hong Kong. claralau.

OBJECTIVE: Regarding the growing use of alternative therapies for

peri- or postmenopausal symptoms, we evaluated the effect of awater

extract of Angelica sinensis (dong quai), used for perior

postmenopausal relief, on the proliferation of estrogen receptor-positive

(MCF-7) and negative (BT-20) breast cancer cells in vitro. DESIGN: The

present study was designed to investigate the growth-modulating effect

of dong quai water extract, alone or in the presence of 17beta-estradiol

and 4-hydroxytamoxifen, on MCF-7 and BT-20 cell cultures using MTT

proliferation assay. RESULTS: The water extract of dong quai dose-

dependently and significantly stimulated the proliferation of MCF-7 cells

with a weak estrogen-agonistic activity in the presence of 17beta-

estradiol, as evidenced by the significant suppression by 4-

hydroxytamoxifen. Meanwhile, the extract significantly exerted a growth-

stimulating effect on BT-20 in a dose-dependent manner with or without

17beta-estradiol. No obvious difference was found in the growth of BT-

20 cells treated with the extract in the presence of 17beta-estradiol or 4-

hydroxytamoxifen. CONCLUSIONS: The water extract of dong quai

stimulated the growth of MCF-7 cells, possibly dependent of weak

estrogen-agonistic activity, and augmented the BT-20 cell proliferation

independent of estrogen receptor-mediated pathway. The present study

provides data regarding the estrogen-like activity of dong quai, which

might assist in decision making on herbal therapy use by women at risk

for both estrogen-sensitive and insensitive breast cancer. Because of

the lack of clinical data demonstrating the potential side effects of dong

quai, its use in herbal preparations for the treatment of peri- or

postmenopausal symptoms, especially in women with breast cancer,

warrants caution pending further study. PMID: 16278617 [PubMed - as

supplied by publisher]

 

Clin Cancer Res. 2005 Nov 1;11(21):7800-6. Effect of Milk Thistle

(Silybum marianum) on the Pharmacokinetics of Irinotecan. van Erp

NP, Baker SD, Zhao M, Rudek MA, Guchelaar HJ, Nortier JW,

Sparreboom A, Gelderblom H. Authors' Affiliations: Departments of

Clinical Pharmacy and Toxicology and Clinical Oncology, Leiden

University Medical Center, Leiden, the Netherlands. PURPOSE: Milk

thistle (Silybum marianum) is one of the most commonly used herbal

therapies, and its principal constituent silybin significantly inhibits

cytochrome P450 isoform 3A4 (CYP3A4) and UDP

glucuronosyltransferase isoform 1A1 (UGT1A1) in vitro. Here, we

investigated whether milk thistle affects the pharmacokinetics of

irinotecan, a substrate for CYP3A4 and UGT1A1, in

humans.EXPERIMENTAL DESIGN: Six cancer patients were treated

with irinotecan (dose, 125 mg/m(2)) given as a 90-minute infusion once

every week. Four days before the second dose, patients received 200

mg milk thistle, thrice a day, for 14 consecutive days. Pharmacokinetic

studies of irinotecan and its metabolites 7-ethyl-10-hydroxycamptothecin

(SN-38), 7-ethyl-10-[3,4,5-trihydroxy-pyran-2-carboxylic acid]-

camptothecin (SN-38-glucuronide), and 7-ethyl-10-[4-N-(5-

aminopentanoic acid)-1-piperidino]-carbonyloxycamptothecin were done

during the first three irinotecan administrations.RESULTS: Short-term (4

days) or more prolonged intake of milk thistle (12 days) had no

significant effect on irinotecan clearance (mean, 31.2 versus 25.4

versus 25.6 L/h; P = 0.16). The area under the curve ratio of SN-38 and

irinotecan was slightly decreased by milk thistle (2.58% versus 2.23%

versus 2.17%; P = 0.047), whereas the relative extent of glucuronidation

of SN-38 was similar (10.8 versus 13.5 versus 13.1; P = 0.64). Likewise,

the area under the curve ratio of 7-ethyl-10-[4-N-(5-aminopentanoic

acid)-1-piperidino]-carbonyloxycamptothecin and irinotecan was

unaffected by milk thistle (0.332 versus 0.285 versus 0.337; P = 0.53).

The maximum plasma concentrations of silybin ranged between 0.0249

and 0.257 mumol/L.CONCLUSIONS: Silybin concentrations after intake

of milk thistle are too low to significantly affect the function of CYP3A4

and UGT1A1 in vivo, indicating that milk thistle is unlikely to alter the

disposition of anticancer drugs metabolized by these enzymes. PMID:

16278402 [PubMed - in process]

 

Autoimmunity. 2005 Sep;38(6):453-61. Dietary consumption of

Echinacea by mice afflicted with autoimmune (type I) diabetes: Effect of

consuming the herb on hemopoietic and immune cell dynamics.

Delorme D, Miller SC. McGill University, Department of Anatomy and

Cell Biology, Montreal, QC, Canada. Epidemiological studies indicate

that the incidence of Type 1 diabetes, an autoimmune disease, is rising

rapidly. However, none of the current therapies produces life long

remission, or can prevent the disease onset. The NOD (non-obese

diabetic) mouse is currently regarded as an excellent animal model of

human Type 1 diabetes. NKT cells are known to be fundamental in

modulating the disease, yet they are numerically and functionally

deficient in mammals bearing this disease. Indeed, the role of NK cells

in inhibiting autoimmunity in general is well established.

Immunoregulatory strategies are currently believed to be the way of the

future with respect to modulating autoimmune diseases. Based on this

hypothesis, and the fact that the herb, Echinacea, is a well

demonstrated immunostimulant of NK cells in normal mice/humans, we

aimed to investigate, in NOD mice, the effect of short term (days) and

long term (months) daily dietary administration of Echinacea, on the

absolute levels of NK cells, and five other classes of hemopoietic and

immune cells, in the bone marrow and spleen. The results revealed that,

in NOD mice, dietary Echinacea, resulted in a significant increase in the

absolute numbers of NK cells, irrespective of feeding duration, in the

spleen, and moreover, it actually stimulated NK cell production in their

bone marrow birth site. We further found that there were transient, early

(days), herb exposure-time-dependent, quantitative changes in several

of the other hemopoietic and immune cells populations in both the bone

marrow and spleen. We conclude that consumption of this herb by NOD

mice, at least, has lead to no negative repercussions with respect to the

hemopoietic and immune lineages, and secondly, the consistent, long-

lasting immunostimulation only of NK cells, may lead to a possible new

approach to the treatment of Type 1 diabetes. PMID: 16278152

[PubMed - in process]

 

In Vivo. 2005 Nov-Dec;19(6):1029-33. Effects of colestimide and/or

Bofu-tsusho-san (Fangfeng Tongsheng San) on plasma and liver lipids

in mice fed a high-fat diet. Sakamoto S, Takeshita S, Sassa S, Suzuki

S, Ishikawa Y, Kudo H. Medical Research Institute, Tokyo Medical and

Dental University, Tokyo, Japan. motoend

Hypercholesterolemia is known to enhance the risk of coronary heart

disease and fatty liver. Colestimide is an anion-exchange resin, which is

not absorbed in the small intestine, decreases the intestinal

reabsorption of bile acids synthesized from cholesterol in the liver and

consequently increases bile acid excretion into the feces. Fangfeng

Tongsheng San contains 18 components and has long been used as an

anti-obesity agent. In the present study, we investigated the effects of

colestimide and/or Fangfeng Tongsheng San in young male mice fed a

high-fat diet. The high-fat diet supplemented with both colestimide and

Fangfeng Tongsheng San markedly reduced the plasma levels of lipids,

the liver weight and number of fatty droplets in the liver cytoplasm, and

the body growth, compared with animals fed a high-fat diet alone.

Neither medicine affected the blood biochemistry. Thus, the

hypocholesterolemic action of colestimide, sometimes bringing light

flatulence, which is improved by simultaneous administration of

Fangfeng Tongsheng San, which activates the thermogenesis of brown

adipose tissue, is suggested to reduce body mass and liver lipids,

lowering the plasma levels of lipids. PMID: 16277017 [PubMed - in

process]

 

Mol Cancer Ther. 2005 Nov;4(11):1747-54. Caspase-dependent

apoptosis induction by guggulsterone, a constituent of Ayurvedic

medicinal plant Commiphora mukul, in PC-3 human prostate cancer

cells is mediated by Bax and Bak. Singh SV, Zeng Y, Xiao D, Vogel

VG, Nelson JB, Dhir R, Tripathi YB. Department of Pharmacology,

University of Pittsburgh, 2.32A Hillman Cancer Center Research

Pavilion, 5117 Centre Avenue, Pittsburgh, PA 15213.

singhs. The present study was undertaken to gain insights

into the molecular mechanism of cell death (apoptosis) by

guggulsterone, a constituent of Ayurvedic medicinal plant Commiphora

mukul, using PC-3 human prostate cancer cells as a model. The viability

of PC-3 cells, but not a normal prostate epithelial cell line (PrEC), was

reduced significantly on treatment with guggulsterone in a

concentration-dependent manner. Guggulsterone-mediated suppression

of PC-3 cell proliferation was not due to perturbation in cell cycle

progression but caused by apoptosis induction characterized by

appearance of subdiploid cells and cytoplasmic histone-associated DNA

fragmentation. Guggulsterone-induced apoptosis was associated with

induction of multidomain proapoptotic Bcl-2 family members Bax and

Bak. Interestingly, the expression of antiapoptotic proteins Bcl-2 and

Bcl-xL was initially increased in guggulsterone-treated PC-3 cells but

declined markedly following a 16- to 24-hour treatment with

guggulsterone. Ectopic expression of Bcl-2 in PC-3 cells failed to confer

significant protection against guggulsterone-induced cell death. On the

other hand, SV40 immortalized mouse embryonic fibroblasts derived

from Bax-Bak double knockout mice were significantly more resistant to

guggulsterone-induced cell killing compared with wild-type cells.

Guggulsterone treatment resulted in cleavage (activation) of caspase-9,

caspase-8, and caspase-3, and guggulsterone-induced cell death was

significantly attenuated in the presence of general caspase inhibitor as

well as specific inhibitors of caspase-9 and caspase-8. In conclusion,

the present study indicates that caspase-dependent apoptosis by

guggulsterone is mediated in part by Bax and Bak. PMID: 16275996

[PubMed - in process]

 

Biomed Pharmacother. 2005 Oct;59 Suppl 1:S132-40. An attempt to

integrate Western and Chinese medicine: rationale for applying Chinese

medicine as chronotherapy against cancer. Seki K, Chisaka M, Eriguchi

M, Yanagie H, Hisa T, Osada I, Sairenji T, Otsuka K, Halberg F.

Shinyamanote Hospital, 3-6-1 Suwacho Higashimurayama-city, Tokyo

189-0021, Japan. Current Western medical treatment lays its main

emphasis on evidence-based medicine (EBM) and cure is assessed by

quantifying the effects of treatment statistically. In contrast, in Chinese

medicine, cure is generally assessed by evaluating the patient's

" pattern " (Zheng) [cf. Glossary] and medicines are prescribed according

to this. We believe that traditional Chinese medicine (TCM) cannot be

evaluated precisely according to Western principles, in which a constant

amount of the same medicine is given to a group of patients to be

evaluated. When assessing cure using TCM, Zheng is more important

than the determination of medical effects. This means that quantitative

evaluation of TCM treatment can be very difficult. In this paper, we

focused on the Yin-Yang [cf. Glossary]balance to determine Zheng, and

at the same time attempted to determine the treatment effects by

applying the concept of regulation of Yin-Yang according to

chronotherapeutic principles. According to Zheng, advanced cancer

patients generally lack both Yin and Yang. Chinese medical treatment

therefore seeks to supplement both Yin and Yang. However, we divided

patients into two groups and compared them with respect to survival.

One group was administered a predominantly Yang (Qi) [cf. Glossary]

tonic herbal treatment during the daytime, while the other group was

administered Yin (Blood) [cf. Glossary] tonics during night time. A

comparison of the results of treatment showed that the patients in the

group receiving Yang (Qi) replenishment during the daytime lived longer

than patients receiving Yin (Blood) nourishment during the night.

Moreover, the patients in the daytime Yang (Qi) replenishment group

also fared significantly better than patients treated solely by Western

methods. PMID: 16275482 [PubMed - in process]

 

Int J Mol Med. 2005 Dec;16(6):1157-62. Antiproliferative and apoptosis-

inducing activity of Brucea javanica extract on human carcinoma cells.

Lau FY, Chui CH, Gambari R, Kok SH, Kan KL, Cheng GY, Wong RS,

Teo IT, Cheng CH, Wan TS, Chan AS, Tang JC. State Key Laboratory

of and Molecular Pharmacology, Department of

Applied Biology and Chemical Technology, Hong Kong Polytechnic

University, Hong Kong, P.R. China. We have recently demonstrated the

antiproliferative and apoptotic activities of herbal traditional Chinese

medicines, including the analomous fruit extract of Gleditsia sinensis,

the fresh juice of Scutellaria barbata and the warmed water extract of

Radix Sophorae Tonkinensis on a series of human carcinoma cells.

Here, we further report the potential anti-cancer activity of the warmed

water extract of Brucea javanica (BJE). Four cancer cell lines, including

A549 non-small cell lung cancer, Hep3B hepatocellular carcinoma,

MDA-MB231 breast cancer and SLMT-1 oesophageal squamous cell

carcinoma, were incubated with BJE and strong apoptotic induction was

observed under inverted microscopic investigation for all of the four cell

lines tested. Using the MDA-MB231 breast cancer cell line as an

experimental model, additional analyses supported the hypothesis that

the mitochondrial membrane potential depolarization pathway was

induced by BJE. The APO-1/Fas receptor death induction pathway was

not activated under the influence of BJE, as studied by staining with Fas

ligand and Fas receptor specific antibodies. Accordingly, only weak

activation of caspase 8 was observed upon BJE treatment. On the other

hand, caspase 3 activity was stimulated up to five-fold in BJE-treated

cells compared to untreated controls. Oligonucleosomal DNA

fragmentation formation was detected by labelling the nucleic acid

ladders with TdT-mediated dUTP nick end labelling. Collectively, BJE-

induced cancer cell death proceeds through a mitochondrial dependent

pathway associated with caspase 3 activation. PMID: 16273300

[PubMed - in process]

 

Int J Mol Med. 2005 Dec;16(6):1109-16. Immune modulatory effects of

Prunella vulgaris L. on monocytes/macrophages. Fang X, Yu MM, Yuen

WH, Zee SY, Chang RC. Laboratory of Neurodegenerative Diseases,

Department of Anatomy, The University of Hong Kong, Pokfulam, Hong

Kong, SAR. Prunella vulgaris L. (Labiatae), a popular Western and

Chinese herbal medicine, has long been associated with anti-viral and

anti-bacterial effects. While its anti-viral effects are attributed mainly to

the inhibition of virus replication, the biological mechanisms of its anti-

bacterial effects remain unknown. As a biological response modifier

(BRM), the polysaccharides isolated from P. vulgaris have been shown

to up-regulate the immune responses of monocytes/macrophages.

However, the immune stimulatory effects seem to contradict its well-

known anti-inflammatory properties. We hypothesized that the anti-

microbial effects exhibited by the polysaccharides isolated from P.

vulgaris encompass both anti-inflammatory and immune stimulatory

effects. One of the polysaccharide fractions PV2IV markedly stimulated

the production of superoxide and nitrite representing nitric oxide from

murine macrophage RAW264.7 and brain macrophage BV2 cells. The

amount of nitrite and superoxide produced after PV2IV stimulation was

as high as that stimulated by bacterial endotoxin lipopolysaccharide

(LPS) in a dose-dependent manner. In addition, PV2IV also increased

cellular protein levels of inducible nitric oxide synthase (iNOS) and

mRNA for tumor necrosis factor-alpha (TNFalpha). Similar to the effects

of a high dose of LPS, the fraction PV2 could trigger activation-induced

cell death (AICD) by stimulating caspase-3 activity and reduction of MTT

uptake in monocytes/macrophages. These results may help our

understanding of the molecular mechanism of P. vulgaris, which

exhibited both immune stimulatory and anti-inflammatory effects against

microbial invasion. PMID: 16273294 [PubMed - in process]

 

Oncol Rep. 2005 Dec;14(6):1599-603. Artesunate in the treatment of

metastatic uveal melanoma - first experiences. Berger TG, Dieckmann

D, Efferth T, Schultz ES, Funk JO, Baur A, Schuler G. Dermatologische

Klinik mit Poliklinik, Hartmannstr. 14, D-91052 Erlangen, Germany.

thomas.berger. Artesunate (ART) is a

derivative of artemisinin, the active principle of the Chinese herb

Artemisia annua L. Artesunate is approved for the treatment of

multidrug-resistant malaria and has an excellent safety profile. It has

been shown that Artesunate, apart from its anti-malarial activity, has

cytotoxic effects on a number of human cancer cell lines, including

leukemia, colon cancer and melanoma. We report on the first long-term

treatment of two cancer patients with ART in combination with standard

chemotherapy. These patients with metastatic uveal melanoma were

treated on a compassionate-use basis, after standard chemotherapy

alone was ineffective in stopping tumor growth. The therapy-regimen

was well tolerated with no additional side effects other than those

caused by standard chemotherapy alone. One patient experienced a

temporary response after the addition of ART to Fotemustine while the

disease was progressing under therapy with Fotemustine alone. The

second patient first experienced a stabilization of the disease after the

addition of ART to Dacarbazine, followed by objective regressions of

splenic and lung metastases. This patient is still alive 47 months after

first diagnosis of stage IV uveal melanoma, a situation with a median

survival of 2-5 months. Despite the small number of treated patients,

ART might be a promising adjuvant drug for the treatment of melanoma

and possibly other tumors in combination with standard chemotherapy.

Its good tolerability and lack of serious side effects will facilitate

prospective randomized trials in the near future. PMID: 16273263

[PubMed - in process]

 

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