Recent Medline Herbal Hits

August 22, 2006

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Asano T, Fujii Y, Numao N, Kageyama Y, Kihara K. The efficiency of

Sairei-to for retroperitoneal fibrosis: two case reports. Hinyokika Kiyo.

2006 Jul;52(7):543-7. Department of Urology, Graduate School, Tokyo

Medical and Dental University. The conventional approach for

management of retroperitoneal fibrosis (RF), an inflammatory process

of retroperitoneal fibro-adipose tissue, leading to the compression and

obstruction of the ureters and other adjacent organs is ureterolysis with

omental wrapping, and an effective alternative to surgery is

immunosupressive medication such as oral corticosteroids. Sairei-to

(TJ-114; Chai-Ling-Tang) is a traditional herbal medicine used to Tx RF

in Japan. It has both anti-inflammatory and anti-allergic effects. Here we

report two cases of RF successfully treated with Sairei-to. One case

was idiopathic and the other was caused by artificial graft-induced

vasculitis. Both cases were treated with Sairei-to following the

decompression of uremia by precutaneous nephrostomy or indwelling

ureteral stents. There was hardly any ureteral obstruction three months

after the administration of Sairei-to. They have been doing well for 12

and 26 months. Sairei-to rarely causes side effects such as

immunodeficiency, gastro-duodenal ulcer and osteoporosis that often

accompany long-term administration of corticosteroids. Sairei-to is a

safe and effective medicine for the treatment of RF. We therefore

recommend Sairei-to as an alternative for corticosteroid therapy. PMID:

16910587 [PubMed - in process]

Suo YP, Wang BY, Hong Z, Yin RT, Wang DQ, Peng ZL. [Comparative

study of that synergistic effect of cisplatin combined with compound

herbal medicinal prescription for tonic quality and activating blood

circulation is on SKOV3 cell proliferation and apoptosis][Article in

Chinese] Sichuan Da Xue Xue Bao Yi Xue Ban. 2006 Jul;37(4):542-6.

Department of Gynecology and Obstetrics, West China Second

Hospital, Sichuan University, Chengdu 610041, China. OBJECTIVE: To

investigate the synergistic effects on cell apoptosis and growing

restriction of SKOV3 cells by the combination of compound herbal

medicinal prescription (CHMP) with cisplatin (DDP). METHODS:

Cisplatin and two CHMP for tonic quality(CHMP1) and activating blood

circulation (CHMP2), which was medicated serum, were prepared and

used to treat the human ovarian carcinoma cell line SKOV3. By serum

pharmacologic method, the growth and apoptosis of SKOV3 cell were

observed at different time points(24,48,72, 96 h) with different

concentrations of medicated serum. Coefficient of drug interaction (CDI)

between CHMP, and CHMP2 was studied by MTT method. The effects

of control group(A group),CHMP1 group(B group),CHMP2 group (C

group), DDP group(D group), CHMP1 + DDP group(E group), CHMP2 +

DDP group(Fgroup)to SKOV3 cell were studied by flow cytometry; and

the cell apoptosis was observed by agarose electrophoresis; the

expressions of TNFR1, caspase-8 on each group were analyzed by

Western blot method. RESULTS: Synergistic effects were found

between herbal medicinal mixtures and DDP, Restraining rate of

SKOV3 and CHMP serum concentration was not in a dose-dependent

manner as DDP was. CDI between CHMPI and CHMPS was found to

be significant difference (CDI of CHMP1, CHMP2 and DDPwas 0.66,

0.58 respectively). It showed that the combined treatment was able to

get better effect than single drug treatment. The performed agarose

electrophoresis revealed the extracted DNA to show a typical ladder

patterns for cell apoptosis. The analysis results of western blot showed

the increased expressions of TNFR1 and caspase-8 after combined

using of medicine, which were accord to the rates of apoptosis.

CONCLUSIONS: CHMP drug granules show the synergistic effects with

DDP, and the suppressing functions in the course of cell proliferation,

and the inducing effect on apoptosis of human ovarian carcinoma cell

line SKOV3 in vitro. And this mechanism is showed to be sponsored by

the activation of TNFR1 and Caspase-8. PMID: 16909597 [PubMed - in

process]

Mensah AY, Houghton PJ, Dickson RA, Fleischer TC, Heinrich M,

Bremner P. In Vitro evaluation of effects of two ghanaian plants

relevant to wound healing. Phytother Res. 2006 Aug 14; [Epub ahead of

print] Department of Pharmacognosy, Faculty of Pharmacy, Kwame

Nkrumah University of Science and Technology (KNUST), Kumasi,

Ghana. Commelina diffusa and Spathodea campanulata are used as

wound-healing agents in Ashanti traditional medicine in Ghana. The

methanol extracts of Commelina diffusa herb and Spathodea

campanulata bark showed some level of antimicrobial activity with C.

diffusa exhibiting selective antifungal activity against Trichophyton

species. The extracts reduced the peroxidation of bovine brain extract

with an IC(50) value of 1.39 mg/mL and 0.24 mg/mL, respectively. In

addition the extracts also exhibited significant antioxidant activity by

protecting MRC-5 cells from hydrogen peroxide induced oxidant injury

at concentrations between 1 microg/mL and 10 microg/mL. The

extracts showed no inhibition of NF-kappaB at 100 microg/mL. The

antioxidant activities and antimicrobial activities suggest that the use of

the plants in wound healing may be based on antioxidant and antiseptic

PMID: 16909445 [PubMed - as supplied by publisher]

Jacobo-Herrera NJ, Vartiainen N, Bremner P, Gibbons S, Koistinaho J,

Heinrich M. F-kappaB modulators from Valeriana officinalis. Phytother

Res. 2006 Aug 14; [Epub ahead of print] Centre for Pharmacognosy

and Phytotherapy, The School of Pharmacy, University of London, UK.

Valeriana officinalis (Valerianaceae) has been of great interest for its

therapeutic uses for treating mild nervous tension and temporary

sleeping problems. In traditional European medicine it has been also

reported as an antiinflammatory remedy. This study reports that the

EtOAc extract of the underground parts of V. officinalis showed

inhibitory activity against NF-kappaB at 100 microg/mL in the IL-6/Luc

assay on HeLa cells and provided protection against excitotoxicity in

primary brain cell cultures at micromolar concentrations. Bioassay-

guided fractionation of the EtOAc extract led to the isolation of three

known sesquiterpenes: acetylvalerenolic acid (1), valerenal (2) and

valerenic acid (3), 1 and 3 were active as inhibitors of NF-kappaB at a

concentration of 100 microg/mL. Acetylvalerenolic acid (1) reduced NF-

kappaB activity to 4%, whereas valerenic acid (3) reduced NF-kappaB

16909443 [PubMed - as supplied by publisher]

Basu S, Hazra B. Evaluation of nitric oxide scavenging activity, In Vitro

and Ex Vivo, of selected medicinal plants traditionally used in

inflammatory diseases. Phytother Res. 2006 Aug 14; [Epub ahead of

print] Department of Pharmaceutical Technology, Jadavpur University,

Calcutta 700032, India. Steroidal and non-steroidal antiinflammatory

drugs, despite their various side effects, are in great demand worldwide.

Alternatively, herbal formulations provide relief to a large percentage of

the population suffering from inflammatory diseases. Therefore, such

practices need to be rationalized through a mechanistic approach.

Thus, four traditional medicinal plants, namely Ventilago madraspatana

Gaertn., Rubia cordifolia Linn., Lantana camara Linn. and Morinda

citrifolia Linn. were selected for a study on the inhibition of nitric oxide

(NO(*)), a key mediator in the phenomenon of inflammation, signifying

the presence of effective antiinflammatory constituents therein. Plant

samples were extracted with different solvents for evaluation of their

inhibitory activity on NO(*) produced in vitro from sodium nitroprusside,

and in LPS-activated murine peritoneal macrophages, ex vivo. Further,

the inhibition of NO(*) synthesis was correlated with the reduction of

iNOS protein expression through Western blot. Notable NO(*)

scavenging activity was exhibited in vitro by some extracts of V.

madraspatana, R. cordifolia and L. camara (IC(50) < 0.2 mg/mL). Most

of them showed marked inhibition (60%-80%), ex vivo, at a dose of 80

microg/mL without appreciable cytotoxic effect on the cultured

macrophages. Immunoblot analysis confirmed that the modulatory

effect of the samples had occurred through suppression of iNOS

[PubMed - as supplied by publisher]

Kumar V. Potential medicinal plants for CNS disorders: an overview.

Phytother Res. 2006 Aug 14; [Epub ahead of print] Department of

Pharmaceutical Sciences, Texas Tech University, Health Sciences

Center, School of Pharmacy, Amarillo, TX 79106, USA. Although very

few drugs are currently approved by regulatory authorities for treating

multi-factorial ailments and disorders of cognition such as Alzheimer's

disease, certain plant-derived agents, including, for example,

galantamine and rivastigmine (a semi-synthetic derivative of

physostigmine) are finding an application in modern medicine. However,

in Ayurveda, the Indian traditional system of medicine which is more

than 5000 years old, selected plants have long been classified as

'medhya rasayanas', from the Sanskrit words 'medhya', meaning

intellect or cognition, and 'rasayana', meaning 'rejuvenation'. These

plants are used both in herbal and conventional medicine and offer

benefits that pharmaceutical drugs lack. In the present article, an

attempt has been made to review the most important medicinal plants,

including Ginkgo biloba, St John's wort, Kava-kava, Valerian, Bacopa

monniera and Convolvulus pluricaulis, which are widely used for their

& Sons, Ltd. PMID: 16909441 [PubMed - as supplied by publisher]

Du S, Deng Y. Studies on the Encapsulation of Oxymatrine into

Liposomes by Ethanol Injection and pH Gradient Method. Drug Dev Ind

Pharm. 2006 Aug;32(7):791-7. Department of Pharmaceutical

Sciences, Shenyang Pharmaceutical University, Shenyang, Liaoning

Province, China. Oxymatrine is the major active alkaloid constituent

extracted from TCM herbs Sophora flavescens Ait (Kushen) and

Sophora alopecuroides (Kudouzi). In recent years, oxymatrine had been

found to posses remarkable hepatoprotective activity and has been

used for treating hepatitis B in clinical therapy in China. In this study, we

attempted to entrap oxymatrine into liposomes to facilitate the delivery

of oxymatrine to the liver and enhance the therapeutic efficiency for

hepatitis. Preformulation investigation was performed to obtain the drug

physicochemical properties such as solubility, pKa, and logP for rational

liposomes preparation design. Liposomes were prepared with soybean

lecithin by ethanol injection and pH gradient loading methods. At the

same time the factors affecting the entrapment efficiencies were

investigated and compared. Ethanol injection method yielded liposomes

with entrapment efficiency less than 20%. The lipid composition and

aqueous medium had some effects on entrapment efficiency. However,

liposomes could be produced with entrapment efficiency above 50% by

pH gradient method. The internal pH buffer capacity, the lipid

composition, and drug-to-lipid ratio greatly influenced the entrapment

efficiency, while the incubation temperature had almost no effect on

entrapment efficiency in the active loading procedure. PMID: 16908416

[PubMed - in process]

Expert Opin Drug Saf. 2006 Sep;5(5):719-28. Links

An evidence-based systematic review of herb and supplement

interactions by the Natural Standard Research Collaboration.Ulbricht C,

Basch E, Weissner W, Hackman D.

Natural Standard Research Collaboration, 1 Broadway, 14th Floor

Mailroom, Cambridge, MA 02142, USA.

questions

Reported utilisation of prescription drug use concurrently with herbal or

vitamin products have increased, placing an estimated 15 million

patients at risk of potential drug-supplement interactions. This

systematic review aims to consolidate relevant herb and supplement

interactions data available for some of the more common classes of

interactions experienced by clinicians. These classes include:

hypoglycaemic/hyperglycaemics; hypotensive/hypertensives, diuretics,

sedatives, cardiac glycosides, monoamine oxidase inhibitors, selective

serotonin reuptake inhibitors, laxatives, immunomodulators, agents that

may increase the risk of bleeding or clotting, agents that may be

hepatotoxic, agents that may have hormonal properties, and agents

with cytochrome P450 enzyme activity. The format is designed to

promote use as a decision support tool for healthcare providers. PMID:

16907661 [PubMed - in process]

Kang SC, Lee CM, Choi H, Lee JH, Oh JS, Kwak JH, Zee OP.

Evaluation of oriental medicinal herbs for estrogenic and

antiproliferative activities. Phytother Res. 2006 Aug 14; [Epub ahead of

print] College of Pharmacy, SungKyunKwan University, Suwon,

Gyonggi-Do, South Korea. Herb extracts commercially used in Asia

were screened for their estrogenic activity with a recombinant yeast

system with both a human estrogen receptor (ER) expression plasmid

and a reporter plasmid. Pueraria lobata (flower) had the highest

estrogenic relative potency (RP, 17-estradiol = 1.00) (7.8e-3) (RP for +

control), followed by Amomum xanthioides (1.3e-3), Glycyrrhiza

uralensis, Zingiber officinale, Rheum palmatum, Curcuma aromatica,

Eriobotrya japonica, Sophora flavescens, Anemarrhena asphodeloides,

Polygonum multiflorum and Pueraria lobata (root) (9.5e-4-1.0e-4), and

Prunus persica, Lycoppus lucidus and Adenophora stricta (9.0e-5-8.0e-

5). In the antiproliferative assay, five human cancer cell lines

representing different tissues (breast, lung and ovary) were used.

Eriobotrya japonica showed strong cytotoxicity in ER-negative breast

cancer (MDA-MB-231), cervix epitheloid (HeLa) and lung (A549)

16906642 [PubMed - as supplied by publisher]

Kiselova Y, Ivanova D, Chervenkov T, Gerova D, Galunska B, Yankova

T. Correlation between the In Vitro antioxidant activity and polyphenol

content of aqueous extracts from bulgarian herbs. Phytother Res. 2006

Aug 14; [Epub ahead of print] Department of Preclinical, Clinical

Pharmacology and Biochemistry, Varna University of Medicine, 9002

Varna, Bulgaria. The water phase antioxidant activity of extracts from

23 Bulgarian medicinal plants was studied in relation to their polyphenol

content in comparison with mate, black tea, honeybush and rooibos

foreign species. Antioxidant activity was measured by the ABTS (2,2'-

azinobis(3-ethylbenzothiazoline-6-sulfonic acid)) cation radical

decolorization assay, and the total polyphenol content was assayed

according to the Folin-Ciocalteu method. Five Bulgarian plant extracts

exhibited higher antioxidant activity than that of mate, which is 21.7% of

all Bulgarian herbs included in this study. These were Alchemilla

vulgaris L. (4.79 +/- 0.14 mm), Sambucus ebulus L. (4.03 +/- 0.07 mm),

Mentha spicata L. (3.90 +/- 0.03 mm), Fragaria vesca L. (3.74 +/- 0.06

mm), Crataegus monogyna Jacq. (3.63 +/- 0.05 mm). Another eight

Bulgarian medicinal plant extracts exhibited an intermediate antioxidant

activity - lower than that of mate and higher than that of honeybush,

which makes 34.8% of all Bulgarian herbs included in the study. More

than half of the herbal extracts included in the present study exhibited

antioxidant activity higher than or comparable to the reference foreign

plants. A positive correlation (r = 0.92) between antioxidant activity and

polyphenol content was found, suggesting that the antioxidant capacity

of the aqueous plant extracts is due to a great extent to their

16906640 [PubMed - as supplied by publisher]

Gramowski A, Jugelt K, Stuwe S, Schulze R, McGregor GP,

Wartenberg-Demand A, Loock J, Schroder O, Weiss DG. Functional

screening of traditional antidepressants with primary cortical neuronal

networks grown on multielectrode neurochips. Eur J Neurosci. 2006

Jul;24(2):455-65. Division of Cell Biology and Biosystems Technology,

Institute of Biological Sciences, University of Rostock, Albert-Einstein-

Strasse, 318059 Rostock, Germany. alexandra.gramowski@uni-

rostock.de We optimized the novel technique of multielectrode

neurochip recordings for the rapid and efficient screening of

neuroactivity. Changes in the spontaneous activity of cultured networks

of primary cortical neurons were quantified to evaluate the action of

drugs on the firing dynamics of complex network activity. The

multiparametric assessment of electrical activity changes caused by

psychoactive herbal extracts from Hypericum, Passiflora and Valeriana,

and various combinations thereof revealed a receptor-specific and

concentration-dependent inhibition of the firing patterns. The spike and

burst rates showed significant substance-dependent effects and

significant differences in potency. The effects of specific receptor

blockades on the inhibitory responses provided evidence that the herbal

extracts act on gamma-amino butyric acid (GABA) and serotonin (5-HT)

receptors, which are recognized targets of pharmacological

antidepressant treatment. A biphasic effect, serotonergic stimulation of

activity at low concentrations that is overridden by GABAergic inhibition

at higher concentrations, is apparent with Hypericum alone and the

triple combination of the extracts. The more potent neuroactivity of the

triple combination compared to Hypericum alone and the additive effect

of Passiflora and Valeriana suggest a synergy between constituent

herbal extracts. The extracts and their combinations affected the set of

derived activity parameters in a concomitant manner suggesting that all

three constituent extracts and their combinations have largely similar

modes of action. This study also demonstrates the sensitivity, selectivity

and robustness of neurochip recordings for high content screening of

complex mixtures of neuroactive substances and for providing

multiparametric information on neuronal activity changes to assess the

therapeutic potential of psychoactive substances. PMID: 16903853

[PubMed - in process]

Chen KZ, Shi JL, Lu MZ, He ZG, Qin RA. [Effects of acupoint thread

implantation and Chinese herb on PTH and TGF-beta1 in the rate of

chronic renal failure][Article in Chinese] Zhongguo Zhen Jiu. 2006

Jul;26(7):511-4. Guiyang City Maternity and Infant Health Institute,

Guizhou 550003, China. ckz025 OBJECTIVE: To probe into

the mechanisms of thread implantation at Zusanli(ST 36) and Chinese

herbs in treatment of chronic renal failure(CRF). METHODS: CRF rat

model was made by Platt subtotal nephrectomy. They were divided into

5 groups, sham operation group, model group, Chinese herbs group,

thread implantation group and thread implantation plus Chinese herbs

group. After treatment of 8 weeks, serum parathyroid hormone (PHT),

transforming growth factor beta1 (TGF-beta1) expression in residual

renal cells, malondialdehyde(MDA) content in the residual renal tissue,

serum urea nitrogen(BUN) and creatinine(Scr), protein in urine and

pathological changes were investigated. RESULTS: The above indexes

after treatment by thread implantation at acupoint, Chinese herbs, and

acupoint thread implantation plus Chinese herbs showed begin

reversion, especially, the most obviously improvement in the acupoint

thread implantation plus Chinese herbs treatment group.

CONCLUSION: The mechanism of acupoint thread implantation and

Chinese herbs in improvement of CRF is related with decrease of PTH,

inhibition of TGF-beta1 expression, decrease of MDA content and

resisting lesion of renal fibrosis. PMID: 16903606 [PubMed - in process]

Gao QT, Cheung JK, Li J, Chu GK, Duan R, Cheung AW, Zhao KJ,

Dong TT, Tsim KW. A Chinese Herbal Decoction, Danggui Buxue

Tang, Prepared from Radix Astragali and Radix Angelicae Sinensis

Stimulates the Immune Responses. Planta Med. 2006 Aug 10; [Epub

ahead of print] Department of Biology, The Hong Kong University of

Science and Technology, Clear Water Bay Road, Hong Kong.

Danggui Buxue Tang (DBT), a Chinese medicinal decoction that is used

commonly for treating women's ailments, contains Radix Astragali and

Radix Angelicae Sinensis. The ratio of Radix Astragali and Radix

Angelicae Sinensis used in DBT should be 5 : 1 as described in China

in 1247 A.D. In order to verify the efficacy of this ancient formulation in

stimulating the immune responses, DBT prepared from different drug

ratios was applied onto cultured T-lymphocytes and macrophages. In

cultured T-lymphocytes, DBT induced markedly cell proliferation,

secretion of interleukin-2 and phosphorylation of extracellular signal-

regulated kinase. In addition, the phagocytosis of cultured macrophages

was increased by DBT treatment. The immunomodulatory effects of

DBT were revealed to be the strongest in the extract derived from the

drug ratio of 5 : 1. The current results verified that the ancient

formulation of DBT has been optimized in stimulating immune

responses. PMID: 16902872 [PubMed - as supplied by publisher]

Cheng CY, Sue YM, Chen CH, Hou CC, Chan P, Chu YL, Chen TH,

Hsu YH. Tetramethylpyrazine Attenuates Adriamycin-Induced Apoptotic

Injury in Rat Renal Tubular Cells NRK-52E. Planta Med. 2006 Aug 10;

[Epub ahead of print] Department of Internal Medicine, Taipei Medical

University-Wan Fang Hospital, Taipei, Taiwan. Tetramethylpyrazine

(TMP), a compound purified from Rhizoma Ligustici, is a widely used

active ingredient in Chinese herbal medicine to treat cardiovascular

diseases on account of its vasodilatory actions and antiplatelet activity.

Studies have shown that TMP can remove oxygen free radicals and

protect rat kidney from ischemia-reperfusion injury. In addition,

adriamycin-induced nephrosis in rats is commonly used in

pharmacological studies of human chronic renal diseases. Apoptosis of

renal tubular cells has been reported in adriamycin-treated rats. To

examine the therapeutic potential of TMP on chronic progressive renal

diseases, adriamycin-induced injury in rat renal tubular cells NRK-52E

has been used to monitor its protective effect. In TUNEL staining, TMP

showed a dose-dependent protective effect against adriamycin-induced

apoptosis in NRK-52E cells. Pretreatment of the cells with 10 or 100

microM of TMP effectively decreased the reactive oxygen species

(ROS) formation induced by adriamycin, as measured in fluorescent

assays. TMP was found to reduce the adriamycin-stimulated activities

of caspase-3, caspase-8 and caspase-9, inhibit adriamycin-induced

release of cytochrome C, and elevate the expression of Bcl-x (L). TMP

was also able to inhibit the death receptor signaling pathway and

suppress the activation of transcription factor NF-kappaB in adriamycin-

treated NRK-52E cells. Based on the results of this study, we suggest

that TMP can attenuate adriamycin-induced oxidative stress and

apoptotic injury in NRK-52E cells, and that it may have therapeutic

potential for patients with renal diseases. TMP: tetramethylpyrazine

LDH: lactate dehydrogenase ROS: reactive oxygen species DCF: 2',7'-

dichlorofluorescein TNF-alpha: tumor necrosis factor-alpha TUNEL:

terminal deoxynucleotidyl transferase-mediated deoxyuridine

triphosphate nick end-labeling. PMID: 16902863 [PubMed - as supplied

by publisher]

Qi XM, Wu GZ, Wu YG, Lin H, Shen JJ, Lin SY. Renoprotective Effect

of Breviscapine through Suppression of Renal Macrophage Recruitment

in Streptozotocin-Induced Diabetic Rats. Nephron Exp Nephrol. 2006

Aug 10;104(4):e147-e157 [Epub ahead of print] Department of

Nephropathy, The First Affiliated Hospital of AnHui Medical University,

Hefei, PR China. Background/Aims: Experimental and clinical evidence

has consistently demonstrated that renal macrophage infiltration is one

of the most important events for the progression of diabetic

nephropathy. Breviscapine is a flavonoid extracted from the Chinese

herb Erigeron breviscapus. Previously, it was shown that treatment with

breviscapine attenuated renal injury in the diabetic rats. The purpose of

this study is to investigate whether the renoprotective effect of

breviscapine is through suppression of renal macrophage recruitment in

diabetic rats. Methods: Diabetes was induced bystreptozotocin injection,

and breviscapine was administered orally at a dose of 20 mg/kg/day for

8 weeks. Control rats received vehicle or breviscapine with the same

schedule. Results: Breviscapine treatment markedly inhibited both an

increase of albuminuria and glomeruli hypertrophy and tubulointerstitial

injury without modifying mean arterial blood pressure and creatinine

clearance. Levels of malondialdehyde and protein kinase C activities

were markedly higher and antioxidant enzyme activities such as

superoxide dismutase, catalase as well as glutathione peroxidase were

significantly lower in the kidneys of diabetic rats than of the control

group, breviscapine administration markedly remitted these changes.

ED-1-positive cells and expression of intercellular adhesion molecule-1

(ICAM-1) and monocyte chemoattractant protein-1 (MCP-1) in glomeruli

and tubulointerstitium were all markedly elevated but were significantly

reduced by breviscapine. Western blot analysis noted that the

expression of transforming growth factor beta1 protein was increased

1.8-fold in the kidney in diabetic rats, breviscapine treatment could

reduce increased expression of TGF-beta1 protein by 47%. Conclusion:

This study describes a novel mechanism by which breviscapine confers

16902319 [PubMed - as supplied by publisher]

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