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Clinical Validation of

Resveratrol in the form of Polydatin and Polygonum Cuspidatum

(Japanese Knotweed)

Clinical Research Abstracts

Antioxidant activity of extract from Polygonum cuspidatum.

Hsu CY, Chan YP, Chang J.

Department of Life Science, Chang Gung University, Tao-Yuan, Taiwan, China. [email protected]

Numerous diseases are induced by free radicals via lipid peroxidation, protein peroxidation and DNA damage. It has been known that a variety of plant extracts have antioxidant activities to scavenge free radicals. Whether Polygonum cuspidatum Sieb. et Zuce has antioxidant activity is unknown. In this study, dried roots of Polygonum cuspidatum were extracted by ethanol and the extract was lyophilized. Free radical scavenging assays, superoxide radical scavenging assays, lipid peroxidation assays and hydroxyl radical-induced DNA strand scission assays were employed to study antioxidant activities. The results indicate that the IC50 value oí Polygonum cuspidatum extract is 110 microg/ml in free radical scavenging assays, 3.2 microg/ml in superoxide radical scavenging assays, and 8 microg/ml in lipid peroxidation assays, respectively. Furthermore, Polygonum cuspidatum extract has DNA protective effect in hydroxyl radical-induced DNA strand scission assays. The total phenolics and flavonoid content of extract is 641.1 +/- 42.6 mg/g and 62.3 +/- 6.0 mg/g. The results indicate that Polygonum cuspidatum extract clearly has antioxidant effects.

PMID: 17657351 [PubMed - indexed for MEDLINE

Comparative analysis of bioactivities of four Polygonum species.

Huang WY, Cai YZ, Xing J, Corke H, Sun M.

School of Biological Sciences, the University of Hong Kong, Pokfulam Road, Hong Kong, PR China.

Many species of Polygonum are rich in bioactive constituents, which contribute to a wide range of medicinal properties. In this study, we assessed the scavenging activity against ABTS.+ and hydroxyl radicals, chelating activity against Fe2+, xanthine oxidase inhibition, antimicrobial activity, and total contents of phenolics and flavonoids in the extracts of leaves and stems or whole plants from four medicinal Polygonum species. Total antioxidant capacities and phenolic contents of Polygonum capitatum, Polygonum Chinensis, Polygonum cuspidatum, and Polygonum multiflorum were 74.60, 53.66, 56.22, and 14.34 mmol trolox/100 g dry weight (DW), and 8.69, 4.15, 6.33, and 1.27 g gallic acid/100 g DW, respectively, significantly higher than those of five dietary vegetables, fruits and spices (spring onion, broccoli, orange, carrot, and ginger). Major bioactive constituents in the tested plant extracts were also investigated using LC-MS. They were mainly phenolic compounds, e. g., flavonoids, phenolic acids and their derivatives, tannins, stilbenes, and anthraquinones. This study shows that, in addition to their roots, the leaves and stems of P. cuspidatum and P. capitatum also exhibit potent antioxidant properties and are a potential resource of natural bioactive antioxidants.

PMID: 18067063 [PubMed - indexed for MEDLINE]

Suppression of 7,12-dimethylbenz(a)anthracene-induced mammary carcinogenesis in rats by resveratrol: role of nuclear factor-kappaB, cyclooxygenase 2, and matrix metalloprotease 9.

Banerjee S, Bueso-Ramos C, Aggarwal BB.

Cytokine Research Laboratory, Department of Bioimmunotherapy, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.

We have reported recently that resveratrol (trans-3,4',5-trihydroxystilbene), a polyphenolic phytoalexin found in grapes, fruits, and root extracts of the weed Polygonum cuspidatum, is a potent inhibitor of nuclear factor (NF)kappaB activation. Because NF-kappaB suppression has been linked with chemoprevention, this prompted us to investigate the chemopreventive potential of resveratrol by testing it against mammary carcinogenesis induced by 7,12-dimethylbenz(a)anthracene (DMBA) in female Sprague Dawley rats. Dietary administration of resveratrol (10 ppm) had no effect on body weight gain and tumor volume but produced striking reductions in the incidence (45%; P < 0.05), multiplicity (55%; P < 0.001), and extended latency period of tumor development relative to DMBA-treated animals. Histopathological analysis of the tumors revealed that DMBA induced ductal carcinomas and focal microinvasion in situ (7 of 7), whereas treatment with resveratrol suppressed DMBA-induced ductal carcinoma. Immunohistochemistry and Western blot analysis revealed that resveratrol suppressed the DMBA-induced cyclooxygenase-2 and matrix metalloprotease-9 expression in the breast tumor. Gel shift analysis showed suppression of DMBA-induced NF-kappaB activation by resveratrol. Treatment of human breast cancer MCF-7 cells with resveratrol also suppressed the NF-kappaB activation and inhibited proliferation at S-G(2)-M phase. Overall, our results suggest that resveratrol suppresses DMBA-induced mammary carcinogenesis, which correlates with downregulation of NF-kappaB, cyclooxygenase-2, and matrix metalloprotease-9 expression.

PMID: 12208745 [PubMed - indexed for MEDLINE]

Drugs Exp Clin Res. 2001;27(5-6):233-48.

Benefits of resveratrol in women's health.

Bagchi D, Das DK, Tosaki A, Bagchi M, Kothari SC.

Department of Pharmacy Sciences, Creighton University School of Pharmacy and Allied Health Professions, 2500 California Plaza, Omaha, NE 68178, USA. [email protected]

Resveratrol and trans-resveratrol are powerful phytoestrogens, present in the skins of grapes and other plant foods and wine, which demonstrate a broad spectrum of pharmacological and therapeutic health benefits. Phytoestrogens are naturally occurring plant-derived nonsteroidal compounds that are functionally and structurally similar to steroidal estrogens, such as estradiol, produced by the body. Various studies, reviewed herein, have demonstrated the health benefits of phytoestrogens in addressing climacteric syndrome including vasomotor symptoms and postmenopausal health risks, as well as their anticarcinogenic, neuroprotective and cardioprotective activities and prostate health and bone formation promoting properties. Conventional HRT drugs have been demonstrated to cause serious adverse effects including stroke and gallbladder disease, as well as endometrial, uterine and breast cancers. Recent research demonstrates that trans-resveratrol binds to human estrogen receptors and increases estrogenic activity in the body. We investigated the effects of protykin, a standardized extract of trans-resveratrol from Polygonum cuspidatum, on cardioprotective function, the incidence of reperfusion-induced arrhythmias and free radical production in isolated ischemic/reperfused rat hearts. The rats were orally treated with two different daily doses of protykin for 3 weeks. Coronary effluents were measured for oxygen free radical production by electron spin resonance (ESR) spectroscopy in treated and drug-free control groups. In rats treated with 50 and 100 mg/kg of protykin, the incidence of reperfusion-induced ventricular fibrillation was reduced from its control value of 83% to 75% (p < 0.05) and 33% (p < 0.05), respectively. Protykin was seen to possess cardioprotective effects against reperfusion-induced arrhythmias through its ability to reduce or remove the reactive oxygen species in ischemic/reperfused myocardium. Taken together, these data suggest that trans-resveratrol supplementation may be a potential alternative to conventional HRT for cardioprotection and osteoporosis prevention and may confer other potential health benefits in women.

PMID: 11951581 [PubMed - indexed for MEDLINE]

Effects of polydatin from Polygonum cuspidatum on lipid profile in hyperlipidemic rabbits.

Xing WW, Wu JZ, Jia M, Du J, Zhang H, Qin LP.

Department of Pharmacognosy, School of Pharmacy, Second Military Medical University, Shanghai 200433, PR China.

Hyperlipidemia is one of the vital coronary risk factors and is positively related to morbidity and mortality of coronary heart disease. There are numerous herbal medicines which are reported to exert good hypolipidemic actions with few side effects. In the present study, the hypolipidemic effects of polydatin, a compound from Polygonum cuspidatum Sieb. et Zucc, on hyperlipidemic rabbits were evaluated. Thirty-two male rabbits were fed a high fat/cholesterol diet for 6 weeks and another eight male rabbits fed a basic diet served as normal control. Three weeks after a high fat/cholesterol diet, the animals were orally administrated polydatin (25, 50, and 100 mg kg(-1) per day) by intubation for 3 weeks. The results showed that polydatin markedly decreased the serum levels of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) in hyperlipidemic rabbits. The ratio of TC to highdensity lipoprotein cholesterol (HDL-C) and the liver coefficient were also reduced. But both polydatin and high fat/cholesterol diet did not evidently affect body weight in hyperlipidemic rabbits. All these results suggest that polydatin from Polygonum cuspidatum has favorable potency to develop a hypolipemic and/or hepatoprotective agent in clinic. However the mechanism of hypolipemic action of polydatin is in need of further clarity.

PMID: 18657948 [PubMed - in process]

Effect of crystal No. 4 of Polygonum cuspidatum on the restoration of pulse pressure and microcirculatory perfusion during shock

[Article in Chinese]

Zhu ZJ.

A model of irreversible hemorrhagic shock was reproduced in rats. Synchronous video tape recording with 2 cameras was used to observe the relationship between the change of blood pressure and that of microcirculation of rat cremaster muscle during shock. It was shown that after antishock treatment the degree of capillary perfusion is closely related with the survival rate and the restoration of pulse pressure is positively correlative with the percentage of open capillaries. The injection of crystal No 4 of Polygonum cuspidatum could restore the pulse pressure to a state above normal level. With the changing of pulse pressure, a pulsatile blood movement occurred in the opening of capillary which impacted and dislodged the plugging or stationary blood cells, leading to reperfusion of capillaries and increase of survival rate.

PMID: 2804740 [PubMed - indexed for MEDLINE]

Effects of trans-resveratrol from Polygonum cuspidatum on bone loss using the ovariectomized rat model.

Liu ZP, Li WX, Yu B, Huang J, Sun J, Huo JS, Liu CX.

Institute of Nutrition and Food Safety, Chinese Center for Disease Control and Prevention, Beijing, People's Republic of China. [email protected]

Trans-Resveratrol (resveratrol) has been shown in several studies to significantly modulate biomarkers of bone metabolism. But, there is no direct evidence supporting its inhibitory effect towards bone loss. In the present study, effects of resveratrol on bone mineral density (BMD) and bone calcium content (BCC) were examined in the ovariectomized (OVX) rat model. Female Wistar rats were divided into four groups: SHAM group (sham-operated), OVX group (OVX control), OVX + ALD group (OVX and treated with 1.0 mg/kg of body weight of alendronate sodium), and OVX + RES group (OVX and treated with 0.7 mg/kg of body weight of resveratrol). Tested materials were given by gavage for 12 weeks after ovariectomy. Results showed that rats in the OVX, OVX + ALD, and OVX + RES groups had significantly higher body weights and feed efficiency than those in the SHAM group (P < .01). The OVX group had significantly lower femoral epiphysis BMD than the SHAM group, and epiphysis BMD in the OVX + ALD and OVX + RES groups was significantly greater than that in the OVX group (P < .05). However, the femoral midpoint BMD was not significantly different among the four groups. Additionally, animals in the OVX group had significantly lower BCC compared with the SHAM group, while the BCC of the OVX + ALD and OVX + RES groups was significantly higher than that of the OVX group (P < .05). These results indicated that resveratrol could increase epiphysis BMD and inhibit the decrease of femur BCC in OVX rats, suggesting that it could play a role in protecting against bone loss induced by estrogen deficiency.

PMID: 15857203 [PubMed - indexed for MEDLINE]

In vitro estrogenic activities of Chinese medicinal plants traditionally used for the management of menopausal symptoms.

Zhang CZ, Wang SX, Zhang Y, Chen JP, Liang XM.

Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Zhongshan Road No. 161, Dalian 116011, PR China.

The estrogenic activity of 70% EtOH extracts of 32 traditional Chinese medicinal plants, selected according to their reported efficacy for the treatment of menopausal symptoms, was assessed using a recombinant yeast system with both a human estrogen receptor expression plasmid and a reporter plasmid. Among them, 11 (34%) species proved to be active. Polygonum cuspidatum had the highest estrogenic relative potency (RP) (3.28 x 10(-3)), followed by Rheumpalmatum (3.85 x 10(-4)), Cassia obtusifolia (3.49 x 10(-4)), Polygonum multiflorum (2.87 x 10(-4)), Epimedium brevicornum (2.30 x 10(-4)), Psoralea corylifolia (1.90 x 10(-4)), Cynomorium songaricum (1.78 x 10(-4)), Belamcanda chinensis (1.26 x 10(-4)), Scutellaria baicalensis (8.77 x 10(-5)), Astragalus membranaceus (8.47 x 10(5)) and Pueraria lobata (6.17 x 10(-5)). The EC(50) value of 17beta-estradiol used as the positive control was 0.205+/-0.025 ng/ml (RP=100). This study gave support to the reported efficacy of Chinese medicines used for hormone replacement therapy.

PMID: 15814262 [PubMed - indexed for MEDLINE]

J Nutr. 2001 Jun;131(6):1844-9.

Resveratrol isolated from Polygonum cuspidatum root prevents tumor growth and metastasis to lung and tumor-induced neovascularization in Lewis lung carcinoma-bearing mice.

Kimura Y, Okuda H.

Second Department of Medical Biochemistry, School of Medicine, Ehime University, Shigenobu-cho, Onsen-gun, Ehime 791-0295, Japan. [email protected]

Resveratrol is a naturally occurring phytoalexine found in medicinal plants. We found that resveratrol, at doses of 2.5 and 10 mg/kg, significantly reduced the tumor volume (42%), tumor weight (44%) and metastasis to the lung (56%) in mice bearing highly metastatic Lewis lung carcinoma (LLC) tumors, but not at a dose of 0.6 mg/kg. Resveratrol did not affect the number of CD4(+), CD8(+) and natural killer (NK)1.1.(+) T cells in the spleen. Therefore, the inhibitory effects of resveratrol on tumor growth and lung metastasis could not be explained by natural killer or cytotoxic Tlymphocyte activation. In addition, resveratrol inhibited DNA synthesis most strongly in LLC cells; its 50% inhibitory concentration (IC(50)) was 6.8 micromol/L. Resveratrol at 100 micromol/L increased apoptosis to 20.6 +/- 1.35% from 12.1 +/- 0.36% (P < 0.05) in LLC cells, and decreased the S phase population to 22.1 +/- 1.03% and 29.2 +/- 0.27% from 35.2 +/- 1.72% (P < 0.05) at concentrations of 50 and 100 micromol/L, respectively. Resveratrol inhibited tumorinduced neovascularization at doses of 2.5 and 10 mg/kg in an in vivo model. Moreover, resveratrol significantly inhibited the formation of capillary-like tube formation from human umbilical vein endothelial cells (HUVEC) at concentrations of 10-100 micromol/L; the degree of the inhibition of capillary-like tube formation by resveratrol was 45.5% at 10 micromol/L, 50.2% at 50 micromol/L and 52.6% at 100 micromol/L. Resveratrol inhibited the binding of vascular endothelial growth factor (VEGF) to HUVEC at concentrations of 10-100 micromol/L, but not at concentrations of 1 and 5 micromol/L. The degree of inhibition of VEGF binding to HUVEC by resveratrol was 16.9% at 10 micromol/L, 53.2% at 50 micromol/L and 47.8% at 100 micromol/L. We suggest that the antitumor and antimetastatic activities of resveratrol might be due to the inhibition of DNA synthesis in LLC cells and the inhibition of LLC-induced neovascularization and tube formation (angiogensis) of HUVEC by resveratrol.

PMID: 11385077 [PubMed - indexed for MEDLINE]

Lipid-lowering effects of polydatin from Polygonum cuspidatum in hyperlipidemic hamsters.

Du J, Sun LN, Xing WW, Huang BK, Jia M, Wu JZ, Zhang H, Qin LP.

Department of Pharmacognosy, School of Pharmacy, Second Military Medical University, No. 325 Guohe Road, Shanghai 200433, PR China. [email protected]

Hyperlipidaemias are common in obese people, and they increase the risk of cardiovascular diseases such as coronary heart disease (CHD) and atherosclerosis (AS). Previous studies have shown that several drugs can depress serum cholesterol. However, they could cause serious side effects in various clinical settings. The objective of the present study was to evaluate the lipid-lowering effects of polydatin in high-fat/cholesterol (HFC)-fed hamsters. The levels of lipids in hamsters were measured enzymatically before and after the administration of polydatin. Significant differences between HFC and HFC+polydatin were detected for those concentrations. Decreased levels of serum TC, TG and LDL-C and the concentrations of hepatic TG were found. Experimental results also showed that polydatin elevated LDL-C/HDL-C and TC/HDL-C ratios. In concert with other effects, serum cholesterol-lowering effect in hamsters may contribute to the regulation properties attributed to polydatin.

PMID: 19106037 [PubMed - indexed for MEDLINE]

Phytoestrogens from the roots of Polygonum cuspidatum (Polygonaceae): structure-requirement of hydroxyanthraquinones for estrogenic activity.

Matsuda H, Shimoda H, Morikawa T, Yoshikawa M.

Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, 607-8412, Kyoto, Japan.

The methanolic extract from the roots of Polygonum (P.) cuspidatum was found to enhance cell proliferation at 30 or 100 microg/mL in MCF-7, an estrogen-sensitive cell line. By bioassay-guided separation from P. cuspidatum with the most potent activity, emodin and emodin 8-O-beta-D-glucopyranoside were isolated as active principles. The methanolic extracts from Polygonum, Cassia, Aloe, and Rheum species, which were known to contain anthraquinones, also showed the MCF-7 proliferation. As a result of the evaluation of various anthraquinones from plant sources and synthetic anthraquinones, aloe-emodin, chrysophanol, chrysophanol 8-O-beta-D-glucopyranoside, and 1,8-dihydroxyanthraquinone showed weak activity. On the other hand, alizalin and 2,6-dihydroxyanthraquinone as well as emodin having the 2- and/or 6-hydroxyl groups showed potent activity. These results show that the unchelated hydroxyl group is essential for strong activity. Emodin and 2,6-dihydroxyanthraquinone also inhibited 17beta-estradiol binding to human estrogen receptors (ERs) with K(i) values of 0.77 and 0.31microM for ERalpha and 1.5 and 0.69 microM for ERbeta. These findings indicate that hydroxyanthraquinones such as emodin are phytoestrogens with an affinity to human estrogen receptors.

PMID: 11459643 [PubMed - indexed for MEDLINE]

Polygoni cuspidati radix inhibits the activation of Syk kinase in mast cells for antiallergic activity.

Lim BO, Lee JH, Ko NY, Mun SH, Kim JW, Kim do K, Kim JD, Kim BK, Kim HS, Her E, Lee HY, Choi WS.

College of Biomedical & Health Science, Konkuk University, Chungju 380-701, Korea.

The antiallergic activity of Polygoni cuspidati radix (PR) and the mechanism of action by which it functions were investigated in this study. The extract of PR exhibited potent inhibitory activity in mast cells; its IC50 values were 62 +/- 2.1 microg/ml for RBL-2H3 mast cells and 46 +/- 3.2 microg/m for bone marrow-derived mast cells by antigen stimulation, and it also suppressed the expression of tumor necrosis factor-alpha and interleukin-4 in RBL-2H3 cells. According to the in vivo animal allergy model, it inhibited a local allergic reaction, passive cutaneous anaphylaxis, in a dose-dependent manner. With regard to its mechanism of action, PR inhibited the activating phosphorylation of Syk, a key signaling protein for the activation of mast cells. It also suppressed Akt and the mitogen-activated protein kinases ERK1/2, p38, and JNK, which are critical for the production of various inflammatory cytokines in mast cells. The results of the study indicate that the antiallergic activity of PR is mediated through the inhibition of histamine release and allergic cytokine production by the inhibition of Syk activating phosphorylation in mast cells.

PMID: 18040066 [PubMed - indexed for MEDLINE]

Protective effect of polygoni cuspidati radix and emodin on Vibrio vulnificus cytotoxicity and infection.

Kim JR, Oh DR, Cha MH, Pyo BS, Rhee JH, Choy HE, Oh WK, Kim YR.

Department of Oriental Medicine Materials, Dongshin University, Jeonnam, 520-714, Republic of Korea.

Vibrio vulnificus, a good model organism of bacterial septicemia, causes fatal septicemia manifesting a fulminating course and a high mortality rate within days. In order to identify new natural substances preventing V. vulnificus infection, a plant library was screened for inhibiting cytotoxicity to host cells by using Trypan blue staining and LDH assay. We found that Polygoni Cuspidati Radix potently suppressed the acute death of HeLa and RAW264.7 cells in a dose dependent manner. Further studies revealed that Polygoni Cuspidati Radix inhibited V. vulnificus growth and survival in HI broth and seawater, respectively. We confirmed that Polygoni Cuspidati Radix contained high level of emodin by thin layer chromatography (TLC). Emodin showed direct antibacterial activity against V. vulnificus. In addition, emodin prevented the morphologic damages and acute death of HeLa cells caused from V. vulnificus. The safety of Polygoni Cuspidati Radix and emodin to host cells was confirmed by MTT assay. Polygoni Cuspidati Radix and emodin protected mice from V. vulnificus infection.

PMID: 19107405 [PubMed - indexed for MEDLINE]

Resveratrol attenuates adenosine diphosphate-induced platelet activation by reducing protein kinase C activity.

Yang YM, Wang XX, Chen JZ, Wang SJ, Hu H, Wang HQ.

Department of CCU, The First Affiliated Hospital, Inner Mongolia Medical College, Hohhot, China.

Inappropriate platelet activation is the key point of thrombogenesis. The aim of the present study was to investigate the effects of resveratrol (RESV), a compound extracted from the Chinese medicinal herb Polygonum cuspidatum sieb et Zucc, on the platelet activation induced by adenosine diphosphate (ADP) and its possible mechanism. The percentage of platelet aggregation and surface P-selectin-positive platelets, and the activity of protein kinase C (PKC) of platelet were observed with platelet aggregometer, flow cytometry and phosphorimaging system, respectively. RESV at 25, 50 and 100 microM showed anti-platelet aggregation and inhibition of surface P-selectin-positive platelets in a concentration-dependent manner. RESV (50 microM) inhibited the activity of PKC in the membrane fraction of platelets and decreased the percentage of membrane associated PKC activity in total PKC activity. Moreover, DL-erythro-1,3-Dihydroxy-2-aminooctadecane, an elective protein kinase C inhibitor (PKCI), and RESV had additive effects of inhibiting the percentage of platelet aggregation and surface P-selectin-positive platelets. It is suggested that RESV may inhibit platelet aggregation, the percentage of surface P-selectin-positive platelets and subsequent thrombus formation. The mechanisms may be partly relative to the decrease of the activity of PKC of platelets.

PMID: 18543392 [PubMed - indexed for MEDLINE]

Resveratrol stimulates glucose transport in C2C12 myotubes by activating AMP-activated protein kinase.

Park CE, Kim MJ, Lee JH, Min BI, Bae H, Choe W, Kim SS, Ha J.

Department of East-West Medicine, Graduate School, Kyung Hee University, Seoul 130-701, Korea.

Trans-Resveratrol (t-RVT), a naturally occurring polyphenol found in Polygonum cuspidatum, grape, and red wine, has been reported to have anti-inflammatory, cardioprotective, and cancer chemopreventive properties. However, antidiabetic effect of t-RVT has not yet been reported. In this study, we show that t-RVT increases glucose uptake in C2C12 myotubes by activating AMP-activated protein kinase (AMPK), uncovering an antidiabetic potential of t-RVT for the first time. AMPK plays a central role in the regulation of glucose and lipid metabolism, and hence it is considered a novel therapeutic target for metabolic syndrome such as type 2 diabetes. t-RVT significantly induced glucose uptake in C2C12 cells, via AMPK activation, but not a phosphatidylinositol-3 kinase (PI-3 kinase) signal pathway. The induced glucose uptake was attenuated by pretreatment with a pharmacological inhibitor for AMPK, indicating that the effect of t-RVT primarily depends on AMPK activation. However, in the presence of insulin, t-RVT also potentiated the effect of insulin on glucose uptake via AMPK activation, which led to further activation of PI-3 kinase/Akt signal pathway.

PMID: 17464184 [PubMed - indexed for MEDLINE]

Resveratrol suppresses TNF-induced activation of nuclear transcription factors NF-kappa B, activator protein-1, and apoptosis: potential role of reactive oxygen intermediates and lipid peroxidation.

Manna SK, Mukhopadhyay A, Aggarwal BB.

Department of Bioimmunotherapy, University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.

Resveratrol (trans-3,4',5-trihydroxystilbene), a polyphenolic phytoalexin found in grapes, fruits, and root extracts of the weed Polygonum cuspidatum, exhibits anti-inflammatory, cell growth-modulatory, and anticarcinogenic effects. How this chemical produces these effects is not known, but it may work by suppressing NF-kappaB, a nuclear transcription factor that regulates the expression of various genes involved in inflammation, cytoprotection, and carcinogenesis. In this study, we investigated the effect of resveratrol on NF-kappaB activation induced by various inflammatory agents. Resveratrol blocked TNF-induced activation of NF-kappaB in a dose- and time-dependent manner. Resveratrol also suppressed TNF-induced phosphorylation and nuclear translocation of the p65 subunit of NF-kappaB, and NF-kappaB-dependent reporter gene transcription. Suppression of TNF-induced NF-kappaB activation by resveratrol was not restricted to myeloid cells (U-937); it was also observed in lymphoid (Jurkat) and epithelial (HeLa and H4) cells. Resveratrol also blocked NF-kappaB activation induced by PMA, LPS, H2O2, okadaic acid, and ceramide. The suppression of NF-kappaB coincided with suppression of AP-1. Resveratrol also inhibited the TNF-induced activation of mitogen-activated protein kinase kinase and c-Jun N-terminal kinase and abrogated TNF-induced cytotoxicity and caspase activation. Both reactive oxygen intermediate generation and lipid peroxidation induced by TNF were suppressed by resveratrol. Resveratrol's anticarcinogenic, anti-inflammatory, and growthmodulatory effects may thus be partially ascribed to the inhibition of activation of NF-kappaB and AP-1 and the associated kinases.

PMID: 10843709 [PubMed - indexed for MEDLINE]

[Studies on active substance of anticancer effect in Polygonum cuspidatum]

[Article in Chinese]

Feng L, Zhang LF, Yan T, Jin J, Tao WY.

The Biopharmaceutical Laboratory, School of Biotechnology, Yangtze University, Wuxi, China. [email protected]

OBJECTIVE: To supply the scientific basis of research and development of the medicinal value of Polygonum cuspidatum. METHODS: One composition was isolated from the roots of Polygonum cuspidatum by cytotoxicity based fractionation and identified by HPLC-MS, UV scanning and IR. The inhibition and morphology of L-02, Hep G2, SHZ-888, MCF-7, MCF-7/ADM cells growth caused by this composition was determined by MTT assay and HE dyeing. RESULTS: This composition was identified as trans-and cis-resveratrol. It could specifically inhibit proliferation of many cancer cells but not human normal liver cell. We investigated the cytotoxicity of resveratrol to adriamycin-resistant MCF-7 cell in virtro. CONCLUSION: Resveratrol is a new anticancer composition which has less toxicity and higher efficiency in Polygonum cuspidatum.

PMID: 17059010 [PubMed - indexed for MEDLINE]

Zhong Yao Cai. 2007 Aug;30(8):974-7.

[Variances of leptin mRNA in the adipose tissue of NAFLD rats intervened with the extracts of Polygonum cuspidatum compound]

[Article in Chinese]

Jiang QL, Pan JY, Ma J, Li YY, Xu BL.

Core Lab, The First Municipal People's Hospital of Guangzhou, Guangzhou 510180, China.

The NAFLD rats were intervened with the extracts of Polygonum cuspidatum compound for 4 weeks. The reverse transcription and real-time quantitative polymerase chain reaction (RT-qPCR) methods were used to detect the relative level of leptin mRNA in the adipose tissue of intervenient and control groups. Their variances of fat and glucose in serum were detected with the biochemical methods. The results showed that the level of leptin mRNA of intervenient group was significantly increased (P <0.05j) and the triglycered and total cholesterol were significantly decreased (P <0.05). The extracts of Polygonum cuspidatum compound could increase leptin mRNA level in adipose tissue and improve the fat metablolism in serum. However, the serum glucose of the intervenient group was a little raised (P>0.05).

PMID: 18074849 [PubMed - indexed for MEDLINE]

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