Dear Lev,

The following papers cover the answer to your question:

1-J Ovarian Res. 2014; 7: 21.

Published online 2014 Feb 13. doi: 10.1186/1757-2215-7-21

PMCID: PMC3940290

Resveratrol potentiates effects of simvastatin on inhibition of rat ovarian theca-interstitial cells steroidogenesis

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3940290/

Abstract

Background

Polycystic ovary syndrome (PCOS) is characterized by ovarian enlargement, hyperplastic theca compartment and increased androgen production due to, at least in part, excessive expression of several key genes involved in steroidogenesis. Previously, our group has demonstrated that simvastatin, competitive inhibitor of 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA reductase), a rate-limiting step of the mevalonate pathway, reduces rat-theca interstitial cell steroidogenesis by inhibiting Cyp17a1 gene expression, the key enzyme of the androgen biosynthesis pathway. Recently, we demonstrated that resveratrol, a bioflavonoid abundant in red grapes, decreases rat theca-interstitial cell steroidogenesis and this suppressive effect is mediated through mechanisms independent of the mevalonate pathway. The present study evaluated the effect of combining simvastatin and resveratrol treatments on rat theca-interstitial cell steroidogenesis.

Methods

Rat theca-interstitial cells isolated from 30 day-old female rats were cultured for up to 48 h with or without simvastatin (1 μM) and/or resveratrol (3-10 μM). Steroidogenic enzymes gene expression was evaluated by quantitative real time PCR and steroid levels were measured by liquid chromatography-mass spectrometry. Comparisons between groups were performed using ANOVA and Tukey test.

Results

Resveratrol potentiated inhibitory effects of simvastatin on androstenedione and androsterone production in theca-interstitial cells. This suppressive effect correlated with profound inhibition in Cyp17a1 mRNA expression in the presence of a combination of resveratrol and simvastatin.

Conclusions

The present findings indicate that resveratrol potentiates the simvastatin-induced inhibitory effect on theca-interstitial cell androgen production, raising the possibility of development of novel treatments of PCOS.

Keywords: Androgens, CYP17A1, Ovarian theca-interstitial cells, Resveratrol, Simvastatin, Steroidogenesis

2-J Nutr. 2007 Dec;137(12):2668-73.

Resveratrol potentiates genistein's antiadipogenic and proapoptotic effects in 3T3-L1 adipocytes.

Rayalam S1, Della-Fera MA, Yang JY, Park HJ, Ambati S, Baile CA.

Author information

 http://www.ncbi.nlm.nih.gov/pubmed/18029481

Abstract

Genistein (G) and resveratrol (R) individually inhibit adipogenesis in 3T3-L1 adipocytes and induce apoptosis in cancer cells. We investigated whether the combination of G and R resulted in enhanced effects on adipogenesis, lipolysis, and apoptosis in 3T3-L1 cells. Preadipocytes and mature adipocytes were treated with G and R individually at 50 and 100 micromol/L (G100; R100) and in combination. Both in preadipocytes and mature adipocytes, G and R individually decreased cell viability dose-dependently, but G100 + R100 further decreased viability by 59 +/- 0.97% (P < 0.001) and 69.7 +/- 1.2% (P < 0.001) after 48 h compared with G100 and R100, respectively. G100 + R100 induced apoptosis 242 +/- 8.7% (P < 0.001) more than the control after 48 h, whereas G100 and R100 individually increased apoptosis only 46 +/- 9.2 and 46 +/- 7.9%, respectively. G and R did not modulate mitogen-activated protein kinase expression by themselves, but G100 + R100 increased Jun-N-terminal kinase phosphorylation by 38.8 +/- 4.4% (P < 0.001) and decreased extracellular signal-regulating kinase phosphorylation by 48 +/- 3.4% (P < 0.001). Individually, G and R at 25 micromol/L (G25; R25) decreased lipid accumulation by 30 +/- 1.7% and 20.07 +/- 4.27%, respectively (P < 0.001). However, G25 + R25 decreased lipid accumulation by 77.9 +/- 3.4% (P < 0.001). Lipolysis assay revealed that neither G25 nor R25 induced lipolysis, whereas G25 + R25 significantly increased lipolysis by 25.5 +/- 4.6%. The adipocyte-specific proteins PPARgamma and CCAAT/enhancer binding protein-alpha were downregulated after treatment with G + R, but no effect was observed with individual compounds. These results indicate that G and R in combination produce enhanced effects on inhibiting adipogenesis, inducing apoptosis, and promoting lipolysis in 3T3-L1 adipocytes. Thus, the combination of G and R is more potent in exerting antiobesity effects than the individual compounds.

3- REVIEW

Synergism between resveratrol and other

phytochemicals: Implications for obesity

and osteoporosis

Srujana Rayalam1

Mary Anne Della-Fera1 and Clifton A. Baile1,2

Mol. Nutr. Food Res. 2011, 55, 1–9 DOI 10.1002/mnfr.201000616

http://ads.uga.edu/documents/Srujana.2.pdf

Resveratrol, a phytoalexin, has gained much attention recently due to its effects on sirtuins. While the anti-cancer properties of resveratrol have been extensively investigated, the antiadipogenic and osteogenic effects of resveratrol are also gaining considerable interest. The finding that resveratrol supplementation mimics caloric restriction prompted researchers to study the effects of resveratrol on lipid metabolism. Mesenchymal stem cells are the precursors for both adipocytes and osteoblasts. In the aging population, differentiation to adipocytes dominates over the differentiation to osteoblasts in bone marrow, contributing to the increased tendency for fractures to occur in the elderly. Thus, an inverse relationship

exists between adipocytes and osteoblasts in the bone marrow. Resveratrol acts on several molecular targets in adipocytes and osteoblasts leading to a decrease in adipocyte number and size and an increase in osteogenesis. Furthermore, resveratrol in combination with genistein and quercetin synergistically decreased adipogenesis in murine and human adipocytes. A recent in vivo study showed that phytochemicals including resveratrol in combination with vitamin D prevented weight gain and bone loss in a postmenopausal rat model. Therefore, combinations of resveratrol with other phytochemicals may lead to potential novel potent

therapies for both obesity and osteoporosis.

Keywords:

Adipocyte life cycle / Multifocal signal modulation therapy / Osteogenesis /

Synergistic activity

Hoping this will be helpful,

Rafik

Yes this is exactly what I needed, thank you!