In vitro studies on dual effect of m-TOR Inhibitors and Egyptian withenia somnifera (Ashwagandha) herb on hepatocellular carcinoma and hepatitis C virus activity / Dina Mofed Ibrahim ; Supervised Salwa Farouk Sabet , Wafaa Abdallah Ahmed , Abdelrahman Nabawi Zekri

Thesis (M.Sc.) - Cairo University - Faculty of Science - Department of Zoology

In the present study, we aimed to evaluate the biological activities of Ashwagandha as a natural product and m-TOR inhibitors drugs as synthetic products on hepatocellular carcinoma and Hepatitis C virus. We treated HepG2 cell lines and Lymphocyte normal cells with different doses of Ashwaganada as well as m-TOR inhibitors drugs (rapamycin, evirloimus and tacrolimus). Cell proliferation was assessed by MTT assay and revealed a marked increase in cytotoxicity of HepG2 cells treated with ashwagandha and those treated with m-TOR inhibitors drugs at doses of IC₅₀ (5 mg/ml, for Ashwagandha and 1oM, 8oM and 0.7oM for rapamycin, evirloimus and tacrolimus respectively). On the other hand, Ashwagandha increased the proliferation of lymphocyte normal cell specifically at25 mg/ml with stimulation index (6.06) compared to control stimulation index (1), but m-TOR inhibitors drugs increased cytotoxicity of lymphocyte normal cells at doses of IC₅₀, 1.5 oM, 6.5 oM, 0.5 oM, for rapamycin, evirloimus and tacrolimus respectively. Also, treatment with ashwagandha significantly increased total anti-oxidant, glutathione-S- transferase and Glutathione reductase activities in HepG2 cell line and lymphocyte treated cells at different concentrations of ASH-WX (p<0.05) for HepG2cells and (p< 0.001) for lymphocytes cells compared to untreated cells. Also, treatment with Ashwagandha resulted in apoptotic induction of HepG2 cells and significant increases of Fas-ligand, caspase 3, 8, 9. Moreover, a significant decrease of TNF-Ü (p<0.05) was observed in Ashwagandha treated cells compared to cells treated with m-TOR inhibitors drugs >0.05

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