Origanum vulgare L.leaf extract alleviates finasteride-induced oxidative stress in mouse liver and kidney

Objective:To investigate the hepatorenoprotective effects of Origanum vulgare L.against finasteride-induced oxidative injury in the liver and kidney of mice.Methods:Liquid chromatography-electrospray ionization-tandem mass spectrometry(LC-ESI/MS)analysis was utilized to yield a fingerprint of Origanum vulgare polyphenolic constituents.Thirty BALB/c mice received 0.5 mL/day distilled water,finasteride(25 mg/kg/day for 10 d),and 100,200,or 400 mg/kg/day finasteride+Origanum vulgare extract with 6 mice per group for five weeks.On day 36,liver and kidney function as well as pro-and antiinflammatory(IFN-γ,IL-12,IL-6,TNF-α,IL-1β,and IL-10)cytokines were measured.The total antioxidant status,nitric oxide(NO),and malondialdehyde levels as well as the activities of NO synthase and catalase were also evaluated.Histopathological study was conducted to assess the effect of Origanum vulgare extract on finasteride-induced renal and hepatic toxicities.Results:Twenty-five major polyphenolic compounds were identified in the Origanum vulgare extract by LC-ESI/MS.Origanum vulgare extract,especially at 200 and 400 mg/kg/day doses,significantly improved liver and kidney biochemical indices,decreased inflammatory cytokines,increased total antioxidant status and NO synthase and catalase activities,as well as decreased plasma NO and malondialdehyde levels in a dose-dependent manner as compared to the finasteride group.Histopathological results further confirmed the protective effect of Origanum vulgare extract.Conclusions:Origanum vulgare extract ameliorates finasterideinduced hepatic and renal biochemical and histopathological alterations,and restores antioxidant/oxidant balance.

Pterostilbene induces cell apoptosis and inhibits lipogenesis in SKOV3 ovarian cancer cells by activation of AMPK-induced inhibition of Akt/mTOR signaling cascade

This study investigates if the anti-tumor effect of Pterostilbene in the SKOV3 ovarian cancer(OC)cell line involves inhibition of cell metabolism and tested in this effect involves modulating AMPK and Akt-induced regulation of mTORC1.Initially,SKOV3 cells were cultured in the humidified conditions in DMEM media for 24 h with or without increasing concentration of Pterostilbene.Then,the cells were incubated with Pterostilbene(IC_(50)=50μM)under similar conditions with or without pre-incubation with Dorsomorphin,an AMPK inhibitor.In a dose-dependent manner,Pterostilbene inhibited SKOV3 cell survival and increased their lysate levels of lactate dehydrogenase(LDH)and single-stranded DNA(ssDNA).When SKOV3 cells were treated with 50μM Pterostilbene,Pterostilbene significantly suppressed cell migration and invasion,reduced lysate levels of lactic acid and the optical density of Oil Red O staining,and increased lysate glucose levels.It also increased levels of malondialdehyde(MDA),reactive oxygen species(ROS),and induced intrinsic cell apoptosis by upregulating protein levels of Bax and cleaved caspase-3 and reducing protein levels of Bcl-2.Besides,Pterostilbene reduced mRNA levels of sterol regulatory element-binding protein 1(SREBP-1),fatty acid synthase(FAS),acetyl CoA carboxylase-1(ACC-1),and AMP-activated protein kinase(AMPK).Furthermore,Pterostilbene increased the protein levels of p-AMPK,p-p53,p-raptor,p-TSC-2,but significantly decreased protein levels of p-Akt,p-TSC-2,p-mTOR,p-S6K1,and p-4E-BP.Treatment with Dorsomorphin(CC)abolished all the anti-tumorigenesis effects afforded by Pterostilbene and prevented Pterostilbene-induced phosphorylation of Akt,p53,and mTOR.In conclusion,the tumorsuppressive effect of Pterostilbene in SKOV3 cells involves the induction of ROS and inhibition of dysregulation cell metabolism mainly due to AMPK-induced Akt-dependent or independent suppression of mTOR.