Yu Gan Long Ameliorates Hepatic Fibrosis by Inhibiting PI3K/AKT,Ras/ERK and JAK1/STAT3 Signaling Pathways in CCl4-induced Liver Fibrosis Rats

Yu Gan Long(YGL)is a Chinese traditional herbal formula which has been reported to attenuate liver fibrosis for many years and we have explored its anti-fibrotic mechanism through blocking transforming growth factor(TGF-β)in the previous study.But the mechanisms associated with platelet-derived growth factor(PDGF)-BB remain obscure.In this study,we further investigated the mechanism of YGL reducing carbon tetrachloride(CCl4)-induced liver fibrosis in rats.Our results showed that YGL suppressed CCl4-induced upregulation of collagen IV(Col IV),type HI precollagen(PCHI),hyaluronuc acid(HA)and laminin(LN),which are implicated in liver fibrosis.Also,YGL reduced theα-smooth muscle actin(α-SMA)expression,which acts as the indicator of liver fibrosis.Furthermore,YGL decreased the serum levels of hepatic stellate cell(HSC)mitogen PDGF-BB and inflammation cytokines,including TNF-α,IL-1β,IL-6.Markers involved in liver fibrosis,such as Ras,p-Raf-1,p-ERK1/2,p-JNK,p-P38,p-PI3K,p-AKT,p-JAKl,p-STAT3 were downregulated significantly after treatment with YGL.Our results indicated that YGL ameliorated CCl4-induced liver fibrosis by reducing inflammation cytokines production,and suppressing Ras/ERK,PI3K/AKT,and JAK1/STAT3 signaling pathways,which provided further evidence towards elucidation of the anti-fibrotic mechanism of YGL.

A Potential Anti-cancer Compound Separated from the Chloroform Extract of the Chinese Medicine Formula Shenqi San

This study examined anti-cancer compounds present in the chloroform extract of the Chinese medicine formula Shenqi San(CE-SS).Silica gel column chromatography,Sephadex LH-20,octadecylsilyl(ODS)column chromatography,and high performance liquid chromatography(HPLC)were used to separate the compounds from CE-SS.The structural formulas of the separated compounds were determined using ID1H and 13C experiments as well as high resolution electrospray ionization mass spectroscopy(HRESIMS).The corresponding results were compared with the reported literature data.A total of six compounds were separated and their structures were identified on the basis of corresponding spectroscopic and physico-chemical properties.They were Saikogenin F(Ⅰ),Prosaikogenin D(Ⅱ),Prosaikogenin F(Ⅲ),p-sitosterol(Ⅳ),3β,16β,23-trihydroxy-13,28-epoxyurs-11-ene-3-O-β-D-glucopyranoside(V),and methyl ursolic acid(VI).The separated compounds were evaluated in vitro for their inhibitory ability against the proliferation of A549 cells via MTT assay.Apoptosis was investigated using Annexin V-FITC/propidium iodide(PI)by flow cytometry.Apoptosis-associated proteins were examined by Western blotting.All the compounds were observed to have inhibitory activities against the proliferation of A549 cells to different degrees.Flow cytometry showed that compound V increased the proportion of apoptotic A549 cells in a dose-dependent manner.Western blotting showed that compound V increased the expression of Bax,cleaved-caspase-3,cleaved-caspase-9 and cleaved-poly ADP-ribose polymerase(PARP),and decreased the expression of Bcl-2.These results indicated that compound V featured a significant inhibitory effect on A549 cells when compared with other compounds,and it may be considered a potential drug against cancers.