Cholestasis is caused by the obstacle of bile formation or secretion and can develop into severe liver diseases. We previously reported the ethanol extract of Schisandra sphenanthera(Wuzhi tablet, WZ) can significantl...Cholestasis is caused by the obstacle of bile formation or secretion and can develop into severe liver diseases. We previously reported the ethanol extract of Schisandra sphenanthera(Wuzhi tablet, WZ) can significantly protect against lithocholic acid(LCA)-induced intrahepatic cholestasis in mice, partially due to the activation of PXR pathway and promotion of liver regeneration.However, the effect of WZ on the bile acids profile and gut microbiome in cholestastic mice remain unknown. In this study, the effect of WZ against LCA-induced liver injury was evaluated and its effect on the bile acids metabolome and gut microbiome profiles in cholestastic mice was further investigated. Targeted metabolomics analysis was performed to examine the change of bile acids in the serum, liver, intestine and feces. The change of intestinal flora were detected by the genomics method. Targeted metabolomics analysis revealed that WZ enhanced the excretion of bile acids from serum and liver to intestine and feces. Genomics analysis of gut microbiome showed that WZ can reverse LCA-induced gut microbiome disorder to the normal level. In conclusion, WZ protects against LCAinduced cholestastic liver injury by reversing abnormal bile acids profiles and alteration of gut microbiome.展开更多
Huang-Qin Decoction(HQD)is a classic prescription for diarrhea in Chinese medicine treatment.Recent studies have demonstrated that HQD and its modified formulation PHY906 could ameliorate irinotecan(CPT-11)induced gas...Huang-Qin Decoction(HQD)is a classic prescription for diarrhea in Chinese medicine treatment.Recent studies have demonstrated that HQD and its modified formulation PHY906 could ameliorate irinotecan(CPT-11)induced gastrointestinal(GI)toxicity and enhance its anticancer therapeutic efficacy.Nevertheless,which constituents in HQD are effective is still unclear so far.The study aims to screen out the key bioactive components combination from HQD that could enhance the anticancer effect of CPT-11.First,the potential bioactive constituents were obtained through system pharmacology strategy.Then the bioactivity of each constituent was investigated synthetically from the aspects of NCM460 cell migration,TNF-αrelease of THP-1-derived macrophage and MTT assay in HCT116 cell.The contribution of each constituent in HQD was evaluated using the bioactive index Ei,which taken the content and bioactivity into comprehensive consideration.And then,the most contributing constituents were selected out to form a keycomponent combination.At last,the bioefficacy of the key-component combination was validated in vitro and in vivo.As a result,a key-component combination(HB4)consisting of four compounds baicalin,baicalein,glycyrrhizic acid and wogonin was screened out.In vitro assessment indicated that HB4 could enhance the effect of CPT-11 on inhibiting cell proliferation and inducing apoptosis in HCT116.Furthermore,the in vivo study confirmed that HB4 and HQD have similar pharmacological activity and could both enhance the antitumor effect of CPT-11 in HCT116 xenograft model.Meanwhile,HB4 could also reduce the CPT-11 induced GI toxicity.展开更多
基金supported by the Natural Science Foundation of China(Nos.81973392,81573489)the National Key Research and Development Program(No.2017YFE 0109900)+4 种基金the Natural Science Foundation of Guangdong(No.2017A030311018)the 111 project(No.B16047)the Key Laboratory Foundation of Guangdong Province(No.2017B030314030)the Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program(No.2017BT01Y093)the National Engineering and Technology Research Center for New drug Druggability Evaluation(Seed Program of Guangdong Province,No.2017B090903004)。
文摘Cholestasis is caused by the obstacle of bile formation or secretion and can develop into severe liver diseases. We previously reported the ethanol extract of Schisandra sphenanthera(Wuzhi tablet, WZ) can significantly protect against lithocholic acid(LCA)-induced intrahepatic cholestasis in mice, partially due to the activation of PXR pathway and promotion of liver regeneration.However, the effect of WZ on the bile acids profile and gut microbiome in cholestastic mice remain unknown. In this study, the effect of WZ against LCA-induced liver injury was evaluated and its effect on the bile acids metabolome and gut microbiome profiles in cholestastic mice was further investigated. Targeted metabolomics analysis was performed to examine the change of bile acids in the serum, liver, intestine and feces. The change of intestinal flora were detected by the genomics method. Targeted metabolomics analysis revealed that WZ enhanced the excretion of bile acids from serum and liver to intestine and feces. Genomics analysis of gut microbiome showed that WZ can reverse LCA-induced gut microbiome disorder to the normal level. In conclusion, WZ protects against LCAinduced cholestastic liver injury by reversing abnormal bile acids profiles and alteration of gut microbiome.
基金the NSFC(Nos.81773861,81302733)Jiangsu Provincial National Science Foundation for Distinguished Young Scholars(No.BK20180027)+3 种基金National Science and Technology Major Project(2017ZX09101001)Double First-Class University projectthe Program for Jiangsu Province Innovative Research Teama project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)gsu Higher Education Institutions(PAPD)。
文摘Huang-Qin Decoction(HQD)is a classic prescription for diarrhea in Chinese medicine treatment.Recent studies have demonstrated that HQD and its modified formulation PHY906 could ameliorate irinotecan(CPT-11)induced gastrointestinal(GI)toxicity and enhance its anticancer therapeutic efficacy.Nevertheless,which constituents in HQD are effective is still unclear so far.The study aims to screen out the key bioactive components combination from HQD that could enhance the anticancer effect of CPT-11.First,the potential bioactive constituents were obtained through system pharmacology strategy.Then the bioactivity of each constituent was investigated synthetically from the aspects of NCM460 cell migration,TNF-αrelease of THP-1-derived macrophage and MTT assay in HCT116 cell.The contribution of each constituent in HQD was evaluated using the bioactive index Ei,which taken the content and bioactivity into comprehensive consideration.And then,the most contributing constituents were selected out to form a keycomponent combination.At last,the bioefficacy of the key-component combination was validated in vitro and in vivo.As a result,a key-component combination(HB4)consisting of four compounds baicalin,baicalein,glycyrrhizic acid and wogonin was screened out.In vitro assessment indicated that HB4 could enhance the effect of CPT-11 on inhibiting cell proliferation and inducing apoptosis in HCT116.Furthermore,the in vivo study confirmed that HB4 and HQD have similar pharmacological activity and could both enhance the antitumor effect of CPT-11 in HCT116 xenograft model.Meanwhile,HB4 could also reduce the CPT-11 induced GI toxicity.
