Integrative lipidomic and transcriptomic study unravels the therapeutic effects of saikosaponins A and D on non-alcoholic fatty liver disease  

作　　者：Xiaojiaoyang Li Junde Ge Yajing Li Yajie Cai Qi Zheng Nana Huang Yiqing Gu Qi Han Yunqian Li Rong Sun Runping Liu 

机构地区：[1]Beijing University of Chinese Medicine,Beijing 100029,China [2]The Second Hospital of Shandong University,Shandong University,Ji'nan 250033,China [3]Advanced Medical Research Institute,Shandong University,Ji'nan 250012,China

出　　处：《Acta Pharmaceutica Sinica B》2021年第11期3527-3541,共15页药学学报（英文版）

基　　金：supported by grants from the National Natural Science Foundation of China(Nos.81773997 and 81073148 to Rong Sun;No.82004029 to Runping Liu;No.82004045 to Xiaojiaoyang Li);Beijing University of Chinese Medicine(No.2020-JYB-ZDGG-038 to Runping Liu,China);supported by grants from Beijing Nova Program of Science&Technology(Nos.Z201100006820025 and Z191100001119088,China);supported by research fund‘Traditional Chinese medicine pharmacology and toxicology expert(No.ts201511107)’from the Taishan Scholar Project of Shandong Province(China)。

摘　　要：Nonalcoholic fatty liver disease(NAFLD)has become one of the most prominent causes of chronic liver diseases and malignancies.However,few therapy has been approved.Radix Bupleuri(RB)is the most frequently used herbal medicine for the treatment of liver diseases.In the current study,we aim to systemically evaluate the therapeutic effects of saikosaponin A(SSa)and saikosaponin D(SSd),the major bioactive monomers in RB,against NAFLD and to investigate the underlying mechanisms.Our results demonstrated that both SSa and SSd improved diet-induced NAFLD.Integrative lipidomic and transcriptomic analysis revealed that SSa and SSd modulated glycerolipid metabolism by regulating related genes,like Lipe and Lipg.SSd profoundly suppressed the fatty acid biosynthesis by downregulating Fasn and Acaca expression and promoted fatty acid degradation by inducing Acox1 and Cpt1 a expression.Bioinformatic analysis further predicted the implication of master transcription factors,including peroxisome proliferator-activated receptor alpha(PPARα),in the protective effects of SSa and SSd.These results were further confirmed in vitro in mouse primary hepatocytes.In summary,our study uncoded the complicated mechanisms underlying the promising anti-steatosis activities of saikosaponins(SSs),and provided critical evidence inspiring the discovery of innovative therapies based on SSa and SSd for the treatment of NAFLD and related complications.

关 键 词：SAIKOSAPONIN Nonalcoholic fatty liver disease LIPIDOME TRANSCRIPTOME Lipid metabolism 

分 类 号：R285.5[医药卫生—中药学]