Insulin resistance is connection to immoderate glucose producing and unusual lipid metabolism,which is principal to diabetes.Rhinacanthus nasutus(L.)Kurz(R.nasutus)is a medicinal and edible plant used for thou-sands o...Insulin resistance is connection to immoderate glucose producing and unusual lipid metabolism,which is principal to diabetes.Rhinacanthus nasutus(L.)Kurz(R.nasutus)is a medicinal and edible plant used for thou-sands of years,and the R.nasutus“tea bags”is widely used as an edible material to treat diabetes.Rhinacanthin C(RC)was reported to be the main active components of R.nasutus,which has the effect of treating diabetes.The study aims to explore the effects and mechanism of RC and Rhinacanthins-rich extract(RRE)on the glycolipid metabolism of HepG2 cells under insulin resistance via network pharmacology,untargeted metabolomics and molecular pharmacology.As a result,network pharmacology analysis predicted that RRE could anti-diabetes by insulin resistance signal pathway.In vitro studies indicated that RC and RRE ameliorated the strangeness of glycolipid metabolism and inhibited the activation of IRS1/PI3K/Akt/GSK 3βsignal pathway in insulin resistant HepG2(IR-HepG2)cells.Untargeted metabolomics analysis showed that RC and RRE could affect sphingolipid metabolism and other metabolic pathways.Furthermore,RC and RRE were found to regulate insulin resistance through sphingolipid metabolism proved by Western blot analysis.Hence,it was suggested that RC and RRE might be involved in the glycolipid metabolism of IR-HepG2 cells through the IRS1/PI3K/AKT/GSK 3βsignal pathway and the sphingolipid metabolic pathway.Overall,this study could provide the active mechanism of the components RC and RRE from R.nasutus in regulating insulin resistance,also it could providenew ideas for the development of functional foods derived from R.nasutus.展开更多
基金supported by a grant from the National Natural Sci-ence Foundation of China(Grant No.32372245,32172169)the grant from Tianjin Municipal Science and Technology Foundation(Grant No.22JCYBJC00160)the grant from National Key Research and Development Program of China(Grant No.2021YFE0110000).
文摘Insulin resistance is connection to immoderate glucose producing and unusual lipid metabolism,which is principal to diabetes.Rhinacanthus nasutus(L.)Kurz(R.nasutus)is a medicinal and edible plant used for thou-sands of years,and the R.nasutus“tea bags”is widely used as an edible material to treat diabetes.Rhinacanthin C(RC)was reported to be the main active components of R.nasutus,which has the effect of treating diabetes.The study aims to explore the effects and mechanism of RC and Rhinacanthins-rich extract(RRE)on the glycolipid metabolism of HepG2 cells under insulin resistance via network pharmacology,untargeted metabolomics and molecular pharmacology.As a result,network pharmacology analysis predicted that RRE could anti-diabetes by insulin resistance signal pathway.In vitro studies indicated that RC and RRE ameliorated the strangeness of glycolipid metabolism and inhibited the activation of IRS1/PI3K/Akt/GSK 3βsignal pathway in insulin resistant HepG2(IR-HepG2)cells.Untargeted metabolomics analysis showed that RC and RRE could affect sphingolipid metabolism and other metabolic pathways.Furthermore,RC and RRE were found to regulate insulin resistance through sphingolipid metabolism proved by Western blot analysis.Hence,it was suggested that RC and RRE might be involved in the glycolipid metabolism of IR-HepG2 cells through the IRS1/PI3K/AKT/GSK 3βsignal pathway and the sphingolipid metabolic pathway.Overall,this study could provide the active mechanism of the components RC and RRE from R.nasutus in regulating insulin resistance,also it could providenew ideas for the development of functional foods derived from R.nasutus.