Estrogen-induced cholestasis(EIC)is a condition associated with intrauterine fetal death,preterm delivery,and meconium in amniotic fluid.The role of sesamol,a major bioactive compound in sesame oil,in alleviating chol...Estrogen-induced cholestasis(EIC)is a condition associated with intrauterine fetal death,preterm delivery,and meconium in amniotic fluid.The role of sesamol,a major bioactive compound in sesame oil,in alleviating cholestasis remains unclear.In this study,we investigated the mechanisms underlying the protective effects of sesamol against cholestatic liver injury using C57BL/6 male mice with 17α-ethynylestradiol(EE)-induced cholestasis,combined with network pharmacology,16S rRNA sequencing,and the in vitro assays.Our results demonstrate that sesamol alleviates cholestatic liver injury by inhibiting inflammation,oxidative stress,and apoptosis.Mechanistically,sesamol activates EGFR/FXR/CYP7A1 signaling pathway,thereby improving bile acid metabolism.Additionally,sesamol modulates the gut microbiota by increasing the relative abundance of Firmicutes and Bacteroidota(P<0.05),which are crucial for bile acid metabolism.Furthermore,we observed a positive correlation(P<0.05)between serum liver injury and cholestasis relative markers and the abundance of certain harmful bacteria(Anaerovorax,Erysipelatoclostridium,Fusobacterium),suggesting that sesamol may protect against EIC through modulation of the liver-gut axis,contributing to the restoration of bile acid homeostasis.This study provides new insights into the potential of sesamol as a functional food ingredient for the prevention and treatment of cholestasis.展开更多
基金supported by the National Natural Science Foundation of China grant 82304503the Anhui Provincial Natural Science Foundation Grant 2308085QH305Guangdong Provincial Key Laboratory of Nutraceuticals and Functional Foods grant 2024SZKFJJ09 to Shuang Zhang.
文摘Estrogen-induced cholestasis(EIC)is a condition associated with intrauterine fetal death,preterm delivery,and meconium in amniotic fluid.The role of sesamol,a major bioactive compound in sesame oil,in alleviating cholestasis remains unclear.In this study,we investigated the mechanisms underlying the protective effects of sesamol against cholestatic liver injury using C57BL/6 male mice with 17α-ethynylestradiol(EE)-induced cholestasis,combined with network pharmacology,16S rRNA sequencing,and the in vitro assays.Our results demonstrate that sesamol alleviates cholestatic liver injury by inhibiting inflammation,oxidative stress,and apoptosis.Mechanistically,sesamol activates EGFR/FXR/CYP7A1 signaling pathway,thereby improving bile acid metabolism.Additionally,sesamol modulates the gut microbiota by increasing the relative abundance of Firmicutes and Bacteroidota(P<0.05),which are crucial for bile acid metabolism.Furthermore,we observed a positive correlation(P<0.05)between serum liver injury and cholestasis relative markers and the abundance of certain harmful bacteria(Anaerovorax,Erysipelatoclostridium,Fusobacterium),suggesting that sesamol may protect against EIC through modulation of the liver-gut axis,contributing to the restoration of bile acid homeostasis.This study provides new insights into the potential of sesamol as a functional food ingredient for the prevention and treatment of cholestasis.
