Bletilla striata polysaccharides alleviate metabolic dysfunctionassociatedsteatotic liver disease through enhancing hepatocyteRelA/HNF1αsignal  

作　　者：Yi-Huai He Li-Li Ou Jin-Lian Jiang Yun-Fen Chen Aikedaimu Abudukeremu Yuan Xue Mao-Yuan Mu Wei-Wei Zhong De-Lin Xu Xuan-Yu Meng Ya-Qun Guan 

机构地区：[1]State Key Laboratory of Pathogenesis,Prevention and Treatment of High Incidence Diseases in Central Asia,Xinjiang Key Laboratory of Molecular Biology for Endemic Diseases,Department of Pathology,School of Basic Medical Sciences,Xinjiang Medical University,Urumqi 830000,Xinjiang Uyghur Autonomous Region,China [2]Department of Infectious Diseases,Affiliated Hospital of Zunyi Medical University,Zunyi 563000,Guizhou Province,China [3]Department of Liver Diseases,Third People’s Hospital of Changzhou,Changzhou 213000,Jiangsu Province,China [4]Department of Intervention Radiology,Affiliated Hospital of Zunyi Medical University,Zunyi 563000,Guizhou Province,China [5]Department of Infectious Diseases,Jingmen Central Hospital,Jingmen 448000,Hubei Province,China [6]Department of Cell Biology,Zunyi Medical University,Zunyi 563099,Guizhou Province,China [7]Xinjiang Second Medical College,Karamay 834000,Xinjiang Uyghur Autonomous Region,China

出　　处：《World Journal of Gastroenterology》2025年第4期88-122,共35页世界胃肠病学杂志(英文)

基　　金：National Natural Science Foundation of China,No.32260089;Science and Technology Research Foundation of Guizhou Province,No.QKHJC-ZK(2022)YB642;Science and Technology Research Foundation of Hubei Province,No.2022BCE030;Science and Technology Research Foundation of Changzhou City,No.CE20225040;Science and Technology Research Foundation of Zunyi City,No.ZSKHHZ(2022)344 and No.ZSKHHZ(2022)360;WBE Liver Fibrosis Foundation,No.CFHPC2025028.

摘　　要：BACKGROUND Bletilla striata polysaccharides(BSP)have antioxidant,immune regulation,and anti-fibrotic activities.However,the therapeutic effect and mechanisms underlying the action of BSP in metabolic dysfunction-associated steatotic liver disease(MASLD)have not been fully understood.AIMTo investigate the therapeutic effects and mechanisms of BSP on MASLD by centering on the hepatocyte nuclearfactor kappa B p65(RelA)/hepatocyte nuclear factor-1 alpha(HNF1α)signaling.METHODSA mouse model of MASLD was induced by feeding with a high-fat-diet(HFD)and a hepatocyte model of steatosiswas induced by treatment with sodium oleate(SO)and sodium palmitate(SP).The therapeutic effects of BSP onMASLD were examined in vivo and in vitro.The mechanisms underlying the action of BSP were analyzed for theireffect on lipid metabolism disorder,endoplasmic reticulum(ER)stress,and the RelA/HNF1αsignaling.RESULTSHFD feeding reduced hepatocyte RelA and HNF1αexpression,induced ER stress,lipid metabolism disorder,andnecroptosis in mice,which were significantly mitigated by treatment with BSP.Furthermore,treatment with BSP orBSP-containing conditional rat serum significantly attenuated the sodium oleate/sodium palmitate(SO/SP)-induced hepatocyte steatosis by decreasing lipid accumulation,and lipid peroxidation,and enhancing theexpression of RelA,and HNF1α.The therapeutic effects of BSP on MASLD were partially abrogated by RELAsilencing in mice and RELA knockout in hepatocytes.RELA silencing or knockout significantly down-regulatedHNF1αexpression,and remodeled ER stress and oxidative stress responses during hepatic steatosis.CONCLUSIONTreatment with BSP ameliorates MASLD,associated with enhancing the RelA/HNF1αsignaling,remodeling ERstress and oxidative stress responses in hepatocytes.

关 键 词：Bletilla striata polysaccharides Metabolic dysfunction-associated steatotic liver disease Nuclear factor kappa B p65/hepatocyte nuclear factor-1 alpha signaling Endoplasmic reticulum stress Oxidative stress Lipid metabolism reprogramming 

分 类 号：R575.5[医药卫生—消化系统]