Picroside Ⅱ promotes HSC apoptosis and inhibits the cholestatic liver fibrosis in Mdr2^(−/−)mice by polarizing M1 macrophages and balancing immune responses  

作　　者：JIA Kexin MA Zhi ZHANG Yinhao XIE Kaihong LI Jianan WU Jianzhi QU Jiaorong LI Fanghong LI Xiaojiaoyang 

机构地区：[1]School of Life Sciences,Beijing University of Chinese Medicine,Beijing 100029,China [2]School of Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing 100029,China

出　　处：《Chinese Journal of Natural Medicines》2024年第7期582-598,共17页中国天然药物（英文版）

基　　金：supported by the National Key Research and Development Program on Modernization of Traditional Chinese Medicine(No.2022YFC3502100);the National Natural Science Foundation of China(No.82274186);the National High-Level Talents Special Support Program;the Young Talents Promotion Project of China Association of Traditional Chinese Medicine(No.2020-QNRC2-01);the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(No.ZYYCXTD-C-202006).

摘　　要：Liver fibrosis is characterized by chronic inflammatory responses and progressive fibrous scar formation.Macrophages play a central role in the pathogenesis of hepatic fibrosis by reconstructing the immune microenvironment.Picroside Ⅱ(PIC Ⅱ),extracted from Picrorhizae Rhizoma,has demonstrated therapeutic potential for various liver damage.However,the mechanisms by which macrophage polarization initiates immune cascades and contributes to the development of liver fibrosis,and whether this process can be influenced by PIC Ⅱ,remain unclear.In the current study,RNA sequencing and multiple molecular approaches were utilized to explore the underlying mechanisms of PIC Ⅱ against liver fibrosis in multidrug-resistance protein 2 knockout(Mdr2^(−/−))mice.Our findings indicate that PIC Ⅱ activates M1-polarized macrophages to recruit natural killer cells(NK cells),potentially via the CXCL16-CXCR6 axis.Additionally,PIC Ⅱ promotes the apoptosis of activated hepatic stellate cells(aHSCs)and enhances the cytotoxic effects of NK cells,while also reducing the formation of neutrophil extracellular traps(NETs).Notably,the anti-hepatic fibrosis effects associated with PIC Ⅱ were largely reversed by macrophage depletion in Mdr2^(−/−)mice.Collectively,our research suggests that PIC Ⅱ is a potential candidate for halting the progression of liver fibrosis.

关 键 词：Liver fibrosis PicrosideⅡ M1 macrophage Hepatic stellate cell Natural killer cell NEUTROPHIL 

分 类 号：R965[医药卫生—药理学]