Cornus officinalis with high pressure wine steaming enhanced anti-hepatic fibrosis: Possible through SIRT3-AMPK axis  

作　　者：Xin Han Yan Ning Xinyue Dou Yiwen Wang Qiyuan Shan Kao Shi Zeping Wang Chuan Ding Min Hao Kuilong Wang Mengyun Peng Haodan Kuang Qiao Yang Xianan Sang Gang Cao 

机构地区：[1]School of Pharmacy,Zhejiang Chinese Medical University,Hangzhou,311400,China

出　　处：《Journal of Pharmaceutical Analysis》2024年第5期758-771,共14页药物分析学报（英文版）

基　　金：supported by the National Natural Science Foundation of China(Grant Nos.:82104394 and 81973481);the Natural Science Foundation of Zhejiang Province(Grant Nos.:LY23H280008 and LQ23H280004);Zhejiang Province Traditional Chinese Medicine Science and Technology Project(Grant No.:2022ZQ033);Zhejiang Chinese Medicine University UniversityLevel Talent Special Project(Grant No.:2021ZR06);Zhejiang Province Postdoctoral Research Project(Grant No.:ZJ2022057).

摘　　要：Cornus officinalis,a medicinal and edible plant known for its liver-nourishing properties,has shown promise in inhibiting the activation of hepatic stellate cells(HSCs),crucial indicators of hepatic fibrosis,especially when processed by high pressure wine steaming(HPWS).Herein,this study aims to investigate the regulatory effects of cornus officinalis,both in its raw and HPWS forms,on inflammation and apoptosis in liver fibrosis and their underlying mechanisms.In vivo liver fibrosis models were established by subcutaneous injection of CCl4,while in vitro HSCs were exposed to transforming growth factor-b(TGF-b).These findings demonstrated that cornus officinalis with HPWS conspicuously ameliorated histopathological injury,reduced the release of proinflammatory factors,and decreased collagen deposition in CCl4-induced rats compared to its raw form.Utilizing ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometer(UHPLC-QTOF-MS)combined with network analysis,we identified that the pharmacological effects of the changed components of cornus officinalis before and after HPWS,primarily centered on the adenosine phosphate(AMP)-activated protein kinase(AMPK)pathway.Of note,cornus officinalis activated AMPK and sirtuin 3(SIRT3),promoting the apoptosis of activated HSCs through the caspase cascade by regulating caspase3,caspase6 and caspase9.small interfering RNA(siRNA)experiments showed that cornus officinalis could regulate AMPK activity and its mediated-apoptosis through SIRT3.In conclusion,cornus officinalis exhibited the ability to reduce inflammation and apoptosis,with the SIRT3-AMPK signaling pathway identified as a potential mechanism underlying the synergistic effect of cornus officinalis with HPWS on anti-liver fibrosis.

关 键 词：Liver fibrosis SIRT3 Cornus officinalis AMPK Caspase6 

分 类 号：R563.1[医药卫生—呼吸系统]