Ephedra Herb extract ameliorates adriamycin-induced nephrotic syndrome in rats via the CAMKK2/AMPK/mTOR signaling pathway  

作　　者：ZHANG Yuhan ZENG Mengnan LI Benke ZHANG Beibei CAO Bing WU Yuanyuan YE Shan XU Ruiqi ZHENG Xiaoke FENG Weisheng 

机构地区：[1]College of Pharmacy,Henan University of Chinese Medicine,Zhengzhou 450000,China [2]The Engineering and Technology Center for Chinese Medicine Development of Henan province,Zhengzhou 450000,China [3]Co-construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan&Education Ministry of P.R.,Zhengzhou 450000,China

出　　处：《Chinese Journal of Natural Medicines》2023年第5期371-382,共12页中国天然药物（英文版）

基　　金：the National Key Research and Development Project(Nos.2019YFC1708802 and 2017YFC1702800);Henan province high-level personnel special support“ZhongYuan One Thousand People Pla”,Zhongyuan Leading Talent(No.ZYQR201810080);the Major Science and Technology Projects in Henan Province:Study on the key technology for quality control and the key characteristics of Rehmannia glutinosa,Dioscorea opposita Thunb.and Achyranthes bidentata Blume from Henan Province(No.171100310500).

摘　　要：This study aimed to investigate the effect and mechanisms of Ephedra Herb(EH)extract on adriamycin-induced nephrotic syndrome(NS),providing an experimental basis for the clinical treatment of NS.Hematoxylin and eosin staining,creatinine,urea nitrogen,and kidn injury molecule-1 were used to evaluate the activities of EH extract on renal function.The levels of inflammatory factors and oxidative stress were detected by kits.The levels of reactive oxygen species,immune cells,and apoptosis were measured by flow cytometry.A network pharmacological approach was used to predict the potential targets and mechanisms of EH extract in the treatment of NS.The protein levels of apoptosis-related proteins and CAMKK2,p-CAMKK2,AMPK,p-AMPK,mTOR and p-mTOR in the kidneys were detected by Western blot.The effective material basis of EH extract was screened by MTT assay.The AMPK pathway inhibitor(compound C,CC)was added to investigate the effect of the potent material basis on adriamycin-induced cell injury.EH extract significantly improved renal injury and relieve inflammation,oxidative stress,and apoptosis in rats.Network pharmacology and Western blot results showed that the effect of EH extract on NS may be associated with the CAMKK2/AMPK/mTOR signaling pathway.Moreover,methylephedrine significantly ameliorated adriamycin-induced NRK-52e cell injury.Methylephedrine also significantly improved the phosphorylation of AMPK and mTOR,which were blocked by CC.In sum,EH extract may ameliorate renal injury via the CAMKK2/AMPK/mTOR signaling pathway.Moreover,methylephedrine may be one of the material bases of EH extract.

关 键 词：Ephedra Herb Methylephedrine ADRIAMYCIN Nephrotic syndrome CAMKK2/AMPK/mTOR pathway 

分 类 号：R965[医药卫生—药理学]