Artemisinin derivative SM934 in the treatment of autoimmune and inflammatory diseases:therapeutic effects and molecular mechanisms  

作　　者：Xiao Tong Li Chen Shi-jun He Jian-ping Zuo 

机构地区：[1]Laboratory of Immunopharmacology,State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China [2]University of Chinese Academy of Sciences,Beijing 100049,China

出　　处：《Acta Pharmacologica Sinica》2022年第12期3055-3061,共7页中国药理学报（英文版）

基　　金：This work was supported by the National Natural Science Foundation of China(Grant Number:81871240);Science and Technology Commission of Shanghai Municipality Natural Science Foundation of Shanghai(Grant Number:22ZR1473700);Science and Technology Commission of Shanghai Municipality(Grant numbers:21S11911000,21S11907700).

摘　　要：Artemisinin and its derivatives are the well-known anti-malarial drugs derived from a traditional Chinese medicine.In addition to antimalarial,artemisinin and its derivatives possess distinguished anti-cancer,anti-oxidant,anti-inflammatory and anti-viral activities,but the poor solubility and low bioavailability hinder their clinical application.In the last decades a series of new water-soluble and oil-soluble derivatives were synthesized.Among them,we have found a water-soluble derivativeβ-aminoarteether maleate(SM934)that exhibits outstanding suppression on lymphocytes proliferation in immunosuppressive capacity and cytotoxicity screening assays with 35-fold higher potency than dihydroartemisinin.SM934 displays significant therapeutic effects on various autoimmune and inflammatory diseases,including systemic lupus erythematosus,antiphospholipid syndrome nephropathy,membranous nephropathy,rheumatoid arthritis,multiple sclerosis,inflammatory bowel disease,and dry eye disease.Here,we summarize the immunomodulatory effects,anti-inflammatory,anti-oxidative and anti-fibrosis activities of SM934 in disease-relevant animal models and present the probable pharmacological mechanisms involved in its therapeutic efficacy.This review also delineates a typical example of natural product-based drug discovery,which might further vitalize natural product exploration and development in pharmacotherapy.

关 键 词：artemisinin derivative β-aminoarteether maleate(SM934) autoimmune and inflammatory diseases T helper cells MACROPHAGES inflammatory cytokines 

分 类 号：R965[医药卫生—药理学]