Acetyl-11-keto-β-boswellic acid restrains the progression of synovitis in osteoarthritis via the Nrf2/HO-1 pathway  

作　　者：Jing Zhou Xueyan Li Zeyu Han Yinhua Qian Lang Bai Qibin Han Maofeng Gao Yi Xue Dechun Geng Xing Yang Yuefeng Hao 

机构地区：[1]Orthopedics and Sports Medicine Center,the Affiliated Suzhou Hospital of Nanjing Medical University,Suzhou 215006,China [2]Gusu School,Nanjing Medical University,Suzhou 215006,China [3]Department of Anesthesia,the Affiliated Suzhou Hospital of Nanjing Medical University,Suzhou 215006,China [4]Department of Foot and Ankle Surgery,Beijing Tongren Hospital,Capital Medical University,Beijing 100730,China [5]Department of Orthopaedics,the First Affiliated Hospital of Soochow University,Suzhou 215006,China [6]Department of Orthopaedics,Changshu Hospital Affiliated to Nanjing University of Traditional Chinese Medicine,Suzhou 215500,China

出　　处：《Acta Biochimica et Biophysica Sinica》2024年第11期1644-1658,共15页生物化学与生物物理学报(英文版)

基　　金：This work was supported by the grants from the National Natural Science Foundation of China(Nos.82072425,81873991,and 81672238);the Program of Jiangsu Science and Technology Department(Nos.BK20211083 and BE2022737);the Program of Suzhou Health Commission(Nos.GSWS2020078 and SZXK202111);the Program of Suzhou Science and Technology Department(No.SKY2023062);the Jiangsu Graduate Student Cultivation Innovative Engineering Graduate Research and Practice Innovation Program(No.SJCX23_0683).

摘　　要：Synovial inflammation plays a key role in osteoarthritis(OA)pathogenesis.Fibroblast-like synoviocytes(FLSs)represent a distinct cell subpopulation within the synovium,and their unique phenotypic alterations are considered significant contributors to inflammation and fibrotic responses.The underlying mechanism by which acetyl-11-keto-β-boswellic acid(AKBA)modulates FLS activation remains unclear.This study aims to assess the beneficial effects of AKBA through both in vitro and in vivo investigations.Network pharmacology evaluation is used to identify potential targets of AKBA in OA.We evaluate the effects of AKBA on FLSs activation in vitro and the regulatory role of AKBA on the Nrf2/HO-1 signaling pathway.ML385(an Nrf2 inhibitor)is used to verify the binding of AKBA to its target in FLSs.We validate the in vivo efficacy of AKBA in alleviating OA using anterior cruciate ligament transection and destabilization of the medial meniscus(ACLT+DMM)in a rat model.Network pharma-cological analysis reveals the potential effect of AKBA on OA.AKBA effectively attenuates lipopolysaccharide(LPS)-induced abnormal migration and invasion and the production of inflammatory mediators,matrix metalloprotei-nases(MMPs),and reactive oxygen species(ROS)in FLSs,contributing to the restoration of the synovial micro-environment.After treatment with ML385,the effect of AKBA on FLSs is reversed.In vivo studies demonstrate that AKBA mitigates synovial inflammation and fibrotic responses induced by ACLT+DMM in rats via activation of the Nrf2/HO-1 axis.AKBA exhibits theoretical potential for alleviating OA progression through the Nrf2/HO-1 pathway and represents a viable therapeutic candidate for this patient population.

关 键 词：OSTEOARTHRITIS fibroblast-like synoviocytes acetyl-11-keto-β-boswellic acid NRF2 oxidative stress reactive oxygen species 

分 类 号：R593.2[医药卫生—内科学]