Abstract
Intervertebral disc degeneration(IDD)is the cause of low back pain(LBP),and recent research has suggested that inflammatory cytokines play a significant role in this process.Maslinic acid(MA),a natural compound found in olive plants(Olea europaea),has anti-inflammatory properties,but its potential for treating IDD is unclear.The current study aims to investigate the effects of MA on TNFα-induced IDD in vitro and in other in vivo models.Our findings suggest that MA ameliorates the imbalance of the extracellular matrix(ECM)and mitigates senescence by upre-gulating aggrecan and collagen Ⅱ levels as well as downregulating MMP and ADAMTS levels in nucleus pulposus cells(NPCs).It can also impede the progression of IDD in rats.We further find that MA significantly affects the PI3K/AKT and NF-κB pathways in TNFα-induced NPCs determined by RNA-seq and experimental verification,while the AKT agonist Sc-79 eliminates these signaling cascades.Furthermore,molecular docking simulation shows that MA directly binds to PI3K.Dysfunction of the PI3K/AKT pathway and ECM metabolism has also been confirmed in clinical specimens of degenerated nucleus pulposus.This study demonstrates that MA may hold promise as a therapeutic agent for alleviating ECM metabolism disorders and senescence to treat IDD.
基金项目
国家自然科学基金(82072473)
国家自然科学基金(82202041)
国家自然科学基金(82202653)
中国博士后科学基金(2021M703730)
Guangdong Basic and Applied Basic Research Foundation(2020A1515110226)
Guangdong Basic and Applied Basic Research Foundation(2022A1515012459)
Guangdong Basic and Applied Basic Research Foundation(2021A1515012619)
Medical Science and Technology Foundation of Guangdong Province(A2023092)
国家科技期刊平台
NSTL
万方数据