阿江榄仁酸通过调节LPS诱导的巨噬细胞ROS/Keap1/Nrf2、MAPK和m TOR通路抑制炎症反应  

Arjunic acid alleviates inflammation via modulating ROS/Keap1/Nrf2,MAPK and mTOR pathways in LPS-stimulated macrophages

作　　者：覃秋怡 李琳 王宜海 徐静雯 何祥久 QIN Qiu-yi;LI Lin;WANG Yi-hai;XU Jing-wen;HE Xiang-jiu(School of Pharmacy,Guangdong Pharmaceutical University,Guangzhou 510006,China;Guangdong Engineering Research Center for Lead Compounds&Drug Discovery,Guangzhou 510006,China)

机构地区：[1]广东药科大学药学院,广东广州510006 [2]广东省先导化合物发现与新药研发工程技术研究中心,广东广州510006

出　　处：《药学学报》2025年第3期595-605,共11页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金面上项目(81773592)。

摘　　要：阿江榄仁酸(arjunic acid,AR)是从橡子中提取的一个主要的三萜类活性成分,具有显著的抗炎活性,但其机制并没有被报道。本研究利用脂多糖(lipopolysaccharide,LPS)诱导的RAW264.7细胞炎症模型探究了AR的抗炎活性,并通过网络药理学预测了AR治疗炎症相关疾病的潜在靶标和通路。进一步利用Griess试剂法、酶联免疫吸附实验(enzyme-linked immunosorbent assay,ELISA)、qRT-PCR和Western blot检测了促炎因子和促炎介质的表达,并同时测定了NF-κB、MAPK、Nrf2/HO-1、PI3K/Akt/mTOR和自噬通路相关蛋白的表达。结果显示,在LPS诱导的RAW264.7细胞炎症模型中,AR抑制了一氧化氮、炎症因子和炎症介质的表达,抑制了NF-κB蛋白的磷酸化和核转录,并降低了JNK和ERK的磷酸化水平。AR通过下调Keap1蛋白激活Nrf2/HO-1通路并抑制活性氧的产生发挥抗炎活性。此外,AR还通过抑制PI3K/Akt/mTOR通路活化了自噬流。综上所述,AR是一种潜在的治疗炎症相关疾病的天然产物。Arjunic acid(AR),a main bioactive triterpenoid isolated from acorns,has been reported to exert pronounced anti-inflammatory activities.However,its anti-inflammatory mechanisms have not been elucidated.In this study,the model of lipopolysaccharide(LPS)-induced inflammation in RAW264.7 cells were established to investigate the anti-inflammatory activity of AR.The potent targets and signaling pathway of AR for the treatment of inflammation-related disease were predicted based on network pharmacology.Furthermore,the expression of pro-inflammatory cytokines and mediators was determined by Griess assay,enzyme-linked immunosorbent assay(ELISA),qRT-PCR,and Western blot.The protein expression of NF-κB,MAPK,Nrf2/HO-1,PI3K/Akt/mTOR,and autophagy signaling pathways were gauged by Western blot.As the result,in the inflammatory model of LPSinduced RAW264.7 cells,AR could significantly inhibit the expression of pro-inflammatory cytokines and mediators,suppress the phosphorylation and translocation of NF-κB,and downregulate the phosphorylation of JNK/ERK signaling pathways.AR also inhibited ROS production and activated the Nrf2/HO-1 signaling pathway by degrading Keap1.Furthermore,AR activated autophagic flux by inhibiting the PI3K/Akt/mTOR signaling pathway.Collectively,AR was a potential natural product for the treatment of inflammation-related diseases.

关 键 词：阿江榄仁酸 橡子 炎症 巨噬细胞 自噬 

分 类 号：R967[医药卫生—药理学]