Ursolic acid exhibits anti-inflammatory effects through blocking TLR4-MyD88 pathway mediated by autophagy. (November 2019)

• Record Type: Journal Article
• Authors: Zhao, Jun; Zheng, Haoyi; Sui, Zhongguo; Jing, Fanbo; Quan, Xianghua; Zhao, Wenwen; Liu, Guangwei
• Is Part Of: Cytokine. Volume 123(2019)
• Publication Date: 2019-11
• Subjects: Inflammation -- Autophagy -- Macrophagy -- Acute kidney injury; AKI acute kidney injury -- BUN blood urea nitrogen -- DEX dexamethasone -- H&E haematoxylin and eosin -- LPS lipopolysaccharide -- TLR4 Toll-Like Receptor 4 -- UA ursolic acid; Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2019.05.013
• Languages: English
• ISSNs: 1043-4666

Abstract

Highlights: Ursolic acid ameliorates acute inflammation by decreasing renal injury and xylene-induced ear oedema in BALB/C mice. Ursolic acid suppresses LPS-induced inflammatory cytokine release via TLR4/MyD88 pathway in RAW264.7 cells. Ursolic acid enhances autophagy to regulate inflammatory response. Abstract: There is an urgent need for effective treatments to reduce the large and growing burden of acute kidney injury (AKI) and its consequences. Inflammation is believed to play a vital role in the pathophysiology of AKI. Macrophage autophagy is considered protective against inflammation. Previous study discovered that ursolic acid (UA), a natural pentacyclic triterpene carboxylic acid found in many plants as apples, bilberries, cranberries and so on, promoted cancer cell autophagy. In the present study, we aimed to explore the effect of UA on ameliorating AKI and the role of macrophage autophagy in the context of inflammation. The data from in vivo experiments showed that pretreatment of mice with UA significantly suppressed xylene-induced ear oedema as well as protected against LPS-induced AKI. Related mechanisms were further studied through in vitro experiment. As expected, UA decreased inflammatory factors TNF-α, IL-6 and IL-1β secretion in macrophages in response to lipopolysaccharide (LPS) stimulation. Furthermore, UA blocked LPS-induced TLR4/MyD88 pathway. More importantly, enhanced autophagy of macrophages by UA through increasing the expression of both LC3B and Beclin-1 led to alter macrophage function. What is more, similar to UA, autophagy inhibitor 3-MA obviously decreased inflammation factors releases hinting the vital role of autophagy in regulating inflammation. In all, above study suggested that UA is a potential anti-inflammatory natural compound for treating AKI by inducing autophagy.