Cucurbitacin B attenuates osteoarthritis development by inhibiting NLRP3 inflammasome activation and pyroptosis through activating Nrf2 / HO ‐1 pathway

作者：Chao Lou, Yuqin Fang, Yifan Mei, Wei Hu, Liaojun Sun, Chen Jin, Hua Chen, Wenhao Zheng · 发表于：Phytotherapy Research · 年份：2024 · DOI：10.1002/ptr.8209 · 被引用次数：27 · 研究领域：Inflammasome and immune disorders、Natural product bioactivities and synthesis、Circular RNAs in diseases

Osteoarthritis (OA) is a complicated joint disorder characterized by inflammation that causes joint destruction. Cucurbitacin B (CuB) is a naturally occurring triterpenoid compound derived from plants in the Cucurbitaceae family. The aim of this study is to investigate the potential role and mechanisms of CuB in a mouse model of OA. This study identified the key targets and potential pathways of CuB through network pharmacology analysis. In vivo and in vitro studies confirmed the potential mechanisms of CuB in OA. Through network pharmacology, 54 potential targets for CuB in treating OA were identified. The therapeutic potential of CuB is associated with the nod-like receptor pyrin domain 3 (NLRP3) inflammasome and pyroptosis. Molecular docking results indicate a strong binding affinity of CuB to nuclear factor erythroid 2-related factor 2 (Nrf2) and p65. In vitro experiments demonstrate that CuB effectively inhibits the expression of pro-inflammatory factors induced by interleukin-1β (IL-1β), including cyclooxygenase-2, inducible nitric oxide synthase, IL-1β, and IL-18. CuB inhibits the degradation of type II collagen and aggrecan in the extracellular matrix (ECM), as well as the expression of matrix metalloproteinase-13 and a disintegrin and metalloproteinase with thrombospondin motifs-5. CuB protects cells by activating the Nrf2/hemeoxygenase-1 (HO-1) pathway and inhibiting nuclear factor-κB (NF-κB)/NLRP3 inflammasome-mediated pyroptosis. Moreover, in vivo experiments show...