Chondroprotective and anti‐inflammatory effects of amurensin H by regulating TLR4/Syk/NF‐κB signals

作者：Pei Ma, Lifeng Yue, Hui Yang, Yannan Fan, Jinye Bai, Shuyi Li, Jiqiao Yuan, Ziqian Zhang, Chun‐Suo Yao, Mingbao Lin, Qi Hou · 发表于：Journal of Cellular and Molecular Medicine · 年份：2019 · DOI：10.1111/jcmm.14893 · 被引用次数：33 · 研究领域：Osteoarthritis Treatment and Mechanisms、Immune Response and Inflammation、Inflammatory mediators and NSAID effects

The low-grade, chronic inflammation initiated by TLR4-triggered innate immune responses has a central role on early osteoarthritis. Amurensin H is a resveratrol dimer with anti-inflammatory and anti-apoptotic effects, while its effects on TLR-4 signals to inhibit osteoarthritis are still unclear. In the present study, treatment with amurensin H for 2 weeks in monosodium iodoacetate-induced mice significantly slows down cartilage degeneration and inflammation using macroscopic evaluation, haematoxylin and eosin (HE) staining and micro-magnetic resonance imaging. In IL-1β-stimulated rat chondrocytes, amurensin H suppresses the production of inflammatory mediators including nitric oxide, IL-6, IL-17, PGE2 and TNF-α using Greiss and ELISA assay. Amurensin H inhibits matrix degradation via decreasing levels of MMP-9 and MMP-13 using Western blot assay, promotes synthesis of type II collagen and glycosaminoglycan using immunostaining and safranin O staining, respectively. Amurensin H inhibits intracellular and mitochondrial reactive oxygen species (ROS) generation, and mitochondrial membrane depolarization using DCFH-DA, MitoSOX Red and JC-1 assay as well. IL-1β stimulates TLR4 activation and Syk phosphorylation in chondrocytes, while amurensin H inhibits TLR4/Syk signals and downstream p65 phosphorylation and translocation in a time and dose-dependent manner. Together, these results suggest that amurensin H exerts chondroprotective effects by attenuating oxidative stress, inflamma...