异甘草素通过抑制 NF-κB 信号通路改善骨关节炎的进展。

Isobavachalcone ameliorates the progression of osteoarthritis by suppressing NF-κB signaling pathway.

机构信息

Department of Orthopedics, Zhengzhou University People's Hospital, Henan Provincial People's Hospital, Zhengzhou 450003, Henan, China; Department of Orthopedics, The First People's Hospital of Shangqiu, Shangqiu 476100, Henan, China.

Department of Orthopedics, Zhengzhou University People's Hospital, Henan Provincial People's Hospital, Zhengzhou 450003, Henan, China.

出版信息

Int Immunopharmacol. 2023 Jun;119:110102. doi: 10.1016/j.intimp.2023.110102. Epub 2023 Apr 24.

DOI:10.1016/j.intimp.2023.110102

PMID:37087870

Abstract

Isobavachalcone (IBC), an active component isolated from Psoralea corylifolia L., has been used extensively to treat a wide range of inflammation-associated diseases. However, little is known regarding the potential effect of IBC in the treatment of osteoarthritis (OA). The purpose of this research was to investigate the potential therapeutic effectsof IBC on OA by performingin vitroand in vivo experiments. Meanwhile, the underlying mechanism responsibles for that effect was also explored. Primary rat chondrocytes were isolated from the knee cartilage, and then pretreated with various concentrations of IBC followed by stimulation with or without LPS (1 µg/ml) for the indicated times. In vitro, the expression levels of iNOS, COX-2, MMP3, MMP13, ADAMTS5, aggrecan, and collagen II were determined by qRT-PCR, western blot, and immunofluorescence staining. In addition, western blot analysis and immunofluorescence were used to assess alterations to the NF-κB signaling pathway. In vivo, an ACLT-induced rat OA model was established in order to determine the protective effect of IBC. The results showed that IBC treatment inhibited the upregulation of inflammatory factors such as iNOS and COX-2 in response to LPS stimulation. Moreover, IBC significantly suppressed the expression of MMP-3, MMP-13, and ADAMTS5 induced by LPS in a dose-dependent manner. Furthermore, the LPS-induced reduction of collagen II and aggrecan was reversed by IBC. Mechanistically, IBC significantly decreased LPS-induced p65 phosphorylation and IκBα degradation as well as suppressed nuclear translocation of p65 in rat chondrocytes as evidenced by western blot analysis and immunofluorescence staining, indicating that IBC effectively inhibited the LPS-induced activation of the NF-κB pathway. In vivo, IBC treatment prevented cartilage degeneration in the ACLT-induced rat model. In summary, our results suggest that IBC may be able to act as a promising therapeutic drug for treating OA.

摘要

异补骨脂查尔酮（IBC）是从补骨脂中分离得到的一种活性成分，已广泛用于治疗多种炎症相关疾病。然而，关于 IBC 治疗骨关节炎（OA）的潜在作用知之甚少。本研究旨在通过体外和体内实验研究 IBC 治疗 OA 的潜在治疗效果，并探讨其潜在的作用机制。原代大鼠软骨细胞从膝关节软骨中分离出来，然后用不同浓度的 IBC 预处理，然后用或不用 LPS（1µg/ml）刺激指定时间。在体外，通过 qRT-PCR、western blot 和免疫荧光染色测定 iNOS、COX-2、MMP3、MMP13、ADAMTS5、聚集蛋白聚糖和胶原 II 的表达水平。此外，western blot 分析和免疫荧光用于评估 NF-κB 信号通路的变化。在体内，建立 ACLT 诱导的大鼠 OA 模型，以确定 IBC 的保护作用。结果表明，IBC 治疗抑制了 LPS 刺激引起的炎症因子如 iNOS 和 COX-2 的上调。此外，IBC 显著抑制了 LPS 诱导的 MMP-3、MMP-13 和 ADAMTS5 的表达呈剂量依赖性。此外，IBC 逆转了 LPS 诱导的胶原 II 和聚集蛋白聚糖的减少。机制上，IBC 显著降低了 LPS 诱导的 p65 磷酸化和 IκBα降解，以及抑制了大鼠软骨细胞中 p65 的核转位，western blot 分析和免疫荧光染色证实了这一点，表明 IBC 有效抑制了 LPS 诱导的 NF-κB 通路的激活。在体内，IBC 治疗可防止 ACLT 诱导的大鼠模型中的软骨退化。综上所述，我们的结果表明，IBC 可能是一种有前途的治疗 OA 的治疗药物。