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在骨关节炎中,新蛇床子素通过JAK2/核因子-κB/hsa-miR-4282途径阻断NLRP3炎性小体,减轻白细胞介素-1β引发的细胞焦亡。

Notopterol mitigates IL-1β-triggered pyroptosis by blocking NLRP3 inflammasome via the JAK2/NF-kB/hsa-miR-4282 route in osteoarthritis.

作者信息

Chen Ko-Ta, Yeh Chi-Tai, Yadav Vijesh Kumar, Pikatan Narpati Wesa, Fong Iat-Hang, Lee Wei-Hwa, Chiu Yen-Shuo

机构信息

Department of Orthopedics, Taipei Medical University Hospital, Taipei, 11031, Taiwan.

Department of Medical Research, Shuang Ho Hospital, Taipei Medical University, New Taipei City, 23561, Taiwan.

出版信息

Heliyon. 2024 Mar 13;10(6):e28094. doi: 10.1016/j.heliyon.2024.e28094. eCollection 2024 Mar 30.

Abstract

OBJECTIVE

Osteoarthritis (OA), the most prevalent form of arthritis, impacts approximately 10% of men and 18% of women aged above 60 years. Currently, a complete cure for OA remains elusive, making clinical management challenging. The traditional Chinese herb , integral to the Juanbi pill for rheumatism, shows promise in safeguarding chondrocytes through its strong anti-inflammatory effects.

METHODS

To explore the protective effect of notopterol and miRNA (has-miR-4248) against inflammation, we simulated an inflammatory environment in chondrocytes cell lines C20A4 and C28/12, focusing on inflammasome formation and pyroptosis.

RESULTS

Our finding indicates notopterol significantly reduced interleukin (IL)-18 and tumor necrosis factor (TNF)-alpha levels in inflamed cells, curtailed reactive oxygen species (ROS) production post-inflammation, and inhibited the JAK2/STAT3 signaling pathway, thus offering chondrocytes protection from inflammation. Importantly, notopterol also hindered inflammasome assembly and pyroptosis by blocking the NF-κB/NLRP3 pathway through hsa-miR-4282 modulation. experiments showed that notopterol treatment markedly decreased Osteoarthritis Research Society International (OARSI) scores in OA mice and boosted hsa-miR-4282 expression compared to control groups.

CONCLUSIONS

This study underscores notopterol's potential as a therapeutic agent in OA treatment, highlighting its capacity to shield cartilage from inflammation-induced damage, particularly by preventing pyroptosis.

摘要

目的

骨关节炎(OA)是最常见的关节炎形式,影响着约10%的60岁以上男性和18%的60岁以上女性。目前,OA的完全治愈仍然难以实现,这使得临床管理具有挑战性。传统中药,是治疗风湿的蠲痹丸的主要成分,因其强大的抗炎作用,在保护软骨细胞方面显示出前景。

方法

为了探究羌活醇和微小RNA(hsa-miR-4248)的抗炎保护作用,我们在软骨细胞系C20A4和C28/12中模拟炎症环境,重点关注炎性小体的形成和细胞焦亡。

结果

我们的研究结果表明,羌活醇显著降低了炎症细胞中白细胞介素(IL)-18和肿瘤坏死因子(TNF)-α的水平,减少了炎症后活性氧(ROS)的产生,并抑制了JAK2/STAT3信号通路,从而为软骨细胞提供抗炎保护。重要的是,羌活醇还通过调节hsa-miR-4282阻断NF-κB/NLRP3途径,阻碍炎性小体的组装和细胞焦亡。实验表明,与对照组相比,羌活醇治疗显著降低了OA小鼠的国际骨关节炎研究学会(OARSI)评分,并提高了hsa-miR-4282的表达。

结论

本研究强调了羌活醇在OA治疗中作为治疗药物的潜力,突出了其保护软骨免受炎症诱导损伤的能力,特别是通过防止细胞焦亡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9a3/10963379/94f214ce4647/gr1.jpg

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