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当归芍药散通过抑制 NF-κB 信号通路改善骨关节炎的进展:一项与生物信息学分析相结合的体内和体外研究。

Danggui-Shaoyao-San (DSS) ameliorates the progression of osteoarthritis via suppressing the NF-κB signaling pathway: an and study combined with bioinformatics analysis.

机构信息

Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong, China.

Guangzhou Hospital of Integrated Traditional and Western Medicine, Guangzhou 510800, Guangdong, China.

出版信息

Aging (Albany NY). 2024 Jan 8;16(1):648-664. doi: 10.18632/aging.205410.

Abstract

BACKGROUND

Osteoarthritis (OA) is a common chronic age-related joint disease characterized primarily by inflammation of synovial membrane and degeneration of articular cartilage. Accumulating evidence has demonstrated that Danggui-Shaoyao-San (DSS) exerts significant anti-inflammatory effects, suggesting that it may play an important role in the treatment of knee osteoarthritis (KOA).

METHODS

In the present study, DSS was prepared and analyzed by high-performance liquid chromatography (HPLC). Bioinformatics analyses were carried out to uncover the functions and possible molecular mechanisms by which DSS against KOA. Furthermore, the protective effects of DSS on lipopolysaccharide (LPS)-induced rat chondrocytes and cartilage degeneration in a rat OA model were investigated and .

RESULTS

In total, 114 targets of DSS were identified, of which 60 candidate targets were related to KOA. The target enrichment analysis suggested that the NF-κB signaling pathway may be an effective mechanism of DSS. , we found that DSS significantly inhibited LPS-induced upregulation of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), matrix metalloproteinase-3 (MMP3), and matrix metalloproteinase-13 (MMP13). Meanwhile, the degradation of collagen II was also reversed by DSS. Mechanistically, DSS dramatically suppressed LPS-induced activation of the nuclear factor kappa B (NF-κB) signaling pathway. , DSS treatment prevented cartilage degeneration in a rat OA model.

CONCLUSIONS

DSS could ameliorate the progression of OA through suppressing the NF-κB signaling pathway. Our findings indicate that DSS may be a promising therapeutic approach for the treatment of KOA.

摘要

背景

骨关节炎(OA)是一种常见的慢性与年龄相关的关节疾病,主要表现为滑膜炎症和关节软骨退变。越来越多的证据表明,当归芍药散(DSS)具有显著的抗炎作用,表明其可能在治疗膝骨关节炎(KOA)中发挥重要作用。

方法

本研究采用高效液相色谱法(HPLC)制备和分析 DSS。通过生物信息学分析,揭示 DSS 防治 KOA 的作用及可能的分子机制。此外,还研究了 DSS 对脂多糖(LPS)诱导的大鼠软骨细胞和软骨退变的保护作用。

结果

共鉴定出 DSS 的 114 个靶标,其中 60 个候选靶标与 KOA 相关。靶标富集分析表明,NF-κB 信号通路可能是 DSS 的有效作用机制。研究发现,DSS 可显著抑制 LPS 诱导的诱导型一氧化氮合酶(iNOS)、环氧化酶-2(COX-2)、白细胞介素-6(IL-6)、基质金属蛋白酶-3(MMP3)和基质金属蛋白酶-13(MMP13)的上调。同时,DSS 还逆转了胶原 II 的降解。机制上,DSS 显著抑制了 LPS 诱导的核因子 kappa B(NF-κB)信号通路的激活。体内研究表明,DSS 治疗可预防大鼠 OA 模型中的软骨退变。

结论

DSS 通过抑制 NF-κB 信号通路可改善 OA 的进展。我们的研究结果表明,DSS 可能是治疗 KOA 的一种有前途的治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/884a/10817397/3ba82cd682f4/aging-16-205410-g001.jpg

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