Liao Qing, Wu Shuang, Li Xiao, Yuan Li-Xia
Traditional Chinese Pharmacological Laboratory, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510000, China.
School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510000, China.
J Ethnopharmacol. 2025 Feb 27;342:119381. doi: 10.1016/j.jep.2025.119381. Epub 2025 Jan 18.
Danggui Niantong Decoction (DGNTD) is a traditional Chinese medicine compound formula that has been demonstrated to possess efficacy in the treatment of rheumatoid arthritis (RA) and osteoarthritis (OA), as well as for dispelling moisture and relieving pain. As mentioned before, DGNTD is essential for synovial inflammation in RA. The primary features of the OA synovial membrane are low-grade inflammation, hyperplasia with enhanced fibroblast-like synoviocytes (FLS) proliferation, and fibrosis, which can cause pain and stiffness. However, it is still unknown how DGNTD functions in the OA synovium.
Clarify the influence of DGNTD on OA synovium and investigate potential mechanisms of action.
The principal constituents of DGNTD were detected using liquid chromatography-mass spectrometry (LC-MS) analysis. To evaluate the effect of DGNTD on synovial inflammation and fibrosis, a transforming growth factor beta (TGF-β)-stimulated rat FLS cell model and a rat OA animal model based on anterior cruciate ligament transection (ACLT) and partial medial meniscectomy (MMx) were employed.
Our results showed that 322 components were detected using LC-MS. In vivo, DGNTD therapy reduced pain, synovial inflammation, and fibrosis. The therapy significantly reduced levels of pain-related molecules, specifically calcitonin gene-related peptide (CGRP) and inducible nitric oxide synthase (iNOS), as well as fibrotic markers, including alpha smooth muscle actin (α-SMA) and type III collagen alpha-1 (Col3a1), in the synovium. A proteomics study demonstrated that DGNTD decreased the fibrotic protein Col3a1. DGNTD reduced the mRNA expression of pro-inflammatory and fibrotic markers (tumor necrosis factor alpha (TNF-α), interleukin-1 beta(IL-1β), interleukin-6(IL-6), α-SMA, Col3a1and TGF-β) in TGF-β-induced FLS. Furthermore, the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and validation results revealed that DGNTD inhibits synovial fibrosis via the phosphatidylinositol 3-kinase (PI3K)/protein Kinase B (AKT) signaling pathway.
DGNTD partially relieves pain, synovitis, and synovial fibrosis by regulating the PI3K/AKT pathway. These findings provide fresh information about the underlying mechanisms and successful therapy of OA, as well as a theoretical and experimental foundation for the clinical management of OA using DGNTD.
当归拈痛汤（DGNTD）是一种中药复方制剂，已被证明在治疗类风湿性关节炎（RA）和骨关节炎（OA）以及祛湿止痛方面具有疗效。如前所述，DGNTD对RA的滑膜炎症至关重要。OA滑膜的主要特征是低度炎症、增生伴成纤维样滑膜细胞（FLS）增殖增强以及纤维化，这可导致疼痛和僵硬。然而，DGNTD在OA滑膜中的作用机制仍不清楚。
阐明DGNTD对OA滑膜的影响并探究其潜在作用机制。
采用液相色谱 - 质谱（LC - MS）分析法检测DGNTD的主要成分。为评估DGNTD对滑膜炎症和纤维化的影响，使用了转化生长因子β（TGF - β）刺激的大鼠FLS细胞模型以及基于前交叉韧带横断（ACLT）和部分内侧半月板切除术（MMx）的大鼠OA动物模型。
我们的结果显示，通过LC - MS检测到322种成分。在体内，DGNTD治疗可减轻疼痛、滑膜炎症和纤维化。该治疗显著降低了滑膜中疼痛相关分子的水平，特别是降钙素基因相关肽（CGRP）和诱导型一氧化氮合酶（iNOS），以及纤维化标志物，包括α平滑肌肌动蛋白（α - SMA）和III型胶原α - 1（Col3a1）。一项蛋白质组学研究表明，DGNTD可降低纤维化蛋白Col3a1。DGNTD降低了TGF - β诱导的FLS中促炎和纤维化标志物（肿瘤坏死因子α（TNF - α）、白细胞介素 - 1β（IL - 1β）、白细胞介素 - 6（IL - 6）、α - SMA、Col3a1和TGF - β）的mRNA表达。此外，京都基因与基因组百科全书（KEGG）分析及验证结果显示，DGNTD通过磷脂酰肌醇3 - 激酶（PI3K）/蛋白激酶B（AKT）信号通路抑制滑膜纤维化。
DGNTD通过调节PI3K/AKT通路部分缓解疼痛、滑膜炎和滑膜纤维化。这些发现为OA的潜在机制和成功治疗提供了新信息，也为使用DGNTD进行OA临床管理提供了理论和实验基础。
