Department of Orthopaedics and Traumatology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China; Key Laboratory for Metabolic Diseases in Chinese Medicine, First College of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
Department of Orthopaedics and Traumatology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
J Ethnopharmacol. 2022 Oct 28;297:115536. doi: 10.1016/j.jep.2022.115536. Epub 2022 Jul 14.
ETHNOPHARMACOLOGICAL RELEVANCE: Shaoyao Gancao Decoction (SG-Tang), originated from the Treatise on Febrile Diseases, is often used to treat OA pain symptoms. Whereas its efficacy has been verified by several clinical studies, the underlying mechanism remained unclear. Network pharmacology and UPLC-QTOF-MS analysis found that calycosin could be regarded as the active components of SG-Tang in treating OA. However, the effect of calycosin on cartilage destruction and the pathogenesis of OA are not known. Therefore, we evaluated the benefits of calycosin for OA and revealed the underlying mechanisms. AIM OF STUDY: Using network pharmacology, UPLC-QTOF-MS analysis and experiments, the active components of SG-Tang were analyzed to explore their potential therapeutic mechanism in OA. MATERIALS AND METHODS: The components of SG-Tang were detected by UPLC-QTOF-MS, and the possible active components and mechanism of SG-Tang in the treatment of OA were screened by network pharmacology. The OA mouse model was constructed by DMM. In total, 30 mice were randomly divided into three groups: Sham, DMM, and DMM + Calycosin. H&E, safranin O/fast green staining and the OARSI scores were used to evaluate joint injury in mice. In addition, OA models were established using chondrocytes treated with 10 ng/mL IL-1β. Treatment groups were treated with 100, 200 or 400 μM calycosin. CCK-8 assay was used for assessing the cytotoxic effects of calycosin. TUNEL staining and Western blotting were used to detect chondrocyte apoptosis. In addition, PI3K/Akt and NF-κB signaling pathway-related markers and cartilage matrix-related indicators were also detected. RESULTS: In vivo studies showed that calycosin inhibited IL-1β-induced IL-6 and TNF-α production, as well as iNOS and COX-2 expression. Meanwhile, calycosin could inhibit IL-1β-induced degradation of cartilage matrix, including downregulation of MMP3, MMP-13, collagen II and aggrecan. NF-κB and PI3K/AKT were also inhibited by calycosin in OA chondrocytes. Furthermore, calycosin inhibited IL-1β-induced apoptosis in mouse chondrocytes. In a mouse model of OA, our results suggest that calycosin has a chondroprotective effect. CONCLUSIONS: According to this study, calycosin may act as a protective agent against OA by inhibiting the PI3K/AKT and NF-κB pathways. Furthermore, this study suggested that calycosin is a potential candidate for the treatment of OA.
民族药理学相关性：芍药甘草汤（SG-Tang）源自《伤寒论》，常用于治疗 OA 疼痛症状。尽管已有几项临床研究证实了其疗效，但具体机制仍不清楚。网络药理学和 UPLC-QTOF-MS 分析发现，毛蕊异黄酮可以作为 SG-Tang 治疗 OA 的活性成分。然而，毛蕊异黄酮对软骨破坏和 OA 发病机制的影响尚不清楚。因此，我们评估了毛蕊异黄酮对 OA 的益处，并揭示了其潜在的作用机制。
研究目的：本研究采用网络药理学、UPLC-QTOF-MS 分析及实验方法，分析 SG-Tang 的活性成分，探讨其治疗 OA 的潜在作用机制。
材料和方法：采用 UPLC-QTOF-MS 检测 SG-Tang 的成分，通过网络药理学筛选 SG-Tang 治疗 OA 的可能活性成分和作用机制。采用 DMM 构建 OA 小鼠模型，共 30 只小鼠随机分为三组：Sham、DMM 和 DMM+毛蕊异黄酮。采用 H&E、番红 O/快绿染色和 OARSI 评分评估小鼠关节损伤情况。此外，采用 10ng/mLIL-1β 处理软骨细胞建立 OA 模型，实验组分别用 100、200 或 400μM 毛蕊异黄酮进行处理。CCK-8 检测毛蕊异黄酮的细胞毒性作用。TUNEL 染色和 Western blot 检测软骨细胞凋亡情况。此外，还检测了 PI3K/Akt 和 NF-κB 信号通路相关标志物及软骨基质相关指标。
结果：体内研究表明，毛蕊异黄酮抑制了 IL-1β 诱导的 IL-6 和 TNF-α的产生，以及 iNOS 和 COX-2 的表达。同时，毛蕊异黄酮可以抑制 IL-1β 诱导的软骨基质降解，包括下调 MMP3、MMP-13、胶原 II 和聚集蛋白聚糖。OA 软骨细胞中 NF-κB 和 PI3K/AKT 也被毛蕊异黄酮抑制。此外，毛蕊异黄酮抑制了 IL-1β 诱导的小鼠软骨细胞凋亡。在 OA 小鼠模型中，我们的结果表明毛蕊异黄酮具有软骨保护作用。
结论：根据本研究，毛蕊异黄酮可能通过抑制 PI3K/AKT 和 NF-κB 通路发挥对 OA 的保护作用。此外，本研究提示毛蕊异黄酮可能是治疗 OA 的一种潜在候选药物。
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