Ethnopharmacological relevance

Darutigenol (DL) is a natural active product derived from the Chinese herbal medicine Sigesbeckia glabrescens (Makino) Makino. It is administered as a traditional Chinese medicine (TCM) to dispel rheumatism, benefit the joints, and detoxify. However, its potential mechanism in the treatment of rheumatoid arthritis (RA) remains unknown.

Aims of the study

The objectives of this research were to determine the effects and elucidate the modes of action of DL on RA-related joint inflammation.

Materials and methods

Network pharmacology and molecular docking were used to screen and validate candidate DL targets for RA treatment, respectively. A DBA/1 mouse rheumatoid arthritis model was induced with bovine type II collagen. Intragastric DL administration was followed by the calculation of the clinical arthritis index. A section of the ankle joint was excised and stained and the pathological changes in it were observed. Enzyme-linked immunosorbent assays (ELISA) and western blotting (WB) were used to clarify the mechanisms of DL in RA treatment.

Results

DL effectively attenuated the inflammation, mitigated the articular cartilage degradation, and bone erosion, and alleviated the inflammatory joints associated with RA. Network pharmacology screened six key targets of DL while molecular docking revealed that it docked well with its protein targets. The DL treatment group presented with significantly less ankle joint redness and swelling, a lower arthritis index scores and serum and bone marrow supernatant IL-6 levels, more complete ankle joint surfaces, and less synovial inflammation, cartilage degradation, and bone erosion than the collagen-induced arthritis (CIA) group. The DL treatment also substantially downregulated the Janus kinase (JAK)1, JAK3, matrix metalloproteinase (MMP)2, MMP9, and phospho-signal transducer and activator of transcription (p-STAT)3 proteins in the joints.

Conclusions

To the best of our knowledge, the present work was the first to demonstrate that DL has significant anti-inflammatory efficacy and reduces cartilage degradation and bone erosion. It also demonstrated that the anti-RA effect of DL may be explained by its ability to inhibit joint inflammation and reduce articular cartilage degradation through the interleukin (IL)-6/JAK1,3/STAT3 axis and downregulate MMP2 and MMP9. Hence, DL might play a therapeutic role in a mouse RA model.

中文翻译：

---

综合网络药理学方法表明，Darutigenol 通过抑制 JAK-STAT3 通路减少小鼠胶原诱导的关节炎模型中的炎症和软骨退化

民族药理学相关性

Darutigenol (DL) 是一种天然活性产物，源自中药草木螽 ( Sigesbeckia glabrescens (Makino) Makino)。它作为传统中药 (TCM) 服用，可祛风湿、益关节和解毒。然而，其治疗类风湿性关节炎 (RA) 的潜在机制仍然未知。

研究目的

本研究的目的是确定 DL 对 RA 相关关节炎症的影响并阐明其作用方式。

材料和方法

网络药理学和分子对接分别用于筛选和验证用于 RA 治疗的候选 DL 靶点。用牛 II 型胶原蛋白诱导 DBA/1 小鼠类风湿性关节炎模型。胃内 DL 给药后计算临床关节炎指数。取一段踝关节进行染色，观察其病理变化。酶联免疫吸附测定 (ELISA) 和蛋白质印迹 (WB) 用于阐明 DL 在 RA 治疗中的机制。

结果

DL 有效减轻炎症，减轻关节软骨退化和骨侵蚀，并减轻与 RA 相关的炎症关节。网络药理学筛选了 DL 的六个关键靶点，而分子对接显示它与其蛋白质靶点对接良好。与胶原蛋白相比，DL治疗组踝关节红肿明显减少，关节炎指数评分和血清及骨髓上清液IL-6水平降低，踝关节表面更完整，滑膜炎症、软骨退化和骨侵蚀更少诱导性关节炎 (CIA) 组。DL 治疗还显着下调关节中的 Janus 激酶 (JAK)1、JAK3、基质金属蛋白酶 (MMP)2、MMP9 和磷酸信号转导和转录激活因子 (p-STAT)3 蛋白。

结论

据我们所知，目前的工作首次证明 DL 具有显着的抗炎功效并减少软骨退化和骨侵蚀。它还表明，DL 的抗 RA 作用可以通过其抑制关节炎症和通过白细胞介素 (IL)-6/JAK1,3/STAT3 轴减少关节软骨退化以及下调 MMP2 和 MMP9 的能力来解释。因此，DL 可能在小鼠 RA 模型中发挥治疗作用。