Department of Graduate School, Beijing University of Chinese Medicine, Beijing, People's Republic of China.
Department of Immunology and Microbiology, School of Life Sciences, Beijing University of Chinese Medicine, Beijing, People's Republic of China.
Drug Des Devel Ther. 2021 Oct 8;15:4259-4273. doi: 10.2147/DDDT.S326029. eCollection 2021.
Hudi enteric-coated capsule (HDC) is a Chinese medicine prescribed to treat ulcerative colitis (UC). However, its anti-inflammatory active ingredients and mechanisms remain unknown. This study aimed to investigate the active components of HDC and explore its potential mechanisms against UC by integrating network pharmacology and experimental verification.
A DSS-induced colitis murine model was established to validate the efficacy of HDC by detecting disease activity index (DAI) and histopathological changes. Network pharmacological analysis was performed to identify the active compounds and core targets of HDC for the treatment of UC. The main compounds in HDC were identified by high-performance liquid chromatography. The relative expressions of HDC's core targets were also determined in vivo. Finally, molecular docking was applied to model the interaction between HDC and target proteins.
In an in vivo experiment, HDC, especially the middle-dose HDC, effectively reduced clinical symptoms of UC, including weight loss, bloody stool, and colon shortening. Besides, the severity of colitis was considerably suppressed by HDC as evidenced by reduced DAI scores. A total of 118 active compounds and 69 candidate targets from HDC closely related to UC progression were identified via network pharmacology. Enrichment analysis revealed that the key targets of HDC correlated with the expressions of , and . Meanwhile, these cytokines were enriched in various biological processes through the IL-17/JAK2/STAT3 signaling pathway. The middle-dose HDC contributed more to ameliorating DSS-induced colitis through this signaling pathway than other dosages. Nine components binding to JAK2, STAT3, IL-17 and IL-6 were identified by molecular docking, confirming again the inhibition effects of HDC on the IL-17/JAK2/STAT3 signaling pathway.
The HDC treatment, particularly the middle-dose, exerted an anti-UC effect in a multi-component, multi-target, and multi-mechanism manner, especially inhibiting the IL-17/JAK2/STAT3 signaling pathway to downregulate the secretion of proinflammatory cytokines.
和胃胶囊（HDC）是一种治疗溃疡性结肠炎（UC）的中药。然而，其抗炎活性成分和机制尚不清楚。本研究旨在通过整合网络药理学和实验验证，研究 HDC 的活性成分及其治疗 UC 的潜在机制。
采用 DSS 诱导的结肠炎小鼠模型，通过检测疾病活动指数（DAI）和组织病理学变化来验证 HDC 的疗效。通过网络药理学分析鉴定 HDC 治疗 UC 的活性化合物和核心靶点。采用高效液相色谱法鉴定 HDC 中的主要化合物。还在体内测定了 HDC 的核心靶点的相对表达。最后，应用分子对接构建 HDC 与靶蛋白的相互作用模型。
在体内实验中，HDC，特别是中剂量 HDC，能有效减轻 UC 的临床症状，包括体重减轻、血便和结肠缩短。此外，HDC 能显著抑制结肠炎的严重程度，表现为 DAI 评分降低。通过网络药理学鉴定出 118 种与 UC 进展密切相关的 HDC 活性化合物和 69 个候选靶点。富集分析表明，HDC 的关键靶点与 的表达有关。同时，这些细胞因子通过 IL-17/JAK2/STAT3 信号通路富集在各种生物学过程中。与其他剂量相比，中剂量 HDC 通过该信号通路对 DSS 诱导的结肠炎的改善作用更大。通过分子对接鉴定出 9 种与 JAK2、STAT3、IL-17 和 IL-6 结合的成分，再次证实了 HDC 对 IL-17/JAK2/STAT3 信号通路的抑制作用。
HDC 治疗，特别是中剂量，以多成分、多靶点、多机制的方式发挥抗 UC 作用，特别是抑制 IL-17/JAK2/STAT3 信号通路，下调促炎细胞因子的分泌。
