Department of Infectious Diseases, Tianjin First Central Hospital, Tianjin, China.
Comb Chem High Throughput Screen. 2023;26(3):559-575. doi: 10.2174/1386207325666220421110032.
Huanglian Jiedu Decoction (HLJDD) was shown to exert a therapeutic effect on pneumonia for a long time in China. However, its pharmacological mechanism remains to be elucidated.
The active compounds and target proteins of HLJDD were screened from TCMSP, and the pneumonia targets were obtained from GeneCards. GO, and KEGG enrichment was applied in this study. Cytoscape established networks with R-Bioconductor. The affinity between components and targets was detected by molecular docking. Finally, active ingredients and targets were selected to be verified in an inflammatory model established in LPS-induced A549 cells. CCK8 proliferation assay and western blot were performed to test the relative indicators.
102 bioactive components and 205 targets from 4 herbs in HLJDD were collected. 68 potential therapeutic targets and 55 corresponding compounds were screened to establish the networks. 4 active compounds (quercetin, wogonin, kaempferol and baicalein) and 5 hub genes (IL6, AKT1, CXCL8, CCL2 and IL1B) were then selected to make molecular docking. The results indicated that quercetin and wogonin had a better affinity with CXCL8, CCL2 or IL1B. In vitro experiments revealed that quercetin and wogonin could decrease the proliferation inhibiting and apoptosis of A549 cells injured by LPS. CXCL8, CCL2 or IL1B were downregulated after quercetin or wogonin treatment, compared with LPS-induced A549 cells (P < 0.01).
The current study suggested that the mechanism of HLJDD treating pneumonia might inhibit apoptosis by targeting inflammatory factors, mainly quercetin and wogonin.
黄连解毒汤（HLJDD）在中国长期以来被证明对肺炎有治疗作用。然而，其药理机制仍有待阐明。
从 TCMSP 筛选 HLJDD 的活性化合物和靶蛋白，并从 GeneCards 和 KEGG 获得肺炎靶标。本研究应用 GO 和 KEGG 富集。Cytoscape 使用 R-Bioconductor 建立网络。通过分子对接检测成分与靶点之间的亲和力。最后，在 LPS 诱导的 A549 细胞炎症模型中验证选择的活性成分和靶点。CCK8 增殖试验和 Western blot 用于测试相关指标。
从 HLJDD 的 4 种草药中收集到 102 种生物活性成分和 205 个靶标。筛选出 68 个潜在治疗靶点和 55 个相应的化合物，建立网络。然后选择 4 种活性化合物（槲皮素、白杨素、山奈酚和黄芩素）和 5 个枢纽基因（IL6、AKT1、CXCL8、CCL2 和 IL1B）进行分子对接。结果表明，槲皮素和白杨素与 CXCL8、CCL2 或 IL1B 具有更好的亲和力。体外实验表明，槲皮素和白杨素可降低 LPS 损伤的 A549 细胞的增殖抑制和凋亡。与 LPS 诱导的 A549 细胞相比，槲皮素或白杨素处理后 CXCL8、CCL2 或 IL1B 下调（P<0.01）。
本研究表明，HLJDD 治疗肺炎的机制可能通过靶向炎症因子（主要是槲皮素和白杨素）抑制细胞凋亡。
