Endocrinology Department, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610072, China.
Geriatric Department, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610072, China.
J Pharm Biomed Anal. 2024 Jun 15;243:116061. doi: 10.1016/j.jpba.2024.116061. Epub 2024 Feb 20.
Diabetes mellitus type 2 and pulmonary fibrosis have been found to be closely related in clinical practice. Diabetic pulmonary fibrosis (DPF) is a complication of diabetes mellitus, but its treatment has yet to be thoroughly investigated. Bu Yang Huan Wu Decoction (BYHWD) is a well-known traditional Chinese prescription that has shown great efficacy in treating pulmonary fibrosis with hypoglycemic and hypolipidemic effects.
The active ingredients of BYHWD and the corresponding targets were retrieved from the Traditional Chinese Medicine Systematic Pharmacology Database (TCMSP) and SymMap2. Disease-related targets were obtained from the GeneCard, OMIM and CTD databases. GO enrichment and KEGG pathway enrichment were carried out using the DAVID database. AutoDock Vina software was employed to perform molecular docking. Molecular dynamics simulations of proteinligand complexes were conducted by Gromacs. Animal experiments were further performed to validate the effects of BYHWD on the selected core targets, markers of oxidative stress, serum lipids, blood glucose and pulmonary fibrosis.
A total of 84 active ingredients and 830 target genes were screened in BYHWD, among which 56 target genes intersected with DPF-related targets. Network pharmacological analysis revealed that the active ingredients can regulate target genes such as IL-6, TNF-α, VEGFA and CASP3, mainly through AGE-RAGE signaling pathway, HIF-1 signaling pathway and TNF signaling pathway. Molecular docking and molecular dynamics simulations suggested that IL6-astragaloside IV, IL6-baicalein, TNFα-astragaloside IV, and TNFα-baicalein docking complexes could bind stably. Animal experiments showed that BYHWD could reduce the expression of core targets such as VEGFA, CASP3, IL-6 and TNF-α. In addition, BYHWD could reduce blood glucose, lipid, and MDA levels in DPF while increasing the activities of SOD, CAT and GSH-Px. BYHWD attenuated the expression of HYP and collagen I, mitigating pathological damage and collagen deposition within lung tissue.
BYHWD modulates lipid metabolism disorders and oxidative stress by targeting the core targets of IL6, TNF-α, VEGFA and CASP3 through the AGE-RAGE signaling pathway, making it a potential therapy for DPF.
在临床实践中发现，2 型糖尿病和肺纤维化密切相关。糖尿病肺纤维化（DPF）是糖尿病的一种并发症，但尚未对其治疗进行彻底研究。补阳还五汤（BYHWD）是一种著名的中药方剂，具有降血糖、降血脂的作用，对肺纤维化有很好的疗效。
从中药系统药理学数据库（TCMSP）和 SymMap2 中检索 BYHWD 的活性成分及其相应靶点；从 GeneCard、OMIM 和 CTD 数据库中获取疾病相关靶点；利用 DAVID 数据库进行 GO 富集和 KEGG 通路富集；采用 AutoDock Vina 软件进行分子对接；采用 Gromacs 进行蛋白质-配体复合物的分子动力学模拟。进一步进行动物实验，验证 BYHWD 对选定的核心靶点、氧化应激标志物、血脂、血糖和肺纤维化的影响。
从 BYHWD 中筛选出 84 种活性成分和 830 个靶基因，其中 56 个靶基因与 DPF 相关靶点相交。网络药理学分析表明，活性成分可通过 AGE-RAGE 信号通路、HIF-1 信号通路和 TNF 信号通路调节 IL-6、TNF-α、VEGFA 和 CASP3 等靶基因。分子对接和分子动力学模拟表明，IL6-黄芪甲苷 IV、IL6-黄芩苷、TNFα-黄芪甲苷 IV 和 TNFα-黄芩苷对接复合物能够稳定结合。动物实验表明，BYHWD 可降低 DPF 中 VEGFA、CASP3、IL-6 和 TNF-α 等核心靶点的表达。此外，BYHWD 可降低 DPF 中的血糖、血脂和 MDA 水平，同时提高 SOD、CAT 和 GSH-Px 的活性。BYHWD 减轻了 HYP 和胶原 I 的表达，减轻了肺组织内的病理损伤和胶原沉积。
BYHWD 通过 AGE-RAGE 信号通路靶向 IL6、TNF-α、VEGFA 和 CASP3 的核心靶点，调节脂质代谢紊乱和氧化应激，为 DPF 的潜在治疗方法。
