Deciphering the molecular mechanism of Bu Yang Huan Wu Decoction in interference with diabetic pulmonary fibrosis via regulating oxidative stress and lipid metabolism disorder.

Autor: Guo J; Endocrinology Department, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610072, China., Zhang Y; Geriatric Department, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610072, China., Zhou R; Geriatric Department, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610072, China., Hao Y; Geriatric Department, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610072, China., Wu X; Geriatric Department, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610072, China., Li G; Geriatric Department, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610072, China., Du Q; Endocrinology Department, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610072, China; TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Chengdu, Sichuan 610072, China. Electronic address: quanydu@cdutcm.edu.cn.
Jazyk: angličtina
Zdroj: Journal of pharmaceutical and biomedical analysis [J Pharm Biomed Anal] 2024 Jun 15; Vol. 243, pp. 116061. Date of Electronic Publication: 2024 Feb 20.
DOI: 10.1016/j.jpba.2024.116061
Abstrakt: Background: 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.
Methods: 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.
Results: 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.
Conclusions: 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.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: