Investigation of Efficacy and Mechanism of Zukamu Granules on Hypoxic Pulmonary Hypertension
10.3870/j.issn.1004-0781.2024.04.011
- VernacularTitle:祖卡木颗粒对低氧性肺动脉高压的药效及机制研究
- Author:
Ruiqi LIU
1
,
2
;
Tianyi YUAN
;
Ranran WANG
;
Ruifang ZHENG
;
Difei GONG
;
Shoubao WANG
;
Jianguo XING
;
Guanhua DU
;
Lianhua FANG
Author Information
1. 中国医学科学院,北京协和医学院药物研究所,天然药物活性物质与功能国家重点实验室,北京 100050
2. 中国医学科学院,北京协和医学院药物研究所,药物靶点研究与新药筛选北京市重点实验室,北京 100050
- Keywords:
Zukamu granules;
Hypoxic pulmonary hypertension;
Network pharmacology;
Pharmacodynamic mecha-nisms;
Bcl-Associated X/B-cell lymphoma;
Phosphoinositide 3-kinase-endothelial nitric oxidase synthase/hypoxia-inducible fac-tor-1α
- From:
Herald of Medicine
2024;43(4):550-560
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore and verify the protective and therapeutic effects and possible mechanisms of Zukamu granules on hypoxia alone and hypoxia+Su5416-induced hypoxic pulmonary hypertension(HPH)in mice.Methods Multiple databases and related literature were used to collect the active ingredients data in Zukamu granules and the HPH-related targets were predicted and obtained.The network construction and enrichment analysis were performed.The HPH mouse models were es-tablished by two-week hypoxia and four-week hypoxia+Su5416 induction,and the relevant indicators and the main pharmacodyna-mic indexes such as right ventricular pressure were tested.Masson staining was used to observe the pathological changes in lung tissues,and Western blotting was used to detect the expression levels of bax,bcl-2,PI3K,p-PI3K,eNOS,and HIF-1α in lung tis-sues.Results A total of 167 active ingredients of Zukamu granules were screened,with 179 intersecting targets with HPH,in-cluding targets like PIK3CA and HIF-1.The validation experimental results showed that Zukamu granules could significantly re-duce right ventricular systolic pressure and right ventricular hypertrophy in HPH mice,and down-regulate the expression of bcl-2 and HIF-1α and up-regulate the expression of bax,PI3K,p-PI3K and eNOS in mice lung tissues.Conclusion Zukamu gran-ules may act against HPH by modulating bax/bcl and PI3K-eNOS/HIF-1α signaling pathways.
