Network pharmacology and experimental validation of Maxing Shigan decoction in the treatment of influenza virus-induced ferroptosis.
10.1016/S1875-5364(23)60457-1
- Author:
Jiawang HUANG
1
;
Xinyue MA
1
;
Zexuan LIAO
1
;
Zhuolin LIU
1
;
Kangyu WANG
2
;
Zhiying FENG
2
;
Yi NING
3
;
Fangguo LU
3
;
Ling LI
4
,
5
Author Information
1. College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha 410208, China.
2. College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha 410208, China.
3. The Medicine School of Hunan University of Chinese Medicine, Changsha 410208, China.
4. College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha 410208, China
5. Hunan Provincial Key Laboratory of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha 410208, China. Electronic address: liling1049@hnucm.edu.cn.
- Publication Type:Journal Article
- Keywords:
Experimental validation;
Ferroptosis;
HIF-1 signaling pathway;
Influenza;
Maxing Shigan decoction;
Network pharmacology
- MeSH:
Animals;
Mice;
Ferroptosis;
Network Pharmacology;
Reactive Oxygen Species;
Vascular Endothelial Growth Factor A;
Influenza A virus;
Iron;
Hypoxia
- From:
Chinese Journal of Natural Medicines (English Ed.)
2023;21(10):775-788
- CountryChina
- Language:English
-
Abstract:
Influenza is an acute viral respiratory infection that has caused high morbidity and mortality worldwide. Influenza A virus (IAV) has been found to activate multiple programmed cell death pathways, including ferroptosis. Ferroptosis is a novel form of programmed cell death in which the accumulation of intracellular iron promotes lipid peroxidation, leading to cell death. However, little is known about how influenza viruses induce ferroptosis in the host cells. In this study, based on network pharmacology, we predicted the mechanism of action of Maxing Shigan decoction (MXSGD) in IAV-induced ferroptosis, and found that this process was related to biological processes, cellular components, molecular function and multiple signaling pathways, where the hypoxia inducible factor-1(HIF-1) signaling pathway plays a significant role. Subsequently, we constructed the mouse lung epithelial (MLE-12) cell model by IAV-infected in vitro cell experiments, and revealed that IAV infection induced cellular ferroptosis that was characterized by mitochondrial damage, increased reactive oxygen species (ROS) release, increased total iron and iron ion contents, decreased expression of ferroptosis marker gene recombinant glutathione peroxidase 4 (GPX4), increased expression of acyl-CoA synthetase long chain family member 4 (ACSL4), and enhanced activation of hypoxia inducible factor-1α (HIF-1α), induced nitric oxide synthase (iNOS) and vascular endothelial growth factor (VEGF) in the HIF-1 signaling pathway. Treatment with MXSGD effectively reduced intracellular viral load, while reducing ROS, total iron and ferrous ion contents, repairing mitochondrial results and inhibiting the expression of cellular ferroptosis and the HIF-1 signaling pathway. Finally, based on animal experiments, it was found that MXSGD effectively alleviated pulmonary congestion, edema and inflammation in IAV-infected mice, and inhibited the expression of ferroptosis-related protein and the HIF-1 signaling pathway in lung tissues.
