Dehydrocorydaline attenuates myocardial ischemia-reperfusion injury via the FoXO signalling pathway: A multimodal study based on network pharmacology, molecular docking, and experimental study

J Ethnopharmacol. 2024 Aug 31;337(Pt 1):118738. doi: 10.1016/j.jep.2024.118738.

Hongzheng Li ¹, Wenwen Yang ², Zucheng Shang ³, Yingdong Lu ⁴, Aling Shen ⁵, Daxin Chen ⁶, Guosheng Lin ⁷, Mengfan Li ⁸, Renfeng Li ⁹, Meizhu Wu ¹⁰, Zhi Guo ¹¹, Hua Qu ¹², Changgeng Fu ¹³, Zikai Yu ¹⁴, Keji Chen ¹⁵

Affiliations

1 Guang'anmen Hospital, China Academy of Chinese Medical Science, Beijing, 100053, China. Electronic address: 20180931809@bucm.edu.cn.
2 Xiyuan Hospital, China Academy of Chinese Medical Science, Beijing, 100091, China. Electronic address: werweny@163.com.
3 Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, China. Electronic address: 2221006017@fjtcm.edu.cn.
4 Guang'anmen Hospital, China Academy of Chinese Medical Science, Beijing, 100053, China. Electronic address: yingdonglu1988@126.com.
5 Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, China. Electronic address: saling86@hotmail.com.
6 Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, China. Electronic address: cdx1125@126.com.
7 Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, China. Electronic address: linguosheng@fjtcm.edu.cn.
8 Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, China. Electronic address: 1220757004@fjtcm.edu.cn.
9 Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, China. Electronic address: 2221006026@fjtcm.edu.cn.
10 Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, China. Electronic address: 1211006008@fjtcm.edu.cn.
11 Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, China. Electronic address: 1231006004@fjtcm.edu.cn.
12 Xiyuan Hospital, China Academy of Chinese Medical Science, Beijing, 100091, China. Electronic address: hua_qu@yeah.net.
13 Xiyuan Hospital, China Academy of Chinese Medical Science, Beijing, 100091, China. Electronic address: fucgbs@163.com.
14 Xiyuan Hospital, China Academy of Chinese Medical Science, Beijing, 100091, China. Electronic address: ztyuzikai@163.com.
15 Xiyuan Hospital, China Academy of Chinese Medical Science, Beijing, 100091, China. Electronic address: kejivip@163.com.

PMID: 39222757 DOI: 10.1016/j.jep.2024.118738

Abstract

Ethnopharmacological relevance: Dehydrocorydaline (DHC), an active component of Corydalis yanhusuo (Y.H. Chou & Chun C. Hsu) W.T. Wang ex Z.Y. Su & C.Y. Wu (Papaveraceae), exhibits protective and pain-relieving effects on coronary heart disease, but the underlying mechanism still remains unknown.

Aim of the study: Network pharmacology and experimental validation both in vivo and in vitro were applied to assess whether DHC can treat myocardial ischemia-reperfusion injury (MIRI) by regulating the forkhead box O (FOXO) signalling pathway to inhibit Apoptosis.

Materials and methods: DHC and MIRI targets were retrieved from various databases. Molecular docking and microscale thermophoresis (MST) determined potential binding affinity. An in vivo mouse model of MIRI was established by ligating the left anterior descending coronary artery. C57BL/6N mice were divided into sham, MIRI, and DHC (intraperitoneal injection of 5 mg/kg DHC) groups. Haematoxylin and eosin, Masson, and immunohistochemical stainings verified DHC treatment effects and the involved signalling pathways. In vitro, H9c2 cells were incubated with DHC and underwent hypoxia/reoxygenation. TUNEL, JC-1, and Reactive Oxygen Species stainings and western blots were used to explore the protective effects of DHC and the underlying mechanisms.

Results: Venny analysis identified 120 common targets from 121 DHC and 23,354 MIRI targets. DHC exhibited high affinity for CCND1, CDK2, and MDM2 (<-7 kcal/mol). In vivo, DHC attenuated decreases in left ventricular ejection fraction and fractional shortening, reduced infarct sizes, and decreased cTnI and Lactate Dehydrogenase levels. In vitro, DHC alleviated Apoptosis and oxidative stress in the hypoxia/reoxygenation model by attenuating ΔΨm disruption; reducing the production of reactive oxygen species; upregulating Bax and CCND1 via the FOXO signalling pathway, as well as cleaved-caspase 8; downregulating the apoptosis-associated proteins Bcl-2, Bid, cleaved-caspase 3, and cleaved-caspase 9; and promoting the phosphorylation of FOXO1A and MDM2.

Conclusion: By upregulating the FOXO signaling pathway to inhibit Apoptosis, DHC exerts a cardioprotective effect, which could serve as a potential therapeutic option for MIRI.

Keywords

Dehydrocorydaline; Experimental validation; Hypoxia/reoxygenation; Myocardial ischemia-reperfusion injury; Network pharmacology.

Products

Cat. No.

Product Name

Description

Target

Research Area
HY-N0674

Dehydrocorydaline

99.77%, Alkaloid

Bcl-2 Family; Caspase; PARP; p38 MAPK; Parasite; Autophagy

Infection; Cancer

Name
Email *

	Sorry, but the email address you supplied was invalid.