Thrombosis inhibited by Corydalis decumbens through regulating PI3K-Akt pathway

Song Chen; Cai-Bo Tian; Li-Yu Bai; Xing-Chao He; Qing-Yu Lu; Yun-Li Zhao; Xiao-Dong Luo

doi:10.1016/j.jep.2024.118177

Thrombosis inhibited by Corydalis decumbens through regulating PI3K-Akt pathway

J Ethnopharmacol. 2024 Apr 10:329:118177. doi: 10.1016/j.jep.2024.118177. Online ahead of print.

Authors

Song Chen¹, Cai-Bo Tian¹, Li-Yu Bai¹, Xing-Chao He¹, Qing-Yu Lu¹, Yun-Li Zhao², Xiao-Dong Luo³

Affiliations

¹ Yunnan Characteristic Plant Extraction Laboratory, Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, Yunnan Key Laboratory of Research and Development for Natural Products, School of Pharmacy, School of Chemical Science and Technology, Yunnan University, Kunming, 650091, PR China.
² Yunnan Characteristic Plant Extraction Laboratory, Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, Yunnan Key Laboratory of Research and Development for Natural Products, School of Pharmacy, School of Chemical Science and Technology, Yunnan University, Kunming, 650091, PR China. Electronic address: zhaoyunli@ynu.edu.cn.
³ Yunnan Characteristic Plant Extraction Laboratory, Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, Yunnan Key Laboratory of Research and Development for Natural Products, School of Pharmacy, School of Chemical Science and Technology, Yunnan University, Kunming, 650091, PR China; State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, PR China. Electronic address: xdluo@ynu.edu.cn.

PMID: 38604510
DOI: 10.1016/j.jep.2024.118177

Abstract

Ethnopharmacological relevance: Corydalis decumbens (Thunb.) Pers. was used as stasis-eliminating medicine traditionally to treat cardiovascular disease potentially attributed to its antithrombotic effect, but lack of pharmacological research on it.

Aim of the study: To investigate the antithrombotic effect of C. decumbens and its preliminary mechanism.

Materials and methods: A carrageenan-induced mouse thrombus model and adenosine diphosphate stimulated platelet aggregation of rabbits were used to confirm the inhibitory effect of C. decumbens extract and compounds on thrombosis in vivo. Then, H₂O₂-induced human umbilical vein endothelial cells (HUVECs) injury model was further adopted to verify the effects of bioactive compounds in vitro. Moreover, in silico network pharmacology analyses and molecular docking were performed to predict the underlying mechanisms, targets, and pathways, and which were further confirmed through western blotting assay.

Results: The administration of total extract (TE), total alkaloids (TA) and tetrahydropalmatine (TET) resulted in a significant reduction in black tail thrombus and congestion, along with a decreasing in platelet aggregation of rabbits. A superior antithrombotic effect indicated the bioactive fraction, and then the isolated bioactive compounds, TET and protopine (PRO) increased cell survival, and decreased reactive oxygen species (ROS) and lactate dehydrogenase (LDH) release in H₂O₂-induced HUVECs injury model. Moreover, the two alkaloids targeted 33 major proteins and influenced 153 pathways in network pharmacology prediction. Among these, HSP90AA1, COX-2, NF-κB/p65, MMP1 and HIF-1α were the key proteins and PI3K-Akt emerged as the major signaling pathway. Further western blotting results supported that five key proteins were downregulated by the two bioactive compounds in H₂O₂-stimulated HUVECs model.

Conclusion: C. decumbens exerted protective effect on thrombosis through inhibiting PI3K-Akt pathway and related key proteins, which supported the traditional use and presented potential antithrombotic alkaloids for further investigation.

Keywords: Corydalis decumbens; Network pharmacology; PI3K-Akt pathway; Platelet aggregation; Protopine; Tetrahydropalmatine; Thrombosis.