Thrombosis inhibited by Corydalis decumbens through regulating PI3K-Akt pathway

doi:10.1016/j.jep.2024.118177

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	Thrombosis inhibited by Corydalis decumbens through regulating PI3K-Akt pathway
	Chen, Song; Tian, Cai-Bo; Bai, Li-Yu; He, Xing-Chao; Lu, Qing-Yu; Zhao, Yun-Li; Luo, Xiao-Dong
	2024
发表期刊	JOURNAL OF ETHNOPHARMACOLOGY
ISSN	0378-8741
卷号	329 页码:118177
摘要	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-kappa B/p65, MMP1 and HIF-1 alpha 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.
DOI	10.1016/j.jep.2024.118177
WOS记录号	WOS:001238502200001
引用统计
文献类型	期刊论文
条目标识符	http://ir.kib.ac.cn/handle/151853/76323
专题	中国科学院昆明植物研究所
推荐引用方式 GB/T 7714	Chen, Song,Tian, Cai-Bo,Bai, Li-Yu,et al. Thrombosis inhibited by Corydalis decumbens through regulating PI3K-Akt pathway[J]. JOURNAL OF ETHNOPHARMACOLOGY,2024,329:118177.
APA	Chen, Song.,Tian, Cai-Bo.,Bai, Li-Yu.,He, Xing-Chao.,Lu, Qing-Yu.,...&Luo, Xiao-Dong.(2024).Thrombosis inhibited by Corydalis decumbens through regulating PI3K-Akt pathway.JOURNAL OF ETHNOPHARMACOLOGY,329,118177.
MLA	Chen, Song,et al."Thrombosis inhibited by Corydalis decumbens through regulating PI3K-Akt pathway".JOURNAL OF ETHNOPHARMACOLOGY 329(2024):118177.

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