Quercetin inhibits platelet activation and ER-stress mediated autophagy in response to extracellular histone

Manikanta, K. and Naveenkumar, S. K. and Hemshekhar, M. and Thushara, R. M. and Mugesh, G. and Kemparaju, K. and Girish, K. S. (2025) Quercetin inhibits platelet activation and ER-stress mediated autophagy in response to extracellular histone. Phytomedicine, 138. ISSN 0944-7113

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Abstract

Background: Cellular histones are DNA-binding nuclear proteins involved in chromatin remodelling and regulation of gene expression. However, extracellular histones act as damage-associated molecular patterns (DAMPs) and contribute to multiorgan damage in conditions with sepsis and diseases with acute critical illnesses. Alongside, histones are associated with thrombocytopenia due to dysfunctional platelets that regulate hemostasis and thrombosis. There is no drug available to prevent histone-induced platelet toxicity. Therefore, we for the first time examined quercetin (QUE) as a novel therapeutic to protect histone-induced platelet toxicity. Purpose: To delineate how histones induce platelet toxicity and investigate the protective efficacy of quercetin (QUE), a natural dietary phytochemical. Study design/method: Histone-treated platelets were evaluated for platelet aggregation/activation markers, various autophagy-related signaling proteins, and cytotoxicity in vitro. For the inhibition study, QUE and other standard inhibitors were pre-treated before stimulation with histones. Further, we injected histones into mice in the presence or absence of QUE and evaluated the tail bleeding, lung toxicity, and circulatory platelet stress markers. Additionally, QUE-treated mice were challenged for histone-primed Collagen-epinephrine-induced pulmonary thromboembolism.

Item Type:	Article
Uncontrolled Keywords:	Platelets,Extracellular histone, Quercetin, Platelet aggregation, ER stress-autophagy
Subjects:	C Chemical Science > Biochemistry
Divisions:	Department of > Biochemistry
Depositing User:	Ms Varalakshmi
Date Deposited:	04 Nov 2025 06:07
Last Modified:	04 Nov 2025 06:07
URI:	http://eprints.uni-mysore.ac.in/id/eprint/17902

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