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Thromb Haemost 2022; 122(05): 739-754
DOI: 10.1055/s-0041-1735192
Cellular Haemostasis and Platelets

Tetrahydrocurcumin Downregulates MAPKs/cPLA2 Signaling and Attenuates Platelet Thromboxane A2 Generation, Granule Secretion, and Thrombus Growth

Weiqi Li‡   *
1   Department of Nutrition, School of Public Health, Dali University, Dali, Yunnan Province, China
,
Yongjie Ma‡   *
1   Department of Nutrition, School of Public Health, Dali University, Dali, Yunnan Province, China
,
Chunmei Zhang
1   Department of Nutrition, School of Public Health, Dali University, Dali, Yunnan Province, China
2   Hekou Customs of the People's Republic of China, Hekou, Yunnan Province, China
,
Binlin Chen
3   Department of Nutrition, Maternity and Child Health Care of Guangxi Zhuang Autonomous Region, Nanning, Guangxi Zhuang Autonomous Region, China
,
Xiandan Zhang
4   Department of Nutrition, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi Zhuang Autonomous Region, China
,
Xin Yu
5   Department of Human Anatomy, School of Basic Medicine, Dali University, Dali, Yunnan Province, China
6   Institute of Translational Medicine for Metabolic Diseases, School of Basic Medicine, Dali University, Dali, Yunnan Province, China
,
Hongyan Shuai
5   Department of Human Anatomy, School of Basic Medicine, Dali University, Dali, Yunnan Province, China
6   Institute of Translational Medicine for Metabolic Diseases, School of Basic Medicine, Dali University, Dali, Yunnan Province, China
,
Qilian He
6   Institute of Translational Medicine for Metabolic Diseases, School of Basic Medicine, Dali University, Dali, Yunnan Province, China
7   Department of Internal Medicine Nursing, School of Nursing, Dali University, Dali, Yunnan Province, China
,
Fuli Ya
1   Department of Nutrition, School of Public Health, Dali University, Dali, Yunnan Province, China
› Author Affiliations Funding This work was supported by the National Natural Science Foundation of China (grant No. 82003451), Yunnan Fundamental Research Projects (grant No. 202001AT070068), and the Start-up Fund for Introduction of High-level Talents to Dali University (grant No. KY2096107240).
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Abstract

Platelet granule secretion plays a key role in atherothrombosis. Curcumin, a natural polyphenol compound derived from turmeric, exerts multiple biological activities. The current study sought to investigate the efficacy of tetrahydrocurcumin (THC, the major active metabolite of curcumin) on platelet granule secretion in vitro and thrombus formation in vivo. We found that THC significantly attenuated agonist-induced granule secretion in human gel-filtered platelets in vitro, including CD62P and CD63 expression and platelet factor 4, CCL5, and adenosine triphosphate release. These inhibitory effects of THC were partially mediated by the attenuation of cytosolic phospholipase A2 (cPLA2) phosphorylation, leading to a decrease in thromboxane A2 (TxA2) generation. Moreover, the MAPK (Erk1/2, JNK1/2, and p38 MAPK) signaling pathways were downregulated by THC treatment, resulting in reduced cPLA2 activation, TxA2 generation, and granule secretion. Additionally, THC and curcumin attenuated murine thrombus growth in a FeCl3-induced mesenteric arteriole thrombosis model in C57BL/6J mice without prolonging the tail bleeding time. THC exerted more potent inhibitory effects on thrombosis formation than curcumin. Through blocking cyclooxygenase-1 activity and thus inhibiting platelet TxA2 synthesis and granule secretion with aspirin, we found that THC did not further decrease the inhibitory effects of aspirin on thrombosis formation. Thus, through inhibiting MAPKs/cPLA2 signaling, and attenuating platelet TxA2 generation, granule secretion, and thrombus formation, THC may be a potent cardioprotective agent.

Keywords

tetrahydrocurcumin - platelet granule - cytosolic phospholipase A2 - thromboxane A2 - thrombosis

* Weiqi Li and Yongjie Ma contributed equally to this work.


Supplementary Material



Publication History

Received: 03 March 2021

Accepted: 19 July 2021

Article published online:
24 August 2021

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