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

Weiqi Li; Yongjie Ma; Chunmei Zhang; Binlin Chen; Xiandan Zhang; Xin Yu; Hongyan Shuai; Qilian He; Fuli Ya

doi:10.1055/s-0041-1735192

Thrombosis and Haemostasis, Table of Contents

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‡^*

¹Department of Nutrition, School of Public Health, Dali University, Dali, Yunnan Province, China

,

Yongjie Ma‡^*

¹Department of Nutrition, School of Public Health, Dali University, Dali, Yunnan Province, China

,

Chunmei Zhang

¹Department of Nutrition, School of Public Health, Dali University, Dali, Yunnan Province, China

²Hekou Customs of the People's Republic of China, Hekou, Yunnan Province, China

,

Binlin Chen

³Department of Nutrition, Maternity and Child Health Care of Guangxi Zhuang Autonomous Region, Nanning, Guangxi Zhuang Autonomous Region, China

,

Xiandan Zhang

⁴Department of Nutrition, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi Zhuang Autonomous Region, China

,

Xin Yu

⁵Department of Human Anatomy, School of Basic Medicine, Dali University, Dali, Yunnan Province, China

⁶Institute of Translational Medicine for Metabolic Diseases, School of Basic Medicine, Dali University, Dali, Yunnan Province, China

,

Hongyan Shuai

⁵Department of Human Anatomy, School of Basic Medicine, Dali University, Dali, Yunnan Province, China

⁶Institute of Translational Medicine for Metabolic Diseases, School of Basic Medicine, Dali University, Dali, Yunnan Province, China

,

Qilian He

⁶Institute of Translational Medicine for Metabolic Diseases, School of Basic Medicine, Dali University, Dali, Yunnan Province, China

⁷Department of Internal Medicine Nursing, School of Nursing, Dali University, Dali, Yunnan Province, China

,

Fuli Ya

¹Department of Nutrition, School of Public Health, Dali University, Dali, Yunnan Province, China

› Author Affiliations

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

Full Text

References

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Supplementary Material

Supplementary Material