Piperine Inhibits the Activities of Platelet Cytosolic Phospholipase A2 and Thromboxane A2 Synthase without Affecting Cyclooxygenase-1 Activity: Different Mechanisms of Action Are Involved in the Inhibition of Platelet Aggregation and Macrophage Inflammatory Response

Nutrients

Dong Ju Son³  Satoshi Akiba²  Jin Tae Hong⁴  Yeo Pyo Yun⁴  Seock Yeon Hwang¹  Young Hyun Park⁵ 

[1] Department of Biomedical Laboratory Science, College of Natural Science, Daejeon 300-716, Korea; E-Mail:;Department of Pathological Biochemistry, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan; E-Mail:;School of Applied Biosciences, Kyungpook National University, Daegu 702-701, Korea; E-Mail:;College of Pharmacy and Center for Innovative Cancer Therapeutics, Chungbuk National University, Cheongju 361-763, Korea; E-Mails:;Department of Food Science and Nutrition, College of Natural Sciences, Soonchunhayng University, Asan 336-745, Korea

关键词: pepper;    piperine;    platelet aggregation;    arachidonic acid;    cyclooxygenase;    phospholipase A₂;    thromboxane A₂ synthase;    prostaglandins;   

DOI  :  10.3390/nu6083336

来源: mdpi

【 摘 要 】

PURPOSE: Piperine, a major alkaloid of black pepper (Piper nigrum) and long pepper (Piper longum), was shown to have anti-inflammatory activity through the suppression of cyclooxygenase (COX)-2 gene expression and enzyme activity. It is also reported to exhibit anti-platelet activity, but the mechanism underlying this action remains unknown. In this study, we investigated a putative anti-platelet aggregation mechanism involving arachidonic acid (AA) metabolism and how this compares with the mechanism by which it inhibits macrophage inflammatory responses; METHODS: Rabbit platelets and murine macrophage RAW264.7 cells were treated with piperine, and the effect of piperine on the activity of AA-metabolizing enzymes, including cytosolic phospholipase A₂ (cPLA₂), COX-1, COX-2, and thromboxane A₂ (TXA₂) synthase, as well as its effect on AA liberation from the plasma membrane components, were assessed using isotopic labeling methods and enzyme immunoassay kit; RESULTS: Piperine significantly suppressed AA liberation by attenuating cPLA₂ activity in collagen-stimulated platelets. It also significantly inhibited the activity of TXA₂ synthase, but not of COX-1, in platelets. These results suggest that piperine inhibits platelet aggregation by attenuating cPLA₂ and TXA₂ synthase activities, rather than through the inhibition of COX-1 activity. On the other hand, piperine significantly inhibited lipopolysaccharide-induced generation of prostaglandin (PG)E₂ and PGD₂ in RAW264.7 cells by suppressing the activity of COX-2, without effect on cPLA₂; CONCLUSION: Our findings indicate that piperine inhibits platelet aggregation and macrophage inflammatory response by different mechanisms.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.