Author:
Huang Wei-Chieh,Jayakumar Thanasekaran,Sheu Joen-Rong,Hsia Chih-Wei,Hsia Chih-Hsuan,Yen Ting-Lin,Chang Chao-Chien
Abstract
Abstract
Background
Platelets play a crucial role in cardiovascular diseases (CVDs) and are activated by endogenous agonists like collagen. These agonists initiate signal transduction through specific platelet receptors, resulting in platelet aggregation. Glabridin, a prenylated isoflavonoid found in licorice root, is known for its significance in metabolic abnormalities. Glabridin has been observed to inhibit collagen-induced platelet aggregation, but the precise mechanisms, specifically concerning NF-κB activation and integrin αIIbβ3 signaling, are not yet fully understood.
Methods
In this study, platelet suspensions were prepared from healthy human blood donors, and the aggregation ability was observed using a lumi-aggregometer. The inhibitory mechanisms of glabridin in human platelets were evaluated through immunoblotting and confocal microscopy. The anti-thrombotic effects of glabridin were assessed by histological analysis of lung sections in acute pulmonary thromboembolism and by examining fluorescein-induced platelet plug formation in mesenteric microvessels in mice.
Results
Glabridin inhibited integrin αIIbβ3 inside-out signals such as Lyn, Fyn, Syk, and integrin β3 activation and NF-κB-mediated signal events, with similar potency to classical inhibitors BAY11-7082 and Ro106-9920. Glabridin and BAY11-7082 inhibited IKK, IκBα, and p65 phosphorylation and reversed IκBα degradation, while Ro106-9920 only reduced p65 phosphorylation and reversed IκBα degradation. BAY11-7082 reduced Lyn, Fyn, Syk, integrin β3, phospholipase Cγ2 and protein kinase C activation. Glabridin reduced platelet plug formation in mesenteric microvessels and occluded vessels in thromboembolic lungs of mice.
Conclusion
Our study revealed a new pathway for activating integrin αIIbβ3 inside-out signals and NF-κB, which contributes to the antiplatelet aggregation effect of glabridin. Glabridin could be a valuable prophylactic or clinical treatment option for CVDs.
Funder
Ministry of Science and Technology of Taiwan
Taipei Medical University
Cathay General Hospital
Cathay General Hospital–Taipei Medical University
Publisher
Springer Science and Business Media LLC
Subject
Complementary and alternative medicine,Pharmacology