2. Academic Validation
  3. Mechanisms of glabridin inhibition of integrin αIIbβ3 inside-out signals and NF-κB activation in human platelets

Mechanisms of glabridin inhibition of integrin αIIbβ3 inside-out signals and NF-κB activation in human platelets

  • Chin Med. 2023 Jun 10;18(1):71. doi: 10.1186/s13020-023-00779-9.
Wei-Chieh Huang # 1,  Thanasekaran Jayakumar 2,  Joen-Rong Sheu # 1 3,  Chih-Wei Hsia 1,  Chih-Hsuan Hsia 4,  Ting-Lin Yen 5,  Chao-Chien Chang 6 7 8 9
Affiliations

Affiliations

  • 1 Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, 110, Taiwan.
  • 2 Department of Ecology and Environmental Sciences, Pondicherry University, Puducherry, 605014, India.
  • 3 Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, 110, Taiwan.
  • 4 Translational Medicine Center, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, 111, Taiwan.
  • 5 Department of Medical Research, Cathay General Hospital, Taipei, 106, Taiwan.
  • 6 Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, 110, Taiwan. [email protected].
  • 7 Department of Cardiovascular Center, Cathay General Hospital, Taipei, 106, Taiwan. [email protected].
  • 8 School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City, 242, Taiwan. [email protected].
  • 9 Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, 110, Taiwan. [email protected].
  • # Contributed equally.
PMID: 37301823 DOI: 10.1186/s13020-023-00779-9
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.

Keywords

Glabridin; Human platelets; NF-κB; Platelet plug formation; Thromboembolic lungs; αIIbβ3 inside-out.

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