Isorhapontigenin, a resveratrol analogue selectively inhibits ADP-stimulated platelet activation.

Isorhapontigenin is a polyphenolic compound found in Chinese herbs and grapes. It is a methoxylated analogue of a stilbenoid, resveratrol, which is well-known for its various beneficial effects including anti-platelet activity. Isorhapontigenin possesses greater oral bioavailability than resveratrol and has also been identified to possess anti-cancer and anti-inflammatory properties. However, its effects on platelet function have not been reported previously. In this study, we report the effects of isorhapontigenin on the modulation of platelet function. Isorhapontigenin was found to selectively inhibit ADP-induced platelet aggregation with an IC50 of 1.85 µM although it displayed marginal inhibition on platelet aggregation induced by other platelet agonists at 100 µM. However, resveratrol exhibited weaker inhibition on ADP-induced platelet aggregation (IC50 > 100 µM) but inhibited collagen induced platelet aggregation at 50 µM and 100 µM. Isorhapontigenin also inhibited integrin αIIbß3 mediated inside-out and outside-in signalling and dense granule secretion in ADP-induced platelet activation but interestingly, no effect was observed on α-granule secretion. Isorhapontigenin did not exert any cytotoxicity on platelets at the concentrations of up to 100 µM. Furthermore, it did not affect haemostasis in mice at the IC50 concentration (1.85 µM). In addition, the mechanistic studies demonstrated that isorhapontigenin increased cAMP levels and VASP phosphorylation at Ser157 and decreased Akt phosphorylation. This suggests that isorhapontigenin may interfere with cAMP and PI3K signalling pathways that are associated with the P2Y12 receptor. Molecular docking studies emphasised that isorhapontigenin has greater binding affinity to P2Y12 receptor than resveratrol. Our results demonstrate that isorhapontigenin has selective inhibitory effects on ADP-stimulated platelet activation possibly via P2Y12 receptor.

Challenges in diagnosing and treating snakebites in a rural population of Tamil Nadu, India: The views of clinicians.

Snakebites cause death, disability and economic devastation to their victims, people who live almost exclusively in rural areas. Annually an estimated two million venomous bites cause as many as 100,000 deaths worldwide as well as hundreds of thousands of deformities and amputations. Recent studies suggest that India has the highest incidence of snakebite and associated deaths worldwide. In this study, we interviewed 25 hospital-based clinicians who regularly treat snakebites in Tamil Nadu, India, in order to gauge their opinions and views on the diagnostic tools and treatment methods available at that time, the difficulties encountered in treating snakebites and improvements to snakebite management protocols they deem necessary. Clinicians identified the improvement of community education, training of medical personnel, development of standard treatment protocols and improved medication as priorities for the immediate future.