Anti-platelet and anti-thrombogenic effects of shikimic acid in sedentary population

Abstract

This ex vivo study was performed to evaluate the anti-platelet and anti-thrombogenic potential of shikimic acid (SA), a plant phenolic metabolite. Fasting blood samples were collected from 22 sedentary participants to analyse the effect of varying concentrations of SA (0.1 mM, 0.2 mM, 0.5 mM, 1 mM and 2 mM) on platelet surface-marker expression, platelet aggregation and biomarkers of thrombogenesis. Monocyte-platelet aggregates (CD14/CD42b) and platelet endothelial cell adhesion molecule-1 (PECAM-1 or CD31), effective indicators of thrombus formation were evaluated. Procaspase-activating compound 1 (PAC-1) and P-selectin or CD62P were used to assess platelet activation-related thrombogenesis. Adenosine diphosphate (ADP) was used to stimulate the P2Y1/P2Y12 pathway of platelet activation to mimic the in vivo thrombogenic pathway. Platelet aggregation studies utilised both ADP and collagen as exogenous platelet agonists to target both P2Y1/P2Y12 and GPVI pathways of thrombus formation. It was observed with flow cytometry that SA produced a significant antiplatelet effect on PAC-1 (p = 0.03 at 2 mM) and CD62P (p = 0.017, p = 0.036 at 1 mM and 2 mM respectively) expression in addition to lowering monocyte-platelet aggregate formation (p = 0.013, p < 0.01 and p < 0.01 at 0.5 mM, 1 mM and 2 mM respectively). SA at 1 mM concentration reduced PECAM-1 expression (p = 0.035), signifying a reduction to endothelial leucocyte migration during thrombus growth. SA did not demonstrate a platelet aggregation inhibitory effect by targeting the GPVI collagen pathway but reduced ADP induced platelet aggregation at 2 mM concentration (p < 0.01 at 2 mM). The results suggest that SA, an active metabolite of polyphenol-rich food intake, could play an important role in reducing platelet activation, aggregation related thrombus formation and biomarkers of thrombogenesis in sedentary individuals.

The effect of anthocyanin supplementation in modulating platelet function in sedentary population: a randomised, double-blind, placebo-controlled, cross-over trial

“…This study demonstrated a decrease in monocyte-platelet aggregate formation by 39 % ( P <0·01) post 4-week ACN supplementation thereby exhibiting a potential role in reducing thrombus acceleration. Due to its ability to mediate leucocyte infiltration, PECAM-1 when highly expressed on leucocyte population has been linked with atherosclerotic involvement ( 29 ) . The decreased expression of PECAM-1 in this study by 14 % ( P <0·05) demonstrates ACN ability to reduce leucocyte migration and aggregate formation in the damaged endothelium that would typically occur during atherogenesis ( 16 ) .…”

“…The decreased expression of PECAM-1 in this study by 14 % ( P <0·05) demonstrates ACN ability to reduce leucocyte migration and aggregate formation in the damaged endothelium that would typically occur during atherogenesis ( 16 ) . In an ex vivo study evaluating the anti-thrombogenic properties of a phenolic metabolite, shikimic acid (SA), a reduced expression of PECAM-1 was observed post-treatment with 1 m m of SA, also demonstrating the ability of polyphenols in minimising thrombus growth ( 29 ) .…”

Hypolipogenic Effect of Shikimic Acid Via Inhibition of MID1IP1 and Phosphorylation of AMPK/ACC

“…Since shikimic acid is a natural compound isolated from the Japanese plant, Illicium verum [12], and seeds of Liquidambar styraciflua (sweetgum) abundant in North America [13] and Chinese star anise ( Illicium verum ), shikimic acid has been used as a base material for production of oseltamivir (Tamiflu) [14]. Also, though shikimic acid is known to have anti-diabetic [15], antibacterial [16], anti-inflammatory [17], analgesic [18], antioxidant [18], and anti-thrombogenic [19] effects, its hypolipogenic mechanism has never been reported. Thus, in the present study, hypolipogenic mechanism of shikimic acid was elucidated in HepG2 and Huh7 hepatocellular carcinoma HCC cells and 3T3-L1 adipocytes in association with AMPK/ACC and MID1IP1 signaling axis.…”

Shotgun metagenomics and metabolomics reveal glyphosate alters the gut microbiome of Sprague-Dawley rats by inhibiting the shikimate pathway

“…f. (Chinese star anise) have been traditionally used to treat skin inflammation and stomach aches (Rabelo et al 2015). Shikimic acid is a plant polyphenolic compound known to protect against oxidative stress (Rabelo et al 2015), and has anti-platelet and anti-thrombogenic effects (Veach et al 2016).…”