Abstract 538: Gum Arabic Acutely Inhibit PCSK9 and Upregulate LDLr in HepG2

Abstract

Introduction: Gum arabic (GA) (Acacia Senegal) is widely used agent in both the pharmaceutical and food industries as an emulsifier and stabilizer. It is a branched complex polysaccharide molecule rich in calcium, potassium, and magnesium in addition to other minerals. Its aqueous solution is either neutral or slightly acidic. Human intake of GA with atorvastatin was reported to significantly reduce plasma low density lipoprotein, and triglyceride. This study is designed to test mechanism (s) of its action on HepG2 cell. Hypothesis: The plasma lipids reduction associated with GA intake is likely associated with PCSK9/LDLr mechanism. Methods: Gum Arabic was dissolved in water and irradiated under UV light for 5 hours. Three final concentrations: 5ng/ml, 100ng/ml and 500 ng/ml were used for treatment of HepG2 cells at 6 hours, 12 hours and 24 hours using 12 well plates. Following treatment cells were collected into Trizol® solution; RNA was extracted for gene expression following Trizol® supplier protocol. cDNA was synthesized and the expression of PSCK9, LDLR and other related genes were tested using real time PCR. Results: The use of viscous (soluble) fiber (e.g., oats, guar, pectin, and psyllium) as therapeutic dietary options to enhance lowering of LDL cholesterol in primary and secondary prevention of CHD was well known, however there is no study to date that have shown the GA cholesterol lowering mechanism(s). In this study cell treated with GA for six hours has resulted in approximately 50 fold reductions of PCSK9 gene expression across the various concentrations, and approximately 25 fold up regulation of LDLr gene. Prolonged treatments beyond the six hours have shown differential responses. Conclusions: This study demonstrates that Gum Arabic has acute anti PCSK9 properties, as well as beneficial LDLr modulation effects. Our data explain the modulatory mechanism of Gum Arabic plasma LDL lowering effects associated with its intake in humans.