Comparing the effectiveness of pterostilbene and sitagliptin on modulating inflammatory levels and inducing autophagy to improve atherosclerosis outcome: A preclinical study in rabbits.

BACKGROUND: Inflammation is the key contributor to the development of atherosclerotic plague. This study aims to evaluate the protective and autophagy induction properties of pterostilbene and sitagliptin on modulating the degree of atherosclerosis in rabbit models treated with an atherogenic diet. METHODS: 80 rabbits were randomly placed into one of four study groups (20 in each group): normal control diet (NC) fed normal diet for eight weeks, atherogenic control (AC) fed atherogenic diet for eight weeks, pterostilbene treated group (PT) fed atherogenic diet with pterostilbene (at 10 mg/kg/day) orally daily for eight weeks, and sitagliptin treated group (ST) fed atherogenic diet with sitagliptin (at 12 mg/kg/day) orally daily for eight weeks. RESULTS: While serum lipids and F2-isoprostane were elevated significantly in the AC study cohort compared to NC study cohort, ( P < 0.001), both pterostilbene and sitagliptin supplementations provided significant improvements in serum lipid parameters and F2-isoprostane in the PT study cohort and ST study cohort, respectively, when compared to the AC study cohort, ( P<0.001). Total cholesterol, triglycerides and LDL levels were significantly reduced among the PT and ST study cohorts as compared to the AC study cohort. This was coupled with a significant rise in LC3B levels (marker of tissue autophagy) among the PT study cohort and the ST study cohort, as compared to the AC study cohort, ( P < 0.001). The RNA expression of mTORC1 was reduced significantly at both PT study cohort and ST study cohort, ( P<0.001). Pterostilbene supplementation induced a significant reduction in tissue expression of PI3K and AKT, ( P<0.01), while sitagliptin induced significant increase in 5' adenosine monophosphate-activated protein kinase (AMPK) levels, ( P<0.001). CONCLUSIONS: The results indicate that pterostilbene and/or sitagliptin supplementation can significantly improve the outcome of atherosclerosis due to their effects on the inflammatory pathways which hinder the progression of atherosclerotic plaque formation.