Pharmacometabonomics of Ginseng Extracts on Vascular Injury Induced by Chronic Homocysteine Treatment.

Abstract

Various biological studies have demonstrated the protective nature of ginseng against vascular injury and also its effects on vasorelaxation and antioxidation. In the present study, a pharmacometabonomics approach was used to predict endogenous metabolite responses to various dose levels of alcoholic and aqueous ginseng extracts. Young adult male Sprague-Dawley rats were administered daily doses of Hcy (50mg/kg, by oral gavage) for 42 days while concurrently being treated with alcoholic or aqueous extracts of Ontario-grown NA ginseng to examine their protective effects against vascular injury. At the end of the study, each rat was sacrificed and plasma samples were collected for metabolite evaluation. Briefly, plasma samples were protein precipitated with methanol, centrifuged and 5µL of supernatant was injected into the mass spectrometer. High resolution accurate mass analysis was performed using the TripleTOF™ 5600 system. Statistical data processing was performed using MarkerView™ software and targeted data analysis for endogenous metabolites was processed by PeakView™ and XIC manager software. Lipid profile was also evaluated using a shotgun lipidomics approach. Lipid data was processed using LipidView™ software. Daily administration of Hcy significantly elevated plasma Hcy levels by more than 2-fold over the control levels. Hcy was significantly reduced to control level by daily treatment with either low or high dose of both types of ginseng extracts. Statistical evaluation of the metabolite profiles separated aqueous and alcoholic extracts and dose levels. Targeted data processing of metabolites involved in the homocysteine metabolism pathway corroborated the working hypothesis of the protective nature of ginseng.