Antioxidant-rich leaf extract ofBarringtonia racemosasignificantly alters thein vitroexpression of genes encoding enzymes that are involved in methylglyoxal degradation III

Abstract

BackgroundBarringtonia racemosais a medicinal plant belonging to theLecythidaceaefamily. The water extract ofB. racemosaleaf (BLE) has been shown to be rich in polyphenols. Despite the diverse medicinal properties ofB. racemosa, information on its major biological effects and the underlying molecular mechanisms are still lacking.MethodsIn this study, the effect of the antioxidant-rich BLE on gene expression in HepG2 cells was investigated using microarray analysis in order to shed more light on the molecular mechanism associated with the medicinal properties of the plant.ResultsMicroarray analysis showed that a total of 138 genes were significantly altered in response to BLE treatment (p< 0.05) with a fold change difference of at least 1.5.SERPINE1was the most significantly up-regulated gene at 2.8-fold whileHAMPwas the most significantly down-regulated gene at 6.5-fold. Ingenuity Pathways Analysis (IPA) revealed that “Cancer, cell death and survival, cellular movement” was the top network affected by the BLE with a score of 44. The top five canonical pathways associated with BLE were Methylglyoxal Degradation III followed by VDR/RXR activation, TR/RXR activation, PXR/RXR activation and gluconeogenesis. The expression of genes that encode for enzymes involved in methylglyoxal degradation (ADH4,AKR1B10andAKR1C2) and glycolytic process (ENO3, ALDOCandSLC2A1) was significantly regulated. Owing to the Warburg effect, aerobic glycolysis in cancer cells may increase the level of methylglyoxal, a cytotoxic compound.ConclusionsBLE has the potential to be developed into a novel chemopreventive agent provided that the cytotoxic effects related to methylglyoxal accumulation are minimized in normal cells that rely on aerobic glycolysis for energy supply.