title: Antioxidant-rich leaf extract of Barringtonia racemosa significantly alters the in vitro expression of genes encoding enzymes that are involved in methylglyoxal degradation III.
abstract: BACKGROUND
  Barringtonia racemosa is a medicinal plant belonging to the Lecythidaceae family. The water extract of B. racemosa leaf (BLE) has been shown to be rich in polyphenols. Despite the diverse medicinal properties of B. racemosa, information on its major biological effects and the underlying molecular mechanisms are still lacking.
  
  
  METHODS
  In 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.
  
  
  RESULTS
  Microarray 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. SERPINE1 was the most significantly up-regulated gene at 2.8-fold while HAMP was 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, AKR1B10 and AKR1C2) and glycolytic process (ENO3, ALDOC and SLC2A1) was significantly regulated. Owing to the Warburg effect, aerobic glycolysis in cancer cells may increase the level of methylglyoxal, a cytotoxic compound.
  
  
  CONCLUSIONS
  BLE 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.
authors.affiliation: Department of Molecular Medicine, Faculty of Medicine, University of Malaya , Kuala Lumpur , Malaysia.
authors.forename: Kin Weng
authors.initials: KW
authors.lastname: Kong
authors.affiliation: Department of Molecular Medicine, Faculty of Medicine, University of Malaya , Kuala Lumpur , Malaysia.
authors.forename: Azlina
authors.initials: A
authors.lastname: Abdul Aziz
authors.affiliation: Department of Molecular Medicine, Faculty of Medicine, University of Malaya , Kuala Lumpur , Malaysia.
authors.forename: Nurhanani
authors.initials: N
authors.lastname: Razali
authors.affiliation: Institute of Biological Sciences, Faculty of Science, University of Malaya , Kuala Lumpur , Malaysia.
authors.forename: Norhaniza
authors.initials: N
authors.lastname: Aminuddin
authors.affiliation: Department of Molecular Medicine, Faculty of Medicine, University of Malaya , Kuala Lumpur , Malaysia.
authors.forename: Sarni
authors.initials: S
authors.lastname: Mat Junit
keywords: Barringtonia racemosa; Gene expression; Ingenuity Pathways Analysis; Leaf extract; Methylglyoxal degradation III; Microarray analysis