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

Abstract

BackgroundBarringtonia 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.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. 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.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.

Evaluation of Anti-proliferative Effects of Barringtonia racemosa and Gallic Acid on Caco-2 Cells

“…Overall, of the 7 genes selected, only the expression of SLC2A1, AREG and ADH4 were consistent with the in-silico analysis previously reported by Kong et al 12 . The previously reported up-regulation of CXCL8 and CEACAM1 expression in HepG2 cells 12 were not observed in any of the treated Caco-2 cells in this study.…”

“…Overall, of the 7 genes selected, only the expression of SLC2A1, AREG and ADH4 were consistent with the in-silico analysis previously reported by Kong et al 12 . The previously reported up-regulation of CXCL8 and CEACAM1 expression in HepG2 cells 12 were not observed in any of the treated Caco-2 cells in this study. This could be due to the sensitivity of the microarray analyses used by Kong et al 12 as well as the differences in cell lines used where HepG2 is an immortalised liver cancer cell while Caco-2 is an epithelial colorectal adenocarcinoma cell.…”

“…The previously reported up-regulation of CXCL8 and CEACAM1 expression in HepG2 cells 12 were not observed in any of the treated Caco-2 cells in this study. This could be due to the sensitivity of the microarray analyses used by Kong et al 12 as well as the differences in cell lines used where HepG2 is an immortalised liver cancer cell while Caco-2 is an epithelial colorectal adenocarcinoma cell. Our group had previously reported that BLE significantly induced the expression of SLC2A1 gene that encodes the primary glucose transporter, GLUT1, in HepG2 cells 12 .…”

“…Our group had previously reported the presence of GA, ellagic acid, protocatechuic acid, quercetin, rutin, and kaempferol in BLE 10,11 . Microarray and in-silico IPA analyses revealed the ability of BLE to alter the expression of genes in HepG2 cells including those associated to methylglyoxal (MG) degradation and glycolytic processes www.nature.com/scientificreports www.nature.com/scientificreports/ with colon cancer as a potential selective target 12 . GA, the most abundant polyphenolic compound in BLE, was selected as a comparative control for this study.…”

Nam Dia long, a Vietnamese folk formula, induces apoptosis in MCF-7 cells through various mechanisms of action

“…We analyzed the effects of NDL treatment for different durations of time, 24 h, 36 h and 48 h. Exposure to plant extracts for 24 h is sufficient to elicit cell responses at the gene expression level [ 33 ]. Longer exposure times allowed analysis of the transcriptional cascade that led to the beginning of cell death at 48 h after NDL treatment [ 7 ].…”