BackgroundChrysin and its analogues, belongs to flavonoid family and possess potential anti-tumour activity. The aim of this study is to determine the molecular mechanism by which chrysin controls cell growth and induce apoptosis in A375 cells.MethodsEffect of chrysin and its analogues on cell viability and cell cycle analysis was determined by MTT assay and flowcytometry. A series of Western blots was performed to determine the effect of chrysin on important cell cycle regulatory proteins (Cdk2, cyclin D1, p53, p21, p27). The fluorimetry and calorimetry based assays was conducted for characterization of chrysin as HDAC inhibitor. The changes in histone tail modification such as acetylation and methylation was studied after chrysin treatment was estimated by immuno-fluorescence and western blot analysis. The expression of Bcl-xL, survivin and caspase-3 was estimated in chrysin treated cells. The effect of chrysin on p21 promoter activity was studied by luciferase and ChIP assays.ResultsChrysin cause G1 cell cycle arrest and found to inhibit HDAC-2 and HDAC-8. Chrysin treated cells have shown increase in the levels of H3acK14, H4acK12, H4acK16 and decrease in H3me2K9 methylation. The p21 induction by chrysin treatment was found to be independent of p53 status. The chromatin remodelling at p21WAF1 promoter induces p21 activity, increased STAT-1 expression and epigenetic modifications that are responsible for ultimate cell cycle arrest and apoptosis.ConclusionChrysin shows in vitro anti-cancer activity that is correlated with induction of histone hyperacetylation and possible recruitment of STAT-1, 3, 5 proteins at STAT (−692 to −684) region of p21 promoter. Our results also support an unexpected action of chrysin on the chromatin organization of p21WAF1 promoter through histone methylation and hyper-acetylation. It proposes previously unknown sequence specific chromatin modulations in the STAT responsive elements for regulating cell cycle progression negatively via the induction of the CDK inhibitor p21WAF1.

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Barringtonia racemosa presents a wide range of therapeutic applications. In the course of identifying bioactives from Indian medicinal plants it was observed that the hexane, ethanol and methanol extracts of B. racemosa seeds displayed potent yeast and intestinal alpha-glucosidase inhibitory activities. The methanol extract was found to be superior among them. However, none of the extracts exhibited pancreatic alpha-amylase inhibitory activity, rather the ethanol and methanol extracts accelerated the alpha-amylase enzyme activity. Interestingly, however, bartogenic acid isolated from the methanol extract inhibited alpha-amylase also. This is the first report identifying alpha-glucosidase inhibitory activity in B. racemosa seed extracts and assigning to bartogenic acid an alpha-glucosidase and amylase inhibitory property. The presence of bartogenic acid in B. racemosa seeds as a major compound is also reported for the first time in this communication.

This research analyzed the major chemical components and multiple antioxidant activities present in the fresh juice of eight vegetables, and studied their influence on starch induced postprandial glycemia in rats. A SDS-PAGE based protein fingerprint of each vegetable juice was also prepared. The yields of juice, chemical components like total proteins, total polyphenols, total flavonoids, total anthocyanins and free radicals like the ABTS˙(+) cation, DPPH, H(2)O(2), scavenging activities and reducing properties for NBT and FeCl(3) showed wide variations. Vegetable juice from brinjal ranked first in displaying total antioxidant capacity. Pretreatment of rats with vegetable juices moderated starch induced postprandial glycemia. The fresh juice from the vegetables ridge gourd, bottle gourd, ash gourd and chayote significantly mitigated postprandial hyperglycemic excursion. Total polyphenol concentrations present in vegetable juices positively influenced ABTS˙(+) scavenging activity and total antioxidant capacity. However, NBT reducing activity of juices was positively affected by total protein concentration. Contrarily, however, high polyphenol content in vegetable juice was observed to adversely affect the postprandial antihyperglycemic activity of vegetable juices. This is the first report exploring antihyperglycemic activity in these vegetable juices and highlights the possible adverse influence of high polyphenol content on the antihyperglycemic activity of the vegetable juices.

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