Purification, crystallization and anticancer activity evaluation of the compound alternariol methyl ether from endophytic fungi Alternaria alternata.

AIMS: Medicinal plant-associated endophytic fungi are important sources of precious bioactive compounds, contributing more than 80% of the natural drugs for various ailments. The present study was aimed at evaluating the anticancer activity of the crystallized compound alternariol methyl ether (AME) against hepatocellular carcinoma (HCC) both in vitro and in vivo from an endophytic fungus residing in the medicinal plant Vitex negundo. METHODS AND RESULTS: The secondary metabolites from the endophytic fungus Alternaria alternata MGTMMP031 were isolated. Purification and characterization of the compound was performed and the potential compound was identified as AME. The crystal structure of AME was unambiguously confirmed by X-ray analysis. AME has been checked for its antibacterial and anticancer properties which showed its effectiveness against various bacteria and demonstrated marked anti-proliferative activity against the human HCC cells (HUH-7) both in vitro and in vivo. Mode of actions included cell cycle arrest, reducing the level of markers enzymes of liver cancer and preventing tumour growth. CONCLUSIONS: Alternariol methyl ether acts as a potential therapeutic target against HCC. The compound was isolated and the crystal structure was obtained for the first time from the endophytic fungus A. alternata MGTMMP031. In the present study, the crystallized structure of AME was obtained by slow evaporation technique. It can be concluded that AME acts as a potential therapeutic target against HCC. SIGNIFICANCE AND IMPACT OF THE STUDY: Endophytic fungi residing in the medicinal plants have strong biological significance and bioactive compounds from these fungi provide better therapeutic targets against diseases.

Antiadipogenic effects of a standardized quassinoids-enriched fraction and eurycomanone from Eurycoma longifolia.

Bioactive compounds of Eurycoma longifolia (EL) jack were previously shown to reduce omentum fat mass and oestradiol-induced fatty uterine adhesion in rats. However, the exact role of EL on adipogenesis remains unknown. This study sought to investigate the effects of an EL standardized quassinoids-enriched fraction (SQEL) and the pure compound, eurycomanone, on adipogenesis in 3T3-L1 preadipocyte cells. 3T3-L1 cells were induced to differentiate and treated for 8 days. The treatment reduced intracellular accumulation of lipid droplets and triglycerides in the differentiating adipocytes and induced lipolysis in matured adipocytes. The expressions of adipogenic transcription factors and markers were also significantly downregulated during the early stage of differentiation. Furthermore, SQEL also suppressed body weight gain, decreased epididymal and perirenal fat pad mass and size, and reduced the accumulation of fat in the livers of C57BL/6J mice fed with normal or high-fat diet that were concurrently given 5 mg/kg and 10 mg/kg (i.p) of SQEL for 12 weeks. SQEL also improved glucose intolerance and decreased the elevated total cholesterol and triglyceride levels in these mice groups. These findings suggest that SQEL could be explored as an alternative pharmacologic agent inhibiting adipogenesis for the prevention of obesity.