ABSTRACT
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.
Subject(s)
Alternaria/chemistry , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Endophytes/chemistry , Lactones/isolation & purification , Lactones/pharmacology , Methyl Ethers/chemistry , Plants, Medicinal/microbiology , Alternaria/isolation & purification , Alternaria/metabolism , Antineoplastic Agents/isolation & purification , Antineoplastic Agents/metabolism , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/physiopathology , Cell Cycle Checkpoints/drug effects , Crystallization , Endophytes/isolation & purification , Endophytes/metabolism , Humans , Lactones/chemistry , Lactones/metabolism , Liver Neoplasms/drug therapy , Liver Neoplasms/physiopathology , Methyl Ethers/isolation & purification , Methyl Ethers/pharmacology , Secondary MetabolismABSTRACT
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.
Subject(s)
Adipocytes/drug effects , Anti-Obesity Agents/therapeutic use , Eurycoma/chemistry , Obesity/drug therapy , Plant Extracts/chemistry , Quassins/therapeutic use , Animals , Anti-Obesity Agents/pharmacology , Male , Mice , Mice, Inbred C57BL , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Quassins/chemistry , Quassins/pharmacology , RatsABSTRACT
Wastewater treatment plant incorporates physical, chemical and biological processes to treat and remove the contaminants. The main drawback of conventional activated sludge process is the huge production of excess sludge, which is an unavoidable byproduct. The treatment and disposal of excess sludge costs about 60% of the total operating cost. The ideal way to reduce excess sludge production during wastewater treatment is by preventing biomass formation within the aerobic treatment train rather than post treatment of the generated sludge. In the present investigation two different mechanical devices namely, Ultrasonic and Shear Gap homogenizers have been employed to disintegrate the aerobic biomass. This study is intended to restrict the multiplication of microbial biomass and at the same time degrade the organics present in wastewater by increasing the oxidative capacity of microorganisms. The disintegrability on biomass was determined by biochemical methods. Degree of inactivation provides the information on inability of microorganisms to consume oxygen upon disruption. The soluble COD quantifies the extent of release of intra cellular compounds. The participation of disintegrated microorganism in wastewater treatment process was carried out in two identical respirometeric reactors. The results show that Ultrasonic homogenizer is very effective in the disruption of microorganisms leading to a maximum microbial growth reduction of 27%. On the other hand, Shear gap homogenizer does not favor the sludge growth reduction rather it facilitates the growth. This study also shows that for better microbial growth reduction, floc size reduction alone is not sufficient but also microbial disruption is essential.
