الفهرس 
Title :A study on the production of pancreatic lipase inhibitors by microorganisms isolated from soil and aquatic environments in Egypt
AbstractOnly 14 pages are availabe for public view
 |  | from | 92 |  |  |
| | | from | 92 | | |
Abstract
Obesity is a major health threat that is increasing dramatically all over the world. Targeting lipid metabolism by inhibiting pancreatic lipase(PL) enzyme is one of the best and safest therapeutic strategiesfor managingobesity. So far,orlistat is the only FDA approved PL inhibitor used for obesity treatment.However, it causes unpleasant side effects. The purpose of the present work was to isolate and characterize new PL inhibitor(s) from soil commensals. Thirty-nine crude mycelial soil extracts were screened for PL inhibitor activity by a quantitative lipase colorimetric assayusing the substrate p-nitrophenylpalmitate and orlistat, as positive control.AspsarO and AspsarN, good PL inhibitor producers, were isolated from an agricultural field soil in Giza, Egypt and were identified as Aspergillus oryzaeand Aspergillus nidulansrespectively, using morphological and moleculartechniques. Optimization of fermentation conditions, for maximum inhibitor production by AspsarO and AspsarN,was performed using a Placket{u2013}Burman design. Incubation at 37{u00B0}C for a period of six days were the most effective parameters for maximizing inhibitor production by both isolates.The dried 100% methanolic fractions of AspsarO and AspsarN had an IC50 of 7.48 og/ml and 5.7 og/ml respectively, compared to3.72 og/ml fororlistat. The 100% methanolicfraction of AspsarOwas selected for larger scale production of PL inhibitor. Further purification using bio-guided chromatographic and 1H and 13C NMR techniques resulted in the isolation of kojic acid with an IC50 of 6.54 og/ml. Kojic acid is a well-known metaboliteproduced by many fungal species,includingAspergillus oryzae.Molecular docking studies showed that the PL inhibitory activity of kojic acid, could be attributed to its interaction with the key amino acids(Lys80, Asn84 and Trp252) in PL enzyme binding sitesin a similar way to orlistat.Administration of 100% methanolic fraction of AspsarO along with a high-fat diet resulted in a reduction in the percentage weight gain, a significant lowering in food intake and serum triglycerides levels in Sprague{u2013}Dawley rats, compared to high-fat diet-fed rats. In conclusion, combining the results of the induced obesity animal model, in silico molecular docking and the lipase inhibitor assay, suggests that kojic acid can be a new therapeutic option for obesity management. Besides its lowering of triglycerides levels in obese patients