Identification of pancreatic lipase inhibiting endophytic secondary metabolites of Aspergillus fischeri VO1R

¹ Institute of Microbiology, Academy of Sciences the Republic of Uzbekistan, A.Kadyri 7B Street, 100128, Tashkent, Uzbekistan
² Institute of Bioorganic Chemistry, Academy of Sciences of the Republic of Uzbekistan, M.Ulugbek Street, 83, 100125, Tashkent, Uzbekistan
³ National University of Uzbekistan named after Mirzo Ulugbek, University Street,4, 100174, Tashkent, Uzbekistan
⁴ Kokand University Andijan branch, 170619, Andijan, Uzbekistan

^* Corresponding author: This email address is being protected from spambots. You need JavaScript enabled to view it.

Abstract

Obesity is considered to be a global problem that can contribute to the development of various diseases such as dyslipidemia, metabolic syndrome, hypertension, and an increased risk of cardiovascular mortality. WHO has identified obesity as one of the leading health problems of the 21st century; with more than 1 billion adult world population overweight, at least 300 million of them are obese. A wide range of therapeutic strategies have been proposed to prevent and treat obesity, including pharmacotherapy, diet therapy, surgery, and behavioral therapy. One of the practical therapeutic approaches to the prevention of obesity is to slow down the absorption of fatty acids by inhibiting pancreatic lipase, the primary digestive enzyme that catalyzes the hydrolysis of ester bonds of tri- and diglycerides to monoglycerides and free fatty acids. The escalating prevalence of obesity necessitates the exploration of novel therapeutic avenues. This study presents a unique approach by presenting data on the extraction and identification of inhibitory secondary metabolites from the total ethyl acetate extract of the endophyte Aspergillus fischeriVO1R from the root of the plant Viola odorata. These metabolites demonstrate a potent ability to suppress the activity of pancreatic lipase by 91.5%. The IC₅₀ value for pancreatic lipase inhibition by A.fischeri VO1R was determined to be 20.5 µg/mL, which is comparable to the reference drug Xenical (Orlistat), exhibiting an IC₅₀ value of 20.6 µg/mL under the same experimental conditions. The highest inhibitory activity was observed in the butanol fraction (84.9%), while the standard drug Xenical (orlistat) exhibited a pancreatic lipase inhibitory activity of 92%. Further separation of the butanol fraction of A.fischeri VO1R by thin-layer chromatography reveals the most active fraction B-2 with Rf 0.75, exhibiting an inhibitory activity of 57.2%. HPLC-MS methods confirm that the inhibitory fraction of B-2 consists of polyphenols identified as cinnamic acid, lariciresinol-sesquilignan, and hydroxyphloretin 2'-O-xylosyl-glucoside.