Hesperidin improves insulin resistance via down-regulation of inflammatory responses: Biochemical analysis and in silico validation


Autoři: Kanwal Rehman aff001;  Syeda Mehak Munawar aff002;  Muhammad Sajid Hamid Akash aff003;  Manal Ali Buabeid aff004;  Tahir Ali Chohan aff005;  Muhammad Tariq aff006;  Komal Jabeen aff001;  El-Shaimaa A. Arafa aff004
Působiště autorů: Department of Pharmacy, University of Agriculture, Faisalabad, Pakistan aff001;  Institute of Physiology and Pharmacology, University of Agriculture, Faisalabad, Pakistan aff002;  Department of Pharmaceutical Chemistry, Government College University, Faisalabad, Pakistan aff003;  Department of Clinical Sciences, College of Pharmacy and Health Sciences, Ajman University, Ajman, United Arab Emirates aff004;  Institute of Pharmaceutical Sciences, University of Veterinary and Animal Sciences, Lahore, Pakistan aff005;  Department of Pharmacology, Lahore Pharmacy College, Lahore, Pakistan aff006
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
doi: 10.1371/journal.pone.0227637

Souhrn

Leptin resistance and co-existing insulin resistance is considered as hallmark of diet-induced obesity. Here, we investigated therapeutic potential of hesperidin to improve leptin and insulin resistance using high fat diet (HFD)-induced obese experimental animal model. We also performed in silico studies to validate therapeutic effectiveness of hesperidin by performing protein-ligand docking and molecular dynamics simulation studies. Group 1 was identified as control group receiving vehicle only. Group 2 was marked as non-treated group receiving 60% HFD. While, other groups were treated daily with orlistat (120 mg/kg/d), hesperidin (55 mg/kg/d), combination of hesperidin (55 mg/kg/d) + orlistat (120 mg/kg/d). Hesperidin alone (P<0.001) and particularly in combination with orlistat (P<0.001), resulted in controlling the levels of HFD-altered biomarkers including random and fasting state of glycemia, leptin and insulin resistance. Similarly, hesperidin also improved the serum and tissue levels of leptin, interleukin-6 and tumor necrosis factor-alpha more significantly (P<0.05) when compared with that of orlistat. These results were found to be in accordance with the results of histopathological examination of pancreas, liver and adipose tissues. In-silico studies also proved that hesperidin binds to leptin receptor with higher affinity as compared to that of orlistat and induces the favorable variations in geometrical conformation of leptin receptor to promote its association with leptin which may lead to the cascades of reactions culminating the lipolysis of fats that may ultimately lead to cure obesity. The results of this study may be a significant expectation among the forthcoming treatment strategies for leptin and insulin resistance.

Klíčová slova:

Biochemical simulations – Free energy – Inflammation – Insulin resistance – Molecular dynamics – Obesity – Protein structure – Leptin


Zdroje

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