Antihyperglycemic Potential of <i>Spondias mangifera</i> Fruits via Inhibition of 11β-HSD Type 1 Enzyme: In Silico and In Vivo Approach
The 11 β- hydroxysteroid dehydrogenase 1 (11 β-HSD1) is hypothesized to play a role in the pathogenesis of type 2 diabetes and its related complications. Because high glucocorticoid levels are a risk factor for metabolic disorders, 11β-HSD1 might be a viable therapeutic target. In this investigation...
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2023-03-01
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author | Shadma Wahab Mohammad Khalid Mohammed H. Alqarni Mohamed Fadul A. Elagib Ghadah Khaled Bahamdan Ahmed I. Foudah Tariq M. Aljarba Mons S. Mohamed Nazik Salih Mohamed Muhammad Arif |
author_facet | Shadma Wahab Mohammad Khalid Mohammed H. Alqarni Mohamed Fadul A. Elagib Ghadah Khaled Bahamdan Ahmed I. Foudah Tariq M. Aljarba Mons S. Mohamed Nazik Salih Mohamed Muhammad Arif |
author_sort | Shadma Wahab |
collection | DOAJ |
description | The 11 β- hydroxysteroid dehydrogenase 1 (11 β-HSD1) is hypothesized to play a role in the pathogenesis of type 2 diabetes and its related complications. Because high glucocorticoid levels are a risk factor for metabolic disorders, 11β-HSD1 might be a viable therapeutic target. In this investigation, docking experiments were performed on the main constituents of <i>Spondias mangifera</i> (SM) oleanolic acid, β-amyrin, and β-sitosterol to ascertain their affinity and binding interaction in the human 11β-hydroxysteroid dehydrogenase-1 enzyme’s active region. The results of in vitro 11β HSD1 inhibitory assay demonstrated that the extract of <i>S. mangifera</i> had a significant (<i>p</i> < 0.05) decrease in the 11-HSD1% inhibition (63.97%) in comparison to STZ (31.79%). Additionally, a non-insulin-dependent diabetic mice model was used to examine the sub-acute anti-hyperlipidemic and anti-diabetic effects of SM fruits. Results revealed that, in comparison to the diabetic control group, SM fruit extract (SMFE) extract at doses of 200 and 400 mg/kg body weight considerably (<i>p</i> < 0.05 and <i>p</i> < 0.01) lowered blood glucose levels at 21 and 28 days, as well as significantly decreased total cholesterol (TC) and triglycerides (TG) and enhanced the levels of high-density lipoprotein (HDL). After 120 and 180 s of receiving 200 and 400 mg/kg SMFE, respectively, disease control mice showed significantly poorer blood glucose tolerance (<i>p</i> < 0.05 and <i>p</i> < 0.01). SMFE extract 200 (<i>p</i> < 0.05), SMFE extract 400 (<i>p</i> < 0.01), and Glibenclamide at a dosage of 5 mg/kg body weight all resulted in statistically significant weight increase (<i>p</i> < 0.01) when compared to the diabetic control group after 28 days of treatment. According to in silico, in vitro, and in vivo validation, SMFE is a prospective medication with anti-diabetic and hypoglycemic effects. |
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spelling | doaj.art-5e8ceae232dc4673929bb2370fb497c82023-11-17T11:48:49ZengMDPI AGJournal of Clinical Medicine2077-03832023-03-01126215210.3390/jcm12062152Antihyperglycemic Potential of <i>Spondias mangifera</i> Fruits via Inhibition of 11β-HSD Type 1 Enzyme: In Silico and In Vivo ApproachShadma Wahab0Mohammad Khalid1Mohammed H. Alqarni2Mohamed Fadul A. Elagib3Ghadah Khaled Bahamdan4Ahmed I. Foudah5Tariq M. Aljarba6Mons S. Mohamed7Nazik Salih Mohamed8Muhammad Arif9Department of Pharmacognosy, College of Pharmacy, King Khalid University, Abha 62529, Saudi ArabiaDepartment of Pharmacognosy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, P.O. Box 173, Al-Kharj 11942, Saudi ArabiaDepartment of Pharmacognosy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, P.O. Box 173, Al-Kharj 11942, Saudi ArabiaDepartment of Periodontics and Community Dental Sciences, College of Dentistry, King Khalid University, Abha 61421, Saudi ArabiaDepartment of Periodontics and Community Dental Sciences, College of Dentistry, King Khalid University, Abha 61421, Saudi ArabiaDepartment of Pharmacognosy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, P.O. Box 173, Al-Kharj 11942, Saudi ArabiaDepartment of Pharmacognosy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, P.O. Box 173, Al-Kharj 11942, Saudi ArabiaDepartment of Pharmacognosy, Faculty of Pharmacy, University of Khartoum, Khartoum 11111, SudanDepartment of Pharmacognosy, Imperial University College, Khartoum 11111, SudanDepartment of Pharmacognosy, Faculty of Pharmacy, Integral University, Lucknow 226026, IndiaThe 11 β- hydroxysteroid dehydrogenase 1 (11 β-HSD1) is hypothesized to play a role in the pathogenesis of type 2 diabetes and its related complications. Because high glucocorticoid levels are a risk factor for metabolic disorders, 11β-HSD1 might be a viable therapeutic target. In this investigation, docking experiments were performed on the main constituents of <i>Spondias mangifera</i> (SM) oleanolic acid, β-amyrin, and β-sitosterol to ascertain their affinity and binding interaction in the human 11β-hydroxysteroid dehydrogenase-1 enzyme’s active region. The results of in vitro 11β HSD1 inhibitory assay demonstrated that the extract of <i>S. mangifera</i> had a significant (<i>p</i> < 0.05) decrease in the 11-HSD1% inhibition (63.97%) in comparison to STZ (31.79%). Additionally, a non-insulin-dependent diabetic mice model was used to examine the sub-acute anti-hyperlipidemic and anti-diabetic effects of SM fruits. Results revealed that, in comparison to the diabetic control group, SM fruit extract (SMFE) extract at doses of 200 and 400 mg/kg body weight considerably (<i>p</i> < 0.05 and <i>p</i> < 0.01) lowered blood glucose levels at 21 and 28 days, as well as significantly decreased total cholesterol (TC) and triglycerides (TG) and enhanced the levels of high-density lipoprotein (HDL). After 120 and 180 s of receiving 200 and 400 mg/kg SMFE, respectively, disease control mice showed significantly poorer blood glucose tolerance (<i>p</i> < 0.05 and <i>p</i> < 0.01). SMFE extract 200 (<i>p</i> < 0.05), SMFE extract 400 (<i>p</i> < 0.01), and Glibenclamide at a dosage of 5 mg/kg body weight all resulted in statistically significant weight increase (<i>p</i> < 0.01) when compared to the diabetic control group after 28 days of treatment. According to in silico, in vitro, and in vivo validation, SMFE is a prospective medication with anti-diabetic and hypoglycemic effects.https://www.mdpi.com/2077-0383/12/6/2152natural productshypoglycemia<i>Spondias mangifera</i>anti-hyperglycemic11β-HSD1in silico |
spellingShingle | Shadma Wahab Mohammad Khalid Mohammed H. Alqarni Mohamed Fadul A. Elagib Ghadah Khaled Bahamdan Ahmed I. Foudah Tariq M. Aljarba Mons S. Mohamed Nazik Salih Mohamed Muhammad Arif Antihyperglycemic Potential of <i>Spondias mangifera</i> Fruits via Inhibition of 11β-HSD Type 1 Enzyme: In Silico and In Vivo Approach Journal of Clinical Medicine natural products hypoglycemia <i>Spondias mangifera</i> anti-hyperglycemic 11β-HSD1 in silico |
title | Antihyperglycemic Potential of <i>Spondias mangifera</i> Fruits via Inhibition of 11β-HSD Type 1 Enzyme: In Silico and In Vivo Approach |
title_full | Antihyperglycemic Potential of <i>Spondias mangifera</i> Fruits via Inhibition of 11β-HSD Type 1 Enzyme: In Silico and In Vivo Approach |
title_fullStr | Antihyperglycemic Potential of <i>Spondias mangifera</i> Fruits via Inhibition of 11β-HSD Type 1 Enzyme: In Silico and In Vivo Approach |
title_full_unstemmed | Antihyperglycemic Potential of <i>Spondias mangifera</i> Fruits via Inhibition of 11β-HSD Type 1 Enzyme: In Silico and In Vivo Approach |
title_short | Antihyperglycemic Potential of <i>Spondias mangifera</i> Fruits via Inhibition of 11β-HSD Type 1 Enzyme: In Silico and In Vivo Approach |
title_sort | antihyperglycemic potential of i spondias mangifera i fruits via inhibition of 11β hsd type 1 enzyme in silico and in vivo approach |
topic | natural products hypoglycemia <i>Spondias mangifera</i> anti-hyperglycemic 11β-HSD1 in silico |
url | https://www.mdpi.com/2077-0383/12/6/2152 |
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