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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Main Authors: 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
Format: Article
Language:English
Published: MDPI AG 2023-03-01
Series:Journal of Clinical Medicine
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Online Access:https://www.mdpi.com/2077-0383/12/6/2152
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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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