In-vivo anti-diabetic and anti-hyperlipidemic effects of natural metabolites from resin of Commiphora mukul and their in-silico to in-vitro target fishing
Diabetes mellitus is a rapidly spreading global metabolic disorder that has serious social, health, and economic consequences. Herein, we have evaluated in vivo antidiabetic and antihyperlipidemic effects of myrrhanone-B and myrrhanol-B (isolated from Commiphora mukul Hook). We observed that treatme...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-09-01
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| Series: | Biomedicine & Pharmacotherapy |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332223010053 |
| _version_ | 1797744104563539968 |
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| author | Waseem Ul Islam Faizullah Khan Muhammad Waqas Saeed Ullah Sobia Ahsan Halim Najeeb Ur Rehman Hanif Khan Mohamed H. Mahmoud Gaber El-Saber Batiha Ajmal Khan Ahmed Al-Harrasi |
| author_facet | Waseem Ul Islam Faizullah Khan Muhammad Waqas Saeed Ullah Sobia Ahsan Halim Najeeb Ur Rehman Hanif Khan Mohamed H. Mahmoud Gaber El-Saber Batiha Ajmal Khan Ahmed Al-Harrasi |
| author_sort | Waseem Ul Islam |
| collection | DOAJ |
| description | Diabetes mellitus is a rapidly spreading global metabolic disorder that has serious social, health, and economic consequences. Herein, we have evaluated in vivo antidiabetic and antihyperlipidemic effects of myrrhanone-B and myrrhanol-B (isolated from Commiphora mukul Hook). We observed that treatment with myrrhanone-B and myrrhanol-B at a dose of 5 and 10 mg/kg body weight for 21 days significantly improved body weight loss, water consumption, and the concentration of blood glucose level (BGL) in alloxan (120 mg/kg) induced diabetic mice, which indicates that the compounds possess strong anti-diabetic activities. In the biochemical analysis, these compounds improved an abnormal level of total cholesterol (TC), triacylglycerol (TG), and low-density lipoprotein cholesterol (LDL-C) to a normal level and increased the high-density lipoprotein cholesterol level (HDLC). Later, drug target of compounds was predicted through in-silico docking which shows that these compounds nicely fit in the active site of α-glucosidase enzyme and mediates excellent interactions with the catalytic residues, Asp214 and Asp349. The in-silico results were confirmed by in-vitro testing of myrrhanone-B and myrrhanol-B against α-glucosidase where both the compounds exhibited excellent inhibitory potency with IC50 values of 19.50 ± 0.71, and 16.11 ± 0.69 µM, respectively. Furthermore, mechanistic study was conducted to observe their binding mechanism, which reflect that myrrhanol-B has mixed type of inhibition (ki = 12.33 ± 0.030 µM), while myrrhanone-B demonstrates competitive type of inhibition (ki =14.53 ± 0.040 µM). |
| first_indexed | 2024-03-12T15:04:57Z |
| format | Article |
| id | doaj.art-ff46307cd95946caaa26b32e62734e3e |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-03-12T15:04:57Z |
| publishDate | 2023-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-ff46307cd95946caaa26b32e62734e3e2023-08-13T04:53:03ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-09-01165115214In-vivo anti-diabetic and anti-hyperlipidemic effects of natural metabolites from resin of Commiphora mukul and their in-silico to in-vitro target fishingWaseem Ul Islam0Faizullah Khan1Muhammad Waqas2Saeed Ullah3Sobia Ahsan Halim4Najeeb Ur Rehman5Hanif Khan6Mohamed H. Mahmoud7Gaber El-Saber Batiha8Ajmal Khan9Ahmed Al-Harrasi10Department of Pharmacy, University of Swabi, Khyber Pakhtunkhwa, PakistanNatural and Medical Sciences Research Center, University of Nizwa, P.O. Box 33, Birkat Al Mauz, Nizwa 616, Sultanate of OmanNatural and Medical Sciences Research Center, University of Nizwa, P.O. Box 33, Birkat Al Mauz, Nizwa 616, Sultanate of OmanNatural and Medical Sciences Research Center, University of Nizwa, P.O. Box 33, Birkat Al Mauz, Nizwa 616, Sultanate of OmanNatural and Medical Sciences Research Center, University of Nizwa, P.O. Box 33, Birkat Al Mauz, Nizwa 616, Sultanate of OmanNatural and Medical Sciences Research Center, University of Nizwa, P.O. Box 33, Birkat Al Mauz, Nizwa 616, Sultanate of OmanDepartment of Cell Systems and Anatomy, School of Medicine, University of Texas Health Science Center at San Antonio, TX 78229, USADepartment of Biochemistry, College of Science, King Saud University, Kingdom of Saudi ArabiaDepartment of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour 22511, AlBeheira, EgyptNatural and Medical Sciences Research Center, University of Nizwa, P.O. Box 33, Birkat Al Mauz, Nizwa 616, Sultanate of Oman; Corresponding authors.Natural and Medical Sciences Research Center, University of Nizwa, P.O. Box 33, Birkat Al Mauz, Nizwa 616, Sultanate of Oman; Corresponding authors.Diabetes mellitus is a rapidly spreading global metabolic disorder that has serious social, health, and economic consequences. Herein, we have evaluated in vivo antidiabetic and antihyperlipidemic effects of myrrhanone-B and myrrhanol-B (isolated from Commiphora mukul Hook). We observed that treatment with myrrhanone-B and myrrhanol-B at a dose of 5 and 10 mg/kg body weight for 21 days significantly improved body weight loss, water consumption, and the concentration of blood glucose level (BGL) in alloxan (120 mg/kg) induced diabetic mice, which indicates that the compounds possess strong anti-diabetic activities. In the biochemical analysis, these compounds improved an abnormal level of total cholesterol (TC), triacylglycerol (TG), and low-density lipoprotein cholesterol (LDL-C) to a normal level and increased the high-density lipoprotein cholesterol level (HDLC). Later, drug target of compounds was predicted through in-silico docking which shows that these compounds nicely fit in the active site of α-glucosidase enzyme and mediates excellent interactions with the catalytic residues, Asp214 and Asp349. The in-silico results were confirmed by in-vitro testing of myrrhanone-B and myrrhanol-B against α-glucosidase where both the compounds exhibited excellent inhibitory potency with IC50 values of 19.50 ± 0.71, and 16.11 ± 0.69 µM, respectively. Furthermore, mechanistic study was conducted to observe their binding mechanism, which reflect that myrrhanol-B has mixed type of inhibition (ki = 12.33 ± 0.030 µM), while myrrhanone-B demonstrates competitive type of inhibition (ki =14.53 ± 0.040 µM).http://www.sciencedirect.com/science/article/pii/S0753332223010053AntidiabeticAntihyperlipdimicMyrrhanone-BMyrrhanol-Bα-glucosidaseDocking |
| spellingShingle | Waseem Ul Islam Faizullah Khan Muhammad Waqas Saeed Ullah Sobia Ahsan Halim Najeeb Ur Rehman Hanif Khan Mohamed H. Mahmoud Gaber El-Saber Batiha Ajmal Khan Ahmed Al-Harrasi In-vivo anti-diabetic and anti-hyperlipidemic effects of natural metabolites from resin of Commiphora mukul and their in-silico to in-vitro target fishing Biomedicine & Pharmacotherapy Antidiabetic Antihyperlipdimic Myrrhanone-B Myrrhanol-B α-glucosidase Docking |
| title | In-vivo anti-diabetic and anti-hyperlipidemic effects of natural metabolites from resin of Commiphora mukul and their in-silico to in-vitro target fishing |
| title_full | In-vivo anti-diabetic and anti-hyperlipidemic effects of natural metabolites from resin of Commiphora mukul and their in-silico to in-vitro target fishing |
| title_fullStr | In-vivo anti-diabetic and anti-hyperlipidemic effects of natural metabolites from resin of Commiphora mukul and their in-silico to in-vitro target fishing |
| title_full_unstemmed | In-vivo anti-diabetic and anti-hyperlipidemic effects of natural metabolites from resin of Commiphora mukul and their in-silico to in-vitro target fishing |
| title_short | In-vivo anti-diabetic and anti-hyperlipidemic effects of natural metabolites from resin of Commiphora mukul and their in-silico to in-vitro target fishing |
| title_sort | in vivo anti diabetic and anti hyperlipidemic effects of natural metabolites from resin of commiphora mukul and their in silico to in vitro target fishing |
| topic | Antidiabetic Antihyperlipdimic Myrrhanone-B Myrrhanol-B α-glucosidase Docking |
| url | http://www.sciencedirect.com/science/article/pii/S0753332223010053 |
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