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Bukhari HA, Afzal M, Al-Abbasi FA, Sheikh RA, Alqurashi MM, Bawadood AS, Alzarea SI, Alamri A, Sayyed N, Kazmi I. In vivo and computational investigation of butin against alloxan-induced diabetes via biochemical, histopathological, and molecular interactions. Sci Rep 2024; 14:20633. [PMID: 39232184 PMCID: PMC11374895 DOI: 10.1038/s41598-024-71577-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Accepted: 08/29/2024] [Indexed: 09/06/2024] Open
Abstract
Herbs have been used as medicines since antiquity, and it has been discovered that the human body responds well to herbal remedies. Research on the effect of butin was conducted in the current study in the alloxan-induced diabetic rat paradigm. A total of 30 Wistar rats were randomly assigned into the following groups (n = 6): I-Normal; II-Alloxan-induced (50 mg/kg); III-Alloxan + butin 25 mg/kg; IV-Alloxan + butin 50 mg/kg; V-Butin per se 50 mg/kg. Various diabetic parameters (blood glucose, insulin, HbA1c), lipid profile, inflammatory (TNF-α, IL-1β, IL-6 and NF-κB), antioxidant enzymes (CAT, SOD and GSH), oxidative stress indicators (MDA), apoptosis marker (caspase-3), hepatic markers (ALT and AST), and histopathological changes were assessed. Additionally, molecular docking and dynamics were performed to evaluate the interaction of butin with target proteins. Butin treatment, at both doses, significantly restored biochemical parameters and preserved pancreatic histopathology in diabetic rats. It effectively modulated blood parameters, lipid profiles, inflammatory markers, apoptosis, antioxidant enzyme activity, oxidative stress, and hepatic markers. Molecular docking revealed that butin binds to proteins such as caspase-3 (1NME), NF-κB (1SVC), and serum insulin (4IBM) with binding affinities of - 7.4, - 6.5, and - 8.2 kcal/mol, respectively. Molecular dynamics simulations further suggested that butin induces significant conformational changes in these proteins. Butin exhibits potential effects against alloxan-induced diabetic rats by restoring biochemical balance, reducing inflammation, and protecting pancreatic tissue. Its binding to key proteins involved in apoptosis and inflammation highlights its therapeutic potential in diabetes management.
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Affiliation(s)
- Hussam A Bukhari
- Department of Pathology, Faculty of Medicine, King Abdulaziz University, 21589, Jeddah, Saudi Arabia
- King Abdulaziz University Hospital, King Abdulaziz University, 21589, Jeddah, Saudi Arabia
| | - Muhammad Afzal
- Pharmacy Program, Department of Pharmaceutical Sciences, Batterjee Medical College, P.O. Box 6231, 21442, Jeddah, Saudi Arabia
| | - Fahad A Al-Abbasi
- Department of Biochemistry, Faculty of Sciences, King Abdulaziz University, 21589, Jeddah, Saudi Arabia
| | - Ryan A Sheikh
- Department of Biochemistry, Faculty of Sciences, King Abdulaziz University, 21589, Jeddah, Saudi Arabia
- Experimental Biochemistry Unit, King Fahd Medical Research Center, King Abdulaziz University, 21589, Jeddah, Saudi Arabia
| | - May M Alqurashi
- Department of Biochemistry, Faculty of Sciences, King Abdulaziz University, 21589, Jeddah, Saudi Arabia
| | - Azizah Salim Bawadood
- Basic Medical Sciences Department, College of Medicine, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia
| | - Sami I Alzarea
- Department of Pharmacology, College of Pharmacy, Jouf University, 72341, Aljouf, Sakaka, Saudi Arabia
| | - Abdulaziz Alamri
- Department of Biochemistry, College of Science, King Saud University, 11451, Riyadh, Saudi Arabia
| | - Nadeem Sayyed
- School of Pharmacy, Glocal University, Saharanpur, 247121, India
| | - Imran Kazmi
- Department of Biochemistry, Faculty of Sciences, King Abdulaziz University, 21589, Jeddah, Saudi Arabia.
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Demirel S. Vasorelaxant effects of biochemical constituents of various medicinal plants and their benefits in diabetes. World J Diabetes 2024; 15:1122-1141. [PMID: 38983824 PMCID: PMC11229960 DOI: 10.4239/wjd.v15.i6.1122] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2023] [Revised: 03/07/2024] [Accepted: 05/06/2024] [Indexed: 06/11/2024] Open
Abstract
Endothelial function plays a pivotal role in cardiovascular health, and dysfunction in this context diminishes vasorelaxation concomitant with endothelial activity. The nitric oxide-cyclic guanosine monophosphate pathway, prostacyclin-cyclic adenosine monophosphate pathway, inhibition of phosphodiesterase, and the opening of potassium channels, coupled with the reduction of calcium levels in the cell, constitute critical mechanisms governing vasorelaxation. Cardiovascular disease stands as a significant contributor to morbidity and mortality among individuals with diabetes, with adults afflicted by diabetes exhibiting a heightened cardiovascular risk compared to their non-diabetic counterparts. A plethora of medicinal plants, characterized by potent pharmacological effects and minimal side effects, holds promise in addressing these concerns. In this review, we delineate various medicinal plants and their respective biochemical constituents, showcasing concurrent vasorelaxant and anti-diabetic activities.
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Affiliation(s)
- Sadettin Demirel
- Medicine School, Physiology Department, Bursa Uludag University, Bursa 16059, Türkiye
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Abdella FI, Toumi A, Boudriga S, Alanazi TY, Alshamari AK, Alrashdi AA, Hamden K. Antiobesity and antidiabetes effects of Cyperus rotundus rhizomes presenting protein tyrosine phosphatase, dipeptidyl peptidase 4, metabolic enzymes, stress oxidant and inflammation inhibitory potential. Heliyon 2024; 10:e27598. [PMID: 38486768 PMCID: PMC10937842 DOI: 10.1016/j.heliyon.2024.e27598] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Revised: 03/03/2024] [Accepted: 03/04/2024] [Indexed: 03/17/2024] Open
Abstract
Diabetes is a significant global health concern that increases the vulnerability to various chronic illnesses. In view of this issue, the current research aimed to examine the effects of administering an extract derived from the tubers of Cyperus rotundus L (CrE) on obesity, type 1 diabetes, and liver-kidney toxicity. Through the utilization of HPLC-DAD analysis, it was discovered that the extract contained several components, including quercetin (47.8%), luteolin glucoside (17%), luteolin (7.56%), apigenin-7-glucoside (6.29%), naringinin (4.52%), and seven others. In vitro experiments they have demonstrated that CrE effectively inhibited key digestive enzymes associated with obesity and type 2 diabetes, such as DPP-4, PTP1B, lipase, and α-amylase, as evidenced by their respective IC50 values are about 23, 51,83, and 67 μg/ml respectively. Furthermore, when diabetic rats were administered CrE, the activity of pancreatic enzymes linked to inflammation, namely 5-lipoxygenase (5-LO), hyaluronidase (HAase), and myeloperoxidase (MPO), was significantly suppressed by 48, 41, 75, and 47%, respectively. Moreover, CrE exhibited protective effects on pancreatic β-cells by inhibiting the formation of thiobarbituric acid reactive substances (TBARS) by 65% and the induction of superoxide Dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) activities by 62, 108, and 112% respectively as compared to diabetic untreated rat. Additionally, CrE significantly inhibited the activities of intestinal, pancreatic, and serum lipase and α-amylase activities. In diabetic rats, CrE administration suppressed glycogen phosphorylase (GP) stimulated glycogen synthase (GS) activities by 45 and 30%; and this increased liver glycogen content by 45%. Furthermore, CrE modulated key hepatic enzymes involved in carbohydrate metabolism, including hexokinase (HK), glucose-6-phosphate dehydrogenase (G6PD), glucose-6-phosphatase (G6P), and fructose-1,6-bisphosphatase (FBP). Notably, the average food and water intake (AFI and AWI) of diabetic rats treated with CrE was reduced by 15 and 16% respectively as compared to those without any treatment. Therefore, this study demonstrated the effectiveness of Cyperus rotundus tubers in preventing and treating obesity and diabetes.
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Affiliation(s)
- Faiza I.A. Abdella
- Department of Chemistry, College of Science, Ha'il University, Ha'il, 81451, Saudi Arabia
| | - Amani Toumi
- Laboratory of Heterocyclic Chemistry Natural Product and Reactivity (LR11ES39), Department of Chemistry, Faculty of Science of Monastir, University of Monastir, Monastir, 5019, Tunisia
| | - Sarra Boudriga
- Laboratory of Heterocyclic Chemistry Natural Product and Reactivity (LR11ES39), Department of Chemistry, Faculty of Science of Monastir, University of Monastir, Monastir, 5019, Tunisia
| | - Tahani Y.A. Alanazi
- Department of Chemistry, College of Science, Ha'il University, Ha'il, 81451, Saudi Arabia
| | - Asma K. Alshamari
- Department of Chemistry, College of Science, Ha'il University, Ha'il, 81451, Saudi Arabia
| | | | - Khaled Hamden
- Laboratory of Bioresources: Integrative Biology and Valorization, Higher Institute of Biotechnology of Monastir, University of Monastir, Monastir, 5000, Tunisia
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Dallali D, Fakhfakh J, Paris C, Hamden K, Varbanov M, Allouche N. Fructooligosaccharides from Cynoglossum tubiflorus: Effect of the molecular size on their antidiabetic activity in high-fat diet and alloxan induced diabetic rats. Bioorg Chem 2024; 143:107100. [PMID: 38211550 DOI: 10.1016/j.bioorg.2024.107100] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2023] [Revised: 12/22/2023] [Accepted: 01/02/2024] [Indexed: 01/13/2024]
Abstract
The use of acetylation followed by silica gel column purification allowed the isolation of eight fructooligosaccharides (FOS) from the ethanol extract of Cynoglossum tubiflorus roots. Each FOS was identified by analyzing its FT-IR, HRMS/MS and NMR data, including 1H, 13C and 2D NMR HH COSY, HMBC and NOESY. In diabetic rats treated with a series of FOS from Glc-(Fru)3 to Glc-(Fru)7, a significant inhibition of intestinal α-amylase was observed. This activity increases proportionally with the FOS molecular size. It was found that they delay the absorption of total cholesterol (TC), ldl-cholesterol (LDL-C) and increase HDL-cholesterol (HDL-C) in a molecular size-dependent manner. This inhibitory effect on the activity of the digestive enzyme causes a significant (p < 0.05) reduction in the level of glucose in the blood as an anti-diabetic action. The ethanolic extract (E.E) exerts a significant effect against α-amylase as well as antihyperglycemic and antihyperlipidemic actions, while its acetylation suppresses these effects. Therefore, this study demonstrates for the first time that pure FOS act as an efficient agent in preventing hyperglycemia and hyperlipidemia and that this action evolves in the same manner with their molecular size.
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Affiliation(s)
- Dhouha Dallali
- Laboratory of Organic Chemistry LR17ES08, Natural Substances Team, Faculty of Sciences of Sfax, University of Sfax, P.B.1171, Sfax 3000, Tunisia
| | - Jawhar Fakhfakh
- Laboratory of Organic Chemistry LR17ES08, Natural Substances Team, Faculty of Sciences of Sfax, University of Sfax, P.B.1171, Sfax 3000, Tunisia.
| | - Cédric Paris
- Laboratory of Biomolecule Engineering (LIBio), Lorraine University, 2 Avenue de la Foret de Haye -TSA, Vandoeuvre Cedex 40602 54518, France
| | - Khaled Hamden
- Laboratory of Bioresources: Integrative Biology and Exploiting, Higher Institute of Biotechnology of Monastir, University of Monastir, Tunisia
| | - Mihayl Varbanov
- L2CM, Université de Lorraine, Centre National de la Recherche Scientifique (CNRS), F-54000 Nancy, France
| | - Noureddine Allouche
- Laboratory of Organic Chemistry LR17ES08, Natural Substances Team, Faculty of Sciences of Sfax, University of Sfax, P.B.1171, Sfax 3000, Tunisia
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Muhammed TM, Jalil AT, Taher WM, Aminov Z, Alsaikhan F, Ramírez-Coronel AA, Ramaiah P, Farhood B. The Effects of Apigenin in the Treatment of Diabetic Nephropathy: A Systematic Review of Non-clinical Studies. Mini Rev Med Chem 2024; 24:341-354. [PMID: 38282447 DOI: 10.2174/1389557523666230811092423] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2023] [Revised: 06/10/2023] [Accepted: 07/13/2023] [Indexed: 01/30/2024]
Abstract
PURPOSE Diabetes is one of the important and growing diseases in the world. Among the most common diabetic complications are renal adverse effects. The use of apigenin may prevent the development and progression of diabetes-related injuries. The current study aims to review the effects of apigenin in the treatment of diabetic nephropathy. METHODS In this review, a systematic search was performed based on PRISMA guidelines for obtaining all relevant studies on "the effects of apigenin against diabetic nephropathy" in various electronic databases up to September 2022. Ninety-one articles were obtained and screened in accordance with the predefined inclusion and exclusion criteria. Seven eligible articles were finally included in this review. RESULTS The experimental findings revealed that hyperglycemia led to the decreased cell viability of kidney cells and body weight loss and an increased kidney weight of rats; however, apigenin administration had a reverse effect on these evaluated parameters. It was also found that hyperglycemia could induce alterations in the biochemical and renal function-related parameters as well as histopathological injuries in kidney cells or tissue; in contrast, the apigenin administration could ameliorate the hyperglycemia-induced renal adverse effects. CONCLUSION The results indicated that the use of apigenin could mitigate diabetes-induced renal adverse effects, mainly through its antioxidant, anti-apoptotic, and anti-inflammatory activities. Since the findings of this study are based on experimental studies, suggesting the use of apigenin (as a nephroprotective agent) against diabetic nephropathy requires further clinical studies.
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Affiliation(s)
- Thikra Majid Muhammed
- Department of Biotechnology, College of Applied Sciences, University of Fallujah, Al-anbar, Iraq
| | - Abduladheem Turki Jalil
- Medical Laboratories Techniques Department, Al-Mustaqbal University College, Babylon, Hilla, 51001, Iraq
| | - Waam Mohammed Taher
- National University of Science and Technology, Thi Qar University, Dhi Qar, Iraq
| | - Zafar Aminov
- Department of Public Health and Healthcare management, Samarkand State Medical University, 18 Amir Temur Street, Samarkand, Uzbekistan
- Department of Scientific Affairs, Tashkent State Dental Institute, 103 Makhtumkuli Str., Tashkent, Uzbekistan
| | - Fahad Alsaikhan
- College of Pharmacy, Prince Sattam Bin Abdulaziz University, Alkharj, Saudi Arabia
| | - Andrés Alexis Ramírez-Coronel
- Azogues Campus Nursing Career, Health and Behavior Research Group (HBR), Psychometry and Ethology Laboratory, Catholic University of Cuenca, Cuenca, Ecuador
- Epidemiology and Biostatistics Research Group, CES University, Medellín, Antioquia, 4440555, Colombia
- Educational Statistics Research Group (GIEE), National University of Education, Cvenca, Ecuador
| | | | - Bagher Farhood
- Department of Medical Physics and Radiology, Faculty of Paramedical Sciences, Kashan University of Medical Sciences, Kashan, Iran
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Zhang X, Tang Y, Lu G, Gu J. Pharmacological Activity of Flavonoid Quercetin and Its Therapeutic Potential in Testicular Injury. Nutrients 2023; 15:2231. [PMID: 37432408 DOI: 10.3390/nu15092231] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2023] [Revised: 04/17/2023] [Accepted: 05/01/2023] [Indexed: 07/12/2023] Open
Abstract
Quercetin is a natural flavonoid widely found in natural fruits and vegetables. Recent studies have shown that quercetin mediates multiple beneficial effects in a variety of organ damage and diseases, and is considered a healthcare supplement with health-promoting potential. Male infertility is a major health concern, and testicular damage from multiple causes is an important etiology. Previous studies have shown that quercetin has a protective effect on reproductive function. This may be related to the antioxidant, anti-inflammatory, and anti-apoptotic biological activities of quercetin. Therefore, this paper reviews the mechanisms by which quercetin exerts its pharmacological activity and its role in testicular damage induced by various etiologies. In addition, this paper compiles the application of quercetin in clinical trials, demonstrating its practical effects in regulating blood pressure and inhibiting cellular senescence in human patients. However, more in-depth experimental studies and clinical trials are needed to confirm the true value of quercetin for the prevention and protection against testicular injury.
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Affiliation(s)
- Xiaohui Zhang
- School of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
| | - Yufeng Tang
- Department of Orthopedic Surgery, The First Affiliated Hospital of Shandong First Medical University, Jinan 250014, China
| | - Guangping Lu
- School of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
| | - Junlian Gu
- School of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
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