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Adeyomoye OI, Adetunji JB, Olaniyan OT, Adetunji CO, Ogunmiluyi OE, Uwejigho RE. Molecular basis of cardioprotective effects of methanol extract of Ficus exasperata in diabetic Wistar rats. Toxicol Rep 2025; 14:102028. [PMID: 40353243 PMCID: PMC12063115 DOI: 10.1016/j.toxrep.2025.102028] [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: 08/20/2024] [Revised: 04/08/2025] [Accepted: 04/09/2025] [Indexed: 05/14/2025] Open
Abstract
Cardiovascular complications are a significant concern in diabetes mellitus. Ficus exasperata Vahl leaf has been traditionally used for diabetes management, yet its impact on cardiovascular biomarkers in diabetic conditions remains unexplored. This study evaluated the effects of methanol extract of Ficus exasperata (MEFE) on antioxidant defense, oxidative stress markers, ion transport enzymes, inflammatory mediators, and cardiovascular gene expression in diabetic Wistar rats. Twenty Wistar rats were divided into four groups (n = 5): control, diabetic untreated, diabetes + MEFE (200 mg/kg), and diabetes + insulin (0.3 IU). Diabetes was induced with alloxan monohydrate (150 mg/kg), and treatments were administered orally for 28 days. Antioxidant enzyme activities (Glutathione peroxidase (GPx), Glutathione reductase (GR), Superoxide dismutase (SOD), Catalase, malondialdehyde and 8-hydroxy-2'-deoxyguanosine), Cardiac biomarkers (Na+/K+ ATPase, Ca2+ ATPase, Creatinine kinase-myocardial band (CK-MB), Troponin I, Troponin T, and Lactatate dehydrogenase), and gene expression of CRP, ACE, P-Selectin, and eNOS were evaluated. Data were analyzed using one-way analysis of variance, expressed as mean ± SEM, and p < 0.05 was considered statistically significant. The diabetic group treated with MEFE (200 mg/kg) significantly increased Ca²⁺ ATPase, SOD, and glutathione reductase activities compared to diabetic untreated. However, malondialdehyde and 8-OHdG levels decreased significantly in diabetes+MEFE (200 mg/kg) compared to diabetes untreated. CK-MB levels increased significantly in diabetes+MEFE (200 mg/kg) compared to diabetic untreated. MEFE reduced ACE and P-selectin expression in diabetes+MEFE (200 mg/kg) compared to diabetic untreated, indicating potential antihypertensive and anti-thrombotic effects. However, it increased CRP levels compared to control, suggesting an inflammatory response. MEFE significantly reduced eNOS expression compared to diabetic untreated, suggesting impaired vascular function. These findings suggest that while Ficus exasperata has some beneficial effects, its impact on inflammatory and cardiac biomarkers necessitates further research to fully understand its therapeutic potential and safety.
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Raza A, Mushtaq MN, Hassan S, Sharif A, Akhtar B, Akhtar MF. Mitigation of Diabetes Mellitus Using Euphorbia helioscopia Leaf Ethanolic Extract by Modulating GCK, GLUT4, IGF, and G6P Expressions in Streptozotocin-Induced Diabetic Rats. J Diabetes Res 2024; 2024:5497320. [PMID: 39329045 PMCID: PMC11424858 DOI: 10.1155/2024/5497320] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2023] [Revised: 06/27/2024] [Accepted: 08/12/2024] [Indexed: 09/28/2024] Open
Abstract
Diabetes mellitus is a metabolic disorder. Synthetic antidiabetics are the commonly used treatment options associated with complications. The objective of this study was to explore the antioxidative and antidiabetic potential of Euphorbia helioscopia whole plant ethanolic extract using in vitro and in vivo models. For that purpose, the antioxidative potential was explored by using 2,2-diphenyl-1-picrylhydrazyl analysis. In vitro antidiabetic potential of the extract was evaluated using amylase inhibitory analysis. In vivo antidiabetic activity of the extract was assessed in diabetic rats using streptozotocin/nicotinamide (60 mg/kg/120 mg/kg) as an inducing agent. Metformin was used as standard. The results indicated the presence of significant quantities of phenolic 82.18 ± 1.28 mgg-1 gallic acid equivalent (GAE) and flavonoid 66.55±1.22 mgg-1 quercetin equivalent (QE) contents in the extract. Quantitation of phytoconstituents exhibited the presence of sinapic acid, myricetin, and quercetin using HPLC analysis. The extract inhibited α-amylase by 84.71%, and an antiglycemic potential of 50.34% was assessed in the OGTT assay. Biochemical analysis demonstrated a reduction in urea, creatinine, cholesterol, low-density lipoprotein, and alkaline phosphatase (p < 0.001) as compared to diabetic control rats at the dose of 500 mg/kg. An upregulation in the expressions of glucokinase, glucose transporter 4, peroxisome proliferator-activated receptor γ, and insulin-like growth factor was observed in treated rats in contrast to G6P expression, which was downregulated upon treatment. In conclusion, this study provided evidence of the antioxidative and antidiabetic potential of E. helioscopia whole plant ethanolic extract through in vitro and in vivo analysis and emphasized its promising role as a natural alternative.
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Affiliation(s)
- Ahmed Raza
- Faculty of PharmacyThe University of Lahore, Lahore 54000, Pakistan
| | | | - Sadia Hassan
- Department of Biomedical Engineering and SciencesSchool of Mechanical and Manufacturing EngineeringNational University of Science and Technology, Islamabad 24090, Pakistan
| | - Ali Sharif
- Department of PharmacologyFaculty of Pharmaceutical and Allied Health SciencesLahore College for Women University, Lahore 54000, Pakistan
| | - Bushra Akhtar
- Department of PharmacyUniversity of Agriculture, Faisalabad 38000, Pakistan
| | - Muhammad Furqan Akhtar
- Riphah Institute of Pharmaceutical SciencesRiphah International UniversityLahore Campus, Lahore 54000, Pakistan
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Han J, Hao X, Fatima M, Chauhdary Z, Jamshed A, Abdur Rahman HM, Siddique R, Asif M, Rana S, Hussain L. Pharmacological Assessment of Aqueous Ethanolic Extract of Thalictrum Foetidum Against Haloperidol-Induced Parkinson's Like Symptoms in Animal Model: A Dose-Dependent Study With Mechanistic Approach. Dose Response 2024; 22:15593258241282020. [PMID: 39224700 PMCID: PMC11367614 DOI: 10.1177/15593258241282020] [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: 05/10/2024] [Accepted: 08/08/2024] [Indexed: 09/04/2024] Open
Abstract
Introduction: Parkinson's disease (PD) is characterized by dopamine deficiency in the corpus striatum due to the degeneration of dopaminergic neurons in the substantia nigra. Symptoms include bradykinesia, resting tremors, unstable posture, muscular rigidity, and a shuffled gait. Thalictrum foetidum is traditionally used for neurodegenerative disorders. Objectives: This study aimed to explore the therapeutic potential of aqueous ethanolic extract of Thalictrum foetidum (AETF) against Parkinson-like symptoms and to investigate its underlying mechanism. Methodology: Thirty-six albino mice were randomly divided into 6 groups (n = 6): normal control, disease control, standard treatment (levodopa/carbidopa, 100/25 mg/kg), and 3 treatment groups (AETF at 200, 400, and 600 mg/kg). One hour before treatment, haloperidol (1 mg/kg, i. p.) was administered to induce Parkinson's disease in all groups except the normal control group. Results: Behavioral analysis showed significant improvement (P < .001) in motor function, muscular coordination, and reduced muscular rigidity and tremors. AETF also reduced oxidative stress. Histological examination of the brain showed reduced Lewy bodies, neurofibrillary tangles, and plaque formation. Conclusion: AETF alleviated PD symptoms by reducing neurodegeneration, modulating oxidative stress, and inhibiting the expression of nuclear factor-κB (NF-κB) and associated inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6).
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Affiliation(s)
- Jiangyu Han
- School of Medicine, Huzhou University, Huzhou, P.R China
| | - Xu Hao
- College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, P.R China
| | - Mishal Fatima
- Department of Pharmacology, Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad, Pakistan
| | - Zunera Chauhdary
- Department of Pharmacology, Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad, Pakistan
| | - Ayesha Jamshed
- Department of Pharmacology, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, Pakistan
| | | | - Rida Siddique
- Department of Pharmacology, Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad, Pakistan
| | - Muhammad Asif
- Department of Pharmacology, Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad, Pakistan
| | - Saba Rana
- Department of Pharmacology, Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad, Pakistan
| | - Liaqat Hussain
- Department of Pharmacology, Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad, Pakistan
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Annicchiarico A, Barile B, Buccoliero C, Nicchia GP, Brunetti G. Alternative therapeutic strategies in diabetes management. World J Diabetes 2024; 15:1142-1161. [PMID: 38983831 PMCID: PMC11229975 DOI: 10.4239/wjd.v15.i6.1142] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Revised: 02/17/2024] [Accepted: 04/12/2024] [Indexed: 06/11/2024] Open
Abstract
Diabetes is a heterogeneous metabolic disease characterized by elevated blood glucose levels resulting from the destruction or malfunction of pancreatic β cells, insulin resistance in peripheral tissues, or both, and results in a non-sufficient production of insulin. To adjust blood glucose levels, diabetic patients need exogenous insulin administration together with medical nutrition therapy and physical activity. With the aim of improving insulin availability in diabetic patients as well as ameliorating diabetes comorbidities, different strategies have been investigated. The first approaches included enhancing endogenous β cell activity or transplanting new islets. The protocol for this kind of intervention has recently been optimized, leading to standardized procedures. It is indicated for diabetic patients with severe hypoglycemia, complicated by impaired hypoglycemia awareness or exacerbated glycemic lability. Transplantation has been associated with improvement in all comorbidities associated with diabetes, quality of life, and survival. However, different trials are ongoing to further improve the beneficial effects of transplantation. Furthermore, to overcome some limitations associated with the availability of islets/pancreas, alternative therapeutic strategies are under evaluation, such as the use of mesenchymal stem cells (MSCs) or induced pluripotent stem cells for transplantation. The cotransplantation of MSCs with islets has been successful, thus providing protection against proinflammatory cytokines and hypoxia through different mechanisms, including exosome release. The use of induced pluripotent stem cells is recent and requires further investigation. The advantages of MSC implantation have also included the improvement of diabetes-related comorbidities, such as wound healing. Despite the number of advantages of the direct injection of MSCs, new strategies involving biomaterials and scaffolds have been developed to improve the efficacy of mesenchymal cell delivery with promising results. In conclusion, this paper offered an overview of new alternative strategies for diabetes management while highlighting some limitations that will need to be overcome by future approaches.
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Affiliation(s)
- Alessia Annicchiarico
- Department of Biosciences, Biotechnologies and Environment, University of Bari Aldo Moro, Bari 70125, Italy
| | - Barbara Barile
- Department of Biosciences, Biotechnologies and Environment, University of Bari Aldo Moro, Bari 70125, Italy
| | - Cinzia Buccoliero
- Department of Biosciences, Biotechnologies and Environment, University of Bari Aldo Moro, Bari 70125, Italy
| | - Grazia Paola Nicchia
- Department of Biosciences, Biotechnologies and Environment, University of Bari Aldo Moro, Bari 70125, Italy
| | - Giacomina Brunetti
- Department of Biosciences, Biotechnologies and Environment, University of Bari Aldo Moro, Bari 70125, Italy
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Muyenga TA, Bamitale SKD, Kibuule D, Sithole S, Mukanganyama S, Rudolph C, Venables L, Hattingh AC, van de Venter M, Ezeala CC. Kigelia africana fruit fractions inhibit in vitro alpha-glucosidase activity: a potential natural alpha-glucosidase inhibitor. BMC Complement Med Ther 2024; 24:230. [PMID: 38867199 PMCID: PMC11167833 DOI: 10.1186/s12906-024-04510-5] [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: 01/18/2024] [Accepted: 05/21/2024] [Indexed: 06/14/2024] Open
Abstract
BACKGROUND Diabetes affects 75% of people in low-income countries, where conventional drugs like metformin are available, but newer drugs like alpha-glucosidase inhibitors are not accessible to most Southern African patients. AIM To evaluate the α-glucosidase and α-amylase inhibitory activities of fractionated aqueous extracts of Kigelia africana fruit (KAFE) and their phytochemical fingerprints using gas chromatography-mass spectrometry (GC-MS). MATERIALS AND METHODS We studied K. africana fruit fractions' inhibitory effects on alpha-glucosidase and alpha-amylase using bioassay-guided fractionation, and analyzed their phytochemical profiles with GC-MS. KEY FINDINGS Both the aqueous extract and ethyl acetate fraction of the aqueous extract exhibited a low dose-dependent inhibition of alpha-amylase activity (p < 0.0001). At a concentration of 500 μg/mL, the aqueous extract caused an alpha-glucosidase inhibition of 64.10 ± 2.7%, with an estimated IC50 of 193.7 μg/mL, while the ethyl acetate fraction had an inhibition of 89.82 ± 0.8% and an estimated IC50 of 10.41 μg/mL. The subfraction G, which had the highest alpha-glucosidase inhibitory activity at 85.10 ± 0.7%, had significantly lower activity than the ethyl acetate fraction. The most bioactive fraction was found to contain 11"(2-cyclopenten-1-yl) undecanoic acid, ( +)- and cyclopentane undecanoic acid as well as the indole alkaloids Akuammilan-17-ol-10-methoxy, N-nitroso-2-methyl-oxazolidine and epoxide Oxirane2.2″ -(1.4-butanediyl) bis-. CONCLUSION The K. africana fruit fraction demonstrated significant alpha-glucosidase inhibitory activity, while its alpha-amylase inhibitory activity was limited. This study suggests a potential natural alpha-glucosidase inhibitor and phytocompounds that could serve as leads for developing antidiabetic agents.
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Affiliation(s)
- Tumelo Akapelwa Muyenga
- Department of Physiological Sciences, School of Medicine and Health Sciences, Mulungushi University, P.O. Box 60009, Livingstone, Zambia.
- Department of Pharmacology and Therapeutics, Faculty of Health and Veterinary Sciences, University of Namibia, Windhoek, Namibia.
| | - Samuel K Dominion Bamitale
- Department of Internal Medicine and Pharmacology, Faculty of Medicine, and Health Sciences, Eastern Cape, Walter Sisulu University, Mthatha, South Africa
| | - Dan Kibuule
- Department of Pharmacology and Therapeutics, Faculty of Health Sciences, Busitema University, Busitema, Uganda
| | - Simbarashe Sithole
- Department of Chemistry and Earth Sciences, University of Zimbabwe, Mt. Pleasant, Harare, Zimbabwe
| | - Stanley Mukanganyama
- Department of Biotechnology and Biotechnology, University of Zimbabwe, Mt. Pleasant, Harare, Zimbabwe
| | - Carlen Rudolph
- Department of Biochemistry and Microbiology, Nelson Mandela University, Port Elizabeth, South Africa
| | - Luanne Venables
- Department of Biochemistry and Microbiology, Nelson Mandela University, Port Elizabeth, South Africa
| | - Anna C Hattingh
- Department of Biochemistry and Microbiology, Nelson Mandela University, Port Elizabeth, South Africa
| | - Maryna van de Venter
- Department of Biochemistry and Microbiology, Nelson Mandela University, Port Elizabeth, South Africa
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Mohamed AAR, Abd-Elhakim YM, Noreldin AE, Khamis T, Elhamouly M, Akela MA, Alotaibi BS, Alosaimi ME, Khalil SS, El-Gamal M, Dahran N, El-Shetry ES. Understanding fenpropathrin-induced pulmonary toxicity: What apoptosis, inflammation, and pyreptosis reveal analyzing cross-links at the molecular, immunohistochemical, and immunofluorescent levels. Food Chem Toxicol 2024; 186:114520. [PMID: 38369055 DOI: 10.1016/j.fct.2024.114520] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2023] [Revised: 02/07/2024] [Accepted: 02/15/2024] [Indexed: 02/20/2024]
Abstract
Fenpropathrin (FN), a pyrethroid has been linked to potential pulmonary toxic effects to humans via incident direct or indirect ingestion. Thus, we aimed to the investigate the underlying mechanisms of lung toxicity upon exposure to FN in the rat model, besides studying whether curcumin (CCM) and curcumin-loaded chitosan nanoformulation (CCM-Chs) can mitigate FN-induced lung damage. Six distinct groups, namely, control, CCM, CCM-Chs, FN, and CCM + FN, CCM-Chs + FN were assigned separately. The inflammatory, apoptotic, and oxidative stress states, histological, immunohistochemical, and immunofluorescence examination of different markers within the pulmonary tissue were applied. The results revealed that the FN-induced tissue damage might be caused by the oxidative stress induction and depressed antioxidant glutathione system in the lungs of rats. Furthermore, FN upregulated the expression of genes related to inflammation, and pyroptosis, and elevated the immunoreactivity of Caspase-3, tumor necrosis factor-α, vimentin, and 4-Hydroxynonenal in pulmonary tissues of FN-exposed rats compared to the control. CCM and CCM-Chs mitigated the FN-induced disturbances, while remarkably, CCM-Chs showed better potency than CCM in mitigating the FN-induced toxicity. In conclusion, this study shows the prominent preventive ability of CCM-Chs more than CCM in combatting the pulmonary toxicity induced by FN. This may be beneficial in developing therapeutic and preventive strategies against FN-induced pulmonary toxicity.
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Affiliation(s)
- Amany Abdel-Rahman Mohamed
- Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44511, Egypt
| | - Yasmina M Abd-Elhakim
- Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44511, Egypt
| | - Ahmed E Noreldin
- Department of Histology and Cytology, Faculty of Veterinary Medicine, Damanhour University, Damanhour, 22511, Egypt
| | - Tarek Khamis
- Department of Pharmacology, Faculty of Veterinary Medicine, Zagazig University, 44511, Zagazig, Egypt; Laboratory of Biotechnology, Faculty of Veterinary Medicine, Zagazig University, 44519, Zagazig, Egypt
| | - Moustafa Elhamouly
- Faculty of Veterinary Medicine, University of Sadat City, Sadat City, Egypt
| | - Mohamed A Akela
- Department of Biology, College of Sciences and Humanities in Al-Kharj, Prince Sattam bin Abdulaziz University, Al-Kharj, 11942, Saudi Arabia
| | - Badriyah S Alotaibi
- Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah bint Abdulrahman University, PO Box 84428, Riyadh 1671, Saudi Arabia.
| | - Manal E Alosaimi
- Department of Basic Sciences, College of Medicine, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia
| | - Samah S Khalil
- Department of Biochemistry, Drug Information Centre, Zagazig University Hospitals, Zagazig University, Egypt
| | - Mohamed El-Gamal
- Forensic Medicine and Clinical Toxicology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt; Medical Experimental Research Center (MERC), Faculty of Medicine, Mansoura University, Mansoura, Egypt; Department of Biological Sciences, Faculty of Science, New Mansoura University, New Mansoura City, Egypt
| | - Naief Dahran
- Department of Anatomy, Faculty of Medicine, University of Jeddah, Jeddah, Saudi Arabia
| | - Eman S El-Shetry
- Department of Anatomy, College of Medicine, University of Hail, Hail, Kingdom of Saudi Arabia; Department of Human Anatomy and Embryology, Faculty of Medicine, Zagazig University, Zagazig, 44511, Egypt
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