دورية أكاديمية
Chrysin loaded nanovesicles ameliorated diabetic peripheral neuropathy. Role of NGF/AKT/GSK-3β pathway.
| العنوان: | Chrysin loaded nanovesicles ameliorated diabetic peripheral neuropathy. Role of NGF/AKT/GSK-3β pathway. |
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| المؤلفون: | El-Marasy SA; Department of Pharmacology, Medical and clinical studies institute, National Research Centre, Giza, Egypt. Electronic address: salma_el_marasy@hotmail.com., AbouSamra MM; Pharmaceutical Technology Department, Pharmaceutical drug industries research institute, National Research Centre, Giza, Egypt., El-Mosallamy AEMK; Department of Pharmacology, Medical and clinical studies institute, National Research Centre, Giza, Egypt., Emam AN; Refractories, Ceramics and Building Materials Department, Advanced Materials Technology and Mineral Researches research institute, National Research Centre, Giza, Egypt., Mabrok HB; Nutrition and food science department, Food industries and nutrition research institute, National Research Centre, Giza, Egypt., Galal AF; Narcotics, Ergogenics and Poisons Department, Medical and clinical studies research institute, National Research Centre, Giza, Egypt., Ahmed-Farid OA; Department of Physiology, Egyptian Drug Authority, Giza, Egypt., Abd El-Rahman SS; Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Cairo, Egypt., Moustafa PE; Department of Pharmacology, Medical and clinical studies institute, National Research Centre, Giza, Egypt. |
| المصدر: | Chemico-biological interactions [Chem Biol Interact] 2023 Apr 25; Vol. 375, pp. 110402. Date of Electronic Publication: 2023 Feb 16. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: Ireland NLM ID: 0227276 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-7786 (Electronic) Linking ISSN: 00092797 NLM ISO Abbreviation: Chem Biol Interact Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Limerick : Elsevier Original Publication: Amsterdam, Elsevier. |
| مواضيع طبية MeSH: | Diabetic Neuropathies*/drug therapy , Diabetes Mellitus*, Rats ; Animals ; Proto-Oncogene Proteins c-akt/metabolism ; Glycogen Synthase Kinase 3 beta ; Rats, Wistar ; Phosphatidylinositol 3-Kinases/metabolism ; Nerve Growth Factor ; Hyperalgesia ; Streptozocin |
| مستخلص: | Diabetic peripheral neuropathy (DPN) is a common diabetic complication. Chrysin (CHY) has many biological properties but poor oral bioavailability. This study investigates the effect of CHY and CHY-loaded nanovesicles (CHY-NVs) on streptozotocin (STZ)-induced DPN in rats. CHY-NVs were prepared by using film hydration method. The formula with the best entrapment efficiency%, lowest particle size, highest zeta potential, and highest in vitro CHY released profile was selected, characterized by Differential scanning calorimetry, Fourier transformation infrared spectroscopy analysis, and examined by Transmission electron microscope. Acute toxicity test, pharmacokinetic study and experimental model of diabetes mellitus were performed on the selected formulation. Wistar rats were considered diabetic by administration of a single intraperitoneal dose of STZ (50 mg/kg). 48 h after STZ administration, hyperglycemic rats were randomly assigned into four groups, one group of untreated hyperglycemic rats and the other three groups received daily oral doses of unloaded NVs, CHY-NVs (25 mg/kg), and CHY-NVs (50 mg/kg), respectively for 21 days. Moreover, five additional groups of healthy rats received: distilled water (control), free CHY, unloaded NVs, and CHY-NVs respectively for 21 days. CHY and CHY-NVs maintained body weight and reduced STZ-induced behavioral changes in rotarod, hind paw cold allodynia, tail cold allodynia, tail flick, and hot plate tests. CHY and CHY-NVs lowered blood glucose, glycated hemoglobin, elevated serum reduced glutathione (GSH), and reduced plasma malondialdehyde (MDA) levels. CHY-NVs elevated phosphatidylinositol 3-kinase (Pi3k), phosphorylated protein kinase B (p-AKT), and reduced nuclear factor kappa B (NF-κB), interleukin-6 (IL-6) in sciatic nerve homogenate. CHY and CHY-NVs increased nerve growth factor (NGF) and decreased glycogen synthase kinase-3β (GSK-3β) gene expressions in the sciatic nerve. In conclusion, CHY and CHY-NVs ameliorated STZ-induced DPN behavioral and histopathological changes via attenuating hyperglycemia, exerting anti-oxidant, anti-inflammatory effects, activating NGF/p-AKT/GSK-3β pathway, and its anti-apoptotic effect. The best pharmacokinetic profile and therapeutic effect was observed in rats treated with CHY-loaded NVs. Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2023 Elsevier B.V. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Chrysin; Chrysin-loaded nanovesicles; Diabetic peripheral neuropathy; Hind paw cold allodynia; NGF/p-AKT/GSK-3β pathway; Tail cold allodynia |
| المشرفين على المادة: | EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) 3CN01F5ZJ5 (chrysin) EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta) EC 2.7.1.- (Phosphatidylinositol 3-Kinases) 9061-61-4 (Nerve Growth Factor) 5W494URQ81 (Streptozocin) |
| تواريخ الأحداث: | Date Created: 20230222 Date Completed: 20230321 Latest Revision: 20230321 |
| رمز التحديث: | 20240829 |
| DOI: | 10.1016/j.cbi.2023.110402 |
| PMID: | 36804429 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1872-7786 |
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| DOI: | 10.1016/j.cbi.2023.110402 |