Attenuation of Streptozotocin-Induced Diabetic Neuropathic Allodynia by Flavone Derivative Through Modulation of GABA-ergic Mechanisms and Endogenous Biomarkers

Theodor Bilharz Research Institute

Bibliographic Information

Authors: Altaf N.; Rehman N.U.; Karim N.; Khan I.; Halim S.A.; Alotaibi B.S.; Hamad R.S.; Batiha G.E.-S.; Tayyeb J.Z.; Turkistani A.; Khan A.; Al-Harrasi A.

Journal: Neurochemical Research

Publisher: Springer

Publication Date: 3 January 2024

Volume / Issue: Volume 49 / Issue 4

Pages: 980–997

ISSN: 3643190

DOI: 10.1007/s11064-023-04078-5

Scopus: View on Scopus

PubMed: 38170385

Document Type: Article

Authors and Affiliations

Altaf N., Department of Pharmacy, University of Malakand, KPK, Chakdara, Lower Dir, Pakistan; Rehman N.U., Natural and Medical Sciences Research Center, University of Nizwa, Birkat al Mouz, Initial Campus, Nizwa, 616, Oman; Karim N., Department of Pharmacy, University of Malakand, KPK, Chakdara, Lower Dir, Pakistan, Department of Pharmacy, University of Peshawar, KPK, Peshawar, Pakistan; Khan I., Department of Pharmacy, University of Swabi, KPK, Swabi, Pakistan; Halim S.A., Natural and Medical Sciences Research Center, University of Nizwa, Birkat al Mouz, Initial Campus, Nizwa, 616, Oman; Alotaibi B.S., Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh, 11671, Saudi Arabia; Hamad R.S., Biological Sciences Department, College of Science, King Faisal University, Al Ahsa, 31982, Saudi Arabia, Central Laboratory, Theodor Bilharz Research Institute, Giza, 12411, Egypt; Batiha G.E.-S., Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, AlBeheira, Damanhour, 22511, Egypt; Tayyeb J.Z., Department of Clinical Biochemistry, College of Medicine, University of Jeddah, Jeddah, 23890, Saudi Arabia; Turkistani A., Department of Pharmacology and Toxicology, College of Medicine, Taif University, Taif, 21944, Saudi Arabia; Khan A., Natural and Medical Sciences Research Center, University of Nizwa, Birkat al Mouz, Initial Campus, Nizwa, 616, Oman; Al-Harrasi A., Natural and Medical Sciences Research Center, University of Nizwa, Birkat al Mouz, Initial Campus, Nizwa, 616, Oman

Abstract

Diabetic neuropathic pain is one of the most devasting disorders of peripheral nervous system. The loss of GABAergic inhibition is associated with the development of painful diabetic neuropathy. The current study evaluated the potential of 3-Hydroxy-2-methoxy-6-methyl flavone (3-OH-2′MeO6MF), to ameliorate peripheral neuropathic pain using an STZ-induced hyperglycemia rat model. The pain threshold was assessed by tail flick, cold, mechanical allodynia, and formalin test on days 0, 14, 21, and 28 after STZ administration accompanied by evaluation of several biochemical parameters. Administration of 3-OH-2′-MeO6MF (1,10, 30, and 100 mg/kg, i.p) significantly enhanced the tail withdrawal threshold in tail-flick and tail cold allodynia tests. 3-OH-2′-MeO6MF also increased the paw withdrawal threshold in mechanical allodynia and decreased paw licking time in the formalin test. Additionally, 3-OH-2′-MeO6MF also attenuated the increase in concentrations of myeloperoxidase (MPO), thiobarbituric acid reactive substances (TBARS), nitrite, TNF-α, and IL 6 along with increases in glutathione (GSH). Pretreatment of pentylenetetrazole (PTZ) (40 mg/kg, i.p.) abolished the antinociceptive effect of 3-OH-2′-MeO6MF in mechanical allodynia. Besides, the STZ-induced alterations in the GABA concentration and GABA transaminase activity attenuated by 3-OH-2′-MeO6MF treatment suggest GABAergic mechanisms. Molecular docking also authenticates the involvement of α2β2γ2L GABA-A receptors and GABA-T enzyme in the antinociceptive activities of 3-OH-2′-MeO6MF. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2024.

Keywords

3-Hydroxy-2-methoxy-6-methyl flavone; Diabetic neuropathy; GABAergic; Gabapentin; Mechanical allodynia; STZ induced neuropathic pain; Analgesics; Animals; Biomarkers; Diabetes Mellitus; Diabetic Neuropathies; Flavones; gamma-Aminobutyric Acid; Hyperalgesia; Molecular Docking Simulation; Neuralgia; Rats; Streptozocin; 3 hydroxy 2 methoxy 6 methylflavone; 4 aminobutyrate aminotransferase; 4 aminobutyric acid A receptor; antidiabetic agent; flavone derivative; glucose; interleukin 6; myeloperoxidase; nitrite; thiobarbituric acid reactive substance; tumor necrosis factor; unclassified drug; 4 aminobutyric acid; analgesic agent; biological marker; 4 aminobutyric acid brain level; allodynia; animal experiment; animal model; antinociception; Article; attenuation; biochemical analysis; body weight; combinatorial chemistry; controlled study; drug structure; formalin test; glucose blood level; high throughput screening; histopathology; long term care; male; molecular docking; neuropathic pain; nonhuman; oxidative stress; pain threshold; sciatic nerve; streptozotocin-induced diabetes mellitus; streptozotocin-induced diabetic neuropathy; tail flick test; thermal hyperalgesia; animal; complication; rat

Citation Information

Scopus Citations: 5

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