title: Fisetin Imparts Neuroprotection in Experimental Diabetic Neuropathy by Modulating Nrf2 and NF-κB Pathways.
abstract: The current study is aimed to assess the therapeutic potential of fisetin, a phytoflavonoid in streptozotocin (STZ)-induced experimental diabetic neuropathy (DN) in rats. Fisetin was administered (5 and 10 mg/kg) for 2 weeks (7th and 8th week) post STZ administration. Thermal and mechanical hyperalgesia were assessed by measuring tactile sensitivity to thermal and mechanical stimuli, respectively. Motor nerve conduction velocity (MNCV) was determined using power lab system and sciatic nerve blood flow (NBF) was determined using laser Doppler system. Nerve sections were processed for TUNEL assay and NF-κB, COX-2 immunohistochemical staining. Sciatic nerve homogenate was used for biochemical and Western blotting analysis. MNCV and sciatic NBF deficits associated with DN were ameliorated in fisetin administered rats. Fisetin treatment reduced the interleukin-6 and tumour necrosis factor-alpha in sciatic nerves of diabetic rats (p < 0.001). Protein expression studies have identified that the therapeutic benefit of fisetin might be through regulation of redox sensitive transcription factors such as nuclear erythroid 2-related factor 2 (Nrf2) and nuclear factor kappa B (NF-κB). Our study provides an evidence for the therapeutic potential of fisetin in DN through simultaneous targeting of NF-κB and Nrf2.
authors.affiliation: Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Hyderabad, Bala Nagar, Hyderabad, TG, 500037, India.
authors.forename: Reddemma
authors.initials: R
authors.lastname: Sandireddy
authors.affiliation: Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Hyderabad, Bala Nagar, Hyderabad, TG, 500037, India.
authors.forename: Veera Ganesh
authors.initials: VG
authors.lastname: Yerra
authors.affiliation: Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Hyderabad, Bala Nagar, Hyderabad, TG, 500037, India.
authors.forename: Prashanth
authors.initials: P
authors.lastname: Komirishetti
authors.affiliation: Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Hyderabad, Bala Nagar, Hyderabad, TG, 500037, India.
authors.forename: Aparna
authors.initials: A
authors.lastname: Areti
authors.affiliation: Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Hyderabad, Bala Nagar, Hyderabad, TG, 500037, India. ashutosh@niperhyd.ac.in.
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Kumar
mesh_terms: D000818:Animals; D051546:Cyclooxygenase 2 / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology; D003929:Diabetic Neuropathies / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology*; D044948:Flavonols; D006930:Hyperalgesia / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009431:Neural Conduction / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000502:physiology; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D005419:Flavonoids; D044948:Flavonols; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; D018696:Neuroprotective Agents; D014409:Tumor Necrosis Factor-alpha; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; C017875:fisetin
keywords: Diabetic neuropathy; Fisetin; NF-κB; Neuroinflammation; Nrf2; Oxidative stress