Kaempferol alleviates neurodegenerative disorders induced by Naja nigricollis venom via mechanisms of antioxidants, anti-inflammatory, dopaminergic and neuronal functions

Abstract

Naja nigricollis venom (NnV) contains neurotoxins that influence neurological functions. Kaempferol is a bioactive compound present in edible plants with numerous pharmacological activities. This study investigated the ameliorative potential of kaempferol against NnV-induced neurotoxicity in rats. Fifty male Wistar rats were randomized into five groups (n = 10). Group 1 rats were the control while 1.0 mg/kg−1 (LD50) of NnV was injected intraperitoneally into rats in groups 2–5 to observed neurotoxicity. Group 2 was untreated post envenomation, while groups 3–5 were treated with polyvalent antivenom, 4 and 8 mg/kg of kaempferol, respectively. The biochemical analysis, neurotoxicity, and pathomorphological defects were assessed in the brain of the envenomed treated rats. Envenomation with NnV elevated oxidative and inflammatory biomarkers, and induced neurotoxicity accompanied with neurobehavioral deficits, and severe pathohistological defects were seen in the brain of untreated envenomed rats. However, treatment with kaempferol significantly (p < 0.05) decreased malondialdehyde (MDA) levels and upregulated levels of reduce glutathione (GSH) antioxidant including superoxide dismutase (SOD) and glutathione peroxidase (GPX) antioxidant enzymes, while inflammatory biomarkers; nitric oxide (NO) levels and myeloperoxidase (MPO) activity significantly decreased in envenomed treated groups. Kaempferol upregulated dopamine concentration with significant suppression of acetylcholinesterase (AchE) activity, and restored neurobehavioral and locomotor activities in envenomed treated rats. Also, severe pathomorphological alterations observed in the cortex of the brain were attenuated after kaempferol treatment. The underlaying ameliorative mechanisms of kaempferol are linked to its antioxidant activity, lipid peroxidation inhibition, anti-inflammatory activity, acetylcholinesterase suppression, and alleviation of dopamine system and neurobehavioral abilities.

Keywords

• Naja nigricollis
• Neurotoxicity
• Envenoming
• Kaempferol
• Oxidative damage
• Inflammation