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Taxifolin Alleviates Metabolic and Neurochemical Alterations in Hippocampus and Cortex of Brain of Rotenone-Toxified Rats in Vivo and Effectively Interacts with Enzymes Involve in Neurotransmission in Silico


 Rotenone is a naturally occurring compound and inhibitor of mitochondrial complex I. Its exposure is toxic and directly affects the function of mitochondrial which leads to neurodegeneration. Taxifolin is a flavonoid that exhibits therapeutic potentials in various neurodegenerative diseases via its anti-oxidative, anti-inflammatory and neuromodulatory properties. In this study, we evaluated the therapeutic potential of taxifolin to alleviate metabolic and neurochemical alterations in the hippocampal and cortical region of brain of rotenone-toxified rats in vivo and to assess its influence on some enzymes involve in neurotransmission in silico. Taxifolin (0.25, 0.5 and 1.0 mg/kg) was orally post-administered to male Wistar rats for 3 days after 10 days subcutaneous administration of rotenone. Activities of mitochondrial complex I, membrane ion pump and lactate dehydrogenase (LDH) were evaluated in the hippocampus and cortex of the brain of rotenone-toxified rats. Markers of neurotransmitter metabolism and oxidative stress were also biochemically estimated and molecular interaction between taxifolin and tyrosine hydroxylase, monoamine oxidase, glutamine synthetase and Na+K+ ATPase was determined by in silico simulation. Taxifolin attenuated dysfunction of mitochondrial, Na+K+ ATPase, LDH and modulate neurotransmitter metabolism. Also, the elicited oxidative stress was mitigated by taxifolin in the hippocampus and cortex of the brain of rotenone-toxified rats. The highest binding affinity was recorded in taxifolin and tyrosine hydroxylase complex. Hydrogen bond and hydrophobic interactions were the two key molecular interaction between the taxifolin and targeted enzymes. Thus, taxifolin significantly exert therapeutic effect against rotenone-induced neurotoxicity in rats via anti-oxidative, as well as mitochondrial and neurotransmitter modulatory activity.