Modulation of key enzymes linked to Parkinsonism and neurologic disorders by Antiaris africana in rotenone-toxified rats

Abstract

BackgroundThe physiopathologies of many neurologic diseases are characterized by related biochemical dysfunctions that could be explored as drug targets. This study evaluated the effect of a methanol leaf extract of Antiaris africana (MEA) on critical bioindices of Parkinsonism and related neurologic dysfunctions in rats with rotenone-induced neurotoxicity.MethodsAnimals were administered 50 or 100 mg/kg MEA for 14 consecutive days. Rotenone (1.5 mg/kg) was administered three times per day on days 13 and 14. Coenzyme Q10 (5 mg/kg) was the reference drug. Complex I activity, dopamine level, activities of acetylcholinesterase, myeloperoxidase, Na+/K+ ATPase and glutamine synthetase, as well as oxidative stress indices were evaluated at the end of the period of treatment.ResultsRotenone-intoxicated group showed disruption of complex 1 activity, dopamine level, and glutamine synthetase activity with negative alterations to activities of acetylcholinesterase, myeloperoxidase, and Na+/K+ ATPase as well as heightened cerebral oxidative stress. MEA restored brain mitochondria functionality, mitigated altered neurochemical integrity, and ameliorated cerebral oxidative stress occasioned by rotenone neurotoxicity. The activity of A. Africana was comparable with that of 5 mg/kg coenzyme Q10.ConclusionsThese results indicated that A. africana displayed therapeutic potential against Parkinsonism and related neurologic dysfunctions and support its ethnobotanical use for the treatment of neurologic disorders.

Dihydroquercetin improves rotenone‐induced Parkinsonism by regulating NF‐κB‐mediated inflammation pathway in rats

“…These events have been linked with rotenone toxicity. [5,62] Interestingly, our findings showed that DHQ attenuated the rotenone-induced disruption of striatal dopaminergic and cholinergic systems in agreement with previous reports. [2,8,17,20,23] Our findings also revealed that altered glutamate metabolism and mitochondrial complex dysfunction were evident in the striatum of rotenone-toxified rats but controlled by DHQ.…”

“…[55] The striatal redox imbalance observed in this study is consistent with the pathological features of PD. [5,56] A compromised antioxidant defense system with oxidative stress is reflected in the reduced activities of protective antioxidant factors such as SOD, GPx, CAT, GSH, and FRAP, and the increased XO activity and MDA, nitrate, and PC levels. [2,4] This may be due to insufficiency of the protective antioxidants, increased peroxidation, and/or protein carbonylation coupled with apoptosis.…”

“…[1,2] Neurochemical alterations involving the dopaminergic, cholinergic, and glutamatergic systems have all been linked to the progression of PD. [5,61] Disturbances in dopaminergic and cholinergic neurotransmission may have pronounced adverse effects on basal ganglia neuronal circuity as seen in PD. These events have been linked with rotenone toxicity.…”

“…A defective complex I is central to the pathogenesis of PD. [5,63] The regulation of glutamate, the principal excitatory neurotransmitter in the CNS, is also important in normal brain functioning. Its interactions with glutamate receptors play a vital role in the mediation of excitatory synaptic transmission.…”

Valeriana officinalis Counteracts Rotenone Effects on Spreading Depression in the Rat Brain in vivo and Protects Against Rotenone Cytotoxicity Toward Rat Glioma C6 Cells in vitro

“…Extracts of medicinal plants have beneficial effects in experimental models both in vivo ( Rezvani et al, 2010 for V. officinalis , and Ilesanmi et al, 2019 for Antiaris africana ) and in vitro ( Areiza-Mazo et al, 2018 for Physalis peruviana ). Therefore, in addition to the CSD model, we analyzed the V. officinalis /rotenone interaction in a set of in vitro experiments in the rat C6 glioma cell culture model ( Grobben et al, 2002 ; Krylova et al, 2019 ).…”