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Abstract Title:

The protective effect of biochanin A against rotenone-induced neurotoxicity in mice involves enhancing of PI3K/Akt/mTOR signaling and beclin-1 production.

Abstract Source:

Ecotoxicol Environ Saf. 2020 Dec 1 ;205:111344. Epub 2020 Sep 22. PMID: 32977283

Abstract Author(s):

Nagla A El-Sherbeeny, Nema Soliman, Amal M Youssef, Noha M Abd El-Fadeal, Taghrid B El-Abaseri, Abdullah A Hashish, Walid Kamal Abdelbasset, Gaber El-Saber Batiha, Sawsan A Zaitone

Article Affiliation:

Nagla A El-Sherbeeny

Abstract:

Rotenone is an insecticide that generates oxidative stress in the CNS and induces locomotor dysfunction and neurodegeneration in rodents. Biochanin A [BioA] is an isoflavone with antioxidant and anti-inflammatory actions. The antioxidant and the modulatory action of BioA on PI3K/Akt/mTOR signaling and autophagy were tested in rotenone-Parkinsonian mice. Mice were allocated into; Group I: oil control group, Group II: rotenone group [1-mg/kg/48h, subcutaneously], group III: rotenone and BioA [10-mg/kg]. Rotenone injection resulted in locomotor disturbances in mice, degeneration in dopaminergic neurons [tyrosine hydroxylase-immunoreactive cells], low striatal dopamine, increased malondialdehyde and decreased level of glutathione. Neuroinflammation was evidenced by upregulation of astrocytes [glia fibrillary acidic protein, GFAP] and elevated levels of cytokines. The phosphorylation of PI3K/Akt/mTOR and the autophagy-related protein, beclin-1, were decreased significantly as indicated by Western blot analysis. BioA treatment enhanced locomotor activity and afforded nigral neuroprotection. The mechanism by which BioA produced this effect includes increased antioxidant defenses, lessened proinflammatory cytokines, increased phosphorylation of PI3K/Akt/mTOR proteins and upregulated beclin-1. Importantly, BioA suppressed the striatal astrocyte marker [GFAP]. Overall, the currents study highlighted that BioA activates PI3K/Akt/mTOR signaling and enhances beclin-1 leading to neuroprotection for nigral dopaminergic neurons.

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