Evaluation of Daidzein Against Rotenone Induced Parkinson’s Disease and a Potential Involvement of Mitochondrial Biogenesis.

Abstract

Parkinson’s disease (PD) ranks as second most prevalent neurodegenerative disorder but is devoid of neuroprotective treatment. Approaches with disease modifying ability with symptomatic relief has become an utmost necessity. Further multifactorial nature of PD presents challenges for efficacy evaluation of any potential test compound. The stated study makes an attempt to address these issues by employing a rotenone induced PD model involving a bilateral intranigral stereotactic rotenone injection for evaluation of the neuroprotective efficacy of Daidzein (DZ). DZ a soy isoflavone, is known for its various health benefits viz. immunomodulation, cardiovascular effects etc. In this study, animals after intranigral rotenone (12 μg) injection, were treated with DZ at a dose of 5, 10 and 20 mg/kg for 30 days. The neurobehavioural evaluation comprised of Rota-rod, Open field and Barnes maze test. The biochemical analysis constituting oxidative stress (Reduced glutathione, superoxide dismutase, catalase and lipid peroxidation), inflammation (TNF-α), mitochondrial alteration (complex I activity and biogenesis) was conducted on mid-brain tissue after 30 days of treatment. The SN and striatum was also subjected to immunohistochemical analysis (IHC) for TH positive neurons and Glial Fibrillary Acidic Protein. The analysis revealed significant improvement by daidzein in motor co-ordination and attenuation in cognitive deficits due to rotenone. The biochemical assessment exhibited significant decrement in oxidative stress as well as inflammation. DZ treatment also prevented complex I inhibition and promoted mitochondrial biogenesis eventually contributing to the neuroprotection apparent in IHC. Thus, the results strongly corroborate the neuroprotective potential of DZ against rotenone induced model of PD.

Mitochondrial dysfunction-targeting therapeutics of natural products in Parkinson’s disease

“…Ursolic acid caused a prominent upregulation of COX1, the downstream gene of PGC-1α, in treated rats at a dose of 10 mg/kg, Frontiers in Pharmacology frontiersin.org manifesting the promotion of mitochondrial biogenesis (Peshattiwar et al, 2020).…”

“…Ursolic acid, a pentacyclic triterpenoid carboxylic acid, is found in many plant species. In rotenone-induced damage rats, treatment with ursolic acid at 5 and 10 mg/kg prevented inhibition of mitochondrial complex I activity in the mid-brain (Peshattiwar et al, 2020). Celastrol, a natural triterpene, protected SH-SY5Y cells from rotenone-induced MMP loss and ROS production (Choi et al, 2014).…”

“…Cytochrome c oxidase (MtCO-1/COX1) is a mtDNA-encoded polypeptide and is a downstream target of PGC-1α. Upregulation of COX1 transcripts provides evidence for the activation of mitochondrial biogenesis and respiratory activity (Peshattiwar et al, 2020). Therefore, the biogenesis of new mitochondria depends on the activation of SIRT1/AMPK/PGC-1α-Nrf-TFAM pathway.…”