Hesperidin downregulates kinases lrrk2 and gsk3ß in a 6-OHDA induced Parkinson's disease model.

The depletion of dopamine in the striatum region and Lewy bodies are the hallmark characteristics of Parkinson's disease. The pathology also includes the upregulation of various Parkinson's disease (PARK) genes and kinases. Two such kinases, LRRK2 and GSK-3ß have been directly implicated in the formation of tau and alpha-synuclein proteins, causing PD. Hesperidin (HES) is a flavanone glycoside that has multiple therapeutic benefits including neuroprotective effects. In this study, we examined the neuroprotective effects of HES against 6-hydroxydopamine (6-OHDA) induced-neurotoxicity in the in-vitro and in-vivo model. Hesperidin significantly protected the SH-SY5Y cells' stress against 6-OHDA induced toxicity by downregulating biomarkers of oxidative stress. Furthermore, HES downregulated the kinases lrrk2 and gsk3ß along with casp3, casp9, and polg in the zebrafish model. The treatment with HES also improved the locomotor pattern of zebrafish that was affected by 6-OHDA. This study suggests that hesperidin could be a drug of choice in targeting kinases against a 6-OHDA model of PD.

Naringenin alleviates 6-hydroxydopamine induced Parkinsonism in SHSY5Y cells and zebrafish model.

6-Hydroxydopamine (6-OHDA) is a neurotoxin that inhibits the mitochondrial complex I causing mitochondrial impairment, aetiology of Parkinson's. Naringenin is a flavanone predominantly present in citrus fruits. Due to its high antioxidant and anti-inflammatory potential, it has been widely studied against various disorders. In this study, the neuroprotective effect of naringenin was determined against 6-OHDA induced toxicity with Levodopa (l-DOPA) as the standard. Naringenin reduced 6-OHDA induced oxidative stress biomarker levels such as CAT, GSH, SOD, and ROS. Naringenin rescued 6-OHDA induced reduction of the mitochondrial membrane potential. Treatment with naringenin improved the locomotion of the 6-OHDA treated zebrafish larvae which showed stagnant swimming patterns. Naringenin was also found to downregulate the expression of some Parkinsonian genes such as casp9, lrrk2, and polg and upregulate pink1. These studies attribute to naringenin as a viable molecule to study further for its neuroprotective effects against 6-OHDA induced neurotoxicity and neurodegeneration.