Fagopyrum tataricum (L.) Gaertn interacts with Gsk-3β/Nrf-2 signalling to protect neurotoxicity in a zebrafish model

Ethnopharmacological relevance: Fagopyrum tataricum (L.) Gaertn is used as a folk medicine in many Asian countries due to its anti-inflammatory, antioxidant, and several other health-promoting properties. It is also prescribed to improve neurocognitive functions and alleviate inflammatory conditions. Aim of the study: Oxidative stress and neuroinflammation plays a crucial role in neurodegenerative conditions. Hence, based on the ethnomedical claims and available literature, the present study investigated neuroprotective efficacy of a seed extract (ft-ext) of Fagopyrum tataricum against acrylamide (ACR)-induced neurotoxicity. Materials and methods: The phytochemical characterization of ft-ext was performed by a high-performance liquid chromatography method. Molecular interactions of the identified compounds of ft-ext were studied using an insilico docking tool. An in-vitro protein denaturation assay was done to check anti-inflammatory activity. The 5 days' post-fertilized zebrafish larvae were exposed to 1 mM and 2.5 mM ACR with or without ft-ext for 72 h to study its neuroprotective efficacy. Real-time polymerase chain reaction and western blotting studies were performed to analyse the oxidative stress-related gene and protein expressions respectively. Results: The extract showed the presence of chlorogenic acid, rutin, caffeic acid, vitexin, syringic acid, quercetin, p-coumaric acid, kaempferol, and ferulic acid. In-vitro protein denaturation assay of ft-ext showed a potent antiinflammatory effect. The ft-ext improved ACR-mediated locomotor deficit and reduced overall mortality in the larvae. The brain lipid peroxidation and protein carbonylation results revealed an elevated level of oxidative stress in the ACR-treated group, which was reduced in ft-ext-treated larvae. The extract treatment increased the expression of nrf2, gpx, and hmox1a, while simultaneously downregulated trxr2 levels in the brain of larvae exposed to ACR. The treatment also showed inactivation of Gsk-3 beta, thus maintaining a normal pool of Nrf2 and beta-catenin. Molecular docking of identified compounds of ft-ext showed possible hydrogen and hydrophobic interactions with Gsk-3 beta. Conclusion: The ft-ext prevents ACR-mediated neurotoxicity by suppressing Gsk-3 beta mediated oxidative stress.

Automated summary

This study investigated the neuroprotective effects of Fagopyrum tataricum seed extract against acrylamide-induced neurotoxicity. The extract showed anti-inflammatory and antioxidant properties, improved locomotor deficits, and reduced oxidative stress. It prevented neurotoxicity by suppressing Gsk-3 beta-mediated oxidative stress.