Hecogenin, a plant-derived small molecule, as a potential therapeutic intervention for neurodegenerative disorders: insights from a zebrafish model
Abstract
Background: Alzheimer’s disease is a neurodegenerative disorder of the brain and the most prevalent form of dementia, affecting approximately 55 million people worldwide. It is characterized by the presence of tau tangles and amyloid-beta plaques. Medicinal plants have been used since ancient times for the treatment of the disease. A plant steroidal saponin compound hecogenin, found in Sida cordifolia, exhibits pharmacological properties like anti-inflammatory and gastroprotective agent, but its neuroprotective potential remains unexplored. The study investigated the neuroprotective properties of hecogenin against aluminium chloride induced toxicity in zebrafish, compared to the standard donepezil.
Methods: In the present study, 6 months old zebrafish (both male and female) were grouped into control, treatment of hecogenin (5 mg/L and 2.5 mg/L), donepezil (1 mg/L) and aluminium chloride treated zebrafish (n = 10 in each group with both the sexes). The neuroprotective effect of hecogenin was compared to the standard with biochemical parameters (oxidative stress markers), behavioral analysis (novel tank diving test and T-maze) and histopathological analysis (H&E and Thioflavin S staining).
Results: The results revealed that hecogenin reduced the oxidative stress biomarkers levels like SOD, MDA, protein carbonyl, GSH and AChE when compared to the standard. T-maze and novel tank diving test revealed that hecogenin was found to exhibit anxiolytic effect by improved cognitive behavior. The histopathological staining of the zebrafish brains with H&E and thioflavin revealed the reduction of amyloid plaques in the hecogenin treated zebrafish model compared to that of the standard drug.
Conclusion: Hecogenin exhibits neuroprotectivity and anxiolytic effects in an aluminium chloride induced AD in zebrafish model. The results indicate that hecogenin is a potential plant derived therapeutic alternative for Alzheimer’s disease management.
Keywords: Alzheimer’s disease, Sida cordifolia, amyloid plaques, anxiolytic effect, neurodegeneration, neuroprotection