GCMS Analysis, Neuroprotective, Cognitive, and Anti-inflammatory Impact of a Polyherbal Therapy in Alcohol-Induced Dementia in Wistar Rats

Dementia is a neurodegenerative disorder that leads to cognitive decline, and unfortunately, treatment options are quite limited. This study explored the neuroprotective, cognitive, and anti-inflammatory effects of polyherbal therapy (PHT) on alcohol-induced dementia in Wistar rats. The PHT was formulated using Lantana camara, Salvia hispanica, Zingiber officinale, Curcuma longa,and Beta vulgarisin a2:1:1:1:1 ratio. Thirty adult female Wistar rats, weighingbetween180 and 200 grams, were split into six groups: a control group (receiving just feed and water), an alcohol group 20 % w/v ethanol (2g/kg,i.g.), an alcohol+ donepezil group (2.5mg/kg), and alcohol+ PHT groups (250,500,and750mg/kg).Treatment was administered once daily, orally, for 21 days to all groups. Animals were assessed for cognitive performance using the elevated plus maze one hour after the 21st day of treatment and on the 24th day for the classic labyrinth maze experiment. On the following day (day 25), the rats were euthanized with an intraperitoneal (i.p.) injection of ketamine hydrobromide at a dose of 50 mg/kg. GC-MS analysis identified key bioactive compounds with neuroprotective and anti-inflammatory properties, including artemetin (18.26%), nobiletin (2.42%), and baicalin (1.37%). Neurobehavioral tests, such as the Classic Labyrinth MazeandElevatedPlusMaze, demonstratedsignificant (p<0.05) improvements in spatiallearning and memoryinthe groups treated with PHT compared to those exposed to alcohol. PHT also reduced pro-inflamm at orycytokines, suchasIL- 6andIL- 1β, inadose-dependentmanner, with the highest dose of 750mg/kg out performing donepezil. Furthermore, histopathological analysis indicated that PHT helped mitigate alcohol-induced neurodegeneration in the hippocampus, resulting in fewer cases of pyknosis and vacuolation. The LD50 of PHT was determined to be 2500mg/kg, suggesting it issafeforuse. Thesefindings imply that PHT provides neuroprotection through mechanisms involving antioxidants and anti-inflammatory effects, presenting a promising multi-target therapeutic strategy for alcohol-induced dementia. More clinical studies are needed to confirm its effectiveness in humans.