Aegle marmelos neuroprotective potential in demyelination rat model through modulation of BDNF, GDNF, HSP-90 and HSP-60.

Multiple sclerosis is a neurodegenerative disorder marked by axonal damage and demyelination; however, existing immunomodulatory treatments are ineffective requiring development of new therapeutic approaches. Aegle marmelos, a traditional medicinal plant rich in bioactive phytochemicals. This study examined the neuroprotective effects of Aegle marmelos ethanolic fruit extract (AME) in a cuprizone (CPZ)-induced MS rat model. AME GC-MS analysis and molecular docking analysis were performed. Sixty Wistar rats were divided into six groups: Control, MS model group (CPZ 0.2% in chow diet for 42 days), standard (fingolimod 15 mg/kg), and AME treatment groups (250, 500, and 750 mg/kg). Following 42 days of treatment neurobehavioural observation, biochemical analysis, neurotransmitters, gene expression for inflammatory cytokines, and histopathological examination were conducted. GC-MS analysis identifies neuroactive substances, including as fatty acids, phytosterols, and phenolic derivatives. Administration of AME reduced CPZ-induced behavioural deficits in a dose-dependent manner; the 750 mg/kg dose showed significant improvements in motor coordination, grip strength, spatial working memory (p < 0.001). Pro-inflammatory mediators were markedly downregulated by RT-PCR, while antioxidant enzyme activities and neurotransmitters concentrations were also restored. AME treatment dose dependently restored serum level of BDNF, GDNF and decreased expression of HSP-90 and 60. AME treatment decreased the elevated expression of inflammatory cytokines, leukotrienes, prostaglandins and oxidative stress markers showing more pronounced antioxidant and anti-inflammatory potential. According to histopathological examination, AME-treated groups showed less demyelination and plaque formation with preserved neuronal architecture. By concurrently reducing oxidative stress, neuroinflammation, and promoting remyelination, these results show that AME exhibits strong neuroprotection. Multiple sclerosis is a neurodegenerative disorder marked by axonal damage and demyelination; however, existing immunomodulatory treatments are ineffective requiring development of new therapeutic approaches. Aegle marmelos, a traditional medicinal plant rich in bioactive phytochemicals. This study examined the neuroprotective effects of Aegle marmelos ethanolic fruit extract (AME) in a cuprizone (CPZ)-induced MS rat model. AME GC-MS analysis and molecular docking analysis were performed. Sixty Wistar rats were divided into six groups: Control, MS model group (CPZ 0.2% in chow diet for 42 days), standard (fingolimod 15 mg/kg), and AME treatment groups (250, 500, and 750 mg/kg). Following 42 days of treatment neurobehavioural observation, biochemical analysis, neurotransmitters, gene expression for inflammatory cytokines, and histopathological examination were conducted. GC-MS analysis identifies neuroactive substances, including as fatty acids, phytosterols, and phenolic derivatives. Administration of AME reduced CPZ-induced behavioural deficits in a dose-dependent manner; the 750 mg/kg dose showed significant improvements in motor coordination, grip strength, spatial working memory (p < 0.001). Pro-inflammatory mediators were markedly downregulated by RT-PCR, while antioxidant enzyme activities and neurotransmitters concentrations were also restored. AME treatment dose dependently restored serum level of BDNF, GDNF and decreased expression of HSP-90 and 60. AME treatment decreased the elevated expression of inflammatory cytokines, leukotrienes, prostaglandins and oxidative stress markers showing more pronounced antioxidant and anti-inflammatory potential. According to histopathological examination, AME-treated groups showed less demyelination and plaque formation with preserved neuronal architecture. By concurrently reducing oxidative stress, neuroinflammation, and promoting remyelination, these results show that AME exhibits strong neuroprotection.