Adnan Khan, Bushra Shal, A. Khan
Feb 15, 2023
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Influential Citations
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Quality indicators
Journal
Phytotherapy Research
Abstract
Multiple sclerosis (MS) is a debilitating neurodegenerative autoimmune disease of the central nervous system (CNS). The current study aimed to investigate the neuroprotective properties of Ajugarin‐I (Aju‐I) against the experimental autoimmune encephalomyelitis (EAE) model of MS and explored the underlying mechanism involved. The protective potential of Aju‐I was first confirmed against glutamate‐induced HT22 cells and hydrogen peroxide (H2O2)‐induced BV2 cells. Next, an EAE model has been established to investigate the mechanisms of MS and identify potential candidates for MS treatment. The behavioral results demonstrated that Aju‐I post‐immunization treatment markedly reduced the EAE‐associated clinical score, motor impairment, and neuropathic pain. Evans blue and fluorescein isothiocyanate extravasation in the brain were markedly reduced by Aju‐I. It effectively restored the EAE‐associated histopathological changes in the brain and spinal cord. It markedly attenuated EAE‐induced inflammation in the CNS by reducing the expression levels of p‐38/JNK/NF‐κB but increased the expression of IkB‐α. It suppressed oxidative stress by increasing the expression of Nrf2 but decreasing the expression of keap‐1. It suppressed EAE‐induced apoptosis in the CNS by regulating Bax/Bcl‐2 and Caspase‐3 expression. Taken together, this study suggests that Aju‐I treatment exhibits neuroprotective properties in the EAE model of MS via regulation of MAPK/NF‐κB, Nrf2/Keap‐1, and Bcl2/Bax signaling.