Molecular Basis behind the Neuroprotective Potential of Beta Sitosterol in Lipopolysaccharide-Induced Wistar Albino Rats
Abstract:
Neurodegenerative disorders are on the rise globally. β-Sitosterol shows potential therapeutic benefits, but its neuroprotective mechanisms remain largely unexplored. This study aimed to assess the neuroprotective effects of β-Sitosterol on pro-inflammatory (NFκB) and antioxidant (NRF-2/KEAP-1) pathways in an in vivo in LPS-induced neurodegeneration model in albino rats. The rats were divided into four groups: normal control, LPS-induced, LPS-induced treated with β-Sitosterol (20 mg/kg/day for 4 weeks), and normal treated with β-Sitosterol. Neurotransmitters (dopamine and serotonin) and antioxidant enzymes (GSH and CAT) were measured by ELISA, and gene expression of NFκB, NRF-2, KEAP-1, IL-6, and IL-18 was assessed by Real-Time RT-PCR. Histopathology of brain tissues was performed. LPS induction significantly decreased neurotransmitters and antioxidant enzymes and upregulated NFκB while downregulating NRF-2 and KEAP-1 mRNA expression. β-Sitosterol treatment normalized these levels (p<0.05) and reduced hyperchromatic pyknotic changes in neuronal nuclei observed in LPS-induced rats. Normal rats treated with β-Sitosterol showed no significant alterations, indicating its safety. These findings suggest β-Sitosterol can reduce neuroinflammation by modulating antioxidant signaling, providing a potential therapeutic approach for neurodegenerative diseases.References:
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