Ciproxifan Attenuates Lipopolysaccharide-Induced Neuroinflammation and Mitochondrial Dysfunctions in Mouse Brain

Vasudevan Mani, Minhajul Arfeen, Abdel-Moneim Hafez Abdel-Moneim and Hussein M. Ali

Background and Objective: Presently, Histamine H₃ Receptor (HH₃R) antagonists have been assured as a potential therapeutic candidate for several CNS-related disorders. In animal experiments, ciproxifan, HH₃R antagonist/inverse agonist causes arousal and attentiveness. This study examined the neuroprotective potential of ciproxifan against Lipopolysaccharides (LPS)-induced neuroinflammation and mitochondrial dysfunctions in mice. Materials and Methods: Ciproxifan(1 and 3 mg kg^–1) was treated orally for 30 days and 4 doses of LPS (250 μg kg^–1, i.p.) was injected for the last 4 days of treatment (27-30 days) to induce neuroinflammation. Brain homogenates were collected at end of the dosing (30 days) for estimation of cytokines [Interleukin-6 (IL-6) and Tumour Necrosis Factor-alpha (TNF-α) as pro-inflammatory cytokines, IL-10 and Transforming Growth Factor-beta 1 (TGF-β₁) as anti-inflammatory cytokines], Cyclooxygenase-2 (COX-2) and Mitochondrial Respiratory Chain Complex (MRCC) enzymes (complexes I, II and IV). Results: Treatment of ciproxifan exhibited its anti-inflammatory effects by significantly reducing the release of both pro-inflammatory cytokines (IL-6 and TNF-α) and COX-2 levels, further, it improved the anti-inflammatory cytokines (IL-10 and TGF-β₁) levels in LPS-challenged mouse brain. Additionally, ciproxifan reversed the brain MRCC (I, II and IV) levels in LPS-induced mice. Conclusion: According to the findings, ciproxifan assured its neuroprotection against LPS-induced neurotoxicity in mice models by reducing neuroinflammation and restoring MRCC enzymes.

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