Mahanimbine‑Induced Neuroprotection via Cholinergic System and Attenuated Amyloidogenesis as well as Neuroinflammation in Lipopolysaccharides‑Induced Mice

Objective: The present study aimed to explore the neuroprotective potential of mahanimbine against lipopolysaccharides (LPS)‑induced memory deficit in Institute of Cancer Research (ICR) mice. Materials and Methods: Group of mice were being fed with mahanimbine (1, 2, and 5 mg/kg, p. o.) for 30 days. Subsequently, neuroinflammation was induced with LPS (250 µg/kg, i. p.) for 4 days. Morris water maze (MWM) assessment was conducted to assess spatial memory. The brain was then collected and subjected to amyloid‑beta (Aβ) (Aβ1‑42 and Aβ1‑40) measurement, acetylcholine (ACh) and acetylcholinesterase (AChE) assays and neuroinflammatory analyses (interleukin [IL]‑1 β, tumor necrosis factor alpha [TNF‑α], IL‑10 transforming growth factor beta [TGF‑β], and cyclooxygenase [COX]). Results: The MWM test showed that treatment with mahanimbine significantly enhanced memory of LPS‑challenged mice by decreasing both escape latency as well as escape distance. Pretreatment of the LPS‑challenged mice with mahanimbine improved central cholinergic transmission by increasing ACh level through inhibition of AChE. It also significantly attenuated Aβ1‑40 level. While anti‑inflammatory cytokines (TGF‑β and IL‑10) were upregulated, mahanimbine significantly inhibited pro‑inflammatory cytokines (IL‑1 β and TNF‑α), the total activity of COX, and expression of COX‑2 gene in LPS‑induced group. Conclusion: The overall findings supported the neuroprotective potential of mahanimbine against LPS‑induced neuroinflammation.