Mahanimbine-induced neuroprotection via cholinergic system and attenuated amyloidogenesis as well as neuroinflammation in lipopolysaccharides-induced mice

Nur Syamimi Mohd Azahan; Vasudevan Mani; Kalavathy Ramasamy; Siong Meng Lim; Richard Muhammad Johari James; Mansour Alsharidah; Ahmad Alhowail; Abu Bakar Abdul Majeed

Articles

Abstract

Pharmacognosy Magazine,2020,16,68,57-63.

DOI:10.4103/pm.pm_202_19

Published:March 2020

Type:Original Article

Authors:

Author(s) affiliations:

Nur Syamimi Mohd Azahan¹, Vasudevan Mani², Kalavathy Ramasamy³, Siong Meng Lim³, Richard Muhammad Johari James⁴, Mansour Alsharidah⁵, Ahmad Alhowail², Abu Bakar Abdul Majeed⁶
¹ Faculty of Pharmacy, Universiti Teknologi MARA, Kampus Puncak Alam, Selangor, Malaysia, Malaysia<
² Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Buraidah, Kingdom of Saudi Arabia
³ Faculty of Pharmacy, Universiti Teknologi MARA, Kampus Puncak Alam, Selangor; Brain Degeneration and Therapeutics Group, Pharmaceutical and Life Sciences Community of Research, Universiti Teknologi MARA, Shah Alam, Malaysia
⁴ Faculty of Pharmacy, Universiti Teknologi MARA, Kampus Puncak Alam, Selangor; Collaborative Drug Discovery Research Group, Pharmaceutical and Life Sciences Community of Research, Universiti Teknologi MARA, Shah Alam, Malaysia
⁵ Integrative Pharmacogenomics Institute, Universiti Teknologi MARA, Selangor, Malaysia
⁶ Faculty of Pharmacy, Universiti Teknologi MARA, Kampus Puncak Alam, Selangor, Malaysia; Department of Physiology, College of Medicine, Qassim University, Buraidah, Kingdom of Saudi Arabia

Abstract:

Background: Murraya koenigii leaves are traditionally used in India and other South Asian countries as a spice in regular food dishes to improve taste and aroma. These leaves are known for the rich content of mahanimbine, a key carbazole alkaloid. Although there are numerous reports that support the neuroprotective role of various alkaloids, the effect of mahanimbine against memory impairment remains to be elucidated. 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) (Aβ1-42and 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 Aβ1-40level. 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.