Abstract
Aims: Murraya koenigii commonly known as curry leaves, is traditionally used in India and other South Asian countries as a spice for its characteristic flavor and aroma. Mahanimbine is a major carbazole alkaloid derived from Murraya koenigii leaves. There are numerous reports that support the neuroprotective role of various alkaloids. The present study investigated the neuroprotective potential of mahanimbine against lipopolysaccharides (LPS)-induced neuronal deficits of SK-N-SH cells and antioxidant potentials in ICR mouse brain.
 Study Design: The targeted compound mahanimbine was subjected to both in vitro and in vivo studies.
 Place and Duration of Study: The study was conducted in Faculty of Pharmacy, Universiti Teknologi MARA, Malaysia and College of Pharmacy, Qassim University, Kingdom of Saudi Arabia between June 2015 and August 2017.
 Methodology: For the in vitro study, SK-N-SH cells were induced with the 100µg/ml of LPS. Then, neuroprotection and reactive oxygen species (ROS) assays were conducted to assess cell viability and the formation of ROS. On the other hand, ICR mice were being fed with mahanimbine (1, 2 and 5 mg/kg, p.o.) for 30 days for in vivo study. Neuroinflammation was thereafter induced by intraperitoneal injection of LPS (250 μg/kg) for 4 days. At the end of the treatment, the animals were sacrificed. The brain was collected for antioxidants assays, measuring oxidative biomarkers such as catalase, reduced glutathione, superoxide dismutase, glutathione reductase, and thiobarbituric acid (TBARs).
 Results: SK-N-SH cells exposed to 100 μg/ml LPS showed a significant cell viability loss and increased level of ROS. However, pre-treatment of SK-N-SH cells with mahanimbine significantly prevented cell loss and consequently attenuated LPS-induced ROS formation. In addition, mahanimbine also inhibited β-secretase (BACE50 = 4µg/mL) that is important for production of β-amyloid (Aβ). For in vivo study, the biochemical analysis of the whole brain detected increased catalase (CAT) and glutathione reductase (GRD) levels, and significantly decreased malondialdehyde (MDA) level in mahanimbine treated groups as compared to LPS-induced but untreated group.
 Conclusion: The overall findings supported the neuroprotective and antioxidant potential of mahanimbine against LPS-induced neurotoxicity.
Highlights
Neuroinflammation is a process involving the activation of astrocytes and microglia cells by inflammatory mediators in various central nervous system (CNS) pathologies, including trauma, stroke, brain infection and neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson's disease (PD) [1]
The present study investigated the neuroprotective potential of mahanimbine against lipopolysaccharides (LPS)-induced neuronal deficits of SK-N-SH cells and antioxidant potentials in ICR mouse brain
The present findings revealed that mahanimbine displayed a significant protection against LPSinduced oxidative stress that might be due to its antioxidants properties
Summary
Neuroinflammation is a process involving the activation of astrocytes and microglia cells by inflammatory mediators in various central nervous system (CNS) pathologies, including trauma, stroke, brain infection and neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson's disease (PD) [1]. Β-secretase (BACE-1) is an important enzyme for the generation of β-amyloid (Aβ) peptide. The formation of Aβ peptide is from the sequential cleavage of amyloid precursor protein (APP) by BACE-1 and γ-secretase through the amyloidogenic pathway [3]. BACE-1 has been reported to be a key enzyme that initiates the pathway to the formation of Aβ proteins that results in the development of neurotic plaques in the brain of AD patients [4]. The BACE-1 inhibition is one of the potential therapies to reduce the Aβ peptide accumulation in the brain region
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
