Neuroprotective Potential of Mahanimbine against Lipopolysaccharides (LPS)-Induced Neuronal Deficits on SK-N-SH Cells and Antioxidant Potentials in ICR Mice Brain

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.