No 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.

In the present study, pharmacological screening of the plant extracts with antioxidant properties was ABSTRACT Introduction: Herbal medicines are widely used in the therapeutic intervention that could delay the onset of Neurodegenerative diseases like, Alzheimer's disease. Despite intensive advancements in the field of research currently available therapeutic strategies are often limited due to their adverse effects. Hence there is a need for the search for novel compounds for effective medications to treat neurocognitive deficits. Objective: The present study focused on acetylcholinesterase inhibitory and neuroprotective activity of Commiphora species plant for their possible use in Alzheimer's disease. Methods: Phytochemical screening, TLC bioautographic and colourimetric assay was performed to quantify their acetylcholinesterase inhibitory activity of ethanolic extracts of the Commiphora species. The MTT assay was carried to evaluate the neuroprotective effect against the Aβ-induced cytotoxicity in SH-SY5Y cell lines. Results: The bark of Commiphora berryi, leaves of Commiphora caudata and Commiphora pubescens were found abundant in flavonoids, glycosides, steroids and terpenoids. Further, the ethanol extract of Commiphora berryi (65.48% ± 0.10) showed the highest acetylcholinesterase inhibitory activity. The Aβ 25-35 induced cell damage was as evidenced at a concentration of 20µM. The neuroprotective effect of the ethanol extracts was examined in neurodegenerative cells induced by Aβ 25-35. On pretreatment with plant extracts, significant improvement in cell viability was observed as 63.42 ± 2.02% (25µg/ml) for Commiphora berryi. The maximum percentage of in-vitro AChE inhibition and neuroprotective effect was effective in the ethanol bark extract of Commiphora berryi. Conclusion: The results are very rousing to continue the screening of more unexplored plant species could be used for the development of novel bioactive compounds to treat the many diseases, especially for Alzheimer's disease.

Murraya koenigii leaves contain mahanimbine, a carbazole alkaloid, reported with improving cholinergic neuronal transmission and reducing neuroinflammation in the CNS. The current research investigated the effects of mahanimbine on age-related memory deficits, oxidative stress, cholinergic dysfunction, amyloid formation, and neuroinflammation in aged mice (16 months old). Mahanimbine was administered (1 and 2 mg/kg, p.o.) daily to groups of aged mice for 30 days. The Morris water maze (MWM) task was performed to study spatial learning (escape latency (EL) and swimming distance (SD)) and memory (probe test). The levels of malondialdehyde (MDA), glutathione (GSH), acetylcholine (ACh), acetylcholinesterase (AChE), β-amyloid (Aβ1-40 and Aβ1-42), β-secretase (BACE-1), as well as neuroinflammation markers (total cyclooxygenase (COX) and COX-2 expression), were measured from the isolated brain. Mahanimbine reduced the EL time and SD in the MWM test. From the probe trial, the mahanimbine-treated group spent more time in the targeted quadrant related to the age-matched control, which indicated the enhancement of memory retention. From the biochemical tests, the treatment decreased MDA, AChE, Aβ1-40, and Aβ1-42, BACE-1, total COX activity, and COX-2 expression. It also raised the brain GSH and ACh levels in aged mice compared to age-matched control. These results have supported the reversal of memory dysfunctions by mahanimbine in aged mice and hypothesized that it could be a potential target to treat age-related neurodegenerative disease.

No abstract