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Gems from past: Neuroprotective effects of Bhilawinol and Anacardic acid against Glutamate-induced excitotoxicity in PC-12 cells.

Rukhsana Nawaz1*, Faisal Khan2, Amina Hassan1, Nailah Mahmood1, Heba T. Ahmed Naser1, Alia Ali M. Al Shamali1 and Fadwa Al Mughairbi1*
  • 1 United Arab Emirates University, United Arab Emirates
  • 2 Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences , University of Karachi, Pakistan

Neurodegeneration is the process of deterioration and ultimately the death of neuronal cells caused by several factors such as oxidative stress, inflammatory changes, mitochondrial dysfunction, excitotoxicity etc. One of the major cause of excitotoxicity is by the over-activation of the glutamatergic system leading to glutamate toxicity and neurodegeneration. L-glutamate is an important neurotransmitter that is involved in almost all functions of the nervous system. Glutamate excitotoxicity leads to cell death via apoptosis/necrosis primarily due to an increase in intracellular calcium levels. Semecarpus Anacardium (SA) has been used for neurologic disorders from a long time in various Asian countries. The major components of these nut extracts include bhilawanols, bioflavonoids, sterols and phenolic compounds. This herb has many medicinal properties including benefits to the central nervous system (CNS), yet its active compounds have not been studied as neuroprotective agents. The main obstacle for drugs to be neuroprotective is the blood-brain barrier. The aim of study was to assess the compounds present in SA for their neuroprotective activity. Methods: Bioinformatic analysis of already known active ingredients of SA showed only two compounds (Bhilawinol and Anacardic acid) to be active in the brain (crossing the blood-brain barrier). These two were further analyzed individually for their neuroprotective effects in glutamate treated (Glu) rat pheochromocytoma cell line of rats (PC12 cells). The cell viability was monitored by MTT and LDH assay. The fluorometric assay was used to measure intracellular calcium (Ca) level and gene expression of proteins involved in the apoptotic pathway was analyzed by qRT-PCR. Results: Bhilawinol (100nM & 200nM) and Anacardic acid (100nM & 200nM) increased cell viability in Glu treated PC-12 cells significantly (p<0.01) after 24 and 48hrs as seen by MTT assay. Similar result was seen in LDH assay, Bhilawinol (100nM & 200nM) and Anacardic acid (100nM & 200nM) decreased Glu induced LDH leakage in PC-12 cells significantly (p<0.01) after 24 and 48hrs. Glutamate treatment increased Ca overload in PC-12 cells, bhilawanol (100nM) and anacardic acid (100nM) treatment decreased Ca levels significantly (p<0.001). The results correlated with a decrease in the level of caspase-3 and an increase in Bcl-2 by both Bhilawinol (100nM) and Anacardic Acid (100nM). The current study thus suggests SA constituents; Bhilawinol, and Anacardic Acid could be ‘magic bullet’ for neurodegenerative diseases.

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Acknowledgements

This research was funded by United Arab Emirates University UPAR grant # G00001944

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Keywords: Anacardic acid, QRT PCR, MTT (3-(4,5-dimethylthiazol-2-yl)−2,5-diphenyltetrazolium bromide) (CID: 64965), LDH – lactate dehydrogenase, Bhilawanol

Conference: 4th International Conference on Educational Neuroscience, Abu Dhabi, United Arab Emirates, 10 Mar - 11 Mar, 2019.

Presentation Type: Poster Presentation

Topic: Educational Neuroscience

Citation: Nawaz R, Khan F, Hassan A, Mahmood N, Ahmed Naser HT, Al Shamali AM and Al Mughairbi F (2019). Gems from past: Neuroprotective effects of Bhilawinol and Anacardic acid against Glutamate-induced excitotoxicity in PC-12 cells.. Conference Abstract: 4th International Conference on Educational Neuroscience. doi: 10.3389/conf.fnhum.2019.229.00033

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Received: 10 Feb 2019; Published Online: 27 Sep 2019.

* Correspondence:
Dr. Rukhsana Nawaz, United Arab Emirates University, Al-Ain, United Arab Emirates, rukshar.gul@gmail.com
Dr. Fadwa Al Mughairbi, United Arab Emirates University, Al-Ain, United Arab Emirates, f.almughairbi@uaeu.ac.ae