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

Abstract

Event Abstract Back to Event 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. Figure 1 Figure 2 Acknowledgements This research was funded by United Arab Emirates University UPAR grant # G00001944 References Adams, M., Gmunder, F., & Hamburger, M. (2007). Plants traditionally used in age related brain disorders—A survey of ethnobotanical. Journal of Ethnopharmacology, 113, 363–381. Aoshima, H., Satoh, T., Sakai, N., Yamada, M., Enokido, Y., Ikeuchi, T. & Hatanaka, H. (1997). Generation of free radicals during lipid hydroperoxide-triggered apoptosis in PC12 cells. Biochimica et Biophysica Acta, 1345, 35–42. Azouaou, S.A., Emhemmed, F., Idris-Khodja, N., Lobstein, A., Schini-Kerth, V., Muller, C.D., & Fuhrmann, G. (2015). Selective ROS-dependent p53-associated anticancer effects of the hypoxoside derivative rooperol on human teratocarcinomal cancer stem-like cells. Invest New Drugs, 33(1), 64–74. Baker, J.T., Borris, R.P., Carte, B., Cordell, G.A., Soejarto, D.D., Cragg, G.M., Gupta, M.P., Iwu, M.M., Madulid, D.R., & Tyler, V.E. (1995). Natural product drug discovery and development: New perspective on international collaboration. Journal of Natural Products, 58, 1325-1357. Chen, Z., Ljunggren, H., Bogdanovic, N., Nennesmo, I., Winblad, B., & Zhu, J. (2002). Excitotoxic neurodegeneration induced by intranasal administration of kainic acid in C57BL/6 mice. Brain Research, 931, 135-145. Ganesan, R., Doss, H.M., & Rasool, M. (2016). Majoon ushba, a polyherbal compound, suppresses pro-inflammatory mediators and RANKL expression via modulating NFкB and MAPKs signaling pathways in fibroblast-like synoviocytes from adjuvant-induced arthritic rats. Immunologic Research, 64(4), 1071–86. Gedam, P. H., Sampathkumar, P. S., & Sivasamban, M. A. (1974). Composition of bhilawanol from semecarpus anacardium. Phytochemistry, 13 (2), 513 – 515. Greenblatt, H.M., Guillou, C., Guenard, D., Argaman, A., Botti, S., Badet, B., Thal, C., Silman, I., Sussman, J.L. (2004). The complex of a bivalent derivative of galanthamine with Torpedo acetylcholinesterase displays drastic deformation of the active-site gorge: implications for structure-based drug design. Journal of the American Chemical Society, 126, 15405–15411. Hemshekhar, M., Santhosh, M.S., Kemparaju, K., & Girish, K.S. (2012). Emerging roles of anacardic acid and its derivatives: a pharmacological overview. Basic & clinical pharmacology & toxicology, 110(2), 122-132. King, L. L. (1957). A unique reported use for the fruit of Semecarpus anacardium L. f. (Anacardiaceae) in ancient arabian and indian medicine. Economic Botany, 11(3), 263–266. Kubo, I., Masuoka, N., Ha, T.J., Tsujimoto, K. (2005). Antioxidant activity of anacardic acids. Food Chemistry, 99, 555-562. 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 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. 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 Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract Supplemental Data The Authors in Frontiers Rukhsana Nawaz Faisal Khan Amina Hassan Nailah Mahmood Heba T Ahmed Naser Alia Ali M Al Shamali Fadwa Al Mughairbi Google Rukhsana Nawaz Faisal Khan Amina Hassan Nailah Mahmood Heba T Ahmed Naser Alia Ali M Al Shamali Fadwa Al Mughairbi Google Scholar Rukhsana Nawaz Faisal Khan Amina Hassan Nailah Mahmood Heba T Ahmed Naser Alia Ali M Al Shamali Fadwa Al Mughairbi PubMed Rukhsana Nawaz Faisal Khan Amina Hassan Nailah Mahmood Heba T Ahmed Naser Alia Ali M Al Shamali Fadwa Al Mughairbi Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.