Sonia Siddiqui*, Faisal Khan , Khawar Saeed Jamali and Syed Ghulam Musharraf Pages 12 - 26 ( 15 )
Background and Objective: Madecassic Acid (MA) is well known to induce neurite elongation. However, its correlation with the expression of fast transient potassium (AKv) channels during neuronal development has not been well studied. Therefore, the present study was designed to investigate the effects of MA on the modulation of AKv channels during neurite outgrowth.Methods: Neurite outgrowth was measured with morphometry software, and Kv4 currents were recorded by using the patch clamp technique. Results: The ability of MA to promote neurite outgrowth is dose-dependent and was blocked by using the mitogen/extracellular signal-regulated kinase (MEK) inhibitor U0126. MA reduced the peak current density and surface expression of the AKv channel Kv4.2 with or without the presence of NaN3. The surface expression of Kv4.2 channels was also reduced after MA treatment of growing neurons. Ethylene glycol tetraacetic acid (EGTA) and an N-methyl-D-aspartate (NMDA) receptor blocker, MK801 along with MA prevented the effect of MA on neurite length, indicating that calcium entry through NMDA receptors is necessary for MA-induced neurite outgrowth. Conclusion: The data demonstrated that MA increased neurite outgrowth by internalizing AKv channels in neurons. Any alterations in the precise density of ion channels can lead to deleterious consequences on health because it changes the electrical and mechanical function of a neuron or a cell. Modulating ion channel’s density is exciting research in order to develop novel drugs for the therapeutic treatment of various diseases of CNS.
Neurite outgrowth, Centella asiatica, madecassic acid, hippocampal neuron, NMDA, patch clamp.
Department of Biochemistry, Dow University of Health Sciences (DUHS), Karachi, Department of Neuroscience, Dr. Panjwani Center for Molecular Medicine and Drug Research (PCMD), International Center for Chemical and Biological Sciences (ICCBS), University of Karachi 75270, Department of Surgery, Dow University of Health Sciences (DUHS), Karachi, HEJ Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi 75270