Centella asiatica improved Insomnia through MAPK/ERK Signaling Pathway: In Silico Study

Abstract

Insomnia is a difficulty to start sleeping or maintaining the quality of sleep. The latest concept of insomnia explains the disintegration of molecules that change the brain’s rhythm of waking and sleeping. Neurotransmitters that stimulate awakening are orexin, histamine, dopamine, serotonin, while those responsible for sleeping are ɣ-aminobutyric acid (GABA), adenosine, serotonin, melatonin, and prostaglandin D2 (PGD2). Mitogen-Activated Protein Kinase (MAPK)/Extracellular Signal-Regulated Kinase (ERK) pathways have a role in various neuroplasticity that also a candidate mechanism that plays a role in sleep plasticity regulation. Centella Asiatica (CA) is a herb which neuroprotectant effect on neurological diseases. CA can provide anti-inflammatory and rejuvenating effects, antioxidant, anxiolytic, stress relief, and improve intelligence. CA has a role in signaling MAPK/ERK pathway. MAPK3 (ERK1) and MAPK1 (ERK2) proteins are targets that are binded by beta-carotene from CA. In this study, based on QSAR analysis, it proved that CA has benefits for insomnia treatment, as ICAM1 expression inhibitor (0.55), nitric oxide antagonist (0.67), anti-inflammatory (0.80), and gastrin inhibitor (0.45). Therefore, it can be predicted that CA can potentially inhibit ICAM-1 and target AKT1 protein. Then, based on molecular docking, Protein Compound Interaction (PCI) results prove that beta carotene is the most potent MAPK1 inhibitor.