Molecular-docking study of anti-stress natural compounds against GABAa receptor portends the novel approach to stress treatment

Abstract

Introduction: During stress our body responds by activating the nervous system and hormones. The stress response is conveyed by hypothalamic-pituitary-adrenal axis and is responsible for neuroendocrine adaptation of stress response. Hypothalamic-pituitary-adrenal activity is governed by corticotrophin releasing hormone neurons. Increased production of corticotrophin releasing hormone is associated with various stress related metabolic and neurological disorders. The activity of CRH neurons is largely regulated by Gamma-aminobutyric acid (GABA) and is controlled by GABAergic inhibition. To lower down the effect of stress, various synthetic drugs are used which target GABAa receptor and activates GABAa activity, producing calming effects but also comes along with various side effects. Hence anti-stress herbs is used as an alternative therapy which helps improving the adrenal system has no side effects and are safe for long term use. Method: Our current study is an attempt to analyze the possible mechanism of action of some compounds commonly present in extracts of different anti-stress herbs by using AutoDockVina. Result: As a result of our docking studies with GABAa protein, we have observed that some herbal compounds such as Rosmarinic Acid and Kaempferol are showing comparable binding affinity towards GABAa receptor, like Lorazepam. Few other compounds sharing common binding site like Lorazepam, indicates that their mechanism of action may also be through activating GABAa receptor.