Finding the Effect of Darjeeling Black-Tea Aromatics in CNS Function through In-silico GluR-Ligand Interaction as a Probable Means

Darjeeling tea ( Camellia sinensis var. sinensis ) is recognized for its unique aroma and taste, associated with mood and cognitive enhancement. However, the underlying neurochemical mechanisms remain elusive. Present study investigated the potential interaction of Darjeeling tea's volatile aromatic compounds with glutamate receptors (GluRs), the predominant excitatory receptors in the central nervous system. We hypothesized that these compounds target GluRs to elicit their effects. An in-silico approach was employed, involving the analysis of physicochemical properties, bioactivity scores, and toxicity profiles of the aroma compounds. Subsequently, molecular docking simulations were performed using retrieved 3D structures of relevant GluRs to predict the binding affinity of selected compounds exhibiting high bioactivity, drug-likeliness, and bioavailability with identification of key amino acid residues within the receptor binding pockets. Our findings revealed α-Ionone and Safranal as prominent ligands exhibiting strong binding interactions. Among metabotropic GluRs, mGluR1 (IEWK), GluR5 (3FUZ), and GluR6 (3G3F) showed the highest affinity. Ionotropic receptor subtypes AMPA (2WJW) and NMDA (7EOR) also displayed significant binding scores where greater structural dynamics found in metabotropic GluRs upon ligand binding compared to ionotropic subtypes. Given the nasal passage as the primary route of exposure, and the presence of GluR-expressing cells along this pathway, the high bioavailability of α-Ionone and Safranal suggests their potential to interact with neuro-glial cells and subsequently influence CNS neurons and microglia/macrophages. In conclusion, the identified binding capability between Darjeeling tea's aromatic ligands and GluRs offers a promising framework for elucidating the mechanisms underlying the tea's effects on mood, psychological states, and immune-physiological responses.