Computational analysis of phytochemicals from Crocus sativus L. and Rosmarinus officinalis L. for potential neuroprotective activity

Abstract

Neurotransmitters such as dopamine and serotonin are chemical messengers essential for normal brain function, and their imbalance has been linked to several mental and neurodegenerative disorders. The present study aims to identify natural compounds from Crocus sativus L. and Rosmarinus officinalis L. with antidepressant or anti-neurodegenerative potential for future therapeutic use, as a safer and cost-effective alternative to synthetic drugs. A series of in silico studies was carried out to achieve this. Phytoconstituents of C. sativus and R. officinalis were retrieved from IMPPAT 2.0 database, and descriptors were generated using PaDEL-Descriptor. Ligands with XlogP values between 1.5 and 2.7 were shortlisted and docked with dopamine D2 receptor (DRD2). The Swiss Target Prediction database was used to identify probable targets of the top compound found in the docking study. DAVID was used for gene ontology and KEGG pathway enrichment analysis. Kaempferol and DMAC-3,8 from C. sativus and cirsimaritin from R. officinalis were identified as potential agonists of the dopamine D2 receptor, as they showed strong binding with the D2 receptor comparable to a standard agonist drug. Machine learning models predicted IC₅₀ values with high accuracy, while pathway analysis of the two lead compounds (kaempferol and cirsimaritin) linked them to some key neuroprotective processes, signifying their potential against depression and other neurodegenerative disorders.