Preparation, In Vivo and Molecular Docking Study of Nano‐Emulsion Obtained From the Isolated Phytoconstituents of <i>Symplocos racemosa</i> for Mitigating Depression

Depression is a prevalent, chronic, and debilitating disorder characterized by high treatment resistance. Symplocos racemosa, containing phenols and triterpenoids, acts as an antidepressant by elevating brain monoamine levels. This study aimed to enhance the targeted delivery of S. racemosa via nano-emulsion and improve its therapeutic efficacy against depression. In addition, it sought to elucidate the molecular mechanisms underlying its effects through molecular docking studies. S. racemosa bark was extracted using methanol and ethyl acetate, yielding six phytoconstituents (ellagic acid, betulinic acid, acetyl oleanolic acid, salireposide, oleanolic acid, and symlocoside) through column chromatography. Molecular docking against MAO-A was performed to confirm significant binding affinity. A chitosan-loaded herbal nano-emulsion containing these phytoconstituents was formulated for enhanced brain delivery tested using animal studies using forced swim test (FST) and actophotometer models. Docking studies confirmed that all the components exhibit a good binding toward MAO-A, comparable to standard moclobemide, and among all salireposide has the most significant and better binding affinity, higher than moclobemide. Nano-emulsion, at both dosages, reduced the immobility time in the FST and increased the locomotor activity in the actophotometer of depressed mice. Nano-emulsion of isolated phytoconstituents from S. racemosa exhibited synergistic effects, effectively managing depression by inhibiting MAO-A.