Evaluating the antidepressant and neuroprotective effect of Drymaria cordata (L.) Willd. Ex Schult against a...

Depression is a major global health issue linked to oxidative stress, neuroinflammation, and neuronal injury. Ethnopharmacological in vitro investigation of medicinal plants is an emerging and significant approach in the discovery of multi-target drug leads for the management of complex disorders such as depression. Drymaria cordata Willd. ex Schult (DC) is a medicinal herb commonly employed in folk medicine for the management of various diseases, such as headaches, convulsions, bronchitis, and eye problems. It has shown several central nervous system (CNS) activities such as anxiolytic, analgesic, anti-nociceptive, antitussive, and anti-amnesic effects, and therefore it has the potential to be relevant in the management of neuropsychiatric disorders such as depression.

The present study aimed to evaluate the antidepressant and neuroprotective activities of the hydroethanolic extract of DC (HEEDC) using a combination of experimental and computational studies.

The phytochemical screening of the HEEDC was carried out, and the in vitro neuroprotective activities were investigated using the MTT assay for cell viability, along with AO/EtBr staining for apoptotic changes and neurite outgrowth. The in vivo antidepressant activities were investigated using the CUMS model in mice after administration of the HEEDC at doses of 100 and 200 mg/kg, in comparison to fluoxetine 20 mg/kg, using behavioral tests such as the sucrose preference test, tail suspension test, and elevated plus maze. Biochemical studies were carried out by estimating the activities of monoamine oxidase-A, along with histopathological studies. LC-MS/MS analysis was performed, followed by network pharmacology, molecular docking, molecular dynamics, and ADME/toxicity studies to identify the lead compounds.

The phytochemical investigation indicated the presence of terpenoids, flavonoids, and phenolic compounds with significant antioxidant activity. HEEDC has shown significant neuroprotective effects through its anti-apoptotic and anti-neurite projection loss activities. HEEDC significantly alleviated depressive-like behaviors in the CUMS model through its effects on sucrose preference, immobility time, and exploratory activities. HEEDC has shown significant effects in reducing monoamine oxidase A activity and improving hippocampal neuronal morphology. The phytoconstituents of HEEDC were identified using LC-MS/MS as 108 compounds, and network pharmacology indicated significant targets such as HIF1A and P53. Molecular docking and dynamics studies indicated the potential of heliotrine and akeboside as significant compounds based on their interactions with the target proteins.

The results suggest that HEEDC possesses potential antidepressant activity along with neuroprotective activity via multi-target mechanisms. Drymaria cordata can be a potential lead compound for developing new antidepressants based on phytochemicals.