Safety, Sedative, and Anxiolytic Evaluation of MECS Hard Capsules Using In Silico and In Vivo Approaches

Insomnia and anxiety disorders have become increasingly prevalent in modern society. The formulation study of MECS hard capsules composed of the medicinal herbs <i>Mimosa pudica</i>, <i>Erythrina variegata</i>, <i>Cinnamomum iners</i>, and <i>Scoparia dulcis</i> in an optimized weight ratio (%) of 40:12:16:32 represents a traditional Vietnamese pharmaceutical preparation. These medicinal plants have long been utilized in traditional medicine for the supportive treatment of insomnia and anxiety. This study aimed to evaluate the safety, sedative, and anxiolytic effects of MECS capsules in <i>Swiss albino</i> mice, while also investigating the interaction affinity of bioactive compounds from the four herbal components through in silico approaches, including molecular docking, ADMET prediction, QSAR modeling, and molecular dynamics (MD) simulations. A total of 11 potential bioactive compounds were identified through a multicriteria decision-making system. Among these, 9 compounds were confirmed in the MECS capsule using UPLC-QToF-MS chromatographic profiling, supporting the in silico screening results. Subchronic toxicity and anxiolytic effects were assessed using the light-dark box (LDB) and elevated plus maze (EPM) behavioral models, with MECS capsules administered at doses of 346 and 692 mg/kg. A sleep recovery model using diazepam was applied to evaluate the sedative properties. Toxicological assessment indicated no adverse effects at the maximum tested dose (<i>D</i> _max) of 39 g/kg of body weight. Furthermore, no deleterious effects were observed during the 60 day subacute toxicity evaluation at either dosage level. Behavioral assessments using the LDB and EPM models demonstrated that MECS capsules reduced anxiety-related behaviors. Diazepam significantly prolonged the sleep duration and shortened sleep onset latency at both doses, confirming the sedative effect of MECS capsules. The combined evidence from docking analysis, ADMET prediction, MDs simulations, and in vivo experimentation in <i>S. albino</i> mice showed the MECS hard capsulesformulated from medicinal herbs with a favorable safety profileexhibited pronounced sedative and anxiolytic activities. These findings suggest that MECS capsules hold promise as a natural-origin therapeutic agent for the treatment of anxiety disorders and insomnia.