Behavioral and Biochemical Effects of Vitexin–Isovitexin-Loaded Microcapsule Combination on Restraint Stress Mouse Model

Chronic stress and anxiety highlight the need for safer natural alternatives to conventional therapies with severe adverse effects, yet the combined behavioral and biochemical effects of vitexin and its structural isomer, isovitexin, remain insufficiently investigated. This study evaluated the effects of a vitexin–isovitexin mixture in both crude and microencapsulated forms under acute and repeated restraint stress. In vitro radical-scavenging activity was assessed via the DPPH assay. In vivo, male Swiss albino mice subjected to acute (4 h) and repeated (4 h × 7 days) restraint stress received oral administration of the mixture (30 mg/kg) 30 min before each stress session, followed by behavioral testing and biochemical analysis; molecular docking was used as an exploratory approach to assess predicted structural compatibility with selected stress-related targets. In vitro, the mixture exhibited DPPH radical-scavenging activity. In vivo, the effects differed between the acute and repeated stress models, with significant changes in several behavioral outcomes, serum cortisol, and GSH levels, whereas MDA and TST responses were less consistent. Molecular docking suggested predicted structural compatibility of vitexin and isovitexin with SERT, 5-HT1A, GABAA, the glucocorticoid receptor, and Keap1. Overall, the VTX-iVTX mixture showed variable effects on stress-related behavioral and biochemical outcomes, with microencapsulation showing effects comparable to the crude form in most parameters and more pronounced effects in selected outcomes.