Antidepressive effects of Maca‐EVs in the UCMS mice. (A) Schematic illustration on the UCMS model establishment and drug administration in the present study. (B) Body weight changes of control and UCMS mice with indicated Maca‐EVs treatments at different time points. Effect of Maca‐EVs on the immobility time in tail suspension test (C) and in forced swimming test (D) of control and UCMS mice with indicated Maca‐EVs treatments. (E) Representative open field test photos of control and UCMS mice with indicated Maca‐EVs treatments. Quantification on the total traveling distance (F) and entries in zone (G) of the open field test. Effect of Maca‐EVs on the latency to eat (H) and to groom (I), and percentage of sucrose preference (J) of control and UCMS mice with indicated Maca‐EVs treatments. All data are presented as mean ± SEM (n = 15–30 experiments for each group). Significance was evaluated by RM two‐way analysis of variance (ANOVA) followed by Tukey's multiple comparisons tests in (B), and significance was evaluated by ordinary one‐way ANOVA followed by Tukey's multiple comparisons test in (C, F, G), Brown–Forsythe and Welch ANOVA tests followed by the Tamhane T2 multiple comparisons test in (D), and the Kruskal–Wallis test followed by Dunn's multiple comparisons test in (H, I, J). Means denoted by a different letter indicated significant differences between groups (p < 0.05). EV, extracellular vesicle; RM, repeated measure; SEM, scanning electron microscope; UCMS, unpredictable chronic mild stress.