pone.0289248.t001 - Agomelatine prevented depression in the chronic restraint stress model through enhanced catalase activity and halted oxidative stress

pone.0289248.t001 - Agomelatine prevented depression in the chronic restraint stress model through enhanced catalase activity and halted oxidative stress</p

Effects of the CRS, AGO, and DFX intervention on immunohistochemistry of CAT protein in the hippocampus of mice.

Immunohistochemistry shows the changes in CAT protein expression in the hippocampus of mice after CRS, AGO, and DFX intervention. (a) Staining of CAT protein. (B) Positive rate of CAT protein expression in the mouse hippocampus. *P<0.05; **P<0.01; ***P<0.001; CAT, catalase; CRS, chronic restraint stress; AGO, agomelatine; DFX, deferasirox; ns, no significant difference. Data are expressed as the mean ± standard deviation and were analyzed by one-way ANOVA, followed by post hoc multiple comparisons (LSD method). n = 3.</p

Effects of the CRS, AGO, and DFX intervention on body weight and behavioral tests.

Depression-like behavior in mice induced by CRS. (a) Initial body weight of the mice. (b) Body weight of the mice after different treatments. (c) Weight gain of the mice. (d) Sucrose preference rate in mice. (e) Forced swimming rest time in mice. (f) The total distance of mice in the central region of the open field test. (g) Total time of mice in the central region in the open field test. (h) The total distance of mice in the open field test. *P<0.05; ** P<0.01; *** P<0.001; CRS, chronic restraint stress; AGO, agomelatine; DFX, deferasirox; ns, no significant difference. Data are expressed as the mean ± standard deviation and were analyzed by one-way ANOVA, followed by post hoc multiple comparisons (LSD method). n = 10.</p

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BackgroundAgomelatine (AGO) is an antidepressant with unique pharmacological effects; however, its underlying mechanisms remain unknown. In this study, we examined agomelatine’s effects on catalase activity, oxidative stress, and inflammation.MethodsChronic restraint stress (CRS) model mice were established over 4 weeks, and AGO 50 mg/kg was administered to different groups alongside a deferasirox (DFX) 10 mg/kg gavage treatment. Behavioral tests were performed to assess the effect of AGO on the remission of depression-like behaviors. Meanwhile, the expression of CAT, the oxidative stress signaling pathway and inflammatory protein markers were assessed using ELISA, qRT-PCR, Western blot, and immunohistochemistry.ResultsFour weeks of AGO treatment significantly improved depression-like behavior in mice through the activation of catalase in the hippocampus and serum of the model mice, increased superoxide dismutase expression, reduced malondialdehyde expression, and reduced oxidative stress damage. Deferasirox was found to offset this therapeutic effect partially. In addition, the inflammatory pathway (including nuclear factor-κB and nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, alpha) was not significantly altered.ConclusionsAGO can exert antidepressant effects by altering oxidative stress by modulating catalase activity.</div

ELISA, Western blot, and PCR results.

Effect of agomelatine on oxidative stress and the NF-кB pathway in CRS mice. (a) CAT activity in the serum of mice under CRS, AGO, and DFX intervention. (b-c) SOD and MDA concentrations in the serum of mice under CRS, AGO, and DFX intervention. (d, g) Representative protein blot results of CAT, NF-кB p65, and IкBα in the mouse hippocampus under CRS and AGO intervention, showing the quantitative density analysis of CAT in the hippocampus (e, f, h). (i-k) mRNA expression levels of CAT, NF-кB, and IкBα in the mouse hippocampus. *P<0.05; **P<0.01; ***P<0.001; CAT, catalase; CRS, chronic restraint stress; AGO, agomelatine; DFX, deferasirox; SOD, superoxide dismutase; MDA, malondialdehyde; ns, no significant difference. Data are expressed as the mean ± standard deviation and were analyzed by one-way ANOVA, followed by post hoc multiple comparisons (LSD method). n = 3–5.</p