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. 2022 Dec 19;27(24):9055.
doi: 10.3390/molecules27249055.

Potential Antioxidant Activity of Apigenin in the Obviating Stress-Mediated Depressive Symptoms of Experimental Mice

Adel Alghamdi  1 , Mansour Almuqbil  2 , Mohammad A Alrofaidi  1 , Abdulhadi S Burzangi  3 , Ali A Alshamrani  4 , Abdullah R Alzahrani  5 , Mehnaz Kamal  6 , Mohd Imran  7 , Sultan Alshehri  8 , Basheerahmed Abdulaziz Mannasaheb  9 , Nasser Fawzan Alomar  10 , Syed Mohammed Basheeruddin Asdaq  9
Affiliations

Potential Antioxidant Activity of Apigenin in the Obviating Stress-Mediated Depressive Symptoms of Experimental Mice

Adel Alghamdi et al. Molecules. .

Abstract

This study aimed to examine the antidepressant properties of apigenin in an experimental mouse model of chronic mild stress (CMS). Three weeks following CMS, albino mice of either sex were tested for their antidepressant effects using the tail suspension test (TST) and the sucrose preference test. The percentage preference for sucrose solution and the amount of time spent immobile in the TST were calculated. The brain malondialdehyde (MDA) levels, catalase activity, and reduced glutathione levels were checked to determine the antioxidant potential of treatments. When compared to the control, animals treated with apigenin during the CMS periods showed significantly shorter TST immobility times. Apigenin administration raised the percentage preference for sucrose solution in a dose-dependent manner, which put it on par with the widely used antidepressant imipramine. Animals treated with apigenin displayed a significantly (p ˂ 0.05) greater spontaneous locomotor count (281) when compared to the vehicle-treated group (245). Apigenin was also highly effective in significantly (p ˂ 0.01) lowering plasma corticosterone levels (17 vs. 28 µg/mL) and nitrite (19 vs. 33 µg/mL) produced by CMS in comparison to the control group. During CMS, a high dose (50 mg/kg) of apigenin was given, which greatly increased the reduced glutathione level while significantly decreasing the brain's MDA and catalase activity when compared to the control group. As a result, we infer that high doses of apigenin may have potential antidepressant effects in animal models via various mechanisms.

Keywords: antidepressant activity; antioxidant potential; apigenin; chronic mild stress; sucrose preference test; tail suspension test.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The effect of apigenin and imipramine on immobility period. Data are expressed in mean ± SEM (n = 8). Data were evaluated using a one-way analysis of variance (ANOVA) and Tukey’s test. *** p < 0.001 when compared to the vehicle control group. LA: low dose of Apigenin (25 mg/kg); HA: high dose of Apigenin (50 mg/kg); Imipramine: standard antidepressant (15 mg/kg); Vehicle; 0.2% carboxy methyl cellulose (CMC).
Figure 2
Figure 2
The effect of apigenin and imipramine on percentage sucrose preference. Data are expressed in mean ± SEM (n = 8). Data were evaluated using a one-way analysis of variance (ANOVA) and Tukey’s test. *** p < 0.001 when compared to the vehicle control group. LA: low dose of Apigenin (25 mg/kg); HA: high dose of Apigenin (50 mg/kg); Imipramine: standard antidepressant (15 mg/kg); Vehicle; 0.2% carboxy methyl cellulose (CMC).
Figure 3
Figure 3
The effect of apigenin and imipramine on the number of locomotor counts. Data are expressed in mean ± SEM (n = 8). Data were evaluated using a one-way analysis of variance (ANOVA) and Tukey’s test. * p < 0.05 when compared to the vehicle control group. LA: low dose of Apigenin (25 mg/kg); HA: high dose of Apigenin (50 mg/kg); Imipramine: standard antidepressant (15 mg/kg); Vehicle; 0.2% carboxy methyl cellulose (CMC).
Figure 4
Figure 4
The effect of apigenin and imipramine changes on plasma nitrite and corticosterone levels. Data are expressed in mean ± SEM (n = 8). Data were evaluated using a one-way analysis of variance (ANOVA) and Tukey’s test. ** p < 0.01; *** p < 0.001 when compared to the vehicle control group. LA: low dose of Apigenin (25 mg/kg); HA: high dose of Apigenin (50 mg/kg); Imipramine: standard antidepressant (15 mg/kg); Vehicle; 0.2% carboxy methyl cellulose (CMC).
Figure 5
Figure 5
The effect of apigenin and imipramine on brain malondialdehyde (MDA) levels. Data are expressed in mean ± SEM (n = 8). Data were evaluated using a one-way analysis of variance (ANOVA) and Tukey’s test. *** p < 0.001 when compared to the vehicle control group. LA: low dose of Apigenin (25 mg/kg); HA: high dose of Apigenin (50 mg/kg); Imipramine: standard antidepressant (15 mg/kg); Vehicle; 0.2% carboxy methyl cellulose (CMC).
Figure 6
Figure 6
The effect of apigenin and imipramine on brain catalase activity. Data are expressed in mean ± SEM (n = 8). Data were evaluated using a one-way analysis of variance (ANOVA) and Tukey’s test. ** p < 0.01 when compared to the vehicle control group. LA: low dose of Apigenin (25 mg/kg); HA: high dose of Apigenin (50 mg/kg); Imipramine: standard antidepressant (15 mg/kg); Vehicle; 0.2% carboxy methyl cellulose (CMC).
Figure 7
Figure 7
The effect of apigenin and imipramine on brain-reduced glutathione levels. Data are expressed in mean ± SEM (n = 8). Data were evaluated using a one-way analysis of variance (ANOVA) and Tukey’s test. *** p < 0.001 when compared to the vehicle control group. LA: low dose of Apigenin (25 mg/kg); HA: high dose of Apigenin (50 mg/kg); Imipramine: standard antidepressant (15 mg/kg); Vehicle; 0.2% carboxy methyl cellulose (CMC).
Figure 8
Figure 8
Experimental protocol of the study.
See this image and copyright information in PMC

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References

    1. Schechter L.E., Ring R.H., Beyer C.E., Hughes Z.A., Khawaja X., Malberg J.E., Rosenzweig-Lipson S. Innovative approaches for the development of antidepressant drugs: Current and future strategies. J. Am. Soc. Exp. Neurother. 2005;2:590–611. doi: 10.1602/neurorx.2.4.590. - DOI - PMC - PubMed
    1. Manji H.K., Drevets W.C., Charney D.S. The cellular neurobiology of depression. Nat. Med. 2001;7:541–547. doi: 10.1038/87865. - DOI - PubMed
    1. Leonard B., Maes M. Mechanistic explanations how cell-mediated immune activation, inflammation and oxidative and nitrosative stress pathways and their sequels and concimatants play a role in the pathophysiology of unipolar depression. Neurosci. Biobehav. Rev. 2012;36:764–785. doi: 10.1016/j.neubiorev.2011.12.005. - DOI - PubMed
    1. Tanabe A., Nomura S., Rinsho N. Pathophysiology of depression. Nihon Rinsho. 2007;65:1585–1590. - PubMed
    1. Maes M., Galecki P., Chang Y.S., Berk M. A review on the oxidative and nitrosative stress (O & NS) pathways in major depression and their possible contribution to the (neuro) degenerative process in that illness. Prog. Neuro-Psychophar. Macol. Biol. Psychiatr. 2011;35:676–692. - PubMed