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. 2023 Nov 10;15(22):4742.
doi: 10.3390/nu15224742.

Antidepressant-like Effect of Oroxylum indicum Seed Extract in Mice Model of Unpredictable Chronic Mild Stress

Chorpeth Chalermwongkul  1 , Charinya Khamphukdee  2 , Juthamart Maneenet  3 , Supawadee Daodee  3 , Orawan Monthakantirat  3 , Chantana Boonyarat  3 , Yutthana Chotritthirong  1 , Suresh Awale  4 , Anake Kijjoa  2   5 , Yaowared Chulikhit  3
Affiliations

Antidepressant-like Effect of Oroxylum indicum Seed Extract in Mice Model of Unpredictable Chronic Mild Stress

Chorpeth Chalermwongkul et al. Nutrients. .

Abstract

Major depressive disorder (MDD) is one life-threatening disorder that is prevalent worldwide. The evident etiology of this disease is still poorly understood. Currently, herbal medicine is gaining more interest as an alternative antidepressant. Oroxylum indicum, which is used in traditional medicine and contains a potential antidepressive compound, baicalein, could have an antidepressive property. An in vitro monoamine oxidase-A (MAO-A) inhibitory assay was used to preliminarily screening for the antidepressant effect of O. indicum seed (OIS) extract. Mice were subjected to unpredictable chronic mild stress (UCMS) for 6 weeks, and the daily administration of OIS extract started from week 4. The mechanisms involved in the antidepressive activity were investigated. The OIS extract significantly alleviated anhedonia and despair behaviors in the UCMS-induced mouse model via two possible pathways: (i) it normalized the HPA axis function via the restoration of negative feedback (decreased FKBP5 and increased GR expressions) and the reduction in the glucocorticoid-related negative gene (SGK-1), and (ii) it improved neurogenesis via the escalation of BDNF and CREB expressions in the hippocampus and the frontal cortex. In addition, an HPLC analysis of the OIS extract showed the presence of baicalin, baicalein, and chrysin as major constituents. All of the results obtained from this study emphasize the potential of OIS extract containing baicalin and baicalein as an effective and novel alternative treatment for MDD.

Keywords: HPA axis; Oroxylum indicum; baicalein; depression; unpredictable chronic mild stress.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Structures of baicalin and its aglycone, baicalein.
Figure 2
Figure 2
Schematic drawing of unpredictable chronic mild stress (UCMS) procedure.
Figure 3
Figure 3
The OIS extract (100 and 500 mg/kg) significantly improved sucrose preference, which was diminished by long-term stress. SPT was performed every week to monitor anhedonia. The results are expressed as mean ± S.E.M. (n = 10 per each group). ### p < 0.001 vs. the non-stress group. ** p < 0.01 and *** p < 0.001 vs. the vehicle-treated UCMS group.
Figure 4
Figure 4
The OIS extract (100 and 500 mg/kg) showed no effect on locomotor function in UCMS-induced mice, as determined using the Y-maze test. The data were analyzed from number of arm entries and expressed as mean ± S.E.M. (n = 10 per each group).
Figure 5
Figure 5
The OIS extract (100 and 500 mg/kg) significantly decreased the immobility time, which was an implication for despair behavior in TST (A) and FST (B). Behavioral tests were performed after treatment for 3 weeks. The results are expressed as mean ± S.E.M. (n = 10 per each group). ### p < 0.001 vs. the non-stress group. * p < 0.05, ** p < 0.01, and *** p < 0.001 vs. the vehicle-treated UCMS group. $ p < 0.05 and $$ p < 0.01 compared with different doses of the OIS extract.
Figure 6
Figure 6
The OIS extract (100 and 500 mg/kg) and imipramine (20 mg/kg) reduced the elevation in the serum corticosterone level induced by the UCMS. The data are expressed as mean ± S.E.M. (n = 5). ### p < 0.001 vs. the non-stress group. *** p < 0.001 vs. the vehicle-treated UCMS group.
Figure 7
Figure 7
The OIS extract (100 and 500 mg/kg) and imipramine (20 mg/kg) alleviated the impaired regulation of the HPA axis by decreasing FKBP5 (A) and SGK-1 (B) mRNA expressions, while improving GR mRNA expression (C) in both affected brain areas. The results are expressed as mean ± S.E.M. (n = 6). ### p < 0.001 vs. the non-stress group. ** p < 0.01 and *** p < 0.001 vs. the vehicle-treated UCMS group. $ p < 0.05, $$ p < 0.01, and $$$ p < 0.001 compared with the different doses of the OIS extract.
Figure 8
Figure 8
The OIS extract in the dose of 500 mg/kg normalized the depletion of neurogenesis and neuroplasticity induced by chronic stress which was determined by mRNA expressions of BDNF (A) and CREB (B) in the same manner as imipramine. The results are expressed as mean ± S.E.M. (n = 6). ### p < 0.001 vs. the non-stress group. * p < 0.05, ** p < 0.01 and *** p < 0.001 vs. the vehicle-treated UCMS group. $ p < 0.05, $$ p < 0.01 and $$$ p < 0.001 compared with different doses of the OIS extract.
Figure 9
Figure 9
Chromatogram of standard: baicalin (1), quercetin (2), kaempferol (3), baicalein (4), chrysin (5), and oroxylin A (6), respectively (A), and the OIS extract (B). Detection wavelength was 275 nm.
Figure 10
Figure 10
The possible molecular mechanisms of OIS extract.
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