Propolis prevents vascular endothelial dysfunction by antiinflammatory effect in rat model of chronic unpredictable mild stress-induced depression


Creative Commons License

Göçmez S. S. , Celebi G. , Ozer C., Demirtas-Sahin T. , Yazır Y. , Duruksu G. , ...More

32nd Congress of the European-College-of-Neuropsychopharmacology (ECNP), Copenhagen, Denmark, 7 - 10 September 2019, vol.29 identifier

Abstract

P.616 Propolis prevents vascular endothelial dysfunction by antiinflammatory effect in rat model of chronic unpredictable mild stress-induced depression

Purpose: Previous studies have shown that chronic stress and depression contributes to development of cardiovascular diseases and are known to be the underlying causes of atherosclerosis pathogenesis [1]. Vascular endothelial dysfunction has been developed during depression [2]. The chronic unpredictable mild stress (CUMS) animal model is very useful and reliable in modelling human depressive disorders [3]. Propolis is a resionous substance collected by honeybees from various plant sources which has antioxidant, anti-inflammatory, vasodilator and antihypertensive effects [4,5]. The aim of this study is to evaluate the effects of propolis on vascular functions in the CUMS-induced depressive rats.

Methods: The water-soluble extract of propolis was prepared from fresh Turkish propolis (Aksuvital Natural Products Company). The main components in this extract were identified by Gas Cromathography-Mass Spectrometry (GC-MS) analysis. Adult male rats were divided into 4 groups (n=8 for each group): control, control+propolis, stress, stress+propolis. The extract of propolis (100 mg/kg) was administered orally for 35 consecutive days to the control+propolis and stress+propolis. In the stress and stress+propolis groups, rats were subjected to different types of stressors daily for a CUMS period of 35 days. At the end of CUMS period, the forced swimming test was applied for evaluation of depression-like behavior. After behavioral test, the rats were sacrificed and then thoracic aorta and blood samples were collected for the biochemical examinations. Corticosterone level was measured in blood samples as stress marker. To analyze the vascular reactivity, the endothelium-dependent and -independent vasorelaxant responses of thoracic aorta were investigated by carbachol (10-8-10-5 M) and sodium nitroprusside (10-8-10-4 M) after preincubation with phenylephrine (10-5 M) in organ chambers. In addition, TNFα levels was assayed in vascular tissues to investigate the presence of antiinflammatory effect of propolis. All data were presented as mean ± standard error of the mean (SEM). Statistical comparions between the groups were performed using one way ANOVA followed by Tukey's post hoc test. p values less than 0.05 were considered to be indicative of significance.

Results: The immobility time in forced swimming test was significantly increased in stress group, indicating depression-like behavior, whereas decreased in stress+propolis group compared to the stress group (p<0.05). In the stress group, endothelium-dependent relaxation to carbachol was significantly decreased compared to control (p<0.05), whereas propolis treatment during CUMS period significantly reversed this response to the controls. Endothelium-independent relaxations to sodium nitroprusside was similar in all groups. Serum corticosterone levels were significantly increased in stress group (p<0.05). The expression analysis in thoracic aorta showed that TNFα expression in the stress group was significantly upregulated compared to that in the control rats (p<0.05), while propolis treatment markedly decreased thoracic TNF-α expression in stressed rats (p<0.05).

Conclusion: The results of the study have shown that the chronic propolis administration may prevent vascular endothelial dysfunction associated with CUMS by antiinflammatory effect. Propolis, has also antidepressant effect, may be a potential drug in the treatment of depression. However, further studies are needed to support these findings.

Disclosure statement: This work was supported by Scientific Research Projects of Kocaeli University, Turkey (BAP 2019/03).

References

[1]
P.H. Black, L.D. Garbutt
Stress, inflammation and cardiovascular disease
J. Psychosom. Res., 52 (2002), pp. 1-23
[2]
J.K. Rybakowski, A. Wykretowicz, A. Heymann-Szlachcinska, H. Wysocki
Impairment of endothelial function in unipolar and bipolar depression
Biol. Psychiat., 60 (8) (2006), pp. 889-891
[3]
P. Willner
The chronic mild stress (CMS) model of depression: History, evaluation and usage
Neurobiol. Stress, 6 (2017), pp. 78-93
[4]
F.L. Hu, H.L. Hepburn, Y.H. Li, M. Chen, S.E. Radloff, S. Daya
Effects of ethanol and water extracts of propolis (bee glue) on acute inflammatory animal models
J. Ethnopharmacol., 100 (2005), pp. 276-283
[5]
H. Maruyama, Y. Sumitou, T. Sakamoto, Y. Araki, H. Hara
Antihypertensive effects of flavonoids isolated from brazilian green propolis in spontaneously hypertensive rats
Biol. Pharm. Bull. Jul, 32 (7) (2009), pp. 1244-1250