Propolis prevents vascular endothelial dysfunction by attenuating inflammation and oxidative damage in the chronic unpredictable stress model of depression in rats

J Pharm Pharmacol. 2023 Nov 23;75(11):1418-1429. doi: 10.1093/jpp/rgad071.

Abstract

Objectives: Chronic stress may lead to depression and vascular endothelial dysfunction. We aimed to evaluate the effects of propolis on vascular functions and the possible mechanisms of its vascular effects in the rat model of chronic unpredictable mild stress (CUMS)-induced depression.

Methods: Male Wistar rats were divided into control, stress (exposure to CUMS), control+propolis and stress+propolis groups (n = 8/each group). CUMS model was induced by exposing rats to various mild stressors daily for 5 weeks. The extract of propolis (100 mg/kg/day) was administered orally to propolis-treated groups for 5 weeks. The depression-like behaviours were assessed with the forced swimming test (FST). Chronic stress resulted in increased immobility response in FST and elevated serum corticosterone levels. Thoracic endothelial functions and expressions of endothelial nitric oxide synthase (eNOS), tumor necrosis factor-alpha (TNFα), interleukin-1beta (IL-1β), Heme oxygenase-1 (HO-1) and superoxide dismutase (SOD) level were assessed.

Key findings: Compared to control group, stress group exhibited a significant decrease in endothelium-dependent relaxations, and eNOS, SOD and HO-1 expressions, whereas a significant increase in the thoracic expressions of TNFα and IL-1β. Propolis ameliorated depression-like behaviours, vascular endothelial dysfunctions and alterations of protein expressions.

Conclusion: Propolis exerted antidepressant-like and vasculoprotective effects in CUMS-induced depression in rats. Chronic propolis treatment may have a protective effect on CUMS-induced vascular endothelial dysfunction by its anti-inflammatory and antioxidant effects.

Keywords: antioxidant; chronic stress; depression; inflammation; propolis; vascular function.

MeSH terms

  • Animals
  • Depression* / drug therapy
  • Depression* / etiology
  • Depression* / prevention & control
  • Disease Models, Animal
  • Inflammation / drug therapy
  • Inflammation / pathology
  • Inflammation / prevention & control
  • Male
  • Oxidative Stress
  • Propolis* / pharmacology
  • Rats
  • Rats, Wistar
  • Stress, Psychological / complications
  • Stress, Psychological / drug therapy
  • Superoxide Dismutase / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Propolis
  • Tumor Necrosis Factor-alpha
  • Superoxide Dismutase