Abstract

Background: Cang-ai volatile oil (CAVO) is a Chinese herbal volatile oil. Previous studies report that CAVO exhibits of anti-depressant and anti-inflammatory effects, and modulates activity of monoamine neurotransmitter. The current study sought to explore whether CAVO exhibits anti-depressant effects of CAVO through inhibition of inflammatory response and regulation of indoleamine 2 and 3-dioxygenase (IDO) mediated tryptophan degradation pathway.Methods: The study established chronic unpredictable mild stress (CUMS) depression-like model using rats. Body weight and food intake of animals were determined, and open field test (OFT), forced swim test (FST), and sucrose preference test (SPT) were performed to explored the behavioral changes of animals. Expression levels of interleukin-6 (IL-6), interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), interleukin-4 (IL-4), interleukin-10 (IL-10), kynurenine (KYN), quinolinic acid (QUIN), tryptophan (Trp), kynurenic acid (KYNA), serotonin (5-HT), and 5-hydroxyindole acetic acid (5-HIAA) in the prefrontal cortex of CUMS rats were determined by ELISA. Co-localization of the microglia markers, Iba1 and IL-6 was determined by immunofluorescence. Western blotting was performed to determine the protein expression level of IDO1.Results: The findings of the current study showed that CAVO increased the body weight and food intake of rats and alleviated depression-like behaviors as shown in OFT, FST, and SPT analysis. ELISA assay showed that CAVO decreased IL-6, IL-1β, TNF-α, and IFN-γ levels and increased levels of IL-4 and IL-10 in the prefrontal cortex of CUMS rats. Analysis showed that CAVO significantly reduced KYN and QUIN levels and the ratio of KYN/Trp, whereas it increased the levels of Trp, KYNA, 5-HT, and 5-HIAA. Immunofluorescence analysis showed that CAVO reduced the number of positive cells with co-localization of microglia markers, Iba1 and IL-6. Western blot analysis showed that CAVO decreased the protein expression level of IDO1 in rats.Conclusion: The findings show that the anti-depressant effects of CAVO are mainly attributed to inhibition of the activation of microglia and downregulation of IDO expression, thus inhibiting the kynurenine pathway and reversing the effects exerted on the 5-HT system.

Highlights

  • Depression is a mental illness characterized by high morbidity, mortality, and disability [1]

  • The current study used body weight gain, food intake, Open Field Test (OFT), Forced Swim Test (FST), and sucrose preference test (SPT) to evaluate the success of the chronic unpredictable mild stress (CUMS) model and the antidepressant effect of Cang-ai volatile oil (CAVO)

  • The findings showed that weight gain and food intake of rats in the model group were lower compared with that of rats in the control group (P < 0.01, Figure 2)

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Summary

Introduction

Depression is a mental illness characterized by high morbidity, mortality, and disability [1]. Clinical studies report that levels of proinflammatory cytokines in the peripheral, cerebrospinal fluid, and hippocampus are significantly higher in patients with depression compared with the levels in health individuals [7, 8]. Animal studies present similar findings that expression levels of pro-inflammatory cytokines are increased in rodent depression-like model animals [9]. Pro-inflammatory cytokines can induce depression-like behaviors in rats [10, 11]. Studies report that neuronal inflammation is induced by pro-inflammatory cytokines such as interleukin-1β (IL1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNFα). Previous studies report that CAVO exhibits of anti-depressant and anti-inflammatory effects, and modulates activity of monoamine neurotransmitter. The current study sought to explore whether CAVO exhibits anti-depressant effects of CAVO through inhibition of inflammatory response and regulation of indoleamine 2 and 3-dioxygenase (IDO) mediated tryptophan degradation pathway

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