RESUMO
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-1ß), 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-1ß, 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.
RESUMO
BACKGROUND: Our previous study in animal models revealed that bilirubin could induce Aß formation and deposition. Bilirubin may be important in neurodegenerative dementia with Aß deposition. Hence, lowering the concentration of the free bilirubin capable of crossing the blood brain-barrier may benefit the treatment of Alzheimer's disease (AD). OBJECTIVES: The objectives of this study were to examine the change in the serum bilirubin and albumin concentrations of dementia patients with Aß deposition, and to determine the effects of intravenous administration of albumin in the treatment of AD. METHODS: Bilirubin and albumin concentrations in dementia patients with Aß deposition were examined. Cell viability and apoptosis were determined in dopaminergic neuron-like cells MN9D treated with bilirubin in the presence of diverse concentrations of serum. Human albumin at a dose of 10 g every 2 weeks for 24 weeks was administered intravenously to AD patients to examine the effect of albumin on AD symptoms. RESULTS: Significantly higher indirect bilirubin (IBIL) concentrations, lower albumin concentrations, and higher ratio of IBIL to albumin (IBIL/ALB) were observed in dementia patients with Aß deposition, including AD, dementia with Lewy bodies, and general paresis of insane. In vitro assays showed that bilirubin-induced injury in cultured dopaminergic neuron-like cells negatively depends on the concentration of serum in the culture medium. General linear model with repeated measures analysis indicated a main effect of group on the change in albumin concentrations and Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory scale (ADCS-ADL) scores, and the main effect of time and group, and group-by-time interaction on the change of Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) scores. Analysis of the combined data of the entire 28 weeks of assessment period using the area under curve convincingly showed significantly improvements in the change of albumin concentrations, ADCS-ADL scores, and CDR-SB scores. CONCLUSION: IBIL and the IBIL/ALB ratio are significantly higher in dementia patients with Aß deposition, and intravenous administration of albumin is beneficial to AD treatment. TRIAL REGISTRATION: The intervention study was registered at http://www.chictr.org.cn (ChiCTR-IOR-17011539). Date of registration: June 1, 2017.
