Crocin ameliorates chronic obstructive pulmonary disease-induced depression via PI3K/Akt mediated suppression of inflammation.

European Journal of Pharmacology(2019)

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摘要
Clinical studies have indicated the co-occurrence of chronic obstructive pulmonary disease (COPD) and psychiatric disorders, for example, comorbid depression. However, the underlying mechanism is rarely addressed. The present study aimed to investigate the mechanism of COPD-induced depression and the psychological and physiological effects of crocin, an active constituent of Crocus sativus L. C57BL/6 mice were randomly exposed to cigarette smoke for 7 weeks to establish COPD animal model. Crocin (50 mg/kg), Dexamethasone (2 mg/kg) and IGF-1 (2 mg/kg) were respectively injected to mice once a day. The FEV1/FVC ratio and the mean alveolus area of lung tissue demonstrated the COPD model was successfully established by cigarette smoke. Crocin administration significantly reversed markers of depression [loss of body weight, sucrose preference, and elevation of immobile time in tail-suspension tests (TST) and in forced swimming tests (FST)]. Besides, crocin treatment significantly inhibited the numbers of inflammatory cells (macrophages, neutrophils, and lymphocytes), suppressed the infiltration of peribronchial inflammatory cells, and reduced the concentration of proinflammatory cytokines in bronchoalveolar lavage (BAL) fluid and lung tissue. Crocin also reduced proinflammatory cytokines in the hippocampus. In exploring associated mechanisms, we discovered that crocin blunted cigarette smoke-induced IκB phosphorylation and degradation, and NF-κBp65 nuclear translocation. IGF-1, an activator of PI3K, abrogated the effect of crocin against cigarette smoke-induced activation of the NF-κB pathway. Together, these results showed that an inflammatory mechanism might be involved in the pathogenesis of COPD with comorbid depression. Crocin exhibited significant effects through the regulation of PI3K/Akt-mediated inflammatory pathways.
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关键词
Chronic obstructive pulmonary disease,Depression,Inflammation,PI3K/Akt/NF-κB,Crocin
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