Abstract
Cerebral venous thrombosis (CVT) often causes human depression, whereas depression-induced low immunity makes the patients susceptible to gastrointestinal infection. Blueberry possesses antidepressant properties which may improve autoimmunity and reduce gastrointestinal infection. Brain-derived neurotrophic factor (BDNF) performs antidepressant function and can be regulated by miR-155, which may be affected by blueberry. To explore the possible molecular mechanism, blueberry compounds were analyzed by high-performance liquid chromatography. Activity of compounds was tested by using HT22 cells. The present study tested 124 patients with CVT-induced mild-to-moderate depressive symptoms (Center for Epidemiologic Studies—Depression Scale [CES-D] ≥16) and gastrointestinal infection. Patients were randomly assigned to blueberry extract group (BG, received 10 mg blueberry extract daily) and placebo group (PG, received 10 mg placebo daily). After 3 months, depression, gastrointestinal infection and lipid profiles were investigated. Serum miR-155 and BDNF were measured using real-time quantitative polymerase chain reaction and or Western Blot. Blueberry treatment improved depressive symptoms and lipid profiles, and also reduced gastrointestinal infection in the BG group (P < 0.05) but those of the PG group (P = 1). These changes were paralleled by increase in serum levels of BDNF and miR-155 (P < 0.05). HPLC analysis showed that blueberry extracts were the main phenolic acids with 0.18, 0.85, 0.26, 0.72, 0.66, 0.4,1, and 1.92 mg/g of gentisic acid, chlorogenic acid, [2]-epicatechin, p-coumaric acid, benzoic acid, p-anisic acid, and quercetin in blueberry extracts, respectively. Phenolics in blueberry are possible causal agents in improving antidepressant activity and reducing gastrointestinal infection. Administration of blueberry increased BDNF expression and miR-155. Blueberry cannot affect BDNF level when miR-155 is overexpressed or inhibited. Phenolics from blueberry reduced gastrointestinal infection of patients with CVT by improving antidepressant activity via upregulation of miR-155-mediated BDNF.
Highlights
Cerebral venous thrombosis (CVT) is an arterial disease, and it often results in cerebral infarction and even potential morbidity
Thrombosis may result in mental retardation (Lohiya et al, 2005), which is often associated with long-term depression (Niere et al, 2012)
Depression is linked with some autoimmune diseases (Benros, 2016), which can increase incidence of bacterial infection (Alam et al, 2014).Epidemiological studies strongly suggest a link between depression and thrombosis (Stein et al, 2017)
Summary
Cerebral venous thrombosis (CVT) is an arterial disease, and it often results in cerebral infarction and even potential morbidity. Abundance of flavonoid-derived products in the gastrointestinal tract has been reported to contribute to health benefits of phenolics (Goto et al, 2012; Wang et al, 2015). Phenolics and their metabolites have been found to transverse blood-brain-barrier and exhibit neuropharmacological properties (Shen et al, 2015; Lan et al, 2016). Information suggest that CVT often causes human depression, whereas depression-induced low immunity makes the patients susceptible to gastrointestinal infection. Blueberry may improve depression-induced autoimmunity disorder and reduce gastrointestinal infection by affecting BDNF level via miR-155. The main bioactive compounds of blueberry juice were measured here
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