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Ameliorative effect of Xiaoyao-jieyu-san on post-stroke depression and its potential mechanisms

Wang, Changde, Wu, Chunlan, Yan, Zhenguo, Cheng, Xiao
Natural medicines 2019 v.73 no.1 pp. 76-84
Western blotting, body weight, cannabinoid receptors, death, gene expression, gene expression regulation, hesperidin, high performance liquid chromatography, histopathology, mass spectrometry, messenger RNA, naringin, norepinephrine, quantitative polymerase chain reaction, quercetin, rats, serotonin, stroke, sucrose, swimming
A stroke is a severe life-threatening disease with high fatality and disability rate. This investigation aimed to study the effect of Xiaoyao-jieyu-san (XYJY) on post-stroke depression (PSD) and its potential mechanisms. PSD rats were prepared using middle cerebral artery embolization (MCAO) and chronic unpredictable mild stress (CUMS), and divided into six groups (n = 10)—sham; MCAO; MCAO + CUMS (PSD); PSD + fluoxetine (1.84 mg/kg/day, 4 weeks); and PSD + XYJY (450 mg/kg/day and 900 mg/kg/day, 4 weeks). Body weight recording, despair swimming test, and sucrose preference test were performed at 0, 3 and 7 weeks. Histopathological examination and levels of 5-hydroxytryptamine (5-HT), norepinephrine (NE) and brain-derived neurotrophic factor (BDNF) in ventral tegmental area-nucleus accumbens (VTA-NAc) tissue were determined at the end of a 7-week period. Real-time polymerase chain reaction PCR was used to determine mRNA expression of 5-HT₁AR and 5-HT₂AR, and Western blot was performed to determine expression of BDNF, corticotrophin-releasing factor (CRF), and cannabinoid receptors (CB₁R and CB₂R) in VTA-NAc tissue. High-performance liquid chromatography coupled with electrospray mass spectroscopy revealed that the constituents of XYJY are mainly paeoniflorin, imperatorin, naringin, arnesene, 2,3,5,4′-tetrahydroxyl-diphenylethylene-2-O-glucoside, kaempferol-3-O-rutinoside, quercetin, hesperidin, cycloastragenol and atractylenolide III. XYJY (900 mg/kg) increased the body weight of PSD rats, while XYJY (450 mg/kg and 900 mg/kg) shortened the duration of immobility and enhanced the sucrose preference of PSD rats. XYJY (450 mg/kg and 900 mg/kg) increased the levels of 5-HT, NE and BNDF, up-regulated mRNA expression of 5-HT₁AR, down-regulated 5-HT₂AR, and up-regulated BNDF, CB₁R, and CB₂R expression in the VTA-NAc tissue of PSD rats but down-regulated CRF. Collectively, the present findings suggested that XYJY has an ameliorative effect on PSD in rats via modulation of BNDF, cannabinoid receptors and CRF in VTA-NAc tissue.