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.
This is a preview of subscription content, log in to check access.
This work was supported by the Shanghai Science and Technology Commission, Shanghai Natural Science Foundation (16ZR1433700).
Compliance with ethical standards
Conflict of interest
The authors declare no conflict of interests exists.
Daglia M, Lorenzo AD, Nabavi SF (2017) Improvement of antioxidant defences and mood status by oral GABA tea administration in a mouse model of post-stroke depression. Nutrients 9:446CrossRefGoogle Scholar
Zhao W, Jiang F, Zhang Z, Zhang J, Ding Y, Ji X (2017) Remote ischemic conditioning: a novel non-invasive approach to prevent post-stroke depression. Front Aging Neurosci 9:270CrossRefGoogle Scholar
Dou DM, Huang LL, Dou J, Wang XX, Wang PX (2018) Post-stroke depression as a predictor of caregivers burden of acute ischemic stroke patients in China. Psychol Health Med 23:541–547CrossRefGoogle Scholar
Sternnezer S, Eyngorn I, Mlynash M, Snider RW, Venkatsubramanian C, Wijman CAC, Buckwalter MS (2017) Depression 1 year after hemorrhagic stroke is associated with late worsening of outcomes. Neurorehabilitation 41:179–187CrossRefGoogle Scholar
Zhang Y, Jiang H, Yue Y, Yin Y, Zhang Y, Liang J, Li S, Wang J, Lu J, Geng D, Wu A, Yuan Y (2017) The protein and mRNA expression levels of glial cell line-derived neurotrophic factor in post stroke depression and major depressive disorder. Sci Rep 7:8674CrossRefGoogle Scholar
Tseng SP, Hsu YC, Chiu CJ, Wu ST (2017) A population-based cohort study on the ability of acupuncture to reduce post-stroke depression. Medicines 4:16CrossRefGoogle Scholar
Hackett ML, Anderson CS, House A, Halteh C (2008) Interventions for preventing depression after stroke. Cochrane Database Syst Rev 40:CD003437Google Scholar
Hou WH, Liang HW, Li CY (2013) Effects of stroke rehabilitation on incidence of post-stroke depression: a population-based cohort study. J Clin Psychiatry 74:e859–e866CrossRefGoogle Scholar
Peng W, Shen W, Lin B, Han P, Li CH, Zhang QY, Ye BZ, Rahman K, Xin HL, Qin LP, Han T (2018) Docking study and antiosteoporosis effects of a dibenzylbutane lignan isolated from Litsea cubeba targeting Cathepsin K and MEK1. Med Chem Res. https://doi.org/10.1007/s00044-018-2215-8Google Scholar
Wang LCD, Shao FY, Hu J, Chen YY (2007) Clinical research of the treatment effects of Xiaoyao-jieyu-san on post-stroke depression and its effects on 5-HT contents in plasma. Lishizhen Med Mater Med Res 18:2943–2944Google Scholar
Wang CD (2007) Clinical research regarding effects of Xiaoyao-jieyu-san on post-stroke depression. Capt Med 3:38Google Scholar
Kim SW, Lee HK, Kim ID, Lee H, Luo L, Park JY, Yoon SH, Lee JK (2016) Robust neuroprotective effects of 2-((2-oxopropanoyl) oxy)-4-(trifluoromethyl) benzoic acid (OPTBA), a HTB/pyruvate ester, in the postischemic rat brain. Sci Rep 6:31843CrossRefGoogle Scholar
Zhang S, Yang P, Li X, Wang X, Song J, Peng W, Wu C (2017) Comparative researches of semen arecae and charred semen arecae on gastrointestinal motility, motilin, substance P, and CCK in chronically stressed rats. Evid Based Complement Alternat Med 2017:1–8Google Scholar
Han P, Han T, Peng W, Wang XR (2013) Antidepressant-like effects of essential oil and asarone, a major essential oil component from the rhizome of Acorus tatarinowii. Pharm Biol 51:589–594CrossRefGoogle Scholar
Jin HJ, Pei L, Li YN, Zheng H, Yang S, Wan Y, Mao L, Xia YP, He QW, Li M, Yue ZY, Hu B (2017) Alleviative effects of fluoxetine on depressive-like behaviors by epigenetic regulation of BDNF gene transcription in mouse model of post-stroke depression. Sci Rep 7:14926CrossRefGoogle Scholar
Millan MJ (2004) The role of monoamines in the actions of established and “novel” antidepressant agents: a critical review. Eur J Pharmacol 500:371–384CrossRefGoogle Scholar
Chen B, Dowlatshahi D, Macqueen GM, Wang JF, Young LT (2001) Increased hippocampal BDNF immunoreactivity in subjects treated with antidepressant medication. Biol Psychiat 50:260–265CrossRefGoogle Scholar
Carvalho AL, Caldeira MV, Santos SD, Duarte CB (2008) Role of the brain-derived neurotrophic factor at glutamatergic synapses. Br J Pharmacol 153:S310–S324CrossRefGoogle Scholar
Dwivedi Y (2009) Brain-derived neurotrophic factor: role in depression and suicide. Neuropsychiatr Dis Treat 5:433–449CrossRefGoogle Scholar
Han K, Jia N, Li J, Yang L, Min LQ (2013) Chronic caffeine treatment reverses memory impairment and the expression of brain BNDF and TrkB in the PS1/APP double transgenic mouse model of Alzheimer’s disease. Mol Med Rep 8:737–740CrossRefGoogle Scholar
Duan D, Chen L, Yang X, Tu Y, Jiao S (2015) Antidepressant-like effect of essential oil isolated from Toona ciliata Roem. var. yunnanensis. J Nat Med 69:191–197CrossRefGoogle Scholar
Scarante FF, Vilaverde C, Detoni VL, Ferreirajunior NC, Guimarães FS, Campos AC (2017) Cannabinoid modulation of the stressed hippocampus. Front Mol Neurosci 10:411CrossRefGoogle Scholar
Wang S, Sun H, Liu S, Wang T, Guan J, Jia J (2016) Role of hypothalamic cannabinoid receptors in post-stroke depression in rats. Brain Res Bull 121:91–97CrossRefGoogle Scholar
Pekala K, Michalak A, Kruk-Slomka M, Budzynska B, Biala G (2018) Impacts of cannabinoid receptor ligands on nicotine- and chronic mild stress-induced cognitive and depression-like effects in mice. Behav Brain Res 347:167–174CrossRefGoogle Scholar
Yin JX, Tian JZ, Shi J, Cheng L, Wang YY (2006) Influence of Chinese herbal extract complex on expression of corticotropin-releasing factor and protein kinasec protein in hippocampus of middle cerebral artery occlusion rats. Chin J Chin Mater Med 31:1983–1986Google Scholar