Effects of Kaixinjieyu, a Chinese herbal medicine preparation, on neurovascular unit dysfunction in rats with vascular depression.

Juhua Pan,Ying Zhang,Xiaoming Lei,Wen Chen,Jun Zheng,Jialong Wang,Yanyun Wang,Hanming Cui,Qihua Liu,Shijing Huang,Duojiao Li

doi:10.1186/s12906-015-0808-z

Abstract

BackgroundKaixinjieyu (KJ), derived from Kaixin and Sini powder, is an effective Chinese herbal medicine preparation used in the treatment of vascular depression (VD). We hypothesize that broad antidepressant effect of KJ results from the improved neurovascular unit (NVU) function via neurogenesis, permeability of blood–brain barrier (BBB) and balance of the fibrinolytic system.MethodsA VD model of rat was established by chronic unpredictable mild stress and separation after ligation of the bilateral common carotid arteries. The rats were treated with KJ and fluoxetine hydrochloride (FLU) for 21 days, respectively. The behavior and cerebral perfusion were investigated and then NVU functions including neurogenesis, permeability of BBB and balance of the fibrinolytic system were studied using a number of biomarkers and TUNEL assay.ResultsKJ significantly increased sucrose preference, moving distance, number of rearing and cortical blood flow. NVU functions measured by brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB) and tissue plasminogen activator (t-PA) proteins and mRNA, zona occludens protein-1 (ZO-1), occludin and claudin-5 proteins increased significantly, whereas, plasminogen activator inhibitor-1 (PAI-1), matrix metalloproteinase-2 (MMP-2) proteins, mRNA and apoptotic rates of neurons decreased significantly with treatment of KJ. FLU has a function similar to KJ in behavior, regulation of BDNF, TrkB, MMP-2, occludin and apoptotic rates of cells.ConclusionsKJ has function of reducing depression-like behavior and improving cerebral hypoperfusion, which might be mediated by the up-regulation of neurogenesis and tight junction of BBB, and balance of the fibrinolytic system. The results imply that KJ is better than FLU in improving cerebral hypoperfusion and the fibrinolytic system.

Highlights

Kaixinjieyu (KJ), derived from Kaixin and Sini powder, is an effective Chinese herbal medicine preparation used in the treatment of vascular depression (VD)
VD rats displayed a decreased sucrose preference compared with the sham group (P < 0.05); rats in KJ-H, KJ-M and fluoxetine hydrochloride (FLU) groups had significant increases in sucrose preference compared with the VD group (P < 0.05, Fig. 1a)
Cerebral perfusion The cortical blood flow (CBF) was reduced in VD rats compared with the sham rats (P < 0.01); rats in KJ-H and KJ-M groups displayed significant increase in the CBF compared with the VD group (P < 0.01, P < 0.05, respectively, Fig. 2)

Summary

Introduction

Kaixinjieyu (KJ), derived from Kaixin and Sini powder, is an effective Chinese herbal medicine preparation used in the treatment of vascular depression (VD). A number of associated diseases of VD means complicated therapeutic strategies [1, 7]. For VD patients, depressive syndrome is not the primary disease but can be considered as one of the clinical manifestations in the wide symptom spectrum of the cerebral small vessel. VD is poorly responsive to antidepressants and the therapeutic strategy is often significantly different from other depressions. White-matter hyper intensities in the left hemisphere [9], especially in the cingulum bundle adjacent to the hippocampus [10], global vascular risk [11], magnetic resonance imaging findings and neuropsychological assessment [12] have been used as predictors of poor response to antidepressants in VD patients

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