Abstract

Chaihu Shugan San (CHSGS) is a traditional Chinese herbal formula that is often used in clinical practice to treat live Qi stagnation syndrome and depression. Fluoxetine is one of the commonly used drugs for the clinical treatment of depression. This study involved a comparison of CHSGS and fluoxetine on antidepression and regulating blood rheology effects with chronic restraint stress- (CRS-) induced depression rat models. Rats were induced depression models by CRS for 4 weeks. Upon successful induction of depression in the rats, the animal was administered CHSGS at 0.6 g/kg/d, 1.2 g/kg/d, or fluoxetine 1.8 mg/kg/d to corresponding groups by gavage for 2 weeks. The changes of CRS rats were determined by behavior observations and sucrose preference test and hypothalamic-pituitary-adrenal cortex (HPA) axis functional status. The changes in monoamine neurotransmitters and related indicators of blood status were detected by enzyme-linked immunosorbent assay (ELISA), blood rheometer, and other methods. The outcome shows that CHSGS is superior to fluoxetine in regulating the appearance and HPA axis function of model rats. In addition, CHSGS and fluoxetine have similar effects in improving blood rheology, and both can alleviate the hypercoagulable state of blood via the platelet 5-hydroxytryptamine receptor 2A (5-HT2A) pathway in rats of depression. It was also observed that CHSGS can improve the blood state of depressed rats by restoring liver coagulation-anticoagulation balance and endothelium-related functions.

Highlights

  • Depression is a mental disorder, which is closely related to chronic diseases such as stroke [1], cardiovascular disease [2], and diabetes [3]

  • Fluoxetine hydrochloride capsules were purchased from Eli Lilly Suzhou Pharmaceutical Co., Ltd. (Jiangsu, China). e dopamine (DA), 5-hydroxytryptamine (5-HT), corticotropin-releasing hormone (CRH), noradrenaline (NE), corticotropin (CORT), 6-keto-protagiandinF1α (6-KetoPGF1α), protein C (PC), free protein S (FPS), antithrombin III (AT-III), tissue-type plasminogen activator (t-PA), PAI-I, P-selectin (Ps), and thromboxane B2 (TXB2) enzyme-linked immunosorbent assay (ELISA) kit were purchased from Beijing Rigorbio Science Development Co., Ltd. (Beijing, China). 5-hydroxytryptamine receptor 2A (5-HT2A), serotonin transporter (SERT), and glutamine transaminase ELISA kit were purchased from Beijing Sino-UK Institute of Technology (Beijing, China)

  • Effects of Chaihu Shugan San (CHSGS) and Fluoxetine on the hypothalamic-pituitary-adrenal cortex (HPA) Axis in CRS Rats. e CRH levels in the hypothalamus and CORT levels in plasma were significantly increased in the model group compared with those of the control group (p < 0.01) (Figures 2(a) and 2(b)). e CRH levels in the hypothalamus and CORT levels in plasma were significantly decreased in the CHSGS + 1.2 g/kg group compared with those of the model group (p < 0.01 or 0.05) (Figures 2(a) and 2(b)). e CORT levels in plasma were significantly decreased in the fluoxetine group compared with those of the model group (p < 0.01 or 0.05) (Figure 2(b)). e CRH levels in the Observed indicators Behavioral state Activity level Emotional response Sleep state

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Summary

Introduction

Depression is a mental disorder, which is closely related to chronic diseases such as stroke [1], cardiovascular disease [2], and diabetes [3]. Studies have pointed out that depression and adverse cardiac events have the same underlying pathological mechanism, including neuroendocrine dysfunction, cardiac autonomic control disorder, endothelial dysfunction, inflammation, and enhanced platelet reactivity [4]. Clinical studies show that the activation and aggregation rates of fibrinogen and platelet in patients with depression are significantly increased [6,7,8], and the levels of fibrinogen and platelet activation are related to the severity of depression [6, 7]. Among the patients with severe anxiety and depression, the levels of blood factor VII, von Willebrand factor, prothrombin fragment 1 + 2, and plasminogen activator inhibitor-1 (PAI-1) are significantly higher than those of the healthy control group [9].

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