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Abstract: Ethnopharmacological relevance: In traditional medicine, Kai Xin San (KXS), composed of ginseng (Panax ginseng), hoelen (Wolfiporia cocos), polygala (Polygala tenuifolia) and Acorus gramineus, is famous for the treatment of emotion-thought disease, such as settling fright, quieting the spirit and nourishing the heart. Aim of the study: The present study investigated the effect of KXS on chronic fatigue syndrome (CFS) mice induced by forced wheel running. Materials and methods: Seventy two healthy adult male Kunming mice were randomly divided into six groups: home cage control group, CFS group, CFS group with Modafinil treatment at 13mg/kg/d doge, KXS treatment at 175mg/kg/d, 350mg/kg/d and 700mg/kg/d doge. CFS mice were induced by forced wheel running with higher speed for 4 weeks and then taken an exhausted exercise. The biochemical parameters including serum lactate dehydrogenase (LDH), serum urea nitrogen (SUN), serum testosterone (T), liver glycogen (LG), muscle glycogen (MG) and muscle lactic acid (MLA) were determined by using commercially available kits. The splenocytes proliferation from mice was examined by MTT method. The levels of interleukin-2 (IL-2) and interleukin-4 (IL-4) secreted by splenocytes were determined by ELISA. Results: CFS mice with KXS administration exhibited less electric shock time when compared with CFS group without drug treatment. The effect of KXS has after demonstrated reduction in SUN, LDH and MLA levels and an increase in T, LG and MG levels. CFS mice with KXS could improve the proliferation of splenocytes compared with CFS group without drug treatment. The cultured splenocytes from CFS mice without KXS supplementation produced more interleukin-2 (IL-2) but less interleukin-4 (IL-4) when compared with home cage control mice. The cultured splenocytes of CFS mice with KXS supplementation produced more interleukin-2 (IL-2) but less interleukin-4 (IL-4) when compared with CFS group without drug treatment. Conclusions: The results of this preliminary study provide evidence that KXS could ameliorate CFS by affecting the physiological markers for fatigue. This study also supported the use of KXS against CFS by improving the proliferation of splenocytes from CFS mice and modulating the disturbance of cytokines induced by CFS. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: Kai-Xin-San (KXS) is a famous traditional Chinese medicine (TCM) formula. It has been used in the treatment of diseases including neurasthenia, Alzheimer''s disease and neurosis. Aim of the study: To provide information on the potential toxicity of KXS, we evaluated the acute and subchronic toxicity in rodents. Materials and methods: In acute study, a single administration of KXS was given orally to mice at doses ranging from 19.67 to 60.04g/kg. In the sub-chronic oral toxicity study, KXS was administered to rats at 0, 1, 3 and 9g/kg for 13 weeks. Moreover, 30 days of post treatment (withdrawal study) was conducted. Mortalities, clinical signs, body weight changes, food and water consumption, haematological and biochemical parameters, gross findings and organ weights were monitored during the study period. Results: In the sub-chronic study in rats, daily oral administration of KXS at the dose of 9g/kg/day result in significant increase in WBC, lymphocyte, alkaline phosphatase, blood sugar and significant decrease in bodyweight, serum Cre, CK and CHO at the last week of treatment. Recovery except for the body weight was observed after 30 days of post treatment. Conclusions: KXS is relatively safe for oral medication. The LD50 of KXS was over 32.59g/kg for mice. The no-observed-adverse-effect-level (NOAEL) was considered to be 19.67g/kg/day for rats. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: Xuefuzhuyu decoction (XFZY) is a well-known traditional Chinese herbal formulation composed of 11 herbs. It is an effective treatment for cardiovascular and chronic liver diseases. The aim of the study is to investigate the role of XFZY on angiogensis in hepatic fibrogenesis, and identify the possible mechanism. Material and methods: Liver fibrosis was induced by intraperitoneal injection of Carbon tetrachloride (CCl4) in C57BL/6 mice for 6 weeks. From week 4 to week 6, the CCl4-injected mice were randomly divided into three groups, followed by oral administration of Sorafenib, XFZY and water for 3 weeks. Biochemical parameters, hydroxyproline (Hyp) content and histological changes of the liver were determined. The expressions of alpha smooth muscle actin (α-SMA), collagen I, CD31 and vascular endothelial grow factor (VEGF) were assessed by immunohistochemistry and western blot. The protein expressions of VEGFR-2, hypoxia inducing factor (HIF)-1α, asymmetric dimethylarginine (ADMA) and dimethylarginine hydrolase (DDAH) 1 were determined by western blot. The mRNA levels of α-SMA, VEGF and HIF-1α were measured by RT-PCR. Results: Both Sorafenib and XFZY improved biochemical parameters of the liver fibrosis mice. A significant reduction in Hyp content was found in the XFZY-treated mice as well as the Sorafenib-treated mice. Changes in histopathology showed that Sorafenib and XFZY decreased inflammatory and fibrotic stages of the liver in fibrosis mice. Compared to CCl4 model group, Sorafenib and XFZY decreased α-SMA, collagen I, CD31, VEGF, VEGFR-2, HIF-1α and ADMA, and increased the expression of DDAH1. Conclusion: XFZY inhibits liver fibrosis not only through inhibiting collagen deposition but also through an antiangiogenic effect on the fibrotic liver. Moreover, the antiangiogenic mechanism of XFZY involves alleviating hypoxia and protecting liver sinusoidal endothelial cell function. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: Kai Xin San (KXS) is a traditional Chinese herbal prescription for the treatment of depression-like disorders, anxiety, and impairment in learning and memory, however, there is very little scientific data concerning the efficacy of this. Aim of the study: The present study aimed to investigate the antidepressant potential of Kai Xin San and its possible mechanisms. Materials and methods: Mouse models of depression including the tail suspension test (TST) and the forced swim test (FST) were used to evaluate the effects of KXS. A possible mechanism was explored in the tests of antagonism of reserpine-induced ptosis, akinesia and hypothermia and 5-HTP induced head-twitch response in mice. The contents of monoamine neurotransmitters including epinephrine (NE), 5-hydroxytryptamine (5-HT) and dopamine (DA) in mice brain were determined by Elisa. Spontaneous motor activities of mice and rotarod test were performed to find whether KXS has excitatory or inhibitory actions on the central nervous system. Results: The results showed that intragastric administration of KXS at 175, 350, 700, 1400mg/kg/day or fluoxetine at 28mg/kg/day for 3 days significantly reduced the duration of immobility in TST and FST, while it showed no effect on the spontaneous motor activity and rotarod performance in mice. However, the effect was not dose-dependent. The pre-treatment with KXS or fluoxetine for 3 days could elevate the contents of NE, 5-HT and DA in mice brain significantly. When the mice were treated with KXS (350mg/kg, p.o) or desipramine (30mg/kg, p.o) for 7 days, both of them could antagonize reserpine-induced ptosis, akinesia and hypothermia. The KXS (350mg/kg) also increased the accumulative number of the 5-HTP-induced head twitch response in mice in 20min when KXS at dosages of 175, 350, 700 and 1400mg/kg/day were performed per os (p.o.) during a 1-day, 3-day or 7-day period. Conclusions: Our results suggested that KXS exerts antidepressant-like effect. A possible mechanism, at least in part, is via the central monoaminergic neurotransmitter system and 5-HT plays a major role. [Copyright &y& Elsevier]