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Abstract Ethnopharmacological relevance As recorded in traditional Chinese medicine (TCM) theory, Genkwa Flos (YH) and Glycyrrhizae Radix et Rhizoma (GC) compose one herbal pair of the so-called "eighteen incompatible medicaments", which indicate pairs of herbs that are mutually incompatible and that theoretically should not be applied simultaneously. However, the theory has been called into question due to a lack of evidence. Aims of study In this study, the incompatibility of YH and GC was investigated based on an assessment of the toxic effects of their combination by traditional safety methods and a modern metabonomic approach. Materials and methods Sprague-Dawley rats were used to evaluate the subacute toxicity of YH and YH-GC. The serum, urine, and several tissues were collected for biochemical analysis, histopathological examination, and metabonomic analysis. Results Rats exposed to a dose of 1.0 g/kg YH (3 times of the Chinese Pharmacopoeia maximum dose) exhibited toxicity of the heart, liver, kidney and testes, and rats exposed to a YH-GC combination (1.0 g/kg YH + 1.0 g/kg GC) exhibited similar hepatotoxicity, which aggravated renal and reproductive toxicity. Following this, a metabonomic study tentatively identified 14 potential biomarkers in the YH group and 10 potential biomarkers in the YH-GC group, and metabolic pathways were then constructed. YH disturbed the pathways of glycerophospholipid metabolism, primary bile acid biosynthesis, and sphingolipid metabolism, while YH-GC combination induced disruptions in phenylalanine, tyrosine and tryptophan biosynthesis, tyrosine metabolism, and glycerophospholipid metabolism. Conclusion The toxicities of YH and YH-GC combination above the Chinese Pharmacopoeia dose were obvious but different. Metabonomics combined with biochemical and histopathological methods can be applied to elucidate the toxicity mechanism of the YH-GC combination that caused liver, kidney and reproductive injuries in rats. Graphical abstract fx1 [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Lymphatic system plays an important role in maintaining the fluid homeostasis and normal immune responses, anatomic or functional obstruction of which leads to lymphedema, and treatments for therapeutic lymphangiogenesis are efficiency for secondary lymphedema. Total saponins of panaxnotoginseng (PNS) are a mixture isolated from Panaxnotoginseng (Burkill) F.H.Chen, which has been used as traditional Chinese medicine in China for treatment of cardio- and cerebro-vascular diseases. The aim of this study was to determine the effect and mechanism of PNS on lymphangiogenesis. Methods The Tg (fli1: egfp; gata1: dsred) transgenic zebrafish embryos were treated with different concentrations of PNS (10, 50, 100 μM) for 48 h with or without the 6 h pretreatment of the 30 μM Vascular endothelial growth factors receptor (VEGFR)-3 kinase inhibitor, followed with morphological observation and lympangiogenesis of thoracic duct assessment. The effect of PNS on cell viability, migration, tube formation and Vascular endothelial growth factors (VEGF)-C mRNA and protein expression of lymphatic endothelial cells (LECs) were determined. The role of phosphatidylinositol-3 (PI-3)-kinase (PI3K), extracellular signal-regulated kinase (ERK)1/2 pathways, c-Jun N-terminal kinase (JNK) and P38 mitogen activated protein kinases (MAPK) signaling in PNS-induced VEGF-C expression of LECs by using pharmacological agents to block each signal. Results PNS promotes lymphangiogenesis of thoracic duct in zebrafish with or without VEGFR3 Kinase inhibitor pre-impairment. PNS promotes proliferation, migration and tube formation of LECs. The tube formation induced by PNS could be blocked by VEGFR3 Kinase inhibitor. PNS induce VEGF-C expression of LEC, which could be blocked by ERK1/2, PI3K and P38MAPK signaling inhibitors. Conclusion PNS activates lymphangiogenesis both in vivo and in vitro by up-regulating VEGF-C expression and activation of ERK1/2, PI3K and P38MAPK signaling. These findings provide a novel insight into the role of PNS in lymphangiogenesis and suggest that it might be an attractive and suitable therapeutic agent for treating secondary lymphedema or other lymphatic system impairment related disease. [ABSTRACT FROM AUTHOR]

Abstract: The behavioral and biochemical effects of total furocoumarins from seeds of Psoralea corylifolia (TFPC) were investigated in the forced swimming test (FST) in mice in comparison with amitriptyline and fluoxetine. TFPC was found to reduce the duration of immobility in the FST without accompanying changes in ambulatory, rearing and grooming behaviors in the open-field test. After a 3-day treatment, TFPC at the doses from 7.5 to 100mg/kg significantly decreased the immobility time. The efficacy of the higher doses exceeded that of amitriptyline at 10 and 20mg/kg and fluoxetine at 13mg/kg. After a 7- or 14-day treatment, TFPC exhibited an inverted U-shaped dose–response relations, maximal effects were obtained at 30mg/kg, when the efficacy appeared to be more than that of amitriptyline and fluoxetine. In animal brain and liver, after 14-day treatment, TFPC significantly inhibited monoamine oxidase A and B (MAO-A and MAO-B) activities with an inverted U-shaped dose-dependent relationship in brain, and with dose-dependent relationship in liver. Moreover, TFPC was more potent for MAO-B than MAO-A, except at the lowest dose, which was similar to amitriptyline and fluoxetine. In addition, TFPC blocked plasma elevated cortisol level, an indicator of the hypothalamic–pituitary–adrenal (HPA) axis. TFPC significantly decreased liver superoxide dismutase (SOD) activity and malondialdehyde (MDA) level, two indicators of oxidative stress, providing an inverted U-shaped dose-dependent relationship. These results suggest that TEPC possesses potent antidepressant properties that are mediated via MAO activity, HPA axis action and oxidative stress in the FST in mice. [Copyright &y& Elsevier]

Rhei Radix et Rhizoma (rhubarb), as the preferred representative of cathartic drugs of traditional Chinese medicine (TCM), has a long history of medicinal use and multifarious functions that produce a wide range of dosage. In modern times, rhubarb and its prescriptions are not only used to treat common clinical diseases, but also achieve good results in the treatment of acute, dangerous, severe and difficult diseases. However, rhubarb also has an alias called "General", which means that its efficacy is relatively rapid. The present study was conducted to simultaneously elucidate dosage-effect relationship of rhubarb of different efficacy, "Removing accumulation with purgation" (E1) and "Clearing heat and purging fire" (E2), providing reference for the safe and effective usage of rhubarb. Three-week-old rats were randomly divided into the normal control group (Con.), model group (Mod.) and rhubarb groups with six doses (0.135, 0.27, 0.81, 1.35, 4.05, 8.1 g/kg). We established a constipation model with gastrointestinal accumulated heat induced by dyspepsia, taking defecation characteristics observed by metabolic cages, alvine pushing rate, gastrointestinal hormones in serum, etc. , as indicators of E1, and taking TG, Na+-K+-ATPase, inflammatory factors and proteins, etc. , as indicators of E2. The factor analytic approach was used to systematically evaluate the two effects and analyze the corresponding dosage-effect relationship. The levels of Gas, AchE, TG, Na+-K+-ATPase, TNF-α, IL-1β, (p-)NF-κB p65, (p-)p38, (p-)ERK and p-JNK in model rats increased significantly while the levels of defecation, fecal water content, MTL, SS, ET, NTS, VIP, JNK and TLR4 decreased. Compared with the Mod., in rhubarb groups, the increase of faeces, alvine pushing rate, most gastrointestinal hormones, etc. , reflected the therapeutic efficacy of E1, and the reduction of TG, Na+-K+-ATPase, expression levels of inflammatory indexes, etc. , reflected the impact of E2. After the analysis, the effective threshold dose ranging from 0.67 to 5.37 g/kg (corresponding to 7.44–59.67 g in the clinic) was in the EC 20 -EC 80 range for E1 treatment and from 0.78 to 5.60 g/kg (equivalently clinical 8.67–62.22 g) was for E2 treatment. And the 1.6- and 1.2-fold rhubarb highest dose of Chinese Pharmacopoeia might be the optimal doses for E1 and E2 respectively. In general, however, the concentration of rhubarb liquid for overall efficacy is suggested to be between middle and highest dose of Chinese Pharmacopoeia. A constipation model was used to elucidate two main effects of rhubarb, which was consistent with the characteristics of TCM syndrome. In the wide range of rhubarb dosage, low doses might have little or no effect and although high concentrations of rhubarb liquid enhanced curative efficacy, it would also have certain side effects on the body. Therefore, scientific-based experiments and rational analysis by mathematical models could contribute to the safe and effective application of rhubarb in the clinic. Image 1 [ABSTRACT FROM AUTHOR]

Abstract Ethnopharmacological relevance Danggui buxue Decoction (DBD) has been frequently used to treat with blood deficiency, which consisted of Danggui (DG) and Huangqi (HQ) at a ratio of 1:5. Accumulating evidence showed that blood deficiency in traditional Chinese medicine (TCM) was similar to anemia in modern medicine. Aim of the study The purpose of this study was to explore its therapeutic mechanism of with network pharmacology approach. Materials and methods We explored the chemical compounds of DBD and used compound ADME screening to identify the potential compounds. Targets for the therapeutic actions of DBD were obtained from the PharmMapper, Swiss, SEA and STITCH. GO analysis and pathway enrichment analysis was performed using the DAVID webserver. Cytoscape was used to visualize the compound-target-pathway network for DBD. The pharmacodynamics and crucial targets were also validated. Results Thirty-six potential active components in DBD and 49 targets which the active components acted on were identified. 47 KEGG pathways which DBD acted on were also come to light. And then, according to KEGG pathway annotation analysis, only 16 pathways seemed to be related to the blood nourishing effect of DBD, such as PI3K-AKT pathway, and so on. Only 32 targets participated in these 16 pathways and they were acted on by 29 of the 36 active compounds. Whole pharmacodynamic experiments showed that DBD had significant effects to blood loss rats. Furthermore, DBD could promote the up-regulation of hematopoietic and immune related targets and the down-regulation of inflammatory related targets. Significantly, with the results of effective rate, molecular docking and experimental validation, we predicted astragaloside IV in HQ, senkyunolide A and senkyunolide K in DG might be the major contributing compounds to DBD's blood enriching effect. Conclusion In this study, a systematical network pharmacology approach was built. Our results provided a basis for the future study of senkyunolide A and senkyunolide K as the blood enriching compounds in DBD. Furthermore, combined network pharmacology with validation experimental results, the nourishing blood effect of DBD might be manifested by the dual mechanism of enhancing immunity and promoting hematopoiesis. Graphical abstract fx1 [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Ginkgo biloba extract (EGb 761) is widely used to treat cerebral disorders. Clinical trials have demonstrated therapeutic benefits of EGb 761 in various vascular diseases. Because the potential pathophysiological mechanisms appear similar to those involved in aneurysmal degeneration, we postulated that EGb 761 might affect the development and progression of experimental abdominal aortic aneurysm (AAA). This study was aimed to investigate whether EGb 761 influences the development of experimental AAAs, and to explore the underlying mechanisms. Material and methods: C57/BL6 mice underwent abluminal application of CaCl2 to the abdominal aorta followed by gavages with either 200mg/kg EGb 761 per day or vehicle. Six weeks after AAA induction, aortic tissue was excised for further examinations. Results: EGb 761 treatment reduced the aneurysm size compared with vehicle-treated controls. EGb 761 had no effect on hemodynamics or macrophage infiltration in the aortic wall. However, nuclear factor κB protein levels were decreased in the aortas of EGb 761 treated animals. The increased ROS production, SOD and CAT activities, and mRNA expression of p47phox nicotinamide adenine dinucleotide phosphate oxidase were attenuated by EGb 761 treatment. Moreover, administration of EGb 761 preserved the destruction of the wavy morphology of the elastin during AAA formation. Zymographic activity of matrix metalloproteinase (MMP)-9 and MMP-2 was lowered in EGb 761 treated mice. Conclusions: These results suggest that treatment with EGb 761 in mice prevented the development of CaCl2-induced AAA. The possible mechanisms include decreased oxidative damage and inflammation, preservation of aortic wall architecture, and altered MMPs activities. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Dragon''s Blood from Dracaena cochinchinensis (Lour.) S.C. Chen (Yunnan, China), as a traditional Chinese medicinal herb, was shown to have certain antithrombotic effects. A new preparation process was used to extract effective components from Dragon''s Blood. A 95% ethanol extract A (EA) and a precipitate B (PB) fraction were obtained and compared. Reliability of the preparation process was validated by pharmacodynamic experiments. Materials and methods: A rat/mouse thrombosis and blood stasis model was developed for this study, and EA and PB effects on thrombosis, platelet functions and blood coagulation activities were analyzed. Results: It was observed that the EA fraction had significantly better inhibitory effects than the PB fraction on thrombosis (p <0.05), platelet aggregation function (p <0.01) and anticoagulation activity (p <0.05–0.01). Conclusions: The results obtained here showed that EA fraction from Dragon''s Blood contained pharmacologically effective compounds with antithrombotic effects, partially improving platelet function and anticoagulation activity. [Copyright &y& Elsevier]

Ethnopharmacological relevance: San-ao Decoction (SA) is a classical prescription, clinically employed to treat asthma in Chinese medicine. Aim of study: The present study was designed to examine whether SA has a protective effect on normal human bronchial epithelium modeled by interleukin-4 (IL-4), in association with eotaxin-3. Materials and methods: SA is made of three traditional Chinese medicines: Herba Ephedrae, Semen Armeniacae amarum and Radix Glycyrrhizae. Apoptosis was measured by fluorescence microscopy and flow cytometry with IL-4 activated NHBE. In addition, eotaxin-3 mRNA''s expression was detected by RT-PCR in NHBE stimulated with IL-4. Results: Fluorescence microscopy and flow cytometry showed that IL-4-induced normal human bronchial epithelium (NHBE) apoptosis, while SA decreased the apoptosis of NHBE with IL-4 stimulation. RT-PCR showed no expression or low expression of eotaxin-3 mRNA on NHBE, IL-4 enhanced the eotaxin-3 mRNA''s expression, and that could be decreased by SA. Conclusions: The results indicate that SA can decrease NHBE''s damage and inflammation through reducing eotaxin-3 mRNA expression. [Copyright &y& Elsevier]

Aim of the study: Panax ginseng C. A. Meyer (ginseng) is a well-known Chinese herb often used in Asian countries for physical strength development. Ginseng polysaccharides are its active component and have a lot of pharmaceutical activities. However, anti-fatigue activity of ginseng polysaccharides has not yet been tested. The current study was designed to evaluate the anti-fatigue activity of ginseng polysaccharides (WGP) in an animal test for fatigue and compare the activities between the neutral (WGPN) and acidic (WGPA) portion in an attempt to determine whether the medicinal uses are supported by pharmacological effects. Materials and methods: WGP, WGPN and WGPA were orally administrated to mice once daily for 15 days. Anti-fatigue activity was assessed using the forced swim test (FST) and serum biochemical parameters were determined by autoanalyzer and commercially available kits. Results: While all compounds were found to reduce immobility in the FST, the effect of WGPA was demonstrated in lower doses compared with WGP and WGPN. Moreover, the FST-induced reduction in glucose (GLU) and glutathione peroxidase (GPx) and increase in creatine phosphokinase (CK), lactic dehydrogenase (LDH) and malondialdehyde (MDA) levels, all indicators of fatigue, were inhibited by the corresponding doses of WGP, WGPN and WGPA. Conclusions: Ginseng polysaccharides have anti-fatigue activity, also reflected in the effects on the physiological markers for fatigue. The acidic polysaccharide is more potent than the neutral polysaccharide. [Copyright &y& Elsevier]