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ObjectiveTo decipher the mechanism of Wenxiao powder in alleviating corticosterone-induced depression-like behaviors in mice. MethodMale ICR mice were randomized into normal， model， paroxetine （20 mg·kg-1）， and low- and high-dose （3.27， 6.54 g·kg-1， respectively） Wenxiao powder groups. The mice in normal and model groups received equal volume of saline. Other groups except the normal group were injected with corticosterone subcutaneously 0.5 h after gavage to induce depression. Mice were tested for depression-like behaviors after drug administration. Enzyme-linked immunosorbent assay （ELISA） was performed to measure the corticosterone content in the serum. Nissl staining was performed to observe the damage of hippocampal neurons. Immunofluorescence staining was employed to observe the expression of double cortin （DCX） in the dentate gyrus （DG） of the hippocampus. Western blot was employed to determine the expression of proteins in the brain-derived neurotrophic factor （BDNF）/tyrosine kinase receptor B （TrkB）/extracellular signal-regulated kinase （ERK）/cAMP-response element-binding protein （CREB） pathway in the hippocampus. ResultCompared with the normal group， the model group showed decreased sucrose preference rate， increased immobility time in the tail suspension test （P<0.01）， and reduced residence time in the central area of the open field and the total movement distance （P<0.05， P<0.01）. In addition， the modeling elevated the corticosterone level in the serum （P<0.01）， decreased the volume and intensified the nuclear staining of hippocampal neurons in the DG area， reduced the expression of DCX in the DG area， and down-regulated the protein levels of BDNF， phosphorylated （p）-TrkB， p-ERK， and p-CREB in the hippocampus （P<0.05， P<0.01）. Compared with the model group， low-dose Wenxiao powder improved the mouse behavivors in the sucrose preference， open field， and tail suspension tests （P<0.05， P<0.01）， and high-dose Wenxiao powder improved the behaviors in the sucrose preference and open field tests （P<0.05， P<0.01）. In addition， Wenxiao powder lowered the serum corticosterone level （P<0.01） and recovered the structure and morphology of neurons with obvious nuclei and presence of Nissl bodies in the DG area of the hippocampus. Moreover， Wenxiao powder at both doses promoted the expression of DCX in the DG area， and high-dose Wenxiao powder up-regulated the protein levels of BDNF， p-TrkB， p-ERK， and p-CREB in the hippocampus （P<0.05， P<0.01）. ConclusionWenxiao powder can alleviate corticosterone-induced depression-like behaviors and promote neurogenesis in mice possibly by activating the BDNF/TrkB/ERK/CREB signaling pathway.
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Depression is a mental disorder characterized by persistent low mood and belongs to the category of "stagnation syndrome" in traditional Chinese medicine （TCM）， with the characteristics of high prevalence， high disability rate， high suicide rate， and high recurrence rate. The pathogenesis of depression is extremely complex and involves factors such as genetics， psychology， and social environment. Currently， clinical antidepressant drugs such as tricyclic and tetracyclic antidepressants， and selective serotonin reuptake inhibitors， have slow onset of action and significant adverse effects with long-term application. Furthermore， clinical statistics show that about one-third of patients do not respond to these types of medications. Enhancing the effectiveness of depression treatment has become a major challenge in the medical field. TCM， based on the holistic view and treatment based on syndrome differentiation， has unique advantages in the prevention and treatment of depression， including stable therapeutic effects， low recurrence rate， minimal side effects， and good patient compliance. As one of the heat-clearing drugs， Gardeniae Fructus has the effects of clearing heat， purging fire， cooling blood， and relieving restlessness， which makes it effective in treating patients with "stagnation syndrome". Literature studies have found that active components of Gardeniae Fructus， such as geniposide， genipin， and crocin， as well as drug pairs such as Gardeniae Fructus-Chuanxiong Rhizoma， Gardeniae Fructus-Acanthopanacis Senticosi Radix et Rhizoma Seu Caulis， and Gardeniae Fructus-Lycii Fructus， and prescriptions such as Zhizichi Tang， Yuejuwan， Zhizi Houpotang， Danzhi Xiaoyaosan， and Jieyu Anshen Granules， have shown significant antidepressant effects. The mechanism of action may be related to regulating the hypothalamic-pituitary-adrenal （HPA） axis， modulating neurotransmitters such as serotonin （5-HT） and dopamine （DA）， increasing brain-derived neurotrophic factor （BDNF） in the hippocampus， enhancing neurogenesis in the hippocampus， and regulating the nuclear factor-kappa B （NF-κB） signaling pathway to inhibit neuroinflammation. This article summarized the research progress on the active components of Gardeniae Fructus， drug pairs， and Chinse medicinal prescriptions containing Gardeniae Fructus， providing references for further promoting the clinical application of Gardeniae Fructus and its prescriptions in the treatment of depression.
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ObjectiveTo investigate the feasibility of ethyl acetate fraction of Ipomoea muricatum （IM-EA） in the prevention and treatment of alcoholic gastric ulcer （GU） and explore its mechanism of action based on network pharmacology and experimental verification. MethodForty SD rats were randomly divided into a control group， a model group， a ranitidine group （2.7 mg·kg-1）， and low- and high-dose IM-EA groups （30，60 mg·kg-1） after adaptive feeding for 7 days. The GU model was replicated by hydrochloric acid in absolute ethanol （150 mmol·L-1） in rats after prophylactic administration for one week. Hematoxylin-eosin （HE） staining and periodic acid-Schiff （PAS） staining were used to preliminarily evaluate the efficacy of IM-EA in the prevention and treatment of GU. Lead compounds of IM-EA were screened out by ADMET， and the SwissTarget platform was used to identify the potential targets for these compounds. GU-related targets were collected through DisGeNET， OMIM， and GeneCards databases， which were mapped to potential IM-EA targets to obtain the potential targets of IM-EA against GU. The STRING database was used to construct the protein-protein interaction （PPI） network to screen the hub targets， and the DAVID platform was used to annotate the biological functions of common targets to explore the underlying mechanism of IM-EA against GU. Autodock Vina software was used for the preliminary verification of the computer simulation. The serum levels of tumor necrosis factor （TNF）-α and interleukin （IL）-6 and the content of prostaglandin E2 （PGE2）， matrix metalloproteinase-9 （MMP-9）， and superoxide dismutase （SOD） in the gastric tissues were determined by enzyme-linked immunosorbent assay （ELISA）. The relative expression levels of core proteins in the mitogen-activated protein kinase （MAPK） signaling pathway， such as Jun oncoprotein， extracellular signal-regulated kinase （ERK）， and p38， in the gastric tissues were detected by Western blot. ResultAs revealed by the results of animal experiments， compared with the control group， the model group showed significantly damaged gastric tissues and reduced secretion of gastric mucus. Compared with the model group， the groups with drug intervention showed reduced ulcer areas in the gastric tissues （P<0.01） and improved gastric histopathological status and gastric mucus secretion， suggesting that IM-EA was effective in the prevention and treatment of GU. Sixteen lead compounds of IM-EA were screened out by ADMET， and 257 potential targets of IM-EA against GU were obtained. The hub nodes in the PPI network included targets of TNF-α， protein kinase B1 （Akt1）， tumor protein 53 （TP53）， epidermal growth factor receptor （EGFR）， and ERK. Biological functional annotation and molecular docking results suggested that the MAPK signaling pathway potentially played a key role in the prevention and treatment of GU by IM-EA， which was synergistic with the vascular endothelial growth factor （VEGF） signaling pathway， phosphoinositide 3-kinase （PI3K）/Akt signaling pathway， and nuclear factor （NF）-κB signaling pathway in anti-inflammation， anti-oxidation， and damage repair. The pharmacological experiment results showed that compared with the control group， the model group showed increased serum IL-6 content （P<0.01）， an increasing trend of TNF-α content， increased MMP-9 content in the gastric tissues （P<0.01）， and decreased SOD content （P<0.05）. Compared with the model group， the IM-EA groups showed decreased TNF-α and IL-6 levels in the serum and PGE2 and MMP-9 levels in the gastric tissues （P<0.01）， and increased SOD content in the gastric tissues （P<0.01）. Compared with the control group， the model group showed up-regulated expression of p-p38， p-Jun， and p-ERK in the gastric tissues （P<0.01） and up-regulated p38 and Jun （P<0.01）. Compared with the model group， the IM-EA groups showed down-regulated p-p38， p-Jun， p-ERK， and p38 in the gastric tissues （P<0.01） and up-regulated relative expression of Jun and ERK （P<0.05）. ConclusionIM-EA has a remarkable effect in the prevention and treatment of alcoholic gastric injury， which may be achieved through the mechanisms of anti-inflammation， anti-oxidation， and wound repair mediated by the MAPK signaling pathway.
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This paper summarized professor ZHANG Lei′s experience in treating scleroderma from “extraordinary pathogens entering collaterals”. The basic pathogenesis of scleroderma is “extraordinary pathogens entering the collaterals”， and extraordinary pathogens can be divided into external and internal categories. External extraordinary pathogens are mostly exogenous wind， cold and damp pathogens， and the pathogenesis is wind， cold and damp invading skin stria and retaining collaterals. Most of the endogenous extraordinary pathogens are turbid phlegm and blood stasis， and the pathogenesis is endogenous phlegm and stasis leaving the channels and overflowing the collaterals， and blocking the collaterals. Blocked by extraordinary pathogens for a long time， the long illness will lead to deficiency and develop into a syndrome of collaterals excess and channels deficiency. Therefore， professor ZHANG creats Tengluo Beverage （藤络饮） as the basic formula to unblock collaterals and dispel pathogens， and recommends to add or subtract it according to the different syndrome and pathogenic characteristics of the edema stage， sclerosis stage， and atrophy stage. In the edema stage， it is advised to expel wind， remove dampness and unblock the collaterals， while in the sclerosis stage， the method of dissolving phlegm， expelling stasis and unblocking collaterals should be used； in the atrophic stage， it is suggested to differentiate the deficiency of qi， blood， yin and yang， and eliminate extraordinary pathogens on the basis of reinforcing healthy qi .
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@#This paper summarized professor ZHANG Lei′s experience in treating scleroderma from “extraordinary pathogens entering collaterals”. The basic pathogenesis of scleroderma is “extraordinary pathogens entering the collaterals”， and extraordinary pathogens can be divided into external and internal categories. External extraordinary pathogens are mostly exogenous wind， cold and damp pathogens， and the pathogenesis is wind， cold and damp invading skin stria and retaining collaterals. Most of the endogenous extraordinary pathogens are turbid phlegm and blood stasis， and the pathogenesis is endogenous phlegm and stasis leaving the channels and overflowing the collaterals， and blocking the collaterals. Blocked by extraordinary pathogens for a long time， the long illness will lead to deficiency and develop into a syndrome of collaterals excess and channels deficiency. Therefore， professor ZHANG creats Tengluo Beverage （藤络饮） as the basic formula to unblock collaterals and dispel pathogens， and recommends to add or subtract it according to the different syndrome and pathogenic characteristics of the edema stage， sclerosis stage， and atrophy stage. In the edema stage， it is advised to expel wind， remove dampness and unblock the collaterals， while in the sclerosis stage， the method of dissolving phlegm， expelling stasis and unblocking collaterals should be used； in the atrophic stage， it is suggested to differentiate the deficiency of qi， blood， yin and yang， and eliminate extraordinary pathogens on the basis of reinforcing healthy qi .
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Gastric cancer is one of the malignancies with high incidence in the world. Xiangsha Liu Junzitang，a common prescription for the prevention and treatment of gastric cancer，has the effects of moving Qi to relieve pain，drying dampness， and invigorating the spleen. It is especially indicated for gastric cancer of the spleen and stomach qi deficiency syndrome. Based on the databases such as CNKI，Wanfang Data，and PubMed，the clinical efficacy and experimental studies of Xiangsha Liu Junzitang for the prevention and treatment of gastric cancer were summarized and sorted out，and the mechanism of Xiangsha Liu Junzitang for the prevention and treatment of gastric cancer was elaborated in order to provide useful references for the clinical and basic research on Xiangsha Liu Junzitang in the field of gastric cancer in the future. In clinical practice，Xiangsha Liu Junzitang can treat gastric precancerous lesions，increase the body immunity of patients with gastric cancer，improve the symptoms of spleen and stomach weakness after gastric cancer surgery，and reduce the adverse reactions of the digestive tract after chemotherapy for gastric cancer. Its clinical efficacy is superior to that of western medicine alone whether it is combined with western medicine or used alone. In the experimental research，Xiangsha Liu Junzitang has the effects of regulating inflammatory factors，inhibiting the proliferation of gastric cancer cells，promoting the apoptosis of gastric cancer cells，and improving the activity of pepsin. Modern pharmacological research has shown that Xiangsha Liu Junzitang can conduct a comprehensive intervention with multiple components and multiple targets. The main components of a single drug contained include saponins，polysaccharides，lactones，volatile oils，organic acids，and others， with the effects of protecting gastric mucosa，regulating endocrine，and promoting apoptosis of epithelial cells in gastric mucosal dysplasia，reflecting the advantages and values of traditional Chinese medicine in the prevention and treatment of gastric cancer.
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Objective:To compare the safety and immunogenicity of Sabin strain-based inactivated poliovirus vaccine (sIPV) and the liquid form of typeⅠ+ Ⅲ bivalent oral poliovirus vaccine (bOPV) administered to infants aged ≥2 months in different schedules.Methods:A randomized, blinded, single-center, parallel-group controlled trial was conducted in Hangzhou from 2017 to 2018. Healthy infants aged ≥2 months were enrolled and randomized to receive the vaccines on a schedule of 2, 3, 4 months. Group 1sIPV+ 2bOPV was given one dose of sIPV and two doses of bOPV; group 2sIPV+ 1bOPV was administrated two doses of sIPV and one dose of bOPV; group 3sIPV received three doses of sIPV. Adverse events (AEs) following vaccination were recorded. Blood samples were collected from the subjects (excluding the quitters or subjects against the trial plan) 28-35 d after the full-course immunization. A microneutralization assay was performed to detect the geometric mean titers (GMTs) of neutralizing antibodies against polio virus of Ⅰ, Ⅱ and Ⅲ types. The seroconversion rates of neutralizing antibodies were also calculated.Results:The overall incidence of AEs following vaccination was 3.57% in 1sIPV+ 2bOPV group, 3.61% in 2sIPV+ 1bOPV group and 1.19% in 3sIPV group (χ 2=1.190, P=0.552) and no severe AEs were reported. The antibody seroconversion rates in 1sIPV+ 2bOPV, 2sIPV+ 1bOPV and 3sIPV groups were respectively 100% (84/84), 100% (83/83) and 100% (84/84) against type Ⅰ poliovirus, 81% (68/84), 96% (80/83) and 99% (83/84) against type Ⅱ poliovirus(χ 2=21.469, P<0.001), and 100% (84/84), 100% (83/84) and 100% (84/84) against type Ⅲ poliovirus. In 1sIPV+ 2bOPV, 2sIPV+ 1bOPV and 3sIPV groups, the GMTs of antibody were 1 024.00, 1 015.48 and 982.61 against type Ⅰ poliovirus ( F=2.742, P=0.066), 16.81, 107.94 and 218.85 against type Ⅱ poliovirus ( F=33.570, P<0.001), and 990.75, 990.36 and 613.92 against type Ⅲ poliovirus ( F=37.886, P<0.001). Conclusions:sIPV and bOPV administered in different schedules showed good safety and immunogenicity in infants aged≥2 months. The GMT and the seroconversion rate of neutralizing antibody against type Ⅱ poliovirus after vaccination were higher in 2sIPV+ 1bOPV and 3sIPV group than in 1sIPV+ 2bOPV group. Higher GMT of neutralizing antibody against type Ⅲ poliovirus was induced in 1sIPV+ 2bOPV and 2sIPV+ 1bOPV groups than in 3sIPV group.
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Objective:To study the anti-depression mechanism of Shugan Jiannao Tiaoyu Tablets(SJTT) and provide evidene for clinical application. Methods: Depressive rat model were established by unpredictable stress with raising alone. Model rats were randomly divided into 5 groups, each 12, then each group was administrated through intragastric perfusion daily with the rate of 1.0ml/100g according to their weight before stimulation: fluoxetine group with 0.75 mg/kg, low-dose group of SJTT with 1.8g/kg, high-dose group of SJTT with 3.6g/kg, normal group and model group with 1.0ml/100g of isotonic Na chloride. The whole course lasted for 21 days from the first day of model making to the day of death. The pathologic character of hippocampus was observed by light microscopic examination. The change of cell ultramicrostructure was observed by transmission electron microscope. The expression of C-FOS and C-JUN were detected by immunohistochemistry. Results: SJTT could reduce the neuron damage of hippocam. Compared with model group, the gray scale of immunoreaction positve cells of C-FOS and C-JUN increased in high dose group of SJTT. Conclusion:SJTT can decrease the neuron damage induced by stress in hippacam and had anti-depression effect.