Wendantang Treats Inflammation in Obesity （Syndrome of Phlegm-dampness） by Regulating PI3K/Akt/mTOR Pathway-mediated Adipocyte Autophagy / 中国实验方剂学杂志

ObjectiveTo observe the effects of Wendantang on the expression of inflammatory cytokines， autophagy markers， and key molecules of phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR） signaling pathway in the adipocytes of the rat model of obesity （syndrome of phlegm-dampness） and to explore the material basis of inflammation in obesity （syndrome of phlegm-dampness） and the underlying mechanism of Wendantang intervention. MethodA total of 126 SD rats were randomized into 2 groups： 16 rats in the blank group and 110 rats in the modeling group. The blank group was fed with a basic diet while the modeling group with a high-fat diet to establish the animal model of obesity （syndrome of phlegm-dampness） for 8 weeks. After successful modeling， 48 obese rats were selected according to their body mass and randomized into a model control group， an orlistat （ORLI， 32.40 mg·kg-1） group， a rapamycin （RAPA， 2 mg·kg-1） group， and low-， medium-， and high-dose （4.45， 8.90， 17.80 g·kg-1， respectively） Wendantang groups， with 8 rats in each group. In addition， 8 rats were randomly selected from the blank group to be set as the normal control group. The corresponding agents in each group were administrated by gavage and the model and control groups were administrated with equal amounts of distilled water once daily for 6 weeks. The body mass， Lee's index， body fat ratio， and obesity rate were measured or calculated. The expression of UNC51-like kinase-1 （ULK1）， Beclin1， human autophagy-related protein 5 （Atg5）， p62， and microtubule-associated protein 1 light chain 3 （LC3） Ⅰ/Ⅱ （markers of autophagy in adipocytes） was detected by the immunohistochemical two-step method. Enzyme-linked immunosorbent assay （ELISA） was employed to determine the expression of tumor necrosis factor （TNF）-α， interleukin-6 （IL-6）， IL-1β， monocyte chemotactic protein-1 （MCP-1）， IL-4， IL-10， IL-13， and transforming growth factor （TGF）-β in adipocytes. Western blot was employed to measure the protein levels of classⅠ-PI3K， phosphatidylinositol triphosphate （PIP3）， Akt， mTORC1， ULK1， TSC1， and TSC2 in adipocytes. ResultCompared with the blank group， the modeling group showed increased body mass and Lee's index （P<0.01）， the obesity rate >20%， and phlegm-dampness syndrome manifestations such as physical obesity， decreased mobility， decreased appetite， lusterless and tight fur， loose stools， decreased responsiveness to the outside world， and decreased water intake. Compared with the normal control group， the model control group showed increased body mass， Lee's index， body fat ratio， adipocyte autophagy marker expression， pro- and anti-inflammatory cytokine levels （P<0.05， P<0.01）， down-regulated protein levels of classⅠ-PI3K， PIP3， Akt， mTORC1， TSC1， and TSC2 （P<0.01）， and up-regulated protein level of ULK1 （P<0.01）. The intervention groups showed lower body mass， body fat ratio， adipocyte autophagy marker protein expression， and protein levels of TNF-α， IL-6， IL-1β， MCP-1， IL-4， and IL-13 than the model control group （P<0.05， P<0.01）. Moreover， the RAPA and Wendantang （medium and high dose） groups showed lowered levels of IL-10 and TGF-β （P<0.01）， and the ORLI group showed down-regulated expression of TGF-β （P<0.01）. The expression of key molecules of the signaling pathway was up-regulated （P<0.05， P<0.01） while that of ULK1 was down-regulated （P<0.01） in all the intervention groups. Compared with the RAPA group， the Wendantang groups showed up-regulated expression of all autophagy marker proteins in adipocytes （P<0.01）. In addition， the low-dose Wendantang group showed elevated levels of inflammatory cytokines （except TNF-α） （P<0.05， P<0.01） and down-regulated expression of all key molecules of the signaling pathway （P<0.05， P<0.01）. The levels of inflammatory cytokines （except IL-16， MCP-1， and IL-10） were elevated in the medium-dose Wendantang group （P<0.05， P<0.01）. The expression of key molecules except PI3K of the signaling pathway was down-regulated in the medium- and high-dose Wendantang groups （P<0.05， P<0.01）. Compared with the ORLI group， low- and medium-dose Wendantang groups showed up-regulated expression of autophagy markers in adipocytes （P<0.01）， and the low-dose group showed elevated levels of inflammatory cytokines （IL-6， IL-4， and TGF-β） （P<0.01） and down-regulated expression of all key molecules of the signaling pathway （P<0.01）. The medium-dose Wendantang group showed up-regulated expression of IL-4 （P<0.01） and down-regulated expression of key molecules except PI3K of the signaling pathway （P<0.05， P<0.01）. The high-dose Wendantang group showed increased body mass， up-regulated expression levels of autophagy markers （ULK1， LC3 Ⅰ/Ⅱ） （P<0.05， P<0.01）， down-regulated expression of PIP3， mTORC1， and TSC1 （P<0.05， P<0.01）， and lowered levels of Beclin1， Atg5， TNF-α， and IL-13 （P<0.05， P<0.01）. ConclusionThe inflammation in obesity （syndrome of phlegm-dampness） is closely associated with the PI3K/Akt/mTOR pathway-mediated adipocyte autophagy. Wendantang can treat the chronic inflammation in obese rats with the syndrome of phlegm-dampness by regulating this signaling pathway and thus improve adipocyte autophagy.

Molecular Mechanism of Wendantang Against Schizophrenia in Rats： An Exploration Based on miRNA-219， NR2B， DISC1 and CaMKⅡγ / 中国实验方剂学杂志

ObjectiveTo study the effects of Wendantang on the expression of miRNA-219， N-methyl-D-aspartate receptor 2B （NR2B）， disrupted in schizophrenia 1 （DISC1）， and Ca2+/calmodulin-dependent protein kinase Ⅱγ （CaMKⅡγ） in the frontal lobe of rats with schizophrenia. MethodSixty rats were randomly divided into six groups， namely normal group， model group， high-， medium-， and low-dose Wendantang groups， and clozapine group， with 10 rats in each group. Rats in high-， medium-， and low-dose Wendantang groups were intragastric with 40， 20， and 10 g·kg-1 Wendantang， and the ones in clozapine group were intragastric with 0.02 g·kg-1 clozapine， those in normal and model group were intragastric with equal volume of normal saline， once a day. After 21 days of administration， rats in all groups except for the normal group were injected with 0.6 mg·kg-1 dizocilpine maleate （MK-801） into the left abdominal cavity for inducing acute schizophrenia. The stereotypic behavior and ataxia in rats were scored according to SAMS and HOFFMAN criteria. The morphological changes in the prefrontal cortex were observed by hematoxylin-eosin （HE） staining. The protein expression levels of NR2B, DISC1 and CaMKⅡγ in the frontal lobe was detected by Western blot. The mRNA expression levels of miRNA-219 was detected by real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）. ResultCompared with normal group， the model group exhibited significantly increased stereotypic behavior and ataxia scores （P<0.01）， karyopyknosis and karyolysis in most neurons of the prefrontal cortex， and down-regulated NR2B， DISC1， and CaMKⅡγ protein expression （P<0.01） and miRNA-219， NR2B， DISC1， and CaMKⅡγ mRNA expression （P<0.01）. Compared with model group， Wendantang high-， medium-， and low-doses group lowered the scores of stereotypic behavior and ataxia at 50， 60 mmin（P<0.05，P<0.01）. In high- and medium-dose Wendantang groups， the neurons in the prefrontal cortex were densely arranged. The karyopyknosis and karyolysis were alleviated to varying degrees. The NR2B protein expression in the frontal lobe was up-regulated （P<0.01）. In the medium- and low-dose Wendantang groups， the DISC1 protein expression in the frontal lobe was up-regulated （P<0.05，P<0.01）. Wendantang at each dose significantly increased the CaMKⅡγ protein expression （P<0.05） and miRNA-219， NR2B， DISC1， and CaMKⅡγ mRNA expression in the frontal lobe （P<0.05，P<0.01）. ConclusionWendantang improves the scores of stereotypical behavior and ataxia， relieves the karyopyknosis and karyolysis of neurons in the prefrontal cortex， and increases the expression levels of miRNA-219， NR2B， DISC1， and CaMKⅡγ of rats with schizophrenia， so as to alleviate the schizophrenic-like symptoms and schizophrenia.

Mechanism of Huanglian Wendantang in Improving IR-HepG2 Based on NLRP3/Caspase-1 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo explore the effect of the serum containing Huanglian Wendantang on pyroptosis in vitro model of insulin resistance and its mechanism. MethodSD rats were randomly divided into two groups， namely Huanglian Wendantang-containing serum group and blank serum group， and given 7.8 g·kg-1·d-1 Huanglian Wendantang and equal volume of normal saline by intragastric administration according to body surface area. Blank serum and medicated serum with different concentration were extracted and prepared. HepG2 cells were treated with sodium palmitate to construct the model of insulin resistance （IR）， and they were randomly divided into control group， model group， metformin hydrochloride group， blank serum group， and Huanglian Wendantang-containing serum high-， medium-， and low-dose groups. After 24 h of cultivation， the cells of each group were treated with insulin for 15 min at concentration of 1×10-7 mol·L-1， and the cell supernatant was collected. The glucose oxidase （GOD-POD） kit was used to determine the glucose content of each group， and calculate the glucose consumption and inhibition rate. The methyl thiazolyl tetrazolium （MTT） assay was used to detect the cell proliferation， thus screening out the optimal dose of serum containing Huanglian Wendantang. HepG2 cells were randomly divided into control group， model group， and Huanglian Wendantang-containing serum group. The levels of interleukin-1β （IL-1β） and interleukin-18 （IL-18） in each group were determined by enzyme-linked immunosorbent assay （ELISA）， and the mRNA and protein expression levels of NOD like receptor protein 3 （NLRP3） in each group were determined by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot. In terms of the mechanism， HepG2 cells were randomly divided into control group， empty vector group， NLRP3 overexpression group， empty vector + IR group， empty vector + IR + Huanglian Wendantang-containing serum group， NLRP3 overexpression + IR group， and NLRP3 overexpression + IR + Huanglian Wendantang-contain serum group. GOD-POD method was used to measure the glucose content of each group cells， and calculate the glucose consumption. ELISA was used to determine the release of IL-1β and IL-18 in each group. Real-time PCR and Western blot assay were used to determine the mRNA and protein expressions of cysteinyl aspartate specific proteinase-1 （Caspase-1）， gasdermin D （GSDMD）， and NLRP3. Immunofluorescence assay was used to detect NLRP3， GSDMD， and Caspase -1 expressions. ResultAs compared with the control group， the glucose consumption in the model group was significantly decreased （P<0.01）. As compared with the model group， the increase of the glucose consumption of IR-HepG2 cells was the most significant in the Huanglian Wendantang-containing serum high-dose group （P< 0.01）. As compared with the control group， the IL-1β and IL-18 release levels and the mRNA and protein expressions of NLRP3 in IR-HepG2 cells were significantly increased （P<0.05， P<0.01）. Huanglian Wendantang effectively reduced IR-HepG2 cell supernatant IL-1β， IL-18， and NLRP3 mRNA and protein expressions as compared with the model group （P<0.05， P<0.01）. Overexpression of NLRP3 significantly reduced the cell glucose consumption as compared with the control group and the empty vector group （P<0.01）， and significantly up-regulated the IL-1β and IL-18 levels and the mRNA and protein levels of NLRP3， Caspase-1， and GSDMD as compared with the empty vector + IR group （P<0.05， P<0.01）. Huanglian Wendantang-containing serum effectively reversed the above indicators as compared with the NLRP3 + IR group （P<0.05， P<0.01）. ConclusionHigh fat-induced insulin sensitivity of IR-HepG2 cells is closely related to inflammation and NLRP3 expression. Huanglian Wendantang-containing serum improves IR-HepG2 cell pyroptosis through the targeted inhibition of NLRP3/Caspase-1 signaling pathway， which provides new therapeutic targets for the prevention and treatment of IR and type 2 diabetes mellitus （T2DM）.

Mechanism of Huanglian Wendantang in Improving IR-HepG2 Based on NLRP3/Caspase-1 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo explore the effect of the serum containing Huanglian Wendantang on pyroptosis in vitro model of insulin resistance and its mechanism. MethodSD rats were randomly divided into two groups， namely Huanglian Wendantang-containing serum group and blank serum group， and given 7.8 g·kg-1·d-1 Huanglian Wendantang and equal volume of normal saline by intragastric administration according to body surface area. Blank serum and medicated serum with different concentration were extracted and prepared. HepG2 cells were treated with sodium palmitate to construct the model of insulin resistance （IR）， and they were randomly divided into control group， model group， metformin hydrochloride group， blank serum group， and Huanglian Wendantang-containing serum high-， medium-， and low-dose groups. After 24 h of cultivation， the cells of each group were treated with insulin for 15 min at concentration of 1×10-7 mol·L-1， and the cell supernatant was collected. The glucose oxidase （GOD-POD） kit was used to determine the glucose content of each group， and calculate the glucose consumption and inhibition rate. The methyl thiazolyl tetrazolium （MTT） assay was used to detect the cell proliferation， thus screening out the optimal dose of serum containing Huanglian Wendantang. HepG2 cells were randomly divided into control group， model group， and Huanglian Wendantang-containing serum group. The levels of interleukin-1β （IL-1β） and interleukin-18 （IL-18） in each group were determined by enzyme-linked immunosorbent assay （ELISA）， and the mRNA and protein expression levels of NOD like receptor protein 3 （NLRP3） in each group were determined by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot. In terms of the mechanism， HepG2 cells were randomly divided into control group， empty vector group， NLRP3 overexpression group， empty vector + IR group， empty vector + IR + Huanglian Wendantang-containing serum group， NLRP3 overexpression + IR group， and NLRP3 overexpression + IR + Huanglian Wendantang-contain serum group. GOD-POD method was used to measure the glucose content of each group cells， and calculate the glucose consumption. ELISA was used to determine the release of IL-1β and IL-18 in each group. Real-time PCR and Western blot assay were used to determine the mRNA and protein expressions of cysteinyl aspartate specific proteinase-1 （Caspase-1）， gasdermin D （GSDMD）， and NLRP3. Immunofluorescence assay was used to detect NLRP3， GSDMD， and Caspase -1 expressions. ResultAs compared with the control group， the glucose consumption in the model group was significantly decreased （P<0.01）. As compared with the model group， the increase of the glucose consumption of IR-HepG2 cells was the most significant in the Huanglian Wendantang-containing serum high-dose group （P< 0.01）. As compared with the control group， the IL-1β and IL-18 release levels and the mRNA and protein expressions of NLRP3 in IR-HepG2 cells were significantly increased （P<0.05， P<0.01）. Huanglian Wendantang effectively reduced IR-HepG2 cell supernatant IL-1β， IL-18， and NLRP3 mRNA and protein expressions as compared with the model group （P<0.05， P<0.01）. Overexpression of NLRP3 significantly reduced the cell glucose consumption as compared with the control group and the empty vector group （P<0.01）， and significantly up-regulated the IL-1β and IL-18 levels and the mRNA and protein levels of NLRP3， Caspase-1， and GSDMD as compared with the empty vector + IR group （P<0.05， P<0.01）. Huanglian Wendantang-containing serum effectively reversed the above indicators as compared with the NLRP3 + IR group （P<0.05， P<0.01）. ConclusionHigh fat-induced insulin sensitivity of IR-HepG2 cells is closely related to inflammation and NLRP3 expression. Huanglian Wendantang-containing serum improves IR-HepG2 cell pyroptosis through the targeted inhibition of NLRP3/Caspase-1 signaling pathway， which provides new therapeutic targets for the prevention and treatment of IR and type 2 diabetes mellitus （T2DM）.

Clinical Efficacy of Modified Huanglian Wendantang in Treatment of Newly Diagnosed Type 2 Diabetes Mellitus with Phlegm (Dampness)-Heat Syndrome / 中国实验方剂学杂志

Objective:To observe the efficacy of modified Huanglian Wendantang in treating newly diagnosed type 2 diabetes mellitus （T2DM） with phlegm （dampness）-heat syndrome， in order to study the effect on islet β cell function and adipocytokines. Method:A total of 130 patients were randomly divided into two groups by random number table （65 cases in each group）. The 60 patients in control group completed the treatment （4 patients fell off or lost visit， 2 were eliminated because of breach of plan）， and the 61 patients in observation group completed the treatment （3 patients fell off， 1 were eliminated）. And 20 healthy volunteers were taken as normal control group. Both groups′ patients got lifestyle interventions and metformin hydrochloride tablets （1 tablet/time， 1 time/day during the meal）. In addition， patients in control group got Huazhuo Qingshen Keli in the morning and at night， 5 g/time， 2 times/day， and patients in observation group got modified Huanglian Wendantang， 1 dose/day. And the treatment was lasted for 3 months. Before and after treatment， levels of fasting blood glucose （FBG）， postprandial 2 blood glucose （PBG）， HbA1c and fasting insulin （FINS）， insulin resistance index （HOMA-IR）， insulin sensitivity index （InISI）， islet β cell function index （HOMA-β）， early insulin secretion index （I30/△G30） and late insulin secretion index （AUCI30~I120/G30~G120）， total cholesterol （TC） and triglycerides （TG）， high-density lipoprotein （HDL-C）， low-density lipoprotein （LDL-C）， adiponectin， TNF -α （TNF-α）， resistin and leptin were detected. And syndrome of phlegm （dampness） combined with heat were scored， and the safety was discussed. Result:The total effective rate in observation group was 91.80% （56/61）， which was higher than 78.33% （47/60） in control group （χ2=4.333， P<0.05）. And the score of phlegm （dampness）-heat syndrome was lower than that in control group （P<0.01）， levels of FBG， PBG， HbA1c， HOMA-IR， AUCI30~I120/G30~G120， TC， TG， LDL-C， TNF-α， leptin and resistin were lower than those in control group （P<0.01）， while levels of I30/△G30， HOMA-β， InISI， HDL-C and adiponectin were higher than those in control group （P<0.01）. There was no adverse reaction related to modified Huanglian Wendantang. Conclusion:In addition to treatment with metformin， modified Huanglian Wendantang can effectively control blood glucose and lipid， regulate adipocyte factor， improve early and late phase insulin secretion， improve the function of β cell and insulin sensitivity of islet， improve IR， with a better comprehensive efficacy and a safety in clinical use.

Protection Mechanism of Addition and Subtraction Therapy of Danshenyin Combined with Wendantang for Myocardial Ischemia in Patients with Stable Angina / 中国实验方剂学杂志

Objective:To observe the efficacy of addition and subtraction therapy of Danshenyin combined with Wendantang in the treatment to stable angina pectoris （SAP） with stagnation of phlegm and blood stasis， and to explore its protection mechanism for myocardial ischemia. Method:One hundred and thirty-two patients were randomly divided into control group and observation group equally. Finished the 63 cases study both in control group and observation group after dropout， loss of follow-up and withdrawal. Patients in control group and observation group got antianginal drugs and the treatment of drug therapy to control the risk factors. All patients were treated with anti-angina drugs and risk factors control drugs. Patients in control group got Danlou Tablets by oral administration， 5 tablets/time， 3 times/day. Patients in observation group got dispensing decoction pieces of Danshenyin and Wendantang 1 dose/day. The treatment continued for 3 months in both groups. Scores of angina attack were graded every week. Before and after treatment， electrocardiogram treadmill exercise test was made to evaluate myocardial ischemia of coronary heart disease， and scores of phlegm stasis block syndrome and Seattle Angina questionnaire （SAQ） were graded for TCM symptoms and quality of life. Levels of hemorheology index， interleukin-6 （IL-6）， tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>）， intercellular adhesion molecule-1 （ICAM-1）， Cystatin C （CysC）， homocysteine （Hcy）， ischemic modified albumin （IMA） and macrophage migration inhibitory factor were detected. In addition， safety was evaluated. Result:After treatment， scores of times， duration， degree of angina pectoris， nitroglycerin dosage of angina pectoris and nitroglycerin dosage in the observation group were lower than those in the control group （<italic>P</italic><0.01）. Total exercise time， duration of ST depression for 1.0 mm， occurrence time of stable angina pectoris， metabolic equivalent and scores of Duke in the observation group were more than those in the control group （<italic>P</italic><0.01）. Score of stagnation of phlegm and blood stasis in the observation group was lower than that in the control group （<italic>P</italic><0.01）， while score of SAQ was higher than that in the control group （<italic>P</italic><0.01）. Levels of IL-6， TNF-<italic>α</italic>， ICAM-1， CysC， IMA， Hcy， MIF， whole blood viscosity （low cut， high cut）， whole blood reducing viscosity， plasma viscosity， platelet aggregation rate and fibrinogen （FIB） in the observation group were lower than those in the control group （<italic>P</italic><0.01）. Effect of angina pectoris in observation group was superior to that in control group （<italic>Z</italic>=2.091， <italic>P</italic><0.01）. No adverse reactions related to Danshenyin combined with Wendantang were found. Conclusion:Addition and subtraction therapy of Danshenyin combined with Wendantang based on the routine western medicine treatment can control the attack of angina pectoris， relieve the symptoms of phlegm and stasis block syndrome， and improve the quality of life for patients with SAP， showing superior clinical efficacy and safety. In addition， it can improve the hemorheology of patients， inhibit the inflammatory reaction， reduce the stenosis or obstruction of lumen in order to improve the degree of myocardial ischemia.

Clinical Efficacy of Midified Wendantang and Xueyaping Recipe in Middle Aged and Young People with Hypertension and Phlegm Dampness Retention / 中国实验方剂学杂志

Objective:To discuss the clinical efficacy of modified Wendantang combined with Xueyaping recipe in the middle aged and young people with hypertension and syndrome of phlegm dampness accumulation， and investigate its effect on metabolism. Method:One hundred and twenty patients were divided into control group and observation group averagely. Patients in both groups got lifestyle intervention and bisoprolol maleate tablets， 5-10 mg/time， 1 time/day. Patients in observation group additionally took modified Wendantang combined with Xueyaping recipe， 1 dose/day. Patients in control group addiiotnally got placebo granules Banxia Tianma Wan， 6 g/time， 2 times/day. The treatment was continued for 12 weeks in both groups. Blood pressure was measured at home to measure the compliance rate of blood pressure during the treatment and after the treatment. Before and after treatment， 24 h mean systolic blood pressure （24 h SBP）， 24 h mean pulse pressure （24 h PP）， 24 h mean diastolic blood pressure （24 h DBP）， blood pressure variability （BPV） ［24 h systolic blood pressure standard deviation （24 h SSD）， 24 h diastolic blood pressure standard deviation （24 h DSD）， systolic blood pressure variation coefficient （nSCV）， and diastolic blood pressure variation coefficient （nDCV） were recorded，compare night coefficients］. Scores of syndrome of phlegm dampness accumulation， body mass index （BMI） and waist hip ratio （WHR） were evaluated. Levels of uric acid （UA）， total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein cholesterin （HDL-C）， low-density lipoprotein cholesterin （LDL-C）， fasting blood glucose （FBG） and fasting insulin （FINS）， insulin resistance index （HOMA-IR）， homocysteine （Hcy）， Cystatin C （CysC）， angiotensin Ⅱ （Ang Ⅱ） and nuclear factor kappa B （NF-<italic>κ</italic>B） were measured. In addition， the safety was evaluated. Result:Compliance rate of blood pressure in observation group was 94.74%（54/57）， higher than 80.70% （46/57） in control group （<italic>χ</italic>²=5.211， <italic>P</italic><0.05）. Levels of 4 h SBP， 24 h DBP， 24 h PP， 24 h SSD， 24 h DSD， nSCV， nDCV， Hcy， CysC， AngⅡ， and NF-<italic>κ</italic>B in observation group were all lower than those detected from control group （<italic>P</italic><0.01）. Score of syndrome of phlegm dampness accumulation was lower than that in control group （<italic>P</italic><0.01）. Levels of UA， TC， TG， LDL-C and HOMA-IR were lower than those in control group （<italic>P</italic><0.05）， while level of HDL-C was higher than that detected from control group （<italic>P</italic><0.05）. Conclusion:Based on lifestyle and western medicine intervention， Wendantang combined with Xueyaping recipe can further control the blood pressure level， reduce the symptoms of phlegm dampness retention syndrome， improve blood pressure variability， improve the compliance rate of blood pressure， improve the metabolism of patients and reduce the risk factors of ASCVD in middle aged and young people with hypertension.

Effect of Huanglian Wendantang on Inflammatory Response and Hepatocyte Burn Death in IGT Rats / 中国实验方剂学杂志

Objective:To investigate whether there is inflammatory reaction and cell pyroptosis in impaired glucose tolerance （IGT） rats induced by high-fat diet and the intervention effect of Huanglian Wendantang. Method:Healthy male SD rats were fed with 45% fat content diet for 20 weeks to replicate the IGT model. The rats in line with the model establish criteria were randomly divided into 3 groups， with 10 rats in each group， another 10 rats were selected as the blank control group. Huanglian Wendantang group was given 7.8 g·kg^-1·d^-1 compound decoction of Huanglian Wendantang， and the positive control group was given 0.05 g·kg^-1·d^-1 aqueous solution of metformin hydrochloride， with the dose volume of 10 mL·kg^-1·d^-1. The blank group and the model group were given the same volume of distilled water. After continuous intragastric administration for 4 weeks， the body weight， body length and abdominal circumferences were measured， the Lee's obesity index was calculated， and the levels of fasting plasma glucose （FPG） and 2-hour plasma glucose （2 h PG） were detected in each group. Serum interleukin-6 （IL-6） content was detected by enzyme-linked immunosorbent assay （ELISA）. The mRNA and protein expressions of nuclear factor kappa B （NF-<italic>κ</italic>B）， cysteinyl aspartate specific proteinase-1 （Caspase-1） and NOD-like receptor protein 3 （NLRP3） in liver tissues were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot. Immunofluorescence was used to detect the expression of Caspase-1 and NLRP3 in rat liver. Hematoxylin and eosin （HE） staining was used to observe the morphology of liver tissue. Result:Compared with blank group， the body weight， abdominal circumference， body length and Lee's index in model group were significantly increased （<italic>P</italic><0.05， <italic>P</italic><0.01）， the levels of FPG and 2 h PG were significantly increased （<italic>P</italic><0.05， <italic>P</italic><0.01）， serum IL-6 content and NF-<italic>κ</italic>B， Caspase-1 and NLRP3 gene and protein expressions in liver tissue were significantly increased （<italic>P</italic><0.01）， immunofluorescence technique showed that Caspase-1 and NLRP3 expressions increased obviously in IGT rat model’s liver tissues， and inflammatory cells infiltration was observed obviously in HE stained rat liver tissue model. Compared with model group， Huanglian Wendantang and metformin hydrochloride groups could effectively reduce the body weight of IGT rats （<italic>P</italic><0.01） and abdominal obesity， and correct the levels of FPG and 2 h PG （<italic>P</italic><0.01）， while effectively reducing serum IL-6 content and gene and protein expressions of NF-<italic>κ</italic>B， Caspase-1 and NLRP3 in liver tissues of IGT rats， and alleviating inflammatory cell infiltration. Conclusion:Inflammatory response exists in IGT model rats induced by high-fat diet. Huanglian Wendantang can obviously reduce its inflammatory response and alleviate liver cell pyroptosis.

Efficacy of Modified Huanglian Wendantang and Shaofu Zhuyutang Against Ovulation Disorder in Combined Phlegm and Stasis-Induced Polycystic Ovary Syndrome / 中国实验方剂学杂志

Objective:To observe the clinical efficacy of modified Huanglian Wendantang and Shaofu Zhuyutang in the treatment of ovulation disorder in patients with polycystic ovary syndrome （PCOS） due to the combined phlegm and stasis-induced and its influence on chronic inflammation. Method:According to the random number table， 100 patients were divided into a control group （50 cases） and an observation group （50 cases）. Apart from lifestyle intervention and oral administration of clomiphene citrate （CC） capsules to induce ovulation， patients in the control group further received Guizhi Fulingwan， 6 g/time， 2 times/day， while those in the observation group were treated with the modified Huanglian Wendantang and Shaofu Zhuyutang， 1 dose/day， for six menstrual cycles. The ovulation， endometrial thickness， proportion of type A endometrium， as well as the pulsatility index （PI） and resistance index （RI） of uterine artery were monitored before and after treatment. The fasting blood glucose （FBG）， fasting insulin （FINS）， luteinizing hormone （LH）， follicle stimulating hormone （FSH）， serum testosterone （T）， estradiol （E₂）， dehydroepiandrosterone sulfate （DHEAS）， tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>）， high-sensitivity C-reactive protein （hs-CRP）， adiponectin （APN）， and interleukin-6 （IL-6） levels before and after treatment were detected， followed by the calculation of homeostasis model assessment-insulin resistance （HOMA-IR） value and the evaluation of ovarian volume and combined phlegm and stasis-induced syndrome score. Result:The overall response rate of the observation group was （44/47） 93.62%， which was higher than （36/46） 78.26% of the control group （<italic>χ</italic>²=4.802， <italic>P</italic><0.05）. The ovulation rate in the observation group was （199/264） 75.38%， higher than （173/272） 63.60% in the control group （<italic>χ</italic>²=8.714， <italic>P</italic><0.01）. The clinical pregnancy rate of the observation group was （11/47） 23.40%， higher than （5/46） 10.87% of the control group， but the difference was not statistically significant （<italic>χ</italic>²=2.564， <italic>P</italic>>0.05）. Compared with the control group， the observation group exhibited reduced PI， RI， LH， T， DHEAS， FINS， FPG， HOMA-IR， TNF-<italic>α</italic>， hs-CRP， and IL-6 （<italic>P</italic><0.01）， but elevated E₂， FSH， and APN （<italic>P</italic><0.01）. Besides， the bilateral ovarian volume and combined phlegm and stasis-induced syndrome score of the observation group were smaller than those of the control group （<italic>P</italic><0.01）， while the endometrial thickness and proportion of type A endometrium were higher （<italic>P</italic><0.01）. Conclusion:On the basis of CC treatment， the modified Huanglian Wendantang and Shaofu Zhuyutang alleviates the ovulation disorder in PCOS patients of combined phlegm and stasis-induced syndrome and regulates IR and chronic inflammation， thus creating a favorable condition for clinical pregnancy， which is worthy of further research.

Effect of Huanglian Wendantang on Classical Pathway of Skeletal Muscle Pyroptosis in IGT Rats / 中国实验方剂学杂志

Objective:To explore the effects of Huanglian Wendantang （HLWDT） on pyroptosis of skeletal muscle in rats with impaired glucose tolerance （IGT） and to explain the mechanism based on NOD-like receptor protein 3 （NLRP3）/cysteine aspartate-specific protease-1 （Caspase-1）/gasdermin D （GSDMD）/interleukin-1<italic>β </italic>（IL-1<italic>β</italic>）/IL-18 signaling pathway. Method:The SD male rats were fed with 45% high-fat diet for 20 weeks to induce the IGT model. After modeling， the rats were randomly divided into a blank group， a model group， a positive control group （metformin hydrochloride， 0.05 g·kg^-1d^-1）， and an HLWDT （7.8 g·kg^-1d^-1） group based on the body weight of rats. The blank group and the model group were fed with the same volume of distilled water. The dose for each group was set as 10 mL·kg^-1d^-1. After four weeks of continuous gavage， blood was collected and serum was separated. The skeletal muscles of rats were stored in liquid nitrogen. Subsequently， serum IL-1<italic>β</italic> and IL-18 were detected by the enzyme-linked immunosorbent assay （ELISA）. The mRNA and protein expression levels of NLRP3， Caspase-1， and GSDMD were detected by real-time quantitative PCR （Real-time PCR） and Western blot， respectively. The expression of GSDMD， IL-1<italic>β</italic>， and IL-18 proteins in skeletal muscle tissues was detected by immunofluorescence. Hematoxylin-eosin （HE） staining was used to observe the pathological changes of skeletal muscles. Result:Compared with the blank group， the model group showed increased IL-1<italic>β</italic> and IL-18 in serum， and NLRP3， Caspase-1， and GSDMD gene and protein expression in skeletal muscle tissues （<italic>P</italic><0.01）. Immunofluorescence assay showed that GSDMD， IL-18， and IL-1<italic>β </italic>protein expression in skeletal muscle tissues of the model group was significantly elevated （<italic>P</italic><0.01）. HE staining showed obvious pathological changes in skeletal muscles. Compared with the model group， the HLWDT group and the positive control group could decrease IL-1<italic>β</italic> and IL-18 in serum and NLRP3， Caspase-1， and GSDMD gene and protein expression in skeletal muscle tissues （<italic>P</italic><0.01）. In addition， immunofluorescence assay revealed that HLWDT could reduce protein expression levels of GSDMD， IL-1<italic>β</italic>， and IL-18 in skeletal muscles of IGT rats （<italic>P</italic><0.01）. The results of HE staining showed that HLWDT could improve the pathological changes of skeletal muscles in IGT rats<bold>.</bold> Conclusion:HLWDT can inhibit skeletal muscle pyroptosis of IGT rats， and the mechanism may be closely related to NLRP3/Caspase-1/GSDMD/IL-18/IL-1<italic>β</italic> signaling pathway.

Effect of Modified Wendantang on LEP, ACC and MCA in Female Nutritional Obese Rats / 中国实验方剂学杂志

<b>Objective::To detect the expression levels of leptin (LEP), acety-coenzyme A carboxylase(ACC) and malonyl-CoA (MCA)-related proteins and their genes in rat tissues, in order to explore the mechanism and dose-effect relationship of modified Wendantang in alleviating lipid metabolism disorder in female nutritional obese rats. <b>Method::Totally 50 SD female rats were randomly divided into 5 groups according to body weight, namely the normal control group, the model control group, and high, medium and low-dose modified Wendantang groups (18.2, 9.1, 4.55 g·kg^-1). Except the normal control group, the remaining rats were fed with " common feed + high fat emulsion + carbonated beverage" to establish the model of nutritional obesity, and then continuously given drugs by gavage for 5 weeks. After the last drug administration to animals in each group, the rats were anaesthetized to collect materials. The serum LEP, and liver and gastrocnemius ACC levels in each group were detected by enzyme-linked immunosorbent assay (ELISA). Quantitative real-time fluorescence polymerase chain reaction (Real-time PCR) was used to detect the expressions of LEP, MCA and ACC2 mRNA in the hypothalamus and liver tissues of each group. <b>Result::Compared with the normal control group, the body weight and fat index of the model control group increased significantly (<italic>P</italic><0.05). Compared with the model control group, the medium-dose modified Wendantang group could significantly down-regulate the expressions of LEP, MCA mRNA in rat hypothalamus (<italic>P</italic><0.01). The low-dose group can significantly down-regulate the expression levels of serum LEP, hypothalamus tissue LEP, MCA mRNA and liver tissue ACC2 mRNA (<italic>P</italic><0.05, <italic>P</italic><0.01). Compared with the high-dose modified Wendantang group and the middle-dose modified Wendantang group had the best effect in down-regulating the expressions of LEP and MCA mRNA in the hypothalamus of rats, which were followed by the low-dose group (<italic>P</italic><0.05, <italic>P</italic><0.01). <b>Conclusion::The mechanism of modified Wendantang against nutritional obesity in female rats is related to the intervention of LEP resistance and the decrease of the expression level of ACC2 mRNA in liver tissue and MCA mRNA in hypothalamus tissue. The middle and low-dose groups have a better effect.

Effect of Wendantang-containing Serum on Apoptosis and Expressions of PI3K，Akt and GSK3β in Astrocytes Under Glutamate Environment / 中国实验方剂学杂志

Objective:To investigate the protective effect of Wendantang-containing serum on astrocytes in glutamate environment and its effect on phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt)/glycogen synthetase kinase 3β (GSK3β) signal pathway. Method:Totally 60 rats were randomly divided into 5 groups, normal group (n=20), clozapine group, and high, medium and low-dose Wendantang groups, with 10 rats in each group. Normal group was given 20 mL·kg-1 normal saline, clozapine group was given 20 mg·kg-1 clozapine, Wendantang groups were given 40, 20, 10 g·kg-1 Wendantang, once a day. Eight days later, the rats were killed, their blood was taken, serum was centrifuged, inactivated, filtrated, sterilized and filled in separate centrifugal tubes. The astrocytes were divided into normal group, model group, clozapine group, and high, medium and low-dose Wendantang groups. The normal group and the model group were cultured with normal serum, and the rest groups were cultured with corresponding drug containing serum. The other groups were treated with 10 mmol·L-1 glutamic acid for 24 hours, and then the apoptosis of astrocytes was detected by flow cytometry. Western blot and Real-time fluorescent quantitative polymerase chain reaction (Real-time PCR) were used to determine protein, and mRNA expressions of PI3K, Akt, GSK3β in astrocytes. Result:Compared with the normal group, apoptosis in model group increased significantly (P<0.01). Compared with the model group, apoptosis in Wendantang groups decreased significantly (P<0.01). Compared with the normal group, protein and phosphorylation expressions of PI3K, Akt, GSK3β in model groups decreased significantly (P<0.05, P<0.01). Compared with the model group, protein and phosphorylation expressions of PI3K, Akt, GSK3β in Wendantang groups increased (P<0.05, P<0.01). Compared with the normal group, expressions of PI3K, Akt and GSK3β mRNA decreased in model group(P<0.01). Compared with the model group, expressions of PI3K, Akt and GSK3β mRNA increased significantly in Wendantang groups group (P<0.05，P<0.01). Conclusion:Wendantang-containing serum can effectively increase expressions of PI3K, Akt and GSK3β, so as to regulate PI3K/Akt/GSK3β signal pathway and protect nerve cells.

Effect of Huanglian Wendantang in Treatment of Metabolic Syndrome / 中国实验方剂学杂志

Metabolic syndrome (MS) is a pathological condition characterized by central obesity, insulin resistance, hypertension, and hyperlipidemia. With the increase of poor dietary habits and lifestyles in modern society, especially the poor living habits of sedentariness and less movement, the prevalence of MS has increased year by year. According to relevant data, the number of MS patients worldwide will reach about 2.568 billion by 2040, which will seriously endanger human life and health. Huanglian Wendantang, as a famous traditional Chinese medicine prescription for clearing away heat and drying dampness, regulating Qi and resolving phlegm, and benefiting the stomach and gall, has been proved to have significant pharmacological effects in lowering blood fat, reducing blood sugar and resisting inflammation by modern pharmacological studies, and widely used in the treatment of metabolic diseases, cardiovascular diseases and other systemic diseases. In recent years, a large number of studies have proved that Huanglian Wendantang has a significant effect on MS. In terms of clinical efficacy, it could significantly improve the pathological state of obesity, dyslipidemia, abnormal glucose metabolism and hypertension in MS patients. Meanwhile, it could also interfere with the inflammatory state, prethrombotic state, abnormal vascular regulation and other potential risk factors in the body, with a high safety and fewer side effects. In terms of experimental study, it could enhance the insulin sensitivity, and improve the insulin resistance of MS animal models and cell models through interventions in insulin signal transduction, inflammatory response, and antioxidant stress. By retrieving PubMed, CNKI, Weipu, Wanfang and other databases, the author summarized the study reports of Huanglian Wendantang on MS in recent years in three aspects: theoretical study, clinical efficacy study and experimental mechanism study, in the expectation of provide some scientific references for in-depth study of the mechanism of Huanglian Wendantang in treating MS and the development and clinical promotion of the prescription.

Effect of Modified Chaiqin Wendantang on Blood Glucose Level and Gastrointestinal Dysfunction in Patients with Diabetic Gastroparesis / 中国实验方剂学杂志

Objective:To explore the effect of modified Chaiqin Wendantang on blood glucose level and gastrointestinal dysfunction in patients with diabetic gastroparesis (DGP) of weak spleen and stomach. Method:A total of 138 patients with DGP of weak spleen and stomach in Hainan Provincial Fourth People's Hospital from February 2017 to March 2019 were enrolled, and divided into two groups according to the random number table methods. Both groups received the routine treatment. In addition to this, study group received Chaiqin Wendantang, while control group received domperidone tablets. Traditional Chinese medicine (TCM) syndrome scores, blood glucose, gastrointestinal function, hemorheology index, gastric emptying function and gastric electrical activity, Pittsburgh Sleep Quality Index (PSQI) scale and clinical efficacy were compared. Result:After treatment, TCM symptom scores and total scores decreased (P<0.05), levels of fasting blood glucose (FBG), 2 hours postprandial blood glucose (2 h PBG), and glycated hemoglobin (HbA1c) decreased (P<0.05), serum motilin (MOT) and gastrin (GAS) levels increased (P<0.05), cholecystokinin (CCK) levels decreased (P<0.05), gastric emptying time shortened, frequency, amplitude and rhythm increased (P<0.05), PSQI score decreased (P<0.05), and whole blood viscosity (WBV) and fibrinogen (FIB) levels decreased (P<0.05), all of those changes were more obvious in study group than control group (P<0.05). The total effective rate in study group was higher than that in control group (P<0.05). During the treatment period, there were no obvious adverse reactions in study group, while there were 2 cases of transient dizziness and headache in control group, which were relieved after several seconds. The recurrence rate in study group was lower than that in control group (P<0.05). Conclusion:Modified Chaiqin Wendantang can effectively ameliorate the symptoms of gastric retention, improve sleep quality, control blood glucose levels, and improve hemodynamics for DGP of weak spleen and stomach patients. Besides, it can improve the gastrointestinal function by reducing serum CCK levels, so as to stimulate the secretion of MOT and GAS, increase gastric motility, shorten gastric emptying time, and promote the recovery of gastric electrical activity. With a high safety and low recurrence rate, it has clinical application value.

Clinical Observation on Shiwei Wendantang in Treating Post-ischemic Stroke Depression of Heart and Gallbladder Qi Deficiency Syndrome / 中国实验方剂学杂志

Objective:To observe the clinical efficacy of Shiwei Wendantang on post-ischemic stroke depression of heart and gallbladder Qi deficiency syndrome. Method:The 80 patients with post-ischemic stroke depression of heart and gallbladder Qi deficiency syndrome were divided into two groups by random number table. 40 cases in control group received oral administration of antidepressant Paroxetine, 20 mg·d-1, and 40 cases in observation group received Shiwei Wendantang, 1 dose/day. The treatment course was 4 weeks in both groups. The clinical efficacy, hamilton depression scale (HAMD-17) score, serum C-reactive protein (CRP), homocysteine (Hcy) level, traditional Chinese medicine(TCM) syndrome score and quality of life score of two groups were observed and compared. Result:After treatment, the curative effect of observation group was better than that of the control group (Z=-2.104，P<0.05), and the total effective rate in observation group was significantly higher than that of control group（χ2 =5.00，P<0.05）. After treatment, the scores of each factor of HAMD-17 scale in observation group were significantly decreased (P<0.05), and the scores of factors of HAMD-17 scale in the control group were also significantly decreased (P<0.05) except despair and anxiety. The decrease of scores in the observation group was more obvious than that in the control group (P<0.05). After treatment, the values of serum CRP and Hcy in two groups were decreased significantly (P<0.01）,and the values of serum CRP and Hcy in observation group were also decreased significantly (P<0.01）.After treatment, the scores of TCM syndromes in observation group were decreased significantly (P<0.01）， while in control group, only the score of urination was significantly decreased（P<0.05）. The scores of quality of life in observation group were all significantly higher than those before treatment (P<0.01）. The scores of SF-36 Health Survey Form in the control group were significantly decreased except for energy and social function (P<0.05). The scores of physical function, physical intelligence, physical pain, social function, and mental health in observation group were significantly higher than those in the control group (P<0.05). Conclusion:As compared with the conventional western medicine treatment, the application of Shiwei Wendantang in the treatment of post-ischemic stroke depression of heart and gallbladder Qi deficiency syndrome, can further reduce the degree of depression of patients, improve the symptoms of depression, and improve the quality of life, with more significant clinical efficacy and comprehensive effect.

Effect of Wendantang-containing Serum on CREB Gene Silencing Hippocampal Neuron Apoptosis and BDNF/TrkB/CREB Signaling Pathway / 中国实验方剂学杂志

Objective:To investigate the effect of Wendantang on cyclic adenosine monophosphate （cAMP）-response element binding protein（CREB） gene silencing hippocampal cell activity， apoptosis and signal pathway of brain-derived neurotrophic factor/protomyosin related receptor kinase B/adenosine cyclophosphate effector binding protein （BDNF/TrkB/CREB）. Method:Wendantang-containing serum was prepared. Animal grouping： SD male rats were randomly divided into high， medium， low-dose groups， clozapine group and normal saline group， with 10 rats in each group， while 15 rats for the normal group. Dosage： 20 mL·kg-1 normal saline was given to normal group N， clozapine 0.02 g·kg-1 was given to dozapine group X， while high， medium and low-dose Wendantang groups were respectively given the same amount of Wendantang concentrated crude drug， with concentrations of 2， 1 and 0.5 g·mL-1 respectively once a day for 8 days continuously， and then blood was taken from femoral artery， and centrifuged for 15 min at 5 000 r·min-1. Supernatant was taken， inactivated， stored at -80 ℃ for standby. The CREB gene silenced hippocampal neuron cell line was constructed through transfection of liposomes into hippocampal cells， and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to verify the effect of small interfering RNA （siRNA） transcription. The mRNA expressions of BDNF， TrkB， CREB and CaMKⅡ in normal hippocampal cells and CREB gene silenced hippocampal cells were measured. Result:Compared with normal group， the apoptosis of the normal gene silencing group was significantly increased （P<0.01）， compared with the normal gene silencing group， the apoptosis of each group was significantly reduced （P<0.01）. As for the mRNA expressions of BDNF， TrkB， CREB and CaMKⅡ， compared with the normal group， the mRNA expression of CREB， BDNF in the normal gene silencing group was significantly decreased （P<0.01）. Compared with the normal gene silencing group， the mRNA expression of BDNF in each administration group was highly increased （P<0.01）， but with no statistically significant difference between TrkB and CaMKⅡ groups. Conclusion:The Wendantang-containing serum could improve the mRNA expression of BDNF， protect hippocampal neurons and prevent cognitive impairment of schizophrenia by regulating BDNF/TrkB/CREB signal pathway.

Material Basis and Action Mechanism of Wendantang in Treatment of Nervous System Diseases / 中国实验方剂学杂志

Wendantang (WDT) is a classical traditional Chinese medicine prescription composed of Pinelliae Rhizoma, Bambuseae Caulis in Taenias, Aurantii Fructus Immaturus, Citri Reticulatae Pericarpium, Zingiberis Rhizoma Recens, Glycyrrhizae Radix et Rhizoma, with the effect in regulating Qi-movement and phlegm and relieving stomach and gallbladder. The clinical studies have proved that WDT has significant therapeutic effects on depression, insomnia, schizophrenia, Alzheimer's disease and other nervous system diseases, but wihtout systematic understanding of material basis and compatibility principle because of the complex chemical composition and the scattered research results. Focusing on the neurological diseases and based on the origin of ancient recipes and modern research examples, the author sorted out and summarized the active ingredients constituting the recipe, paid attention to the effect of the compatibility on the composition and efficacy transmission, and judged the rationality of composition intention and selection. On this basis, it comprehensively identifies the potential components and effective paths that can well treat the nervous system diseases, and had the overall understanding about mutual relationship between composition and efficiency. In this article, we expect to find its scientific basis of effective materials and the key technology of quality standards, and define the direction of future research, so as to provide valuable reference for secondary development and new preparations designed of classic prescriptions.

Effect of Wendantang on Related Inflammatory Factors and Expression of STAT3 as a Key Molecule in JAK2/STAT3 Pathway of Rats with Obesity Phlegm-dampness Syndrome / 中国实验方剂学杂志

Objective:To observe the effect of Wendantang on tumor necrosis factor-α (TNF-α),interleukin(IL)-6,IL-17,IL-22 and other related inflammatory factors in peripheral blood and the expression of STAT3[the key molecule of Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3) signal pathway in hypothalamus] mRNA and protein of obese rats with syndrome of phlegm-dampness,so as to explore the internal mechanism of Wendantang in interfering obesity with syndrome of phlegm-dampness. Method:A total of 100 rats were randomly divided into blank group(30 rats) and modeling group(70 rats),rats in the blank group was fed with basic feed and the modeling group was fed with high-fat feed for 6 weeks.Animal model of obesity with syndrome of phlegm-dampness was established by the method in literature.After successful modeling,16 obese rats were selected and randomly divided into the model group and Wendantang intervention group with 8 rats in each group,and another 8 rats in the blank group were randomly selected as the normal group.Rats in Wendantang intervention group were given 15 g·kg-1 of crude drug by gavage,while the model group and the normal group were given the same amount of distilled water for gavage once a day for 6 weeks.No eating but no prohibiting drinking before dealing with 12 h and then taking samples after anesthesia.The body weight,Lee's index and obesity rate of rats were measured,the levels of blood lipids[total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol(LDL-C) and high density lipoprotein cholesterol(HDL-C)] of rats were detected with a full-automatic biochemical analyzer according to the requirements of the kit,the expression of TNF-α,IL-17,IL-22 and IL-6 in peripheral blood of rats was detected with enzyme-linked immunosorbent assay(ELISA),STAT3 mRNA expression in hypothalamus of rats was detected with real-time fluorescence quantitative polymerase chain reaction(Real-time PCR) and the expression of STAT3 protein in hypothalamus of rats was detected with Western blot. Result:The high-fat feed feeding could successfully replicate the obese rat model,and the obesity rate of rats in the modeling group was greater than 20%,and compared with the blank group,the body weight and Lee's index of rats in the modeling group were significantly increased(PPPPPPPPPPPConclusion:Wendantang has a good effect on improving phlegm-dampness in obese rats,and the mechanism may be related to regulating JAK2/STAT3 signal pathway then to improve the chronic inflammatory state of the body,and all of which provides a scientific basis for Wendantang in intervening obesity with syndrome of phlegm-dampness.

Effect of Wendantang on PI3K,Akt and GSK3β of Hippocampus in Rats with Schizophrenia / 中国实验方剂学杂志

Objective: To research the effect of Wendantang on phosphatidylinositol-3-kinases(PI3K)/protein kinase B(Akt)/glycogen synthase kinase 3β(GSK3β) signaling pathway of hippocampus in rats with schizophrenia. Method: Sixty SD rats were randomly divided six groups:normal group (A), model group (B), Clozapine group (C), high-dosage group Wendantang (D), medium-dosage Wendantang group (E) and low-dosage Wendantang group (F), with 10 rats in each group. The rats of normal group and model group were given normal saline. The rats of Clozapine group were given 20 mg·kg-1 Clozapine. The rats of high-dosage, medium-dosage, low-dosage Wendantang groups were respectively given 40,20,10 g·kg-1 Wendantang, once a day, for 21 days.Two hours later after the last administration with Wendantang or saline,except for group A, groups B,C,D,E,F were intraperitoneally given MK-801 0.6 mg·kg-1 to establish the rat schizophrenia model. After modeling, the changes in stereotyped behavior of each group were observed and recorded. After three days,the rats were put to death,and the hippocampus tissue were tested. According to Sams Dodd and Hoffman's standard, the stereotyped behavior of rats was scored. The protein expressions of PI3K, Akt and GSK3β of hippocampus were determined by Western blot. The mRNA expressions of PI3K, Akt and GSK3β of hippocampus were tested by Real-time PCR. Result: Compared with A, the stereotyped behavior score of the B was significantly increased (Pβ protein and mRNA of hippocampus were significantly decreased (PPβ protein and PI3K, Akt and GSK3β mRNA of hippocampus (PPConclusion: Wendantang could regulate the PI3K/Akt/GSK3 signaling pathway by improving the stereotyped behavior and increasing the expressions of PI3K, Akt, GSK3β of hippocampus in rats with schizophrenia, so as to achieve the purpose of treating schizophrenia.