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ObjectiveTo observe the effect of modified Erchentang on the expression of key molecules in the Jagged1/Notch1/Hes1 signaling pathway in lung tissues of rats with chronic obstructive pulmonary disease （COPD） and explore its anti-inflammatory effect and molecular mechanism on COPD through the Jagged1/Notch1/Hes1 signaling pathway. MethodSixty SD rats were randomly divided into normal group， model group， low-， medium-， and high-dose modified Erchentang groups （5， 10， 20 g·kg-1）， and γ-secretase inhibitor DAPT group （0.02 g·kg-1）， with 10 rats in each group. The COPD model was induced in rats by cigarette smoking combined with intratracheal instillation of lipopolysaccharide （LPS）. Rats were treated with corresponding drugs by gavage， while those in the normal group and the model group were treated with the same amount of normal saline by gavage. The serum levels of Notch1， soluble intercellular adhesion molecule-1 （sICAM-1）， activated leukocyte cell adhesion molecule （ALCAM）， and soluble vascular adhesion molecule-1 （sVCAM-1） were detected by enzyme-linked immunosorbent assay （ELISA）. The mRNA expression of Jagged1， Notch1， and Hes1 was detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The protein expression of Jagged1， Notch1， Notch1 intracellular domain （NICD1）， and Hes1 in lung tissues of rats was detected by immunohistochemistry （IHC）. ResultCompared with the normal group， the model group showed increased serum content of Notch1， sICAM-1， ALCAM， and sVCAM-1 （P<0.01）， increased mRNA expression of Jagged1， Notch1， and Hes1 in lung tissues （P<0.01）， and increased protein expression of Jagged1， Notch1， NICD1， and Hes1 （P<0.01）. Compared with the model group， the medium- and high-dose modified Erchentang groups and the DAPT group showed decreased serum content of Notch1， sICAM-1， ALCAM， and sVCAM-1 （P<0.05， P<0.05）， down-regulated mRNA expression of Jagged1， Notch1， and Hes1 （P<0.05， P<0.01）， and reduced protein expression of Jagged1， Notch1， NICD1， and Hes1（P<0.05， P<0.01）. ConclusionModified Erchentang may inhibit the inflammatory response in the lung of COPD rats， and its mechanism may be related to the resistance of inflammatory injury in the lung by decreasing the mRNA expression of Jagged1， Notch1， and Hes1 and inhibiting the release of Notch1， sICAM-1， ALCAM， and sVCAM-1.
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ObjectiveTo study the effect of modified Erchentang on the expression of key molecules in the high mobility group Box 1 protein （HMGB1）/receptor for advanced glycation endproduct （RAGE）/nuclear factor-κB （NF-κB） signaling pathway in bronchioles of rats with chronic obstructive pulmonary disease （COPD）， to explore the mechanism of modified Erchentang against bronchiolar inflammation of COPD rats via HMGB1/RAGE/NF-κB signaling pathway. MethodSixty SD rats were randomly divided into normal group， model group， modified Erchentang low-， medium- and high-dose groups （5， 10， 20 g·kg-1·d-1） and ethyl pyruvate （HMGB1 inhibitor） group， with 10 in each group. The COPD rat model was prepared by cigarette smoke combined with tracheal injection of lipopolysaccharide （LPS）. After modeling， the modified Erchentang groups were given corresponding drugs （ig） and Ringer's solution （4 mL， ip）， while the EP group was treated with equal volume of normal saline （ig） and EP （0.04 g·kg-1·d-1， ip）. The normal group and the model group received equal volume of normal saline （ig） and Ringer's solution （ip） for 21 consecutive days. The contents of HMGB1， chemokine （C-X-C motif） ligand 1 （CXCL1）， CXCL2 and monocyte chemotactic protein-1 （MCP-1） in bronchoalveolar lavage fluid （BALF） were detected by enzyme-linked immunosorbent assay （ELISA）. The mRNA expressions of HMGB1， RAGE and NF-κB p65 were determined by Real-time polymerase chain reaction （Real-time PCR）， and the protein expressions of HMGB1， RAGE， p-NF-κB p65， and alpha-smooth muscle actin （α-SMA） in bronchioles tissue of rats were determined by immunohistochemistry （IHC）. ResultCompared with the conditions in the normal group， the forced vital capacity （FVC）， forced expiratory volume in the first second （FEV1） and FEV1/FVC in the model group were decreased （P<0.01） while the contents of HMGB1， CXCL1， CXCL2 and MCP-1 in BALF were increased （P<0.01）. And the model group presented higher mRNA expressions of HMGB1， RAGE and NF-κB p65 （P<0.01） and protein expressions of HMGB1， RAGE， p-NF-κB p65 and α-SMA （P<0.05， P<0.01） than the normal group. Compared with the model group， the modified Erchentang medium- and high-dose groups had increased FEV1/FVC （P<0.05， P<0.01）， lowered contents of HMGB1， CXCL1， CXCL2 and MCP-1 in BALF （P<0.05， P<0.05）， and reduced mRNA expressions of HMGB1， RAGE and NF-κB p65 （P<0.05， P<0.01） and protein expressions of HMGB1， RAGE， p-NF-κB p65 and α-SMA （P<0.05， P<0.01）. ConclusionModified Erchentang can resist bronchiolar inflammation of COPD rats. The mechanism may be related to down-regulating the mRNA expressiona of HMGB1 and RAGE， inhibiting the activity of NF-κB， and reducing the release of HMGB1， CXCL1， CXCL2 and MCP-1， thus suppressing the inflammatory injury and abnormal repair of bronchioles.
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ObjectiveTo investigate the molecular mechanism of the anti-inflammatory effect of Erchentang in the lung tissue of the rat model of chronic obstructive pulmonary disease （COPD） via the heparin-binding factor （Midkine）/transmembrane receptor protein （Notch2）/Hey1 signaling pathway. MethodSixty SD rats were randomized into normal group， model group， modified Erchentang （5， 10， 20 g·kg-1·d-1） groups， and Notch1 pathway inhibitor （γ-secretase inhibitor， DAPT， 0.02 g·kg-1） group， with 10 rats in each group. The rat model of COPD was established by cigarette smoke combined with lipopolysaccharide （LPS）. After the modeling， the rats were administrated with corresponding drugs by gavage， and those in the normal and model groups were administrated with normal saline by gavage for 21 days. The levels of Midkine， cytokine-induced neutrophil chemoattractant-1 （CINC-1）， macrophage-derived chemokine （MDC）， chemokine ligand 5 （CXCL5）， neutrophil elastase （NE）， and nuclear factor-kappa B （NF-κB） p65 in bronchoalveolar lavage fluid （BALF） were determined by enzyme-linked immunosorbent assay （ELISA）. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and immunohistochemistry were respectively employed to determine the mRNA and protein levels of Midkine， Notch2， and Hey1 in the lung tissue. ResultCompared with the normal group， the modeling increased the levels of Midkine， CINC-1， MDC， CXCL5， NE， and NF-κB p65 in BALF （P<0.01） and up-regulated the mRNA and protein levels of Midkine， Notch2， and Hey1 in the lung tissue （P<0.01）. Compared with the model group， medium- and high-dose modified Erchentang and DAPT lowered the levels of Midkine， CINC-1， MDC， CXCL5， and NF-κB p65 in BALF （P<0.01） and down-regulated the mRNA levels of Midkine， Notch2， and Hey1 （P<0.01）. ConclusionModified Erchentang may inhibit the inflammation in COPD rats by down-regulating the expression of Midkine， Notch2， and Hey1 and reducing the content of Midkine， CINC-1， MDC， and CXCL5.
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ObjectiveTo explore the clinical efficacy and safety of the combination of Erchentang and Bixie Fenqingyin in the treatment of patients with acute cerebral infarction accompanied by hyperuricemia of phlegm and blood stasis blocking collaterals syndrome to provide a new method and evidence for the treatment of acute cerebral infarction with hyperuricemia. MethodA total of 132 eligible patients with acute cerebral infarction accompanied by hyperuricemia of phlegm and blood stasis blocking collaterals syndrome admitted to the Putuo Hospital of Shanghai University of Traditional Chinese Medicine（TCM） from May 2021 to May 2022 were randomly divided into a Chinese medicine group， a western medicine group， and a control group， with 44 cases in each group. All three groups received routine western medical treatment for acute cerebral infarction. Additionally， the Chinese medicine group received Erchentang combined with Bixie Fenqingyin， the western medicine group received Benzbromarone tablets， and the control group did not receive any uric acid-lowering treatment. The treatment duration was four weeks. The modified Rankin Scale （mRS） score after three months of onset， as well as the National Institutes of Health Stroke Scale （NIHSS） scores， TCM syndrome scores， serum uric acid （SUA） levels， serum C-reactive protein （CRP） and interleukin-6 （IL-6） levels， serum superoxide dismutase （SOD） and malondialdehyde （MDA） levels， and other safety indicators were observed before and after treatment. ResultA total of 129 cases completed the trial observation， with 43 cases in the Chinese medicine group， 42 cases in the western medicine group， and 44 cases in the control group. The rate of good prognosis in the Chinese medicine group （83.7%，36/43） was higher than that in the western medicine group （64.3%，27/42） and the control group （40.9%，18/44） （χ2=4.184，16.930，P<0.05）， and the western medicine group was superior to the control group （χ2=4.707，P<0.05）. After treatment， the NIHSS scores， TCM syndrome scores， SUA， CRP， IL-6， and MDA levels of the patients in all three groups decreased， while the SOD levels increased compared with those before treatment （P<0.05）. Among them， the improvement in NIHSS score was better in the Chinese medicine group and the western medicine group than in the control group （P<0.05）. The Chinese medicine group showed the greatest improvement in TCM syndrome （P<0.05）， while the western medicine group showed the greatest reduction in uric acid levels （P<0.05）. No significant abnormalities in safety indicators were observed before and after treatment in the three groups， and no serious adverse reactions were reported. ConclusionThe combination of Erchentang and Bixie Fenqingyin can significantly improve the prognosis， early neurological deficits， and TCM syndromes of patients acute cerebral infarction accompanied by hyperuricemia of phlegm and blood stasis blocking collaterals syndrome. It can also lower uric acid levels and inhibit inflammatory and oxidative stress reactions.
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Objective:To observe the clinical efficacy of Erchentang combined with Sanzi Yangqintang in the treatment of cough variant asthma （CVA） in children with phlegm-evil accumulation lung syndrome and its influence on airway inflammation and airway hyperresponsiveness （AHR）. Method:A total of one hundred and sixteen children were randomly divided into observation group and control group 58 cases in each group. Patients in both groups took montelukast sodium chewable tablets orally， 5 mg/time， once daily， at night before bedtime. In observation group， patients took Erchentang and Sanzi Yangqintang modified granules orally. While patients in control group took Erchentang and Sanzi Yangqintang placebo granules orally. Treatment course continued six weeks for two groups. Before and after treatment， the cough symptom scores and phlegm evil accumulating lung syndrome scores were recorded every week. The cough remission time and cough disappearance time were recorded， followed up for 24 weeks to record cough recurrence. Leicester Cough quality of life questionnaire （LCQ） was scored before and after treatment. The ratio of induced sputum eosinophils （EOS） and the levels of interleukin-4 （IL-4）， IL-5， IL-12， IL-13 were measured before and after treatment. The cumulative doses of exhaled nitric oxide （FeNO） and methacholine （PD20） were measued before and after therapy. Safety evaluation was conducted. Result:The scores of cough symptom and phlegm-evil accumulation lung syndrome at different time points were decreased gradually in two groups of children after treatment （<italic>F</italic><sub>control group</sub>=5.277， <italic>F</italic><sub>observation group</sub>=7.636，<italic>P</italic><0.01）. The scores of cough symptom and phlegm-evil accumulation in the lung syndrome of observation group were lower than those in control group （<italic>P</italic><0.01） at the same period. The durations of cough relief and cough disappearance in observation group were shorter than those in control group （<italic>P</italic><0.01）. Within 24 weeks of follow-up， the recurrence rate of children in observation group was 68.97% （40/58）， lower than 84.48% （49/58） in control group （<italic>χ</italic><sup>2</sup>=3.917，<italic>P</italic><0.05）. Children in observation group had fewer relapses than those in control group （<italic>P</italic><0.01）. The total LCQ scores and scores of all dimensions in observation group were higher than those in control group （<italic>P</italic><0.01）. The EOS， IL-4， IL-5 and IL-13 levels in observation group were lower than the data in control group， and IL-12 level was higher than that in control group （<italic>P</italic><0.01）. FeNO of children in observation group was lower than that in control group （<italic>P</italic><0.01）， while PD20 was more than that of control group （<italic>P</italic><0.01）. The total effective rate of clinical curative effect of children in observation group was 96.55% （56/58）， which was higher than 82.76% （48/58） in control group （<italic>χ</italic><sup>2</sup>=5.948，<italic>P</italic><0.05）. Conclusion:Erchentang combined with Sanzi Yangqintang for children with CVA phlegm evil accumulation lung syndrome can further control the symptoms of cough， shorten the course of cough， improve the quality of life， and reduce airway inflammation and AHR， reduce the recurrence rate. The clinical efficacy is better than using montelukast only， and it is safe and has good clinical value.
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Objective:To observe the regulatory effect of modified Erzhu Erchentang on metabolization of polycystic ovary syndrome （PCOS） with spleen deficiency and phlegm dampness syndrome. Method:Patients 140 cases were divided into control group and observation group. Both groups were given metformin hydrochloride tablets， 500 mg/time， 3 times/day. Control group was given Yuejun Erchen pills， 0.5 g/time， 3 times/day， while observation group was given modified Erzhu Erchentang， 1 dose/day. The course of treatment lasted for 24 weeks. Before and after treatment， levels of fasting blood glucose （FBG）， fasting insulin （FINS）， glycosylated hemoglobin Alc （HbA1c）， 2-hour postprandial blood glucose （2 h PG）， blood lipid， waist circumference （WC）， body mass index （BMI）， waist hip ratio （WHR）， luteinizing hormone （LH）， follicle stimulating hormone （FSH）， serum testosterone （T）， estradiol （E<sub>2</sub>）， dehydroepiandrosterone sulfate （DHEAS）， sex hormone binding globulin （SHBG）， leptin （LP）， adiponectin （APN）， resistin， visfatin and tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>） were detected. Homeostasis model assessment insulin resistance （HOMA-IR） was calculated， modified Erzhu Erchentang was scored， and recovery of menstruation and ovulation and ovarian volume were recorded. Result:Levels of FBG， 2 h PG， HbA1c， FINS， HOMA-IR， triglyceride （TG）， total cholesterol （TC）， low-density lipoprotein cholesterol （LDL-C）， LH， FSH， T， E<sub>2</sub>， DHEAS， LP， resistin， visfatin and TNF-<italic>α</italic> in observation group were lower than those in control group （<italic>P</italic><0.01）， and levels of BMI， WC and WHR were lower than those of control group （<italic>P</italic><0.05）. And levels of high-density lipoprotein cholesterol （HDL-C）， SHBG and APN were higher than those in control group （<italic>P</italic><0.01）. Score of modified Erzhu Erchentang was lower than that in control group （<italic>P</italic><0.01）， and ovarian volume was smaller than that in control group （<italic>P</italic><0.01）. The normal rate of BMI was 49.23% （32/65）， which was higher than 30.30% （20/66） in control group （<italic>χ</italic><sup>2</sup>=5.151， <italic>P</italic><0.05）. The normal rate of blood lipid was 93.85% （61/65）， which was higher than 81.82 % （54/66） in control group （<italic>χ</italic><sup>2</sup>=4.418， <italic>P</italic><0.05）. The normal rate of blood glucose was 96.92% （63/65）， which was higher than 86.36% （57/66） in control group （<italic>χ</italic><sup>2</sup>=4.474， <italic>P</italic><0.05）. Conclusion:In addition to adipocytokines， modified Erzhu Erchentang could regulate adipokines of patients of PCOS with spleen deficiency and phlegm dampness， improve glucose， lipid metabolism and overweight， adjust endocrine hormone， reduce clinical symptoms and improve ovarian structure， so as to create conditions for conception.
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Objective:To discuss the clinical efficacy of modified Danshenyin and Erchentang in treating carotid atherosclerosis （CAS）， and the effect on intimal injury. Method:Patients （151 cases） were divided into control group （75 cases） and observation group （76 cases）. Specifically， 69 cases in control finished the treatment （4 cases fell off in follow-up， and 2 cases were eliminated）， and 69 cases in observation group finished the treatment （3 cases fell off in follow-up， and 4 cases were eliminated）. Patients in both group got atorvastatin calcium tablets， 10 mg/time， 1 time/day， and aspirin enteric-coated tablets， 100 mg/time， 1 time/day. Patients in control group got Hedan tablets， 2 tablets/time， 3 times/day. Patients in observation group got modified Danshenyin and Erchentang， 1 dose/day. The treatment lasted for 4 months. Before and after treatment， color Doppler ultrasound of carotid artery was detected， and carotid intima-media thickness （IMT）， plaque number， plaque area， plaque thickness and hemodynamics were recorded. Levels of nitric oxide （NO）， endothelin-1 （ET-1）， von Willebrand factor （vWF）， soluble intercellular adhesion molecule-1 （sICAM-1）， vascular endothelial growth factor （VEGF）， matrix metalloproteinase-9 （MMP-9）， triglyceride （TG）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， whole-blood low-shear viscosity （LBV）， whole-blood high-shear viscosity （HBV）， plasma viscosity （PV）， platelet aggregation rate （PAR）， fibrinogen （FIB）， homocysteine （Hcy）， interleukin-6 （IL-6）， IL-10， tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>）， serum superoxide dismutase （SOD）， malondialdehyde （MDA）， oxidized low density lipoprotein （ox LDL） and circulating glutathione peroxidase （GSH-Px） were detected before and after treatment. And the safety was evaluated. Result:After treatment， IMT， number， area and thickness of plaque in observation group were less than those in control group （<italic>P</italic><0.01）. Peak systolic velocity and end diastolic velocity in observation group were higher than those in control group （<italic>P</italic><0.01）， while pulsatility index and resistance index were lower than those in control group （<italic>P</italic><0.01）. And levels of ET-1， vWF， sICAM-1， VEGF， MMP-9， TG， TC， LDL-C， LBV， HBV， PV， PAR， FIB， Hcy， IL-6， TNF-<italic>α</italic>， MDA and ox-LDL were lower than those in control group （<italic>P</italic><0.01）， whereas levels of NO， HDL-C， IL-10， SOD and GSH-Px were higher than those in control group （<italic>P</italic><0.01）. And there was no adverse reaction caused by traditional Chinese medicine. Conclusion:Modified Danshenyin and Erchentang can reduce plaque， improve hemodynamics and hemorheology， and regulate blood lipid metabolism and vascular endothelial factor， with anti-inflammatory and anti-oxidation damages. It can protect vascular intima， and inhibit the occurrence and development of CAS， with a safety in clinical use.
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Objective:To observe the effect of modified Erchentang on the expression of CXC chemokine ligand (CXCL) 8-CXC chemotaxis factor receptor (CXCR) 1/2 genes in the lung tissue of rats with chronic obstructive pulmonary disease (COPD), in order to explore the anti-inflammatory molecular mechanism of Erchentang on COPD. Method:Forty SD rats were randomly divided into normal group, model group, Jizhi syrup group and modified Erchentang group. COPD models in rats were prepared by cigarette smoke and dripping lipopolysaccharide (LPS) in the trachea. After modeling, normal and model groups were intragastrically given normal saline solution, Jizhi syrup group was given Jizhi syrup（10 g·kg-1），and modified Erchentang group was given intragastrically corresponding herbal drugs (10 g·kg-1) for 14 days. The levels of chemokines CXCL1, CXCL8 were detected by enzyme-linked immunosorbent assay in rat bronchoalveolar lavage fluid (BALF). The mRNA expressions of CXCL8, CXCR1 and CXCR2 were detected by quantitative real time PCR (Real-time PCR). Western blot was used to detect the levels of CXCL8, CXCR1 and CXCR2 protein, the pathological changes of lung tissues were observed by hematoxylin-eosin(HE) staining,and immunohistochemistry (IHC) method was used to detect the expressions of CXCL8, CXCR1 and CXCR2 protein in the lung tissue of all the groups. Result:The levels of chemokines CXCL1, CXCL8 in rats BALF were increased significantly (P<0.01), the expressions of CXCL8，CXCR1 and CXCR2 mRNA and protein were increased significantly (P<0.05, P<0.01) in model group compared with normal group. Compared with model group, the expressions of CXCL8, CXCR1 and CXCR2 mRNA and protein were decreased significantly (P<0.05), and the levels of chemokines CXCL1, CXCL8 in rats BALF were decreased significantly (P<0.01) in modified Erchentang. Conclusion:Modified Erchentang has an anti-inflammatory effect on COPD. The mechanism may be related to inhibiting the expressions of CXCL8, CXCR1, CXCR2 mRNA and protein, and reducing the release of chemokines CXCL1, CXCL8.
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Objective:To compare the effect and mechanisms of modified Erchentang and Xuefu Zhuyutang on high-fat diet-induced apolipoprotein-E knockout (ApoE-/-) mice nonalcoholic fatty liver disease (NAFLD). Method:Ten C57/BL6J mice were taken as normal control group and fed with normal feed. Totally 30 ApoE-/- mice were fed with high-fat diet to establish a disease model for 4 weeks. After 4 weeks, the 30 ApoE-/- mice were divided into model group, Xuefu Zhuyutang group (hereinafter referred to as Huoxue group) and modified Erchentang group (hereinafter referred to as Huatan group) by random number table method, with 10 in each group. The normal group and the model group were intragastrically administered with normal saline. The drug-administered group was intragastrically administered at a dosage that was ten times of the adult dose, once a day, for 8 weeks. Serum and liver were collected after the end of the 12-week experiment. The serum lipid and liver function levels of each group were measured, and the liver pathological morphology was observed. Protein and mRNA expressions of liver inflammatory mediators interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), matrix metalloproteinase-9 (MMP-9), monocyte chemotactic factor-1 (MCP-1) were detected by Real-time fluorescence quantitative polymerase chain reaction(Real-time PCR) and Western blot. Result:The results of serum lipids and liver function showed that compared with the normal group, serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) in the model group were significantly increased, while serum high-density lipoprotein (HDL) was significantly reduced (P<0.01). Compared with the model group, serum TG ，LDL and ALT were significantly decreased, HDL was significantly increased in the Huoxue group (P<0.05). The serum levels of TC, TG， LDL, AST and ALT in the Huatan group were significantly decreased，HDL was significantly increased (P<0.05，P<0.01), and TG was decreased. The mice serum HDL in the Huatan group was higher than that in the Huoxue group. The serum ALT in the Huoxue group was lower than that in the Huatan group. The pathological observation showed that compared with the normal group, hepatocytes in the model group had severe steatosis with many lipid droplet vacuoles, suggesting that the mouse NAFLD model was successful. Compared with the model group, each administration group alleviated hepatocyte steatosis, with no significant difference between the two administration groups. Western blot and Real-time PCR results showed that compared with the normal group, protein and mRNA expression levels of TNF-α, IL-1β, MCP-1, and MMP-9 in the model group were significantly increased (P<0.05，P<0.01). Compared with the model group, the Huoxue group significantly down-regulated the expressions of IL-1β, MCP-1 protein and MCP-1 mRNA(P<0.05，P<0.01). The Huatan group significantly reduced the expressions of IL-1β, TNF-α, MMP-9, MCP-1 protein, TNF-α and MMP-9 mRNA(P<0.05，P<0.01). Conclusion:Modified Erchentang and Xuefu Zhuyutang can alleviate the therapeutic effect of NAFLD mice to a certain extent, modified Erchentang has a better therapeutic effect.
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Objective:To observe the relationship between serum homocysteine (Hcy), nitric oxide (NO), high-sensitivity C-reactive protein (hs-CRP) as well as the number and degree of coronary lesions, and the effect of Liu Junzitang combined with Erchentang on Hcy, NO, hs-CRP in patients with coronary heart disease (CHD), so as to explore the protector effect of Liu Junzitang combined with Erchentang on CHD patients. Method:A total of 76 inpatients with phlegm turbidity and internal resistance (CHD) from the Cardiovascular Department of Jiangxi University of Traditional Chinese Medicine（TCM） from November 2016 to April 2019 were selected to analyze the relationship between Hcy, NO, hs-CRP as well as the number and degree of coronary lesions. By lottery, the 76 patients were randomly divided into observation group and control group, with 38 patients in each group. Patients in the control group were given conventional therapy, while patients in the observation group were given Liu Junzitang combined with Erchentang in addition to conventional therapy. The experimental period was 3 months. TCM symptom scores of the two groups before and after administration were evaluated. Hcy, NO, hs-CRP, triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and total cholesterol (TC), apolipoprotein A1 (Apo A1), apolipoprotein B (Apo B), N-terminal B-type natriuretic peptide (NT-proBNP), left ventricular ejection fraction (LVEF) indicators of the two groups were measured before and after administration. Result:The levels of Hcy and hs-CRP were positively correlated with the number and degree of coronary lesions. The level of NO was negatively correlated with the number and degree of coronary lesions. TCM symptom scores were different between the two groups after treatment. Compared with the control group, the TCM symptom score in the observation group was decreased more significantly (P<0.05). The two groups could reduce Hcy, hs-CRP and increase in NO to a certain extent (P<0.05). Compared with the control group, the observation group showed reduction in Hcy, hs-CRP and increase in NO more significantly (P<0.05). After treatment in both groups, TG, LDL, TC, Apo A1, Apo B and HDL were reduced (P<0.05) compared with before treatment. Compared with the control group, the observation group showed decrease in TG, LDL, TC, Apo A1, Apo B and increase in HDL more significantly (P<0.05). Both groups could increase LVEF and decrease NT-proBNP after treatment (P<0.05). Compared with the control group, the observation group increased LVEF and decreased NT-proBNP more significantly (P<0.05). Conclusion:The levels of Hcy and hs-CRP were positively correlated with coronary lesions, while the level of NO was negatively correlated with coronary lesions. Modified Liu Junzitang and Erchentang may be correlated with inhibition of Hcy, hs-CRP and CHD and increase of patient's NO level, thereby reducing the patient's blood lipids, improving the patient's heart function, and improving the patient's clinical symptoms.
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Objective:To study the effect of modified Erchentang on levels of interleukin-12 (IL-12), interferon-γ (IFN-γ), interleukin-9 (IL-9), interleukin-4 (IL-4) and interleukin-13 (IL-13) in plasma and bronchoalveolar lavage fluid (BALF) of all rats, as well as expressions of interleukin-4 (IL-4) receptor (IL-4R1) and interleukin-13 (IL-13) receptor (IL-13RA1) in bronchioles tissue of rats with chronic obstructive pulmonary disease (COPD). Method:Fifty SD rats were randomly divided into 5 groups, namely normal group, model group, and low, middle and high-dose modified Erchentang groups (5, 10, 20 g·kg-1), with 10 rats in each group. COPD in rat was prepared by using cigarette smoke combined with dripping lipopolysaccharide (LPS) in trachea. After the modeling, normal and model groups were given normal saline solution through intragastric (ig) administration, while other groups were given corresponding herbal drugs (5, 10, 20 g·kg-1) intragastrically (ig) for 14 days. The levels of IL-12, IFN-γ, IL-9, IL-4 and IL-13 in plasma and BALF were detected by Enzyme-linked immunosorbent assay (ELISA) method， and immunohistochemistry (IHC) method was used to detect the expressions of IL-4R1 and IL-13RA1 in bronchioles tissue of all of the groups. Result:Compared with the normal group, the levels of IL-12 and IFN-γ were decreased significantly (P<0.01), but the levels of IL-9, IL-4 and IL-13 in plasma and BALF were significantly increased (P<0.01), and the expressions of IL-4R1 and IL-13RA1 in bronchioles tissue were increased significantly (P<0.01) in model group. Compared with the model group, the levels of IL-12 and IFN-γ were increased significantly, while the levels of IL-9, IL-4 and IL-13 in plasma and BALF were decreased significantly (P<0.01), and the expressions of IL-4R1 and IL-13RA1 in bronchioles tissue were decreased significantly (P<0.01) in modified Erchentang groups (10, 20 g·kg-1). Conclusion:Modified Erchentang has effects in resisting inflammatory and protecting tissue structure of bronchioles. Its mechanism may be correlated with increasing the levels of IL-12, IFN-γ and reducing the levels of IL-9, IL-4 and IL-13 in plasma and BALF, and inhibiting the expressions of IL-4R1 and IL-13RA1 in bronchioles tissue.
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Objective::To observe the effect of Erchentang, Chaihu Shugansan, Erchentang+ Chaihu Shugansan and metformin on insulin receptor substrate-1(IRS-1)and insulin receptor substrate-2(IRS-2)mRNA and protein expression in liver tissues of model rats with polycystic ovary syndrome(PCOS), and to explore the biological mechanism of relieving depression and resolving phlegm to improve insulin resistance of polycystic ovary syndrome. Method::A model of polycystic ovary syndrome was replicated in rats by subcutaneous injection of dehydroepiandrosterone(DHEA) under the neck and back.The control group was the normal group, The model rats were divided into model group, Erchentang group(9.135 g·kg-1), Chaihu Shugansan group(6.615 g·kg-1), Erchentang+ Chaihu Shugansan group (Hefang group, 9.135 g·kg-1+ 6.615 g·kg-1), and metformin group(0.158 mg·kg-1). The corresponding drugs were given by intragastric administration once a day for 4 weeks. The ovarian and liver tissues of rats were isolated, and serum testosterone(T)and estradiol(E2)hormone levels in each group were detected by enzyme-linked immunosorbent assay(ELISA), the histopathological changes of ovary in each group were detected by hematoxylin-eosin (HE) staining, IRS-1 and IRS-2 mRNA and protein expression levels in rat liver tissues were detected by quantitative real-time fluorescence PCR(Real-time PCR)and Western blot. Result::Compared with normal group, the serum T and E2 level of model group were significantly decreased (P<0.01), the histology of ovary showed a large number of saccate dilated follicles, thin granular cell layer and rare corpus luteum, IRS-1, IRS-2 mRNA and protein levels in liver tissues decreased significantly (P<0.01). Compared with model group, the serum T and E2 level of each group significantly decreased (P<0.01), histopathology of ovarian tissue showed that the number of saccular dilated follicles decreased, and the granulosa cell layer thickened, showing follicles of all levels, IRS-1, IRS-2 mRNA and protein expression were significantly increased in Erchentang group(P<0.05, P<0.01), IRS-1 mRNA and protein expression were significantly increased in Chaihu Shugansan group(P<0.01), IRS-2 mRNA and protein expression were on the rise, IRS-1 mRNA and protein expression and IRS-2 mRNA expression were significantly increased in the Hefang group (P<0.05), while IRS-2 mRNA was on the rise, IRS-1 protein and IRS-2 mRNA and protein expression were significantly increased in metformin group (P<0.01), while IRS-1 mRNA showed an upward trend. Conclusion::Erchentang improved the insulin resistance of PCOS model rats more significantly than Chaihu Shugansan, and its mechanism may be related to IRS-1, IRS-2 mRNA and protein expression levels of key signaling molecules regulating insulin signal transduction pathway.
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Objective:By the method of network pharmacology， the mechanism of Pinelliae Rhizoma and Citri Exocarpium Rubrum in the treatment of metabolic syndrome was explored. Method:Effective components of Pinelliae Rhizoma and Citri Exocarpium Rubrum were retrieved by TCMSP database，and then selected by ADME parameters. TCMID，BATMAN-TCM，SymMap，TCM-MESH database were used to supplement effective components of TCMSP. TCMSP target prediction model was used to predict potential targets of drugs. DRUGBANK，DisGeNET，CTD，GeneCards，OMIM，PharmGkb，KEGG，DiGSeE databases were retrieved to obtain the targets of metabolic syndrome，and the chips were downloaded and analyzed through GEO database No.GSE98895 to screen out the differential genes of normal people and patients with metabolic syndrome，and supplement the target databases of metabolic syndrome. The intersections of Pinelliae Rhizoma-Citri Exocarpium Rubrum and metabolic syndrome disease targets were obtained by Rstudio 3.6.2. The above intersection targets were imported into the Metascape database for module analysis and overall GO（Biological Process），KEGG and Reactome pathway analysis. The core targets were selected from the intersection targets by using the cytohubba plug-in，the core genes were input into the database of BioGPS，Genecards to analyze the tissue distribution and subcellular distribution，and the core targets were assigned by using the database of DisGeNET. Result:A total of 34 active components and 120 targets of Pinelliae Rhizoma and Citri Exocarpium Rubrum were screened out，and 115 targets were obtained after the intersection of Rstudio 3.6.2. The results of Metascape module analysis and whole analysis were mostly the same，mainly involving the biological processes， such as ligand receptor interaction，calcium ion，cGMP-PKG，cholinergic synapse，thyroid hormone，insulin. The cytohubba plug-in was used to screen out 17 targets，involving 17 key genes， such as VEGFA and NOS3. The tissue and subcellular distribution of the core targets mainly included lymphoblasts，CD33+_myeloid cells，amygdala，pineal and cytoplasmic matrix，mitochondria. The main proteins were signal molecules，kinases and nucleic acids. Conclusion:Pinelliae Rhizoma and Citri Exocarpium Rubrum could treat metabolic syndrome through complex biological processes and pathways，such as blood circulation，ligand receptor interaction of nerve activity，cGMP-PKG，interleukin-related action，calcium ion. This indicates that traditional Chinese medicine（TCM） treated diseases through multi-component，multi-target，multi biological processes，multi-channel and other ways（which is also proved by the distribution of core genes in the tissue，subcellular and protein ascription information），indicating the superiority of the holism concept of TCM. Erchetang and its similar prescriptions are suitable for treating metabolic syndrome，which also indicates that the principle of "treating different diseases with the same therapy" of TCM is not only reflected at the theoretical level； and network pharmacology needs to be further proved in the combination with experimental verification.
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Objective:To observe the clinical efficacy and safety of modified Erchentang (Juhong Tanke liquid) on children bronchitis with syndrome of sputum, cough, dys-expectoration, wheezing and pulmonary function. Method:A total of 200 children patients aged below 24 months were randomly divided into control group and observation group by random number table, with 100 cases in each group. Children in each group received basic clinical treatment, while children in treatment group was also given modified Erchentang (Juhong Tanke liquid), 2-5 mL each time, 3 times a day. Both groups were treated for 15 days. Clinical respiratory tract symptom and sign scores, cough, sputum, dys-expectoration and wheezing were evaluated and compared. Pulmonary function was detected before and after treatment for 15 days. Analysis parameters were respiratory rate (RR), tidal volume per kilogram (VT/kg), inspiratory/expiratory (TI/TE), peak time of expiratory flow (TPTEF), time to peak ratio (TPTEF/TE), peak expiratory flow (PEF), volume in peak time of expiratory flow (VPTEF), volume ratio in peak flow (PFV), terminal flows per peak expiratory flow (25/PF), rate of mid-expiratory to mid-inspiratory flow (ME/MI), respiratory resistance (Rrs), functional residual capacity per kilogram (FRC/kg) and compliance per kilogram (Crs/kg). Result:After treatment for 5 days, both groups have obviously alleviation in sputum, cough, dys-expectoration wheezing and airway function. After treatment for 5 days, sputum, cough, dys-expiratory and wheezing in treatment group were all alleviated comparing with those of control group (PConclusion:Modified Erchentang (Juhong Tanke liquid) has shown marked efficacy in children bronchitis to alleviate clinical symptoms and improve pulmonary function, with no adverse reaction, and thus is worth further promotion and application in clinic.
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Objective: To discuss the efficacy of Erzhu Erchentang on major cardiovascular risk factors caused by type 2 diabetes mellitus (T2DM)with phlegm turbidity and blood stasis syndrome, and its anti-inflammatory effect. Method: One hundred and forty-two patients were randomly divided into control group and observation group by random number table. Patients in control group got insulin or oral hypoglycemic drugs for controlling blood sugar, aspirin enteric-coated tablets, 100 mg/time, 1 time/day, telmisartan tablets, 40 mg/time, 1 time/day, atorvastatin, 10 mg/time, 1 time/day, and non-drug interventions. In addition to the therapy of control group, patients in observation group were also given modified Erzhu Erchentang, 1 dose/day, 5 times/week. The course of treatment was 24 weeks. And a 24-week follow-up was recorded. And levels of fasting blood glucose (FPG), 2 h postprandial blood glucose (2 hPG), glycosylated hemoglobin (HbA1c), systolic blood pressure (SBP), diastolic blood pressure (DBP), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HLD-C) and low-density lipoprotein (LDL-C) were detected. And the occurrence of major cardiovascular events, cerebrovascular events and peripheral vascular events were recorded. Before and after treatment, levels of body mass index (BMI), carotid intima-media thickness (IMT), framingham risk (FRS) and waist-hip ratio (WHR) were assessed. And procalcitonin (PCT), homocysteine (Hcy), hypersensitive C-reactive protein (hs-CRP), cystatin C (CysC) and matrix metalloproteinase-9 (MMP-9) were measured. Result: After treatment, levels of 2 hPG, HbA1c, SBP, DBP, TC, TG, LDL-C, IMT and BMI in observation group were lower than those in control group (PPχ2=4.775, Pχ2=5.639, PZ=2.165, PPConclusion: In addition to the comprehensive therapy of conventional western medicine, modified Erzhu Erchentang can increase the reduce serum inflammatory factors and control the high risk factors of cardiovascular disease of patients with T2DM, so as to reduce the major cardiovascular events.
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Objective: To study the effect of modified Erchentang on expressions of Toll-like receptor 4 (TLR4), myeloid differentiation factor (MyD88) and nuclear factor-κB (NF-κB) genes in the lung tissue homogenate of rats with chronic obstructive pulmonary disease (COPD). Method: Forty SD rats were randomly divided into normal group, model group, modified Erchentang group and EVP4593 (NF-κB inhibitor) group. Rat COPD models were prepared through cigarette smoke and tracheal dripping with lipopolysaccharide (LPS). After the modeling, normal and model groups were intragastrically given normal saline solution, EVP4593 group was given EVP4593(1 mg · kg-1) through subcutaneous injection, and modified Erchentang group was given corresponding herbal drugs intragastrically (10 g · kg-1) for 14 days. The levels of high mobility group box 1(HMGB1), chemokines CXCL-2, CXCL-3 and monocyte chemoattractant protein-1 (MCP-1) in rats serum were detected by enzyme-linked immunosorbent assay in rats serum. The expressions of Toll-like receptors 4(TLR4), myeloid differentiation factor (MyD88) and nuclear factor-κB p65 (NF-κB p65) mRNA were detected by Real-time fluorescence quantitative PCR (Real-time PCR) method. Western blot were used to detect the levels of TLR4, MyD88, NF-κB p65 and p-NF-κB p65 protein. Immunohistochemistry (IHC) method was used to detect the localization and expressions of TLR4, MyD88 and p-NF-κB p65 protein in the lung tissue. Result: The mRNA and protein expressions of TLR4, MyD88 and NF-κB p65 were increased significantly (PPκB p65 mRNA and protein were decreased significantly (PConclusion: Modified Erchentang may inhibit the inflammatory response of COPD effectively. The mechanism may be related to the inhibition of the expressions of the signal molecule genes involved in the TLR4/MyD88/NF-κB pathway and the reduction of the release of HMGB1, CXCL-2, CXCL-3 and MCP-1.
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Objective: To observe the effect of modified Erchentang on the expressions of NLRP3 inflammasome genes in peripheral blood mononuclear cells (PBMCs) and the levels of interleukin-1β(IL-1β)and interleukin-18(IL-18)and chemokine8 (CXCL8) in lung tissue of rats with chronic obstructive pulmonary disease (COPD), in order to explore the molecular mechanism of modified Erchentang against inflammation of COPD. Method: Forty SD rats were randomly divided into normal control group, model group, MCC950 (NLRP3 inhibitor) group and modified Erchentang group. The COPD model of rats was prepared by using cigarette smoke and dripping with lipopolysaccharide (LPS). During the modeling period (from the 1st to the 30th day), the MCC950 group received a single intraperitoneal injection with 60 mg · kg-1 on the first day of the experiment,and the modified Erchentang group was given intragastric administration with 10 g · kg-1, once every 2 days. From the 31st to the 45th day, the MCC950 group was intraperitoneally injected with 3 mg · kg-1, once every 2 days, the modified Erchentang group was given intragastric administration with 10 g · kg-1, twice a day, and the normal group and the model group received normal saline (NS) with 10 g · kg-1, twice a day. The levels of interleukin-1β(IL-1β), interleukin-18(IL-18) and chemokine8 (CXCL8) in rats lung tissue homogenate were detected by enzyme-linked immunosorbent assay (ELISA). The expressions of NLRP3, apoptosis-associated speck-like protein (ASC) and cysteinyl aspartate specific proteinase-1 (Caspase-1) mRNA in PBMCs were measured by Real-time fluorescence quantitative PCR (Real-time PCR). Western blot was used to detect the levels of NLRP3, ASC and Caspase-1 proteins in PBMCs. Immunohistochemical(IHC)method was used to detect the expressions of NLRP3, ASC and Caspase-1 proteins in lung tissues. Result: The expressions of NLRP3, ASC and Caspase-1 mRNA and protein were increased significantly (PPPβ and CXCL8 in lung tissue homogenate in model group were significantly higher than those in the control group. However, compared with model group, the levels of IL-18, IL-1β and CXCL8 were decreased significantly (PPConclusion: NLRP3 inflammasome is involved in the inflammatory response in COPD rats. Modified Erchentang may inhibit the inflammatory response of COPD effectively. The mechanism may be correlated with the reduction of NLRP3, ASC and Caspase-1 gene expressions, and the inhibition of the release of IL-18, IL-1β and CXCL8.
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Objective: To observe the effect of modified Erchentang on the expression of interleukin-19 (IL-19), interleukin-20 (IL-20)and their receptor IL-20R1, IL-20R2 in bronchioles of rats with chronic obstructive pulmonary disease (COPD), and to explore the molecular mechanism of modified Erchentang on anti-inflammatory of COPD. Method: The model of rat with COPD was established by cigarette smoke combined with lipopolysaccharide (LPS). The experimental rats were randomly divided into 6 groups:normal group, model group, modified Erchentang high, medium and low dose group, and Jizhitangjiang group. Normal group and model group fed with normal saline 4 mL · d-1, modified Erchentang high, middle, low dosage group(20,10,5 g · kg-1 · d-1).The dosage of Jizhitangjiang group was 12 g · kg-1 · d-1, all groups were given intragastric administration for 14 days, twice a day. To observe the general situation of rats.To evaluate the pulmonary function of rats. To detect the contents of IL-10, IL-19 and IL-20 in serum by enzyme-linked immunosorbent assay (ELISA).To observe the pathological changes of bronchiole tissue by light microscopy.To detect the expression of IL-20R1 and IL-20R2 in bronchiole tissue by immunohistochemistry. Result: Compared with normal group, peak expiratory flow(PEF), forced expiratory volume in one second(FEV1), forced vital capacity (FVC), and FEV1/FVC in model group were significantly increased (PPP1 and in bronchioles tissue significantly increased (P1, FVC, FEV1/FVC of Jizhitangjiang group, modified Erchentang high, medium and low dosage group were significantly increased(PPP1 and IL-20R2 in bronchioles tissue was significantly decreased (PConclusion: Modified Erchentang can improve the lung function and protect the tissue structure of bronchioles in COPD rats, which may be related to the inhibition of the expression of IL-19, IL-20 and their receptor IL-20R1, IL-20R2 in bronchioles of rats with modified Erchentang.
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Objective: To explore the effect of modified Erchentang on the signal pathway of β2 adrenergicreceptor(β2AR)/arrestin beta 2(β-arrestin2) in rats with chronic obstructive pulmonary disease (COPD), and the expression of interleukin-17(IL-17) in serum, lung homogenate and bronchoalveolar lavage fluid. Method: Seventy SD rats were randomly divided into seven groups:normal group, model group, modified Erchentang with high, medium and low doses (40, 20, 10 g · kg-1 · d-1), Xiaokechuan group (5 g · kg-1 · d-1), modified Erchentang group (5 g · kg-1 · d-1), 10 rats in each group. The rat model of COPD was established by smoking and lipopolysaccharide (LPS) intratracheal drip. After successful modeling, the treatment group was given intragastric administration, while the normal group and the model group were given the same amount of saline. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of IL-17 in serum, lung homogenate and bronchoalveolar lavage fluid of rats. Real-time fluorescence quantitative PCR (Real-time PCR) was used to detect the expression of β2AR gene. Western blot was used to detect the expression of β2AR protein in lung tissue. The expression of β2AR and β-arrestin2 in lung tissue was detected by immunohistochemistry. Result: Compared with the normal group, the expression of β2AR protein in lung tissue of model group was significantly decreased(Pβ2AR protein in lung tissue was significantly increased(PPβ2AR in model group was significantly lower(Pβ2AR in high, medium and low dose group, Xiaokechuan group and modified Erchentang group was significantly higher(PPPPConclusion: Modified Erchentang may increase the expression of β2AR and β-arrestin2 and decrease the content of IL-17 in order to resist inflammation and improve pulmonary function in COPD rats.
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Objective: To explore the effect of modified Erchentang on peroxisome proliferator-activated receptor gamma (PPARγ) protein and gene expressions in lung tissue of chronic obstructive pulmonary disease (COPD) rat model, and the expressions of interleukin-6 (IL-6), interleukin-10 (IL-10) and tumor necrosis factor-alpha (TNF-α) in serum, lung homogenate and bronchoalveolar lavage fluid. Method: Seventy SD rats were randomly divided into seven groups:normal group, model group, high, medium and low-dose modified Erchentang groups (40, 20, 10 g · kg-1 · d-1), Xiaokechuan group (5 g · kg-1 · d-1), and Erchentang group (5 g · kg-1 · d-1). The rat COPD model was established through smoking and intratracheal instillation of lipopolysaccharide (LPS). After successful modeling, the treatment group was given drug by gavage, while the normal group and the model group were given the same amount of saline. The concentrations of IL-6, IL-10 and TNF-α in serum, lung homogenate and bronchoalveolar lavage fluid(BALF) of rats were measured by enzyme-linked immunosorbent assay (ELISA). Real-time fluorescence quantitative PCR (Real-time PCR) was used to detect the expression of peroxisome proliferator-activated receptor gamma (PPARγ), and immunohistochemistry (IHC) and Western blot were used to detect the expression of PPARγ in lung tissue. Result: Compared with the normal group, the levels of IL-6 and TNF-α in serum, lung homogenate and BALF of the model group rats increased significantly (PPγ mRNA in lung tissue of rats in model group were significantly decreased (Pγ protein was significantly inhibited(Pα in serum, lung homogenate and BALF of each treatment group decreased to varying degrees(Pα in the middle-dose Erchentang group were particularly significant. The PPARγ mRNA and protein expressions in lung tissue of rats in each treatment group were increased to varying degrees (PConclusion: Modified Erchentang may improve pulmonary inflammation and pulmonary function in COPD rats by increasing the expression of PPARγ and the content of IL-10 and decreasing the contents of IL-6 and TNF-α.