Objective: To explore the therapeutic effect of Linggui Zhugan Decoction on nonalcoholic fatty liver disease through in vivo animal experiments, and to explore the mechanism of action of Linggui Zhugan Decoction in th...Objective: To explore the therapeutic effect of Linggui Zhugan Decoction on nonalcoholic fatty liver disease through in vivo animal experiments, and to explore the mechanism of action of Linggui Zhugan Decoction in the intervention of nonalcoholic fatty liver disease through network pharmacology and molecular docking technology. Methods: A rat model of non- alcoholic fatty liver disease was established after 20 weeks of high-fat feeding, and the rats were divided into six groups, normal group, model group, simvastatin group (4 mg/kg), low- dose group of Linggui Zhugan Decoction (2.1 g/kg), medium-dose group of Linggui Zhugan Decoction (4.2 g/kg), and high-dose group of Linggui Zhugan Decoction (8.4 g/kg), and the liver morphological changes of HE staining and oil red O staining after the intervention of Linggui Zhugan Decoction were observed, and the microplate reader detected aspartate aminotransferase, alanine aminotransferase, Four levels of blood lipids. Network pharmacology combined with molecular docking was used to screen the potential mechanism and target of Linggui Zhugan Decoction for the intervention of non-alcoholic fatty liver disease. Results: Linggui Zhugan Decoction significantly improved the levels of alanine aminotransferase and alanine aminotransferase in model rats (P<0.05). HE staining and oil red O staining showed that Linggui Zhugan Decoction significantly reduced liver lipid deposition in rats in the model group. Linggui Zhugan Decoction could significantly reduce the quadruplical levels of blood lipids in model rats (P<0.05). Network pharmacology screened out 10 key targets and 5 key signaling pathways;The molecular docking results showed that the first 20 active ingredients all had good binding ability to the top 10 targets. Conclusion: The results show that Linggui Zhugan Decoction has the effect of regulating blood lipids and improving liver tissue lesions in non-alcoholic fatty liver disease, and preliminarily verifies the regulatory effect of Linggui Zhugan Decoction on lipid metabolism-related genes.展开更多
OBJECTIVE:To identify Cald1 as a novel regulator of Linggui Zhugan decoction(苓桂术甘汤)for improving insulin resistance in vivo and in vitro.METHODS:Sprague-Dawley rats were randomly assigned to 3 groups that were re...OBJECTIVE:To identify Cald1 as a novel regulator of Linggui Zhugan decoction(苓桂术甘汤)for improving insulin resistance in vivo and in vitro.METHODS:Sprague-Dawley rats were randomly assigned to 3 groups that were received a normal rat chow diet,high-fat diet(HFD),and an HFD plus LGZGD,respectively.The homeostatic model assessment(HOMA)-insulin resistance(IR)index was used to determine IR.Gene microarray methodology was used to identify differentially expressed genes(DEGs)in the three groups of rats.The DEGs associated with IR were confirmed by quantitative real-time polymerase chain reaction.Additionally,Mouse 3 T3-L1 pre-adipocytes were differentiated into mature 3 T3-L1 adipocytes,which were then treated with tumor necrosis factor(TNF)-αto induce cellular IR.Lipid accumulations were identified by Oil Red O staining.Glucose uptake was assessed using the3 H-2-DG test.RESULTS:In this study,we found Cald1 was further screened to validate its biological function in3 T3-L1 adipocytes induced to develop IR.In vitro experiments showed that insulin-stimulated 3 H-2-DG uptake by IR 3 T3-L1 adipocytes was increased after LGZGD intervention,which was associated with a down-regulation of Cald1 expression.CONCLUSION:LGZGD ameliorates HFD-induced IR in rats and TNF-αinduced IR in adipocytes by down-regulating Cald1 expression.展开更多
Objective:To investigate the inhibitory effect of Linggui Zhugan Decoction(LZD,苓桂术甘汤)on the ventricular remodeling(VR)after acute myocardial infarction(AMI)and related mRNA and proteins expression in transforming...Objective:To investigate the inhibitory effect of Linggui Zhugan Decoction(LZD,苓桂术甘汤)on the ventricular remodeling(VR)after acute myocardial infarction(AMI)and related mRNA and proteins expression in transforming growth factor-beta 1(TGF-β1)/Smad signaling pathway,and explain its putative mechanism.Methods:A VR model was generated by ligation of coronary artery in mice.Two weeks after surgery,60 mice were randomly divided into the model group,the sham-operation group(distilled water),the positive control group(2.4 mg/kg simvastatin),and the low-,medium-and high-dose LZD groups(2.1,4.2,8.4 g crude drug/kg,respectively)by a random number table,10 mice in each group.Mice in each group was treated for 4 weeks.Changes of hemodynamics indices and cardiac weight index were detected by the PowerLab data acquisition and analysis recording instrument.Morphology changes of myocardial tissue were observed by hematoxylin-eosin and Masson staining.The expressions of TGF-β1,Smad2,Smad3,p-Smad2 and p-Smad3 in myocardial tissue were detected by Western blotting.The mRNA expressions of TGF-β1,Smad2 and Smad3 were detected by reverse transcription-quantitative polymerase chain reaction(RT-qPCR).The expressions of matrix metalloprotein 2(MMP2),MMP9,collagenⅠand collagen Ⅲ were observed by immunohistochemical methods.Results:VR mice showed significant dysfunction in hemodynamic indices and cardiac structure and function.Compared with the shamoperation group,myocardial tissue damage,interstitial fibrosis occurred in the model mice,left ventricular systolic pressure(LVSP),left ventricular pressure maximum contraction rate(+dp/dtmax)and left ventricular pressure maximum relaxation rate(-dp/dtmax)decreased significantly(all P<0.01),while left ventricular end-diastolic pressure(LVEDP),cardiac weight index and left ventricular weight index elevated significantly,meanwhile TGF-β1,p-Smad2,p-Smad3,Smad2,Smad3,MMP2,MMP9,collagen Ⅰ,collagen Ⅲ protein expressions in myocardial tissue and TGF-β1 Smad2 and Smad3 mRNA expressions increased significantly(all P<0.01).Compared with the model group,LZD could significantly improve the pathological changes of myocardial tissue,increase LVSP,+dp/dtmax and-dp/dtmaxf lower LVEDP,reduce the whole heart weight index and left ventricular weight index and inhibit the over-expressions of TGF-β1f p-Smad2,p-Smad3,Smad2,Smad3,MMP2,MMP9,collagenⅠand collagenⅢproteins in myocardial tissue and mRNA expressions of TGF-β1 Smad2 and Smad3(P<0.05 or P<0.01).Conclusion:LZD can significantly suppress VR induced by AMI,and its underlying mechanism may be associated with its inhibitory effect on the TGF-β1/Smad signaling pathway.展开更多
OBJECTIVE:To observe the protective effects of modified Linggui Zhugan Decoction combined with short-term very low calorie diets(VLCDs) on cardiovascular risk factors in obese patients with impaired glucose tolerance(...OBJECTIVE:To observe the protective effects of modified Linggui Zhugan Decoction combined with short-term very low calorie diets(VLCDs) on cardiovascular risk factors in obese patients with impaired glucose tolerance(IGT).METHODS:Eighty-five obese patients with IGT of spleen hypofunction and dampness accumulation type were randomly divided into treated group(n=45)and control group(n=40).The treated group was given Linggui Zhugan Decoction combined short-term VLCDs.The control group was given basic weight-reduction treatment.The total course was 6 months.Changes of fasting plasma glucose(FPG),2-hour postprandial blood glucose(2hPG),glycosylated hemoglobin(HbA1c),fasting insulin(FINS),lipid metabolism,blood pressure,body mass index(BMI) and waist circumference(WC) were observed,and the outcomes were reviewed after the treatment.RESULTS:Compared with the control group,the levels of FPG,2hPG,HbA1c,FINS,HOMA-IR decreased significantly(P<0.05),and the indexes of total cholesterol(TC),triglyceride(TG),low-density lipoprotein(LDL),systolic blood pressure(SBP),diastolic blood pressure(DBP),BMI and WC were improved significantly(P<0.05) in the treated group.The transformation rate of normal glucose tolerance(NGT) was higher in treatment group than control group(P<0.01).No severe adverse reaction was found in the therapeutic course.CONCLUSION:The modified Linggui Zhugan Decoction combined with short-term VLCDs has good protective effects on cardiovascular risk factors as a treatment intervention for IGT with obesity,as it could improve glycometabolism,significantly decrease the levels of blood pressure,blood lipids,BMI,WC and effectively cut-off and reverse the development of diabetes mellitus.展开更多
Objective:To evaluate the effects of the modified Linggui Zhugan Decoction(加味苓桂术甘汤) combined with short-term very low calorie diets(VLCDs) on glycemic control in newly diagnosed type 2 diabetes mellitus(T2DM) p...Objective:To evaluate the effects of the modified Linggui Zhugan Decoction(加味苓桂术甘汤) combined with short-term very low calorie diets(VLCDs) on glycemic control in newly diagnosed type 2 diabetes mellitus(T2DM) patients.Methods:A total of 20 subjects with newly diagnosed T2DM were treated with the modified Linggui Zhugan Decoction(one-month administration) combined with short-term VLCDs(5 days),and 3-months follow-up.A standard 75-g oral-glucose-tolerance test(OGTT) indexes fasting plasma glucose(FPG),post-prandial 0.5 h and 2 h plasma glucose(P0.5hPG,P2hPG),glycated hemoglobin A1C(GHbA1C),body weight,body mass index(BMI),insulin function,insulin resistance index,incidence of hypoglycemia,and the liver and renal functions were evaluated before and after treatment.Correlations of BMI with insulin function and insulin resistance were also assessed.Results:After the treatment,the patients' plasma glucose decreased steadily,FPG decreased from 5.8±0.9 mmol/L at pre-treatment to 5.0±0.6 mmol/L at 3-months follow-up(P<0.05),and P2hPG decreased from 11.7±3.8 mmol/L at pre-treatment to 6.9±0.9 mmol/L at 3-months follow-up(P<0.01).The level of GHbA1C declined from(6.47±1.24)% at pre-treatment to(6.14±0.99)% at 3-months follow-up(P<0.01).Body weight and BMI also declined significantly.Insulin resistance index was improved obviously and no event of hypoglycemia occurred.Part of the patients companied with fatty liver had a transient increase in hepatic transaminase during the treatment,but it turned to normal after the treatment.Conclusions:The modified Linggui Zhugan Decoction combined with short-term VLCDs can be safely implemented for steady glycemic control in newly diagnosed T2DM patients.展开更多
基金Anhui Natural Science Foundat ion General Project(No.2208085MH277)。
文摘Objective: To explore the therapeutic effect of Linggui Zhugan Decoction on nonalcoholic fatty liver disease through in vivo animal experiments, and to explore the mechanism of action of Linggui Zhugan Decoction in the intervention of nonalcoholic fatty liver disease through network pharmacology and molecular docking technology. Methods: A rat model of non- alcoholic fatty liver disease was established after 20 weeks of high-fat feeding, and the rats were divided into six groups, normal group, model group, simvastatin group (4 mg/kg), low- dose group of Linggui Zhugan Decoction (2.1 g/kg), medium-dose group of Linggui Zhugan Decoction (4.2 g/kg), and high-dose group of Linggui Zhugan Decoction (8.4 g/kg), and the liver morphological changes of HE staining and oil red O staining after the intervention of Linggui Zhugan Decoction were observed, and the microplate reader detected aspartate aminotransferase, alanine aminotransferase, Four levels of blood lipids. Network pharmacology combined with molecular docking was used to screen the potential mechanism and target of Linggui Zhugan Decoction for the intervention of non-alcoholic fatty liver disease. Results: Linggui Zhugan Decoction significantly improved the levels of alanine aminotransferase and alanine aminotransferase in model rats (P<0.05). HE staining and oil red O staining showed that Linggui Zhugan Decoction significantly reduced liver lipid deposition in rats in the model group. Linggui Zhugan Decoction could significantly reduce the quadruplical levels of blood lipids in model rats (P<0.05). Network pharmacology screened out 10 key targets and 5 key signaling pathways;The molecular docking results showed that the first 20 active ingredients all had good binding ability to the top 10 targets. Conclusion: The results show that Linggui Zhugan Decoction has the effect of regulating blood lipids and improving liver tissue lesions in non-alcoholic fatty liver disease, and preliminarily verifies the regulatory effect of Linggui Zhugan Decoction on lipid metabolism-related genes.
基金Supported by the 2016 Shenzhen Science and Technology Commission project fund(Mechanisms of Traditional Chinese Medicine Fasting treatment on insulin resistance caused by spleen deficiency and phlegm dampness based on proteomics,No.JCYJ20160427185421516)。
文摘OBJECTIVE:To identify Cald1 as a novel regulator of Linggui Zhugan decoction(苓桂术甘汤)for improving insulin resistance in vivo and in vitro.METHODS:Sprague-Dawley rats were randomly assigned to 3 groups that were received a normal rat chow diet,high-fat diet(HFD),and an HFD plus LGZGD,respectively.The homeostatic model assessment(HOMA)-insulin resistance(IR)index was used to determine IR.Gene microarray methodology was used to identify differentially expressed genes(DEGs)in the three groups of rats.The DEGs associated with IR were confirmed by quantitative real-time polymerase chain reaction.Additionally,Mouse 3 T3-L1 pre-adipocytes were differentiated into mature 3 T3-L1 adipocytes,which were then treated with tumor necrosis factor(TNF)-αto induce cellular IR.Lipid accumulations were identified by Oil Red O staining.Glucose uptake was assessed using the3 H-2-DG test.RESULTS:In this study,we found Cald1 was further screened to validate its biological function in3 T3-L1 adipocytes induced to develop IR.In vitro experiments showed that insulin-stimulated 3 H-2-DG uptake by IR 3 T3-L1 adipocytes was increased after LGZGD intervention,which was associated with a down-regulation of Cald1 expression.CONCLUSION:LGZGD ameliorates HFD-induced IR in rats and TNF-αinduced IR in adipocytes by down-regulating Cald1 expression.
基金Supported by the National Natural Science Foundatio of China(No.30973707,81373533,81202631)the Natural Science Foundation of Anhui Province(NO.1508085QH192,1608085QH222)。
文摘Objective:To investigate the inhibitory effect of Linggui Zhugan Decoction(LZD,苓桂术甘汤)on the ventricular remodeling(VR)after acute myocardial infarction(AMI)and related mRNA and proteins expression in transforming growth factor-beta 1(TGF-β1)/Smad signaling pathway,and explain its putative mechanism.Methods:A VR model was generated by ligation of coronary artery in mice.Two weeks after surgery,60 mice were randomly divided into the model group,the sham-operation group(distilled water),the positive control group(2.4 mg/kg simvastatin),and the low-,medium-and high-dose LZD groups(2.1,4.2,8.4 g crude drug/kg,respectively)by a random number table,10 mice in each group.Mice in each group was treated for 4 weeks.Changes of hemodynamics indices and cardiac weight index were detected by the PowerLab data acquisition and analysis recording instrument.Morphology changes of myocardial tissue were observed by hematoxylin-eosin and Masson staining.The expressions of TGF-β1,Smad2,Smad3,p-Smad2 and p-Smad3 in myocardial tissue were detected by Western blotting.The mRNA expressions of TGF-β1,Smad2 and Smad3 were detected by reverse transcription-quantitative polymerase chain reaction(RT-qPCR).The expressions of matrix metalloprotein 2(MMP2),MMP9,collagenⅠand collagen Ⅲ were observed by immunohistochemical methods.Results:VR mice showed significant dysfunction in hemodynamic indices and cardiac structure and function.Compared with the shamoperation group,myocardial tissue damage,interstitial fibrosis occurred in the model mice,left ventricular systolic pressure(LVSP),left ventricular pressure maximum contraction rate(+dp/dtmax)and left ventricular pressure maximum relaxation rate(-dp/dtmax)decreased significantly(all P<0.01),while left ventricular end-diastolic pressure(LVEDP),cardiac weight index and left ventricular weight index elevated significantly,meanwhile TGF-β1,p-Smad2,p-Smad3,Smad2,Smad3,MMP2,MMP9,collagen Ⅰ,collagen Ⅲ protein expressions in myocardial tissue and TGF-β1 Smad2 and Smad3 mRNA expressions increased significantly(all P<0.01).Compared with the model group,LZD could significantly improve the pathological changes of myocardial tissue,increase LVSP,+dp/dtmax and-dp/dtmaxf lower LVEDP,reduce the whole heart weight index and left ventricular weight index and inhibit the over-expressions of TGF-β1f p-Smad2,p-Smad3,Smad2,Smad3,MMP2,MMP9,collagenⅠand collagenⅢproteins in myocardial tissue and mRNA expressions of TGF-β1 Smad2 and Smad3(P<0.05 or P<0.01).Conclusion:LZD can significantly suppress VR induced by AMI,and its underlying mechanism may be associated with its inhibitory effect on the TGF-β1/Smad signaling pathway.
基金Supported by International Science and Technology Cooperation Program of Guangdong Province(No.2009B050700 022)
文摘OBJECTIVE:To observe the protective effects of modified Linggui Zhugan Decoction combined with short-term very low calorie diets(VLCDs) on cardiovascular risk factors in obese patients with impaired glucose tolerance(IGT).METHODS:Eighty-five obese patients with IGT of spleen hypofunction and dampness accumulation type were randomly divided into treated group(n=45)and control group(n=40).The treated group was given Linggui Zhugan Decoction combined short-term VLCDs.The control group was given basic weight-reduction treatment.The total course was 6 months.Changes of fasting plasma glucose(FPG),2-hour postprandial blood glucose(2hPG),glycosylated hemoglobin(HbA1c),fasting insulin(FINS),lipid metabolism,blood pressure,body mass index(BMI) and waist circumference(WC) were observed,and the outcomes were reviewed after the treatment.RESULTS:Compared with the control group,the levels of FPG,2hPG,HbA1c,FINS,HOMA-IR decreased significantly(P<0.05),and the indexes of total cholesterol(TC),triglyceride(TG),low-density lipoprotein(LDL),systolic blood pressure(SBP),diastolic blood pressure(DBP),BMI and WC were improved significantly(P<0.05) in the treated group.The transformation rate of normal glucose tolerance(NGT) was higher in treatment group than control group(P<0.01).No severe adverse reaction was found in the therapeutic course.CONCLUSION:The modified Linggui Zhugan Decoction combined with short-term VLCDs has good protective effects on cardiovascular risk factors as a treatment intervention for IGT with obesity,as it could improve glycometabolism,significantly decrease the levels of blood pressure,blood lipids,BMI,WC and effectively cut-off and reverse the development of diabetes mellitus.
基金supported by International Science and Technology Cooperation Program of Guangdong Province (No. 2009B050700022)
文摘Objective:To evaluate the effects of the modified Linggui Zhugan Decoction(加味苓桂术甘汤) combined with short-term very low calorie diets(VLCDs) on glycemic control in newly diagnosed type 2 diabetes mellitus(T2DM) patients.Methods:A total of 20 subjects with newly diagnosed T2DM were treated with the modified Linggui Zhugan Decoction(one-month administration) combined with short-term VLCDs(5 days),and 3-months follow-up.A standard 75-g oral-glucose-tolerance test(OGTT) indexes fasting plasma glucose(FPG),post-prandial 0.5 h and 2 h plasma glucose(P0.5hPG,P2hPG),glycated hemoglobin A1C(GHbA1C),body weight,body mass index(BMI),insulin function,insulin resistance index,incidence of hypoglycemia,and the liver and renal functions were evaluated before and after treatment.Correlations of BMI with insulin function and insulin resistance were also assessed.Results:After the treatment,the patients' plasma glucose decreased steadily,FPG decreased from 5.8±0.9 mmol/L at pre-treatment to 5.0±0.6 mmol/L at 3-months follow-up(P<0.05),and P2hPG decreased from 11.7±3.8 mmol/L at pre-treatment to 6.9±0.9 mmol/L at 3-months follow-up(P<0.01).The level of GHbA1C declined from(6.47±1.24)% at pre-treatment to(6.14±0.99)% at 3-months follow-up(P<0.01).Body weight and BMI also declined significantly.Insulin resistance index was improved obviously and no event of hypoglycemia occurred.Part of the patients companied with fatty liver had a transient increase in hepatic transaminase during the treatment,but it turned to normal after the treatment.Conclusions:The modified Linggui Zhugan Decoction combined with short-term VLCDs can be safely implemented for steady glycemic control in newly diagnosed T2DM patients.
