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 explore the influence of Linggui Zhugan Decoction(LGZGD)on high glucose induced podocyte autophagy Methods LGZGD containing serum were prepared by intragastric administation of 4.2 g·kg^(-1)(low dose...Objective To explore the influence of Linggui Zhugan Decoction(LGZGD)on high glucose induced podocyte autophagy Methods LGZGD containing serum were prepared by intragastric administation of 4.2 g·kg^(-1)(low dose),8.4 g·kg^(-1)(medium dose),and 12.6 g·kg^(-1)(high dose)LGZGD into SD rats respectively.MPC5 and AB8/13 cells were treated with 60 mmol/L glucose to establish diabetic nephropathy podocyte model in vitro.Podocytes,MPC5 and AB8.13,were divided into control group,high glucose group,low dose LGZGD group,medium dose LGZGD group,and high dose LGZGD group,respectively.For the three LGZGD groups,before LGZGD intervention,podocytes were treated with 60 mmol/L glucose for 3 days.After treated with LGZGD containing serum,cells were collected to analyze cell migration using Transwell assay,proliferation using CCK8,apoptosis and cell cycle using flow cytometry,,autophagosome formation using transmission electron microscopy,and expression levels of Beclin-1,Atg5,LC3II/I,and P62 proteins using western blot.Results Compared with the control group,the proliferation and migration of MPC5 and AB8.13 cells in high glucose group showed slightly decreased,whereas these parameters restored after intervention with low and medium concentrations of LGZGD,with the medium dose LGZGD having the best effect.Flow cytometry analysis showed that the medium dose LGZGD group had a lower apoptosis rate(P<0.05)and higher survival rate(P>0.05)compared to the high dose group.High glucose arrested podocytes in G1 phase,whereas LGZGD shifted podocytes from being predominant in G1 phase to increasing into G2.High dose LGZGD significanly reduced increased autophagosome formation due to high glucose in both podocytes(P<0.05).Western blot analysis showed that Beclin-1,Atg5,LC3Ⅱ/Ⅰ,and P62 expressions were increased in MPC5 cells treated with high glucose,and reversed after adminstration of low and medium doses of LGZGD(P<0.05).Conclusion LGZGD reduced apoptosis and enhanced autophagy in high glucose treated podocytes via regulating Beclin-1/LC3II/I/Atg5 expression.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
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
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.
文摘Objective To explore the influence of Linggui Zhugan Decoction(LGZGD)on high glucose induced podocyte autophagy Methods LGZGD containing serum were prepared by intragastric administation of 4.2 g·kg^(-1)(low dose),8.4 g·kg^(-1)(medium dose),and 12.6 g·kg^(-1)(high dose)LGZGD into SD rats respectively.MPC5 and AB8/13 cells were treated with 60 mmol/L glucose to establish diabetic nephropathy podocyte model in vitro.Podocytes,MPC5 and AB8.13,were divided into control group,high glucose group,low dose LGZGD group,medium dose LGZGD group,and high dose LGZGD group,respectively.For the three LGZGD groups,before LGZGD intervention,podocytes were treated with 60 mmol/L glucose for 3 days.After treated with LGZGD containing serum,cells were collected to analyze cell migration using Transwell assay,proliferation using CCK8,apoptosis and cell cycle using flow cytometry,,autophagosome formation using transmission electron microscopy,and expression levels of Beclin-1,Atg5,LC3II/I,and P62 proteins using western blot.Results Compared with the control group,the proliferation and migration of MPC5 and AB8.13 cells in high glucose group showed slightly decreased,whereas these parameters restored after intervention with low and medium concentrations of LGZGD,with the medium dose LGZGD having the best effect.Flow cytometry analysis showed that the medium dose LGZGD group had a lower apoptosis rate(P<0.05)and higher survival rate(P>0.05)compared to the high dose group.High glucose arrested podocytes in G1 phase,whereas LGZGD shifted podocytes from being predominant in G1 phase to increasing into G2.High dose LGZGD significanly reduced increased autophagosome formation due to high glucose in both podocytes(P<0.05).Western blot analysis showed that Beclin-1,Atg5,LC3Ⅱ/Ⅰ,and P62 expressions were increased in MPC5 cells treated with high glucose,and reversed after adminstration of low and medium doses of LGZGD(P<0.05).Conclusion LGZGD reduced apoptosis and enhanced autophagy in high glucose treated podocytes via regulating Beclin-1/LC3II/I/Atg5 expression.
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.
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.
