1.Effect of Mori Folium-Ginseng Radix et Rhizoma on Glucose and Lipid Metabolism and Mechanism in Mouse Model of Type 2 Diabetes Mellitus
Congyi LIU ; Ning WANG ; Jingjing XU ; Tingting WANG ; Na ZHENG ; Zimeng HUANG ; Lingling QIN ; Lili WU ; Tonghua LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):20-28
ObjectiveTo study the effect of the herb pair Mori Folium-Ginseng Radix et Rhizoma (HMG) on glucose and lipid metabolism in the mouse model of type 2 diabetes mellitus and decipher the possible treatment mechanism. MethodsThe db/db mice were chosen as the mouse model of type 2 diabetes mellitus and then treated with HMG at low and high doses (1.56, 3.12 g∙kg-1, respectively) or metformin (0.26 g∙kg-1) by gavage for 6 weeks. The normal group and the model group were treated with double distilled water at the same time according to body weight. The 8-h fasting blood glucose and body weight were measured once a week. The oral glucose tolerance test (OGTT) was conducted at the 6th week of dosing. The mice were sacrificed after the end of dosing. Serum levels of lipids [total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL), and low-density lipoprotein cholesterol (LDL)], liver function indicators [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)], non-esterified fatty acids (NEFA), glycosylated serum protein (GSP), serum glucose (GLU), fasting insulin (FINS), and renal function indicators [creatinine (Crea) and blood urea nitrogen (BUN)] were measured by enzyme-linked immunosorbent assay. The protein levels of peroxidase proliferator-activating receptor gamma (PPARγ), acetyl coenzyme A carboxylase (ACC), and sterol regulatory element-binding protein-1 (SREBP-1) were determined by Western blot. The pathological changes in the liver and pancreas were examined. ResultsCompared with the normal group, the model group presented increased body weight, elevated levels of blood glucose, TG, TC, AST, ALT, GLU, NEFA, GSP, and HDL-C, up-regulated protein levels of ACC and SREBP-1, and down-regulated protein level of PPARγ (P<0.01). Meanwhile, the model group presented a large amount of lipid droplets and steatosis in the liver, as well as karyopyknosis and lymphocyte infiltration in the pancreas. Compared with the model group, the high- and low-dose HMG groups showed decreased body weight, declined levels of blood glucose, TG, TC, AST, ALT, GLU, NEFA, and GSP, and elevate level of HDL-C (P<0.05, P<0.01). Moreover, the two groups showcased reduced lipid droplets and steatosis in the liver, as well as enlarged islets with clear boundaries and alleviated lymphocyte infiltration and karyopyknosis. Western blot results showed that the high-dose herb pair group demonstrated down-regulated protein levels of ACC and SREBP-1 and up-regulated protein level of PPARγ (P<0.01). ConclusionThe HMG can effectively improve the glucose and lipid metabolism in db/db mice by regulating the expression of PPARγ, SREBP-1, and ACC.
2.Effect of Mori Folium-Ginseng Radix et Rhizoma on Glucose and Lipid Metabolism and Mechanism in Mouse Model of Type 2 Diabetes Mellitus
Congyi LIU ; Ning WANG ; Jingjing XU ; Tingting WANG ; Na ZHENG ; Zimeng HUANG ; Lingling QIN ; Lili WU ; Tonghua LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):20-28
ObjectiveTo study the effect of the herb pair Mori Folium-Ginseng Radix et Rhizoma (HMG) on glucose and lipid metabolism in the mouse model of type 2 diabetes mellitus and decipher the possible treatment mechanism. MethodsThe db/db mice were chosen as the mouse model of type 2 diabetes mellitus and then treated with HMG at low and high doses (1.56, 3.12 g∙kg-1, respectively) or metformin (0.26 g∙kg-1) by gavage for 6 weeks. The normal group and the model group were treated with double distilled water at the same time according to body weight. The 8-h fasting blood glucose and body weight were measured once a week. The oral glucose tolerance test (OGTT) was conducted at the 6th week of dosing. The mice were sacrificed after the end of dosing. Serum levels of lipids [total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL), and low-density lipoprotein cholesterol (LDL)], liver function indicators [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)], non-esterified fatty acids (NEFA), glycosylated serum protein (GSP), serum glucose (GLU), fasting insulin (FINS), and renal function indicators [creatinine (Crea) and blood urea nitrogen (BUN)] were measured by enzyme-linked immunosorbent assay. The protein levels of peroxidase proliferator-activating receptor gamma (PPARγ), acetyl coenzyme A carboxylase (ACC), and sterol regulatory element-binding protein-1 (SREBP-1) were determined by Western blot. The pathological changes in the liver and pancreas were examined. ResultsCompared with the normal group, the model group presented increased body weight, elevated levels of blood glucose, TG, TC, AST, ALT, GLU, NEFA, GSP, and HDL-C, up-regulated protein levels of ACC and SREBP-1, and down-regulated protein level of PPARγ (P<0.01). Meanwhile, the model group presented a large amount of lipid droplets and steatosis in the liver, as well as karyopyknosis and lymphocyte infiltration in the pancreas. Compared with the model group, the high- and low-dose HMG groups showed decreased body weight, declined levels of blood glucose, TG, TC, AST, ALT, GLU, NEFA, and GSP, and elevate level of HDL-C (P<0.05, P<0.01). Moreover, the two groups showcased reduced lipid droplets and steatosis in the liver, as well as enlarged islets with clear boundaries and alleviated lymphocyte infiltration and karyopyknosis. Western blot results showed that the high-dose herb pair group demonstrated down-regulated protein levels of ACC and SREBP-1 and up-regulated protein level of PPARγ (P<0.01). ConclusionThe HMG can effectively improve the glucose and lipid metabolism in db/db mice by regulating the expression of PPARγ, SREBP-1, and ACC.
3.Protein biomarker screening and functional analysis of salivary exosomes in patients with ulcerative colitis
Congyi YANG ; Xiaowen ZHENG ; Jingyi CHEN ; Jun XU ; Feng CHEN ; Yang CHEN ; Ning CHEN
Journal of Peking University(Health Sciences) 2025;57(5):895-902
Objective:To identify protein markers that may be associated with ulcerative colitis(UC)by analyzing differential proteins in the salivary exosomes from newly diagnosed patients with active UC and healthy controls(HC),and to investigate the function of salivary exosome-specific high-expression proteins in UC patients and their potential role in the pathogenesis of UC.Methods:All patients and healthy controls were recruited from Peking University People's Hospital.Whole saliva was obtained from 37 patients with newly diagnosed active ulcerative colitis(n=37)and apparently healthy controls(n=10).Salivary exosomes were extracted from samples,and the proteins within the exosomes were identi-fied by liquid chromatograph-mass spectrometer(LC-MS/MS).The differentially expressed protein genes underwent gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)enrichment analysis using the DAVID tool.In vitro,macrophages were co-cultured with salivary exosomes from UC group and those from HC group,respectively,and real-time quantitative polymerase chain reaction(qPCR)was used to detect levels of CD80+and CD86+.Additionally,ELISA was performed to measure secretion levels of interleukin-6(IL-6),interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α)in the cell supernatant.Results:A total of 259 proteins were co-expressed in saliva exosomes from UC group and HC group,among which 11 proteins were highly expressed in the UC group,including PDIA4,A2M,EEF2,C3,PSMA2,PSMB6,PSMA1,IGHG1,IGHG3,IGHG4 and SERPING1,while 4 proteins were lowly expressed in UC group,including TCN1,SLPI and SERPING.Functional analysis of these 15 pro-teins,along with 129 specific proteins found only in the UC patients and 69 specific proteins found only in HC patients,respectively,was conducted using GO/KEGG.The results revealed that in the UC group,proteasome-related proteins such as PSMA1,PSMA2 and PSMB6 expressions were increased in salivary ex-osomes while many key molecules involved in complement cascade pathways,such as C3 were up-regu-lated.In vitro co-culture experiments demonstrated that compared with healthy controls,the salivary exo-somes of the UC patients in active stage could play a pro-inflammatory role by promoting the transformation of macrophages into M1 type cells that secrete inflammatory factors IL-1β,IL-6 and TNF-α.Conclusion:Salivary exosomes in the UC patients may have the function of promoting inflammation.Analysis of protein levels in the saliva of the UC patients and healthy controls revealed significant differences in the expression levels of 15 co-expressed proteins between the two groups.Among them,C3,PSMA2,PSMB6 and PSMA1 were found to be mainly related to immune and inflammatory reactions in the UC group.These findings sug-gest that proteins with high specific expression in salivary exosomes of the UC patients have the potential to be used as a disease marker for UC diagnosis and may contribute to the pathogenesis of UC.
4.Mechanistic study on the male flower of Eucommia ulmoides-Sanchi flower herb pair for improving glucose and lipid metabolism in type 2 diabetes mellitus model mice
Ning WANG ; Congyi LIU ; Ying DING ; Xinyu ZHONG ; Zimeng HUANG ; Na ZHENG ; Qiu'e ZHANG ; Ruifeng YANG ; Lili WU ; Lingling QIN ; Tonghua LIU
Journal of Beijing University of Traditional Chinese Medicine 2025;48(10):1390-1403
Objective Based on the traditional Chinese medicine theory of"simultaneous regulation of the liver and kidney,"this study integrated network pharmacology prediction,molecular docking,and animal experimental validation to analyze the multi-target regulatory network of Duzhong Xionghua(the male flower of Eucommia ulmoides)-Sanqi Hua(Sanchi flower)herb pair(hereinafter called"herb pair")in modulating glucolipid metabolic disorders in type 2 diabetes mellitus(T2DM),thereby elucidating its underlying molecular mechanism.Methods Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,China National Knowledge Infrastructure,VIP Database for Chinese Technical Periodicals,and Wanfang Data were used to obtain the active ingredients of the male flower of Eucommia ulmoides and Sanchi flower.PubChem Compound,SwissTargetPrediction,and SuperPred were used to screen and predict the targets of the drugs;The Human Gene Database,The Online Mendelian Inheritance in Man,and Therapeutic Target Database were used to screen the key gene targets of T2DM.A"component-target-pathway"network diagram was constructed using Cytoscape software,and Gene Ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were employed to identify the functions of the relevant target genes and pathways.Molecular docking was used to verify the binding activities of the core components and the key targets.For animal experiments,spontaneous T2DM model mice were used,in which the normal group consisted of six mice(wild type)from the same litter,and the 24 successfully modeled mice were randomly divided into model,metformin(0.26 g/kg),high-dose herb pair(2.6 g/kg),and low-dose herb pair groups(1.3 g/kg)according to the blood glucose levels and body weights,with six mice per group.The drugs were administered by gavage daily for six consecutive weeks.The body weight and fasting blood glucose(FBG)levels were measured weekly,and an oral glucose tolerance test was performed in the fifth week.At the end of drug administration,body weight,naso-anal length,liver and bilateral epididymal adipose mass were measured;pathological changes in the liver were observed using HE staining;serum levels of aspartate transaminase(AST),alanine amino-transferase(ALT),total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C)were detected using colorimetric assay;and liver tissue phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)/glycogen synthase kinase-3β(GSK-3β)signaling pathway protein expressions were determined using Western blotting.Results Network pharmacology screening identified 38 active components and 669 potential targets of the herb pair.Intersection analysis with 1,275 T2DM-related targets yielded 185 common targets.Protein-protein interaction network analysis and pathway enrichment revealed the PI3K/AKT signaling pathway as a key mechanism.Molecular docking confirmed the strong binding affinity of the core components to key targets such as AKT1,suggesting that the herb pair may activate the PI3K/AKT pathway and inhibit GSK-3β activity via beta-sitosterol etc.Animal experiments demonstrated that,compared with the model group,the metformin group exhibited reduced FBG,AST,and ALT levels(P<0.01),but failed to improve body weight,Lee's index,or epididymal fat coefficient.Both herb pair doses significantly lowered Lee's index,hepatic index,and the epididymal fat coefficient(P<0.01),with the low-dose herb pair group showing attenuated body weight gain in mice.In contrast,the high-dose herb pair group exhibited decreased FBG,improved glucose tolerance,reduced TC,TG,and LDL-C levels,and increased HDL-C level(all P<0.01).HE staining revealed that all metformin and the herb pair markedly restored hepatic structure and alleviated steatosis in model mice,with more pronounced effects in the high-dose group than in the low-dose group.Western blotting result indicated that in the low-dose herb pair group,phospho-PI3K(p-PI3K),AKT,and phospho-GSK-3β(p-GSK-3β)protein expressions significantly increased(P<0.05 or P<0.01),whereas GSK-3β decreased(P<0.05).The high-dose group exhibited enhanced PI3K,p-PI3K,AKT,phospho-AKT,and p-GSK-3β protein expressions(all P<0.01),accompanied by reduced GSK-3β expression(P<0.01).Conclusion The male flower of Eucommia ulmoides-Sanchi flower herb pair may ameliorate T2DM-related glucolipid metabolic disorders by modulating the PI3K/AKT/GSK-3β pathway.
5.Feature of Cardiovascular-kidney-metabolic Syndrome Among Ethnic Minorities in Yunnan,China
Nuerguli TUERDI ; Xue CAO ; Yujie ZHANG ; Zixuan DONG ; Weiping LI ; Fan LI ; Xin WANG ; Congyi ZHENG ; Yixin TIAN ; Chenye CHANG ; Xuyan PEI ; Qinglan JIA ; Jialu YANG ; Zengwu WANG
Chinese Circulation Journal 2025;40(10):1022-1029
Objectives:To investigate the epidemiological characteristics and ethnic differences of cardiovascular-kidney-metabolic syndrome(CKM)among the Hani,Dai,Bai,and Lisu populations in Yunnan Province,and to provide evidence for developing effective prevention and control strategies for CKM.Methods:A cross-sectional survey was conducted among four ethnic minority groups.A total of 3 906 permanent residents aged 18 years and older were enrolled using a multistage cluster random sampling method.CKM stages(0-4)were defined based on the 2023 American Heart Association criteria,stages 3-4 were classified as advanced CKM.Descriptive statistics and chi-square tests were used to compare the prevalence of CKM stages across ethnic groups.Modified Poisson regression was applied to estimate relative risk(RR)and 95%confidence intervals(CI)for factors associated with advanced CKM.Results:The prevalence rates of CKM stage 1 and above among the Hani,Dai,Bai and Lisu ethnic groups were 80.1%,87.3%,84.8%and 67.8%,respectively.The prevalence of CKM was generally higher in males than in females,and the prevalence of CKM increased significantly with age.The Dai ethnic group had the highest prevalence of advanced CKM(24.7%,95%CI:22.1%-27.4%),while the Lisu ethnic group had the lowest prevalence of advanced CKM(13.7%,95%CI:11.5%-15.9%).Modified Poisson regression analysis showed that older age and higher body mass index were common risk factors for advanced CKM across all four ethnic groups.Additionally,except for the Lisu ethnic group,the other three ethnic groups had specific individual risk factors:among the Hani ethnic group,low educational attainment(RR=2.18,95%CI:1.12-4.25)and low income(RR=1.47,95%CI:1.00-2.18)were the primary risk factors of CKM.Among the Dai ethnic group,smoking(RR=1.60,95%CI:1.07-2.37)and a family history of cardiovascular disease(RR=1.61,95%CI:1.14-2.27)are the primary risk factors of CKM.Among the Bai ethnic group,male gender(RR=0.48,95%CI:0.29-0.79)was the primary risk factor of CKM.Conclusions:The prevalence of CKM stage 1 or higher is relatively high among the four minority ethnic groups in Yunnan province.There are significant differences in staging characteristics and primary risk factors across ethnic groups,necessitating the development of stratified,differentiated intervention strategies to achieve precise prevention and control and ethnic health equity in terms of CKM.
6.Research Progress on Traditional Chinese Medicine Treatment of Nonalcoholic Fatty Liver Based on NF-κB Signaling Pathway
Congyi LIU ; Na ZHENG ; Jingjing XU ; Ning WANG ; Zimeng HUANG ; Ying DING ; Lingling QIN ; Lili WU ; Tonghua LIU
World Science and Technology-Modernization of Traditional Chinese Medicine 2025;27(9):2553-2568
Non-alcoholic fatty liver disease(NAFLD)is a progressive liver disease caused by factors other than alcohol caused by heterotopic fat accumulation in the liver.In recent years,the incidence rate has been increasing,and there is no specific clinical drug.Studies have found that nuclear transcription factor κB(NF-κB)can activate inflammation and oxidative stress,which plays an important role in the pathogenesis of NAFLD.Traditional Chinese medicine is convenient to obtain and cheap.It can treat NAFLD through multiple channels with good clinical efficacy,and no obvious side effects have been found till now.Many studies have shown that traditional Chinese medicine can inhibit the occurrence and development of NAFLD by inhibiting the NF-κB signaling pathway.This article summarizes the research results of traditional Chinese medicine in treating NAFLD based on the NF-κB signaling pathway since 2021,for several traditional Chinese medicine extracts(flavonoids,terpenoids,polysaccharides,glycosides,alkaloids and phenolic compounds)and traditional Chinese medicine compound(Shugan Jianpi Fang,Erhuang Quzhi Granules,Fuzi Lizhong Decoction,Huangqin Decoction,Qinlian Hongqu Decoction,Jiangzhi Granules),which can inhibit the further development of NAFLD by improving liver inflammatory response,oxidative stress response,fibrosis,apoptosis,autophagy and pyroptosis through the NF-κB signaling pathway,in order to provide new ideas for future new drug development and clinical medication.
7.Feature of Cardiovascular-kidney-metabolic Syndrome Among Ethnic Minorities in Yunnan,China
Nuerguli TUERDI ; Xue CAO ; Yujie ZHANG ; Zixuan DONG ; Weiping LI ; Fan LI ; Xin WANG ; Congyi ZHENG ; Yixin TIAN ; Chenye CHANG ; Xuyan PEI ; Qinglan JIA ; Jialu YANG ; Zengwu WANG
Chinese Circulation Journal 2025;40(10):1022-1029
Objectives:To investigate the epidemiological characteristics and ethnic differences of cardiovascular-kidney-metabolic syndrome(CKM)among the Hani,Dai,Bai,and Lisu populations in Yunnan Province,and to provide evidence for developing effective prevention and control strategies for CKM.Methods:A cross-sectional survey was conducted among four ethnic minority groups.A total of 3 906 permanent residents aged 18 years and older were enrolled using a multistage cluster random sampling method.CKM stages(0-4)were defined based on the 2023 American Heart Association criteria,stages 3-4 were classified as advanced CKM.Descriptive statistics and chi-square tests were used to compare the prevalence of CKM stages across ethnic groups.Modified Poisson regression was applied to estimate relative risk(RR)and 95%confidence intervals(CI)for factors associated with advanced CKM.Results:The prevalence rates of CKM stage 1 and above among the Hani,Dai,Bai and Lisu ethnic groups were 80.1%,87.3%,84.8%and 67.8%,respectively.The prevalence of CKM was generally higher in males than in females,and the prevalence of CKM increased significantly with age.The Dai ethnic group had the highest prevalence of advanced CKM(24.7%,95%CI:22.1%-27.4%),while the Lisu ethnic group had the lowest prevalence of advanced CKM(13.7%,95%CI:11.5%-15.9%).Modified Poisson regression analysis showed that older age and higher body mass index were common risk factors for advanced CKM across all four ethnic groups.Additionally,except for the Lisu ethnic group,the other three ethnic groups had specific individual risk factors:among the Hani ethnic group,low educational attainment(RR=2.18,95%CI:1.12-4.25)and low income(RR=1.47,95%CI:1.00-2.18)were the primary risk factors of CKM.Among the Dai ethnic group,smoking(RR=1.60,95%CI:1.07-2.37)and a family history of cardiovascular disease(RR=1.61,95%CI:1.14-2.27)are the primary risk factors of CKM.Among the Bai ethnic group,male gender(RR=0.48,95%CI:0.29-0.79)was the primary risk factor of CKM.Conclusions:The prevalence of CKM stage 1 or higher is relatively high among the four minority ethnic groups in Yunnan province.There are significant differences in staging characteristics and primary risk factors across ethnic groups,necessitating the development of stratified,differentiated intervention strategies to achieve precise prevention and control and ethnic health equity in terms of CKM.
8.Research on the pattern and influencing factors of cardiometabolic multimorbidity in China
Yifei WANG ; Zengwu WANG ; Congyi ZHENG ; Xin WANG ; Yixin TIAN ; Xue CAO ; Ruihua FENG
Chinese Journal of Cardiology 2025;53(7):792-798
Objective:To investigate the prevalence, comorbidity patterns, and associated factors of cardiometabolic multimorbidity (CMM) in China.Methods:From 2012 to 2015, a total of 34 994 residents aged ≥35 years were enrolled using a stratified multistage random sampling method across 31 provinces, autonomous regions, and municipalities in China. Data were collected through questionnaires, covering demographic characteristics, behavioral and lifestyle factors, and self-reported history of cardiometabolic diseases. CMM was defined as the coexistence of two or more cardiometabolic diseases in the same individual. Association rule analysis using the Apriori algorithm from the arules package was employed to identify strong CMM patterns. Multivariable logistic regression was employed to explore factors associated with CMM.Results:The mean age of the participants was 55.6 years. Among them, 15 926 were male (45.51%). The prevalence of cardiometabolic multimorbidity (CMM) was 11.25% (3 937/34 994). A total of 35 distinct CMM combinations (each with a frequency ≥10) were identified. The most prevalent dyad, triad, and tetrad comorbidity patterns were hypertension+hyperlipidemia (1 036 cases), hypertension+hyperlipidemia+diabetes (352 cases), and hypertension+stroke+hyperlipidemia+diabetes (54 cases), respectively. Nine strong CMM patterns were identified using the Apriori association rule algorithm. Multivariable logistic regression analysis showed that older age (≥70 years: OR=17.39,95% CI 13.92-21.71, P<0.01), junior high school education ( OR=1.31, 95% CI 1.17-1.48, P<0.01), senior high school or above education ( OR=1.45, 95% CI 1.27-1.65, P<0.01), retirement ( OR=3.09, 95% CI 2.76-3.46, P<0.01), unemployment or being laid-off ( OR=1.16, 95% CI 1.06-1.28, P<0.01), a family history of cardiometabolic disease ( OR=4.37, 95% CI 4.04-4.72, P<0.01), regular smoking ( OR=1.38, 95% CI 1.24-1.53, P<0.05), and occasional smoking ( OR=1.21, 95% CI 1.00-1.49, P<0.01) were significantly associated with an increased risk of CMM. Conclusion:The prevalence of cardiometabolic multimorbidity in China is relatively high, with the most common comorbidity patterns involving combinations of hypertension and hyperlipidemia, often accompanied by diabetes and stroke. Older age, retirement status, smoking, and a family history of cardiovascular disease are associated with an increased risk of both single and multiple cardiometabolic conditions. Greater attention should be paid to individuals with a single cardiometabolic disorder due to their elevated risk of developing multimorbidity.
9.Mechanistic study on the male flower of Eucommia ulmoides-Sanchi flower herb pair for improving glucose and lipid metabolism in type 2 diabetes mellitus model mice
Ning WANG ; Congyi LIU ; Ying DING ; Xinyu ZHONG ; Zimeng HUANG ; Na ZHENG ; Qiu'e ZHANG ; Ruifeng YANG ; Lili WU ; Lingling QIN ; Tonghua LIU
Journal of Beijing University of Traditional Chinese Medicine 2025;48(10):1390-1403
Objective Based on the traditional Chinese medicine theory of"simultaneous regulation of the liver and kidney,"this study integrated network pharmacology prediction,molecular docking,and animal experimental validation to analyze the multi-target regulatory network of Duzhong Xionghua(the male flower of Eucommia ulmoides)-Sanqi Hua(Sanchi flower)herb pair(hereinafter called"herb pair")in modulating glucolipid metabolic disorders in type 2 diabetes mellitus(T2DM),thereby elucidating its underlying molecular mechanism.Methods Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,China National Knowledge Infrastructure,VIP Database for Chinese Technical Periodicals,and Wanfang Data were used to obtain the active ingredients of the male flower of Eucommia ulmoides and Sanchi flower.PubChem Compound,SwissTargetPrediction,and SuperPred were used to screen and predict the targets of the drugs;The Human Gene Database,The Online Mendelian Inheritance in Man,and Therapeutic Target Database were used to screen the key gene targets of T2DM.A"component-target-pathway"network diagram was constructed using Cytoscape software,and Gene Ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were employed to identify the functions of the relevant target genes and pathways.Molecular docking was used to verify the binding activities of the core components and the key targets.For animal experiments,spontaneous T2DM model mice were used,in which the normal group consisted of six mice(wild type)from the same litter,and the 24 successfully modeled mice were randomly divided into model,metformin(0.26 g/kg),high-dose herb pair(2.6 g/kg),and low-dose herb pair groups(1.3 g/kg)according to the blood glucose levels and body weights,with six mice per group.The drugs were administered by gavage daily for six consecutive weeks.The body weight and fasting blood glucose(FBG)levels were measured weekly,and an oral glucose tolerance test was performed in the fifth week.At the end of drug administration,body weight,naso-anal length,liver and bilateral epididymal adipose mass were measured;pathological changes in the liver were observed using HE staining;serum levels of aspartate transaminase(AST),alanine amino-transferase(ALT),total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C)were detected using colorimetric assay;and liver tissue phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)/glycogen synthase kinase-3β(GSK-3β)signaling pathway protein expressions were determined using Western blotting.Results Network pharmacology screening identified 38 active components and 669 potential targets of the herb pair.Intersection analysis with 1,275 T2DM-related targets yielded 185 common targets.Protein-protein interaction network analysis and pathway enrichment revealed the PI3K/AKT signaling pathway as a key mechanism.Molecular docking confirmed the strong binding affinity of the core components to key targets such as AKT1,suggesting that the herb pair may activate the PI3K/AKT pathway and inhibit GSK-3β activity via beta-sitosterol etc.Animal experiments demonstrated that,compared with the model group,the metformin group exhibited reduced FBG,AST,and ALT levels(P<0.01),but failed to improve body weight,Lee's index,or epididymal fat coefficient.Both herb pair doses significantly lowered Lee's index,hepatic index,and the epididymal fat coefficient(P<0.01),with the low-dose herb pair group showing attenuated body weight gain in mice.In contrast,the high-dose herb pair group exhibited decreased FBG,improved glucose tolerance,reduced TC,TG,and LDL-C levels,and increased HDL-C level(all P<0.01).HE staining revealed that all metformin and the herb pair markedly restored hepatic structure and alleviated steatosis in model mice,with more pronounced effects in the high-dose group than in the low-dose group.Western blotting result indicated that in the low-dose herb pair group,phospho-PI3K(p-PI3K),AKT,and phospho-GSK-3β(p-GSK-3β)protein expressions significantly increased(P<0.05 or P<0.01),whereas GSK-3β decreased(P<0.05).The high-dose group exhibited enhanced PI3K,p-PI3K,AKT,phospho-AKT,and p-GSK-3β protein expressions(all P<0.01),accompanied by reduced GSK-3β expression(P<0.01).Conclusion The male flower of Eucommia ulmoides-Sanchi flower herb pair may ameliorate T2DM-related glucolipid metabolic disorders by modulating the PI3K/AKT/GSK-3β pathway.
10.Research Progress on Traditional Chinese Medicine Treatment of Nonalcoholic Fatty Liver Based on NF-κB Signaling Pathway
Congyi LIU ; Na ZHENG ; Jingjing XU ; Ning WANG ; Zimeng HUANG ; Ying DING ; Lingling QIN ; Lili WU ; Tonghua LIU
World Science and Technology-Modernization of Traditional Chinese Medicine 2025;27(9):2553-2568
Non-alcoholic fatty liver disease(NAFLD)is a progressive liver disease caused by factors other than alcohol caused by heterotopic fat accumulation in the liver.In recent years,the incidence rate has been increasing,and there is no specific clinical drug.Studies have found that nuclear transcription factor κB(NF-κB)can activate inflammation and oxidative stress,which plays an important role in the pathogenesis of NAFLD.Traditional Chinese medicine is convenient to obtain and cheap.It can treat NAFLD through multiple channels with good clinical efficacy,and no obvious side effects have been found till now.Many studies have shown that traditional Chinese medicine can inhibit the occurrence and development of NAFLD by inhibiting the NF-κB signaling pathway.This article summarizes the research results of traditional Chinese medicine in treating NAFLD based on the NF-κB signaling pathway since 2021,for several traditional Chinese medicine extracts(flavonoids,terpenoids,polysaccharides,glycosides,alkaloids and phenolic compounds)and traditional Chinese medicine compound(Shugan Jianpi Fang,Erhuang Quzhi Granules,Fuzi Lizhong Decoction,Huangqin Decoction,Qinlian Hongqu Decoction,Jiangzhi Granules),which can inhibit the further development of NAFLD by improving liver inflammatory response,oxidative stress response,fibrosis,apoptosis,autophagy and pyroptosis through the NF-κB signaling pathway,in order to provide new ideas for future new drug development and clinical medication.

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