BACKGROUND Jianpi Gushen Huayu Decoction(JPGS)has been used to clinically treat diabetic nephropathy(DN)for many years.However,the protective mechanism of JPGS in treating DN remains unclear.AIM To evaluate the therap...BACKGROUND Jianpi Gushen Huayu Decoction(JPGS)has been used to clinically treat diabetic nephropathy(DN)for many years.However,the protective mechanism of JPGS in treating DN remains unclear.AIM To evaluate the therapeutic effects and the possible mechanism of JPGS on DN.METHODS We first evaluated the therapeutic potential of JPGS on a DN mouse model.We then investigated the effect of JPGS on the renal metabolite levels of DN mice using non-targeted metabolomics.Furthermore,we examined the effects of JPGS on c-Jun N-terminal kinase(JNK)/P38-mediated apoptosis and the inflammatory responses mediated by toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB)/NOD-like receptor family pyrin domain containing 3(NLRP3).RESULTS The ameliorative effects of JPGS on DN mice included the alleviation of renal injury and the control of inflammation and oxidative stress.Untargeted metabolomic analysis revealed that JPGS altered the metabolites of the kidneys in DN mice.A total of 51 differential metabolites were screened.Pathway analysis results indicated that nine pathways significantly changed between the control and model groups,while six pathways significantly altered between the model and JPGS groups.Pathways related to cysteine and methionine metabolism;alanine,tryptophan metabolism;aspartate and glutamate metabolism;and riboflavin metabolism were identified as the key pathways through which JPGS affects DN.Further experimental validation showed that JPGS treatment reduced the expression of TLR4/NF-κB/NLRP3 pathways and JNK/P38 pathway-mediated apoptosis related factors.CONCLUSION JPGS could markedly treat mice with streptozotocin(STZ)-induced DN,which is possibly related to the regulation of several metabolic pathways found in kidneys.Furthermore,JPGS could improve kidney inflammatory responses and ameliorate kidney injuries in DN mice via the TLR4/NF-κB/NLRP3 pathway and inhibit JNK/P38 pathwaymediated apoptosis in DN mice.展开更多
This study aimed to provide a comprehensive review of the research progress in Chinese medicine in the treatment of endocrine metabolic diseases in 2023,covering traditional Chinese medicine(TCM)monomers,TCM extracts,...This study aimed to provide a comprehensive review of the research progress in Chinese medicine in the treatment of endocrine metabolic diseases in 2023,covering traditional Chinese medicine(TCM)monomers,TCM extracts,and TCM combinations,including non-alcoholic fatty liver disease,type 2 diabetes mellitus and its complications,obesity,hyperuricaemia,and thyroid disorders.After systematic sorting and summary,we found that in 2023,the research focusing on the application of TCM for endocrine metabolic diseases was still on the mechanism of action at the cellular and molecular levels,which not only influenced the classical pathways of lipid metabolism,but also delved into the key mechanisms of anti-inflammation,anti-oxidation,anti-insulin resistance,and so on.Additionally,TCM has shown remarkable results in the treatment of endocrine metabolic diseases by improving intestinal flora disorders and abnormal cellular iron death.These research results provide valuable ideas,methods,and tools for TCM in the prevention and treatment of endocrine metabolic diseases,and provide important references and guidance for future research and practice.展开更多
Background:This study aims to investigate the therapeutic effect of Wa medicine Niang-Mu-Liang medicinal liquor(NML)on rats with diabetes mellitus erectile dysfunction(DMED)and its impact on the ferroptosis signaling ...Background:This study aims to investigate the therapeutic effect of Wa medicine Niang-Mu-Liang medicinal liquor(NML)on rats with diabetes mellitus erectile dysfunction(DMED)and its impact on the ferroptosis signaling pathway.Methods:Thirty Sprague-Dawley rats were randomly divided into three groups:Control,DMED,and NML.After establishing the DMED model,treatments were administered for 8 weeks.After the administration,apomorphine hydrochloride tests were conducted to measure the mass and organ index of testes and epididymides,sperm concentration and viability in each group.Penile corpus cavernosum tissues were stained with hematoxylin and eosin.Nitric oxide and cyclic guanosine monophosphate levels in the penile corpus cavernosum tissues were determined using biochemical kits and enzyme-linked immunosorbent assay,while the expression of proteins related to the ferroptosis signaling pathway was measured by Western blot.Results:Compared to the DMED group,the DMED rats treated with NML showed significantly increased erection frequency,testicular and epididymal mass and index,sperm count and viability,along with noticeable improvement in the pathological morphology of penile corpus cavernosum.The content of nitric oxide and cyclic guanosine monophosphate,and the expression of ferritin heavy chain,ferritin light chain,and glutathione peroxidase 4 proteins in penile corpus cavernosum tissue were elevated,while the expression of transferrin and STEAP3 proteins was reduced.Conclusion:NML can improve erectile function in DMED rats by inhibiting the ferroptosis signaling pathway.展开更多
Colon cancer(CRC)is one of the most common malignancies globally,ranking third in terms of new cancer cases and second as a cause of cancer deaths[1].In recent 30 years,the incidence and mortality rates of CRC in Chin...Colon cancer(CRC)is one of the most common malignancies globally,ranking third in terms of new cancer cases and second as a cause of cancer deaths[1].In recent 30 years,the incidence and mortality rates of CRC in China have been increasing,gradually exceeding the global levels[2].Due to the fact that most CRC patients are diagnosed at the advanced stage,the treatment of this disease is challenging and often ineffective.Therefore,prevention and early diagnosis of CRC are crucial.展开更多
Diabetic kidney disease(DKD)is a clinical syndrome that is one of the major causes of end-stage renal disease(ESRD).The pathogenesis of DKD is complex and multifaceted,with most studies indicating its association with...Diabetic kidney disease(DKD)is a clinical syndrome that is one of the major causes of end-stage renal disease(ESRD).The pathogenesis of DKD is complex and multifaceted,with most studies indicating its association with genetics,advanced glycosylation end-product deposition,polyol pathway and protein C activation,lipid metabolism abnormalities,microcirculatory dysfunction,oxidative stress,inflammatory factors,and the kallikrein-kinin system.Epigenetics is the science studying gene expression regulation without changes in the DNA sequence.In recent years,increasing evidence has shown that epigenetic mechanisms play a crucial role in the initiation and progression of DKD.For instance,epigenetic modifications such as DNA methylation,histone modifications,and non-coding RNAs can influence the expression of DKD-related genes,thereby regulating the development and progression of DKD.On the other hand,metabolic memory is an important concept in DKD research.Metabolic memory refers to the phenomenon where cells maintain a certain metabolic state even after the disappearance of metabolic stress factors.This state can influence cell function and fate.In DKD,metabolic stress factors such as hyperglycemia can lead to metabolic memory in renal cells,affecting their function and fate,ultimately leading to the development and progression of DKD.Therefore,to further explore the pathogenesis of DKD,research on epigenetics should be strengthened,aiming to provide new ideas and methods for the prevention and treatment of DKD.展开更多
Background:Shaoyao decoction(SYD)has been found widespread clinical use in treating ulcerative colitis(UC).However,the mechanism underlying SYD impact on UC remains elusive.Materials and methods:We preliminarily evalu...Background:Shaoyao decoction(SYD)has been found widespread clinical use in treating ulcerative colitis(UC).However,the mechanism underlying SYD impact on UC remains elusive.Materials and methods:We preliminarily evaluated the therapeutic effect of SYD intervention in a dextran sulfate sodium-induced UC mouse model by analyzing the body weight change,disease activity index score,colon length,and HE staining results of colon tissue in each group of mice.Subsequently,we determined pro-inflammatory cytokines level and blood coagulation markers in the colon tissues of mice in each group to evaluate the effect of SYD intervention on colonic inflammatory response and coagulation function in UC mice.Results:Our findings emphasize the significant therapeutic effect of SYD on UC,including slowed down body weight loss,reduced disease activity index score,increased colon length,and reduced inflammatory infiltration in colon tissue.Moreover,SYD intervention significantly downregulated the levels of pro-inflammatory cytokines IL-1β,IL-6,and IL-17A in the colon.Furthermore,SYD intervention reversed the coagulation-related indicators such as prothrombin time,fibrinogen,P-selectin,D-dimer,and platelet glycomembrane protein IIb/IIIa.Conclusion:Our results elucidate the substantial therapeutic impact of SYD on UC mice.Importantly,the therapeutic mechanism of SYD in addressing UC potentially involves the inhibiting of inflammatory response mediated by hypercoagulability.展开更多
Erectile dysfunction(ED)is one of the important complications of diabetes,which is very common in diabetic patients,affecting more than half of male patients,and the incidence of the disease is about 3.5 times that of...Erectile dysfunction(ED)is one of the important complications of diabetes,which is very common in diabetic patients,affecting more than half of male patients,and the incidence of the disease is about 3.5 times that of the normal population.The pathogenesis of diabetic erectile dysfunction(DMED)is complex,involving nerve,vascular,endocrine,muscular and psychological aspects.At present,the therapeutic approaches of DMED include drug therapy,surgery,physical therapy and so on.This article provides a review of current research on the pathogenesis and treatment of DMED.Further elucidation of the pathogenesis of DMED and the development of new therapeutic approaches are of great significance for the prevention and treatment of DMED.展开更多
Background:To explore the effects and mechanisms of Bu-Yang-Huan-Wu Decoction on pulmonary fibrosis in mice.Methods:Forty-five C57BL/6J mice were randomly divided into three groups:Control,Model,and Bu-Yang-Huan-Wu De...Background:To explore the effects and mechanisms of Bu-Yang-Huan-Wu Decoction on pulmonary fibrosis in mice.Methods:Forty-five C57BL/6J mice were randomly divided into three groups:Control,Model,and Bu-Yang-Huan-Wu Decoction.Pulmonary fibrosis was elicited in mice through a solitary intratracheal administration of 2.5 mg/kg bleomycin.For the control group,mice were given a solitary intratracheal administration of a comparable volume of PBS.Treatment began on the first day after the successful model establishment and lasted for 21 days.The survival rate and body weight of the mice were recorded daily,and on the 22nd day,bronchoalveolar lavage fluid was collected to determine total cells and total protein.The wet/dry weight ratio of lung tissue and hydroxyproline were measured.Lung tissue pathology was observed using hematoxylin and eosin staining and Masson staining.The mRNA expression of epithelial-mesenchymal transition-related proteins(E-cadherin and vimentin)was detected by RT-qPCR,and their protein expression was analyzed by western blot.Results:Compared to the model group,the Bu-Yang-Huan-Wu Decoction treatment notably enhanced both the survival rate and body weight in pulmonary fibrosis mice,significantly reduced lung tissue wet/dry weight ratio,total cells,and protein in bronchoalveolar lavage fluid,and hydroxyproline content.The pathological morphology of lung tissue was significantly improved,with increased expression of the epithelial cell marker E-cadherin mRNA and protein,and decreased expression of the mesenchymal cell marker vimentin mRNA and protein.Conclusion:Bu-Yang-Huan-Wu Decoction can improve the degree of bleomycin-induced pulmonary fibrosis in mice by inhibiting epithelial-mesenchymal transition.展开更多
Sepsis is a life-threatening multiple organ dysfunction syndrome caused by the imbalance of the immune response to infection,featuring complex and variable conditions,and is one of the leading causes of mortality in I...Sepsis is a life-threatening multiple organ dysfunction syndrome caused by the imbalance of the immune response to infection,featuring complex and variable conditions,and is one of the leading causes of mortality in ICU patients.Lung injury is a common organ damage observed in sepsis patients.Macrophages and Th17 cells,as crucial components of innate and adaptive immunity,play pivotal roles in the development of sepsis-induced acute lung injury(ALI).This review summarizes the alterations and mechanisms of macrophages and Th17 cells in sepsis-induced ALI.By focusing on the“cross-talk”between macrophages and Th17 cells,this review aims to provide a solid theoretical foundation for further exploring the therapeutic targets of traditional Chinese medicine formulas in the treatment of sepsis complicated with ALI,thereby offering insights and guidance for the clinical application of traditional Chinese medicine in managing sepsis-associated ALI.展开更多
Non-alcoholic fatty liver disease(NAFLD)is a chronic liver disease closely related to metabolic disorders that pose a serious threat to human health.Currently,no specific drugs are available for treating the aetiology...Non-alcoholic fatty liver disease(NAFLD)is a chronic liver disease closely related to metabolic disorders that pose a serious threat to human health.Currently,no specific drugs are available for treating the aetiology of NAFLD in clinical practice.Mitochondria have various biological functions inside the cell.Studies have found that mitochondrial fission and fusion are closely related to NAFLD.Therefore,identifying therapeutic targets for NAFLD through mitochondrial fission and fusion is crucial.Particularly in the field of traditional Chinese medicine,good therapeutic effects have been achieved in the treatment of NAFLD by protecting mitochondrial fusion and fission.Therefore,this article reviews the relationship between mitochondrial dynamics and NAFLD as well as the treatment of NAFLD through the regulation of mitochondrial fission and fusion with traditional Chinese medicine to provide a reference for the clinical application of traditional Chinese medicine in regulating mitochondrial fission and fusion functions to treat NAFLD.展开更多
Non-alcoholic fatty liver disease(NAFLD)is a kind of metabolic disorder characterized by excessive fat deposition in the liver and ranging from simple steatosis(simple NAFLD)to nonalcoholic steatohepatitis(NASH),cirrh...Non-alcoholic fatty liver disease(NAFLD)is a kind of metabolic disorder characterized by excessive fat deposition in the liver and ranging from simple steatosis(simple NAFLD)to nonalcoholic steatohepatitis(NASH),cirrhosis,and hepatocellular carcinoma[1].It has recently been increasing annually;for example,it was recently estimated to have a global prevalence of 32.4%,which seriously threatens human health[2].Thus,the discovery of new therapeutic targets is of great importance because there is no specified drug for the treatment of NAFLD.On the other hand,the pathogenesis of NAFLD is complicated and still unclear.Recent studies have proposed ferroptosis as related to the disease progressions of NAFLD.Preliminary evidence indicated that ferroptosis in hepatocytes and hepatic macrophages could induce NASH and that complex regulatory mechanisms were involved.In the future,inhibition of ferroptosis may hopefully become an emerging target in treating NAFLD.展开更多
Intestinal aging is emerging as a major public health problem The world has entered an aging society,and it is expected that the global population aged 60 years or older will reach 1.5 billion by 2035[1].Aging is grad...Intestinal aging is emerging as a major public health problem The world has entered an aging society,and it is expected that the global population aged 60 years or older will reach 1.5 billion by 2035[1].Aging is gradually becoming a major public health issue,posing a significant challenge to healthcare systems[2].It is a complex natural physiological process involving the irreversible degeneration of body cells,tissues,and organs,and it is a major risk factor for many chronic diseases.展开更多
Pulmonary hypertension(PH)is a progressive disorder affecting the pulmonary circulation,characterized by a grim prognosis that often culminates in right heart failure and mortality.Pulmonary vascular remodeling stands...Pulmonary hypertension(PH)is a progressive disorder affecting the pulmonary circulation,characterized by a grim prognosis that often culminates in right heart failure and mortality.Pulmonary vascular remodeling stands out as the predominant feature in the pathogenesis and pathological alterations of PH.Whereas,the pathogenic factors of PH are intricate,involving multiple interacting elements,and the mechanism behind pulmonary vascular remodeling remains not entirely comprehended.In this context,inflammation,chemokines,and gut microbiota may make a intricate and interrelated difference during the process of pulmonary vascular remodeling.展开更多
Ischemic stroke(IS)is the main killer that endangers the health and life of middle-aged and elderly people worldwide.Inflammatory response plays a key regulatory role in the pathogenesis of IS.After cerebral ischemia,...Ischemic stroke(IS)is the main killer that endangers the health and life of middle-aged and elderly people worldwide.Inflammatory response plays a key regulatory role in the pathogenesis of IS.After cerebral ischemia,leukocytes rapidly accumulate,penetrate blood vessels and infiltrate brain tissue,thereby activating pro-inflammatory factors in the infarct area to exacerbate nerve damage.Neutrophil extracellular traps(NETs)are fibrous mesh structures released by activated neutrophils outside the cell,which can clear pathogens and cell debris,induce inflammatory responses and exacerbate cerebral ischemia-reperfusion(CI/R)injury.Various traditional Chinese medicines and their main components can improve neurological function defects after IS,and inhibit the formation of NETs,which opens up a new direction for the study of traditional Chinese medicines in the prevention and treatment of IS.展开更多
Non-alcoholic fatty liver disease(NAFLD),also known as MAFLD,is a chronic liver disease characterized by dyslipidemia and excessive steatosis in hepatocytes[1].With the acceleration of urbanization,the problems of phy...Non-alcoholic fatty liver disease(NAFLD),also known as MAFLD,is a chronic liver disease characterized by dyslipidemia and excessive steatosis in hepatocytes[1].With the acceleration of urbanization,the problems of physical activity reduction and nutritional imbalance are becoming increasingly prominent.The prevalence of NAFLD has reached 25%globally[2],and it is also showing a trend of continuous growth and younger onset ag[3].Although numerous studies have confirmed that the pathogenesis of NAFLD may be related to genetic susceptibility,gene polymorphism,intestinal microenvironment disorder,insulin resistance,and other factors[4],the"two-hit"theory also reveals the mechanism of the occurrence of some NAFLD,there is still a lack of effective and stable drugs that can inhibit the progression of NAFLD to liver fibrosis and even liver cancer in the treatment of NAFLD[5].展开更多
prevalence.A number of clinical workers and researchers have made great efforts to understand the pathogenesis and clinical characteristics and develop effective drugs for treatment.However,no effective drugs with ant...prevalence.A number of clinical workers and researchers have made great efforts to understand the pathogenesis and clinical characteristics and develop effective drugs for treatment.However,no effective drugs with antiviral effects on severe acute respiratory syndrome coronavirus 2 have been discovered currently.Traditional Chinese medicine(TCM)has gained abundant experience in the treatment of infectious diseases for thousands of years.In this review,the authors summarized the clinical outcome,pathogensis and current application of TCM on coronavirus disease 2019.Further,we discussed the potential mechanisms and the future research directions of TCM against severe acute respiratory syndrome coronavirus 2.展开更多
Background:Chai-Ling decoction(CLD),derived from a modification of Xiao-Chai-Hu(XCH)decoction and Wu-Ling-San(WLS)decoction,has been used to treat the early-stage of coronavirus disease 2019(COVID-19).However,the mech...Background:Chai-Ling decoction(CLD),derived from a modification of Xiao-Chai-Hu(XCH)decoction and Wu-Ling-San(WLS)decoction,has been used to treat the early-stage of coronavirus disease 2019(COVID-19).However,the mechanisms of CLD in COVID-19 remain unknown.In this study,the potential mechanisms of CLD in COVID-19 were preliminarily investigated based on network pharmacology and molecular docking method.Methods:Initially,the active components and targets of CLD were screened based on Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and PharmMapper database.The targets of COVID-19 were obtained from GeneCards database.The protein-protein interaction network was established using STRING database to analyze the key targets.Gene Oncology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes analysis were also conducted to evaluate the pathways related to the targets of CLD on COVID-19.Moreover,the compound-target-pathway network was established using Cytoscape 3.2.7.Subsequently,the molecular docking method was performed to select the active compounds with high binding affinity on severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and angiotensin-converting enzyme 2(ACE2),which is the key target of SARS-CoV-2 in entering target cells.The possible binding sites were also visualized by a three-dimensional graph.Results:Network pharmacology analysis showed that there were 106 active components and 160 targets of CLD.Additionally,251 targets related to COVID-19 were identified,and 24 candidates of CLD on COVID-19 were selected.A total of 283 GO terms of CLD on COVID-19 were identified,and 181 pathways were screened based on GO and Kyoto Encyclopedia of Genes and Genomes analyses.CLD might alleviate the inflammatory response and improve lung injury to treat COVID-19 through interleukin 17 signaling,T helper cell 17 differentiation,tumor necrosis factor signaling,and hypoxia inducible factor-1 signaling.Besides,molecular docking indicated that beta-sitosterol,kaempferol,and stigmasterol were the top three candidates in CLD with the highest affinity to SARS-CoV-2 and ACE2.Conclusion:Our study identifies the potential mechanisms of CLD on COVID-19 and beta-sitosterol,kaempferol,and stigmasterol may be the key compounds that exert antiviral effects against SARS-CoV-2.展开更多
Background:Currently,the treatment of liver diseases remains an unsolved problem due to its complicated etiology and pathogenesis.Traditional Chinese medicine(TCM)has been used for liver disease treatment for thousand...Background:Currently,the treatment of liver diseases remains an unsolved problem due to its complicated etiology and pathogenesis.Traditional Chinese medicine(TCM)has been used for liver disease treatment for thousands of years.Disease treatment using TCM compounds conforms to the concept of“holism”,which coincides with the complicated pathogenic mechanisms of liver diseases.However,the mechanisms have not been clearly explained due to the complex components and multi-targets,which is a big obstacle TCM’s popularity and application.In recent years,studying the mechanisms and identifying the novel ingredients in herbal medicines are becoming a hot spot for many researchers.Therefore,we obtained literature in PubMed and summarized the progress of TCM’s active ingredients and formulas in treating various liver diseases in 2019.Based on the literature,flavonoids,polysaccharides,saponins,and alkaloids,as well as Chinese medicine formulas,such as Ba-Bao pill and Yin-Chen-Hao decoction,have attracted much attention.In addition,we also focused on the application of new omics analysis techniques,such as metabolomics,network pharmacology,and other omics analyses in the study of TCM formulas.展开更多
Background:In this study,we preliminarily investigated the mechanism of Yin-Chai-Xiao-Du decoction for the treatment of COVID-19 by the method of network pharmacology.Methods:The potential targets and pathways of Yin-...Background:In this study,we preliminarily investigated the mechanism of Yin-Chai-Xiao-Du decoction for the treatment of COVID-19 by the method of network pharmacology.Methods:The potential targets and pathways of Yin-Chai-Xiao-Du decoction for the treatment of COVID-19 were examined using network pharmacology;the ingredient and active targets of Yin-Chai-Xiao-Du decoction were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and PharmMapper databases;the COVID-19-related targets were obtained from the online Mendelian inheritance in man,GeneCards,and GeneMANIA databases;the STRING database and Cytoscape were used to build a protein-protein interaction network,and a Network Analyzer tool was used to perform topology analysis to screen for the key ingredients and targets;the ClueGO and KOBAS 3.0 databases were for the enrichment analysis of gene function(Gene Oncology)and gene pathway(Kyoto Encyclopedia of Genes and Genomes);the herb-ingredient-target-pathway network diagram was constructed by Cytoscape.Results:The core herbs screened by the network pharmacological analysis were Jinyinhua(Lonicerae japonicae flos),Lianqiao(Forsythia suspensa),Chaihu(Bupleuri radix),Huangqin(Scutellariae radix),Yinchen(Herba Artemisiae Scopariae),Guanghuoxiang(Pogostemonis herba),Roudoukou(Semen myristicae)and Qinghao(Artemisiae annuae herba).A total of 293 active ingredients were screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,and the key ingredients were quercetin,kaempferol,isorhamnetin,stigmasterol,beta-sitosterol,and luteolin.Yin-Chai-Xiao-Du decoction has 138 COVID-19-related targets,and the key targets were mitogen-activated protein kinase 3,interleukin-6,tumor necrosis factor,vascular endothelial growth factor A,and CC motif ligand 2.Kyoto Encyclopedia of Genes and Genomes analysis revealed 120 enriched gene pathways,and the key pathways were signaling by interleukins,immune system,cytokine signaling in the immune system,and the signaling pathways of interleukin-17,tumor necrosis factor,and relaxin.Conclusion:The core herbs of Yin-Chai-Xiao-Du decoction are Jinyinhua(Lonicerae japonicae flos),Lianqiao(Forsythia suspensa),Chaihu(Bupleuri radix),Huangqin(Scutellariae radix),Yinchen(Herba Artemisiae Scopariae),Guanghuoxiang(Pogostemonis herba),Roudoukou(Semen myristicae)and Qinghao(Artemisiae annuae herba).The key ingredients are quercetin,kaempferol,isorhamnetin,stigmasterol,and beta-sitosterol;the critical targets are luteolin,interleukin-6,mitogen-activated protein kinase 3,tumor necrosis factor,and CC motif ligand 2;and the core signaling pathways are those mediated by interleukin-17,tumor necrosis factor,and relaxin.展开更多
Background:Non-alcoholic fatty liver disease(NAFLD)can cause insulin resistance(IR)and diabetes.Our previous studies have demonstrated that Jian-Gan-Xiao-Zhi decoction(JGXZ)could be effective for the treatment of NAFL...Background:Non-alcoholic fatty liver disease(NAFLD)can cause insulin resistance(IR)and diabetes.Our previous studies have demonstrated that Jian-Gan-Xiao-Zhi decoction(JGXZ)could be effective for the treatment of NAFLD and IR.However,the possible mechanism underlying the effects of JGXZ on NAFLD and IR remains unknown.Methods:Fifty rats received a high-fat high-carbohydrate(HFHC)diet for 12 weeks to induce NAFLD.After 4 weeks of HFHC treatment,rats were orally treated with JGXZ(8,16,and 32 g/kg weight)for 8 weeks.Ten rats in the control group received standard chow.In the positive control group,rats were orally treated with metformin(90 mg/kg weight)for 8 weeks.After JGXZ and metformin treatment,H&E staining was conducted on rat livers and serum biochemical markers,including alanine aminotransferase(ALT),aspartate aminotransferase(AST),triglyceride(TG),and total cholesterol(TC),were measured using test kits.Moreover,a fasting blood glucose test and an oral glucose tolerance test(OGTT)were conducted.Serum levels of insulin were determined using ELISA kit,and the homeostatic model assessment of insulin resistance(HOMA-IR)was calculated.The levels of total insulin receptor substrate-1(IRS1),AMP-activated protein kinase-α(AMPKα)and c-Jun N-terminal kinase(JNK)as well as the levels of phosphorylation of IRS1(p-IRS1),phosphorylation of AMPK(p-AMPK)and phosphorylation of JNK(p-JNK)were measured using western blotting.Results:The body weights in JGXZ low-,middle-,and high-dose groups were lower than those in the model group(P<0.05,P<0.01,P<0.01,respectively).The serum levels of AST(P<0.05 in JGXZ middle-and high-dose groups),ALT(P<0.01 in JGXZ middle-dose group and P<0.05 in JGXZ high-dose group),TG(P<0.01 in JGXZ middle-and high-dose groups),and TC(P<0.01)upon JGXZ treatment were lower those than in NAFLD model rats.H&E staining showed that JGXZ treatment reduced steatosis of the hepatocytes in NAFLD model rats.JGXZ decreased the levels of fasting blood glucose(P<0.01),HOMA-IR(P<0.01),AUC(area under the curve)of the OGTT(P<0.05)and p-IRS1(P<0.01 in JGXZ middle-and high-dose groups,P<0.05 in JGXZ low-dose groups).Moreover,JGXZ regulated the hepatic AMPKα/JNK pathway in NAFLD model rats,which reflected the induction of p-AMPKαand inhibition of p-JNK.Conclusion:This study showed that JGXZ improved liver function and reduced steatosis of the hepatocytes in NAFLD model rats.Moreover,JGXZ improved IR in NAFLD model rats.The possible mechanism underlying the effects of JGXZ on NAFLD and IR involves the modulation of the AMPK/JNK pathway.展开更多
基金Supported by the Scientific Foundation of Administration of Traditional Chinese Medicine of Hebei Province,China,No.2023257.
文摘BACKGROUND Jianpi Gushen Huayu Decoction(JPGS)has been used to clinically treat diabetic nephropathy(DN)for many years.However,the protective mechanism of JPGS in treating DN remains unclear.AIM To evaluate the therapeutic effects and the possible mechanism of JPGS on DN.METHODS We first evaluated the therapeutic potential of JPGS on a DN mouse model.We then investigated the effect of JPGS on the renal metabolite levels of DN mice using non-targeted metabolomics.Furthermore,we examined the effects of JPGS on c-Jun N-terminal kinase(JNK)/P38-mediated apoptosis and the inflammatory responses mediated by toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB)/NOD-like receptor family pyrin domain containing 3(NLRP3).RESULTS The ameliorative effects of JPGS on DN mice included the alleviation of renal injury and the control of inflammation and oxidative stress.Untargeted metabolomic analysis revealed that JPGS altered the metabolites of the kidneys in DN mice.A total of 51 differential metabolites were screened.Pathway analysis results indicated that nine pathways significantly changed between the control and model groups,while six pathways significantly altered between the model and JPGS groups.Pathways related to cysteine and methionine metabolism;alanine,tryptophan metabolism;aspartate and glutamate metabolism;and riboflavin metabolism were identified as the key pathways through which JPGS affects DN.Further experimental validation showed that JPGS treatment reduced the expression of TLR4/NF-κB/NLRP3 pathways and JNK/P38 pathway-mediated apoptosis related factors.CONCLUSION JPGS could markedly treat mice with streptozotocin(STZ)-induced DN,which is possibly related to the regulation of several metabolic pathways found in kidneys.Furthermore,JPGS could improve kidney inflammatory responses and ameliorate kidney injuries in DN mice via the TLR4/NF-κB/NLRP3 pathway and inhibit JNK/P38 pathwaymediated apoptosis in DN mice.
基金supported by the Yunnan Provincial First-Class Discipline Innovation and Research Fund Key Project(ZYXZD202405)the Yunnan Provincial Science and Technology Department Traditional Chinese Medicine Joint Project(202001AZ070001-026).
文摘This study aimed to provide a comprehensive review of the research progress in Chinese medicine in the treatment of endocrine metabolic diseases in 2023,covering traditional Chinese medicine(TCM)monomers,TCM extracts,and TCM combinations,including non-alcoholic fatty liver disease,type 2 diabetes mellitus and its complications,obesity,hyperuricaemia,and thyroid disorders.After systematic sorting and summary,we found that in 2023,the research focusing on the application of TCM for endocrine metabolic diseases was still on the mechanism of action at the cellular and molecular levels,which not only influenced the classical pathways of lipid metabolism,but also delved into the key mechanisms of anti-inflammation,anti-oxidation,anti-insulin resistance,and so on.Additionally,TCM has shown remarkable results in the treatment of endocrine metabolic diseases by improving intestinal flora disorders and abnormal cellular iron death.These research results provide valuable ideas,methods,and tools for TCM in the prevention and treatment of endocrine metabolic diseases,and provide important references and guidance for future research and practice.
基金supported by the Yunnan Provincial Science and Technology Department Science and Technology Plan Project (202101AZ070001-064).
文摘Background:This study aims to investigate the therapeutic effect of Wa medicine Niang-Mu-Liang medicinal liquor(NML)on rats with diabetes mellitus erectile dysfunction(DMED)and its impact on the ferroptosis signaling pathway.Methods:Thirty Sprague-Dawley rats were randomly divided into three groups:Control,DMED,and NML.After establishing the DMED model,treatments were administered for 8 weeks.After the administration,apomorphine hydrochloride tests were conducted to measure the mass and organ index of testes and epididymides,sperm concentration and viability in each group.Penile corpus cavernosum tissues were stained with hematoxylin and eosin.Nitric oxide and cyclic guanosine monophosphate levels in the penile corpus cavernosum tissues were determined using biochemical kits and enzyme-linked immunosorbent assay,while the expression of proteins related to the ferroptosis signaling pathway was measured by Western blot.Results:Compared to the DMED group,the DMED rats treated with NML showed significantly increased erection frequency,testicular and epididymal mass and index,sperm count and viability,along with noticeable improvement in the pathological morphology of penile corpus cavernosum.The content of nitric oxide and cyclic guanosine monophosphate,and the expression of ferritin heavy chain,ferritin light chain,and glutathione peroxidase 4 proteins in penile corpus cavernosum tissue were elevated,while the expression of transferrin and STEAP3 proteins was reduced.Conclusion:NML can improve erectile function in DMED rats by inhibiting the ferroptosis signaling pathway.
基金This study is supported by National Natural Science Foundation of China(82374320,82060864).
文摘Colon cancer(CRC)is one of the most common malignancies globally,ranking third in terms of new cancer cases and second as a cause of cancer deaths[1].In recent 30 years,the incidence and mortality rates of CRC in China have been increasing,gradually exceeding the global levels[2].Due to the fact that most CRC patients are diagnosed at the advanced stage,the treatment of this disease is challenging and often ineffective.Therefore,prevention and early diagnosis of CRC are crucial.
文摘Diabetic kidney disease(DKD)is a clinical syndrome that is one of the major causes of end-stage renal disease(ESRD).The pathogenesis of DKD is complex and multifaceted,with most studies indicating its association with genetics,advanced glycosylation end-product deposition,polyol pathway and protein C activation,lipid metabolism abnormalities,microcirculatory dysfunction,oxidative stress,inflammatory factors,and the kallikrein-kinin system.Epigenetics is the science studying gene expression regulation without changes in the DNA sequence.In recent years,increasing evidence has shown that epigenetic mechanisms play a crucial role in the initiation and progression of DKD.For instance,epigenetic modifications such as DNA methylation,histone modifications,and non-coding RNAs can influence the expression of DKD-related genes,thereby regulating the development and progression of DKD.On the other hand,metabolic memory is an important concept in DKD research.Metabolic memory refers to the phenomenon where cells maintain a certain metabolic state even after the disappearance of metabolic stress factors.This state can influence cell function and fate.In DKD,metabolic stress factors such as hyperglycemia can lead to metabolic memory in renal cells,affecting their function and fate,ultimately leading to the development and progression of DKD.Therefore,to further explore the pathogenesis of DKD,research on epigenetics should be strengthened,aiming to provide new ideas and methods for the prevention and treatment of DKD.
文摘Background:Shaoyao decoction(SYD)has been found widespread clinical use in treating ulcerative colitis(UC).However,the mechanism underlying SYD impact on UC remains elusive.Materials and methods:We preliminarily evaluated the therapeutic effect of SYD intervention in a dextran sulfate sodium-induced UC mouse model by analyzing the body weight change,disease activity index score,colon length,and HE staining results of colon tissue in each group of mice.Subsequently,we determined pro-inflammatory cytokines level and blood coagulation markers in the colon tissues of mice in each group to evaluate the effect of SYD intervention on colonic inflammatory response and coagulation function in UC mice.Results:Our findings emphasize the significant therapeutic effect of SYD on UC,including slowed down body weight loss,reduced disease activity index score,increased colon length,and reduced inflammatory infiltration in colon tissue.Moreover,SYD intervention significantly downregulated the levels of pro-inflammatory cytokines IL-1β,IL-6,and IL-17A in the colon.Furthermore,SYD intervention reversed the coagulation-related indicators such as prothrombin time,fibrinogen,P-selectin,D-dimer,and platelet glycomembrane protein IIb/IIIa.Conclusion:Our results elucidate the substantial therapeutic impact of SYD on UC mice.Importantly,the therapeutic mechanism of SYD in addressing UC potentially involves the inhibiting of inflammatory response mediated by hypercoagulability.
基金supported by the Joint Project of Yunnan Provincial Science and Technology Department and Yunnan University of Chinese Medicine:Exploring the Mechanism of Yiqi Tongluo Decoction from Wa Ethnic Medicine in Regulating Autophagy to Relieve Diabetic Peripheral Neuropathy Based on the PI3K/mTOR Pathway(No.202101AZ070001-064).
文摘Erectile dysfunction(ED)is one of the important complications of diabetes,which is very common in diabetic patients,affecting more than half of male patients,and the incidence of the disease is about 3.5 times that of the normal population.The pathogenesis of diabetic erectile dysfunction(DMED)is complex,involving nerve,vascular,endocrine,muscular and psychological aspects.At present,the therapeutic approaches of DMED include drug therapy,surgery,physical therapy and so on.This article provides a review of current research on the pathogenesis and treatment of DMED.Further elucidation of the pathogenesis of DMED and the development of new therapeutic approaches are of great significance for the prevention and treatment of DMED.
文摘Background:To explore the effects and mechanisms of Bu-Yang-Huan-Wu Decoction on pulmonary fibrosis in mice.Methods:Forty-five C57BL/6J mice were randomly divided into three groups:Control,Model,and Bu-Yang-Huan-Wu Decoction.Pulmonary fibrosis was elicited in mice through a solitary intratracheal administration of 2.5 mg/kg bleomycin.For the control group,mice were given a solitary intratracheal administration of a comparable volume of PBS.Treatment began on the first day after the successful model establishment and lasted for 21 days.The survival rate and body weight of the mice were recorded daily,and on the 22nd day,bronchoalveolar lavage fluid was collected to determine total cells and total protein.The wet/dry weight ratio of lung tissue and hydroxyproline were measured.Lung tissue pathology was observed using hematoxylin and eosin staining and Masson staining.The mRNA expression of epithelial-mesenchymal transition-related proteins(E-cadherin and vimentin)was detected by RT-qPCR,and their protein expression was analyzed by western blot.Results:Compared to the model group,the Bu-Yang-Huan-Wu Decoction treatment notably enhanced both the survival rate and body weight in pulmonary fibrosis mice,significantly reduced lung tissue wet/dry weight ratio,total cells,and protein in bronchoalveolar lavage fluid,and hydroxyproline content.The pathological morphology of lung tissue was significantly improved,with increased expression of the epithelial cell marker E-cadherin mRNA and protein,and decreased expression of the mesenchymal cell marker vimentin mRNA and protein.Conclusion:Bu-Yang-Huan-Wu Decoction can improve the degree of bleomycin-induced pulmonary fibrosis in mice by inhibiting epithelial-mesenchymal transition.
基金supported by the National Natural Science Foundation of China(No.82104581,No.82060864).
文摘Sepsis is a life-threatening multiple organ dysfunction syndrome caused by the imbalance of the immune response to infection,featuring complex and variable conditions,and is one of the leading causes of mortality in ICU patients.Lung injury is a common organ damage observed in sepsis patients.Macrophages and Th17 cells,as crucial components of innate and adaptive immunity,play pivotal roles in the development of sepsis-induced acute lung injury(ALI).This review summarizes the alterations and mechanisms of macrophages and Th17 cells in sepsis-induced ALI.By focusing on the“cross-talk”between macrophages and Th17 cells,this review aims to provide a solid theoretical foundation for further exploring the therapeutic targets of traditional Chinese medicine formulas in the treatment of sepsis complicated with ALI,thereby offering insights and guidance for the clinical application of traditional Chinese medicine in managing sepsis-associated ALI.
文摘Non-alcoholic fatty liver disease(NAFLD)is a chronic liver disease closely related to metabolic disorders that pose a serious threat to human health.Currently,no specific drugs are available for treating the aetiology of NAFLD in clinical practice.Mitochondria have various biological functions inside the cell.Studies have found that mitochondrial fission and fusion are closely related to NAFLD.Therefore,identifying therapeutic targets for NAFLD through mitochondrial fission and fusion is crucial.Particularly in the field of traditional Chinese medicine,good therapeutic effects have been achieved in the treatment of NAFLD by protecting mitochondrial fusion and fission.Therefore,this article reviews the relationship between mitochondrial dynamics and NAFLD as well as the treatment of NAFLD through the regulation of mitochondrial fission and fusion with traditional Chinese medicine to provide a reference for the clinical application of traditional Chinese medicine in regulating mitochondrial fission and fusion functions to treat NAFLD.
文摘Non-alcoholic fatty liver disease(NAFLD)is a kind of metabolic disorder characterized by excessive fat deposition in the liver and ranging from simple steatosis(simple NAFLD)to nonalcoholic steatohepatitis(NASH),cirrhosis,and hepatocellular carcinoma[1].It has recently been increasing annually;for example,it was recently estimated to have a global prevalence of 32.4%,which seriously threatens human health[2].Thus,the discovery of new therapeutic targets is of great importance because there is no specified drug for the treatment of NAFLD.On the other hand,the pathogenesis of NAFLD is complicated and still unclear.Recent studies have proposed ferroptosis as related to the disease progressions of NAFLD.Preliminary evidence indicated that ferroptosis in hepatocytes and hepatic macrophages could induce NASH and that complex regulatory mechanisms were involved.In the future,inhibition of ferroptosis may hopefully become an emerging target in treating NAFLD.
基金supported by Natural Science Foundation of Tianjin(23JCZXJC00180),S&T Program of Hebei(23379902L).
文摘Intestinal aging is emerging as a major public health problem The world has entered an aging society,and it is expected that the global population aged 60 years or older will reach 1.5 billion by 2035[1].Aging is gradually becoming a major public health issue,posing a significant challenge to healthcare systems[2].It is a complex natural physiological process involving the irreversible degeneration of body cells,tissues,and organs,and it is a major risk factor for many chronic diseases.
文摘Pulmonary hypertension(PH)is a progressive disorder affecting the pulmonary circulation,characterized by a grim prognosis that often culminates in right heart failure and mortality.Pulmonary vascular remodeling stands out as the predominant feature in the pathogenesis and pathological alterations of PH.Whereas,the pathogenic factors of PH are intricate,involving multiple interacting elements,and the mechanism behind pulmonary vascular remodeling remains not entirely comprehended.In this context,inflammation,chemokines,and gut microbiota may make a intricate and interrelated difference during the process of pulmonary vascular remodeling.
文摘Ischemic stroke(IS)is the main killer that endangers the health and life of middle-aged and elderly people worldwide.Inflammatory response plays a key regulatory role in the pathogenesis of IS.After cerebral ischemia,leukocytes rapidly accumulate,penetrate blood vessels and infiltrate brain tissue,thereby activating pro-inflammatory factors in the infarct area to exacerbate nerve damage.Neutrophil extracellular traps(NETs)are fibrous mesh structures released by activated neutrophils outside the cell,which can clear pathogens and cell debris,induce inflammatory responses and exacerbate cerebral ischemia-reperfusion(CI/R)injury.Various traditional Chinese medicines and their main components can improve neurological function defects after IS,and inhibit the formation of NETs,which opens up a new direction for the study of traditional Chinese medicines in the prevention and treatment of IS.
文摘Non-alcoholic fatty liver disease(NAFLD),also known as MAFLD,is a chronic liver disease characterized by dyslipidemia and excessive steatosis in hepatocytes[1].With the acceleration of urbanization,the problems of physical activity reduction and nutritional imbalance are becoming increasingly prominent.The prevalence of NAFLD has reached 25%globally[2],and it is also showing a trend of continuous growth and younger onset ag[3].Although numerous studies have confirmed that the pathogenesis of NAFLD may be related to genetic susceptibility,gene polymorphism,intestinal microenvironment disorder,insulin resistance,and other factors[4],the"two-hit"theory also reveals the mechanism of the occurrence of some NAFLD,there is still a lack of effective and stable drugs that can inhibit the progression of NAFLD to liver fibrosis and even liver cancer in the treatment of NAFLD[5].
文摘prevalence.A number of clinical workers and researchers have made great efforts to understand the pathogenesis and clinical characteristics and develop effective drugs for treatment.However,no effective drugs with antiviral effects on severe acute respiratory syndrome coronavirus 2 have been discovered currently.Traditional Chinese medicine(TCM)has gained abundant experience in the treatment of infectious diseases for thousands of years.In this review,the authors summarized the clinical outcome,pathogensis and current application of TCM on coronavirus disease 2019.Further,we discussed the potential mechanisms and the future research directions of TCM against severe acute respiratory syndrome coronavirus 2.
基金university-level project on curing disease in 2018 of Tianjin University of Traditional Chinese Medicine(XJ201801).
文摘Background:Chai-Ling decoction(CLD),derived from a modification of Xiao-Chai-Hu(XCH)decoction and Wu-Ling-San(WLS)decoction,has been used to treat the early-stage of coronavirus disease 2019(COVID-19).However,the mechanisms of CLD in COVID-19 remain unknown.In this study,the potential mechanisms of CLD in COVID-19 were preliminarily investigated based on network pharmacology and molecular docking method.Methods:Initially,the active components and targets of CLD were screened based on Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and PharmMapper database.The targets of COVID-19 were obtained from GeneCards database.The protein-protein interaction network was established using STRING database to analyze the key targets.Gene Oncology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes analysis were also conducted to evaluate the pathways related to the targets of CLD on COVID-19.Moreover,the compound-target-pathway network was established using Cytoscape 3.2.7.Subsequently,the molecular docking method was performed to select the active compounds with high binding affinity on severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and angiotensin-converting enzyme 2(ACE2),which is the key target of SARS-CoV-2 in entering target cells.The possible binding sites were also visualized by a three-dimensional graph.Results:Network pharmacology analysis showed that there were 106 active components and 160 targets of CLD.Additionally,251 targets related to COVID-19 were identified,and 24 candidates of CLD on COVID-19 were selected.A total of 283 GO terms of CLD on COVID-19 were identified,and 181 pathways were screened based on GO and Kyoto Encyclopedia of Genes and Genomes analyses.CLD might alleviate the inflammatory response and improve lung injury to treat COVID-19 through interleukin 17 signaling,T helper cell 17 differentiation,tumor necrosis factor signaling,and hypoxia inducible factor-1 signaling.Besides,molecular docking indicated that beta-sitosterol,kaempferol,and stigmasterol were the top three candidates in CLD with the highest affinity to SARS-CoV-2 and ACE2.Conclusion:Our study identifies the potential mechanisms of CLD on COVID-19 and beta-sitosterol,kaempferol,and stigmasterol may be the key compounds that exert antiviral effects against SARS-CoV-2.
基金This study was supported by Science and Technology Projects in Key Fields of Traditional Chinese Medicine of Tianjin Municipal Health Commission(No.2020006)Tianjin Administration of Traditional Chinese Medicine,Integrated Chinese and Western Medicine Scientific Research Project of Tianjin Municipal Health Commission(No.2017073).
文摘Background:Currently,the treatment of liver diseases remains an unsolved problem due to its complicated etiology and pathogenesis.Traditional Chinese medicine(TCM)has been used for liver disease treatment for thousands of years.Disease treatment using TCM compounds conforms to the concept of“holism”,which coincides with the complicated pathogenic mechanisms of liver diseases.However,the mechanisms have not been clearly explained due to the complex components and multi-targets,which is a big obstacle TCM’s popularity and application.In recent years,studying the mechanisms and identifying the novel ingredients in herbal medicines are becoming a hot spot for many researchers.Therefore,we obtained literature in PubMed and summarized the progress of TCM’s active ingredients and formulas in treating various liver diseases in 2019.Based on the literature,flavonoids,polysaccharides,saponins,and alkaloids,as well as Chinese medicine formulas,such as Ba-Bao pill and Yin-Chen-Hao decoction,have attracted much attention.In addition,we also focused on the application of new omics analysis techniques,such as metabolomics,network pharmacology,and other omics analyses in the study of TCM formulas.
基金This study was supported by the National Key Research and Development Program(No.2018YFC1704800)the Chinese Medicine Standardization Project of State Administration of Traditional Chinese Medicine(No.SATCM-2015-BZ125).
文摘Background:In this study,we preliminarily investigated the mechanism of Yin-Chai-Xiao-Du decoction for the treatment of COVID-19 by the method of network pharmacology.Methods:The potential targets and pathways of Yin-Chai-Xiao-Du decoction for the treatment of COVID-19 were examined using network pharmacology;the ingredient and active targets of Yin-Chai-Xiao-Du decoction were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and PharmMapper databases;the COVID-19-related targets were obtained from the online Mendelian inheritance in man,GeneCards,and GeneMANIA databases;the STRING database and Cytoscape were used to build a protein-protein interaction network,and a Network Analyzer tool was used to perform topology analysis to screen for the key ingredients and targets;the ClueGO and KOBAS 3.0 databases were for the enrichment analysis of gene function(Gene Oncology)and gene pathway(Kyoto Encyclopedia of Genes and Genomes);the herb-ingredient-target-pathway network diagram was constructed by Cytoscape.Results:The core herbs screened by the network pharmacological analysis were Jinyinhua(Lonicerae japonicae flos),Lianqiao(Forsythia suspensa),Chaihu(Bupleuri radix),Huangqin(Scutellariae radix),Yinchen(Herba Artemisiae Scopariae),Guanghuoxiang(Pogostemonis herba),Roudoukou(Semen myristicae)and Qinghao(Artemisiae annuae herba).A total of 293 active ingredients were screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,and the key ingredients were quercetin,kaempferol,isorhamnetin,stigmasterol,beta-sitosterol,and luteolin.Yin-Chai-Xiao-Du decoction has 138 COVID-19-related targets,and the key targets were mitogen-activated protein kinase 3,interleukin-6,tumor necrosis factor,vascular endothelial growth factor A,and CC motif ligand 2.Kyoto Encyclopedia of Genes and Genomes analysis revealed 120 enriched gene pathways,and the key pathways were signaling by interleukins,immune system,cytokine signaling in the immune system,and the signaling pathways of interleukin-17,tumor necrosis factor,and relaxin.Conclusion:The core herbs of Yin-Chai-Xiao-Du decoction are Jinyinhua(Lonicerae japonicae flos),Lianqiao(Forsythia suspensa),Chaihu(Bupleuri radix),Huangqin(Scutellariae radix),Yinchen(Herba Artemisiae Scopariae),Guanghuoxiang(Pogostemonis herba),Roudoukou(Semen myristicae)and Qinghao(Artemisiae annuae herba).The key ingredients are quercetin,kaempferol,isorhamnetin,stigmasterol,and beta-sitosterol;the critical targets are luteolin,interleukin-6,mitogen-activated protein kinase 3,tumor necrosis factor,and CC motif ligand 2;and the core signaling pathways are those mediated by interleukin-17,tumor necrosis factor,and relaxin.
基金This work was performed at the Yunnan University of Chinese Medicine,China,and was supported by the National Natural Science Foundation of China(8156150405)Natural Science Foundation of Tianjin(KL721).
文摘Background:Non-alcoholic fatty liver disease(NAFLD)can cause insulin resistance(IR)and diabetes.Our previous studies have demonstrated that Jian-Gan-Xiao-Zhi decoction(JGXZ)could be effective for the treatment of NAFLD and IR.However,the possible mechanism underlying the effects of JGXZ on NAFLD and IR remains unknown.Methods:Fifty rats received a high-fat high-carbohydrate(HFHC)diet for 12 weeks to induce NAFLD.After 4 weeks of HFHC treatment,rats were orally treated with JGXZ(8,16,and 32 g/kg weight)for 8 weeks.Ten rats in the control group received standard chow.In the positive control group,rats were orally treated with metformin(90 mg/kg weight)for 8 weeks.After JGXZ and metformin treatment,H&E staining was conducted on rat livers and serum biochemical markers,including alanine aminotransferase(ALT),aspartate aminotransferase(AST),triglyceride(TG),and total cholesterol(TC),were measured using test kits.Moreover,a fasting blood glucose test and an oral glucose tolerance test(OGTT)were conducted.Serum levels of insulin were determined using ELISA kit,and the homeostatic model assessment of insulin resistance(HOMA-IR)was calculated.The levels of total insulin receptor substrate-1(IRS1),AMP-activated protein kinase-α(AMPKα)and c-Jun N-terminal kinase(JNK)as well as the levels of phosphorylation of IRS1(p-IRS1),phosphorylation of AMPK(p-AMPK)and phosphorylation of JNK(p-JNK)were measured using western blotting.Results:The body weights in JGXZ low-,middle-,and high-dose groups were lower than those in the model group(P<0.05,P<0.01,P<0.01,respectively).The serum levels of AST(P<0.05 in JGXZ middle-and high-dose groups),ALT(P<0.01 in JGXZ middle-dose group and P<0.05 in JGXZ high-dose group),TG(P<0.01 in JGXZ middle-and high-dose groups),and TC(P<0.01)upon JGXZ treatment were lower those than in NAFLD model rats.H&E staining showed that JGXZ treatment reduced steatosis of the hepatocytes in NAFLD model rats.JGXZ decreased the levels of fasting blood glucose(P<0.01),HOMA-IR(P<0.01),AUC(area under the curve)of the OGTT(P<0.05)and p-IRS1(P<0.01 in JGXZ middle-and high-dose groups,P<0.05 in JGXZ low-dose groups).Moreover,JGXZ regulated the hepatic AMPKα/JNK pathway in NAFLD model rats,which reflected the induction of p-AMPKαand inhibition of p-JNK.Conclusion:This study showed that JGXZ improved liver function and reduced steatosis of the hepatocytes in NAFLD model rats.Moreover,JGXZ improved IR in NAFLD model rats.The possible mechanism underlying the effects of JGXZ on NAFLD and IR involves the modulation of the AMPK/JNK pathway.