Natural regulatory T cells and bifunctional regulatory T cells:potential targets of traditional Chinese medicine in treating colitis-associated colon cancer

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.

Pathogenesis and treatment of diabetes mellitus-related erectile dysfunction: current therapies and potential challenges

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.

Inhibiting the formation of neutrophil extracellular trapping: a potential mechanism of Chinese medicine in the treatment of ischemic stroke

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.

Repairing mitochondrial dysfunction:potential mechanisms of natural products in the treatment of NAFLD

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].

Traditional Chinese medicine for treatment of coronavirus disease 2019:a review

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.

Network pharmacology studies on the effect of Chai-Ling decoction incoronavirus disease 2019

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.

Jian-Gan-Xiao-Zhi decoction ameliorates high-fat high-carbohydrate diet-induced non-alcoholic fatty liver disease and insulin resistance by regulating the AMPK/JNK pathway

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.

Hua-Zhuo-Kai-Yu decoction inhibits apoptosis in nonalcoholic fatty liver disease

Background:Hua-Zhuo-Kai-Yu decoction(HZKY)is an empirical formula in traditional Chinese medicine that is derived from the classic ancient prescription Da-Chai-Hu decoction.It has been demonstrated to have good clinical effects on nonalcoholic fatty liver disease(NAFLD).However,the mechanism by which HZKY acts on NAFLD remains unclear.In this study,network pharmacology was used to predict the potential targets of HZKY in NAFLD.Additionally,in vivo studies were conducted to validate the crucial pathways determined using network pharmacology.Methods:Active compounds in HZKY were screened using the Traditional Chinese Medicine Systems Pharmacology and Analysis Platform and Traditional Chinese Medicine Integrated Database,and the potential targets of compounds in HZKY were predicted using Traditional Chinese Medicine Systems Pharmacology and Analysis Platform,Traditional Chinese Medicine Integrated Database,Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine,and PUBCHEM.In addition,targets involved in NAFLD were obtained from the GeneCards and Online Mendelian Inheritance in Man databases,and the potential targets of HZKY in NAFLD were identified based on the common potential targets between HZKY and NAFLD.Cytoscape 3.7.2 was used to visualize crosstalk and identify the key genes from the potential targets of HZKY in NAFLD.Kyoto Encyclopedia of Genes and Genomes analysis was conducted to predict the pathways by which HZKY acts on NAFLD.Rats were fed with a high-fat diet for 12 weeks to induce NAFLD and were then orally administered HZKY.Serum lipid levels and hematoxylin and eosin and oil red O staining results were assessed to determine the effects of HZKY in NALFD.Furthermore,the mechanisms of action of HZKY in NAFLD,as determined using network pharmacology,were validated based on the inhibition of apoptosis in the liver using Western blotting.Results:A total of 269 potential targets of 130 active compounds in HZKY were identified(oral bioavailability≥30%and drug-like≥0.18),and 62 targets were selected after being compared with the targets of NAFLD.Bcl-2-associated X protein(BAX),caspase3(CASP3),and caspase9(CASP9)were the key genes with the highest values of network connectivity.In addition,45 Kyoto Encyclopedia of Genes and Genomes pathways,including apoptosis,fatty acid synthesis,and estrogen signaling,were enriched according to the selected genes of HZKY.In vivo studies showed that the serum levels of total cholesterol,triglyceride,and low-density lipoprotein cholesterol were significantly elevated and the serum level of high-density lipoprotein cholesterol was decreased in the model group compared with those in the control group(P<0.01 for all).The expressions of BAX,CASP9,and CASP3 were upregulated in the model group compared with those in the control group(P<0.05,P<0.01,and P<0.01,respectively),while HZKY treatment decreased the body weights and serum levels of total cholesterol,triglyceride,and low-density lipoprotein cholesterol and increased the serum levels of high-density lipoprotein cholesterol in NAFLD model rats(P<0.05,P<0.01,P<0.05,and P<0.05,respectively).Hematoxylin and eosin and oil red O staining indicated that HZKY treatment reduced steatosis in the hepatocytes.Moreover,HZKY treatment inhibited apoptosis in the liver by downregulating the expressions of BAX,CASP3,and CASP9(P<0.05,P<0.01,and P<0.05,respectively).Conclusion:Our study demonstrates that HZKY improves NAFLD by inhibiting apoptosis in the liver by reducing the levels of BAX,CASP3,and CASP9.

Effector mechanism of Yunnan medicine “Yiqi Tongluo soup” in alleviating diabetic peripheral neuropathy by promoting autophagy

Objective:This study aimed to evaluate the effector mechanism of Yiqi Tongluo soup in alleviating diabetic peripheral neuropathy.Methods:Thirty male SD rats were divided into the control group,mode1 group,and Yiqi Tongluo group.Each group consists of 10 rats.Except for the normal group,a high-sugar and high-fat diet combined with streptozocin injection were administered to the groups to constnuct the type 2 diabetes mellitus model.Then,6.48 g/kg of Yiqi Tongluo soup was administered to the Yiqi Tongluo group every day by gavage.An equal volume of physiological saline was administered to the control and model groups every day by gavage.During the experiment,changes in blood glucose and nerve conduction velocity were monitored in all groups.After the experiment,hematoxylin and eosin and luxol fast blue staining were carried out,and morphological changes in the sciatic nerve and myelin sheath in all groups were observed.Western blot was used to observe changes in expression levels of autophagy related proteins,Beclin-1,LC3,and P62.Results:Blood glucose significantly increased,and nerve conduction velocity significantly decreased in the model group.Yiqi Tongluo soup significantly decreased blood glucose level while simultaneously increasing nerve conduction velocity.Hematoxylin and eosin and luxol fast blue myelin sheath staining results showed that Yiqi Tongluo soup could improve sciatic nerve disorder,irregular myelin sheath morphology,and demyelination in type 2 diabetes mellitus rats.Western blot results showed that Beclin-1 and LC3I/LC3I expression levels in the model group significantly decreased,while P62 level significantly increased.Compared with the model group,Beclin-1 and LC3II/LC3I expression levels significantly increased and P62 levels significantly decreased in the Yiqi Tongluo group.Conclusion:Yiqi Tongluo soup can inhibit diabetic peripheral neuropathy by increasing autophagy.

Advances in traditional Chinese medicine for liver disease therapy in 2021

Liver diseases and their co-morbidities represent a major public health problem.Owing to its progressive pathogenesis and lack of effective treatment,liver disease has become one of the most important causes of death worldwide.Traditional Chinese medicine(TCM)has potential advantages in the prevention and treatment of liver diseases,including high safety,remarkable curative effects,and low toxicity and side effects.In 2021,TCM extracts and their derivatives,TCM compounds,and ethnic medicines showed good efficacy in the treatment of liver diseases.The main mechanisms and representative drugs of TCM can be summarized by the use of amygdalin,dicoumarol,quercetin,and ancient ephedrine decoction to treat hepatitis by inhibiting viral replication,as well as the use of Gentianae Radix,lupeol,Zornia diphylla(L.)Pers.,and Chinese patent medicine Liuwei Wuling tablet to alleviate acute liver injury by improving oxidative stress and inflammatory responses in the body.In the treatment of alcoholic liver disease and metabolic-associated fatty liver disease,the mechanism of TCM is the inhibition of oxidative stress,improving metabolism,regulating intestinal microflora,and enhancing intestinal barrier function.The representative TCM for alcoholic liver disease includes astragaloside,puerarin,patchouli alcohol,and Mori Fructus polysaccharide,while those for metabolic-associated fatty liver disease include saikosaponin,dehydroabietic acid,hesperetin,berberine,and Panax Notoginseng saponins.Additionally,germacrone,forsythin,geniposide,and protocatechuic acid can inhibit the activation or migration of stellate cells and improve liver fibrosis.Toosendanin,paeoniflorin,chrysin,and the classical prescription Huanglian decoction can significantly inhibit the proliferation of liver cancer cells and promote their apoptosis for the treatment of hepatocellular carcinoma.The activation of the farnesol X receptor pathway can improve bile metabolism in the liver,thus,significantly alleviating cholestatic liver disease.Its representative drugs include the TCM extracts pterostilbene and arbutin.In this review,we summarize the advances made in research on TCM used in the treatment of liver diseases in 2021,providing a reference for further development of TCM for the prevention and treatment of liver diseases.

Advances in Chinese medicine treatment and research on endocrine diseases in 2021

This paper reviews the progress in treatment regimens involving traditional Chinese medicine and research on common clinical endocrine diseases in 2021,to provide a reliable basis for the traditional Chinese medicine treatment of endocrine diseases.In 2021-2022,research on traditional Chinese medicine for endocrine diseases has been focused on pathogenesis.We have summarized the results of the use of traditional Chinese medicine and herbal extracts for treating common endocrine system diseases in 2021,focusing on the following aspects.(1)Chinese herbal extracts or active ingredients,such as echinatin,breviscapine,and puerarin,can treat metabolic-associated fatty liver disease by inhibiting inflammation and oxidative stress,improving lipid metabolism,and regulating intestinal flora.(2)Chinese herbal extracts or active ingredients,such as Juglandis Semen extracts,Momordica charantia saponins,and Anemarrhenae Rhizoma extracts can treat type 2 diabetes by reducing insulin resistance,improving pancreatic beta cell function,and regulating intestinal microbial disorders.(3)Chinese herbal extracts or active ingredients,such as berberine,astragaloside IV,and Scutellariae Barbatae Herba polysaccharides,can treat diabetes-related complications by improving mitochondrial function,regulating autophagy,and inhibiting apoptosis and pyroptosis.(4)Chinese herbal medicines and herbal extracts or active ingredients,such as berberrubine and Resedaodorata,can treat hyperuricemia by activating the Janus kinase 2/signal transducers and activators of transcription 3 signaling pathway and inhibiting toll-like receptor 4/NOD-like receptor family,pyrin domain-containing protein 3 signaling to increase urate excretion.(5)Herbal extracts or active ingredients,such as ginsenoside Rb1,corylin,and Scutellariae Radix polysaccharides,can exert anti-obesity effects by promoting the browning of white adipocytes,activation of brown adipose tissue,and regulation of intestinal flora.(6)Chinese herbal extracts or active ingredients,such as diosgenin and Prunellae Spica extract,are able to treat thyroid-related diseases by inhibiting nucleotide-binding oligomerization domain-like receptor protein 3 inflammatory vesicle activation,regulating the expression of proliferating cell nuclear antigen,and cadherin 1,and upregulating the ubiquitination of interferon regulatory factor 4.

Integration of multi-omics in investigations on the mechanisms of action of Chinese herbal medicine interventions in metabolic diseases

The rapid development of bioinformatics has provided novel approaches and methods for exploring the mechanisms of disease treatment via Chinese herbal medicines.Compound Chinese herbal medicines formulas have complex compositions and are characterized by their multiple constituents and diverse array of biological targets.Therefore,the mechanisms of action of most compound Chinese herbal medicines formulas cannot be adequately explained using a single pathway.Omics technologies describe high-throughput-based analytical and detection techniques,which include transcriptomics,proteomics,and metabolomics and provide multilayer parameter information that can be integrated to characterize the overall relationships involved in the therapeutic effects of Chinese herbal medicines formulas.Through their combination with network biology and drug effect networks,omics technologies also enable investigations into the mechanisms of disease treatment in traditional Chinese medicine.The integration of multiple omics technologies is in line with the concept of holism in traditional Chinese medicine and provides an approach for combining modern science and technology with traditional Chinese medicine theories.In recent years,omics technologies have been widely used to elucidate the mechanisms of action of Chinese herbal medicines.The latest studies employing multi-omics integration for investigating the mechanisms of action of Chinese herbal medicines interventions in metabolic diseases have devoted greater attention to in-depth explorations of disease pathogenesis.This paper provides a review of the following multi-omics technologies,which are used in research on the treatment of common metabolic diseases(e.g.,type-2 diabetes mellitus,nonalcoholic fatty liver disease):network pharmacology combined with metabolomics,16S rRNA sequencing combined with transcriptomics,16S rRNA sequencing combined with metabolomics,and 16S rRNA sequencing combined with network pharmacology and metabolomics.

Research progress of epigenetic modification in autophagy regulation

Autophagy can maintain the homeostasis of cells by removing the accumulated proteins,damaged organelles and pathogens.Studies have shown that autophagy is closely related to a variety of life activities,and its dysfunction often leads to tumor,degenerative diseases and other diseases.Epigenetic modification is widely involved in autophagy and plays an important role in the occurrence and development of many diseases.In order to further understand the mechanism of autophagy,we review the related signaling pathways and epigenetic modifications of autophagy.

The relationship between mitochondrial autophagy and diabetes mellitus and the intervention effect of traditional Chinese Medicine

Mitochondria are the main site of oxidative phosphorylation in cells,and their functional homeostasis is important for maintaining the balance of cellular energy metabolism.Mitophagy is a protective mechanism by which cells selectively degrade and remove damaged or excess mitochondria by autophagy,thereby maintaining the stability of mitochondrial quantity and quality in cells.Recent studies have shown that mitophagy imbalance is involved in developing diabetes mellitus type 2,and regulating mitophagy provides a new idea to study the mechanism of action of traditional Chinese medicine in treating diabetes mellitus type 2.First,this study summarizes the relationship between mitophagy and diabetes mellitus type 2;second,we review studies on mitophagy modulation in diabetes mellitus type 2 using traditional Chinese medicine.

The mechanistic study on Wa medicine Niang-Mu-Liang medicinal liquor mitigating diabetes mellitus erectile dysfunction in rats by inhibiting ferroptosis

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.

Ethanol extract of Ardisiae Japonicae Herba inhibits hepatoma carcinoma cell proliferation in vitro through regulating lipid metabolism

Objective:The aim of this study is to discover the possible working mechanisms of Ardisiae Japonicae Herba(AJH)on hepatoma carcinoma(HCC).Methods:In this study,ethanol extract of AJH was prepared and used to treat HCC cell in vitro.Furthermore,a genomic wide RNA sequencing(RNA-seq)was performed to screen deregulated genes in HCC cells after the treatment of AJH extract.The gene and protein expression related to lipid metabolism in HCC cells were also investigated to validate the results obtained from RNA-seq.Results:AJH extract could inhibit HCC cell proliferation in vitro.RNA-seq analysis has identified 1,601 differentially expressed genes(DEGs,fold change≥2.0 or fold change≤0.5,P<0.05)in HCC after AJH extract treatment,which included 225 up-regulated genes and 1,376 down-regulated genes.KEGG pathway analysis of DEGs demonstrated that lipid metabolism was a potential pathway related to AJH treatment.In agreement with the RNA-seq data,q PCR and Western-blot analysis indicated that expression of genes and proteins related to lipid metabolism(SREBP1,ACC,ACLY and FASN)were significantly downregulated in AJH treatment group as compared with the control group.Furthermore,AJH extract could also decrease lipid contents and cellular free fatty acid levels in HCC cells.Conclusion:Ethanol extract of AJH could inhibit HCC cell proliferation in vitro,the possible mechanism may be related to the inhibition of lipid metabolism.