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.

Mechanism of Baihu Renshen decoction on T2DM rats based on mitochondrial autophagy mediated by PINK1/Parkin

Background:This study will be aimed at investigating the effects of Baihu Renshen decoction(BHRS)on type 2 diabetes rats and on macromolecular enzyme 1(PINK1)/E3 ubiquitin protein ligase(Parkin)pathway.Methods:The experiment was divided into four groups:control group,model group,metformin group and BHRS low-dose group and high-dose group.Forty male rats were selected as samples and randomly assigned to at least one test group.Finally,there are 18 rats in each group.Except for the control group,the rats within the different teams got a high-fat diet associate in nursing an intraperitoneal injection of streptozotocin to make a type 2 diabetes mellitus(T2DM)rat model.The organic chemistry and inflammatory indexes of rats in every cluster were analyzed and compared once four weeks of intragastric administration of comparable reagents to review the therapeutic impact of BHRS on T2DM.In addition,we determined the pathological changes of ductal gland tissue of T2DM rats after treatment,and compared the expression of mitochondrial phagocytosis related proteins in ductal gland tissue of rats in each group.Results:FBG,LDL-C,TC,TG,MDA,IL-1,IL-6,TNF-,and mitophagy-related proteins COXIV,P62,VDAC1,and TOM20 were elevated in the model group compared to the control group,while HDL-C,SOD,GSH-Px,and mitophagy-related proteins PINK1,Parkin,and LC3II/I were decreased(P<0.05 or P<0.01).The expressions of FBG,TC,TG,LDL-C,MDA,IL-1,IL-6,TNF-,and mitophagy-related proteins COXIV,P62,VDAC1,and TOM20 were lowered in the BHRS group,while the expressions of HOMA-,HDL-C,SOD,GSH-Px,and mitophagy-related proteins PINK1,Parkin,and LC3II/I were(P<0.05 or P<0.01).After therapy with BHRS,hematoxylin-eosin staining showed that the intensity of pancreatic acinar staining increased,and islet cells became clear boundaries that were,regularly arranged,and with reduced vacuoles reduced.Conclusion:BHRS has a clear therapeutic effect on T2DM,which may be achieved by regulating mitochondrial autophagy through the PINK1/Parkin pathway.

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.

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.