Objective:To investigate the therapeutic efficacy and underlying mechanisms of LiZhong Tang in the context of non-alcoholic fatty liver disease(NAFLD).Methods:High-fat feed was used to induce NAFLD in rats,Blood and l...Objective:To investigate the therapeutic efficacy and underlying mechanisms of LiZhong Tang in the context of non-alcoholic fatty liver disease(NAFLD).Methods:High-fat feed was used to induce NAFLD in rats,Blood and liver samples were collected to facilitate a comparative analysis of rat body mass and liver wet weight and calculate the liver index.Liver pathology was observed,while serum transaminase and blood lipid levels were measured.The protein expression levels of PINK1,Parkin,and LC-3II in rat liver were detected using Western Blot analysis.Results:Compared with the control group,the NAFLD rats exhibited a significant increase in body weight,liver wet weight,liver index,transaminase levels,and blood lipid levels.The expression levels of PINK1,Parkin,and LC3-II protein were significantly decreased(P<0.01).Following intervention with Lizhong Tang,rats in each herbal treatment group displayed a decrease in body weight,liver wet weight,liver index,se-rum transaminase,and blood lipid levels.The expression levels of PINK1,Parkin,and LC-3II rebounded(P<0.05),with the high-dose group demonstrating the most pronounced effects(P<0.01).Histopathological examination of liver tissue revealed that rats in the model group displayed disrupted hepatic lobule structure,swollen hepatocytes,disordered arrangement,and a multi-tude of varying-sized lipid vacuoles within the cytoplasm.Conversely,rats treated with different doses of the herbal remedy exhibited improvements in liver tissue pathology,with the high-dose group showing the most notable enhancement.Conclusion:Lizhong Tang can improve NAFLD disease by regulating mitochondrial autophagy.展开更多
With a long industrial chain and a powerful ability to drive other industries,the automobile manufacturing industry has a prominent strategic position in the national economy.In recent years,many countries have put on...With a long industrial chain and a powerful ability to drive other industries,the automobile manufacturing industry has a prominent strategic position in the national economy.In recent years,many countries have put on their agenda the digitalization of the automobile manufacturing industry,leading to an connected,autonomous,shared,and electric(also known as CASE)①development trend in the industry.As one of the six major automobile industry clusters in China,the Chengdu-Chongqing economic circle has achieved initial results in the digital transformation of the automobile manufacturing industry.However,the region is still faced with some constraints,such as insufficient digital infrastructure,relatively slow development of new automobile products,insufficient innovation ability of the automobile industry,and complex digital transformation of small and medium-sized automobile enterprises(automobile SMEs).This paper intends to construct a framework for the mechanism of action of the digital transformation in the automobile manufacturing industry,analyze the effects of the digital transformation of the automobile manufacturing industry in the Chengdu-Chongqing economic circle,and propose feasible paths for the digital transformation of the automobile manufacturing industry in the region by drawing on domestic and international experience in this regard.The specific paths include:(a)Smoothing the“dual-core”data chain to facilitate the digital transformation of the automobile manufacturing industry;(b)Developing the new energy vehicle(NEV)industry to upgrade the quality of automobile products;(c)Achieving corner overtaking in the digital transformation of the automobile manufacturing industry with digital technology;(d)Jointly building the automobile industrial park to promote the digital transformation of the industry;(e)Addressing problems facing automobile SMEs in digital transformation via targeted policy tools.展开更多
Objective:To study the mechanism of action and therapeutic effect of modified Qiwei Baishu powder in diabetic patients.Methods:From January 2021 to January 2022,80 diabetic patients were recruited in our study and div...Objective:To study the mechanism of action and therapeutic effect of modified Qiwei Baishu powder in diabetic patients.Methods:From January 2021 to January 2022,80 diabetic patients were recruited in our study and divided into two groups by the random number table method.Group A was treated with modified Qiwei Baishu powder,whereas group B was treated with western medicine.The therapeutic effect,traditional Chinese medicine(TCM)syndrome score,blood sugar level,and incidence of adverse reaction were compared between the two groups.Result:The therapeutic effect in group A was significantly higher than that in group B(P<0.05);the TCM syndrome scores of group A were significantly lower than those of group B(P<0.05);the fasting blood glucose(FBG),2 hour-postprandial blood glucose(PBG),and glycosylated hemoglobin(HbA1c)levels of group A were significantly lower than those of group B(P<0.05);the incidence of adverse reaction in group A was significantly lower than that in group B(P<0.05).Conclusion:On the basis of western medicine,the addition of modified Qiwei Baishu powder can maintain stable blood sugar levels in patients and alleviate diabetic symptoms;thus,it is not only effective,but also safe for clinical use in diabetes.展开更多
Despite that some approved drugs and genetically engineered vaccines against hepatitis B virus(HBV)are available for HBV patients,HBV infection is still a severe public health problem in the world.All the approved the...Despite that some approved drugs and genetically engineered vaccines against hepatitis B virus(HBV)are available for HBV patients,HBV infection is still a severe public health problem in the world.All the approved therapeutic drugs(including interferonalpha and nucleoside analogues)have their limitations.No drugs or therapeutic methods can cure hepatitis B so far.Therefore,it is urgently needed to discover and develop new anti-HBV drugs,especially nonnucleoside agents.Naturally originated compounds with enormous molecular complexity and diversity offer a great opportunity to find novel anti-HBV lead compounds with specific antiviral mechanisms.In this review,the natural products against HBV are discussed according to their chemical classes such as terpenes,lignans,phenolic acids,polyphenols,lactones,alkaloids and flavonoids.Furthermore,novel mode of action or new targets of some representative anti-HBV natural products are also discussed.The aim of this review is to report new discoveries and updates pertaining to anti-HBV natural products in the last 20years,especially novel skeletons and mode of action.Although many natural products with various skeletons have been reported to exhibit potent anti-HBV effects to date,scarcely any of them are found in the list of conventional anti-HBV drugs worldwide.Additionly,in anti-HBV mechanism of action,only a few references reported new targets or novel mode of action of antiHBV natural products.展开更多
The management of bacterial infections is becoming a major clinical challenge due to the rapid evolution of antibiotic resistant bacteria.As an excellent candidate to overcome antibiotic resistance,antimicrobial pepti...The management of bacterial infections is becoming a major clinical challenge due to the rapid evolution of antibiotic resistant bacteria.As an excellent candidate to overcome antibiotic resistance,antimicrobial peptides(AMPs)that are produced from the synthetic and natural sources demonstrate a broad-spectrum antimicrobial activity with the high specificity and low toxicity.These peptides possess distinctive structures and functions by employing sophisticated mechanisms of action.This comprehensive review provides a broad overview of AMPs from the origin,structural characteristics,mechanisms of action,biological activities to clinical applications.We finally discuss the strategies to optimize and develop AMP-based treatment as the potential antimicrobial and anticancer therapeutics.展开更多
Leucine-rich repeat kinase 1 (LRRK1) plays a critical role in regulating cytoskeletal organization, osteoclast activity, and bone resorption with little effect on bone formation parameters. Deficiency of Lrrk1 in mice...Leucine-rich repeat kinase 1 (LRRK1) plays a critical role in regulating cytoskeletal organization, osteoclast activity, and bone resorption with little effect on bone formation parameters. Deficiency of Lrrk1 in mice causes a severe osteopetrosis in the metaphysis of the long bones and vertebrae bones, which makes LRRK1 an attractive alternative drug target for the treatment of osteoporosis and other high-turnover bone diseases.This review summarizes recent advances on the functions of the Lrrk1-related family members, Lrrk1deficiency-induced skeletal phenotypes, LRRK1 structure–function, potential biological substrates and interacting proteins, and the mechanisms of LRRK1 action in osteoclasts.展开更多
Nagilactones are tetracyclic natural products isolated from various Podocarpus species.These lactone-based compounds display a range of pharmacological effects,including antifungal,anti-atherosclerosis,anti-inflammato...Nagilactones are tetracyclic natural products isolated from various Podocarpus species.These lactone-based compounds display a range of pharmacological effects,including antifungal,anti-atherosclerosis,anti-inflammatory and anticancer activities reviewed here.The most active derivatives,such as nagilactones C,E and F,exhibit potent anticancer activities against different cancer cell lines and tumor models.A comprehensive analysis of their mechanism of action indicates that their anticancer activity mainly derives from three complementary action:(i)a drug-induced inhibition of cell proliferation coupled with a cell cycle perturbation and induction of apoptosis,(ii)a blockade of the epithelial to mesenchymal cell transi-tion contributing to an inhibition of cancer cell migration and invasion and(iii)a capacity to modulate the PD-L1 immune checkpoint.Different molecular effectors have been implicated in the antitumor activity,chiefly the AP-1 pathway blocked upon activation of the JNK/c-Jun axis.Nag-C is a potent inhibitor of protein synthesis binding to eukaryotic ribosomes and inhibition of different protein kinases,such as RIOK2 and JAK2,has been postulated with Nag-E.The literature survey on nagilactones highlights the therapeutic potential of these little-known terpenoids.The mechanistic analysis also provides useful information for structurally related compounds(podolactones,oidiolactones,inumakilactones)isolated from Podo-carpus plants.展开更多
Biflavonoids are divided in two classes:C-C type compounds represented by the dimeric compound amentoflavone and C-O-C-type compounds typified by hinokiflavone(HNK)with an ether linkage between the two connected apige...Biflavonoids are divided in two classes:C-C type compounds represented by the dimeric compound amentoflavone and C-O-C-type compounds typified by hinokiflavone(HNK)with an ether linkage between the two connected apigenin units.This later sub-group of bisflavonyl ethers includes HNK,ochnaflavone,delicaflavone and a few other dimeric compounds,found in a variety of plants,notably Selaginella species.A comprehensive review of the anticancer properties and mechanism of action of HNK is provided,to highlight the anti-proliferative and anti-metastatic activities of HNK and derivatives,and HNK-containing plant extracts.The anticancer effects rely on the capacity of HNK to interfere with the ERK1-2/p38/NFκB signaling pathway and the regulation of the expression of the matrix metalloproteinases MMP-2 and MMP-9(with a potential direct binding to MMP-9).In addition,HNK was found to function as a potent modulator of pre-mRNA splicing,inhibit-ing the SUMO-specific protease SENP1.As such,HNK represents a rare SENP1 inhibitor of natural origin and a scaffold to design synthetic compounds.Oral formulations of HNK have been elaborated to enhance its solubility,to facilitate the compound delivery and to enhance its anticancer efficacy.The review shed light on the anticancer potential of C-O-C-type biflavonoids and specifically on the pharmacological profile of HNK.This compound deserves further attention as a regu-lator of pre-mRNA splicing,useful to treat cancers(in particular hepatocellular carcinoma)and other human pathologies.展开更多
Objective:To predict the mechanism of action of San Huang lotion for topical treatment of eczema at the level of network pharmacology and molecular docking technology.Methods:The active ingredients and corresponding t...Objective:To predict the mechanism of action of San Huang lotion for topical treatment of eczema at the level of network pharmacology and molecular docking technology.Methods:The active ingredients and corresponding targets of San Huang lotion were collected using the TCMSP data platform and UniProt;the relevant gene targets of San Huang lotion were collected using the GeneCards database,OMIM database,TTD database,and DrugBank database;the intersection targets of San Huang lotion and eczema were obtained by creating avenn diagram;the key active ingredients and targets were screened by constructing a disease-active ingredient-target map,and the key active ingredients and core targets were screened out by constructing disease-active ingredient-target diagrams and PPInetwork diagrams;GOand KEGGenrichment analyses were conducted using the metascapewebsite and the higher significant entries were selected to produce bar charts and bubble plots.Finally,molecular docking of key active ingredients and core targets was performed.Results:A total of 134 active ingredients and 3,320 eczema-related target genes were screened for San Huang lotion,and 126 intersecting targets were obtained for San Huang lotion and eczema.The five key active ingredients of San Huang lotion for topical treatment of eczema and six core targets ofAKT1,TNF,IL6,IL1B,TP53andVEGFA were obtained by drug-active ingredient-target map and PPInetwork map.The GOand KEGGenrichment analysis showed that the topical treatment of eczema withSanHuanglotion might be mediated throughIL-17signaling pathway,TNFsignaling pathway and Th17cell differentiation pathway.The molecular docking results showed that the docking binding energy of key active ingredients and core targets was mostly less than-5 kcal/mol,and the docking was good.Conclusion:The quercetin,luteolin,wogonin,formononetin,beta-sitosterol and other active ingredients in San Huang lotion may act on eczema through AKT1,TNF,IL6,IL1B,TP53,VEGFA and other targets,and through IL-17signaling pathway,TNFsignaling pathway,Th17cell differentiation and other pathways.展开更多
[Objectives] This study was conducted to investigate the mechanism of action of glyasperin A in the treatment of atherosclerosis using a network pharmacology approach. [Methods] Targets related to atherosclerosis were...[Objectives] This study was conducted to investigate the mechanism of action of glyasperin A in the treatment of atherosclerosis using a network pharmacology approach. [Methods] Targets related to atherosclerosis were searched in GeneCards database. An active ingredient-disease-target network was constructed by Cytoscape 3.7.1. A target protein interaction network was constructed by String database. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed on the DAVID database. [Results] Glyasperin A acted on 36 atherosclerosis-related targets, and the biofunctional and pathway enrichment analyses showed that it was mainly involved in response to xenobiotic stimulus, drug transport across blood-brain barrier, lipid oxidation, barrier, and lipid oxidation, etc. The results showed that glyasperin A acted on 36 atherosclerosis-related targets. The biofunctional and pathway enrichment analyses showed that it was mainly involved in response to xenobiotic stimulus, drug transport across blood-brain barrier, lipid oxidation, positive regulation of protein localization to nucleus, and hepoxilin biosynthetic process, and it played an anti-fatigue role through signal pathways such as serotonergic synapse, efferocytosis, arachidonic acid metabolism, chemical carcinogenesis-receptor activation and platelet activation. [Conclusions] Glyasperin A has multi-target and multi-pathway effects in the treatment of atherosclerosis. This study provides reference for further research on glyasperin A in the treatment of atherosclerosis.展开更多
Cerebral ischemia-reperfusion is a process in which the blood supply to the brain is temporarily interrupted and subsequently restored.However,it is highly likely to lead to further aggravation of pathological damage ...Cerebral ischemia-reperfusion is a process in which the blood supply to the brain is temporarily interrupted and subsequently restored.However,it is highly likely to lead to further aggravation of pathological damage to ischemic tissues or the nervous system.,and has accordingly been a focus of extensive clinical research.As a traditional Chinese medicinal formulation,Sanhua Decoction has gradually gained importance in the treatment of cerebrovascular diseases.Its main constituents include Citrus aurantium,Magnolia officinalis,rhubarb,and Qiangwu,which are primarily used to regulate qi.In the treatment of neurological diseases,the therapeutic effects of the Sanhua Decoction are mediated via different pathways,including antioxidant,anti-inflammatory,and neurotransmitter regu-latory pathways,as well as through the protection of nerve cells and a reduction in cerebral edema.Among the studies conducted to date,many have found that the application of Sanhua Decoction in the treatment of neurological diseases has clear therapeutic effects.In addition,as a natural treatment,the Sanhua Decoction has received widespread attention,given that it is safer and more effective than traditional Western medicines.Consequently,research on the mechanisms of action and efficacy of the Sanhua Decoctions in the treatment of cerebral ischemia-reperfusion injury is of considerable significance.In this paper,we describe the pathogenesis of cerebral ischemia-reperfusion injury and review the current status of its treatment to examine the therapeutic mechanisms of action of the Sanhua Decoction.We hope that the findings of the research presented herein will contribute to a better understanding of the efficacy of this formulation in the treatment of cerebral ischemia-reperfusion,and provide a scientific basis for its application in clinical practice.展开更多
Psoriasis is a kind of immune-mediated, chronic, inflammatory skin disease, which is often associated with different degrees of psychological disorders. Specifically, there is a significant correlation between psorias...Psoriasis is a kind of immune-mediated, chronic, inflammatory skin disease, which is often associated with different degrees of psychological disorders. Specifically, there is a significant correlation between psoriasis and depression, and they show the relationships of reciprocal causation and mutual promotion. Psoriasis with depression is more harmful than simple psoriasis, and its prognosis is worse, which brings a huge burden to the family and society and is worthy of clinical attention. Based on the pathogenic factors of western medicine and pathogenesis of traditional Chinese medicine in psoriasis with depression, the paper summarized and elaborated the research progress on the mechanism of traditional Chinese medicine in the treatment of psoriasis with depression, in order to provide new ideas for clinical treatment.展开更多
Objective:To explore the potential mechanism of action of quercetin in the treatment of diarrhea irritable bowel syndrome(IBS-D).Methods:The potential targets of quercetin were obtained from the TCMSP,SwissTar-getPred...Objective:To explore the potential mechanism of action of quercetin in the treatment of diarrhea irritable bowel syndrome(IBS-D).Methods:The potential targets of quercetin were obtained from the TCMSP,SwissTar-getPrediction,and BATMAN-TCM databases.The targets of IBS-D were obtained by searching the GeneCards database with"diarrhea irritable bowel syndrome"as the keyword,and the targets of quercetin and IBS-D were intersected.The PPI network was constructed by Cytoscape 3.7.1 software.The intersected targets were imported into the DAVID database for GO functional analysis and KEGG pathway enrichment analysis.The binding ability of quercetin to the core targets was observed using molecular docking.Based on this,we established an IBS-D rat model,administered quercetin for intervention,and experimentally validated the network pharmacology prediction results by HE staining and ELISA assay.Results:Network pharmacology analysis showed that TP53,TNF-α,AKT1,VEGF-A,IL-6 factors and MAPK,PI3K-Akt signaling pathway as the core targets and pathways of quercetin for the treatment of IBS-D.The results of animal experiments revealed that quercetin could inhibit the secretion of TP53,TNF-α,AKT1,VEGF-A,IL-1βand IL-6,reduce the inflammatory response and improve IBS-D.Conclusion:Quercetin could protect colon tissue by regulating the expression of TP53,TNF-α,AKT1,VEGF-A,IL-1βand IL-6,thereby treating IBS-D.展开更多
Autoimmune hepatitis is an inflammatory liver disease primarily mediated by T cell.It has not been fully elucidated about the pathogenesis,and it is presently thought to be related to genetic susceptibility,infection ...Autoimmune hepatitis is an inflammatory liver disease primarily mediated by T cell.It has not been fully elucidated about the pathogenesis,and it is presently thought to be related to genetic susceptibility,infection and environmental triggers,and abnormal autoimmune regulation.Recent studies have found that traditional Chinese medicine can improve the biochemical indicators and clinical symptoms of patients with autoimmune hepatitis.This article reviews the specific mechanism of traditional Chinese medicine on treating autoimmune hepatitis in order to propose new ideas for its clinical diagnosis and treatment.展开更多
Albizzia julibrissin is empirically used as an antidepressant in clinical practice.Preclinical studies have indicated that its total extracts or bioactive constituents exerted antidepressant-like responses in animal m...Albizzia julibrissin is empirically used as an antidepressant in clinical practice.Preclinical studies have indicated that its total extracts or bioactive constituents exerted antidepressant-like responses in animal models,providing the molecular basis to reveal its underlying mechanism of action.While attempts have been made to understand the antidepressant effect of A.julibrissin,many fundamental questions regarding its mechanism of action remain to be addressed at the molecular and systems levels.In this review,we conclusively discussed the mechanism of action of A.julibrissin and A.julibrissin formulae by reviewing recent preclinical and clinical studies conducted by using depressive animal models and depressive patients.Several representative bioactive constituents and formulae were highlighted as examples,and their mechanisms of action were discussed.In addition,some representative A.julibrissin formulae that have been shown to be compatible with conventional antidepressants in clinical practice were also reviewed.Furthermore,we discussed the future research directions to reveal the underlying mechanism of A.julibrissin at the molecular and systems levels in depression treatment.The integrated study using both the molecular and systematic approaches is required not only for improving our understanding of its molecular basis and mechanisms of action,but also for providing a way to discover novel agents or approaches for the effective and systematic treatment of depression.展开更多
BACKGROUND Diabetic nephropathy(DN)stands as the most prevalent chronic microvascular complication of diabetes mellitus.Approximately 50%of DN patients progress to end-stage renal disease,posing a substantial health b...BACKGROUND Diabetic nephropathy(DN)stands as the most prevalent chronic microvascular complication of diabetes mellitus.Approximately 50%of DN patients progress to end-stage renal disease,posing a substantial health burden.AIM To employ network pharmacology and molecular docking methods to predict the mechanism by which glycyrrhetinic acid(GA)treats DN,subsequently validating these predictions through experimental means.METHODS The study initially identified GA targets using Pharm Mapper and the TCMSP database.Targets relevant to DN were obtained from the Genecards,OMIM,and TTD databases.The Venny database facilitated the acquisition of intersecting targets between GA and DN.The String database was used to construct a protein interaction network,while DAVID database was used to conducted Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis and Gene Ontology(GO)analysis.Molecular docking experiments were performed using Autodock software with selected proteins.Experimental validation was conducted using renal proximal tubular cells(HK-2)as the study subjects.A hyperglycemic environment was simulated using glucose solution,and the effect of GA on cell viability was assessed through the cell counting kit-8 method.Flow cytometry was employed to detect cell cycle and apoptosis,and protein immunoblot(western blot)was used to measure the expression of proteins of the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway and insulin resistance pathway,including insulin receptor(INSR),PI3K,p-PI3K,AKT,p-AKT,and glycogen synthase kinase-3(GSK3).RESULTS A total of 186 intersecting targets between GA and DN were identified,which were associated with 144 KEGGrelated enrichment pathways,375 GO biological process entries,45 GO cellular component entries,and 112 GO cellular function entries.Molecular docking demonstrated strong binding of GA to mitogen-activated protein kinase(MAPK)-1,SRC,PIK3R1,HSP90AA1,CASPASE9,HARS,KRAS,and MAPK14.In vitro experiments revealed that GA inhibited HK-2 cell viability,induced cell cycle arrest at the G2/M phase,and reduced apoptosis with increasing drug concentration.Western blot analysis showed that GA differentially up-regulated GSK3 protein expression,up-regulated AKT/p-AKT expression,down-regulated INSR,AKT,p-AKT,PI3K,and p-PI3K protein expression,and reduced p-PI3K/PI3K levels under high glucose conditions.CONCLUSION GA may protect renal intrinsic cells by modulating the PI3K/AKT signaling pathway,thereby inhibiting HK-2 cell viability,reducing HK-2 cell apoptosis,and inducing cell cycle arrest at the G0/G1 phase.展开更多
BACKGROUND Jiawei Jiaotai Pill is commonly used in clinical practice to reduce apoptosis,increase insulin secretion,and improve blood glucose tolerance.However,its mechanism of action in the treatment of diabetic card...BACKGROUND Jiawei Jiaotai Pill is commonly used in clinical practice to reduce apoptosis,increase insulin secretion,and improve blood glucose tolerance.However,its mechanism of action in the treatment of diabetic cardiomyopathy(DCM)remains unclear,hindering research efforts aimed at developing drugs specifically for the treatment of DCM.AIM To explore the pharmacodynamic basis and molecular mechanism of Jiawei Jiaotai Pill in DCM treatment.METHODS We explored various databases and software,including the Traditional Chinese Medicine Systems Pharmacology Database,Uniport,PubChem,GenCards,String,and Cytoscape,to identify the active components and targets of Jiawei Jiaotai Pill,and the disease targets in DCM.Protein-protein interaction network,gene ontology,and Kyoto Encyclopedia of Genes and Genomes analyses were used to determine the mechanism of action of Jiawei Jiaotai Pill in treating DCM.Molecular docking of key active components and core targets was verified using AutoDock software.RESULTS Total 42 active ingredients and 142 potential targets of Jiawei Jiaotai Pill were identified.There were 100 common targets between the DCM and Jiawei Jiaotai Pills.Through this screening process,TNF,IL6,TP53,EGFR,INS,and other important targets were identified.These targets are mainly involved in the positive regulation of the mitogen-activated protein kinase(MAPK)MAPK cascade,response to xenobiotic stimuli,response to hypoxia,positive regulation of gene expression,positive regulation of cell proliferation,negative regulation of the apoptotic process,and other biological processes.It was mainly enriched in the AGE-RAGE signaling pathway in diabetic complications,DCM,PI3K-Akt,interleukin-17,and MAPK signaling pathways.Molecular docking results showed that Jiawei Jiaotai Pill's active ingredients had good docking activity with DCM's core target.CONCLUSION The active components of Jiawei Jiaotai Pill may play a role in the treatment of DCM by reducing oxidative stress,cardiomyocyte apoptosis and fibrosis,and maintaining metabolic homeostasis.展开更多
Background:To explore the pharmacological mechanism of the anti-hepatitis B virus of Phyllanthus urinaria L.through network pharmacological analysis and experimental validation.Method:The active ingredient,target of a...Background:To explore the pharmacological mechanism of the anti-hepatitis B virus of Phyllanthus urinaria L.through network pharmacological analysis and experimental validation.Method:The active ingredient,target of action and target of action related to hepatitis B were clarified by searching the herb group identification,GeneCards and OMIM databases,and the protein interaction relationship was obtained by using the String database,and the protein interaction network map was constructed by using Cytoscape software.We also performed gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis of key targets of the anti-hepatitis B action of Phyllanthus urinaria L.and predicted the core targets and pathways of Phyllanthus urinaria L.anti-hepatitis B.The main targets predicted by network pharmacology were then validated by HepG2.2.15 cell experiments.Results:By searching active ingredient targets and hepatitis B disease targets,a total of 19 active ingredients and 64 related targets of action were retrieved from Phyllanthus urinaria L.,and a total of 51 common targets were obtained by mapping the obtained hepatitis B disease targets and drug targets.protein protein interaction network analysis indicated that targets including TNF,JUN,AKT1,IL-10,IL-1B,CAT,HMOX1,NFE2L2,and CASP3 and other targets may be the core targets.gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that the treatment of hepatitis B by Phyllanthus urinaria L.mainly included inflammation and oxidation-related processes,and the signaling pathways mainly included fluid shear stress and atherosclerosis,VEGF,and hepatocellular carcinoma.The results of the in vitro test showed that after the action of different concentrations of the extracts of the Phyllanthus urinaria L.in the safe concentration range on cells HepG2.2.15,HBsAg,HBeAg and hepatitis B virus DNA levels were significantly inhibited,and NFE2L2 and HMOX1 were affecting hepatitis B virus transcription and replication by regulating the oxidative stress response.Conclusion:Using an integrated network pharmacology approach,this study revealed the active components and potential targets of Phyllanthus urinaria L.for the treatment of the hepatitis B virus,providing a theoretical basis for the research and clinical application of Phyllanthus urinaria L..展开更多
Objective:Based on network pharmacology and molecular docking technology to explore the mechanism of Professor Cao Enze's application of Panax notoginseng in the treatment of membranous nephropathy.Methods:TCMSP d...Objective:Based on network pharmacology and molecular docking technology to explore the mechanism of Professor Cao Enze's application of Panax notoginseng in the treatment of membranous nephropathy.Methods:TCMSP database was used to obtain the effective components and corresponding target information of Panax notoginseng,and Gene Cards database was used to obtain the disease target genes of membranous nephropathy.The intersection targets of the two were taken and the Venn diagram was drawn.The STRING database was used to obtain the protein interaction relationship,and the PPI network diagram was constructed by Cytoscape 3.9.1 software to screen out the core targets of Panax notoginseng in the treatment of membranous nephropathy.GO function and KEGG pathway enrichment analysis were performed using the David database to obtain the potential pathway of Panax notoginseng in the treatment of membranous nephropathy.Finally,Autodock software was used to verify the molecular docking of the main active components of the drug with the core targets.Results:A total of 7 effective components such as quercetin,ginsenoside rh2,Mandenol and Stigmasterol were retrieved,and 127 potential targets of Panax notoginseng in the treatment of membranous nephropathy were screened out.By PPI network topology analysis,23 core targets such as JUN,TP53,RELA,AKT1 and MAPK1 were screened out.GO functional enrichment analysis contained 703 biological processes,55 cell components and 121 molecular functions,and KEGG signal pathway enrichment analysis enriched 171 signal pathways.The results of molecular docking showed that there was a strong binding ability between the main core targets and the main components of Panax notoginseng.Conclusion:Through network pharmacology,it is concluded that Panax notoginseng treats membranous nephropathy through multiple targets and multiple pathways,which provides a theoretical basis for subsequent basic research.展开更多
[Objectives] The paper was to explore the mechanism of capsicum ( Capsicum annuum L.) in treating type 2 diabetes mellitus (T2DM) and search for new targets. [Methods] The active ingredients of capsicum were queried f...[Objectives] The paper was to explore the mechanism of capsicum ( Capsicum annuum L.) in treating type 2 diabetes mellitus (T2DM) and search for new targets. [Methods] The active ingredients of capsicum were queried from TCMSP database to obtain the corresponding target proteins. The related targets of T2DM were screened from GeneCards database, and the target intersection of active ingredients of capsicum and diabetes mellitus was obtained via Venny software. The protein-protein interaction (PPI) network of the compounds was constructed using STRING database, and the GO bio-function and KEGG pathway enrichment were further analyzed using Metascape database. [Results] Through TCMSP database query and conditional screening, 14 candidate active molecules, 93 potential targets and 225 related pathways were obtained. [Conclusions] The results of GO and KEGG enrichment analysis show that the main active ingredients of capsicum play a role in the treatment of T2DM by regulating cancer pathways, chemical carcinogenesis—receptor activation, proteoglycans in cancer, and prostate cancer pathways, which will provide an important theoretical basis for subsequent research.展开更多
基金Youth Fund of Guangxi Natural Science Foundat ion (No.2020GXNSFBA297133)Guangxi Traditional Chinese Medicine Administration Science and Technology Project (No.GZSY20-60)+1 种基金Natural Science Youth Fund of Guangxi University of Traditional Chinese Medicine (No.2020QN020)Guangxi Qihuang Scholar Training Project.
文摘Objective:To investigate the therapeutic efficacy and underlying mechanisms of LiZhong Tang in the context of non-alcoholic fatty liver disease(NAFLD).Methods:High-fat feed was used to induce NAFLD in rats,Blood and liver samples were collected to facilitate a comparative analysis of rat body mass and liver wet weight and calculate the liver index.Liver pathology was observed,while serum transaminase and blood lipid levels were measured.The protein expression levels of PINK1,Parkin,and LC-3II in rat liver were detected using Western Blot analysis.Results:Compared with the control group,the NAFLD rats exhibited a significant increase in body weight,liver wet weight,liver index,transaminase levels,and blood lipid levels.The expression levels of PINK1,Parkin,and LC3-II protein were significantly decreased(P<0.01).Following intervention with Lizhong Tang,rats in each herbal treatment group displayed a decrease in body weight,liver wet weight,liver index,se-rum transaminase,and blood lipid levels.The expression levels of PINK1,Parkin,and LC-3II rebounded(P<0.05),with the high-dose group demonstrating the most pronounced effects(P<0.01).Histopathological examination of liver tissue revealed that rats in the model group displayed disrupted hepatic lobule structure,swollen hepatocytes,disordered arrangement,and a multi-tude of varying-sized lipid vacuoles within the cytoplasm.Conversely,rats treated with different doses of the herbal remedy exhibited improvements in liver tissue pathology,with the high-dose group showing the most notable enhancement.Conclusion:Lizhong Tang can improve NAFLD disease by regulating mitochondrial autophagy.
文摘With a long industrial chain and a powerful ability to drive other industries,the automobile manufacturing industry has a prominent strategic position in the national economy.In recent years,many countries have put on their agenda the digitalization of the automobile manufacturing industry,leading to an connected,autonomous,shared,and electric(also known as CASE)①development trend in the industry.As one of the six major automobile industry clusters in China,the Chengdu-Chongqing economic circle has achieved initial results in the digital transformation of the automobile manufacturing industry.However,the region is still faced with some constraints,such as insufficient digital infrastructure,relatively slow development of new automobile products,insufficient innovation ability of the automobile industry,and complex digital transformation of small and medium-sized automobile enterprises(automobile SMEs).This paper intends to construct a framework for the mechanism of action of the digital transformation in the automobile manufacturing industry,analyze the effects of the digital transformation of the automobile manufacturing industry in the Chengdu-Chongqing economic circle,and propose feasible paths for the digital transformation of the automobile manufacturing industry in the region by drawing on domestic and international experience in this regard.The specific paths include:(a)Smoothing the“dual-core”data chain to facilitate the digital transformation of the automobile manufacturing industry;(b)Developing the new energy vehicle(NEV)industry to upgrade the quality of automobile products;(c)Achieving corner overtaking in the digital transformation of the automobile manufacturing industry with digital technology;(d)Jointly building the automobile industrial park to promote the digital transformation of the industry;(e)Addressing problems facing automobile SMEs in digital transformation via targeted policy tools.
文摘Objective:To study the mechanism of action and therapeutic effect of modified Qiwei Baishu powder in diabetic patients.Methods:From January 2021 to January 2022,80 diabetic patients were recruited in our study and divided into two groups by the random number table method.Group A was treated with modified Qiwei Baishu powder,whereas group B was treated with western medicine.The therapeutic effect,traditional Chinese medicine(TCM)syndrome score,blood sugar level,and incidence of adverse reaction were compared between the two groups.Result:The therapeutic effect in group A was significantly higher than that in group B(P<0.05);the TCM syndrome scores of group A were significantly lower than those of group B(P<0.05);the fasting blood glucose(FBG),2 hour-postprandial blood glucose(PBG),and glycosylated hemoglobin(HbA1c)levels of group A were significantly lower than those of group B(P<0.05);the incidence of adverse reaction in group A was significantly lower than that in group B(P<0.05).Conclusion:On the basis of western medicine,the addition of modified Qiwei Baishu powder can maintain stable blood sugar levels in patients and alleviate diabetic symptoms;thus,it is not only effective,but also safe for clinical use in diabetes.
基金Supported by Zhejiang Provincial Natural Science Foundation of China,No.LY14H310010Public Welfare Technology Applied Research Project of Zhejiang Province?Experimental Animal Science and Technology Project,No.2013C37020Key Project of Chinese Ministry of Education,No.212073
文摘Despite that some approved drugs and genetically engineered vaccines against hepatitis B virus(HBV)are available for HBV patients,HBV infection is still a severe public health problem in the world.All the approved therapeutic drugs(including interferonalpha and nucleoside analogues)have their limitations.No drugs or therapeutic methods can cure hepatitis B so far.Therefore,it is urgently needed to discover and develop new anti-HBV drugs,especially nonnucleoside agents.Naturally originated compounds with enormous molecular complexity and diversity offer a great opportunity to find novel anti-HBV lead compounds with specific antiviral mechanisms.In this review,the natural products against HBV are discussed according to their chemical classes such as terpenes,lignans,phenolic acids,polyphenols,lactones,alkaloids and flavonoids.Furthermore,novel mode of action or new targets of some representative anti-HBV natural products are also discussed.The aim of this review is to report new discoveries and updates pertaining to anti-HBV natural products in the last 20years,especially novel skeletons and mode of action.Although many natural products with various skeletons have been reported to exhibit potent anti-HBV effects to date,scarcely any of them are found in the list of conventional anti-HBV drugs worldwide.Additionly,in anti-HBV mechanism of action,only a few references reported new targets or novel mode of action of antiHBV natural products.
基金supported by grants from the National Natural Science Foundation of China (81770176)the special support plan for Zhejiang Province High-Level Talents (2019R52011)。
文摘The management of bacterial infections is becoming a major clinical challenge due to the rapid evolution of antibiotic resistant bacteria.As an excellent candidate to overcome antibiotic resistance,antimicrobial peptides(AMPs)that are produced from the synthetic and natural sources demonstrate a broad-spectrum antimicrobial activity with the high specificity and low toxicity.These peptides possess distinctive structures and functions by employing sophisticated mechanisms of action.This comprehensive review provides a broad overview of AMPs from the origin,structural characteristics,mechanisms of action,biological activities to clinical applications.We finally discuss the strategies to optimize and develop AMP-based treatment as the potential antimicrobial and anticancer therapeutics.
基金supported by National Institutes of Health grant AR066831-01ASBMR GAP grant to Weirong R Xingsupported by a senior research career scientist award from the Department of Veteran’s Affairs
文摘Leucine-rich repeat kinase 1 (LRRK1) plays a critical role in regulating cytoskeletal organization, osteoclast activity, and bone resorption with little effect on bone formation parameters. Deficiency of Lrrk1 in mice causes a severe osteopetrosis in the metaphysis of the long bones and vertebrae bones, which makes LRRK1 an attractive alternative drug target for the treatment of osteoporosis and other high-turnover bone diseases.This review summarizes recent advances on the functions of the Lrrk1-related family members, Lrrk1deficiency-induced skeletal phenotypes, LRRK1 structure–function, potential biological substrates and interacting proteins, and the mechanisms of LRRK1 action in osteoclasts.
文摘Nagilactones are tetracyclic natural products isolated from various Podocarpus species.These lactone-based compounds display a range of pharmacological effects,including antifungal,anti-atherosclerosis,anti-inflammatory and anticancer activities reviewed here.The most active derivatives,such as nagilactones C,E and F,exhibit potent anticancer activities against different cancer cell lines and tumor models.A comprehensive analysis of their mechanism of action indicates that their anticancer activity mainly derives from three complementary action:(i)a drug-induced inhibition of cell proliferation coupled with a cell cycle perturbation and induction of apoptosis,(ii)a blockade of the epithelial to mesenchymal cell transi-tion contributing to an inhibition of cancer cell migration and invasion and(iii)a capacity to modulate the PD-L1 immune checkpoint.Different molecular effectors have been implicated in the antitumor activity,chiefly the AP-1 pathway blocked upon activation of the JNK/c-Jun axis.Nag-C is a potent inhibitor of protein synthesis binding to eukaryotic ribosomes and inhibition of different protein kinases,such as RIOK2 and JAK2,has been postulated with Nag-E.The literature survey on nagilactones highlights the therapeutic potential of these little-known terpenoids.The mechanistic analysis also provides useful information for structurally related compounds(podolactones,oidiolactones,inumakilactones)isolated from Podo-carpus plants.
基金This research did not receive any specific grant from funding agencies in the public,commercial,or not-for-profit sectors。
文摘Biflavonoids are divided in two classes:C-C type compounds represented by the dimeric compound amentoflavone and C-O-C-type compounds typified by hinokiflavone(HNK)with an ether linkage between the two connected apigenin units.This later sub-group of bisflavonyl ethers includes HNK,ochnaflavone,delicaflavone and a few other dimeric compounds,found in a variety of plants,notably Selaginella species.A comprehensive review of the anticancer properties and mechanism of action of HNK is provided,to highlight the anti-proliferative and anti-metastatic activities of HNK and derivatives,and HNK-containing plant extracts.The anticancer effects rely on the capacity of HNK to interfere with the ERK1-2/p38/NFκB signaling pathway and the regulation of the expression of the matrix metalloproteinases MMP-2 and MMP-9(with a potential direct binding to MMP-9).In addition,HNK was found to function as a potent modulator of pre-mRNA splicing,inhibit-ing the SUMO-specific protease SENP1.As such,HNK represents a rare SENP1 inhibitor of natural origin and a scaffold to design synthetic compounds.Oral formulations of HNK have been elaborated to enhance its solubility,to facilitate the compound delivery and to enhance its anticancer efficacy.The review shed light on the anticancer potential of C-O-C-type biflavonoids and specifically on the pharmacological profile of HNK.This compound deserves further attention as a regu-lator of pre-mRNA splicing,useful to treat cancers(in particular hepatocellular carcinoma)and other human pathologies.
基金supported by Innovative Talent Promotion Plan-Key Technology Innovation Team Plan(2017KCT-27).
文摘Objective:To predict the mechanism of action of San Huang lotion for topical treatment of eczema at the level of network pharmacology and molecular docking technology.Methods:The active ingredients and corresponding targets of San Huang lotion were collected using the TCMSP data platform and UniProt;the relevant gene targets of San Huang lotion were collected using the GeneCards database,OMIM database,TTD database,and DrugBank database;the intersection targets of San Huang lotion and eczema were obtained by creating avenn diagram;the key active ingredients and targets were screened by constructing a disease-active ingredient-target map,and the key active ingredients and core targets were screened out by constructing disease-active ingredient-target diagrams and PPInetwork diagrams;GOand KEGGenrichment analyses were conducted using the metascapewebsite and the higher significant entries were selected to produce bar charts and bubble plots.Finally,molecular docking of key active ingredients and core targets was performed.Results:A total of 134 active ingredients and 3,320 eczema-related target genes were screened for San Huang lotion,and 126 intersecting targets were obtained for San Huang lotion and eczema.The five key active ingredients of San Huang lotion for topical treatment of eczema and six core targets ofAKT1,TNF,IL6,IL1B,TP53andVEGFA were obtained by drug-active ingredient-target map and PPInetwork map.The GOand KEGGenrichment analysis showed that the topical treatment of eczema withSanHuanglotion might be mediated throughIL-17signaling pathway,TNFsignaling pathway and Th17cell differentiation pathway.The molecular docking results showed that the docking binding energy of key active ingredients and core targets was mostly less than-5 kcal/mol,and the docking was good.Conclusion:The quercetin,luteolin,wogonin,formononetin,beta-sitosterol and other active ingredients in San Huang lotion may act on eczema through AKT1,TNF,IL6,IL1B,TP53,VEGFA and other targets,and through IL-17signaling pathway,TNFsignaling pathway,Th17cell differentiation and other pathways.
基金Supported by Project of Science and Technology Department of Guizhou Province([2019]1401ZK[2021]-546)Guizhou Provincial Health Commission(gzwkj2021-464)。
文摘[Objectives] This study was conducted to investigate the mechanism of action of glyasperin A in the treatment of atherosclerosis using a network pharmacology approach. [Methods] Targets related to atherosclerosis were searched in GeneCards database. An active ingredient-disease-target network was constructed by Cytoscape 3.7.1. A target protein interaction network was constructed by String database. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed on the DAVID database. [Results] Glyasperin A acted on 36 atherosclerosis-related targets, and the biofunctional and pathway enrichment analyses showed that it was mainly involved in response to xenobiotic stimulus, drug transport across blood-brain barrier, lipid oxidation, barrier, and lipid oxidation, etc. The results showed that glyasperin A acted on 36 atherosclerosis-related targets. The biofunctional and pathway enrichment analyses showed that it was mainly involved in response to xenobiotic stimulus, drug transport across blood-brain barrier, lipid oxidation, positive regulation of protein localization to nucleus, and hepoxilin biosynthetic process, and it played an anti-fatigue role through signal pathways such as serotonergic synapse, efferocytosis, arachidonic acid metabolism, chemical carcinogenesis-receptor activation and platelet activation. [Conclusions] Glyasperin A has multi-target and multi-pathway effects in the treatment of atherosclerosis. This study provides reference for further research on glyasperin A in the treatment of atherosclerosis.
基金Supported by Key Project of Henan Provincial Administration of Traditional Chinese Medicine,No.2017ZY1020General Public Relations Project of Henan Provincial Department of Science and Technology,No.212102311123General Research Project of the National Administration of Traditional Chinese Medicine,No.GZY-KJS-2021-017.
文摘Cerebral ischemia-reperfusion is a process in which the blood supply to the brain is temporarily interrupted and subsequently restored.However,it is highly likely to lead to further aggravation of pathological damage to ischemic tissues or the nervous system.,and has accordingly been a focus of extensive clinical research.As a traditional Chinese medicinal formulation,Sanhua Decoction has gradually gained importance in the treatment of cerebrovascular diseases.Its main constituents include Citrus aurantium,Magnolia officinalis,rhubarb,and Qiangwu,which are primarily used to regulate qi.In the treatment of neurological diseases,the therapeutic effects of the Sanhua Decoction are mediated via different pathways,including antioxidant,anti-inflammatory,and neurotransmitter regu-latory pathways,as well as through the protection of nerve cells and a reduction in cerebral edema.Among the studies conducted to date,many have found that the application of Sanhua Decoction in the treatment of neurological diseases has clear therapeutic effects.In addition,as a natural treatment,the Sanhua Decoction has received widespread attention,given that it is safer and more effective than traditional Western medicines.Consequently,research on the mechanisms of action and efficacy of the Sanhua Decoctions in the treatment of cerebral ischemia-reperfusion injury is of considerable significance.In this paper,we describe the pathogenesis of cerebral ischemia-reperfusion injury and review the current status of its treatment to examine the therapeutic mechanisms of action of the Sanhua Decoction.We hope that the findings of the research presented herein will contribute to a better understanding of the efficacy of this formulation in the treatment of cerebral ischemia-reperfusion,and provide a scientific basis for its application in clinical practice.
基金National Natural Science Foundation of China(No.81973846)Heilongjiang Province Traditional Chinese Medicine Research Fund Projec(No.t ZHY2022-132)。
文摘Psoriasis is a kind of immune-mediated, chronic, inflammatory skin disease, which is often associated with different degrees of psychological disorders. Specifically, there is a significant correlation between psoriasis and depression, and they show the relationships of reciprocal causation and mutual promotion. Psoriasis with depression is more harmful than simple psoriasis, and its prognosis is worse, which brings a huge burden to the family and society and is worthy of clinical attention. Based on the pathogenic factors of western medicine and pathogenesis of traditional Chinese medicine in psoriasis with depression, the paper summarized and elaborated the research progress on the mechanism of traditional Chinese medicine in the treatment of psoriasis with depression, in order to provide new ideas for clinical treatment.
基金National Natural Science Foundation of China(No.82160890)Guangxi Health Appropriate Technology Development and Application Project(No.GZSY23-21)+1 种基金Graduate Education Innovation Project,Guangxi University of Traditional Chinese Medicine(No.YCSW2023383)Research Program of Guangxi University of Traditional Chinese Medicine(No.2019MS016)。
文摘Objective:To explore the potential mechanism of action of quercetin in the treatment of diarrhea irritable bowel syndrome(IBS-D).Methods:The potential targets of quercetin were obtained from the TCMSP,SwissTar-getPrediction,and BATMAN-TCM databases.The targets of IBS-D were obtained by searching the GeneCards database with"diarrhea irritable bowel syndrome"as the keyword,and the targets of quercetin and IBS-D were intersected.The PPI network was constructed by Cytoscape 3.7.1 software.The intersected targets were imported into the DAVID database for GO functional analysis and KEGG pathway enrichment analysis.The binding ability of quercetin to the core targets was observed using molecular docking.Based on this,we established an IBS-D rat model,administered quercetin for intervention,and experimentally validated the network pharmacology prediction results by HE staining and ELISA assay.Results:Network pharmacology analysis showed that TP53,TNF-α,AKT1,VEGF-A,IL-6 factors and MAPK,PI3K-Akt signaling pathway as the core targets and pathways of quercetin for the treatment of IBS-D.The results of animal experiments revealed that quercetin could inhibit the secretion of TP53,TNF-α,AKT1,VEGF-A,IL-1βand IL-6,reduce the inflammatory response and improve IBS-D.Conclusion:Quercetin could protect colon tissue by regulating the expression of TP53,TNF-α,AKT1,VEGF-A,IL-1βand IL-6,thereby treating IBS-D.
文摘Autoimmune hepatitis is an inflammatory liver disease primarily mediated by T cell.It has not been fully elucidated about the pathogenesis,and it is presently thought to be related to genetic susceptibility,infection and environmental triggers,and abnormal autoimmune regulation.Recent studies have found that traditional Chinese medicine can improve the biochemical indicators and clinical symptoms of patients with autoimmune hepatitis.This article reviews the specific mechanism of traditional Chinese medicine on treating autoimmune hepatitis in order to propose new ideas for its clinical diagnosis and treatment.
基金funded by the Innovation Research of the Postgraduates of Guangzhou University (2020GDJC-M28)funded by the Guangdong Basic and Applied Basic Research Foundation (2019A1515011569 and2021A1515012067)National Natural Science Foundation of China (32071233)
文摘Albizzia julibrissin is empirically used as an antidepressant in clinical practice.Preclinical studies have indicated that its total extracts or bioactive constituents exerted antidepressant-like responses in animal models,providing the molecular basis to reveal its underlying mechanism of action.While attempts have been made to understand the antidepressant effect of A.julibrissin,many fundamental questions regarding its mechanism of action remain to be addressed at the molecular and systems levels.In this review,we conclusively discussed the mechanism of action of A.julibrissin and A.julibrissin formulae by reviewing recent preclinical and clinical studies conducted by using depressive animal models and depressive patients.Several representative bioactive constituents and formulae were highlighted as examples,and their mechanisms of action were discussed.In addition,some representative A.julibrissin formulae that have been shown to be compatible with conventional antidepressants in clinical practice were also reviewed.Furthermore,we discussed the future research directions to reveal the underlying mechanism of A.julibrissin at the molecular and systems levels in depression treatment.The integrated study using both the molecular and systematic approaches is required not only for improving our understanding of its molecular basis and mechanisms of action,but also for providing a way to discover novel agents or approaches for the effective and systematic treatment of depression.
基金Supported by Ningxia Natural Science Foundation,No.2022AAC02039National Natural Science Foundation of China,No.81860894,82260879,81674096Ningxia Innovation Team of the Foundation and Clinical Researches of Diabetes and its Complications,No.NXKJT2019010.
文摘BACKGROUND Diabetic nephropathy(DN)stands as the most prevalent chronic microvascular complication of diabetes mellitus.Approximately 50%of DN patients progress to end-stage renal disease,posing a substantial health burden.AIM To employ network pharmacology and molecular docking methods to predict the mechanism by which glycyrrhetinic acid(GA)treats DN,subsequently validating these predictions through experimental means.METHODS The study initially identified GA targets using Pharm Mapper and the TCMSP database.Targets relevant to DN were obtained from the Genecards,OMIM,and TTD databases.The Venny database facilitated the acquisition of intersecting targets between GA and DN.The String database was used to construct a protein interaction network,while DAVID database was used to conducted Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis and Gene Ontology(GO)analysis.Molecular docking experiments were performed using Autodock software with selected proteins.Experimental validation was conducted using renal proximal tubular cells(HK-2)as the study subjects.A hyperglycemic environment was simulated using glucose solution,and the effect of GA on cell viability was assessed through the cell counting kit-8 method.Flow cytometry was employed to detect cell cycle and apoptosis,and protein immunoblot(western blot)was used to measure the expression of proteins of the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway and insulin resistance pathway,including insulin receptor(INSR),PI3K,p-PI3K,AKT,p-AKT,and glycogen synthase kinase-3(GSK3).RESULTS A total of 186 intersecting targets between GA and DN were identified,which were associated with 144 KEGGrelated enrichment pathways,375 GO biological process entries,45 GO cellular component entries,and 112 GO cellular function entries.Molecular docking demonstrated strong binding of GA to mitogen-activated protein kinase(MAPK)-1,SRC,PIK3R1,HSP90AA1,CASPASE9,HARS,KRAS,and MAPK14.In vitro experiments revealed that GA inhibited HK-2 cell viability,induced cell cycle arrest at the G2/M phase,and reduced apoptosis with increasing drug concentration.Western blot analysis showed that GA differentially up-regulated GSK3 protein expression,up-regulated AKT/p-AKT expression,down-regulated INSR,AKT,p-AKT,PI3K,and p-PI3K protein expression,and reduced p-PI3K/PI3K levels under high glucose conditions.CONCLUSION GA may protect renal intrinsic cells by modulating the PI3K/AKT signaling pathway,thereby inhibiting HK-2 cell viability,reducing HK-2 cell apoptosis,and inducing cell cycle arrest at the G0/G1 phase.
基金Supported by Natural Science Basic Research Plan in the Shaanxi Province of China,No.2021JM-549,The Plan Project of Shaanxi Provincial Administration of Traditional Chinese Medicine,No.2021-ZZ-JC011The Second Youth Science and Technology Talents Project of Shaanxi Provincial Administration of Traditional Chinese Medicine,No.2023-ZQNY-017.
文摘BACKGROUND Jiawei Jiaotai Pill is commonly used in clinical practice to reduce apoptosis,increase insulin secretion,and improve blood glucose tolerance.However,its mechanism of action in the treatment of diabetic cardiomyopathy(DCM)remains unclear,hindering research efforts aimed at developing drugs specifically for the treatment of DCM.AIM To explore the pharmacodynamic basis and molecular mechanism of Jiawei Jiaotai Pill in DCM treatment.METHODS We explored various databases and software,including the Traditional Chinese Medicine Systems Pharmacology Database,Uniport,PubChem,GenCards,String,and Cytoscape,to identify the active components and targets of Jiawei Jiaotai Pill,and the disease targets in DCM.Protein-protein interaction network,gene ontology,and Kyoto Encyclopedia of Genes and Genomes analyses were used to determine the mechanism of action of Jiawei Jiaotai Pill in treating DCM.Molecular docking of key active components and core targets was verified using AutoDock software.RESULTS Total 42 active ingredients and 142 potential targets of Jiawei Jiaotai Pill were identified.There were 100 common targets between the DCM and Jiawei Jiaotai Pills.Through this screening process,TNF,IL6,TP53,EGFR,INS,and other important targets were identified.These targets are mainly involved in the positive regulation of the mitogen-activated protein kinase(MAPK)MAPK cascade,response to xenobiotic stimuli,response to hypoxia,positive regulation of gene expression,positive regulation of cell proliferation,negative regulation of the apoptotic process,and other biological processes.It was mainly enriched in the AGE-RAGE signaling pathway in diabetic complications,DCM,PI3K-Akt,interleukin-17,and MAPK signaling pathways.Molecular docking results showed that Jiawei Jiaotai Pill's active ingredients had good docking activity with DCM's core target.CONCLUSION The active components of Jiawei Jiaotai Pill may play a role in the treatment of DCM by reducing oxidative stress,cardiomyocyte apoptosis and fibrosis,and maintaining metabolic homeostasis.
基金the support from Social Development Project(No.ZDYF2019139)Natural Science Foundation of Hainan Province(No.ZDYF2023SHFZ116).
文摘Background:To explore the pharmacological mechanism of the anti-hepatitis B virus of Phyllanthus urinaria L.through network pharmacological analysis and experimental validation.Method:The active ingredient,target of action and target of action related to hepatitis B were clarified by searching the herb group identification,GeneCards and OMIM databases,and the protein interaction relationship was obtained by using the String database,and the protein interaction network map was constructed by using Cytoscape software.We also performed gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis of key targets of the anti-hepatitis B action of Phyllanthus urinaria L.and predicted the core targets and pathways of Phyllanthus urinaria L.anti-hepatitis B.The main targets predicted by network pharmacology were then validated by HepG2.2.15 cell experiments.Results:By searching active ingredient targets and hepatitis B disease targets,a total of 19 active ingredients and 64 related targets of action were retrieved from Phyllanthus urinaria L.,and a total of 51 common targets were obtained by mapping the obtained hepatitis B disease targets and drug targets.protein protein interaction network analysis indicated that targets including TNF,JUN,AKT1,IL-10,IL-1B,CAT,HMOX1,NFE2L2,and CASP3 and other targets may be the core targets.gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that the treatment of hepatitis B by Phyllanthus urinaria L.mainly included inflammation and oxidation-related processes,and the signaling pathways mainly included fluid shear stress and atherosclerosis,VEGF,and hepatocellular carcinoma.The results of the in vitro test showed that after the action of different concentrations of the extracts of the Phyllanthus urinaria L.in the safe concentration range on cells HepG2.2.15,HBsAg,HBeAg and hepatitis B virus DNA levels were significantly inhibited,and NFE2L2 and HMOX1 were affecting hepatitis B virus transcription and replication by regulating the oxidative stress response.Conclusion:Using an integrated network pharmacology approach,this study revealed the active components and potential targets of Phyllanthus urinaria L.for the treatment of the hepatitis B virus,providing a theoretical basis for the research and clinical application of Phyllanthus urinaria L..
基金2022 Anhui Provincial Health Research Project (No.AHWJ2022b041)2021 Anhui Provincial Key Medical and Health Specialty Construction Project (No.Anhui Health Letter 2021-273)。
文摘Objective:Based on network pharmacology and molecular docking technology to explore the mechanism of Professor Cao Enze's application of Panax notoginseng in the treatment of membranous nephropathy.Methods:TCMSP database was used to obtain the effective components and corresponding target information of Panax notoginseng,and Gene Cards database was used to obtain the disease target genes of membranous nephropathy.The intersection targets of the two were taken and the Venn diagram was drawn.The STRING database was used to obtain the protein interaction relationship,and the PPI network diagram was constructed by Cytoscape 3.9.1 software to screen out the core targets of Panax notoginseng in the treatment of membranous nephropathy.GO function and KEGG pathway enrichment analysis were performed using the David database to obtain the potential pathway of Panax notoginseng in the treatment of membranous nephropathy.Finally,Autodock software was used to verify the molecular docking of the main active components of the drug with the core targets.Results:A total of 7 effective components such as quercetin,ginsenoside rh2,Mandenol and Stigmasterol were retrieved,and 127 potential targets of Panax notoginseng in the treatment of membranous nephropathy were screened out.By PPI network topology analysis,23 core targets such as JUN,TP53,RELA,AKT1 and MAPK1 were screened out.GO functional enrichment analysis contained 703 biological processes,55 cell components and 121 molecular functions,and KEGG signal pathway enrichment analysis enriched 171 signal pathways.The results of molecular docking showed that there was a strong binding ability between the main core targets and the main components of Panax notoginseng.Conclusion:Through network pharmacology,it is concluded that Panax notoginseng treats membranous nephropathy through multiple targets and multiple pathways,which provides a theoretical basis for subsequent basic research.
基金Supported by National Natural Science Foundation of China(81560702)Inner Mongolia Natural Science Foundation(2022LHMS08021).
文摘[Objectives] The paper was to explore the mechanism of capsicum ( Capsicum annuum L.) in treating type 2 diabetes mellitus (T2DM) and search for new targets. [Methods] The active ingredients of capsicum were queried from TCMSP database to obtain the corresponding target proteins. The related targets of T2DM were screened from GeneCards database, and the target intersection of active ingredients of capsicum and diabetes mellitus was obtained via Venny software. The protein-protein interaction (PPI) network of the compounds was constructed using STRING database, and the GO bio-function and KEGG pathway enrichment were further analyzed using Metascape database. [Results] Through TCMSP database query and conditional screening, 14 candidate active molecules, 93 potential targets and 225 related pathways were obtained. [Conclusions] The results of GO and KEGG enrichment analysis show that the main active ingredients of capsicum play a role in the treatment of T2DM by regulating cancer pathways, chemical carcinogenesis—receptor activation, proteoglycans in cancer, and prostate cancer pathways, which will provide an important theoretical basis for subsequent research.