Exploring the pharmacological mechanism of Wuzhuyu decoction on hepatocellular carcinoma using network pharmacology

BACKGROUND Wuzhuyu decoction,a traditional Chinese medicinal formula,is effective in treating hepatocellular carcinoma(HCC).AIM To explore the potential mechanism of action of Wuzhuyu decoction against HCC.METHODS The active components of each Chinese herbal medicinal ingredient in Wuzhuyu decoction and their targets were obtained from the Traditional Chinese Medicine Database and Analysis Platform.HCC was used as a search query in GeneCards,Online Mendelian Inheritance in Man,Malacards,DisGeNET,Therapeutic Target Database,and Comparative Toxicogenomics Database.The overlapping targets of the Wuzhuyu decoction and HCC were defined,and then protein-protein interaction,Gene Ontology,and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed.CytoHubba was used to select hub genes,and their binding activities and key active components were verified using molecular docking.RESULTS A total of 764 compounds,77 active compounds,and 204 potential target genes were identified in Wuzhuyu decoction.For HCC,9468 potential therapeutic target genes were identified by combining the results from the six databases and removing duplicates.A total of 179 overlapping targets of Wuzhuyu decoction and HCC were defined,including 10 hub genes(tumor necrosis factor,interleukin-6,AKT1,TP53,caspase-3,mitogen-activated protein kinase 1,epidermal growth factor receptor,MYC,mitogen-activated protein kinase 8,and JUN).There were six main active components(quercetin,kaempferol,ginsenoside Rh2,rutaecarpine,β-carotene,andβ-sitosterol)that may act on hub genes to treat HCC in Wuzhuyu decoction.Kyoto Encyclopedia of Genes and Genomes enrichment analysis mainly involved the mitogen-activated protein kinase,p53,phosphatidylinositol-4,5-bisphosphate 3-kinase-Akt,Janus kinase-signal transducer of activators of transcription,and Hippo signaling pathways.Further verification based on molecular docking results showed that the small molecule compounds(quercetin,kaempferol,ginsenoside Rh2,rutaecarpine,β-carotene,andβ-sitosterol)contained in Wuzhuyu decoction generally have excellent binding affinity to the macromolecular target proteins encoded by the top 10 genes.

Clinical antitumor application and pharmacological mechanisms of Dahuang Zhechong Pill

Cancer still has elevated morbidity and mortality,which undoubtedly impacts the life quality of affected individuals.Remarkable advances have been made in cancer therapy,although the toxicities of traditional therapies remain an obvious challenge.Dahuang Zhechong Pill(DHZCP),developed by Zhongjing Zhang in the Synopsis of the Golden Chamber,represents an effective anticancer traditional Chinese medicine(TCM).In this review,it was found that DHZCP is therapeutically utilized in liver,lung,gastric,pancreatic and other cancers in clinic.Pharmacological evidence showed that its anti-tumor mechanisms mainly involve induced cell cycle arrest,apoptosis and autophagy,as well as suppressed tumor cell proliferation,obstructed angiogenesis and metastasis,enhanced immunity,and reversal of multidrug resistance.The present review provides a solid basis for the clinical application of DHZCP and may promote the wide use of TCM in clinical antitumor application.

Study on the mechanism of SND in the treatment of anxiety disorders based on network pharmacology, molecular docking and experiment validation

Background:Sini decoction(SND)is a classic traditional Chinese medicine(TCM)formulation that can be used to treat anxiety-related disorders,but the active substance and underlying molecular mechanism of its anxiolytic effects are unknown.In this study,network pharmacology,molecular docking research and experimental verification methods were used to preliminarily explore the bioactive compounds and potential target mechanisms of SND anxiolytic.Methods:The active components and corresponding targets of SND were collected by TCMSP.GeneCards,OMIM,PharmGkb,TTD and Drugbank were used to search for the targets of anxiety disorders.The core target of SND in the treatment of anxiety was screened by PPI.R language was used to analyze the intersection targets of SND in the treatment of anxiety disorders by GO and KEGG enrichment analysis.AutoDock Vina was used for molecular docking,and Discovery Studio was used for visual conformation analysis after docking.The anti-anxiety effect and molecular mechanism of SND were studied by in vivo experiment.Results:Based on network pharmacological analysis,we obtained 112 active ingredients and 350 effective targets related to anxiety from SND.In PPI analysis,26 targets such as STAT3,MAPK3,MAPK1,MAPK14,SRC,HSP90AA1,TP53 and PIK3CA were identified as core targets.GO and KEGG analysis showed that the anxiolytic mechanism of SND may be related to the neuroactive ligand-receptor interaction pathway and inflammatory pathway.Molecular docking showed that quercetin,naringenin,licochalcone A had high affinity with JAK2,MAPK14 and MAPK3.Animal experiments have shown that SND reverses the upregulation of GluN2B(NMDAR)and GluA1(AMPAR)proteins,and SND improves anxiety disorders by regulating glutamate transmitter levels,which may be related to neuroactive ligand-receptor interaction pathways,particularly glutamate receptors.Conclusion:This study shows that SND can improve FS-induced behavioral changes in mice and can modulate hippocampal synapse-associated protein defects,partially reversing glutamate receptor expression through the neuroactive ligand-receptor interaction pathway,and further improved anxiety disorders.At the same time,combined with network pharmacology and molecular docking,the key components,core targets and related pathways of SND are discussed,which shows that the active components of SND play an effective role in anxiety through multi-targets and multi-pathways,which provides a reference for the material basis and mechanism of SND.

Network pharmacology used to decode potential active ingredients in Ferula assafoetida and mechanisms for the application to Alzheimer’s disease

Background:Alzheimer’s disease(AD)is a neurodegenerative disease that primarily manifests as progressive memory loss and cognitive impairment.Traditional herbal medicines may be helpful in the discovery of new anti-AD drugs.Studies have shown that Ferula assafoetida has neuroprotective and memory-enhancing effects,which may be beneficial for the treatment of AD.However,the combination of active ingredients and their mechanisms remain unclear.Therefore,we aimed to identify potential active ingredients in F.assafoetida and their mechanisms of action against AD by using network pharmacology.Methods:In our study,an integrated network pharmacological approach,that included adsorption,distribution,metabolism and excretion screening,target identification,network construction,topological analysis,gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis,and molecular docking,was used to predict the pharmacological material basis and potential mechanisms through which these ingredients may treat and prevent AD.Results:The results indicated that 12 key active ingredients,obtained by topological analysis(including farnesiferol a,conferol,farnesiferol b,ferulic acid,etc.),may be the primary pharmacological components that may ameliorate AD.The 2 key significant pathways identified are the cholinergic synapse signaling pathway(critical targets include ACHE,CHRM1,CHRM2,MAPK1,PIK3CA,PIK3CB,PIK3CD,and PIK3CG)and the AD signaling pathway(critical targets include APP,BACE1,GSK3B,MAPK1,NCSTN,NOS1,PSEN1).These critical targets are closely related to the regulation of three typical pathological features of AD[central nervous system(CNS)cholinergic hypofunction,amyloid-β(Aβ)plaques,and hyperphosphorylated tau proteins].Finally,14 critical targets in the 2 key significant pathways were validated by molecular docking analysis.Conclusion:F.assafoetida may be effective for alleviating AD symptoms,through multi-component,multi-target,and multi-pathway synergistic effects,associated with the multiple pathogenesis hypotheses of AD.Our study may provide certain clues for the further development and utilization of this natural herbal medicine.

Pharmacological research progress of ursolic acid for the treatment of liver diseases

Ursolic acid is a natural pentacyclic triterpenoid with various pharmacological activities such as anti-inflammatory,hepatoprotective,antitumor,and hypoglycemic activity.This natural product is widely present in many common Chinese herbal medicines such as Hedyotis diffusa and Prunella vulgaris.The present review highlights the pharmacological research progress of ursolic acid in liver disease,with a focus on providing directions for future research and clinical practice of ursolic acid.Modern studies have demonstrated that ursolic acid can adjust the activities of enzymes such as superoxide dismutase and NADPH oxidase to balance oxidative stress,reduce inflammation,as well as to repair damaged liver.Research also showed that ursolic acid targeted lipid metabolic genes,activating autophagy and reducing lipid deposition in hepatocytes,further preventing the progress of fatty liver.Besides,the combination of ursolic acid with caspase-3 was able to prevent apoptosis and relieve liver injury.Furthermore,ursolic acid was showed to target the intestine by alleviating mucosal injury and restoring the balance of the intestinal microecology and protect liver through the enterohepatic axis.In terms of antitumor activity,ursolic acid targeted several tumor suppressor genes including gene of phosphate and tension homology deleted on chromsome ten and p53,and affected the expression of cyclin and apoptosis-related proteins involving Bax,Bcl-2,and Bcl-x,which acted on signal transduction pathways including phosphatidylinositol-3-kinase/protein kinase B,extracellular regulated protein kinases and proteina fosforilata 21 wide-type actiated factorlp 1.The same compound interacted with caspases,resulting in inhibition of cell proliferation and induction of apoptosis.In addition,ursolic acid also exerted anticancer activity through inhibiting angiogenesis,tumor invasion and metastasis,and improving immunity.Other studies have noted the importance of nano-preparations of ursolic acid for its clinical applications.This review provides essential information on the role of ursolic acid in liver protection.Further research on the mechanisms of action of ursolic acid would be useful for its pharmaceutical development and clinical application.

Mechanism of panax notoginseng in treating vitreous hemorrhage based on network pharmacology

Objective:To investigate the possible molecular mechanism of panax notoginseng in the treatment of vitreous hemorrhage(VH).Methods:The active components of Panax notoginseng were screened by TCMSP database and the corresponding targets were collected.Vh-related gene targets were derived from GeneCards and OMIM database,and the target of Panax notoginseng was mapped to disease target genes.STRING database and Cytoscape 3.7.2 software were used to construct the protein-protein interaction(PPI)network diagram and the interaction network of"Pantoginseng-active ingredient-VH-target protein",and the core action target genes were screened out.Finally,gene body(GO)biological process and metabolic pathway enrichment analysis of KEGG were performed on the potential therapeutic targets.Results:We identified 8 active components,162 active component targets,1387 VHrelated genes and 75 candidate targets for VH.In the"Panax notoginseng-active ingredient-VH-target protein"interaction network,there are 82 nodes in total.The core target genes include AKT1,CASP3,VEGF-A,IL-6 and MMP-9.143 major enrichment pathways were identified by GO and KEGG enrichment analysis.The key signal pathways include age-RAGE signaling pathway,fluid shear stress and atherosclerosis,etc.,and the significant molecular functions include cytokine activity,receptor ligand activity,cytokine receptor binding,etc.Conclusion:The potential molecular mechanism of panax notoquinone in the treatment of VH is closely related to the biological processes of anti-angiogenesis,anti-inflammation,regulation of apoptosis and oxidative stress,and AKT1,CASP3,VEGF-A,IL-6 and MMP-9 may be the core target genes.

Use of Network Pharmacology and Molecular Docking to Investigate the Mechanism by Which Ginseng Ameliorates Hypoxia

Hypoxia is a common pathological process in various clinical diseases and is characterized by abnormal changes in metabolism, function, and morphological structure of tissues resulting from insufficient oxygen supply or oxygen barriers in tissues. In particular, hypoxia in vital organs such as the brain and heart is an important cause of death;. The prevention of tissue hypoxia and the

Traditional Chinese medicine for transformation of gastric precancerous lesions to gastric cancer:A critical review

Gastric cancer(GC)is a common gastrointestinal tumor.Gastric precancerous lesions(GPL)are the last pathological stage before normal gastric mucosa transforms into GC.However,preventing the transformation from GPL to GC remains a challenge.Traditional Chinese medicine(TCM)has been used to treat gastric disease for millennia.A series of TCM formulas and active compounds have shown therapeutic effects in both GC and GPL.This article reviews recent progress on the herbal drugs and pharmacological mechanisms of TCM in preventing the transformation from GPL to GC,especially focusing on antiinflammatory,anti-angiogenesis,proliferation,and apoptosis.This review may provide a meaningful reference for the prevention of the transformation from GPL to GC using TCM.

Explore the mechanism of Yueju pill in treating depressive polycystic ovary syndrome based on internet pharmacology

Background:This study aimed to identify the main active components,targets and pathways of Yueju pill,explore its mechanism in the treatment of depressive polycystic ovary syndrome,so as to provide proofs for expanding the clinical application of Yueju pill.Methods:The active components and targets of Yueju pill were retrieved from the traditional Chinese medicine system pharmacology(TCMSP)database and analysis platform.GeneCards and OMIM were used to search the disease targets of polycystic ovary syndrome and depression.The intersection genes of drug and disease were obtained via venny.R.STRING 11.0 was adopted to construct PPI network,then we obtained the hub genes with count.R.Utilized Cytoscape 3.7.2 to construct the"drug-disease-active ingredientsproteins"network.Finally,the Bioconductor tools of gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)were applied to the enrichment of biological functions and pathways.Results:There were 37 compounds in the prescription of Yueju pill,and 83 intersection genes of Yueju pill and PCOS-Depression.The significant genes were IL6,VEGFA,EGF,MAPK1,ESR1,MAPK8,EGFR and MAPK14.Through the enrichment of GO and KEGG,we found 106 biological processes and 129 signaling pathways were related to the treatment of depressive polycystic ovary syndrome with Yueju pill.Conclusions:Our study could provide sufficient data in supporting Yueju pill to treat polycystic ovary syndrome,while the purpose of anti-depression should be achieved by relieving the systemic symptoms.This study would provide fresh insights for expanding the clinical application of Yueju pill.

A comprehensive review of research progress in Chinese medicines for primary liver cancer treatment

Primary liver cancer seriously threatens human health,affects the quality of life,and has a high mortality rate.Traditional Chinese medicine(TCM)has long been used in the prevention,treatment,and adjuvant treatment of primary liver cancer.Clinical trials were conducted in recent years to evaluate the efficacy and safety of TCM.The mechanism of action of TCM in primary liver cancer treatment also received extensive attention.This study summarizes the common monomial Chinese herbal medicines and their components,formulae,and the proprietary Chinese medicines used to treat primary liver cancer.Common medicines include Chansu(Bufonis venenum),Kushen(Sophorae flavescentis radix),Renshen(Ginseng radix et rhizoma),and Jianghuang(Curcumae longae rhizoma).This study also reviewed the literature on liver cancer treatment using TCM.The results confirmed the safety and efficacy of TCM in liver cancer treatment.The possible mechanisms involved are also listed,including influencing the cell cycle,inducing cancer cell apoptosis and autophagy,inhibiting cancer cell angiogenesis and metastasis,regenerating the microenvironment and DNA methylation,and regulating the innate immune response.For primary liver cancer patients who often have a long disease course,Chinese herbal medicine often plays a role in protecting and conditioning the body.Research aimed at finding more traditional Chinese herbal medicines and their mechanisms of action should be promoted.This study aimed to provide a scientific reference for further research and the rational clinical application of TCM for primary liver cancer treatment.

Gaps and feasibility of fixed-dose combination strategy in the development of modern Chinese medicine

isTraditional Chinese medicine(TCM)is a highly complex chemical substance system,which not only reflected in the complexity of the chemical components and their interrelationships,but also in the intricacy of the prescription’s connection with the human body.Component compatibility strategy has been proposed for developing modern TCM since 2005 and established comprehensive relevant technologies and research approaches.Moreover,to meet the safety and efficacy of current pharmaceuticals,research on fixed-dose combination drugs is directed by modern scientific theories,conforms to TCM compatibility principles and clarifies material basis and pharmacological mechanisms and component-effect correlations.This review summarized gaps and feasibility of fixed-dose combination strategy in the development of modern TCM research and assessed their advantages and disadvantages in light of contemporary drug combination research practices.

The anti-pulmonary fibrosis of Salvia miltiorrhiza Bunge: A systematic review

The characteristics of PF are diffuse alveolitis and disruption of alveolar structure leading to pulmonary interstitial fibrosis.At the same time,pulmonary fibrosis reduces lung volume and restricts ventilation,ultimately leading to hypoxemia and respiratory failure.In clinical guidelines,Nintedanib or Pirfenidone is often used for treatment.However,the two drugs,although they may slow the progression of the disease,cannot stop,or reverse fibrosis and generally result in a variety of toxic side effects.In 184-220 A.D.,it was already recorded in Supplementary Records of Famous Physicians that the function of SMB was to invigorate blood circulation and disperse blood stasis.In modern medical research,the active ingredients of SMB have likewise been found to be used in treatments such as anti-fibrosis,anti-inflammatory,antithrombotic,antioxidant,microcirculatory improvement,and antineoplastic.In this review,a comprehensive search of the former literature on SMB and pulmonary fibers was conducted using databases including PubMed,CNKI,the National Science and Technology Library,Hindawi,Chinese Science and Technology Journal Database,and the Scientific Network Database.Meanwhile,this review presents the mechanisms of the active ingredients in SMB which have anti-pulmonary fibrosis effects through the signal pathways,cytokines,inflammation response,oxidative stress,apoptosis,and matrix metalloproteinases.SMB could offer a direction for therapy for pulmonary fibrosis by identifying the possible active components and exploring the potential mechanisms.Those could provide a reference for further research and application of SMB in the treatment of pulmonary fibrosis.

Advances in Studies on Pharmacological Functions of Ligustilide and their Mechanisms

The article reviewed the research progress of ligustilide in recent years and elaborated its pharmacological functions and mechanisms in detail, especially in ischemic brain injury. Its mechanism includes reducing cerebral infarct volumes and improving neurobehavioral deficits, anti-oxidant and anti-apoptosis, antithrombotic activity, calcium channel blockers function, and effect on erythropoietin. Other pharmacological effects of ligustilide including inhibiting vascular smooth muscle cell proliferation, anti-inflammatory and analgesic effects, effects on LPS-induced endotoxic shock, inhibiting constriction effect, suppression of the central nervous system, and ameliorating the memory impairment induced by scopolamine and so on, are also introduced. Ligustilide has potential pharmacological value, which provides a reference for its further research and development.

Systems Pharmacology Uncovers Multiple Mechanisms of Erxian Decoction (二仙汤) for Treatment of Premature Ovarian Failure

Objective:To predict the chemical compositions and drug targets and to systematically dissect the pharmacological mechanism of Erxian Decoction(二仙汤,EXD)as a treatment for premature ovarian failure(POF)using a systems pharmacology approach.Methods:The compounds present in EXD were obtained from three databases.The active ingredient was identified by analyzing the values of oral bioavailability(OB),drug-like ness(DL),and Lipin ski's rule(LR).The active in gredients were further searched in research articles,drug targets in the DrugBank database,and the C-T and T-P networks,as well as by pathway analysis using the Cytoscape platform.Results:A total of 728 compounds were identified in EXD.Of these,59 were identified as active compounds that conformed to the criteria with OB>30%and DL>0.18.By further searches in the literature,126 related targets were ide ntified that could in teract with the active compounds.Additi on ally,it was found that the beneficial effects of EXD in POF are probably exerted via regulation of the immline system,modulation of estrogen levels,and anti-oxidative activities,and that it may act in a synergistic or cooperative manner with other therapeutic agents.Conclusions:The systems pharmacology approach is a comprehensive system that was used to elucidate the pharmacological mechanism of EXD as a treatment for POF.The results of this study will also facilitate the application of traditional medicine in modern treatment strategies.

Potential of natural medicines for treatment of osteoporosis:a narrative review

OBJECTIVE:To organize the fragmented information available in the literature to describe and summarize the extracts used by natural medicines in the treatment of bone loss,and to provide evidence and support for the potential use of natural medicines in the treatment of osteoporosis.METHODS:A literature survey for relevant information regarding the osteogenesis of Dongkuiguo(Fructus Malvae Verticillatae),Machixian(Herba Portulacae Oleraceae).etc.,was conducted using PubM ed,ScienceDirect,MEDLINE,Springer LINK and Google Scholar electronic databases from the years 2000-2020.RESULTS:Dongkuiguo(Fructus Malvae Verticillatae),Machixian(Herba Portulacae Oleraceae).etc.,both inhibit the activity of osteoclasts and reduce bone resorption by regulation of signaling pathways through interacting with signaling molecules.CONCLUSIONS:In this review,the current knowledge of the novel medicines with osteogenesis properties were summarized and their potential in the treatment of bone loss were demonstrated,but the lack of research on the regulation of the signaling pathway’s mechanism of action,and the corresponding theoretical basis for the application of natural medicines in clinical osteoporosis,made it difficult to be widely applied and promoted in clinical practice.Further experiments with some of the medicines and the mechanisms is needed to realize their potential as osteoporosis treatments.

Research progress on Cordyceps militaris polysaccharides

Cordyceps militaris is a famous medicinal and edible fungus,whose polysaccharides are important biologically active substances.In recent years,the molecular structure and pharmacological functions of C.militaris polysaccharides were fully studied.However,the potential mechanism of their pharmacological functions and their chemical modification have not been systematically elucidated.Moreover,the obtention and usage of C.militaris polysaccharides present several issues,including low polysaccharide yields and poor pharmacological functions in industrial production.This review presents the latest results on the pharmacological mechanism of C.militaris,including information on how to improve C.militaris industrial production through stabilization of the strain to prevent degeneration and chemical modifications of its polysaccharides.In addition,this article examines C.militaris fermentation conditions,the polysaccharides extraction methods developed for industrial production,and the strategies to increase the yield of polysaccharides and improve their pharmacological functions.This review could provide a theoretical basis for future research on C.militaris polysaccharides,and also serve as an important reference value in the field of functional foods and medicine.

Evolution of the Management of Colorectal Cancer Using Integrative Medicine

Colorectal cancer（CRC） remains one of the major causes of cancer death worldwide.In recent years,the development of new and effective management options,such as fluoro-2-deoxy-D-glucose（FDG） positron emission tomography（PET）,total mesorectal excision（TME） and monoclonal antibody novel ＂targeted＂ therapies has led to a considerable improvement in the outcome of this disease.In China,studies on CRC using integrative medicine（IM） have made remarkable progress.We therefore review the recent developments in CRC treatment through IM and Western medicine,including research studies such as the exploitation of Chinese herbs for the disruption of the tumor cell cycle or inhibition of tumor cell proliferation,induction of tumor cell apoptosis,improvement of the immune system,and the curative effect of chemotherapy.We also examine clinical studies such as those on special prescriptions and medicines and IM in anti-cancer therapy. Particularly,we analyze the advantages and disadvantages of management with IM,and propose a suggestion for the management of colorectal cancer with IM,such as screening for effective prescriptions.We also analyze Chinese medicine,studying the pharmacologic mechanism of its anti-cancer effect,further strengthening the study of IM on CRC.

Phytochemistry and pharmacology of ornamental gingers,Hedychium coronarium and Alpinia purpurata:a review

In this review, the phytochemistry and pharmacology of two ornamental gingers, Hedychium coronarium （butterfly ginger） and Alpinia purpurata （red ginger）, are updated, and their botany and uses are described. Flowers of H. coronarium are large, showy, white, yellow or white with a yellow centre and highly fragrant. Inflorescences of A. purpurata are erect spikes with attractive red or pink bracts. Phytochemical investigations on the rhizomes of H. coronarium generated research interest globally. This resulted in the isolation of 53 labdane-type diterpenes, with little work done on the leaves and flowers. Pharmacological properties of H. coronarium included antioxidant, antibacterial, antifungal, cytotoxic, chemopreventive, anti-allergic, larvicidal, anthelminthic, analgesic, anti-inflammatory, anti-urolithiatic, anti-angiogenic, neuro- pharmacological, fibrinogenolytic, coagulant and hepatoprotective activities. On the contrary, little is known on the phytochemistry of A. purpurata with pharmacological properties of antioxidant, antibacterial, larvicidal, cytotoxic and vasodilator activities reported in the leaves and rhizomes. There is much disparity in terms of research effort within and between these two ornamental gingers.