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

Pharmacological activities and herb-drug interactions of Panax ginseng and its chemical components:a review

OBJECTIVE Panax ginseng C.A.Meyer(ginseng)is a well-known medicinal plant worldwide and a key ingredient in many commercially-available health products.It is used as a tonic for invigoration and for tification in times of fatigue and debility or declining capacity for work and concentration.Previous in-house study has surveyed over three hundred ginseng and ginseng products(including P.ginseng,P.quinquefolius,P.notoginseng,P.pseudoginseng)available in Singapore.This review presents an overview of the pharmacological activities and herb-drug interactions of P.ginseng and its ginsenosides.METHODS Literature searches of PubMed and ScienceDirect were done to identify pharmacological activities and herb-drug interactions of P.ginseng,its extracts and its chemical components,including ginsenosides.Studies of whole plant extracts include both White ginseng and Red ginseng.The studies for the pharmacological activities of whole plant extract were limited to those published from 2009 to 2015.There was no restriction on the time frame of other studies.Terms such as″P.ginseng″,″Ginsenosides″were searched.Studies found included in vitro assays,in vivo animal studies,human clinical trials as well as individual case reports.RESULTS A total of 112 studies were found on whole plant extracts and 257 studies on its individual components.Whole plant extracts of ginseng were found to possess over fifty different pharmacological activities,while its individual components exhibit parts of this spectrum.P.ginseng was found to interact with drugs such as 5-fluorouracil,irinotecan,mitomycin C,docetaxel,cisplatin,alcohol,midazolam,warfarin,phenelzine,raltegravir and imatinib.CONCLUSION P.ginseng and its components exhibit a wide range of pharmacological activities and interact with some drugs.There remain much opportunities for future research.

Pharmacognosy of Brazilian Ginseng ( Pfaffia paniculata)

[ Objective ] This study aimed to explore the pharmacognostical features of Brazilian ginseng （ Pfaffia paniculata）, anti to provide a theoretical basis ior its development and utilization. [ Method ] Morphological traits of Brazilian ginseng root were observed with traditional methods. Then, the root, stem and [e＇,ff of Brazilian ginseng were sliced, and observed under a microscope. The physical and chemical properties of root extract were detected. [ Result] Brazilian ginseng root is elongated and cylindrical, with obvious longitudinal ridges and sparse root marks, some irregularly shaped lenticels on the sm＇face. The cork layer of crosssection has five or more rows of cork cells. The abnormal vascular bundles are arranged in two to three rings. There are two to three central vascular bundles. The wood fibers it, powder are long, with one bifurcate end. The vessels have bordered pits. The sand crystals are scattered or in the parenchyma surrounding the fibers. The mucilage cells are oval and widely exist. Physical and chemical experiments showed that the rool of Brazilian ginseng eantains sterols or trilerpenes and saponins. [ Conclusion] The results will provide a theoretical basis for the pharmacological identificatian of Brazilian ginseng.

Explore the Mechanism of Ginseng on Breast Cancer Based on Network Pharmacology

Objective:To analyze the active mechanism of ginseng on breast cancer and its target mechanism.Methods:The Chinese medicine system pharmacology technology platform(TCMSP)database was used to screen out potential chemically active substances and related target proteins in ginseng.The genome annotation database platform(Genecards)was used to predict the target targets of breast cancer,and the uniprot database was used to query and Corresponding gene names,with the help of Cytoscape(3.7.2)software,to build a visualization of the"drug-disease-target"network diagram,construct a protein interaction network through the String database platform,and then use the Bioconductor platform and R language GO enrichment Analysis and KEGG enrichment analysis.Results:Through screening,22 effective chemical components of ginseng,15 key chemicals related to breast cancer,and 35 common targets of ginseng-breast cancer were obtained.The core genes of PPI were MAPK8,AR,RELA,and CASP8.,CYP1A1,CASP3,NCOA1,NR3C1,ICAM1,NCOA2,PGR,AKR1C3,CYP1B1,CYP3A4,GSTP1;Obtain 68 GO biological processes including,and 83 KEGG-related signaling pathways involving TNF signaling pathway,toxoplasmosis pathway Influenza A pathway,fluid shear stress and atherosclerosis pathway,prostate cancer pathway,etc.Conclusion:Ginseng can achieve anti-breast cancer effect through multiple ways,which lays the foundation for the future extraction of effective ingredients to treat breast cancer.

Effect of Sini Decoction plus Ginseng on COVID-19 based on network pharmacological analysis

Objective:To explore the effect of Sini Decoction plus Ginseng on COVID-19 based on network pharmacological analysis.Methods:TCMSP platform was used to search the compounds of Sini Decoction plus Ginseng with oral bioavailability(OB)≥30%and drug-likeness(DL)≥0.18,and the results were input into the UniProt database and converted into standard target names;Genecards and OMIM database were used to find COVID-19 target,and the intersection targets were obtained and Venn diagram was drawn.Cytoscape 3.7.2 was applied to make the network diagram of composition-disease-target;The interaction database platform-String was used to analyze the target protein interaction,and the data were input into the software of Cytoscape 3.7.2 to make the network diagram;David database was used to analyze the accumulation of Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathways of drug-disease intersection targets.The component target pathway network was constructed by using Cytoscape 3.7.2.Results:Altogether,112 active components of Sini Decoction plus Ginseng were screened,corresponding to 234 targets.Besides,261 COVID-19 targets were obtained after screening,and the Venn map showed that 50 targets were intersected.Quercetin,kaempferol,naringenin,andβ-sitosterol were found to have higher moderate values shown by the component-disease-target network.The target proteins with high PPI network analysis value were IL-6,MAPK8,MAPK3,MAPK1,TP53,TNF,and CASP3.GO enrichment function analysis showed that 341 biological processes,33 cell components,and 50 molecular functions were involved,which showed inflammatory reaction,cell response to lipopolysaccharide,exogenous apoptosis signal pathway,positive regulation of RNA polymeraseⅡpromoter transcription,cytokine activity,chemokine activity,heme binding,and other biological processes.KEGG signaling pathway enrichment function analysisshowed that there were 112 signaling pathways.It included TNF signaling pathway,tuberculosis,influenza A,PI3K Akt signaling pathway,HIF-1 signaling pathway,and Toll-like receptor signaling pathway.According to the component-target-pathway network diagram,quercetin,kaempferol,naringenin,andβ-sitosterol in Sini Decoction plus Ginseng may act on IL-6,MAPK8,MAPK3,MAPK1,TP53,TNF,CASP3,and other targets through TNF signaling pathway,MAPK signaling pathway,Tolllike receptor signaling pathway,PI3K-Akt signaling pathway,and HIF-1 signaling pathway.Conclusion:Sini Decoction plus Ginseng can affect COVID-19 through multiple active components,multiple targets,and multiple pathways.

Molecular Mechanism of Ginseng in Treating Nephrotic Syndrome Based on Network Pharmacology and Experimental Verification

[Objectives]To study the potential molecular mechanism of ginseng in treating nephrotic syndrome(NS)by using network pharmacology,molecular docking and experimental verification methods.[Methods]The active components and targets of ginseng were obtained through the network pharmacology database,and the potential targets for the treatment of NS were predicted.The STRING data platform and Cytoscape software were used to construct protein interaction network,and carry out GO and KEGG enrichment analysis.Molecular docking of active components of ginseng and core targets was performed.The in vitro experiment verified the improvement effect of kaempferol,a key active ingredient of ginseng,on podocyte injury.[Results]After screening,17 active components of ginseng and 38 key targets for treating NS were obtained.GO and KEGG enrichment analysis showed that NF-κB,MAPK and other inflammatory pathways were involved.Molecular docking results show that the core components had good binding activity to key targets.The results of in vitro experiments show that kaempferol can reduce the phosphorylation level of AKT1,down-regulate the expression levels of NF-κB p65 and p-NF-κB p65,play an anti-inflammatory effect by inhibiting the activation of NF-κB pathway,and improve podocyte injury.[Conclusions]Ginseng may play a role in the treatment of NS by regulating multiple targets and pathways such as inflammatory response,substance metabolism,and signal transduction.

Transcriptome-Wide Identification and Functional Analysis of PgSQE08-01 Gene in Ginsenoside Biosynthesis in Panax ginseng C.A.Mey.

Panax ginseng C.A.Mey.is an important plant species used in traditional Chinese medicine,whose primary active ingredient is a ginsenoside.Ginsenoside biosynthesis is not only regulated by transcription factors but also controlled by a variety of structural genes.Nonetheless,the molecular mechanism underlying ginsenoside biosynthesis has always been a topic in the discussion of ginseng secondary metabolites.Squalene epoxidase(SQE)is a key enzyme in the mevalonic acid pathway,which affects the biosynthesis of secondary metabolites such as terpenoid.Using ginseng transcriptome,expression,and ginsenoside content databases,this study employed bioinformatic methods to systematically analyze the genes encoding SQE in ginseng.We first selected six PgSQE candidates that were closely involved in ginsenoside biosynthesis and then identified PgSQE08-01 to be highly associated with ginsenoside biosynthesis.Next,we constructed the overexpression vector pCAMBIA3301-PgSQE08-01 and the RNAi vector pART27-PgSQE08-01 and transformed ginseng adventitious roots using Agrobacterium rhizogenes,to obtain positive hairy-root clones.Thereafter,quantitative reverse transcriptionpolymerase chain reaction and high-performance liquid chromatography were used to determine the expression of relevant genes and ginsenoside content,respectively.Then,we focused on the function of PgSQE08-01 gene,which was noted to be involved in ginsenoside biosynthesis.Thus,these findings not only provided a molecular basis for the identification of important functional genes in ginseng but also enriched genetic resources for the biosynthesis of ginsenosides using synthetic biology.

The pharmacokinetics of aspirin in combination with total ginsenoside of ginseng stems and leaves in rats

Objective:To investigate the effect of total ginsenoside of ginseng stems and leaves (TGSL) on the pharmacokinetics of aspirin in rats.Methods:Sprague-Dawley rats were randomly divided into two groups (n =6),a combined group that received TGSL (625 mg/kg body weight) and aspirin (10 mg/kg body weight) by gavage,and an aspirin group that received aspirin (10 mg/kg body weight) by gavage.The concentration of salicylic acid,an important metabolite of aspirin,was determined by highperformance liquid chromatography in supernatant from blood obtained from the orbital sinus at various time points to examine the effect of TGSL on aspirin.Results:The results showed that the Tmax of salicylic acid was [0.92 (0.58)] hours in the aspirin group and [2.50 (1.22)] hours in the combined group,and was statistically significantly different between the groups (p <.05).Conclusions:TGSL can affect the pharmacokinetics of aspirin at Tmax in rats.

Efficacy of ginseng-based Renshenguben oral solution for cancer-related fatigue among patients with advanced-stage hepatocellular carcinoma:A prospective multicenter cohort study

Background:Cancer-related fatigue(CRF)is a common and debilitating symptom experienced by patients with advanced-stage cancer,especially those undergoing antitumor therapy.This study aimed to evaluate the efficacy and safety of Renshenguben(RSGB)oral solution,a ginseng-based traditional Chinese medicine,in alleviating CRF in patients with advanced hepatocellular carcinoma(HCC)receiving antitumor treatment.Methods:In this prospective,open-label,controlled,multicenter study,patients with advanced HCC at BCLC stage C and a brief fatigue inventory(BFI)score of≥4 were enrolled.Participants were assigned to the RSGB group(RSGB,10 mL twice daily)or the control group(with supportive care).Primary and secondary endpoints were the change in multidimensional fatigue inventory(MFI)score,and BFI and functional assessment of cancer therapy-hepatobiliary(FACT-Hep)scores at weeks 4 and 8 after enrollment.Adverse events(AEs)and toxicities were assessed.Results:A total of 409 participants were enrolled,with 206 assigned to the RSGB group.At week 4,there was a trend towards improvement,but the differences were not statistically significant.At week 8,the RSGB group exhibited a significantly lower MFI score(P<0.05)compared to the control group,indicating improved fatigue levels.Additionally,the RSGB group showed significantly greater decrease in BFI and FACT-Hep scores at week 8(P<0.05).Subgroup analyses among patients receiving various antitumor treatments showed similar results.Multivariate linear regression analyses revealed that the RSGB group experienced a significantly substantial decrease in MFI,BFI,and FACT-Hep scores at week 8.No serious drug-related AEs or toxicities were observed.Conclusions:RSGB oral solution effectively reduced CRF in patients with advanced HCC undergoing antitumor therapy over an eight-week period,with no discernible toxicities.These findings support the potential of RSGB oral solution as an adjunctive treatment for managing CRF in this patient population.

Screening of Two Biocontrol Strains of Bacillus subtilis against Ginseng Soil-borne Disease and Their Antifungal Activities

[ Objective] The paper was to obtain biocontrol strains with good control effects against ginseng soil-borne disease through screening. [ Method] Dilu- tion plate method and plate confrontation culture method were used to isolate and screen biocontrol bacteria from the rhizosphere soil of diseased ginseng. The strains were identified through morphology, physiological and biochemical characteristics and 16S rDNA. [ Result ] With Rhizoctonia solani, Fusarium oxysporum and Fu- sarium solani as the indicator strains, two biocontrol strains B59 and X1 with strong antagonistic effects were screened from the rhizosphere soil of diseased ginseng in Tieli farm of Heilongjiang Province, and they were identified to be Bacillus subtilis. The inhibition rates of two biocontrol strains against eight different fungi were all greater than 90%. The primary study indicated that B59 and X1 strains could secrete antifungal active substances. [ Conclusion] Two biocontrol Bacillus subti- lis strains 1359 and X1 all had strong antagonistic effect against ginseng soil-borne disease, which had certain potential for development and utilization.

Dynamic of Soil Microorganisms from Root Region of Ginseng with Different Growing Years

Objective To see the dynamic of fungi, bacilli and actinomyces communities from root region of ginseng with different growing years.Method With ginseng root region soils from several sampling sites of Jilin Province as materials, concentrations of fungi, bacilli and antinomyces were evaluated by spread-plate method. Result Though there are differences on statistic data among soil samples, commonly with the increasing of growing years, concentration of fungi in ginseng root region increased, which were on the contrary for bacilli and antinomyces, and bacilli changed even more significant than antinomyces. Conclusion Concentrations of soil microorganisms can be influenced by soil type, planting mode and growing years simultaneously, but growing years influenced even more significantly.

Establishment of Optimization Conditions of SRAP-PCR System in Ginseng

[Objective]The research aimed study the amplification condition of SRAP-PCR of ginseng genome and set up the optimized amplification system/[Method]The effects of template DNA,primer,dNTP mixture and Mg^2＋ on PCR results were discussed.[Result] The optimized amplification procedure was as follows：pre-denaturing at 94 ℃ for 2 min;denaturing at 94 ℃ for 30 s,annealing at 48 ℃ for 30 s and extending at 72 ℃ for 1 min,40 cycles;extending at 72 ℃ for 7 min.The optimum reaction system was as follows：30 ng DNA template,2.0 μM upstream primer and downstream primer,0.3 mM dNTP mixture,2.5 Mm Mg2＋,the total volume was 25 μl.[Conclusion]The optimization amplification system for SRAP-PCR of ginseng was set up,which provided rapid and simplified test methods with good repeatability for SRAP analysis of the genetic relationship and genetic diversity of ginseng.

人参(Panax ginseng)根系分泌物成分对人参致病菌的化感效应

采用室内培养结合生物学测定的试验方法,研究了不同浓度人参(Panax ginseng)根系分泌物成分苯甲酸、邻苯二甲酸二异丁酯、十六酸和2,2二-(4羟-苯基)丙烷对人参立枯丝核菌(Rhizoctonia solani)、黑斑菌(Alternaria panax)、疫病菌(Phytophthora cactorum)、菌核菌(Sclerotinia schinseng)、锈腐菌(Cylindrocarpon destructans)和绿色木霉菌(Trichoderma viride)菌落生长及孢子萌发的化感效应。结果显示,不同浓度人参根系分泌物成分对人参致病菌及绿色木霉菌的化感效应存在显著差异。苯甲酸浓度与人参立枯丝核菌、菌核菌和锈腐菌菌落生长以及人参黑斑菌、锈腐菌孢子萌发呈负相关,与人参黑斑菌、绿色木霉菌菌落生长呈正相关;对人参疫病菌菌落生长的化感效应表现为低浓度和高浓度抑制,中浓度促进。邻苯二甲酸二异丁酯浓度与人参立枯丝核菌、黑斑菌、菌核菌和绿色木霉菌菌落生长以及人参黑斑菌孢子萌发呈负相关;对人参锈腐菌菌落生长和孢子萌发表现为低浓度和高浓度抑制,中浓度促进;对人参疫病菌菌落生长表现为低浓度和中浓度抑制,高浓度促进。2,2二-(4羟-苯基)丙烷浓度与人参立枯丝核菌、黑斑菌、疫病菌、绿色木霉菌菌落生长以及人参黑斑菌、锈腐菌孢子萌发呈负相关;对人参菌核菌、锈腐菌菌落生长表现中浓度促进,高浓度抑制。十六酸浓度与人参锈腐菌、疫病菌和绿色木霉菌菌落生长呈正相关,与人参锈腐菌孢子萌发呈负相关,对黑斑菌孢子萌发表现为中浓度抑制。4种根系分泌物的等量混合物浓度与人参致病菌及拮抗木霉菌菌落生长速率呈负相关。

Study on Detection of Organochlorine Pesticide Residue in Ginseng

To investigate the residue situation of pesticides in ginseng, total 17 samples of ginseng-growing soil, ginseng roots and ginseng seeds were collected from 5 regions of Fusong County, and the contents of organochlorine pesticide residues in the samples were detected by using ultrasonic-assisted extraction and gas chromatography with acetone-ligroin as the solvent, thereby providing suitable recommendations and scientific basis for the selection of ginseng-growing soil.

Pharm Web网站及其药学信息资源的检索与利用

对互联网上重要的药学信息资源网站PharmWeb及其涵盖的相关资源进行研究,对其特征进行分析,并对其检索方法进行介绍。

人参(Panax ginseng)的氮过剩现象──人参氮毒原因初探

1985-1990年间，我们在长白县及公主岭进行的四次NPK三要素试验中，发现氮肥抑制了人参生长发育，降低了产量（5％显著水准），而倍量氮肥，减产达1％显著水平。继续研究证明，人参硝酸还原酶活力（NRA）甚低，追施氮肥使组织，积累，促进了呼吸作用，植株干物中N、Si及Cu、Zn、Fe、Mn含量增加，Ca、Mg、K、Na等阳离子减少，表现出氮毒征象。本文称氮过剩症，它是指氮素供应超过了由极低NRA催化的转化代谢速率，而引起的一种毒害现象。

The Mediation of Defense Responses of Ginseng Cells to an Elicitor from Cell Walls of Colletotrichum lagerarium by Plasma Membrane NAD(P)H Oxidases

NAD(P)H oxidases were detected in suspension cultured cells of ginseng (Panax ginseng C. A. Meyer). The activities of these enzymes were induced by an elicitor (Cle) extracted from cell walls of Col-letotrichum lagerarium. In addition, Cle induced an oxidative burst and enhanced the synthesis of saponin, activity of phenylalanine ammonialyase (PAL) , accumulation of chalcone synthase (CHS) and the transcription of a hydroxyproline-rich glycoprotein gene ( hrgp ) . Pre-treatments with DPI and quinacrine (two inhibitors of mammalian neutrophil plasma membrane NADPH oxidase) for 30 min prior to Cle addition blocked the NAD(P)H oxidase activity induced by Cle. These inhibitors also inhibited the release of H2C2, the synthesis of saponin, PAL activity and CHS accumulation. Our data revealed homology between plasma membrane NAD(P)H oxidases of mammalian neutrophil cells and ginseng suspension cells. They also indicated that deactivated NAD(P)H oxidases catalysed the release of H2O2 and that H2O2 was functioning as a second messenger stimulating PAL activity, saponin synthesis and hrgp transcription. Elevations of Ca2 + and protein phos-phorylation/dephosphorylation were required for this defense process. We propose that NAD(P)H oxidases mediate the processes of Cle-induced defense responses in ginseng suspensions, and postulate the existence of a signalling cascade including extracellular Cle stimulation, activation of plasma membrane NAD(P)H oxidases, release of H2O2, and the intracellular responses of metabolism and gene transcription in ginseng suspension cells.

Activation of Plasma Membrane NADPH Oxidase and Generation of H_2O_2 Mediate the Induction of PAL Activity and Saponin Synthesis byEndogenous Elicitor in Suspension-Cultured Cells of Panax ginseng

Endogenous elicitor, termed cellulase-degraded cell wall (CDW), was prepared from the cell wall of suspension-cultured ginseng (Panax ginseng C.A. Meyer) cells via cellulase degradation. CDW activated the NADPH oxidase activity of isolated plasma membranes and stimulated in vivo H2O2 generation in ginseng cell suspensions. CDW also increased the activity of phenylalanine ammonia lyase (PAL), expression of a P. ginseng squalene epoxidase (sqe) gene and saponin synthesis. NADPH oxidase inhibitors inhibited both in vitro NADPH oxidase activity and in vivo H2O2 generation. Induction of PAL activity, saponin synthesis and sqe gene expression were all inhibited by such inhibitor treatments and reduced by incubation with catalase and HA scavengers. These data indicate that activation of NADPH oxidase and generation of H2O2 are essential signalling events mediating defence responses induced by the endogenous elicitor(s) present in CDW.

Research Progress on the Control of Ginseng Gray Mold

This review article describes the research progresses on the control of ginseng gray mold, summarizes domestic and international related experimental re-sults and literature data using chemical fungicide, plant extracts, microbial prepara-tion and antagonistic bacteria to control ginseng gray mold, and final y puts forward the existing problem and future research direction of the treatment and control of ginseng gray mold.

参照美国Pharm.D.模式的临床药学教学模式探索

目的:探索我国药学本科生临床药学课程的教学、培养模式。方法:参照美国Pharm.D.教学模式,向31名药学本科生授课并以案例分析实践形式进行强化训练,课后以问卷形式调查学生对学习效果与教学方式的反馈。结果:学生在课堂上有较好的互动,对课堂内容掌握程度较高。问卷调查结果显示,学生自认为学习效果一般(3.47/5)而对于教学方法的认可度较高(4.13/5)。结论:理论学习结合案例学习的教学方式可行性高,值得推广。