Panax notoginseng saponins(PNS)are a class of effective ingredients in Notoginseng Radix et Rhizoma,a well-known herbal medicine called San-Qi in Chinese.After oral administration,PNS inevitably interacts with gut mic...Panax notoginseng saponins(PNS)are a class of effective ingredients in Notoginseng Radix et Rhizoma,a well-known herbal medicine called San-Qi in Chinese.After oral administration,PNS inevitably interacts with gut microbiota,and thus affect the pharmacokinetic profiles and pharmacological effects.To date,studies concering gut microbiota-mediated metabolism of PNS have not been reviewed systematically.Herein,we outline the metabolic profiles of Panax notoginseng saponins mediated by gut microbiota,as well as its role in the pharmacokinetics and pharmacodynamics on the basis of reported data.The metabolic pathways of primary saponins are proposed,and step-by-step deglycosylation is found to be the primary degradation pathways of PNS mediated by gut microbiota.Specific microorganisms and enzymes involved in the metabolic processes were summarized.Gut microbiota is deeply involved in the metabolism of PNS,affects the pharmacokinetic profiles,and produces a series of active metabolites.These metabolites were documented to play an essential role in the efficacy of the parent compounds.Future studies should focus on strengthening the real-world evidence,defining the interaction between gut microbiota and PNS,and developing the strategy for modulating gut microbiota to enhance the bioavailability and efficacy of PNS.These information would be useful for further research and clinical application of PNS.展开更多
Background:Panax notoginseng(PNE)is a prominent traditional Chinese medicine with extensive beneficial effects on the immune system.However,the precise mechanism of PNE in treating inflammatory bowel disease(IBD)remai...Background:Panax notoginseng(PNE)is a prominent traditional Chinese medicine with extensive beneficial effects on the immune system.However,the precise mechanism of PNE in treating inflammatory bowel disease(IBD)remains unclear.Methods:We first used an extensive metabolomics approach utilizing UPLC-ESI-Q TRAP-MS/MS to identify the metabolite components of PNE aqueous extract.Moreover,the mechanism of PNE in treating IBD was investigated through in silico analysis including RNA-seq analysis,Network pharmacology and Molecular docking.Then a Drosophila toxin-induced intestinal inflammation model was employed to investigate further.Results:A total of 1,543 metabolites of PNE aqueous extract were characterized using UPLC-ESI-Q TRAP-MS/MS.In silico analyses showed that 97 IBD hub targets were targeted by 21 PNE ingredients.Kyoto Encyclopedia of Genes and Genomes results indicated that PNE may play an anti-IBD role through the Mitogen-activated protein kinase(MAPK)signaling pathway and other immune-related signaling pathways.Moreover,11 top hits compounds of PNE show a good affinity binding to IBD targets.The experimental results demonstrated that PNE can effectively improve the survival rate of adult Drosophila while also inhibit the excessive proliferation and differentiation of intestinal stem cells induced by sodium dodecyl sulfate.Furthermore,PNE notably lower the epithelial cell mortality,the accumulation of reactive oxygen species and the activation of oxidative stress-associated jun-Nterminal kinase(JNK)pathway.Conclusion:Our data suggests that PNE aqueous extract has a significant protective impact on the intestinal homeostasis of Drosophila.These findings establish a basis for utilizing PNE in clinical investigations and managing IBD.展开更多
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 als...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.展开更多
Panax ginseng(PG)and Panax notoginseng(PN)are highly valuable Chinese medicines(CM).Although both CMs have similar active constituents,their clinical applications are clearly different.Over the past decade,RNA sequenc...Panax ginseng(PG)and Panax notoginseng(PN)are highly valuable Chinese medicines(CM).Although both CMs have similar active constituents,their clinical applications are clearly different.Over the past decade,RNA sequencing(RNA-seq)analysis has been employed to investigate the molecular mechanisms of extracts or monomers.However,owing to the limited number of samples in standard RNA-seq,few studies have systematically compared the effects of PG and PN spanning multiple conditions at the transcriptomic level.Here,we developed an approach that simultaneously profiles transcriptome changes for multiplexed samples using RNA-seq(TCM-seq),a high-throughput,low-cost workflow to molecularly evaluate CM perturbations.A species-mixing experiment was conducted to illustrate the accuracy of sample multiplexing in TCM-seq.Transcriptomes from repeated samples were used to verify the robustness of TCM-seq.We then focused on the primary active components,Panax notoginseng saponins(PNS)and Panax ginseng saponins(PGS)extracted from PN and PG,respectively.We also characterized the transcriptome changes of 10 cell lines,treated with four different doses of PNS and PGS,using TCM-seq to compare the differences in their perturbing effects on genes,functional pathways,gene modules,and molecular networks.The results of transcriptional data analysis showed that the transcriptional patterns of various cell lines were significantly distinct.PGS exhibited a stronger regulatory effect on genes involved in cardiovascular disease,whereas PNS resulted in a greater coagulation effect on vascular endothelial cells.This study proposes a paradigm to comprehensively explore the differences in mechanisms of action between CMs based on transcriptome readouts.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
The compositions and contents of ginsenbsides in Panax ginseng,P.quinquefolium and P.notoginseng were determined and compared by reversed-phase High-Performance Liquid Chro- matography(HPLC).The method was performed o...The compositions and contents of ginsenbsides in Panax ginseng,P.quinquefolium and P.notoginseng were determined and compared by reversed-phase High-Performance Liquid Chro- matography(HPLC).The method was performed on an Alltech Adsorbosphere HS C_(18) column,using 5×10^(-3)M NaH_2PO_4-H_3PO_4 buffer solution(pH 3.0)and acetonitrile-water(50:50)as gradient eluents. The baseline separation of ginsenosides Rb_1,Rb_2,Rb_1,Rc,Rd,Rf,Ro,and Re+Rg_1 was obtained in one analytical run.The ginsenosides are directly detected at 203 nm.The detection limit is 40μg at a signal to noise ratio of 3:1.The improved sample preparation and clean-up prior to injection with SEP-PAK C_(18)cartridge strongly reduced the front peaks caused by the impurities in the methanolic extracts of samples to afford a smooth baseline and clear background.The HPLC patterns of methanolic extracts mainly including the ginsenosides were found capable of serving as chemical fingerprints to differentiate the three species from each other.It was also found that there are no significant diffe- rences of the HPLC patterns between the wild Panax ginseng and the cultivated,the white and the red ginsengs,Chinese and Korean red ginsengs,and the tap roots of Panax ginseng collected in four consecutive months,only certain differences in contents of ginsenosides do exist.The contents of the nine major ginsenosides present in the rhizome,tap root and rootlet as well as the leaf of Panax quinquefolium were also determined and compared.展开更多
Panax japonicus and its approximation varieties,such as Rhizoma Panacis Majoris and Panax japonicus C. A. Mey. var.major (Burk.) C.Y. Wu et K.M. Feng belong to Panax,which are less commonly used traditional Chinese ...Panax japonicus and its approximation varieties,such as Rhizoma Panacis Majoris and Panax japonicus C. A. Mey. var.major (Burk.) C.Y. Wu et K.M. Feng belong to Panax,which are less commonly used traditional Chinese medicine. Because of similar traits and effectiveness,they were always used as one type of medicine for a long time. Aiming at this phenomenon,the chemical composition and contents of P. japonicus and its approximation varieties from different area were compared in order to provide a chemical basis for clarifying the classification of the genus.展开更多
Objective] The aim of this study was to simultaneously isolate and identify the main pathogenic fungi of the root rot, black spot and round spot from the Panax notoginseng plants cultivated in Wenshan Eparchy of Yunna...Objective] The aim of this study was to simultaneously isolate and identify the main pathogenic fungi of the root rot, black spot and round spot from the Panax notoginseng plants cultivated in Wenshan Eparchy of Yunnan Province of China. [Method] The pathogenic fungi were isolated and purified by using potato dextrose agar (PDA) medium. The morphological identification was accomplished first according to the colony forms of the fungi when cultivated in vitro, then accord-ing to the symptom characteristics and colony forms of the re-isolated fungi in the reverse inoculation experiments. The molecular identification was performed accord-ing to the amplification and alignment of the internal transcribed space (ITS) se-quences of the fungi. The increases of the diameters and thickness of the colonies of the fungi cultivated in vitro were employed to indicate the growth rates of the fungi. [Results] The consistency of the colony forms and symptom characteristics and the 96%-99% similarities revealed in the ITS sequence alignments al proved that the main pathogenic fungi of the root rot, black spot and round spot of the P. notoginseng plants raised in Wenshan were Cylindrocarpon didymium, Alternaria panax and Mycocentrospora acerina, respectively. When cultivated in vitro in the same temperature, humidity and il umination, the increases of the colony diameters and thickness of C. didymium were the highest, fol owed by those of A. panax, then those of M. acerina. During different cultivation periods, the differences of the colony diameters and thickness of the three fungi al reached extremely significant level. However, at the same cultivation time, the differences of the diameters and thickness among the three fungi only reached significant level. [Conclusion] The main pathogenic fungi which result in the root rot, black spot and round spot of the P. notoginseng in Wenshan are C. didymium, A. panax and M. acerina, respec-tively. When these three diseases break out at the same time, the root rot wil spread fastest, fol owed orderly by the black spot and the round spot.展开更多
[Objective] This study aimed to identify red pigment of Panax notoginseng fruits and explore the correlation between pigment content and total saponins of the fruits. [Method] The red pigment of Panax notoginseng frui...[Objective] This study aimed to identify red pigment of Panax notoginseng fruits and explore the correlation between pigment content and total saponins of the fruits. [Method] The red pigment of Panax notoginseng fruits was preliminarily identi- fied with specific color reactions and UV-vis spectra, and the contents of the pigment and total saponins were determined via spectrophotometry. [Result] The red hues of the fruits were contributed by anthocyanins and/or the anthocyanidins. The contents of anthocyanins and total saponins of the fruits both decreased along with thinning of the red hues. The content difference of the anthocyanins in fruits with different red hues reached extremely significant level, but that of total saponins just reached significant level. [Conclusion] The red pigment of P. notoginseng fruits is anthocyanins which are of extremely significant positive correlation with total saponins in contents.展开更多
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 oxidas...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.展开更多
[Objective] This study was conducted to screen suitable fungicides to con-trol ginseng leaf blight caused by Alternaria panax_Whetz. [Method] The antifungal activity of seven fungicides against A. panax_ was determine...[Objective] This study was conducted to screen suitable fungicides to con-trol ginseng leaf blight caused by Alternaria panax_Whetz. [Method] The antifungal activity of seven fungicides against A. panax_ was determined based on mycelial growth rate in vitro. [Result] The results of in vitro antibiotic activity assay showed that there were significant differences in inhibition rate among different concentration treatments of each of the seven fungicides. Toxicity test results showed that among the seven fungicides, difenoconazole had the smal est EC50 (0.61 mg/L), fol owed by streptomycin and captan, with EC50 value lower than 100 mg/L. [Conclusion] A fungicide which had strong antifungal activity on A. panax was screened out, and the results wil provide a theoretical basis for further field trial.展开更多
Nerve growth factor(NGF) promotes axonal growth in PC12 cells primarily by regulating the RTK-RAS-MEK-ERK pathway. Panaxydol, a polyacetylene isolated from Panax notoginseng, can mimic the effects of NGF. Panaxydol ...Nerve growth factor(NGF) promotes axonal growth in PC12 cells primarily by regulating the RTK-RAS-MEK-ERK pathway. Panaxydol, a polyacetylene isolated from Panax notoginseng, can mimic the effects of NGF. Panaxydol promotes neurite outgrowth in PC12 cells, but its molecular mechanism remains unclear. Indeed, although alkynol compounds such as panaxydol can increase intracellular cyclic adenosine 3′,5′-monophosphate(cAMP) levels and the ERK inhibitor U0126 inhibits alkynol-induced axonal growth, how pathways downstream of cAMP activate ERK have not been investigated. This study observed the molecular mechanism of panaxydol-, NGF-and forskolin-induced PC12 cell axon growth using specific signaling pathway inhibitors. The results demonstrated that although the RTK inhibitor SU5416 obviously inhibited the growth-promoting effect of NGF, it could not inhibit the promoting effect of panaxydol on axonal growth of PC12 cells. The adenylate cyclase inhibitor SQ22536 and cAMP-dependent protein kinase inhibitor RpcAMPS could suppress the promoting effect of forskolin and panaxydol on axonal growth. The ERK inhibitor U0126 inhibited axonal growth induced by all three factors. However, the PKA inhibitor H89 inhibited the promoting effect of forskolin on axonal growth but could not suppress the promoting effect of panaxydol. A western blot assay was used to determine the effects of stimulating factors and inhibitors on ERK phosphorylation levels. The results revealed that NGF activates the ERK pathway through tyrosine receptors to induce axonal growth of PC12 cells. In contrast, panaxydol and forskolin increased cellular cAMP levels and were inhibited by adenylyl cyclase inhibitors. The protein kinase A inhibitor H89 completely inhibited forskolin-induced axonal outgrowth and ERK phosphorylation, but could not inhibit panaxydol-induced axonal growth and ERK phosphorylation. These results indicated that panaxydol promoted axonal growth of PC12 cells through different pathways downstream of cAMP. Considering that exchange protein directly activated by cAMP 1(Epac1) plays an important role in mediating cAMP signaling pathways, RNA interference experiments targeting the Epac1 gene were employed. The results verified that Epac1 could mediate the axonal growth signaling pathway induced by panaxydol. These findings suggest that compared with NGF and forskolin, panaxydol elicits axonal growth through the cAMP-Epac1-Rap1-MEK-ERK-CREB pathway, which is independent of PKA.展开更多
[Objective] The aim of this study was to investigate the content changes and their correlations of the photosynthetic pigment,phenols,including total phenols,total flavonoids and anthocyanins,and total saponins of the...[Objective] The aim of this study was to investigate the content changes and their correlations of the photosynthetic pigment,phenols,including total phenols,total flavonoids and anthocyanins,and total saponins of the one-year-old P.notoginseng plants under supplemental UV-B stress in fields.[Method] The one-year-old plants were irradiated by UV-B in field for 1 min per day,and the plants under the UV-B lamp were regarded as a circle center,achieving an annular leaf-sampling.The photosynthetic pigment,phenols and total saponins of the leaves were determined spectrophotometrically.[Result] With the increase of sampling radius,the supplemental UV-B intensity decreased significantly,the contents of chlorophyll (Chl) a,Chl b,Chl (a+b),carotenoid (Car) and total photosynthetic pigment (Chl+Car) of the leaves increased extremely significantly,the Chl a/b and total phenol content (TPC) decreased extremely significantly,but the Chl (a+b)/Car changes were not significant.The contents of total flavonoids,anthocyanins and saponins all increased due to the increasing of UV-B,displaying dose effects.The UV-B intensity was positively correlated with the Chl a/b,and negatively with the Chl a,Chl b,Chl (a+ b),Car and (Chl+Car) contents; and the two of TPC,total flavonoid content (TFC),total anthocyanin content (TAC) and total saponin content (TSC) were positively correlated,all reaching extremely significant level.The UV-B intensity was positively and significantly correlated with the total flavonoid content (TFC),negatively and significantly with the Chl (a+b)/Car,and positively and insignificantly with the TPC,TAC and TSC.[Conclusion] For one-year-old plants of P.notoginseng,UV-B can decrease the contents of the Chl a,Chl b,Chl (a+b),Car and (Chl+Car) and increase the Chl a/b and TPC,and,furthermore,induce the increases of the TFC,TAC and TSC in a dose-dependent manner.However,UV-B can hardly change the Chl (a+b)/Car.The supplemental UV-B of well-suited dose might be one of the effective measures to improve the TSC of P.notoginseng.展开更多
An ocotillone type ginsenoside, together with 2 known ginsenosides was isolated from leaves of Panax ginseng and identified as pseudoginsenoside RT 5 on the basis of chemical and physicochemical evidences. It h...An ocotillone type ginsenoside, together with 2 known ginsenosides was isolated from leaves of Panax ginseng and identified as pseudoginsenoside RT 5 on the basis of chemical and physicochemical evidences. It has been so far the first example of ocotillone type ginsenoside discovered in Panax ginseng and its plausible biotransformation pathway also discussed.展开更多
[Objectives]This paper aimed to prepare derivatives of protopanaxadiol from Panax notoginseng(Burk.)FH Chen with acid anhydrides and study their anti-tumor activity.[Methods]The 3-hydroxyl group of protopanaxadiol was...[Objectives]This paper aimed to prepare derivatives of protopanaxadiol from Panax notoginseng(Burk.)FH Chen with acid anhydrides and study their anti-tumor activity.[Methods]The 3-hydroxyl group of protopanaxadiol was subjected to structural modification and reacted with acid anhydrides to prepare derivatives,in order to improve the anti-tumor activity of protopanaxadiol.None of the five compounds designed and synthesized had been reported in the literature,and they were novel compounds.The anti-tumor activity of the derivatives was studies using MTS method.Taking cisplatin and paclitaxel as positive control drugs,the bioactivity of the compounds 1-5 on anti-tumor cell lines(HL-60 cells,SMMC-7721 cells,A-549 cells,MCF-7 cells and SW480 cells)in vitro was screened.[Results]The compound 5 showed inhibitory effect on HL-60 cells,SMMC-7721 cells and A-549 cells.[Conclusions]The acid anhydride esterification method is simple to operate and easy to control.This study has reference value for the structural modification and anti-tumor activity research of protopanaxadiol from P.notoginseng(Burk.)FH Chen.展开更多
Aim To establish a method for differentiating commercial samples of Panax species including notoginseng, cultivated ginseng (Chinese ginseng and Korean ginseng), wild ginseng, red ginseng, three types of American gi...Aim To establish a method for differentiating commercial samples of Panax species including notoginseng, cultivated ginseng (Chinese ginseng and Korean ginseng), wild ginseng, red ginseng, three types of American ginsengs, and one American ginseng preparation with their HPLC fingerprints for assnrning the quality of different commercial samples of Panax species. Methods HPLC-UV method was used to establish their fingerprints, Zorbax Extend C18 (250 mm×4.6 mm, 5 μm) was used as the analytical column, and acetonitrile/KH2PO4 aqueous solution was used as the mobile phase with gradient elution. Results The fingerprints of different commercial samples of Panax species varied in their holistic chromatograms and some specific constituents. Conclusion This method is reliable, reproducible and simple, It could be applied in the routine authentication of different commercial samples of Panax species展开更多
Five minor compounds isolated from the leaves of Panax ginseng C. A. Meyer were characterized as 20(R)-protopanaxatriol (1), daucosterin (2), 3β, 12β-dihydroxy-dammar-20 (22), 24-diene-3-O-β-D-glucopyranosi...Five minor compounds isolated from the leaves of Panax ginseng C. A. Meyer were characterized as 20(R)-protopanaxatriol (1), daucosterin (2), 3β, 12β-dihydroxy-dammar-20 (22), 24-diene-3-O-β-D-glucopyranoside (3), 20 (R)-protopanaxadiol-3-O-β-D-glucopyranoside (4) and ginsenoside-Rh2 (5), respectively, on the basis of spectral analyses and chemical evidence. The two new saponins, 3 and 4, were named as ginsenoside-Rh3 and 20(R)-ginsenoside-Rh2.Nine other major saponins obtained simultaneously were identical with ginsenoside-Rh1(6),-Rg3 (7), -Rg2 (8), -Rg1 (9),-Re(10),-Rd (11), -Rc (12), -Rb2(13) and Rb1 (14), respectively.展开更多
Aim To quantitatively determine five nucleosides and nucleobases, including cytidine, uridine, guanosine, adenosine and uracil in different parts of Panax notoginseng. Methods Separation was performed on a Zorbax SB-A...Aim To quantitatively determine five nucleosides and nucleobases, including cytidine, uridine, guanosine, adenosine and uracil in different parts of Panax notoginseng. Methods Separation was performed on a Zorbax SB-Aq column using a gradient elution with mobile phase of 8 mmol^L-1 ammonium acetate aqueous solution (A) and methanol (B). The assay was carried out at a flow rate of 1 mL·min^-1 at 25 ℃ with the diode-array detection at 260 nm. Results Cytidine, uridine, guanosine, adenosine and uracil had good linearity in the ranges of 1.79 - 57.40 μg·mL^-1 (r^2 = 1.0000), 3.30 - 105.60 μg·mL^-1 (r^2 = 1.0000), 3.09 - 98.80 μg·mL^ -1(r^2 = 0.9999), 2.77 - 88.60 μg·mL^-1 (r^2 = 1.0000) and 0.38 - 12.30 μg·mL ^-1 (r^2 = 1.0000) with average recoveries of 93.9%, 96.5%, 92.7%, 93.2% and 98.8%, respectively. The content of cytidine, uridine, guanosine, adenosine and uracil in different parts of P. notogingeng were significantly different. Conclusion This is the first report on quantitative determination of nucleosides and nucleobases in P notoginseng.展开更多
基金supported by Guangdong Basic and Applied Basic Research Foundation(No.2022A1515012039)Guangzhou Science and Technology Plan Project(No.2024A03J0360).
文摘Panax notoginseng saponins(PNS)are a class of effective ingredients in Notoginseng Radix et Rhizoma,a well-known herbal medicine called San-Qi in Chinese.After oral administration,PNS inevitably interacts with gut microbiota,and thus affect the pharmacokinetic profiles and pharmacological effects.To date,studies concering gut microbiota-mediated metabolism of PNS have not been reviewed systematically.Herein,we outline the metabolic profiles of Panax notoginseng saponins mediated by gut microbiota,as well as its role in the pharmacokinetics and pharmacodynamics on the basis of reported data.The metabolic pathways of primary saponins are proposed,and step-by-step deglycosylation is found to be the primary degradation pathways of PNS mediated by gut microbiota.Specific microorganisms and enzymes involved in the metabolic processes were summarized.Gut microbiota is deeply involved in the metabolism of PNS,affects the pharmacokinetic profiles,and produces a series of active metabolites.These metabolites were documented to play an essential role in the efficacy of the parent compounds.Future studies should focus on strengthening the real-world evidence,defining the interaction between gut microbiota and PNS,and developing the strategy for modulating gut microbiota to enhance the bioavailability and efficacy of PNS.These information would be useful for further research and clinical application of PNS.
基金supported by the National Natural Science Foundation of China(31900366)atural Science Foundation of Liaoning Province(2023-MSLH-295)+2 种基金atural Science Foundation Initiation fund of Shenyang Medical College(20201001)Liaoning University Student Innovation and Entrepreneurship Research Fund Orders(20229033)sponsored by the Key Laboratory of Research on Pathogenesis of Allergen provoked Allergic Disease,Liaoning Province(2018-30).
文摘Background:Panax notoginseng(PNE)is a prominent traditional Chinese medicine with extensive beneficial effects on the immune system.However,the precise mechanism of PNE in treating inflammatory bowel disease(IBD)remains unclear.Methods:We first used an extensive metabolomics approach utilizing UPLC-ESI-Q TRAP-MS/MS to identify the metabolite components of PNE aqueous extract.Moreover,the mechanism of PNE in treating IBD was investigated through in silico analysis including RNA-seq analysis,Network pharmacology and Molecular docking.Then a Drosophila toxin-induced intestinal inflammation model was employed to investigate further.Results:A total of 1,543 metabolites of PNE aqueous extract were characterized using UPLC-ESI-Q TRAP-MS/MS.In silico analyses showed that 97 IBD hub targets were targeted by 21 PNE ingredients.Kyoto Encyclopedia of Genes and Genomes results indicated that PNE may play an anti-IBD role through the Mitogen-activated protein kinase(MAPK)signaling pathway and other immune-related signaling pathways.Moreover,11 top hits compounds of PNE show a good affinity binding to IBD targets.The experimental results demonstrated that PNE can effectively improve the survival rate of adult Drosophila while also inhibit the excessive proliferation and differentiation of intestinal stem cells induced by sodium dodecyl sulfate.Furthermore,PNE notably lower the epithelial cell mortality,the accumulation of reactive oxygen species and the activation of oxidative stress-associated jun-Nterminal kinase(JNK)pathway.Conclusion:Our data suggests that PNE aqueous extract has a significant protective impact on the intestinal homeostasis of Drosophila.These findings establish a basis for utilizing PNE in clinical investigations and managing IBD.
基金This work was supported by an award from the Department of Science and Technology of Jilin Province(20210402043GH and 20210204063YY).
文摘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.
基金This work was supported by the National Natural Science Foundation of China(Grant Nos.:81973701 and 81903767)the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(Grant No.:ZYYCXTD-D-202002)the Natural Science Foundation of Zhejiang Province(Grant No.:LZ20H290002).
文摘Panax ginseng(PG)and Panax notoginseng(PN)are highly valuable Chinese medicines(CM).Although both CMs have similar active constituents,their clinical applications are clearly different.Over the past decade,RNA sequencing(RNA-seq)analysis has been employed to investigate the molecular mechanisms of extracts or monomers.However,owing to the limited number of samples in standard RNA-seq,few studies have systematically compared the effects of PG and PN spanning multiple conditions at the transcriptomic level.Here,we developed an approach that simultaneously profiles transcriptome changes for multiplexed samples using RNA-seq(TCM-seq),a high-throughput,low-cost workflow to molecularly evaluate CM perturbations.A species-mixing experiment was conducted to illustrate the accuracy of sample multiplexing in TCM-seq.Transcriptomes from repeated samples were used to verify the robustness of TCM-seq.We then focused on the primary active components,Panax notoginseng saponins(PNS)and Panax ginseng saponins(PGS)extracted from PN and PG,respectively.We also characterized the transcriptome changes of 10 cell lines,treated with four different doses of PNS and PGS,using TCM-seq to compare the differences in their perturbing effects on genes,functional pathways,gene modules,and molecular networks.The results of transcriptional data analysis showed that the transcriptional patterns of various cell lines were significantly distinct.PGS exhibited a stronger regulatory effect on genes involved in cardiovascular disease,whereas PNS resulted in a greater coagulation effect on vascular endothelial cells.This study proposes a paradigm to comprehensively explore the differences in mechanisms of action between CMs based on transcriptome readouts.
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.
文摘The compositions and contents of ginsenbsides in Panax ginseng,P.quinquefolium and P.notoginseng were determined and compared by reversed-phase High-Performance Liquid Chro- matography(HPLC).The method was performed on an Alltech Adsorbosphere HS C_(18) column,using 5×10^(-3)M NaH_2PO_4-H_3PO_4 buffer solution(pH 3.0)and acetonitrile-water(50:50)as gradient eluents. The baseline separation of ginsenosides Rb_1,Rb_2,Rb_1,Rc,Rd,Rf,Ro,and Re+Rg_1 was obtained in one analytical run.The ginsenosides are directly detected at 203 nm.The detection limit is 40μg at a signal to noise ratio of 3:1.The improved sample preparation and clean-up prior to injection with SEP-PAK C_(18)cartridge strongly reduced the front peaks caused by the impurities in the methanolic extracts of samples to afford a smooth baseline and clear background.The HPLC patterns of methanolic extracts mainly including the ginsenosides were found capable of serving as chemical fingerprints to differentiate the three species from each other.It was also found that there are no significant diffe- rences of the HPLC patterns between the wild Panax ginseng and the cultivated,the white and the red ginsengs,Chinese and Korean red ginsengs,and the tap roots of Panax ginseng collected in four consecutive months,only certain differences in contents of ginsenosides do exist.The contents of the nine major ginsenosides present in the rhizome,tap root and rootlet as well as the leaf of Panax quinquefolium were also determined and compared.
基金Supported by the National Natural Foundation of China(30873383)~~
文摘Panax japonicus and its approximation varieties,such as Rhizoma Panacis Majoris and Panax japonicus C. A. Mey. var.major (Burk.) C.Y. Wu et K.M. Feng belong to Panax,which are less commonly used traditional Chinese medicine. Because of similar traits and effectiveness,they were always used as one type of medicine for a long time. Aiming at this phenomenon,the chemical composition and contents of P. japonicus and its approximation varieties from different area were compared in order to provide a chemical basis for clarifying the classification of the genus.
基金Supported by the National Natural Science Foundation of China(31060045,31260091,31460065)~~
文摘Objective] The aim of this study was to simultaneously isolate and identify the main pathogenic fungi of the root rot, black spot and round spot from the Panax notoginseng plants cultivated in Wenshan Eparchy of Yunnan Province of China. [Method] The pathogenic fungi were isolated and purified by using potato dextrose agar (PDA) medium. The morphological identification was accomplished first according to the colony forms of the fungi when cultivated in vitro, then accord-ing to the symptom characteristics and colony forms of the re-isolated fungi in the reverse inoculation experiments. The molecular identification was performed accord-ing to the amplification and alignment of the internal transcribed space (ITS) se-quences of the fungi. The increases of the diameters and thickness of the colonies of the fungi cultivated in vitro were employed to indicate the growth rates of the fungi. [Results] The consistency of the colony forms and symptom characteristics and the 96%-99% similarities revealed in the ITS sequence alignments al proved that the main pathogenic fungi of the root rot, black spot and round spot of the P. notoginseng plants raised in Wenshan were Cylindrocarpon didymium, Alternaria panax and Mycocentrospora acerina, respectively. When cultivated in vitro in the same temperature, humidity and il umination, the increases of the colony diameters and thickness of C. didymium were the highest, fol owed by those of A. panax, then those of M. acerina. During different cultivation periods, the differences of the colony diameters and thickness of the three fungi al reached extremely significant level. However, at the same cultivation time, the differences of the diameters and thickness among the three fungi only reached significant level. [Conclusion] The main pathogenic fungi which result in the root rot, black spot and round spot of the P. notoginseng in Wenshan are C. didymium, A. panax and M. acerina, respec-tively. When these three diseases break out at the same time, the root rot wil spread fastest, fol owed orderly by the black spot and the round spot.
基金Supported by the National Natural Science Foundation of China(No.31060045,31260091)~~
文摘[Objective] This study aimed to identify red pigment of Panax notoginseng fruits and explore the correlation between pigment content and total saponins of the fruits. [Method] The red pigment of Panax notoginseng fruits was preliminarily identi- fied with specific color reactions and UV-vis spectra, and the contents of the pigment and total saponins were determined via spectrophotometry. [Result] The red hues of the fruits were contributed by anthocyanins and/or the anthocyanidins. The contents of anthocyanins and total saponins of the fruits both decreased along with thinning of the red hues. The content difference of the anthocyanins in fruits with different red hues reached extremely significant level, but that of total saponins just reached significant level. [Conclusion] The red pigment of P. notoginseng fruits is anthocyanins which are of extremely significant positive correlation with total saponins in contents.
文摘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.
基金Supported by National Natural Science Fondation of China(31260067)Collegeenterprise Cooperation Project of Yanbian University[(2015)6]~~
文摘[Objective] This study was conducted to screen suitable fungicides to con-trol ginseng leaf blight caused by Alternaria panax_Whetz. [Method] The antifungal activity of seven fungicides against A. panax_ was determined based on mycelial growth rate in vitro. [Result] The results of in vitro antibiotic activity assay showed that there were significant differences in inhibition rate among different concentration treatments of each of the seven fungicides. Toxicity test results showed that among the seven fungicides, difenoconazole had the smal est EC50 (0.61 mg/L), fol owed by streptomycin and captan, with EC50 value lower than 100 mg/L. [Conclusion] A fungicide which had strong antifungal activity on A. panax was screened out, and the results wil provide a theoretical basis for further field trial.
基金supported partly by the National Natural Science Foundation of China,No.30873057,81171245a grant from the Key Basic Project of Shanghai Municipal Science and Technology Commission of China,No.08JC1413600,11JC1406600
文摘Nerve growth factor(NGF) promotes axonal growth in PC12 cells primarily by regulating the RTK-RAS-MEK-ERK pathway. Panaxydol, a polyacetylene isolated from Panax notoginseng, can mimic the effects of NGF. Panaxydol promotes neurite outgrowth in PC12 cells, but its molecular mechanism remains unclear. Indeed, although alkynol compounds such as panaxydol can increase intracellular cyclic adenosine 3′,5′-monophosphate(cAMP) levels and the ERK inhibitor U0126 inhibits alkynol-induced axonal growth, how pathways downstream of cAMP activate ERK have not been investigated. This study observed the molecular mechanism of panaxydol-, NGF-and forskolin-induced PC12 cell axon growth using specific signaling pathway inhibitors. The results demonstrated that although the RTK inhibitor SU5416 obviously inhibited the growth-promoting effect of NGF, it could not inhibit the promoting effect of panaxydol on axonal growth of PC12 cells. The adenylate cyclase inhibitor SQ22536 and cAMP-dependent protein kinase inhibitor RpcAMPS could suppress the promoting effect of forskolin and panaxydol on axonal growth. The ERK inhibitor U0126 inhibited axonal growth induced by all three factors. However, the PKA inhibitor H89 inhibited the promoting effect of forskolin on axonal growth but could not suppress the promoting effect of panaxydol. A western blot assay was used to determine the effects of stimulating factors and inhibitors on ERK phosphorylation levels. The results revealed that NGF activates the ERK pathway through tyrosine receptors to induce axonal growth of PC12 cells. In contrast, panaxydol and forskolin increased cellular cAMP levels and were inhibited by adenylyl cyclase inhibitors. The protein kinase A inhibitor H89 completely inhibited forskolin-induced axonal outgrowth and ERK phosphorylation, but could not inhibit panaxydol-induced axonal growth and ERK phosphorylation. These results indicated that panaxydol promoted axonal growth of PC12 cells through different pathways downstream of cAMP. Considering that exchange protein directly activated by cAMP 1(Epac1) plays an important role in mediating cAMP signaling pathways, RNA interference experiments targeting the Epac1 gene were employed. The results verified that Epac1 could mediate the axonal growth signaling pathway induced by panaxydol. These findings suggest that compared with NGF and forskolin, panaxydol elicits axonal growth through the cAMP-Epac1-Rap1-MEK-ERK-CREB pathway, which is independent of PKA.
基金Supported by the National Natural Science Foundation of China(31060045,31260091)~~
文摘[Objective] The aim of this study was to investigate the content changes and their correlations of the photosynthetic pigment,phenols,including total phenols,total flavonoids and anthocyanins,and total saponins of the one-year-old P.notoginseng plants under supplemental UV-B stress in fields.[Method] The one-year-old plants were irradiated by UV-B in field for 1 min per day,and the plants under the UV-B lamp were regarded as a circle center,achieving an annular leaf-sampling.The photosynthetic pigment,phenols and total saponins of the leaves were determined spectrophotometrically.[Result] With the increase of sampling radius,the supplemental UV-B intensity decreased significantly,the contents of chlorophyll (Chl) a,Chl b,Chl (a+b),carotenoid (Car) and total photosynthetic pigment (Chl+Car) of the leaves increased extremely significantly,the Chl a/b and total phenol content (TPC) decreased extremely significantly,but the Chl (a+b)/Car changes were not significant.The contents of total flavonoids,anthocyanins and saponins all increased due to the increasing of UV-B,displaying dose effects.The UV-B intensity was positively correlated with the Chl a/b,and negatively with the Chl a,Chl b,Chl (a+ b),Car and (Chl+Car) contents; and the two of TPC,total flavonoid content (TFC),total anthocyanin content (TAC) and total saponin content (TSC) were positively correlated,all reaching extremely significant level.The UV-B intensity was positively and significantly correlated with the total flavonoid content (TFC),negatively and significantly with the Chl (a+b)/Car,and positively and insignificantly with the TPC,TAC and TSC.[Conclusion] For one-year-old plants of P.notoginseng,UV-B can decrease the contents of the Chl a,Chl b,Chl (a+b),Car and (Chl+Car) and increase the Chl a/b and TPC,and,furthermore,induce the increases of the TFC,TAC and TSC in a dose-dependent manner.However,UV-B can hardly change the Chl (a+b)/Car.The supplemental UV-B of well-suited dose might be one of the effective measures to improve the TSC of P.notoginseng.
文摘An ocotillone type ginsenoside, together with 2 known ginsenosides was isolated from leaves of Panax ginseng and identified as pseudoginsenoside RT 5 on the basis of chemical and physicochemical evidences. It has been so far the first example of ocotillone type ginsenoside discovered in Panax ginseng and its plausible biotransformation pathway also discussed.
基金Supported by Science&Technology Department of Yunnan Province-Kunming Medical University Joint Fund for Applied Basic Research[2017FE468(-001)]NSFC-Yunnan Joint Fund[U1502226].
文摘[Objectives]This paper aimed to prepare derivatives of protopanaxadiol from Panax notoginseng(Burk.)FH Chen with acid anhydrides and study their anti-tumor activity.[Methods]The 3-hydroxyl group of protopanaxadiol was subjected to structural modification and reacted with acid anhydrides to prepare derivatives,in order to improve the anti-tumor activity of protopanaxadiol.None of the five compounds designed and synthesized had been reported in the literature,and they were novel compounds.The anti-tumor activity of the derivatives was studies using MTS method.Taking cisplatin and paclitaxel as positive control drugs,the bioactivity of the compounds 1-5 on anti-tumor cell lines(HL-60 cells,SMMC-7721 cells,A-549 cells,MCF-7 cells and SW480 cells)in vitro was screened.[Results]The compound 5 showed inhibitory effect on HL-60 cells,SMMC-7721 cells and A-549 cells.[Conclusions]The acid anhydride esterification method is simple to operate and easy to control.This study has reference value for the structural modification and anti-tumor activity research of protopanaxadiol from P.notoginseng(Burk.)FH Chen.
基金Program for Changjiang Scholar and InnovativeTeam in University(Grant No.985-2-063-112) National Supporting Program for TCM from Ministry of Science andTechnology of China(Grant No.2006BAI08B03-03).
文摘Aim To establish a method for differentiating commercial samples of Panax species including notoginseng, cultivated ginseng (Chinese ginseng and Korean ginseng), wild ginseng, red ginseng, three types of American ginsengs, and one American ginseng preparation with their HPLC fingerprints for assnrning the quality of different commercial samples of Panax species. Methods HPLC-UV method was used to establish their fingerprints, Zorbax Extend C18 (250 mm×4.6 mm, 5 μm) was used as the analytical column, and acetonitrile/KH2PO4 aqueous solution was used as the mobile phase with gradient elution. Results The fingerprints of different commercial samples of Panax species varied in their holistic chromatograms and some specific constituents. Conclusion This method is reliable, reproducible and simple, It could be applied in the routine authentication of different commercial samples of Panax species
文摘Five minor compounds isolated from the leaves of Panax ginseng C. A. Meyer were characterized as 20(R)-protopanaxatriol (1), daucosterin (2), 3β, 12β-dihydroxy-dammar-20 (22), 24-diene-3-O-β-D-glucopyranoside (3), 20 (R)-protopanaxadiol-3-O-β-D-glucopyranoside (4) and ginsenoside-Rh2 (5), respectively, on the basis of spectral analyses and chemical evidence. The two new saponins, 3 and 4, were named as ginsenoside-Rh3 and 20(R)-ginsenoside-Rh2.Nine other major saponins obtained simultaneously were identical with ginsenoside-Rh1(6),-Rg3 (7), -Rg2 (8), -Rg1 (9),-Re(10),-Rd (11), -Rc (12), -Rb2(13) and Rb1 (14), respectively.
文摘Aim To quantitatively determine five nucleosides and nucleobases, including cytidine, uridine, guanosine, adenosine and uracil in different parts of Panax notoginseng. Methods Separation was performed on a Zorbax SB-Aq column using a gradient elution with mobile phase of 8 mmol^L-1 ammonium acetate aqueous solution (A) and methanol (B). The assay was carried out at a flow rate of 1 mL·min^-1 at 25 ℃ with the diode-array detection at 260 nm. Results Cytidine, uridine, guanosine, adenosine and uracil had good linearity in the ranges of 1.79 - 57.40 μg·mL^-1 (r^2 = 1.0000), 3.30 - 105.60 μg·mL^-1 (r^2 = 1.0000), 3.09 - 98.80 μg·mL^ -1(r^2 = 0.9999), 2.77 - 88.60 μg·mL^-1 (r^2 = 1.0000) and 0.38 - 12.30 μg·mL ^-1 (r^2 = 1.0000) with average recoveries of 93.9%, 96.5%, 92.7%, 93.2% and 98.8%, respectively. The content of cytidine, uridine, guanosine, adenosine and uracil in different parts of P. notogingeng were significantly different. Conclusion This is the first report on quantitative determination of nucleosides and nucleobases in P notoginseng.