Background:Panacis Quinquefolii Radix(PQR)is known for its ability to nourish“Qi”(it serves as the driving force for the functional activities of the body’s organs and meridians,promoting and regulating various phy...Background:Panacis Quinquefolii Radix(PQR)is known for its ability to nourish“Qi”(it serves as the driving force for the functional activities of the body’s organs and meridians,promoting and regulating various physiological functions)and“Yin”(it represents the material foundation of the human body.It plays a role in nourishing,moistening,and cooling the body).Notoginseng Radix et Rhizoma(NRR)is recognized for its properties of resolving blood stasis(it refers to a pathological condition characterized by impaired or stagnant blood circulation within the body).Changes in the compatibility ratio of these herbs often lead to variations in their chemical composition and efficacy.However,the specific alterations in chemical composition and efficacy resulting from compatibility adjustments remain unclear.We aimed to compare the material basis and their effects of different compatibility ratios of PQR and NRR on“Qi”deficiency and blood stasis syndrome(QBS).Methods:This study employed UPLC-Q/TOF-MS to identify effective compounds in the compatibility of PQR and NRR and utilized UPLC-TQ-MS/MS to analyze the dissolution of 16 saponins in PQR and NRR at 9 different ratios.A rat model of QBS was established,and the efficacy of PQR and NRR in treating this syndrome was assessed using hemorheology and coagulation analyses.Results:The study results show that PQR and NRR exhibit significant efficacy,effectively reducing blood viscosity induced by platelet aggregation and lowering inflammatory markers such as IL-6,IL-10,TXB2 and ET associated with vascular injury.Moreover,this combination regulates ATP and ADP levels,enhances energy metabolism,and promotes overall health.A total of 104 compounds in the compatibility of PQR and NRR were identified.The ratios of 1:2 and 1:3 showed the highest total saponin content,but the ratio of 1:1 demonstrated a superior pharmacological effect for the treatment of QBS.Conclusion:In summary,the compatibility of PQR and NRR not only shows the complex interactions between traditional Chinese medicinal materials,but also provides a new idea and method for the treatment of QBS.展开更多
Panax notoginseng saponins(PNS)is the primary active component of the traditional Chinese medicine P.notoginseng.This compound exhibits a range of pharmacological effects,including anti-inflammatory,antioxidant,and an...Panax notoginseng saponins(PNS)is the primary active component of the traditional Chinese medicine P.notoginseng.This compound exhibits a range of pharmacological effects,including anti-inflammatory,antioxidant,and antiplatelet aggregation properties,as well as the enhancement of microcirculation.The extensive research on the modernization of traditional Chinese medicine has garnered significant attention regarding the application of PNS in the treatment of cardiovascular diseases.Research has demonstrated that PNS interventions significantly improve the pathological progression of cardiovascular disease through synergistic effects involving multiple targets and pathways.This paper summarizes the pharmacological mechanisms,clinical research advancements,safety,and potential adverse reactions associated with PNS in the treatment of cardiovascular diseases,in order to provide theoretical references for future research and practical applications in this field.展开更多
OBJECTIVE:To investigate the effect and mechanism of Sanqi(Radix Notoginseng)in treating periodontitis.METHODS:The active components and periodontitis targets were analyzed through network pharmacology and molecular d...OBJECTIVE:To investigate the effect and mechanism of Sanqi(Radix Notoginseng)in treating periodontitis.METHODS:The active components and periodontitis targets were analyzed through network pharmacology and molecular docking.A rat model of periodontitis was established and rats were treated by continuous intragastric administration of Sanqi(Radix Notoginseng)at different doses for 30 d.The alveolar bone structure was observed by micro-CT,the periodontal tissue structure was observed by hematoxylin-eosin staining,and the related proteins changes was detected by immunohistochemical staining.RESULTS:Sanqi(Radix Notoginseng)and periodontitis had a total of 96 coincident targets that were significantly enriched in the interleukin 17(IL-17),tumor necrosis factor(TNF),and advanced glycation endproducts and the receptor of advanced glycation endproducts signaling pathways.The active compound quercetin had good binding activity with interleukin 6(IL-6),vascular endothelial growth factor A(VEGFA),matrix metallopeptidase 9(MMP9),tumor necrosis factorα(TNF-α),Jun proto-oncogene(JUN),and C-X-C motif chemokine ligand 8(CXCL8)in periodontitis.Compared with normal group,the distance from the cementoenamel junction(CEJ)to the alveolar bone(AB)was increased,alveolar bone absorption was obvious,the periodontal tissue structure was disorganized,and IL-6 and TNF-αwere upregulated in periodontitis group;meanwhile,the distance from CEJ to AB was significantly decreased,alveolar bone resorption was reduced,periodontal tissue structure was improved,the expression of IL-6,TNF-α,IL-17 and retinoid-ralated orphan receptorγt(RORγt)were decreased,Forkhead Box P3(FOXP3)and IL-10 were increased after Sanqi(Radix Notoginseng)treatment.CONCLUSIONS:Sanqi(Radix Notoginseng)improves the structure of alveolar bone and gum,and reduces inflammation;the mechanism involve in inhibiting IL-17 signaling pathway to suppress Th17 and promote Treg cells differentiation.展开更多
Panax notoginseng is a traditional Chinese medicine containing various constituents,including the saponins,polysaccharides,polyacetylenes,amino acids,etc.It has beneficial functions,such as the anti-inflammatory,antit...Panax notoginseng is a traditional Chinese medicine containing various constituents,including the saponins,polysaccharides,polyacetylenes,amino acids,etc.It has beneficial functions,such as the anti-inflammatory,antitumor,hepatoprotective,and anti-aging effects.Among these,P.notoginseng polysaccharides(PNPs)have been exploited because of their extensive pharmacological effects,being ranked as one of the current research hotspots,especially for the functional foods and medical practice.In this review,the literature related to PNPs in the past 20 years was surveyed and analyzed using both the China National Knowledge Infrastructure(CNKI)and Web of Science(WOS)databases.The visualization diagram shows that current studies on PNPs mainly focus on the antioxidant and immunomodulatory activities and structural characterization.In addition,the extraction,separation,purification,chemical analysis,structural characteristics,bioactivities,and applications of PNPs are outlined,in detail,aimed to provide valuable information for the further study,development,and utilization regarding PNPs.展开更多
Thrombosis is a leading cause of mortality and morbidity in patients suffering from polycythemia vera(PV).Drug pair Salviae Miltiorrhizae Radix et Rhizoma(Danshen,DS)and Notoginseng Radix et Rhizoma(Sanqi,SQ)is common...Thrombosis is a leading cause of mortality and morbidity in patients suffering from polycythemia vera(PV).Drug pair Salviae Miltiorrhizae Radix et Rhizoma(Danshen,DS)and Notoginseng Radix et Rhizoma(Sanqi,SQ)is common traditional Chinese medicine(TCM)used in clinical practice to promote blood circulation and eliminate blood stasis.In this study,network pharmacology and molecular docking were used to analyze the potentially active ingredients and underlying mechanisms of drug pair DS-SQ against thrombosis after PV.These results show that 54 targets are related to both disease and the drug pair.Nineteen core targets,including IL-6 and AKT1,were screened.Luteolin and tanshinone IIa from DS as well as quercetin from SQ might be the major substances in the treatment of thrombosis after PV.KEGG enrichment analysis demonstrated that the lipid and atherosclerosis signaling pathway might play a significant role.These results provide valuable insights and a reference for the use of drug pair DS-SQ in management of thrombosis after PV and lay a foundation for further exploration of pharmacological effects.展开更多
Stem-leaf saponins from Panax notoginseng(SLSP)comprise numerous PPD-type saponins with diverse pharmacological properties;however,their role in Parkinson's disease(PD),characterized by microglia-mediated neuroinf...Stem-leaf saponins from Panax notoginseng(SLSP)comprise numerous PPD-type saponins with diverse pharmacological properties;however,their role in Parkinson's disease(PD),characterized by microglia-mediated neuroinflammation,remains unclear.This study evaluated the effects of SLSP on suppressing microglia-driven neuroinflammation in experimental PD models,including the 1-methyl-4-phenylpyridinium(MPTP)-induced mouse model and lipopolysaccharide(LPS)-stimulated BV-2 microglia.Our findings revealed that SLSP mitigated behavioral impairments and excessive microglial activation in models of PD,including MPTP-treated mice.Additionally,SLSP inhibited the upregulation of inducible nitric oxide synthase(i NOS)and cyclooxygenase-2(COX2)and attenuated the phosphorylation of PI3K,protein kinase B(AKT),nuclear factor-κB(NFκB),and inhibitor of NFκB proteinα(IκBα)both in vivo and in vitro.Moreover,SLSP suppressed the production of inflammatory markers such as interleukin(IL)-1β,IL-6,and tumor necrosis factor alpha(TNF-α)in LPS-stimulated BV-2cells.Notably,the P2Y2R agonist partially reversed the inhibitory effects of SLSP in LPStreated BV-2 cells.These results suggest that SLSP inhibit microglia-mediated neuroinflammation in experimental PD models,likely through the P2Y2R/PI3K/AKT/NFκB signaling pathway.These novel findings indicate that SLSP may offer therapeutic potential for PD by attenuating microglia-mediated neuroinflammation.展开更多
To develop a HPIX-UV-MS method for identifying the constituents in theChinese drug Notoginseng (the root of Panax notoginseng). Methods A Phenomenex Luna C_(18) column(250 mm x 4.6 mm ID, 5 μm) was utilized. Water co...To develop a HPIX-UV-MS method for identifying the constituents in theChinese drug Notoginseng (the root of Panax notoginseng). Methods A Phenomenex Luna C_(18) column(250 mm x 4.6 mm ID, 5 μm) was utilized. Water containing 0.005% formic acid (A) and acetonitrilecontaining 0.005% formic acid (B) were used as gradient eluents. UV spectra were recorded in range195 - 400 nm. Both positive and negative ion ESI modes were used. Results The constituents inNotoginseng were well separated and detected. Fourteen compounds were identified by comparing theirretention time and ESI-MS data with those obtained from the reference compounds. Forty-one compoundswere deduced by data analysis of MS and literature; among them, yesanchinosides-H and -E,chikusetsusaponin-L_5, malonyl-ginsenoside-R_(g_1), the isomers of notoginsenosides-J, -A, -R_1, -G,-R_2, and ginsenoside-Rh_3 were discovered in Notoginseng for the first time. Conclusion Thismethod gives high sensitivity and good separation, and is suitable for identifying the constituentsin Notoginseng. This result is helpful for further phytochemical research on Notoginseng. Based onthis result, further quality control can be studied.展开更多
In the present study, we established an UPLC-QTOF-MSE based metabolomic approach in order to evaluate the holistic qualities and compare the quality difference by finding characteristic components of Panax notoginseng...In the present study, we established an UPLC-QTOF-MSE based metabolomic approach in order to evaluate the holistic qualities and compare the quality difference by finding characteristic components of Panax notoginseng extracts （PNE） and Xuesaitong （XST） injection samples from different manufacturers. The data were processed through unsupervised principal component analysis （PCA） and supervised orthogonal partial least squared discrimination analysis （OPLS-DA） to compare the quality differences. Two-dimensional PCA score plots showed a tendency to separate the XST injections and extracts, and most XST injection samples were clearly clustered into two groups. Especially, the injections from He and YB companies were distinguished into two groups. In addition, only injection samples of Hu company were near the cluster of PNE. To explore the potential chemical components contributing most to the differences between XST injection samples from different manufacturers and PNE, an S-plot was constructed following the OPLS-DA. Ginsenoside Rd, ginsenoside Rgl, ginsenoside Re, ginsenoside Rbl, 20（S）-ginsenoside Rhl, gypenoside VII, ginsenoside Rg2, ginsenoside Rh4, ginsenoside Rkl or Rgs, notoginsenoside Fc, 20（R）-ginsenoside Rg3, ginsenoside F2 and protopanaxadiol were recognized as characteristic chemical markers that contributed most to reflect the difference between XST injections and PNE. Ginsenoside Rd, ginsenoside Rgl, ginsenoside Re, ginsenoside Rbl and gypenoside VII were revealed as index components contributing most to the differences of PNE and XST injections, and quantitative analysis of these components could ensure the consistent quality of XST injections. Based on the fact that the injections should be standardized with the characteristic components as quality control chemical markers, it is most important to keep the quality of extracts of raw materials stable and reliable.展开更多
To overcome the issues of high cost and continuous cropping obstacles in facility cultivation of Panax notoginseng_ F. H. Chen, satisfy the market demand, save the production cost, improve the utilization rate of fore...To overcome the issues of high cost and continuous cropping obstacles in facility cultivation of Panax notoginseng_ F. H. Chen, satisfy the market demand, save the production cost, improve the utilization rate of forest land, increase the in-come of forest farmers and protect the ecological environment, the cultivation tech-niques of high-quality P. notoginseng seedlings from Wenshan, Yunnan under four kinds of forests （walnut forest, China fir forest, grape forest and kiwi forest） were in-vestigated in this study. The results showed that the height growth, crown diameter, survival rate and 3-year-old tuber weight of P. notoginseng_under walnut forest were higher than those under the other three kinds of forests; the height growth, crown diameter, survival rate and 3-year-old tuber weight of P. notoginseng under China fir forest were higher than those under grape forest and kiwi forest; and the crown di-ameter and survival rate under grape forest were higher, and the height growth and tuber weight under grape forest were lower than those under kiwi forest. Walnut is a broad-leaved deciduous tree species, so large-scale cultivation of P. notoginseng_should be conducted under broadleaf deciduous forest with canopy density around 0.8, taking advantage of the cool environment and rich humus layer under forest. This cultivation technology could save labor, shade, fertilizer and other costs, and accord with the ecological habit and the growth rules of P. notoginseng, thus im-proving yield and achieving high economic benefit.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
Acute ischemic stroke has become a major disease burden with high mortality and morbidity rates. There is a lack of evidence-based medicine confirming the efficacy of common treatments. Panax notoginseng saponins, the...Acute ischemic stroke has become a major disease burden with high mortality and morbidity rates. There is a lack of evidence-based medicine confirming the efficacy of common treatments. Panax notoginseng saponins, the main active ingredient of radix notoginseng, have a neuro- protective role in ischemic brain injury, and have been popularized as a maintenance treatment for acute cerebral infarction and its sequelae. We conducted literature searches on the Web of Science, ClinicalTrials.gov, Cochrane Collaboration, CNKI, Wanfang and the China Scientific ＆ Technological Achievements Database and analyzed the experimental and clinical outcomes of studies investigating the use of radix notoginseng in the treatment of ischemic brain injury to improve the understanding of relevant research trends and existing problems. We found that over the past 10 years, China has maintained its interest in Panax notoginseng research, while such studies are scarce on the Web of Science. However, Chinese researchers often focus on the neuroprotective role of radix notoginseng in ischemic brain injury, but there are no large-scale clinical data to confirm its efficacy and safety. There remains a need for more rigorous large-sample randomized controlled clinical trials with long-term follow-up, to determine whether radix notoginseng lowers stroke recurrence and improves patient＇s quality of life.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
In the present study, the potential inhibition behaviors of notoginseng total saponins(NS), safflower total flavonoids(SF), and their combination(CNS) towards three major isoforms of UDP-glucuronosyltransferases(UGTs)...In the present study, the potential inhibition behaviors of notoginseng total saponins(NS), safflower total flavonoids(SF), and their combination(CNS) towards three major isoforms of UDP-glucuronosyltransferases(UGTs) in human liver microsomes(HLMs) were investigated to study the mechanism of the synergistic effect of CNS.Etoposide, trifluoperazine and azidothymidine were selected as the probe drugs to elucidate the activities of UGT1A1, 1A4 and 2B7 by UPLC-MS/MS method, respectively.The results showed that CNS, NS and SF significantly inhibited the activities of UGT1A1, 1A4 and 2B7(P<0.05) with the IC_(50) values less than 30 mg/mL.Furthermore, the inhibitory effects of CNS towards UGT1A1, 1A4 and 2B7 were stronger than those of NS and SF(P<0.05).In conclusion, the combination of NS and SF could increase their inhibitory effects on UGT1A1, 1A4 and 2B7 activities in HLMs and might be conducive to reduce the phase II metabolism of the effective constituents in CNS.The potential herb-drug interactions of CNS based on UGT enzymes provided a useful experimental basis for its further research and development.展开更多
Chronic alcohol consumption induces hepatic steatosis, the early stage of alcoholic liver disease （ALD）. The aim ofpresent study is to investigate the protective effect ofPanax notoginseng saponins （PNS） against c...Chronic alcohol consumption induces hepatic steatosis, the early stage of alcoholic liver disease （ALD）. The aim ofpresent study is to investigate the protective effect ofPanax notoginseng saponins （PNS） against chronic ethanol-induced hepaticsteatosis in vivo. Mice were pair-fed a modified Lieber-DeCarli liquid diet containing alcohol or isocaloric maltose dextrin ascontrol diet with or without PNS （200 mg/kg, BW） for 8 weeks. Animals supplemented with PNS were protected against hepaticlipid accumulation induced by chronic ethanol exposure. Accordingly, PNS could significantly decrease the elevation of plasmatriglyceride, plasma enzyme activities, i.e. alanine aminotransferase （ALT） and aspartate aminotransferase （AST）, and hepaticTNF-ct and IL-6 levels which were induced by chronic alcohol exposure. In addition, PNS markedly reduced the lipolysis ofwhite adipose tissue （WAT） that stimulated by alcohol feeding through the inhibiting protein expression of phosphorylation ofhormone-sensitive lipase （p-HSL）, rather than total HSL. Furthermore, alcohol exposure also enhanced fatty acid uptake capacityin liver by elevated hepatic CD36 expression, which could attenuated by PNS treatment. These results demonstrate that PNSsupplementation protects against chronic ethanol-induced hepatic steatosis, which is associated with ameliorating dysfunctionallipid metabolism of WAT and the reduced inflammatory cytokines. Our findings suggested that PNS might be potential to bedeveloped as an effective agent for the treatment of chronic alcoholic steatosis.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
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
Traditional extraction methods of total saponins of Panax notoginseng include cold soaking method,water decoction method,alcohol reflux method,percolation method,macroporous resin adsorption method,and accelerated sol...Traditional extraction methods of total saponins of Panax notoginseng include cold soaking method,water decoction method,alcohol reflux method,percolation method,macroporous resin adsorption method,and accelerated solvent extraction( ASE) method. Modern extraction methods include ultrasonic extraction,microwave assisted extraction,supercritical CO_2 extraction,microbial fermentation assisted extraction,neural network model optimized extraction method,and multi-stage countercurrent extraction method. This paper discussed principles of these methods and compared their advantages and disadvantages.展开更多
基金funded by the Entrusted service project of Shaanxi Administration of Traditional Chinese Medicine(ZYJXG-L23001)2023 Sanqin Talent Special Support Program Innovation and Entrepreneurship Team Project,and Sci-Tech Innovation Talent System Construction Program of Shaanxi University of Chinese Medicine(2023).
文摘Background:Panacis Quinquefolii Radix(PQR)is known for its ability to nourish“Qi”(it serves as the driving force for the functional activities of the body’s organs and meridians,promoting and regulating various physiological functions)and“Yin”(it represents the material foundation of the human body.It plays a role in nourishing,moistening,and cooling the body).Notoginseng Radix et Rhizoma(NRR)is recognized for its properties of resolving blood stasis(it refers to a pathological condition characterized by impaired or stagnant blood circulation within the body).Changes in the compatibility ratio of these herbs often lead to variations in their chemical composition and efficacy.However,the specific alterations in chemical composition and efficacy resulting from compatibility adjustments remain unclear.We aimed to compare the material basis and their effects of different compatibility ratios of PQR and NRR on“Qi”deficiency and blood stasis syndrome(QBS).Methods:This study employed UPLC-Q/TOF-MS to identify effective compounds in the compatibility of PQR and NRR and utilized UPLC-TQ-MS/MS to analyze the dissolution of 16 saponins in PQR and NRR at 9 different ratios.A rat model of QBS was established,and the efficacy of PQR and NRR in treating this syndrome was assessed using hemorheology and coagulation analyses.Results:The study results show that PQR and NRR exhibit significant efficacy,effectively reducing blood viscosity induced by platelet aggregation and lowering inflammatory markers such as IL-6,IL-10,TXB2 and ET associated with vascular injury.Moreover,this combination regulates ATP and ADP levels,enhances energy metabolism,and promotes overall health.A total of 104 compounds in the compatibility of PQR and NRR were identified.The ratios of 1:2 and 1:3 showed the highest total saponin content,but the ratio of 1:1 demonstrated a superior pharmacological effect for the treatment of QBS.Conclusion:In summary,the compatibility of PQR and NRR not only shows the complex interactions between traditional Chinese medicinal materials,but also provides a new idea and method for the treatment of QBS.
文摘Panax notoginseng saponins(PNS)is the primary active component of the traditional Chinese medicine P.notoginseng.This compound exhibits a range of pharmacological effects,including anti-inflammatory,antioxidant,and antiplatelet aggregation properties,as well as the enhancement of microcirculation.The extensive research on the modernization of traditional Chinese medicine has garnered significant attention regarding the application of PNS in the treatment of cardiovascular diseases.Research has demonstrated that PNS interventions significantly improve the pathological progression of cardiovascular disease through synergistic effects involving multiple targets and pathways.This paper summarizes the pharmacological mechanisms,clinical research advancements,safety,and potential adverse reactions associated with PNS in the treatment of cardiovascular diseases,in order to provide theoretical references for future research and practical applications in this field.
基金Scientific Research Fund of Education Department of Yunnan Province Project:Potential Targets and Molecular Mechanisms of Sanqi(Radix Notoginseng),an Active Component of Yunnan Baiyao,in the Treatment of Periodontitis(No.2022Y204)Special Project for The Selection of High-level Scientific and Technological Talents and Innovation Teams-technical Innovation Talents Training Object Project:Technical Innovation Personnel Training Object Project(202405AD350005)。
文摘OBJECTIVE:To investigate the effect and mechanism of Sanqi(Radix Notoginseng)in treating periodontitis.METHODS:The active components and periodontitis targets were analyzed through network pharmacology and molecular docking.A rat model of periodontitis was established and rats were treated by continuous intragastric administration of Sanqi(Radix Notoginseng)at different doses for 30 d.The alveolar bone structure was observed by micro-CT,the periodontal tissue structure was observed by hematoxylin-eosin staining,and the related proteins changes was detected by immunohistochemical staining.RESULTS:Sanqi(Radix Notoginseng)and periodontitis had a total of 96 coincident targets that were significantly enriched in the interleukin 17(IL-17),tumor necrosis factor(TNF),and advanced glycation endproducts and the receptor of advanced glycation endproducts signaling pathways.The active compound quercetin had good binding activity with interleukin 6(IL-6),vascular endothelial growth factor A(VEGFA),matrix metallopeptidase 9(MMP9),tumor necrosis factorα(TNF-α),Jun proto-oncogene(JUN),and C-X-C motif chemokine ligand 8(CXCL8)in periodontitis.Compared with normal group,the distance from the cementoenamel junction(CEJ)to the alveolar bone(AB)was increased,alveolar bone absorption was obvious,the periodontal tissue structure was disorganized,and IL-6 and TNF-αwere upregulated in periodontitis group;meanwhile,the distance from CEJ to AB was significantly decreased,alveolar bone resorption was reduced,periodontal tissue structure was improved,the expression of IL-6,TNF-α,IL-17 and retinoid-ralated orphan receptorγt(RORγt)were decreased,Forkhead Box P3(FOXP3)and IL-10 were increased after Sanqi(Radix Notoginseng)treatment.CONCLUSIONS:Sanqi(Radix Notoginseng)improves the structure of alveolar bone and gum,and reduces inflammation;the mechanism involve in inhibiting IL-17 signaling pathway to suppress Th17 and promote Treg cells differentiation.
基金supported by the National Key R&D Program of China(2022YFC3501805)the Science and Technology Program of Tianjin in China(23ZYJDSS00030)+2 种基金the National Natural Science Foundation of China(82374030)the Science&Technology Development Fund of Tianjin Education Commission for Higher Education(2021KJ127)Tianjin Outstanding Youth Fund(23JCJQJC00030).
文摘Panax notoginseng is a traditional Chinese medicine containing various constituents,including the saponins,polysaccharides,polyacetylenes,amino acids,etc.It has beneficial functions,such as the anti-inflammatory,antitumor,hepatoprotective,and anti-aging effects.Among these,P.notoginseng polysaccharides(PNPs)have been exploited because of their extensive pharmacological effects,being ranked as one of the current research hotspots,especially for the functional foods and medical practice.In this review,the literature related to PNPs in the past 20 years was surveyed and analyzed using both the China National Knowledge Infrastructure(CNKI)and Web of Science(WOS)databases.The visualization diagram shows that current studies on PNPs mainly focus on the antioxidant and immunomodulatory activities and structural characterization.In addition,the extraction,separation,purification,chemical analysis,structural characteristics,bioactivities,and applications of PNPs are outlined,in detail,aimed to provide valuable information for the further study,development,and utilization regarding PNPs.
基金supported by grant from the Project of the National Natural Science Foundation of China(Grant No.82060028)funded by the Yunnan Blood Disease Clinical Medical Center(Grant No.2023YJZX-XY05)+2 种基金the Yunnan Health Commission(L2019003)to TSthe Yunnan Provincial Key Laboratory of Clinical Virology(Grant No.202205AG070005)the Yunnan Provincial Key Laboratory of Innovative Application of Traditional Chinese Medicine.
文摘Thrombosis is a leading cause of mortality and morbidity in patients suffering from polycythemia vera(PV).Drug pair Salviae Miltiorrhizae Radix et Rhizoma(Danshen,DS)and Notoginseng Radix et Rhizoma(Sanqi,SQ)is common traditional Chinese medicine(TCM)used in clinical practice to promote blood circulation and eliminate blood stasis.In this study,network pharmacology and molecular docking were used to analyze the potentially active ingredients and underlying mechanisms of drug pair DS-SQ against thrombosis after PV.These results show that 54 targets are related to both disease and the drug pair.Nineteen core targets,including IL-6 and AKT1,were screened.Luteolin and tanshinone IIa from DS as well as quercetin from SQ might be the major substances in the treatment of thrombosis after PV.KEGG enrichment analysis demonstrated that the lipid and atherosclerosis signaling pathway might play a significant role.These results provide valuable insights and a reference for the use of drug pair DS-SQ in management of thrombosis after PV and lay a foundation for further exploration of pharmacological effects.
基金supported by the Educational Commission of Shanghai in China(No.2021LK114)the Organizational Key Research and Development Program of Shanghai University of Traditional Chinese Medicine(No.2023YZZ02)the Xinglin Young Talent Program at Shanghai University of Traditional Chinese Medicine(No.A1-U17205010430)。
文摘Stem-leaf saponins from Panax notoginseng(SLSP)comprise numerous PPD-type saponins with diverse pharmacological properties;however,their role in Parkinson's disease(PD),characterized by microglia-mediated neuroinflammation,remains unclear.This study evaluated the effects of SLSP on suppressing microglia-driven neuroinflammation in experimental PD models,including the 1-methyl-4-phenylpyridinium(MPTP)-induced mouse model and lipopolysaccharide(LPS)-stimulated BV-2 microglia.Our findings revealed that SLSP mitigated behavioral impairments and excessive microglial activation in models of PD,including MPTP-treated mice.Additionally,SLSP inhibited the upregulation of inducible nitric oxide synthase(i NOS)and cyclooxygenase-2(COX2)and attenuated the phosphorylation of PI3K,protein kinase B(AKT),nuclear factor-κB(NFκB),and inhibitor of NFκB proteinα(IκBα)both in vivo and in vitro.Moreover,SLSP suppressed the production of inflammatory markers such as interleukin(IL)-1β,IL-6,and tumor necrosis factor alpha(TNF-α)in LPS-stimulated BV-2cells.Notably,the P2Y2R agonist partially reversed the inhibitory effects of SLSP in LPStreated BV-2 cells.These results suggest that SLSP inhibit microglia-mediated neuroinflammation in experimental PD models,likely through the P2Y2R/PI3K/AKT/NFκB signaling pathway.These novel findings indicate that SLSP may offer therapeutic potential for PD by attenuating microglia-mediated neuroinflammation.
基金NationalBasicResearchProgramofChina (No .G19990 5 44 0 6)NationalNaturalScienceFoundationofChina(No .3 9970 898)
文摘To develop a HPIX-UV-MS method for identifying the constituents in theChinese drug Notoginseng (the root of Panax notoginseng). Methods A Phenomenex Luna C_(18) column(250 mm x 4.6 mm ID, 5 μm) was utilized. Water containing 0.005% formic acid (A) and acetonitrilecontaining 0.005% formic acid (B) were used as gradient eluents. UV spectra were recorded in range195 - 400 nm. Both positive and negative ion ESI modes were used. Results The constituents inNotoginseng were well separated and detected. Fourteen compounds were identified by comparing theirretention time and ESI-MS data with those obtained from the reference compounds. Forty-one compoundswere deduced by data analysis of MS and literature; among them, yesanchinosides-H and -E,chikusetsusaponin-L_5, malonyl-ginsenoside-R_(g_1), the isomers of notoginsenosides-J, -A, -R_1, -G,-R_2, and ginsenoside-Rh_3 were discovered in Notoginseng for the first time. Conclusion Thismethod gives high sensitivity and good separation, and is suitable for identifying the constituentsin Notoginseng. This result is helpful for further phytochemical research on Notoginseng. Based onthis result, further quality control can be studied.
文摘In the present study, we established an UPLC-QTOF-MSE based metabolomic approach in order to evaluate the holistic qualities and compare the quality difference by finding characteristic components of Panax notoginseng extracts （PNE） and Xuesaitong （XST） injection samples from different manufacturers. The data were processed through unsupervised principal component analysis （PCA） and supervised orthogonal partial least squared discrimination analysis （OPLS-DA） to compare the quality differences. Two-dimensional PCA score plots showed a tendency to separate the XST injections and extracts, and most XST injection samples were clearly clustered into two groups. Especially, the injections from He and YB companies were distinguished into two groups. In addition, only injection samples of Hu company were near the cluster of PNE. To explore the potential chemical components contributing most to the differences between XST injection samples from different manufacturers and PNE, an S-plot was constructed following the OPLS-DA. Ginsenoside Rd, ginsenoside Rgl, ginsenoside Re, ginsenoside Rbl, 20（S）-ginsenoside Rhl, gypenoside VII, ginsenoside Rg2, ginsenoside Rh4, ginsenoside Rkl or Rgs, notoginsenoside Fc, 20（R）-ginsenoside Rg3, ginsenoside F2 and protopanaxadiol were recognized as characteristic chemical markers that contributed most to reflect the difference between XST injections and PNE. Ginsenoside Rd, ginsenoside Rgl, ginsenoside Re, ginsenoside Rbl and gypenoside VII were revealed as index components contributing most to the differences of PNE and XST injections, and quantitative analysis of these components could ensure the consistent quality of XST injections. Based on the fact that the injections should be standardized with the characteristic components as quality control chemical markers, it is most important to keep the quality of extracts of raw materials stable and reliable.
基金Supported by Central Financial Forestry Science and Technology Extension Project of China([2016]XT001)Science and Technology Development Project of Hunan Province(S2014F209021)~~
文摘To overcome the issues of high cost and continuous cropping obstacles in facility cultivation of Panax notoginseng_ F. H. Chen, satisfy the market demand, save the production cost, improve the utilization rate of forest land, increase the in-come of forest farmers and protect the ecological environment, the cultivation tech-niques of high-quality P. notoginseng seedlings from Wenshan, Yunnan under four kinds of forests （walnut forest, China fir forest, grape forest and kiwi forest） were in-vestigated in this study. The results showed that the height growth, crown diameter, survival rate and 3-year-old tuber weight of P. notoginseng_under walnut forest were higher than those under the other three kinds of forests; the height growth, crown diameter, survival rate and 3-year-old tuber weight of P. notoginseng under China fir forest were higher than those under grape forest and kiwi forest; and the crown di-ameter and survival rate under grape forest were higher, and the height growth and tuber weight under grape forest were lower than those under kiwi forest. Walnut is a broad-leaved deciduous tree species, so large-scale cultivation of P. notoginseng_should be conducted under broadleaf deciduous forest with canopy density around 0.8, taking advantage of the cool environment and rich humus layer under forest. This cultivation technology could save labor, shade, fertilizer and other costs, and accord with the ecological habit and the growth rules of P. notoginseng, thus im-proving yield and achieving high economic benefit.
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.
基金supported by a grant from the Scientific Research Project during the Twelvth Five-Year Period of Jilin Provincial Educational Bureau in China,No.2013-441a grant from the Scientific Research Project of Jilin Provincial Health Bureau in China,No.2012Z102
文摘Acute ischemic stroke has become a major disease burden with high mortality and morbidity rates. There is a lack of evidence-based medicine confirming the efficacy of common treatments. Panax notoginseng saponins, the main active ingredient of radix notoginseng, have a neuro- protective role in ischemic brain injury, and have been popularized as a maintenance treatment for acute cerebral infarction and its sequelae. We conducted literature searches on the Web of Science, ClinicalTrials.gov, Cochrane Collaboration, CNKI, Wanfang and the China Scientific ＆ Technological Achievements Database and analyzed the experimental and clinical outcomes of studies investigating the use of radix notoginseng in the treatment of ischemic brain injury to improve the understanding of relevant research trends and existing problems. We found that over the past 10 years, China has maintained its interest in Panax notoginseng research, while such studies are scarce on the Web of Science. However, Chinese researchers often focus on the neuroprotective role of radix notoginseng in ischemic brain injury, but there are no large-scale clinical data to confirm its efficacy and safety. There remains a need for more rigorous large-sample randomized controlled clinical trials with long-term follow-up, to determine whether radix notoginseng lowers stroke recurrence and improves patient＇s quality of life.
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.
基金National Natural Science Foundation of China(Grant No.81573684)National Key Technology R&D Program "New Drug Innovation" of China(Grant No.2018ZX09711001-008-003)Beijing Municipal Science and Technology Project(Grant No.Z181100002218028)
文摘In the present study, the potential inhibition behaviors of notoginseng total saponins(NS), safflower total flavonoids(SF), and their combination(CNS) towards three major isoforms of UDP-glucuronosyltransferases(UGTs) in human liver microsomes(HLMs) were investigated to study the mechanism of the synergistic effect of CNS.Etoposide, trifluoperazine and azidothymidine were selected as the probe drugs to elucidate the activities of UGT1A1, 1A4 and 2B7 by UPLC-MS/MS method, respectively.The results showed that CNS, NS and SF significantly inhibited the activities of UGT1A1, 1A4 and 2B7(P<0.05) with the IC_(50) values less than 30 mg/mL.Furthermore, the inhibitory effects of CNS towards UGT1A1, 1A4 and 2B7 were stronger than those of NS and SF(P<0.05).In conclusion, the combination of NS and SF could increase their inhibitory effects on UGT1A1, 1A4 and 2B7 activities in HLMs and might be conducive to reduce the phase II metabolism of the effective constituents in CNS.The potential herb-drug interactions of CNS based on UGT enzymes provided a useful experimental basis for its further research and development.
基金Research Committee of the University of Macao(Grant No.MYRG123-ICMS12 and MYRG111-ICMS13)from Macao Science and Technology Development Fund(Grant No.010/2013/A1)
文摘Chronic alcohol consumption induces hepatic steatosis, the early stage of alcoholic liver disease （ALD）. The aim ofpresent study is to investigate the protective effect ofPanax notoginseng saponins （PNS） against chronic ethanol-induced hepaticsteatosis in vivo. Mice were pair-fed a modified Lieber-DeCarli liquid diet containing alcohol or isocaloric maltose dextrin ascontrol diet with or without PNS （200 mg/kg, BW） for 8 weeks. Animals supplemented with PNS were protected against hepaticlipid accumulation induced by chronic ethanol exposure. Accordingly, PNS could significantly decrease the elevation of plasmatriglyceride, plasma enzyme activities, i.e. alanine aminotransferase （ALT） and aspartate aminotransferase （AST）, and hepaticTNF-ct and IL-6 levels which were induced by chronic alcohol exposure. In addition, PNS markedly reduced the lipolysis ofwhite adipose tissue （WAT） that stimulated by alcohol feeding through the inhibiting protein expression of phosphorylation ofhormone-sensitive lipase （p-HSL）, rather than total HSL. Furthermore, alcohol exposure also enhanced fatty acid uptake capacityin liver by elevated hepatic CD36 expression, which could attenuated by PNS treatment. These results demonstrate that PNSsupplementation protects against chronic ethanol-induced hepatic steatosis, which is associated with ameliorating dysfunctionallipid metabolism of WAT and the reduced inflammatory cytokines. Our findings suggested that PNS might be potential to bedeveloped as an effective agent for the treatment of chronic alcoholic steatosis.
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.
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.
基金Supported by the 12 th Five-Year TCM Key Discipline Chinese Medicine Chemistry Construction Program of State Administration of Traditional Chinese Medicine(Guo Zhong Yi Yao Ren Jiao Fa[2012]32)Key Discipline Chinese Medicine Chemistry Construction Program of Guangxi(Gui Jiao Ke Yan[2013]16)+2 种基金Natural Science Foundation Project of Guangxi(2013GXNSFAA019240)Program of Key Laboratory of Guangxi Universities on National Medicine in Youjiang River Basin(Gui Jiao Ke Yan[2014]14)Innovation and Entrepreneurship Ethnical Medicine Teaching Team Program of Guangxi Zhuang Autonomous Region(Gui Jiao Gao Jiao[2015]93&Gui Jiao Gao Jiao[2016]6)
文摘Traditional extraction methods of total saponins of Panax notoginseng include cold soaking method,water decoction method,alcohol reflux method,percolation method,macroporous resin adsorption method,and accelerated solvent extraction( ASE) method. Modern extraction methods include ultrasonic extraction,microwave assisted extraction,supercritical CO_2 extraction,microbial fermentation assisted extraction,neural network model optimized extraction method,and multi-stage countercurrent extraction method. This paper discussed principles of these methods and compared their advantages and disadvantages.
