Baicalin(BA) is the most well-known flavonoid present in Radix Scutellariae. The aim of this study was to explore whether the pharmacokinetic behavior of BA in rat brain can be affected by Panax notoginsenosides(PNS),...Baicalin(BA) is the most well-known flavonoid present in Radix Scutellariae. The aim of this study was to explore whether the pharmacokinetic behavior of BA in rat brain can be affected by Panax notoginsenosides(PNS), and to assess the possible mechanism for the observed effects. Specific HPLC and HPLC/MS/MS methods were developed and validated for the determination of BA in the rat plasma and brain using carbamazepine as an internal standard. BA was found to enter rat brain quickly after a single intravenous dose. When co-administered with PNS, clearance(CL) of BA from rat plasma decreased by 50.00%, while the area under the curve AUC0-t and AUC0-∞ increased 94.69% and 87.68%, respectively. On the other hand, some pharmacokinetic parameters of BA in rat brain had obvious differences after PNS was administered, such as an increase in Tmax from 5 min to 15 min, an increase in AUC0-t and AUC0-∞ by 42.75% and 29.39%, respectively, as well as a decrease in CL by 27.95%. Together, these results indicate that PNS can decrease the elimination rate of BA from rat plasma, promote the penetration of BA into rat brain, increase the concentration and slow down the elimination of BA from rat brain. The data provide important information that compatibility with PNS can promote the consequent effects of BA for the treatment of encephalopathy.展开更多
Liquid chromatography hybrid ion trap/time-of-flight mass spectrometry possesses both the MS^n ability of ion trap and the excellent resolution of a time-of-flight and has been widely used to identify drug metabolites...Liquid chromatography hybrid ion trap/time-of-flight mass spectrometry possesses both the MS^n ability of ion trap and the excellent resolution of a time-of-flight and has been widely used to identify drug metabolites and determine trace multi-components in natural products. Collision energy, one of the most important factors in acquiring MS^n information, could be set freely in the range of 10%–400%. Herein, notoginsenosides were chosen as model compounds to build a novel methodology for the collision energy optimization. Firstly, the fragmental patterns of the representatives for the authentic standards of protopanaxadiol-type and protopanaxatriol-type notoginsenosides were obtained based on accurate MS^2 and MS^3 measurements via liquid chromatography hybrid ion trap/time-of-flight mass spectrometry. The extracted ion chromatograms of characteristic product ions of notoginsenosides in Panax Notoginseng Extract were produced under a series of collision energies and compared to screen the optimum collision energies values for MS^2 and MS^3. The results demonstrated that the qualitative capability of liquid chromatography hybrid ion trap/time-of-flight mass spectrometry was greatly influenced by collision energies, and 50% of MS^2 collision energy was found to produce the highest collision-induced dissociation efficiency for notoginsenosides. Addtionally, the highest collision-induced dissociation efficiency appeared when the collision energy was set at 75% in the MS^3 stage.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
Aim An industrial enzyme β-glucanase was used to transfortn notoginsenoside Fe for the first time. Methods Notoginsenoside Fe was isolated from the leave saponin of Panax notoginseng （Burk.） Chen FH. The enzymatica...Aim An industrial enzyme β-glucanase was used to transfortn notoginsenoside Fe for the first time. Methods Notoginsenoside Fe was isolated from the leave saponin of Panax notoginseng （Burk.） Chen FH. The enzymatically transformed compounds were detected by HPLC and two transformed compounds were identified as 20 （S） -protopanaxadiol-20- O- α-L-arabinofuranosyl （ 1→6 ） - β-gluco- pyranoside, ginsenoside-Mc） and 20（S）-protopanaxadiol-20-O-β-D-glucopyranoside compound-K （C-K） respectively on the basis of their ^1H NMR and ^13 C NMR spectral data. Results Based on the enzymolytic kinetic curve, the transformation rate of notoginsenoside Fe reached 95% after 24 h. Conclusion The enzymatic transformation pathway of notoginsenoside Fe by β-glucanase has been proposed as notoginsenoside Fe→ginsenoside Mc→C-K.展开更多
A method coupling ultra-performance liquid chromatography(UPLC) with quadrupole time-of-flight mass spectrometer(Qtof MS) using the electrospray ionization(ESI) source was developed for the identification of the major...A method coupling ultra-performance liquid chromatography(UPLC) with quadrupole time-of-flight mass spectrometer(Qtof MS) using the electrospray ionization(ESI) source was developed for the identification of the major saponins from Panax notoginseng powder(PNP). Ten different PNP samples were analyzed and evaluated for their quality by similarity evaluation and principle component analysis(PCA). Based on the accurate mass, summarized characteristic fragmentation behaviors, retention times of different types of saponins, related botanical biogenesis, and reported chromatographic behavior of saponins, fifty-one common peaks were effectively separated and identified, including 28 protopanaxadiol saponins and 18 protopanaxatriol saponins. Simultaneously, 15 significant discrepancy compounds were identified from the disqualified PNP samples. The established UPLC/Qtof MS fingerprint method was successfully applied for profiling and identifying the major saponins of PNP, providing a fast quality evaluation tool for distinguishing the authentic PNP and the adulterated products.展开更多
AIM： To assess the effect of notoginsenoside R1 on hepatic microcirculatory disturbance induced by gut ischemia/reperfusion （I/R） in mice. METHODS： The superior mesenteric artery （SMA） of C57/BL mice was ligated...AIM： To assess the effect of notoginsenoside R1 on hepatic microcirculatory disturbance induced by gut ischemia/reperfusion （I/R） in mice. METHODS： The superior mesenteric artery （SMA） of C57/BL mice was ligated for 15 min to induce gut ischemia followed by 30-rain reperfusion. In another set of experiments, R1 was continuously infused （10 mg/kg per hour） from 10 min before I/R until the end of the investigation to study the influence of R1 on hepatic microcirculatory disturbance induced by gut I/R. Hepatic microcirculation was observed by inverted microscopy, and the vascular diameter, red blood cell （RBC） velocity and sinusoid perfusion were estimated. Leukocyte rolling and adhesion were observed under a laser confocal microscope. Thirty and 60 min after reperfusion, lactate dehydrogenase （LDH）, alanine aminotransferase （ALl＇） and aspartate transaminase （AST） in peripheral blood were determined. The expression of adhesion molecules CD11b/CD18 in neutrophils and tumor necrosis factor- alpha （TNF-α）, interleukin-6 （IL-6） and monocyte chemotactic protein-1 （MCP-1） in plasma were evaluated by flow Oltometry. E-selectin and intercellular adhesion molecule-1 （ICAM-1） in hepatic tissue were examined by immunofluorescence.RESULTS： After gut I/R, the diameters of terminal portal venules and central veins, RBC velocity and the number of perfused sinusoids were decreased, while the leukocyte rolling and adhesion, the expression of E-selectin in hepatic vessels and CD18 in neutrophils, IL-6, MCP-1, LDH, ALT and AST were increased. R1 treatment attenuated these alterations except for IL-6 and MCP-1. CONCLUSION： R1 prevents I/R-induced hepatic microcirculation disturbance and hepatocyte injury, The effect of R1 is related to its inhibition of leukocyte rolling and adhesion by inhibiting the expression of E-selectin in endothelium and CD18 in neutrophils.展开更多
Notoginsenoside R-111, a novel hexanordammarane glycoside was isolated from the roots of Panax nototginseng, as a minor constituent. Its structure was determined as 6-O-(beta -D-glucopyranosyl)-3 beta ,6 alpha ,12 bet...Notoginsenoside R-111, a novel hexanordammarane glycoside was isolated from the roots of Panax nototginseng, as a minor constituent. Its structure was determined as 6-O-(beta -D-glucopyranosyl)-3 beta ,6 alpha ,12 beta -trihydroxy-22,23,24,25,26,27-hexanordammaran-20-one(1), by means of spectroscopic methods.展开更多
The demand for non-toxic and biodegradable shale inhibitors is growing in the drilling industry.In this paper,the effect of notoginsenoside(NS)as a new,environmentally friendly inhibitor of shale hydration is systemat...The demand for non-toxic and biodegradable shale inhibitors is growing in the drilling industry.In this paper,the effect of notoginsenoside(NS)as a new,environmentally friendly inhibitor of shale hydration is systematically studied for the first time.The inhibition performance of NS was evaluated via inhibition evaluation tests,including mud ball immersion tests,linear expansion tests,shale rolling recovery tests,and compressive strength tests.The inhibition mechanism of NS was analyzed using Fourier transform infrared spectroscopy(FTIR),contact angle measurements,particle size distribution determination,thermogravimetric analysis(TGA),and scanning electron microscopy(SEM).The experimental results demonstrate that NS is able to adhere to the clay surface,forming a hydrophobic film that prevents the entry of water molecules and inhibiting the hydration dispersion of the clay.Because of this,NS can maintain the original state of bentonite pellets in water,which can effectively reduce the swelling rate of bentonite,increase the recovery rate of shale drill cuttings,maintain the strength of the shale,and therefore maintain the stability of the borehole wall during drilling.In addition,NS is non-toxic,degradable,and compatible with water-based drilling fluids.The above advantages make NS a promising candidate for use as an environmentally friendly shale inhibitor.展开更多
Two new dammarane glycosides named notoginsenoside T-1 and T-2 were isolated from the mild acid hydrolysis products of the root saponins of Panax notoginseng. On the basis of spectroscopic evidences, their structures ...Two new dammarane glycosides named notoginsenoside T-1 and T-2 were isolated from the mild acid hydrolysis products of the root saponins of Panax notoginseng. On the basis of spectroscopic evidences, their structures were elucidated to be 6-O-beta -D-glucopyranosyl-24(25)-epoxy-3 beta ,6 alpha ,12 beta ,23 xi -tetrahydroxydammar-20(22)(E)-ene 1 and 6-O-beta -D-glucopyranosyl-24(25)-epoxy-23 xi -methoxyl-3 beta ,6 alpha ,12 beta -trihydroxydamm-ar-20(22)(E)-ene 2, respectively.展开更多
Four new dammarane-type triterpenoid saponins,namely notoginsenosides SFt1-SFt4(1-4)were isolated from the steamed leaves of Panax notoginseng(Burk.)F.H.Chen(Araliaceae),together with 17 known saponins.Their structure...Four new dammarane-type triterpenoid saponins,namely notoginsenosides SFt1-SFt4(1-4)were isolated from the steamed leaves of Panax notoginseng(Burk.)F.H.Chen(Araliaceae),together with 17 known saponins.Their structures were established on the basis of detailed spectroscopic analyses and acidic hydrolysis.The known ginsenosides Rk2 and Rh3 were obtained from P.notoginseng for the first time.All of these new saponins showed no in vitro cytotoxicity against five human cancer cell lines(HL-60,SMMC-7712,A-549,MCF-7,and SW480).展开更多
The management of colorectal cancer(CRC)poses a significant challenge,necessitating the development of innovative and effective therapeutics.Our research has shown that notoginsenoside Ft1(Ng-Ft1),a small molecule,mar...The management of colorectal cancer(CRC)poses a significant challenge,necessitating the development of innovative and effective therapeutics.Our research has shown that notoginsenoside Ft1(Ng-Ft1),a small molecule,markedly inhibits subcutaneous tumor formation in CRC and enhances the proportion of CD8^(+)T cells in tumor-bearing mice,thus restraining tumor growth.Investigation into the mechanism revealed that Ng-Ft1 selectively targets the deubiquitination enzyme USP9X,undermining its role in shieldingβ-catenin.This leads to a reduction in the expression of downstream effectors in the Wnt signaling pathway.These findings indicate that Ng-Ft1 could be a promising small-molecule treatment for CRC,working by blocking tumor progression via the Wnt signaling pathway and augmenting CD8^(+)T cell prevalence within the tumor environment.展开更多
Objective To explore the preventive effects and possible mechanisms of action of notoginsenoside(NGS)and tanshinone IIA(TSN)in inflammation-related colorectal cancer(IRCC)in mice.Methods Eighty-eight male C57BL/6 mice...Objective To explore the preventive effects and possible mechanisms of action of notoginsenoside(NGS)and tanshinone IIA(TSN)in inflammation-related colorectal cancer(IRCC)in mice.Methods Eighty-eight male C57BL/6 mice were randomly assigned to 11 groups(n=8 each group).Azomethane oxide+dextran sulfate(AOM+DSS)model control(model),NGS lowdose(l-NGS),NGS medium-dose(m-NGS),NGS high-dose(h-NGS),TSN low-dose(l-TSN),TSN medium-dose(m-TSN),TSN high-dose(h-TSN),(NGS+TSN)low-dose[l-(NGS+TSN)],(NGS+TSN)medium-dose[m-(NGS+TSN)],(NGS+TSN)high-dose[h-(NGS+TSN)],and blank groups were established.The first 10 groups were intraperitoneally injected with AOM to induce inflammatory colon cancer,whereas the blank group was intraperitoneally injected with 0.9%NaCl solution.The first 10 groups drank a 2.5%sodium DSS aqueous solution continuously from day 5 for three cycles(one cycle:five days,every three weeks),and the blank group was allowed free access to water.Drug groups were administered NGS(low,medium,or high dose),TSN(low,medium,or high dose),or NGS+TSN(low,medium,or high dose),and the model and blank groups were administered saline by lavage until the end of the experiment.The general activity,body weight,and survival rate of and incidence of adenocarcinoma in mice were detected and the expression of cyclooxygenase 2(COX-2)was detected by immunohistochemistry.Results(1)The survival rate of mice with IRCC in the h-NGS,m-TSN,h-TSN,m-(NGS+TSN),and h-(NGS+TSN)groups was significantly increased than that in other groups(P<0.05).(2)The incidence of tumors in the h-(NGS+TSN),m-TSN,and l-NGS groups was significantly lower than that in the model group(P<0.05).(3)The expression level of COX-2 in tumor tissues of mice in the m-(NGS+TSN)and h-(NGS+TSN)groups was significantly lower than that in the model group(P<0.05).Conclusion Tumor formation was inhibited by m-TSN and h-(NGS+TSN)treatments in mice with IRCC,and h-(NGS+TSN)treatment inhibited the COX-2 pathway.展开更多
Objective:To obtain a formulation with high bioavailability through evaluation of the stability of three types of Xuesaitong capsules in the stomachs and intestines of rats.We compared the stability of the Panax notog...Objective:To obtain a formulation with high bioavailability through evaluation of the stability of three types of Xuesaitong capsules in the stomachs and intestines of rats.We compared the stability of the Panax notoginsenoside R1 as well as the ginsenosides Rg1,Rb1,Re,and Rd in different formulations.Methods:Artificial stomach fluid(ASF)and artificial intestinal fluid(AIF)were prepared.Stability of three types of Xuesaitong capsules was examined for 4 h in stomachs and 24 h in intestines.Samples were analyzed at different times by high-performance liquid chromatography.Percent content of NGR1,GRg1,GRb1,GRe,and GRd at different times was calculated.Results:Hard capsules incubated in ASF disintegrated within 2e3 min,whereas soft capsules disintegrated within 7e8 min.Components in hard capsules were dissolved rapidly in water,with content of each compound reaching 90%in 5 min,and degradation of each compound reaching 30e50%after incubation for 240 min.Dissolution and degradation of each component in soft capsules with a water-soluble base tended to balance at 30 e90 min.Contents in soft capsules with a lipid-soluble base showed slow dissolution after ASF incubation for 120 min.Five saponins in identical types of capsules incubated in ASF had similar stability curves.Contents of hard capsules and soft capsules with a watersoluble base degraded rapidly within 30 min and reached a plateau when Xuesaitong capsules were incubated in AIF.展开更多
[Objectives] To study the effects and mechanism of notoginsenoside Rg1 on the spatial learning and memory and phosphorylated tau protein in the AD( Alzheimer's Disease) model rat. [Methods]The AD model rat was rep...[Objectives] To study the effects and mechanism of notoginsenoside Rg1 on the spatial learning and memory and phosphorylated tau protein in the AD( Alzheimer's Disease) model rat. [Methods]The AD model rat was replicated by injection of Aβ_(25-35) in the left lateral ventricles of SD rats. The low dose( 25 mg/kg),middle dose( 50 mg/kg) and high dose( 100 mg/kg) notoginsenoside Rg1 was used for intragastric administration,respectively,two times every day. After 4 weeks,the Morris water maze test was done to detect the learning and memory capacity,and the immunoblotting,immunohistochemical methods were used to detect the changes in the phosphorylation level and distribution of tau protein in hippocampus of the rats. [Results] After the intracerebroventricular injection of Aβ_(25-35),the learning and memory capacity of the model rats was significantly lower than the learning and memory capacity of the normal control rats. The immunoblotting test results showed that the phosphorylation level of tau protein threonine 231 site( Thr231) in hippocampus was significantly increased,and the nonphosphorylation level was significantly decreased. The morphological testing results showed that the phosphorylation level of tau protein Thr231 of AD model rats was increased markedly in region of DG,CA1 and CA3 of the hippocampus. The intervention of the middle dose notoginsenoside Rg1 could significantly improve the learning and memory capacity of the model rats in Morris water maze. The notoginsenoside Rg1 in three different doses could all reduce the phosphorylation level of tau protein Thr231 in the hippocampal DG,CA1,CA3 regions,and there were no significant differences among the three doses. [Conclusions]The notoginsenoside Rg1 could improve Aβ_(25-35)-induced spatial learning and memory impairment of the AD model rats,and decreased the phosphorylation level of tau protein in hippocampus.展开更多
Two new triterpenoid saponins, named ginsenoside Rh10（1） and notoginsenoside ST-6（2）, were isolated from notoginseng medicinal fungal substance. Their structures were elucidated by a combination of 1D and 2D NMR, ...Two new triterpenoid saponins, named ginsenoside Rh10（1） and notoginsenoside ST-6（2）, were isolated from notoginseng medicinal fungal substance. Their structures were elucidated by a combination of 1D and 2D NMR, MS and chemical analysis.展开更多
Pulmonary arterial hypertension (PAH) is a serious disease which is characterized by increased vascular resistance and pressure. We have previously hypothesized that panax notoginseng saponins (PNS) might attenuate pu...Pulmonary arterial hypertension (PAH) is a serious disease which is characterized by increased vascular resistance and pressure. We have previously hypothesized that panax notoginseng saponins (PNS) might attenuate pulmonary vasoconstriction under hypoxia and hypercapnia condition. This study aims to investigate the effect of notoginsenoside R<sub>g1</sub>, a main ingredient of PNS, with various concentrations (8, 40, 100 mg/L, respectively) on extracellular signal regulated kinase (ERK1/2) signaling pathway in pulmonary arterial smooth muscle cells (PASMCs). In addition, PASMCs were randomly divided into six groups: SD rat under normoxic condition as control group (N group), hypoxia hypercapnia group (H group), DMSO control group (HD group), R<sub>g1</sub>-treatment groups (R<sub>gL</sub>R<sub>gM</sub> and R<sub>gH</sub> group). Western-blot and RT-PCR were used to test the expression of p-ERK protein and the expression of ERK1 mRNA and ERK2 mRNA. This study provided the evidence that the expression of p-ERK protein and the expression of ERK1 mRNA and ERK2 mRNA in HD group and H group were obviously higher than that in N group (P < 0.01), Whereas the level of ERK1/2 mRNA in R<sub>g1</sub>-treatment groups was significantly lower than that in HD group and H group (P < 0.01), and the proper concentration of R<sub>g1</sub> is 40 mg/L. These results suggested that notoginsenoside R<sub>g1</sub> can attenuate pulmonary vasoconstriction which may lead to HHPV through reducing the expression of ERK1/2.展开更多
[Objectives]To optimize the water extraction process of Chinese Herbal Compound Man Gan Ning and establish a method for its extraction and content determination.[Methods]The L9(34)orthogonal test was carried out,the c...[Objectives]To optimize the water extraction process of Chinese Herbal Compound Man Gan Ning and establish a method for its extraction and content determination.[Methods]The L9(34)orthogonal test was carried out,the comprehensive scores of ginsenoside Rb1 content,notoginsenoside R1 content,tanshinone I content and saikosaponin A content in the compound extract were used as evaluation indicators to explore the effects of water addition,the water addition,decoction time and decoction times on the water extraction process,and verification tests were carried out.[Results]The optimized water extraction process was as follows:adding 9 times of water in the first extraction,and extracting for 90 min;adding 7 times of water in the second extraction,and extracting for 60 min;adding 7 times of water in the third extraction,and extracting for 60 min.[Conclusions]The optimized water extraction process is stable and feasible,and can be used for the extraction of various herbs in Compound Man Gan Ning.It can also provide experimental basis for the formulation development of Compound Man Gan Ning sustained release tablet.展开更多
Notoginsenoside R1, the main active ingredient of Panax notoginseng saponins (PNS), has been proposed to play fatal roles in the development of hypoxic hypercapnia-induced pulmonary vasoconstriction (HHPV). Subsequent...Notoginsenoside R1, the main active ingredient of Panax notoginseng saponins (PNS), has been proposed to play fatal roles in the development of hypoxic hypercapnia-induced pulmonary vasoconstriction (HHPV). Subsequently, pulmonary arterial smooth muscle cells (PASMCs) lead to pulmonary vascular system remodeling and chronic pulmonary disease in the development of HHPV. Despite considerable studies have contributed to pulmonary disease, the mechanism of how Notoginsenoside R1 affects HHPV remains unclear. In this view, we will discuss the effect of notoginsenoside R1 by investigating the expression of p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway in PASMCs under hypoxia and hypercapnia condition. The third order PASMCs of Sprague Dawley (SD) rats were cultured with various concentrations (8, 40, 100 mg/L, respectively) of Notoginsenoside R1. Our data showed that the protein and mRNA expression levels of p-38 MAPK were higher in hypoxic hypercapnia group compared with hypoxic DMSO and normoxia control groups (p 1 treatment groups, the level of p-p38 MAPK protein and p38 MAPK mRNA were significantly decreased with different degrees (p 1 treatment may contribute to attenuate HHPV via decreasing the protein and mRNA expression levels of p-38 MAPK.展开更多
基金supported by the National Natural Science Foundation of China(No.81274118)the Key New Drug Creation and Development Program of China(No.2012 ZX09103-201)the National Key Technology R&D Program(No.2012BAI29B08)
文摘Baicalin(BA) is the most well-known flavonoid present in Radix Scutellariae. The aim of this study was to explore whether the pharmacokinetic behavior of BA in rat brain can be affected by Panax notoginsenosides(PNS), and to assess the possible mechanism for the observed effects. Specific HPLC and HPLC/MS/MS methods were developed and validated for the determination of BA in the rat plasma and brain using carbamazepine as an internal standard. BA was found to enter rat brain quickly after a single intravenous dose. When co-administered with PNS, clearance(CL) of BA from rat plasma decreased by 50.00%, while the area under the curve AUC0-t and AUC0-∞ increased 94.69% and 87.68%, respectively. On the other hand, some pharmacokinetic parameters of BA in rat brain had obvious differences after PNS was administered, such as an increase in Tmax from 5 min to 15 min, an increase in AUC0-t and AUC0-∞ by 42.75% and 29.39%, respectively, as well as a decrease in CL by 27.95%. Together, these results indicate that PNS can decrease the elimination rate of BA from rat plasma, promote the penetration of BA into rat brain, increase the concentration and slow down the elimination of BA from rat brain. The data provide important information that compatibility with PNS can promote the consequent effects of BA for the treatment of encephalopathy.
基金supported by the National Nature Science Foundation of China(Nos.81273589,81374054)the Nature Science Foundation of Jiangsu Province(BK20131311)+2 种基金the fundamental research special fund of China Pharmaceutical University(PT2014 YK0081)Jiangsu Provincial Promotion Foundation for the Key Laboratory of Drug Metabolism and Pharmacokinetics(BM2012012)Jiangsu Key Laboratory of Drug Design and Optimization
文摘Liquid chromatography hybrid ion trap/time-of-flight mass spectrometry possesses both the MS^n ability of ion trap and the excellent resolution of a time-of-flight and has been widely used to identify drug metabolites and determine trace multi-components in natural products. Collision energy, one of the most important factors in acquiring MS^n information, could be set freely in the range of 10%–400%. Herein, notoginsenosides were chosen as model compounds to build a novel methodology for the collision energy optimization. Firstly, the fragmental patterns of the representatives for the authentic standards of protopanaxadiol-type and protopanaxatriol-type notoginsenosides were obtained based on accurate MS^2 and MS^3 measurements via liquid chromatography hybrid ion trap/time-of-flight mass spectrometry. The extracted ion chromatograms of characteristic product ions of notoginsenosides in Panax Notoginseng Extract were produced under a series of collision energies and compared to screen the optimum collision energies values for MS^2 and MS^3. The results demonstrated that the qualitative capability of liquid chromatography hybrid ion trap/time-of-flight mass spectrometry was greatly influenced by collision energies, and 50% of MS^2 collision energy was found to produce the highest collision-induced dissociation efficiency for notoginsenosides. Addtionally, the highest collision-induced dissociation efficiency appeared when the collision energy was set at 75% in the MS^3 stage.
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Aim An industrial enzyme β-glucanase was used to transfortn notoginsenoside Fe for the first time. Methods Notoginsenoside Fe was isolated from the leave saponin of Panax notoginseng （Burk.） Chen FH. The enzymatically transformed compounds were detected by HPLC and two transformed compounds were identified as 20 （S） -protopanaxadiol-20- O- α-L-arabinofuranosyl （ 1→6 ） - β-gluco- pyranoside, ginsenoside-Mc） and 20（S）-protopanaxadiol-20-O-β-D-glucopyranoside compound-K （C-K） respectively on the basis of their ^1H NMR and ^13 C NMR spectral data. Results Based on the enzymolytic kinetic curve, the transformation rate of notoginsenoside Fe reached 95% after 24 h. Conclusion The enzymatic transformation pathway of notoginsenoside Fe by β-glucanase has been proposed as notoginsenoside Fe→ginsenoside Mc→C-K.
基金supported by Science and Technology Program of Tianjin(No.12TXGCCX03800)
文摘A method coupling ultra-performance liquid chromatography(UPLC) with quadrupole time-of-flight mass spectrometer(Qtof MS) using the electrospray ionization(ESI) source was developed for the identification of the major saponins from Panax notoginseng powder(PNP). Ten different PNP samples were analyzed and evaluated for their quality by similarity evaluation and principle component analysis(PCA). Based on the accurate mass, summarized characteristic fragmentation behaviors, retention times of different types of saponins, related botanical biogenesis, and reported chromatographic behavior of saponins, fifty-one common peaks were effectively separated and identified, including 28 protopanaxadiol saponins and 18 protopanaxatriol saponins. Simultaneously, 15 significant discrepancy compounds were identified from the disqualified PNP samples. The established UPLC/Qtof MS fingerprint method was successfully applied for profiling and identifying the major saponins of PNP, providing a fast quality evaluation tool for distinguishing the authentic PNP and the adulterated products.
基金Supported by Tianjin Tasly Group, Tianjin, China
文摘AIM： To assess the effect of notoginsenoside R1 on hepatic microcirculatory disturbance induced by gut ischemia/reperfusion （I/R） in mice. METHODS： The superior mesenteric artery （SMA） of C57/BL mice was ligated for 15 min to induce gut ischemia followed by 30-rain reperfusion. In another set of experiments, R1 was continuously infused （10 mg/kg per hour） from 10 min before I/R until the end of the investigation to study the influence of R1 on hepatic microcirculatory disturbance induced by gut I/R. Hepatic microcirculation was observed by inverted microscopy, and the vascular diameter, red blood cell （RBC） velocity and sinusoid perfusion were estimated. Leukocyte rolling and adhesion were observed under a laser confocal microscope. Thirty and 60 min after reperfusion, lactate dehydrogenase （LDH）, alanine aminotransferase （ALl＇） and aspartate transaminase （AST） in peripheral blood were determined. The expression of adhesion molecules CD11b/CD18 in neutrophils and tumor necrosis factor- alpha （TNF-α）, interleukin-6 （IL-6） and monocyte chemotactic protein-1 （MCP-1） in plasma were evaluated by flow Oltometry. E-selectin and intercellular adhesion molecule-1 （ICAM-1） in hepatic tissue were examined by immunofluorescence.RESULTS： After gut I/R, the diameters of terminal portal venules and central veins, RBC velocity and the number of perfused sinusoids were decreased, while the leukocyte rolling and adhesion, the expression of E-selectin in hepatic vessels and CD18 in neutrophils, IL-6, MCP-1, LDH, ALT and AST were increased. R1 treatment attenuated these alterations except for IL-6 and MCP-1. CONCLUSION： R1 prevents I/R-induced hepatic microcirculation disturbance and hepatocyte injury, The effect of R1 is related to its inhibition of leukocyte rolling and adhesion by inhibiting the expression of E-selectin in endothelium and CD18 in neutrophils.
文摘Notoginsenoside R-111, a novel hexanordammarane glycoside was isolated from the roots of Panax nototginseng, as a minor constituent. Its structure was determined as 6-O-(beta -D-glucopyranosyl)-3 beta ,6 alpha ,12 beta -trihydroxy-22,23,24,25,26,27-hexanordammaran-20-one(1), by means of spectroscopic methods.
基金financially supported by the National Natural Science Foundation of China(Grants 51904328)the Natural Science Foundation of China(Grants 52074330)
文摘The demand for non-toxic and biodegradable shale inhibitors is growing in the drilling industry.In this paper,the effect of notoginsenoside(NS)as a new,environmentally friendly inhibitor of shale hydration is systematically studied for the first time.The inhibition performance of NS was evaluated via inhibition evaluation tests,including mud ball immersion tests,linear expansion tests,shale rolling recovery tests,and compressive strength tests.The inhibition mechanism of NS was analyzed using Fourier transform infrared spectroscopy(FTIR),contact angle measurements,particle size distribution determination,thermogravimetric analysis(TGA),and scanning electron microscopy(SEM).The experimental results demonstrate that NS is able to adhere to the clay surface,forming a hydrophobic film that prevents the entry of water molecules and inhibiting the hydration dispersion of the clay.Because of this,NS can maintain the original state of bentonite pellets in water,which can effectively reduce the swelling rate of bentonite,increase the recovery rate of shale drill cuttings,maintain the strength of the shale,and therefore maintain the stability of the borehole wall during drilling.In addition,NS is non-toxic,degradable,and compatible with water-based drilling fluids.The above advantages make NS a promising candidate for use as an environmentally friendly shale inhibitor.
基金the members of analytic group of Laboratory of Phytochemistry, Kunming Institute of Botany, Chinese Academy of Sciences.
文摘Two new dammarane glycosides named notoginsenoside T-1 and T-2 were isolated from the mild acid hydrolysis products of the root saponins of Panax notoginseng. On the basis of spectroscopic evidences, their structures were elucidated to be 6-O-beta -D-glucopyranosyl-24(25)-epoxy-3 beta ,6 alpha ,12 beta ,23 xi -tetrahydroxydammar-20(22)(E)-ene 1 and 6-O-beta -D-glucopyranosyl-24(25)-epoxy-23 xi -methoxyl-3 beta ,6 alpha ,12 beta -trihydroxydamm-ar-20(22)(E)-ene 2, respectively.
基金This work was supported by the 973 Program of Ministry of Science and Technology of China(2011CB915503).
文摘Four new dammarane-type triterpenoid saponins,namely notoginsenosides SFt1-SFt4(1-4)were isolated from the steamed leaves of Panax notoginseng(Burk.)F.H.Chen(Araliaceae),together with 17 known saponins.Their structures were established on the basis of detailed spectroscopic analyses and acidic hydrolysis.The known ginsenosides Rk2 and Rh3 were obtained from P.notoginseng for the first time.All of these new saponins showed no in vitro cytotoxicity against five human cancer cell lines(HL-60,SMMC-7712,A-549,MCF-7,and SW480).
基金supported by Shanghai Pujiang Program(No.20PJ1413000)the National Natural Science Foundation of China(No.82173106,82130115,81290108033,82004004,and 82074011)。
文摘The management of colorectal cancer(CRC)poses a significant challenge,necessitating the development of innovative and effective therapeutics.Our research has shown that notoginsenoside Ft1(Ng-Ft1),a small molecule,markedly inhibits subcutaneous tumor formation in CRC and enhances the proportion of CD8^(+)T cells in tumor-bearing mice,thus restraining tumor growth.Investigation into the mechanism revealed that Ng-Ft1 selectively targets the deubiquitination enzyme USP9X,undermining its role in shieldingβ-catenin.This leads to a reduction in the expression of downstream effectors in the Wnt signaling pathway.These findings indicate that Ng-Ft1 could be a promising small-molecule treatment for CRC,working by blocking tumor progression via the Wnt signaling pathway and augmenting CD8^(+)T cell prevalence within the tumor environment.
基金We thank for the funding support from the University Research Funding Project of the Hunan Provincial Department of Education(No.15C1406).
文摘Objective To explore the preventive effects and possible mechanisms of action of notoginsenoside(NGS)and tanshinone IIA(TSN)in inflammation-related colorectal cancer(IRCC)in mice.Methods Eighty-eight male C57BL/6 mice were randomly assigned to 11 groups(n=8 each group).Azomethane oxide+dextran sulfate(AOM+DSS)model control(model),NGS lowdose(l-NGS),NGS medium-dose(m-NGS),NGS high-dose(h-NGS),TSN low-dose(l-TSN),TSN medium-dose(m-TSN),TSN high-dose(h-TSN),(NGS+TSN)low-dose[l-(NGS+TSN)],(NGS+TSN)medium-dose[m-(NGS+TSN)],(NGS+TSN)high-dose[h-(NGS+TSN)],and blank groups were established.The first 10 groups were intraperitoneally injected with AOM to induce inflammatory colon cancer,whereas the blank group was intraperitoneally injected with 0.9%NaCl solution.The first 10 groups drank a 2.5%sodium DSS aqueous solution continuously from day 5 for three cycles(one cycle:five days,every three weeks),and the blank group was allowed free access to water.Drug groups were administered NGS(low,medium,or high dose),TSN(low,medium,or high dose),or NGS+TSN(low,medium,or high dose),and the model and blank groups were administered saline by lavage until the end of the experiment.The general activity,body weight,and survival rate of and incidence of adenocarcinoma in mice were detected and the expression of cyclooxygenase 2(COX-2)was detected by immunohistochemistry.Results(1)The survival rate of mice with IRCC in the h-NGS,m-TSN,h-TSN,m-(NGS+TSN),and h-(NGS+TSN)groups was significantly increased than that in other groups(P<0.05).(2)The incidence of tumors in the h-(NGS+TSN),m-TSN,and l-NGS groups was significantly lower than that in the model group(P<0.05).(3)The expression level of COX-2 in tumor tissues of mice in the m-(NGS+TSN)and h-(NGS+TSN)groups was significantly lower than that in the model group(P<0.05).Conclusion Tumor formation was inhibited by m-TSN and h-(NGS+TSN)treatments in mice with IRCC,and h-(NGS+TSN)treatment inhibited the COX-2 pathway.
文摘Objective:To obtain a formulation with high bioavailability through evaluation of the stability of three types of Xuesaitong capsules in the stomachs and intestines of rats.We compared the stability of the Panax notoginsenoside R1 as well as the ginsenosides Rg1,Rb1,Re,and Rd in different formulations.Methods:Artificial stomach fluid(ASF)and artificial intestinal fluid(AIF)were prepared.Stability of three types of Xuesaitong capsules was examined for 4 h in stomachs and 24 h in intestines.Samples were analyzed at different times by high-performance liquid chromatography.Percent content of NGR1,GRg1,GRb1,GRe,and GRd at different times was calculated.Results:Hard capsules incubated in ASF disintegrated within 2e3 min,whereas soft capsules disintegrated within 7e8 min.Components in hard capsules were dissolved rapidly in water,with content of each compound reaching 90%in 5 min,and degradation of each compound reaching 30e50%after incubation for 240 min.Dissolution and degradation of each component in soft capsules with a water-soluble base tended to balance at 30 e90 min.Contents in soft capsules with a lipid-soluble base showed slow dissolution after ASF incubation for 120 min.Five saponins in identical types of capsules incubated in ASF had similar stability curves.Contents of hard capsules and soft capsules with a watersoluble base degraded rapidly within 30 min and reached a plateau when Xuesaitong capsules were incubated in AIF.
基金Supported by National Natural Science Foundation of China(81673856,81573865)China Postdoctoral Science Foundation(2016M592319,2017T100542)+1 种基金Youth Project of Hubei University of Traditional Chinese Medicine(Zhong Yi Xiao Zi2015182)PhD Research Foundation of Hubei University of Traditional Chinese Medicine(Zhong Yi Dang Zi201425)
文摘[Objectives] To study the effects and mechanism of notoginsenoside Rg1 on the spatial learning and memory and phosphorylated tau protein in the AD( Alzheimer's Disease) model rat. [Methods]The AD model rat was replicated by injection of Aβ_(25-35) in the left lateral ventricles of SD rats. The low dose( 25 mg/kg),middle dose( 50 mg/kg) and high dose( 100 mg/kg) notoginsenoside Rg1 was used for intragastric administration,respectively,two times every day. After 4 weeks,the Morris water maze test was done to detect the learning and memory capacity,and the immunoblotting,immunohistochemical methods were used to detect the changes in the phosphorylation level and distribution of tau protein in hippocampus of the rats. [Results] After the intracerebroventricular injection of Aβ_(25-35),the learning and memory capacity of the model rats was significantly lower than the learning and memory capacity of the normal control rats. The immunoblotting test results showed that the phosphorylation level of tau protein threonine 231 site( Thr231) in hippocampus was significantly increased,and the nonphosphorylation level was significantly decreased. The morphological testing results showed that the phosphorylation level of tau protein Thr231 of AD model rats was increased markedly in region of DG,CA1 and CA3 of the hippocampus. The intervention of the middle dose notoginsenoside Rg1 could significantly improve the learning and memory capacity of the model rats in Morris water maze. The notoginsenoside Rg1 in three different doses could all reduce the phosphorylation level of tau protein Thr231 in the hippocampal DG,CA1,CA3 regions,and there were no significant differences among the three doses. [Conclusions]The notoginsenoside Rg1 could improve Aβ_(25-35)-induced spatial learning and memory impairment of the AD model rats,and decreased the phosphorylation level of tau protein in hippocampus.
基金supported by National Science and Technology Supporting Plan of China (No. 2012BAI29B05)
文摘Two new triterpenoid saponins, named ginsenoside Rh10（1） and notoginsenoside ST-6（2）, were isolated from notoginseng medicinal fungal substance. Their structures were elucidated by a combination of 1D and 2D NMR, MS and chemical analysis.
文摘Pulmonary arterial hypertension (PAH) is a serious disease which is characterized by increased vascular resistance and pressure. We have previously hypothesized that panax notoginseng saponins (PNS) might attenuate pulmonary vasoconstriction under hypoxia and hypercapnia condition. This study aims to investigate the effect of notoginsenoside R<sub>g1</sub>, a main ingredient of PNS, with various concentrations (8, 40, 100 mg/L, respectively) on extracellular signal regulated kinase (ERK1/2) signaling pathway in pulmonary arterial smooth muscle cells (PASMCs). In addition, PASMCs were randomly divided into six groups: SD rat under normoxic condition as control group (N group), hypoxia hypercapnia group (H group), DMSO control group (HD group), R<sub>g1</sub>-treatment groups (R<sub>gL</sub>R<sub>gM</sub> and R<sub>gH</sub> group). Western-blot and RT-PCR were used to test the expression of p-ERK protein and the expression of ERK1 mRNA and ERK2 mRNA. This study provided the evidence that the expression of p-ERK protein and the expression of ERK1 mRNA and ERK2 mRNA in HD group and H group were obviously higher than that in N group (P < 0.01), Whereas the level of ERK1/2 mRNA in R<sub>g1</sub>-treatment groups was significantly lower than that in HD group and H group (P < 0.01), and the proper concentration of R<sub>g1</sub> is 40 mg/L. These results suggested that notoginsenoside R<sub>g1</sub> can attenuate pulmonary vasoconstriction which may lead to HHPV through reducing the expression of ERK1/2.
基金Supported by Project of National Natural Science Foundation of China(81360524)Project for Improving Basic Research Ability of Middle Aged and Young Teachers in Colleges and Universities of Guangxi in 2019(2019KY0341)+2 种基金National Traditional Chinese Medicine Characteristic Technology Heritage Talent Training Program(20184828005)Youth Foundation Project of Guangxi University of Chinese Medicine(2019QN036)Program of Scientific Research Third-level Laboratory"Chinese(Zhuang)Medicine Chemical and Quality Analysis Laboratory"of State Administration of Traditional Chinese Medicine(Guo Zhong Yi Yao Fa 2009[21]).
文摘[Objectives]To optimize the water extraction process of Chinese Herbal Compound Man Gan Ning and establish a method for its extraction and content determination.[Methods]The L9(34)orthogonal test was carried out,the comprehensive scores of ginsenoside Rb1 content,notoginsenoside R1 content,tanshinone I content and saikosaponin A content in the compound extract were used as evaluation indicators to explore the effects of water addition,the water addition,decoction time and decoction times on the water extraction process,and verification tests were carried out.[Results]The optimized water extraction process was as follows:adding 9 times of water in the first extraction,and extracting for 90 min;adding 7 times of water in the second extraction,and extracting for 60 min;adding 7 times of water in the third extraction,and extracting for 60 min.[Conclusions]The optimized water extraction process is stable and feasible,and can be used for the extraction of various herbs in Compound Man Gan Ning.It can also provide experimental basis for the formulation development of Compound Man Gan Ning sustained release tablet.
文摘Notoginsenoside R1, the main active ingredient of Panax notoginseng saponins (PNS), has been proposed to play fatal roles in the development of hypoxic hypercapnia-induced pulmonary vasoconstriction (HHPV). Subsequently, pulmonary arterial smooth muscle cells (PASMCs) lead to pulmonary vascular system remodeling and chronic pulmonary disease in the development of HHPV. Despite considerable studies have contributed to pulmonary disease, the mechanism of how Notoginsenoside R1 affects HHPV remains unclear. In this view, we will discuss the effect of notoginsenoside R1 by investigating the expression of p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway in PASMCs under hypoxia and hypercapnia condition. The third order PASMCs of Sprague Dawley (SD) rats were cultured with various concentrations (8, 40, 100 mg/L, respectively) of Notoginsenoside R1. Our data showed that the protein and mRNA expression levels of p-38 MAPK were higher in hypoxic hypercapnia group compared with hypoxic DMSO and normoxia control groups (p 1 treatment groups, the level of p-p38 MAPK protein and p38 MAPK mRNA were significantly decreased with different degrees (p 1 treatment may contribute to attenuate HHPV via decreasing the protein and mRNA expression levels of p-38 MAPK.
