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Objective To evaluate the safety of the low glucoside composites of Epimedii Folium and clarify the pharmacokinetic characteristics of its five low glucosides.Methods Four groups of KM mice were orally administrated of corn oil,1 968,2 625 and 3 500 mg·kg-1 low glucoside composites of Epimedii Folium,respectively.Then,the living conditions,toxic symptoms,and death of the mice were observed for 7 consecutive days.After the mice were dissected,the viscera/body ratio and the viscera/brain ratio were calculated.Besides,the contents of alanine aminotransferase(ALT)and aspartate transaminase(AST)in plasma were determined by ELISA,and the pathological changes of the liver were observed by HE staining.C57BL/6J mice were intravenously or orally administered of baohuoside I,baohuoside II,sagittatoside A,sagittatoside B and sagittatoside C.Then,blood samples were collected at different time points.The plasma concentrations of the five low glucosides were measured by UHPLC-MS/MS.Results When compared with the control group,no significant differences were found in the body mass,viscera/body ratio,viscera/brain ratio,contents of ALT and AST in plasma after oral administration of different doses of low glucoside composites to mice.Moreover,no pathological changes or damages were found in the liver sections.After intravenous injection,the AUC0-t values of baohuoside Ⅰ,baohuoside Ⅱ,sagittatoside A,sagittatoside B and sagittatoside C in mice were 4.82,82.54,276.64,88.77 and 178.02 min·μg·mL-1,respectively.Meanwhile,the t1/2 values were 60.42,115.27,67.63,131.61 and 129.87 min,respectively.After oral administration,the AUC0-t values of the five low glucosides were 31.64,18.59,3.48,2.41 and 2.42 min·μg·mL-1,respectively.The Cmax values were 147.23,86.76,15.58,24.34 and 26.12 ng·mL-1,respectively.The tmax values were 21.00,78.00,78.00,30.00 and 28.00 min,respectively.The bioavailability of baohuosideⅠ,baohuosideⅡ,sagittatoside A sagittatoside B and sagittatoside C were 1.91%,0.51%,0.05%,0.06%and 0.04%,respectively.Conclusion The low glucoside composites of Epimedii Folium has high safety,and no hepatotoxicity were observed at dose of 3 500 mg·kg-1.The 5 low glucosides are quickly absorbed and rapidly eliminated in mice,and all of them have low bioavailability.
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The obstruction of post-insulin receptor signaling is the main mechanism of insulin-resistant diabetes. Progestin and adipoQ receptor 3 (PAQR3), a key regulator of inflammation and metabolism, can negatively regulate the PI3K/AKT signaling pathway. Here, we report that gentiopicroside (GPS), the main bioactive secoiridoid glycoside of Gentiana manshurica Kitagawa, decreased lipid synthesis and increased glucose utilization in palmitic acid (PA) treated HepG2 cells. Additionally, GPS improved glycolipid metabolism in streptozotocin (STZ) treated high-fat diet (HFD)-induced diabetic mice. Our findings revealed that GPS promoted the activation of the PI3K/AKT axis by facilitating DNA-binding protein 2 (DDB2)-mediated PAQR3 ubiquitinated degradation. Moreover, results of surface plasmon resonance (SPR), microscale thermophoresis (MST) and thermal shift assay (TSA) indicated that GPS directly binds to PAQR3. Results of molecular docking and cellular thermal shift assay (CETSA) revealed that GPS directly bound to the amino acids of the PAQR3 NH2-terminus including Leu40, Asp42, Glu69, Tyr125 and Ser129, and spatially inhibited the interaction between PAQR3 and the PI3K catalytic subunit (P110α) to restore the PI3K/AKT signaling pathway. In summary, our study identified GPS, which inhibits PAQR3 expression and directly targets PAQR3 to restore insulin signaling pathway, as a potential drug candidate for the treatment of diabetes.
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Acidosis, regardless of hypoxia involvement, is recognized as a chronic and harsh tumor microenvironment (TME) that educates malignant cells to thrive and metastasize. Although overwhelming evidence supports an acidic environment as a driver or ubiquitous hallmark of cancer progression, the unrevealed core mechanisms underlying the direct effect of acidification on tumorigenesis have hindered the discovery of novel therapeutic targets and clinical therapy. Here, chemical-induced and transgenic mouse models for colon, liver and lung cancer were established, respectively. miR-7 and TGF-β2 expressions were examined in clinical tissues (n = 184). RNA-seq, miRNA-seq, proteomics, biosynthesis analyses and functional studies were performed to validate the mechanisms involved in the acidic TME-induced lung cancer metastasis. Our data show that lung cancer is sensitive to the increased acidification of TME, and acidic TME-induced lung cancer metastasis via inhibition of miR-7-5p. TGF-β2 is a direct target of miR-7-5p. The reduced expression of miR-7-5p subsequently increases the expression of TGF-β2 which enhances the metastatic potential of the lung cancer. Indeed, overexpression of miR-7-5p reduces the acidic pH-enhanced lung cancer metastasis. Furthermore, the human lung tumor samples also show a reduced miR-7-5p expression but an elevated level of activated TGF-β2; the expressions of both miR-7-5p and TGF-β2 are correlated with patients' survival. We are the first to identify the role of the miR-7/TGF-β2 axis in acidic pH-enhanced lung cancer metastasis. Our study not only delineates how acidification directly affects tumorigenesis, but also suggests miR-7 is a novel reliable biomarker for acidic TME and a novel therapeutic target for non-small cell lung cancer (NSCLC) treatment. Our study opens an avenue to explore the pH-sensitive subcellular components as novel therapeutic targets for cancer treatment.
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Inhibitor of nuclear factor kappa-B kinase subunit beta (IKKβ) is one of important kinases in inflammation to phosphorylate inhibitor of nuclear factor kappa-B (IκBα) and then activate nuclear factor kappa-B (NF-κB). Inhibition of IKKβ has been a therapeutic strategy for inflammatory and autoimmune diseases. Here we report that IKKβ is constitutively activated in healthy donors and healthy Ikkβ C46A (cysteine 46 mutated to alanine) knock-in mice although they possess intensive IKKβ-IκBα-NF-κB signaling activation. These indicate that IKKβ activation probably plays homeostatic role instead of causing inflammation. Compared to Ikkβ WT littermates, lipopolysaccharides (LPS) could induce high mortality rate in Ikkβ C46A mice which is correlated to breaking the homeostasis by intensively activating p-IκBα-NF-κB signaling and inhibiting phosphorylation of 5' adenosine monophosphate-activated protein kinase (p-AMPK) expression. We then demonstrated that IKKβ kinase domain (KD) phosphorylates AMPKα1 via interacting with residues Thr183, Ser184, and Thr388, while IKKβ helix-loop-helix motifs is essential to phosphorylate IκBα according to the previous reports. Kinase assay further demonstrated that IKKβ simultaneously catalyzes phosphorylation of AMPK and IκBα to mediate homeostasis. Accordingly, activation of AMPK rather than inhibition of IKKβ could substantially rescue LPS-induced mortality in Ikkβ C46A mice by rebuilding the homeostasis. We conclude that IKKβ activates AMPK to restrict inflammation and IKKβ mediates homeostatic function in inflammation via competitively phosphorylating AMPK and IκBα.
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The COVID-19 pandemic and the SARS-CoV-2 with its variants have posed unprecedented challenges worldwide. Existing vaccines have limited effectiveness against the SARS-CoV-2 variants. Therefore, novel vaccines to match current mutated viral lineages with long-term protective immunity are urgently in demand. In the current study, we for the first time designed a recombinant Adeno-Associated Virus 5 (rAAV5)-based vaccine named as rAAV-COVID-19 vaccine (Covacinplus) by using RBD-plus of spike protein with both the single-stranded and the self-complementary AAV5 delivering vectors (ssAAV5 and scAAAV5), which provides excellent protection from SARS-CoV-2 infection. A single dose vaccination induced the strong immune response against SARS-CoV-2. The induced neutralizing antibodies (NAs) titers were maintained at a high peak level of over 1:1024 even after more than one year of injection and accompanied with functional T-cells responses in mice. Importantly, both ssAAV- and scAAV-based RBD-plus vaccines exhibited high levels of serum NAs against current circulating variants including variants Alpha, Beta, Gamma and Delta. SARS-CoV-2 virus challenge test showed that ssAAV5-RBD-plus vaccine protected both young and old age mice from SARS-CoV-2 infection in the upper and the lower respiratory tracts. Moreover, whole genome sequencing demonstrated that AAV vector DNA sequences were not found in the genome of the vaccinated mice after one year vaccination, demonstrating excellent safety of the vaccine. Taken together, this study suggests that rAAV5-based vaccine is powerful against SARS-CoV-2 and its variants with long-term protective immunity and excellent safety, which has great potential for development into prophylactic vaccination in human to end this global pandemic.
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Based on the requirements of first-class undergraduate talents training in pharmacy in the new era, this paper summarizes and analyzes the law, current situation and actual situation of pharmaceutical talents training in TCM colleges and universities in China, and discusses the reform and practice of first-class pharmaceutical talents training in terms of talent training mode reform, teaching staff construction, curriculum system optimization, teaching mode innovation, quality assurance system construction and innovation and entrepreneurship education in combination with the construction experience of national first-class undergraduate specialty construction point in the pharmacy of Guangzhou University of Chinese Medicine, so as to further improve the quality of personnel training and provide a reference for excellent pharmaceutical personnel training.
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Traditional Chinese medicine (TCM) formulas have attracted increasing attention worldwide in the past few years for treating complex disease including rheumatoid arthritis. However, their mechanisms are complex and remain unclear. Guan-Jie-Kang (GJK), a prescription modified from "Wu Tou Decoction," was found to significantly relieve arthritis symptoms in rats with adjuvant-induced arthritis after 30-day treatment, especially in the 24 g/kg/day group. By analyzing 1749 targets related to 358 compounds in the five herbs of GJK, we identified the possible anti-arthritis pathways of GJK, including the calcium signaling and metabolic pathways. Bone damage levels were assessed by micro-computed tomography, and greater bone protective effect was observed with GJK treatment than with methotrexate. Receptor activator of nuclear factor κB ligand (RANKL)-RANK signaling, which is related to calcium signaling, was significantly regulated by GJK. Moreover, a target metabolomics assay of serum was conducted; 17 metabolic biomarkers showed significant correlations with treatment. An integrated pathway analysis revealed that pyruvate metabolism, purine metabolism, and glycolysis metabolism were significantly associated with the effects of GJK in arthritis treatment. Thus, this study establishes a new omics analytical method integrated with bioinformatics analysis for elucidating the multi-pathway mechanisms of TCM.
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Objective To investigate the short-term clinical effect of CT guided 125Ⅰ radioactive particle therapy in superficial malignant tumor. Methods The clinic data of 28 patients with metastatic superficial malignant tumor in our hospital were analyzed retrospectively.All patients were treated with CT guided 125Ⅰ radioactive particle therapy.The short-term effects,1 year survival rate and 1 year progression free survival rate of the patients were compared.Results Objective remission rate(ORR)and disease control rate(DCR)after 6 months were 92.86% and 100.00%.1 year overall survival and 1 year progression free survival were 96.43%(27/28)and 82.14%(23/28), respectively.The median overall survival and median progression free survival were 26.978 months (95%CI:22.558-31.399)and 16.932 months (95 % CI:14 .471-19.393).There were 27 cases of 0-Ⅱ degree adverse reactions,1 case of grade Ⅲ adverse reactions and no grade Ⅳ adverse reactions.No signs of 125Ⅰ radioactive particle translocation,vascular embolism and vascular rupture were found. Conclusion 125Ⅰ radioactive particle treatment of superficial malignant tumor has a definite short-term curative effect,with overall survival and progression free survival longer and higher safety,which can be considered in clinical application.
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Objective:To study the clinical effect and safety of ubenimex capsules and SOX chemotherapy on the advanced gastric cancer.Methods:90 patients with advanced gastric cancer who were treated in our hospital from September 2013 to September 2015 were selected and randomly divided into the observation group (n=45) and the control group (n=45).The patients in the control group were treated with SOX chemotherapy,while the patients in the observation group were treated with ubenimex capsules on the basis of control group.Then the serum levels of MMP-2 and MMP-9,the immune functions,the clinical efficacy,the adverse reactions and survival rate of two groups were observed and compared before and after the treatment.Results:After treatment,the CD4+,CD4+/CD8+ in the observation group were higher than those of the control group (P<0.05);The levels of MMP2 and MMP-9 in the observation group were lower than those of the control group (P<0.05);The total effective rate of the observation group was higher than that of the control group [68.89%(31/45) vs 48.89%(22/45)] (P<0.05);The incidence of thrombocytopenia,leukopenia,nausea and vomiting and abnormal liver functions in the observation group was lower than that of the control group (P<0.05);The survival rate of the observation group was higher than that of the control group at 6 months and 12 months [93.33% (42/45) vs 77.78% (35/45),82.22% (37/45) vs 57.78% (26/45)](P<0.05).Conclusion:Compared with SOX chemotherapy alone,ubenimex capsules and SOX chemotherapy could effectively improve the immune function,enhance the long-term survival rate with high safety of patients with advanced gastric cancer.
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<p><b>OBJECTIVE</b>To prepare pravastatin sodium-loaded chitosan microspheres to allow sustained drug release.</p><p><b>METHODS</b>The drug-loaded chitosan microspheres were prepared by using genipin as the cross-linker. The influences of molecular weight of chitosan, volume ratio of oil and water, reaction temperature, and stirring speed on the formation of chitosan microspheres were investigated. The morphology of the microspheres was observed using scanning electron microscopy. The encapsulation efficiency, swelling ratio under different pH conditions, and in vitro drug release were measured.</p><p><b>RESULTS</b>The in vitro release of pravastatin sodium could last for at least 31 days. The drug release rate varied with the reaction condition. The drug entrapment efficiency of the microsphere was 54.7%. The optimal processing conditions were as follows: chitosan viscosity of 200-400 mPa·s, oil-water proportion of 10:1, stirring speed of 850 r/min, and reaction temperature at 40 degrees celsius;.</p><p><b>CONCLUSION</b>The pravastatin sodium-loaded microspheres show good sustained drug release property, and the drug release rate can be modified by controlling the cross-linking time.</p>
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Quitosano , Reactivos de Enlaces Cruzados , Preparaciones de Acción Retardada , Iridoides , Microscopía Electrónica de Rastreo , Microesferas , Pravastatina , QuímicaRESUMEN
Borneol is a traditional Chinese medicine that can promote drug absorption from the gastrointestinal tract and distribution to the brain. However, stomach irritation may occur when high doses of borneol are used. In the present work, gastrodin, the main bioactive ingredient of the traditional Chinese drug "Tianma" (Rhizoma Gastrodiae) was used as a model drug to explore reasonable application of borneol. Sustained-release solid dispersions (SRSDs) for co-loading gastrodin and borneol were prepared using ethylcellulose as a sustained release matrix and hydroxy-propyl methylcellulose as a retarder. The dispersion state of drug within the SRSDs was analyzed by using scanning electron microscopy, differential scanning calorimetry, and powder X-ray diffractometry. The results indicated that both gastrodin and borneol were molecularly dispersed in an amorphous form. Assay of in vitro drug release demonstrated that the dissolution profiles of gastrodin and borneol from the SRSDs both fitted the Higuchi model. Subsequently, gastric mucosa irritation and the brain targeting of the SRSDs were evaluated. Compared with the free mixture of gastrodin and borneol, brain targeting of SRSDs was slightly weaker (brain targeting index: 1.83 vs. 2.09), but stomach irritation obviously reduced. Sustained-release technology can be used to reduce stomach irritation caused by borneol while preserving sufficient transport capacity for oral brain-targeting drug delivery.
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<p><b>OBJECTIVE</b>Dehydroandrographolide (DP) from Andrographis paniculata (Burm. F.) Nees is a potential anticancer agent. This study aimed to investigate the oral bioavailability and intestinal disposition of DP to provide useful information for the development of DP as a new candidate anticancer drug.</p><p><b>METHODS</b>The pharmacokinetics of DP was evaluated in rats, and its intestinal disposition was determined using cultured Caco-2 cells and a single-pass rat intestinal perfusion model.</p><p><b>RESULTS</b>The oral bioavailability of DP was 11.92% in rats. The apparent permeability coefficient (P(app)) of DP from the basolateral side (B) to the apical side (A) (5.37×10(-5) cm/s) of the Caco-2 model was roughly equal to that from A to B (4.56×10(-5) cm/s), suggesting no involvement of the efflux transporter(s). In the perfusion model, no significant difference was found in the effective permeability (P*(eff)) of DP between the 4 segments of the intestine. No significant metabolism of DP was detected in the intestinal perfusates. The amount of DP found in the bile was only about 0.1% of the absorbed amount. The P*(eff) and bile amounts of DP were not significantly increased by P-glycoprotein (P-gp) inhibitor or breast cancer resistant protein (BCRP) inhibitor (P>0.05).</p><p><b>CONCLUSION</b>The bioavailability of DP was 11.92% in rats. DP has good absorption and metabolism stability in the intestine. The efflux transporters such as P-gp and BCRP do not participate in DP transport.</p>
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Animales , Humanos , Masculino , Ratas , Administración Oral , Disponibilidad Biológica , Transporte Biológico , Células CACO-2 , Diterpenos , Farmacocinética , Absorción Intestinal , Intestinos , Metabolismo , Ratas Sprague-DawleyRESUMEN
The primary objective was to develope a UPLC method for determine the concentration of buspirone hydroxychloride in plasma and to evaluate the effects of Aconiti Laterlis Radix and Aconiti Laterlis Radix compatibility of Glycyrrhizae Radix on CYP3A4 in vivo. ACQUITY UPLC BEH C18 column (2.1 mm x 10 mm, 1.7 microm) was used for the gradient elution with a 2.0 mmol x L(-1) ammonium acetate (pH 7.4, A)-acetonitrile (B) solution, 0-2.2 min, 10% - 60% B, 2.2-2.5 min, 60% B, 2.5-3.0 min, 60%-75% B, 3.0-3.5 min, 75% B, 3.5-4.0 min, 75%-10% B, at the flow rate of 0.3 mL x min(-1) at room temperature. The UV wavelenght was detected at 243 nm. The linear calibration curve ranged between 0.078 125-20.0 microg (r = 0.9975). The average recovery (n = 6) of buspirone hydroxychloride was 85.62% (RSD 6.8%). The results showed that this method has good specificity and repeatability, and which can be used for the determination of buspirone hydrochlorid in serum. In animial studies, single dose Aconiti Laterlis Radix extract treatment (0.5 g x kg(-1)) decreased buspirone hydroxychloride AUC(0-2 h) (52.8%, P = 0.020), increased CL/F (122%, P = 0.045). Compared to the saline treatment group, Aconiti Laterlis Radix compatibility of Glycyrrhizae Radix extract treatment has no effect on CYP3A4 in rat. The results indicated that Aconiti Laterlis Radix extract induced CYP3A4 while Aconiti Laterlis Radix compatibility of Glycyrrhizae Radix extract had no effect on CYP3A4 in vivo. Aconiti Laterlis Radix had been detoxified when be used as compatibility of Glycyrrhizae Radix.
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Animales , Masculino , Ratas , Aconitum , Química , Cromatografía Líquida de Alta Presión , Métodos , Citocromo P-450 CYP3A , Sistema Enzimático del Citocromo P-450 , Genética , Metabolismo , Medicamentos Herbarios Chinos , Expresión Génica , Glycyrrhiza , Química , Interacciones de Hierba-Droga , Ratas Sprague-DawleyRESUMEN
<p><b>OBJECTIVE</b>To investigate the intestinal absorption characteristics of gastrodigenin.</p><p><b>METHOD</b>In vitro everted gut sac model and in situ rat single-pass intestinal perfusion model were used to evaluate the absorption characteristics of gastrodigenin in the different intestinal segments. The concentrations of gastrodigenin in the samples were determined by Ultra Performance Liquid Chromatography (UPLC) method, and the relevant absorption parameters were calculated.</p><p><b>RESULT</b>In the everted gut sac tests, no significant difference of absorption among the four segments was observed. A positive correlation was found between drug concentration and the accumulated absorption amount (Q). At the concentration of 400 mg x L(-1), the Q of gastrodigenin in the duodenum, jejunum, ileum and colon were 224.33, 225.81, 233.18 and 189.25 microg, respectively. The in situ rat single-pass intestinal perfusion tests showed that there was also no significant difference of absorption among the four segments. The absorption rates (A) of gastrodigenin in the duodenum, jejunum, ileum and colon were 45.8%, 48.39%, 47.00%, 54.35%, respectively.</p><p><b>CONCLUSION</b>Gastrodigenin can be well absorbed via passive diffusion in the intestine. The absorption rates of gastrodigenin in the different intestinal segments show no regioselectivity.</p>
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Animales , Masculino , Ratas , Alcoholes Bencílicos , Farmacocinética , Cromatografía Liquida , Métodos , Absorción Intestinal , Intestinos , Metabolismo , Medicina Tradicional China , Modelos Biológicos , Perfusión , Métodos , Ratas Sprague-DawleyRESUMEN
Objective To establish an HPLC method for determination of gastrodigenin concentration in brain tissue of mice and investigate its pharmacokinetics after intragastric administration of gastrodin.Methods The brain homogenate was extracted with acetoacetate and analyzed by HPLC method.The separation was performed on a Diamonsil C18 column(250 mm ? 4.6 mm,5 ?m) under the following chromatographic conditions: mobile phase,acetonitrile-water(10.5∶89.5);column temperature,25 ℃;flow rate,1.0 mL/min;detection wavelength,221 nm;and sampling amount,20 ?L.Results The calibration curve showed good linearity within the concentration range of 50-1 616 ng/mL(r= 0.999 6).The relative recoveries were 93.8%-95.1%,and the RSDs of the intra-and inter-day precision were less than 10%.The concentration-time profile of gastrodigenin in brain tissue of mice showed double peaks(tmax1=15 min,tmax2=90 min).The AUC was 52 822.5 ng?min/g,and t1/2(ke) was 54.8 min.Conclusion The analytical method established for assay of gastrodigenin in brain tissue of mice is sensitive and accurate.The result indicates that gastrodin could rapidly distribute to the brain,be metabolized into gastrodigenin,and be eliminated after oral administration.
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Objective: To study the technological parameters of the enrichment purification process of Baohe Pills with macroporous resin. Methods: With the enriched degree of hesperidin of Pericarpium Citri Reticulatae of Baohe Pills as a marker, the optimum technological parameters of the enrichment process were studied. Results: The optimum process is that 5mL of the extract of BaoHe Pills (500mg/mL) was adsorbed for 30min with a column of macroporous resin (R15mm?H100mm) and the resin was washed with 100mL of distilled water, then the hesperidin was eluted from the macroporous resin with 100mL of 50% ethanol. Conclusion: The elutive rate of hesperidin was above 95% by means of the macroporous resin. So this process enriching the active components of Baohe Pills is feasible.
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Objective: To study the technological parameters of the purification process of ginsenosides with macroreticular resin. Methods: The adsorptive characteristics and elutive parameters of the process were studied by taking the elutive and purified ratio of ginsenosides as marker. Results: 45ml of the extractive of ginseng (5.88mg/ml) was purified with a column of macroreticular resin (R15mm?H90mm, dried weight 2.52g) and washed with 100ml of distilled water, then eluted with 100ml of 50% ethanol. Conclusion: With macroreticular resin to adsorb and purify, the elutive ratio of ginsenosides was above 90% and the purity reached 60.1%. So this process of applying macroreticular resin to adsorb and purify ginsenosides is feasible.
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OBJECTIVE:To study the absorptive characteristics of ginsenoside Rb3 in Caco-2 cell monolayer model. METHO-DS:The ginsenoside Rb3 cell samples underwent high speed centrifugation, then the supernatant was collected and determined by LC-ESI-MS/MS method in which the mobile phase consisted of acetonitrile-1 mmol?L-1 ammonium formate water solution (34 ∶ 66) with ginsenoside Rg2 as internal standard, and the tandem mass spectrometry was operated in negative electrospray ionization in a multiple reaction monitoring (MRM) mode, with detection ions m/z1077.7→m/z 783.4 for ginsenoside Rb3 and m/z 783.6→m/z 475.1 for ginsenoside Rg2.The concentration of ginsenoside Rb3 across the Caco-2 cell monolayer model was determined and the apparent permeability coefficient(Papp) of ginsenoside Rb3 was calculated. RESULTS: The calibration curve for ginsenoside Rb3 was linear in the range of 50~2 000 ng?mL-1,with intra-day precision and inter-day precision at less than 15%. P(AP-BL) from apical side (AP) to basolateral side (BL) was 3.22?10-6 cm?s-1, whereas P(BL-AP) from BL to AP was 6.0?10-6 cm?s-1,and the ratio of P(BL-AP)/P(AP-BL) was 1.86.CONCLUSION:The LC-ESI/MS/MS method is simple and sensitive, and it is applicable for the study of the absorptive characteristics of ginsenoside Rb3 in Caco-2 cell monolayer model.