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Acute cerebral infarction is a severe type of ischemic stroke that can be divided into anterior circulation cerebral infarction and posterior circulation cerebral infarction (PCCI). PCCI affects the structure of the posterior circulation brain, because posterior part of the brain, which has more complex anatomical structures and more prone to posterior circulation vascular variation. Therefore, improving the prognosis of PCCI patients is necessary.To explore the effect of medical care linkage-continuous management mode (MCLMM) on endovascular interventional therapy (EIT) for PCCI.Sixty-nine patients with PCCI who received EIT and conventional nursing intervention were selected as the control group, and 78 patients with PCCI who received EIT and MCLMM intervention were selected as the observation group. The incidence of postoperative complications, compliance and disease self-management behavior after six months of intervention, modified Rankin scale (mRS) and Barthel index (BI) scores in the acute phase and after one year of intervention, and recurrence within one year were compared between the two groups.The total incidence rate of postoperative complications in the observation group (7.69%) was lower than that in the control group (18.84%) (MCLMM can reduce the incidence of complications after EIT for PCCI, improve patient compliance behavior and disease self-management ability, and promote the recovery of neurological function.

The present study aimed to investigate the effects of steamed notoginseng single-flavored medicine, herb pairs, compound medicine on anemia rats induced by N-acetyl phenyl hydrazine (APH) to explore the underlying hematinic regulation mechanisms. Rats were randomly divided into seven groups: control group (CG); model group (MG); positive control group (PCG); steamed notoginseng group (SNG); ginseng group (GG); herbal pair group (HPG) and compound prescription group (CPG). Day 12 of the experiment, the blood routine examination of the rats was measured. At the same time, the rats' plasma and urine samples were collected. An Ultra-performance Liquid Chromatography-Quadrupole-Time-of-Flight / Mass Spectrometry (UPLC-Q-TOF/MS) with unsupervised principal component analysis (PCA) and supervised partial least squares discriminant analysis (PLS-DA) combined analytical method was established for metabolomics study of steamed notoginseng. Compared with the CG, red blood cell (RBC) and hemoglobin (Hb) levels in the MG were significantly lower (P l -valine and arachidonic acid, and 14 biomarkers up-regulated such as protoporphyrin IX and nicotinamide; 28 metabolites such as proline, histidine, phenylalanine, l -arginine and l -tyrosine were up-regulated in urine of the MG. The metabolic level of biomarkers could be changed to a normal state after the rats were given steamed notoginseng, herb pairs, and compound prescriptions. It is presumed that steamed notoginseng plays a role in blood enriching through 12 metabolic pathways, including valine, leucine and isoleucine biosynthesis, phenylalanine, tyrosine and tryptophan biosynthesis, retinol metabolism and so on.

Dihydrosanguinarine (DS) is one of the main chemical constituents of Corydalis bungeana Turcz. which demonstrates anti-inflammatory, antioxidant, and antimicrobial in vitro. The present study aimed to investigate the anti-inflammatory effect and its underlying mechanism of DS in vivo. The network pharmacology method was used to predict the anti-inflammatory target of DS, and it was found that PI3K-AKT signal transduction pathway was the most obvious, and the anti-inflammatory effect of DS was more specific in liver. Herein, we used AKT inhibitor AZD 5363 to block PI3K-AKT signaling pathway, to carry out animal experiments to verify the predicted results of network pharmacology. The results showed that DS exerts protective effects on LPS-induced liver inflammation in mice, and the anti-inflammatory effect of DS was attenuated after inhibiting AKT. To elucidate the potential molecular mechanisms, we performed RNA-sequence analysis in liver tissues. Transcriptome analysis showed that the "TNF signaling pathway" and "IL-17 signaling pathway" had the highest enrichment of differentially expressed genes (DEGs). Then, TNF/IL-17/PI3K-AKT signal pathways were analyzed by GSEA. It was found that AKT3, CCL2, FOS, IL-17A, IL-17RA, IL-17RE, PI3KCA, TRAF3IP2, CREB5, ICAM-1, VCAM-1, IL-1β, IL-6, TNF-α and CXCL1/2/3 were significantly regulated by DS. The results of RNA-seq immuneCC predictive showed that DS could inhibit the inflammatory response mainly by reducing the degree of macrophage infiltration induced by LPS. At the same time, we use RT-qPCR, IF, WB techniques to verify the core anti-inflammatory differential genes of DS at the gene and protein expression level, confirming that DS can regulate the inflammatory response by regulating the gene expression level of TNF/IL-17/PI3K-AKT signal pathway. We also used HPLC-Q-TOF/MS technology to explore the biotransformation products of DS in the blood and liver of mice under inflammatory conditions and established the docking model of DS and its transformed compound with TNF-α, IL-17A, AKT3 and IL-6, which is the key target from RNA-seq analysis in this study. The results showed that DS strongly interacted with four proteins in the form of prototypes and demethylated products and exhibited anti-inflammatory effects. Our research shows that DS exerts its anti-hepatitis effect mainly by inhibiting the excessive infiltration of macrophages in mice liver induced by LPS and down-regulating the expression of genes related to TNF/IL-17/PI3K-AKT pathway. This study provides a new perspective on the potential therapeutic application of DS and the plasticity of anti-LPS-induced liver inflammation in DS.

Corydalis Bungeanae Herba is often used to treat a variety of inflammatory diseases in traditional Chinese medicine. In order to determine its chemical material basis, the components of Corydalis Bungeanae Herba were isolated by automated purification system. Flavonoids and alkaloids were prepared, and all such components were identified by mass spectrometry. The effects of the components on the production of inflammatory mediators and pharmacological mechanisms in the lipopolysaccharide(LPS)-induced RAW264.7 cell inflammation model were examined. Mouse macrophages(RAW264.7) were first treated with LPS. The relationship between cell viability and LPS concentration was observed. Then, the effects of flavonoids components and alkaloid components with different administration concentrations on cell viability were detected to determine the maximum administration concentration. Secondly, 2.5, 5, 10 and 20 μg·mL~(-1) flavonoids components and alkaloid components were added respectively to observe the effects and mechanism of different concentrations of flavonoids components and alkaloid components on LPS-induced inflammation of RAW264.7 macrophages. Griess reagent assay was used to detect NO content in cell supernatant. The inflammatory cytokines(TNF-α, IL-1β and IL-6) in cell supernatant were determined by ELISA method. Western blot method was used to detect the intracellular nuclear factor(NF-κB) IκBα phosphorylation(p-IκBα), p65 phosphorylation(p-p65) and protein expression of TLR4, TLR2. The results showed that the alkaloid components inhibited the production of NO, TNF-α, IL-1β and IL-6 in a dose-dependent mannerin the concentration range of 2.5-20 μg·mL~(-1). In inflammation upstream pathways, the inhibitory effect of the alkaloid components on the TLR2 expression level was weaker than that of TLR4. In inflammation downstream, alkaloid components significantly inhibited phosphorylation of IκBα and p65 in a dose-dependent manner. These data suggested that the alkaloid components were the material basis components of Corydalis Bungeanae Herba, and its anti-inflammatory mechanism might be related to inhibiting the transmission of inflammatory signals in TLRs/NF-κB signaling pathways dominated by TLR4, interfering with the activation of inflammatory genes and inhibiting their over expression, and down-regulating the secretion level of inflammatory factors.

Ginsenosides F4 and Rg6 (GF4 and GRg6), two main active components of steamed notoginseng or red ginseng, are dehydrated disaccharide saponins. In this work, biotransformation of ginsenosides F4 and Rg6 in zebrafish was investigated by qualitatively identifying their metabolites and then proposing their possible metabolic pathways. The prediction of possible metabolism of ginsenosides F4 and Rg6 using zebrafish model which can effectively simulate existing mammals model was early and quickly performed. Metabolites of ginsenosides F4 and Rg6 after exposing to zebrafish for 24 h were identified by Ultraperformance Liquid Chromatography/Quadrupole-Time-of-Flight Mass Spectrometry. A total of 8 and 6 metabolites of ginsenosides F4 and Rg6 were identified in zebrafish, respectively. Of these, 7 and 5, including M1, M3−M5, M7−M9 and N1 (N5), N2, N4 (N9), N7−N8 were reported for the first time as far as we know. The mechanisms of their biotransformation involved were further deduced to be desugarization,...

Ethnopharmacological relevance Nauclea officinalis Pierrc ex Pitard. is a Chinese medicinal herb that contains high level of alkaloids which is the most abundant and active constituent. Strictosamide isolated from Nauclea officinalis Pierrc ex Pitard. showed significant effects on inflammatory response, compared with pumiloside, 3- epi -pumiloside, vincosamide, 3α,5α-tetrahydrodeoxycordifoline lactam and naucleamide A-10-O-β-D-glucopyranoside of this plant. Aim of study we investigated the biological activities of the six compounds mentioned-above, and the underlying molecular mechanism exerted by the most potent one, strictosamide. Materials and methods The effects of strictosamide and other five compounds on the inhibitory activity of nitric oxide (NO) were screened by Griess test. The contents of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in media were detected by using Enzyme-linked immunosorbent (ELISA) kits. The effects on the mRNA expression of nitric oxide synthase (iNOS), TNF-α and IL-1β of strictosamide were further investigated by RT-qPCR. Western blot assay was conducted to illustrate the effects of strictosamide on iNOS and phosphorylation of p65, inhibitor of NF-κB (IκB)-α, IκB-kinase (IKK)-α as well as p-extracellular signal-regulated kinase (ERK), p-c-jun N-terminal kinase (JNK) and p-p38 in the protein levels. Results Strictosamide potently suppressed the productions of NO, TNF-α and IL-1β in LPS-induced RAW 264.7 macrophages, and it dose-dependently alleviated the LPS-simulated protein level of iNOS as well as the mRNA expressions of iNOS, TNF-α and IL-1β. In addition, molecular data revealed that strictosamide markedly decreased the expressions of p-p65, p-IκBα and p-IKKα. Furthermore, strictosamide significantly attenuated LPS-induced the phosphorylation of p38, ERK and JNK. Conclusions At present study, the results indicated that the anti-inflammatory activity of strictosamide was associated with the restraint of NO, TNF-α and IL-1β via negative regulation of both NF-κB and mitogen-activated protein kinases (MAPKs) in LPS-induced RAW 264.7 cells.

In this paper,ultra performance liquid chromatography coupled with time-of-flight mass spectrometry( UPLC-Q-TOFMS) technique was used to study the effects of steamed notoginseng on endogenous markers in plasma of rats with hemolytic anemia induced by N-acetyl phenyl hydrazine( APH). The aim was to find out the potential biomarkers and possible blood enriching mechanism of steamed notoginseng on hemolytic anemia rats. In the experiment,steamed notoginseng medicine pair( steamed notoginseng-ginseng)and compound medicines( Sanqi Yangxue Capsules) were used respectively to intervene in APH-induced hemolytic anemia model rats.Then blood routine indexes such as red blood cells( RBC),hemoglobin( Hb) and related organ indexes were determined. As compared with the blank group,the RBC and Hb levels in the model group were substantially decreased( P0. 01),while the liver and spleen organ indexes were increased( P0. 05). The results of blood routine and organ index demonstrated that the blood deficiency model was successfully established. Steamed notoginseng can significantly increase the RBC level of rats( P0. 01),and the related indicators of each drug group had a trend of returning to normal levels,verifying the blood enriching effect of steamed notoginseng. The UPLC-Q-TOF-MS technique,principal component analysis( PCA) and partial least squares-discrimination analysis( PLS-DA) were used to analyze the metabolic profiles between the normal group and the model group. Twenty-six potential biomarkers for hemolytic anemia were screened in plasma. Nine metabolites such as retinol,L-valine,and arachidonic acid were down-regulated in the blood deficiency rats,and 17 metabolites such as protoporphyrin Ⅸ and niacinamide were up-regulated. The metabolic level of biomarkers could be changed to a normal state after rats were given with steamed notoginseng,drug pairs,and compound prescriptions. It can be speculated that steamed notoginseng may play a role of blood tonifying by improving biosynthesis of valine,leucine and isoleucine,as well as metabolic pathways such as retinol metabolism and arachidonic acid metabolism.

Ethnopharmacological relevance Corydalis bungeana Turcz. (C. bungeana) is one of traditionally used medicines in China and possesses various biological effects, such as anti-inflammatory, antibacterial activity and inhibition of the immune function of the host. Aim of the study we studied the anti-inflammatory effect and molecular mechanism involved of C. bungeana both in vitro and in vivo model system in which the inflammatory response was induced by LPS treatment. Materials and methods Anti-inflammatory activity of C. bungeana was investigated by LPS-induced RAW 264.7 macrophages and BALB/c mice. The production and expression of pro-inflammatory cytokines were evaluated by Griess reagent, ELISA kits and RT-qPCR, respectively. Phosphorylation status of IκBα and p65 was illustrated by western blot assay. Results C. bungeana reduced the secretion of NO, TNF-α, IL-6 and IL-1β through inhibiting the protein expression of iNOS, TNF-α, IL-6 and IL-1β in vitro and in vivo. Western blot analysis suggested that C. bungeana supressed NF-κB activation via regulating the phosphorylation of IκBα and p65. Immunohistochemical assay also demostrated the histological inflammatory change in liver tissue. Conclusions The results indicate that C. bungeana supresses the activation of NF-κB signaling pathway through inhibiting phosphorylation of IκBα and p65, which results in good anti-inflammatory effect. In addition, C. bungeana attenuates inflammatory reaction by supressing the expression of various inflammatory cytokines both in vivo and in vitro.

Ethnopharmacological relevance Nauclea officinalis has been traditionally used in China for the treatment of fever, pneumonia and enteritidis etc. This study aims to investigate effects of N. officinalis on the inflammatory response as well as the possible molecular mechanism in LPS-stimulated RAW 264.7 murine macrophage cells. Materials and methods Anti-inflammatory activity of N. officinalis (10, 20, 50, and 100 µg/mL) was investigated by using LPS-induced RAW 264.7 macrophages. The NO production was determined by assaying nitrite in culture supernatants with the Griess reagent. The levels of TNF-α, IL-6 and IL-1β in culture media were measured with ELISA kits. Real time fluorescence quantitative PCR was detected for mRNA expression of iNOS, TNF-α, IL-6 and IL-1β. Western blot assay was performed to illustrate the inhibitory effects of N. officinalis on phosphorylation of IκB-α and NF-κB p65. Results Treatment with N. officinalis (10–100 µg/mL) dose-dependently inhibited the production as well as mRNA expression of NO, TNF-α, IL-6 and IL-1β in RAW 264.7 macrophages. Western blot assay suggested that the mechanism of the anti-inflammatory effect was associated with the inhibition of phosphorylation of IκB-α and NF-κB p65. Conclusions The results indicated that N. officinalis potentially inhibited the activation of upstream mediator NF-κB signaling pathway via suppressing phosphorylation of IκB-α and NF-κB p65 to inhibit LPS-stimulated inflammation.

Nauclea officinalis has long been used in China for the treatment of cold, fever, swelling of throat, pink eyes, and so on; however, the in vivo integrated metabolism of its multiple bioactive components remains unknown. In this paper, an ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) method was established to identify chemical constituents in N. officinalis and metabolites in rat biological fluids after oral administration of N. officinalis. First, 40 chemical constituents in N. officinalis were detected within 19min by UPLC-QTOF/MS. Among them, 18 alkaloids and 7 phenolic acids and iridoids were identified or tentatively characterized. Secondly, 22 metabolites were identified after oral administration of N. officinalis extract, including 3, 9, 6 and 4 metabolites in the plasma, feces, urine and bile samples, respectively. Finally, the metabolic pathway was proposed, which were the hydroxylation, the hydroxylation of deglycosyation product of parent compound, the hydroxylation and dehydrogenation product of parent compound, and acetylation. Among these, hydroxylation was considered as the main metabolic processes. This work suggests that the integrative metabolism approach makes a useful template for drug metabolism research of traditional Chinese medicine (TCM).

UPLC-QTOF-MS/MS was used to identify metabolites in rat blood, urine and feces after the administration of n-butanol extract derived from steamed notoginseng. The metabolic process of saponins came from steamed notoginseng was analyzed. The metabolites were processed by PeakView software, and identified according to the structural characteristics of prototype compounds and the accurate qualitative and quantitative changes of common metabolic pathways. Four saponins metabolites were identified based on MS/MS information of metabolites, namely ginsenoside Rh₄, Rk₃, Rk₁, Rg₅,and their 15 metabolites were verified. The metabolic pathways of the four ginsenosides in n-butanol extract included glucuronidation, desugar, sulfation, dehydromethylation, and branch loss. The metabolites of main active saponin components derived from steamed Panax notoginseng were analyzed from the perspective of qualitative analysis. And the material basis for the efficacy of steamed notoginseng was further clarified.

Ethnopharmacological relevance Gynura segetum (GS) is an herbal medicine containing Pyrrolizidine Alkaloids (PAs) that causes hepatic sinusoidal obstruction syndrome (HSOS). Aim of the study To discover potential biomarkers and metabolic mechanisms involved in the hepatotoxicity induced by GS. Methods SD rats were randomly divided into 4 groups including Saline, the decoction of GS high, medium and low dosage at dosages of 3.75 g • kg−1, 7.5 g • kg−1 and 15 g • kg−1. A metabolomics approach using Ultraperformance Liquid Chromatography -Quadrupole-Time-of-Flight / Mass Spectrometry (UPLC-Q-TOF/MS) was developed to perform the plasma and urinary metabolic profiling analysis, and identified differential metabolites by comparing the saline control group and decoction of GS groups. Results The herbal was presented dosage-dependent led to ingravescence of hepatotoxicity after the rats were consecutively given with the decoction of GS at varied dosages. A total of 18 differential metabolites of decoction of GS-induced hepatotoxicity were identified, while 10 of them including arginine, proline, glutamate, creatine, valine, linoleic acid, arachidonic acid, sphinganine, phytosphingosine, and citric acid could be discovered in urine and plasma, and primarily involved in Amino acid metabolism, Lipids metabolism and Energy metabolism. Conclusions The results suggested that the differential metabolites of arginine, creatine, valine, glutamine and citric acid were verified as potential markers of GS-induced hepatotoxicity via the regulation of multiple metabolic pathways primarily involving in Amino acids metabolism and Energy metabolism.

To establish an Ultra Performance Liquid Chromatography fingerprint of Corydalis bungeana from different habitats.UPLC-PDA was adopted to analysis ten batches of Corydalis bungeana from different habitats with Phenomenex Luna C₁₈ column (250 mm x 4.6 mm, 5 µm) eluted with the mobile phase of acetonitrile and 0. 02% triethylamine in a gradient mode. The flow rate was 0.3 mL/min and the column temperature was 30 °C. The detection wavelength was set at 289 nm.The fingerprints of ten batches of Corydalis bungeana from different habitats had 13 common peaks, three of them were identified. The similarities were larger than 0.80. Ten batches of samples were divided into three categories by cluster analysis. Three principal components were ob- served via principal component analysis and the value of three principal components accounted for 89. 607% of the total variance. Two major chemical components of Corydalis bungeana were confirmed.The high-performance and rapid method is successfully used for fingerprint analysis and can be used to evaluate the quality of Corydalis bungeana.

To analyze and compare the protective effects of active components in different ethyl acetate extracts (EAEEPs) from Eclipta prostrate, in order to study the comparison of materials bases protecting normal human bronchial epithelial (NHBE) cells. The MTT assay was taken to compare the protective effect of different EAEEPs on cigarette smoke extracts (CSE) -induced NHBE cells. The ultra-performance liquid chromatography (UPLC) was applied to analyze the content of phenolic acid, coumaric grass ether and flavonoid in EAEEPs. According to the results, all of the eight EAEEPs (0-200 mg x L(-1)) showed certain protective effect on NHBE cells, with statistical difference. Specifically, the total mass of EAEEP VII (89.15 mg x L(-1)) and EAEEP VIII (57.44 mg x L(-1)), which showed the strongest activity, was not the highest, while EAEEP III (132.25 mg x L(-1)) displayed the highest total mass. In the combination with the "component structure" theory, the analysis showed a significant difference in the mass structure among phenolic acid, coumaric grass ether and flavonoid in EAEEP VIII and EAEEP VIII, which were 1.0: 1. 0: 0.5 and 1.0: 1.9: 0.8, respectively. The results suggested a specific optimal "component structure" relationship may exist in EAEEP, which could provide reference for the material base study and quality control.

Danmu injection and Danmu tablet are two widely used traditional Chinese medicine made of Nauclea officinalis (commonly known as Danmu), in which the alkaloids are the major active substances. In this paper, an ultra fast liquid chromatography–tandem mass spectrometry (UFLC–MS/MS) method was developed for simultaneous determination and the pharmacokinetic characteristics study of six main active alkaloids (naucleamide A-10-O-β- d -glucopyranosid, naucleamide G, pumiloside, 3-epi-pumiloside, strictosamide and vincosamide) of the two above-mentioned Danmu preparations in rat plasma. In the course of the experiment, following sample preparation by protein precipitation with methanol–ethyl acetate (2:1, v/v), the nitrogen-dried extraction was reconstituted in methanol and assayed on a C18 column using a gradient elution program with mobile phase consisting of acetonitrile and water containing 0.1% formic acid. The MS detection was performed in positive ionization mode with selected ion transitions. The established method was fully validated and proved to be sensitive and specific with lower limits of quantification (LLOQs) all less than 0.32 ng/mL in rat plasma and matrix effects ranged from 88.87 to 108.27%. Good linearities of six alkaloids were obtained in respective concentration ranges ( r 2 > 0.995). The average extract recoveries for each compound at three quality control concentration levels were no less than 79.70%, and the precision and accuracy were within the acceptable limits. The validated method was successfully applied to the pharmacokinetic study of six alkaloid components of Danmu injection and tablet in rat plasma. The obtained results may be helpful to reveal the action mechanism and guide the clinical application of Danmu preparations.

Danmu is one of common medicines in folks of Li nationality, with such effects in clearing heat and removing toxicity, antisepsis and anti-inflammation. Danmu injection, which is developed with Danmu herbs, has been clinically applied for years and showed curative efficacy. Currently, though many studies have been conducted to analyze chemical constituents in Danmu in details, its pharmacodynamic material basis related to disease prevention and treatment has not been defined. Furthermore, as the quality control methods for Danmu and its preparations remain restricted to single index component and irrational to some extent, it fails to ensure their inherent quality. On the basis of the summary of previous study results, as well as the "component structural theory" of the material basis, we established a "multi-dimensional structure quality control technology system" that is capable of reflecting the integrity of effects of Danmu injection and component structure hierarchy, and performed a dynamic monitoring over the whole process from medicinal materials and preparation products, so as to ensure the inherent quality of Danmu injection.

To study the effective substances of tea for chemoprevention of lung cancer based on Principal Component Analysis (PCA).UPLC was used to determine the content of each component in tea, MTT was used to analyze the survival of CSE-induced NHBE cells. DTNB and the colorimetric assay were used to detect the rate of GSH/GSSG, PCA was used to calculate the correlation coefficient matrix, eigen values and variance of contribution ratio to chemoprevention of lung cancer.Longjing (L) was the most effective one to protect NHBE cells from damaging, and the IC50 of L for prevention of NHBE cells was 0.2559 mg/mL and could make the GSH/GSSG ratio recovery ranging from 0.142 to 0.858 in a dose-dependent manner. The contribution of GCG prevention of lung cancer was 79.602% and that of GA was 11.037% by PCA.Different kinds of tea have different protective effect on NHBE cells. GCGC and GA are the main active ingredients in tea for chemoprevention of lung cancer by PCA.

An ultra performance liquid chromatography coupled with photodiode array detector and time-of-flight tandem mass spectrometry (UPLC–PDA –TOF-MS) method was developed for the quality assessment of Danmu preparations, a commonly used traditional Chinese medicine. Thirty-three compounds from Danmu preparations were simultaneously detected; among them, 14 compounds were unequivocally identified based on their retention behaviors, UV spectrum, MS and MS n data by comparing with reference substances, and the others were tentatively characterized by literatures. Twelve of 33 compounds were simultaneously determined by UPLC–PDA, and the validation of the quantitative method, including recoveries, linearity, sensitivity, precision and repeatability was carried out and the results demonstrated to be satisfied the requirements of quantitative analysis. The results suggested that the established method would be a powerful and reliable analytical tool for quality control of Danmu preparations and the characterization of multi-constituent in complex chemical system.

Background: Danmu injection, a traditional Chinese medicine (TCM) preparation made from Nauclea officinalis , has been commonly used for the treatment of cold, fever, swelling of throat in China. However, the chemical constituents in Danmu injection have not been clarified yet. Objective: a HPLC/DAD/ESI-MS n method was developed for qualitative and quantitative analysis of the components in Danmu injection. Materials and Methods: The chromatographic separation was performed on a Welch Material XB-C18 (4.6mm × 250mm, 5μm) using gradient elution with acetonitrile (A) and water containing 0.1% formic acid (B) as mobile phase at a flow rate of 1.0 ml/min. Results: Twenty-five compounds, including phenolic acid and phenol glycoside, iridous glycoside and glycoalkaloid were identified or tentatively deduced on the base of their retention behaviors, UV absorption, MS and MS n data with those elucidated references or literature. In addition, eleven compounds were simultaneously determined by HPLC-DAD, which was validated and successfully applied for determination of major components in Danmu injection. Conclusion: The results suggested that the established qualitative and quantitative method would be a powerful and reliable analytical tool for the characterization of multi-constituent in complex chemical system and quality control of Danmu injection.

In order to study the chemical constituents in the water extract of the stem of Nauclea officinalis, column chromatography over D101 macroporous resin and silica gel and an automatic purification system were used to isolate and purify the chemical constituents from the extract. Nine compounds were obtained. By analysis of the physicochemical properties and spectral data, their structures were identified as naucleamide G (1), 3, 4-dimethoxyphenol-beta-D-apiofuranosyl (1--6)-beta-D-glucopyranoside (2), kelampayoside A (3), 3alpha, 5alpha-tetrahydrodeoxycordifoline lactam (4), naucleamide A-10-O-beta-D-glucopyranoside (5), pumiloside (6), 3-epi-pumiloside (7), strictosamide (8) and vincosamide (9), separately. Among them, compound 1 is a new compound, compound 2 was found in plants of the genus Nauclea for the first time, and compounds 3 and 4 were isolated from this plant for the first time.

In this study, ultra-performance liquid chromatography (UPLC)/quadrupole-time-of-flight mass spectrometry (QTOF-MS) was applied to the rapid analysis of 20(S)-protopanaxadiol (PPD) metabolites in rats after oral administration, enabling the structural characterization of 23 metabolites in plasma, bile, urine, and feces. 16 of these, including M1–M5, M9, and M11–M15, have not been previously reported. The results also indicated that demethylation, dehydration, dehydrogenation, oxidation, deoxidation, and glucuronidation were the major metabolic reactions of PPD in vivo. This study provides important information about the metabolism of PPD which will be helpful for fully understanding its mechanism of action. Furthermore, structural modification of PPD in vivo may aid in obtaining new chemical derivatives for pharmacological screening.

Baohuoside I is an effective anti-cancer drug currently used for a variety of cancers in vitro. Unfortunately, baohuoside I has a very poor solubility in both water and in organic solvents. Besides that, it is subject to significant efflux. This work therefore aimed at evaluating the ability of mixed micelles to solubilize baohuoside I, increase permeability and inhibit efflux of baohuoside I to promote oral absorption. A novel (TPGS-baohuoside I-phospholipid complex) mixed micelles was formed by phospholipid complex and TPGS to increase the solubility, enhance permeability, and inhibit efflux of baohuoside I. Micelle formation was confirmed by differential scanning calorimetry and transmission electron microscopy. The average diameters and efflux ratio of mixed micelles decreased as the ratio of TPGS increased with a respective increase in solubility of baohuoside I. Nevertheless, a slow release of baohuoside I from loaded micelles was noted. The results showed that at a 1:9 ratio for baohuoside I-phospholipid complex: TPGS in mixed micelles, solubility of baohuoside I increased up to 88 fold while the efflux ratio decreased by 85%. Their smaller size and higher zeta potential values indicated that mixed micelles would be easily absorbed and more stable. The relative bioavailability of the micelles (AUC(0-∞)) compared with baohuoside I (AUC(0-∞)) was 533%, demonstrating great potential for clinical application. Hence, the novel micelles formed with phospholipid complex and TPGS considerably increased drug concentration in the media and enhanced absorption.

In the present study, an icariside II-phospholipid complex was prepared, and its physicochemical properties including UV spectrum, IR spectrum, differential scanning calorimetry (DSC) were tested. Furthermore, the absorption of icariside II and icariside II-phospholipid complex was compared in a Caco-2 cell culture model. The results show that icariside II-phospholipid complex could significantly increase the A-B transport of icariside II (P0.01), with A-B Papp of (3.92 +/- 0.50) x 10(-6) cm/s compared to control (2.05 +/- 0.18) x 10(-6) cm/s (increased by 91%). Likewise, the B-A transport of icariside II was significantly enhanced (P0.01), with Papp of (15.3 +/- 0.72) x 10(-6) cm/s (control) to (22.4 +/- 1.4) x 10(-6) cm/s (46% increase). Efflux ratio of icariside II decreased by 23.5% after forming icariside II-phospholipid complex. The therefore, it could be concluded that phospholipid complexation can increase the intestinal absorption of icariside II.

The main purpose of this study was to evaluate the intestinal absorption and the antineoplastic effect of the poorly water-soluble drug celastrol when liposomes were used as oral drug delivery system. Liposomes were prepared by the ethanol-injection method. An optimized liposome formulation composed of phospholipid, cholesterol and Tween-80 resulted in favorable encapsulation efficiency at 98.06 ± 0.94%. Homogeneous and stable particle size of 89.6 ± 7.3 nm and zeta potential of −(87.7 ± 5.8) mV were determined by laser particle size analyzer. Subsequently, the four-site perfusion rat intestinal model revealed that celastrol-loaded liposomes had improved effective permeability compared to the free drug in four intestinal segments (p < 0.05). Moreover, celastrol-loaded liposomes could also inhibit the tumor growth in C57BL/6 mice. These results suggest that liposomes could be a promising perioral carrier for celastrol.