Latest ArticlesIn our study of the chemical constituents of the dried mature fruits of Arctium lappa L., ten compounds were isolated by various chromatography methods and preparative HPLC. Their structures were elucidated as (7R, 8R)-4, 7, 9, 9'-tetrahydroxy-3, 3'-dimethoxy-8-4'-oxyneolign-7'-ene-9'-O-β-D-glucopyranoside (1), (7R, 8R)-4, 7, 9, 9'-tetrahydroxy-3, 3'-dimethoxy-8-O-4'-neolignan-9'-O-β-D-glucopyranoside (2), (7R, 8R)-4, 7, 9, 9'-tertahydroxy-3, 3'-dimethoxy-8-4'-oxyneolignan (3), (7S, 8R)-dihydrodehydrodiconiferylalcohol-4-O-β-D-glucopyranoside (4), (7S, 8R, 7'R, 8'R)-pinoresinol-4, 4'-di-O-β-D-glucopyranoside (5), (8S, 7'S, 8'R)-4, 4', 9'-trihydroxy-3, 3'-dimethoxy-7', 9-epoxylignan-7-oxo-4'-O-β-D-glucopyranoside (6), 2-methoxy-4-hydroxyphenol-1-O-β-D-xylopyranosyl-(1→6)-O-β-D-glucopyranoside (7), 3-methoxy-4-hydroxyphenol-1-O-β-D-xylopyranosyl-(1→6)-O-β-D-glucopyranoside (8), 4-hydroxy-3-methoxybenzylalcohol-4-O-β-D-xylopyranosyl-(1→6)-O-β-D-glucopyranoside (9) and 2-phenethyl β-primeveroside (10) by their spectroscopic data (IR, UV, CD, MS, HR-ESI-MS, and 1D and 2D NMR) and comparison to literature data. Compound 1 is a new 8-O-4'-neolignan. Compounds 2-10 were isolated from the dried mature fruits of Arctium lappa L. for the first time.
The study was aimed to investigate the correlation between the immunocompetence and the fingerprints of supernatant extracts from Radix Astragali by multi-index integrated evaluation, and reveal the material basis of Radix Astragali improving the immunological function. After oral administration 10 batch of supernatant extracts from Radix Astragali on immunosuppressed mice, phagocytic index, delayed type hypersensitivity (DTH) degree, organs index and the level of cytokines IFN-γ, IL-4 (ELISAs) were measured, and each common peak from HPLC-DAD/HPLC-ELSD fingerprints were correlated with the above data. A number of components in supernatant extracts of Radix Astragali display a substantial correlation with the immunocompetence. Supernatant extracts of Radix Astragali can significantly enhance immunological function on mice, which is related to various components in Radix Astragali.
The study was aimed to establish a liquid chromatography-tandem mass spectrometric method for the determination of the duloxetine concentration in rat plasma, and compare the pharmacokinetics in normal and diabetes mellitus rat models. Diazepam was used as an internal standard. The separation was achieved on a Waters Xterra® RP18 column (100 mm × 4.6 mm, 3.5 μm) with a mobile phase consisting of methanol-0.3% formic acid containing 5 mmol·L-1 ammonium acetate (75:25) at the flow rate of 0.6 mL·min-1. Electrospray ionization source was applied and operated in the positive multiple reaction monitoring mode. A good linearity of duloxetine was obtained in the concentration range of 10-5 000 ng·mL-1. The rat models of diabetes mellitus were established by intraperitoneal injection of streptozotocin. The same dose of duloxetine (40 mg·kg-1) was given by intragastric administration to the normal and diabetic rats. Blood samples were collected from the orbital venous plexus to determinate duloxetine concentration in the plasma. The pharmacokinetic parameters were calculated by DAS software. Statistical analysis was performed by SPSS software. The major pharma-cokinetic parameters of diabetes group were as follows: Cmax was 1 185 ± 190.0 ng·mL-1; AUC0-∞ was 8 398 ± 1 835 ng·mL-1·h; tmax was 1.6 ± 0.4 h; t1/2z was 3.6 ± 0.9 h. The major pharmacokinetic parameters of normal group were as follows: Cmax was 368.1 ± 40.7 ng·mL-1; AUC0-∞ was 4145 ± 640.1 ng·mL-1·h; tmax was 1.6 ± 0.3 h; t1/2z was 4.1 ± 0.8 h. The results of pharmacokinetic experiments suggest that the exposure amount of duloxetine in diabetic rats is twice higher than that in normal rats.
To develop a taste-masking oral preparation of azithromycin for pediatrics, the reversed lipid nano-micelle techniques were used to mask the bitterness of azithromycin. Dry emulsion (DE) for taste-masking was prepared by solidifying the reversed-micelle oil solution containing azithromycin. Colloidal silicon dioxide was used as absorbent and solid carrier. Solidification was confirmed through dying test and observed by scanning electron microscope (SEM). The DE formulation was characterized by X-ray powder diffraction and SEM in order to investigate the crystal state of drug. Reconstitution emulsion droplet size and morphology were also determined using Nano ZS90 Zetasizer and transmission electron microscopy (TEM). The taste testing was performed in two different ways, namely, human taste panel test and the measurement of the amount of drug released in simulated oral cavity condition. The intestinal mucosal irritation test of DE formulation was also investigated in rats in comparison with commercial product (Zithromax). The optimal taste-masking formulation of azithromycin can be re-dispersed immediately with mean diameter of 530.1 nm after agitation in water. The results of taste testing showed that the bitterness of azithromycin was successfully masked by DE formulation similar with Zithromax at the same dose, moreover reduced intestinal irritation compared to Zithromax. These results indicate that the DE formulation for taste-masking of azithromycin is promising and valuable in the future development of azithromycin for pediatrics.
To develop a cell-penetrating peptide with high membrane penetrating ability and effective antitumor activity, we designed and synthesized an analogue of penetratin, [Cys-CPT2, 9] penetratin, by substitution of Gln2 and Asn9 with Cys-CPT. We investigated the transmembrane activity and antitumor activity of [Cys-CPT2, 9] penetratin. The fluorescence intensity of [Cys-CPT2, 9] penetratin in HeLa cells was observed by laser confocal microscopy and flow cytometry, and the cell uptake mechanism of [Cys-CPT2, 9] penetratin was evaluated by using different endocytic inhibitors, finally the anti-tumor activity of [Cys-CPT2, 9] penetratin was tested by MTT assay. The results showed that the membrane activity of [Cys-CPT2, 9] penetratin was significantly enhanced in laser confocal microscopy and flow cytometry assay, and the intracellular fluorescence intensity was 5 times higher than penetratin. The cell uptake mechanism study of [Cys-CPT2, 9] penetratin indicated that it mainly entered the cell through the clathrin and endocytosis. Moreover, [Cys-CPT2, 9] penetratin exhibited anti-tumor activity against HeLa cells, and its inhibitory effect on cancer cells was stronger than CPT. [Cys-CPT2, 9] penetratin is a new cell-penetrating peptide with high translocation ability, and has anti-tumor activity against HeLa cells.
This study was aimed to build a new photo-sensitive co-delivery liposomes which combine photodynamic therapy with chemotherapy to reverse drug resistance of breast cancer. Photodynamic photosen-sitizer chlorin e6 trimethyl ester (Ce6tM) and chemotherapeutic drug doxorubicin hydrochloride (DOX) were loaded into the liposomes (liposomes loaded with Ce6tM and DOX, CDL) by thin-film hydration extrusion and ammonium sulfate active loading methods. CDL was characterized with cryo-transmission electron microscopy (Cryo-TEM), dynamic light scattering particle size, zeta potentials and photo-sensitive DOX release behaviors in vitro. CDL cytotoxicity, singlet oxygen production, DOX accumulation, intracellular ATP level and cell cycle analysis in MCF7/ADR cells were evaluated. Finally, the tissue distribution of DOX and antitumor effects of CDL in BALB/c-nu nude mice bearing MCF7/ADR tumor were investigated. The results showed that the particle size of obtained CDL was 90.7 ± 1.1 nm and distributed uniformly. CDL possessed outstanding properties of photo-sensitive drug release profile. The accumulated release of DOX reached (96.52 ± 0.11)% in 2 min under 671 nm laser irradiation (2 W·cm-2). Interestingly, DOX in CDL could maintain rapid release after 671 nm laser irradiation with low power and short time (15 s, 0.25 W·cm-2). This phenomenon was caused by oxidation of unsaturated phospholipids in CDL under 671 nm laser irradiation and had nothing to do with the slightly elevated temperature. Photo-sensitive drug release behavior contributed to increased DOX accumulation in MCF7/ADR cells. The half inhibition concentration (IC50) of DOX in CDL laser group in MCF7/ADR cells was decreased by 601.9-fold compared with no laser group, which could be related to increased accumulation of DOX, decreased ATP levels and cell cycle arrest in MCF7/ADR cells. With the help of CDL, DOX accumulation in tumor was increased and in cardiac toxicity was reduced in vivo. CDL laser group showed a good anti-tumor effect. The tumor inhibition rate was (94.7 ± 6.2)%. These results suggest that CDL has a promising potential in reversing drug resistance of breast cancer.
Lepidium apetalum was used as an experimental material in this study. By analyzing the tran-scriptome data of L. apetalum and application of the specific primers, cDNA of cinnamate-4-hydroxylase (C4H) gene was isolated from L. apetalum and named as LaC4H (GenBank accession No. KX064050). Meanwhile, the bioinformatic analysis, prokaryotic expression, purification, tissue-specific expression analysis and expres-sion analysis after methyl jasmonate (MeJA) treatment were carried out. The results indicated that: ① The open reading frame (ORF) of LaC4H was 1 518 bp, which encoded a protein of 505 amino acid residues, with a predicted molecular mass of 57.73 kD. ② Bioinformatic analysis showed that LaC4H protein contained the conserved sequences of cytochrome P450 (CYP450) and 5 substrate recognition sites (SRSs) of CYP73A1, therefore LaC4H protein was a member of CYP450 superfamily. The phylogenetic analysis indicated that LaC4H protein showed the highest homology with C4H protein from cruciferous plants (such as AtC4H from Arabidopsis thaliana). ③ Through the construction of the prokaryotic expression vector pET-32a-LaC4H, the recombinant LaC4H protein was successfully expressed in E. coli BL21 (DE3) cells and the recombinant LaC4H protein was purified by Ni2+ affinity chromatography. ④ Real-time PCR analysis indicated that LaC4H was expressed in a high transcript level in stems, lower levels in leaves and flowers, the lowest level in roots. After MeJA treatment, the expression level of LaC4H in leaves was increased significantly to reach the highest level at 48 h. Furthermore, the expression levels of LaC4H were positively correlated with the flavonoids contents in leaves. The results of this study provide the fundamental information on LaC4H gene in the flavonoids biosyn-thesis pathway of L. apetalum.
This paper was prepared to analyze and discuss the main content of the Botanical Drug Development Guidance for Industry by United States FDA's (the draft version of the 2015), especially focused on the guidelines for clinical research (mainly in late-stage clinical studies) recommendations and requirements sectiones. The key and difficult issues in the late clinic study were analyzed and discussed, and a series of countermeasures were proposed in this paper. At the same time, combined with the case of approved botanical drug products, analysis of the guidelines for the development of plant drug regulations, the enlightenment were presented in the last part, to guide the research and development of traditional Chinese medicine and the internationalization of Chinese medicine.
Neural stem cells (NSCs) posse the specialty of tumor tropism and be able to migrate specifically to tumor cells. NSCs are also cross the blood brain barrier. NSCs keep in touch with tumor cells preferentially under the tumor microenvironment, and surround the target cells. Based on these characteristics, NSCs can be used as a carrier for therapeutic virus, enzymes/prodrugs, genes or suicide genes, etc. which are selectively delivered to the glioma cells. NSCs may be modified by a variety of different genes to establish a reliable, safe and effective therapy for glioma.
L-Glutamate is an important amino acid in protein. It has many physiological functions, such as nutrient metabolism, energy supply, immune response, oxidative stress, and signaling pathways regulation. Recent studies have found that glutamate prevents gastrointestinal damage induced by non-steroidal anti-inflammatory drugs (NSAIDs) and promotes the healing of the lesions. It can inhibit colonization of Helicobacter pylori and cell apoptosis caused by NH3. Hence, it has a potential value in protection of gastrointestinal from damage caused by NSAIDs and Helicobacter pylori. This article provides a review of the metabolism and physiological function of glutamate and its protective mechanisms of gastrointestinal injury caused by NSAIDs and Helicobacter pylori, which may serve as a reference in the study of glutamate in drug development.
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