Development of novel microemulsion-based hydrogel for topical delivery of sinomenium

The objective of the present investigation was to develop and evaluate microemulsion-based hydrogel (MBH) for the topical delivery of sinomenium. The solubility of sinomenium in oils and surfactants was evaluated to identify components of the microemulsion, the pseudo-ternary phase diagrams were developed to identify the area of microemulsion existence and obtain the optimization Km (the weight ratio of surfactant to cosurfactant). The transdermal ability of various microemulsion formulations were evaluated in vitro using Franz diffusion cells fitted with rat skins and sinomenium was analyzed by HPLC. The permeation of microemulsions accorded with the Fick’s first diffusion law and the optimal formulation of the microemulsion was obtained. The MBH formulation containing 2 % sinomenium was prepared with Carbomer 940 as the gelling matrix. Stability test showed that MBH stored at 4°C and 25 °C for 3 months had no significant change in physicochemical properties. Pharmacokinetic study in vivo was conducted using rabbits, and the area under curve of plasma concentration-time (AUC0→∞) of MBH was 1.27 times greater than that of the hydrogel. These results indicated that MBH might be a promising vehicle for the transdermal delivery of sinomenium.Colegio de Farmacéuticos de la Provincia de Buenos Aire

High Throughput mRNA Sequencing Reveals Potential Therapeutic Targets of Tao-Hong-Si-Wu Decoction in Experimental Middle Cerebral Artery Occlusion

Background: Experimental and clinical studies have shown that Tao-Hong-Si-Wu decoction (THSWD) improved neurological deficits resulting from Middle Cerebral Artery Occlusion (MCAO). However, the mechanisms of action of THSWD in MCAO have not been characterized. In this study, the mRNA transcriptome was used to study various therapeutic targets of THSWD.Methods: RNA-seq was used to identify differentially expressed genes (DEGs). MCAO-induced up-regulated genes (MCAO vs. control) and THSWD-induced down-regulated genes (compared to MCAO) were identified. Intersection genes were defined as up-regulated differentially expression genes (up-DEGs) identified as MCAO-induced gene expression that were reversed by THSWD. Genes down-regulated by MCAO and up-regulated by THSWD were grouped as another series of intersections. Biological functions and signaling pathways were determined by gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses. In addition, several identified genes were validated by RT-qPCR.Results: A total of 339 DEGs were filtered based on the 2 series (MCAO vs. control and MCAO vs. THSWD), and were represented by genes involved in cell cycle (rno04110), ECM–receptor interaction (rno04512), complement and coagulation cascades (rno04610), focal adhesion (rno04510), hematopoietic cell lineage (rno04640), neuroactive ligand–receptor interaction (rno04080), cocaine addiction (rno05030), amphetamine addiction (rno05031), nicotine addiction (rno05033), fat digestion and absorption (rno04975), glycerophospholipid metabolism (rno00564), and others. The protein–protein interaction (PPI) network consisted of 202 nodes and 1,700 connections, and identified two main modules by MOCDE.Conclusion: Cell cycle (rno04110), ECM–receptor interaction (rno04512), complement and coagulation cascades (rno04610), focal adhesion (rno04510), hematopoietic cell lineage (rno04640), and neuroactive ligand–receptor interactions (rno04080) are potential therapeutic targets of THSWD in MCAO. This study provided a theoretical basis for THSWD prevention of neurological deficits resulting from intracerebral hemorrhage

Pharmacokinetics, tissue distribution, excretion, and metabolism of a novel antitumor agent, gambogenic acid, in rats

The plasma pharmacokinetics, tissue distribution, excretion, and metabolism of gambogenic acid (GNA), potential antitumor candidate, were investigated in rats. GNA showed linear pharmacokinetic characteristics in rats within the test dose (1, 2, and 4 mg/kg). The t1/2β was 40.38-41.16 min. GNA showed an extensive distribution into multiple tissues, and the bile excretion is the major pathway of excretion, accounting for 52.12 %. About 40 % of GNA might undergo metabolism in vivo and the main phase I metabolites of GNA may be 10-hydroxygambogenic acid and 9,10-epoxygambogenic acid.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Pharmacokinetics, tissue distribution, excretion, and metabolism of a novel antitumor agent, gambogenic acid, in rats

The plasma pharmacokinetics, tissue distribution, excretion, and metabolism of gambogenic acid (GNA), potential antitumor candidate, were investigated in rats. GNA showed linear pharmacokinetic characteristics in rats within the test dose (1, 2, and 4 mg/kg). The t1/2β was 40.38-41.16 min. GNA showed an extensive distribution into multiple tissues, and the bile excretion is the major pathway of excretion, accounting for 52.12 %. About 40 % of GNA might undergo metabolism in vivo and the main phase I metabolites of GNA may be 10-hydroxygambogenic acid and 9,10-epoxygambogenic acid.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Pharmacokinetics, tissue distribution, excretion, and metabolism of a novel antitumor agent, gambogenic acid, in rats

The plasma pharmacokinetics, tissue distribution, excretion, and metabolism of gambogenic acid (GNA), potential antitumor candidate, were investigated in rats. GNA showed linear pharmacokinetic characteristics in rats within the test dose (1, 2, and 4 mg/kg). The t1/2β was 40.38-41.16 min. GNA showed an extensive distribution into multiple tissues, and the bile excretion is the major pathway of excretion, accounting for 52.12 %. About 40 % of GNA might undergo metabolism in vivo and the main phase I metabolites of GNA may be 10-hydroxygambogenic acid and 9,10-epoxygambogenic acid.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Transcriptomic landscape of Dendrobium huoshanense and its genes related to polysaccharide biosynthesis

Dendrobium huoshanense has long been used to treat various diseases in oriental medicine. In order to study its gene expression profile, transcripts involved in the biosynthesis of precursors of polysaccharides, as well as mechanisms underlining morphological differences between wild and cultivated plants, three organs of both wild type and cultivated D. huoshanense were collected and sequenced by Illumina HiSeq4000 platform, yielding 919,409,540 raw reads in FASTQ format. After Trinity de novo assembly and quality control, 241,242 nonredundant contigs with the average length of 967.5 bp were generated. qRT-PCR experiment on the selected transcripts showed the transcriptomic data were reliable. BLASTx was conducted against NR, SwissProt, String, Pfam, and KEGG. Gene ontology annotation revealed more than 40,000 contigs assigned to catalytic activity and metabolic process, suggesting its dynamic physiological activities. By searching KEGG pathway, six genes potentially involved in mannose biosynthetic pathway were retrieved. Gene expression analysis for stems between wild and cultivated D. huoshanense resulted in 956 genes differentially expressed. Simple sequence repeats (SSRs) analysis revealed 143 SSRs with the unit size of 4 and 3,437 SSRs the size of 3. The obtained SSRs are the potential molecular markers for discriminating distinct cultivars of D. huoshanense

Serum Containing Tao-Hong-Si-Wu Decoction Induces Human Endothelial Cell VEGF Production via PI3K/Akt-eNOS Signaling

Tao-Hong-Si-Wu decoction (TSD) is a famous traditional Chinese medicine (TCM) and widely used for ischemic disease in China. TSD medicated serum was prepared after oral administration of TSD (1.6 g/kg) twice a day for 3 days in rats. TSD medicated serum induced human umbilical vein endothelial cells (HUVECs) proliferation, VEGF secretion, and nitric oxide (NO) production. These promoted effects of TSD were partly inhibited by treatment with PI3K inhibitor (LY294002) or eNOS inhibitor (L-NAME), respectively, and completely inhibited by treatment with LY294002 and L-NAME simultaneously. Western blot analysis findings further indicated that TSD medicated serum upregulated p-Akt and p-eNOS expressions, which were significantly inhibited by LY294002 or L-NAME and completely inhibited by both LY294002 and L-NAME; these results indicated that TSD medicated serum induced HUVECs VEGF expression via PI3K/Akt-eNOS signaling. TSD medicated serum contains hydroxysafflor yellow A, ferulic acid, and ligustilide detected by UPLC with standards, so these effect of TSD medicated serum may be associated with these three active compounds absorbed in serum

Qualitative and quantitative analyses of three bioactive compounds in traditional chinese medicine gamboge by HPLC-PDA-ESI/MSⁿ

A high performance liquid chromatography photo diode array UV detection electrospray ionization tandem mass spectrometry (HPLC-PDA-ESI/MSn) method was developed and validated for the quality evaluation of gamboge (dryed resin exuded from the stems of Garcinia hanburyi). The contents of the three bioactive constituents (gambogenic acid, R-gambogic acid and S-gambogic) were determined by using HPLC–PDA, and their chemical structures were identified by HPLC-PDA-ESI/MSn.The limits of detection and quantitation were between 0.039-0.048 μg/mL and 0.13-0.16 μg/mL. The intra- and inter- assay precisions, in terms of percent relative standard deviation, are less than 3.7 and 4.8 %, respectively . The accuracy, in terms of recovery percentage, ranged from 96.86 to 101.70 %. Good linearity (correlation coefficient > 0.9996) for each calibration curve of standards. HPLC-PDA-ESI/MSn was use to analyze caged xanthones in gamboge. A total of 16 peaks were identified or tentatively characterized. The results indicated that the method could be considered to be a simple, rapid and reliable method for the quality evaluation of gamboge.Colegio de Farmacéuticos de la Provincia de Buenos Aire

New bisesquiterpenoid lactone from the wild rhizome of <i>Atractylodes macrocephala</i> Koidz grown in Qimen

<p>The rhizomes of <i>Atractylodes macrocephala</i> are used as both a food source and traditional Chinese medicine in China. A phytochemical investigation was carried out on wild <i>A. macrocephala</i> grown in Qimen County in eastern China, and yielded a novel bisesquiterpenoid lactone, namely, biatractylenolide II (<b>1</b>), along with two known compounds, atractylenolide II (<b>2</b>) and taraxeryl acetate (<b>3</b>). The structure and relative configuration of the new compound were elucidated mainly by 1D and 2D NMR spectroscopic methods in combination with HRESIMS experiments. This paper describes the isolation and structural elucidation of the new bisesquiterpenoid lactone (<b>1</b>).</p

Amphiphilic Block Copolymer Poly (Acrylic Acid)-B-Polycaprolactone as a Novel pH-sensitive Nanocarrier for Anti-Cancer Drugs Delivery: In-vitro and In-vivo Evaluation

Gambogenic acid (GNA) has been demonstrated with outstanding antitumor activity as a potential antitumor drug in recent years. However, the low solubility and deficient bioavailability of GNA seriously hinder its practical application in the clinic area. In this study, a novel amphiphilic block copolymer, poly (acrylic acid)-b-polycaprolactone (PAA-b-PCL) is prepared and assembled into pH-responsive polymeric micelles (PMs) as one mold of drug delivery system (DDS) with unique properties. Relevant investigation on PMs exhibits excellent carrying potential and pH-dependent release performance for GNA. The drug loading capacity (DLC) and drug loading efficiency (DLE) for GNA-loaded PMs can be achieved as high as 15.20 &#177; 0.07% and 83.67 &#177; 0.49%, respectively. The in vitro experiments indicate that the GNA releasing time, cytotoxicity, and cellular uptake are significantly enhanced. Especially, the peak concentration (Cmax) and area under the curve (AUC) are promoted sharply in the GNA-loaded PMs concentration-time curve. This study not only provides a novel way to widen the application of anticancer GNA in the future, but also extends the potential of stimuli-responsive copolymers to biomedical applications