Two new 2,3-seco triterpenoids from Rubus pirifolius Smith / 药学学报

Eight compounds were isolated from the ethyl acetate fraction of the 80% aqueous ethanol extract of the roots and stems of Rubus pirifolius Smith by AB-8 macroporous resin, silica gel, ODS, Sephadex LH-20 column chromatography, and semi-preparative HPLC. Their structures were identified by spectral analysis such as 1D/2D NMR, MS, UV, IR and by comparison with literature information as rubussecotriterpene A (1), rubussecotriterpene B (2), cecropiacic acid (3), cecropiacic acid 3-methyl ester (4), alphitolic acid (5), betulinic acid (6), betulin (7), and obtusalin (8). Compounds 1 and 2 are new compounds, and compounds 3-8 were isolated from this plant for the first time.

Preparation and characterization of linolenic acid-chitosan micelle for doxorubicin oral delivery and its in situ intestinal absorption in rats / 药学学报

In this study, a novel oral drug delivery system based on linolenic acid-modified chitosan (CS-LA) micelle was developed to improve the oral bioavailability of doxorubicin (DOX), which was proven by its in vivo intestinal absorption in rats. The DOX-loaded CS-LA micelles (CS-LA@DOX) were prepared by the dialysis method. The synthesized micelle material was identified by proton nuclear magnetic resonance spectroscopy (1H-NMR) and Fourier transform infrared spectroscopy (FT-IR). A series of the micelle properties, including particle size distribution, zeta potential, encapsulation efficiency (EE), drug loading (DL), micromorphology, polymorphy, and critical micelle concentration (CMC) were characterized or tested. The in vitro release of micelles was observed by the dialysis method, and the absorption-promoting effect of micelles was investigated by intestinal circulation experiments in rats. The animal welfare and experimental procedures were in accordance with the regulations of the Animal Ethics Committee of Guilin Medical University. The results of 1H-NMR and FT-IR showed that CS and LA were covalently bound via an amide linkage. The DOX encapsulated in the micelle core was in an amorphous state. The as-prepared micelles in the transmission electron microscope (TEM) image showed regular spherical shapes and uniform sizes with a series of excellent characteristics including (119.2 ± 2.1) nm of mean particle size [polymer dispersity index (PDI), 0.190 ± 0.08], +12.1 mV of zeta potential, (70.23 ± 0.74) % of EE, (8.77 ± 0.02) % of DL and 51.75 μg·mL-1 of CMC. Compared with the reference, DOX hydrochloride, the proposed micelle drug delivery system showed an obvious sustained-release effect in vitro release; and enhanced drug absorption in the small intestine of rats.

Application Advantages of Nanoemulsion in Field of Traditional Chinese Medicine Preparation：A Review / 中国实验方剂学杂志

As a new technology with unique drug delivery advantages， nanoemulsion has been widely used in the field of traditional Chinese medicine （TCM） preparations. By searching， classifying and sorting out the literature reports at home and abroad in recent years， this paper systematically expounded the application advantages and production mechanism of nanoemulsion in delivering effective components of TCM from three aspects of improving oral bioavailability， enhancing targeting effect and delaying drug release. The current formulation optimization strategies， preparation processes and quality evaluation indicators commonly used in TCM nanoemulsion were summarized. Based on the research status of TCM nanoemulsion with different active components， the common problems and possible solutions in the development of TCM nanoemulsion were discussed， and the future research hotspots and directions of TCM nanoemulsion were prospected. This article clarifies the feasibility of nanoemulsion for enriching the selection of TCM dosage forms， which can provide reference for the subsequent rational design and improvement of TCM preparations. At the same time， it is revealed that the research focus of TCM nanoemulsion in the future lies in the integrated research of TCM compounds， and shows a trend of multi-disciplinary joint and targeted research.

Pharmacokinetic study on five components in phthalide target areas of Chaxiong and its β-CD inclusion compounds based on UPLC-MS/MS / 中国中药杂志

This study aims to establish a method for the determination of the concentration of five main components of phthalide target areas of Chaxiong(CPTA) and its inclusion of β-CD in the plasma of rats, and determine the pharmacokinetic parameters, absolute bioavailability and relative bioavailability of CPTA/β-CD inclusion compound in vivo. The plasma concentrations of senkyunolide A, N-butylphthalide, new osthol lactone, Z-ligustilide and butenyl phthalide were determined with UPLC-MS/MS. The content determination was conducted at the chromatographic conditions as follows: Shim-pack GIST C_(18)-AQ HP column(2.1 mm×100 mm, 3 μm), mobile phase of 0.1% formic acid solution(A)-acetonitrile(B), gradient elution, flow rate of 0.3 mL·min~(-1), column temperature of 35 ℃ and injection volume of 2 μL. The mass spectra were obtained with electrospray ion source(ESI), positive ion mode and multi reaction monitoring. CPTA/β-CD inclusion compound was prepared by grinding method, DAS 2.0 software was used to model the data, and the absolute bioavailability of CPTA and relative bioavailability of inclusion compound were calculated. Finally, the methods for the determination of five components of senkyunolide A, N-butylphthalide, new osthol lactone, Z-ligustilide and butenyl phthalide in CPTA, were successfully established. The linear relationship among the five components was good within their respective ranges, r>0.99. The absolute bioavailability of the five components in rats was 22.30%, 16.32%, 21.90%, 10.16% and 12.43%, respectively. After CPTA/β-CD inclusion was prepared, the relative bioavailability of the five components was 138.69%, 198.39%, 218.01%, 224.54% and 363.55%, respectively, significantly improved. This method is rapid, accurate and sensitive, so it is suitable for the pharmacokinetic study of extracts in traditional Chinese medicine and their preparations.

Effect and mechanism of total flavonoids of Lichi Semen on CCl_4-induced liver fibrosis in rats, and prediction of Q-marker / 中国中药杂志

This paper was to investigate the effect of total flavonoids of Lichi Semen(TFL) on carbon tetrachloride(CCl_4)-induced liver fibrosis in rats, analyze and predict its mechanism of action and potential quality markers(Q-marker). Firstly, male SD rats were taken and injected subcutaneously with a 40% CCl_4-vegetable oil solution twice a week for 8 consecutive weeks to establish a rat model of liver fibrosis. The rats with liver fibrosis were randomly divided into model group, silybin group(43.19 mg·kg~(-1)), Fuzheng Huayu Capsules group(462.75 mg·kg~(-1)), and TFL groups(100 mg·kg~(-1) and 25 mg·kg~(-1)), with normal rats as a blank group, 10 rats in each group. Except for the blank group, the rats in the other groups were subcutaneously injected with 40% CCl_4-vegetable oil solution of a maintenance dose, once a week. The rats in various treatment groups received corresponding doses of drugs, while the rats in the blank group and model group received the same volume of normal saline once a day for 4 weeks. At the end of the experiment, blood was collected from the abdominal aorta and the liver tissues were collected. The levels of total bilirubin(TBiL), direct bilirubin(DBiL), indirect bilirubin(IBiL), alanine aminotransferase(ALT), and aspartate aminotransferase(AST) in serum were detected by using an automatic biochemical detector. Masson staining was used to observe the histopathological changes of rat liver. Then, the chemical compositions of TFL were collected, and the action targets of these chemical compositions were predicted through SWISS database and reverse molecular docking server(DRAR-CPI). After screening of disease targets of liver fibrosis by Gene Cards database, the protein-protein interaction was analyzed with use of STRING database, and GO(gene ontology) analysis and KEGG(Kyoto encyclopedia of genes and genomes) enrich analysis were also carried out. Moreover, an iTRAQ proteomics technology was used to determine protein expression in liver tissues of rats in TFL, model and blank groups to verify the targets. Furthermore, Cytoscape software was used to establish and visualize the network of chemical components, targets and pathways, and predict the potential Q-marker of TFL. The results showed that the levels of TBiL, DBiL, IBiL, ALT, and AST in the model group were significantly higher than those in the blank normal group(P<0.05), and the above levels in the treatment groups were lower than those in the model group, but with no significant differences. Masson staining showed that the liver damage and the degree of fibrosis were severe in the model group, and were relieved to different degrees in the treatment groups. Then, 74 chemical components were screened, which could act on 865 targets such as EGFR and SRC, participating in the regulation of cancer pathways, PI3 K-Akt signaling pathway, HIF-1 signaling pathway and other signaling pathways closely related to liver fibrosis. Pinocembrin, quercetin, epicatechin, procyanidin A2, naringenin, nobiletin, phlorizin and rutin showed the highest correlation with liver fibrosis-related targets and pathways. Proteomics results showed that a total of 18 proteins among the 45 proteins predicted by internet pharmacology were identified, among which 6 proteins were significantly expressed, including 5 up-regulated proteins and 1 down-regulated protein. The protein expression of ALB, PLG, HSP90 AA1, EGFR and MAP2 K1 was significantly returned to a normal state in the TFL treatment groups. In conclusion, TFL may demonstrate the anti-hepatic fibrosis and potential hepatoprotective effects by regulating the expression of ALB, PLG, HSP90 AA1, EGFR and MAP2 K1, which may be associated with the regulation of multiple signaling pathways related to liver fibrosis such as PI3 K-Akt pathway. Pinocembrin, quercetin, epicatechin, procyanidin A2, naringenin, nobiletin, phlorizin and rutin could be regarded as potential Q-markers of TFL for quality control.

Development and characterization of TPGS modified proniosomes of docetaxel / 中国中药杂志

A novel oral delivery system that TPGS modified docetaxel proniosomes, DTX-TPGS-PN, was developed and the characterization after hydration was observed. Firstly, Doce-TPGS-PN was optimized by investing the factors, including the type of surfactant, methods of adding TPGS, content of TPGS and the molar ratio of span40/cholesterol, which may affecting the particle size, encapsulation efficiency and instantaneous release of drug in the formulation. Then, the morphology, particle size, Zeta potential, encapsulation efficiency and in vitro release of the formulation were evaluated. The result showed that hydrated nanoparticles of DTX-TPGS-PNs were (93 ± 6.5) nm in size,(-83.95 ± 3.69) mV in zeta potential, (97.31 ± 0.60)% in encapsulation efficiency, exhibiting spherical morphology and biphasic release process that a low burst effect within the first 0.5 hour and a relative-sustained release for the next several hours in PBS. These results indicate the oral delivery system of DTX-TPGS-PN was successfully built with good properties.

Progress in regulation effect of aromatic refreshing traditional Chinese medicine on BBB permeability and its mechanism / 中国中药杂志

The blood-brain barrier (BBB) protects the brain against unwanted substances, while, at the same time, limits the transport of many drugs into the brain. Aromatic refreshing traditional Chinese medicine (TCM) can induce resuscitation and modify the permeability of BBB, promoting other drugs entering into the brain with brain protection effect. This paper mainly reviews the research progress in regulation effects and mechanism of usual aromatic refreshing TCM, such as borneol, moschus, styrax, benzoinum and Tatarinow Sweetflag Rhizome, on BBB permeability. To broaden the application of these drugs in modern pharmaceutics in the future, the relatively research should emphasis on combining aromatic refreshing TCM with new formulations and technologies in pharmaceutics, providing novel promising strategies for brain diseases therapy.

Acute pulmonary toxicity of rats caused by different sized SiO2 nanoparticles / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To study the pulmonary toxicity to rats induced by different sized SiOz particles.</p><p><b>METHODS</b>One hundred and five male SD rats were divided into seven groups randomly according to their weight. Experimental rats were exposed to 20, 50, 80, 140, 280 and 800 nm SiO2 particles at the dose of 400 mg/m3 by inhalation for 2 hours respectively. The control group was exposed without SiO2 particles. At the 24th, 48th, 72th hour after exposure, five rats were sacrificed at each time point and the total cellular scores, total protein, lactate dehydrogenase (LDH) in BALF and the histopathological changes in lungs were observed.</p><p><b>RESULTS</b>The total cellular score, total protein and lactate dehydrogenase in bronchoalveolar lavage fluid (BALF) of all experimental groups were higher than the control group. Between 800 nm group and the control group, there were no significant changes in total cellular sare, total protein and LDH in BALF (P > 0.05). At 48 h, the total cellular score of 280 nm group had no significantly change compared with the control group, but the total protein and LDH in BALF of 280 nm group were significantly higher than the control group (P < 0.05). The total cellular score at 24 h and the total protein at 24, 48 h had no significantly changes compared with the control group, but other indexes of 140 nm group were significantly higher than the control group. All the indexes of the 20, 50, 80 nm group were significantly higher than the control group (P < 0.05), and higher than 800 nm group mostly time. The TCS, total protein and LDH in BALF increased firstly and then reduced. The experimental group visible part pulmonary alveolus gap varying degree proliferation accumulation, its periphery has massive phlogocyte accumulation,such as granular cells and macrophage.</p><p><b>CONCLUSION</b>Under this condition ,the SiO2 particles can cause lung damage more serious with the smaller diameter SiO2 particles. As time going on, the damage caused by SiO2 particles is not so serious as before.</p>

Determination of apparent aqueous solubility and apparent oil-water partition coefficients of three bufadienolides composition / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate apparent aqueous solubility and apparent oil-water partition coefficients of three bufadienolides composition.</p><p><b>METHOD</b>A high performance liquid chromatography method was established to determine apparent aqueous solubility of three bufadienolides composition; apparent oil-water partition coefficients of three bufadienolides composition was determined by shaking flask method.</p><p><b>RESULT</b>The solubility of three bufadienolides composition reached the top value, 76.29 microg x mL(-1) (RBG), 51.85 microg x mL(-1) (CBG), 32.76 microg x mL(-1) (BL) respectively and a total of 160.9 microg x mL(-1) in the condition of 37 degrees C and pH 7.0, therefore three bufadienolides composition can be defined as insoluble products. The solubility of the three decreased in weak acid or base environment to some extent. RBG, CBG, BL are liposoluble components and the sequence of log P is RBG > BL > CBG.</p><p><b>CONCLUSION</b>RBG, CBG, BL is water-insoluble and hydrophobic. Surfactants can be applied to increase the solubility of three bufadienolides composition.</p>

Studies on preparation of sinomenine hydrochloride-loaded bovine serum albumin microspheres / 中国中药杂志

<p><b>OBJECTIVE</b>To prepare Sinomenine hydrochloride-loaded bovine serum albumin microspheres (SM-BSA-MS).</p><p><b>METHOD</b>SM-BSA-MS was prepared by spray drying technique. The morphology, drug-loading and release in vitro of SM-BSA-MS was studied.</p><p><b>RESULT</b>The diameters of SM-BSA-MS were in the range of 1-3 m. The drug loading of microspheres, formulated with different drug/albumin ratios as 1, 2, 1:1, 2:1, were 31.6%, 47.7% and 67.9% , respectively. And the drug entrapment efficiencies of different drug/albumin ratios were higher than 94%. The results of in vitro release experiments showed that the drug loaded microspheres have the properties of sustained-release compared with the Sinomenine hydrochloride injection. Different release characteristics could be obtained by adjusting the prescription composition and the thermal denaturation condition.</p><p><b>CONCLUSION</b>Spray drying technique is a simple and feasible method for preparing SM-BSA-MS. The drug loaded microspheres had high drug-loading and sustained-release effect.</p>

Optimization preparation of chansu-loaded solid lipid nanoparticles by central composite design and response surface method / 中国中药杂志

<p><b>OBJECTIVE</b>To optimize the formulation of chansu-loaded solid lipid nanoparticles (Cs-SLN).</p><p><b>METHOD</b>Cs-SLN was prepared by cold homogenization technique. The effects of influence factors such as the weight of compritol 888 ATO, soybean lecithin and poloxamer 188, on mean diameter, entrapment efficiency, drug loading and overall desirability were investigated by using central composite design and response surface method. The data were imitated using multi-linear equation and second-order polynomial equation.</p><p><b>RESULT</b>The latter was prior to the former considering from multiple correlation coefficients. Under the optimal conditions, the mean diameter, entrapment efficiency, drug loading of the Cs-SLN were 71.5 nm, 92.45% and 5.26%.</p><p><b>CONCLUSION</b>The optimized preparation technique for Cs-SLN is stable, feasible and high inclusion rate. It can be used for production of Cs-SLN.</p>

Freeze-drying of silymarin-loaded solid lipid nanoparticles (SM-SLN) / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate lyophilization of SM-SLN.</p><p><b>METHOD</b>The parameters of lyophilization process was optimized. In addition, the protective effect of various types and concentrations of cryoprotectants were tested by shape, colour and disparity.</p><p><b>RESULT</b>The mixture of 2% lactose and 2% glucose could better prevent nanoparticles from aggregating, the optimal lyophilization process was followed: precooled at -45 degrees C for 10 hr; primary drying at -25 degrees C for 5 hr; secondary drying at 10 degrees C for 3 hr; finally drying at 30 degrees C for 6 hr.</p><p><b>CONCLUSION</b>Changes in particle size distribution during lyophilization could be minimized by optimizing the parameters of the lyophilization process and adding supporting agent.</p>

Effect of particle size on oral absorption of silymarin-loaded solid lipid nanoparticles / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate effect of particle size on oral absorption of silymarin-loaded solid lipid nanoparuicles.</p><p><b>METHOD</b>Solid lipid nanoparticles (SLN) of various sizes (150 nm, 500 nm and 1000 nm) using Compritol 888 ATO as the material and silymarin (SM) as a model drug were prepared. Silybinin concentration in plasma of rats were determined by RP-HPLC with UV detector. The main pharmacokinetic parameters were calculated by 3p97.</p><p><b>RESULT</b>Results showed that the AUC of 150 nm SLN was 2.08 fold that of 500 nm SLN and 2.54 fold of 1000 nm SLN treated orally to rats (P < 0.05). The oral bioavailability of 150 nm SLN was remarkably higher than the other two size SLN.</p><p><b>CONCLUSION</b>This has important implications in designing of SM-SLN as a new oral drug delivery system.</p>