[Thermosensitive gel of polysaccharide from Ganoderma applanatum combined with paclitaxel for mice with 4T1 breast cancer].

Polysaccharide from Ganoderma applanatum has the activities of anti-tumor and enhancing immune function. There were no reports on antitumor effect of its intratumoral injection. In this study, the polysaccharide was extracted from G. applanatum by water extraction and alcohol precipitation, and purified by ceramic membrane after removing protein by Sevage method. The total polysaccharide content from G. applanatum(PGA)was about 63%. The combination of PGA and paclitaxel showed synergistic effect on cytotoxicity of 4 T1 cells at lower concentrations in vitro. In addition, the growth curve of 4 T1 cells showed that PGA could retard the growth of 4 T1 cells gradually. The PGA thermosensitive gel(PGA-TG)was prepared by using poloxamer 188 and 407. The gel temperature was 36 ℃, and the PGA-TG could effectively slow down the release rate of PGA in vitro. 4 T1 breast cancer-bearing mice were used as a model to evaluate the therapeutic effect of intratumoral injection of PGA combined with tail vein injection of nanoparticle albumin-bound paclitaxel(nab-PTX). In high and low dose PGA groups, each mice was given with 2.25, 1.125 mg PGA respectively, twice in total, and the dosage of paclitaxel was 15 mg·kg~(-1), once every 3 days, for a total of five times. The tumor inhibition rate was 29.65% in the high dose PGA-TG group, 58.58% in the nab-PTX group, 63.37% in low dose PGA-TG combined with nab-PTX group, and 68.10% in high dose PGA-TG combined with nab-PTX group respectively. The inhibitory effect in high dose PGA-TG group combined with nab-PTX on tumors was significantly higher than that in nab-PTX group(P<0.05). The results showed that paclitaxel therapy combined with intratumoral injection of PGA-TG could improve the therapeutic effect for 4 T1 mice and reduce the side effects of chemotherapy.

[Effect of ginseng rare ginsenoside components combined with paclitaxel on A549 lung cancer].

Traditional Chinese medicine combined with anticancer drugs is a new direction of clinical cancer therapy in recent years. In this study, the optimal ratio of ginseng rare ginsenoside components and paclitaxel was optimized by MTT method, and the proliferative, apoptotic and anti-tumor effects of lung cancer A549 cells were investigated. It was found that the inhibitory effect on the proliferation of lung cancer A549 cells was the same as that on paclitaxel when the ratio of rare ginseng rare ginsenoside components to paclitaxel was 4∶6. Further studies showed that the combined therapy significantly increased the inductive effect of apoptosis in A549 cells, and up-regulated the expression of caspase-3 protein and down-regulated the ratio of Bcl-2/Bax. The tumor-bearing mice model showed that the combination therapy of ginseng rare ginsenoside components and paclitaxel could significantly inhibit the growth of tumor and alleviate the toxic and side effects of paclitaxel on liver. A multi-component system of ginseng rare ginsenoside components-paclitaxel was established in this paper. The proliferation and growth of lung cancer A549 cells were inhibited by paclitaxel-induced apoptosis, the dosage of paclitaxel and the toxicity of paclitaxel were reduced, and the effect of anti-lung cancer was enhanced, which provided a theoretical basis for later studies and clinical application.

[Research and application of hepatotoxicity evaluation technique of traditional Chinese medicine].

The safety of traditional Chinese medicine (TCM) has received the widespread attention in recent years. Hepatotoxicity of TCM is one of the key problems of the safety of TCM. This article summarized research progress and application prospect in the mechanism of TCM hepatotoxicity, biomarkers, toxic omics database, prevention of hepatotoxicity of the liver cell lines, subcellular fraction, three-dimensional cultivation models, the model animals, aiming to provide theoretical basis for TCM toxicity evaluation and technical guidelines, thus promoting the development of TCM toxicity studies. Hope for Chinese medicine liver toxicity evaluation method provides the theoretical foundation and technical guidelines, promote the development and improvement of TCM liver toxicity research system.

[Effect of D-cellobiose on oral bioavailability of gentiopicroside].

In this study, the effect of D-cellobiose on oral bioavailability of gentiopicroside (GPS) was investigate. The influence of D-cellobiose on GPS was achieved by calculating the residual GPS after being degraded with ß-glucosidase or intestinal flora, and the data demonstrated D-cellobiose could inhibit the degradation of GPS in intestines; in bioavailability experiment, D-cellobiose could significantly improve the oral bioavailability (P<0.05) of GPS at the mass ratio of 1∶5, 1∶10 (GPS-D-cellobiose). D-cellobiose applied in this study may improve the oral bioavailability of GPS through delaying the degradation in intestines.

[Research thoughts on tumor immune responses by polysaccharide of Chinese medicine via oral administration].

Tumor immunotherapy is one of the most significant scientific progresses. The idea of applying the traditional Chinese theory of "the balance of Yin and Yang" to treat cancer is in accordance with that of modern tumor immune strategy. Researches indicated that polysaccharide of Chinese medicine through regulation in immune responses could offer better paradigm for tumor immune treatment under the traditional Chinese theory. However, current studies related to tumor immunotherapy largely focus on the immunity enhancement while lack of the exploration of suppressive factors. Meanwhile, the complex analysis and detection on composition as well as structure definitely increase the difficulty in mechanism of oral absorption and function in vivo. To better exploit novel Chinese medicine of polysaccharide for tumor immune treatment, this article will provide some constructive thoughts on regulation of tumor immune responses based on up to date researches of structure-function relationship, absorbent process and molecular mechanisms responsible for tumor immune as well.

[Solidification of magnolol phospholipid complex with polyvingypyrrolidone].

In this study, magnolol phospholipid complex (MPC) was prepared and solidified with polyvingypyrrolidone (PVPP). The influence of PVPP on MPC's flowability, dissolution and oral bioavailability was investigated. The results of phase characterization using differential scanning calorimetry (DSC), infrared spectroscopy (IR), and scanning electron microscopy (SEM) showed that magnolol existed in solidified powder and MPC in an amorphous state. In flowability and dissolution experiments, solidified powder showed significant superiority. At the same time, it showed a higher oral bioavailability compared with MPC, with AUC0-∞ of 73.47 µg•h•mL⁻¹ vs. 63.48 µg•h•mL⁻¹. This process for solidifying powder with PVPP is simple and convenient.

[Relationship between hepatic drug-metabolizing enzymes CYP450 and traditional Chinese medicine-induced hepatotoxicity].

In recent years, with the emergence of new methods and technologies in traditional Chinese medicines metabolism, the relationship between medicine metabolism and cytochrome P450 has gradually been revealed. The research on P450 drug metabolizing enzymes can be used to predict the side effects of traditional Chinese medicines and explore the relationship between compatibility of medicines and toxicity reducing and efficacy enhancing. This paper aims to summarize the progress of CYP450 research, the mechanism of hepatic drug-metabolizing enzymes in the process of drug-metabolism and the relationship between CYP450 and medicine hepatotoxicity. Furthermore, we set out the regulation effects of typical traditional Chinese medicines on CYP450 to provide a reliable basis for the rational use of Chinese medicines.

Optimization and anticancer activity in vitro and in vivo of baohuoside I incorporated into mixed micelles based on lecithin and Solutol HS 15.

Baohuoside I, extracted from the Herba epimedii, is an effective but a poorly soluble antitumor drug. To improve its solubility, formulation of baohuoside I-loaded mixed micelles with lecithin and Solutol HS 15 (BLSM) has been performed in this study. We performed a systematic comparative evaluation of the antiproliferative effect, cellular uptake, antitumor efficacy, and in vivo tumor targeting of these micelles using non-small cell lung cancer (NSCLC) A549 cells. Results showed that the obtained micelles have a mean particle size of around 62.54 nm, and the size of micelles was narrowly distributed. With the improved cellular uptake, BLSM displayed a more potent antiproliferative action on A549 cell lines than baohuoside I; half-maximal inhibitory concentration (IC50) was 6.31 versus 18.28 µg/mL, respectively. The antitumor efficacy test in nude mice showed that BLSM exhibited significantly higher antitumor activity against NSCLC with lesser toxic effects on normal tissues. The imaging study for in vivo targeting demonstrated that the mixed micelles formulation achieved effective and targeted drug delivery. Therefore, BLSM might be a potential antitumor formulation.

[Study on totai flavonoids of Epimedium assisted with soybean polysaccharide spray-drying powder].

In order to evaluate the characteristics of the spray drying of total flavonoids of Epimedium extracts assisted with soybean polysaccharide, a certain percentage of soybean polysaccharide or polyvidone were added to the total flavonoids of Epimedium extract to conduct the spray drying. The effect of soybean polysaccharides against the wall sticking effect of the spray drying was detected, as well as the powder property of total flavonoids of Epimedium spray drying powder and the dissolution in vitro behavior of the effective component. Compared with the total flavonoids of Epimedium spray drying powder, soybean polysaccharide revealed a significant anti-wall sticking effect. The spray drying power which had no notable change in the grain size made a increase in the fluidity, improvement in the moisture absorption and remarkable rise in the dissolution in vitro behavior. It was worth further studying the application of soybean polysaccharide in spray drying power of traditional Chinese medicine.

[Study on solid dispersion of precipitated calcium carbonate-based oleanolic acid].

Oleanolic acid-precipitated calcium carbonate solid dispersion was prepared by using solvent evaporation method. The microscopic structure and physicochemical properties of solid dispersion were analyzed using differential scanning calorimetry and scanning electron microscopy (SEM). And its in vitro release also was investigated. The properties of the precipitated calcium carbonate was studied which was as a carrier of oleanolic acid solid dispersion. Differential scanning calorimetry analysis suggested that oleanolic acid may be present in solid dispersion as amorphous substance. The in vitro release determination results of oleanolic acid-precipitated calcium carbonate (1: 5) solid dispersion showed accumulated dissolution rate of.oleanolic acid was up to 90% at 45 min. Accelerating experiment showed that content and in vitro dissolution of oleanolic acid solid dispersion did not change after storing over 6 months. The results indicated that in vitro dissolution of oleanolic acid was improved greatly by the solid dispersion with precipitated calcium carbonate as a carrier. The solid dispersion is a stabilizing system which has actual applied value.

[Study on porous starch as solid dispersion carrier of total Epimedium flavonoids].

In order to evaluate the characteristic of porous starch (PS) as the solid dispersions carrier of the total Epimedium flavonoids (TEF), the PS was used. The dissolution of icariin was selected as an indicator to analyze the differences of dissolution between TEF and its solid dispersion. TEF was characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and X-ray powder diffraction (XRD). Solid dispersion was irregular block and no powder characteristics of TEF and PS could be seen in SEM, DSC and XRD analysis suggested that TEF may be present in solid dispersion as amorphous substance. The dissolution rate of icariin has been improved significantly when the proportion of TEF and PS was 1:2. PS as a traditional solid dispersion carrier is worthy of further study.

[Study on sustained release preparations of Epimedium component].

The formulation for sustained release tablet of Epinedium component was selected and the evaluation equation of in vitro release was established. The liquidity of component was improved with the help of colloidal silica aided by spray drying, which would be the main drug in the sustained release tablets. Dissolution was selected as an evaluation index to investigate skeletal material type, fillers, impact porogen, lubricants and other materials on the quality of sustained release tablet. The sustained release tablets were prepared by dry compression. Formulation of sustained release preparations was main drug 35%, HPMC K(4M) 20% and HPMC K(15M) 10% as skeleton material, MCC 31% as filler, PEG6000 2% as porogen and magnesium stearate 2% as lubricant. The sustained release tablets released up to 80% in 8 h. The zero order equation, primary equation and Higuchi equation could simulate the release characteristics of sustained release tablets in vitro, the correlation coefficients r were larger than 0.96. The primary equation was most similar in vitro release characteristics and its correlation coefficient r was 0.9950. The preparation method is simple and the results of formulation selection are reliable. It can be used to guide the production of Epimedium component sustained release preparations.

[Advance in studies on anti-cancer activity and mechanism of flavonoids].

Flavonoids are natural products that are ubiquitous in the natural world, with wide physiological activities and low toxic and side effects. In recent years, their anti-tumor effect has caused widespread concern and studies. According to the findings, flavonoids have prominent effects in preventing and treating lung cancer, breast cancer, colon cancer, prostate cancer, liver cancer, leukemia, ovarian cancer, gastric cancer and so on. Their anti-tumor mechanisms mainly include anti-oxidation, anti-free radical, induction of apoptosis of cancer cells, impact on cell cycle, immune regulation, inhibition of tumor angiogenesis, inhibition of COX-2, inhibition of telomerase activity and so on. This article focuses on the advance in domestic and foreign studies on anti-cancer activity and mechanism of flavonoids, in order to provide theoretical basis and research ideas for the further development and clinical application of flavonoids.

[Evaluation on contribution rate of each component total salvianolic acids and characterization of apparent oil/water partition coefficient].

The difference between three representative components of total salvianolic acids in pharmacodynamic activity were compared by three different pharmacological experiments: HUVECs oxidative damage experiment, 4 items of blood coagulation in vitro experiment in rabbits and experimental myocardial ischemia in rats. And the effects of contribution rate of each component were calculated by multi index comprehensive evaluation method based on CRITIC weights. The contribution rates of salvianolic acid B, rosmarinic acid and Danshensu were 28.85%, 30.11%, 41.04%. Apparent oil/water partition coefficient of each representative components of total salvianolic acids in n-octyl alcohol-buffer was tested and the total salvianolic acid components were characterized based on a combination of the approach of self-defined weighting coefficient with effects of contribution rate. Apparent oil/water partition coefficient of total salvianolic acids was 0.32, 1.06, 0.89, 0.98, 0.90, 0.13, 0.02, 0.20, 0.56 when in octanol-water/pH 1.2 dilute hydrochloric acid solution/ pH 2.0, 2.5, 5.0, 5.8, 6.8, 7.4, 7.8 phosphate buffer solution. It provides a certain reference for the characterization of components.

[Solidification of volatile oil with graphene oxide].

To evaluate the properties of solidifying volatile oil with graphene oxide, clove oil and zedoary turmeric oil were solidified by graphene oxide. The amount of graphene oxide was optimized with the eugenol yield and curcumol yield as criteria. Curing powder was characterized by differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). The effects of graphene oxide on dissolution in vitro and thermal stability of active components were studied. The optimum solidification ratio of graphene oxide to volatile oil was 1:1. Dissolution rate of active components had rare influence while their thermal stability improved after volatile oil was solidified. Solidifying herbal volatile oil with graphene oxide deserves further study.

[Ultrasound assisted the enzymolysis of ginsenosides to prepare pare ginseng saponin Compound K].

To prepare ginseng saponin Compound K with ultrasound-assisted total zymolytic ginseng saponins. The conversion rate was taken as the index to detect the pre-treatment factors such as ultrasonic power and ultrasonic time, as well as the impact of enzymatic factors, such as pH value, temperature, concentration of substrate, dosage of enzyme and reaction time, on the conversion rate. The response surface method was used to optimize the preparation conditions. The enzymolytic products were identified with MS, 1H-NMR and 13C-NMR. The results showed that the optimum conditions of the ultrasound-assisted enzymolysis were 250 W for ultrasonic power, 15 min for ultrasonic time, 5.5 for enzymolytic pH, 50 degrees C for enzymolytic temperature, 36 h for enzymolytic time, 4:5 for enzymolytic dosage: substrate and 1.0 g x L(-1) for concentration of substrate. The relative molecular mass of reaction products was 622.4. Therefore, the nuclear magnetic map verified that the reaction product was rare ginseng saponin Compound K. Under the above conditions, based on the total zymolytic ginseng saponins, the conversion rate of rare ginseng saponin Compound K was 6.91% in proportion to the total of ginsenosides. The process features gentle reaction conditions, high conversion rate and simple and reliable process, which is suitable for industrial production.

[Effect of suet oil on formation of self-assembled micelles of flavonoids in Epimedium].

In this paper, the action of suet oil in the preparation of self-assembled micelles of the active flavonoids in Epimedium in the simulated human environment was researched. Twelve suet oil samples were collected from different growing areas and different positions of sheep or goat to simulate the formation of micelles. Then the effects of the fatty acids in suet oil on the preparation of self-assembled micelles were studied furthermore. The results showed that the micelles had a dispersed state and spherical smooth surface. To compare the diameter, potential, encapsulation efficiency and drug loading of the 12 batches micelles, the micelles prepared by the suet oil from Qinghai were more stable and had a higher encapsulation efficiency. The fatty acids in suet oil could promote the formation of self-assembled micelles, but the whole suet oil had a better effect. Above all the study, we confirmed that the suet oil promoted the formation of self-assembled micelles of the flavonoids in Epimedium, it laid foundation for further research about increasing the efficacy of Epimedium and improved the absorption of the active flavonoids in Epimedium.

[Compared with colloidal silica and porous silica as baicalin solid dispersion carrier].

OBJECTIVE: To compare the dissolution characteristics of colloidal silica and porous silica as the solid dispersion carrier, with baicalin as the model drug. METHOD: The baicalin solid dispersion was prepared by the solvent method, with colloidal silica and porous silica as the carriers. In the in vitro dissolution experiment, the solid dispersion was identified by scanning electron microscopy, differential scanning and X-ray diffraction. RESULT: The solid dispersion carriers prepared with both colloidal silica and porous silica could achieve the purpose of rapid release. Along with the increase in the proportion of the carriers, the dissolution rate is accelerated to more than 80% within 60 min. Baicalin existed in the solid dispersion carriers in the non-crystalline form. CONCLUSION: The release behaviors of the baicalin solid dispersion prepared with two types of carrier were different. Among the two solid dispersion carriers, porous silica dissolved slowly than colloidal silica within 60 min, and they showed similar dissolutions after 60 min.

[Preparation of baicalin-chitooligosaccharide compound and its characterization].

To apply chitooligosaccharide in the preparation of baicalin compound, in order to increase the drug dissolution in vitro, and investigate the basic property of the compound. Baicalin-chitooligosaccharide compound was prepared by using the solvent method. The structure and physicochemical properties of compound were analyzed by using differential scanning calorimetry (DSC), scanning electron microscopy (SEM), X-ray powder diffraction (XRD) and infrared vibrational spectrum (IR), and its dissolution behavior was also investigated. The results showed that the compound prepared at baicalin-chitooligosaccharide molar ratio of 1 : 1 could significantly improve the dissolution of baicalin. The results of DSC and XRD analysis suggested that baicalin may exist in an amorphous state. IR results indicated the interaction between baicalin and chitooligosaccharide. The baicalin-chitooligosaccharide compound could significantly improve dissolution in vitro of drug.

[Effects of micronization on micromeritics properties of baicalin].

Baicalin extremely fine powder was made by using ball-mill and the effect of micronization on the micromeritics properties of baicalin was studied and analyzed. The microstructures of baicalin ordinary and extremely fine powder were compared by scanning electron microscope, differential scanning calorimeter and X-ray diffraction and the powder characteristic of them was investigated. The hygroscopicity was studied. The effect of micronization on the dissolution of baicalin was investigated. The results showed that the chemical constituents of baicalin were not changed after micronization with better compressibility. It was confirmed that micronization technology had a certain application value in promoting the insoluble component of baicalin absorption with higher dissolution.