Intestinal OCTN2-and MCT1-targeted drug delivery to improve oral bioavailability

Various drug transporters are widely expressed throughout the intestine and play important roles in absorbing nutrients and drugs,thus providing high quality targets for the design of prodrugs or nanoparticles to facilitate oral drug delivery.In particular,intestinal carnitine/organic cation transporter 2(OCTN2)and mono-carboxylate transporter protein 1(MCT1)possess high transport capacities and complementary distributions.Therefore,we outline recent developments in transporter-targeted oral drug delivery with regard to the OCTN2 and MCT1 proteins in this review.First,basic information of the two transporters is reviewed,including their topological structures,characteristics and functions,expression and key features of their substrates.Furthermore,progress in transporter-targeting prodrugs and nanoparticles to increase oral drug delivery is discussed,including improvements in the oral absorption of anti-inflammatory drugs,antiepileptic drugs and anticancer drugs.Finally,the potential of a dual transporter-targeting strategy is discussed.

Determination of Chlorogenic Acid in Stems of Mussaenda pubescens Ait.f.by High Performance Liquid Chromatography

[Objectives] This study was conducted to establish a method for determination of chlorogenic acid in Mussaenda pubescens Ait.f.[Methods]HPLC used SHISEIDO C_(18) MG Ⅱ column( 5 μm,4.6 mml.D.× 250 mm) as chromatographic column and acetonitrile-0.4% phosphoric acid solution( 9∶91) as mobile phase.The separation was performed at a flow rate of 1.0 ml/min and a column temperature of 30 ℃,and the detection wavelength was set at 327 nm.[Results]Chlorogenic acid had a good linear relation in the range of 0.254 7-2.547 5 μg( R2= 0.999 9).The recovery rate was 97.8%,RSD = 1.82%( n = 9).[Conclusions]The content of chlorogenic acid in M.pubescens was determined by ultrasonic extraction and HPLC.The method was simple,stable and reliable and could be used for the quality control of M.pubescens.

Identification and Analysis of Chemical Components in Zhideke Granules by UPLC-Q-Orbitrap HRMS

[Objectives]To identify and analyze chemical components in Zhideke Granules by ultra performance liquid chromatography-quadrupole/electrostatic field orbitrap high resolution mass spectrometry(UPLC-Q-Orbitrap HRMS).[Methods]Zhideke Granules were isolated on a Thermo Hypersil Gold C18 column(2.1 mm×100 mm,1.9μm).The mobile phase was 0.1%formic acid acetonitrile and 0.1%formic acid aqueous solution(containing 10 mmol ammonium acetate)with gradient elution.Chemical components in Zhideke Granules were rapidly isolated and identified by HRMS in the positive and negative ion mode with full scan data-dependent two stage threshold-triggered mass modes(Full MS/dd-MS2).[Results]The secondary fragment ion information of the target compound was selected and compared with the compound reported in the databases and related literatures for further confirmation.In total,30 chemical compounds were identified,including 12 flavonoids and glycosides,9 organic acids,3 nitrogen-containing compounds,and 6 other components.[Conclusions]In this study,the UPLC-Q-Orbitrap HRMS was used for the first time to analyze the chemical components in Zhideke Granules.It is intended to provide a reference for the quality evaluation and further study of pharmacodynamic materials of Zhideke Granules.

Research Progress of Triterpenoid Secondary Metabolites in Cucurbitaceae Plants

In this paper,the advances in study on triterpenoids in Trichosanthes,Hemsleya,Gynostemma,Actinostemma and Siraitia Merr. plants were reviewed.Terpenoids are the main secondary metabolites of Cucurbitaceae and have obvious pharmacological activity. It is noteworthy that in these plants,there are a variety of triterpenoids,which are diverse in structure. Triterpenoid saponins have greater potential for development.

Discussion on the Quality Evaluation Method of Traditional Chinese Medicine Compound Preparations

As an important representative of the modernization of the Chinese medicine industry,traditional Chinese medicine(TCM)compound preparations are an indispensable part of the development of TCM.The complex ingredients and unclear action mechanism of TCM compound preparations restrict the development of TCM.In line with this problem,the modern TCM research has made extensive remarkable achievements.From the single indicator in the past to multiple indicator,the research on the combination of TCM fingerprints and pharmacodynamics also has made great progress.The introduction of quality evaluation methods such as the"quantitative analysis of multi-components by a single marker","dose-effect"indicator,"Bioactive Equivalent Combinatorial Components"(BECCs)and TCM quality markers have brought new ideas for quality control of TCM compound preparations.

Study on Chemical Constituents of Ethanol Extract from Yao Medicine Cissampelopsis spelaeicola

[Objectives]The research aimed to study the chemical constituents of ethanol extract from Yao medicine Cissampelopsis spelaeicola.[Methods]The petroleum ether,ethyl acetate and n-butanol fractions from 75%ethanol extract of C.spelaeicola were isolated and purified by silica gel,SephadexLH-20 gel column and AB-8 macroporous resin column,etc.The structures of the compounds were analyzed and identified by physicochemical properties and spectral data(mass spectrometry,hydrogen spectrum and carbon spectrum).[Results]Twelve compounds were isolated and identified from 75%ethanol extract of C.spelaeicola.β-sitostero(I)and stigmasterol(II)were isolated from petroleum ether fraction;p-hydroxybenzoic acid(III),β-daucossterol(IV),protocatechuic acid(V),6β-hydroxyeremophi-7(11)-en-12,8β-olide(VI),10β-hydroxyeremophil-7(11)-en-8,12-olide(VII),10β-hydroxyeremophi-7(11),8(9)-dien-8,12-olide(VIII),quercetin(IX),hyperin(X)and 4α-hydroxy-eudesman-11-ene(XI)were isolated from ethyl acetate fraction;quercetin-3-O-robinobioside(XII)was isolated from n-butanol fraction.Compounds I-XII were isolated from C.spelaeicola for the first time.[Conclusions]The study can lay material foundation for activity study of C.spelaeicola.

Experimental Study of Pratia Extact on Acute Liver Injury in Mice

[Objectives] This study was conducted to observe the protective effect of Pratia extract on acute liver injury in mice.[Methods] Mice were randomly divided into 6 groups according to body weight,10 in each group: normal control group,ethanol-induced/CCl4 liver injury model,low-dose,middle-dose and high-dose Pratia extract groups,and bifendatatum group.Except the blank group,other groups were given 50% ethanol intragastrically at a dose of 12 ml/kg to cause acute alcoholic liver injury,or intraperitoneally injected with 10% CCl4 soybean oil solution to cause acute CCl4 liver injury.The serum ALT and AST activity were measured as well as liver SOD and MDA concentrations.[Results] Pratia extract effectively reduced serum ALT and AST,decreased MDA content and increased liver tissue SOD activity.[Conclusions] Pratia extract has certain protective effect on acute liver injury.

Anti-tumor Effect and Mechanism of Pratia Extract on H22 Tumor-bearing Mice

[Objectives]This study was conducted to investigate the inhibitory effect of pratia extract on H22 tumor-bearing mice and the effects on immune organs.[Methods]With the application of H22 liver tumor-bearing mice as an animal model,the animals were divided into such three Pratia extract groups as the high,medium and low dose groups(400,200 and 100 mg/kg)and cyclophosphamide CTX group(20 mg/kg).15 d after the administration,the animals were killed by cervical dislocation,and the tumors,thymuses and spleens were taken and weighed,followed by the calculation of the tumor inhibitory rate and the thymus and spleen index,and the serum tumor necrosis factor-α(TNF-α)and interleukin-2(IL-2)levels were determined by ELISA assay.[Results]The inhibitory rates were 54.1,32.6 and 8.2%,respectively,and there were significant differences from the model group(P<0.05);and the spleen index of the tumor-bearing mice was reduced,while the thymus index was improved.The serological results showed that the drug-administrated groups significantly improved the IL-2 levels in the tumor-bearing mice,but had no effects on TNF-α.[Conclusions]Pratia extract has an antitumor effect on H22 tumor-bearing mice,and show certain dose-effect relationship,and its mechanism may be related to enhancing the immune function in tumor-bearing mice by regulating IL-2.

Bioinformatic Analysis of ARF7 in Huperzia serrata

[Objectives]This paper aims to study the function of the ARF7 gene family of Huperzia serrata.[Methods]Based on the full-length transcriptome sequencing results of H.serrata,the unigenes of 17 H.serrata ARF7 candidate genes were analyzed using biogenetics technology.[Results]The molecular weight of the ARF7 proteins ranges from 11.28 to 608.54 kDa.HsARF7-4,HsARF7-5,HsARF7-8,HsARF7-9,HsARF7-10,HsARF7-13,HsARF7-16 and HsARF7-17 are basic proteins;all the proteins are unstable;except that HsARF7-6 and HsARF7-15 are hydrophilic,the rest are lipophilic proteins;there are 197 types of cis-acting elements,and 17 of the proteins contain as more as 20 acting elements such as GTGANTG10,CBFHV,GT1CONSENSUS,NODCON2GM,CAATBOX1,MYBCORE,GATABOX,WRKY71OS and RAV1AAT;HsARF7-1,HsARF7-2,HsARF7-4,HsARF7-6,HsARF7-8,HsARF7-10,HsARF7-12,HsARF7-14 and HsARF7-16 all have the 6 types of motif predicted;the proteins have domains such as PABP-1234 super family,RRM_SF super famliy,PRK10263 super family,AUX_IAA super family and MFS super family;the proteins all can cross cell membrane and have no signal peptide,and they are all located in the nucleus.On the level of secondary structure,the proportion ofβ-sheet is the smallest.In HsARF7-7 and HsARF7-9,α-helix has the largest proportion,and in the remaining proteins,random coil has the largest proportion;and tertiary structure prediction found that HsARF7-1,HsARF7-2,HsARF7-4,HsARF7-14 and HsARF7-17 have a tertiary structure of polyadenylate-binding protein,and HsARF7-7 has a tertiary structure of auxin-induced protein iaa4.[Conclusions]The above analysis results can provide a certain theoretical basis for further research on the biological function and regulatory mechanism of the ARF gene of H.serrata in the future,and provide a reference for the study of the growth and development of H.serrata.

Study on Chemical Composition of the Ethyl Acetate Extract of Pratia

[Objectives]This study was conducted to further reveal the chemical basis of the anti-tumor pharmacological activity of pratia.[Methods]The chemical composition of the ethyl acetate extract of pratia was systematically studied by macroporous resin column chromatography,silica gel column chromatography and Sephadex LH-20 repeated silica gel column chromatography and spectroscopy.[Results]Eight compounds were separated from the ethyl acetate extract of pratia,among which six were identified,namely diosmin (1),diosmetin (2),linarin (3),quercetin (4),apigenin (5) and luteolin (6).All the compounds were separated from this plant for the first time.[Conclusions]This study provides reference for the identification of the physiological activity of pratia.

Study on Response Surface Methodology Optimization for Extraction Process of Cyclocarya paliurus Extract and Its Blood Sugar-lowering Effect

[Objectives]This study was conducted to discuss the mechanism of the blood sugar-lowering effect of Cyclocarya paliurus extract.[Methods]With C.paliurus leaves as the raw material,the ethyl acetate-butyl acetate microwave extraction process of C.paliurus was studied.With the yield of C.paliurus extract as an evaluation index,single-factor experiments were carried out on such 6 factors as the dry C.paliurus leaf powder size,solid-to-liquid ratio,extraction time,microwave frequency,microwave power,and microwave extraction time,and the extraction and purification process was further optimized by response surface analysis.The normal mice and the hyperglycemic mice modeled by alloxan were injected with C.paliurus extract to study the blood sugar-lowering effects of different groups of C.paliurus extract.[Results]The optimal process combination for the extraction of C.paliurus leaves was obtained:dry C.paliurus powder size 90-100 mesh,solid-to-liquid ratio 1∶20(g/ml),extraction time 192 min,microwave frequency 2500 MHz,microwave power 490 W,and extraction time 248 s.Under these conditions,the yield of C.paliurus extract reached the maximum,95.10%,reaching 99.83%of the predicted value.The blood sugar-lowering test on mice showed that the C.paliurus extract had a good effect on lowering blood sugar,indicating that C.paliurus extract can improve the free radical scavenging capacity to a certain extent.[Conclusions]This study provides certain reference for the in-depth study of the physiological effects of C.paliurus extract and the comprehensive development and utilization of C.paliurus extract.

Research Progress on the Application of Graphene in the Field of Biomedicine

Graphene is the thinest nanomaterial known in the world,which has unique electronic mobility,super specific surface area,high mechanical strength,excellent corrosion resistance and surface chemical structure.Due to its special nanostructure and excellent physical and chemical properties,graphene has a broad application prospect in the fields of electronics,optics,magnetism,biomedicine,catalysis,energy storage and sensors.In order to better develop and utilize graphene data,this paper reviewed the structural characteristics of graphene,as well as its research progress in biosensors,bio-imaging,aerogel and other biomedical fields,hoping to provide scientific basis for better development of graphene and the development of graphene pharmaceutical products.

Advances in Research of Cichorium intybus L.in Preventing and Treating Hyperuricemia

With the rapid social development,people s living habits have undergone great changes.Fast-paced lifestyles have led to an increase in people s unhealthy living habits,especially in diet,such as unreasonable dietary structure and irregular diet.In this situation,the number of patients with hyperuricemia has also been increasing,and the hyperuricemia trend is becoming younger.Clinically,western medicines for lowering uric acid are commonly used,which are not safe and have the risk of injuring the liver and kidney functions.Cichorium intybus L.as a medicinal and edible material,plays an important role in treating the hyperuricemia.Recent studies have shown that C.intybus has significant effect of lowering the uric acid.This paper reviewed the experimental studies of C.intybus inhibiting uric acid production and promoting uric acid excretion,discussed its therapeutic effects and action mechanism,to provide a reference for the development of C.intybus drugs for lowering the uric acid.

Application of Rubidium in the Field of Medicine and Health

With the continuous development of science and technology,the role of rare and precious metal resources in medical treatment,economy and strategy has become increasingly prominent.This paper reviewed the application research of rare precious metal rubidium(Rb)in the field of medicine and health,mainly including the application significance of Rb in the field of medical and health,typical applications and problems in the field of medicine and health,and the important research significance of the research and development of medicine.

Development of a wheat aphid population dynamics model based on cusp catastrophe theory

Aphids are a major global wheat,pest that can cause considerable loss of yield.Modeling of aphid population dynamics is an integral part of management strategies to manage or control aphid populations.In this paper,first,a wheat aphid population dynamics model was developed based on a logistic model and theⅠlollingⅢfunctional response,which includes three factors:temperature,natural enemies and insecticide.Second,this model fitted with a cusp catastrophe model to describe how abrupt changes in the wheat aphid population were influenced by these factors,Finally,the system was validated with field data from 2016 to 2018.The bifurcation set of the cusp catastrophe model was deemod to be the quantified dynamic control threshold,so an outbreak of aphid's population can be explained according to the variation of control variables.In short,this aphid population model was successfully validated on survey data,which can be used to guide the prevention and control of aphids.

Analysis and control of a non-smooth population model with impulsive effects

In this paper, a non-smooth population model with impulsive effects is proposed by combining discontinuity and non-smoothness. According to the qualitative theory of differential equations, the global analysis of the model is discussed. Using the theory of impulsive differential equations, the existence conditions of order one periodic solution are obtained. And the impulsive controllers are designed to make the pest populations stay at the refuge level. Some simulations are carried out to prove the results.

Optimal harvest of an interval model of carbon sink fisheries with multi-trophic levels

Considering the uncertainty of kelp-abalone-sea cucumber population, an interval model of carbon sink fisheries with multi-trophic levels is proposed. The equilibria of the model are identified and the corresponding stabilities are discussed. And the existence of bionomic equilibrium of the model is investigated. Next the optimal controller is designed to obtain the optimal harvest using Pontryagin＇s maximum principle. Numerical simulations are carried to prove the results.

BIFURCATION CONTROL OF A PREDATOR-PREY MODEL BASED ON NUTRITION KINETICS

The existence conditions of Hopf bifurcation for a predator prey model based on nutri- tion kinetics are given. The two results may appear as follows： one is that the model has a stable periodic trajectory from Hopf bifurcation, which shows the system is in an eco- logical balance; the other is that periodic trajectory from Hopf bifurcation is unstable, which indicates the system is in a sharp or catastrophic loss of stability. For the latter, a bifurcation controller is designed to make the periodic trajectory stable. Finally, some simulations are carried out to prove the results.