Learning and memory decline is an important manifestation of aging, seriously affecting the health and life quality of the elderly. Aging-related learning and memory decline is often accompanied by decreased levels of norepinephrine, dopamine and serotonin neurotransmitters in the relevant brain regions. Monoamine neurotransmitters in different brain regions bind to receptors and regulate synaptic plasticity, which play an important role in learning and memory. This article reviews the changes of monoamine neurotransmitters in different brain regions, the mechanisms in regulation of learning and memory, and the factors causing abnormal levels of neurotransmitters in the process of aging in order to better understand the mechanisms of senile learning and memory decline to facilitate drug research.

Integrin is a class of important cell surface molecules involved in cell proliferation, differentiation, adhesion and migration processes, which play an important role in a variety of pathological processes. In recent years, with the research in integrin regulation and the treatment of tumor, tissue fibrosis, and other fields, integrin has gradually become a new target in the diagnosis and treatment of diseases. In this article, we provide a summary on the advances of the regulation of integrin gene expression.

The acquired immunodeficiency syndrome (AIDS) is a serious infectious disease infected by human immunodeficiency virus type 1 (HIV-1). HIV-1 nucleocapsid protein 7 (HIV-1 NCp7) plays an important role in the progress of virus reverse transcription and integration. Thus, the central role and conservative nature of the NCp7 protein make it an attractive target for development of novel anti-HIV agents. This review summarizes the research progress of HIV-1 NCp7 inhibitors in the past decade.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease of the brain. Due to the uncertain pathogenesis, prevention and treatment of AD is difficult. Clinic symptoms of AD including progressive loss of memory and spatial orientation are rooted in synaptic and neuronal loss. Unsuccessful clinical trials of several candidate drugs based on amyloid hypothesis and tau hypothesis have led to exploration of new approaches. Neuro-inflammation characterized by dysfunction in microglia is believed to be the hallmark of AD and also the initiator of downstream responses in neurodegeneration. Alleviate microglia activation and neuro-inflammation may delay AD development. In this paper, we describe the current literature on interaction between microglia and neuron, and review the progress in AD drug discovery and neuro-inflammatory inhibitors for treatment of AD.

As a new carrier of intercellular information, the exosomes is widely regarded as a natural drug carrier for its extensive distribution, non-immunity and targeting in human body. Chinese herbal drugs act at multiple targets and through different pathways in the prevention and treatment of diseases, but the preparation is relatively simple, there is a low solubility in the effective ingredients and low bioavailability, which limit the efficacy of the medicine. Using the new drug delivery approach of the exosomes, it is better to deliver the effective components to target cells. In this review, we reviewed the biological characteristics of exosomes and its application as a carrier of Chinese herbal drugs.

This study was designed to investigate the effect of Huangqin Tang (HQT) on gut microbiota of ulcerative colitis (UC) rats, and to explore the relationship between Huangqin Tang and ulcerative colitis and gut microbiota. Fifteen male Wistar rats were randomly divided into control group, trinitrobenzene sulfonic acid (TNBS) group and TNBS + HQT group. The model of UC rats with cell immunoreactivity was made established using the compound method (TNBS and ethanol). After 10 days of administration, 15 fecal samples were collected and total DNA was extracted from the samples to get total DNA. The primers were designed on bacterial 16S rRNA V3-V4 region sequences and Illumina Miseq platform was used for high-throughput sequencing. It was found that the principal component analysis (PCA), the principal co-ordinates analysis (PCoA) and the non-metric multidimensional scale analysis (NMDS) based on the Beta diversity distance showed that there were significant differences in the composition of the gut microbiota among the three groups (P < 0.05). Compared with the control group, the Lactobacillus of the TNBS group was significantly decreased (P < 0.05), and the Lachnospiraceae, Desulfovibrio, Roseburia, Ruminococcaceae were significantly increased (P < 0.05). Compared with the TNBS group, the Lactobacillus in the TNBS + HQT group was significantly increased (P < 0.01), and the Alistipes was significantly decreased (P < 0.05). The study suggests that the Huangqin Tang plays a role in the treatment of ulcerative colitis partially through regulating the structure of the gut microbiota.

The aim of this study was to investigate the regulatory effect of the total glycoside extracted from leaves of Rehmannia (TLR) and Dihuangye total glycoside capsule (DTG) on intestinal microflora in diabetic nephropathy rats. Forty-eight rats were randomly divided into the control group (C), model group (M), Huangkui capsule group (0.75 g·kg^-1·d^-1, HK), irbesartan group (27 mg·kg^-1·d^-1, YX), TLR low dose group (4.3 g·kg^-1·d^-1, DHYL), TLR high dose group (7.2 g·kg^-1·d^-1, DHYH), DTG low dose group (216 mg·kg^-1·d^-1, JNL), DTG high dose group (360 mg·kg^-1·d^-1, JNH). Rat model of diabetic nephropathy was induced by intraperitoneal injection of small dose of streptozotocin (45 mg·kg^-1, STZ) and feeding high-fat diet and 5% glucose drinking water. After oral administration for two weeks, the 16S rDNA sequencing method was used to study the effects of the TLR and DTG on intestinal flora in diabetic nephropathy rats. The results showed that compared with the control group, the intestinal flora of diabetic nephropathy rats had changed from phylum units to the genus units. Moreover, the proportion of lactobacilli in the intestinal bacteria of the model group was significantly decreased, and the proportion of lactobacilli in the administration group was increased, especially the YX group, TLR low dose group and DTG low dose group. The data suggest that the total glycosides of Rehmannia glutinosa improved the disorder of intestinal flora in STZ-induced diabetic nephropathy rats.

The aim of present study was to explore the effect of triptolide derivative LB-1 on imiquimod (IMQ) induced psoriasiform inflammation in BALB/c mice, and to investigate the immune mechanism of LB-1 in the prevention and treatment of psoriasis. In the present study, topical application of IMQ for seven days induced the psoriasiform inflammation in BALB/c mice. This is a promising mouse model of psoriasis for the natural immune reaction compared to those induced by xenograft, trangenic or gene knockout. psoriasis area and severity index (PASI) score, hematoxylin-eosin (HE) staining and flowcytometry were employed to investigate the changes of psoriasiform inflammation, histopathological response and percentage of T cells, respectively. The result showed that LB-1 significantly attenuated the psoriasiform inflammation. Com-pared with model group, PASI score were decreased in the LB-1 group. In the isolated immunocytes of spleen, LB-1 decreased percentage of CD8⁺ (P < 0.01) T cells and increased the ratio of CD4⁺/CD8⁺ T cells at the dosage of 2 mg·kg^-1 (P < 0.01), whereas LB-1 raised percentage of CD4⁺ T cells and CD3⁺ T cells at the dosage of 4 mg·kg^-1. In conclusion, the present study demonstrated that LB-1 attenuated psoriasiform inflammation induced by imiquimod in BALB/c mice. The mechanism of LB-1 action may be related to change percentage of CD4⁺ T, CD8⁺ T cells in the spleen. These results provide a basis for LB-1 or other triptolide derivative in the intervention of psoriasis in the future.

This study was conducted to investigate the effects of Danlou (correspondence between prescription and syndrome) tablet and Shengmai capsule (non-correspondence between prescription and syndrome) on mini-swine phlegm-stasis syndrome of coronary heart disease (CHD). 24 mini-swines were randomly divided into normal control group, model group, Danlou tablet group (0.24 g·kg^-1) and Shengmai capsule group (0.14 g·kg^-1). Phlegm-stasis syndrome of coronary heart disease was established by high-fat feeding and coronary intervention balloon injury. After 8 weeks of administration, blood lipid levels and blood rheology was detected. Echocardiography was used to examine the changes in heart function, and the extent of infarction was determined by nitro blue tetrazolium (NBT) staining method. The main symptoms, accompanied symptoms, tongue and pulse signs of the coronary heart disease mini-swine with phlegm-stasis syndrome were observed according to the symptom-graded scoring method. The results showed that Danlou tablet decreased serum total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) (P < 0.05 or P < 0.01), improved the blood rheology (P < 0.01) and cardiac function, increased the left ventricular ejection fraction (EF) and fraction shortening (FS) value (P < 0.05 or P < 0.01), reduced the myocardial infarction area/ventricular area (P < 0.01), significantly lowered the scores of four diagnosis in traditional Chinese medicine (P < 0.05 or P < 0.01). Shengmai capsule improved the hemorheology indices (P < 0.05 or P < 0.01), EF and FS value (P < 0.05), reduced the tongue and pulse signs scores (P < 0.05). However, Shengmai capsule failed to show therapeutic effects on blood lipid metabolism, the myocardial infarction area and primary symptom and syndrome score. The results suggest that as a drug for the treatment of Qi and Yin deficiency syndrome of CHD, Danlou tablet has limited therapeutic effects on phlegm-stasis syndrome of CHD. Only by the prescription correspondence with syndrome, using drug for the treatment of phlegm-stasis syndrome of CHD to treat phlegm-stasis syndrome of CHD, the prescription has a comprehensive therapeutic effect.

This study was designed to investigate the inhibitory effects of regorafenib (REG) on the catalytic activities of 12 kinds of human UGT isoforms and human liver microsomes (HLM) in vitro. The broader potential of REG to perpetrate drug-drug interactions (DDI) arising from UGT enzyme inhibition is predicted by in vitro-vivo extrapolation (IV-IVE). Fifty mixed HLM and 12 kinds of recombinant UGTs were utilized as enzyme sources to evaluation the inhibitory effects of REG against UGTs. 4-Methylumbelliferone (4-MU) as a nonselective substrate of UGTs except for UGT1A4, N-(3-carboxypropyl)-4-hydroxy-1, 8-napht-halimide (NCHN) and N-butyl-4-(4-hydroxyphenyl)-1, 8-naphthalimide (NPHN) as the specific fluorescent substrate of UGT1A1, and trifluoperazine (TFP) as the specific substrate of UGT1A4. The half maximal inhibitory concentration (IC₅₀) was calculated via the nonlinear regression analysis using Graphpad Prism 6.0, the inhibition kinetic types were selected and evaluated based on the intersection location of Lineweaver-Burk plot and Dixon plot, and K_i values were determined by the second plot of slopes. The potential DDI risk based on UGT1A1 inhibition was also evaluated through the in vitro parameters. The results demonstrated that REG displayed strong inhibitory effects against UGT1A1, 1A7, 1A9, and 2B7. The IC₅₀ values were from 0.15 to 6.6 μmol·L^-1 and K_i values from 0.027 to 14 μmol·L^-1. The REG exerted competitive inhibition against UGT1A1-mediated 4-MU-O-glucuronidation and UGT1A1-mediated NPHN-O-glucuronidation, while the inhibition of NCHN-4-O-glucuronide by REG was suited to noncompetitive inhibition in both HLM and recombinant UGT1A1. Likewise, REG exhibited a mixed efficacy in inhibition of UGT1A7-, UGT1A9-, and UGT2B7-catalyzed 4-MU-O-glucuronidation. The AUC ratio of UGT1A1 specific substrates NPHN and NCHN can be increased by 101% to 302% and 13% to 109%, respectively. These results suggest that much caution should be exercised when REG is co-administered with UGT1A1 substrates.

The relationship between PEPT1 (peptide transporter) and drug efficacy has drawn more and more attention in the treatment of disease. PEPT1 represents a promising strategy for improvement of drug bioavailability and an important starting point for clinical rationalization of drug selection. The effect of PEPT1 on transport and pharmacokinetics of amoxicillin was investigated under hypoxia condition at high altitude in rat. The mRNA and protein expressions of PEPT1 were increased by 36.87%, 216.21%, 577.8% and 535.9% respectively in the hypoxia group in the small intestine and kidney of rats. However, the mRNA and protein expressions of PEPT1 were reduced by 43.90% and 84.7% in the liver. Compared with the control group, the AUC, t_max, C_max, MRT and t_1/2 of amoxicillin were significantly enhanced by 312.17%, 63.04%, 110.93%, 67.11% and 16.96% respectively in the hypoxia group, while the CL was significantly decreased by 74.51%. After acute exposure to high altitude, the expressions of drug transporter PEPT1 were distinctly changed in rat tissues, which can affect the pharmacokinetics of amoxicillin.

Using ligustrazine as the leading compound, we designed and synthesized ten novel ligustrazine derivatives, whose structures were determined by ¹H NMR, ¹³C NMR and MS. Inhibitory effects of the new compounds on the proliferation of A549, A549/DDP and HBE cells were detected by MTT assay. The inhibi-tory activity of the synthesized compounds on migration and invasion of A549 cells were evaluated through scratch assay and transwell assay. Mechanism of the inhibition on migration and invasion was investigated by Western blotting. In addition, the cell cycle was analyzed with flow cytometry. The results showed that, both compounds Z8 and Z10 have an anti-proliferative activity, and the potencies of inhibition of tumor-cell migration and invasion were attributed to the down-regulation of MMP-2 and MMP-9. The compounds Z8 and Z10 could also enhance G2/M arrest in A549 cell as revealed by cell cycle analysis.

To investigated the chemical constituents of the roots of Psidium guajava, we isolated seven compounds by silica gel column chromatography.These include oleanane derivatives, 2 α, 3β, 6β, 23-tetrahydroxylurs-12, 20(30)-dien-28-oic acid β-D-glucopyranoside (1), 2α, 3β, 6β, 23-tetrahydroxylurs-12, 18-dien-28-oic acid β-D-glucopyranoside (2), 2α, 3β, 23-trihydroxylurs-12, 18-dien-28-oic acid β-D-glucopyranoside (3), nigaichigoside F1(4), asiaticoside C (5), 2α, 3β, 6β, 19α, 23-pentahydroxylurs-12, 18-dien-28-oic acid β-Dglucopyranoside (6) and 2α, 3β, 19α, 23-tetrahydroxylurs-12-en-28-oic acid (7).Their structures were elucidated on the basis of spectral analysis with reference to the published data.Compound 1 is brand new, compounds 2-6 were first isolated from this plant.The new compound was evaluated for their cytotoxic activity against human hepatoma Bel 7402 in vitro.The results were expressed as the ratio of inhibiting Bel 7402 cells growth by comparing to untreated cells.The new compound (concentration:25 μmol·L^-1) showed the ratio values of 52.5%.

This study was designed to screen the antiemetic components of Euodia rutaecarpa, and elucidate its material basis on the spectrum-effect correlation analysis. The UHPLC-Q-TOF/MS (UHPLC-quadrupole time-of-flight mass spectrometry) technology was used to obtain the fingerprint of Euodia rutaecarpa extracts. The perfusion of copper sulfate was used as a model to study the antiemetic effect by vomiting. The orthogonal partial least squares (OPLS) method was used to analyze the spectrum-effect relationship. The results indicated the following compounds were the potential antiemetic components such as rutin, limonin, narcissoside, chrysoeriol-7-O-rutinoside, hyperoside, isorhamnetin-3-O-β-D-galactoside, 1-methyl-2-undecyl-4(1H)-quinolone, 1-methyl-2-[(Z)-4-nonenyl]-4(1H)-quinolone. This study provides the experimental basis in use of Euodia rutaecarpa in the future, and provides the research methods and ideas for the similar study on the pharmacodynamic material basis of traditional Chinese medicine.

This study was designed to investigate the metabolites of 5F-AMB by human liver microsomes model in vitro. 5F-AMB was added in the reaction mixture to simulate the metabolic process in human hepatocytes in vivo, and then to determine the reaction points and pathways of metabolism by ultra performance liquid chromatography (UPLC) coupled to high resolution mass spectrum (HR-MS). 5F-AMB generated 9 metabolites in total in the human liver microsomes model. Ester hydrolysis, combination of ester hydrolysis and oxidative defluorination, combination of ester hydrolysis and hydroxylation on pentyl chain moiety and combination of ester hydrolysis and hydroxylation on indazole ring moiety reactions were its main metabolic pathways. The method is fast and efficient so that the ester hydrolysis, combination of ester hydrolysis and oxidative defluorination, combination of ester hydrolysis and hydroxylation on pentyl chain moiety and combination of ester hydrolysis and hydroxylation on indazole ring moiety metabolites of 5F-AMB can be used as the suitable and potential biomarkers in the urine samples.

This study aims to establish a novel gene-activated matrix that mimics the structure and function of extracellular matrix (ECM-m-GAM). The structure, mechanical property and release profile were also characterized. Firstly, the liposome/DNA lipoplex (LPD) was modified with cell penetrating peptide TAT. The obtained TAT-LPD was then mixed with RGD grafting hyaluronic acid solution. After addition of the matrix metalloproteinase (MMPs) sensitive crosslinker (HS-MMP-SH), hyaluronic acid was crosslinked and TAT-LPD was encapsulated in the subsequently formed hydrogel. As a result, the cell adhesion factor RGD, MMPs sensitive substrate and the efficient gene transfer vector TAT-LPD were all integrated in the hyaluronic acid hydrogel, which was named as ECM-m-GAM. The release profile of DNA from ECM-m-GAM in different release medium was evaluated with PicoGreen kits. The results suggested that the mean diameter of the spherical TAT-LPD was (263.0 ±4.30) nm. TAT-LPD was successfully encapsulated in ECM-m-GAM, which had the typical porous network structure of hydrogels. The mechanical strength of GAM was enhanced with the increasing of hyaluronic acid content. When the content was 4%, the elastic modulus of GAM reached 1 600 Pa. The highly elastic GAM may be suitable for implantation and tissue regeneration. The DNA release showed significant MMPs sensitive property. Especially, the released DNA still existed in form of nanoparticles. Bone marrow mesenchymal stem cells (BMSCs) were successfully transfected with GAM and the green fluorescent protein was expressed. The results have laid a solid foundation for future study of the cell transfection and tissue regeneration.

Legumain, a kind of asparaginyl endopeptidase, is overexpressed in highly metastatic and highly aggressive tumor, which can undergo an enzymatic hydrolysis of substrates. We proposed a legumain-responsive functional gold nanoparticle (GNP) drug delivery system (GNPs-A & C), which was consist of Ala-Ala-Asn-Cys-Lys (AK) modified GNPs (GNPs-AK) and 2-cyano-6-aminobenzothiazole (CABT) modified GNPs (GNPs-CABT). In the circulation system, the GNPs-A & C could passively target to the tumor site through the enhanced permeability and retention (EPR) effect. Then the overexpressed legumain specifically cleave the peptide to exposure the 1, 2-thiolamino group, which could take place click reaction with the cyano group of CABT, leading to the aggregation of two GNPs, these aggregates of GNPs with increased size were more likely to retain within tumor site. In vivo fluorescent imaging demonstrated GNPs-A & C could acquire an enhanced accumulation in legumain-overexpressed C6 tumor. Importantly, after tethering DOX, the GNPs-DOX-A & C showed an excellent anti-tumor effect with reduced cardiotoxicity.

Direct-PCR technology was using a 15 minutes heat-lysis step instead of DNA extraction to get DNA templates with small amount of plant materials followed by sensitive PCR process to amplify target genes. In order to facilitate DNA barcoding in medicinal herb identification with Direct-PCR, we collected different tissues from 80 medicinal plants as material to amplify the ITS fragments. Through optimizing the PCR reaction, ITS of 80 plant samples was all successfully amplified. PCR products were sequenced and to do Blast analysis. These results suggest that Direct-PCR would improve the efficiency of DNA barcoding in the application of medicinal herb molecular authentication.

Auxin response factor (ARF) is an important transcription factor for auxin signal transduction pathway, which regulates virtually every aspect of plant growth and development from embryogenesis to senescence. Nine full-length genes of ARF transcription factors were obtained from transcriptome dataset of Scutellaria baicalensis Georgi using the bioinformatics methods. The nucleotide and protein characteristics, subcellular localization, senior structural domains and conservative forecasts of those ARF transcription factors were analyzed. The phylogenetic tree showed that the nine ARFs in S. baicalensis were clustered together with ARF transcription factors in Arabidopsis thaliana, Oryza sativa subsp. Japonica and Nicotiana attenuate. The results of gene expression showed that:① The expression levels of ARF1, ARF3, ARF4, ARF8, ARF20 and ARF24 were upregulated after 100 μmol·L^-1 GA₃ treatment. However, the expression levels of ARF6 and ARF18 were downregulated; ② Those ARF genes were mainly expressed in the flowers of S. baicalensis; ③ There was a significant correlation between ARF genes and the genes involved in flavonoid biosynthesis. Our results provide a basis for further understanding the molecular regulation mechanism of flavonoid biosynthesis in S. baicalensis.