Latest ArticlesThe 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, tmax, Cmax, MRT and t1/2 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.
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.
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.
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.
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 Ki 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 Ki 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 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.
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.
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.
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.
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