Latest ArticlesIt is generally assumed that study of in vitro dissolution can reveal the in vivo behavior and bioavailability of a drug. The dissolution test indisputably plays a vital role in the research and development of pharmaceutical preparations as well as routine quality control of approved drugs. In order to develop an ideal dissolution method, the physicochemical properties of drug and the characteristics of its dosage form should be considered, and a proper dissolution condition be established to simulate the in vivo dissolution behavior of drugs. The new dissolution method should have the required characteristics of accuracy and durability, but also could distinguish pharmaceutic preparations with different quality. In recent years, there have been more and more reports on the establishment and verification of dissolution methods for oral solid dosage forms. However, there is very few review articles on the topic. According to the latest guidelines by domestic and foreign drug organizations, this review paper is prepared to summarize the most important skills and progress in the development of dissolution methods for oral solid preparations. The aim is to provide a reference for the development and validation of new dissolution methods.
This study was designed to explore the antidepressant mechanism of Bupleuri radix through establishing the active components-targets network and protein interactions network and analyzing the functions and pathways of targets. The main active ingredients of Bupleuri radix were obtained by TCMSP, literature study and the results of our own work. Based on the DRAR-CPI, GeneCards and OMIM were used to predict and screen the active components of Bupleuri radix. The Cytoscape software was used to construct the active components-targets network of Bupleuri radix. The protein interactions network was constructed using the String database and Cytoscape software. The relation of the main active ingredients and targets were validated by Systems Dock Web Site. The GO and KEGG pathways involved in the targets were analyzed by DAVID. Using DisGeNET database to attribute the type of targets. The results showed that 15 active components and 50 targets of Bupleuri radix were involved. The network results showed that the process of metabolism, regulation and response to stress were mainly involved, by adjusting the PI3K-AKT, MAPK, Rap1, Ras, FoxO, neurotrophin and other signaling pathways to play its antidepressant effect. This study reflects the characteristics of multicomponents-multi-targets and multi-pathways of Bupleuri radix, which provides new ideas and clues for further research on the mechanism of anti-depressive effects of Bupleuri radix.
The study is aimed to investigate the anti-depressant effect of puerarin in rat model of depression induced by chronic unpredictable mild stress (CUMS) and to explore the relevant mechanism. We established the depression rat model using CUMS. Rats were randomly divided into control, CUMS model, CUMS +fluoxetine (10 mg·kg-1) and CUMS +puerarin (50, 100, 200 mg·kg-1) groups. Drugs or vehicle were administrated after stress induction for 21 days. Open-field test (OFT), sucrose preference tests (SPT) and forced swim test (FST) were used to evaluate the anti-depressant effects of puerarin. The reactive oxygen species (ROS), prostaglandin E2 (PGE2) level, superoxide dismutase (SOD) and catalase (CAT) activities in hippocampus were determined by ELISA. Expression of IL-1β, TNF-α, and IL-10 was measured by qRT-PCR and Western blot analysis. Behavioral test suggests that crossing score, rearing score in OFT and sucrose preference index in SPT of model group were significantly lower than the control group (P < 0.01), while immobility time in FST was significantly increased (P < 0.01). Compared with those in control group, the ROS and PGE2 level increased significantly (P < 0.01), SOD and CAT activities were decreased significantly (P < 0.01), the mRNA and protein level of IL-1β, TNF-α, and IL-10 were increased significantly (P < 0.05 or P < 0.01) in rats of CUMS. Puerarin and fluoxetine ameliorated those changes induced by CUMS. Puerarin improved the depression-like behaviors of rats induced by CUMS, and the mechanism may involve in the antioxidant and anti-inflammatory effects.
The study is aimed to evaluate the anti-HIV-1 effect of chloroquine in combination with antihuman immunodeficiency virus (HIV) drugs, and inhibition of plasmacytoid dendritic cells (pDC) activation and type Ⅰ interferon (IFN-I) production by Toll-like receptor 7 (TLR7) agonist stimulation. We investigated the anti-HIV-1ⅢB, HIV-1KM018 activity of chloroquine and chloroquine combined with rategrivir (RAL), enfuvirtide (T-20), indinavir (IDV) and efavirenz (EFV) in vitro by luciferase activity assay system and ELISA method for p24 antigen. We measured the effect of chloroquine on the activation of pDC in combination with RAL and IDV, respectively. Quantitative PCR was used to evaluate the activity of chloroquine in combination with RAL and IDV in the upregulation of interferon (IFN)-α and IFN-β. Chloroquine showed less cytotoxicity to C8166, TZM-bl and PBMC cells, and the 50% cytotoxic concentration values were 85.02 ±0.28, 73.67 ±5.10 and 91.84 ±4.10 μmol·L-1, respectively. The anti-HIV-1ⅢB activity of chloroquine combination with RAL, T-20, IDV and EFV were moderate in synergy, strong in synergy, additive and moderate antagonism, respectively. The anti-HIV-1KM018 activity of chloroquine in combination with RAL, IDV were moderate synergy, minor synergy. There was no significant difference between the chloroquine monotherapy and chloroquine combined with RAL, IDV in the down-regulation of pDC activation and IFN-α, IFN-β expression levels. We have found that chloroquine combined with different anti-HIV drugs represent different degrees of synergism, antagonism or additive anti-HIV-1 effect. Chloroquine in combination with RAL and IDV did not have influence on the inhibitory effect of chloroquine on pDC activation and type Ⅰ interferon secretion induced by TLR7 agonist. The results suggest that chloroquine may be used to enhance the therapeutic activities of anti-HIV medicines.
Alcoholic liver disease (ALD) includes a spectrum of disorders ranging from asymptomatic steatosis, alcoholic steatohepatitis (ASH), fibrosis and cirrhosis. According to epidemical statistics, ALD has been ranked as the second major cause of liver diseases in China. Many animal models have been made in the study of potential therapies. However, in most of the models, the pathological changes are not always consistent with those in patients. There are three widely used short-term animal models of ALD:the acute alcoholic liver injury model, Gao-binge steatohepatitis model and CCl4-alcohol diet induced liver fibrosis model. In this study, we evaluated the pathological responses of these models and compared the responses with the clinical parameters. The liver/body weight ratio was increased and liver histological lesions were induced in alcoholic groups in the three models, while the levels of biochemical parameters and inflammatory factors were affected by different type of treatments. In the acute alcoholic model, the mRNA levels of interleukin-6 (IL-6) and C-C motif chemokine receptor-2 (CCL2) were surprisingly decreased, which was consistent with the transcriptome profile in patients (P < 0.05), but the serum ALT and AST level, were not changed. In Gao-binge model, both AST/ALT and triglyceride levels were significantly induced by alcoholic consumption (P < 0.05), along with the gene expression levels of hepatic IL-6 and CCL2 (P < 0.05). These data were similar in tendency to the pathological indicators of hepatitis patients. In liver fibrosis model, although histological section indicated obvious fibrotic lesion and little lipid accumulations, other indexes were barely changed. In conclusion, the Gao-binge model induced similar pathological patterns to those of steatohepatitis patients. Gao-binge model might be ideal for study of ALD, especially alcoholic steatohepatitis. In addition, we also found that hepatic gene expression of CCL2 was impacted differently at various stages of ALDs, which can be considered as a potential biomarker.
The effects of catechin on inflammatory response of BV-2 cells were investigated using the lipopolysaccharide (LPS) model. BV-2 cells were incubated with LPS (1 mg·L-1) for 12 h in the microglia inflammatory model in vitro. After catechin and LPS co-incubation for 12 h, MTT, ELISA and Western blot were used to detect cell viability, cytokines, cell migration and protein expression. In addition, transwell assay was conducted to investigate the effect of catechin on cell chemokaxis. Catechin did not show any cytotoxicity effect on BV-2 cells, but reversed the change in cell morphology and inhibited the release of TNF-α and IL-1β, cell chemotaxis and phosphorylation of NF-κB/p65. In conclusion, Catechin could inhibit the LPS-induced inflammatory response in BV-2 cells.
Rhein (4, 5-dihydroxyanthraquinone-2-carboxylic acid) is the primary anthraquinone in the roots of rhubarb. A recent study showed that rhein can inhibit tumor cell proliferation and induce apoptosis in human tumor cells. However, the clinical application of rhein has been hampered by its poor bioavailability, low aqueous solubility and gastrointestinal disorders. In current study, twenty-four target compounds were designed and synthesized by coupling various hydrophilic alkanolamines to the 2-carboxyl of rhein, and their structures were established by IR, HR-MS, 1H NMR spectra. Solubility test showed that all compounds were 10.04 to 15.08 mg·mL-1 in water, which was 220 to 330-fold better than that of rhein (0.045 6 mg·mL-1). All of rhein derivatives displayed more potent anti-tumor activity than rhein, and most of them were comparable to adriamycin, particularly, compound 4t exhibited IC50 value of 2.08 μmol·L-1, more effective than adriamycin (IC50=2.35 μmol·L-1). Hydroxyapatite adsorption experiment suggests that compound 4t has a better bone affinity than that of tetracycline.
Twenty target compounds were synthesized by the reduction reaction of HUANG Minglong and Friedel-Crafts acylation reaction in this study. The inhibitory effects of the new compounds were tested on NO production in LPS-induced mouse macrophage RAW264.7 cells, a cellular inflammation model. The structure-activity relationships were discussed. The structures of target compounds were confirmed by ESI-MS, 1H NMR and 13C NMR. In vitro activity experiments showed that 18 compounds had certain anti-inflammatory effects at the concentration of 40 μmol·L-1, of which 9a, 8b, 7c and 9c showed strong anti-inflammatory activities, and IC50 of 7c and 9c were comparable to the positive control drug ibuprofen.
Tacrolimus is commonly used in the treatment for the refractory primary nephrotic syndrome (PNS) in the pediatric patients. Data were retrospectively obtained from 100 children with 357 tacrolimus trough concentrations in our center between May 2010 and March 2016. Information of age, sex, body weight, drug dose, co-therapy medications, laboratory tests and sampling time were collected. The population pharmacokinetic model was developed using nonlinear mixed effect modeling (NONMEM) software. A one-compartment model with first-order absorption and elimination best described the data. The population estimate of apparent clearance (CL/F) and apparent volume of distribution (V/F) was 6.54 L·h-1 and 86.2 L, respectively. Body weight (WT, kg), daily dose of tacrolimus (DD, mg·day-1) and co-therapy azole antifungal agent have a significant impact on the CL/F. The final PPK model of CL/F was:CL/F=6.54×${\left( {\frac{{{\rm{WT}}}}{{25}}} \right)^k}$×${\left( {\frac{{{\rm{DD}}}}{{1.5}}} \right)^{0.293}}$×0.657Azole, K=$\frac{{{\rm{W}}{{\rm{T}}^{ - 30.9}}}}{{{\rm{W}}{{\rm{T}}^{ - 30.9}} + {{10.4}^{ - 30.9}}}} $. When combined with azole antifungal agents, Azole was 1, whereas vice versa was 0. This is the first PPK study of tacrolimus conducted in pediatric patients with PNS, which may facilitate individualized drug therapy of tacrolimus.
A simple and sensitive method was developed for quantitation of obeticholic acid in rat plasma with liquid chromatography-tandem mass spectrometry (LC-MS/MS). After liquid-liquid extraction by methyl tert-butyl ether, the chromatographic separation was carried out on an ACE Excel 2 Super C18 column (50 mm×2.1 mm ID, 1.7 μm) with a gradient mobile phase consisting of acetonitrile and 2 mmol·L-1 ammonium formate at a flow rate of 0.2 mL·min-1. The quantitation analysis was performed using multiple reaction monitoring (MRM) at the specific ion transitions of m/z418.9[M-H]-→401.2 for obeticholic acid and m/z469.0[M-H]-→ 425.2 for glycyrrhetinic acid (internal standard) in the negative ion mode with electrospray ionization (ESI) source. This validated LC-MS/MS method yielded a good linearity over the range of 5 -5 000 ng·mL-1 with the lower limit of quantitation (LLOQ) of 5 ng·mL-1. The intra and inter-assay precisions (RSD) were all less than 9.82% and the accuracy (RE) was within ±6.90%. The extraction recovery of obeticholic acid was from 85.4% to 88.5%, and the matrix effect of obeticholic acid ranged from 78.9% to 82.5%. Stability test suggest that obeticholic acid in rat plasma was stable for 24 h on workbench, up to 1 month at -70℃, and after three cycles of freeze-thaw. Extracted samples were stable for more than 24 h in an auto-sampler at 6℃. The precision was less than 7.25%, and the accuracy was within ±11.2%, after being diluted 10 times by blank rat plasma. The method has been successfully applied to a pharmacokinetic study of obeticholic acid in rats following oral administration at the dose of 2.5 mg·kg-1.
No. 86 Xueyuan South Road, Haidian District, Beijing
010-62662699(Operation and Technical Support)
qkjq@cast.org.cn
Copyright © 2025 China Association for Science and Technology. All rights reserved. For all open access content, the relevant licensing terms apply.
Sponsored by the Office of the Leading Group for Cybersecurity and Informatization of CAST, and supported by Science and Technology Review Publishing House
