OBJECTIVESynthetical evaluation of promoting effect of some kinds of transdermal enhancers was carried through.

METHODDiclofenac sodium was used as model, and azone and l-menthol and synthetic borneol and olieic acid and essential oil from Cnidium monnieri were used as transdermal enhancers. Transdermal absorption experimentation of diclofenac sodium on the device of penetrating skins in vitro was done. Cumulation of permeation amount and penetrating rates and steady fluxes and lag times were observed, and grey relational cluster method was used to evaluate the promoting effect of some kinds of transdermal enhancers.

RESULTAs for promoting effect on diclofenac sodium, azone and l-menthol were the best, and synthetic borneol and olieic acid ranked behind.

CONCLUSIONGrey relational cluster method can evaluate promoting effect objectively and fairly.

Administration, Cutaneous ; Animals ; Azepines ; pharmacology ; Bornanes ; pharmacology ; Cluster Analysis ; Cnidium ; chemistry ; Diclofenac ; administration & dosage ; pharmacokinetics ; Male ; Menthol ; pharmacology ; Oils, Volatile ; isolation & purification ; pharmacology ; Rabbits ; Skin Absorption ; drug effects

OBJECTIVE: To investigate the effects and mechanism of bromodomain and extra-terminal (BET) inhibitor JQ1 on the double-expressor lymphoma (DEL) cell lines. METHODS: Protein expressions of cMyc and BCL-2 in 3 lymphoma cell lines were checked by Western blot so as to identify DEL cell lines. CCK-8 assay was used to detect the effects of JQ1 on anti-proliferation in the DEL cell lines. Western blot and RT-PCR were used to measure the protein and mRNA expressions of cMyc, BCL-2 and BCL-6 in DEL cell lines which treated by JQ1. Flow cytometry was used to detect the effect of JQ1 on cell apoptosis. RESULTS: Based on the expressions of cMyc and BCL-2, the SU-DHL6 and OCILY3 cell lines were confirmed as DEL cell lines. CCK-8 assay showed that the proliferation of DEL cell lines was inhibited by JQ1, which was similar to non-DEL cell lines and mainly regulated the expression of cMyc and BCL-6 but not BCL-2. JQ1 had no effects on apoptosis in the DEL cell lines. CONCLUSION BET inhibitor JQ1 has anti-tumor effect in the DEL cell lines, thus providing evidence for the therapeutic potential of BET inhibitor JQ1.
Apoptosis ; Azepines/pharmacology* ; Cell Line, Tumor ; Cell Proliferation ; Humans ; Proto-Oncogene Proteins c-myc/metabolism* ; Sincalide/pharmacology* ; Triazoles/pharmacology* ; Xenograft Model Antitumor Assays

OBJECTIVETo evaluate the effect of the compound of Dan-shen root and azone for scar treatment.

METHODSThe rat skin in vitro and the human skin in vitro and vivo were separately examined their permeability of the mixture of the Dan-shen root and azone. The 301 patients with hypertrophic scar were randomly divided into two groups: one treated with elastic cloth paste (including silicone) contained in Dan-shen root with azone, and the another treated with only elastic cloth paste (including silicone).

RESULTSThe permeability of Dan-shen root with azone, passing through the rat skin in vitro and the human skin in vitro and vivo was significantly higher than both the distilled water and the normal saline (P < 0.05). In the clinical study for treatment of the hypertrophic scars, the efficient rate of the group with the Dan-shen root with azone was significantly higher than the control (91.4% vs. 71.3%) (P < 0.01).

CONCLUSIONThe Dan-shen root with azone could be easier to permeate the skin and more effective to treat the hypertrophic scar.

Adolescent ; Adult ; Aged ; Animals ; Azepines ; pharmacology ; Child ; Child, Preschool ; Cicatrix ; drug therapy ; Drugs, Chinese Herbal ; pharmacology ; Female ; Fibrinolytic Agents ; pharmacology ; Humans ; Male ; Middle Aged ; Phenanthrolines ; pharmacology ; Phytotherapy ; Rats ; Skin ; drug effects ; pathology ; Treatment Outcome

OBJECTIVETo study the effect of different penetration enhancers on the in vitro transdermal permeation of 1-tethrahydropalmatine (L-THP) through rat skin.

METHODBoth natural and chemical synthesis penetration enhancers were applied singly or jointly to investigate the skin permeation rates of l-THP. The skin permeation profiles were evaluated by Valian-Chien permeation cells with isolated rat skin. HPLC-UV method was established to determine the concentration of l-THP in samples.

RESULTAs chemical synthesis penetration enhancer was used alone, 8% azone was observed to be the optimal penetration enhancer with the maximal penetration rate of 21.153 microg x cm(-20 x h(-1). Although 2% menthol crystal or 5% eucalyptus oil was effective as a natural penetration enhancer when used alone, the average penetration rate reached only half of that of 8% azone. The penetration potency of either menthol oil or menthol crystal combined with 8% azone was more effective than that of azone alone (P < 0.05).

CONCLUSIONEither menthol oil or menthol crystal combined with 8% azone is effective on transdermal penetration of l-THP in vitro. There is significant synergistic effect when natural penetration enhancers combined with chemical synthesis penetration enhancers.

Administration, Cutaneous ; Animals ; Azepines ; pharmacology ; Berberine Alkaloids ; analysis ; pharmacokinetics ; Drug Synergism ; Eucalyptus ; chemistry ; Male ; Menthol ; pharmacology ; Oils, Volatile ; pharmacology ; Permeability ; drug effects ; Rats ; Rats, Sprague-Dawley ; Skin ; drug effects ; metabolism ; Skin Absorption ; drug effects

OBJECTIVETo investigate the different permeation enhancers on the transdermal permeation of Xiao'er Niuhuang tuire cataplasms (XNTC).

METHODUsing improved franz-type diffusion cell with excised rat skin in vitro as the transdermal barrier, the content of permeated geniposide was determined by HPLC to study the kinetic parameters such as cumulative permeation quantity and permeation rate.

RESULTThe result showed that the process of penetrating of geniposide in XNTC through skin could be in accordance with zero-rade releasing equation and XNTC was stable during the course of experiment.

CONCLUSION5% Propylene glycol (PG)-azone (2:3) has the best permeation-enhancing effect, and the results provided a primary basis for the future research on Xiao'er Niuhuang tuire cataplasms.

Animals ; Azepines ; pharmacology ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; chemistry ; In Vitro Techniques ; Iridoids ; chemistry ; Pharmaceutical Vehicles ; pharmacology ; Propylene Glycol ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Skin ; drug effects ; metabolism ; Skin Absorption ; drug effects

OBJECTIVETo investigate the effect of different permeation enhancer on transdermal permeation of anemonin through human skin.

METHODThe permeation experiments were performed using human skin on modified Franz diffusion cells in vitro. The concentrations of anemonin in receptor compartment at specified time points were determined by HPLC. The steady flux and the cumulative quantity of anemonin through skin were calculated.

RESULTThe flux of anemonin permeating through human skin from 30% ethanol, 50% ethanol solution and a combination of 3% laurocapm -5% polysorbate 20 and 30% ethanol -3 % laurocapm -5% polysorbate 20 of anemonin was (9.30 +/- 0.32), (18.56+/-0.58), (7.29+/-0.35), (13.77+/-0. 16) microg x cm(-2) x h(-1) and 7.9, 15.9, 6.2, 11.8 times higher than from saturated water solution respectively.

CONCLUSIONEthanol and laurocapm can remarkably improve the transdermal permeation of anemonin and the anemonin have the potential to be developed to new transdermal preparation.

Administration, Cutaneous ; Azepines ; pharmacology ; Clematis ; chemistry ; Ethanol ; pharmacology ; Furans ; administration & dosage ; isolation & purification ; pharmacokinetics ; Humans ; In Vitro Techniques ; Permeability ; drug effects ; Plants, Medicinal ; chemistry ; Skin ; drug effects ; metabolism ; Skin Absorption ; drug effects

OBJECTIVETo investigate the molecular mechanism of action of BET bromodomain inhibitor JQ1 in treating airway remodeling in asthmatic mice.

METHODSA total of 24 mice were randomly divided into control group, ovalbumin (OVA)-induced asthma group (OVA group), and JQ1 intervention group (JQ1+OVA group), with 8 mice in each group. OVA sensitization/challenge was performed to establish a mouse model of asthma. At 1 hour before challenge, the mice in the JQ1+OVA group were given intraperitoneal injection of JQ1 solution (50 μg/g). Bronchoalveolar lavage fluid (BALF) and lung tissue samples were collected at 24 hours after the last challenge, and the total number of cells and percentage of eosinophils in BALF were calculated. Pathological staining was performed to observe histopathological changes in lung tissue. RT-PCR and Western blot were used to measure the mRNA and protein expression of E-cadherin and vimentin during epithelial-mesenchymal transition (EMT).

RESULTSCompared with the control group, the OVA group had marked infiltration of inflammatory cells in the airway, thickening of the airway wall, increased secretion of mucus, and increases in the total number of cells and percentage of eosinophils in BALF (P<0.01). Compared with the OVA group, the JQ1+OVA group had significantly alleviated airway inflammatory response and significant reductions in the total number of cells and percentage of eosinophils in BALF (P<0.01). Compared with the control group, the OVA group had significant reductions in the mRNA and protein expression of E-cadherin and significant increases in the mRNA and protein expression of vimentin (P<0.01); compared with the OVA group, the JQ1+OVA group had significant increases in the mRNA and protein expression of E-cadherin and significant reductions in the mRNA and protein expression of vimentin (P<0.01); there were no significant differences in these indices between the JQ1+OVA group and the control group (P>0.05).

CONCLUSIONSMice with OVA-induced asthma have airway remodeling during EMT. BET bromodomain inhibitor JQ1 can reduce airway inflammation, inhibit EMT, and alleviate airway remodeling, which provides a new direction for the treatment of asthma.

Airway Remodeling ; drug effects ; Animals ; Asthma ; drug therapy ; Azepines ; pharmacology ; Cadherins ; analysis ; genetics ; Epithelial-Mesenchymal Transition ; Female ; Mice ; Nuclear Proteins ; antagonists & inhibitors ; Ovalbumin ; immunology ; RNA, Messenger ; analysis ; Transcription Factors ; antagonists & inhibitors ; Triazoles ; pharmacology ; Vimentin ; analysis ; genetics

Farnesoid X receptor (FXR) belongs to the nuclear receptor superfamily. It is highly related to the formation of metabolic syndrome and the glucose homeostasis, and therefore represents an important drug target against metabolic diseases and diabetes. In recent years, great progress has been made in the agonists, antagonists, and crystal structures of FXR. The diverse FXR ligands and their structure-activity relationship are reviewed in this article. The advances in the crystal structures of FXR in complex with different ligands are also introduced.
Animals ; Anticholesteremic Agents ; chemical synthesis ; chemistry ; pharmacology ; Azepines ; chemical synthesis ; chemistry ; pharmacology ; Benzene Derivatives ; chemical synthesis ; chemistry ; pharmacology ; Chenodeoxycholic Acid ; analogs & derivatives ; chemical synthesis ; chemistry ; pharmacology ; Crystallization ; Humans ; Indoles ; chemical synthesis ; chemistry ; pharmacology ; Isoxazoles ; chemical synthesis ; chemistry ; pharmacology ; Ligands ; Molecular Structure ; Multienzyme Complexes ; chemical synthesis ; chemistry ; pharmacology ; Pregnenediones ; chemical synthesis ; chemistry ; pharmacology ; Receptors, Cytoplasmic and Nuclear ; agonists ; antagonists & inhibitors ; metabolism ; Structure-Activity Relationship

In adipocytes, insulin stimulates glucose transport primarily by promoting the translocation of GLUT4 to the plasma membrane. Requirements for Ca2+/ calmodulin during insulin-stimulated GLUT4 translocation have been demonstrated; however, the mechanism of action of Ca2+ in this process is unknown. Recently, myosin II, whose function in non-muscle cells is primarily regulated by phosphorylation of its regulatory light chain by the Ca2+/calmodulin-dependent myosin light chain kinase (MLCK), was implicated in insulin-stimulated GLUT4 translocation. The present studies in 3T3- F442A adipocytes demonstrate the novel finding that insulin significantly increases phosphorylation of the myosin II RLC in a Ca2+-dependent manner. In addition, ML-7, a selective inhibitor of MLCK, as well as inhibitors of myosin II, such as blebbistatin and 2,3-butanedione monoxime, block insulin- stimulated GLUT4 translocation and subsequent glucose transport. Our studies suggest that MLCK may be a regulatory target of Ca2+/calmodulin and may play an important role in insulin-stimulated glucose transport in adipocytes.
Protein Transport/drug effects ; Phosphorylation ; Naphthalenes/pharmacology ; Myosin-Light-Chain Kinase/antagonists & inhibitors/*metabolism ; Myosin Type II/*metabolism ; Mice ; Insulin/*pharmacology ; Glucose Transporter Type 4/*metabolism ; Enzyme Inhibitors/pharmacology ; Dose-Response Relationship, Drug ; Calmodulin/antagonists & inhibitors/physiology ; Azepines/pharmacology ; Animals ; Adipocytes/cytology/*drug effects/metabolism ; 3T3 Cells

OBJECTIVETo study the effects of different penetration enhancers on the transcutaneous permeability of lappaconitine gel in vitro and therefore to screen out the effective accelerator to enhance the permeation rate of lappaconitine.

METHODUsing improved Franz-type diffusion cell and excised big mouse skin in vitro as transdermal barrier, the kinetics parameters such as cumulative permeation quantity, permeation rate and permeation lagged time were determined by HPLC. The enhancement ability of four different enhancers such as azone (Azone), propylene glycol (PG), oleic acid (OA) and lauryl alcohol (LA), was investigated when used either uniquely or combinatively each other at random.

RESULTWhen used combinatively, Azone + PG, LA + PG, OA + PG can enhance the cumulative permeation quantity, OA + PG was the best one among them.

CONCLUSIONThe selection of the best penetration enhancers provided reference for lappaconitine transdermal delivery.

Aconitine ; administration & dosage ; analogs & derivatives ; pharmacokinetics ; Administration, Cutaneous ; Analgesics, Non-Narcotic ; administration & dosage ; pharmacokinetics ; Animals ; Azepines ; pharmacology ; Dodecanol ; pharmacology ; Drug Combinations ; Drug Synergism ; Female ; In Vitro Techniques ; Male ; Oleic Acid ; pharmacology ; Propylene Glycol ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Skin Absorption ; drug effects