OBJECTIVETo investigate the effect of Deferasirox on the micro-angiogenesis in narrow pedicle flap through Epithelial-Mesenchymal Transition.

METHODS32 male rats were randomly divided into group I and II which were subdivided into Ia and Ib, IIa and IIb, 8 rats in each group. The rats were administrated intragastrically for 7 days with Deferasirox 100 mg/kg in group Ia and IIa, with the same dose of N. S. in group Ib and IIb. After that, narrow pedicle flaps were formed on the rats back. In group I, the subcutaneous vascular network was observed intraoperatively. The flap survival rate was recorded. In group II , specimens were collected at the distal end of flaps 3 days after operation. IHC and Western Blot were done to examine the expression of CD34, E-cadherin, Vimentin. The microvessel density was also calculated.

RESULTSThe subcutaneous micro-angiogenesis in group Ia was more exuberant than that in group Ib. The narrow pedicle flaps in group Ia survived completely, while the survival rate was 62.5% in group Ib (P < 0.05). The percentage of flap survival area for Ia and Ib was (100 +/- 0.00) % and (84.06 +/- 4.42)% (P < 0.05). The expression of E-cadherin in IIa was lower than that in IIb, while the expression of Vimentin and CD34 were higher in IIa, showing statistically difference (P < 0.05).

CONCLUSIONDeferasirox can improve the flap micro-angiogenesis through inducing epithelial-mesenchymal transition, so as to improve the survival rate of narrow pedicle flap.

Animals ; Benzoates ; pharmacology ; Epithelial-Mesenchymal Transition ; drug effects ; Male ; Rats ; Rats, Sprague-Dawley ; Surgical Flaps ; blood supply ; Triazoles ; pharmacology

OBJECTIVETo study the effects of four trace elements Mn, Fe, Zn and Cu on growth of the 2nd- and the 3rd-years Paeonia lactiflora.

METHODThe experiment was designed as randomized blocks. The data of physiological parameters such as fresh weight of root, numbers of bud and root division, length and diameter of the root and the contents of paeoniflorin in root were measured after fertilized with the four trace elements. Also the contents of the four trace elements in soil and roots, stem and leaves of P. lactiflora were detected by atomic absorption spectrometry.

RESULT AND CONCLUSIONThe growth of the P. lactiflora was improved and the content of paeoniflorin was increased by proper level of Mn, Fe, Zn and Cu, but depressed by the higher level. Only Zn can be accumulated in the roots of P. lactiflora.

Benzoates ; metabolism ; Bridged-Ring Compounds ; metabolism ; Copper ; pharmacology ; Glucosides ; metabolism ; Iron ; pharmacology ; Manganese ; pharmacology ; Monoterpenes ; Paeonia ; drug effects ; growth & development ; metabolism ; Spectrophotometry, Atomic ; Zinc ; pharmacology

This study aims to detect the expression of metabotropic glutamate receptors (mGluRs) in lung carcinoma A549 cells, and to investigate the effects of mGluR8 and mGluR4 activation on the growth of A549 cells in vitro. The mRNA expression levels of the 8 subtypes of mGluRs in A549 cells were determined by real-time PCR. Immunohistochemistry was used to analyze the protein expression of mGluR4 and mGluR8 in A549 cells and lung tissue sections obtained from lung adenocarcinoma patients. To observe the effects of mGluR8 and mGluR4 activation on the growth of A549 cells, the cultured cells were treated with (S)-3,4-DCPG (an agonist of mGluR8) and VU0155041 (an agonist of mGluR4), respectively, and then the cell viability was analyzed by CCK-8 kit, the percentage of DNA synthesis was detected by EdU incorporation, and the apoptosis of the cells was measured by hoechst 33258 staining and flow cytometry. The results showed that there were low expressions of mGluR1, mGluR5, mGluR6, mGluR7 mRNA, no expression of mGluR2 and mGluR3 mRNA, and high expressions of mGluR8 and mGluR4 mRNA in A549 cells. Accordingly, there were also mGluR4 and mGluR8 protein expressions in the A549 cells and the lung adenocarcinoma tissue sections. VU0155041 had no effect on the growth of A549 cells, but (S)-3,4-DCPG significantly decreased the cells' growth in a dose-dependent manner and increased the apoptosis of the cells. The results revealed a role of mGluR8 in the growth and apoptosis of A549 cells and suggested a potential target for clinical treatment of lung cancer.
Anilides ; pharmacology ; Apoptosis ; Benzoates ; pharmacology ; Cell Cycle ; Cell Line, Tumor ; Cell Proliferation ; Cyclohexanecarboxylic Acids ; pharmacology ; Glycine ; analogs & derivatives ; pharmacology ; Humans ; Lung Neoplasms ; pathology ; Receptors, Metabotropic Glutamate ; physiology

OBJECTIVETo study the effects of blood enriching on mouse model of blood deficiency syndrome of Paeoniae Radix Alba and Paeoniae Radix Rubra, paeoniflorin and albiflorin.

METHODBuilding the mouse model of blood deficiency syndrome induced by compound method of bleeding, starved feeding and exhausting of swimming, extract from Paeoniae Radix Alba and Paeoniae Radix Rubra were given during modeling. The amount of RBC, HGB were detected after the treatment. Based on the amount results of RBC, HGB and the paeoniflorin content, albiflorin content in Paeoniae Radix Alba and Paeoniae Radix Rubra, the same model and the same method were used to comparatively study the effect of blood enriching of paeoniflorin and albiflorin.

RESULTAt the 7th day, the amount of RBC and HGB in model mice was significantly increased (P <0. 01) by 2 g kg-1 Paeoniae Radix Alba and 2 g kg-1 Paeoniae Radix Rubra. At the 14th day, the amount of RBC and HGB in model mice was significantly increased (P <0. 01) by 2 g kg-1 Paeoniae Radix Alba. The amount of RBC and HGB in mice treated with Paeoniae Radix Rubra had an increasing trend compared with the same dose of Paeoniae Radix Rubra, but the difference was not significant. In another experiment with the same model, the amount of RBC and HGB in model mice was significantly increased (P<0.01) by 120 mg kg-1 paeoflorin and 120 mg kg-1 albiflorin at the 7th day, meanwhile, 60 mg kg-1 and 30 mg kg-1 albiflorin also increased the amount of RBC and HGB. At the 14th day, 120 mg kg-1 paeoflorin and all doses of albiflorin increased the amount of RBC and HGB. Comepared with that of the same dose of paeoniflorin, the amount of RBC in mice was significantly increased (P <0. 05) by 30 mg kg-1 albiflorin and 120 mg kg-1 albiflorin; the amount of HGB was significantly increased (P <0. 05) by 30 mg kg -1 albiflorin.

CONCLUSIONPaeoniae Radix Alba has a better effect of blood enriching than Paeoniae Radix Rubra. Albiflorin is more effective in blood enriching than paeoniflorin. Combining these, it infers that albiflorin involves in the better blood enriching effect of Paeoniae Radix Alba.

Animals ; Benzoates ; pharmacology ; Bridged-Ring Compounds ; pharmacology ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; Erythrocytes ; drug effects ; Glucosides ; pharmacology ; Hemoglobins ; drug effects ; Male ; Mice ; Monoterpenes ; Paeonia ; chemistry

OBJECTIVETo study the effects of telmisartan on voltage dependant potassium channel (Kv) expression in lymphocytes from spontaneously hypertensive rat (SHR).

METHODSPeripheral blood was collected from male SHR aged 16 and 4 weeks. Peripheral lymphocytes were separated from heparinized whole blood by standard Ficoll-Hypaque density gradient centrifugation. The whole-cell Kv currents were recorded with patch-clamp technique in the absence and presence of telmisartan(10, 30, 100 µmol/L). Real-time PCR was used to determine Kv1.3 mRNA expression in lymphocytes.

RESULTS(1) The currents density of Kv was higher in lymphocytes from 16 weeks-old SHR [ (119.0 ± 9.6) pA/pF] than from 4 weeks-old SHR [(59.0 ± 7.2) pA/pF, P < 0.05]. (2) Currents density was positively correlated with systolic blood pressure in 16 weeks-old SHR (r = 0.837, P < 0.05). (3) The lymphocytes Kv 1.3 mRNA expression was significantly higher in 16-weeks-old SHR than in 4-weeks-old SHR (P < 0.05). (4) Telmisartan reduced the whole-cell Kv currents in a concentration-dependent manner (10.5 ± 3.4)% at 10 µmol/L, (45.8 ± 3.7)% at 30 µmol/L and (81.6 ± 4.2)% at 100 µmol/L, P < 0.01.

CONCLUSIONSThe lymphocyte Kv channel is upregulated in 16 weeks-old SHR suggesting a role of Kv in the pathophysiology of hypertension. Kv current in lymphocyte could be significantly blocked by telmisartan in a concentration dependent manner.

4-Aminopyridine ; pharmacology ; Animals ; Benzimidazoles ; pharmacology ; Benzoates ; pharmacology ; Lymphocytes ; drug effects ; metabolism ; Male ; Patch-Clamp Techniques ; Potassium Channels, Voltage-Gated ; drug effects ; Rats ; Rats, Inbred SHR ; metabolism

OBJECTIVETo synthesize novel aryl-substituent benzyl acid compounds targeting HIV gp41 and characterize their anti-HIV activities.

METHODSTwelve analogues of aryl-substituent benzyl acid were designed and synthesized by Suzuki- Miyaura cross-coupling and Knoevenagel condensation reactions using halo-benzyl acid or 3-carboxybenzeneboronic acid as the raw material. The inhibitory activities of these compounds on gp41 six-helix bundle formation were tested by ELISA, and their anti-HIV activities were determined using a luciferase assay.

RESULTSThe structures of the compounds were characterized by nuclear magnetic resonance and mass spectrography. Among the 12 compounds, 5 (7b, 7c, 7d, 7e, and 7g) could inhibit the gp41 six-helix bundle formation, and 7d showed the most potent effect, and could also inhibit the replication of HIV-1 SF33 strain with an IC(50) of 20 µmol/L.

CONCLUSIONThe synthesized aryl-substituent benzyl acid compound 7d could inhibit HIV replication by blocking the gp41 six-helix bundle formation.

Anti-HIV Agents ; chemical synthesis ; pharmacology ; Benzoates ; chemical synthesis ; pharmacology ; Drug Design ; HIV-1 ; drug effects ; Hydrocarbons, Aromatic ; chemical synthesis ; pharmacology ; Virus Replication ; drug effects

Benzimidazoles ; pharmacology ; Benzoates ; pharmacology ; Cell Proliferation ; drug effects ; Humans ; Muscle, Smooth, Vascular ; cytology ; Myocytes, Smooth Muscle ; cytology ; drug effects ; Tetrazoles ; pharmacology ; Valine ; analogs & derivatives

OBJECTIVETo study the effect of peroxisome proliferator activated receptor γ (PPAR-γ) agonist on the angiotensin converting enzyme 2 (ACE2) mRNA expression in monocyte-derived macrophages of essential hypertensive patients.

METHODSTotally 57 essential hypertensive patients were randomly divided into three groups: conventional treatment group (n=18), telmisartan group (n=19), and benazepril group (n=20); 20 patients with normal blood pressure were also selected as the control group. Monocyte-derived macrophages were isolated from blood samples of patients in all four groups. The expression of ACE2 mRNA in monocyte-derived macrophages was detected by RT-PCR before treatment and 4 and 12 weeks after treatment.

RESULTSFour and 12 weeks after treatment, the systolic pressure and diastolic pressure of telmisartan group and benazepril group were significantly lower than that of the conventional treatment group (all P<0.01), and the systolic pressure and diastolic pressure of telmisartan group were significantly lower than that of the benazepril group(both P<0.01) .The expression of ACE2 mRNA in monocyte-derived macrophages were significantly lower in essential hypertensive patients than that in control group (P<0.01). After having been treated for 4 weeks and 12 weeks, the expression of ACE2 mRNA in monocyte-derived macrophages of hypertensive patients in telmisartan and benazepril groups were significantly higher than that in conventional treatment group (all P<0.01), and the expression of ACE2 mRNA in telmisartan group was significantly higher than that in benazepril group (both P<0.01).

CONCLUSIONPPAR-γ agonist could increase the ACE2 mRNA expression in monocyte-derived macrophages of essential hypertensive patients.

Aged ; Benzazepines ; pharmacology ; Benzimidazoles ; pharmacology ; Benzoates ; pharmacology ; Female ; Humans ; Hypertension ; drug therapy ; enzymology ; Macrophages ; enzymology ; Male ; Middle Aged ; PPAR gamma ; agonists ; Peptidyl-Dipeptidase A ; genetics ; metabolism ; RNA, Messenger ; genetics

Crude elicitor of one endophytic fungi (belong to Cunninghamella sp., named AL4) induced multiple responses in Atractylodes lancea suspension cells, including rapid generation of nitric oxide (NO) and hydrogen peroxide (H2O2), sequentially followed by enhancement of essential oil production. Adding NO-specific scavenger 2-4-carboxyphenyl-4,4,5, 5-tetramethylimidazol ine-1-oxyl-3-oxide (cPTIO) and H2O2 scavenger catalase (CAT) could block elicitor-induced NO and H2O2 generation respectively, but could all partly block elicitor-induced essential oil biosynthesis. Adding NO-donor sodium nitroprusside (SNP) and H2O2 could all promote essential oil accumulation in A. lancea cells, but the effect of both was different. These results strongly suggested that NO and H2O2 may all act as signaling molecule to mediate AL4 elicitor promoting essential oil accumulation in suspension cells of A. lancea. Furthermore, adding cPTIO and CAT contemporarily could not completely inhibit essential oil accumulation induced by AL4 elicitor. This result suggested that AL4 elicitor could also promote essential oil accumulation in suspension cells of A. lancea by other means.
Atractylodes ; cytology ; metabolism ; Benzoates ; pharmacology ; Catalase ; pharmacology ; Cells, Cultured ; Cunninghamella ; physiology ; Hydrogen Peroxide ; metabolism ; Imidazoles ; pharmacology ; Nitric Oxide ; metabolism ; Oils, Volatile ; analysis ; metabolism

The present study aims to predict the action targets of antidepressant active ingredients of Xiaoyaosan to understand the "multi-components, multi-targets and multi-pathways" mechanism. Using network pharmacology, the reported antidepressant active ingredients in Xiaoyaosan (saikosaponin A, saikosaponin C, saikosaponin D, ferulic acid, Z-ligustilide, atractylenolide I, atractylenolide II, atractylenolide III, paeoniflorin, albiflorin, liquiritin, glycyrrhizic acid and pachymic acid), were used to predict the targets of main active ingredients of Xiaoyaosan according to reversed pharmacophore matching method. The prediction was made via screening of the antidepressive drug targets approved by FDA in the DrugBank database and annotating the information of targets with the aid of MAS 3.0 biological molecular function software. The Cytoscape software was used to construct the Xiaoyaosan ingredients-targets-pathways network. The network analysis indicates that the active ingredients in Xiaoyaosan involve 25 targets in the energy metabolism-immune-signal transmutation relevant biological processes. The antidepressant effect of Xiaoyaosan reflects the features of traditional Chinese medicine in multi-components, multi-targets and multi-pathways. This research provides a scientific basis for elucidation of the antidepressant pharmacological mechanism of Xiaoyaosan.
Antidepressive Agents ; pharmacology ; Benzoates ; Bridged-Ring Compounds ; Coumaric Acids ; Drug Evaluation, Preclinical ; Drugs, Chinese Herbal ; pharmacology ; Flavanones ; Glucosides ; Glycyrrhizic Acid ; Lactones ; Medicine, Chinese Traditional ; Monoterpenes ; Sesquiterpenes ; Software