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1.
Article in English | WPRIM | ID: wpr-922766

ABSTRACT

Crassostrea sikamea (C.sikamea) is an important edible and medicinal seafood in China. In the present study, a compound named flazin was separated and identified from the ethyl acetate extract of C.sikamea (EAECs) for the first time. In addition, the 3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetra zolium (MTS) assay revealed that EAECs and flazin inhibited the transformation of splenic lymphocytes in vitro. Moreover, flazin (20 μg·mL


Subject(s)
Animals , Carbolines , Crassostrea , Furans , Lymphocytes , Rats , Rats, Sprague-Dawley , Spleen
2.
Article in English | WPRIM | ID: wpr-888788

ABSTRACT

Terpenoid indole (TIAs) and β-carboline alkaloids (BCAs), such as suppressant reserpine, vasodilatory yohimbine, and antimalarial quinine, are natural compounds derived from strictosidine. These compounds can exert powerful pharmacological effects but be obtained from limited source in nature. the whole biosynthetic pathway of TIAs and BCAs, The Pictet-Spengler reaction catalyzed by strictosidine synthase (STR; EC: 4.3.3.2) is the rate-limiting step. Therefore, it is necessary to investigate their biosynthesis pathways, especially the role of STR, and related findings will support the biosynthetic generation of natural and unnatural compounds. This review summarizes the latest studies concerning the function of STR in TIA and BCA biosynthesis, and illustrates the compounds derived from strictosidine. The substrate specificity of STR based on its structure is also summarized. Proteins that contain six-bladed four-stranded β-propeller folds in many organisms, other than plants, are listed. The presence of these folds may lead to similar functions among organisms. The expression of STR gene can greatly influence the production of many compounds. STR is mainly applied to product various valuable drugs in plant cell suspension culture and biosynthesis in other carriers.


Subject(s)
Alkaloids/biosynthesis , Carbolines/metabolism , Carbon-Nitrogen Lyases , Indoles/metabolism , Terpenes/metabolism
3.
Journal of Experimental Hematology ; (6): 1109-1118, 2021.
Article in Chinese | WPRIM | ID: wpr-888525

ABSTRACT

OBJECTIVE@#To investigate the effect and involved mechanism of RSL3 on ferroptosis action in acute leukemia cells MOLM13 and its drug-resistant cells.@*METHODS@#After MOLM13 treated with RSL3, CCK-8 assay was performed to detect cell viability, flow cytometry was used to detect the reactive oxygen species (ROS) level of the cells, RT-qPCR and Western blot were used to detect the expression of glutathione peroxidase 4 (GPX4). After MOLM13/IDA and MOLM13/Ara-C, the drug-resistant cell lines were constructed, the ferroptosis induced by RSL3 was observed. Bone marrow samples were collected from patients with acute monocytic leukemia. RT-qPCR and Western blot were performed to detect the expression of related genes and proteins involved in ferroptosis pathway.@*RESULTS@#RSL3 significantly inhibited the cell viability of MOLM13 and increased the intracellular ROS level, which were partially reversed by ferrostatin-1. The mRNA and protein expression of GPX4 decreased in MOLM13 treated with RSL3. RSL3 inhibited the viability of MOLM13/IDA and MOLM13/Ara-C cells more strongly than that of non-drug resistant cells, also increased the intracellular ROS level . The cytotoxic effects were partially reversed by ferrostatin-1. The mRNA and protein expressions of GPX4 in MOLM13/IDA and MOLM13/Ara-C cells were higher than those in non-drug resistant cells. The mRNA and protein levels of GPX4 in bone marrow of relapsed/refractory acute mononuclear leukemia patients were higher than those of ordinary acute mononuclear leukemia patients.@*CONCLUSION@#RSL3 can induce non-drug resistant cells MOLM13 ferroptosis by inhibiting GPX4 activity. MOLM13/IDA and MOLM13/Ara-C are more sensitive to RSL3 compared with non-drug resistant cells MOLM13, which may be caused by the differences in GPX4 expression. The expressions of GPX4 mRNA and protein in relapsed/refractory acute mononuclear leukemia are higher than those in ordinary acute mononuclear leukemia.


Subject(s)
Carbolines , Cell Line , Child , Ferroptosis , Humans , Leukemia, Myeloid, Acute , Pharmaceutical Preparations
4.
Article in Chinese | WPRIM | ID: wpr-771508

ABSTRACT

To explore the mechanism of β-carboline alkaloids inhibiting the migration and invasion of SGC-7901 cells and its correlation with FAK gene expression,CCK-8 method was used to determine the inhibitory rate of β-carboline alkaloids on the proliferation of gastric cancer SGC-7901 cells under different concentrations.The effect of β-carboline alkaloids on the migration and invasion of SGC-7901 cells was used by Transwell compartment.Detection of mRNA and protein expression of FAK genes were used by qRT-PCR and Western blot.Then si-FAK-1051 recombinant plasmid was transfected into SGC-7901 cells.FAK gene silencing effect was identified by qRT-PCR and Western blot technique again.Finally,the effects of FAK gene silencing on proliferation and migration of gastric cancer SGC-7901 cells were detected by CCK-8 kit and Transwell chamber assay respectively.With the increase of the concentration ofβ-carboline alkaloids,the inhibitory rate of SGC-7901 cells in human gastric cancer cells increased gradually,with IC5013.364 mg·L-1.The number of SGC-7901 cells of Transwell compartment in the positive experimental group(5-FU,5 mg·L-1) and the β-carboline alkaloids group decreased significantly(P<0.01) and the number of SGC-7901 cells in the β-carboline alkaloids group was significantly lower than that in the positive experimental group(P<0.01).Compared with the blank control group,the mRNA and protein expression level of FAK genes in the positive experimental group was significantly lower than that in the experimental group of β-carboline alkaloids(P<0.05).After transfection of si-FAK-1051 into gastric cancer SGC-7901 cells,the expression of mRNA and protein of FAK gene was significantly down regulated(P<0.05).SGC-7901 cell proliferation and cell migration ability also decreased significantly(P<0.05).β-carboline alkaloids are more effective than 5-FU in inhibiting migration and invasion of gastric cancer SGC-7901 cells,and the mechanism may be related to the inhibition of mRNA and protein expression of FAK gene by β-carboline alkaloids.


Subject(s)
Alkaloids , Pharmacology , Carbolines , Pharmacology , Cell Line, Tumor , Cell Movement , Cell Proliferation , Focal Adhesion Kinase 1 , Genetics , Gene Expression Regulation, Neoplastic , Gene Silencing , Humans , Neoplasm Invasiveness , Stomach Neoplasms , Drug Therapy , Pathology
5.
Article in English | WPRIM | ID: wpr-812370

ABSTRACT

Angiogenesis is a crucial process in the development of inflammatory diseases, including cancer, psoriasis and rheumatoid arthritis. Recently, several alkaloids from Picrasma quassioides had been screened for angiogenic activity in the zebrafish model, and the results indicated that 1-methoxycarbony-β-carboline (MCC) could effectively inhibit blood vessel formation. In this study, we further confirmed that MCC can inhibit, in a concentration-dependent manner, the viability, migration, invasion, and tube formation of human umbilical vein endothelial cells (HUVECs) in vitro, as well as the regenerative vascular outgrowth of zebrafish caudal fin in vivo. In the zebrafish xenograft assay, MCC inhibited the growth of tumor masses and the metastatic transplanted DU145 tumor cells. The proteome profile array of the MCC-treated HUVECs showed that MCC could down-regulate several angiogenesis-related self-secreted proteins, including ANG, EGF, bFGF, GRO, IGF-1, PLG and MMP-1. In addition, the expression of two key membrane receptor proteins in angiogenesis, TIE-2 and uPAR, were also down-regulated after MCC treatment. Taken together, these results shed light on the potential therapeutic application of MCC as a potent natural angiogenesis inhibitor via multiple molecular targets.


Subject(s)
Angiogenesis Inhibitors , Chemistry , Pharmacology , Animals , Carbolines , Chemistry , Pharmacology , Cell Movement , Cell Proliferation , Epidermal Growth Factor , Genetics , Metabolism , Fibroblast Growth Factors , Genetics , Metabolism , Human Umbilical Vein Endothelial Cells , Cell Biology , Metabolism , Humans , Insulin-Like Growth Factor I , Genetics , Metabolism , Neovascularization, Physiologic , Picrasma , Chemistry , Plant Extracts , Chemistry , Pharmacology , Receptor, TIE-2 , Genetics , Metabolism , Zebrafish , Embryology
6.
Article in English | WPRIM | ID: wpr-773581

ABSTRACT

Angiogenesis is a crucial process in the development of inflammatory diseases, including cancer, psoriasis and rheumatoid arthritis. Recently, several alkaloids from Picrasma quassioides had been screened for angiogenic activity in the zebrafish model, and the results indicated that 1-methoxycarbony-β-carboline (MCC) could effectively inhibit blood vessel formation. In this study, we further confirmed that MCC can inhibit, in a concentration-dependent manner, the viability, migration, invasion, and tube formation of human umbilical vein endothelial cells (HUVECs) in vitro, as well as the regenerative vascular outgrowth of zebrafish caudal fin in vivo. In the zebrafish xenograft assay, MCC inhibited the growth of tumor masses and the metastatic transplanted DU145 tumor cells. The proteome profile array of the MCC-treated HUVECs showed that MCC could down-regulate several angiogenesis-related self-secreted proteins, including ANG, EGF, bFGF, GRO, IGF-1, PLG and MMP-1. In addition, the expression of two key membrane receptor proteins in angiogenesis, TIE-2 and uPAR, were also down-regulated after MCC treatment. Taken together, these results shed light on the potential therapeutic application of MCC as a potent natural angiogenesis inhibitor via multiple molecular targets.


Subject(s)
Angiogenesis Inhibitors , Chemistry , Pharmacology , Animals , Carbolines , Chemistry , Pharmacology , Cell Movement , Cell Proliferation , Epidermal Growth Factor , Genetics , Metabolism , Fibroblast Growth Factors , Genetics , Metabolism , Human Umbilical Vein Endothelial Cells , Cell Biology , Metabolism , Humans , Insulin-Like Growth Factor I , Genetics , Metabolism , Neovascularization, Physiologic , Picrasma , Chemistry , Plant Extracts , Chemistry , Pharmacology , Receptor, TIE-2 , Genetics , Metabolism , Zebrafish , Embryology
7.
Arq. bras. cardiol ; 104(1): 85-89, 01/2015. graf
Article in English | LILACS | ID: lil-741125

ABSTRACT

Resistant hypertension (RHTN) is a multifactorial disease characterized by blood pressure (BP) levels above goal (140/90 mmHg) in spite of the concurrent use of three or more antihypertensive drugs of different classes. Moreover, it is well known that RHTN subjects have high prevalence of left ventricular diastolic dysfunction (LVDD), which leads to increased risk of heart failure progression. This review gathers data from studies evaluating the effects of phosphodiesterase-5 (PDE-5) inhibitors (administration of acute sildenafil and short-term tadalafil) on diastolic function, biochemical and hemodynamic parameters in patients with RHTN. Acute study with sildenafil treatment found that inhibition of PDE-5 improved hemodynamic parameters and diastolic relaxation. In addition, short-term study with the use of tadalafil demonstrated improvement of LVDD, cGMP and BNP-32 levels, regardless of BP reduction. No endothelial function changes were observed in the studies. The findings of acute and short-term studies revealed potential therapeutic effects of IPDE-5 drugs on LVDD in RHTN patients.


A Hipertensão arterial resistente (HAR) é uma doença multifatorial caracterizada por níveis pressóricos acima das metas (140/90 mmHg), a despeito de tratamento farmacológico otimizado de 3 ou mais fármacos anti-hipertensivos de diferentes classes. Pacientes diagnosticados como hipertensos resistentes apresentam alta prevalência de disfunção diastólica do ventrículo esquerdo (DDVE) que proporciona risco aumentado para insuficiência cardíaca. Esta revisão reúne dados de estudos prévios avaliando os efeitos dos inibidores de fosfodiesterase-5 (PDE-5) (administração aguda de sildenafil e de curto prazo de tadalafil) na função diastólica e nos parâmetros bioquímicos e hemodinâmicos em pacientes com HAR. O estudo agudo com sildenafil demonstrou que a inibição da PDE-5 melhorou os parâmetros hemodinâmicos e de relaxamento diastólico. Além disso, o estudo curto prazo com o uso de tadalafil revelou melhora da DDVE e dos níveis de GMPc e BNP-32, independente de redução de pressão arterial. A função endotelial não apresentou alteração com ambos os tratamentos. Os resultados dos estudos agudo e de curto prazo sugerem efeitos terapêuticos potenciais dos fármacos inibidores da PDE-5 na disfunção diastólica em pacientes com HAR.


Subject(s)
Humans , Heart Failure, Diastolic/drug therapy , Hypertension/drug therapy , /therapeutic use , Ventricular Dysfunction, Left/drug therapy , Carbolines/therapeutic use , Drug Resistance , Diastole/drug effects , Heart Failure, Diastolic/physiopathology , Hypertension/physiopathology , Medical Illustration , Piperazines/therapeutic use , Purines/therapeutic use , Sildenafil Citrate , Sulfonamides/therapeutic use , Tadalafil , Treatment Outcome , Ventricular Dysfunction, Left/physiopathology
8.
Journal of Medicinal Plants. 2015; 14 (55): 43-57
in English | IMEMR | ID: emr-173950

ABSTRACT

Background: Sustainable and commercial production of secondary metabolites is a critical issue when dealing with its clinical application. Efforts are still being made to look for biotic or abiotic elicitors with more efficient and universal effects on the improvement of secondary metabolites


Objective: In order to evaluate the suitability of different biotic elicitors on P. harmala L. cell suspension cultures was established to enhance the beta-carboline alkaloids [harmaline and harmine] production


Methods: The elicitation of cell suspension cultures of Peganum harmala L. was done by adding various fungal mycelium homogenates [Aspergillus flavus, Alternaria alternate, Coriolus versicolor, Fusarium oxysporum, Mucor sp, Penicillium notatum, and Rhizopus stonifer], Casein hydrolysate and Saccharomyces cerevisiae at different concentrations. The cell cultures of P. harmala L. were subcultured on MS medium with optimal treatment of biotic elicitor. CAMAG analytical HPTLC system was used for estimation of harmaline and harmine after extraction of beta-carboline alkaloids


Results: The maximum harmine production [91.2 +/- 1.8 microg g[-1] DW] was observed at 1000 mg l[-1] S. cerevisiae in cell suspension culture of P. harmala L. [1.68 fold over than the control]. Also the results showed that supplement of 75-100 mg l-1 casein hydrolysate in cell cultures media increased biomass of cell culture and harmaline and harmine production [1.61 and 1.46 times over than the control, respectively]


Conclusion: The conclusion of the research showed that by applying biotic elicitors, we can reach to higher secondary metabolites [harmaline and harmine] in cell suspension culture of P. harmala L. We suggest future investigation on using other elicitors like bacterial extract or signal transduction compounds in cell suspension culture of P. harmala L. in order to increase the production of different kind of secondary metabolites


Subject(s)
Carbolines , Alkaloids , Cell Culture Techniques , Harmaline , Harmine
9.
National Journal of Andrology ; (12): 214-218, 2015.
Article in Chinese | WPRIM | ID: wpr-319517

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the protective effect of phosphodiesterase type 5 inhibitors (tadalafil) on the testis following testicular ischemia-reperfusion injury in rats.</p><p><b>METHODS</b>Eighty-four healthy adult male SD rats were randomly and equally divided into groups A (sham operation), B (testicular torsion + low-dose tadalafil), C (testicular torsion + high-dose tadalafil), and D (testicular torsion + placebo). Models were established in the latter three groups by 7200 torsion of the right testis for 2 hours. The animals in groups A and B were treated by gavage with tadalafil at the dose of 0. 5 mg per kg per day, those in group C at 2 mg per kg per day, and those in group D with saline at the same dose. After 3, 7, and 14 days of treatment, the torsioned testes were harvested for evaluation of the superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in the testis tissue. The pathological changes in the testis were observed under the light microscope.</p><p><b>RESULTS</b>At 3, 7, and 14 days, the SOD activity was (254.46 +/- 7.43), (278.49 +/- 8.33), and (317.99 +/- 3.31) nU/mg prot in group B, and (277.12 +/- 8.80), (309.40 +/- 2.14), and (320.39 +/- 4.72) nU/mg prot in group C, all obviously higher than in D ([223.21 +/- 4.65], [231.45 +/- 4.16] and [248.28 +/- 5.74] nU/mg prot), while the MDA content was lower in the former two groups than in the latter. At 3 and 7 days, the SOD activity was significantly higher and the MDA level significantly lower in group C than in B (both P < 0.01) , while at 14 days, neither showed any remarkable differences between the two groups (P > 0.05). No obvious histopathological change was observed in the testis tissue of group A. At 3 and 7 days, pathological examination of the testis tissue revealed significant differences in the number of seminiferous epithelial layers, testicular histological score, and seminiferous tubule diameter in group B (P < 0.01), but the three indexes at 14 days in group B and at 7 days in group C exhibited no remarkable differences from those at 14 days in group A.</p><p><b>CONCLUSION</b>Tadalafil can alleviate testicular ischemia-reperfusion injury following testis torsion/detorsion in a time- and dose-dependent manner.</p>


Subject(s)
Animals , Biomarkers , Metabolism , Carbolines , Pharmacology , Dose-Response Relationship, Drug , Male , Malondialdehyde , Metabolism , Phosphodiesterase 5 Inhibitors , Pharmacology , Random Allocation , Rats , Rats, Sprague-Dawley , Reperfusion Injury , Seminiferous Tubules , Pathology , Spermatic Cord Torsion , Superoxide Dismutase , Metabolism , Tadalafil , Testis , Metabolism , Pathology , Time Factors
10.
Int. braz. j. urol ; 40(4): 546-552, Jul-Aug/2014. tab, graf
Article in English | LILACS | ID: lil-723954

ABSTRACT

Purpose The aim of this study was to define if tadalafil causes detrusor muscle impairment and to observe the effect of combination of tadalafil with tamsulosin on the lower urinary tract of rats with bladder outlet obstruction (BOO) induced by chronic nitric oxide deficiency. Materials and Methods Thirty-one male rats were randomized to following groups: 1 - control; 2 - L-Nitroarginine methyl ester (L-NAME); 3 - Tamsulosin + L-NAME, 4 Tadalafil+L-NAME; and 5 - Tamsulosin + Tadalafil + L-NAME. At the end of the treatment period (30 days), all animals were submitted to urodynamic study. Results The administration of L-NAME increased the number of non-voiding contractions (NVC) (1.04 ± 0.22), volume threshold (VT) (1.86 ± 0.35), and micturition cycle (MC) (1.34 ± 0.11) compared with control (0.52 ± 0.06, 0.62 ± 0.06, and 0.67 ± 0.30), respectively. The administration of tamsulosin reduced the number of NVC (0.57 ± 0.42) and VT (0.76 ± 0.24 ) compared with L-NAME group. Co-treatment with tadalafil decreased the number of VT (0.85 ± 0.53) and MC (0.76 ± 0.22) compared with L-NAME group. The combination of tamsulosin with tadalafil improved the number of NVC (0.56 ± 0.18), VT (0.97 ± 0.52) and MC (0.68 ± 0.30) compared with L-NAME group. Conclusion In rats with BOO induced by chronic nitric oxide deficiency, tadalafil did not cause impairment in detrusor muscle and seems to have an addictive effect to tamsulosin because the combination decreased non voiding contractions as well the number of micturition cycles. .


Subject(s)
Animals , Male , Carbolines/administration & dosage , Sulfonamides/administration & dosage , Urinary Bladder Neck Obstruction/drug therapy , Urological Agents/administration & dosage , Drug Therapy, Combination , NG-Nitroarginine Methyl Ester/administration & dosage , Nitric Oxide/deficiency , /administration & dosage , Random Allocation , Rats, Wistar , Reproducibility of Results , Treatment Outcome , Urinary Bladder Neck Obstruction/etiology , Urination/drug effects
11.
Int. braz. j. urol ; 40(3): 390-399, may-jun/2014. tab, graf
Article in English | LILACS | ID: lil-718249

ABSTRACT

Purpose Characterize persistence and adherence to phosphodiesterase type - 5 inhibitor (PDE5I) on-demand therapy over 6 months among Brazilian men in an observational, non-interventional study of Latin American men naïve to PDE5Is with erectile dysfunction (ED). Materials and Methods Men were prescribed PDE5Is per routine clinical practice. Persistence was defined as using ≥ 1 dose during the previous 4 - weeks, and adherence as following dosing instructions for the most recent dose, assessed using the Persistence and Adherence Questionnaire. Other measures included the Self - Esteem and Relationship (SEAR) Questionnaire, and International Index of Erectile Function (IIEF). Multivariate logistic regression was used to identify factors associated with persistence/adherence. Results 104 Brazilian men were enrolled; mean age by treatment was 53 to 59 years, and most presented with moderate ED (61.7%). The prescribed PDE5I was sildenafil citrate for 50 (48.1%), tadalafil for 36 (34.6%), vardenafil for 15 (14.4%), and lodenafil for 3 patients (2.9%). Overall treatment persistence was 69.2% and adherence was 70.2%; both were numerically higher with tadalafil (75.0%) versus sildenafil or vardenafil (range 60.0% to 68.0%). Potential associations of persistence and/or adherence were observed with education level, ED etiology, employment status, and coronary artery disease. Improvements in all IIEF domain scores, and both SEAR domain scores were observed for all treatments. Study limitations included the observational design, brief duration, dependence on patient self - reporting, and limited sample size. Conclusion Approximately two-thirds of PDE5I-naive, Brazilian men with ED were treatment persistent and adherent after 6 months. Further study is warranted to improve long-term outcomes of ED treatment. .


Subject(s)
Adult , Aged , Humans , Male , Middle Aged , Erectile Dysfunction/drug therapy , Medication Adherence , /therapeutic use , Brazil , Carbolines/therapeutic use , Educational Status , Imidazoles/therapeutic use , Patient Satisfaction , Prospective Studies , Piperazines/therapeutic use , Purines/therapeutic use , Statistics, Nonparametric , Surveys and Questionnaires , Sulfones/therapeutic use , Time Factors , Treatment Outcome , Triazines/therapeutic use
12.
Article in Chinese | WPRIM | ID: wpr-300211

ABSTRACT

A RP-HPLC method was developed to evaluate the quality of Picrasmae Ramulus et Folium by simultaneous determination of five constituents including 1-hydroxymethyl-beta-carboline (1), 1-methoxicabony-beta-carboline (2), 4-methoxy-5-hydroxy-canthin-6-one (3), 4, 5-dimethoxy-canthin-6-one (4) and maackiain (5) in Picrasmae Ramulus et Folium. The samples were separated on a Kromasil RP-C18 (4.6 mm x 250 mm, 5 microm) column eluted with acetonitrile and 0.1% phosphoric acid as mobile phases in gradient mode. The detection wavelength was set at 254 nm. The calibration curves and linearity of the above five standards were determined as (1) Y = 6 525.6X + 37.25 (0.009-1.780 microg, r = 0.996 8), (2) Y = 3 662.3X + 41.55 (0.005-0.920 microg, r = 0.999 5), (3) Y = 3763.1X + 146.87 (0.015-3.060 microg, r = 0.999 0), (4) Y = 2 174.1X + 21.52 (0.003-0.620 microg, r = 0.999 5), and (5) Y = 276.25X + 7.65 (0.010-1.960 microg, r = 0.998 9), respectively. The method is simple and repeatable, and can be used for the quality assessment of Picrasmae Ramulus et Folium.


Subject(s)
Alkaloids , Calibration , Carbolines , Chromatography, High Pressure Liquid , Methods , Chromatography, Reverse-Phase , Methods , Flavonoids , Indole Alkaloids , Picrasma , Chemistry , Plant Leaves , Chemistry , Plant Stems , Chemistry , Pterocarpans , Reproducibility of Results
13.
Acta Pharmaceutica Sinica ; (12): 490-496, 2014.
Article in Chinese | WPRIM | ID: wpr-245057

ABSTRACT

A series of novel tetrahydrocarboline derivatives was designed and synthesized in order to discover more potent peroxisome proliferator-activated receptor (PPAR) alpha/gamma dual regulators. The structures of these compounds were confirmed by 1H NMR and HR-MS; their PPAR-regulating activities were evaluated in vitro. Compounds 6h, 6n, 6p and 6q exhibited more potent PPARalpha agonistic activities than the control drug WY14643, while compounds 60, 6g, 6i and 6q exhibited more potent PPARgamma agonistic activities than the control drug rosiglitazone. Compound 6q was discovered as a potent PPARalpha/gamma dual agonist and deserves further investigation.


Subject(s)
Animals , Carbolines , Chemistry , Pharmacology , Cells, Cultured , Drug Design , Hypoglycemic Agents , Chemistry , Pharmacology , Molecular Structure , PPAR alpha , PPAR gamma , Peroxisome Proliferator-Activated Receptors , Pyrimidines , Metabolism , Structure-Activity Relationship , Thiazolidinediones , Metabolism , Transfection
14.
Chinese Journal of Cardiology ; (12): 474-480, 2014.
Article in Chinese | WPRIM | ID: wpr-316430

ABSTRACT

<p><b>OBJECTIVE</b>To evaluate the therapy efficacy of iloprost combined with low dose tadalafil in adult congenital heart disease (CHD) patients with severe pulmonary arterial hypertension (PAH).</p><p><b>METHODS</b>Adult CHD patients with severe PAH were included and divided into the sequential combination therapy group [iloprost: 10 µg/inhalation, 6 times per day for 6 months, and then add oral tadalafil (5 mg/d) till 12 months, n = 32] and upfront combination therapy group [iloprost: 10 µg/inhalation, 6 times per day combined with oral tadalafil (5 mg) for 12 months, n = 36]. Data on 6 min walking test (6MWT), Borg dyspnea score, oxygen saturation measurement, WHO classification, and cardiac catheterization were obtained at baseline, 6 and 12 months.</p><p><b>RESULTS</b>Seventy-two patients were enrolled in the study and 68 patients completed the study. Pulmonary vascular resistance (PVR) was significantly reduced in the sequential combination therapy group[ (12.96 ± 6.48 ) Wood U vs. (16.94 ± 8.11) Wood U, P < 0.05] and in the upfront combination therapy group [(12.45 ± 7.32) Wood U vs. (16.73 ± 9.28) Wood U, P < 0.05] while pulmonary blood flow [(6.77 ± 3.17) L/min vs. (5.08 ± 2.36) L/min, P < 0.05; (6.95 ± 3.32) L/min vs. (5.03 ± 2.32) L/min, P < 0.05], the 6 MWD were significantly increased [(458 ± 59) m vs. (427 ± 65) m, P < 0.05; (494 ± 59) m vs. (436 ± 62) m, P < 0.01], the Borg dyspnea score (2.04 ± 0.72 vs. 2.52 ± 0.79, P < 0.05; 1.72 ± 0.73 vs. 2.51 ± 0.77, P < 0.01) was significantly improved in both groups at 6 months compared to baseline levels. In the upfront combination therapy group, venous oxygen saturation [(68.4 ± 9.3)% vs. (62.9 ± 9.5)%, P < 0.05] and systemic oxygen saturation during exercise[ (87.2 ± 9.7)% vs. (83.1 ± 15.6)%, P < 0.05]at 6 months were also significantly improved compared to baseline. At month 12, significantly lowered pulmonary artery pressure, PVR, Rp/Rs and increased pulmonary blood flow and cardiac index were evidenced in both groups compared to baseline.</p><p><b>CONCLUSION</b>Iloprost combined with low dose tadalafil regimen can effectively reduce PVR, increase 6MWD, and improve cardiopulmonary function in adults CHD patients with severe PAH. Compared with the sequential therapy regimen, the upfront combination therapy regimen can more rapidly improve the clinical symptoms of patients.</p>


Subject(s)
Adolescent , Adult , Carbolines , Therapeutic Uses , Female , Follow-Up Studies , Heart Defects, Congenital , Drug Therapy , Humans , Hypertension, Pulmonary , Drug Therapy , Iloprost , Therapeutic Uses , Male , Middle Aged , Tadalafil , Treatment Outcome , Young Adult
15.
National Journal of Andrology ; (12): 267-272, 2014.
Article in Chinese | WPRIM | ID: wpr-309722

ABSTRACT

<p><b>OBJECTIVE</b>To observe the clinical effect of low-dose once-daily tadalafil combined with Shuganyiyang Capsules in the treatment of mild-to-moderate erectile dysfunction (ED).</p><p><b>METHODS</b>Ninety patients with mild-to-moderate ED were equally randomized to groups A, B and C to receive Shuganyiyang Capsules, tadalafil, and tadalafil + Shuganyiyang Capsules, respectively. The scores of the patients on IIEF-5 and SF-PAIRS (15-Item Short Form of Psychological Interpersonal Relationship Scales) were recorded before and at 1 and 3 months after treatment.</p><p><b>RESULTS</b>The IIEF-5 scores of groups A, B and C were 10.13 +/- 1.55, 11.00 + 1.60 and 10.73 +/- 1.91 before treatment, and 13.77 +/- 2.11, 17.77 +/- 2.13 and 17.17 +/- 3.84 at 1 month after treatment, significantly higher in B and C than in A (P <0. 001) , but with no remarkable difference between B and C (P =0. 411). At 3 months after treatment, the IIEF-5 scores were 15.77 +/- 2.05, 18.07 +/- 2.24 and 19.37 +/- 3.76 in the three groups, dramatically higher in B and C than in A (P <0.001) as well as in C than in B (P<0.05). The scores on sexual self-confidence, sexual spontaneity and time concerns in SF-PAIRS were 3.90 +/-0.80, 8.67 +/- 1.94 and 14.43 +/- 1.92 before medication, 5.83 +/- 1.02, 9.90 +/- 1.75 and 11.17 +/- 1.68 at 1 month and 6.73 +/- 0.98, 11.07 +/- 2.08 and 10.67 +/-1.60 at 3 months after medication in group A; 4.17 +/- 0.87, 9.37 +/-1.43 and 14.47 +/-1.57 before medication, 6.47 +/-0.78, 10.83 +/- 2.18 and 10.20 +/-1.56 at 1 month and 6.83 +/-0.91, 11.30 +/- 1.88 and 9.47 +/- 1.57 at 3 months in group B; and 4.23 +/-0. 94, 9.50 +/- 1.89 and 14.67 +/- 2.91 before medication, 8.03 +/- 1.67, 13.43 +/-1.10 and 9.70 +/-1.21 at 1 month and 8.93 +/- 1.78, 14.70 +/- 1.26 and 8. 87 +/- 0. 97 at 3 months in group C. Compared with the baseline, the SF-PAIRS scores of the three groups were all significantly improved after treatment (P <0. 05) , and markedly higher in C than in the other two groups (P <0.05).</p><p><b>CONCLUSION</b>Low-dose once-daily tadalafil combined with Shuganyiyang Capsules is obviously effective in the treatment of mild-to-moderate ED, which not only improves the patients'erectile function, sexual self-confidence and sexual spontaneity, but also reduces their time concerns.</p>


Subject(s)
Adult , Carbolines , Therapeutic Uses , Drugs, Chinese Herbal , Therapeutic Uses , Erectile Dysfunction , Drug Therapy , Humans , Male , Tadalafil , Treatment Outcome
16.
Acta Pharmaceutica Sinica ; (12): 225-229, 2014.
Article in Chinese | WPRIM | ID: wpr-297989

ABSTRACT

Eight compounds were isolated from the stems of Brucea mollis by various chromatographic techniques such as column chromatography on silica gel and Sephadex LH-20, and preparative HPLC, and their structures were elucidated as bruceolline O (1), 1-(1-beta-glucopyranosyl)-1H-indole-3-carbaldehyde (2), canthin-6-one (3), 11-hydroxycanthin-6-one (4), 9-methoxycanthin-6-one (5), 4-methoxycanthin-6-one (6), infractin (7), and beta-carboline-1-propionic acid (8). The cytotoxic activities of compounds 1-8 against HCT-8 and A549 human cell lines were determined, but none of them exhibited significant activity (IC 50 > 10 micromol x L(-1)). Among them, compound 1 is a new indole alkaloid, and compounds 2 and 5-7 were isolated from this plant for the first time.


Subject(s)
Antineoplastic Agents, Phytogenic , Chemistry , Pharmacology , Brucea , Chemistry , Carbolines , Chemistry , Pharmacology , Cell Line, Tumor , Humans , Indole Alkaloids , Chemistry , Pharmacology , Molecular Structure , Plant Stems , Chemistry , Plants, Medicinal , Chemistry
17.
National Journal of Andrology ; (12): 133-137, 2014.
Article in Chinese | WPRIM | ID: wpr-267964

ABSTRACT

<p><b>OBJECTIVE</b>To evaluate the safety and effect of L-carnitine combined with tadalafil in the treatment of late-onset hypogonadism (LOH) with erectile dysfunction (ED).</p><p><b>METHODS</b>We randomly divided 140 cases of LOH with ED aged 40 -70 years into a treatment and a control group to receive L-carnitine + tadalafil and testosterone undecanoate + tadalafil, respectively. After 8 weeks of treatment, we obtained the scores on IIEF-5 and Aging Male Symptoms (AMS), observed changes in the levels of sex hormones, analyzed the results of the routine blood test and PSA level, and evaluated the safety of medication.</p><p><b>RESULTS</b>Finally, 110 cases were included, 60 in the treatment group and 50 in the control. After 8 weeks of medication, the IIEF-5 and AMS scores were significantly improved as compared with the baseline both in the treatment group (17.7 +/- 3.5 vs 10.2 +/- 2.7 and 36.2 +/- 6.5 vs 48.8 +/- 5.8) and in the control group (16.7 +/- 2.6 vs 9.3 +/- 2.4 and 35.8 +/- 6.6 vs 50.7 +/- 5.0) (both P < 0.05), with no significant differences between the two groups (P > 0.05). As for the safety of medication, there were no significant differences between the two groups before and after treatment (P > 0.05). Two patients in the control group showed a PSA level > 4 microg/L, which was confirmed to be caused by prostatitis during follow-up.</p><p><b>CONCLUSION</b>L-carnitine combined with tadalafil is safe and effective for the treatment of LOH with ED.</p>


Subject(s)
Adult , Aged , Carbolines , Therapeutic Uses , Carnitine , Therapeutic Uses , Erectile Dysfunction , Drug Therapy , Humans , Hypogonadism , Drug Therapy , Male , Middle Aged , Tadalafil , Treatment Outcome
18.
National Journal of Andrology ; (12): 14-18, 2014.
Article in Chinese | WPRIM | ID: wpr-267950

ABSTRACT

<p><b>OBJECTIVE</b>To evaluate the safety and efficacy of tadalafil on demand and on time in men with erectile dysfunction.</p><p><b>METHODS</b>We conducted a multi-centered randomized controlled study on 120 ED males, who were assigned to take tadalafil at 10 mg/ 20 mg on demand before sexual activity and at the same dose on time twice a week for 8 weeks. Before and at 4 and 8 weeks after treatment, and 1 month after withdrawal, we obtained the scores on IIEF-5, ED Inventory of Treatment Satisfaction (EDITS) and the short form of Psychological and Interpersonal Relationship Scales (SF-PAIRS) , and compared the safety and efficacy of medication between the two groups of patients.</p><p><b>RESULTS</b>Totally, 110 patients accomplished the trial, 56 in the on-time and 54 in the on-demand group. At 4 and 8 weeks of medication and 1 month after withdrawal, the IIEF-5 scores were improved in both the on-time and on-demand groups, even more significantly in the former than in the latter at 8 weeks of treatment (21.6 +/- 2.9 vs 18.5 +/- 1.7) and 1 month after withdrawal (20.9 +/- 2.1 vs 17.9 +/- 2.3) (P < 0.05). The EDITS scores were significantly higher in the on-time than in the on-demand group at 8 weeks of treatment (31.7 +/- 6.9 vs 28.6 +/- 5.8) and 1 month after withdrawal (30.6 +/- 4.7 vs 27.9 +/- 6.5) (P < 0.05). The scores on the sexual self-confidence, spontaneity and time-concern domains of SF-PAIRS were remarkably improved after medication as compared with the baseline (P < 0.05), even more significantly in the on-time than in the on-demand group at 1 month after withdrawal. Both dosing schedules were well tolerated and no significant differences were observed in safety between the two groups.</p><p><b>CONCLUSION</b>On-time dosing of tadalafil is efficacious and well tolerated in the treatment of ED, and has an even better effect than on-demand dosing at 8 weeks of medication and 1 month after withdrawal.</p>


Subject(s)
Adult , Carbolines , Therapeutic Uses , Drug Administration Schedule , Erectile Dysfunction , Drug Therapy , Humans , Male , Middle Aged , Phosphodiesterase Inhibitors , Therapeutic Uses , Prospective Studies , Tadalafil , Treatment Outcome
19.
Braz. j. otorhinolaryngol. (Impr.) ; 79(6): 727-733, Nov-Dec/2013. tab
Article in Portuguese | LILACS | ID: lil-697686

ABSTRACT

O uso de inibidores da fosfodiesterase do tipo 5 como sildenafil, vardenafil e tadalafil tem aumentado atualmente e alguns destes pacientes vêm apresentando perda auditiva neurossensorial súbita. OBJETIVO: Apresentar dois casos de pacientes que apresentaram surdez súbita em uso eventual do medicamento e revisar estudos sobre o uso de inibidores da fosfodiesterase do tipo 5 e surdez súbita. MÉTODO: Estudo analítico de dois casos e revisão sobre o tema no banco de dados da Pubmed/ MedLine e Bireme utilizando as palavras-chave inibidores da fosfodiesterase e surdez súbita e seus correlatos na língua inglesa. RESULTADOS: Os pacientes analisados são jovens, sem comorbidades, em uso de inibidores da fosfodiesterase do tipo 5 e após terapia combinada para o tratamento da surdez súbita, apenas um deles obteve melhora auditiva. Nove estudos científicos foram encontrados. Estudos pré-clínicos e clínicos, transversais e prospectivos foram revisados. CONCLUSÃO: O aumento da ocorrência na prática clínica e relatos científicos na literatura sugerem que o uso de inibidores da fosfodiesterase do tipo 5 seja encarado como fator de risco para surdez súbita. Novos estudos com amostras maiores e grupo controle são necessários para investigar esta associação. .


Phosphodiesterase type 5 Inhibitors, such as sildenafil, vardenafil and tadalafil have been increasingly used today and some of the users have developed sudden sensorineural hearing loss. OBJECTIVE: To present two patients with sudden deafness developed after an occasional use of the drug and review studies on the use of phosphodiesterase type 5 inhibitors and sudden hearing loss. METHOD: Analytical study of two cases and review of the subject matter in the Pubmed/Medline and Bireme databases using the keywords: phosphodiesterase type 5 inhibitors and sudden deafness and its correlates in the English language. RESULTS: The patients analyzed are young without additional disorders, using phosphodiesterase type 5 inhibitors, and after combination treatment for sudden hearing loss only one had hearing improvement. We found nine scientific studies and reviewed preclinical studies, clinical trials, prospective and cross-sectional investigations. CONCLUSION: Increased occurrence in clinical practice and scientific reports in the literature suggest that the phosphodiesterase type 5 inhibitors are considered a risk factor for sudden deafness. Further studies with larger samples and control groups are needed for better assessing this association. .


Subject(s)
Adult , Humans , Male , Carbolines/therapeutic use , Hearing Loss, Sensorineural/drug therapy , Hearing Loss, Sudden/drug therapy , Imidazoles/therapeutic use , /therapeutic use , Piperazines/therapeutic use , Sulfones/therapeutic use , Drug Therapy, Combination , Purines/therapeutic use , Treatment Outcome , Triazines/therapeutic use
20.
An. bras. dermatol ; 88(4): 617-619, ago. 2013. graf
Article in English | LILACS | ID: lil-686522

ABSTRACT

Fixed drug eruptions (FDE) are commonly reported type of mucocutaneous drug eruption. The aim of this paper is to present a patient with multiple mucocutaneous erythema fixum type lesions caused by oral tadalafil use. A short course of topical corticosteroid therapy resulted in complete resolution of all lesions leaving residual hyperpigmentation of the involved skin sites. Mucosal oral lesions were effectively treated with gingival hyaluronic acid 0.2% gel. Conclusion: when assessing a patient of any age with drug eruptions, a thorough personal history should be obtained, in particular data on regular or recreational use of phospodiesterase type 5 inhibitors.


A erupção fixa por droga é um tipo de erupção mucocutânea comumente relatada, provocada pela administração de de drogas. O objetivo deste artigo é apresentar um paciente com múltiplas lesões mucocutâneas do tipo do eritema fixo, causadas pelo uso do tadalafil oral. Um breve período de tratamento com corticosteroides tópicos levou à completa resolução de todas as lesões, deixando hiperpigmentação residual nas áreas cutâneas envolvidas. As lesões da mucosa oral foram tratadas efetivamente com gel de ácido hialurônico gengival a 0,2%. Conclusão: ao avaliar o paciente com erupção fixa por druga, de qualquer idade, deve ser obtido seu histórico pessoal completo, especialmente dados sobre uso regular ou recreativo de inibidores de fosfodiesterase tipo 5.


Subject(s)
Adult , Humans , Male , Carbolines/adverse effects , Drug Eruptions/etiology , /adverse effects , Adrenal Cortex Hormones/therapeutic use , Drug Eruptions/drug therapy , Treatment Outcome
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