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1.
Metab Brain Dis ; 34(1): 319-329, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30515710

RESUMO

Allicin, one of the main biologically active compounds derived from garlic, was previously reported to possess multiple pharmacological activities. Whether allicin protected against chronic social defeat stress (CSDS) induced depressive-like behaviors remained unknown. Thus, our present study for the first time investigated the potential antidepressant effects and the mechanisms of allicin on the CSDS mice model. Thirty minutes before social defeat stress, allicin (2, 10, 50 mg/kg) was treated by intraperitoneal injection. The duration times of CSDS model establishment and allicin intervene were 10 days. Subsequently, the force swimming test (FST), social interaction test (SIT), and sucrose preference test (SPT) were applied for behavioral assessments. The levels of inflammation mediators were determined by commercial ELISA kits. The concentration of iron was tested, and relative protein expressions were measured by western blot. Oxidative stress and apoptosis markers were also detected by commercial kits and western blot. The behavioral defects induced by social defeat stress were obviously improved by allicin. Microglia activation, as well as inflammatory cytokines elevation in the hippocampus of CSDS also down-regulated by administration of allicin. Furthermore, content of iron and protein expressions of key components in iron metabolism were remarkably aberrant changed in the CSDS mice hippocampus, meanwhile, allicin ameliorated this phenomenon. Allicin decreased the production of reactive oxygen species (ROS), malondialdehyde (MDA), and protein carbonyl, and the protein expression of NOX4, as well as up-regulated the activities of superoxide dismutase (SOD) and Nrf2/HO-1 pathway. In addition, allicin attenuated the enhanced neuronal apoptosis. Finally, allicin supplementation inhibited the Nucleotide-binding oligomerization domain containing 3 (NLRP3) inflammasome hyperactivity, and the expressions of inflammasome components, such as ACS, caspase-1, and IL-1ß in the hippocampus of CSDS mice. Allicin attenuated depressive-like behaviors of CSDS mice through reducing neuroinflammation, ameliorating iron abnromal accumulation, balacing oxidative stress, and attenuation neuronal apoptosis in the hippocampus via suppression of NLRP3 inflammasome.


Assuntos
Antidepressivos/uso terapêutico , Comportamento Animal/efeitos dos fármacos , Depressão/tratamento farmacológico , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Estresse Psicológico/complicações , Ácidos Sulfínicos/uso terapêutico , Animais , Antidepressivos/farmacologia , Depressão/etiologia , Depressão/metabolismo , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Comportamento Social , Predomínio Social , Estresse Psicológico/metabolismo , Ácidos Sulfínicos/farmacologia
2.
Eur J Med Chem ; 162: 679-734, 2019 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-30496988

RESUMO

Sulfur (SVI) based moieties, especially, the sulfonyl or sulfonamide based analogues have showed a variety of pharmacological properties, and its derivatives propose a high degree of structural diversity that has established useful for the finding of new therapeutic agents. The developments of new less toxic, low cost and highly active sulfonamides containing analogues are hot research topics in medicinal chemistry. Currently, more than 150 FDA approved Sulfur (SVI)-based drugs are available in the market, and they are widely used to treat various types of diseases with therapeutic power. This comprehensive review highlights the recent developments of sulfonyl or sulfonamides based compounds in huge range of therapeutic applications such as antimicrobial, anti-inflammatory, antiviral, anticonvulsant, antitubercular, antidiabetic, antileishmanial, carbonic anhydrase, antimalarial, anticancer and other medicinal agents. We believe that, this review article is useful to inspire new ideas for structural design and developments of less toxic and powerful Sulfur (SVI) based drugs against the numerous death-causing diseases.


Assuntos
Descoberta de Drogas , Enxofre/uso terapêutico , Química Farmacêutica/métodos , Humanos , Ácidos Sulfínicos/uso terapêutico , Sulfonamidas/uso terapêutico , Terapêutica/métodos
3.
Food Funct ; 9(9): 4865-4875, 2018 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-30160278

RESUMO

Osteoarthritis (OA) is characterized by the degeneration and destruction of articular cartilage. Allicin, a dietary garlic active constituent, exerts anti-inflammatory effects on several diseases. However, its effects on OA have not been clearly elucidated. In this study, we explored the effects of allicin on OA in both in vitro and in vivo models. Allicin inhibited interleukin-1ß (IL-1ß) induced overproduction of nitric oxide, inducible nitric oxide synthase, prostaglandin E2, and cyclooxygenase-2, as well as pro-inflammatory cytokines tumor necrosis factor alpha and interleukin-6 in chondrocytes in a dose-dependent manner. Meanwhile, allicin reversed the overproduction of metalloproteinase-13 and a disintegrin and metalloproteinase with thrombospondin motifs-5 and the decrease of aggrecan and type II collagen. Furthermore, allicin dramatically suppressed IL-1ß-stimulated PI3K/Akt/NF-κB activation in chondrocytes. In vivo, treatment with allicin prevented the destruction of cartilage and inhibited PI3K/Akt/NF-κB activation in the cartilage of mice OA models. Taken together, these results indicate that allicin may be a potential therapeutic agent for OA.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Condrócitos/metabolismo , Suplementos Nutricionais , Modelos Animais de Doenças , Osteoartrite do Joelho/terapia , Ácidos Sulfínicos/uso terapêutico , Animais , Conservadores da Densidade Óssea/efeitos adversos , Conservadores da Densidade Óssea/metabolismo , Sobrevivência Celular , Células Cultivadas , Condrócitos/citologia , Condrócitos/patologia , Suplementos Nutricionais/efeitos adversos , Progressão da Doença , Feminino , Regulação da Expressão Gênica , Humanos , Interleucina-1beta/antagonistas & inibidores , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Masculino , Camundongos Endogâmicos C57BL , NF-kappa B/agonistas , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Osteoartrite do Joelho/metabolismo , Osteoartrite do Joelho/patologia , Osteoartrite do Joelho/fisiopatologia , Fosfatidilinositol 3-Quinase/química , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/agonistas , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/metabolismo , Distribuição Aleatória , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Transdução de Sinais , Ácidos Sulfínicos/efeitos adversos , Ácidos Sulfínicos/metabolismo
4.
Oxid Med Cell Longev ; 2018: 1780956, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30050645

RESUMO

The present study investigated the efficacy of allicin as an antibacterial, anti-inflammatory, antioxidant, and immunostimulant agent in reducing the severity of Pasteurella multocida (P. multocida) type B infection in rabbits. Fifty New Zealand rabbits, 5 weeks old, were divided equally into five groups. Except for group 1, all groups were intranasally infected with P. multocida type B (2 × 105 colony forming units/ml/rabbit). Then, group 3 rabbits were orally treated with allicin (50 mg/kg BW) for 5 days, group 4 rabbits received a single oral dose of norfloxacin 30% (100 mg/kg BW), while group 5 rabbits were treated with a combination of norfloxacin and allicin. Hematological, serum biochemical, inflammatory cytokine, immunological, and histopathological analyses were performed. Results revealed that rabbits, infected with P. multocida type B, exhibited macrocytic hypochromic anemia and leukocytosis with a significant elevation in the phagocytic percentage and index. Moreover, significant reductions in serum total protein, albumin, globulin, and immunoglobulin (IgG and IgM) levels were observed in infected rabbits. Infected rabbits showed significant increases in serum inflammatory cytokine (TNF-α and IL-6), alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, and serum bilirubin (total, direct, and indirect) levels. Further, P. multocida infection induced oxidative stress as demonstrated by the significant reduction in serum levels of reduced glutathione and superoxide dismutase enzyme and marked elevation in serum malondialdehyde. Treatment with allicin, norfloxacin, or their combination significantly ameliorated the alterations in all studied parameters. In conclusion, allicin could ameliorate the inflammation and oxidative stress, induced by P. multocida type B infection in rabbits.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Norfloxacino/uso terapêutico , Infecções por Pasteurella/sangue , Infecções por Pasteurella/tratamento farmacológico , Pasteurella multocida/patogenicidade , Ácidos Sulfínicos/uso terapêutico , Alanina Transaminase/sangue , Albuminas/metabolismo , Fosfatase Alcalina/sangue , Animais , Bilirrubina/sangue , Globulinas/metabolismo , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Interleucina-6/sangue , L-Lactato Desidrogenase/sangue , Masculino , Malondialdeído/sangue , Pasteurella multocida/efeitos dos fármacos , Coelhos , Superóxido Dismutase/sangue , Fator de Necrose Tumoral alfa/sangue
5.
Cell Physiol Biochem ; 47(2): 641-653, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29794468

RESUMO

BACKGROUND/AIMS: Cholangiocarcinoma (CCA) is a malignant tumor that is resistant to chemotherapy, so new therapeutic agents are needed. Allicin which is rapidly converted from allin by allinase, is one of the most biologically active compounds in freshly crushed garlic and has been shown to have strong anti-tumor effects. Our aim was to explore the molecular mechanism by which allicin affects the cell proliferation and invasion of CCA. METHODS: Cell viability and apoptosis were measured using the CCK-8 assay, colony formation assay, and flow cytometry. Cell migration and invasion were evaluated by wound healing and Transwell assays, respectively. The expression of several proteins involved in cell apoptosis and invasion were assessed by Western blot. The activation of STAT3 signaling was detected by Western blot and immunofluorescence staining. The involvement of SHP-1 was determined using small interfering RNA (siRNA). Moreover, a nude mouse model of human CCA was established to assess the anti-tumor effects of allicin in vivo. RESULTS: Allicin significantly suppressed CCA cell proliferation by activating the caspase cascade, inducing apoptosis, and reducing the expression of proteins downstream of STAT3, such as B-cell lymphoma 2 (Bcl-2), while upregulating Bcl-2-associated X (Bax) protein. In addition, allicin inhibited the migration, invasion, and epithelial-mesenchymal transition (EMT) of CCA cells. Moreover, the protein expression of MMP-2 and MMP-9 was significantly downregulated in CCA cells treated with allicin compared with CCA cells treated with control. Mechanistic investigations indicated that allicin upregulated SHP-1 expression in CCA, and pervanadate treatment reversed the allicin-induced downregulation of STAT3. Moreover, suppression of SHP-1 by siRNA overturned the effect of allicin on the induction of SHP-1 and inhibition of STAT3 activation. Additionally, treatment with allicin attenuated tumor growth in the nude mouse model of CCA. CONCLUSIONS: Our findings suggest that allicin suppresses cell proliferation and invasion via STAT3 signaling and may be a potential therapeutic agent for CCA.


Assuntos
Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Proteína Tirosina Fosfatase não Receptora Tipo 6/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Ácidos Sulfínicos/farmacologia , Animais , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Neoplasias dos Ductos Biliares/tratamento farmacológico , Neoplasias dos Ductos Biliares/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Colangiocarcinoma/tratamento farmacológico , Colangiocarcinoma/patologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Humanos , Metaloproteinases da Matriz/metabolismo , Camundongos , Camundongos Nus , Proteína Tirosina Fosfatase não Receptora Tipo 6/antagonistas & inibidores , Proteína Tirosina Fosfatase não Receptora Tipo 6/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Fator de Transcrição STAT3/genética , Ácidos Sulfínicos/química , Ácidos Sulfínicos/metabolismo , Ácidos Sulfínicos/uso terapêutico , Transplante Heterólogo
6.
Arch Ital Urol Androl ; 90(1): 59-64, 2018 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-29633800

RESUMO

OBJECTIVE: To assess the efficacy and safety of an association of diallyl thiosulfinate with nuciferine and diosgenin in the treatment of a group of patients suffering from premature ejaculation (PE), primary or secondary to erectile dysfunction (ED). MATERIALS AND METHODS: From July 2015 to October 2016, 143 patients (mean age 25.3; range 18-39) affected by PE completed the study and were finally analyzed in this phase I study. All patients, after clinical assessment and laboratory evaluation were asked to take an association of diallyl thiosulfinate with nuciferine and diosgenin as oral tablet, once a day, on alternate days, for three months. At the baseline and after three months of treatment, each patient was asked to complete the following questionnaires: International Index of Erectile Function (IIEF-5), Premature Ejaculation Diagnostic Tool (PEDT), Male Sexual Health Questionnaire (MSHQ). RESULTS: A statistical significant improvement in terms of erectile function, comparing the IIEF-5 value at baseline and follow- up visit was found (respectively IIEF-5: 8.7 vs 14.01; p < 0.001). Moreover, at follow-up visit, 97/143 men (67.8%) referred a subjective improvement of the erection quality and a better control of the ejaculation (PROs). The IELT improved too between the baseline evaluation and the follow-up visit (p < 0.001). CONCLUSION: In conclusion, our study, even if supported by preliminary results, showed how Diallyl Thiosulfinate, Nuciferine and Diosgenin is able to improve the control of ejaculation in patients suffering from PE, primary or secondary to ED without any significant adverse effects.


Assuntos
Aporfinas/uso terapêutico , Diosgenina/uso terapêutico , Ejaculação Precoce/tratamento farmacológico , Ácidos Sulfínicos/uso terapêutico , Adolescente , Adulto , Aporfinas/efeitos adversos , Diosgenina/efeitos adversos , Quimioterapia Combinada , Disfunção Erétil/tratamento farmacológico , Humanos , Masculino , Ereção Peniana , Projetos Piloto , Saúde Sexual , Ácidos Sulfínicos/efeitos adversos , Resultado do Tratamento , Adulto Jovem
7.
Eur J Med Chem ; 151: 520-532, 2018 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-29655084

RESUMO

A novel series of methylsulfonyl phenyl derivatives has been designed and synthesized to evaluate their COX-2 inhibitory activity along with anti-convulsant potential. In-vitro evaluation revealed that two compounds MTL-1 and MTL-2 appeared as most potent and selective COX-2 inhibitors in the entire series. Anti-convulsant activity of both potent COX-2 inhibitors was assessed in sc-PTZ induced seizure test and MTL-1 excellently protected animals against PTZ induced seizure at the dose of 30 mg/kg. MTL-1 also indicates long duration of action in time course study and displayed significant seizure protection up to 6 h of drug administration. Further, the anti-epileptogenic effect of MTL-1 has been examined in PTZ induced chronic model of epilepsy. The results indicated that MTL-1 had a significant anti-epileptogenic effect in PTZ kindled rats as compared to Etoricoxib (ETX) and PTZ alone treated group. Additionally, MTL-1 successfully improved cognition deficit in PTZ kindled rats, which was confirmed by social recognition, novel object recognition and light-dark chamber tests. Moreover, molecular docking and molecular simulation (MD simulation) studies were also performed to elucidate the interaction of MTL-1 with the active site of COX-2 and results showed that MTL-1 suitably binds within active site of COX-2. To investigate the safety profile of MTL-1, a sub-acute toxicity study was also performed and MTL-1 emerged as a new non-toxic chemical entity. Thus, the present investigation discovered a potent and safe COX-2 inhibitor, which is endowed with an effective anti-epileptic action.


Assuntos
Anticonvulsivantes/química , Anticonvulsivantes/uso terapêutico , Inibidores de Ciclo-Oxigenase 2/química , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Convulsões/tratamento farmacológico , Animais , Anticonvulsivantes/farmacologia , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase 2/farmacologia , Desenho de Drogas , Epilepsia/induzido quimicamente , Epilepsia/tratamento farmacológico , Epilepsia/enzimologia , Humanos , Masculino , Metilação , Simulação de Acoplamento Molecular , Pentilenotetrazol , Ratos , Ratos Wistar , Convulsões/induzido quimicamente , Convulsões/enzimologia , Ácidos Sulfínicos/química , Ácidos Sulfínicos/farmacologia , Ácidos Sulfínicos/uso terapêutico
8.
Int J Mol Sci ; 18(9)2017 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-28926934

RESUMO

Recent studies suggest that allicin may play a role in chronic kidney disease (CKD), reducing hypertension and oxidative stress and improving renal dysfunction. In the present study, CKD was induced by 5/6 nephrectomy and the animals were divided into four treatment groups as follows: control (C), CKD, CKD+allicin (40 mg/kg pathway oral) (CKDA), and CKD+Losartan (20 mg/kg) (CKDL). After CKD induction, the rats developed hypertension from week 3 to the end of the study. This was associated with increased creatinine and blood urea nitrogen (BUN) levels in serum, increased albuminuria, increased urinary excretion of N-acetyl-ß-d-glucosaminidase (NAG), increased nephrin expression, and incrased histological alterations in the cortex. The levels of angiotensin receptors and endothelial nitric oxide synthase (eNOS) were decreased in the renal cortex from the CKD group. Otherwise, lipid and protein oxidation were higher in the CKD group than in the control group. A disturbance was observed in the expression levels of the nuclear factor erythroid 2-related factor 2/Kelch ECH associating protein 1 system (Nrf2/keap1) and the antioxidant enzymes catalase, superoxide dismutase, and heme oxygenase-1. Allicin or losartan treatments relieved renal dysfunction, hypertension, and oxidative stress. In addition, both treatments showed the same efficacy on the expression of angiotensin receptors, the nephrin, Nrf2/keap1 pathway, and eNOS. Further in silico analyses suggest that allicin and losartan could have a common mechanism involving interaction with AT1 receptors. Allicin showed antihypertensive, antioxidant, and nephroprotective effects. The beneficial effects showed by allicin are similar, or even better, than those of losartan. In fact, the effect of allicin on blood pressure and renal function is comparable to reductions seen with losartan, a prescription drug commonly used as a first-line therapy.


Assuntos
Anti-Hipertensivos/uso terapêutico , Antioxidantes/uso terapêutico , Losartan/uso terapêutico , Insuficiência Renal Crônica/tratamento farmacológico , Ácidos Sulfínicos/uso terapêutico , Acetilglucosaminidase/urina , Animais , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/efeitos adversos , Antioxidantes/administração & dosagem , Antioxidantes/efeitos adversos , Creatinina/sangue , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Rim/metabolismo , Losartan/administração & dosagem , Losartan/efeitos adversos , Masculino , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Óxido Nítrico Sintase Tipo III/genética , Óxido Nítrico Sintase Tipo III/metabolismo , Estresse Oxidativo , Ratos , Ratos Wistar , Receptores de Angiotensina/genética , Receptores de Angiotensina/metabolismo , Ácidos Sulfínicos/administração & dosagem , Ácidos Sulfínicos/efeitos adversos , Ureia/sangue
9.
J Gastrointest Cancer ; 48(4): 314-320, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28828709

RESUMO

OBJECTIVE: Gastric cancer is one of the most common causes of cancer-related death worldwide. Medicinal plants are one of the main sources for discovery of new pharmacological agents especially for treatment of cancers. The aim of the present study is to review pharmacotherapeutic aspects of three mostly studied phytochemicals including curcumin, quercetin, and allicin for management of gastric cancer. METHODS: Scopus, PubMed, Web of Science, and Google Scholar were searched for the effects of curcumin, quercetin, allicin, and their analogs in gastric cancer. Data were collected up to November 2015. The search terms were "curcumin," "quercetin," "allicin," and "gastric cancer" or "cancer." RESULTS: Curcumin demonstrated anti-angiogenic, anti-proliferative, anti-metastatic, pro-apoptotic, and anti-helicobacter activities. Quercetin inhibited cell growth and induced apoptosis, necrosis, and autophagy as well as anti-Helicobacter activity. Allicin showed apoptotic and anti-Helicobacter properties. All three natural compounds had low bioavailability. CONCLUSIONS: Although preclinical studies demonstrated the activity of curcumin, quercetin, and allicin in gastric cancer, clinical trials are needed to confirm their effectiveness. Applying their possible synergistic action and suitable drug delivery system in clinical studies can be also an attractive approach with the purpose of finding new extremely efficient anti-gastric cancer agents. Curcumin, quercetin, and allicin seem to be good candidates for management of gastric cancer through their pro-apoptotic, anti-proliferative, and anti-helicobacter activities.


Assuntos
Anti-Infecciosos/uso terapêutico , Curcumina/uso terapêutico , Compostos Fitoquímicos/uso terapêutico , Quercetina/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Ácidos Sulfínicos/uso terapêutico , Anti-Infecciosos/farmacologia , Curcumina/farmacologia , Humanos , Compostos Fitoquímicos/farmacologia , Quercetina/farmacologia , Neoplasias Gástricas/patologia , Ácidos Sulfínicos/farmacologia
10.
Artigo em Inglês | MEDLINE | ID: mdl-28703780

RESUMO

Bacterial infections of cutaneous leishmaniasis cause skin ulcers on mice, resulting in increased tissue deterioration, and these infections can be controlled with liquid allicin. To isolate and identify the incidences of real secondary bacterial infections in mice, we performed the current study by injecting mice (n = 50) with Leishmania major. L. major infections were initiated by an intramuscular injection of 0.1 mL Roswell Park Memorial Institute (RPMI 1640 media/mouse (107 promastigote/mL)). Scarring appeared 2-6 weeks after injection, and the bacteria were isolated from the skin ulcer tissues. Allicin (50 µL/mL) and ciprofloxacin (5 µg; Cip 5) were used for controlling L. major and bacteria. One hundred samples from skin ulcers of mice were examined, and 200 bacterial colonies were isolated. Forty-eight different genera and species were obtained and identified by Gram staining and physiological and biochemical characterization using identification kits. All samples were positive for secondary bacterial infections. Of the isolates, 79.16% were identified as Gram-negative bacteria, and 28.84% were identified as Gram-positive bacteria; only one yeast species was found. Interestingly, pure allicin liquid at a concentration 50 µL/mL exhibited antibacterial activity against a wide range of Gram-negative and some Gram-positive bacteria, in addition to yeast, and was 71.43% effective. Antimicrobial resistance patterns of all genera and species were determined using 15 different antibiotics. Allicin (50 µL/mL) and Cip 5 were the most effective against L. major and 92.30% of isolated bacteria. Stenotrophomonas maltophilia was the most resistant bacterium to the tested antibiotics with a survival rate of 73.33%, and it exhibited resistance to allicin.


Assuntos
Anti-Infecciosos/uso terapêutico , Ciprofloxacino/uso terapêutico , Infecções por Bactérias Gram-Negativas , Infecções por Bactérias Gram-Positivas , Leishmaniose Cutânea , Ácidos Sulfínicos/uso terapêutico , Animais , Anti-Infecciosos/farmacologia , Ciprofloxacino/farmacologia , Feminino , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/isolamento & purificação , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/etiologia , Infecções por Bactérias Gram-Negativas/microbiologia , Bactérias Gram-Positivas/efeitos dos fármacos , Bactérias Gram-Positivas/isolamento & purificação , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/etiologia , Infecções por Bactérias Gram-Positivas/microbiologia , Leishmaniose Cutânea/complicações , Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Cutânea/microbiologia , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Ácidos Sulfínicos/farmacologia , Leveduras/efeitos dos fármacos , Leveduras/isolamento & purificação
11.
J Diabetes Res ; 2017: 3159798, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29675430

RESUMO

Background: Diabetic foot ulcers are one disabling complication of diabetes mellitus. Pirfenidone (PFD) is a potent modulator of extracellular matrix. Modified diallyl disulfide oxide (M-DDO) is an antimicrobial and antiseptic agent. Aim: To evaluate efficacy of topical PFD + M-DDO in a randomized, double-blind trial versus ketanserin in the treatment of noninfected chronic DFU. Methods: Patients received PFD + M-DDO or ketanserin for 6 months. Relative ulcer volume (RUV) was measured every month; biopsies were taken at baseline and months 1 and 2 for histopathology and gene expression analysis for COL-1α, COL-4, KGF, VEGF, ACTA2 (α-SMA), elastin, fibronectin, TGF-ß1, TGF-ß3, HIF-1α, and HIF-1ß. Results: Reduction of median RUV in the PFD + M-DDO group was 62%, 89.8%, and 99.7% at months 1-3 and 100% from months 4 to 6. Ketanserin reduced RUV in 38.4%, 56%, 60.8%, 94%, 94.8%, and 100% from the first to the sixth month, respectively. Healing score improved 4.5 points with PFD + M-DDO and 1.5 points with ketanserin compared to basal value. Histology analysis revealed few inflammatory cells and organized/ordered collagen fiber bundles in PFD + M-DDO. Expression of most genes was increased with PFD + M-DDO; 43.8% of ulcers were resolved using PFD + M-DDO and 23.5% with ketanserin. Conclusion: PFD + M-DDO was more effective than ketanserin in RUV reduction.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Pé Diabético/tratamento farmacológico , Piridonas/uso terapêutico , Cicatrização/efeitos dos fármacos , Adulto , Idoso , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico , Anti-Inflamatórios não Esteroides/farmacologia , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Ketanserina/farmacologia , Ketanserina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Piridonas/farmacologia , Ácidos Sulfínicos/farmacologia , Ácidos Sulfínicos/uso terapêutico , Resultado do Tratamento
12.
Chin J Integr Med ; 23(8): 589-597, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27412589

RESUMO

OBJECTIVE: To study the effects of allicin on cardiac function and underlying mechanism in rat model of myocardial infarction (MI). METHODS: Ninety-four Wistar rats were randomly assigned to 6 groups (n=14-16 per group): sham control group [underwent thoracotomy without left anterior descending (LAD) occlusion and only received an injection of the same amount of citrate buffer], MI control group (subjected to LAD occlusion and only received an injection of same amount of citrate buffer), positive control group (subjected to LAD occlusion and received an injection of diltiazem hydrochloride at the dose of 1.5 mg/kg), and MI + allicin groups (subjected to LAD occlusion and received an injection of allicin at the doses of 1.2, 1.8, and 3.6 mg/kg). All of the drugs were administered intraperitoneally daily for 21 days. The infarct area was measured by myocardial staining. Hematoxylin-eosin staining was used to observe the pathological changes. Cardiac function parameters were assessed by echocardiography. The myocardial apoptotic index was estimated by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining. The expression of Bax and Bcl-2 were detected by quantificational real-time polymerase chain reaction and Western blot. RESULTS: Treatment with allicin could attenuate the myocardial infarct area (P<0.05) and relieve the changes of the myocardium. The left ventricular anterior wall diastolic and systolic thicknesses were increased in the allicin-treated groups (P<0.05), while there was no signifificant difference in the left ventricular posterior wall diastolic and systolic thickness (P>0.05). The left ventricular internal diameter in systole, ejection fraction, fractional shortening, and stroke volume were dramatically elevated in allicin-treated rats (P<0.05). Allicin dose-dependently reduced creatine kinase and lactate dehydrogenase levels (P<0.05). The myocardial apoptotic index was also markedly lowered, and Bax expression was signifificantly decreased, whereas Bcl-2 expression exhibited an opposite trend in allicin-treated rats (P<0.05). CONCLUSION: Allicin appears to exert a cardioprotective effect that may be linked to blocking Bcl-2/Bax signaling pathway-denpendent apoptosis, further improving cardiac function.


Assuntos
Apoptose/efeitos dos fármacos , Testes de Função Cardíaca/efeitos dos fármacos , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/patologia , Ácidos Sulfínicos/uso terapêutico , Animais , Creatina Quinase/sangue , Modelos Animais de Doenças , Regulação para Baixo/efeitos dos fármacos , Marcação In Situ das Extremidades Cortadas , L-Lactato Desidrogenase/sangue , Masculino , Infarto do Miocárdio/sangue , Infarto do Miocárdio/diagnóstico por imagem , Miocárdio/patologia , Ratos Wistar , Ácidos Sulfínicos/farmacologia , Proteína X Associada a bcl-2/metabolismo
13.
J Sci Food Agric ; 97(4): 1359-1366, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27363537

RESUMO

BACKGROUND: Studies in animal models have shown that allicin, a major biologically active component of garlic, can play a role in the prevention of tissue fibrosis in the liver, lung and heart, mainly related to the inhibition of fibroblast proliferation, fibrogenic cytokine secretion and extracellular matrix synthesis. This study aimed to investigate the protective effects of allicin on renal damage in streptozotocin (STZ)-induced diabetic rats. STZ-induced diabetic rats were administered allicin (15, 30 and 45 mg · kg-1 · day-1 ) via daily intra-gastric gavage for 12 weeks. The levels of fasting blood glucose (FBG), blood urea nitrogen (BUN), serum creatinine (sCr), lipid and 24 h urine albumin excretion (UAE) were measured at the end of weeks 4, 8 and 12. The renal histopathology and the expression levels of collagen I, transforming growth factor ß1 (TGF-ß1) and phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2) were measured using immunohistochemistry and/or western blotting. RESULTS: In 12 week STZ-induced diabetic rats, severe hyperglycemia and albuminuria were markedly developed. Treatment with allicin for 12 weeks ameliorated diabetes-induced morphological alterations of the kidney and decreased FBG, BUN, sCr, triglyceride (TG) and 24 h UAE in diabetic rats. The expression levels of collagen I, TGF-ß1 and p-ERK1/2 were significantly decreased by allicin treatment. CONCLUSION: These results suggested that allicin may play a protective role in diabetic nephropathy via the TGF-ß1/ERK pathway in diabetic rats. © 2016 Society of Chemical Industry.


Assuntos
Allium/química , Glicemia/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Rim/efeitos dos fármacos , Fitoterapia , Ácidos Sulfínicos/uso terapêutico , Albuminas/metabolismo , Albuminúria/tratamento farmacológico , Albuminúria/etiologia , Animais , Nitrogênio da Ureia Sanguínea , Colágeno Tipo I/metabolismo , Creatinina/sangue , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/patologia , Nefropatias Diabéticas/induzido quimicamente , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Hiperglicemia/tratamento farmacológico , Hiperglicemia/etiologia , Rim/metabolismo , Rim/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Fosforilação , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Raízes de Plantas , Ratos Sprague-Dawley , Estreptozocina , Ácidos Sulfínicos/farmacologia , Fator de Crescimento Transformador beta1/metabolismo , Triglicerídeos/sangue
14.
Oxid Med Cell Longev ; 2016: 3850402, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27990229

RESUMO

This work was performed to study the effect of allicin on hypertension and cardiac function in a rat model of CKD. The groups were control, CKD (5/6 nephrectomy), and CKD-allicin treated (CKDA) (40 mg/kg day/p.o.). Blood pressure was monitored (weekly/6 weeks). The cardiac function, vascular response to angiotensin II, oxidative stress, and heart morphometric parameters were determined. The CKD group showed hypertension and proteinuria. The coronary perfusion and left ventricular pressures were decreased in CKD group. In contrast, the vascular response to angiotensin II and expression of angiotensin II type 1 receptor (AT1R) were increased. These data were associated with the increment in morphometric parameters (weight of heart and left ventricle, heart/BW and left ventricular mass index, and wall thickness). Concurrently, the oxidative stress was increased and correlated inversely with the expression of Nrf2, Keap1, and antioxidant enzymes Nrf2-regulated. Allicin treatment attenuated hypertension and improved the renal and the cardiac dysfunctions; furthermore, it decreased the vascular reactivity to angiotensin II, AT1R overexpression, and preserved morphometric parameters. Allicin also downregulated Keap1 and increased Nrf2 expression, upregulated the antioxidant enzymes, and reduced oxidative stress. In conclusion, allicin showed an antihypertensive, nephroprotective, cardioprotective, and antioxidant effects, likely through downregulation of AT1R and Keap1 expression.


Assuntos
Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/fisiopatologia , Ácidos Sulfínicos/uso terapêutico , Animais , Antioxidantes/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Testes de Função Cardíaca , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/patologia , Ventrículos do Coração/fisiopatologia , Hipertensão/complicações , Hipertensão/metabolismo , Rim/efeitos dos fármacos , Rim/fisiopatologia , Testes de Função Renal , Masculino , Miocárdio/enzimologia , Miocárdio/patologia , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Perfusão , Ratos Wistar , Receptor Tipo 1 de Angiotensina/metabolismo , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/metabolismo , Ácidos Sulfínicos/farmacologia , Sístole/efeitos dos fármacos
15.
Mol Med Rep ; 14(4): 3086-92, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27573340

RESUMO

Allicin is a major component of garlic, extracted as an oily liquid. The present study was designed to investigate the beneficial effects of allicin on traumatic spinal cord injury (TSCI) in mice, and whether the effects are mediated via regulation of the heat shock protein 70 (HSP70), v­akt murine thymoma viral oncogene homolog 1 (Akt) and inducible nitric oxide synthase (iNOS) pathways. Adult BALB/c mice (30­40 g) received a laminectomy at the T9 vertebral level as a model of TSCI. In the present study, treatment of the TSCI mice with allicin significantly increased their Basso, Beattie and Bresnahan (BBB) scores (P<0.01) and reduced the spinal cord water content (P<0.01). This protective effect was associated with the inhibition of oxidative stress and inflammatory responses in TSCI mice. Western blot analysis demonstrated that allicin increased the protein levels of HSP70, increased the phosphorylation of Akt and reduced the iNOS protein expression levels in TSCI mice. Additionally, treatment with allicin significantly reduced the levels of ROS and enhanced the NADH levels in TSCI mice. Collectively, these data demonstrate that the effects of allicin on TSCI are mediated via regulation of the HSP70, Akt and iNOS pathways in mice.


Assuntos
Antioxidantes/uso terapêutico , Proteínas de Choque Térmico HSP70/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Traumatismos da Medula Espinal/tratamento farmacológico , Medula Espinal/efeitos dos fármacos , Ácidos Sulfínicos/uso terapêutico , Animais , Antioxidantes/química , Alho/química , Camundongos , Camundongos Endogâmicos BALB C , Fármacos Neuroprotetores/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Recuperação de Função Fisiológica , Medula Espinal/metabolismo , Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/fisiopatologia , Ácidos Sulfínicos/química
16.
PLoS One ; 11(8): e0161296, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27537199

RESUMO

BACKGROUND: Leishmania is a unicellular protozoan parasite that produces several human diseases, ranging from localized self-healing cutaneous lesions to deadly visceral infections. OBJECTIVE: The effect of allicin on the growth of Leishmania major (L. major) promastigotes was evaluated under in vitro conditions. Moreover, the efficacy of a topical allicin cream was examined in BALB/c (Bagg albino, laboratory-bred strain of the House Mouse) mice with cutaneous leishmanial lesions compared to the currently used drug, sodiumstibogluconate (pentostam). METHODS: Cytotoxiciy and promastigote proliferation were measured. Different concentrations (50, 100, 150, and 200 µM) of liquid allicin were tested on L. major promastigotes twice: after 24 and 48 hours using an MTT colorimetric assay. In the in vivo condition, the efficacies of allicin cream and liquid allicin at two concentrations (0.15 µM/mouse and 0.30 µM/mouse) were evaluated. Serum factors of the control and treated groups were tested to evaluate the toxic effects of allicin on the liver and kidney. RESULTS: Allicin at a concentration of 50 µM inhibited the growth of Leishmania promastigotes. Topical application of allicin cream reduced lesion sizes in mice. No significant differences in biochemical analysis were observed between the control and treated groups. CONCLUSIONS: Allicin has antileishmanial effects under in vitro and in vivo conditions and may be used in clinical applications.


Assuntos
Antiprotozoários/uso terapêutico , Leishmania major/efeitos dos fármacos , Leishmaniose Cutânea/tratamento farmacológico , Ácidos Sulfínicos/uso terapêutico , Administração Cutânea , Animais , Antiprotozoários/administração & dosagem , Feminino , Camundongos , Camundongos Endogâmicos BALB C/parasitologia , Creme para a Pele , Ácidos Sulfínicos/administração & dosagem
17.
J Nutr ; 146(2): 403S-409S, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26764335

RESUMO

For centuries, garlic has been shown to exert substantial medicinal effects and is considered to be one of the best disease-preventative foods. Diet is important in the maintenance of health and prevention of many diseases including cardiovascular disease (CVD). Preclinical and clinical evidence has shown that garlic reduces risks associated with CVD by lowering cholesterol, inhibiting platelet aggregation, and lowering blood pressure. In recent years, emerging evidence has shown that hydrogen sulfide (H2S) has cardioprotective and cytoprotective properties. The active metabolite in garlic, allicin, is readily degraded into organic diallyl polysulfides that are potent H2S donors in the presence of thiols. Preclinical studies have shown that enhancement of endogenous H2S has an impact on vascular reactivity. In CVD models, the administration of H2S prevents myocardial injury and dysfunction. It is hypothesized that these beneficial effects of garlic may be mediated by H2S-dependent mechanisms. This review evaluates the current knowledge concerning the cardioprotective effects of garlic-derived diallyl polysulfides.


Assuntos
Alho/química , Coração/efeitos dos fármacos , Sulfeto de Hidrogênio/uso terapêutico , Miocárdio , Fitoterapia , Extratos Vegetais/uso terapêutico , Ácidos Sulfínicos/uso terapêutico , Fármacos Cardiovasculares/farmacologia , Fármacos Cardiovasculares/uso terapêutico , Humanos , Sulfeto de Hidrogênio/metabolismo , Sulfeto de Hidrogênio/farmacologia , Extratos Vegetais/farmacologia , Sulfetos/farmacologia , Sulfetos/uso terapêutico , Ácidos Sulfínicos/farmacologia
18.
Life Sci ; 143: 114-23, 2015 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-26546416

RESUMO

AIMS: This study aims to investigate the effect of allicin on motor functions and histopathologic changes after spinal cord injury and the mechanism underlying its neuroprotective effects. MAIN METHODS: The motor function of rats was evaluated with the Basso, Beattie, and Bresna test. Histopathologic changes were evaluated by hematoxylin and eosin and Nissl staining. Spinal cord oxidative stress markers were determined by measuring glutathione and malondialdehyde content and superoxide dismutase activity using commercial kits. Inflammatory factors were determined by measuring tumor necrosis factor-α, interleukin-1ß and interleukin-6 using ELISA assay. Apoptosis was examined using TUNEL staining. The effect of allicin on Nrf2 protein levels and localization was assessed using immunofluorescence staining and Western blotting analysis. KEY FINDINGS: Results demonstrated that allicin accelerated the motor functional recovery and protected neuron damage against spinal cord injury (SCI). SCI-induced oxidative stress, inflammatory response and cell apoptosis in the spinal cord were also prevented by allicin. In addition, we observed that SCI increased Nrf2 nuclear expression, and allicin treatment further increased Nrf2 nuclear translocation in neurons and astrocytes. siRNA-mediated Nrf2 gene knockdown completely blocked the effect of allicin on spinal cord tissue. SIGNIFICANCE: Our finding suggests that allicin promotes the recovery of motor function after SCI in rats, and this effect may be related to its anti-oxidant, anti-inflammatory and anti-apoptotic effects. Allicin mediated Nrf2 nuclear translocation may be involved in the protective effect as well.


Assuntos
Modelos Animais de Doenças , Fármacos Neuroprotetores/uso terapêutico , Traumatismos da Medula Espinal/prevenção & controle , Ácidos Sulfínicos/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Relação Dose-Resposta a Droga , Feminino , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Ratos , Ratos Sprague-Dawley , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/patologia , Ácidos Sulfínicos/farmacologia , Resultado do Tratamento
19.
PLoS One ; 10(11): e0142768, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26556805

RESUMO

INTRODUCTION: Prosthetic mesh infection constitutes one of the major complications following hernia repair. Antimicrobial, non-antibiotic biomaterials have the potential to reduce bacterial adhesion to the mesh surface and adjacent tissues while avoiding the development of novel antibiotic resistance. This study assesses the efficacy of presoaking reticular polypropylene meshes in chlorhexidine or a chlorhexidine and allicin combination (a natural antibacterial agent) for preventing bacterial infection in a short-time hernia-repair rabbit model. METHODS: Partial hernia defects (5 x 2 cm) were created on the lateral right side of the abdominal wall of New Zealand White rabbits (n = 21). The defects were inoculated with 0.5 mL of a 106 CFU/mL Staphylococcus aureus ATCC25923 strain and repaired with a DualMesh Plus antimicrobial mesh or a Surgipro mesh presoaked in either chlorhexidine (0.05%) or allicin-chlorhexidine (900 µg/mL-0.05%). Fourteen days post-implant, mesh contraction was measured and tissue specimens were harvested to evaluate bacterial adhesion to the implant surface (via sonication, S. aureus immunolabeling), host-tissue incorporation (via staining, scanning electron microscopy) and macrophage response (via RAM-11 immunolabeling). RESULTS: The polypropylene mesh showed improved tissue integration relative to the DualMesh Plus. Both the DualMesh Plus and the chlorhexidine-soaked polypropylene meshes exhibited high bacterial clearance, with the latter material showing lower bacterial yields. The implants from the allicin-chlorhexidine group displayed a neoformed tissue containing differently sized abscesses and living bacteria, as well as a diminished macrophage response. The allicin-chlorhexidine coated implants exhibited the highest contraction. CONCLUSIONS: The presoaking of reticular polypropylene materials with a low concentration of chlorhexidine provides the mesh with antibacterial activity without disrupting tissue integration. Due to the similarities found with the antimicrobial DualMesh Plus material, the chlorhexidine concentration tested could be utilized as a prophylactic treatment to resist infection by prosthetic mesh during hernia repair.


Assuntos
Antibacterianos/uso terapêutico , Clorexidina/uso terapêutico , Herniorrafia/métodos , Infecções Estafilocócicas/prevenção & controle , Ácidos Sulfínicos/uso terapêutico , Telas Cirúrgicas , Animais , Materiais Biocompatíveis , Bioensaio , Coelhos , Staphylococcus aureus , Resultado do Tratamento
20.
Urologia ; 82(4): 238-41, 2015.
Artigo em Italiano | MEDLINE | ID: mdl-26391664

RESUMO

The aim of the study is to evaluate the efficacy of Diallil-Tiosulphinate, Nuciepherine and Diosgenin in the treatment of erectile dysfunction. In our study were selected 120 men affected by erectile dysfunction. They were filled in a self-administered questionnaire International Index of Sexual Medicine. 74 of them reported a moderate erectile dysfunction and 46 reported a severe ED. All patients were treated with Tadalafil 5 mg once a day for 90 days. They were re-evaluated with the same questionnaire after three months of therapy. In 75% of the patients there was an improvement of IIEF-5 score. Only the 90 patients responders to Tadalafil once a day were randomized and divided into two groups, each formed by 45 subjects. The group A was treated with the association of Diallil-Tiosulfinate, Nucipherine and Diosgenin on alternate days. The patients of group B were treated with placebo. After three months, there was a new evaluation with IIEF-5 score. In group A we reported a maintenance of improvement post-Tadalafil in 36 patients;in group B, only 18 patients have maintained the previous improvement, according to IIEF-5 score. The ?2 test is 13,38, with a p-value of about 0,00013.The maintenance's odds ratio, confronting the two groups, is 6 with a confidence's interval of 95%. The study shows that the utilization of the association therapy in patients with erectile dysfunction responders to Tadalafil once a day is able to duplicate the odds of maintenance's improvement compared to placebo.


Assuntos
Aporfinas/uso terapêutico , Diosgenina/uso terapêutico , Disfunção Erétil/tratamento farmacológico , Inibidores da Fosfodiesterase 5/uso terapêutico , Ácidos Sulfínicos/uso terapêutico , Tadalafila/administração & dosagem , Humanos , Masculino , Método Simples-Cego
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