Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 134
Filtrar
1.
Biochem Biophys Res Commun ; 505(2): 485-491, 2018 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-30268504

RESUMO

Adverse side effects of conventional chemotherapy, acquired resistance and fatal tumor metastasis of human colorectal cancer (CRC) are propelling the exploration for novel selective anticarcinogens. Solasodine is a main active component isolated from Solanum incanum L that exhibited a potent stemness and invasion inhibitory effect on human colorectal cancer HCT116 cells. Colony Spheroid formation assay showed that solasodine dose-dependently prohibited HCT116 cell stemness. CD133, CD44, Nanog, Oct-4 and Sox-2 were inhibited by solasodine to reverse stemness and similar mechanism was stimulated in vivo. Transwell and scratch wound assays revealed that solasodine impeded HCT116 cell invasion and migration potential strengthened by TGF-ß1. Moreover, solasodine attenuated TGF-ß1-induced EMT and decreased MMPs while in vivo study showed the same trend. The results of this study implied that solasodine may be a novel therapeutic drug for CRC treatment.


Assuntos
Antineoplásicos/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Alcaloides de Solanáceas/farmacologia , Animais , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Movimento Celular , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica/genética , Alcaloides de Solanáceas/química , Alcaloides de Solanáceas/uso terapêutico , Fator de Crescimento Transformador beta1/farmacologia
2.
Biomed Pharmacother ; 105: 606-615, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29890469

RESUMO

Solanine A is a novel steroidal alkaloid isolated from Solanum nigrum Linn., a medicinal and edible plant which is widely used for treating various inflammatory diseases. In this study, we found that solanine A markedly suppressed the production of nitric oxide (NO) and prostaglandin E2 (PGE2) in lipopolysaccharide/interferon-γ (LPS/IFNγ)-stimulated RAW264.7 cells, and attenuated xylene, carrageenan and agar-induced inflammation in mice. The mRNA levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX2), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and -1ß (IL-1ß), as well as C-X-C motif chemokine ligand-9 (CXCL9), were significantly decreased by solanine A. Furthermore, solanine A also suppressed LPS/IFNγ-induced protein expression of iNOS and COX2. Mechanistically, solanine A inhibited the nuclear translocation of nuclear factor-κB (NF-κB) through the prevention of NF-κB p65 and inhibitory κB-α (IκBα) phosphorylation and IκBα degradation, and it also suppressed activation of extracellular regulated protein kinases (ERK), signal transducers and activators of transcription-1 (STAT1) and serine/threonine protein kinase Akt in LPS/IFNγ-stimulated RAW264.7 macrophages and agar-induced granuloma model in mice. Taken together, solanine A exhibits a potent anti-inflammatory activity in LPS/IFNγ- activated macrophages and animal models of inflammation through inhibition of NF-κB, ERK1/2, Akt and STAT1 signaling pathways, suggesting that solanine A may be a valuable leading compound in the treatment of inflammatory diseases.


Assuntos
Anti-Inflamatórios/farmacologia , Edema/tratamento farmacológico , Granuloma/tratamento farmacológico , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Alcaloides de Solanáceas/farmacologia , Solanum nigrum/química , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/uso terapêutico , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Edema/imunologia , Granuloma/imunologia , Interferon gama/farmacologia , Lipopolissacarídeos/farmacologia , Ativação de Macrófagos/imunologia , Macrófagos/imunologia , Masculino , Camundongos Endogâmicos ICR , Alcaloides de Solanáceas/isolamento & purificação , Alcaloides de Solanáceas/uso terapêutico
3.
J Dermatol Sci ; 90(3): 295-302, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29530340

RESUMO

BACKGROUND: Currently available topical treatments for actinic keratosis (AK) are associated with substantial side-effects. OBJECTIVES: To evaluate the efficacy and safety of topical SR-T100 gel in treating AK. METHODS: A multicenter, randomized, double-blinded phase III trial was conducted. Patients with at least two clinically visible AK were enrolled and a punch biopsy was performed on one of the AK to confirm the diagnosis. This study consisted of up to 16-week treatment and 8-week post-treatment periods. Medication was applied daily with occlusive dressing. RESULTS: 123 subjects were recruited and 113 were randomized. 76 subjects were in the SR-T100 and 37 in the vehicle arms. In SR-T100 and vehicle groups, 32.39% and 17.14% of subjects achieved complete clearance, respectively. For 75% partial clearance of lesions, 71.83% and 37.1% of subjects achieved this goal in SR-T100 and vehicle group, respectively. When comparing SR-T100 to vehicle, the odds ratio of complete clearance was 2.14 (p = 0.111), and odds ratio of partial clearance was 4.36 (p < 0.001). Severe local reactions were reported by only one subject using SR-T100. CONCLUSION: The imitation of the study was that not all the treated AK lesions were confirmed by histopathology. The diagnostic uncertainty may contribute to the high partial clearance rate in the vehicle group since the clinical-diagnosed AK showed higher clearance rate compared to histopathology-confirmed AK. The use of occlusive dressing was another possible explanation for high placebo effects. The results suggested that topical SR-T100 gel may be an effective and safe treatment for field therapy of AK.


Assuntos
Fármacos Dermatológicos/uso terapêutico , Ceratose Actínica/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Alcaloides de Solanáceas/uso terapêutico , Administração Cutânea , Idoso , Idoso de 80 Anos ou mais , Biópsia , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Géis , Humanos , Ceratose Actínica/patologia , Masculino , Pessoa de Meia-Idade , Placebos , Pele/patologia , Taiwan , Resultado do Tratamento
4.
Int Urol Nephrol ; 50(3): 441-449, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29299824

RESUMO

PURPOSE: To investigate the correlation between urethral instability (URI) and overactive bladder (OAB) in children. METHODS: We retrospectively investigated 126 children with OAB and 36 children without OAB using synchro-cystourethrometry. The prevalence of detrusor overactivity (DO) and URI, and the diagnostic sensitivity of DO alone and DO combined with URI, was compared. The OAB children with URI voluntarily received transcutaneous electrical pudendal nerve stimulation with anisodamine (stimulation group, SG) or anisodamine alone (non-stimulation group, NSG). The effectiveness of treatment was evaluated. Average voided volume (AVV), maximum voided volume (MVV), and number of voids per day (NV) were collected and analyzed. RESULTS: In OAB children, the prevalence of DO and URI was 51.6 and 32.5%, respectively. The prevalence of URI was 5.6% in controls. The prevalence of URI was significantly higher in OAB children. The diagnostic sensitivity and Youden index of DO combined with URI were higher than DO alone. In SG, 45.7% of children were cured, with a ≥ 50% improvement rate of 82.9%, while no child was cured, with a ≥ 50% improvement rate of 36.8% in NSG. A significant increase in AVV and MVV together, with a decrease in NV, was seen in SG. There was a significant difference in visual analogue scale values between SG and NSG (P < 0.01). CONCLUSIONS: Urethral instability plays an essential role in the pathogenesis and progression of OAB in children. Synchro-cystourethrometry is a useful urodynamic technology to precisely diagnose OAB, and transcutaneous electrical pudendal nerve stimulation may be an effective treatment for OAB children induced by URI.


Assuntos
Agonistas alfa-Adrenérgicos/uso terapêutico , Alcaloides de Solanáceas/uso terapêutico , Estimulação Elétrica Nervosa Transcutânea , Doenças Uretrais/terapia , Bexiga Urinária Hiperativa/diagnóstico , Bexiga Urinária Hiperativa/terapia , Criança , Terapia Combinada , Feminino , Humanos , Masculino , Nervo Pudendo , Estudos Retrospectivos , Doenças Uretrais/complicações , Doenças Uretrais/fisiopatologia , Bexiga Urinária/fisiopatologia , Bexiga Urinária Hiperativa/etiologia , Bexiga Urinária Hiperativa/fisiopatologia , Micção , Urodinâmica
5.
Mol Med Rep ; 17(1): 1253-1260, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29115503

RESUMO

The aim of the present study was to investigate the cardioprotective effects of anisodamine against myocardial ischemia/reperfusion (I/R) injury and the molecular mechanisms involved. The present results demonstrated that anisodamine attenuated myocardial infarct sizes, decreased the levels of creatine kinase and lactate dehydrogenase, whereas it increased the left ventricular (LV) systolic pressure, the LV end­diastolic pressure, and the LV pressure maximum rising and falling rates in a myocardial I/R rat model. In addition, anisodamine was revealed to suppress oxidative stress, inflammatory factor production and myocardial cell apoptosis, as demonstrated by the downregulation of caspase­3 and apoptosis regulator BAX protein expression. The production of reactive oxygen species was decreased and the protein expression of inducible nitric oxide synthase (iNOS) was downregulated, whereas the expression of endothelial NOS was enhanced. In addition, the activity of nicotinamide­adenine dinucleotide phosphate oxidase (Nox) was suppressed and the expression of Nox4 was downregulated in rats with myocardial I/R injury. In conclusion, the results of the present study suggested that anisodamine exerted a cardioprotective effect against myocardial I/R injury in rats, through the inhibition of oxidative stress, the suppression of inflammatory processes and the inhibition of myocardial cell apoptosis.


Assuntos
Anti-Inflamatórios/farmacologia , Cardiotônicos/farmacologia , Infarto do Miocárdio/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Alcaloides de Solanáceas/farmacologia , Animais , Anti-Inflamatórios/uso terapêutico , Apoptose/efeitos dos fármacos , Cardiotônicos/uso terapêutico , Caspase 3/sangue , Avaliação Pré-Clínica de Medicamentos , Expressão Gênica/efeitos dos fármacos , Mediadores da Inflamação/sangue , Masculino , Infarto do Miocárdio/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Miocárdio/patologia , NADPH Oxidase 4/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Alcaloides de Solanáceas/uso terapêutico , Proteína X Associada a bcl-2/metabolismo
6.
Cell Physiol Biochem ; 43(6): 2310-2326, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29073599

RESUMO

BACKGROUND/AIMS: Solamargine, one natural photochemical component from traditional plants, has been shown to have anti-cancers properties. We previously showed that solamargine inhibited the growth of non-small-cell lung cancer (NSCLC) cells through suppression of prostaglandin E2 (PGE2) receptor EP4 gene and regulation of downstream signaling pathways. However, the detailed mechanism underlying this, especially in combination of metformin, a known AMPK activator, still remained to be determined. METHODS: Cell viability was measured using a 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and colorimetric 5-bromo-2-deoxyuridine (BrdU) ELISA methods, respectively. Western blot analysis and immunohistochemistry were performed to examine the phosphorylation and protein expressions of signal transducer and activator of transcription 3 (Stat3), SP1, forkhead box O3a (FOXO3a), and insulin-like growth factor (IGF)-IGF binding protein 1 (IGFBP1). The expression of IGFBP1 mRNA was measured by quantitative real time PCR (qRT-PCR). Silencing of FOXO3a and IGFBP1 were examined by siRNA procedures. Exogenously expression of SP1, FOXO3a, and IGFBP1 were carried out by transient transfection assays. The promoter activity of IGFBP1 was tested using Secrete-PairTM Dual Luminescence Assay Kit. A xenografted tumor model was used to further test the effect of solamargine in combining with metformin in vivo. RESULTS: We further demonstrated that solamargine inhibited growth and induced cell cycle arrest in other NSCLC cell lines. Through mechanism-based approaches, we showed that solamargine decreased the phosphorylation of Stat3; In addition, solamargine induced FOXO3a, whereas reduced SP1 protein levels; all of which were abrogated in cells with overexpressed Stat3 gene. Interestingly, there is interaction between FOXO3a and SP1. Moreover, solamargine increased mRNA, protein expression and promoter activity of IGFBP1, which was not observed in cells with overexpressed SP1 or with silenced FOXO3a genes. Finally, ablation of IGFBP1 expression by siRNA blocked the effect of solamargine on cell growth inhibition. More importantly, there was a synergy of combination of solamargine and metformin. Similar findings were also observed in vivo. CONCLUSION: Our results show that solamargine increases IGFBP1 gene expression through inactivation of Stat3, followed by regulation and reciprocal interaction of FOXO3a and SP1 in vitro and in vivo. This ultimately leads to suppression of human lung cancer cell growth. Moreover, this is a synergy of solamargine in combination with metformin in this process. This study unravels a novel mechanism underlying the anti-lung cancer effects of solamargine in combination of metformin, and suggests a potential new lung cancer associated therapy.


Assuntos
Proteína Forkhead Box O3/metabolismo , Expressão Gênica/efeitos dos fármacos , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Metformina/toxicidade , Fator de Transcrição STAT3/metabolismo , Alcaloides de Solanáceas/toxicidade , Fator de Transcrição Sp1/metabolismo , Células A549 , Animais , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Proteína Forkhead Box O3/antagonistas & inibidores , Proteína Forkhead Box O3/genética , Humanos , Imuno-Histoquímica , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/antagonistas & inibidores , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Neoplasias Pulmonares , Metformina/uso terapêutico , Camundongos , Camundongos Nus , Fosforilação/efeitos dos fármacos , Regiões Promotoras Genéticas , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Transdução de Sinais/efeitos dos fármacos , Alcaloides de Solanáceas/uso terapêutico , Transplante Heterólogo
7.
Biomed Pharmacother ; 94: 446-457, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28779706

RESUMO

Over the past few years, it was suggested that a rational approach to treat cancer in clinical settings requires a multipronged approach that augments improvement in systemic efficiency along with modification in cellular phenotype leads to more efficient cell death response. Recently, the combinatory delivery of traditional chemotherapeutic drugs with natural compounds proved to be astonishing to deal with a variety of cancers, especially that are resistant to chemotherapeutic drugs. The natural compounds not only synergize the effects of chemotherapeutics but also minimize drug associated systemic toxicity. In this review, our primary focus was on antitumor effects of natural compounds. Previously, the drugs from natural sources are highly precise and safer than drugs of synthetic origins. Many natural compounds exhibit anti-cancer potentials by inducing apoptosis in different tumor models, in-vitro and in-vivo. Furthermore, natural compounds are also found equally useful in chemotherapeutic drug resistant tumors. Moreover, these Phyto-compounds also possess numerous other pharmacological properties such as antifungal, antimicrobial, antiprotozoal, and hepatoprotection. Aglycone solasodine and solanidine derivatives are the utmost important steroidal glycoalkaloids that are present in various Solanum species, are discussed here. These natural compounds are highly cytotoxic against different tumor cell lines. As the molecular weight is concerned; these are smaller molecular weight chemotherapeutic agents that induce cell death response by initiating apoptosis through both extrinsic and intrinsic pathways.


Assuntos
Diosgenina/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Alcaloides de Solanáceas/uso terapêutico , Animais , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Diosgenina/química , Humanos , Modelos Biológicos , Alcaloides de Solanáceas/química
8.
J Dig Dis ; 18(8): 453-460, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28677349

RESUMO

OBJECTIVE: Acute gastric or intestinal spasm-like pain is common in clinical setting. Hyoscine butylbromide (HBB), an anti-cholinergic agent, relieves pain in stomach and bowel cramps by inhibiting smooth muscle contractility. In this study, we aimed to compare the efficacy and safety of parenteral HBB and anisodamine for treating acute gastric or intestinal pain. METHODS: In this randomized, controlled, double-blind, parallel-group, multicenter non-inferiority trial, 299 Chinese patients were randomly assigned to HBB or anisodamine in a ratio of 1:1. They were administrated a single dose of either HBB 20 mg or anisodamine 10 mg, and a second dose was given when needed. The primary end-point was the difference in pain intensity (PID) from the pre-dose baseline at 20 min after the first injection. RESULTS: Altogether 295 patients completed the protocol (153 in the HBB and 142 in the anisodamine group). For the primary end-point, the PID was -4.09 (95% confidence interval [CI]: -4.41, -3.76) for the HBB group and -3.66 (95% CI: -4.02, -3.31) for the anisodamine group (P < 0.0001 for non-inferiority). The percentage of patients with at least one adverse event was lower in the HBB group than in the anisodamine group (13.1% vs 17.6%), but there was no statistical significance (P = 0.279). The most frequent adverse events were thirst (7.8%) and dry mouth (2.6%) in the HBB group, and thirst (7.0%), dry mouth (3.5%) and nodal arrhythmia (2.1%) in the anisodamine group. CONCLUSIONS: HBB 20 mg was not inferior to anisodamine 10 mg in pain relief of patients with acute gastric or intestinal spasm-like pain. Both drugs were safe and well tolerated.


Assuntos
Dor Abdominal/tratamento farmacológico , Dor Aguda/tratamento farmacológico , Brometo de Butilescopolamônio/uso terapêutico , Antagonistas Muscarínicos/uso terapêutico , Alcaloides de Solanáceas/uso terapêutico , Espasmo/tratamento farmacológico , Adulto , Brometo de Butilescopolamônio/efeitos adversos , Cólica/tratamento farmacológico , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antagonistas Muscarínicos/efeitos adversos , Medição da Dor/métodos , Alcaloides de Solanáceas/efeitos adversos , Resultado do Tratamento
9.
J Cell Mol Med ; 21(2): 222-233, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27620163

RESUMO

Lung cancer is the most common cancer and the leading cause of cancer deaths worldwide. We previously showed that solamargine, one natural phytochemicals from traditional plants, inhibited the growth of lung cancer cells through inhibition of prostaglandin E2 (PGE2 ) receptor EP4. However, the potential downstream effectors of EP4 involving in the anti-lung cancer effects of solamargine still remained to be determined. In this study, we further verified that solamargine inhibited growth of non-small-cell lung cancer (NSCLC) cells in multiple cell lines. Mechanistically, solamargine increased phosphorylation of ERK1/2. Moreover, solamargine inhibited the protein expression of DNA methyltransferase 1 (DNMT1) and c-Jun, which were abrogated in cells treated with MEK/ERK1/2 inhibitor (PD98059) and transfected with exogenously expressed DNMT1 gene, respectively. Interestingly, overexpressed DNMT1 gene antagonized the effect of solamargine on c-Jun protein expression. Intriguingly, overexpressed c-Jun blocked solamargine-inhibited lung cancer cell growth, and feedback resisted the solamargine-induced phosphorylation of ERK1/2. A nude mouse xenograft model implanted with lung cancer cells in vivo confirmed the results in vitro. Collectively, our results show that solamargine inhibits the growth of human lung cancer cells through reduction of EP4 protein expression, followed by increasing ERK1/2 phosphorylation. This results in decrease in DNMT1 and c-Jun protein expressions. The inter-correlations between EP4, DNMT1 and c-Jun and feedback regulation of ERK1/2 by c-Jun contribute to the overall responses of solamargine in this process. This study uncovers an additional novel mechanism by which solamargine inhibits growth of human lung cancer cells.


Assuntos
DNA (Citosina-5-)-Metiltransferases/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/patologia , Terapia de Alvo Molecular , Proteínas Proto-Oncogênicas c-jun/metabolismo , Receptores de Prostaglandina E Subtipo EP4/metabolismo , Alcaloides de Solanáceas/farmacologia , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/enzimologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , DNA (Citosina-5-)-Metiltransferase 1 , Ativação Enzimática/efeitos dos fármacos , Retroalimentação Fisiológica/efeitos dos fármacos , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Camundongos Nus , Fosforilação/efeitos dos fármacos , Alcaloides de Solanáceas/uso terapêutico
10.
Sci Rep ; 6: 37709, 2016 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-27874086

RESUMO

Previously we showed that Ani (anisodamine)/Neo (neostigmine) combination produced anti-shock effect via activating α7 nicotinic acetylcholine receptor (α7nAChR). In this study, we aim to investigate the therapeutic effect and underlying mechanisms of Ani/Neo combination in acute lethal crush syndrome (CS). In rat and rabbit CS models, Ani/Neo combination increased the 24 h survival rates, improved hemodynamics and decreased the levels of creatine kinase, MB isoenzyme of creatine kinase, blood urea nitrogen, creatinine, K+ in serum. It also decreased the levels of H2O2, myeloperoxidase (MPO) and nitric oxide (NO) in serum and compressed muscle in rat CS model. In wild-type (WT) mice with CS, Ani/Neo combination increased 24 h survival rate and decreased the levels of H2O2, MPO, NO, TNFα, IL-6 and IL-10 in compressed muscle. These effects were attenuated by α7nAChR knockout (KO). Moreover, Ani/Neo combination prevented the decrease of phosphorylation of Janus kinase 2 (JAK2) and phosphorylation of signal transducer and activator of transcription 3 (STAT3) induced by CS. These effects of Ani/Neo in CS mice were cancelled by methyllycaconitine (α7nAChR antagonist) and α7nAChR KO. Collectively, our results demonstrate that Ani/Neo combination could produce therapeutic effects in CS. The underlying mechanism involves the activation of α7nAChR-dependent JAK2-STAT3 signaling pathway.


Assuntos
Síndrome de Esmagamento/tratamento farmacológico , Janus Quinase 2/metabolismo , Neostigmina/administração & dosagem , Neostigmina/uso terapêutico , Fator de Transcrição STAT3/metabolismo , Alcaloides de Solanáceas/administração & dosagem , Alcaloides de Solanáceas/uso terapêutico , Receptor Nicotínico de Acetilcolina alfa7/metabolismo , Animais , Pressão Sanguínea/efeitos dos fármacos , Nitrogênio da Ureia Sanguínea , Creatina Quinase/sangue , Creatinina/sangue , Síndrome de Esmagamento/sangue , Síndrome de Esmagamento/fisiopatologia , Citocinas/metabolismo , Modelos Animais de Doenças , Eletrólitos/sangue , Frequência Cardíaca/efeitos dos fármacos , Peróxido de Hidrogênio/sangue , Camundongos Knockout , Músculos/metabolismo , Óxido Nítrico/sangue , Peroxidase/sangue , Substâncias Protetoras/farmacologia , Substâncias Protetoras/uso terapêutico , Coelhos , Ratos , Transdução de Sinais , Análise de Sobrevida , Sístole/efeitos dos fármacos , Fatores de Tempo
11.
Aesthet Surg J ; 36(7): NP219-24, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27075374

RESUMO

Injection of hyaluronic acid (HA) filler is a common aesthetic procedure. Impairment of vision, although rare, is a devastating complication of this procedure, which may not be reversible. We report on a patient who experienced visual acuity impairment and ischemic oculomotor nerve palsy after injection of HA into the nasal dorsum. In this case, clinical signs improved within 14 days of treatment. We also provide a review of the mechanism, clinical features, risk factors, and prevention and treatment strategies relating to embolization of ocular circulation after injection of HA. Vision loss is a rare but devastating complication of injection of hyaluronic acid (HA) in the face. Visual acuity seldom recovers completely. We report on a 22-year-old Asian woman who experienced obstruction of a branch of the retinal artery after injection of HA to augment her nose. The patient's visual acuity declined shortly after the procedure, and ophthalmoplegia occurred. Combination treatment was administered to restore the perfusion and oxygen supply to the retina and optic nerve. Within 14 days of rigorous treatment, the patient experienced improvement in visual acuity, extraocular movement, and visual field defects. LEVEL OF EVIDENCE 5: Risk.


Assuntos
Arteriopatias Oclusivas/induzido quimicamente , Arteriopatias Oclusivas/tratamento farmacológico , Técnicas Cosméticas/efeitos adversos , Ácido Hialurônico/efeitos adversos , Transtornos da Visão/induzido quimicamente , Transtornos da Visão/tratamento farmacológico , Adulto , Alprostadil/uso terapêutico , Dexametasona/uso terapêutico , Dextranos/uso terapêutico , Feminino , Humanos , Metacrilatos/uso terapêutico , Cavidade Nasal , Oftalmoplegia/induzido quimicamente , Oftalmoplegia/tratamento farmacológico , Oxigênio/uso terapêutico , Artéria Retiniana/fisiopatologia , Alcaloides de Solanáceas/uso terapêutico , Timolol/uso terapêutico , Tobramicina/uso terapêutico , Vitamina B 12/análogos & derivados , Vitamina B 12/uso terapêutico , Adulto Jovem
12.
Br J Pharmacol ; 173(11): 1719-27, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27010563

RESUMO

In cases of organophosphate poisoning, patients are treated with a combination of antidotes. In addition to these poison-directed antidotes, patients may require extra oxygen and artificial ventilation; other modalities may also be needed due to the wide range of toxic effects. Anisodamine is a belladonna alkaloid, and like other drugs from this family is non subtype-selective muscarinic, and a nicotinic cholinoceptor antagonist, which has been employed in traditional Chinese medicine. As a muscarinic antagonist, it displays similar pharmacological effects to atropine and scopolamine. However, anisodamine is not only less potent than atropine and scopolamine but also less toxic. Current in vitro and animal model studies have demonstrated that anisodamine has protective effects in a variety of diseases. Organophosphate poisoning involves not only the central and peripheral nervous systems, but also the cardiac and respiratory systems, as well as activation of inflammatory processes and oxidative stress. Therefore, the anticholinergic and additional activities of anisodamine appear to be relevant and justify its consideration as an addition to the existing remedies. However, more research is needed, as at present data on the role of anisodamine in the management of organophosphate poisoning are limited. Here, we review the beneficial effects of anisodamine on processes relevant to organophosphate poisoning.


Assuntos
Antídotos/uso terapêutico , Intoxicação por Organofosfatos/tratamento farmacológico , Alcaloides de Solanáceas/uso terapêutico , Animais , Humanos
13.
Antimicrob Agents Chemother ; 60(5): 2732-8, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26883711

RESUMO

Little has been done during the past 100 years to develop new antileishmanial drugs. Most infected individuals live in poor countries and have a low cash income to be attractive targets to pharmaceutical corporations. Two heterosidic steroids, solamargine and solasonine, initially identified as major components of the Brazilian plant Solanum lycocarpum, were tested for leishmanicidal activity. Both alkaloids killed intracellular and extracellular Leishmania mexicana parasites more efficiently than the reference drug sodium stibogluconate. A total of 10 µM each individual alkaloid significantly reduced parasite counts in infected macrophages and dendritic cells. In vivo treatment of C57BL/6 mice with a standardized topical preparation containing solamargine (45.1%) and solasonine (44.4%) gave significant reductions in lesion sizes and parasite counts recovered from lesions. Alkaloids present different immunochemical pathways in macrophages and dendritic cells. We conclude that this topical preparation is effective and a potential new and inexpensive treatment for cutaneous leishmaniasis.


Assuntos
Gluconato de Antimônio e Sódio/uso terapêutico , Antiprotozoários/uso terapêutico , Extratos Vegetais/uso terapêutico , Alcaloides de Solanáceas/uso terapêutico , Alcaloides/química , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Dendríticas/parasitologia , Feminino , Citometria de Fluxo , Frutas/química , Leishmania mexicana/efeitos dos fármacos , Leishmania mexicana/patogenicidade , Macrófagos/parasitologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Extratos Vegetais/química
14.
Bioorg Med Chem Lett ; 26(7): 1715-9, 2016 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-26920798

RESUMO

Anisodamine was isolated from the medicinal herb, it was used in the treatment of gastrointestinal smooth muscle spasm, infective toxic shock and organophosphorus intoxication. But there is no report about anisodamine with α-glucosidase inhibitory activity. In order to find novel α-glucosidase inhibitors, a series of α-substituted arylacetates derivatives have been synthesized based on the active unit of anisodamine. In α-glucosidase assay, compound 9 in Schiff base form and compound 22 in ester form show strong inhibition against α-glucosidase with IC50 value of 46.81µM and 83.76µM, respectively. Compounds 9 and 22 exhibit comparable good antidiabetic activities as commercial drug Glimepiride. In addition, Schiff bases of α-substituted arylacetates show antitumor activities against human cancer cell lines, where compound 9 with thiourea moiety performs the best antitumor activity. We anticipate that our research will provide potential candidate scaffolds for antidiabetic drug design.


Assuntos
Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Alcaloides de Solanáceas/química , Alcaloides de Solanáceas/farmacologia , Acetatos/síntese química , Acetatos/química , Acetatos/farmacologia , Acetatos/uso terapêutico , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Inibidores de Glicosídeo Hidrolases/síntese química , Inibidores de Glicosídeo Hidrolases/uso terapêutico , Humanos , Hipoglicemiantes/síntese química , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Neoplasias/tratamento farmacológico , Ratos , Alcaloides de Solanáceas/síntese química , Alcaloides de Solanáceas/uso terapêutico , Relação Estrutura-Atividade , alfa-Glucosidases/metabolismo
16.
Int J Stroke ; 10(5): 737-44, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25727643

RESUMO

BACKGROUND: Increasing endogenous acetylcholine by neostigmine decreased the ischemic cerebral injury. The off-target action on muscarinic receptor produced a variety of adverse effects and limited the clinical application on stroke. AIM: We combined neostigmine with anisodamine and investigated the neuroprotection and mechanism. METHODS: Male Sprague-Dawley rats were subjected to middle cerebral artery occlusion. Neuroprotective action of neostigmine in combination with anisodamine at varying ratios was examined to determine the optimal combination as well as ideal therapeutic window. Potential involvement of α7 nicotinic acetylcholine receptor was examined by measuring the infarct size, the expression of proinflammatory cytokines, and the biomarkers of apoptosis in α7 nicotinic acetylcholine receptor knockout mice. A set of in vitro experiments was conducted in RAW264.7 cells to probe into potential molecular mechanisms. RESULTS: The neostigmine/anisodamine combination conferred neuroprotection. The protection was most potent at a ratio of 1:500. At such a ratio, the combination increased the binding of acetylcholine to α7 nicotinic acetylcholine receptor and reduced proinflammatory cytokines. The neuroprotection was evident only in wild-type and not in α7 nicotinic acetylcholine receptor knockout mice. The combination significantly decreased the expression of Bad and Bax, and increased Bcl-2 and Bcl-xl in α7 nicotinic acetylcholine receptor wild-type mice but not in knockout mice. The combination did not affect caspase-8, cleaved caspase-8, or caspase-12. CONCLUSIONS: Current study identified the optimal combination of neostigmine and anisodamine against ischemic stroke, and indicated that the acetylcholine-α7 nicotinic acetylcholine receptor is involved in the protective effects.


Assuntos
Infarto da Artéria Cerebral Média , Neostigmina/uso terapêutico , Neuroprostanos/uso terapêutico , Alcaloides de Solanáceas/uso terapêutico , Receptor Nicotínico de Acetilcolina alfa7/metabolismo , Animais , Encéfalo/metabolismo , Linhagem Celular Transformada , Citocinas/sangue , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/genética , Infarto da Artéria Cerebral Média/complicações , Infarto da Artéria Cerebral Média/tratamento farmacológico , Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/patologia , Masculino , Camundongos , Camundongos Knockout , Doenças do Sistema Nervoso/etiologia , Ligação Proteica/efeitos dos fármacos , Ligação Proteica/genética , Distribuição Aleatória , Ratos , Fatores de Tempo , Receptor Nicotínico de Acetilcolina alfa7/genética
18.
Cell Biochem Biophys ; 73(3): 707-16, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27259314

RESUMO

Anisodamine is an ancient Chinese medicine derived from Tibet as a belladonna alkaloid, which is usually used for improvement of blood circulation in patients with organ phosphorus poisoning or shock. In this study, for the first time, we report its cardioprotective effects on preventing ischemia/reperfusion (I/R) injury of patients with acute myocardial infarction (AMI), and decreasing the myocardial infarction area and severity in heart of Sprague-Dawley (SD) rats. Our results suggest a potential molecular mechanism of anisodamine against the I/R injury in cardiomyocytes is associated with its anti-apoptotic effect. Anisodamine treatment decreases the expression of caspase-3 and caspase-8, and increases Bcl-2/Bax ratio in cardiomyocytes. Our data suggest that anisodamine can provide significant cardioprotection against I/R injury, potentially through the suppression of cardiomyocytes apoptosis.


Assuntos
Apoptose , Cardiotônicos/uso terapêutico , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Miócitos Cardíacos/efeitos dos fármacos , Alcaloides de Solanáceas/uso terapêutico , Adulto , Idoso , Animais , Cardiotônicos/farmacologia , Linhagem Celular , Células Cultivadas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Traumatismo por Reperfusão Miocárdica/etiologia , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miócitos Cardíacos/metabolismo , Intervenção Coronária Percutânea/efeitos adversos , Ratos , Ratos Sprague-Dawley , Alcaloides de Solanáceas/farmacologia
19.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 26(12): 849-54, 2014 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-25476074

RESUMO

OBJECTIVE: To investigate the value of drug intervention for difficult weaning from mechanical ventilation. METHODS: A prospective single-blind randomized controlled trial was conducted. 120 patients with difficult weaning from mechanical ventilation encountered in Department of Critical Care Medicine of Peking University Third Hospital from January 2008 to December 2013 were included, and the patients were divided into treatment group and control group according to random number table, with 60 cases in each group. Patients received furosemide therapy in the treatment group 3 days before weaning up to 48 hours after weaning in order to control negative liquid balance. Enema was given the day before weaning to reduce abdominal pressure. On the weaning day, all of the patients received nitroglycerin and beta blocker or cedilanid to prevent or control elevation of blood pressure and heart rate in the process of weaning. All patients in treatment group received anisodamine in small dosage 2 hours before extubation. The patients in control group received conventional treatment without drug intervention. Baseline indexes of two groups were compared, including the heart rate, respiration rate (RR), mean arterial pressure (MAP), pulse blood oxygen saturation (SpO2), blood gas, hemoglobin (HG), albumin (ALB) and creatinine (Cr). The main reasons of difficulty in weaning, sedative and analgesic drug selection, presence of abdominal discomfort before weaning, interval between sputum suction before extubation, liquid balance at the beginning of the investigation and at time of weaning, 24 hours and 48 hours after weaning, failures of spontaneous breathing test (SBT), length of mechanical ventilation,length of ICU stay, and total length of mechanical ventilation and total length of ICU stay during hospitalization. RESULTS: There was no statistically significant difference in the heart rate, RR, MAP, SpO2, blood gas, HG, ALB, Cr at the beginning of the investigation between the two groups. The main reasons for difficult weaning in both groups of patients were respiratory dysfunction, cardiac insufficiency, and central nervous system dysfunction. The use of propofol combined dexmedetomidine in the treatment group was more frequent than the control group [16.7% (10/60)vs. 1.7% (1/60), χ² = 8.107, P=0.004], and there was no statistically significant difference in the use of other combinations of sedative drugs between the two groups. Abdominal discomfort before weaning was milder in treatment group as compared with control group [10.0% (6/60) vs. 25.0% (15/60), χ² = 4.675, P=0.031]. The interval between sputum suction before extubation in the treatment group was significantly longer than that of the control group [hours: 1 (1, 2) vs. 1 (1, 1), Z=-2.209, P= 0.027]. SBT failure was less frequent in treatment group compared with control group [times: 0 (0, 1) vs. 1 (1, 2), Z=-6.561, P=0.000]. Liquid balance was better in the treatment group than the control group at time of weaning, 24 hours and 48 hours after weaning [at time of weaning: -567.71(-755.95,-226.41) vs. 1 256.76 (472.48, 1 796.63), Z=-9.038, P=0.000; 24 hours after weaning: -5.03 (-530.28, 245.09) vs. 342.28 (125.36, 613.25), Z=-4.711, P=0.000; 48 hours after weaning: 115.50 (-450.26,485.00) vs. 330.00 (16.25,575.25), Z=-1.932, P=0.053]. Compared with control group, length of mechanical ventilation [days: 1.0 (1.0, 2.0) vs. 2.0 (2.0, 3.0), Z=-6.545, P=0.000], ICU stay time [days: 3.0 (3.0, 4.0) vs. 4.0 (4.0, 5.0), Z=-6.545, P=0.000], and total length of mechanical ventilation [days: 8.0 (6.0,12.0) vs. 11.0 (8.0, 15.0), Z=-4.091, P=0.000] and total length of ICU stay during hospitalization [days: 12.5 (9.2, 19.0) vs. 17.0 (12.0, 29.5), Z=-2.722, P=0.000] were all significantly shorter in the treatment group. CONCLUSIONS: Adjuvant drugs therapy is helpful in patients weaning from the mechanical ventilation, and can shorten length of mechanical ventilation and ICU stay time. Propofol, combined dexmedetomidine, is helpful for weaning.


Assuntos
Dexmedetomidina/uso terapêutico , Propofol/uso terapêutico , Desmame do Respirador/métodos , Pressão Sanguínea , Furosemida/uso terapêutico , Humanos , Hipnóticos e Sedativos/uso terapêutico , Tempo de Internação , Oximetria , Estudos Prospectivos , Respiração Artificial , Método Simples-Cego , Alcaloides de Solanáceas/uso terapêutico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA