RESUMO
Background Numerous food wastes have been identified to possess potent bioactive compounds used for the treatment of several diseases. Therefore this study evaluated the potentials of cardiac and quercetin glycosides extracted from Dacryodes edulis seeds to reverse vascular and endothelial damage (VAED). Methods The glycoside composition of the seeds was extracted using standard methods and characterized by gas chromatography. We then recruited rats with L-NAME-induced VAED based on confirmatory biomarkers cardiac troponin (CnT), cellular adhesion molecule (VCAM-1), lipoprotein associated phospholipase A2 (Lp-PLA2), RAAS, VWF, endothelin, eNOx, and homocysteine. Only rats that showed total alterations of all biomarkers were recruited into the respective experimental groups and treated with either metaprolol succinate (met.su) + losartan or glycoside extracts of D. edulis seeds (NPSG). Results Chromatographic isolation of glycosides in the seed showed predominance of artemetin (1.59 mg/100 g), amygdalin (3.68 mg/100 g), digitoxin (19.21 mg/100 g), digoxin (27.23 mg/100 g), avicularin (133.59 mg/100 g), and hyperoside (481.76 mg/100 g). We observed decreased water intake and higher heart beats under vascular damage as the experiment progressed up to the fourth week. The met.su + losartan and H.D NPSG proved effective in restoring troponin, but both doses of NPSG normalized the VCAM-1 and RAAS activities excluding aldosterone and Lp-PLA2. Among the endothelial dysfunction biomarkers, H.D NPSG produced equivalent effects to met.su + losartan towards restoring the eNOx and VWF activities, but showed higher potency in normalizing the endothelin and Hcy levels. Conclusions We thus propose that the synergistic effect of the isolated glycosides from D. edulis shown in our study proved potent enough at high doses in treatment of vascular and endothelial dysfunction.
Assuntos
Burseraceae/química , Glicosídeos Cardíacos/farmacologia , Extratos Vegetais/farmacologia , Quercetina/farmacologia , Animais , Biomarcadores/metabolismo , Glicosídeos Cardíacos/administração & dosagem , Glicosídeos Cardíacos/isolamento & purificação , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/patologia , Losartan/farmacologia , Masculino , Metoprolol/farmacologia , Camundongos , NG-Nitroarginina Metil Éster , Extratos Vegetais/administração & dosagem , Quercetina/administração & dosagem , Quercetina/isolamento & purificação , Ratos , SementesRESUMO
Non-small-cell lung cancer (NSCLC) dominates over 85% of all lung cancer cases. Epidermal growth factor receptor (EGFR) activating mutation is a common situation in NSCLC. In the clinic, molecular-targeting with Gefitinib as a tyrosine kinase inhibitor (TKI) for EGFR downstream signaling is initially effective. However, drug resistance frequently happens due to additional mutation on EGFR, such as substitution from threonine to methionine at amino acid position 790 (T790M). In this study, we screened a traditional Chinese medicine (TCM) compound library consisting of 800 single compounds in TKI-resistance NSCLC H1975 cells, which contains substitutions from leucine to arginine at amino acid 858 (L858R) and T790M mutation on EGFR. Attractively, among these compounds there are 24 compounds CC50 of which was less than 2.5 µM were identified. We have further investigated the mechanism of the most effective one, Digitoxin. It showed a significantly cytotoxic effect in H1975 cells by causing G2 phase arrest, also remarkably activated 5' adenosine monophosphate-activated protein kinase (AMPK). Moreover, we first proved that Digitoxin suppressed microtubule formation through decreasing α-tubulin. Therefore, it confirmed that Digitoxin effectively depressed the growth of TKI-resistance NSCLC H1975 cells by inhibiting microtubule polymerization and inducing cell cycle arrest.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Glicosídeos Cardíacos/administração & dosagem , Digitoxina/administração & dosagem , Resistencia a Medicamentos Antineoplásicos/genética , Microtúbulos/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/biossíntese , Apoptose/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/genética , Glicosídeos Cardíacos/química , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Digitoxina/química , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Receptores ErbB/biossíntese , Receptores ErbB/genética , Gefitinibe , Regulação Neoplásica da Expressão Gênica , Humanos , Medicina Tradicional Chinesa , Microtúbulos/patologia , Mutação , Quinazolinas/uso terapêutico , Tubulina (Proteína)/biossíntese , Tubulina (Proteína)/genéticaAssuntos
Insuficiência Cardíaca/tratamento farmacológico , Hipertensão/complicações , Molsidomina/uso terapêutico , Nifedipino/uso terapêutico , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Glicosídeos Cardíacos/administração & dosagem , Diuréticos/administração & dosagem , Avaliação de Medicamentos , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Molsidomina/administração & dosagem , Nifedipino/administração & dosagemRESUMO
One hundred patients with angina pectoris were studied to determine the antianginal effectiveness of senzit, fenigidin and trasicor. The calcium antagonists senzit and fenigidin were found to have high antianginal effect (44% and 78%, respectively) in patients with stable angina pectoris. It was found advisable to use the two drugs in combination with cardiac glycosides in patients with heart failure. A study showed the high antianginal effect of trasicor in postinfarction patients with refractory angina of effort.