RESUMO
Autophagy plays an important role in the pathogenesis of cardiovascular diseases. Dysregulation of autophagy may have a huge effect on cardiac hypertrophy induced by overload pressure although reports on autophagy and cardiac hypertrophy have been contradictory. Some studies showed that autophagy activation attenuated cardiac hypertrophy. However, others suggested that inhibition of autophagy would be protective. Different research models or different pathways involved could be responsible for it. Cardiac hypertrophy may be alleviated through regulation of autophagy. This review aims to highlight the pathways and therapeutic targets identified in the prevention and treatment of cardiac hypertrophy by regulating autophagy.
Assuntos
Autofagia , Cardiomegalia , Animais , Camundongos , Estrutura Molecular , Cardiomegalia/etiologia , Cardiomegalia/metabolismo , Cardiomegalia/patologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Camundongos Endogâmicos C57BLRESUMO
Guanxinjing capsules (GXJCs) are used in traditional Chinese medicine as a common therapy for coronary heart disease (CHD) complicated with depression. In this study, we aimed to identify the main active constituents in GXJCs and to investigate the mechanisms of GXJC action on CHD complicated with depression. The chemical constituent profile of the GXJC was identified by UHPLC-LTQ-Orbitrap assay, and oral bioavailability was evaluated to screen the GXJC drug-like chemical constituents. A total of 16 GXJC drug-like chemical constituents were identified. Then, putative targets of the GXJC drug-like chemical constituents were predicted using MedChem Studio, with 870 genes found to be the putative targets of these molecules. After that, a GXJC putative target-known CHD/depression therapeutic target network was constructed, and four topological features, including degree, betweenness, closeness and K-coreness, were calculated. According to the topological feature values of the GXJC putative targets, 14 main active constituents were identified because their corresponding putative targets had topological importance in the GXJC putative target-known CHD/depression therapeutic target network, which were defined as the candidate targets of GXJC against CHD complicated with depression. Functionally, these candidate targets were significantly involved in several CHD/depression-related pathways, including repairing pathological vascular changes, reducing platelet aggregation and inflammation, and affecting patient depression. This study identified a list of main active constituents of GXJC acting on CHD complicated with depression using an integrative pharmacology-based approach that combined active chemical constituent identification, drug target prediction and network analysis. This method may offer an efficient way to understand the pharmacological mechanisms of traditional Chinese medicine prescriptions.
Assuntos
Doença das Coronárias/tratamento farmacológico , Depressão/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa/métodos , Transdução de Sinais/efeitos dos fármacos , Biologia de Sistemas/métodos , Administração Oral , Disponibilidade Biológica , Cápsulas , Cromatografia Líquida de Alta Pressão , Doença das Coronárias/complicações , Doença das Coronárias/metabolismo , Doença das Coronárias/psicologia , Depressão/etiologia , Depressão/metabolismo , Depressão/psicologia , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/efeitos adversos , Medicamentos de Ervas Chinesas/farmacocinética , Humanos , Mapas de Interação de Proteínas , Espectrometria de Massas por Ionização por Electrospray , Espectrofotometria Ultravioleta , Resultado do TratamentoRESUMO
This paper aimed to predict the active ingredients and action targets of Compound Uncaria Hypotensive Tablet for hypertension based on network pharmacology, and discuss its possible "multi-components, multi-targets, and multi-pathways" mechanism for treatment of hypertension. The integrative pharmacological platform of traditional Chinese medicine (TCM-IP) was used to construct the component target-disease target network of Compound Uncaria Hypotensive Tablet, and the internet analysis method was used to screen the key nodes, on which the pathway enrichment analysis was carried out to explore its possible biological process in the treatment of hypertension. Target network analysis showed that, 35 predicted active ingredients of Compound Uncaria Hypotensive Tablet had a strong interaction with the prostaglandin endogenous peroxidase synthase (PTGS1, PTGS2), ATP synthetase (ATP1A1, ATP5A1, ATP5C1, ATP5B) and other 29 major proteins. Network enriched analysis showed that Compound Uncaria Hypotensive Tablet participated in the regulation of hypertension in different processes of pathology, through 15 pathways such as regulating blood pressure, G protein coupled receptor activation, adrenergic myocardial cell signal transduction and platelet activation. This study revealed the potential active compounds and possible mechanism of Compound Uncaria Hypotensive Tablet for treatment of hypertension, providing theoretical references for further systematic laboratory experiments on effective compounds and action mechanism of Compound Uncaria Hypotensive Tablet.