RESUMO
BACKGROUND: Chronic heart failure (CHF) is actually a disease caused by an imbalanced energy metabolism between myocardial energy demand and supply, ultimately resulting in abnormal myocardial cell structure and function. Energy metabolism imbalance plays an important role in the pathological process of chronic heart failure (CHF). Improving myocardial energy metabolism is a new strategy for the treatment of CHF. Shengxian decoction (SXT), a well-known traditional Chinese medicine (TCM) formula, has good therapeutic effects on the cardiovascular system. However, the effects of SXT on the energy metabolism of CHF is unclear. In this study, we probed the regulating effects of SXT on energy metabolism in CHF rats using various research methods. METHODS: High-performance liquid chromatography (HPLC) analysis was used to perform quality control of SXT preparations. Then, SD rats were randomly assigned into 6 groups: sham, model, positive control (trimetazidine) and high-, middle-, and low-dose SXT groups. Specific reagent kits were used to detect the expression levels of ALT and AST in rats' serum. Echocardiography was used to evaluate cardiac function. H&E, Masson and TUNEL staining were performed to examine myocardial structure and myocardial apoptosis. Colorimetry was used to determine myocardial ATP levels in experimental rats. Transmission electron microscopy was used to observe the ultrastructure of myocardial mitochondria. ELISA was used to estimate CK, cTnI, and NT-proBNP levels, and LAãFFAãMDAãSOD levels. Finally, Western blotting was used to examine the protein expression of CPT-1, GLUT4, AMPK, p-AMPK, PGC-1α, NRF1, mtTFA and ATP5D in the myocardium. RESULTS: HPLC showed that our SXT preparation method was feasible. The results of ALT and AST tests indicate that SXT has no side effect on the liver function of rats. Treatment with SXT improved cardiac function and ventricular remodelling and inhibited cardiomyocyte apoptosis and oxidative stress levels induced by CHF. Moreover, CHF caused decrease ATP synthesis, which was accompanied by a reduction in ATP 5D protein levels, damage to mitochondrial structure, abnormal glucose and lipid metabolism, and changes in the expression of PGC-1α related signal pathway proteins, all of which were significantly alleviated by treatment with SXT. CONCLUSION: SXT reverses CHF-induced cardiac dysfunction and maintains the integrity of myocardial structure by regulating energy metabolism. The beneficial effect of SXT on energy metabolism may be related to regulating the expression of the PGC-1α signalling pathway.
Assuntos
Proteínas Quinases Ativadas por AMP , Insuficiência Cardíaca , Ratos , Animais , Ratos Sprague-Dawley , Proteínas Quinases Ativadas por AMP/metabolismo , Insuficiência Cardíaca/tratamento farmacológico , Miocárdio/metabolismo , Trifosfato de Adenosina/metabolismoRESUMO
In this study, five known sesquiterpene lactones (STL) with an α-methylene-γ-lactone motif, including two eudesmanolides, 1ß-hydroxyalantolactone (1) and ivangustin (2), and three 1,10-seco-eudesmanolides, 1-O-acetylbritannilactone (3), 1,6-O,O-diacetylbritannilactone (4), and 6α-O-(2- methylbutyryl)britannilactone (5) were isolated from the flower heads of the medicinal plant Inula britannica. Their structures were characterized by spectroscopic methods. X-ray data of 2 is reported for the first time. Among them, eudesmanolides 1 and 2 exhibited remarkable cytotoxicity against HEp2, SGC-7901 and HCT116 human cancer cell lines, comparable with etoposide (Vp-16) used as reference drug. Furthermore, treatment of HEp2 cells with 1 induced apoptosis associated with cleaved procaspase-3 and PARP. The biological assays carried out with normal cells (CHO) revealed that all sesquiterpenes were weakly selective against the cancer cell lines tested.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Inula/química , Sesquiterpenos/farmacologia , Animais , Antineoplásicos Fitogênicos/química , Linhagem Celular Tumoral , Flores/química , Humanos , Lactonas/química , Lactonas/farmacologia , Estrutura Molecular , Sesquiterpenos/químicaRESUMO
Phosphorus (P) is a critical macronutrient required for numerous functions in plants and is one of the limiting factors for plant growth. Phosphate availability has a strong effect on root system architecture. Expansins are encoded by a superfamily of genes that are organized into four families, and growing evidence has demonstrated that expansins are involved in almost all aspects of plant development, especially root development. In the current study, we demonstrate that expansins may be involved in increasing phosphorus availability by regulating the growth and development of plant roots. Multiple expansins (five α- and nine ß-expansin genes) were up- or down-regulated in response to phosphorus and showed different expression patterns in wheat. Meanwhile, the expression level of TaEXPB23 was up-regulated at excess-P condition, suggesting the involvement of TaEXPB23 in phosphorus adaptability. Overexpression of the TaEXPB23 resulted in improved phenotypes, particularly improved root system architecture, as indicated by the increased number of lateral roots in transgenic tobacco plants under excess-P and low-P conditions. Thus, these transgenic plants maintained better photosynthetic gas exchange ability than the control under both P-sufficient and P-deficient conditions.