RESUMEN
BACKGROUND AND OBJECTIVES: Chinese herbal drug Da-Cheng-Qi decoction (DCQD) has been widely used for decades to treat acute pancreatitis (AP). Previous trials are mostly designed to state the potential mechanisms of the therapeutic effects rather than to detect its whole effect on metabolism. This study aimed to investigate the efficacy of DCQD on metabolism in AP. METHODS: Twenty-two male adult Sprague-Dawley rats were randomized into three groups. AP was induced by retrograde ductal infusion of 3.5% sodium taurocholate solution in DCQD and AP group, while 0.9% saline solution was used in sham operation (SO) group. Blood samples were obtained 12 h after drug administration and a 600 MHz superconducting Nuclear Magnetic Resonance (NMR) spectrometer was used to detected plasma metabolites. Principal Components Analysis (PCA) and Partial Least Squares-Discriminant Analysis after Orthogonal Signal Correction (OSC-PLS-DA) were applied to analyze the Longitudinal Eddy-delay (LED) and Carr-Purcell-Meiboom-Gill (CPMG) spectra. RESULTS: Differences in concentrations of metabolites among the three groups were detected by OSC-PLS-DA of 1HNMR spectra (both LED and CPMG). Compared with SO group, DCQD group had higher levels of plasma glycerol, glutamic acid, low density lipoprotein (LDL), saturated fatty acid (FA) and lower levels of alanine and glutamine, while the metabolic changes were reversed in the AP group. CONCLUSIONS: Our results demonstrated that DCQD was capable of altering the changed concentrations of metabolites in rats with AP and 1HNMR-based metabolomic approach provided a new methodological cue for systematically investigating the efficacies and mechanisms of DCQD in treating AP.
Asunto(s)
Medicamentos Herbarios Chinos/farmacocinética , Medicamentos Herbarios Chinos/uso terapéutico , Pancreatitis/tratamiento farmacológico , Pancreatitis/metabolismo , Alanina/sangre , Animales , Biotransformación , LDL-Colesterol/sangre , Ácidos Grasos/sangre , Ácido Glutámico/sangre , Glutamina/sangre , Glicerol/sangre , Espectroscopía de Resonancia Magnética , Masculino , Metabolómica , Ratas , Ratas Sprague-DawleyRESUMEN
Considerable evidence indicates that apoptosis plays a critical role in acute myocardial infarction. We have previously shown that Guan-Xin-Er-Hao (GXEH), a Chinese medicine formula, attenuates postischemia myocardial apoptosis. The present study was designed to determine the mechanisms by which GXEH exerts its antiapoptotic effect. Adult male Sprague-Dawley rats were randomized to receive vehicle or GXEH (5 or 15 g/kg) orally 30 min before ischemia and subjected to myocardial ischemia of 3 h (apoptosis peak) or 24 h (necrosis peak) for determination of infarct size. Compared with rats receiving vehicle, those rats treated with GXEH (15 g/kg) showed significantly reduced infarct size, the reduced myocardial apoptosis, as judged by the decreases in TUNEL-positive staining (22.40 +/- 5.68% vs. 40.31 +/- 10.58%, p < 0.01), and the decrease in the degree of caspase-3 activation (82.97 +/- 10.54 vs. 159.95 +/- 9.16 mumol cleaved acetyl-Asp-Glu-Val-Asp-p-nitroanilide/mg protein, p < 0.01). Treatment with GXEH (15 g/kg) significantly reduced the release of mitochondrial cytochrome c, a primary mediator of apoptosis, the degree of caspase-9 activation, and the Bax/Bcl-2 ratio. Caspase-9 cleaves and activates caspase-3. Bax promotes apoptosis, while Bcl-2 inhibits apoptosis. Thus, the antiapoptotic mechanisms of GXEH may involve the mitochondrial cytochrome c-mediated caspase-3 activation in cardiomyocytes after acute myocardial infarction. Taken together, GXEH tilted the balance between Bax and Bcl-2 toward an antiapoptotic state, decreased mitochondrial cytochrome c release, reduced caspase-9 activation, and attenuated subsequent caspase-3 activation and postischemic myocardial apoptosis in rats. GXEH may be used as a promising agent for future treatment of cardiovascular diseases.