Role of Nrf2 pathway in flutamide-induced mitochondrial biogenesis / 中国临床药理学与治疗学

AIM: To investigate the effect of flutamide on mitochondrial biogenesis and the regulating effect of anoxidative pathway Nrf2 on it. METHODS: Human hepatocyte HepG2 cells were treated with flutamide (0-50 μmol/L) for 24 h, then mtDNA copy number and protein expression of mitochondrial biogenesis were detected by RT-PCR and WB. The effects of ERK1/2 and the role of Nrf2 pathway in mitochondrial biogenesis were further observed by gene knockdown and protein activation/inhibition methods. RESULTS: Flutamide interfered mitochondrial biogenesis concentration-dependently, the mtDNA copy number, ERK1/2 and PGC-1α proteins increased with the dose. ERK1/2 inhibition and activation regulated flutamide-induced mtDNA copy number and PGC-1α expression, and inhibition of Nrf2 pathway also affected flutamide-induced mtDNA copy number and expression of PGC-1α, as well as ERK1/2 expression. CONCLUSION: Flutamide affects mitochondrial biogenesis, and the antioxidant pathway Nrf2 may be involved in the regulation of flutamine-induced mitochondrial biogenesis by regulating ERK1/2.

Meta-analysis of randomized controlled trials on the efficacy of daikenchuto on improving intestinal dysfunction after abdominal surgery

PURPOSE: Intestinal dysfunction is one of the most common complications in patients after abdominal surgery. Daikenchuto (DKT), a traditional herbal medicine, is recently employed to improve postoperative intestinal dysfunction. The aim of this meta-analysis was to assess the efficacy of DKT in improving intestinal dysfunction after abdominal surgery. METHODS: PubMed, Embase, and the Cochrane library were systematically searched to identify randomized controlled trails (RCTs) in adult patients undergoing abdominal surgery, who were randomly distributed to administrate DKT and placebo. The primary outcomes included the time to first postoperative flatus or bowel movement. We used random-effects models to calculate summary mean differences (MDs) with 95% confidence intervals (CIs). RESULTS: Nine RCTs totaling 1,212 patients (618 in DKT, 594 in control group) were included in our study. Compared with control group, DKT can effectively improve postoperative intestinal dysfunction by shortening the time to first postoperative flatus (MD, −0.41; 95% confidence interval [CI], −0.66 to −0.16; P = 0.001) with significant heterogeneity (I2 = 71%, P = 0.004), and bowel movement (MD, −0.65; 95% CI, −0.97 to −0.32; P < 0.001) without significant heterogeneity (I2 = 40%, P = 0.14). Sensitivity analyses by indication of surgery and type of surgery yielded similar results. CONCLUSION: These data provide limited evidence that DKT shows efficacy on improving intestinal dysfunction after abdominal surgery. However, the results should be interpreted cautiously, due to the heterogeneity of the studies included. Thus, the efficacy of DKT on improving postoperative intestinal dysfunction warrants further investigation.