AIM OF THE STUDY: The purpose of this study was to determine the anti-inflammatory activity of the ethanol extract of E. maculata resin exudate, its methylene chloride and n-butanol fractions, as well as the isolated compounds.
MATERIALS AND METHODS: the ethanol extract was partitioned by methylene chloride, and n-butanol saturated with water. The fractions were chromatographed to isolate pure compounds. In-vivo anti-inflammatory activity of the ethanol extract, the fractions at a dose of 200 mg/kg, and the isolated compounds (20 mg/kg) was estimated using carrageenan-induced rat paws edema method against indomethacin (20 mg/kg). The activity was supported by histopathological and biochemical parameters.
RESULTS: Three isolated compounds were identified as aromadendrin (C1), 7-O-methyl aromadendrin (C2), and naringenin (C3). Our findings demonstrated that the tested fractions significantly reduced the paw edema starting from the 3rd to the 5th hour as compared to the positive control, compounds C2 and C3 showed the greatest significant reduction in paw edema. The ethanol extract, fractions, C2, and C3 demonstrated an anti-inflammatory potential through reducing the levels of TNF-α, IL-6, and PGE2, as well as COX-2 protein expression compared to the negative control. These results were supported by molecular docking, which revealed that the isolated compounds had high affinity to target COX-1 and COX-2 active sites with docking scores ranging from -7.3 to -9.6 kcal mol-1 when compared to ibubrofen (-7.8 and -7.4 kcal mol-1, respectively). Molecular dynamics simulations were also performed and confirmed the docking results.
CONCLUSION: The results supported the traditional anti-inflammatory potency of E. maculata Hook, and the biochemical mechanisms underlying this activity were highlighted, opening up new paths for the development of potent herbal anti-inflammatory medicine. Finally, our findings revealed that E. maculata resin constituents could be considered as promising anti-inflammatory drug candidates.
BACKGROUND: Data are conflicting on the optimal strategy to reduce CAAKI and related complications after percutaneous coronary intervention (PCI).
METHODS: The PRESERVE (Prevention of Serious Adverse Events Following Angiography) trial used a 2 × 2 factorial design to randomize 5,177 patients with stage III or IV chronic kidney disease undergoing angiography to IV 1.26% sodium bicarbonate or IV 0.9% sodium chloride and 5 days of oral acetylcysteine or placebo. A subgroup analysis was conducted of the efficacy of these interventions in patients who underwent PCI during the study angiographic examination. The primary endpoint was a composite of death, need for dialysis, or persistent kidney impairment at 90 days; CAAKI was a secondary endpoint.
RESULTS: A total of 1,161 PRESERVE patients (mean age 69 ± 8 years) underwent PCI. The median estimated glomerular filtration rate was 50.7 ml/min/1.73 m2 (interquartile range: 41.7 to 60.1 ml/min/1.73 m2), and 952 patients (82%) had diabetes mellitus. The primary endpoint occurred in 15 of 568 patients (2.6%) in the IV sodium bicarbonate group and 24 of 593 patients (4.0%) in the IV sodium chloride group (odds ratio: 0.64; 95% confidence interval: 0.33 to 1.24; p for interaction = 0.41) and in 23 of 598 patients (3.8%) in the acetylcysteine group and 16 of 563 patients (2.8%) in the placebo group (odds ratio: 1.37; 95% confidence interval: 0.71 to 2.62; p for interaction = 0.29). There were no significant between-group differences in the rates of CAAKI.
CONCLUSIONS: Among patients with CKD undergoing PCI, there was no benefit of IV sodium bicarbonate over IV sodium chloride or of acetylcysteine over placebo for the prevention of CAAKI or intermediate-term adverse outcomes.