AIM OF THE STUDY: Endothelial barrier dysfunction is a pathological hallmark of many diseases and can be caused by lipopolysaccharides (LPS) stimulation. Therefore, this study aims to investigate the possible barrier protective effects of tHGA upon LPS-stimulated inflammatory responses in human umbilical vein endothelial cells (HUVECs).
MATERIALS AND METHODS: HUVECs were pretreated with tHGA prior to LPS stimulation, where inflammatory parameters including permeability, monocyte adhesion and migration, and release of pro-inflammatory mediators were examined. Additionally, the effect of tHGA on F-actin rearrangement and adhesion protein expression of LPS-stimulated HUVECs was evaluated.
RESULTS: It was found that pretreatment with tHGA inhibited monocyte adhesion and transendothelial migration, reduced endothelial hyperpermeability and secretion of prostaglandin E2 (PGE2). Additionally, tHGA inhibited cytoskeletal rearrangement and adhesion protein expression on LPS-stimulated HUVECs.
CONCLUSION: As the regulation of endothelial barrier dysfunction can be one of the therapeutic strategies to improve the outcome of inflammation, tHGA may be able to preserve vascular barrier integrity of endothelial cells following LPS-stimulated dysfunction, thereby endorsing its potential usefulness in vascular inflammatory diseases.
OBJECTIVE: To investigate the effect of zerumbone on HDM extract-induced airway epithelial barrier dysfunction.
MATERIALS AND METHODS: Human bronchial epithelial cells 16HBE14o- were incubated with 100 μg/mL HDM extract and treated with non-cytotoxic concentrations of zerumbone (6.25 μM, 12.5 μM, and 25 μM) for 24 h. The epithelial junctional integrity and permeability were evaluated through transepithelial electrical resistance (TEER) and fluorescein isothiocynate (FITC)-Dextran permeability assays, respectively. The localization of junctional proteins, occludin and zona occludens (ZO)-1, was studied using immunofluorescence (IF) while the protein expression was measured by western blot.
RESULTS: Zerumbone inhibited changes in junctional integrity (6.25 μM, p ≤ .05; 12.5 μM, p ≤ .001; 25 μM, p ≤ .001) and permeability (6.25 μM, p ≤ .05; 12.5 μM, p ≤ .01; 25 μM, p ≤ .001) triggered by HDM extract in a concentration-dependent manner. This protective effect could be explained by the preservation of occludin (12.5 μM, p ≤ .01 and 25 μM, p ≤ .001) and ZO-1 (12.5 μM, p ≤ .05 and 25 μM, p ≤ .001) localization, rather than the prevention of their cleavage.
DISCUSSION AND CONCLUSION: Zerumbone attenuates HDM extract-induced epithelial barrier dysfunction which supports its potential application for the treatment of inflammation-driven airway diseases such as asthma.
MATERIALS AND METHODS: The MEZZ was prepared by macerating oven-dried (50 degrees C) powdered rhizomes (1.2 kg) of Z. zerumbet in 80% methanol in a ratio of 1:20 (w/v) for 48 h. The supernatant was collected, filtered and evaporated to dryness under reduced pressure (50 degrees C) yielding approximately 21.0 g of the crude dried extract. The crude dried extract was stored at -20 degrees C prior to use and was dissolved in normal saline (0.9% NaCl) immediately before administration at concentrations required to produce doses of 25, 50 and 100 mg/kg.
RESULTS: All dosages of MEZZ showed significant (p < 0.05) antiedema activity when assessed using the carrageenan-induced paw edema test and the cotton-pellet-induced granuloma test. The MEZZ exhibited significant (p < 0.05) antinociceptive activity when assessed by the writhing, hot plate and formalin tests. Pretreatment with naloxone (5 mg/kg) significantly decreased the latency of discomfort produced by the 100 mg/kg dose of MEZZ in the hot plate test.
CONCLUSION: MEZZ produced antiinflammatory and antinociceptive activities which may involve the inhibition of bradykinin-, prostaglandin-, histamine- and opioid-mediated processes.