No abstract

Recent evidence indicates that a deficiency of 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) may influence asthma pathogenesis; however, its roles in regulating specific molecular transcription mechanisms remain unclear. We aimed to investigate the effect of 1,25(OH)2D3 on the expression and enzyme activity of histone deacetylase 2 (HDAC2) and its synergistic effects with dexamethasone (Dx) in the inhibition of inflammatory cytokine secretion in a rat asthma model. Healthy Wistar rats were randomly divided into 6 groups: control, asthma, 1,25(OH)2D3 pretreatment, 1,25(OH)2D3 treatment, Dx treatment, and Dx and 1,25(OH)2D3 treatment. Pulmonary inflammation was induced by ovalbumin (OVA) sensitization and challenge (OVA/OVA). Inflammatory cells and cytokines in the bronchoalveolar lavage (BAL) fluid and histological changes in lung tissue were examined. Nuclear factor kappa B (NF-κB) p65 and HDAC2 expression levels were assessed with Western blot analyses and quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). Enzyme activity measurements and immunohistochemical detection of HDAC2 were also performed. Our data demonstrated that 1,25(OH)2D3 reduced the airway inflammatory response and the level of inflammatory cytokines in BAL. Although NF-κB p65 expression was attenuated in the pretreatment and treatment groups, the expression and enzyme activity of HDAC2 were increased. In addition, 1,25(OH)2D3 and Dx had synergistic effects on the suppression of total cell infusion, cytokine release, and NF-κB p65 expression, and they also increased HDAC2 expression and activity in OVA/OVA rats. Collectively, our results indicated that 1,25(OH)2D3might be useful as a novel HDAC2 activator in the treatment of asthma.

Liver fibrosis is the main pathological feature of various chronic liver diseases that can progress to cirrhosis. However, no effective treatment strategy for liver fibrosis is available. Phytic acid (PA) is a natural plant compound found in cereals, legumes, and rapeseed. Currently, there are few reports on its relationship with liver fibrosis. Herein, we explored the effects of PA on liver fibrosis. In this study, the liver fibrosis model was constructed by intraperitoneal injection of CCl4 and intragastric administration of sodium phytate (100 mg/kg) or silymarin (100 mg/kg) five times a week. The CCl4 injection could significantly increase the content of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum and induce the damage of liver cells, infiltration of inflammatory factors, and deposition of collagen fibers in the liver tissue. Compared to the CCl4 group, PA significantly reduced AST and ALT. Also, PA alleviated liver damage and reduced inflammatory cell infiltration, collagen deposition area, and hydroxyproline (Hyp) content in the liver tissue, as well as downregulated α-smooth muscle actin (α-SMA) and collagen I (Col-1). Mechanistically, PA downregulated PI3K, p-AKT, p-p65, and p-IκBα in the liver tissue and reduced the release of inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). In conclusion, PA might ameliorate liver fibrosis by inhibiting the NF-κB and PI3K/AKT signaling pathways.