Silica dioxide nanoparticles (SiONPs) have been applied to several fields, such as drug delivery and gene therapy. However, SiONPs are a constituent of fine dust and can induce excessive inflammatory responses in the lungs via the airways. Silibinin, a major component of silymarin, has been known for its anti-oxidant and anti-inflammatory effects. In the present study, we explored the protective effects of silibinin against SiONPs-induced airway inflammation and explored its underlying mechanism of action, focusing on thioredoxin-interacting protein (TXNIP)/mitogen-activated protein kinases (MAPKs) in vitro and in vivo. In SiONPs-stimulated NCI-H292 airway epithelial cells, silibinin treatment effectively suppressed the elevation of the mRNA expression of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1β, which was accompanied by the reduction in the expression of TXNIP, MAPKs, and activator protein-1 (AP-1). In SiONPs-treated mice, silibinin administration inhibited the increase in inflammatory cell counts and proinflammatory mediators, and it alleviated airway inflammation by SiONPs exposure. In addition, silibinin administration effectively suppressed the elevation of TXNIP/MAPKs/AP-1 signaling by SiONPs exposure. Taken together, silibinin effectively inhibited SiONPs-induced inflammatory responses, and this effect was closely related to the inhibition of TXNIP/MAPK/AP-1 signaling. These results suggested that silibinin might be useful for reducing pulmonary inflammation induced by SiONPs.

Garlic (Allium sativum) has traditionally been used as a medicinal food and exhibits various beneficial activities, such as antitumor, antimicrobial, hypolipidemic, antiarthritic, and hypoglycemic activities. The aim of this study was to explore the preventive effect of garlic oil (GO) and its organosulfur component diallyl disulfide (DADS) on cigarette smoke (CS)-induced airway inflammation. Mice were exposed to CS daily for 1 h (equivalent to eight cigarettes per day) for two weeks, and intranasally instilled with lipopolysaccharide (LPS) on day 12 after the initiation of CS exposure. GO and DADS were administered to mice by oral gavage, both at rates of 20 and 40 mg/kg, for 1 h before CS exposure for two weeks. In the bronchoalveolar lavage fluid, GO and DADS inhibited the elevation in the counts of inflammatory cells, particularly neutrophils, which were induced in the CS and LPS (CS + LPS) group. This was accompanied by the lowered production (relative to the CS + LPS group) of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α. Histologically, GO and DADS inhibited the CS- and LPS-induced infiltration of inflammatory cells into lung tissues. Additionally, GO and DADS inhibited the phosphorylation of extracellular signal-regulated kinase and the expression of matrix metalloproteinase-9 in the lung tissues. Taken together, these findings indicate that GO and DADS could be a potential preventive agent in CS-induced airway inflammation.

Asthma, a heterogeneous disease of the airways, is common around the world, but little is known about the molecular mechanisms underlying the interactions between DNA methylation and gene expression in relation to this disease. The seeds of Descurainia sophia are traditionally used to treat coughs, asthma and edema, but their effects on asthma have not been investigated by multi-omics analysis. We undertook this study to assess the epigenetic effects of ethanol extract of D. sophia seeds (DSE) in an ovalbumin (OVA)-induced mouse model of asthma. We profiled genome-wide DNA methylation by Methyl-seq and characterized the transcriptome by RNA-seq in mouse lung tissue under three conditions: saline control, OVA-induced, and DSE-treated. In total, 1995 differentially methylated regions (DMRs) were identified in association with anti-asthmatic effects, most in promoter and coding regions. Among them, 25 DMRs were negatively correlated with the expression of the corresponding 18 genes. These genes were related to development of the lung, respiratory tube and respiratory system. Our findings provide insights into the anti-asthmatic effects of D. sophia seeds and reveal the epigenetic targets of anti-inflammatory processes in mice.

Scrophulariae Radix, derived from the dried roots of Scrophularia ningpoensis Hemsl. or S. buergeriana Miq, is a traditional herbal medicine used in Asia to treat rheumatism, arthritis, and pharyngalgia. However, the effects of Scrophularia buergeriana, S. koraeinsis, and S. takesimensis on osteoclast formation and bone resorption remain unclear. In this study, we investigated the morphological characteristics and harpagoside content of S. buergeriana, S. koraiensis, and S. takesimensis, and compared the effects of ethanol extracts of these species using nuclear factor (NF)-κB ligand (RANKL)-mediated osteoclast differentiation. The harpagoside content of the three Scrophularia species was analyzed by high-performance liquid chromatography–mass spectrometry (HPLC/MS). Their therapeutic effects were evaluated by tartrate-resistant acid phosphatase (TRAP)-positive cell formation and bone resorption in bone marrow-derived macrophages (BMMs) harvested from ICR mice. We confirmed the presence of harpagoside in the Scrophularia species. The harpagoside content of S. buergeriana, S. koraiensis, and S. takesimensis was 1.94 ± 0.24 mg/g, 6.47 ± 0.02 mg/g, and 5.50 ± 0.02 mg/g, respectively. Treatment of BMMs with extracts of the three Scrophularia species inhibited TRAP-positive cell formation in a dose-dependent manner. The area of hydroxyapatite-absorbed osteoclasts was markedly decreased after treatment with the three Scrophularia species extracts. Our results indicated that the three species of the genus Scrophularia might exert preventive effects on bone disorders by inhibiting osteoclast differentiation and bone resorption, suggesting that these species may have medicinal and functional value.

Silicon dioxide nanoparticles (SiONPs), which are metal oxide nanoparticles, have been used in a wide variety of applications. In this study, acute pulmonary responses were examined after the intranasal instillation of SiONPs in mice primed with or without lipopolysaccharide (LPS, intranasal, 5 µg/mouse). The exposure to SiONPs increased the inflammatory cell counts and proinflammatory cytokines in the bronchoalveolar lavage fluid. SiONPs induced airway inflammation with increases in the phosphorylation of mitogen-activated protein kinases (MAPKs). The ratios of the inflammatory responses induced by the SiONPs were increased in the acute pulmonary disease model primed by LPS. Taken together, SiONPs exhibited toxicity to the respiratory system, which was associated with MAPK phosphorylation. In addition, the exposure to SiONPs exacerbated any existing inflammatory pulmonary diseases. These data showed the additive, as well as synergistic, interaction effects of SiONPs and LPS. We conclude that the exposure to SiONPs causes potential toxicity in humans, especially those with respiratory diseases.