• Journal of Food Hygiene and Safety
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• v.37 no.3
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• pp.189-197
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• 2022

Asthma is a chronic inflammatory disease characterized by recurring symptoms, airflow obstruction, and bronchial hyper-responsiveness. The onset of asthma for most patients begins early in life, and current asthma treatment with anti-inflammatory agents can have adverse effects, eventually leading to impaired quality of life. In the pathogenesis of asthma, macrophages and basophils play a vital role during progression. Macrophages not only induce inflammation by secreting inflammatory cytokines but also promote DNA damage and mucus production through nitric oxide (NO) production. Basophils enhance eosinophil recruitment and aggravate asthma through the FcεRIα receptor with high affinity for histamine and IgE. Therefore, in this study, we investigated whether the activation of macrophages and basophils is suppressed by the individual extracts of 28 natural products. RAW 264.7 cells (mouse macrophages) were treated with the natural products in LPS, and 4 natural product extracts resulted in decreased NO production. In β-hexosaminidase assay using RBL-2H3 cells (rat basophils), 19 natural product extracts decreased β-hexosaminidase production. In NO production and β-hexosaminidase assay using macrophages and basophils, 3 natural product extracts (Plantago asiatica, Centella asiatica, and Perilla frutescens var. japonica) significantly inhibited NO production and β-hexosaminidase release. Overall, we examined the inhibitory effects of 28 natural product extracts on macrophage and basophil activity, and the findings demonstrated the potential of natural product extracts for treating asthma and macrophage- and basophil-related diseases.

• Journal of Life Science
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• v.34 no.7
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• pp.443-452
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• 2024

This study aimed to examine the influence of 3,6-anhydroxygalactose (L-AHG) on the pro-inflammatory M1 polarization and pro-inflammatory responses observed in the RAW264.7 mouse macrophage cell line following stimulation with lipopolysaccharides (LPS). L-AHG exhibited a significant and dose-dependent inhibition of inducible nitric oxide synthase (iNOS) expression, a hallmark of M1 polarization, and subsequent NO production in LPS-stimulated RAW264.7 cells. Furthermore, the LPS-induced upregulation of cyclooxygenase-2 (COX-2), which drives the production of prostaglandin E2, an inflammatory mediator, was also inhibited by L-AHG. L-AHG did not affect the LPS-triggered Toll-like receptor 4 (TLR4)-mediated pro-inflammatory signaling pathway, which culminated in the activation of transforming growth factor-β-activated kinase 1 (TAK1). However, it was observed to inhibit the generation of reactive oxugen species (ROS) in a dose-dependent manner, as well as the TAK1-driven activation of JNK and p38 MAPK. Given that the active p38 MAPK is known to contribute to the assembly of active nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, which catalyzes the intracellular generation of pro-inflammatory ROS in LPS-stimulated macrophages, the dose-dependent reduction in the LPS-induced ROS generation by L-AHG may be mainly due to the prevention of TAK1-driven activation of p38 MAPK. Together, these results demonstrate that the L-AHG-mediated inhibition of the TAK1-JNK/p38 MAPK activation phase of the pro-inflammatory signaling pathway in LPS-stimulated RAW264.7 cells by L-AHG represents a promising mechanism for suppressing M1 polarization and pro-inflammatory responses in macrophages.

• Tuberculosis and Respiratory Diseases
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• v.49 no.6
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• pp.691-702
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• 2000

Background : Acute lung injury (ALI) is a commonly encountered respiratory disease and its prognosis is poor when the treatment is not provided promptly and properly. However no specific pharmacologic treatment is currently available for ALI, although recently several supportive drugs have been under scrutiny. We studied anti-inflammatory effects of pentoxifylline (PF), a methylated xanthine, and ONO-5046, a synthetic neutrophil elastase inhibitor on lipopolysaccharide (LPS)-induced ALI in vitro. Methods : To establish an in vitro model of LPS-induced ALI, primary rat alveolar macrophages and peripheral neutrophils in various ratios (1:0, 5:1, 1:1, 1:5, 0:1) were co-cultured with transformed rat alveolar epithelial cells (L2 cell line) or vascular endothelial cells (IP2-E4 cell line) under LPS stimulation. Each experiment was divided into five groups-control, LPS, LPS+PF, LPS+ONO, and LPS+PF+ONO. We compared LPS-induced superoxide anion productions from primary rat alveolar macrophages and peripheral neutrophils in various ratios, and the resultant cytotoxicity on L2 cells or IP2-E4 cells between groups. In addition we also compared the productions of tumor necrosis factor (TNF)-$\alpha$ interleukin (IL)-$1{\beta}$, monocyte chemotactic protein(MCP)-1, IL-6, and IL-10 as well as mRNA expressions of TNF-$\alpha$ inducible nitric oxide synthetase(iNOS), and MCP-1 from LPS-stimulated primary rat alveolar macrophages between groups. Results : (1) PF and ONO-5046 in each or both showed a trend to suppress LPS-induced superoxide anion productions from primary rat alveolar macrophages and peripheral neutrophils regardless of their ratio, except for the LPS+PF+ONO group with the 1:5 ratio, although statistical significance was limited to a few selected experimental conditions. (2) PF and ONO-5046 in each or both showed a trend to prevent IP2-E4 cells from LPS-induced cytotoxicity by primary rat alveolar macrophages and peripheral neutrophils regardless their ratio, although statistical significance was limited to a few selected experimental conditions. the effects of PF and/or ONO-5046 on LPS-induced L2 cell cytotoxicity varied according to experimental conditions. (3) PF showed a trend to inhibit LPS-induced productions of INF-$\alpha$ MCP-1, and IL-10 from primary rat alveolar macrophages. ONO-5046 alone didnot affect the LPS-induced productions of proinflammatory cytokines from primary rat alveolar macrophages but the combination of PF and ONO-5046 showed a trend to suppress LPS-induced productions of INF-$\alpha$ and IL-10 PF and ONO-5046 in each or both showed a trend to increase LPS-induced IL-$\beta$ and IL-6 productions from primary rat alveolar macrophages. (4) PF and ONO-5046 in each or both showed a trend to attenuate LPS-induced mRNA expressions of TNF-$\alpha$ and MCP-1 from primary rat alveolar macrophages but at the same time showed a trend increase iNOS mRNA expression. Conclusion : These results suggest that PF and ONO-5046 may play a role in attenuating inflammation in LPS-induced ALI and that further study is needed to use these drugs as a new supportive therapeutic strategy for ALI.