Osthole mitigates progressive IgA nephropathy by inhibiting reactive oxygen species generation and NF-κB/NLRP3 pathway
| Autor: | Hui-Ling Chen, Shuk-Man Ka, Yung-Jen Tsai, Louis Kuoping Chao, Ann Chen, Sung-Sen Yang, Shun-Min Yang, Kuo-Feng Hua, Jia-Ming Chang, Tzu-Yang Kao |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Blotting
Western lcsh:Medicine Apoptosis Kidney urologic and male genital diseases Nephropathy chemistry.chemical_compound Mice Coumarins NLR Family Pyrin Domain-Containing 3 Protein Medicine Animals lcsh:Science chemistry.chemical_classification Inflammation Reactive oxygen species Multidisciplinary business.industry Superoxide Macrophages lcsh:R NF-kappa B Kidney metabolism Glomerulonephritis NF-κB Inflammasome Glomerulonephritis IGA medicine.disease Calcium Channel Blockers medicine.anatomical_structure chemistry Caspases Immunology Mesangial Cells Cancer research lcsh:Q business Carrier Proteins Reactive Oxygen Species medicine.drug Signal Transduction Research Article |
| Zdroj: | PLoS ONE, Vol 8, Iss 10, p e77794 (2013) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Renal reactive oxygen species (ROS) and mononuclear leukocyte infiltration are involved in the progressive stage (exacerbation) of IgA nephropathy (IgAN), which is characterized by glomerular proliferation and renal inflammation. The identification of the mechanism responsible for this critical stage of IgAN and the development of a therapeutic strategy remain a challenge. Osthole is a pure compound isolated from Cnidiummonnieri (L.) Cusson seeds, which are used as a traditional Chinese medicine, and is anti-inflammatory, anti-apoptotic, and anti-fibrotic both in vitro and in vivo. Recently, we showed that osthole acts as an anti-inflammatory agent by reducing nuclear factor-kappa B (NF-κB) activation in and ROS release by activated macrophages. In this study, we examined whether osthole could prevent the progression of IgAN using a progressive IgAN (Prg-IgAN) model in mice. Our results showed that osthole administration resulted in prevention of albuminuria, improved renal function, and blocking of renal progressive lesions, including glomerular proliferation, glomerular sclerosis, and periglomerular mononuclear leukocyte infiltration. These findings were associated with (1) reduced renal superoxide anion levels and increased Nrf2 nuclear translocation, (2) inhibited renal activation of NF-κB and the NLRP3 inflammasome, (3) decreased renal MCP-1 expression and mononuclear leukocyte infiltration, (4) inhibited ROS production and NLRP3 inflammasome activation in cultured, activated macrophages, and (5) inhibited ROS production and MCP-1 protein levels in cultured, activated mesangial cells. The results suggest that osthole exerts its reno-protective effects on the progression of IgAN by inhibiting ROS production and activation of NF-κB and the NLRP3 inflammasome in the kidney. Our data also confirm that ROS generation and activation of NF-κB and the NLRP3 inflammasome are crucial mechanistic events involved in the progression of the renal disorder. |
| Databáze: | OpenAIRE |
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