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- E-ISSN 2288-3339
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- P-ISSN1010-0695
- E-ISSN2288-3339
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Effects of Sotosaja-hwan on the Generation of ROS, RNS, and on the Expression of NF-κB-dependent Proteins in ob/ob Mouse
Journal of Korean Medicine / Journal of Korean Medicine, (P)1010-0695; (E)2288-3339
2009, v.30 no.1, pp.51-63
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(2009). Effects of Sotosaja-hwan on the Generation of ROS, RNS, and on the Expression of NF-κB-dependent Proteins in ob/ob Mouse. Journal of Korean Medicine, 30(1), 51-63.
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Abstract
Objectives: Peroxynitrite (ONOO－), superoxide anion radical (･O2－) and nitric oxide (NO) are cytotoxic because they can oxidize several cellular components such as proteins, lipids and DNA. They have been implicated in the aging processes, and age-related diseases such as Alzheimer's disease, rheumatoid arthritis, cancer, diabetes, obesity and atherosclerosis. The aim of this study was to investigate the ONOO－, NO, ･O2－ scavenging and NF-κB related anti-inflammatory activities of Sotosaja-hwan in ob/ob mice. Methods: Mice were grouped and treated for 5 weeks as follows. Both the normal lean (C57/BL6J black mice) and control obese (ob/ob mice) groups have received standard chow. The experimental groups were fed with a diet of chow supplemented with 30 and 90 mg Sotosaja-hwan per 1 kg of body weight for 14 days. For this study, the fluorescent probes, namely 2’,7’-dichlorodihydrofluorescein diacetate (DCFDA), 4,5-diaminofluorescein (DAF-2) and dihydrorhodamine 123 (DHR 123) were used. Western blotting was performed using anti-phospho-IκB-α, anti-IKK-α, anti-NF-κB (p50, p65), anti-COX-2, anti-iNOS, anti-VCAM-1 and anti-MMP-9 antibodies, respectively. Results: Sotosaja-hwan inhibited the generation of ONOO－, NO and ･O2－ in the lipopolysaccharide (LPS)-treated mouse kidney postmitochondrial fraction in vitro. The generation of ONOO－, NO, ･O2－ and PGE2 were inhibited in the Sotosaja-hwan-administered ob/ob mice groups. The GSH/GSSG ratio was decreased in the ob/ob mice, whereas the ratio was improved in the Sotosaja-hwan-administered groups. Sotosaja-hwan inhibited the protein expression levels of phospho-IκB-α, IKK-α, NF-κB (p50, p65), COX-2, iNOS, VCAM-1 and MMP-9 genes. Conclusions: These results suggest that Sotosaja-hwan is an effective ONOO－, ･O2－ and NO scavenger and has NF-κB related anti-inflammatory activity in ob/ob mice. Therefore, Sotosaja-hwan might be a potential therapeutic drug against the inflammation process and inflammation-related diseases.
- keywords
- Sotosaja-hwan, peroxynitrite, nitric oxide, reactive oxygen species, IKK-α, IκB-α, NF-κB, COX-2, iNOS
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