五精丸이 ob/ob mouse에서 Redox Status 및 NF-κB Signaling에 미치는 영향

다국어 초록 (Multilingual Abstract)

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 effects of Ojunghwan on the generation of peroxynitrite (ONOO-), nitric oxide (NO) and superoxide anion radical (·O2-), and on the expression of NF-κB-dependent inflammatory proteins in ob/ob mice. 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 the standard chow. The experimental groups were fed with a diet of chow supplemented with 30 and 90 mg Ojung-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 blot 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. Ojunghwan 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 Ojunghwan-administered ob/ob mice groups. The GSH/GSSG ratio was decreased in the ob/ob mice, whereas that were improved in the Ojunghwan-administered groups. Ojunghwan inhibited the expression of phospho-IκB-α, IKK-α, NF-κB (p50, p65), COX-2, iNOS, VCAM-1 and MMP-9 genes. These results suggest that Ojunghwan is an effective scavenger of ONOO-, ·O2-, NO and PGE2, and has an inhibitory effect on the expression of NF-κB-dependent inflammatory genes in ob/ob mice. Therefore, Ojunghwan might be used as a potential therapeutic drug against the inflammation process and inflammation- related diseases.

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