Journal
ARCHIVES OF PHARMACAL RESEARCH
Volume 37, Issue 8, Pages 1032-1038Publisher
PHARMACEUTICAL SOC KOREA
DOI: 10.1007/s12272-014-0332-6
Keywords
Aging; COX-2; Dimethyl lithospermate; iNOS; Reactive species; ONOO-
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Funding
- Pusan National University
- Korean National Research Foundation (NRF) - Korean government (MEST) [2009-0083538]
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Oxidative stress has been proposed to be a major cause of aging and many age-related diseases. Peroxynitrite (ONOO-), formed from the reaction of superoxide (O-aEuro cent(2) (-)) and nitric oxide (NO), is a cytotoxic species that can oxidize various cellular components, such as proteins, lipids, and DNA. The present study investigated whether dimethyl lithospermate (DML), isolated from Salvia miltiorrhiza, modulates age-related increases of ONOO-, NO, and reactive species (RS) levels and expressions of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). For this study, 20-month-old rats were intraperitoneally injected with 5 or 10 mg/kg/day of DML, and 6-month-old rats were used as young control animals. Our results indicated that DML reduces ONOO- levels in a dose-dependent manner. The data also revealed that DML has significant inhibitory effects on NO metabolites and RS generation in a dose-dependent manner during aging. Furthermore, the results of Western blot analysis revealed that DML treatment reduces age-associated increases in COX-2 and iNOS expressions. Thus, this study found that DML caused the decrease of renal oxidative stress and COX-2 and iNOS expressions in aged rats. The significance of the present study is the finding of DML in its potential application against the aging process.
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