Choi Yeon Ja, Kim Hyung Suk, Lee Juyoun, Chung Jin, Lee Jun Sik, Choi Jae Sue, Yoon Taek Rim, Kim Hyung Keun, Chung Hae Young
Molecular Inflammation Research Center for Aging Intervention (MRCA), College of Pharmacy, Pusan National University, Busan, 609-735, South Korea.
Arch Pharm Res. 2014 Aug;37(8):1032-8. doi: 10.1007/s12272-014-0332-6. Epub 2014 Jan 29.
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 ((•)O2 (-)) 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.
氧化应激被认为是衰老和许多与年龄相关疾病的主要原因。过氧亚硝酸盐（ONOO(-)）由超氧化物（(•)O2 (-)）和一氧化氮（NO）反应形成，是一种细胞毒性物质，可氧化各种细胞成分，如蛋白质、脂质和DNA。本研究调查了从丹参中分离出的二甲基丹参酸盐（DML）是否能调节与年龄相关的ONOO(-)、NO和活性物质（RS）水平的增加，以及环氧合酶-2（COX-2）和诱导型一氧化氮合酶（iNOS）的表达。在本研究中，给20个月大的大鼠腹腔注射5或10 mg/kg/天的DML，并将6个月大的大鼠作为年轻对照动物。我们的结果表明，DML以剂量依赖的方式降低ONOO(-)水平。数据还显示，在衰老过程中，DML对NO代谢产物和RS的产生具有显著的剂量依赖性抑制作用。此外，蛋白质印迹分析结果显示，DML处理可降低与年龄相关的COX-2和iNOS表达的增加。因此，本研究发现DML可导致老年大鼠肾脏氧化应激以及COX-2和iNOS表达的降低。本研究的意义在于发现了DML在对抗衰老过程中的潜在应用价值。
