School of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, College of Pharmacy, China Medical University, Taichung, Taiwan.
J Agric Food Chem. 2011 Oct 26;59(20):11211-8. doi: 10.1021/jf200576f. Epub 2011 Sep 27.
Excess production of nitric oxide (NO) by inducible NO synthase (iNOS) in activated macrophages is linked to acute and chronic inflammation. Thus, it would be valuable to develop inhibitors of NO production and/or iNOS for potential therapeutic use. This study investigated the anti-inflammatory effects of 6β-acetoxy-7α-hydroxyroyleanone (AHR), a compound isolated from the bark of Taiwania cryptomerioides Hayata, using lipopolysaccharide (LPS)-stimulated mouse macrophage (RAW 264.7) ex vivo and carrageenan (Carr)-induced mouse paw edema model in vivo. When RAW 264.7 macrophages were treated with different concentrations of AHR (0, 0.31, 0.62, 1.25, and 2.50 μg/mL) together with LPS (100 ng/mL), a significant concentration-dependent inhibition of NO production was detected. Western blotting revealed that AHR blocked protein expression of iNOS and cyclooxygenase-2 (COX-2) in LPS-stimulated RAW 264.7 macrophages, significantly. In the anti-inflammatory test, AHR (1.25 and 2.50 mg/kg) decreased paw edema at 4 and 5 h after λ-carrageenan (Carr) administration and increased the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in the liver tissue. It was also demonstrated that AHR significantly attenuated the malondialdehyde (MDA) level in the edema paw at 5 h after Carr injection. AHR (0.62, 1.25, and 2.50 mg/kg) decreased the NO levels on both edema paw and serum at 5 h after Carr injection. Also, AHR diminished the serum tumor necrosis factor (TNF-α) at 5 h after Carr injection. Western blotting revealed that AHR (2.50 mg/kg) decreased Carr-induced iNOS and COX-2 expressions at 5 h in the edema paw. An intraperitoneal (ip) injection treatment with AHR also diminished neutrophil infiltration into sites of inflammation, as did indomethacin (Indo). The anti-inflammatory activities of AHR might be related to the decrease in the levels of MDA, iNOS, and COX-2 in the edema paw and to the increase in the activities of CAT, SOD, and GPx in the liver through the suppression of TNF-α and NO.
诱导型一氧化氮合酶（iNOS）过度产生的一氧化氮（NO）与急性和慢性炎症有关。因此，开发用于潜在治疗用途的 NO 产生和/或 iNOS 抑制剂将是有价值的。本研究使用脂多糖（LPS）刺激的小鼠巨噬细胞（RAW 264.7）体外和角叉菜胶（Carr）诱导的小鼠爪肿胀模型体内研究了 6β-乙酰氧基-7α-羟基罗汉酮（AHR）的抗炎作用，AHR 是从台湾翠柏树皮中分离得到的化合物。当 RAW 264.7 巨噬细胞用不同浓度的 AHR（0、0.31、0.62、1.25 和 2.50μg/mL）与 LPS（100ng/mL）一起处理时，检测到 NO 产生的浓度依赖性抑制作用。Western blot 显示 AHR 阻断了 LPS 刺激的 RAW 264.7 巨噬细胞中 iNOS 和环加氧酶-2（COX-2）的蛋白表达。在抗炎试验中，AHR（1.25 和 2.50mg/kg）在角叉菜胶（Carr）给药后 4 和 5 小时减少了爪肿胀，并增加了肝组织中过氧化氢酶（CAT）、超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GPx）的活性。还表明，AHR 显著降低了 Carr 注射后 5 小时水肿爪中的丙二醛（MDA）水平。AHR（0.62、1.25 和 2.50mg/kg）在 Carr 注射后 5 小时降低了水肿爪和血清中的 NO 水平。此外，AHR 还降低了 Carr 注射后 5 小时的血清肿瘤坏死因子（TNF-α）水平。Western blot 显示，AHR（2.50mg/kg）在水肿爪中降低了 Carr 诱导的 iNOS 和 COX-2 表达在 5 小时。腹腔（ip）注射 AHR 还减少了中性粒细胞浸润到炎症部位，如同哚美辛（Indo）一样。AHR 的抗炎活性可能与水肿爪中 MDA、iNOS 和 COX-2 水平的降低以及 CAT、SOD 和 GPx 活性的增加有关，通过抑制 TNF-α 和 NO。
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