Shen Shing-Chuan, Lee Woan-Ruoh, Lin Hui-Yi, Huang Ho-Chun, Ko Ching-Huai, Yang Ling-Ling, Chen Yen-Chou
Department of Dermatology, School of Medicine, Taipei Medical University, Taipei, Taiwan.
Eur J Pharmacol. 2002 Jun 20;446(1-3):187-94. doi: 10.1016/s0014-2999(02)01792-2.
Flavonoids are widely distributed in plants, but their biological functions are still unclear. In the present study, in vitro and in vivo experiments were performed to demonstrate the inhibitory activities of rutin, wogonin, and quercetin on lipopolysaccharide-induced nitric oxide (NO) and prostaglandin E(2) production in RAW 264.7 macrophages, primary peritoneal macrophages, and Balb/c mice, respectively. In vitro results showed that wogonin and quercetin dose-dependently suppressed lipopolysaccharide-induced NO production in RAW 264.7 macrophages and primary peritoneal macrophages without a notable cytotoxic effect on either cell types associated with a decrease in inducible nitric oxide synthase (iNOS) protein expression in both cells. Rutin, at 80 microM only, had a slight but obvious inhibitory effect on lipopolysaccharide-induced NO production in primary peritoneal macrophages. Both wogonin and quercetin attenuated lipopolysaccharide-induced prostaglandin E(2) production in vitro. Intravenous injection of lipopolysaccharide (10 mg/kg, i.v.) resulted in a time-dependent induction of NO production in serum, and pretreatment with the L-arginine analog N-nitro-L-arginine methyl ester (L-NAME) blocked this induction. Intravenous pretreatment of Balb/c mice with rutin, wogonin or quercetin for 1 h followed by lipopolysaccharide treatment significantly inhibited lipopolysaccharide-induced NO production, but no inhibition of prostaglandin E(2) production was found. A decrease in iNOS protein, but not cyclooxygenase-2 protein, was detected in liver and lung specimens of lipopolysaccharide-treated Balb/c mice in the presence of rutin, wogonin or quercetin. In conclusion, data obtained both in vitro and in vivo suggest that wogonin and quercetin exert inhibitory activity on lipopolysaccharide-induced NO production through suppression of iNOS expression.
黄酮类化合物广泛分布于植物中，但其生物学功能仍不清楚。在本研究中，分别进行了体外和体内实验，以证明芦丁、汉黄芩素和槲皮素对脂多糖诱导的RAW 264.7巨噬细胞、原代腹腔巨噬细胞和Balb/c小鼠中一氧化氮（NO）和前列腺素E2产生的抑制活性。体外实验结果表明，汉黄芩素和槲皮素能剂量依赖性地抑制脂多糖诱导的RAW 264.7巨噬细胞和原代腹腔巨噬细胞中NO的产生，且对两种细胞类型均无明显细胞毒性作用，同时两种细胞中诱导型一氧化氮合酶（iNOS）蛋白表达均降低。仅80微摩尔的芦丁对脂多糖诱导的原代腹腔巨噬细胞中NO的产生有轻微但明显的抑制作用。汉黄芩素和槲皮素在体外均能减弱脂多糖诱导的前列腺素E2的产生。静脉注射脂多糖（10毫克/千克，静脉注射）导致血清中NO的产生呈时间依赖性诱导，而用L-精氨酸类似物N-硝基-L-精氨酸甲酯（L-NAME）预处理可阻断这种诱导。用芦丁、汉黄芩素或槲皮素对Balb/c小鼠进行静脉预处理1小时，然后进行脂多糖处理，可显著抑制脂多糖诱导的NO产生，但未发现对前列腺素E2产生的抑制作用。在存在芦丁、汉黄芩素或槲皮素的情况下，在脂多糖处理的Balb/c小鼠的肝脏和肺组织标本中检测到iNOS蛋白减少，但环氧化酶-2蛋白未减少。总之，体外和体内实验获得的数据表明，汉黄芩素和槲皮素通过抑制iNOS表达对脂多糖诱导的NO产生发挥抑制活性。
