Anti-inflammatory effect of heme oxygenase 1: Glycosylation and nitric oxide inhibition in macrophages
Anti-inflammatory effect of heme oxygenase 1: Glycosylation and nitric oxide inhibition in macrophages
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DOI：
10.1002/jcp.20160
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发表时间：
2005-02-01
影响因子：
5.6
通讯作者：
Chen, YC
中科院分区：
文献类型：
--
作者：
Lin, HY;Shen, SC;Chen, YC
黄酮类化合物，包括苷元、橙皮素（HT; 5，7，3-三羟基-4 '-甲氧基-黄烷酮）和柚皮素（NE; 5，7，4 '-三羟基黄烷酮）和糖基、橙皮苷（HD; 5，7，3 '-三羟基-4'-甲氧基-黄烷酮7-鼠李糖苷）和柚皮苷（NI; 5，7，4 ′-三羟基黄烷酮7-鼠李糖葡萄糖苷），的重要性，芸香糖在C7的黄酮类化合物的抑制作用，脂多糖（LPS）诱导的一氧化氮产生的巨噬细胞。HT和NE，但不是他们各自的糖苷HD和NI，诱导血红素加氧酶1（HO-1）蛋白的表达在存在或不存在的LPS和LPS诱导的一氧化氮（NO）的生产和诱导型一氧化氮合酶（iNOS）的表达在RAW 264.7，J774A.1，和巯基乙酸引起的腹腔巨噬细胞显示时间和剂量依赖性抑制。HO-1诱导剂氯化血红素和NE或NI对LPS诱导的NO产生和iNOS表达的抑制作用被鉴定，HO酶抑制剂锡原卟啉（SnPP）减弱HT、NE和氯化血红素对LPS诱导的NO产生的抑制作用。NE和HT对RAW264.7细胞中iNOSmRNA和蛋白的稳定性无影响。通过高效液相色谱（HPLC）分析，根据糖苷配基HT和NE的产生，通过使用橙皮苷酶（HDase）和柚苷酶（NIase）的酶消化去除HD和NI的C7处的芸香糖对LPS诱导的NO产生产生抑制活性。此外，由LPS或脂磷壁酸（LTA）产生的NO的量在HO-1过表达细胞（HO-1/RAW 264.7）中与亲本细胞（RAW 264.7）中相比显著减少。本研究结果为黄酮类化合物抑制LPS诱导的NO生成提供了科学依据，表明黄酮类化合物抑制LPS诱导的iNOS和NO生成的机制中，C7位芸香糖是负性的，HO-1参与了黄酮类化合物抑制LPS诱导的iNOS和NO生成的机制。(C)2004 Wiley-Liss，Inc.
Flavonoids including the aglycones, hesperetin(HT;5,7,3-trihydroxy-4'-methoxy-flavanone), and naringenin (NE; 5,7,4'-trihydroxy flavanone) and glycones, hesperidin (HD; 5,7,3'-trihydroxy-4'-methoxy-flavanone 7-rhamnoglucoside) and naringin (NI; 5,7,4'-trihydroxy flavanone 7-rhamno glucoside), were used to examine the importance of rutinose at C7 on the inhibitory effects of flavonoids on lipopolysaccharide (LPS)-induced nitric oxide production in macrophages. Both HT and NE, but not their respective glycosides HD and NI, induced heme oxygenase 1 (HO-1) protein expression in the presence or absence of LPS and showed time and dose-dependent inhibition of LPS-induced nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression in RAW264.7, J774A.1, and thioglycolate-elicited peritoneal macrophages. Additive inhibitory effect of an HO-1 inducer hemin and NE or NI on LPS-induced NO production and iNOS expression was identified, and HO enzyme inhibitor tin protoporphyrin (SnPP) attenuated the inhibitory effects of HT, NE, and hemin on LPS-induced NO production. Both NE and HT showed no effect on iNOS mRNA and protein stability in RAW264.7 cells. Removal of rutinose at C7 of HD and NI by enzymatic digestion using hesperidinase (HDase) and naringinase (NIase) produce inhibitory activity on LPS-induced NO production, according to the production of the aglycones, HT and NE, by high-performance liquid chromatography (HPLC) analysis. Furthermore, the amount of NO produced by LPS or lipoteichoic acid (LTA) was significantly reduced in HO-1-overexpressing cells (HO-1/RAW264.7) compared to that in parental cells (RAW264.7). Results of the present study provide scientific evidence to suggest that rutinose at C7 is a negative moiety in flavonoid inhibition of LPS-induced NO production, and that HO-1 is involved in the inhibitory mechanism of flavonoids on LPS-incluced iNOS and NO production. (C) 2004 Wiley-Liss, Inc.