Prevention of endotoxin-induced uveitis in rats by plant sterol guggulsterone.
Prevention of endotoxin-induced uveitis in rats by plant sterol guggulsterone.
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DOI：
10.1167/iovs.09-4873
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发表时间：
2010-10
影响因子：
4.4
通讯作者：
Ramana KV
中科院分区：
文献类型：
--
作者：
Kalariya NM;Shoeb M;Reddy AB;Zhang M;van Kuijk FJ;Ramana KV
研究古古甾酮（一种抗氧化剂和抗肿瘤剂）在内毒素诱导的大鼠葡萄膜炎（EIU）中的抗炎作用，并阐明与眼部炎症相关的潜在分子机制。 EIU是通过皮下注射脂多糖（LPS）（150微克）在用古古甾酮（30毫克/千克体重，腹腔注射）或其载体处理的Lewis大鼠中诱导的。 24小时后处死大鼠，摘除眼睛并收集房水(AqH)。通过特异性 ELISA 测定 AqH 中浸润细胞的数量、基质金属蛋白酶 2 (MMP-2)、一氧化氮 (NO) 和前列腺素 E2 (PGE2) 的水平。使用抗体阵列测量 AqH 中各种炎症细胞因子的表达。免疫组化法测定MMP-2、iNOS、Cox-2、磷酸-IκB、磷酸-NF-κB的表达。人原代非色素睫状上皮细胞 (HNPEC) 用于确定古古甾酮对 LPS 诱导的炎症反应的体外功效。与对照相比，EIU 大鼠眼 AqH 的浸润细胞数、总蛋白和炎症标记物（如 MMP-2、NO 和 PGE2）显着增加，古古甾酮治疗可防止 EIU 诱导的增加。此外，古古甾酮还阻止多种眼组织中 MMP-2、iNOS 和 Cox-2 蛋白以及 IκB 和 NF-κB 的表达。此外，在培养的 HNPEC 中，古古甾酮抑制 LPS 诱导的炎症蛋白表达。我们的结果首次证明植物甾醇古古甾酮可抑制 EIU 的眼部炎症，表明补充古古甾酮可能是治疗眼部炎症的一种新方法。
To investigate the anti-inflammatory effects of guggulsterone, an antioxidant and anti-tumor agent, in endotoxin-induced uveitis (EIU) in rats and to elucidate the underlying molecular mechanism(s) related to ocular inflammation. EIU was induced by subcutaneous injection of lipopolysaccharide (LPS) (150 ug) in Lewis rats treated with guggulsterone (30 mg/kg body wt, i.p) or its carrier. After 24 h the rats were sacrificed, eyes were enucleated and aqueous humors (AqH) were collected. The number of infiltrating cells, levels of metrix metalloproteinase-2 (MMP-2), nitric oxide (NO), and prostaglandin E2 (PGE2) were determined in AqH by specific ELISAs. An antibody array was used to measure the expression of various inflammatory cytokines in AqH. The expression of MMP-2, iNOS, Cox-2, phospho-IκB and phospho-NF-κB were determined immunohistochemically. Human primary non-pigment ciliary epithelial cells (HNPECs) were used to determine the in vitro efficacy of guggulsterone on LPS-induced inflammatory response. Compared to control, the EIU rat eye AqH had significantly higher number of infiltrating cells, total protein, and inflammatory markers such as MMP-2, NO, and PGE2 and treatment of guggulsterone prevented EIU-induced increases. Further, guggulsterone also prevented the expression of MMP-2, iNOS, and Cox-2 proteins as well as IκB and NF-κB in various eye tissues. Moreover, in cultured HNPECs guggulsterone inhibited LPS-induced expression of inflammatory proteins. Our results for the first time demonstrate that the plant sterol guggulsterone suppresses the ocular inflammation in EIU suggesting that supplementation of guggulsterone could be a novel approach for the treatment of ocular inflammation.
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影响因子：
3.4
作者：
Duygulu, F;Evereklioglu, C;Ascioglu, O
通讯作者：
Ascioglu, O
影响因子：
4.4
作者：
Kim, Eugene Y.;Moudgil, Kamal D.
通讯作者：
Moudgil, Kamal D.
影响因子：
11.2
作者：
Ahn, Kwang Seok;Sethi, Gautam;Aggarwal, Bharat B.
通讯作者：
Aggarwal, Bharat B.
影响因子：
2
作者：
FRANKS, WA;LIMB, GA;DUMONDE, DC
通讯作者：
DUMONDE, DC
影响因子：
4.8
作者：
Shishodia, S;Aggarwal, BB
通讯作者：
Aggarwal, BB