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玻璃体内羽扇醇:一种治疗非感染性葡萄膜炎的新潜在治疗策略。

Intravitreal lupeol: A new potential therapeutic strategy for noninfectious uveitis.

机构信息

Department of Pharmaceutical Products, Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.

Pharmaceutical Research and Development, Ezequiel Dias Foundation, Belo Horizonte, Minas Gerais, Brazil.

出版信息

Biomed Pharmacother. 2021 Nov;143:112145. doi: 10.1016/j.biopha.2021.112145. Epub 2021 Sep 7.

Abstract

Lupeol is a pentacyclic triterpene with known anti-inflammatory effects. However, its role in the treatment of noninfectious uveitis has not been explored. This work investigated anti-inflammatory activity of lupeol in ocular tissues with in vitro and in vivo models. First, we evaluated the effect of lupeol (100 µM) on inflammatory response induced by lipopolysaccharide (LPS) in retinal pigment epithelium cells (ARPE-19) by measuring levels of released interleukins (IL-6 and IL-8). Then, we investigated the anti-inflammatory action of intravitreal lupeol in a rodent model of panuveitis induced by Mycobacterium bovis Calmette-Guérin Bacillus (BCG). Rats were submitted to electroretinography and clinical analyses on days 3, 7, and 15 after uveitis induction. In addition, histopathological analysis, and indirect quantification of myeloperoxidase (MPO) and N-acetylglucosaminidase (NAG) in the posterior segment were performed. Treatment with lupeol (100 µM) significantly decreased IL-6 and IL-8 levels in comparison to untreated LPS-activated ARPE-19 cells. This reduction was similar to that detected in ARPE-19 cells treated with dexamethasone. The results of the in vivo assay demonstrated that intravitreal lupeol is able to modulate inflammation in the anterior and posterior segment of the rat eyes, indicating that it should be further investigated as a novel potential candidate for management of uveitis.

摘要

羽扇豆醇是一种具有已知抗炎作用的五环三萜。然而,它在治疗非感染性葡萄膜炎中的作用尚未得到探索。本研究通过体外和体内模型研究了羽扇豆醇在眼组织中的抗炎活性。首先,我们通过测量释放的白细胞介素(IL-6 和 IL-8)的水平,评估了羽扇豆醇(100μM)对脂多糖(LPS)诱导的视网膜色素上皮细胞(ARPE-19)炎症反应的影响。然后,我们研究了玻璃体内给予羽扇豆醇对牛分枝杆菌卡介苗(BCG)诱导的全葡萄膜炎啮齿动物模型的抗炎作用。在葡萄膜炎诱导后第 3、7 和 15 天,对大鼠进行视网膜电图和临床分析。此外,还进行了组织病理学分析以及后段髓过氧化物酶(MPO)和 N-乙酰氨基葡萄糖苷酶(NAG)的间接定量。与未经 LPS 激活的 ARPE-19 细胞相比,用 100μM 羽扇豆醇处理可显著降低 IL-6 和 IL-8 水平。这种降低与用地塞米松处理的 ARPE-19 细胞相似。体内试验的结果表明,玻璃体内给予羽扇豆醇能够调节大鼠眼前后段的炎症,表明它应该作为葡萄膜炎治疗的一种新的潜在候选药物进一步研究。

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