Yang Zhengtao, Zhou Ershun, Wei Dong, Li Depeng, Wei Zhengkai, Zhang Wen, Zhang Xichen
College of Veterinary Medicine, Jilin University, Changchun 130062, Jilin Province, PR China.
College of Veterinary Medicine, Jilin University, Changchun 130062, Jilin Province, PR China.
Int Immunopharmacol. 2014 Aug;21(2):354-60. doi: 10.1016/j.intimp.2014.05.019. Epub 2014 May 27.
Emodin, an anthraquinone derivative isolated from the rhizomes of Rheum palmatum, has been reported to have a protective effect against lipopolysaccharide (LPS)-induced mastitis. However, the underlying molecular mechanisms are not well understood. The aim of this study was to investigate the molecular mechanisms of emodin in modifying lipopolysaccharide (LPS)-induced signaling pathways in mouse mammary epithelial cells (MEC). The pro-inflammatory cytokines were determined by ELISA. Nuclear factor-κB (NF-κB), inhibitory kappa B (IκBα) protein, p38, extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and PPAR-γ were determined by Western blotting. The results showed that emodin suppressed tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), iNOS and COX-2 expression. We also found that emodin inhibited LPS-induced NF-κB activation, IκBα degradation, phosphorylation of ERK, JNK and P38. Furthermore, emodin could activate PPAR-γ and the anti-inflammatory effects of emodin can be reversed by GW9662, a specific antagonist for PPAR-γ. In conclusion, our results demonstrate that emodin activates PPAR-γ, thereby attenuating LPS-induced inflammatory response.
大黄素是从掌叶大黄根茎中分离出的一种蒽醌衍生物，据报道其对脂多糖（LPS）诱导的乳腺炎具有保护作用。然而，其潜在的分子机制尚不清楚。本研究旨在探讨大黄素对小鼠乳腺上皮细胞（MEC）中脂多糖（LPS）诱导的信号通路进行调节的分子机制。通过酶联免疫吸附测定法（ELISA）测定促炎细胞因子。通过蛋白质免疫印迹法测定核因子-κB（NF-κB）、抑制性κB（IκBα）蛋白、p38、细胞外信号调节激酶（ERK）、c-Jun氨基末端激酶（JNK）和过氧化物酶体增殖物激活受体-γ（PPAR-γ）。结果表明，大黄素可抑制肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、诱导型一氧化氮合酶（iNOS）和环氧化酶-2（COX-2）的表达。我们还发现，大黄素可抑制LPS诱导的NF-κB激活、IκBα降解、ERK、JNK和P38的磷酸化。此外，大黄素可激活PPAR-γ，且大黄素的抗炎作用可被PPAR-γ特异性拮抗剂GW9,662逆转。总之，我们的结果表明，大黄素激活PPAR-γ，从而减轻LPS诱导的炎症反应。
