EMCD, a hypoglycemic triterpene isolated from Momordica charantia wild variant, attenuates TNF-α-induced inflammation in FL83B cells in an AMP-activated protein kinase-independent manner
EMCD, a hypoglycemic triterpene isolated from Momordica charantia wild variant, attenuates TNF-α-induced inflammation in FL83B cells in an AMP-activated protein kinase-independent manner
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DOI：
10.1016/j.ejphar.2012.05.033
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发表时间：
2012-08-15
影响因子：
5
通讯作者：
Lin, Chen-Chen
中科院分区：
文献类型：
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作者：
Cheng, Hsueh-Ling;Kuo, Ching-Yi;Lin, Chen-Chen
胰岛素抵抗是2型糖尿病的致病因素，而胰岛素抵抗的发生与肿瘤坏死因子- α (tnf - α)等因素诱导的慢性炎症密切相关。苦瓜（Momordica charantia），也被称为苦瓜，已被用作草药，据报道可以改善炎症和高血糖症。先前，从M. charantia L.野生变种WB24中纯化的三萜5 β，19-环氧-25-甲氧基-葫芦-6,23-二烯-3 β，19-二醇（EMCD）被发现可以激活amp激活的蛋白激酶（AMPK），并在tnf α处理的FL83B细胞中具有降糖作用。AMPK已成为开发抗糖尿病药物的靶点，并被认为具有抗炎症作用。目前的研究旨在研究EMCD是否可能通过AMPK抑制tnf - α诱导的炎症。采用Western blotting和逆转录-聚合酶链反应对FL83B细胞tnf - α诱导的炎症进行表征。因此，细胞内诱导型一氧化氮合酶（iNOS）、核因子κ B p65亚基（nf - κ B）、蛋白酪氨酸磷酸酶- 1b、tnf - α和白细胞介素-1 β等炎症标志物的表达被tnf - α显著升高，EMCD明显抑制tnf - α诱导的这些标志物的表达。当EMCD与表没食子儿茶素-3-没食子酸酯（EGCG）同时测试时，EMCD显示出比EGCG更明显的抗炎活性。EGCG是绿茶中的一种儿茶素，据报道具有抗炎作用。对其潜在机制的研究表明，EMCD抑制了I κ B激酶（IKK）复合物和nf - κ B通路的激活，其作用可能不依赖于AMPK。总的来说，EMCD的多种功能表明它可能是治疗糖尿病并发症和其他炎症相关疾病的潜在药物。(C) 2012 Elsevier B.V.版权所有
Insulin resistance is a causative factor for type 2 diabetes, whereas the development of insulin resistance is closely related to chronic inflammation induced by factors such as tumor necrosis factor-alpha (TNF-alpha). Momordica charantia, also known as bitter melon, has been used as an herbal medicine and reported to ameliorate inflammation and hyperglycemia. Previously, a triterpene 5 beta,19-epoxy-25-methoxy-cucurbita-6,23-diene-3 beta,19-diol (EMCD), purified from M. charantia L. wild variant WB24, was found to activate AMP-activated protein kinase (AMPK) and have a hypoglycaemic effect in TNF-alpha-treated FL83B cells. AMPK has been a target for developing anti-diabetic medicine and suggested to play a role in anti-inflammation. The current study aims to investigate if EMCD might repress TNF-alpha-induced inflammation via AMPK. TNF-alpha-induced inflammation in FL83B cells was characterized using Western blotting and reverse transcriptase-polymerase chain reaction. Consequently, the expression of inflammatory markers including inducible nitric oxide synthase (iNOS), the p65 subunit of nuclear factor-kappa B (NF-kappa B), protein-tyrosine phosphatase-1B, TNF-alpha and interleukin-1 beta were significantly elevated by TNF-alpha in the cell, and EMCD obviously suppressed the TNF-alpha-induced expression of these markers. When the effect of EMCD was tested simultaneously with epigallocatechin-3-gallate (EGCG), a catechin from green tea reported to be anti-inflammatory, EMCD showed a more obvious anti-inflammatory activity than EGCG did. Investigation of the underlying mechanism suggested that EMCD inhibited the activation of the I kappa B kinase (IKK) complex and the NF-kappa B pathway, and the effect was likely independent of AMPK. Collectively, the multiple functions of EMCD suggest it to be a potential agent in treating diabetic complications and other inflammation-related disorders. (C) 2012 Elsevier B.V. All rights reserved.