ent-kaur-16-en-19-oic Acid, isolated from the roots of Aralia continentalis, induces activation of Nrf2.
ent-kaur-16-en-19-oic Acid, isolated from the roots of Aralia continentalis, induces activation of Nrf2.
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DOI：
10.1016/j.jep.2011.08.024
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发表时间：
2011-10-11
影响因子：
5.4
通讯作者：
Joo, Myungsoo
中科院分区：
文献类型：
--
作者：
Lyu, Ji Hyo;Lee, Geum San;Kim, Kyun Ha;Kim, Hyung-Woo;Cho, Su-In;Jeong, Seung-Il;Kim, Hong-Jun;Ju, Young-Seung;Kim, Ho-Kyoung;Sadikote, Ruxana T.;Christman, John W.;Oh, Sei-Ryang;Lee, Hyeong-Kyu;Ahn, Kyung-Seop;Joo, Myungsoo
过度炎症可导致组织损伤和重要器官功能障碍。因此，调节炎症反应是一种可行的治疗方法。在亚洲国家，各种炎症性疾病通常可以有效地用草药治疗，包括五加科（Araliaceae）的长白木（Aralia continentalis Kitagawa）根提取物。在这里，我们研究了贝壳杉烯酸（ent-kaur-16-en-19-oic acid：KA），一种从长白木（Aralia continentalis Kitagawa）根中提取的二萜类化合物对炎症的影响。Western印迹和RT-PCR分析表明，KA诱导的Nrf 2的核定位低至1 nM的浓度和KA治疗诱导的Nrf 2依赖性基因，如GCLC和HO-1的表达。KA对内毒素处理的RAW 264.7细胞胞浆IκB-α降解、RelA（p65）核定位和NF-κB转录活性无影响。与这些数据一致，KA治疗未能抑制代表性促炎介质（包括考克斯-2、一氧化氮、IL-1β、TNF-α和IL-12）的基因表达，表明KA对NF-κB活化无重要影响。总之，这些结果表明KA是Nrf 2的有效激活剂，并表明A.至少部分地，通过激活Nrf 2介导的。
Excessive inflammation can lead to tissue damage and dysfunction of vital organs. Hence, regulating inflammatory response is a viable therapeutic approach. In Asian countries, various inflammatory diseases have often effectively been treated with herbal remedies including the root extract of Aralia continentalis Kitagawa (Araliaceae). Here, we investigated the effect of kaurenoic acid (ent-kaur-16-en-19-oic acid: KA), a diterpenoid that is extracted from Aralia continentalis Kitagawa root, on inflammation. Western blot and RT-PCR analyses show that KA induced the nuclear localization of Nrf2 as low as 1 nM in concentration and that KA treatment induced the expression of Nrf2 dependent genes such as GCLC and HO-1. On the other hand, KA did not affect the degradation of cytoplasmic IκB-α, the nuclear localization of RelA (p65), and NF-κB transcriptional activity in RAW 264.7 cells treated with endotoxin. Consistent with these data, KA treatment failed to suppress gene expression of representative pro-inflammatory mediators including COX-2, nitric oxide, IL-1β, TNF-α, and IL-12, indicating that KA did not have an important impact on NF-κB activation. Together, these results show that KA was an effective activator of Nrf2, and suggest that the beneficial effects of A. continentalis Kitagawa root extract are, at least in part, mediated by activating Nrf2.
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影响因子：
7.4
作者：
Reuter, Simone;Gupta, Subash C.;Chaturvedi, Madan M.;Aggarwal, Bharat B.
通讯作者：
Aggarwal, Bharat B.
影响因子：
7.9
作者：
Choi, Ran Joo;Shin, Eun Myoung;Kim, Yeong Shik
通讯作者：
Kim, Yeong Shik
影响因子：
11.2
作者：
Liby, K;Hock, T;Sporn, MB
通讯作者：
Sporn, MB
影响因子：
4.8
作者：
Alam, J;Stewart, D;Cook, JL
通讯作者：
Cook, JL
影响因子：
5.3
作者：
Cullinan, SB;Gordan, JD;Diehl, JA
通讯作者：
Diehl, JA