Pharmacokinetics and Pharmacodynamics of Curcumin in regulating anti-inflammatory and epigenetic gene expression.
Pharmacokinetics and Pharmacodynamics of Curcumin in regulating anti-inflammatory and epigenetic gene expression.
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DOI：
10.1002/bdd.2136
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发表时间：
2018-06
影响因子：
2.1
通讯作者：
Kong AN
中科院分区：
文献类型：
--
作者：
Boyanapalli SSS;Huang Y;Su Z;Cheng D;Zhang C;Guo Y;Rao R;Androulakis IP;Kong AN
慢性炎症是癌症发展的关键驱动力。由诱导型一氧化氮合酶（iNOS）调节的亚硝酸盐水平在炎症中起关键作用。姜黄素是一种存在于姜黄根中的天然产物，其抗氧化和抗炎作用已被广泛研究，但姜黄素在抑制促炎标志物和表观遗传调节剂方面的急性药代动力学（PK）和药效学（PD）仍不清楚。在这项研究中，我们评估了姜黄素诱导的抑制大鼠淋巴细胞中脂多糖（LPS）介导的炎症的PK和PD。将LPS单独或与姜黄素一起静脉内给予雌性Sprague-Dawley大鼠。分析血浆样品的姜黄素浓度，并定量淋巴细胞中的mRNA表达。分析了几种炎症和表观遗传调节剂的相对基因表达。为了研究姜黄素浓度与iNOS、TNF-α和IL-6基因表达之间的关系，使用Jusko间接反应模型（IDR）整合描述延迟反应的转运室（TC）进行PK/PD建模。姜黄素的浓度-时间曲线呈双指数下降，这是很好地描述了两房室药代动力学模型。重要的是，我们的研究结果表明，LPS诱导淋巴细胞中促炎标志物的基因表达，在约3小时达到峰值表达，姜黄素抑制给予LPS的动物中的基因表达。这些影响很好地捕捉使用IDR模型和IDR模型与过境车厢。总之，PK/PD建模方法可能为在未来的临床试验中评估姜黄素的急性抗炎和表观遗传作用提供一个强大的定量框架。
Chronic inflammation is a key driver of cancer development. Nitrite levels, which are regulated by inducible nitric oxide synthase (iNOS), play a critical role in inflammation. While the anti-oxidant and anti-inflammatory effects of curcumin, a natural product present in the roots of Curcuma longa have been widely studied, the acute pharmacokinetics (PK) and pharmacodynamics (PD) of curcumin in suppressing pro-inflammatory markers and epigenetic modulators remain unclear. In this study, we evaluated the PK and PD of curcumin-induced suppression of lipopolysaccharide (LPS)-mediated inflammation in rat lymphocytes. LPS was administered intravenously either alone or with curcumin to female Sprague-Dawley rats. Plasma samples were analyzed for curcumin concentration and mRNA expression was quantified in lymphocytes. Relative gene expression of several inflammatory and epigenetic modulators was analyzed. To investigate the relationship between curcumin concentration and iNOS, TNF-α, and IL-6 gene expression, PK/PD modeling using Jusko’s indirect response model (IDR) integrating transit compartments (TC) describing the delayed response was conducted. The concentration-time profile of curcumin exhibited a bi-exponential decline, which was well described by a two-compartmental pharmacokinetic model. Importantly our results demonstrate that LPS induced gene expression of pro-inflammatory markers in lymphocytes, with peak expression at approximately 3 h and curcumin suppressed the gene expression in animals administered with LPS. These effects were well captured using the IDR model and an IDR model with the transit compartments. In summary, the PK/PD modeling approach could potentially provide a robust quantitative framework for evaluating the acute anti-inflammatory and epigenetic effects of curcumin in future clinical trials.
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影响因子：
4.1
作者：
Boyanapalli SS;Paredes-Gonzalez X;Fuentes F;Zhang C;Guo Y;Pung D;Saw CL;Kong AN
通讯作者：
Kong AN
影响因子：
3.7
作者：
Qu X;Pröll M;Neuhoff C;Zhang R;Cinar MU;Hossain MM;Tesfaye D;Große-Brinkhaus C;Salilew-Wondim D;Tholen E;Looft C;Hölker M;Schellander K;Uddin MJ
通讯作者：
Uddin MJ
影响因子：
--
作者：
Lao, Christopher D;Ruffin, Mack T 4th;Brenner, Dean E
通讯作者：
Brenner, Dean E
影响因子：
4.5
作者：
Deng, Yushuang;Lu, Xi;Yu, Gang
通讯作者：
Yu, Gang
DOI：
10.1155/2015/678218
发表时间：
2015
期刊：
Evidence-based complementary and alternative medicine : eCAM
影响因子：
--
作者：
Gutierres VO;Campos ML;Arcaro CA;Assis RP;Baldan-Cimatti HM;Peccinini RG;Paula-Gomes S;Kettelhut IC;Baviera AM;Brunetti IL
通讯作者：
Brunetti IL