Absorption, Metabolic Stability, and Pharmacokinetics of Ginger Phytochemicals.
Absorption, Metabolic Stability, and Pharmacokinetics of Ginger Phytochemicals.
复制标题
DOI：
10.3390/molecules22040553
复制
发表时间：
2017-03-30
期刊：
影响因子：
--
通讯作者：
Aneja R
中科院分区：
文献类型：
--
作者：
Mukkavilli R;Yang C;Singh Tanwar R;Ghareeb A;Luthra L;Aneja R
We have previously demonstrated promising anticancer efficacy of orally-fed whole ginger extract (GE) in preclinical prostate models emphasizing the importance of preservation of the natural “milieu”. Essentially, GE primarily includes active ginger phenolics viz., 6-gingerol (6G), 8-gingerol (8G), 10-gingerol (10G), and 6-shogaol (6S). However, the druglikeness properties of active GE phenolics like solubility, stability, and metabolic characteristics are poorly understood. Herein, we determined the physicochemical and biochemical properties of GE phenolics by conducting in vitro assays and mouse pharmacokinetic studies with and without co-administration of ketoconazole (KTZ). GE phenolics showed low to moderate solubility in various pH buffers but were stable in simulated gastric and intestinal fluids, indicating their suitability for oral administration. All GE phenolics were metabolically unstable and showed high intrinsic clearance in mouse, rat, dog, and human liver microsomes. Upon oral administration of 250 mg/kg GE, sub-therapeutic concentrations of GE phenolics were observed. Treatment of plasma samples with β-glucuronidase (βgd) increased the exposure of all GE phenolics by 10 to 700-fold. Co-administration of KTZ with GE increased the exposure of free GE phenolics by 3 to 60-fold. Interestingly, when the same samples were treated with βgd, the exposure of GE phenolics increased by 11 to 60-fold, suggesting inhibition of phase I metabolism by KTZ but little effect on glucuronide conjugation. Correlating the in vitro and in vivo results, it is reasonable to conclude that phase II metabolism seems to be the predominant clearance pathway for GE phenolics. We present evidence that the first-pass metabolism, particularly glucuronide conjugation of GE phenolics, underlies low systemic exposure.
登录
查看更多内容
姜的6个shogaol提取物上调细胞和小鼠的抗氧化剂防御系统。
DOI：
10.3390/molecules17078037
发表时间：
2012-07-04
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Bak MJ;Ok S;Jun M;Jeong WS
通讯作者：
Jeong WS
影响因子：
2.7
作者：
Aktan, Fugen;Henness, Sheridan;Ammit, Alaina J.
通讯作者：
Ammit, Alaina J.
DOI：
10.1016/j.bbrc.2007.08.012
发表时间：
2007-10-12
影响因子：
3.1
作者：
Ishiguro, Kazuhiro;Ando, Takafumi;Goto, Hidemi
通讯作者：
Goto, Hidemi
影响因子：
3.9
作者：
Chen, Huadong;Lv, Lishuang;Sang, Shengmin
通讯作者：
Sang, Shengmin
影响因子：
7.2
作者：
Gan, Fei-Fei;Nagle, Amrita A.;Chew, Eng-Hui
通讯作者：
Chew, Eng-Hui