Enhancement of naringenin bioavailability by complexation with hydroxypropyl-β-cyclodextrin. [corrected].
Enhancement of naringenin bioavailability by complexation with hydroxypropyl-β-cyclodextrin. [corrected].
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DOI：
10.1371/journal.pone.0018033
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发表时间：
2011-04-06
期刊：
影响因子：
3.7
通讯作者：
Nahmias Y
中科院分区：
文献类型：
--
作者：
Shulman M;Cohen M;Soto-Gutierrez A;Yagi H;Wang H;Goldwasser J;Lee-Parsons CW;Benny-Ratsaby O;Yarmush ML;Nahmias Y
葡萄柚中含有丰富的黄酮苷元，即柚皮素，它是葡萄柚中苦味的原因，已被证明在体外和体内都具有降血脂和抗炎作用。最近，我们的研究小组证明，柚皮素抑制丙型肝炎病毒（HCV）的生产，而其他人则证明了其在治疗高脂血症和糖尿病的潜力。然而，柚皮素的口服生物利用度低，严重限制了其临床潜力。在本研究中，我们证明了柚皮素的溶解度通过与β-环糊精（FDA批准的赋形剂）络合而增强。具体而言，羟丙基-β-环糊精（HPβCD）使柚皮素的溶解度增加了400倍以上，并且其通过肠上皮的Caco-2模型的转运增加了11倍。当喂食大鼠时，柚皮素与HPβCD的复合物使其血浆浓度增加，AUC值增加7.4倍，Cmax增加14.6倍。此外，与单独使用柚皮素相比，在进餐前服用复合物可使VLDL水平降低42%，葡萄糖清除率增加64%。这些作用与肝脏和骨骼肌中的PPAR共激活物PGC 1 α表达增加相关。组织学和血液化学分析表明，这种给药途径与肠、肾或肝损伤无关。这些结果表明，柚皮素与HPβCD的复合物是一种可行的选择，用于口服递送柚皮素作为治疗实体，用于治疗血脂异常、糖尿病和HCV感染。
The abundant flavonoid aglycone, naringenin, which is responsible for the bitter taste in grapefruits, has been shown to possess hypolipidemic and anti-inflammatory effects both in vitro and in vivo. Recently, our group demonstrated that naringenin inhibits hepatitis C virus (HCV) production, while others demonstrated its potential in the treatment of hyperlipidemia and diabetes. However, naringenin suffers from low oral bioavailability critically limiting its clinical potential. In this study, we demonstrate that the solubility of naringenin is enhanced by complexation with β-cyclodextrin, an FDA approved excipient. Hydroxypropoyl-β-cyclodextrin (HPβCD), specifically, increased the solubility of naringenin by over 400-fold, and its transport across a Caco-2 model of the gut epithelium by 11-fold. Complexation of naringenin with HPβCD increased its plasma concentrations when fed to rats, with AUC values increasing by 7.4-fold and Cmax increasing 14.6-fold. Moreover, when the complex was administered just prior to a meal it decreased VLDL levels by 42% and increased the rate of glucose clearance by 64% compared to naringenin alone. These effects correlated with increased expression of the PPAR co-activator, PGC1α in both liver and skeletal muscle. Histology and blood chemistry analysis indicated this route of administration was not associated with damage to the intestine, kidney, or liver. These results suggest that the complexation of naringenin with HPβCD is a viable option for the oral delivery of naringenin as a therapeutic entity with applications in the treatment of dyslipidemia, diabetes, and HCV infection.
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影响因子：
4.7
作者：
Kanaze, F. I.;Bounartzi, M. I.;Niopas, I.
通讯作者：
Niopas, I.
DOI：
10.1073/pnas.0906820106
发表时间：
2009-09-15
影响因子：
11.1
作者：
Kidambi, Srivatsan;Yarmush, Rubin S.;Nahmias, Yaakov
通讯作者：
Nahmias, Yaakov
影响因子：
6.3
作者：
Jung, UJ;Kim, HJ;Choi, MS
通讯作者：
Choi, MS
影响因子：
7.7
作者：
Borradaile, NM;de Dreu, LE;Huff, MW
通讯作者：
Huff, MW
影响因子：
7.2
作者：
Liu, Li;Shan, Song;Cheng, Yi-Yu
通讯作者：
Cheng, Yi-Yu