Piperine modulates permeability characteristics of intestine by inducing alterations in membrane dynamics: Influence on brush border membrane fluidity, ultrastructure and enzyme kinetics
Piperine modulates permeability characteristics of intestine by inducing alterations in membrane dynamics: Influence on brush border membrane fluidity, ultrastructure and enzyme kinetics
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DOI：
10.1078/0944-7113-00114
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发表时间：
2002-04-01
期刊：
影响因子：
7.9
通讯作者：
Zutshi, U
中科院分区：
文献类型：
--
作者：
Khajuria, A;Thusu, N;Zutshi, U
胡椒碱（1-乙酰哌啶）是胡椒属植物胡椒中的一种主要生物碱。和胡椒（Piper longum Linn.）它被证明具有生物利用度增强活性与各种结构和治疗不同的药物。然而，提高生物利用度的机制尚不清楚。我们推测胡椒碱的生物利用度增强属性可能是由于增加吸收，这可能是由于改变膜脂质动力学和改变在肠道中的酶的构象。使用非极性荧光探针芘（测量碳氢化合物核心的流体性质）进行膜流动性研究的结果显示，肠刷状缘膜（BBM）流动性增加。由于酶动力学的改变，甜菜碱也刺激亮氨酸氨基肽酶和甘氨酰-甘氨酸二肽酶的活性。这表明，胡椒碱可以调节膜动力学，由于其非极性的性质，通过与周围的脂质和蛋白质附近的疏水部分，这可能会降低膜脂质的趋势，作为硬脂酸限制酶蛋白，从而修改酶的构象。胡椒碱的超微结构研究表明，微绒毛长度增加，游离核糖体和肠细胞内质网上的核糖体显著增加，这表明细胞骨架成分或膜蛋白的合成或周转可能参与所观察到的效果。总之，这表明胡椒碱可能会诱导膜动力学和渗透特性的改变，沿着诱导与细胞骨架功能相关的蛋白质合成，导致小肠吸收表面的增加，从而有助于通过上皮屏障的有效渗透。
Piperine (1-Piperoyl piperidine) is a major alkaloid of Piper nigrum Linn. and Piper longum Linn. It is shown to possess bioavailability-enhancing activity with various structurally and therapeutically diverse drugs. The mechanism of enhancing the bioavailability, is, however, not understood. We hypothesize that piperine's bioavailability-enhancing property may be attributed to increased absorption, which may be due to alteration in membrane lipid dynamics and change in the conformation of enzymes in the intestine. Results of membrane fluidity studies using an apolar fluorescent probe, pyrene (which measures the fluid properties of hydrocarbon core), showed an increase in intestinal brush border membrane (BBM) fluidity. Piperine also stimulated Leucine amino peptidase and Glycyl-glycine dipeptidase activity, due to the alteration in enzyme kinetics. This suggests that piperine could modulate the membrane dynamics due to its apolar nature by interacting with surrounding lipids and hydrophobic portions in the protein vicinity, which may decrease the tendency of membrane lipids to act as stearic constrains to enzyme proteins and thus modify enzyme conformation. Ultra structural studies with piperine showed an increase in microvilli length with a prominent increase in free ribosomes and ribosomes on the endoplasmic reticulum in enterocytes, suggesting that synthesis or turnover of cytoskeletal components or membrane proteins may be involved in the observed effect. In conclusion, it is suggested that piperine may be inducing alterations in membrane dynamics and permeation characteristics, along with induction in the synthesis of proteins associated with cytoskeletal function, resulting in an increase in the small intestine absorptive surface, thus assisting efficient permeation through the epithelial barrier.