生物黏附輔料對葛根總黃酮類化合物在Caco-2細(xì)胞模型中轉(zhuǎn)運(yùn)的影響

Ying Li; Yi-qun Song; Chun-yan Zhu; Ying Li; Yi-qun Song; Chun-yan Zhu

Archive > Volume 11 Issue 1 > 2019,11(1):78-85. DOI:10.1016/j.chmed.2018.10.001 Prev Next

生物黏附輔料對葛根總黃酮類化合物在Caco-2細(xì)胞模型中轉(zhuǎn)運(yùn)的影響

Original articles

Effect of bioadhesive excipients on absorption of total flavonids from Puerariae Lobatae Radix transporting across Caco-2 cell monolayer

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摘要:

目的:葛根總黃酮（PTF）可治療心腦血管疾病，但膜通透性差，口服生物利用度低。一些輔料如卡波姆、殼聚糖和羥丙基甲基纖維素可以提高口服生物利用度。傳統(tǒng)的體外評價(jià)技術(shù)，包括大鼠腸灌流和細(xì)胞模型，不能評價(jià)PTF整體的吸收機(jī)制。方法:本研究評價(jià)輔料的黏附性及對PTF在Caco-2細(xì)胞單層模型中轉(zhuǎn)運(yùn)的影響。采用cDNA微陣列測定PTF和PTF+輔料給藥后的Caco-2細(xì)胞的基因表達(dá)變化，從基因水平揭示輔料對PTF整體吸收的影響機(jī)制。結(jié)果:體外黏附和Caco-2細(xì)胞轉(zhuǎn)運(yùn)實(shí)驗(yàn)表明，與單獨(dú)PTF相比，加入輔料后對胃黏膜具有更高的黏附性，且在Caco-2細(xì)胞模型中的轉(zhuǎn)運(yùn)效率更高。PTF與輔料的相互作用顯著改變了某些基因的表達(dá)，可能影響PTF的吸收效率。結(jié)論:不同的生物黏附聚合物能提高PTF的腸道吸收，可能與ATP結(jié)合盒(ABC)和溶質(zhì)載體轉(zhuǎn)運(yùn)體(SLC)的表達(dá)基因有關(guān)。

Abstract:

Objective: Pueraria total flavonids (PTF) can treat cardiovascular and cerebrovascular diseases, but it has poor membrane permeability and oral bioavailability. Some excipients, such as carbomer, chitosan, and hydroxypropyl methylcellulose, can improve the oral bioavailability. Traditional in vitro evaluation techniques, including the rat intestinal perfusion and cell line models, cannot evaluate PTF absorption and holistic transporters. Methods: This study evaluated excipients’ adhesiveness and effect on PTF transport across Caco-2 cell monolayer. cDNA microarrays identified gene expression changes in Caco-2 cells exposed to PTF and PTF with excipients, and revealed the mechanism underlying the effect of excipients on PTF absorption. Results: In vitro adhesion and transport experiments across Caco-2 showed that excipients had higher adhesiveness to gastric mucosa and transport efficiency across Caco-2 cells than PTF alone. The interaction of PTF with excipients significantly changed the expression of some genes, which might influence the absorption rate of PTF. Conclusion: Different bioadhesive polymers can improve intestinal absorption of PTF, which was related to some genes affiliated to the ATP-binding cassette (ABC) and solute carrier transporter (SLC) to some extent.

關(guān)鍵詞:

吸收機(jī)制;生物黏附性;生物黏附輔料;Caco-2細(xì)胞;基因分析;葛根總黃酮

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This work was supported by CAMS Innovation Fund for Medical Sciences (CIFMS)(No.2016-I2M-1-012).

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