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Archive > Volume 15 Issue 1 > 2023,15(1):117-122. DOI:https://doi.org/10.1016/j.chmed.2022.09.004 Prev Next

大黃活性成分及其復(fù)方制劑在體外和在體模型上腸吸收特性比較

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Comparison of intestinal absorption characteristics between rhubarb traditional Chinese medicine preparation and activity ingredients using in situ and in vitro model

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    摘要:
    目的 中藥活性成分的腸吸收特性對(duì)于其口服制劑的臨床療效是非常重要的。本研究旨在考察中藥大黃活性成分在單體混合狀態(tài)和復(fù)方制劑狀態(tài)下，腸吸收特性和機(jī)制的差異性。方法 采用大鼠在體單向腸灌流模型，考察大黃蒽醌成分（rhubarb anthraquinone ingredients，RAI）及其制劑提取物（Shen-Kang extract，SKE）在各腸段吸收行為。采用體外Caco-2細(xì)胞單層模型考察兩者的雙向跨膜轉(zhuǎn)運(yùn)特性。結(jié)果 在體實(shí)驗(yàn)結(jié)果表明SKE和RAI中蒽醌活性成分的主要吸收腸段一致；RAI中蘆薈大黃素、大黃素和大黃酚的有效滲透系數(shù)高于SKE中3種成分，而大黃酸的有效滲透系數(shù)低于SKE中大黃酸。體外實(shí)驗(yàn)結(jié)果表明，RAI中大黃酸、大黃素和大黃酚的表觀滲透系數(shù)高于SKE中相應(yīng)成分，而蘆薈大黃素的表觀滲透系數(shù)則低于SKE；進(jìn)一步比較了4種大黃蒽醌成分的溢出比（efflux ratio, ER），各成分ER值在SKE和RAI中相似。其中大黃酸的細(xì)胞轉(zhuǎn)運(yùn)量呈現(xiàn)明顯的時(shí)間、濃度依賴性，ER值＜1，推測(cè)轉(zhuǎn)運(yùn)機(jī)制以被動(dòng)擴(kuò)散為主；蘆薈大黃素的ER值＞1，大黃素和大黃酚的ER值＞1.5，且加入P-糖蛋白抑制劑維拉帕米和多藥耐藥蛋白抑制劑MK-571后，三種成分ER值均降低，表明蘆薈大黃素、大黃素、大黃酚的細(xì)胞轉(zhuǎn)運(yùn)受外排蛋白介導(dǎo)影響。結(jié)論 4種大黃蒽醌成分在單體混合狀態(tài)和復(fù)方制劑狀態(tài)下具有相似的吸收機(jī)制和不同的吸收行為。本研究通過不同模型對(duì)腸吸收特性的綜合考察，有助于更進(jìn)一步理解中藥活性成分在復(fù)雜組成環(huán)境中的吸收特性。

    Abstract:
    Objective: The intestinal absorption characteristics of active ingredients are very important for oral administration of traditional Chinese medicine (TCM) to achieve the desired therapeutic effect. However, a deeper understanding about active ingredients absorption characteristics is still lack. The aim of this study was to investigate the absorption properties and mechanism of rhubarb active ingredients in TCM preparation and pure form. Methods: The intestinal absorption behavior of active ingredients in Shenkang extract (SKE) and rhubarb anthraquinone ingredients (RAI) were investigated by in situ single-pass intestinal perfusion model. And the bidirectional transport characteristics of these active ingredients were assessed by in vitro Caco-2 cell monolayer model. Results: In situ experiment on Sprague-Dawley rats, the effective permeability coefficient values of aloeemodin, emodin and chrysophanol in RAI were higher than those in SKE, and the value of rhein in RAI was lower than that in SKE. But the easily absorbed segments of intestine were consistent for all ingredients, whether in SKE or in RAI. In vitro experiment, the apparent permeability coefficient values of rhein, emodin and chrysophanol in RAI were higher than those in SKE, and this value of aloe-emodin in RAI was lower than that in SKE. But their efflux ratio (ER) values in SKE and RAI were all similar. Conclusion: Four rhubarb anthraquinone ingredients in SKE and RAI have similar absorption mechanism and different absorption behavior, and the microenvironment of the study models influenced their absorption behavior. The results may provide an aid for understanding of the absorption characteristics of the TCM active ingredients in complex environments and the complementarities of different research models.

    關(guān)鍵詞:
    吸收特性;Caco-2細(xì)胞單層模型;大黃蒽醌;單向腸灌注模型;中藥

    Keywords:


    Project Supported:
    The authors thank Xi’an ShijiShengkang Pharmaceutical Industry Co. Ltd. for providing Shenkang Injection for this study. This work was supported by the National Natural Science Foundation of China (No. 81673397) and the Natural Science Basic Research Plan in Shaanxi Province of China (No. 2020JM-023).

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