Abstract
Gualou Xiebai Decoction (GXD), a classic prescription, is widely used to dealing with inflammatory diseases in China for thousands of years. Abnormal metabolic state of bile acids (BAs) is confirmed to cause intestinal epithelial barrier dysfunction. In preliminary work, we observed that GXD could decrease intestinal permeability in hyperlipidemia mice. The present study aimed to explore the protective effect of GXD on intestinal mucosa in vitro. Caco-2 cell monolayer permeability among different groups was determined by measuring the concentrations of FITC-dextran in the lower compartments and transepithelial electrical resistance (TEER). Meanwhile, mRNA and protein expressions of tight junctions (TJs) were investigated. Generation of intracellular reactive oxygen species (ROS) and the ratio of cell apoptosis induced by BAs were assessed by fluorescence probe and flow cytometry. GXD was shown to keep the cell monolayer in low permeable status, increase TEER and mRNA and protein expressions of occludin (Ocln) and zonula occluden 2 (ZO2) remarkably in cells challenged with cholic acid (CA), deoxycholic acid (DCA) and glycocholic acid (GCA). However, no significant effects were uncovered against the pathological effects of taurocholic acid (TCA). Meanwhile, generation of ROS and increased levels of apoptotic cells caused by CA, DCA and GCA were dramatically decreased by GXD, which were not observed on TCA. GXD could significantly attenuate intestinal barrier dysfunction induced by BAs via TJs regulation, oxidative stress suppression and cell apoptosis decrease, but such effects and behind mechanisms differed among different kinds of BAs.
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Data availability
The datasets used or analysed during the current study are available from the corresponding author on reasonable request.
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Statistical analysis was carried out with GraphPad Prism 7 and IBM SPSS 20.0 software.
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Funding
The study was supported by the Military Science Foundation of China (no. CLB18J036), Fujian Natural Science Foundation (no. 2018J01354) and Clinical Research Fund of 900TH Hospital of PLA (no. 2020L08).
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Jiyuan Su and Dongmei Zhang contributed to the conception of the study;
Jiyuan Su and Zhiqing He performed the experiment;
Jiyuan Su, Zhiqing He, Zonggui Wu and Dongmei Zhang contributed significantly to analysis and manuscript preparation;
Jiyuan Su and Zhiqing He performed the data analyses and wrote the manuscript;
Yunhua Yu and Mingfang Lu helped perform the analysis with constructive discussions.
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Su, J., He, Z., Yu, Y. et al. Gualou Xiebai Decoction ameliorates increased Caco-2 monolayer permeability induced by bile acids via tight junction regulation, oxidative stress suppression and apoptosis reduction. J Bioenerg Biomembr 54, 45–57 (2022). https://doi.org/10.1007/s10863-021-09927-y
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DOI: https://doi.org/10.1007/s10863-021-09927-y