Self-assembled aggregations in Coptis chinensis decoction dynamically regulate intestinal tissue permeability through Peyer's patch-associated immunity
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摘要:
Abstract:
Objective To investigate the dynamic regulation of self-assembled aggregations (SAA) in Coptis chinensis (C. chinensis) decoction on the permeability of intestinal tissue and the mechanism underlying. Methods The effects of SAA on berberine (Ber) absorption were respectively analyzed in an in situ intestinal perfusion model and in an Ussing Chamber jejunum model with or without Peyer's patches (PPs). The expression levels of ZO-1, Occludin and Claudin-1 were detected by immunofluorescence to evaluate the tight junction (TJ) between intestinal epithelium cells. The expression levels of T-box-containing protein expressed in T cells, signal transducers and activators of tranion-6, retinoic acid receptor-related orphan receptor γt and forkhead box P3 in PPs were detected by the reverse transcription-polymerase chain reaction and the secretions of interferon-γ (IFN-γ), interleukin-4 (IL-4), interleukin-17 (IL-17) and transforming growth factor-β (TGF-β) in PPs were evaluated by immunohistochemistry, to reflect the differentiation of T lymphocyte in PPs to helper T (Th) cell 1, Th2, Th17 and regulatory T (Treg) cell. To confirm the correlation between SAA in C. chinensis decoction, PPs-associated immunity and intestinal epithelium permeability, SAA were administrated on an Ussing Chamber jejunum model with immunosuppressed PPs and evaluated its influences on intestinal tissue permeability and TJ proteins expression. Results SAA in C. chinensis decoction could dose-dependently promote Ber absorption in jejunum segment, with the participation of PPs. The dose-dependent and dynamical regulations of SAA on permeability of intestinal tissue and TJ proteins expression level between intestinal epithelium cells occurred along with the dynamically changed T lymphocyte differentiation and immune effectors secretion in PPs. The administration of SAA on immunosuppressed PPs exhibited dose-dependent PPs activation, inducing dynamic promotion on intestinal tissue permeability and inhibition on TJ proteins expression. Conclusion SAA can improve the Ber absorption in small intestine, through the PPs-associated immunity induced dynamic regulation on intestinal tissue permeability and TJ proteins expression. These findings might enlighten the research of traditional Chinese medicine decoction.
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This work was supported by the National Natural Science Foundation of China (grant numbers 81874348, 81303239), the Natural Science Foundation of Anhui Province (grant numbers 1908085J29), the Key Research and Development Plan of Anhui Province (grant number 201904b11020023), the Open Project of State Key Laboratory of Natural Medicines (grant number SKLNMKF202007), the Provincial Foundation for Excellent Young Talents of Colleges and Universities of Anhui Province (grant number gxyqZD2018052), and the Anhui Provincial Department of Education (grant number KJ2018A0282).
