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Licorice-Yuanhua Herbal Pair Induces Ileum Injuries Through Weakening Epithelial and Mucous Barrier Functions: Saponins, Flavonoids, and Di-Terpenes All Involved

In traditional Chinese Medicine (TCM), the licorice-yuanhua herbal pair is one of the most representative incompatible herbal pairs recorded in the “eighteen incompatible herbal pairs” theory. Previous studies of our research group have demonstrated several gut-related side-effects induced by the li...

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Autores principales: Yu, Jingao, Zhang, Dongbo, Liang, Yanni, Zhang, Zhen, Guo, Jianming, Chen, Yanyan, Yan, Yafeng, Liu, Hongbo, Lei, Liyan, Wang, Zheng, Tang, Zhishu, Tang, Yuping, Duan, Jin-ao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7378851/
https://www.ncbi.nlm.nih.gov/pubmed/32765254
http://dx.doi.org/10.3389/fphar.2020.00869
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author Yu, Jingao
Zhang, Dongbo
Liang, Yanni
Zhang, Zhen
Guo, Jianming
Chen, Yanyan
Yan, Yafeng
Liu, Hongbo
Lei, Liyan
Wang, Zheng
Tang, Zhishu
Tang, Yuping
Duan, Jin-ao
author_facet Yu, Jingao
Zhang, Dongbo
Liang, Yanni
Zhang, Zhen
Guo, Jianming
Chen, Yanyan
Yan, Yafeng
Liu, Hongbo
Lei, Liyan
Wang, Zheng
Tang, Zhishu
Tang, Yuping
Duan, Jin-ao
author_sort Yu, Jingao
collection PubMed
description In traditional Chinese Medicine (TCM), the licorice-yuanhua herbal pair is one of the most representative incompatible herbal pairs recorded in the “eighteen incompatible herbal pairs” theory. Previous studies of our research group have demonstrated several gut-related side-effects induced by the licorice-yuanhua herbal pair. In this study, we investigated whether and why this incompatible herbal pair could induce gut tissue damage. After licorice-yuanhua treatment, the duodenum, ileum, and colon and serum biomarkers of mice were examined by pathological staining, Western blot, and ELISA assays. The IEC-6 cells and LS174T cells were treated with licorice saponins, yuanhua flavonoids, and di-terpenes; iTRAQ-labeled proteomic technology was then used to explore their synergistic effects on mucosa cells, followed by verification of ZO-1 and MUC-2 protein expressions. The results showed that the licorice-yuanhua herbal pair induced ileum tissue injuries, including epithelial integrity loss, inflammation, and edema. These injuries were verified to be related to epithelial and mucous barrier weakening, such as downregulated ileum ZO-1 and MUC-2 protein expressions. Proteomic analysis also suggested that glycyrrhizic acid and genkwanin synergistically influence tight junction pathways in LS174T cells. Furthermore, licorice saponins, yuanhua flavonoids, and di-terpenes dose/structure-dependently downregulate ZO-1 and MUC-2 protein expressions in mucosa cells. Our study provides different insights into the incompatibility mechanisms and material basis of the licorice-yuanhua herbal pair, especially that besides toxic di-terpenes, licorice saponins and yuanhua flavonoids, which are commonly known to be non-toxic compounds, can also take part in the gut damage induced by the licorice-yuanhua herbal pair.
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spelling pubmed-73788512020-08-05 Licorice-Yuanhua Herbal Pair Induces Ileum Injuries Through Weakening Epithelial and Mucous Barrier Functions: Saponins, Flavonoids, and Di-Terpenes All Involved Yu, Jingao Zhang, Dongbo Liang, Yanni Zhang, Zhen Guo, Jianming Chen, Yanyan Yan, Yafeng Liu, Hongbo Lei, Liyan Wang, Zheng Tang, Zhishu Tang, Yuping Duan, Jin-ao Front Pharmacol Pharmacology In traditional Chinese Medicine (TCM), the licorice-yuanhua herbal pair is one of the most representative incompatible herbal pairs recorded in the “eighteen incompatible herbal pairs” theory. Previous studies of our research group have demonstrated several gut-related side-effects induced by the licorice-yuanhua herbal pair. In this study, we investigated whether and why this incompatible herbal pair could induce gut tissue damage. After licorice-yuanhua treatment, the duodenum, ileum, and colon and serum biomarkers of mice were examined by pathological staining, Western blot, and ELISA assays. The IEC-6 cells and LS174T cells were treated with licorice saponins, yuanhua flavonoids, and di-terpenes; iTRAQ-labeled proteomic technology was then used to explore their synergistic effects on mucosa cells, followed by verification of ZO-1 and MUC-2 protein expressions. The results showed that the licorice-yuanhua herbal pair induced ileum tissue injuries, including epithelial integrity loss, inflammation, and edema. These injuries were verified to be related to epithelial and mucous barrier weakening, such as downregulated ileum ZO-1 and MUC-2 protein expressions. Proteomic analysis also suggested that glycyrrhizic acid and genkwanin synergistically influence tight junction pathways in LS174T cells. Furthermore, licorice saponins, yuanhua flavonoids, and di-terpenes dose/structure-dependently downregulate ZO-1 and MUC-2 protein expressions in mucosa cells. Our study provides different insights into the incompatibility mechanisms and material basis of the licorice-yuanhua herbal pair, especially that besides toxic di-terpenes, licorice saponins and yuanhua flavonoids, which are commonly known to be non-toxic compounds, can also take part in the gut damage induced by the licorice-yuanhua herbal pair. Frontiers Media S.A. 2020-07-16 /pmc/articles/PMC7378851/ /pubmed/32765254 http://dx.doi.org/10.3389/fphar.2020.00869 Text en Copyright © 2020 Yu, Zhang, Liang, Zhang, Guo, Chen, Yan, Liu, Lei, Wang, Tang, Tang and Duan http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Yu, Jingao
Zhang, Dongbo
Liang, Yanni
Zhang, Zhen
Guo, Jianming
Chen, Yanyan
Yan, Yafeng
Liu, Hongbo
Lei, Liyan
Wang, Zheng
Tang, Zhishu
Tang, Yuping
Duan, Jin-ao
Licorice-Yuanhua Herbal Pair Induces Ileum Injuries Through Weakening Epithelial and Mucous Barrier Functions: Saponins, Flavonoids, and Di-Terpenes All Involved
title Licorice-Yuanhua Herbal Pair Induces Ileum Injuries Through Weakening Epithelial and Mucous Barrier Functions: Saponins, Flavonoids, and Di-Terpenes All Involved
title_full Licorice-Yuanhua Herbal Pair Induces Ileum Injuries Through Weakening Epithelial and Mucous Barrier Functions: Saponins, Flavonoids, and Di-Terpenes All Involved
title_fullStr Licorice-Yuanhua Herbal Pair Induces Ileum Injuries Through Weakening Epithelial and Mucous Barrier Functions: Saponins, Flavonoids, and Di-Terpenes All Involved
title_full_unstemmed Licorice-Yuanhua Herbal Pair Induces Ileum Injuries Through Weakening Epithelial and Mucous Barrier Functions: Saponins, Flavonoids, and Di-Terpenes All Involved
title_short Licorice-Yuanhua Herbal Pair Induces Ileum Injuries Through Weakening Epithelial and Mucous Barrier Functions: Saponins, Flavonoids, and Di-Terpenes All Involved
title_sort licorice-yuanhua herbal pair induces ileum injuries through weakening epithelial and mucous barrier functions: saponins, flavonoids, and di-terpenes all involved
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7378851/
https://www.ncbi.nlm.nih.gov/pubmed/32765254
http://dx.doi.org/10.3389/fphar.2020.00869
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