Paeoniflorin ameliorates chronic colitis via the DR3 signaling pathway in group 3 innate lymphoid cells

Shaowei Huang; Xueqian Xie; Bo Xu; Zengfeng Pan; Junjie Liang; Meiling Zhang; Simin Pan; Xiaojing Wang; Meng Zhao; Qing Wang; Jinyan Chen; Yanyang Li; Lian Zhou; Xia Luo

doi:10.1016/j.jpha.2024.01.008

Volume 14 Issue 6

Jun. 2024

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Article Navigation > Journal of Pharmaceutical Analysis > 2024 > 14(6): 100940

Shaowei Huang, Xueqian Xie, Bo Xu, Zengfeng Pan, Junjie Liang, Meiling Zhang, Simin Pan, Xiaojing Wang, Meng Zhao, Qing Wang, Jinyan Chen, Yanyang Li, Lian Zhou, Xia Luo. Paeoniflorin ameliorates chronic colitis via the DR3 signaling pathway in group 3 innate lymphoid cells[J]. Journal of Pharmaceutical Analysis, 2024, 14(6): 100940. doi: 10.1016/j.jpha.2024.01.008

Citation:

Shaowei Huang, Xueqian Xie, Bo Xu, Zengfeng Pan, Junjie Liang, Meiling Zhang, Simin Pan, Xiaojing Wang, Meng Zhao, Qing Wang, Jinyan Chen, Yanyang Li, Lian Zhou, Xia Luo. Paeoniflorin ameliorates chronic colitis via the DR3 signaling pathway in group 3 innate lymphoid cells[J]. Journal of Pharmaceutical Analysis, 2024, 14(6): 100940. doi: 10.1016/j.jpha.2024.01.008

Citation:

Shaowei Huang, Xueqian Xie, Bo Xu, Zengfeng Pan, Junjie Liang, Meiling Zhang, Simin Pan, Xiaojing Wang, Meng Zhao, Qing Wang, Jinyan Chen, Yanyang Li, Lian Zhou, Xia Luo. Paeoniflorin ameliorates chronic colitis via the DR3 signaling pathway in group 3 innate lymphoid cells[J]. Journal of Pharmaceutical Analysis, 2024, 14(6): 100940. doi: 10.1016/j.jpha.2024.01.008

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Paeoniflorin ameliorates chronic colitis via the DR3 signaling pathway in group 3 innate lymphoid cells

doi: 10.1016/j.jpha.2024.01.008

a. School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, 510006, China;
b. School of Basic Medicine, Guangzhou University of Chinese Medicine, 510006, China;
c. First Clinical Medical College, Guangzhou University of Chinese Medicine, 510000, China

Funds:

This work was supported by the National Natural Science Foundation of China (Grant No.: 82074092), Natural Science Foundation of Guangdong Province, China (Grant No.: 2021A1515012219), and Guangzhou University of Chinese Medicine “Double First-Class” and High-level University Discipline Collaborative Innovation Team Project, China (Grant No.: 2021xk81), and Graduate Research Innovation Project of Guangzhou University of Chinese Medicine, China. Finally, we appreciate the School of Basic Medicine, Guangzhou University of Chinese Medicine for technical support.

Received Date: Aug. 29, 2023
Accepted Date: Jan. 28, 2024
Rev Recd Date: Jan. 22, 2024
Publish Date: Feb. 01, 2024

Abstract

Abstract

Inhibiting the death receptor 3 (DR3) signaling pathway in group 3 innate lymphoid cells (ILC3s) presents a promising approach for promoting mucosal repair in individuals with ulcerative colitis (UC). Paeoniflorin, a prominent component of Paeonia lactiflora Pall., has demonstrated the ability to restore barrier function in UC mice, but the precise mechanism remains unclear. In this study, we aimed to delve into whether paeoniflorin may promote intestinal mucosal repair in chronic colitis by inhibiting DR3 signaling in ILC3s. C57BL/6 mice were subjected to random allocation into 7 distinct groups, namely the control group, the 2% dextran sodium sulfate (DSS) group, the paeoniflorin groups (25, 50, and 100 mg/kg), the anti-tumor necrosis factor-like ligand 1A (anti-TL1A) antibody group, and the IgG group. We detected the expression of DR3 signaling pathway proteins and the proportion of ILC3s in the mouse colon using Western blot and flow cytometry, respectively. Meanwhile, DR3-overexpressing MNK-3 cells and 2% DSS-induced Rag1^-/- mice were used for verification. The results showed that paeoniflorin alleviated DSS-induced chronic colitis and repaired the intestinal mucosal barrier. Simultaneously, paeoniflorin inhibited the DR3 signaling pathway in ILC3s and regulated the content of cytokines (interleukin-17A, granulocyte-macrophage colony stimulating factor, and interleukin-22). Alternatively, paeoniflorin directly inhibited the DR3 signaling pathway in ILC3s to repair mucosal damage independently of the adaptive immune system. We additionally confirmed that paeoniflorin-conditioned medium (CM) restored the expression of tight junctions in Caco-2 cells via coculture. In conclusion, paeoniflorin ameliorates chronic colitis by enhancing the intestinal barrier in an ILC3-dependent manner, and its mechanism is associated with the inhibition of the DR3 signaling pathway.
- Paeoniflorin,
- Ulcerative colitis,
- Intestinal mucosal barrier,
- DR3 signaling pathway,
- Group 3 innate lymphoid cells

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References(34)

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