Platycodonis Radix Alleviates LPS-Induced Lung Inflammation through Modulation of TRPA1 Channels
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Published:2023-07-05
Issue:13
Volume:28
Page:5213
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ISSN:1420-3049
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Container-title:Molecules
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language:en
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Short-container-title:Molecules
Author:
Yang Tan1, Zhao Shuang1, Yuan Yu1, Zhao Xiaotong2ORCID, Bu Fanjie3, Zhang Zhiyuan1, Li Qianqian1, Li Yaxin4, Wei Zilu1, Sun Xiuyan1, Zhang Yanqing3, Xie Junbo1
Affiliation:
1. College of Traditional Chinese Pharmacy, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China 2. Department of Chemistry, Cleveland State University, Cleveland, OH 44115, USA 3. College of Biotechnology and Food Science, Tianjin University of Commerce, Tianjin 300134, China 4. Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10065, USA
Abstract
Platycodonis Radix (PR), a widely consumed herbal food, and its bioactive constituents, platycodins, have therapeutic potential for lung inflammation. Transient Receptor Potential Ankyrin 1 (TRPA1), which is essential for the control of inflammation, may be involved in the development of inflammation in the lungs. The aim of this study was to determine the TRPA1-targeted effects of PR against pulmonary inflammation and to investigate the affinity of PR constituents for TRPA1 and their potential mechanisms of action. Using a C57BL/6J mouse lipopolysaccharides (LPS) intratracheal instillation pneumonia model and advanced analytical techniques (UPLC-Q-TOF-MS/MS, molecular docking, immuno-fluorescence), five platycodins were isolated from PR, and the interaction between these platycodins and hTRPA1 was verified. Additionally, we analyzed the impact of platycodins on LPS-induced TRPA1 expression and calcium influx in BEAS-2B cells. The results indicated that PR treatment significantly reduced the severity of LPS-triggered inflammation in the mouse model. Interestingly, there was a mild increase in the expression of TRPA1 caused by PR in healthy mice. Among five isolated platycodins identified in the PR extract, Platycodin D3 (PD3) showed the highest affinity for hTRPA1. The interaction between platycodins and TRPA1 was verified through molecular docking methods, highlighting the significance of the S5–S6 pore-forming loop in TRPA1 and the unique structural attributes of platycodins. Furthermore, PD3 significantly reduced LPS-induced TRPA1 expression and calcium ion influx in BEAS-2B cells, substantiating its own role as an effective TRPA1 modulator. In conclusion, PR and platycodins, especially PD3, show promise as potential lung inflammation therapeutics. Further research should explore the precise mechanisms by which platycodins modulate TRPA1 and their broader therapeutic potential.
Funder
National Natural Science Foundation of China Tianjin “131” innovative talent team
Subject
Chemistry (miscellaneous),Analytical Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Molecular Medicine,Drug Discovery,Pharmaceutical Science
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