Abstract
Acute pancreatitis (AP) is a common acute abdominal disease with high mortality and mortality rates. Increasing evidences clarified that Traditional Chinese Medicine (TCM) adjuvant therapy for AP can be used and it gives a positive effect. Quercetin (3,3′,4′,5,7-pentahydroxyflavone, QE) is a type of flavone compound with positive effect on cancer and inflammation prevention. The current study aims to identify the effect of QE on AP and potential molecular effect. In this case, caerulein (CAE) induced AP cell and mice model were used. QE alleviated inflammatory mediators TNF-α, IL-6, and IL-10 in experiments. In addition, miR-216b was increased based on QE treatment. In further study, MAP2K6 of p38/MAPK signaling pathway was identified as a direct target of miR-216b, and QE inhibited p38/MAPK signaling pathway through up-regulating miR-216b. Our study also first confirmed that long non-coding RNA NEAT1 is a direct target of miR-216b and can be suppressed by QE. Because of the target, NEAT1, miR-216b, and MAP2K6 formed a competitive endogenous RNA (ceRNA) network. Besides direct target mediated by QE, it also decreased TNF-α which down-regulated TRAF2 and MAP3K5 located on upstream of p38/MAPK signaling and formed a feedback loop. In conclusion, QE has a protective effect on AP through inhibiting p38/MAPK signaling pathway by up-regulating miR-216b and suppressing TNF-α.
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The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
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BS and WC contributed to the study conception and design. Material preparation, data collection, and analysis were performed by BS, LZ, XZ, JZ, YL, and WB. The first draft of the manuscript was written by BS and WC, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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All animal studies have been approved by Ethics Committee of Beijing Shijitan Hospital, CMU with Admission Number 2019-72-T25, and the study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.
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Sheng, B., Zhao, L., Zang, X. et al. Quercetin inhibits caerulein-induced acute pancreatitis through regulating miR-216b by targeting MAP2K6 and NEAT1. Inflammopharmacol 29, 549–559 (2021). https://doi.org/10.1007/s10787-020-00767-7
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DOI: https://doi.org/10.1007/s10787-020-00767-7