PMID- 38216100 OWN - NLM STAT- MEDLINE DCOM- 20240226 LR - 20240226 IS - 1872-7573 (Electronic) IS - 0378-8741 (Linking) VI - 325 DP - 2024 May 10 TI - Qing Xia Jie Yi Formula granules alleviated acute pancreatitis through inhibition of M1 macrophage polarization by suppressing glycolysis. PG - 117750 LID - S0378-8741(24)00050-3 [pii] LID - 10.1016/j.jep.2024.117750 [doi] AB - ETHNOPHARMACOLOGICAL RELEVANCE: Herbal formulas from Traditional Chinese Medicine are common and well-established practice for treating acute pancreatitis (AP) patients. However, little is known about their bioactive ingredients and mechanisms, such as their targets and pathways to inhibit inflammation. AIM OF THE STUDY: This study aimed to evaluate the effect of Qing Xia Jie Yi Formula (QXJYF) granules on AP and discuss the molecular mechanisms involved. MATERIALS AND METHODS: Major compounds in QXJYF granules were identified using UPLC-quadrupole-Orbitrap mass spectrometry (UPLC-Q-Orbitrap MS). The effect of QXJYF granules on experimental AP models both in vitro and in vivo, and detailed mechanisms were clarified. Two AP models were induced in mice by intraperitoneally injections of caerulein or L-arginine, and QXJYF granules were used to treat AP mice in vivo. Histological evaluation of pancreas and lung, serum amylase and lipase levels, serum inflammatory cytokines, inflammatory cell infiltration and macrophage phenotype were assessed. Bone marrow derived macrophages (BMDMs) were cultured and treated with QXJYF granules in vitro. BMDM phenotype and glycolysis levels were measured. Lastly, clinical effect of QXJYF granules on AP patients was verified. Predicted severe AP (pSAP) patients eligible for inclusion were assessed for enrollment. RESULTS: Nine major compounds were identified in QXJYF granules. Data showed that QXJYF granules significantly alleviated AP severity both in caerulein and L-arginine-induced AP models in vivo, pancreatic injury and inflammatory cell infiltration, systematic inflammation, lung injury and inflammatory cell infiltration were all improved after QXJYF treatment. QXJYF granules significantly reduced M1 macrophages during AP both in vivo and in vitro; besides, the mRNA expression levels of M1 genes such as inos, Tnfalpha, Il1beta and Il6 were significantly lower after QXJYF treatment in M1 macrophages. Mechanistically, we found that HK2, PFKFB3, PKM, LDHalpha levels were increased in M1 macrophages, but significantly decreased after QXJYF treatment. Clinical data indicated that QXJYF granules could significantly reduce CRP levels and shorten the duration of organ failure, thereby reducing the incidence of SAP and preventing pSAP patients from progressing to SAP. CONCLUSION: QXJYF granules alleviated AP through the inhibition of M1 macrophage polarization by suppressing glycolysis. CI - Copyright (c) 2024 Elsevier B.V. All rights reserved. FAU - Han, Xiao AU - Han X AD - Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Bao, Jingpiao AU - Bao J AD - Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Ni, Jianbo AU - Ni J AD - Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Li, Bin AU - Li B AD - Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Song, Pengli AU - Song P AD - Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Wan, Rong AU - Wan R AD - Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Wang, Xingpeng AU - Wang X AD - Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Hu, Guoyong AU - Hu G AD - Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: guoyong.hu@shgh.cn. FAU - Chen, Congying AU - Chen C AD - Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: congyin.chen@shgh.cn. LA - eng PT - Journal Article DEP - 20240110 PL - Ireland TA - J Ethnopharmacol JT - Journal of ethnopharmacology JID - 7903310 RN - 888Y08971B (Ceruletide) RN - 94ZLA3W45F (Arginine) SB - IM MH - Humans MH - Mice MH - Animals MH - *Pancreatitis/metabolism MH - Ceruletide/adverse effects MH - Acute Disease MH - Inflammation/drug therapy MH - Macrophages MH - Arginine OTO - NOTNLM OT - Acute pancreatitis OT - Glycolysis OT - Lung injury OT - Macrophage polarization OT - Qing Xia Jie Yi Formula granules COIS- Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2024/01/13 00:42 MHDA- 2024/02/26 06:43 CRDT- 2024/01/12 19:33 PHST- 2023/11/06 00:00 [received] PHST- 2023/12/28 00:00 [revised] PHST- 2024/01/09 00:00 [accepted] PHST- 2024/02/26 06:43 [medline] PHST- 2024/01/13 00:42 [pubmed] PHST- 2024/01/12 19:33 [entrez] AID - S0378-8741(24)00050-3 [pii] AID - 10.1016/j.jep.2024.117750 [doi] PST - ppublish SO - J Ethnopharmacol. 2024 May 10;325:117750. doi: 10.1016/j.jep.2024.117750. Epub 2024 Jan 10.