Qingjie Huagong decoction inhibits pancreatic acinar cell pyroptosis by regulating circHipk3/miR-193a-5p/NLRP3 pathway

  • Phytomedicine. 2024 Apr:126:155265. doi: 10.1016/j.phymed.2023.155265.
MinChao Feng  1 ,  BaiJun Qin  2 ,  Fang Luo  1 ,  XiaoDong Zhu  1 ,  KunRong Liu  3 ,  Kai Li  1 ,  DongYang Wu  4 ,  GuoZhong Chen  5 ,  XiPing Tang  6
Affiliations
  • 1. The First Clinical School of Medicine, Guangxi University of Traditional Chinese Medicine, Nanning 530000, China.
  • 2. Department of Gastroenterology, Chongqing Traditional Chinese Medicine Hospital, Chongqing 400021, China.
  • 3. Department of Gastroenterology, The First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine, 89-9 Dongge Road, Nanning 530023, China.
  • 4. School of Pharmacy, Guangxi University of Traditional Chinese Medicine, Nanning 530000, China.
  • 5. Department of Gastroenterology, The First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine, 89-9 Dongge Road, Nanning 530023, China. Electronic address: [email protected].
  • 6. Endoscopy Center, Guangxi Medical University Cancer Hospital, 71 Hedi Road, Nanning 530021, China. Electronic address: [email protected].
PMID: 38422649 DOI: 10.1016/j.phymed.2023.155265
Abstract

Background: Safer and more effective drugs are needed for the treatment of acute pancreatitis (AP). Qingjie Huagong decoction (QJHGD) has been applied to treat AP for many years and has shown good clinical effects. However, the potential mechanism has not yet been determined.

Purpose: To investigate the role and underlying mechanism of the effects of QJHGD on AP both in vitro and in vivo.

Methods: QJHGD was characterized by UHPLC-Q-Orbitrap-MS. The protective effect of QJHDG and the underlying mechanism were investigated in MPC-83 cells in vitro. A caerulein-induced AP model was established to evaluate the protective effect of QJHGD in mice. CCK-8 assays were used to detect cell viability. The contents of inflammatory mediators were determined by ELISA. Expression levels of circRNA, miRNA and mRNA were determined by qRT-PCR. Protein expression was determined using Western blot. Pancreatic tissues were assessed by hematoxylin and eosin staining as well as immunohistochemical and immunofluorescence analyses. Pull-down and luciferase activity assays were performed to determine the regulatory relationships of circHipk3, miR-193a-5p and NLRP3.

Results: Our results confirmed that mmu-miR-193a-5p was sponged by mmu-circHipk3, and NLRP3 was a target of miR-193a-5p. In vitro experiments showed that QJHGD enhanced MPC-83 cell viability by regulating circHipk3 sponging mir-193a-5 targeting NLRP3 and inhibiting pyroptosis-related factors. Finally, we showed that QJHGD ameliorated pancreatic tissue injury in AP mice via this pathway.

Conclusion: This study demonstrate that QJHDG exerted its anti-AP effects via the circHipk3/miR-193a-5p/NLRP3 pathway, revealing a novel mechanism for the therapeutic effect of QJHDG on AP.

Keywords
Acute pancreatitis; CircHipk3; Pyroptosis; Qingjie Huagong decoction; miR-193a-5P.
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