2. Academic Validation
  3. Micheliolide ameliorates severe acute pancreatitis in mice through potentiating Nrf2-mediated anti-inflammation and anti-oxidation effects

Micheliolide ameliorates severe acute pancreatitis in mice through potentiating Nrf2-mediated anti-inflammation and anti-oxidation effects

  • Int Immunopharmacol. 2024 Dec 25;143(Pt 2):113490. doi: 10.1016/j.intimp.2024.113490.
Chen-Yu Wu 1,  Ke-Qi Wang 1,  Yu-Ying Qin 1,  Hong-Wei Wang 2,  Min-Min Wu 2,  Xian-Dong Zhu 3,  Xin-Yu Lu 4,  Mian-Mian Zhu 1,  Chao-Sheng Lu 5,  Qing-Qing Hu 6
Affiliations

Affiliations

  • 1 Department of Pediatrics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China; Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
  • 2 Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
  • 3 Department of Thyroid Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
  • 4 Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China; The First Clinical Medical College of Wenzhou Medical University, Wenzhou 325000, China.
  • 5 Department of Pediatrics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China; Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China. Electronic address: lucs363@163.com.
  • 6 Department of Pediatrics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China; Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China. Electronic address: huqingqing1513@sina.com.
PMID: 39467351 DOI: 10.1016/j.intimp.2024.113490
Abstract

Severe acute pancreatitis (SAP) is an acute inflammatory injury disease with significant mortality rate and currently without effective strategy being available. Inflammation and oxidative stress play central roles in the etiology of SAP. Micheliolide (MCL), an active monomeric component isolated from Michelia champaca, has been proved its multiple therapeutic properties including anti-inflammatory, antioxidant and anti-cancer. Nevertheless, the therapeutic effect and underlying mechanism of MCL in SAP still remain unclear. Here, we found that caerulein with lipopolysaccharide (LPS)-induced SAP murine models exhibited severe pancreatic injury, including necrosis, edema, and vacuolation of acinar cells in the pancreas, elevated serum levels of amylase and Lipase, and reduced number of the exocrine cells. As expected, MCL treatment alleviated these side effects. Mechanistically, MCL triggered nuclear factor erythroid 2-related factor 2 (Nrf2) activation, thereby activating Nrf2-regulated antioxidative pathways and inhibiting nuclear factor kappa B p65 (NF-κB p65)-mediated inflammatory response, resulting in protection against pancreatic injury in SAP mice. In addition, Nrf2 gene deficiency abolished the beneficial effects of MCL on SAP-induced pancreatic inflammation and oxidative stress and blocked the ability of MCL to alleviate the pancreatic injury in SAP mice. Collectively, these findings indicated that the suppression of SAP-induced pancreatic injury by MCL was at least in part due to Nrf2-mediated anti-oxidation effect and inhibition of inflammation.

Keywords

Micheliolide; Nuclear factor erythroid 2-related factor 2; Nuclear factor kappa B p65; Severe acute pancreatitis.

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