Curcumin nanoparticles mitigate early inflammation in severe acute pancreatitis by modulating peritoneal macrophage polarization via Nrf2/HO-1 pathway activation

doi:10.3748/wjg.118140

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Gastroenterol. Jul 7, 2026; 32(25): 118140
Published online Jul 7, 2026. doi: 10.3748/wjg.118140

Curcumin nanoparticles mitigate early inflammation in severe acute pancreatitis by modulating peritoneal macrophage polarization via Nrf2/HO-1 pathway activation

Lin Yang, Dong-Xu Liao, Xiao-Yu Wang, Yong-Hong Fan, Zhu-Lin Luo, Yi Wen

Lin Yang, Dong-Xu Liao, Xiao-Yu Wang, Yi Wen, College of Medicine, Southwest Jiaotong University, Chengdu 610031, Sichuan Province, China

Yong-Hong Fan, Department of Basic Medical Laboratory, The General Hospital of Western Theater Command, Chengdu 610083, Sichuan Province, China

Zhu-Lin Luo, Yi Wen, Department of General Surgery & Tissue Stress Injury and Functional Repair Key Laboratory of Sichuan Province, The General Hospital of Western Theater Command, Chengdu 610083, Sichuan Province, China

Co-corresponding authors: Zhu-Lin Luo and Yi Wen.

Author contributions: Yang L and Liao DX contributed to conceptualization, methodology, and software; Yang L, Liao DX and Wen Y designed the research; Yang L, Wang XY and Liao DX performed the research; Yang L and Fan YH conducted data curation, and original draft preparation; Wang XY contributed to visualization and investigation; Luo ZL and Wen Y supervised the research; Fan YH is responsible for validation; Yang L contributed to writing, reviewing, and editing of the article. Wen Y and Luo ZL revised the manuscript, and they are designated as co-corresponding authors. All authors have read and approved the final version to be published.

AI contribution statement: We did not use any AI tools. All the core parts of this manuscript - including the abstract, introduction, materials and methods, results, discussion, and conclusion - were independently written by the author team without using any AI tools. We did not use AI tools for language polishing, translation, data analysis, or writing assistance. The design of the study, data interpretation, and conclusion formation did not use any AI tools. All the images in this manuscript were drawn manually, not generated by AI.

Supported by National Natural Science Foundation of China, No. 32471419; National Key Clinical Specialty Project, No. 41732113; and Independent Innovation Project of General Hospital of Western Theater Command, No. 2024-YGLC-B03.

Institutional animal care and use committee statement: All animal experimental protocols were reviewed and approved by the Animal Ethics Committee of the General Hospital of the Western Theater Command (Approval No. 2025EC10-ky038), and were strictly conducted in accordance with international guidelines for the care and use of laboratory animals.

Conflict-of-interest statement: The authors declare that there is no conflict of interest related to this study.

ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.

Data sharing statement: No additional data are available.

Corresponding author: Yi Wen, MD, Department of General Surgery & Tissue Stress Injury and Functional Repair Key Laboratory of Sichuan Province, The General Hospital of Western Theater Command, No. 270 Rongdu Road, Jinniu District, Chengdu 610083, Sichuan Province, China. 13980881194@163.com

Received: December 25, 2025
Revised: February 3, 2026
Accepted: March 17, 2026
Published online: July 7, 2026
Processing time: 188 Days and 9.7 Hours

Abstract

BACKGROUND

Severe acute pancreatitis (SAP) is a life-threatening inflammatory disease whose inflammatory response is closely associated with dysregulated polarization of peritoneal macrophages (PMs). Curcumin possesses potent anti-inflammatory and antioxidant properties, but its low solubility and bioavailability limit clinical application. Nanotechnology offers an effective strategy to enhance its therapeutic efficacy; however, the mechanism by which curcumin nanoparticles (Cur-NPs) modulate PMs polarization in SAP, particularly through nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway, remains unclear.

AIM

To investigate the effect of Cur-NPs on PMs polarization in SAP rats via the Nrf2/HO-1 pathway, thereby alleviating early inflammatory

METHODS

An SAP model was established in Sprague-Dawley rats. In vivo experiments were divided into Sham, SAP, Cur-NPs-50, Cur-NPs-100, Cur-NPs-150, and Cur-NPs-only groups. Pancreatic tissue histopathology, serum inflammatory cytokines, and enzymatic indicators were assessed. Following PMs isolation, M1/M2 markers and Nrf2/HO-1 expression were assessed via flow cytometry (CD86, CD163, CD68, and CD45), western blotting, and reverse transcription quantitative polymerase chain reaction. In vitro experiments involved isolating rat primary PMs and coculturing them with SAP ascites fluid (SAP-AF). Groups included: Control, SAP-AF, SAP-AF + Cur-NPs, SAP-AF + Nrf2 agonist [tert-butylhydroquinone (TBHQ)], SAP-AF + Cur-NPs + Nrf2 inhibitor (SAP + ML385), TBHQ, and Nrf2 inhibitor (ML385). The effects of Cur-NPs on PM polarization and the Nrf2/HO-1 pathway were validated via ELISA, immunofluorescence, and flow cytometry.

RESULTS

We prepared Cur-NPs with excellent stability, sustained-release properties, and biosafety. In the SAP rat model, Cur-NPs mitigated pancreatic tissue damage, reduced serum amylase and lipase activity, and significantly suppressed release of pro-inflammatory cytokines tumor necrosis factor-α and interleukin (IL)-1β. Mechanistically, Cur-NPs induced polarization of PMs from proinflammatory M1 to anti-inflammatory M2 phenotypes both in vivo and in vitro, manifested by downregulation of M1 markers (inducible NO synthase and CD86) and upregulation of M2 markers (CD163 and IL-10). Further studies confirmed that Cur-NPs activated the downstream HO-1 signaling pathway by promoting Nrf2 nuclear translocation. This activation not only suppressed phosphorylation of key proteins in the nuclear factor kappa-B pathway but also significantly alleviated oxidative stress, evidenced by reduced malondialdehyde and restored superoxide dismutase activity. The Nrf2-specific agonist TBHQ was able to mimic the aforementioned effects of Cur-NPs in a similar manner. Conversely, the Nrf2-specific inhibitor ML385 abolished the therapeutic effect of Cur-NPs.

CONCLUSION

Cur-NPs mitigate early inflammation and injury in SAP by activating the Nrf2/HO-1 pathway, which drives polarization of PMs toward the anti-inflammatory M2 phenotype, suggesting a potential therapeutic direction for SAP.

Keywords: Severe acute pancreatitis; Peritoneal macrophages; Cell polarization; Curcumin; Nanoparticles

Core Tip: This study provides the first evidence that curcumin nanoparticles (Cur-NPs) alleviate the early inflammatory response in severe acute pancreatitis by activating nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway to regulate polarization of peritoneal macrophages. Cur-NPs significantly ameliorated pancreatic tissue damage and reduced serum levels of inflammatory factors. Cur-NPs exerted therapeutic effects by inducing a shift in macrophage polarization from the proinflammatory M1 to anti-inflammatory M2 phenotype. Activation of the HO-1 pathway via promoted Nrf2 nuclear translocation mediated the suppressive effect of Cur-NPs on the nuclear factor kappa-B signaling pathway and oxidative stress.