Article

Punicalagin Suppresses LPS-induced Inflammatory Responses in Murine Macrophages via JAK/STAT Signaling Pathway and Zymosan-induced Mice Paw Edema

Huan Yan1,2, Abilaiti Gulimire2,3, Junyu Zhu4, Huaping Liang4, Zhengyi Gu2,3★★ Corresponding author

  1. 1College of Public Health, Xinjiang Medical University, Urumqi, CHINA.
  2. 2Xinjiang Institute of Materia Medica, Urumqi, CHINA.
  3. 3College of Pharmacy, Xinjiang Medical University, Urumqi, CHINA.
  4. 4Department of The Field Surgery, Institute of The Third Affiliated Hospital of Army Medical University, National Key Laboratory of Trauma, Burn and Compound Injury, Chongqing, CHINA.

CORRESPONDENCE

Zhengyi Gu

Xinjiang Institute of Materia Medica, Urumqi, CHINA.

zhengyi087@126.com

Received: 18-08-2020; Revised: 15-12-2020; Accepted: 11-03-2021.

Volume 55, Issue 2 · pp. 550–555 · PUBLISHED 2021 · DOI: 10.5530/ijper.55.2.93

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ABSTRACT

Aim: To investigate the anti-inflammatory activity of punicalagin (PUN) on mouse macrophages and the underlying mechanisms. Materials and Methods: Mouse primary peritoneal macrophages (PMs) were treated with lipopolysaccharide (LPS; 10μg/ml) and/ or PUN (50μM) for 4, 8 and 12 hr. The expression levels of inducible nitric oxide synthase (iNOS), interleukin (IL)-1β, IL-6, IL-12P40 and CCL-2 mRNAs were analyzed by qRT-PCR. Total iNOS, MAPK and JAK/STAT protein levels were measured by Western blotting and the secreted levels of IL-1β, IL-6, IL-12P40 and IL-1270 by ELISA. Acute paw edema was induced in mice with zymosan and the animals were treated with high (50 mg/kg), medium (25 mg/kg) and low (12.5 mg/kg) doses of PUN. The levels of IL-1β, IL-6, CCL-2 and other related inflammatory factors and chemokines in the mouse paw tissue homogenates were detected by ELISA. Results: Compared to the LPS-treated cells, PUN significantly decreased the levels of inflammatory cytokines and other factors (P<0.05). In addition, high dose of PUN down regulated p-ERK, p-JAK1, p-STAT1 and p-STAT3, without significantly affecting p-p38 and p-JNK. Finally, acute paw edema in the mouse model was alleviated within 12h of high-dose PUN administration, which also inhibited inflammatory cytokines and chemokines. Conclusion: PUN inhibits macrophage-mediated inflammation and the secretion of inflammatory cytokines/chemokines by targeting the ERK/MAPK and JAK/STAT signaling pathways.

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    Yan, H., Gulimire, A., Zhu, J., Liang, H., & Gu, Z. (2021). Punicalagin Suppresses LPS-induced Inflammatory Responses in Murine Macrophages via JAK/STAT Signaling Pathway and Zymosan-induced Mice Paw Edema. Indian Journal of Pharmaceutical Education and Research, 55(2), 550–555. https://doi.org/10.5530/ijper.55.2.93