Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Dec;39(6):1289-1301.
doi: 10.1007/s10557-024-07659-w. Epub 2024 Dec 24.

Emodin Suppresses NLRP3/GSDMD-induced Inflammation via the TLR4/MyD88/NF-κB Signaling Pathway in Atherosclerosis

Bozhi Ye #  1   2 , Xueli Cai #  2 , Xiaohe Liang #  2 , Yunxuan Chen  2 , Shanshan Dai  3 , Zhuqi Huang  2 , Weijian Huang  2 , Lei Zhang  2 , Zixuan Wang  2 , Jincheng Xing  2 , Xianhui Lai  4 , Zhouqing Huang  5 , Zhuyin Jia  6
Affiliations

Emodin Suppresses NLRP3/GSDMD-induced Inflammation via the TLR4/MyD88/NF-κB Signaling Pathway in Atherosclerosis

Bozhi Ye et al. Cardiovasc Drugs Ther. 2025 Dec.

Abstract

Purpose: Inflammatory responses induced by NLRP3 inflammasome contribute to the progression of atherosclerosis. This study seeks to investigate the effect of emodin on the NLRP3 inflammasome in atherogenesis and to probe the underlying mechanism.

Methods: ApoE-knockout (ApoE-/-) mice were treated with a high-fat diet (HFD) for 12 weeks and intragastrically with emodin for 6 weeks. Human mononuclear cell line THP-1 was pretreated with emodin or signaling pathway inhibitors and induced into macrophages using phorbol 12-myristate 13-acetate (PMA) for 48 h. The NLRP3-mediated inflammatory response was studied both in vivo and in vitro. The level of the inflammation was detected by western blot, real-time PCR analysis, and ELISA.

Results: Emodin attenuated atherosclerotic lesions in HFD-treated ApoE-/- mice. Emodin dramatically decreased the expression of NLRP3, GSDMD, IL-1β, and IL-18 in HFD-treated ApoE-/- mice and PMA-induced macrophages. Moreover, emodin significantly hindered the activation of nuclear factor kappa-B (NF-κB) by inhibiting the formation of the TLR4/MyD88 complex in PMA-induced macrophages.

Conclusion: Our data demonstrate that emodin can inhibit the development of atherosclerotic plaques by alleviating NLRP3/GSDMD-induced inflammation through repressing the TLR4/MyD88/NF-κB signaling pathway in macrophages. This finding suggests that emodin can be a potential candidate for the treatment of atherosclerosis.

Keywords: Atherosclerosis; Emodin; GSDMD; NF-κB; NLRP3 inflammasome.

PubMed Disclaimer

Conflict of interest statement

Declarations. Ethics Approval: All of the experimental protocols received approval from the Laboratory Animal Ethics Committee, and the Laboratory Animal Centre of the First Affiliated Hospital of Wenzhou Medical University (WYYY-IACUC-AEC-2024–055) approved this study. Consent to Participate: Not applicable. Consent for Publication: Not applicable. Conflicts of 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. The authors report no conflict of interest in this work.

References

    1. Libby P. Inflammation in atherosclerosis. Nature. 2002;420(6917):868–74. https://doi.org/10.1038/nature01323 . - DOI - PubMed
    1. Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature. 1993;362(6423):801–9. https://doi.org/10.1038/362801a0 . - DOI - PubMed
    1. Lamkanfi M, Kanneganti TD. Nlrp3: an immune sensor of cellular stress and infection. Int J Biochem Cell Biol. 2010;42(6):792–5. https://doi.org/10.1016/j.biocel.2010.01.008 . - DOI - PubMed - PMC
    1. De Nardo D, Latz E. NLRP3 inflammasomes link inflammation and metabolic disease. Trends Immunol. 2011;32(8):373–9. https://doi.org/10.1016/j.it.2011.05.004 . - DOI - PubMed - PMC
    1. Schroder K, Tschopp J. The inflammasomes. Cell. 2010;140(6):821–32. https://doi.org/10.1016/j.cell.2010.01.040 . - DOI - PubMed

MeSH terms

LinkOut - more resources