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Sulfated Galactofucan from Sargassum Thunbergii Attenuates Atherosclerosis by Suppressing Inflammation Via the TLR4/MyD88/NF-κB Signaling Pathway

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Abstract

Purpose

Sulfated galactofucan (SWZ-4), which was extracted from Sargassum thunbergii, has recently been reported to show anti-inflammatory and anticancer properties. The present study aimed to evaluate whether SWZ-4 attenuates atherosclerosis in apolipoprotein E-knockout (ApoE-KO) mice by suppressing the inflammatory response through the TLR4/MyD88/NF-κB signaling pathway.

Methods

Male ApoE-KO mice were fed with a high-fat diet for 16 weeks and intraperitoneally injected with SWZ-4. RAW246.7 cells were treated with lipopolysaccharide (LPS) and SWZ-4. Atherosclerotic lesions were measured by Sudan IV and oil red O staining. Serum lipid profiles, inflammatory cytokines, and mRNA and protein expression levels were evaluated.

Results

SWZ-4 decreased serum TNF-α, IL-6 and IL-1 levels, but did not reduce blood lipid profiles. SWZ-4 downregulated the mRNA and protein expression of TLR4 and MyD88, reduced the phosphorylation of p65, and attenuated atherosclerosis in the ApoE-KO mice (p < 0.01). In LPS-stimulated RAW 264.7 cells, SWZ-4 inhibited proinflammatory cytokine production and the mRNA expression of TLR4, MyD88, and p65 and reduced the protein expression of TLR4 and MyD88 and the phosphorylation of p65 (p < 0.01).

Conclusion

These results suggest that SWZ-4 may exert an anti-inflammatory effect on ApoE-KO atherosclerotic mice by inhibiting the TLR4/MyD88/NF-κB signaling pathway in macrophages and therefore may be a treatment for atherosclerosis.

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Data Availability

All the data in this study are available upon reasonable request from the corresponding author.

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Funding

The study was supported by the Scientific and Technological Projects for Medicine and Health of Zhejiang Province (Grant No. 2021KY426).

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Author notes

  1. Kefu Zhu and Xihao Wang contributed equally to this work.

Authors and Affiliations

  1. Department of Cardiology, Zhejiang Hospital, Hangzhou, 310013, Zhejiang Province, China

    Kefu Zhu, Yingzheng Weng, Jiangjie Lou, Shaoze Wu & Lijiang Tang

  2. The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, 310000, Zhejiang Province, China

    Xihao Wang & Lijiang Tang

  3. Zhejiang Provincial Key Lab of Geriatrics, Department of Geriatrics, Zhejiang Hospital, Hangzhou, 310013, Zhejiang Province, China

    Genxiang Mao & Yizhong Bao

  4. College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, 310014, Zhejiang Province, China

    Weihua Jin

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  1. Kefu Zhu
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Contributions

KF Zhu and XH Wang contributed equally to this article. All authors contributed to the design and interpretation of the study and to further drafts.

Corresponding author

Correspondence to Lijiang Tang.

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Ethics Approval

The study was approved by the Institutional Animal Care and Use Committee (IACUC) at the Animal Lab Center of Zhejiang Academy of Medical Sciences.

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Zhu, K., Wang, X., Weng, Y. et al. Sulfated Galactofucan from Sargassum Thunbergii Attenuates Atherosclerosis by Suppressing Inflammation Via the TLR4/MyD88/NF-κB Signaling Pathway. Cardiovasc Drugs Ther 38, 69–78 (2024). https://doi.org/10.1007/s10557-022-07383-3

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