Low molecular weight Fucoidan induces M2 macrophage polarization to attenuate inflammation through activation of the AMPK/mTOR autophagy pathway

Mingyu Chen; Jiahao Wang; Pengfei Zhang; Zichao Jiang; Sijie Chen; Shuailong Liang; Tianliang Ma; Haiqin Liao; Wanlin Tan; Chengcheng Niu; Long Wang

doi:10.1016/j.ejphar.2024.177134

Low molecular weight Fucoidan induces M2 macrophage polarization to attenuate inflammation through activation of the AMPK/mTOR autophagy pathway

Eur J Pharmacol. 2024 Nov 13:177134. doi: 10.1016/j.ejphar.2024.177134. Online ahead of print.

Authors

Mingyu Chen¹, Jiahao Wang², Pengfei Zhang³, Zichao Jiang³, Sijie Chen⁴, Shuailong Liang³, Tianliang Ma⁵, Haiqin Liao⁴, Wanlin Tan⁴, Chengcheng Niu⁴, Long Wang⁶

Affiliations

¹ Hunan Engineering Research Center of Biomedical Metal and Ceramic Implants, Xiangya Hospital, Central South University, Changsha, China; Department of Ultrasound Diagnosis, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China; Research Center of Ultrasonography, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China; Clinical Research Center for Ultrasound Diagnosis and Treatment in Hunan Province, China.
² The School of Medicine, Nankai University, Tianjin, 300071, China.
³ Hunan Engineering Research Center of Biomedical Metal and Ceramic Implants, Xiangya Hospital, Central South University, Changsha, China; Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
⁴ Department of Ultrasound Diagnosis, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China; Research Center of Ultrasonography, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China; Clinical Research Center for Ultrasound Diagnosis and Treatment in Hunan Province, China.
⁵ Department of Orthopedics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
⁶ Hunan Engineering Research Center of Biomedical Metal and Ceramic Implants, Xiangya Hospital, Central South University, Changsha, China; Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China; Hunan Key Laboratary of Aging Biology, Xiangya Hospital, Central South University, 87 Xiangya Road, Kaifu District, Changsha, Hunan 410008, China.

PMID: 39547407
DOI: 10.1016/j.ejphar.2024.177134

Abstract

Fucoidan, a sulfated polysaccharide with a complex structure, has gradually become the focus of biomedical research due to its remarkable biological activity and low toxicity. In this research, it was noted that low molecular weight fucoidan (LMWF) exhibited significant antimicrobial effects on Methicillin-resistant Staphylococcus aureus (MRSA) and promoted polarization towards M2 macrophages, leading to a substantial reduction in inflammatory responses within the lipopolysaccharide (LPS)-activated macrophages. We further explored the mechanism underlying the anti-inflammation activity. Our findings indicated that LMWF significantly enhanced the phosphorylation level of AMP-activated protein kinase (AMPK), inhibited the phosphorylation of the mammalian target of rapamycin (mTOR), and enhanced the expression of LC3II. Meanwhile, Compound C (CC) substantially reversed the anti-inflammation effect of LMWF, indicating that the AMPK pathway plays a pivotal role in this effect. In in vivo research, LMWF revealed impressive anti-inflammatory potential. LMWF treatment significantly eliminated MRSA and ameliorated inflammatory symptoms in mice's MRSA-infected skin wound model. Further analysis using Western Blot (WB) indicated significant AMPK/mTOR signaling pathway activation in mice treated with LMWF, which led to accelerated polarization of macrophages from the M1 to the M2 phenotype. In summary, we systematically explored the mechanism by which LMWF exerts anti-inflammatory effects through in vitro and in vivo experiments. It was confirmed that LMWF effectively induced the conversion of macrophages to an anti-inflammatory M2 phenotype by activating the AMPK/mTOR pathway. Simultaneously, LMWF effectively eradicated MRSA and accelerated wound healing in mice. This finding provides an important theoretical basis for further research on fucoidan.

Keywords: AMPK/mTOR; Fucoidan; M2 macrophage; anti-inflammatory; macrophage polarization.