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

被引:0
作者
Chen, Mingyu [1 ,2 ,4 ,5 ]
Wang, Jiahao [6 ]
Zhang, Pengfei [1 ,3 ]
Jiang, Zichao [1 ,3 ]
Chen, Sijie [2 ,4 ,5 ]
Liang, Shuailong [1 ,3 ]
Ma, Tianliang [7 ]
Liao, Haiqin [2 ,4 ,5 ]
Tan, Wanlin [2 ,4 ,5 ]
Niu, Chengcheng [2 ,4 ,5 ]
Wang, Long [1 ,3 ,8 ,9 ]
机构
[1] Cent South Univ, Xiangya Hosp, Hunan Engn Res Ctr Biomed Met & Ceram Implants, Changsha, Peoples R China
[2] Cent South Univ, Xiangya Hosp 2, Dept Ultrasound Diag, Changsha 410011, Hunan, Peoples R China
[3] Cent South Univ, Xiangya Hosp, Dept Orthoped, Changsha 410008, Hunan, Peoples R China
[4] Cent South Univ, Xiangya Hosp 2, Res Ctr Ultrasonog, Changsha 410011, Hunan, Peoples R China
[5] Clin Res Ctr Ultrasound Diag & Treatment Hunan Pro, Changsha, Hunan, Peoples R China
[6] Nankai Univ, Sch Med, Tianjin 300071, Peoples R China
[7] Zhejiang Univ, Sch Med, Affiliated Hosp 1, Dept Orthoped, Hangzhou, Peoples R China
[8] Cent South Univ, Xiangya Hosp, Natl Clin Res Ctr Geriatr Disorders, Changsha, Peoples R China
[9] Cent South Univ, Xiangya Hosp, Hunan Key Laboratary Aging Biol, 87 Xiangya Rd, Changsha 410008, Hunan, Peoples R China
关键词
Long Wang a; Fucoidan; AMPK/mTOR; M2; macrophage; Macrophage polarization; Anti-inflammatory; INJURY;
D O I
10.1016/j.ejphar.2024.177134
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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.
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页数:13
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