Alginate oligosaccharide prevents renal ischemia-reperfusion injury in rats via MRC1-mediated pathway

Bai-En Liang; Luo-Sha Long; Xin-Yan Wu; Mei-Ying Huang; Ying Lai; Xi Yuan; Ming-Hui Wang; Meng Li; Qi-Qi Zheng; Hai-Ling Zhang; Man-Chun Chen; Zhen-de Liu; Xin Geng; Qian-Qian Lyu; Wei-Dong Wang; Qing-Hua Liu; Wei-Zhi Liu; Chun-Ling Li

doi:10.1038/s41401-025-01545-3

Alginate oligosaccharide prevents renal ischemia-reperfusion injury in rats via MRC1-mediated pathway

Acta Pharmacol Sin. 2025 Apr 22. doi: 10.1038/s41401-025-01545-3. Online ahead of print.

Authors

Bai-En Liang^{1

2}, Luo-Sha Long^{1

3}, Xin-Yan Wu^{1

2}, Mei-Ying Huang^{1

2}, Ying Lai⁴, Xi Yuan^{1

3}, Ming-Hui Wang^{1

3}, Meng Li^{1

2}, Qi-Qi Zheng^{1

3}, Hai-Ling Zhang^{1

2}, Man-Chun Chen^{1

3}, Zhen-de Liu⁵, Xin Geng^{6

7}, Qian-Qian Lyu^{6

7}, Wei-Dong Wang^{1

2}, Qing-Hua Liu^{8

9}, Wei-Zhi Liu^{10

11}, Chun-Ling Li^{12

13}

Affiliations

¹ Institute of Hypertension, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.
² Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.
³ Department of Physiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.
⁴ Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.
⁵ Haitang (Jiangsu) Biotechnology Co Ltd, Nantong, 226100, China.
⁶ Fang Zongxi Center, MoE Key Laboratory of Marine Genetics and Breeding, College of Marine Life Sciences, Ocean University of China, Qingdao, 266003, China.
⁷ Laboratory for Marine Biology and Biotechnology, Qingdao Marine Science and Technology Center, Qingdao, 266237, China.
⁸ Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, NHC Key Laboratory of Clinical Nephrology (Sun Yat-sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou, 510080, China. liuqhua6@mail.sysu.edu.cn.
⁹ Department of Nephrology, Jieyang People's Hospital, Jieyang, 522000, China. liuqhua6@mail.sysu.edu.cn.
¹⁰ Fang Zongxi Center, MoE Key Laboratory of Marine Genetics and Breeding, College of Marine Life Sciences, Ocean University of China, Qingdao, 266003, China. liuweizhi@ouc.edu.cn.
¹¹ Laboratory for Marine Biology and Biotechnology, Qingdao Marine Science and Technology Center, Qingdao, 266237, China. liuweizhi@ouc.edu.cn.
¹² Institute of Hypertension, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China. lichl3@mail.sysu.edu.cn.
¹³ Department of Physiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China. lichl3@mail.sysu.edu.cn.

PMID: 40263568
DOI: 10.1038/s41401-025-01545-3

Abstract

Acute kidney injury (AKI) is a clinical syndrome that is defined as a sudden decline in renal function and characterized by inflammation and tubular injury. Alginate oligosaccharide (AOSC), a natural product obtained from alginate by acidolysis and hydrolysis, shows activities of antioxidant, immunomodulation, and anti-inflammation. In this study, we investigated the potential of AOSC in the treatment of AKI. Renal ischemia-reperfusion (I/R) was induced in male rats by clipping both the renal artery and vein for 45 min followed by reperfusion for 24 h. The rats were treated with AOSC (100 mg/kg, i.g.) before surgery. At the end of the experiments, both kidneys were collected for protein, mRNA measurement, or histological analysis. We showed that AOSC pretreatment significantly improved glomerular and tubular function in the kidney of I/R rats. AOSC markedly inhibited I/R-induced activation of TLR4/MyD88/NF-κB/IL-1β inflammatory signaling and prevented apoptosis in the kidney. In HK2 cells subjected to hypoxia/reoxygenation (H/R) stimulation, AOSC (250-1000 μg/ml) dose-dependently prevented pro-inflammatory responses and cell apoptosis. Transcriptomic analysis revealed that I/R increased the expression levels of mannose receptor type C1 (MRC1) in the kidney, which was markedly inhibited by AOSC. Molecular docking showed that AOSC interacted with E725, N727, E733, T743, S745, and N747 of MRC1 through hydrogen bonds. MRC1 gene knockout significantly improved renal function and attenuated I/R-induced kidney inflammation and apoptosis in mice. In line with this, AOSC failed to prevent I/R-induced kidney injury in MRC1 gene knockout mice. UPLC analysis showed that the protection of AOSC in HK2 cells subjected to H/R was likely attributed to MRC1-mediated intracellular endocytosis. In conclusion, AOSC prevents I/R-induced AKI, which is at least partially mediated by MRC1.

Keywords: acute kidney injury; alginate oligosaccharide; ischemia-reperfusion injury; mannose receptor type C1.