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Article

In Vivo Absorption of Iron Complexes of Chondroitin Sulfates with Different Molecular Weights and Their Anti-Inflammation and Metabolism Regulation Effects on LPS-Induced Macrophages

1
SKL of Marine Food Processing & Safety Control, National Engineering Research Center of Seafood, Collaborative Innovation Center of Seafood Deep Processing, National & Local Joint Engineering Laboratory for Marine Bioactive Polysaccharide Development and Application, Liaoning Key Laboratory of Food Nutrition and Health, School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, China
2
College of Pharmacy, Ningxia Medical University, Yinchuan 750004, China
*
Author to whom correspondence should be addressed.
Foods 2025, 14(19), 3356; https://doi.org/10.3390/foods14193356 (registering DOI)
Submission received: 13 August 2025 / Revised: 23 September 2025 / Accepted: 25 September 2025 / Published: 27 September 2025
(This article belongs to the Special Issue Food Bioactives: Innovations, Mechanisms, and Future Applications)

Abstract

The present study investigated the effects of hierarchical molecular weights and iron chelation on the in vivo absorption and the inflammatory bioactivity of chondroitin sulfate (CS). Firstly, CS, chondroitin sulfate-iron complex (CS-Fe), and low-molecular-weight chondroitin sulfate-iron complex (LCS-Fe) were fluorescently labeled and characterized. Then, the plasma concentration–time profiles and fluorescence imaging results demonstrated that LCS-Fe was more efficiently absorbed into the bloodstream and showed a higher Cmax (415.16 ± 109.50 μg/mL) than CS-Fe (376.60 ± 214.10 μg/mL) and CS (135.27 ± 236.82 μg/mL), and it clearly accumulated in the liver. Furthermore, the anti-inflammatory effect of CS-Fe and LCS-Fe was assayed in LPS-induced macrophages, and LCS-Fe and CS-Fe both showed a better inhibitory effect on NO production, COX-2 and IL-1β gene expression levels compared to CS. Additionally, targeted metabolic analysis of macrophages using LC-MS/MS revealed that CS, CS-Fe, and LCS-Fe could reverse approximately one quarter of the LPS-induced differential metabolites, and the biosynthesis of valine, leucine, and isoleucine was the most significantly involved metabolic pathway. Notably, the molecular weight reduction and iron chelation could both enhance the bioavailability and anti-inflammatory efficacy of CS.
Keywords: chondroitin sulfate; iron complex; in vivo absorption; tissue distribution; anti-inflammation; metabolic analysis chondroitin sulfate; iron complex; in vivo absorption; tissue distribution; anti-inflammation; metabolic analysis

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MDPI and ACS Style

Du, Q.; Zheng, J.; Kong, F.; Wu, X.; Ai, C.; Song, S. In Vivo Absorption of Iron Complexes of Chondroitin Sulfates with Different Molecular Weights and Their Anti-Inflammation and Metabolism Regulation Effects on LPS-Induced Macrophages. Foods 2025, 14, 3356. https://doi.org/10.3390/foods14193356

AMA Style

Du Q, Zheng J, Kong F, Wu X, Ai C, Song S. In Vivo Absorption of Iron Complexes of Chondroitin Sulfates with Different Molecular Weights and Their Anti-Inflammation and Metabolism Regulation Effects on LPS-Induced Macrophages. Foods. 2025; 14(19):3356. https://doi.org/10.3390/foods14193356

Chicago/Turabian Style

Du, Qianqian, Jiachen Zheng, Fanhua Kong, Xiuli Wu, Chunqing Ai, and Shuang Song. 2025. "In Vivo Absorption of Iron Complexes of Chondroitin Sulfates with Different Molecular Weights and Their Anti-Inflammation and Metabolism Regulation Effects on LPS-Induced Macrophages" Foods 14, no. 19: 3356. https://doi.org/10.3390/foods14193356

APA Style

Du, Q., Zheng, J., Kong, F., Wu, X., Ai, C., & Song, S. (2025). In Vivo Absorption of Iron Complexes of Chondroitin Sulfates with Different Molecular Weights and Their Anti-Inflammation and Metabolism Regulation Effects on LPS-Induced Macrophages. Foods, 14(19), 3356. https://doi.org/10.3390/foods14193356

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