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  3. Decoding the pharmacokinetics of intravenous lentinan: A multiscale journey from the blood to hepatic Kupffer cells' lysosomes

Decoding the pharmacokinetics of intravenous lentinan: A multiscale journey from the blood to hepatic Kupffer cells' lysosomes

  • Carbohydr Polym. 2026 Feb 15:374:124706. doi: 10.1016/j.carbpol.2025.124706.
Xu Mu 1,  Jinglin Wang 2,  Shuai Wan 1,  Jingyi Wang 1,  Lei Huang 3,  Nire Wu 1,  Yuxue Zhan 3,  Yuxuan Liu 1,  Yu Zhang 4,  Ziming Zheng 5,  Kan Ding 6,  Kaiping Wang 7
Affiliations

Affiliations

  • 1 Tongji School of Pharmacy, Huazhong University of Science and Technology, 430030, Wuhan, China.
  • 2 Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, China; Hubei Key Laboratory of Natural Active Polysaccharides, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, Hubei, China; Hubei Province Clinical Research Center for Precision Medicine for Critical Illness, 430030, Wuhan, China.
  • 3 Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, China.
  • 4 Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, China; Hubei Key Laboratory of Natural Active Polysaccharides, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, Hubei, China; Hubei Province Clinical Research Center for Precision Medicine for Critical Illness, 430030, Wuhan, China. Electronic address: [email protected].
  • 5 Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, China; Hubei Key Laboratory of Natural Active Polysaccharides, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, Hubei, China. Electronic address: [email protected].
  • 6 Glycochemistry and Glycobiology Lab, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, PR China; Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Science, Zhongshan, 528400, China. Electronic address: [email protected].
  • 7 Tongji School of Pharmacy, Huazhong University of Science and Technology, 430030, Wuhan, China; Hubei Key Laboratory of Natural Active Polysaccharides, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, Hubei, China. Electronic address: [email protected].
PMID: 41371850 DOI: 10.1016/j.carbpol.2025.124706
Abstract

Lentinan (LNT), a natural polysaccharide, has been widely used as an immunomodulator in clinical therapy for decades. However, due to the difficulty of detection, its pharmacokinetics after intravenous injection have been less studied, limiting its further application. The aim of this study was to investigate the complete fate of intravenous LNT and the related mechanisms. Utilizing the latest radioisotope detection method, we quantified the blood concentration of intravenous LNT and confirmed the biphasic elimination characteristic of LNT. We obtained the relevant pharmacokinetic parameters, with T1/2α and T1/2β values of 0.304 and 5.934 h, respectively. Subsequent in vivo distribution studies demonstrated that Kupffer cells (KCs) were associated with the hepatic distribution and metabolism of LNT. In vitro experiments showed that LNT was transported to lysosomes for metabolism after it entered KCs. Mechanistic studies revealed that Complement Receptor 3 (CR3) recognizes and binds to LNT. In addition, the CR3/Src/Syk/FAK signaling pathway mediated the uptake of LNT by KCs and influenced the subsequent metabolism by regulating lysosomal acidification. In conclusion, this study revealed the in vivo fate and the related mechanisms of LNT from the macroscopic to microscopic levels, which will facilitate further explorations and studies of LNT and Other β-glucans.

Keywords

CR3; Intravenous lentinan; Lysosomal acidification; Multiscale pharmacokinetics; Radio-HPGPC.

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