Decoding the pharmacokinetics of intravenous lentinan: A multiscale journey from the blood to hepatic Kupffer cells' lysosomes
文献类型:期刊论文
| 作者 | Mu, Xu1; Wang, Jinglin2,3,4; Wan, Shuai1; Wang, Jingyi1; Huang, Lei2; Wu, Nire1; Zhan, Yuxue2; Liu, Yuxuan1; Zhang, Yu2,3,4; Zheng, Ziming2,3 |
| 刊名 | CARBOHYDRATE POLYMERS
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| 出版日期 | 2026-02-15 |
| 卷号 | 374页码:17 |
| 关键词 | Intravenous lentinan Multiscale pharmacokinetics Radio-HPGPC CR3 Lysosomal acidification |
| ISSN号 | 0144-8617 |
| DOI | 10.1016/j.carbpol.2025.124706 |
| 通讯作者 | Zhang, Yu(zhangwkp@163.com) ; Zheng, Ziming(zhengziming19@hust.edu.cn) ; Ding, Kan(dingkan@simm.ac.cn) ; Wang, Kaiping(wkpzcq@163.com) |
| 英文摘要 | 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 T1/2 alpha and T1/2(3 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 (3-glucans. |
| WOS关键词 | BETA-GLUCAN ; STRUCTURAL-CHARACTERIZATION ; DIFFERENTIAL REGULATION ; MEDIATED PHAGOCYTOSIS ; ATPASE ; POLYSACCHARIDES ; ACTIVATION ; MATURATION ; RECEPTORS ; DECTIN-1 |
| 资助项目 | National Natural Science Foun-dation of China[82104282] ; National Natural Science Foun-dation of China[U23A20536] ; National Natural Science Foun-dation of China[82074111] ; National Natural Science Foun-dation of China[82104299] ; Hubei Science & Technology Department, China[2025CCB010] ; Interdisciplinary Research Program of HUST[2023JCYJ038] ; Analysis and Testing Center of Huazhong University of Science and Technology |
| WOS研究方向 | Chemistry ; Polymer Science |
| 语种 | 英语 |
| WOS记录号 | WOS:001627818400001 |
| 出版者 | ELSEVIER SCI LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/322070] ![]() |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Zhang, Yu; Zheng, Ziming; Ding, Kan; Wang, Kaiping |
| 作者单位 | 1.Huazhong Univ Sci & Technol, Tongji Sch Pharm, Wuhan 430030, Peoples R China 2.Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Pharm, Wuhan 430030, Peoples R China 3.Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Hubei Key Lab Nat Act Polysaccharides, Wuhan 430022, Hubei, Peoples R China 4.Hubei Prov Clin Res Ctr Precis Med Crit Illness, Wuhan 430030, Peoples R China 5.Chinese Acad Sci, Shanghai Inst Mat Med, Glycochem & Glycobiol Lab, Shanghai 201203, Peoples R China 6.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan 528400, Peoples R China |
| 推荐引用方式 GB/T 7714 | Mu, Xu,Wang, Jinglin,Wan, Shuai,et al. Decoding the pharmacokinetics of intravenous lentinan: A multiscale journey from the blood to hepatic Kupffer cells' lysosomes[J]. CARBOHYDRATE POLYMERS,2026,374:17. |
| APA | Mu, Xu.,Wang, Jinglin.,Wan, Shuai.,Wang, Jingyi.,Huang, Lei.,...&Wang, Kaiping.(2026).Decoding the pharmacokinetics of intravenous lentinan: A multiscale journey from the blood to hepatic Kupffer cells' lysosomes.CARBOHYDRATE POLYMERS,374,17. |
| MLA | Mu, Xu,et al."Decoding the pharmacokinetics of intravenous lentinan: A multiscale journey from the blood to hepatic Kupffer cells' lysosomes".CARBOHYDRATE POLYMERS 374(2026):17. |
入库方式: OAI收割
来源:上海药物研究所
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