Biosafety of hyperbranched polylysine and its regulatory effect on non-alcoholic fatty liver and gut microbiota

Yanxin Xiang; Min Liang; Mengyao Feng; Yan Peng; Xiaowei Liu; Xingcheng Nie; Xiaoqian He; Luping Yu; Qiaoju Hu; Xiaofei Dong; Wenxing Liu; Changyou Gao

doi:10.1016/j.bbrc.2025.152253

Biosafety of hyperbranched polylysine and its regulatory effect on non-alcoholic fatty liver and gut microbiota

Biochem Biophys Res Commun. 2025 Jun 24:777:152253. doi: 10.1016/j.bbrc.2025.152253. Online ahead of print.

Authors

Yanxin Xiang¹, Min Liang², Mengyao Feng², Yan Peng², Xiaowei Liu¹, Xingcheng Nie², Xiaoqian He², Luping Yu², Qiaoju Hu², Xiaofei Dong³, Wenxing Liu⁴, Changyou Gao⁵

Affiliations

¹ MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, No. 866 Yuhangtang Road, Hangzhou, 310058, China; Zhejiang Engineering Research Center for Interface Technology of Medical Polymers and Devices, Shaoxing Key Laboratory of Healthcare Materials and Application Technology, and Center for Healthcare Materials, Shaoxing Institute, Zhejiang University, Shaoxing, 312099, China.
² Zhejiang Engineering Research Center for Interface Technology of Medical Polymers and Devices, Shaoxing Key Laboratory of Healthcare Materials and Application Technology, and Center for Healthcare Materials, Shaoxing Institute, Zhejiang University, Shaoxing, 312099, China.
³ MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, No. 866 Yuhangtang Road, Hangzhou, 310058, China; Zhejiang Engineering Research Center for Interface Technology of Medical Polymers and Devices, Shaoxing Key Laboratory of Healthcare Materials and Application Technology, and Center for Healthcare Materials, Shaoxing Institute, Zhejiang University, Shaoxing, 312099, China. Electronic address: dongx8@zju.edu.cn.
⁴ MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, No. 866 Yuhangtang Road, Hangzhou, 310058, China; Zhejiang Engineering Research Center for Interface Technology of Medical Polymers and Devices, Shaoxing Key Laboratory of Healthcare Materials and Application Technology, and Center for Healthcare Materials, Shaoxing Institute, Zhejiang University, Shaoxing, 312099, China. Electronic address: wenxingliu@zju.edu.cn.
⁵ MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, No. 866 Yuhangtang Road, Hangzhou, 310058, China; Zhejiang Engineering Research Center for Interface Technology of Medical Polymers and Devices, Shaoxing Key Laboratory of Healthcare Materials and Application Technology, and Center for Healthcare Materials, Shaoxing Institute, Zhejiang University, Shaoxing, 312099, China. Electronic address: cygao@zju.edu.cn.

PMID: 40580724
DOI: 10.1016/j.bbrc.2025.152253

Abstract

Hyperbranched polylysine (HBPL) has shown broad-spectrum antibacterial activity and cell adhesion promoting effect, which are inherited mainly from its ε- and α-structures, respectively. Although the effectiveness of HBPL in wound anti-infection, tissue regeneration and surface modification has been thoroughly demonstrated, its systematic biosafety evaluation and influence on bacterial cohorts in the gut remain unknown. In this study, the biosafety of HBPL was systematically analyzed via endotoxin detection, cytotoxicity test, and acute systemic toxicity test (oral and intravenous injection). On the basis of its excellent biocompatibility (i.e. endotoxin-free, low cytotoxicity, LD50 (oral) ≥ 5000 mg/kg and intravenous injection safety), HBPL was added to high-fat feed for mice. Serum biochemical and hepatic histopathological results revealed that feeding HBPL can significantly reduce lipid accumulation and thus improve mouse liver functions. Additionally, HBPL assists in optimizing gut microbiota via increasing the abundance of beneficial probiotics, including Akkermansia, Butyricicoccus and Romboutsia. These findings suggest that an appropriate dose of HBPL can significantly ameliorate NAFLD through simultaneous lipase inhibition and gut microbiota modulation, providing new insights into the potential application of HBPL in NAFLD treatment.

Keywords: Biosafety; Gut microbiota; Hyperbranched polylysine; Lipase inhibition; Non-alcoholic fatty liver (NAFLD).