Protective effect of lycorine hydrochloride against diabetic nephropathy in high-fat diet and streptozotocin-induced diabetic mice

Abstract

Diabetic nephropathy (DN) poses a significant risk to individuals with diabetes. Inflammation plays a crucial role in DN pathogenesis. Lycorine hydrochloride (LH) is derived from Lycoris radiata (L'Hér.). This herb has been identified as a potent anti-inflammatory molecule. Further studies indicated that LH displayed therapeutic potential against metabolic disorders, renal dysfunction, and fibrosis in a high-fat diet and streptozotocin-induced (HFD/STZ)-induced DN mouse model. Mechanistically, LH mitigated renal inflammation in DN mice by targeting NF-κB pathways and the NLRP3 inflammasome verified by in vivo study. In vitro, LH inhibited NLRP3 inflammasome activation induced by nigericin (Ng), monosodium urate (MSU), and ATP, reduced caspase-1 activation, and IL-1β release. Additionally, LH suppressed the NF-κB IS-induced activation, prevented nuclear translocation of NF-κB, and subsequently reduced the expression of downstream proteins COX2 and iNOS. Collectively, these results indicated that LH primarily improved hyperglycemia-induced renal function by reducing inflammation by targeting NF-κB and NLRP3 inflammasome, implying it is a promising therapeutic agent for DN.

Keywords

Diabetic nephropathy / Lycorine hydrochloride / NF-κB / NLRP3 inflammasome

Ethical approval of studies and informed consent

All animal experiments in the study were approved by the Laboratory Animal Ethical and Welfare Committee of Shandong University Cheeloo College of Medicine (Approval NO. 18026).

Funding information

This research was financially supported by the National Natural Science Foundation of China (Nos. 81874341 and 82274065); Toxicology of Traditional Chinese Medicines, a high-level priority subject in Chinese medicine in the National Administration of Traditional Chinese Medicine (zyyzdxk-2023296); and the Cutting Edge Development Fund of Advanced Medical Research Institute (GYY2023QY01).

Availability of data and material

The data generated or analyzed in this study have been included in a published article. These data will be available upon reasonable request.

CRediT authorship contribution statement

Kai-Li Fang: Investigation, Formal analysis, Visualization, Data curation. Xin-Yu Qi: Writing - original draft. Qing-Tong Han: Conceptualization, Methodology. Lu-Zhou Chen: Investigation, Data curation. Xiao-Ning Wang: Investigation, Project administration. Zhen-Peng Xu: Conceptualization, Methodology. Lu-Qing Shang: Investigation, Project administration. Tao Shen: Supervision, Funding acquisition, Writing - review & editing. All authors have read and approved the final manuscript.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Appendix A. Supplementary data

Supplementary data to this article can be found online at https://doi.org/10.1016/j.pscia.2024.100035.

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