2. Academic Validation
  3. Liensinine alleviates type 2 diabetes mellitus through modulating the pancreatic β cell function and gut microbiota

Liensinine alleviates type 2 diabetes mellitus through modulating the pancreatic β cell function and gut microbiota

  • Genes Nutr. 2025 Dec 24;20(1):29. doi: 10.1186/s12263-025-00789-2.
Yunfei Luo 1 2,  Xuchang Liu 3,  Yan Zhang 4,  Jiaxin Wu 5,  Yujie Wang 1,  Jing Nie 6,  Ying Ying 7,  Shibo Huang 8 9
Affiliations

Affiliations

  • 1 The Clinical Trial Research Center, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, P. R. China.
  • 2 School of Basic Medicine, Nanchang Medical College, Nanchang, Jiangxi, 330052, P. R. China.
  • 3 Queen Mary School, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330031, P. R. China.
  • 4 Department of Endocrinology and Metabolism, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, P. R. China.
  • 5 The First Clinical Medical School, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330031, P. R. China.
  • 6 Department of Anatomy, School of Basic Medicine, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, P. R. China.
  • 7 Jiangxi Provincial Key Laboratory of Prevention and Treatment of Infectious Diseases, Jiangxi Medical Center for Critical Public Health Events, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330052, P. R. China.
  • 8 The Clinical Trial Research Center, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, P. R. China. [email protected].
  • 9 School of Basic Medicine, Nanchang Medical College, Nanchang, Jiangxi, 330052, P. R. China. [email protected].
PMID: 41444518 DOI: 10.1186/s12263-025-00789-2
Abstract

Background: Herbal compounds are widely recognized for their ​​diverse biological activities, often targeting multiple pathways simultaneously. However, the hypoglycemic effect of liensinine and its underlying mechanisms remain poorly understood. This study aims to clarify how liensinine exerts its blood glucose-lowering effects, with a focus on its impact on pancreatic function and the gut microbiota.

Methods: Thus, male C57BL/6 mice were randomly assigned to two dietary groups: a standard chow diet or a high-fat diet (HFD) for 4 weeks. Subsequently, type 2 diabetes mellitus (T2DM) was induced in HFD-fed mice using streptozotocin (STZ) injection, and the model was maintained for an additional four weeks. The mice were then further divided into four experimental groups: Control (standard chow), Negative Control (NC, chow-fed mice treated with liensinine at 60 mg/kg), Model (HFD + STZ-induced T2DM mice), and T2DM + Lien (T2DM mice treated with liensinine). The study employed Western blot, Immunofluorescence, and RT-qPCR techniques.

Results: Liensinine alleviated pancreatic injury and hepatic steatosis. It promoted islet cell proliferation, restored normal islet architecture, and balanced alpha- and beta-cell masses. Additionally, liensinine upregulated the expression of METTL3/14 (methyltransferases involved in RNA modification) and pancreatic duodenal homeobox 1 (PDX-1, a key regulator of pancreatic development). Meanwhile, liensinine reduced the abundance of Firmicutes, Lactobacillus, and Actinobacteriota, alongside increased levels of Bacteroides, Akkermansia, and norank_f_Muribaculaceae, concomitant with elevated short chain fatty acids (SCFAs) production in T2DM mice.

Conclusions: In conclusion, these findings indicate that liensinine holds promise as a natural therapeutic agent, exerting beneficial effects on T2DM by ameliorating islet β-cell dysfunction and modulating gut microbiota.

Keywords

Gut microbiota; Liensinine; METTL3/14; Pancreatic β-cell function; Short chain fatty acids; Type 2 diabetes mellitus.

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