2. Academic Validation
  3. The liver kinase B1 mediates the therapeutic efficacy of nuciferine against hepatic lipid accumulation in diabetic KKAy mice

The liver kinase B1 mediates the therapeutic efficacy of nuciferine against hepatic lipid accumulation in diabetic KKAy mice

  • Phytomedicine. 2026 Mar:152:157807. doi: 10.1016/j.phymed.2026.157807.
Yan Guo 1,  Huijian Chen 1,  Tongqing Li 1,  Mi Huang 1,  Pengxin Liu 1,  Nabijan Mohammadtursun 2,  Li Kang 3,  Ainiwaer Aikemu 2,  Xinzhou Yang 4
Affiliations

Affiliations

  • 1 International Cooperation Base for Active Substances in Traditional Chinese Medicine in Hubei Province, School of Pharmaceutical Sciences, South-Central Minzu University, 182 Min-Zu Road, Wuhan 430074, China.
  • 2 College of Life Sciences, Xinjiang Normal University, Urumqi 830054, China.
  • 3 International Cooperation Base for Active Substances in Traditional Chinese Medicine in Hubei Province, School of Pharmaceutical Sciences, South-Central Minzu University, 182 Min-Zu Road, Wuhan 430074, China. Electronic address: [email protected].
  • 4 International Cooperation Base for Active Substances in Traditional Chinese Medicine in Hubei Province, School of Pharmaceutical Sciences, South-Central Minzu University, 182 Min-Zu Road, Wuhan 430074, China; Xinjiang Key Laboratory of Hotan Characteristic Chinese Traditional Medicine Research, Xinjiang Hetian College, Hotan 848000, China. Electronic address: [email protected].
PMID: 41650502 DOI: 10.1016/j.phymed.2026.157807
Abstract

Background: Type-2 diabetes mellitus (T2DM) is a metabolic disorder characterized by Insulin resistance (IR) and β-cell dysfunction. Nuciferine (NCF), derived from Plants such as Nelumbo nucifera Gaertn., is an alkaloid with anti-obesity/T2DM effects. However, how NCF acts on hepatic lipid accumulation in T2DM treatment is not fully understood.

Purpose: This study aims to investigate how NCF reverses hepatic steatosis and treats T2DM through the LKB1/AMPK/mTOR pathway.

Methods: High-fat diet-fed KK-Ay mice were used to establish an in vivo diabetic model. Insulin stimulation was used to establish hepatocyte models of IR.

Results: We found that NCF reduced body weight and blood glucose levels in diabetic mice. NCF also decreased the number of lipid droplets and triglyceride levels in liver. Furthermore, NCF reduced the overexpression of p-mTOR and the lipogenesis-related protein in liver of diabetic mice, while it elevated the protein levels of p-LKB1, p-AMPK, and p-ACC. In HepG2-IR cells, NCF significantly inhibited lipid accumulation via the LKB1/AMPK/mTOR pathway. When LKB1 or AMPK antagonists were used or LKB1 was knocked down by siRNA, the inhibitory effect of NCF on lipid accumulation was blocked.

Conclusion: NCF inhibited hepatic lipid accumulation via the LKB1/AMPK/mTOR pathway, thereby contributing to the treatment of T2DM.

Keywords

Hepatic lipid accumulation; LKB1/AMPK/mTOR pathway; Nuciferine; Type-2 diabetes mellitus.

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