2. Academic Validation
  3. Puerarin ameliorates metabolic dysfunction-associated fatty liver disease by inhibiting ferroptosis and inflammation

Puerarin ameliorates metabolic dysfunction-associated fatty liver disease by inhibiting ferroptosis and inflammation

  • Lipids Health Dis. 2023 Nov 24;22(1):202. doi: 10.1186/s12944-023-01969-y.
Mengmeng Yang 1,  Longqing Xia 1,  Jia Song 1,  Huiqing Hu 1,  Nan Zang 1,  Jingwen Yang 1,  Ying Zou 1,  Liming Wang 1,  Xiaoyue Zheng 1,  Qin He 1 2 3 4,  Jidong Liu 1 2 3 4,  Fuqiang Liu 1 2 3 4,  Kai Liang 1 2 3 4,  Lei Sun 1 2 3 4,  Li Chen 5 6 7 8
Affiliations

Affiliations

  • 1 Department of Endocrinology, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, China.
  • 2 Institute of Endocrine and Metabolic Diseases of Shandong University, Jinan, Shandong, China.
  • 3 Key Laboratory of Endocrine and Metabolic Diseases, Shandong Province Medicine & Health, Jinan, Shandong, China.
  • 4 Jinan Clinical Research Center for Endocrine and Metabolic Disease, Jinan, Shandong, China.
  • 5 Department of Endocrinology, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, China. chenli3@email.sdu.edu.cn.
  • 6 Institute of Endocrine and Metabolic Diseases of Shandong University, Jinan, Shandong, China. chenli3@email.sdu.edu.cn.
  • 7 Key Laboratory of Endocrine and Metabolic Diseases, Shandong Province Medicine & Health, Jinan, Shandong, China. chenli3@email.sdu.edu.cn.
  • 8 Jinan Clinical Research Center for Endocrine and Metabolic Disease, Jinan, Shandong, China. chenli3@email.sdu.edu.cn.
PMID: 38001459 DOI: 10.1186/s12944-023-01969-y
Abstract

Metabolic dysfunction-associated fatty liver disease (MAFLD) is frequently linked to type 2 diabetes mellitus (T2DM), and both conditions exacerbate the progression of the other. However, there is currently no standardized treatment or drug for MAFLD. In this study, A MAFLD animal model through a high-fat diet (HFD) along with administration of streptozotocin (STZ), and palmitic acid (PA)-induced AML12 cells were treated by puerarin. The objective of this study was to assess the therapeutic effect of puerarin, a flavonoid substance that possesses various pharmacological properties, on MAFLD. The results showed that puerarin administration enhanced glucose tolerance and Insulin sensitivity, while also mitigating liver dysfunction and hyperlipidemia in MAFLD mice. Moreover, puerarin attenuated oxidative stress levels and inflammation in the liver. Transmission electron microscopy and Western blot analysis indicated that puerarin inhibited Ferroptosis in vivo. Further mechanistic investigations revealed that puerarin upregulated SIRT1 expression, increased nuclear factor erythroid 2-related factor 2 (Nrf2) protein levels, and facilitated translocation into the nucleus. The protective effect of puerarin on PA-induced AML12 cells was diminished by the utilization of EX-527 (a SIRT1 Inhibitor) and Nrf2 siRNA. Overall, the results demonstrate that puerarin ameliorates MAFLD by suppressing Ferroptosis and inflammation via the SIRT1/Nrf2 signaling pathway. The results emphasize the possible medicinal application of puerarin for managing MAFLD.

Keywords

Ferroptosis; Inflammation; Metabolic dysfunction-associated fatty Liver Disease; Nrf2; Puerarin; SIRT1.

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