Related Experiment Video

Updated: Jun 23, 2026

Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis
08:55

Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis

Published on: August 7, 2018

Diosgenin inhibits necroptosis to alleviate NAFLD by blocking the RIPK1/RIPK3/MLKL pathway

Muxi Qi1, Guoliang Yin1, Shujun Wang1

  • 1First College of Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, PR China.

The Journal of Nutritional Biochemistry
|June 20, 2026
PubMed

Insights

Diosgenin effectively treats non-alcoholic fatty liver disease (NAFLD) by inhibiting RIPK1-dependent necroptosis. This natural compound reduces liver damage and lipid accumulation, offering a promising therapeutic avenue for NAFLD patients.

Area of Science:

  • Hepatology
  • Cell Biology
  • Pharmacology

Background:

  • Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver condition globally.
  • Necroptosis, a programmed cell death pathway involving RIPK1, RIPK3, and MLKL, plays a role in liver injury.
  • Diosgenin (DG), a steroidal saponin, has known lipid-lowering and anti-inflammatory effects, but its mechanism in NAFLD is unclear.

Purpose of the Study:

  • To investigate the therapeutic effects and underlying mechanisms of diosgenin (DG) in a rat model of non-alcoholic fatty liver disease (NAFLD).
  • To determine if DG modulates necroptosis signaling in NAFLD pathogenesis.
  • To elucidate the role of Receptor-interacting protein kinase-1 (RIPK1) in DG's protective effects against NAFLD.

Main Methods:

  • Established a high-fat diet (HFD)-induced NAFLD rat model and treated with diosgenin (DG).
  • Utilized free fatty acid (FFA)-induced HepG2 cells to assess DG's effects on necroptosis.
  • Manipulated RIPK1 expression (inhibition and overexpression) in vitro to confirm its role in DG's mechanism.
  • Investigated the involvement of Tumor necrosis factor-α (TNF-α) signaling pathway.

Main Results:

  • Diosgenin administration mitigated hepatic damage and lipid deposition in HFD-induced NAFLD rats.
  • DG significantly downregulated TNF-α, TNFR1, and TRADD, inhibiting upstream necroptosis signaling.
  • DG suppressed necroptosis by reducing RIPK1, RIPK3, and MLKL phosphorylation in vivo and in vitro.
  • Inhibition of RIPK1 enhanced DG's protective effects, while RIPK1 overexpression partially reversed them.

Conclusions:

  • Diosgenin exerts a protective effect against NAFLD by targeting the RIPK1-dependent necroptosis pathway.
  • DG ameliorates liver injury and lipid accumulation through modulation of key necroptosis signaling molecules.
  • This study provides a theoretical basis for utilizing natural compounds like DG in NAFLD management.
Keywords:
DiosgeninLipid accumulationNAFLDNatural productNecroptosisTNF-RIPK1/3 pathway

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