Stevioside Alleviates Con A-Induced Liver Injury by Activating the AMPK/NRF2 Signaling Pathway

Area of Science:

• Pharmacology and Toxicology
• Hepatology
• Natural Product Chemistry

Background:

• Stevioside, derived from *Stevia rebaudiana*, is an FDA-approved dietary supplement with known anti-inflammatory, antioxidant, and antiapoptotic properties.
• The therapeutic potential of stevioside against concanavalin A (Con A)-induced liver injury is not well understood.
• Understanding stevioside's mechanisms in liver injury could reveal new therapeutic strategies.

Purpose of the Study:

• To investigate the protective effects of stevioside on concanavalin A (Con A)-induced liver injury in a mouse model.
• To elucidate the underlying molecular mechanisms responsible for stevioside's hepatoprotective actions.
• To identify potential molecular targets of stevioside in the context of liver injury.

Main Methods:

• A concanavalin A (Con A)-induced mouse liver injury model was employed.
• Liver damage was assessed using serum biochemistry and histopathology.
• Hepatic transcriptomics, molecular docking, CETSA, and DARTS assays were used to identify key pathways and targets.
• In vitro studies on RAW264.7 cells and in vivo genetic/pharmacological inhibition of key pathways were conducted.

Main Results:

• Stevioside treatment dose-dependently reduced serum hepatic injury markers and ameliorated histopathological liver damage.
• Stevioside attenuated Con A-induced hepatitis and hepatocyte apoptosis, alleviating oxidative stress.
• Transcriptomic analysis indicated enrichment in oxidoreductase activity pathways.
• Molecular docking, CETSA, and DARTS assays identified AMPK as a critical target.
• Stevioside activated the AMPK/NRF2 signaling pathway, confirmed by in vitro and in vivo experiments.

Conclusions:

• Stevioside exhibits significant hepatoprotective effects against Con A-induced liver injury.
• The mechanism involves the activation of the AMPK/NRF2 signaling pathway via direct interaction with AMPK.
• Stevioside demonstrates potential as a therapeutic agent for preventing and treating liver diseases.
• This research provides a foundation for novel liver injury treatments utilizing stevioside.