The Potential Alleviating Property Against NAFLD by Ganoderma lucidum With Bacteria-Enzyme Synergistic Fermentation

Manhui Sun1,2, Kecheng Li1,2, Zhenzhen Wang1,2

  • 1School of Biological and Chemical Engineering, Zhejiang University of Science and Technology Hangzhou China.

Insights

Ganoderma lucidum fermentation broth (FBG) effectively reduces lipid accumulation and improves antioxidant status. Ganoderic acid F (GAF) from FBG alleviates hepatic lipid buildup by activating the EEF1A2/p-AMPK/PPAR-α pathway.

Area of Science:

  • Mycology
  • Biochemistry
  • Pharmacology

Background:

  • Ganoderma lucidum is a medicinal mushroom known for its bioactive triterpenoids, especially ganoderic acids.
  • Traditional water extraction may not be optimal for isolating these compounds.
  • Fermentation offers a promising alternative for enhancing bioactive compound extraction.

Purpose of the Study:

  • To optimize a bacteria-enzyme synergistic fermentation broth of Ganoderma lucidum (FBG).
  • To investigate the effects of FBG and its key component, ganoderic acid F (GAF), on lipid metabolism and oxidative stress.
  • To elucidate the molecular mechanism underlying GAF's action in hepatic lipid accumulation.

Main Methods:

  • Optimized Ganoderma lucidum fermentation using Lactobacillus rhamnosus.
  • Administered FBG to assess its impact on lipid profiles, oxidative stress markers, and antioxidant enzyme activities.
  • Employed network pharmacology and molecular docking to identify GAF's molecular targets.
  • Utilized ELISA to validate GAF's effects on key proteins in lipid metabolism signaling pathways.

Main Results:

  • Optimized FBG fermentation with Lactobacillus rhamnosus yielded high levels of ganoderic acid F (GAF).
  • FBG administration significantly reduced lipid deposition, total cholesterol, triglycerides, LDL-C, ROS, and MDA.
  • FBG treatment increased HDL-C, SOD, and CAT activities.
  • GAF demonstrated strong interactions with NALCN and EEF1A2 targets.
  • GAF reduced lipid accumulation and upregulated EEF1A2, p-AMPK, and PPAR-α protein expression in vitro.

Conclusions:

  • Optimized FBG is a potent alternative for Ganoderma lucidum extraction, rich in GAF.
  • GAF effectively alleviates hepatic lipid accumulation and oxidative stress.
  • GAF exerts its beneficial effects by activating the EEF1A2/p-AMPK/PPAR-α signaling pathway, highlighting its therapeutic potential for metabolic disorders.