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

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.