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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.
Abstract:
Ganoderma lucidum is an edible and medicinal fungus. Triterpenoids, particularly ganoderic acids, represent the principal bioactive constituents in Ganoderma lucidum. Bacteria-enzyme synergistic fermentation broth of Ganoderma lucidum (FBG) was optimized as a potential alternative to traditional water-extracted Ganoderma lucidum (WEG). The optimized parameters with Lactobacillus rhamnosus fermentation exhibited the highest content of ganoderic acid F (GAF). Administration of FBG led to a pronounced decline in lipid deposition and contents of intracellular total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), reactive oxygen species (ROS), and malonic dialdehyde (MDA). The FBG treatment also markedly increased the activities of high-density lipoprotein cholesterol (HDL-C), superoxide dismutase (SOD), and catalase (CAT). The results of network pharmacology analysis and molecular docking suggested that GAF exhibits a robust interaction with the core targets sodium leak channel, nonselective (NALCN) and eukaryotic translation elongation factor 1 alpha 2 (EEF1A2). Enzyme-linked immunosorbent assay (ELISA) results demonstrated that GAF could effectively reduce lipid accumulation while upregulating EEF1A2, phosphorylated AMP-activated protein kinase (p-AMPK), and peroxisome proliferator-activated receptor alpha (PPAR-α) protein expression. Collectively, these findings indicate that GAF alleviates free fatty acid (FFA)-induced hepatic lipid accumulation through activation of the EEF1A2/p-AMPK/PPAR-α signaling pathway, suggesting a potential mechanism involving AMPK-related pathways.
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.