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Targeting the AMP-activated protein kinase pathway: the active metabolites of botanical drugs represent potential strategies for treating metabolic-associated fatty liver disease

Summary

Fatty liver disease is becoming increasingly common and current medications have side effects like dangerously low blood sugar. This review shows that natural plant-based compounds and traditional Chinese herbs can activate a key protein (AMPK) in the body that helps burn fat and regulate sugar levels. Over 30 different plant compounds from foods and herbs like ginger, curcumin, and ganoderma mushrooms have been shown to improve fatty liver disease by activating this protein through multiple beneficial mechanisms.

Background

Metabolic-associated fatty liver disease (MAFLD) is a chronic liver condition marked by fat accumulation, inflammation, and fibrosis, driven by metabolic disorders. MAFLD is the most prevalent chronic liver disease globally with a prevalence of 25% and rising, closely linked to obesity, type 2 diabetes, and cardiovascular diseases. Current antidiabetic drugs used for MAFLD management have significant side effects including hypoglycemia.

Objective

This review analyzes and summarizes how botanical drugs and their active metabolites activate AMP-activated protein kinase (AMPK) to improve glucose and lipid metabolism disorders and mitochondrial homeostasis in MAFLD treatment. The aim is to provide a broader perspective for the development of botanical drugs as therapeutic strategies for MAFLD.

Results

The review identified numerous botanical drugs and metabolites that activate AMPK including herbal formulas (QGJZF, Ganoderma lucidum, Wulingsan), and monomeric metabolites from flavonoids, phenols, terpenoids, and other compounds. These compounds improve glucose and lipid metabolism, reduce oxidative stress, suppress inflammation, and regulate mitochondrial dysfunction through AMPK activation and related signaling pathways.

Conclusion

AMPK-based targeted therapy is a feasible approach for MAFLD treatment, with botanical drugs and their active metabolites showing promising prospects due to high safety and low toxicity. Future research should involve multi-omics analysis, metabolite identification, clinical validation, and pre-clinical toxicology studies to support clinical translation of these botanical drug therapies.
  • Published in:Frontiers in Pharmacology,
  • Study Type:Literature Review,
  • Source: PMID: 41573724
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