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Ganoapplanilactone C from Ganoderma applanatum Ameliorates Metabolic Dysfunction-Associated Steatotic Liver Disease via AMPK/mTOR-Mediated Lipid Regulation in Zebrafish

Summary

Researchers found that a compound called ganoapplanilactone C from the medicinal mushroom Ganoderma applanatum can protect the liver from fat accumulation and damage caused by high-fat diets. In zebrafish studies, this compound worked better than a common cholesterol drug at reducing liver fat and improving liver health. The compound appears to work by activating a protein called AMPK that helps regulate how the body processes fats and reduces inflammation.

Background

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent liver disease globally, characterized by fat accumulation in the liver. Ganoderma applanatum, a medicinal mushroom used in traditional Chinese medicine, contains bioactive triterpenoids with potential therapeutic properties. This study investigates ganoapplanilactone C (GATC), a unique triterpenoid with a C-23 spiro 5/7 system, for its efficacy against MASLD.

Objective

To isolate and characterize bioactive compounds from Ganoderma applanatum and evaluate ganoapplanilactone C’s potential to ameliorate metabolic dysfunction-associated steatotic liver disease through lipid regulation and AMPK/mTOR pathway activation in a zebrafish model.

Results

GATC demonstrated superior lipid-reducing effects compared to atorvastatin at 5 μM concentration in zebrafish. Histopathological analysis confirmed GATC’s protective effects on liver tissue. GATC activated the AMPK/mTOR pathway, increased antioxidant enzyme levels, reduced inflammatory cytokines, and modulated metabolites involved in lipid and amino acid metabolism.

Conclusion

GATC emerges as a promising therapeutic agent for MASLD through activation of the AMPK/mTOR signaling pathway and regulation of lipid metabolism. The compound’s unique C-23 spiro 5/7 system and hydroxyl group are critical for its efficacy, suggesting G. applanatum-derived compounds have significant potential for prevention and treatment of metabolic liver disease.
  • Published in:Antioxidants (Basel),
  • Study Type:Experimental Study,
  • Source: PMID: 40563272, DOI: 10.3390/antiox14060637
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