Moringa oleifera Improves MAFLD by Inducing Epigenetic Modifications

Area of Science:

• Hepatology and metabolic disease research.
• Molecular biology and gene expression analysis.
• Natural product pharmacology.

Background:

• Metabolic Associated Fatty Liver Disease (MAFLD) ranges from simple steatosis to NASH.
• Investigating natural compounds for MAFLD/NASH is crucial.
• Moringa oleifera is a potential therapeutic agent.

Purpose of the Study:

• To evaluate the hepatoprotective effects of Moringa oleifera aqueous extract in a mouse model of NASH.
• To analyze the impact of Moringa on hepatic miRNAs, gene and protein expression.
• To assess histological and biochemical changes in NASH-induced mice treated with Moringa.

Main Methods:

• High-fat diet (HFD) induced NASH in C57BL/6J mice for 16 weeks.
• Moringa extract administered orally during the final 8 weeks of HFD.
• Evaluated insulin tolerance, HOMA-IR, serum markers, hepatic miRNA and protein expression (SIRT1, AMPKα, SREBP1c), and liver histology (H&E, Masson's trichrome, Sirius red).
• Hepatic transcriptome analysis using microarrays.

Main Results:

• Moringa treatment improved insulin tolerance and HOMA-IR, decreased SREBP1c, and increased SIRT1.
• Downregulation of miR-21a-5p, miR-103-3p, miR-122-5p, and miR-34a-5p observed.
• Significant reduction in hepatic inflammation, macrosteatosis, fibrosis, collagen deposition, and αSMA reactivity.
• Transcriptome analysis revealed downregulation of genes involved in DNA damage response, ER stress, lipid biosynthesis, and insulin resistance.

Conclusions:

• Moringa oleifera extract demonstrated significant hepatoprotective effects against NASH progression.
• The extract ameliorated key pathological features of NASH, including steatosis, inflammation, and fibrosis.
• Moringa modulated molecular pathways related to insulin resistance, lipogenesis, and ER stress, suggesting therapeutic potential for MAFLD/NASH.