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Amelioration of melittin on adjuvant-induced rheumatoid arthritis: Integrated transcriptome and metabolome

Linfu Yang1, Xiying He2, Yunfei Xue1

  • 1Yunnan Provincial Engineering and Research Center for Sustainable Utilization of Honey Bee Resources, Eastern Bee Research Institute, College of Animal Science and Technology, Yunnan Agricultural University, Kunming 650201, China.

International Journal of Biological Macromolecules
|May 12, 2024
PubMed
Abstract

Insights

Melittin (MLT) effectively alleviates rheumatoid arthritis (RA) symptoms in rats by reducing joint inflammation and damage. This study details MLT

Area of Science:

  • Immunology
  • Pharmacology
  • Genomics

Background:

  • Rheumatoid arthritis (RA) is a chronic autoimmune disease with limited curative treatments.
  • Conventional RA therapies like dexamethasone and methotrexate have potential adverse effects.
  • Melittin (MLT) shows promise as a natural anti-rheumatic agent, but its molecular mechanisms in RA require further investigation.

Purpose of the Study:

  • To investigate the therapeutic efficacy of Melittin (MLT) in a rat model of rheumatoid arthritis (RA).
  • To elucidate the molecular mechanisms underlying MLT's anti-RA effects through transcriptomic and metabolomic analyses.
  • To validate the modulation of key RA-related genes and assess MLT's binding interactions with inflammatory mediators.

Main Methods:

  • Rheumatoid arthritis was induced in rats using Complete Freund's Adjuvant (CFA) and treated with MLT.
  • Transcriptomic and metabolomic analyses were performed to identify MLT-modulated pathways and biomarkers.
  • Quantitative real-time PCR (qRT-PCR) and molecular docking simulations (AutoDock Vina) were used for validation and interaction studies.

Main Results:

  • MLT treatment significantly reduced joint redness, swelling, inflammatory cell infiltration, and joint damage.
  • Transcriptomic and metabolomic data indicated MLT's regulation of cytokine/immune response pathways and biomarkers like Sphingomyelin, fatty acids, and flavonoids.
  • qRT-PCR confirmed MLT's downregulation of key inflammation genes (Il6, Jak2, Stat3, Ptx3), and molecular docking showed stable MLT binding to TNF-α and IL-1β.

Conclusions:

  • Melittin (MLT) demonstrates significant therapeutic efficacy in alleviating rheumatoid arthritis (RA).
  • This study provides comprehensive insights into MLT's impact on gene expression and metabolic profiles in RA.
  • MLT represents a potential natural therapeutic agent for managing rheumatoid arthritis.
Keywords:
MelittinMetabolomeMolecular dockingRheumatoid arthritisTranscriptome

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