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Melissa officinalis Regulates Lipopolysaccharide-Induced BV2 Microglial Activation via MAPK and Nrf2 Signaling

J Microbiol Biotechnol. 2024 Dec 28;34(12):2474-2483. doi: 10.4014/jmb.2409.09020. Epub 2024 Oct 29.

Abstract

Neuroinflammation and microglial activation play critical roles in neurodegenerative diseases such as Alzheimer's and Parkinson's disease. Modulating microglial activation may help prevent the progression of these disorders. This study aimed to investigate the effects and mechanisms of Melissa officinalis ethanol extract on lipopolysaccharide (LPS)-induced microglial activation in BV2 cells. Cell viability and nitric oxide (NO) production were assessed using MTT assay and Griess reagent, while inflammatory cytokine levels were measured by qPCR. Key inflammatory pathways, including MAPK, TLR4, and antioxidant biomarkers, were analyzed through western blot and immunofluorescence. Rosmarinic acid content in M. officinalis was determined using high-performance liquid chromatography (HPLC). The results demonstrated that M. officinalis ethanol extract significantly inhibited LPS-induced NO production and reduced inflammatory cytokine expression. Additionally, it downregulated inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TLR4, NF-κB, and MAPK signaling pathways (p38, JNK, ERK), while increasing the expression of antioxidant markers, including Nrf2, HO-1, catalase, and SOD2. In conclusion, M. officinalis ethanol extract exerts neuroprotective effects by modulating inflammation and enhancing antioxidant defenses, suggesting its potential in the prevention and treatment of inflammation-related neurodegenerative diseases.

Keywords: BV2 microglia; Melissa officinalis; Nrf2; TLR4; neurodegenerative disease; neuroinflammation.

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Cell Line
  • Cell Survival* / drug effects
  • Cinnamates / pharmacology
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Cytokines* / metabolism
  • Depsides / pharmacology
  • Lipopolysaccharides*
  • MAP Kinase Signaling System / drug effects
  • Melissa* / chemistry
  • Mice
  • Microglia* / drug effects
  • Microglia* / metabolism
  • NF-E2-Related Factor 2* / metabolism
  • NF-kappa B / metabolism
  • Neuroprotective Agents / pharmacology
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism
  • Nitric Oxide* / metabolism
  • Plant Extracts* / pharmacology
  • Rosmarinic Acid
  • Signal Transduction / drug effects
  • Toll-Like Receptor 4* / metabolism

Substances

  • NF-E2-Related Factor 2
  • Lipopolysaccharides
  • Plant Extracts
  • Nitric Oxide
  • Nfe2l2 protein, mouse
  • Toll-Like Receptor 4
  • Cytokines
  • Nitric Oxide Synthase Type II
  • Rosmarinic Acid
  • Antioxidants
  • NF-kappa B
  • Depsides
  • Cinnamates
  • Neuroprotective Agents
  • Cyclooxygenase 2