Basis with RNA-Seq and WGCNA to explore the effect of Frankincense essential oil on dextran sodium sulfate-induced ulcerative colitis through MAPK/NF-κB signaling

Fitoterapia. 2024 Jan:172:105744. doi: 10.1016/j.fitote.2023.105744. Epub 2023 Nov 10.

Abstract

Purpose: Frankincense has been shown in studies to have healing benefits for people with ulcerative colitis (UC). However, its underlying mechanisms have not been fully investigated. The objective of this study was to explore the potential molecular mechanisms of Frankincense essential oil (FREO) in improving dextran sodium sulfate (DSS)-induced UC from multiple perspectives.

Methods: The FREO components were analyzed by GC-MS, and the interactions between the key active components and the mechanism of FREO were determined based on RNA-seq, "quantity-effect" weighting coefficient network pharmacology, WGCNA and pharmacodynamic experiments. The protection of FREO against DSS-induced UC mice was assessed by behavioral and pathological changes through mice. The expression of pro-inflammatory cytokines was measured using enzyme-linked immunosorbent assay. The expression of MAPK and NF-κB-related proteins by the Western Blotting and immunohistochemistry method.

Results: Treatment with FREO significantly improved the symptoms of weight loss, diarrhea, stool blood, and colon shortening in UC mice. Reduced intestinal mucosal damage and the degree of inflammatory cell infiltration in the colon. Decreased TNF-α and IL-6 levels in mice's serum and inhibited phosphorylation of ERK, p65 in MAPK and NF-κB signaling.

Conclusion: FREO may decrease the inflammatory response to reduce the symptoms of UC by modulating the MAPK/ NF-κB pathway. This may be due to the synergistic interaction of the effective ingredient Hepten-2-yl tiglate, 6-methyl-5-, Isoneocembrene A and P-Cymene. This study provides a promising drug candidate and a new concept for the treatment of UC.

Keywords: Frankincense essential oil; MAPK; NF-κB; Transcriptome sequencing; Ulcerative colitis.

MeSH terms

  • Animals
  • Colitis* / drug therapy
  • Colitis, Ulcerative* / chemically induced
  • Colitis, Ulcerative* / drug therapy
  • Colitis, Ulcerative* / pathology
  • Colon / metabolism
  • Colon / pathology
  • Dextran Sulfate / adverse effects
  • Dextran Sulfate / metabolism
  • Dextrans / metabolism
  • Dextrans / pharmacology
  • Dextrans / therapeutic use
  • Disease Models, Animal
  • Frankincense* / metabolism
  • Frankincense* / pharmacology
  • Frankincense* / therapeutic use
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Molecular Structure
  • NF-kappa B / metabolism
  • Oils, Volatile* / pharmacology
  • RNA-Seq
  • Sulfates*

Substances

  • NF-kappa B
  • Dextrans
  • Frankincense
  • Oils, Volatile
  • sodium sulfate
  • Dextran Sulfate
  • Sulfates