Therapeutic effect of ginkgetin on smoke-induced airway inflammation by down-regulating the c/EBPβ signaling pathway and CCL2 expression

J Ethnopharmacol. 2024 Sep 15:331:118284. doi: 10.1016/j.jep.2024.118284. Epub 2024 May 10.

Abstract

Ethnopharmacological relevance: Ginkgo biloba leaf and seed have been traditionally used in ancient China for the treatment of cough and asthma. However, there is limited literature available on the anti-COPD effects and mechanisms of Ginkgo biloba.

Aims of the study: The aim of this study was to comprehensively investigate the therapeutic potential of ginkgo extracts in COPD through a combination of in vivo and in vitro functional experiments. Transcriptomic analyses were also employed to uncover novel molecular mechanisms underlying the therapeutic effects of ginkgetin in COPD.

Materials and methods: The therapeutic efficacy of ginkgo extracts was assessed in a COPD model. The anti-inflammatory effects of ginkgetin and its underlying molecular mechanisms were examined in A549 cells treated with cigarette smoke extract (CSE). Additionally, transcriptomic analyses were conducted to identify novel molecular pathways influenced by ginkgetin. These findings were further validated using quantitative real-time polymerase chain reaction (qPCR) and Western blot techniques.

Results: The ethyl acetate extract of Ginkgo biloba L. seeds and ginkgetin treatment significantly reduced cytokine production in COPD mice. Following drug administration, lung function improved in different groups. The transcriptome data strongly supports the inhibitory effect of ginkgetin on CSE-induced inflammation through the downregulation of the c/EBPβ signaling pathway and subsequent inhibition of CCL2 expression.

Conclusion: Our results demonstrate that ginkgetin, one of the biflavones found in Ginkgo biloba, exhibits inhibitory effects on smoke-induced airway inflammation. This effect is achieved through the downregulation of the c/EBPβ signaling pathway and the reduction of CCL2 expression.

Keywords: COPD; Ginkgetin; Ginkgo biloba; Transcriptomics; c/EBPβ.

MeSH terms

  • A549 Cells
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Biflavonoids* / pharmacology
  • Biflavonoids* / therapeutic use
  • Chemokine CCL2* / genetics
  • Chemokine CCL2* / metabolism
  • Disease Models, Animal
  • Down-Regulation* / drug effects
  • Ginkgo Extract
  • Ginkgo biloba* / chemistry
  • Humans
  • Lung / drug effects
  • Lung / metabolism
  • Lung / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use
  • Pulmonary Disease, Chronic Obstructive* / drug therapy
  • Signal Transduction* / drug effects
  • Smoke / adverse effects

Substances

  • Biflavonoids
  • Chemokine CCL2
  • ginkgetin
  • Plant Extracts
  • Smoke
  • Anti-Inflammatory Agents
  • Ccl2 protein, mouse
  • Ginkgo biloba extract
  • Ginkgo Extract