Isobavachin, a main bioavailable compound in Psoralea corylifolia, alleviates lipopolysaccharide-induced inflammatory responses in macrophages and zebrafish by suppressing the MAPK and NF-κB signaling pathways

J Ethnopharmacol. 2024 Mar 1:321:117501. doi: 10.1016/j.jep.2023.117501. Epub 2023 Nov 25.

Abstract

Ethnopharmacological relevance: Psoralea corylifolia L. (PC) is widely used in traditional medicines to treat inflammatory and infectious diseases. Isobavachin (IBC) is a bioavailable prenylated flavonoid derived from PC that has various biological properties. However, little information is available on its anti-inflammatory effects and mechanisms of action.

Aim of the study: In this study, we aimed to determine the anti-inflammatory effects of IBC in vitro and in vivo by conducting a mechanistic study using murine macrophages.

Materials and methods: We evaluated the modulatory effects of IBC on the production of pro-inflammatory cytokines and mediators in murine macrophages. In addition, we examined whether IBC inhibits lipopolysaccharide (LPS)-induced inflammatory responses in a zebrafish model. Alterations in inflammatory response-associated genes and proteins were determined using quantitative reverse transcriptional polymerase chain reaction (RT-qPCR) and Western blotting analysis.

Results: IBC markedly reduced the overproduction of inflammatory mediators, pro-inflammatory cytokines, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), phosphorylation of mitogen-activated protein kinase (MAPK) and nuclear translocation of nuclear factor-kappa B (NF-κB) in macrophages induced by lipopolysaccharides (LPS). In addition, excessive NO, ROS, and neutrophil level induced by LPS, were suppressed by IBC treatment in a zebrafish inflammation model.

Conclusions: Collectively, bioavailable IBC inhibited on the inflammatory responses by LPS via MAPK and NF-κB signaling pathways in vitro and in vivo, suggesting that it may be a potential modulatory agent against inflammatory disorders.

Keywords: Anti-inflammatory agents; Isobavachin; Macrophages; Psoralea corylifolia; Zebrafish.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / metabolism
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Cytokines / metabolism
  • Flavonoids / pharmacology
  • Lipopolysaccharides / pharmacology
  • Macrophages
  • Mice
  • Mitogen-Activated Protein Kinases* / metabolism
  • NF-kappa B / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • Psoralea* / metabolism
  • Signal Transduction
  • Zebrafish

Substances

  • Mitogen-Activated Protein Kinases
  • NF-kappa B
  • Lipopolysaccharides
  • isobavachin
  • Flavonoids
  • Cytokines
  • Anti-Inflammatory Agents
  • Nitric Oxide Synthase Type II
  • Cyclooxygenase 2