New Application of Psoralen and Angelicin on Periodontitis With Anti-bacterial, Anti-inflammatory, and Osteogenesis Effects

Front Cell Infect Microbiol. 2018 Jun 5:8:178. doi: 10.3389/fcimb.2018.00178. eCollection 2018.

Abstract

Psoralen and angelicin are two effective compounds isolated from psoraleae, a traditional Chinese medicine. They have a wide range of applications for bone disease treatment and immune modulation. In this study, we explored their new applications for the treatment of periodontal diseases. This study aimed to investigate the effects of psoralen and angelicin on Porphyromonas gingivalis growth and P. gingivalis-derived lipopolysaccharide (Pg-LPS)-induced inflammation, and further to evaluate their effects on osteogenesis. Finally, the effects of angelicin on a mouse model of periodontitis were also investigated. The results showed that psoralen and angelicin had beneficial dose-dependent effects regarding the inhibition of planktonic P. gingivalis and biofilms of P. gingivalis. There were no significant differences in the viability of monocyte-like THP-1 cells and human periodontal ligament cells (hPDLCs) treated with either psoralen or angelicin compared to the untreated control cells. Psoralen and angelicin also markedly decreased the mRNA expression and release of inflammatory cytokines (interleukin [IL]-1β and IL-8) by THP-1 cells in a dose-dependent manner. They significantly enhanced the alkaline phosphatase (ALP) activity of hPDLCs and up-regulated the expression of osteogenic proteins (runt-related transcription factor 2 [RUNX2], distal-less homeobox 5 [DLX5], and osteopontin [OPN]). Angelicin significantly attenuated alveolar bone loss and inflammation response in the mice with periodontitis. In conclusion, our data demonstrated that psoralen and angelicin could inhibit the growth of planktonic P. gingivalis and P. gingivalis biofilm. It is also the first report on the anti-inflammatory effect of psoralen and angelicin against Pg-LPS. They also had an osteogenesis-potentiating effect on hPDLCs. The in vivo study also indicated the effect of angelicin regarding protection against periodontitis. Our study highlighted the potential ability of psoralen and angelicin to act as novel natural agents to prevent and treat periodontitis.

Keywords: angelicin; anti-bacteria; anti-inflammation; osteogenesis; psoralen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaline Phosphatase / metabolism
  • Alveolar Bone Loss / diagnostic imaging
  • Alveolar Bone Loss / pathology
  • Alveolar Bone Loss / prevention & control
  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Anti-Inflammatory Agents / pharmacology*
  • Biofilms / drug effects
  • Bone Morphogenetic Proteins / drug effects
  • Bone Morphogenetic Proteins / genetics
  • Cell Survival / drug effects
  • Core Binding Factor Alpha 1 Subunit / metabolism
  • Cytokines / metabolism
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Combinations
  • Ficusin / chemistry
  • Ficusin / pharmacology*
  • Furocoumarins / chemistry
  • Furocoumarins / pharmacology*
  • Gene Expression / drug effects
  • Homeodomain Proteins / metabolism
  • Humans
  • Inflammation
  • Interleukin-1beta / metabolism
  • Interleukin-8 / metabolism
  • Lipopolysaccharides / adverse effects
  • Male
  • Medicine, Chinese Traditional
  • Mice
  • Mice, Inbred C57BL
  • Microbial Sensitivity Tests
  • Osteogenesis / drug effects*
  • Osteopontin / metabolism
  • Periodontal Diseases / drug therapy
  • Periodontal Ligament
  • Periodontitis / diagnostic imaging
  • Periodontitis / drug therapy*
  • Periodontitis / pathology
  • Periodontitis / prevention & control*
  • Porphyromonas gingivalis / drug effects
  • Porphyromonas gingivalis / growth & development
  • RNA, Messenger / metabolism
  • THP-1 Cells
  • Transcription Factors / metabolism
  • Up-Regulation

Substances

  • Anti-Bacterial Agents
  • Anti-Inflammatory Agents
  • Bone Morphogenetic Proteins
  • Core Binding Factor Alpha 1 Subunit
  • Cytokines
  • DLX5 protein, human
  • Drug Combinations
  • Furocoumarins
  • Homeodomain Proteins
  • Interleukin-1beta
  • Interleukin-8
  • Lipopolysaccharides
  • RNA, Messenger
  • RUNX2 protein, human
  • SPP1 protein, human
  • Transcription Factors
  • Osteopontin
  • angelicin
  • Alkaline Phosphatase
  • Ficusin