Anti-inflammatory and wound healing activities of calophyllolide isolated from Calophyllum inophyllum Linn

PLoS One. 2017 Oct 11;12(10):e0185674. doi: 10.1371/journal.pone.0185674. eCollection 2017.


Due to the high-cost and limitations of current wound healing treatments, the search for alternative approaches or drugs, particularly from medicinal plants, is of key importance. In this study, we report anti-inflammatory and wound healing activities of the major calophyllolide (CP) compound isolated from Calophyllum inophyllum Linn. The results showed that CP had no effect on HaCaT cell viability over a range of concentrations. CP reduced fibrosis formation and effectively promoted wound closure in mouse model without causing body weight loss. The underlying molecular mechanisms of wound repair by CP was investigated. CP markedly reduced MPO activity, and increased M2 macrophage skewing, as shown by up-regulation of M2-related gene expression, which is beneficial to the wound healing process. CP treatment prevented a prolonged inflammatory process by down-regulation of the pro-inflammatory cytokines-IL-1β, IL-6, TNF-α, but up-regulation of the anti-inflammatory cytokine, IL-10. This study is the first to indicate a plausible role for CP in accelerating the process of wound healing through anti-inflammatory activity mechanisms, namely, by regulation of inflammatory cytokines, reduction in MPO, and switching of macrophages to an M2 phenotype. These findings may enable the utilization of CP as a potent therapeutic for cutaneous wound healing.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Biomarkers / metabolism
  • Calophyllum / chemistry*
  • Cell Survival / drug effects
  • Coumarins / isolation & purification*
  • Coumarins / pharmacology*
  • Cytokines / metabolism
  • Gene Expression Regulation / drug effects
  • Humans
  • Inflammation Mediators / metabolism
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Male
  • Mice
  • Peroxidase / metabolism
  • RAW 264.7 Cells
  • Seeds / chemistry
  • Skin / drug effects
  • Skin / pathology
  • Sodium Dodecyl Sulfate
  • Spleen / drug effects
  • Spleen / pathology
  • Wound Healing / drug effects*


  • Anti-Inflammatory Agents
  • Biomarkers
  • Coumarins
  • Cytokines
  • Inflammation Mediators
  • Sodium Dodecyl Sulfate
  • calophyllolid
  • Peroxidase

Grant support

This research was supported by a grant from Soc Trang Department of Science and Development, Viet Nam (21/HĐ/SKHCN-QLKHCN). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.