Trans-Cinnamaldehyde Increases Random Pattern Flap Survival Through Activation of the Nitric Oxide Pathway

Drug Des Devel Ther. 2021 Feb 18:15:679-688. doi: 10.2147/DDDT.S297458. eCollection 2021.

Abstract

Background: The application of random pattern skin flaps is limited in plastic surgery reconstruction due to necrosis. Trans-cinnamaldehyde has antibacterial, anticancer, and antioxidant properties. In this study, we aimed to investigate the effect of trans-cinnamaldehyde on skin flap survival and its possible mechanism regarding nitric oxide.

Materials and methods: One hundred forty male Sprague-Dawley rats were randomly divided into seven groups (n = 20 each group). After the dorsal flap was raised, different doses of trans-cinnamaldehyde (10, 20, and 30 mg/kg) were immediately given by oral gavage in the three different groups. To assess the possible involvement of the nitric oxide system, NG-nitro-L-arginine methyl ester (L-NAME, a nonselective nitric oxide synthase inhibitor) was used in this study. All flap samples were incised on postoperative day 7.

Results: Our results showed that flap survival was increased significantly in the 20 mg/kg (P < 0.001) trans-cinnamaldehyde (TC) group compared to the control group or 30 mg/kg TC group. This protective function was restrained by coadministration of L-NAME with 20 mg/kg TC. The results of histopathology, laser Doppler, arteriography mediated with oxide-gelatine, and fluorescent staining all showed a significant increase in capillary count, collagen deposition, angiogenesis, and flap perfusion. Immunohistochemistry results revealed a significant increase in the expression of CD34, eNOS, and VEGF.

Conclusion: Trans-cinnamaldehyde increased flap survival through the nitric oxide synthase pathway and contributed to angiogenesis. A concentration of 20 mg/kg trans-cinnamaldehyde was recommended in this study.

Keywords: angiogenesis; flap necrosis; flap perfusion; random pattern flap; trans-cinnamaldehyde.

MeSH terms

  • Acrolein / administration & dosage
  • Acrolein / analogs & derivatives*
  • Acrolein / pharmacology
  • Administration, Oral
  • Animals
  • Dose-Response Relationship, Drug
  • Graft Survival / drug effects*
  • Molecular Structure
  • Nitric Oxide / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Stereoisomerism
  • Structure-Activity Relationship
  • Surgical Flaps*

Substances

  • Nitric Oxide
  • Acrolein
  • cinnamaldehyde