Effect of ethanolic propolis extract on TNF-α, caspase-3 expression and histopathological findings in hypoxic skin flaps: an experimental study in rats

Authors

  • Kevin Piether Department of General Surgery, Sebelas Maret University, Surakarta, Central of Java, Indonesia
  • Amru Sungkar Department of Plastic Surgery, Sebelas Maret University, Surakarta, Central of Java, Indonesia https://orcid.org/0009-0009-7963-0745
  • Kristanto Y. Yarsa Department of Oncology Surgery, Sebelas Maret University, Surakarta, Central of Java, Indonesia
  • Brian Wasita Department of Anatomic Pathology, Sebelas Maret University, Surakarta, Central of Java, Indonesia

DOI:

https://doi.org/10.18203/2349-2902.isj20262447

Keywords:

Propolis, Skin flap, Hypoxia, TNF-α, Caspase-3, Apoptosis

Abstract

Background: Hypoxia remains a major cause of skin flap failure due to excessive production of reactive oxygen species (ROS), which triggers inflammation and apoptosis through increased expression of tumor necrosis factor-alpha (TNF-α) and caspase-3. Propolis contains bioactive compounds with antioxidant and anti-inflammatory properties that may improve skin flap survival under hypoxic conditions. This study aimed to evaluate the effect of ethanolic propolis extract on TNF-α expression, caspase-3 expression, and histopathological changes in a hypoxic skin flap model.

Methods: An experimental post-test only control group study was conducted using 24 male Rattus norvegicus divided into four groups (n=6/group): control, P1, P2, and P3. Different flap dimensions (1/3, 1/2, and 2/3) were used to induce varying degrees of hypoxia. Ethanolic extract of Gunung Lawu propolis was administered orally at a dose of 800 mg/kg bw/day for seven days. TNF-α and caspase-3 levels were measured using enzyme-linked immunosorbent assay (ELISA). Histopathological evaluation included necrosis, acute inflammation, and re-epithelialization. Statistical analysis was performed using one-way ANOVA followed by post hoc tests and Kruskal–Wallis analysis.

Results: Propolis administration significantly reduced TNF-α levels in all treatment groups compared with controls (p<0.001), with the greatest reduction observed in the P3 group (55.5%). Caspase-3 expression was also significantly decreased (p<0.001), with the highest reduction found in the P3 group (79.5%). Histopathological assessment demonstrated lower necrosis and acute inflammation scores and higher re-epithelialization scores in treatment groups; however, these differences were not statistically significant (p>0.05).

Conclusions: Ethanolic propolis extract effectively attenuated inflammatory and apoptotic responses in hypoxic skin flaps by reducing TNF-α and caspase-3 expression. Although histopathological improvements were observed, they did not reach statistical significance. Propolis may serve as a promising adjunctive therapy to enhance skin flap viability.

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Published

2026-07-28

How to Cite

Piether, K., Sungkar, A., Yarsa, K. Y., & Wasita, B. (2026). Effect of ethanolic propolis extract on TNF-α, caspase-3 expression and histopathological findings in hypoxic skin flaps: an experimental study in rats . International Surgery Journal, 13(8), 1302–1309. https://doi.org/10.18203/2349-2902.isj20262447

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Original Research Articles