Background: Papaya (Carica papaya Linn) is a tropical fruit plant known for its medicinal benefits, including wound healing. Objective: This study aimed to analyze and compare the potential of papaya leaf, fruit, and seed extracts in accelerating incision wound healing in male Wistar rats. Additionally, we compared the flavonoid content and stability of the extracts in cream formulations. Materials and Methods: Creams containing 30% ethanol extracts of papaya leaf, fruit, and seeds were prepared and applied to the backs of male Wistar rats for two weeks. The wound diameter, epithelial thickness, fibroblast count, macrophage count, collagen density, and VEGF expression were measured after two weeks. Results: Our findings revealed no significant differences between the effects of the papaya leaf, fruit, and seed ethanol extracts on wound diameter, epithelial thickness, fibroblast count, macrophage count, and collagen density (p > 0.05). There were also no significant differences when compared to the negative control group (p > 0.05). The highest flavonoid content was found in the ethanol extract of papaya leaves. Application of the ethanol extract creams of leaf, fruit, and seeds had a significant effect on angiogenesis, as evidenced by VEGF expression (p = 0.002). Conclusion: Papaya leaf, fruit, and seed extracts are promising products for wound healing. Further research is recommended to conduct periodic histopathological examinations during the wound healing process and to explore different extract concentrations for optimal results.
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