Abstract

Background:
Delayed wound healing is a significant complication of diabetes mellitus (DM). In Indonesia, Peperomia pellucida leaves exhibit anti-inflammatory activity due to their phenolic and flavonoid compounds.

Aim:
This study aimed to evaluate the efficacy of Peperomia pellucida Leaf Ethanol Extract (PPLEE) Ointment for healing acute wounds through modulation of angiogenesis, neovascularization, and epithelialization in an acute streptozotocin-Nicotinamide (STZ-NA) induced diabetic rat.

Methods:
A total of 30 rats were randomized into 5 groups. The groups were divided into : Normal (N), Negative Control (C-), Positive Control (C+), Treatment 1, DM rats with 12% ointment (T1), and Treatment 2, DM rats with 16% ointment (T2). Groups C-, C+, T1, and T2 received STZ-NA injections for 5 days. Five groups underwent excision wounds on the backs of rats. All groups received wound care according to the procedure for 15 days. Rats were sacrificed, and tissue was collected for ELISA (TNF-α, IL-6, TGF-β, MDA, and VEGF), while neovascularization and epithelialization were assessed histopathologically.

Results:
The study clearly showed that topical application of PPLEE at a 16% dose can reduce inflammation, as indicated by markers TNF-α, IL-6, TGF-β, and MDA (p value < 0.001). The angiogenesis process was better characterized by VEGF (p-value < 0.001), by mature neovascularization tissue (p-value < 0.001), and by epithelialization tissue in the intervention group, which showed almost complete epithelialization (p-value < 0.001). The wound closure fraction showed that the T2 group showed nearly the same wound closure as the N group (p value

Key words: Angiogenesis; Epithelialization; Neovascularization; Peperomia pellucida leaf extract ointment; Diabetic wound.