Acute dermal toxicity and wound healing effects of Salvia palaestina Benth. in vivo: Targeting inflammation, oxidative stress, and apoptosis.

The study investigates acute dermal toxicity and wound healing effects of a traditional medicinal herb, Salvia palaestina Benth leaf extracts (SPLE), in the excisional wound model. Thirty-six SD rats for acute dermal toxicity were aligned into three cages (n = 12), and for the wound experiment, thirty rats were wounded on their dorsal necks and aligned randomly into five groups (n = 6), treated with saline (untreated), 10% Tween 20 (blank), intrasite gel (reference), 2.5% SPLE, or 5% SPLE for 15 days. The results demonstrated the non-toxic effects of topical SPLE application, while also accelerating wound contraction and reducing the inflammatory process. After 15 days of application, SPLE (2.5% and 5%) enhanced wound closure by 80.28% and 85.91%, respectively, relative to the initial wound size. The histopathological observation of SPLE (2.5% and 5%)-treated wound skin revealed increased re-epithelialization, increased hydroxyproline by 5.4, 3.5, and 4.1-fold, and more fibroblast deposition than untreated rats. SPLEs' anti-apoptotic (negatively modulating Bax protein) and cell proliferation effects (increasing PCNA expression) were linked with their promoting action on epidermal growth via diminishing cell death, keratinocyte proliferation/migration, and encouraging vascularization. Moreover, SPLE (2.5 and 5%)-treated rats showed reduced oxidative stress and inflammatory process, increasing SOD by 43.1, 123.9%; CAT by 139.7, 154.3%, along with lowering MDA by 16.9%, 38.8%, respectively. In parallel with lowering TNF-α by 50.1%, 68.9%; CRP by 41.6, 47.7%; IL-6 by 50.7, 61.3%, altogether promoting a balanced, faster wound recovery. In conclusion, SPLE exhibited a non-toxic and pro-healing effect, modulating several cellular processes, which make it a viable therapeutic source for wound management.