Systemic Phagocytic Activity and Topical Repair Effects of Pelargonium graveolens L’Hér Extract with Reduced Nociceptive Response: In Vivo Models

Background: Pelargonium graveolens is traditionally used for its anti-inflammatory and wound-healing properties. However, its effects on phagocytosis, nociception, and tissue repair remain poorly characterized. Methods: Polysaccharides were identified in the extract. Tyrosinase, elastase, and collagenase inhibitory activities were evaluated in vitro. Systemic phagocytosis was assessed by the carbon clearance assay in rats (n = 6/group; oral extract, 300 and 600 mg/kg for 12 days). Anti-inflammatory and antinociceptive activities were evaluated using carrageenan-induced paw oedema (n = 5/group; topical 3% and 6% cream) and plantar thermal tests (n = 6/group), respectively. Wound healing was evaluated separately using only the topical 6% cream for 15 days in rats (n = 6/group; topical 6% cream), followed by histopathological evaluation. Results: The extract contained D-glucose (72.76 ± 3.64 µg/mL) and polysaccharides (2.89 ± 1.55 mg GE/g DE). It inhibited tyrosinase (IC50 = 340.80 ± 28.61 µg/mL), elastase (IC50 = 761.67 ± 14.62 µg/mL), and collagenase (IC50 = 456.55 ± 6.14 µg/mL) in a concentration-dependent manner. Phagocytic activity increased, reaching a phagocytic index of 0.023 ± 0.005 at 600 mg/kg. Topical 3% and 6% creams were evaluated for anti-inflammatory activity, with the 6% cream showing the highest effect (83.36 ± 0.78% inhibition at 240 min) and increased paw withdrawal latency (4.10–4.35 s at 90 min). The 6% cream was associated with progressive wound contraction, reaching 79.01 ± 43.64% by day 9. However, after adjustment for baseline wound area, no statistically significant overall treatment effect was detected. Histopathological analysis showed greater collagen deposition, vascularization-associated histological features, and re-epithelialization in the treatment group compared with the vehicle group. Conclusions: Oral administration enhanced systemic phagocytic activity, while topical application produced anti-inflammatory and antinociceptive effects. The 6% formulation showed promising wound-healing effects, although no statistically significant overall treatment effect was detected after adjustment for baseline wound area. Further studies are warranted to elucidate the underlying mechanisms and establish the safety profile of the formulations.