Comparative appraisal of wound healing potential of Melia azedarach L. and its biogenic zinc oxide nanoparticles: An in vitro and in vivo approach

Background: Melia azedarach L. (Chinaberry tree) has notable ethnomedicinal uses. Purpose: Current research aims to compare the wound healing potential of M. azedarach extracts to its biogenic zinc oxide nanoparticles (ZnO Nps). Study Design: This study employed an experimental approach to evaluate the wound-healing potential of Melia azedarach extracts and their biogenic zinc oxide nanoparticles (ZnO Nps). Organic (MA-CME) and aqueous (MA-AqE) leaf extracts were prepared, followed by phytochemical analysis to determine flavonoid and phenolic content, with polyphenolics quantified by RP-HPLC. Biogenic ZnO Nps were then synthesized from each extract and investigated for stability and morphology. Bioassays were used to test the extracts' antibacterial, cytotoxic, and antioxidant activities, as well as their nanoparticles. Wound healing efficiency was assessed utilizing an in vivo rat excision model, with a focus on tissue regeneration indicators such as hydroxyproline, glutathione, catalase, peroxidase, and lipid peroxidation. This experimental design allowed for a comprehensive assessment of the therapeutic effects of M. azedarach extracts and their ZnO Nps on wound healing. Methods: MA-CME and MA-AqE of M. azedarach leaves were prepared using different solvents. Phytochemical evaluations included total flavonoid and phenolic content, while RP-HPLC quantified polyphenolics. Biogenic ZnO Nps of both extracts (MA-CME Nps and MA-AqE Nps) were prepared & characterized. All samples were evaluated for bioassays such as antibacterial, cytotoxic, and antioxidant activity, i.e., total antioxidant capacity (TAC), total reducing power (TRP), and free radical scavenging activity (FRAP). The in vivo wound healing potential was evaluated using a rat excision model. Results: MA-CME depicted the highest total phenolic and flavonoid content (45.3 ± 0.63 µg gallic acid and 32.1 ± 0.35 µg quercetin equivalent/mg). RP-HPLC revealed significant gallic acid i.e., 21.8 ± 0.04 µg/mg in MA-CME. Maximum FRAP (27.3 ± 0.29%), TAC, and TRP (209.1 ± 0.32 and 156.3 ± 0.61 µg ascorbic acid equivalent/mg respectively) were measured in MA-CME Nps. MA-CME Nps demonstrated substantial antioxidant, antibacterial, and hemocompatible properties. Wound healing was evidenced by accelerated closure and tissue regeneration with significant increase in hydroxyproline, glutathione, catalase, and peroxidase content by MA-CME Nps (2%) i.e., 13.7 ± 0.08 µg/mg, 9.7 ± 0.34 mmol/mg, 3 ± 0.02 and 7.4 ± 0.4 U/mg tissue respectively along with restrained lipid peroxidation (0.91 ± 0.14 mmol/mg tissue). Conclusions: The findings suggest that MA-CME Nps (2% w/w) showed strong potential as effective wound healing agents.