Mechanistic Wound Healing of Ficus trijuja Leaf Extract and Its Lipid Nanocapsule Supported by Metabolomic Profiling and In Vivo Studies

Abstract

This study explores the metabolic profile and wound-healing capabilities of Ficus trijuja, a species within the Moraceae family, for the first time. Ficus plants contain a variety of secondary metabolites such as flavonoids, triterpenoids, and alkaloids, known for their antioxidant, anti-inflammatory, and cytotoxic properties. Previous studies demonstrated the effectiveness of Ficus extracts in wound healing, with evidence of improved wound contraction, strength, and faster epithelization. This study shows the impact of F. trijuja extract in a gel base as well as when delivered through a lipid nanocapsules (LNCs) formula, on all phases of wound-healing in rats, by determining the expression levels of their key markers. The results indicated that treatment with F. trijuja extract accelerated wound healing, particularly when applied through lipid nanocapsulation, which shows comparable efficacy to standard treatments like MEBO® with approximately 2.62% improvement in wound healing when compared to MEBO® itself. Understanding these molecular markers offers insights for developing targeted therapies to optimize wound healing and prevent complication development. To unravel the phytochemical composition of F. trijuja extract, LC-HRESIMS analysis was implemented, which revealed 24 secondary metabolites belonging to different classes of flavonoids, terpenoids, and megastigmane. In conclusion, both Ficus trijuja gel and its nanoformulation have proven efficacy in wound healing in vivo and can be further investigated for potential clinical use.