Abstract

This study aims to design a naturally based skin anti-aging cosmeceutical. Different plant extracts were screened for their anti-tyrosinase, anti-hyaluronidase and antioxidant activities in order to develop a multi-mechanistic herbal formula (HF) that targets various skin aging mechanisms. Based on the results, Arctium Lappa L., Camellia sinensis (L.) Kuntze, Hibiscus sabdariffa L., Glycyrrhiza glabra L., Moringa oleifera Lam., Salix alba L. and Stevia rebaudiana Bertoni were selected. Tentatively, 131 metabolites were identified in HF using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). HF was incorporated into a nanoemulsion-based gel (HFN gel) to enhance its permeability and in vivo activity. The optimized nanoemulsion showed an excellent particle size (PS) with high zeta potential (ZP) and a sustained release profile at pH 5.2, besides, transmission electron microscopy (TEM) exhibited a spherical shape. A three-month stability study demonstrated the high physical and chemical stability of HFN gel with enhanced permeability performance through the skin as compared to a conventional dosage form. The in vivo anti-aging activity was evaluated in C57BL/6 mice subjected to daily subcutaneous injections of D-galactose followed by topical application of HF and HFN gels at concentrations of 1% and 2% w/w. Our findings indicated that HFN gels can mitigate the skin aging changes induced by D-galactose in a dose-dependent manner. It augmented the overall antioxidant capacity of the skin. HFN gel significantly inhibited nuclear factor kappa B (NF-κB) and interleukin-1-beta (IL-1β) expression via modulating the Nrf2/HO-1 pathway, thereby preserving the integrity of skin oxidative capacity. Western blot analysis showed that HF and HFN gels significantly reduced the expression of matrix metalloproteinase-1 (MMP-1).