Parameria laevigata (Juss.) Moldenke healing wound via PI3K/AKT/MAPK pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Parameria laevigata has traditionally been used for treatment of traumas caused by falls, fractures, contusions and strains, but its efficacy in wound healing related to the traditional use has not yet been supported by experiments.

AIM OF THE STUDY: To validate the effects of P. laevigata in diabetic wound healing, and explore bioactive components and potential pathway.

MATERIALS AND

METHODS

The effects of P. laevigata on wound healing were evaluated using diabetic mice. Bioactive compounds were obtained by bio-guided isolation, and their bioactivities were evaluated using cellular models. Metabolomics, network pharmacology and molecular docking were applied to explore pathway, which were further validated by reverse transcription-quantitative polymerase chain reaction.

RESULTS

P. laevigata enhanced wound healing of diabetic mice roughly equal to bFGF by reducing inflammation and oxidative stress. It reduced O-acetyl-L-serine, and increased 2-pyrocatechuic acid and 5-methylcytidine metabolite levels of skin tissues. Moreover, it downregulated Tnf-α, Il-1β, Il-6 and Nf-κb p65 mRNA, and also upregulated Il-10 mRNA, likely contributing to the modulation of PI3K/AKT/MAPK signaling pathway. In addition, four bioactive compounds were isolated, which might protect endothelial cells from lipopolysaccharide-induced damage and enhance angiogenesis by binding proteins such as IRS, PI3K, AKT, RAS, ERK, TNF-α, IL-1β, IL-6, IL-10 and NF-κB.

CONCLUSIONS

P. laevigata with four compounds exhibited bioactivity on wound healing, might involving the PI3K/AKT/MAPK signaling pathway.