Bioactive Saponins of Primula vulgaris Huds. Promote Wound Healing through Inhibition of Collagenase and Elastase Enzymes: in Vivo, in Vitro and in Silico Evaluations.

Primula vulgaris Huds. leaves and roots were used to treat skin damage and inflammation in Anatolian Folk Medicine. This study aimed to assess the ethnopharmacological use of the plant using in vivo, in vitro, and in silico test models. Linear incision and circular excision wound models were used to determine the in vivo wound-healing potential of the plant extracts and fractions. In vitro assays including hyaluronidase, collagenase, and elastase inhibitory activities were carried out for the active compounds to discover their activity pathways. Structure-based molecular modeling was performed to understand inhibitory mechanisms regarding collagenase and elastase at the molecular level. The butanol fraction of the roots of P. vulgaris showed the highest wound-healing activity. Through activity-guided fractionation and isolation techniques, primulasaponin I (1) and primulasaponin I methyl ester (2) were stated as the major active compounds. These compounds exerted their activities through the inhibition of collagenase and elastase enzymes. Primulasaponin I methyl ester isolated from butanol fraction was found to be the strongest agent, especially with the values of 29.65 % on collagenase and 38.92 % on elastase inhibitory activity assays, as well as molecular docking studies. The present study supports scientific data for the traditional use of P. vulgaris and the wound healing properties of the plant can be referred to secondary metabolites as especially saponins found in the roots.