A Passiflora edulis Fruit Extract with an Increase in Vitamin D3 Level in Skin Epidermis: In Silico and In Vitro Research

Vitamin D3 deficiency is a common concern in dermatology and aging, yet its topical supplementation is restricted in the EU, and direct precursors are unstable. Stimulating the skin’s endogenous vitamin D3 biosynthesis using phytochemicals represents a promising alternative. This research reveals the potential of a natural Passiflora edulis (passion fruit) extract to stimulate vitamin D3 synthesis in the skin epidermis. An in silico screening of phytochemicals using molecular docking and Molecular Mechanics/Poisson–Boltzmann Surface Area (MM/PBSA) analysis was performed to identify compounds with affinity for the vitamin D receptor (VDR) and lathosterol oxidase, a key enzyme in the vitamin D3 biosynthesis pathway. While several flavonoids showed high predicted vitamin D receptor affinity, genistein, which has been reported to occur in P. edulis fruit extracts, exhibited favorable docking scores and was predicted to interact with the active site of lathosterol oxidase. Subsequent in vitro experiments on HaCaT keratinocytes and an ex vivo human skin model demonstrated that the P. edulis extract significantly increased vitamin D3 amount, both under UVB irradiation and, notably, in its absence. The P. edulis extract significantly increased vitamin D3 level in HaCaT keratinocytes by up to 274.04% without UVB exposure and demonstrated a synergistic effect with UVB, enhancing production by a further 61.41% compared to UVB alone (p < 0.001). In the ex vivo model, the extract alone increased vitamin D3 levels by 153.31%, and its combination with UVB resulted in a 54.82% higher yield compared to the UVB control (p < 0.01). These findings highlight the promising potential of P. edulis fruit extract as a natural cosmeceutical ingredient for enhancing cutaneous vitamin D3 synthesis, offering a novel approach to supporting skin health through dermatocosmetics.