A Novel multi-fruit acids formula design on molecular basis for skin brightening via a system biology approach

Fruit acids have long been recognized as highly effective actives with world-wide popularity, covering skin peeling, anti-acne, anti-wrinkle applications, and skin depigmentation.

There are complicated interconnections between the fruit acid formula and skin pigmentation behaviors. However, the lack of systematic researches on multi-ingredient formula restricted our understanding on its mechanism. Therefore, it is of great necessity to study the interactions and cascades among components, potential gene targets, signaling pathways, and biological processes via a system biology approach.

We used system biology, molecular fingerprint, and structural biology to calculate and collect target information of the functional formula. Gene Ontology (GO) enrichment analysis was further applied to study the biological processes and pathways of the formula, and a multi-level network model of "component - molecular target - signaling pathway - skin disease" was established. Besides, the zebrafish model was utilized to verify the formula.

We obtained 69 hub targets by constructing a protein-protein interaction (PPI) network based on the intersection between multi-fruit acids formula (mandelic acid, lactobionic acid, niacinamide, and hydroxytyrosol) and skin indications targets (whitening-sebum balance). In vitro zebrafish models, including pigmentation, antioxidant, and radiation protection models, showed that the current formula significantly alleviated pigmentation intensity and intracellular free radical content, thus proving the efficacy of skin brightening and UV irradiation protection.

This research uncovered the underlying mechanism of multi-fruit acids formula and predicted its function in skin brightening and UV irradiation prevention.