Ethnopharmacological relevance: Sapindus mukorossi Gaertn. (S. mukorossi), known as 'mu huan zi' in Chinese folklore, belongs to the family Sapindaceae and it has been traditionally used for treating coughing and excessive salivation, removing freckle, whitening skin, etc. Evidence-based medicine also verified the antimicrobial, anti-tyrosinase and anti-acne activity of S. mukorossi extract, suggesting that it has the potential to be a pharmaceutical and cosmetic additive.

Aim of the study: The present study was intended to evaluate the freckle-removing and skin-whitening activities of S. mukorossi extracts, and further analyzing the potential anti-acne mechanism.

Methods: Saponin fractions were purified by using the semi-preparative high-performance liquid chromatography, and their antibacterial activity was detected against Propionibacterium acnes (P. acnes), which was the leading cause of inflamed lesions in acne vulgaris. The anti-lipase and anti-tyrosinase activities were assayed using a commercial kit, while the potential anti-acne mechanism was predicted on the basis of the network pharmacology. Active components of saponin fraction were identified by HPLC-MS analysis. Furthermore, the different toxicity level of compounds was predicted according to the quantitative structure-activity relationship, and the first application of crude extract and saponin fraction to facial masks was analyzed based on the comprehensive evaluation method.

Results: The saponin fraction (F4) purified from the fermentation liquid-based water extract (SWF) showed the best antibacterial activity against P. acnes ATCC 6919 with the MIC of 0.06 mg/mL, which was 33-fold of its parent SWF (with the MIC of 2.0 mg/mL). Compared with SWF, the application of F4 caused greater inhibition rates on lipase and tyrosinase. Chemical constituents of F4 were evaluated, from which four oleanane-type triterpenoid saponins were detected to contribute to the above biological activities of F4. The mechanism of the four compounds on anti-acne was predicted, and seven targets such as PTGS2 and F2RL1 were obtained to be important for the treatment of acne. The four compounds were also predicted to have different levels of toxicity to various species, and they were not harmful to rats. Besides, F4 and SWF were applied to facial masks and there was no significant influence on the physicochemical properties including pH, stability, and sensory characteristics.

Conclusion: This work demonstrated that oleanane-type triterpenoid saponins were speculated to contribute to the skin-whitening, freckle-removing, and anti-acne activities of F4. These findings will facilitate the development of the S. mukorossi extract and the allied products as the new and natural anti-acne agent and cosmetic additives.