Protective Effects of Linearthin and Other Chalcone Derivatives from Aspalathus linearis (Rooibos) against UVB Induced Oxidative Stress and Toxicity in Human Skin Cells.

Abstract

Skin cells suffer continuous damage from chronic exposure to ultraviolet light (UV) that may result in UV-induced oxidative stress and skin thinning. This has necessitated the formulation of cosmeceutical products rich in natural antioxidants and free radical scavengers. Aspalathus linearis (rooibos) is an endemic South African fynbos plant growing naturally in the Western Cape region. The plant is rich in phenolics and other bioactives with a wide spectrum of health benefits. The chemical study of an acetonic extract of green A. linearis afforded a novel compound named linearthin (1) and two known dihydrochalcones, aspalathin (2) and nothofagin (3). The chemical structure of the novel compound was elucidated based on spectroscopic data analysis. The bio-evaluation of the isolated chalcones in vitro for protection against UVB-induced oxidative stress were systematically assessed by examining cell viability, metabolic activity, apoptosis, and cytotoxicity using HaCaT and SK-MEL-1 skin cells models. It was observed that pre-treatment with tested samples for 4- and 24 h at low concentrations were sufficient to protect skin cells from UVB-induced damage in vitro as evidenced by higher cell viability and improved metabolic activity in both keratinocytes (HaCaT) and melanocytes (SK-MEL-1). The results further show that the pre-treatment regimen employed by this study involved some degree of cellular adaptation as evidenced by higher levels of reduced glutathione with a concomitant decrease in lipid peroxidation and lowered caspase 3 activity. Furthermore, compound 1 was most cytoprotective against UVB irradiation of HaCaT cell line (over 24 h) with an IC50 of 282 µg/mL and SK-MEL-1 cell line with IC50 values of 248.3 and 142.6 µg/mL over 4 and 24 h, respectively. On the other hand, HaCaT cells exposed to 2 over 4 h before UVB irradiation showed the highest degree of cytoprotection with an IC50 of 398.9 µg/mL among the four studied samples. These results show that linearthin (1) and the two glycoside dihydrochalcone of A. linearis have the potential to be further developed as antioxidant cosmeceutical ingredients that may protect skin against UVB-induced damage.