Siegesbeckiae Herba Extract and Chlorogenic Acid Ameliorate the Death of HaCaT Keratinocytes Exposed to Airborne Particulate Matter by Mitigating Oxidative Stress

Abstract

Airborne particulate matter with a size of 10 μm or less (PM10) can cause oxidative damages and inflammatory reactions in the skin. This study was conducted to discover natural products that are potentially useful in protecting the skin from PM10. Among the hot water extracts of a total of 23 medicinal plants, Siegesbeckiae Herba extract (SHE), which showed the strongest protective effect against PM10 cytotoxicity, was selected, and its mechanism of action and active constituents were explored. SHE ameliorated PM10-induced cell death, lactate dehydrogenase (LDH) release, lipid peroxidation, and reactive oxygen species (ROS) production in HaCaT cells. SHE decreased the expression of KEAP1, a negative regulator of NRF2, and increased the expression of NRF2 target genes, such as HMOX1 and NQO1. SHE selectively induced the enzymes involved in the synthesis of GSH (GCL-c and GCL-m), the regeneration of GSH (GSR and G6PDH), and GSH conjugation of xenobiotics (GSTκ1), rather than the enzymes that directly scavenge ROS (SOD1, CAT, and GPX1). SHE increased the cellular content of GSH and mitigated the oxidation of GSH to GSSG caused by PM10 exposure. Of the solvent fractions of SHE, the n-butyl alcohol (BA) fraction ameliorated cell death in both the absence and presence of PM10. The BA fraction contained a high amount of chlorogenic acid. Chlorogenic acid reduced PM10-induced cell death, LDH release, and ROS production. This study suggests that SHE protects cells from PM10 toxicity by increasing the cellular antioxidant capacity and that chlorogenic acid may be an active phytochemical of SHE.