Phytochemical Composition, Cytoprotective and Antioxidant Activity of Werneria glaberrima Against H2O2-Induced Oxidative Stress in Human SH-SY5Y Neuroblastoma Cells

Plants from extreme environments such as the Atacama Desert are an underexplored source of novel bioactive metabolites, since intense UV radiation, thermal amplitude, and water scarcity force resident flora to rely on specialized biochemical defenses. Werneria glaberrima, a high-Andean species used in northern Chile as a traditional medicinal plant for uterine pain and to facilitate childbirth, is chemically characterized by prenylated acetophenones, benzofuran derivatives, and triterpenes. Although antioxidant activity has been shown in the taxonomically related high-Andean species Senecio nutans, the antioxidant and redox-modulating activity of W. glaberrima remains unexplored. Oxidative stress, an imbalance between reactive oxygen species (ROS) production and antioxidant capacity, contributes to the pathophysiology of cancer, cardiovascular disease, diabetes, and neurodegenerative disorders. Here, we characterized the phytochemical composition of the total extract (TE) of W. glaberrima and evaluated the biocompatibility and cytoprotection of the TE and three isolated metabolites, Wg-1 (ent-kaurenoic acid), Wg-2 (dihydrobenzofuran 6-hydroxytremetone), and Wg-3 (4-hydroxy-3-prenylacetophenone), in human SH-SY5Y neuroblastoma cells. We also assessed their ability to attenuate the intracellular pro-oxidant environment induced by hydrogen peroxide (H2O2). The TE was biocompatible and cytoprotective, whereas Wg-2 showed the broadest biocompatibility window among the isolated metabolites. Pretreatment with TE or Wg-1 protected SH-SY5Y cells against damage induced by different H2O2 concentrations, and decreased H2O2-induced DCF oxidation at the concentration tested. These results provide the first chemical characterization of the TE of W. glaberrima and initial in vitro evidence of the cytoprotective and antioxidant potential of this extract and Wg-1.