Protective Effect of Castanopsis sieboldii Extract against UVB-Induced Photodamage in Keratinocytes.

Ultraviolet B (UVB) rays disrupt the skin by causing photodamage via processes such as reactive oxygen species (ROS) production, endoplasmic reticulum (ER) stress, DNA damage, and/or collagen degradation. Castanopsis sieboldii is an evergreen tree native to the southern Korean peninsula. Although it is known to have antioxidant and anti-inflammatory effects, its protective effect against photodamage in keratinocytes has not been investigated. Thus, in the present study, we investigated the effect of 70% ethanol extract of C. sieboldii leaf (CSL3) on UVB-mediated skin injuries and elucidated the underlying molecular mechanisms. CSL3 treatment restored the cell viability decreased by UVB irradiation. Moreover, CSL3 significantly inhibited UVB- or tert-butyl hydroperoxide-mediated ROS generation in HaCaT cells. ER stress was inhibited, whereas autophagy was upregulated by CSL3 treatment against UVB irradiation. Additionally, CSL3 increased collagen accumulation and cell migration, which were decreased by UVB exposure. Notably, epigallocatechin gallate, the major component of CSL3, improved the cell viability decreased by UVB irradiation through regulation of ER stress and autophagy. Conclusively, CSL3 may represent a promising therapeutic candidate for the treatment of UVB-induced skin damage.

Ferroptosis contribute to hepatic stellate cell activation and liver fibrogenesis.

Ferroptosis is a widely known regulator of cell death in connection with the redox state as a consequence of the depletion of glutathione or accumulation of lipid peroxidation. Hepatic stellate cells (HSCs) play a pivotal role in the progression of hepatic fibrosis by increasing the production and secretion of the extracellular matrix. However, the role of ferroptosis in HSC activation and liver fibrogenesis has not been clearly elucidated. The ferroptosis inducer RAS-selective lethal 3 (RSL3) or erastin treatment in HSCs caused cell death. This effect was suppressed only after exposure to ferroptosis inhibitors. We observed induction of ferroptosis by RSL3 treatment in HSCs supported by decreased glutathione peroxidase 4, glutathione deficiency, reactive oxygen species generation, or lipid peroxidation. Interestingly, RSL3 treatment upregulated the expression of plasminogen activator inhibitor-1, a representative fibrogenic marker of HSCs. In addition, treatment with ferroptosis-inducing compounds increased c-JUN phosphorylation and activator protein 1 luciferase activity but did not alter Smad phosphorylation and Smad-binding element luciferase activity. Chronic administration of iron dextran to mice causes ferroptosis of liver in vivo. The expression of fibrosis markers, such as alpha-smooth muscle actin and plasminogen activator inhibitor-1, was increased in the livers of mice with iron accumulation. Hepatic injury accompanying liver fibrosis was observed based on the levels of alanine aminotransferase, aspartate aminotransferase, and hematoxylin and eosin staining. Furthermore, we found that both isolated primary hepatocyte and HSCs undergo ferroptosis. Consistently, cirrhotic liver tissue of patients indicated glutathione peroxidase 4 downregulation in fibrotic region. In conclusion, our results suggest that ferroptosis contribute to HSC activation and the progression of hepatic fibrosis.