## 4 Discussion
Oral intake of hyaluronic acid can help to recover water loss in the stratum corneum of the face [26]. Under UVB irradiation, the reduced HAS2 gene expression is downregulated in skin fibroblasts, resulting in a reduction in hyaluronic acid synthesis [27]. The results of this study demonstrated that UAE increased hyaluronic acid contents in skin tissue via the upregulation of the HAS gene family expression. Thus, UAE contributed to improving the UVB-induced loss of skin water by increasing hyaluronic acid through HAS gene regulation. UVB, the most energetic UV wavelength, directly causes DNA breakdown and induces ROS generation, which leads to DNA damage, lipid peroxidation, and impairment of mitochondrial membrane potential, ultimately inducing apoptosis of epidermal keratinocytes and dermal fibroblast [19]. The death of these skin cells results in the breakdown of ECM components through MMP activation and the secretion of inflammatory cytokines, which accelerates skin aging [19]. In the present study, UAE inhibited apoptosis in the UVB-exposed dorsal back skin tissue of mice, as assessed by immunohistochemistry using cleaved caspase-3 and cleaved PARP antibodies. UV radiation generates two primary types of DNA damage, cyclobutene pyrimidine dimers (CPD) and pyrimidine 6-4 pyrimidine photoproducts (6-4 PP) [28]. The main cellular response to 6-4 PP is the activation of the apoptosis pathway, whereas the response to CPD seems to mainly involve cell cycle arrest [28]. Although UAE inhibited UVB-induced apoptosis in mice tissue, further research is required to determine the details of the UAE and UV-induced DNA photoproducts. Our data also showed UAE alleviated UVB-induced reduction of GSH content by upregulating the gene expression of _GSH reductase_ and inhibited UVB-induced lipid peroxidation and superoxide anion production through the transcriptional regulation of _NOX2_. Immunohistochemistryichemical analysis using NT or 4-HNE staining demonstrated potent antioxidant activities of UAE. The degradation of ECM during photoaging is closely related to ROS-mediated cellular responses [29]. Specifically, the expression of MMP1 is increased by UV irradiation, which is also stimulated by ROS, and plays a decisive role in photoaging [20; 24]. The antioxidant activity of UAE may contribute to the effects of UAE on ECM protein regulation. In addition, p53/p21 pathway can contribute to cellular adaptive responses to UVB damage associated with DNA repair, cell cycle arrest, and apoptosis [30]. UVB exposure can suppress p21 expression associated with increased apoptosis, whereas p21 overexpression may serve to reduce antioxidant defense capacity against UVB irradiation [31]. In the current study, UAE showed significant inhibitory effects on lipid peroxidation and apoptosis in UVB-irradiated dorsal back tissue of mice, but the detailed underlying molecular mechanisms related to the p53/p21 pathway require further study. UAE alleviated UVB-induced skin edema as the local inflammatory state of the skin and inhibited the UVB-induced neutrophil inflammatory response (MPO activity) in the skin. The infiltration of inflammatory cells, including neutrophils, may contribute to regulate MMP expression [20]. UV radiation triggers the secretion of IL-1 to initiate the inflammatory response in the skin and inhibits IL-10 to promote the survival of skin cells damaged by UV irradiation [20; 32]. Our data showed that UAE reduced the UVB-induced IL-1\(\beta\) secretion, whereas it increased the release of IL-10. UV can trigger ROS-mediated inflammatory responses through the activation of several kinase cascades, such as Akt, JNK, ERK, and p38 mitogen-activated protein kinase (MAPK). UVB irradiation activates Akt, and p38 MAPK, and triggers underlying inflammatory responses, as well as UVB-induced apoptosis of keratinocytes, which is primarily associated with p38 MAPK activation rather than JNK or ERK [33].