Wongkarn Supapit, Chewonarin Teera, Ruangsuriya Jetsada, Taya Sirinya, Dejkriengkraikul Pornngarm, Yodkeeree Supachai
Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
Functional Food Research Unit, Multidisciplinary Research Institute, Chiang Mai University, Chiang Mai 50200, Thailand.
Int J Mol Sci. 2025 Apr 5;26(7):3418. doi: 10.3390/ijms26073418.
Ultraviolet B (UVB) radiation is a key factor contributing to photodamage in epidermal cells. This study investigated the protective effects of Thua Nao, a Thai fermented soybean product, against UVB-induced damage in human epidermal keratinocytes (HaCaT) and the underlying mechanisms. Thua Nao extract fractions were prepared using a solvent partition method. We found that the dichloromethane fraction (TN-DC), along with its isoflavones daidzein and glycitein, significantly protected against UVB-induced HaCaT cell death. This protection involved inhibiting caspase-9 and caspase-3 activation, thus preventing apoptosis. Additionally, treatment with TN-DC, daidzein, and glycitein suppressed the UVB-induced production of inflammatory mediators, including interleukin-6 (IL-6), IL-8, inducible nitric oxide synthase, and cyclooxygenase-2. These protective effects were associated with reduced intracellular reactive oxygen species and enhanced the levels of antioxidant enzymes, including superoxide dismutase and glutathione peroxidase 4. Signaling pathway analysis revealed that TN-DC activated the pro-survival ERK1/2 and Akt pathways while decreased the phosphorylation of JNK in UVB-exposed cells. On the other hand, daidzein and glycitein enhanced ERK1/2 activation and reduced the phosphorylation of JNK and p38 MAPKs. The involvement of ERK1/2 and Akt activation in cell survival was confirmed using specific inhibitors. Thus, TN-DC and its isoflavones protects keratinocytes from UVB-induced oxidative damage and inflammation by modulating MAPKs and Akt signaling.
紫外线B(UVB)辐射是导致表皮细胞光损伤的关键因素。本研究调查了泰国发酵豆制品豆瑙对UVB诱导的人表皮角质形成细胞(HaCaT)损伤的保护作用及其潜在机制。采用溶剂分配法制备豆瑙提取物馏分。我们发现二氯甲烷馏分(TN-DC)及其异黄酮大豆苷元和染料木素能显著保护HaCaT细胞免受UVB诱导的细胞死亡。这种保护作用包括抑制半胱天冬酶-9和半胱天冬酶-3的激活,从而防止细胞凋亡。此外,用TN-DC、大豆苷元和染料木素处理可抑制UVB诱导的炎症介质的产生,包括白细胞介素-6(IL-6)、IL-8、诱导型一氧化氮合酶和环氧化酶-2。这些保护作用与细胞内活性氧的减少和抗氧化酶水平的提高有关,包括超氧化物歧化酶和谷胱甘肽过氧化物酶4。信号通路分析显示,TN-DC激活了促生存的ERK1/2和Akt通路,同时降低了UVB照射细胞中JNK的磷酸化。另一方面,大豆苷元和染料木素增强了ERK1/2的激活,降低了JNK和p38丝裂原活化蛋白激酶的磷酸化。使用特异性抑制剂证实了ERK1/2和Akt激活在细胞存活中的作用。因此,TN-DC及其异黄酮通过调节丝裂原活化蛋白激酶和Akt信号通路保护角质形成细胞免受UVB诱导的氧化损伤和炎症。