Xiao Juanjuan, Lu Hui, Ma Tengfei, Ni Xiaofang, Chang Teding, Liu Man, Li Nijie, Lu Peijiang, Ke Changshu, Tian Qin, Zou Ling, Wang Fei, Wang Wei, Zhang Lu, Yuan Ping, Liu Lin, Zhang Jianmin, Shi Fei, Duan Qiuhong, Zhu Feng
Cancer Research Institute, The Affiliated Hospital of Guilin Medical University, Guilin, China.
Guangxi Health Commission Key Laboratory of Novel Onco-Kinases in Target Therapy, The Affiliated Hospital of Guilin Medical University, Guilin, China.
Front Pharmacol. 2022 Jul 22;13:881042. doi: 10.3389/fphar.2022.881042. eCollection 2022.
Excessive solar ultraviolet (SUV) radiation often causes dermatitis, photoaging, and even skin cancer. In the pathological processes of SUV-induced sunburn, JNK is activated by phosphorylation, and it in turn phosphorylates its downstream transcription factors, such as ATF2 and c-jun. The transcription factors further regulate the expression of pro-inflammatory genes, such as IL-6 and TNF-α, which ultimately leads to dermatitis. Therefore, inhibiting JNK may be a strategy to prevent dermatitis. In this study, we screened for worenine as a potential drug candidate for inhibiting sunburn. We determined that worenine inhibited the JNK-ATF2/c-jun signaling pathway and the secretion of IL-6 and TNF-α in cell culture and , confirming the role of worenine in inhibiting sunburn. Furthermore, we determined that worenine bound and inhibited JNK2 activity through the MST, kinase, and kinase assays. Therefore, worenine might be a promising drug candidate for the prevention and treatment of SUV-induced sunburn.
过多的太阳紫外线(SUV)辐射常导致皮炎、光老化,甚至皮肤癌。在SUV诱导晒伤的病理过程中,JNK通过磷酸化被激活,进而使其下游转录因子如ATF2和c-jun磷酸化。这些转录因子进一步调节促炎基因如IL-6和TNF-α的表达,最终导致皮炎。因此,抑制JNK可能是预防皮炎的一种策略。在本研究中,我们筛选出渥瑞宁作为抑制晒伤的潜在候选药物。我们确定渥瑞宁在细胞培养中抑制JNK-ATF2/c-jun信号通路以及IL-6和TNF-α的分泌,证实了渥瑞宁在抑制晒伤中的作用。此外,我们通过 MST、激酶和激酶分析确定渥瑞宁结合并抑制JNK2活性。因此,渥瑞宁可能是预防和治疗SUV诱导晒伤的有前景的候选药物。