背景:内质网(ER)应激是由长期暴露于紫外线B辐射(UVB)引发的关键毒性信号事件,这显著加剧了照射皮肤的光损伤反应。因此,能够抑制内质网应激的药物的鉴定可以作为解决UVB诱导的光损伤治疗中未满足的临床需求的有希望的治疗策略.
方法:使用UVB照射的小鼠模型,并进行持续9周的人参提取物的局部给药。维生素E用作阳性对照。给药9周后,皮肤外观,表皮增生,炎症细胞浸润,凋亡,测量胶原蛋白含量。用6mJ/cm2的UVB照射角质形成细胞以建立体外模型。使用qRT-PCR在体内和体外研究ER应激和细胞凋亡的水平,免疫印迹,和免疫荧光。
结果:在筛选的来自13种不同植物物种的14种提取物中,人参,李母,山茶花对UVB诱导的内质网胁迫有抑制作用。值得注意的是,人参可有效抑制辐照的角质形成细胞和Balb/C小鼠皮肤中的胶原蛋白降解和凋亡。此外,VMP1的沉默显著阻碍了人参提取物对UVB照射的角质形成细胞的保护作用,表明人参通过靶向促进VMP1发挥其保护作用。
结论:我们的数据表明,人参提取物通过促进VMP1介导的ER应激抑制对UVB辐射诱导的光损伤具有治疗作用。
BACKGROUND: The endoplasmic reticulum (ER) stress is a crucial toxic signaling event triggered by chronic exposure to Ultraviolet B radiation (
UVB), which significantly exacerbate photodamage responses in the irradiated skin. Therefore, the identification of agents capable of inhibiting ER stress could serve as a promising therapeutic strategy for addressing the unmet clinical needs in the treatment of
UVB-induced photodamage.
METHODS: A
UVB-irradiated mouse model was used and topical administration of Panax ginseng extract was carried out for a duration of 9 weeks. Vitamin E was used as a positive control. After 9 weeks of administration, the skin appearance, epidermal hyperplasia, infiltration of inflammatory cells, apoptosis, and collagen content were measured. The keratinocytes were irradiated with 6 mJ/cm2
UVB to establish an in vitro model. The levels of ER stress and apoptosis were investigated both in vivo and in vitro using qRT-PCR, immunoblotting, and immunofluorescence.
RESULTS: Among the 14 extracts derived from 13 distinct plant species that were screened, Panax ginseng, Prunus mume, and Camellia japonica showed inhibitory effect on UVB-induced ER stress. Notably, Panax ginseng effectively inhibits collagen degradation and apoptosis in both irradiated keratinocytes and Balb/C mice skin. Furthermore, the silencing of VMP1 significantly impeded the cellular protective effect of Panax ginseng extract on UVB-irradiated keratinocytes, indicating that Panax ginseng exerts its protective effects through targeted promotion of VMP1.
CONCLUSIONS: Our data suggest that Panax ginseng extract possess a therapeutical effect on
UVB radiation-induced photodamage by promoting VMP1-mediated inhibition of ER stress.