Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, China.
R&D Center, Infinitus (China) Company Ltd, Guangzhou, China.
Phytomedicine. 2024 Nov;134:156010. doi: 10.1016/j.phymed.2024.156010. Epub 2024 Aug 30.
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.
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/cm 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.
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.
Our data suggest that Panax ginseng extract possess a therapeutical effect on UVB radiation-induced photodamage by promoting VMP1-mediated inhibition of ER stress.
内质网（ER）应激是慢性暴露于紫外线 B 辐射（UVB）引发的关键毒性信号事件，可显著加重辐照皮肤的光损伤反应。因此，鉴定能够抑制 ER 应激的药物可能成为治疗 UVB 诱导的光损伤的一种有前途的治疗策略。
建立 UVB 照射的小鼠模型，并进行为期 9 周的人参提取物局部给药。维生素 E 作为阳性对照。给药 9 周后，测量皮肤外观、表皮增生、炎症细胞浸润、细胞凋亡和胶原含量。用 6 mJ/cm2 的 UVB 照射角质形成细胞，建立体外模型。采用 qRT-PCR、免疫印迹和免疫荧光法，在体内和体外研究 ER 应激和细胞凋亡水平。
在筛选的 13 种不同植物来源的 14 种提取物中，人参、李和山茶显示出抑制 UVB 诱导的 ER 应激的作用。值得注意的是，人参有效抑制了辐照角质形成细胞和 Balb/C 小鼠皮肤中的胶原降解和细胞凋亡。此外，沉默 VMP1 显著阻碍了人参提取物对 UVB 照射的角质形成细胞的细胞保护作用，表明人参通过靶向促进 VMP1 发挥其保护作用。
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。
