Cosmetics Safety and Efficacy Evaluation Center, West China Hospital, Sichuan University, No. 5, Gong Xing Road, Chengdu, Sichuan, 610041, PR China; Sichuan Engineering Technology Research Center of Cosmetic, No. 5, Gong Xing Road, Chengdu, Sichuan, 610041, PR China; Department of Dermatology, West China Hospital, Sichuan University, No. 37, Guo Xue Xiang, Chengdu, Sichuan, 610041, PR China.
Cosmetics Safety and Efficacy Evaluation Center, West China Hospital, Sichuan University, No. 5, Gong Xing Road, Chengdu, Sichuan, 610041, PR China; Sichuan Engineering Technology Research Center of Cosmetic, No. 5, Gong Xing Road, Chengdu, Sichuan, 610041, PR China.
Biomed Pharmacother. 2020 Jan;121:109600. doi: 10.1016/j.biopha.2019.109600. Epub 2019 Nov 7.
UVB is a high energy source that causes the major risk factor for sunburn and skin tumor. However, photochemical interactions lead to beneficial effects such as synthesis of vitamin D and corticosteroids. Therefore, a reasonable therapeutic regime is advocated to reduce UVB injuries but makes use of synthesizing sunlight metabolite. Many natural compounds improving plant cells resistant to oxidative stress by the harnessing of solar energy may be also used to protect human cells. Although many nature plants have shown photoprotective effects on skin, the mechanisms underlying of the effects are still ambiguous.
This study evaluates the protective effects of cultivated Cordyceps against UVB-induced damage in human keratinocytes and identifies the photoprotective mechanisms using a transcriptomic network approach.
Cordyceps extract compositions were investigated by HPLC analysis. Cell survival, reactive oxygen species (ROS) generation, HO content, aquaporin 3 (AQP3) level and DNA damage were determined upon UVB irradiation in the presence of Cordyceps extract. In addition, next-generation sequencing was used to profile transcriptomic alteration of 20 mJ/cm UVB and non-UV. Finally, a network pharmacology method was applied to study Cordyceps extract-related natural compounds and their UVB-induced differentially change targets using the Cytoscape 3.7.1 software.
Adenosine and mannitol were the major contents in Cordyceps extract. Cordyceps caused a significant diminished in intracellular UVB-induced oxidative stress, including ROS production and intracellular HO content. Besides, AQP3 which mediated intracellular signal transmission and transported HO into cells was significantly increased in the presence of Cordyceps extract against UVB irradiation. In addition, DNA repair effect of Cordyceps extract after UV irradiation was proven to be effective by comet assay. Moreover, KEGG analysis showed steroid hormone biosynthesis, ovarian steroidogenesis, fat digestion and absorption were enriched in top 3 between 20 mJ/cm UVB and non-UV. Gene ontology (Go) analysis showed that steroid metabolic process, sterol metabolic process, and cholesterol metabolic process were enriched in top3 biology process. By using network analysis, 125 potential bioactive ingredients in Cordyceps and 201 targets were identified. Finally, signal pathway analyses suggested that the protective effects of Cordyceps compounds against low dose UVB‑induced changes might target PPAR signaling pathway, cholesterol metabolism, and ovarian steroidogenesis.
Cordyceps extract may be an ideal product for external use of skin which could not only avoid UVB-induced adverse effects, but also could application of metabolite products by UVB such us steroid hormone and vitamin D3.
ETHNOPHARMACOLOGICAL 相关性：UVB 是一种高能源，会导致晒伤和皮肤肿瘤的主要风险因素。然而，光化学反应会产生有益的影响，如维生素 D 和皮质类固醇的合成。因此，提倡采用合理的治疗方案来减少 UVB 损伤，但同时利用阳光代谢物的合成。许多天然化合物可以通过利用太阳能来提高植物细胞对氧化应激的抵抗力，也可以用于保护人类细胞。尽管许多天然植物对皮肤有光保护作用，但作用机制仍不清楚。
本研究评估了培养的蛹虫草对人角质形成细胞中 UVB 诱导损伤的保护作用，并通过转录组网络方法确定了其光保护机制。
通过 HPLC 分析研究蛹虫草提取物的组成。在存在蛹虫草提取物的情况下，通过检测细胞存活率、活性氧 (ROS) 生成、HO 含量、水通道蛋白 3 (AQP3) 水平和 DNA 损伤来确定 UVB 照射后的情况。此外，还使用下一代测序技术来分析 20mJ/cm2 UVB 和非 UV 照射下的转录组变化。最后，应用网络药理学方法研究蛹虫草提取物相关的天然化合物及其在 UVB 诱导下的差异变化靶点，使用 Cytoscape 3.7.1 软件。
腺苷和甘露醇是蛹虫草提取物的主要成分。蛹虫草提取物显著减少了细胞内 UVB 诱导的氧化应激，包括 ROS 生成和细胞内 HO 含量。此外，在存在蛹虫草提取物的情况下，AQP3 显著增加，AQP3 介导细胞内信号转导并将 HO 运入细胞。此外，通过彗星试验证明了蛹虫草提取物在 UV 照射后的 DNA 修复作用是有效的。此外，KEGG 分析表明，20mJ/cm2 UVB 和非 UV 之间富集的前 3 个通路为甾体激素生物合成、卵巢类固醇生成、脂肪消化和吸收。GO 分析表明，类固醇代谢过程、固醇代谢过程和胆固醇代谢过程在生物学过程中富集在前 3 位。通过网络分析，鉴定出蛹虫草中 125 种潜在的生物活性成分和 201 个靶点。最后，信号通路分析表明，蛹虫草化合物对低剂量 UVB 诱导变化的保护作用可能靶向 PPAR 信号通路、胆固醇代谢和卵巢类固醇生成。
蛹虫草提取物可能是一种理想的外用皮肤产品，既能避免 UVB 引起的不良反应，又能应用 UVB 产生的代谢产物，如甾体激素和维生素 D3。
