Zheng Shuo-Lei, Wang Yu-Mei, Chi Chang-Feng, Wang Bin
Zhejiang Provincial Engineering Technology Research Center of Marine Biomedical Products, School of Food and Pharmacy, Zhejiang Ocean University, Zhoushan 316022, China.
National and Provincial Joint Engineering Research Centre for Marine Germplasm Resources Exploration and Utilization, School of Marine Science and Technology, Zhejiang Ocean University, Zhoushan 316022, China.
Antioxidants (Basel). 2024 Feb 28;13(3):294. doi: 10.3390/antiox13030294.
Scientific evidence attests that the epidermis receives excessive ultraviolet B (UVB) radiation, triggering the generation of substantial quantities of reactive oxygen species (ROS), which disrupted the delicate equilibrium of oxidation-reduction, leading to oxidative stress and inflammation. The historical use of honeysuckle polyphenols (HPs) has garnered our attention due to their efficacy in inhibiting oxidative damage. In this study, HPs were prepared from honeysuckle flowers employing an ultrasonic-assisted extraction method and quantitatively analyzed by a LC-MS/MS, and the mechanisms underlying HPs' antioxidative and anti-inflammatory effects on a UVB-irradiated HaCaT cell model were systematically investigated. The results showed that HPs had a significant cellular repair effect on UVB-irradiated HaCaT cells ( < 0.001). The mechanism of action indicated that HPs could allow Nrf2 to enter the nucleus by regulating the dissociation of Nrf2 from Keap1, which further increases the activity of downstream proteases (SOD and CAT), increases ROS scavenging, and reduces the intracellular malondialdehyde (MDA) level. In addition, HPs could down-regulate Toll-like receptor 4 (TLR4) and inhibit NF-κB (P65) dissociating from IκBα, resulting in a decrease in NF-κB (P65) entry into the nucleus and a decrease in inflammatory factors (TNF-α, IL-6, and IL-1β). In addition, four key compounds in HPs, including chlorogenic acid, quercetin, isorhamnetin, and luteolin, were selected to verify the mechanism of HPs repairing UVB damage using molecular docking techniques. The experiment suggested that four key active compounds could effectively occupy the Kelch homologue (Kelch) structural domain of Keap1, competitively bind with Nrf2, and facilitate the promotion of Nrf2 binding, ultimately enhancing the translocation of Nrf2 into the nucleus. In addition, four key active compounds could effectively interact with NF-κB (P65) through hydrogen bonding, van der Waals forces, and electrostatic forces to inhibit its entry into the nucleus. In summary, HPs can effectively repair the damage of HaCaT cells by UVB radiation and can be used to develop health and cosmetic products for the treatment of UV radiation-induced diseases.
科学证据表明，表皮受到过量的中波紫外线（UVB）辐射，会引发大量活性氧（ROS）的产生，这破坏了氧化还原的微妙平衡，导致氧化应激和炎症。金银花多酚（HPs）因其在抑制氧化损伤方面的功效，引起了我们的关注。在本研究中，采用超声辅助提取法从金银花中制备了HPs，并通过液相色谱-串联质谱（LC-MS/MS）进行定量分析，系统地研究了HPs对UVB照射的HaCaT细胞模型的抗氧化和抗炎作用机制。结果表明，HPs对UVB照射的HaCaT细胞具有显著的细胞修复作用（<0.001）。作用机制表明，HPs可通过调节Nrf2与Keap1的解离，使Nrf2进入细胞核，进而增加下游蛋白酶（超氧化物歧化酶和过氧化氢酶）的活性，增强ROS清除能力，降低细胞内丙二醛（MDA）水平。此外，HPs可下调Toll样受体4（TLR4），抑制NF-κB（P65）从IκBα解离，导致NF-κB（P65）进入细胞核减少，炎症因子（肿瘤坏死因子-α、白细胞介素-6和白细胞介素-1β）减少。此外，选择HPs中的四种关键化合物，包括绿原酸、槲皮素、异鼠李素和木犀草素，利用分子对接技术验证HPs修复UVB损伤的机制。实验表明，四种关键活性化合物可有效占据Keap1的 Kelch 同源结构域（Kelch），与Nrf2竞争性结合，促进Nrf2结合，最终增强Nrf2向细胞核的转位。此外，四种关键活性化合物可通过氢键、范德华力和静电力与NF-κB（P65）有效相互作用，抑制其进入细胞核。综上所述，HPs可有效修复UVB辐射对HaCaT细胞的损伤，可用于开发治疗UV辐射诱导疾病的健康和化妆品。
