Verma Ankit, Kushwaha Hari N, Srivastava Ajeet K, Srivastava Saumya, Jamal Naseem, Srivastava Kriti, Ray Ratan Singh
Photobiology Laboratory, System Toxicology and Health Risk Assessment Group, Vishvigyan Bhawan 31, Mahatma Gandhi Marg, Lucknow 226001, Uttar Pradesh, India; Department of Radiodiagnosis, King George's Medical University, Lucknow, Uttar Pradesh 226003, India; Department of Radiotherapy, King George's Medical University, Lucknow, Uttar Pradesh 226003, India.
Photobiology Laboratory, System Toxicology and Health Risk Assessment Group, Vishvigyan Bhawan 31, Mahatma Gandhi Marg, Lucknow 226001, Uttar Pradesh, India.
J Photochem Photobiol B. 2017 Jul;172:139-148. doi: 10.1016/j.jphotobiol.2017.05.018. Epub 2017 May 19.
Chronic ultraviolet radiation (UV-R) exposure causes skin disorders like erythema, edema, hyperpigmentation, photoaging and photocarcinogenesis. Recent research trends of researchers have focused more attention on the identification and use of photo stable natural agents with photoprotective properties. Piperine (PIP), as a plant alkaloid, is an important constituent present in black pepper (Piper nigrum), used widely in ayurvedic and other traditional medicines and has broad pharmacological properties. The study was planned to photoprotective efficacy of PIP in human keratinocyte (HaCaT) cell line. We have assessed the UV-R induced activation of transcription factor NF-κB in coordination with cell death modulators (Bax/Bcl-2 and p21). The LC-MS/MS analysis revealed that PIP was photostable under UV-A/UV-B exposure. PIP (10μg/ml) attenuates the UV-R (A and B) induced phototoxicity of keratinocyte cell line through the restoration of cell viability, inhibition of ROS, and malondialdehyde generation. Further, PIP inhibited UV-R mediated DNA damage, prevented micronuclei formation, and reduced sub-G1 phase in cell cycle, which supported against photogenotoxicity. This study revealed that PIP pretreatment strongly suppressed UV-R induced photodamages. Molecular docking studies suggest that PIP binds at the active site of NF-κB, and thus, preventing its translocation to nucleus. In addition, transcriptional and translational analysis advocate the increased expression of NF-κB and concomitant decrease in IkB-α expression under UV-R exposed cells, favouring the apoptosis via Bax/Bcl-2 and p21 pathways. However, PIP induced expression of IkB-α suppress the NF-κB activity which resulted in suppression of apoptotic marker genes and proteins that involved in photoprotection. Therefore, we suggest the applicability of photostable PIP as photoprotective agent for human use.
长期暴露于紫外线辐射（UV-R）会导致皮肤疾病，如红斑、水肿、色素沉着、光老化和光致癌作用。研究人员最近的研究趋势更加关注具有光保护特性的光稳定天然剂的鉴定和应用。胡椒碱（PIP）作为一种植物生物碱，是黑胡椒（Piper nigrum）中的重要成分，广泛应用于阿育吠陀和其他传统医学中，具有广泛的药理特性。本研究旨在探讨PIP对人角质形成细胞（HaCaT）细胞系的光保护作用。我们评估了UV-R诱导的转录因子NF-κB的激活，并与细胞死亡调节因子（Bax/Bcl-2和p21）进行了协同研究。液相色谱-串联质谱（LC-MS/MS）分析表明，PIP在UV-A/UV-B照射下具有光稳定性。PIP（10μg/ml）通过恢复细胞活力、抑制活性氧（ROS）和丙二醛生成，减轻UV-R（A和B）诱导的角质形成细胞系的光毒性。此外，PIP抑制UV-R介导的DNA损伤，防止微核形成，并减少细胞周期中的亚G1期，这支持了其抗光遗传毒性的作用。本研究表明，PIP预处理能强烈抑制UV-R诱导的光损伤。分子对接研究表明，PIP结合在NF-κB的活性位点，从而阻止其转位至细胞核。此外，转录和翻译分析表明，在UV-R照射的细胞中，NF-κB的表达增加，而IkB-α的表达随之减少，这有利于通过Bax/Bcl-2和p21途径诱导细胞凋亡。然而，PIP诱导的IkB-α表达抑制了NF-κB的活性，从而导致参与光保护的凋亡标记基因和蛋白质的表达受到抑制。因此，我们建议光稳定的PIP可作为人类光保护剂应用。
