海洋盐生植物来源的多酚通过丝裂原活化蛋白激酶信号通路抑制神经胶质瘤细胞生长。

Marine halophyte derived polyphenols inhibit glioma cell growth through mitogen-activated protein kinase signaling pathway.

机构信息

Department of Zoology, Lady Doak College, Madurai Kamaraj University, Thallakulam, Madurai 625002, India.

BioMeditech and Tays Cancer Center, Tampere University Hospital, P.O. Box 553, 33101 Tampere, Finland; Molecular Signaling Group, Faculty of Medicine and Health Technology, Tampere University, P.O. Box 553, 33101 Tampere, Finland.

出版信息

Biomed Pharmacother. 2023 Mar;159:114288. doi: 10.1016/j.biopha.2023.114288. Epub 2023 Jan 20.

DOI:10.1016/j.biopha.2023.114288

PMID:36682245

Abstract

Plants that are pharmacologically significant require intensive phytochemical characterization for bioactive profiling of the compounds, which has enabled their safe use in ayurvedic medicine. The present study is focused on the phytochemical analyses, quantitative estimation and profiling of secondary metabolites of leaf extract, as well as the antioxidant and cytotoxic activity of the potent halophytes such as Avicennia marina, Ceriops tagal, Ipomoea pes-caprae, and Sonneratia apetala. The in vitro antioxidant property was investigated using DPPH, ferric reducing antioxidant capacity (FRAP) assay. Bioactive compounds such as phenols, flavonoids, saponin and alkaloids were quantitatively estimated from the extracts of A.marina, C.tagal, I.pes-capra and S.apetala, which possessed higher phenol content than the other studied halophytes. The extracts at 200 µg/ml revealed higher antioxidant activity than the standard ascorbic acid and it functions as a powerful oxygen free radical scavenger with 77.37%, 75.35% and 72.84% for S.apetala, I.pes-caprae and C.tagal respectively and with least IC for I.pes-caprae (11.95 µg/ml) followed by C.tagal (49.94 µg/ml). Cell viability and anti-proliferative activity of different polyphenolic fractions of C.tagal (CT1 and CT2) and I.pes-caprae fraction (IP) against LN229, SNB19 revealed Ipomoea as the promising anti-cytotoxic fraction. IP-derived polyphenols was further subjected to apoptosis, migration assay, ROS and caspase - 3 and - 7 to elucidate its potentiality as a therapeutic drug. IP-polyphenols was found to have higher percentage of inhibition than the CT1 and CT2 polyphenols of C.tagal on comparison with TMZ. All the above-mentioned in-vitro analysis further validated the ability of IP-polyphenols inducing cell death via ROS-mediated caspase dependent pathway. Further, proteomic and phospho-proteomic analysis revealed the potential role of IP-polyphenols in the regulation of cell proliferation through MMK3, p53, p70 S6 kinase and RSK1 proteins involved in mitogen-activated protein kinase signaling pathway. Our analysis confirmed the promising role of I.pes-caprae derived polyphenols as an anti-metastatic compound against GBM cells.

摘要

具有药理意义的植物需要进行深入的植物化学特征分析，以对化合物进行生物活性分析，从而实现其在顺势疗法中的安全使用。本研究集中于对叶提取物的次生代谢产物进行植物化学分析、定量估计和分析，以及对盐生植物如互花米草、桐花树、番薯和海桑的抗氧化和细胞毒性活性进行研究。使用 DPPH 和铁还原抗氧化能力 (FRAP) 测定法来研究体外抗氧化特性。从互花米草、桐花树、番薯和海桑的提取物中定量估计了生物活性化合物，如酚类、类黄酮、皂苷和生物碱，这些植物的酚类含量高于其他研究的盐生植物。在 200µg/ml 时，提取物表现出比标准抗坏血酸更高的抗氧化活性，并且作为一种强大的氧自由基清除剂，其对海桑、番薯和桐花树的清除率分别为 77.37%、75.35%和 72.84%，对番薯的最低 IC 为 11.95µg/ml，其次是桐花树（49.94µg/ml）。不同桐花树（CT1 和 CT2）和番薯多酚类馏分（IP）对 LN229 和 SNB19 的细胞活力和抗增殖活性表明，番薯是有前途的抗细胞毒性馏分。进一步对 IP 衍生的多酚类物质进行凋亡、迁移试验、ROS 和 caspase-3 和 -7 分析，以阐明其作为治疗药物的潜力。与 TMZ 相比，发现 IP 多酚类物质对 CT1 和 CT2 多酚类物质的抑制百分比更高。所有上述体外分析进一步验证了 IP 多酚类物质通过 ROS 介导的 caspase 依赖性途径诱导细胞死亡的能力。此外，蛋白质组学和磷酸化蛋白质组学分析表明，IP 多酚类物质通过参与丝裂原活化蛋白激酶信号通路的 MMK3、p53、p70 S6 激酶和 RSK1 蛋白，在细胞增殖的调节中发挥潜在作用。我们的分析证实了番薯衍生多酚类物质作为抗 GBM 细胞转移化合物的有希望的作用。