Department of Pharmacognosy, Faculty of Pharmacy, Ain-Shams University, 11566, Cairo, Egypt.
Department of Biotechnology, College of Life Science, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan; Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan, 33302, Taiwan; Research Center for Chinese Herbal Medicine, Research Center for Food and Cosmetic Safety, and Graduate Institute of Health Industry Technology, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, 33302, Taiwan.
Phytochemistry. 2020 Sep;177:112429. doi: 10.1016/j.phytochem.2020.112429. Epub 2020 Jun 16.
Ellagitannins have a marked antioxidant effect and can prevent liver injury induced by free radicals. An undescribed ellagitannin named styphelioidin was isolated from Melaleuca styphelioides Sm. The structure of styphelioidin was elucidated by using various spectroscopic methods. The hepatoprotective activity of styphelioidin (25, 50, and 100 μM) was tested using the CCl-challenged HepG2 cell model by measuring alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in HepG2 cells treated with styphelioidin for 1 h followed by 40 mM CCl. Glutathione (GSH), superoxide dismutase activity (SOD) and lipid peroxidation (MDA) were evaluated to determine the mechanisms of the hepatoprotective activity. Styphelioidin significantly reduced the levels of ALT, AST, and MDA at all tested concentrations. Moreover, it conferred a marked increase in the GSH levels and the SOD activity compared to the CCl-treated groups. Styphelioidin also exerted DPPH· radical-scavenging effects with an IC value of 3.67 μM. Results indicated the hepatoprotective therapeutic potential of styphelioidin comparable to silymarin. Moreover, anti-inflammatory activity was assessed and styphelioidin inhibited fMLF/CB-induced elastase release in human neutrophils with IC 2.51 μM. Cell-free experiments with human neutrophil elastase indicated a direct enzymatic inhibitory effect of styphelioidin on the enzyme activity (IC 2.58 μM). The potential of styphelioidin to interact with human neutrophil elastase binding sites was further confirmed by molecular docking of styphelioidin into human neutrophil elastase crystal structure using AutoDock 4.2. Styphelioidin represents a potent hepatoprotective and antioxidant agent with effects on ALT, AST, MDA, GSH, and SOD comparable to silymarin. The beneficial anti-elastase properties hold the potential for drug development against elastase-related inflammatory diseases. This study highlights a promising natural hepatoprotective and anti-inflammatory candidate derived from M. styphelioides.
鞣花单宁具有明显的抗氧化作用，可以预防自由基引起的肝损伤。一种未被描述的鞣花单宁名为石蒜醇苷，从千层树（Melaleuca styphelioides Sm.）中分离出来。通过使用各种光谱方法阐明了石蒜醇苷的结构。通过测量用石蒜醇苷处理的 HepG2 细胞中丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）水平，测试了石蒜醇苷（25、50 和 100 μM）在 CCl 挑战的 HepG2 细胞模型中的肝保护活性，随后用 40 mM CCl 处理 HepG2 细胞 1 小时。评估了谷胱甘肽（GSH）、超氧化物歧化酶活性（SOD）和脂质过氧化（MDA）以确定肝保护活性的机制。石蒜醇苷在所有测试浓度下均显著降低 ALT、AST 和 MDA 的水平。此外，与 CCl 处理组相比，它显著增加了 GSH 水平和 SOD 活性。石蒜醇苷还表现出 DPPH·自由基清除作用，IC 值为 3.67 μM。结果表明石蒜醇苷具有与水飞蓟素相当的肝保护治疗潜力。此外，评估了抗炎活性，石蒜醇苷抑制 fMLF/CB 诱导的人中性粒细胞弹性蛋白酶释放，IC 2.51 μM。用人中性粒细胞弹性蛋白酶进行无细胞实验表明，石蒜醇苷对酶活性具有直接的酶抑制作用（IC 2.58 μM）。通过使用 AutoDock 4.2 将石蒜醇苷对接入人中性粒细胞弹性蛋白酶晶体结构，进一步证实了石蒜醇苷与人中性粒细胞弹性蛋白酶结合位点相互作用的潜力。石蒜醇苷是一种有效的肝保护和抗氧化剂，其对 ALT、AST、MDA、GSH 和 SOD 的作用与水飞蓟素相当。有益的抗弹性酶特性为开发针对弹性酶相关炎症性疾病的药物提供了潜力。本研究强调了一种有前途的源自千层树的天然肝保护和抗炎候选物。
