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 CCl4-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 CCl4. 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 CCl4-treated groups. Styphelioidin also exerted DPPH· radical-scavenging effects with an IC50 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 IC50 2.51 μM. Cell-free experiments with human neutrophil elastase indicated a direct enzymatic inhibitory effect of styphelioidin on the enzyme activity (IC50 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.

中文翻译：

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从白千层中分离的鞣花单宁的抗炎、保肝和抗氧化活性

鞣花单宁具有显着的抗氧化作用，可以预防自由基引起的肝损伤。从 Melaleuca styphelioides Sm 中分离出一种名为 styphelioidin 的未描述的鞣花单宁。使用多种光谱方法阐明了花椒苷的结构。使用 CCl4 攻击的 HepG2 细胞模型，通过测量用 styphelioidin 处理的 HepG2 细胞中的丙氨酸氨基转移酶 (ALT) 和天冬氨酸氨基转移酶 (AST) 水平来测试 styphelioidin（25、50 和 100 μM）的保肝活性，然后 40 mM CCl4。评估谷胱甘肽 (GSH)、超氧化物歧化酶活性 (SOD) 和脂质过氧化 (MDA) 以确定保肝活性的机制。在所有测试浓度下，Styphelioidin 都显着降低了 ALT、AST 和 MDA 的水平。而且，与 CCl4 处理组相比，它使 GSH 水平和 SOD 活性显着增加。Styphelioidin 还发挥 DPPH· 自由基清除作用，IC50 值为 3.67 μM。结果表明甜菊素的保肝治疗潜力与水飞蓟素相当。此外，还评估了抗炎活性，并且在人中性粒细胞中，styphelioidin 抑制 fMLF/CB 诱导的弹性蛋白酶释放，IC50 为 2.51 μM。用人中性粒细胞弹性蛋白酶进行的无细胞实验表明，甜菊素对酶活性有直接的酶抑制作用 (IC50 2.58 μM)。通过使用 AutoDock 4.2 将 styphelioidin 分子对接到人类中性粒细胞弹性蛋白酶晶体结构中，进一步证实了 styphelioidin 与人类中性粒细胞弹性蛋白酶结合位点相互作用的潜力。Styphelioidin 是一种有效的保肝和抗氧化剂，对 ALT、AST、MDA、GSH 和 SOD 的影响与水飞蓟素相当。有益的抗弹性蛋白酶特性具有开发针对弹性蛋白酶相关炎症疾病的药物的潜力。这项研究突出了一种有希望的天然保肝和抗炎候选物，来自 M. styphelioides。