School of Food and Biological Engineering, Hefei University of Technology, Hefei, 230009, P. R. China.
Center of Scientific Research, Anhui Medical University, Hefei, 230032, P. R. China.
Chem Biodivers. 2022 Aug;19(8):e202200471. doi: 10.1002/cbdv.202200471. Epub 2022 Jul 14.
Dendrobium huoshanense flowers have been widely used for liver protection in China. This work was aimed to discover the natural products with activity of mitigating alcoholic hepatocyte injury from Dendrobium huoshanense flowers via bioactivity-guided isolation, and to clarify the underlying mechanisms of these natural products. As a result, three flavonoids, 3'-O-methylquercetin-3-O-β-D-galactopyranoside (1), 3'-O-methylquercetin-3-O-β-D-glucopyranoside (2) and quercetin-3-O-β-D-glucopyranoside (3), were firstly isolated from D. huoshanense flowers. Results exhibited that flavonoids 1-3 could enhance the cell viability, decrease the expression of ALT and AST, inhibit the cell apoptosis, alleviate the oxidative stress, and mitigate the inflammatory response of alcohol-induced L02 cells. Mechanism study exhibited that flavonoids 1-3 could increase the expression of Nrf2 as well as its downstream antioxidation genes of alcohol-induced L02 cells, while ML-385 (Nrf2 inhibitor) could abolish the inhibitory effects of 1-3 on alcohol-induced hepatocyte injury. Flavonoids 1-3 could also reduce the phosphorylation levels of IκBα and NF-κB p65 of alcohol-induced L02 cells, while SC75741 (NF-κB inhibitor) could not enhance the inhibitory effects of 1-3 on alcohol-induced L02 cells injury. The data above indicated that flavonoids 1-3 could inhibit alcohol-induced hepatocyte injury, which might be attributed to alleviating oxidative stress and mitigating inflammatory response by activating Nrf2 and inhibiting NF-κB pathways.
霍山石斛花在中国被广泛用于肝脏保护。本研究旨在通过活性导向分离，从霍山石斛花中发现具有减轻酒精性肝细胞损伤活性的天然产物，并阐明这些天然产物的作用机制。结果首次从霍山石斛花中分离得到三种黄酮类化合物：3'-O-甲基槲皮素-3-O-β-D-半乳糖苷（1）、3'-O-甲基槲皮素-3-O-β-D-葡萄糖苷（2）和槲皮素-3-O-β-D-葡萄糖苷（3）。结果表明，黄酮类化合物 1-3 能够提高细胞活力，降低 ALT 和 AST 的表达，抑制细胞凋亡，减轻氧化应激，减轻酒精诱导的 L02 细胞炎症反应。机制研究表明，黄酮类化合物 1-3 能够增加酒精诱导的 L02 细胞中 Nrf2 及其下游抗氧化基因的表达，而 ML-385（Nrf2 抑制剂）能够消除 1-3 对酒精诱导的肝细胞损伤的抑制作用。黄酮类化合物 1-3 还能够降低酒精诱导的 L02 细胞中 IκBα和 NF-κB p65的磷酸化水平，而 SC75741（NF-κB 抑制剂）不能增强 1-3 对酒精诱导的 L02 细胞损伤的抑制作用。上述数据表明，黄酮类化合物 1-3 能够抑制酒精性肝细胞损伤，这可能归因于通过激活 Nrf2 并抑制 NF-κB 途径来减轻氧化应激和炎症反应。
