Chen Jingcai, Zhang Qi, Wang Ruhui, Yang Yong, Wang Yu, Liu Xiang, Zhang Xiaomei, Qiao Xingfang, Zhong Guoyue, Wei Jiangping, Wang Yunhong, Yang Rongping
Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.
Chongqing Academy of Chinese Materia Medica, Chongqing, 400060, China; Zunyi Medical University, Guizhou, 563006, China.
J Ethnopharmacol. 2023 May 23;308:116230. doi: 10.1016/j.jep.2023.116230. Epub 2023 Feb 9.
Meconopsis quintuplinervia Regel (MQR) belongs to the opium poppy tree plant species, and it has heat purging, detoxification, diuretic, anti-inflammatory, and analgesic effects.
MQR has liver-protective properties and can alleviate liver heat. Therefore, this study aimed to observe the effect of MQR extract on acute alcoholic liver injury in mice and explore the mechanism of action of ethyl acetate extract of MQR (MQR-E) on alcohol-induced liver injury in combination with the network pharmacology.
To induce acute alcoholic liver injury, 52% of edible wine was administered at 12 mL/kg for 14 days. The pharmacodynamic results were used to screen the active site. MQR-E composition was analyzed based on UPLC-Q-TOF-MS, and relevant MQR-E and alcoholic liver disease (ALD) targets were screened using an online database. Then, Venn analysis of drug and disease-related targets was performed to obtain cross-targets. We investigated the protein-protein interaction network (PPI) of overlapping targets, the core targets were screened using the STRING database, and the DAVID database was chosen for GO and KEGG enrichment analysis of the central targets.
Each of the four MQR extracts ameliorated alcoholic liver injury to varying degrees; the best results were achieved with MQR-E. MQR-E reduces liver index, serum transaminases, and fat accumulation, and attenuates ethanol-induced histopathological changes. The activities of hepatic superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) were increased, the content of malondialdehyde (MDA) was significantly reduced compared to the EtOH group, and MQR-E effectively mitigated the oxidative stress induced by ethanol in the liver. Thirty-six compounds were identified, and flavonoids were the most abundant. PPI network topology analysis was employed to assess 32 core targets: IL-6, TNF, STAT3, PPARA, and other inflammation and lipid metabolism related genes. Pathway analysis of GO and KEGG enrichment showed that the regulation of inflammatory factors and lipid metabolism were primarily involved.
We concluded that MQR-E had protective effects against acute alcohol-induced liver injury in mice, and the mechanism could be linked to the inhibition of lipid peroxidation and oxidative stress. The mechanism by which MQR-E ameliorated ALD primarily involved regulating inflammatory factors and lipid metabolism based on the prediction of the network pharmacology.
五脉绿绒蒿（MQR）属于罂粟科植物，具有清热、解毒、利尿、抗炎和镇痛作用。
MQR具有肝脏保护特性，可清肝热。因此，本研究旨在观察MQR提取物对小鼠急性酒精性肝损伤的影响，并结合网络药理学探讨五脉绿绒蒿乙酸乙酯提取物（MQR-E）对酒精性肝损伤的作用机制。
为诱导急性酒精性肝损伤，以12 mL/kg的剂量给予52%的食用酒，持续14天。药效学结果用于筛选活性部位。基于超高效液相色谱-四极杆飞行时间质谱（UPLC-Q-TOF-MS）分析MQR-E的成分，并使用在线数据库筛选相关的MQR-E和酒精性肝病（ALD）靶点。然后，对药物和疾病相关靶点进行韦恩分析以获得交叉靶点。我们研究了重叠靶点的蛋白质-蛋白质相互作用网络（PPI），使用STRING数据库筛选核心靶点，并选择DAVID数据库对核心靶点进行基因本体（GO）和京都基因与基因组百科全书（KEGG）富集分析。
四种MQR提取物均不同程度地改善了酒精性肝损伤；MQR-E的效果最佳。MQR-E降低肝脏指数、血清转氨酶和脂肪堆积，并减轻乙醇诱导的组织病理学变化。与乙醇组相比，肝超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-PX）的活性增加，丙二醛（MDA）含量显著降低，并且MQR-E有效减轻了乙醇在肝脏中诱导的氧化应激。鉴定出36种化合物，其中黄酮类化合物含量最为丰富。采用PPI网络拓扑分析评估32个核心靶点：白细胞介素-6（IL-6）、肿瘤坏死因子（TNF）、信号转导和转录激活因子3（STAT3）、过氧化物酶体增殖物激活受体α（PPARA）以及其他与炎症和脂质代谢相关的基因。GO和KEGG富集的通路分析表明，主要涉及炎症因子调节和脂质代谢。
我们得出结论，MQR-E对小鼠急性酒精性肝损伤具有保护作用，其机制可能与抑制脂质过氧化和氧化应激有关。基于网络药理学预测，MQR-E改善ALD的机制主要涉及调节炎症因子和脂质代谢。
