Department of Pharmacy, Zunyi Medical University, Zunyi, China, 563000.
Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, China.
Comb Chem High Throughput Screen. 2023;26(15):2718-2729. doi: 10.2174/1386207326666230330150211.
Lindl. (DNL) is effective for the treatment of alcoholic liver disease (ALD), but the underly mechanism is still unclear.
This research aimed to investigate the effects and mechanism of the aqueous extract of Lindl (AEDNL) in ALD rats based on a metabolomics approach.
In this study, 18 Sprague-Dawley male rats were randomly divided into control, model, and AEDNL groups (n=six). Rats in the AEDNL group were given AEDNL (152 mg/kg) intragastric administration from the first day for 30 consecutive days. From day 15 to day 30, model and AEDNL groups were given 30% ethanol (10 ml/kg) after 4 h of daily administration. Then, serum and liver samples were collected for biochemical analysis, histopathological examination, and Ultra Performance Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry (UPLC-Q-TOF/MS) determination for metabolomic analysis.
Compared with the model group, the liver/body weight index and serum levels of TC, LDL-C, and TBIL in the AEDNL group were significantly decreased. Hepatocyte cord arrangement, hepatocyte balloon, and fat vacuolization were significantly improved in the AEDNL group. Metabolism profiles were changed in the model and AEDNL groups. Seven and two common differential metabolites (Guanosine3',5'-cyclic monophosphate, and Glutaric acid) were found in serum and liver, respectively. In addition, the hepatoprotective effect of AEDNL on ALD was related to steroid hormone biosynthesis, riboflavin metabolism, and glycerophospholipid metabolism.
The research could provide novel evidence of the protective effects of AEDNL on ALD.
Lindl.（DNL）可有效治疗酒精性肝病（ALD），但其作用机制尚不清楚。
本研究旨在基于代谢组学方法探讨 Lindl. 水提物（AEDNL）对 ALD 大鼠的作用及机制。
本研究中，18 只雄性 Sprague-Dawley 大鼠随机分为对照组、模型组和 AEDNL 组（每组 6 只）。AEDNL 组大鼠连续 30 天每天给予 AEDNL（152mg/kg）灌胃。从第 15 天到第 30 天，模型组和 AEDNL 组在每天给药后 4 小时给予 30%乙醇（10ml/kg）。然后收集血清和肝组织样本，进行生化分析、组织病理学检查和超高效液相色谱-四极杆飞行时间质谱（UPLC-Q-TOF/MS）代谢组学分析。
与模型组相比，AEDNL 组大鼠肝体比和血清 TC、LDL-C、TBIL 水平显著降低，肝细胞索排列、肝细胞气球样变和脂肪空泡化明显改善。模型组和 AEDNL 组的代谢谱发生了变化。在血清和肝脏中分别发现了 7 个和 2 个共同的差异代谢物（鸟苷 3'，5'-环单磷酸和戊二酸）。此外，AEDNL 对 ALD 的保肝作用与甾体激素生物合成、核黄素代谢和甘油磷脂代谢有关。
本研究可为 AEDNL 对 ALD 的保护作用提供新的证据。
