Quantitative Profiling of Oxylipin Reveals the Mechanism of Pien-Tze-Huang on Alcoholic Liver Disease

Abstract

Alcoholic liver disease (ALD) is a liver disease caused by long-term alcohol consumption. ROS-mediated oxidative stress is the leading cause of ALD. Pien-Tze-Huang (PZH), a traditional formula, is famous in China. This study was designed to evaluate the effects and explore the potential mechanisms of PZH in ALD. Forty mice were randomly divided into five groups: control group (normal diet + vehicle), model group (ethanol diet + vehicle), PZH-L group (ethanol diet + PZH (0.125 g/kg)), PZH-M group (ethanol diet + PZH (0.25 g/kg)), and PZH-H group (ethanol diet + PZH (0.5 g/kg)). The mice were sacrificed, and their liver and blood samples were preserved. Liver steatosis, triglyceride (TG), total cholesterol, serum alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels were assayed. Malondialdehyde (MDA), glutathione peroxidase (GSH-PX), and total superoxide dismutase were identified using commercial kits. Oxylipins were profiled, and the data were analyzed. The AMPK/ACC/CPT1A pathway was identified using real-time polymerase chain reaction and western blotting. The PZH-H intervention significantly alleviated hepatic steatosis and injury and reduced the levels of liver TG and serum ALT and AST. In addition, MDA levels were markedly reduced, and GSH-PX activity significantly increased after PZH-H intervention. Finally, PZH-H increased the levels of 17-HETE, 15-HEPE, 9-HOTrE, 13-HOTrE, and 5,6-dihydroxy-8Z,11Z,14Z,17Z-eicosatetraenoic acid, and reduced PGE2 levels. PZH-H intervention also promoted the phosphorylation of AMPK and ACC, and the expression of CPT1A. In conclusion, PZH reduced oxidative stress and alleviated hepatic steatosis and injury. The mechanism was correlated with the oxylipin metabolites/AMPK/ACC/CPT1A axis.

Suppression of endoplasmic reticulum stress-associated pathways and hepatocyte apoptosis participates in the attenuation of betulinic acid on alcohol-provoked liver injury in mice

“…ALD is a common clinical liver disease caused by long-term or short-term heavy alcohol consumption. 33 In the early stage, it usually manifests with alcoholic fatty liver and then gradually develops into AH, liver fibrosis, and liver cirrhosis. 25 With the rapid increase in the incidence of ALD worldwide, it has become an important public health problem.…”

Exploring the effect of Yinzhihuang granules on alcoholic liver disease based on pharmacodynamics, network pharmacology and molecular docking

“…Western medicine can improve liver injury to some extent, but it is easy to tolerate and the clinical effect is not significant [ 11 , 12 ]. Traditional Chinese medicine has a long history in the treatment of ALD and has accumulated a lot of valuable experience and characteristic drugs, which are a great treasure for drug development [ 13 – 15 ].…”

A Review of Herbal Resources Inducing Anti-Liver Metastasis Effects in Gastrointestinal Tumors via Modulation of Tumor Microenvironments in Animal Models

“…As shown in Table 2 , 9 of the 15 candidates previously reported beneficial effects against at least one of the three pathologic conditions. Four compounds (curcumin, emodin, honokiol, and tanshinone II-A) and two decoctions ( Juzen-taiho-to and Pien tze huang ) previously showed beneficial effects on three pathologic states [ 26 , 27 , 28 , 29 , 37 , 38 , 41 , 42 ]. Deoxyelephantopin showed positive effects against liver inflammation [ 40 ], while extracts of both Annona muricata L. and Celastrus orbiculatus T. showed effects on liver steatosis and inflammation [ 30 , 33 , 34 , 39 ].…”

“…As shown in Table 2, 9 of the 15 candidates previously reported beneficial effects against at least one of the three pathologic conditions. Four compounds (curcumin, emodin, honokiol, and tanshinone II-A) and two decoctions (Juzen-taiho-to and Pien tze huang) previously showed beneficial effects on three pathologic states [26][27][28][29]37,38,41,42]. Deoxyelephantopin showed positive effects against…”

“…Steatosis, inflammation, and fibrosis [37,38] Pientzehuang Colon CT-26 (oi) and decoction (po) [7] Decreases TGF-β, increases E-cadherin, and suppresses N-cadherin expression at the original site (colon)…”