Exploring the mechanism of PingTang No.5 capsule on nonalcoholic fatty liver disease through network pharmacology and experimental validation

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease and is associated with high morbidity and mortality. Pogostemon cablin (Blanco) Benth/Huo Xiang (HX) is a perennial herb with unique anti-oxidant and anti-inflammatory properties, and thus, can positively affect liver function. In this study, we used network pharmacology to predict the potential mechanism of HX on NAFLD. Pharmacological experiments were used to verify the effect of HX on the functions of NAFLD. Network pharmacology identified nine components that interacted with 82 NAFLD-related targets, revealing four target genes: TNF, IL6, TP53, and AKT1. HX prevents the development and progression of NAFLD through different pathways and targets with quercetin-regulated lipid metabolism, anti-inflammatory, and anti-oxidant pathways playing an essential role in the treatment of NAFLD. Compared with feeding HFD, HX significantly attenuated lipid accumulation in vivo with mice and also in vitro with mouse liver cells. A high dose of HX decreased hepatocyte lipid accumulation and the abundance of SREBF1 and FASN. Validation experiments revealed that HX inhibited the activation of NF-κB/IκB signaling and decreased the release and levels of pro-inflammatory factors (TNF-α and IL-6). These data suggest that HX can attenuate abnormal lipid metabolic responses and enhance antioxidant mechanisms. Thus, the pharmacological effects from plants used in traditional Chinese medicine are achievde through a multi-level response.

Download Full-text

Gynostemma pentaphyllum Attenuates the Progression of Nonalcoholic Fatty Liver Disease in Mice: A Biomedical Investigation Integrated with In Silico Assay

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2018/8384631 ◽

2018 ◽

Vol 2018 ◽

pp. 1-13 ◽

Cited By ~ 8

Author(s):

Ming Hong ◽

Zhe Cai ◽

Lei Song ◽

Yongqiang Liu ◽

Qi Wang ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

In Silico ◽

Fatty Liver Disease ◽

Critical Role ◽

Network Pharmacology ◽

Gynostemma Pentaphyllum ◽

Nonalcoholic Fatty Liver ◽

Mitochondrial Fatty Acid

Nonalcoholic fatty liver disease (NAFLD) is the most common type of liver disease in developed countries. Oxidative stress plays a critical role in the progression of NAFLD. Modern pharmacological study and clinical trials have demonstrated the remarkable antioxidant activity of Gynostemma pentaphyllum (GP) in chronic liver disease. One aim of this study was to explore the potential protective effects and mechanisms of action of GP extract on NAFLD. The in vivo results showed that GP extract could alleviate fatty degeneration and haptic fibrosis in NAFLD mice. For exploring the hepatoprotective mechanisms of GP, we used network pharmacology to predict the potential active components of GP and their intracellular targets in NAFLD. Based on the network pharmacology results, we further utilized biomedical assays to validate this in silico prediction. The results showed that Gypenoside XL could upregulate the protein level of PPARα in NAFLD; the transcription level of several PPARα downstream target genes such as acyl-CoA oxidase (ACO) and carnitine palmitoyltransferase-1 (CPT-1) also increased after Gypenoside XL treatment. The overexpression of ACO and CPT-1 may involve the hepatoprotective effects of GP and Gypenoside XL on NAFLD by regulating mitochondrial fatty acid β-oxidation.

Download Full-text

Research on the Mechanism of Qushi Huayu Decoction in the Intervention of Nonalcoholic Fatty Liver Disease Based on Network Pharmacology and Molecular Docking Technology

BioMed Research International ◽

10.1155/2020/1704960 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12

Author(s):

Shan-shan Gao ◽

Ji-jia Sun ◽

Xin Wang ◽

Yi-yang Hu ◽

Qin Feng ◽

...

Keyword(s):

Molecular Docking ◽

Liver Disease ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Signaling Pathway ◽

Active Ingredient ◽

Fatty Liver Disease ◽

Network Pharmacology ◽

Chemical Components ◽

Nonalcoholic Fatty Liver

Objective. To use network pharmacology and molecular docking technology in predicting the main active ingredients and targets of Qushi Huayu Decoction (QHD) treatment in Nonalcoholic Fatty Liver Disease (NAFLD) and explore the potential mechanisms of its multi-component-multi-target-multi-pathway. Materials and Methods. The main chemical components of QHD were searched using traditional Chinese medicine system pharmacology technology platform (TCMSP) and PubChem database. The main chemical components of the prescription were ADMET screened by the ACD/Labs software. The main active ingredient was screened by 60% oral bioavailability, and 60% of “bad” ingredients were removed from the drug-like group. Swiss Target Prediction, the SEA, and HitPick systems were sequentially used to search for the target of each active ingredient, and a network map of the QHD’s target of the active ingredient was constructed. Genome annotation database platforms (GeneCards, OMIM, and DisGeNET) were used to predict action targets related to fatty liver disease. “Drug-Disease-Target” network diagram could be visualized with the help of Cytoscape (3.7.1) software. UniProt and STRING database platforms were used to build a protein interaction network. The KEGG signal pathway and DAVID platform were analyzed for biological process enrichment. Results. A total of 128 active ingredients and 275 corresponding targets in QHD were discovered through screening. 55 key target targets and 27 important signaling pathways were screened, such as the cancer pathway, P13K-AKT signaling pathway, PPAR signaling pathway, and other related signaling pathways. Conclusions. The present study revealed the material basis of QHD and discussed the pharmacological mechanism of QHD in fatty liver, thus providing a scientific basis for the clinical application and experimental research of QHD in the future.

Download Full-text