Exploring the Mechanism of Dangguiliuhuang Decoction Against Hepatic Fibrosis by Network Pharmacology and Experimental Validation
Dangguiliuhuang decoction (DGLHD) has been demonstrated to be effective in treating inflammatory, hepatic steatosis, and insulin resistance. In the study, we tried to elucidate the pharmacological efficacy and mechanism of DGLHD against liver fibrosis and predicate potential active ingredients and t...
Main Authors: | , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Frontiers Media S.A.
2018-03-01
|
Series: | Frontiers in Pharmacology |
Subjects: | |
Online Access: | http://journal.frontiersin.org/article/10.3389/fphar.2018.00187/full |
id |
doaj-9b0174ab959b4b16b96342c58908e48c |
---|---|
record_format |
Article |
spelling |
doaj-9b0174ab959b4b16b96342c58908e48c2020-11-24T23:05:06ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122018-03-01910.3389/fphar.2018.00187347092Exploring the Mechanism of Dangguiliuhuang Decoction Against Hepatic Fibrosis by Network Pharmacology and Experimental ValidationHui Cao0Senlin Li1Rui Xie2Na Xu3Ying Qian4Hongdan Chen5Qinyu Hu6Yihong Quan7Zhihong Yu8Junjun Liu9Ming Xiang10School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaSchool of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaSchool of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaSchool of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaSchool of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaSchool of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaSchool of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Traditional Chinese Medicine, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Traditional Chinese Medicine, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaSchool of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaSchool of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDangguiliuhuang decoction (DGLHD) has been demonstrated to be effective in treating inflammatory, hepatic steatosis, and insulin resistance. In the study, we tried to elucidate the pharmacological efficacy and mechanism of DGLHD against liver fibrosis and predicate potential active ingredients and targets via network analysis and experimental validation. In the formula, we totally discovered 76 potential active ingredients like baicalein, berberine, and wogonin, and 286 corresponding targets including PTGS (prostaglandin-endoperoxide synthase) 2, PPAR (peroxisome proliferator-activated receptors) -γ, and NF-κB (nuclear factor-κB). Pathway and functional enrichment analysis of these putative targets indicated that DGLHD obviously influenced NF-κB and PPAR signaling pathway. Consistently, DGLHD downregulated levels of ALT (alanine transaminase) and AST (aspartate transaminase), reduced production of proinflammatory cytokines-TNF (tumor necrosis factor) -α and IL (Interleukin) -1β in serum and liver from mice with hepatic fibrosis, and inhibited hepatic stellate cell (HSC)-T6 cells proliferation. DGLHD decreased TGF (transforming growth factor) -β1 and α-SMA (smooth muscle actin) expression as well, maintained MMP (matrix metalloprotein) 13-TIMP (tissue inhibitor of metalloproteinases) 1 balance, leading to mitigated ECM (extracellular matrix) deposition in vivo and in vitro. Moreover, our experimental data confirmed that the alleviated inflammation and ECM accumulation were pertinent to NF-κB inhibition and PPAR-γ activation. Overall, our results suggest that DGLHD aims at multiply targets and impedes the progression of hepatic fibrosis by ameliorating abnormal inflammation and ECM deposition, thereby serving as a novel regimen for treating hepatic fibrosis in clinic.http://journal.frontiersin.org/article/10.3389/fphar.2018.00187/fullDangguiliuhuang decoctionhepatic fibrosisnetwork pharmacologyPPAR-γNF-κB |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hui Cao Senlin Li Rui Xie Na Xu Ying Qian Hongdan Chen Qinyu Hu Yihong Quan Zhihong Yu Junjun Liu Ming Xiang |
spellingShingle |
Hui Cao Senlin Li Rui Xie Na Xu Ying Qian Hongdan Chen Qinyu Hu Yihong Quan Zhihong Yu Junjun Liu Ming Xiang Exploring the Mechanism of Dangguiliuhuang Decoction Against Hepatic Fibrosis by Network Pharmacology and Experimental Validation Frontiers in Pharmacology Dangguiliuhuang decoction hepatic fibrosis network pharmacology PPAR-γ NF-κB |
author_facet |
Hui Cao Senlin Li Rui Xie Na Xu Ying Qian Hongdan Chen Qinyu Hu Yihong Quan Zhihong Yu Junjun Liu Ming Xiang |
author_sort |
Hui Cao |
title |
Exploring the Mechanism of Dangguiliuhuang Decoction Against Hepatic Fibrosis by Network Pharmacology and Experimental Validation |
title_short |
Exploring the Mechanism of Dangguiliuhuang Decoction Against Hepatic Fibrosis by Network Pharmacology and Experimental Validation |
title_full |
Exploring the Mechanism of Dangguiliuhuang Decoction Against Hepatic Fibrosis by Network Pharmacology and Experimental Validation |
title_fullStr |
Exploring the Mechanism of Dangguiliuhuang Decoction Against Hepatic Fibrosis by Network Pharmacology and Experimental Validation |
title_full_unstemmed |
Exploring the Mechanism of Dangguiliuhuang Decoction Against Hepatic Fibrosis by Network Pharmacology and Experimental Validation |
title_sort |
exploring the mechanism of dangguiliuhuang decoction against hepatic fibrosis by network pharmacology and experimental validation |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Pharmacology |
issn |
1663-9812 |
publishDate |
2018-03-01 |
description |
Dangguiliuhuang decoction (DGLHD) has been demonstrated to be effective in treating inflammatory, hepatic steatosis, and insulin resistance. In the study, we tried to elucidate the pharmacological efficacy and mechanism of DGLHD against liver fibrosis and predicate potential active ingredients and targets via network analysis and experimental validation. In the formula, we totally discovered 76 potential active ingredients like baicalein, berberine, and wogonin, and 286 corresponding targets including PTGS (prostaglandin-endoperoxide synthase) 2, PPAR (peroxisome proliferator-activated receptors) -γ, and NF-κB (nuclear factor-κB). Pathway and functional enrichment analysis of these putative targets indicated that DGLHD obviously influenced NF-κB and PPAR signaling pathway. Consistently, DGLHD downregulated levels of ALT (alanine transaminase) and AST (aspartate transaminase), reduced production of proinflammatory cytokines-TNF (tumor necrosis factor) -α and IL (Interleukin) -1β in serum and liver from mice with hepatic fibrosis, and inhibited hepatic stellate cell (HSC)-T6 cells proliferation. DGLHD decreased TGF (transforming growth factor) -β1 and α-SMA (smooth muscle actin) expression as well, maintained MMP (matrix metalloprotein) 13-TIMP (tissue inhibitor of metalloproteinases) 1 balance, leading to mitigated ECM (extracellular matrix) deposition in vivo and in vitro. Moreover, our experimental data confirmed that the alleviated inflammation and ECM accumulation were pertinent to NF-κB inhibition and PPAR-γ activation. Overall, our results suggest that DGLHD aims at multiply targets and impedes the progression of hepatic fibrosis by ameliorating abnormal inflammation and ECM deposition, thereby serving as a novel regimen for treating hepatic fibrosis in clinic. |
topic |
Dangguiliuhuang decoction hepatic fibrosis network pharmacology PPAR-γ NF-κB |
url |
http://journal.frontiersin.org/article/10.3389/fphar.2018.00187/full |
work_keys_str_mv |
AT huicao exploringthemechanismofdangguiliuhuangdecoctionagainsthepaticfibrosisbynetworkpharmacologyandexperimentalvalidation AT senlinli exploringthemechanismofdangguiliuhuangdecoctionagainsthepaticfibrosisbynetworkpharmacologyandexperimentalvalidation AT ruixie exploringthemechanismofdangguiliuhuangdecoctionagainsthepaticfibrosisbynetworkpharmacologyandexperimentalvalidation AT naxu exploringthemechanismofdangguiliuhuangdecoctionagainsthepaticfibrosisbynetworkpharmacologyandexperimentalvalidation AT yingqian exploringthemechanismofdangguiliuhuangdecoctionagainsthepaticfibrosisbynetworkpharmacologyandexperimentalvalidation AT hongdanchen exploringthemechanismofdangguiliuhuangdecoctionagainsthepaticfibrosisbynetworkpharmacologyandexperimentalvalidation AT qinyuhu exploringthemechanismofdangguiliuhuangdecoctionagainsthepaticfibrosisbynetworkpharmacologyandexperimentalvalidation AT yihongquan exploringthemechanismofdangguiliuhuangdecoctionagainsthepaticfibrosisbynetworkpharmacologyandexperimentalvalidation AT zhihongyu exploringthemechanismofdangguiliuhuangdecoctionagainsthepaticfibrosisbynetworkpharmacologyandexperimentalvalidation AT junjunliu exploringthemechanismofdangguiliuhuangdecoctionagainsthepaticfibrosisbynetworkpharmacologyandexperimentalvalidation AT mingxiang exploringthemechanismofdangguiliuhuangdecoctionagainsthepaticfibrosisbynetworkpharmacologyandexperimentalvalidation |
_version_ |
1725627575056728064 |