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Network pharmacology-based prediction of active compounds in the Wenyang Jiedu Huayu formula acting on acute-on-chronic liver failure with experimental support in vitro and in vivo

Acute-on-chronic liver failure (ACLF) is characterized by undermined liver function, massive necrosis/apoptosis of hepatocytes, and hepatic inflammatory cell recruitment, leading to multiorgan failure. Traditional Chinese medicine (TCM) has been widely applied in clinical and experimental studies of...

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Autores principales: Tang, Dan, Wang, Ruo-Yu, Sun, Ke-Wei, Wu, Yunan, Ding, Lin, Mo, Yang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9631206/
https://www.ncbi.nlm.nih.gov/pubmed/36339606
http://dx.doi.org/10.3389/fphar.2022.1003479
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author Tang, Dan
Wang, Ruo-Yu
Sun, Ke-Wei
Wu, Yunan
Ding, Lin
Mo, Yang
author_facet Tang, Dan
Wang, Ruo-Yu
Sun, Ke-Wei
Wu, Yunan
Ding, Lin
Mo, Yang
author_sort Tang, Dan
collection PubMed
description Acute-on-chronic liver failure (ACLF) is characterized by undermined liver function, massive necrosis/apoptosis of hepatocytes, and hepatic inflammatory cell recruitment, leading to multiorgan failure. Traditional Chinese medicine (TCM) has been widely applied in clinical and experimental studies of ACLF. In this study, 23 compounds with 6,386 drug targets were obtained from Wenyang Jiedu Huayu (WYJDHY), and 8,096 genes were identified as ACLF disease targets, among which 3,132 were overlapping co-targets. Expression profile analysis identified 105 DEGs among the co-targets, which were associated with biological activities such as lymphocyte activation, immune response regulation, and pathways such as Th17 cell differentiation and NF-κB signaling. After PPI analysis and network construction, atractylenolide I (AT-1) has been identified as the hub active ingredient of the WYJDHY formula. LPS stimulation inhibited rat hepatocytes’ BRL 3A cell viability, promoted cell apoptosis, increased the levels of ALT, AST, IL-6, and VCAM-1 within the culture medium, and activated NF-κB signaling, whereas AT-1 treatment significantly attenuated LPS-induced toxicity on BRL 3A cells. Furthermore, the NF-κB signaling inhibitor PDTC exerted effects on LPS-stimulated BRL 3A cells similar to those of AT-1, and the combination of PDTC and AT-1 further attenuated LPS-induced toxicity on BRL 3A cells. In vivo, AT-1 alone or with PDTC improved the symptoms and local inflammation in ACLF model rats. In conclusion, 23 active ingredients of six herbs in the WYJDHY formula were retrieved, and 105 co-targets were differentially expressed in ACLF. AT-1 exerts protective effects on LPS-stimulated hepatocytes and ACLF rats, possibly by inhibiting the NF-κB pathway.
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spelling pubmed-96312062022-11-04 Network pharmacology-based prediction of active compounds in the Wenyang Jiedu Huayu formula acting on acute-on-chronic liver failure with experimental support in vitro and in vivo Tang, Dan Wang, Ruo-Yu Sun, Ke-Wei Wu, Yunan Ding, Lin Mo, Yang Front Pharmacol Pharmacology Acute-on-chronic liver failure (ACLF) is characterized by undermined liver function, massive necrosis/apoptosis of hepatocytes, and hepatic inflammatory cell recruitment, leading to multiorgan failure. Traditional Chinese medicine (TCM) has been widely applied in clinical and experimental studies of ACLF. In this study, 23 compounds with 6,386 drug targets were obtained from Wenyang Jiedu Huayu (WYJDHY), and 8,096 genes were identified as ACLF disease targets, among which 3,132 were overlapping co-targets. Expression profile analysis identified 105 DEGs among the co-targets, which were associated with biological activities such as lymphocyte activation, immune response regulation, and pathways such as Th17 cell differentiation and NF-κB signaling. After PPI analysis and network construction, atractylenolide I (AT-1) has been identified as the hub active ingredient of the WYJDHY formula. LPS stimulation inhibited rat hepatocytes’ BRL 3A cell viability, promoted cell apoptosis, increased the levels of ALT, AST, IL-6, and VCAM-1 within the culture medium, and activated NF-κB signaling, whereas AT-1 treatment significantly attenuated LPS-induced toxicity on BRL 3A cells. Furthermore, the NF-κB signaling inhibitor PDTC exerted effects on LPS-stimulated BRL 3A cells similar to those of AT-1, and the combination of PDTC and AT-1 further attenuated LPS-induced toxicity on BRL 3A cells. In vivo, AT-1 alone or with PDTC improved the symptoms and local inflammation in ACLF model rats. In conclusion, 23 active ingredients of six herbs in the WYJDHY formula were retrieved, and 105 co-targets were differentially expressed in ACLF. AT-1 exerts protective effects on LPS-stimulated hepatocytes and ACLF rats, possibly by inhibiting the NF-κB pathway. Frontiers Media S.A. 2022-10-20 /pmc/articles/PMC9631206/ /pubmed/36339606 http://dx.doi.org/10.3389/fphar.2022.1003479 Text en Copyright © 2022 Tang, Wang, Sun, Wu, Ding and Mo. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Tang, Dan
Wang, Ruo-Yu
Sun, Ke-Wei
Wu, Yunan
Ding, Lin
Mo, Yang
Network pharmacology-based prediction of active compounds in the Wenyang Jiedu Huayu formula acting on acute-on-chronic liver failure with experimental support in vitro and in vivo
title Network pharmacology-based prediction of active compounds in the Wenyang Jiedu Huayu formula acting on acute-on-chronic liver failure with experimental support in vitro and in vivo
title_full Network pharmacology-based prediction of active compounds in the Wenyang Jiedu Huayu formula acting on acute-on-chronic liver failure with experimental support in vitro and in vivo
title_fullStr Network pharmacology-based prediction of active compounds in the Wenyang Jiedu Huayu formula acting on acute-on-chronic liver failure with experimental support in vitro and in vivo
title_full_unstemmed Network pharmacology-based prediction of active compounds in the Wenyang Jiedu Huayu formula acting on acute-on-chronic liver failure with experimental support in vitro and in vivo
title_short Network pharmacology-based prediction of active compounds in the Wenyang Jiedu Huayu formula acting on acute-on-chronic liver failure with experimental support in vitro and in vivo
title_sort network pharmacology-based prediction of active compounds in the wenyang jiedu huayu formula acting on acute-on-chronic liver failure with experimental support in vitro and in vivo
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9631206/
https://www.ncbi.nlm.nih.gov/pubmed/36339606
http://dx.doi.org/10.3389/fphar.2022.1003479
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