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An Integrative Pharmacology Model for Decoding the Underlying Therapeutic Mechanisms of Ermiao Powder for Rheumatoid Arthritis

As a systemic inflammatory arthritis disease, rheumatoid arthritis (RA) is complex and hereditary. Traditional Chinese medicine (TCM) has evident advantages in treating complex diseases, and a variety of TCM formulas have been reported that have effective treatment on RA. Clinical and pharmacologica...

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Autores principales: Wu, Jie, Wang, Kexin, Liu, Qinwen, Li, Yi, Huang, Yingying, Liu, Yujie, Cai, Jieqi, Yin, Chuanhui, Li, Xiaowei, Yu, Hailang, Meng, Wei, Wang, Handuo, Lu, Aiping, Li, Yazi, Guan, Daogang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8905663/
https://www.ncbi.nlm.nih.gov/pubmed/35281924
http://dx.doi.org/10.3389/fphar.2022.801350
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author Wu, Jie
Wang, Kexin
Liu, Qinwen
Li, Yi
Huang, Yingying
Liu, Yujie
Cai, Jieqi
Yin, Chuanhui
Li, Xiaowei
Yu, Hailang
Meng, Wei
Wang, Handuo
Lu, Aiping
Li, Yazi
Guan, Daogang
author_facet Wu, Jie
Wang, Kexin
Liu, Qinwen
Li, Yi
Huang, Yingying
Liu, Yujie
Cai, Jieqi
Yin, Chuanhui
Li, Xiaowei
Yu, Hailang
Meng, Wei
Wang, Handuo
Lu, Aiping
Li, Yazi
Guan, Daogang
author_sort Wu, Jie
collection PubMed
description As a systemic inflammatory arthritis disease, rheumatoid arthritis (RA) is complex and hereditary. Traditional Chinese medicine (TCM) has evident advantages in treating complex diseases, and a variety of TCM formulas have been reported that have effective treatment on RA. Clinical and pharmacological studies showed that Ermiao Powder, which consists of Phellodendron amurense Rupr. (PAR) and Atractylodes lancea (Thunb.) DC. (ALD), can be used in the treatment of RA. Currently, most studies focus on the anti-inflammatory mechanism of PAR and ALD and are less focused on their coordinated molecular mechanism. In this research, we established an integrative pharmacological strategy to explore the coordinated molecular mechanism of the two herbs of Ermiao Powder in treating RA. To explore the potential coordinated mechanism of PAR and ALD, we firstly developed a novel mathematical model to calculate the contribution score of 126 active components and 85 active components, which contributed 90% of the total contribution scores that were retained to construct the coordinated functional space. Then, the knapsack algorithm was applied to identify the core coordinated functional components from the 85 active components. Finally, we obtained the potential coordinated functional components group (CFCG) with 37 components, including wogonin, paeonol, ethyl caffeate, and magnoflorine. Also, functional enrichment analysis was performed on the targets of CFCG to explore the potential coordinated molecular mechanisms of PAR and ALD. The results indicated that the CFCG could treat RA by coordinated targeting to the genes involved in immunity and inflammation-related signal pathways, such as phosphatidylinositol 3‑kinase/protein kinase B signaling pathway, mitogen-activated protein kinase signaling pathway, tumor necrosis factor signaling pathway, and nuclear factor-kappa B signaling pathway. The docking and in vitro experiments were used to predict the affinity and validate the effect of CFCG and further confirm the reliability of our method. Our integrative pharmacological strategy, including CFCG identification and verification, can provide the methodological references for exploring the coordinated mechanism of TCM in treating complex diseases and contribute to improving our understanding of the coordinated mechanism.
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spelling pubmed-89056632022-03-10 An Integrative Pharmacology Model for Decoding the Underlying Therapeutic Mechanisms of Ermiao Powder for Rheumatoid Arthritis Wu, Jie Wang, Kexin Liu, Qinwen Li, Yi Huang, Yingying Liu, Yujie Cai, Jieqi Yin, Chuanhui Li, Xiaowei Yu, Hailang Meng, Wei Wang, Handuo Lu, Aiping Li, Yazi Guan, Daogang Front Pharmacol Pharmacology As a systemic inflammatory arthritis disease, rheumatoid arthritis (RA) is complex and hereditary. Traditional Chinese medicine (TCM) has evident advantages in treating complex diseases, and a variety of TCM formulas have been reported that have effective treatment on RA. Clinical and pharmacological studies showed that Ermiao Powder, which consists of Phellodendron amurense Rupr. (PAR) and Atractylodes lancea (Thunb.) DC. (ALD), can be used in the treatment of RA. Currently, most studies focus on the anti-inflammatory mechanism of PAR and ALD and are less focused on their coordinated molecular mechanism. In this research, we established an integrative pharmacological strategy to explore the coordinated molecular mechanism of the two herbs of Ermiao Powder in treating RA. To explore the potential coordinated mechanism of PAR and ALD, we firstly developed a novel mathematical model to calculate the contribution score of 126 active components and 85 active components, which contributed 90% of the total contribution scores that were retained to construct the coordinated functional space. Then, the knapsack algorithm was applied to identify the core coordinated functional components from the 85 active components. Finally, we obtained the potential coordinated functional components group (CFCG) with 37 components, including wogonin, paeonol, ethyl caffeate, and magnoflorine. Also, functional enrichment analysis was performed on the targets of CFCG to explore the potential coordinated molecular mechanisms of PAR and ALD. The results indicated that the CFCG could treat RA by coordinated targeting to the genes involved in immunity and inflammation-related signal pathways, such as phosphatidylinositol 3‑kinase/protein kinase B signaling pathway, mitogen-activated protein kinase signaling pathway, tumor necrosis factor signaling pathway, and nuclear factor-kappa B signaling pathway. The docking and in vitro experiments were used to predict the affinity and validate the effect of CFCG and further confirm the reliability of our method. Our integrative pharmacological strategy, including CFCG identification and verification, can provide the methodological references for exploring the coordinated mechanism of TCM in treating complex diseases and contribute to improving our understanding of the coordinated mechanism. Frontiers Media S.A. 2022-02-23 /pmc/articles/PMC8905663/ /pubmed/35281924 http://dx.doi.org/10.3389/fphar.2022.801350 Text en Copyright © 2022 Wu, Wang, Liu, Li, Huang, Liu, Cai, Yin, Li, Yu, Meng, Wang, Lu, Li and Guan. 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
Wu, Jie
Wang, Kexin
Liu, Qinwen
Li, Yi
Huang, Yingying
Liu, Yujie
Cai, Jieqi
Yin, Chuanhui
Li, Xiaowei
Yu, Hailang
Meng, Wei
Wang, Handuo
Lu, Aiping
Li, Yazi
Guan, Daogang
An Integrative Pharmacology Model for Decoding the Underlying Therapeutic Mechanisms of Ermiao Powder for Rheumatoid Arthritis
title An Integrative Pharmacology Model for Decoding the Underlying Therapeutic Mechanisms of Ermiao Powder for Rheumatoid Arthritis
title_full An Integrative Pharmacology Model for Decoding the Underlying Therapeutic Mechanisms of Ermiao Powder for Rheumatoid Arthritis
title_fullStr An Integrative Pharmacology Model for Decoding the Underlying Therapeutic Mechanisms of Ermiao Powder for Rheumatoid Arthritis
title_full_unstemmed An Integrative Pharmacology Model for Decoding the Underlying Therapeutic Mechanisms of Ermiao Powder for Rheumatoid Arthritis
title_short An Integrative Pharmacology Model for Decoding the Underlying Therapeutic Mechanisms of Ermiao Powder for Rheumatoid Arthritis
title_sort integrative pharmacology model for decoding the underlying therapeutic mechanisms of ermiao powder for rheumatoid arthritis
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8905663/
https://www.ncbi.nlm.nih.gov/pubmed/35281924
http://dx.doi.org/10.3389/fphar.2022.801350
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