Integrating strategies of metabolomics, network pharmacology, and experiment validation to investigate the processing mechanism of Epimedium fried with suet oil to warm kidney and enhance yang

Introduction: Epimedium, a traditional Chinese medicine (TCM) commonly used in ancient and modern China, is one of the traditional Chinese medicines clinically used to treat kidney yang deficiency syndrome (KYDS). There are differences in the efficacy of Epimedium before and after processing, and th...

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Main Authors: E. Sun, Ran Huang, Ke Ding, Ling Wang, Jian Hou, Xiaobin Tan, Yingjie Wei, Liang Feng, Xiaobin Jia
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-01-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2023.1113213/full
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author E. Sun
E. Sun
Ran Huang
Ran Huang
Ke Ding
Ling Wang
Jian Hou
Xiaobin Tan
Xiaobin Tan
Yingjie Wei
Yingjie Wei
Liang Feng
Xiaobin Jia
Xiaobin Jia
author_facet E. Sun
E. Sun
Ran Huang
Ran Huang
Ke Ding
Ling Wang
Jian Hou
Xiaobin Tan
Xiaobin Tan
Yingjie Wei
Yingjie Wei
Liang Feng
Xiaobin Jia
Xiaobin Jia
author_sort E. Sun
collection DOAJ
description Introduction: Epimedium, a traditional Chinese medicine (TCM) commonly used in ancient and modern China, is one of the traditional Chinese medicines clinically used to treat kidney yang deficiency syndrome (KYDS). There are differences in the efficacy of Epimedium before and after processing, and the effect of warming the kidney and enhancing yang is significantly enhanced after heating with suet oil. However, the active compounds, corresponding targets, metabolic pathways, and synergistic mechanism of frying Epimedium in suet oil to promote yang, remain unclear.Methods: Herein, a strategy based on comprehensive GC-TOF/MS metabolomics and network pharmacology analysis was used to construct an “active compounds-targets-metabolic pathways” network to identify the active compounds, targets and metabolic pathways involved. Subsequently, the targets in kidney tissue were further validated by real-time quantitative polymerase chain reaction (RT-qPCR). Histopathological analysis with physical and biochemical parameters were performed.Results: Fifteen biomarkers from urine and plasma, involving five known metabolic pathways related to kidney yang deficiency were screened. The network pharmacology results showed 37 active compounds (13 from Epimedium and 24 from suet oil), 159 targets, and 267 pathways with significant correlation. Importantly, integrated metabolomics and network pharmacologic analysis revealed 13 active compounds (nine from Epimedium and four from suet oil), 7 corresponding targets (ALDH2, ARG2, GSTA3, GSTM1, GSTM2, HPGDS, and NOS2), two metabolic pathways (glutathione metabolism, arginine and proline metabolism), and two biomarkers (Ornithine and 5-Oxoproline) associated with improved kidney yang deficiency by Epimedium fried with suet oil.Discussion: These finds may elucidate the underlying mechanism of yang enhancement via kidney warming effects. Our study indicated that the mechanism of action mainly involved oxidative stress and amino acid metabolism. Here, we demonstrated the novel strategies of integrating metabolomics and network pharmacology in exploring of the mechanisms of traditional Chinese medicines.
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spelling doaj.art-249f938676cf40b8932af67fb44ea6c22023-01-25T06:24:25ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122023-01-011410.3389/fphar.2023.11132131113213Integrating strategies of metabolomics, network pharmacology, and experiment validation to investigate the processing mechanism of Epimedium fried with suet oil to warm kidney and enhance yangE. Sun0E. Sun1Ran Huang2Ran Huang3Ke Ding4Ling Wang5Jian Hou6Xiaobin Tan7Xiaobin Tan8Yingjie Wei9Yingjie Wei10Liang Feng11Xiaobin Jia12Xiaobin Jia13The Third Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, ChinaKey Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Academy of Traditional Chinese Medicine, Nanjing, ChinaThe Third Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, ChinaAffiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, ChinaThe Third Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, ChinaThe Third Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, ChinaKey Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Academy of Traditional Chinese Medicine, Nanjing, ChinaThe Third Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, ChinaKey Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Academy of Traditional Chinese Medicine, Nanjing, ChinaThe Third Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, ChinaKey Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Academy of Traditional Chinese Medicine, Nanjing, ChinaSchool of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, ChinaThe Third Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, ChinaSchool of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, ChinaIntroduction: Epimedium, a traditional Chinese medicine (TCM) commonly used in ancient and modern China, is one of the traditional Chinese medicines clinically used to treat kidney yang deficiency syndrome (KYDS). There are differences in the efficacy of Epimedium before and after processing, and the effect of warming the kidney and enhancing yang is significantly enhanced after heating with suet oil. However, the active compounds, corresponding targets, metabolic pathways, and synergistic mechanism of frying Epimedium in suet oil to promote yang, remain unclear.Methods: Herein, a strategy based on comprehensive GC-TOF/MS metabolomics and network pharmacology analysis was used to construct an “active compounds-targets-metabolic pathways” network to identify the active compounds, targets and metabolic pathways involved. Subsequently, the targets in kidney tissue were further validated by real-time quantitative polymerase chain reaction (RT-qPCR). Histopathological analysis with physical and biochemical parameters were performed.Results: Fifteen biomarkers from urine and plasma, involving five known metabolic pathways related to kidney yang deficiency were screened. The network pharmacology results showed 37 active compounds (13 from Epimedium and 24 from suet oil), 159 targets, and 267 pathways with significant correlation. Importantly, integrated metabolomics and network pharmacologic analysis revealed 13 active compounds (nine from Epimedium and four from suet oil), 7 corresponding targets (ALDH2, ARG2, GSTA3, GSTM1, GSTM2, HPGDS, and NOS2), two metabolic pathways (glutathione metabolism, arginine and proline metabolism), and two biomarkers (Ornithine and 5-Oxoproline) associated with improved kidney yang deficiency by Epimedium fried with suet oil.Discussion: These finds may elucidate the underlying mechanism of yang enhancement via kidney warming effects. Our study indicated that the mechanism of action mainly involved oxidative stress and amino acid metabolism. Here, we demonstrated the novel strategies of integrating metabolomics and network pharmacology in exploring of the mechanisms of traditional Chinese medicines.https://www.frontiersin.org/articles/10.3389/fphar.2023.1113213/fullEpimediummetabolomicsnetwork pharmacologyprocessing mechanismkidney yang deficiency syndrome
spellingShingle E. Sun
E. Sun
Ran Huang
Ran Huang
Ke Ding
Ling Wang
Jian Hou
Xiaobin Tan
Xiaobin Tan
Yingjie Wei
Yingjie Wei
Liang Feng
Xiaobin Jia
Xiaobin Jia
Integrating strategies of metabolomics, network pharmacology, and experiment validation to investigate the processing mechanism of Epimedium fried with suet oil to warm kidney and enhance yang
Frontiers in Pharmacology
Epimedium
metabolomics
network pharmacology
processing mechanism
kidney yang deficiency syndrome
title Integrating strategies of metabolomics, network pharmacology, and experiment validation to investigate the processing mechanism of Epimedium fried with suet oil to warm kidney and enhance yang
title_full Integrating strategies of metabolomics, network pharmacology, and experiment validation to investigate the processing mechanism of Epimedium fried with suet oil to warm kidney and enhance yang
title_fullStr Integrating strategies of metabolomics, network pharmacology, and experiment validation to investigate the processing mechanism of Epimedium fried with suet oil to warm kidney and enhance yang
title_full_unstemmed Integrating strategies of metabolomics, network pharmacology, and experiment validation to investigate the processing mechanism of Epimedium fried with suet oil to warm kidney and enhance yang
title_short Integrating strategies of metabolomics, network pharmacology, and experiment validation to investigate the processing mechanism of Epimedium fried with suet oil to warm kidney and enhance yang
title_sort integrating strategies of metabolomics network pharmacology and experiment validation to investigate the processing mechanism of epimedium fried with suet oil to warm kidney and enhance yang
topic Epimedium
metabolomics
network pharmacology
processing mechanism
kidney yang deficiency syndrome
url https://www.frontiersin.org/articles/10.3389/fphar.2023.1113213/full
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