Integrating Network Analysis and Metabolomics to Reveal Mechanism of Huaganjian Decoction in Treatment of Cholestatic Hepatic Injury

Qin Dong; Jiao Chen; Yan Ping Jiang; Zong Ping Zhu; Yong Feng Zheng; Jin Ming Zhang; Zhen Zhang; Wen Qing Chen; Shi Yi Sun; Lan Pang; Xin Yan; Wan Liao; Chao Mei Fu

doi:10.3389/fphar.2021.773957

Integrating Network Analysis and Metabolomics to Reveal Mechanism of Huaganjian Decoction in Treatment of Cholestatic Hepatic Injury

Qin Dong
, Jiao Chen
, Yan Ping Jiang
, Zong Ping Zhu
, Yong Feng Zheng
, Jin Ming Zhang
, Zhen Zhang
, Wen Qing Chen
, Shi Yi Sun
, Lan Pang
, Xin Yan
, Wan Liao^*
, Chao Mei Fu^*

^*Corresponding author for this work

Department of Biology

Research output: Contribution to journal › Journal article › peer-review

3 Citations (Scopus)

Abstract

Huaganjian decoction (HGJD) was first recorded in the classic “Jing Yue Quan Shu” during the Ming dynasty, and it has been extensively applied in clinical practice to treat liver diseases for over 300 years in China. However, its bioactive constituents and relevant pharmacological mechanism are still unclear. In this study, a strategy integrating network analysis and metabolomics was applied to reveal mechanism of HGJD in treating cholestatic hepatic injury (CHI). Firstly, we observed the therapeutic effect of HGJD against CHI with an alpha-naphthylisothiocyanate (ANIT) induced CHI rat model. Then, we utilized UPLC-Q-Exactive MS/MS method to analyze the serum migrant compounds of HGJD in CHI rats. Based on these compounds, network analysis was conducted to screen for potential active components, and key signaling pathways interrelated to therapeutic effect of HGJD. Meanwhile, serum metabolomics was utilized to investigate the underlying metabolic mechanism of HGJD against CHI. Finally, the predicted key pathway was verified by western blot and biochemical analysis using rat liver tissue from in vivo efficacy experiment. Our results showed that HGJD significantly alleviated ANIT induced CHI. Totally, 31 compounds originated from HGJD have been identified in the serum sample. PI3K/Akt/Nrf2 signaling pathway related to GSH synthesis was demonstrated as one of the major pathways interrelated to therapeutic effect of HGJD against CHI. This research supplied a helpful strategy to determine the potential bioactive compounds and mechanism of traditional Chinese medicine.

Original language	English
Article number	773957
Number of pages	16
Journal	Frontiers in Pharmacology
Volume	12
DOIs	https://doi.org/10.3389/fphar.2021.773957
Publication status	Published - 19 Jan 2022

User-Defined Keywords

cholestatic hepatic injury
huaganjian decoction
metabolomics
network analysis
serum pharmacochemistry

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3389/fphar.2021.773957

Cite this

Dong, Q., Chen, J., Jiang, Y. P., Zhu, Z. P., Zheng, Y. F., Zhang, J. M., Zhang, Z., Chen, W. Q., Sun, S. Y., Pang, L., Yan, X., Liao, W., & Fu, C. M. (2022). Integrating Network Analysis and Metabolomics to Reveal Mechanism of Huaganjian Decoction in Treatment of Cholestatic Hepatic Injury. Frontiers in Pharmacology, 12, Article 773957. https://doi.org/10.3389/fphar.2021.773957

@article{2863c63fbec949b79a65012b3715d7f4,

title = "Integrating Network Analysis and Metabolomics to Reveal Mechanism of Huaganjian Decoction in Treatment of Cholestatic Hepatic Injury",

abstract = "Huaganjian decoction (HGJD) was first recorded in the classic “Jing Yue Quan Shu” during the Ming dynasty, and it has been extensively applied in clinical practice to treat liver diseases for over 300 years in China. However, its bioactive constituents and relevant pharmacological mechanism are still unclear. In this study, a strategy integrating network analysis and metabolomics was applied to reveal mechanism of HGJD in treating cholestatic hepatic injury (CHI). Firstly, we observed the therapeutic effect of HGJD against CHI with an alpha-naphthylisothiocyanate (ANIT) induced CHI rat model. Then, we utilized UPLC-Q-Exactive MS/MS method to analyze the serum migrant compounds of HGJD in CHI rats. Based on these compounds, network analysis was conducted to screen for potential active components, and key signaling pathways interrelated to therapeutic effect of HGJD. Meanwhile, serum metabolomics was utilized to investigate the underlying metabolic mechanism of HGJD against CHI. Finally, the predicted key pathway was verified by western blot and biochemical analysis using rat liver tissue from in vivo efficacy experiment. Our results showed that HGJD significantly alleviated ANIT induced CHI. Totally, 31 compounds originated from HGJD have been identified in the serum sample. PI3K/Akt/Nrf2 signaling pathway related to GSH synthesis was demonstrated as one of the major pathways interrelated to therapeutic effect of HGJD against CHI. This research supplied a helpful strategy to determine the potential bioactive compounds and mechanism of traditional Chinese medicine.",

keywords = "cholestatic hepatic injury, huaganjian decoction, metabolomics, network analysis, serum pharmacochemistry",

author = "Qin Dong and Jiao Chen and Jiang, \{Yan Ping\} and Zhu, \{Zong Ping\} and Zheng, \{Yong Feng\} and Zhang, \{Jin Ming\} and Zhen Zhang and Chen, \{Wen Qing\} and Sun, \{Shi Yi\} and Lan Pang and Xin Yan and Wan Liao and Fu, \{Chao Mei\}",

note = "This work was supported by the Sichuan Provincial Key Research and Development Program (No. 2020YFS0567); the National Natural Science Foundation of China (Grant Nos. 81403103, 82073994); the International Cooperation Project of Science and Technology Department of Sichuan Province (Grant No. 2018HH0122); Chengdu Science and Technology Bureau International Science and Technology Cooperation Project (Grant No. 2017-GH02-00054-HZ). Publisher Copyright: {\textcopyright} 2022 Dong, Chen, Jiang, Zhu, Zheng, Zhang, Zhang, Chen, Sun, Pang, Yan, Liao and Fu.",

year = "2022",

month = jan,

day = "19",

doi = "10.3389/fphar.2021.773957",

language = "English",

volume = "12",

journal = "Frontiers in Pharmacology",

issn = "1663-9812",

publisher = "Frontiers Media S.A.",

}

TY - JOUR

T1 - Integrating Network Analysis and Metabolomics to Reveal Mechanism of Huaganjian Decoction in Treatment of Cholestatic Hepatic Injury

AU - Dong, Qin

AU - Chen, Jiao

AU - Jiang, Yan Ping

AU - Zhu, Zong Ping

AU - Zheng, Yong Feng

AU - Zhang, Jin Ming

AU - Zhang, Zhen

AU - Chen, Wen Qing

AU - Sun, Shi Yi

AU - Pang, Lan

AU - Yan, Xin

AU - Liao, Wan

AU - Fu, Chao Mei

N1 - This work was supported by the Sichuan Provincial Key Research and Development Program (No. 2020YFS0567); the National Natural Science Foundation of China (Grant Nos. 81403103, 82073994); the International Cooperation Project of Science and Technology Department of Sichuan Province (Grant No. 2018HH0122); Chengdu Science and Technology Bureau International Science and Technology Cooperation Project (Grant No. 2017-GH02-00054-HZ). Publisher Copyright: © 2022 Dong, Chen, Jiang, Zhu, Zheng, Zhang, Zhang, Chen, Sun, Pang, Yan, Liao and Fu.

PY - 2022/1/19

Y1 - 2022/1/19

N2 - Huaganjian decoction (HGJD) was first recorded in the classic “Jing Yue Quan Shu” during the Ming dynasty, and it has been extensively applied in clinical practice to treat liver diseases for over 300 years in China. However, its bioactive constituents and relevant pharmacological mechanism are still unclear. In this study, a strategy integrating network analysis and metabolomics was applied to reveal mechanism of HGJD in treating cholestatic hepatic injury (CHI). Firstly, we observed the therapeutic effect of HGJD against CHI with an alpha-naphthylisothiocyanate (ANIT) induced CHI rat model. Then, we utilized UPLC-Q-Exactive MS/MS method to analyze the serum migrant compounds of HGJD in CHI rats. Based on these compounds, network analysis was conducted to screen for potential active components, and key signaling pathways interrelated to therapeutic effect of HGJD. Meanwhile, serum metabolomics was utilized to investigate the underlying metabolic mechanism of HGJD against CHI. Finally, the predicted key pathway was verified by western blot and biochemical analysis using rat liver tissue from in vivo efficacy experiment. Our results showed that HGJD significantly alleviated ANIT induced CHI. Totally, 31 compounds originated from HGJD have been identified in the serum sample. PI3K/Akt/Nrf2 signaling pathway related to GSH synthesis was demonstrated as one of the major pathways interrelated to therapeutic effect of HGJD against CHI. This research supplied a helpful strategy to determine the potential bioactive compounds and mechanism of traditional Chinese medicine.

AB - Huaganjian decoction (HGJD) was first recorded in the classic “Jing Yue Quan Shu” during the Ming dynasty, and it has been extensively applied in clinical practice to treat liver diseases for over 300 years in China. However, its bioactive constituents and relevant pharmacological mechanism are still unclear. In this study, a strategy integrating network analysis and metabolomics was applied to reveal mechanism of HGJD in treating cholestatic hepatic injury (CHI). Firstly, we observed the therapeutic effect of HGJD against CHI with an alpha-naphthylisothiocyanate (ANIT) induced CHI rat model. Then, we utilized UPLC-Q-Exactive MS/MS method to analyze the serum migrant compounds of HGJD in CHI rats. Based on these compounds, network analysis was conducted to screen for potential active components, and key signaling pathways interrelated to therapeutic effect of HGJD. Meanwhile, serum metabolomics was utilized to investigate the underlying metabolic mechanism of HGJD against CHI. Finally, the predicted key pathway was verified by western blot and biochemical analysis using rat liver tissue from in vivo efficacy experiment. Our results showed that HGJD significantly alleviated ANIT induced CHI. Totally, 31 compounds originated from HGJD have been identified in the serum sample. PI3K/Akt/Nrf2 signaling pathway related to GSH synthesis was demonstrated as one of the major pathways interrelated to therapeutic effect of HGJD against CHI. This research supplied a helpful strategy to determine the potential bioactive compounds and mechanism of traditional Chinese medicine.

KW - cholestatic hepatic injury

KW - huaganjian decoction

KW - metabolomics

KW - network analysis

KW - serum pharmacochemistry

UR - https://www.scopus.com/pages/publications/85124001817

U2 - 10.3389/fphar.2021.773957

DO - 10.3389/fphar.2021.773957

M3 - Journal article

AN - SCOPUS:85124001817

SN - 1663-9812

VL - 12

JO - Frontiers in Pharmacology

JF - Frontiers in Pharmacology

M1 - 773957

ER -

Integrating Network Analysis and Metabolomics to Reveal Mechanism of Huaganjian Decoction in Treatment of Cholestatic Hepatic Injury

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