A network pharmacology-integrated metabolomics strategy for clarifying the action mechanisms of Schisandrae Chinensis Fructus for treating drug-induced liver injury by acetaminophen

Li, Xiankuan; Li, Mengyuan; Deng, Sha; Tian, Yu; Ma, Yucong; Yang, Huijuan; Zhang, Jian; Zheng, Yuankai; Ma, Lin

doi:10.1016/j.bmc.2020.115992

Cited by 20 publications

(10 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…ΚΕGG analysis demonstrated the enrichment of hub genes in cancer as well as infection pathways, which corroborated the antiinflammatory role of HYJJ. In the formula, combating inflammation was the principal target accomplished by eight herbs, such as ACD, ZR, GF, PGM (Jin et al, 2020), PB (Tian et al, 2020), SCF (Li et al, 2020;Li et al, 2021), PCW as well as CC (Csikos et al, 2020). In addition to inflammation, the recovery of gut motility and orchestration of the gut innervation were also underlined.…”

Section: Discussionmentioning

confidence: 99%

“…Among these herbs, the combination of ACD, ZR and GF also termed by Si-Ni decoction has shown proven efficacy for septic shock (Chen et al, 2011), sepsis (Brislinger et al, 2018;Zeng et al, 2019) by interfering with apoptosis and inflammatory responses (Aly et al, 2005;Endo et al, 2017;Yang et al, 2017;Endo et al, 2018;Bai et al, 2020). In the context of SI-NI decoction, the anti-inflammatory function has been emphasized by the addition of PGM (Jin et al, 2020), PB (Tian et al, 2020), SCF (Panossian & Wikman, 2008;Li et al, 2020;Li et al, 2021), PCW as well as CC (Csikos et al, 2020). Moreover, focusing on the impaired gastrointestinal functions, AMK is included to improve gastrointestinal motility (Zhu et al, 2018;Yang et al, 2019) and restore immune homeostasis (Xiang et al, 2020), while CR maintains homeostasis of the gut microbiota (Chen et al, 2020) and inhibits inflammation (Ho & Lin, 2008;Herath et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Network Pharmacology-Based Validation of the Efficacy of Huiyangjiuji Decoction in the Treatment of Experimental Colitis

Cheng

Zhu

et al. 2021

Front. Pharmacol.

View full text Add to dashboard Cite

Ulcerative colitis (UC) is the major type of inflammatory bowel disease (IBD) characterized by an overactive immune responses and destruction of the colorectal epithelium with intricate pathological factors. In China, Huiyangjiuji decoction (HYJJ) has been widely administered against inflammation, but the underlying mechanical mechanisms are not known. A murine model of colitis was established by orally feeding 4% dextran sodium sulfate for 5 days. Intestinal organoids (IOs) were treated with TNFα (Tumor necrosis factor-α) as an ex-vivo UC model. A scratch assay combined with a co-culture system that incubated murine epithelial cell line (IEC-6) with macrophages (Mφs) was utilized to assess epithelial recovery under inflammatory conditions. Network pharmacology analysis was performed to elucidate the mechanism of HYJJ decoction. In the present study, we confirmed that HYJJ considerably alleviated of DSS-induced colitis, as evidenced by the improved intestinal injury and fecal albumin, as well as feces blood. Network pharmacology analysis identified the active components in HYJJ formula, and KEGG enrichment analysis indicated that HYJJ-target genes were enriched in pathogen-induced infections, cancer-related as well as inflammatory pathways. Consistently, RNA-sequencing demonstrated that HYJJ treated inhibited cytokine-cytokine interaction, IBD as well as TNF signaling pathways, confirming the anti-inflammatory and anti-neoplastic role of HYJJ decoction. In-vitro experimental evidence confirmed the suppression of pro-interleukins by HYJJ, including IL-2, IL-10 and IL-12. Moreover, the contribution of HYJJ to mucosal healing was corroborated by ex-vivo experiments, in which HYJJ rescued TNFα-compromised IOs functions, i.e., elevated mitochondrial stress (MOS) and impaired regeneration capacity. IEC-6 cells co-culture with Mφs from HYJJ-treated experimental colitis mice showed an improved migration capacity as compared to those incubated with Mφs from untreated colitis mice. We conclude that HYJJ re-establishes homeostasis of the gut epithelium during colitis by suppressing inflammation and orchestrating cytokines interaction.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Network Pharmacology-Based Validation of the Efficacy of Huiyangjiuji Decoction in the Treatment of Experimental Colitis

Cheng

Zhu

et al. 2021

Front. Pharmacol.

View full text Add to dashboard Cite

show abstract

“…SCR as an adaptor protein participated in a wide range of signal transduction events [54]. The increased gene expression of SCR was associated with improved liver injury, which was reflected by regulating the ErbB signaling pathway and arachidonic acid metabolism pathway [55]. STAT3 is an important transcription factor associated with liver injury [56].…”

Section: Ppi Analysis and Acquisition Of Key Potential Targetsmentioning

confidence: 99%

Systematic characterization of the absorbed components of Ligustri Lucidi Fructus and their metabolic pathways in rat plasma by ultra‐high‐performance liquid chromatography‐Q‐Exactive Orbitrap tandem mass spectrometry combined with network pharmacology

Zhang

Xiong

Fang

et al. 2021

J of Separation Science

View full text Add to dashboard Cite

Ligustri Lucidi Fructus is a dried and mature fruit of Ligustrum lucidum Ait., which has the effects of nourishing liver and kidney. Herein, an accurate and sensitive method was established for the separation and identification of the absorbed constituents and metabolites of Ligustri Lucidi Fructus in rat plasma based on ultra‐high‐performance liquid chromatography‐Q‐Exactive Orbitrap tandem mass spectrometry. A total of 73 prototype constituents and 148 metabolites were identified or characterized in administered plasma, and the possible metabolic pathways of constituents mainly involved hydroxylation, sulfation, demethylation, and glucuronidation. Besides, the network pharmacology was further investigated to illuminate its potential mechanism of treatment for liver injury by the biological targets regulating related pathways. Network pharmacological analysis showed that target components through 399 targets regulate 220 pathways. The docking results showed that 36 key target components were closely related to liver injury. Overall, the study clearly presented the metabolic processes of Ligustri Lucidi Fructus and gave a comprehensive metabolic profile of Ligustri Lucidi Fructus in vivo first. Combining with network pharmacology and molecular docking discovered potential drug targets and disclose the biological processes of Ligustri Lucidi Fructus, which will be a viable step toward uncovering the secret mask of study for traditional Chinese medicine.

show abstract

“…Metabolomics investigates the dynamic changes of small molecules in living organisms (Yang et al, 2022). It is often used to reveal the mechanism of action of drugs (X. Li et al, 2021). MS and nuclear magnetic resonance (NMR) techniques are mainstream analytical methods in metabolomics research (He et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

“…It is often used to reveal the mechanism of action of drugs (X. Li et al, 2021). MS and nuclear magnetic resonance (NMR) techniques are mainstream analytical methods in metabolomics research (He et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Metabolomics and serum pharmacochemistry revealed the preventive mechanism of Gushudan in kidney‐yang‐deficiency‐syndrome rats

Lü

Feng

et al. 2023

Biomedical Chromatography

View full text Add to dashboard Cite

Kidney-yang-deficiency-syndrome (KYDS) is a metabolic disease caused by neuroendocrine disorder. Gushudan (GSD) is a traditional Chinese medicine prescription with the effect of nourishing kidney and strengthening bones. In this study, the mechanism of preventive effect of GSD on KYDS was explored by integrating metabolomics and serum pharmacochemistry. Reversed-phase/hydrophilic interaction chromatography-ultra-high-performance liquid chromatography-Quadrupole-Orbitrap high-resolution mass spectrometry (RP/HILIC-UHPLC-Q-Orbitrap HRMS)based serum metabolomics indicated metabolic disturbances of KYDS rats, and 50 potential biomarkers including L-threonine, succinic acid and phytosphingosine were obtained, which were mainly involved in alanine, aspartate and glutamate metabolism, citrate cycle (tricarboxylic acid cycle) and glycerophospholipid metabolism, among others. Serum pharmacochemistry identified 29 prototypical ingredients and 9 metabolites of GSD after administration, such as icaritin and xanthotoxol. The combination of 10 serum migration ingredients in GSD, including icaritin and osthole, with 7 important targets, including AKT serine/threonine kinase 1 (AKT1) and MAPK14, was found to be key for GSD to prevent KYDS in the network pharmacology study. This study provided a new idea for the research of pathogenesis of diseases and the pharmacodynamic mechanism of traditional Chinese medicine.

show abstract

A network pharmacology-integrated metabolomics strategy for clarifying the action mechanisms of Schisandrae Chinensis Fructus for treating drug-induced liver injury by acetaminophen

Cited by 20 publications

References 27 publications

Network Pharmacology-Based Validation of the Efficacy of Huiyangjiuji Decoction in the Treatment of Experimental Colitis

Network Pharmacology-Based Validation of the Efficacy of Huiyangjiuji Decoction in the Treatment of Experimental Colitis

Systematic characterization of the absorbed components of Ligustri Lucidi Fructus and their metabolic pathways in rat plasma by ultra‐high‐performance liquid chromatography‐Q‐Exactive Orbitrap tandem mass spectrometry combined with network pharmacology

Metabolomics and serum pharmacochemistry revealed the preventive mechanism of Gushudan in kidney‐yang‐deficiency‐syndrome rats

Contact Info

Product

Resources

About