Integration of transcriptomics and metabolomics confirmed hepatoprotective effects of steamed shoot extracts of ginseng (Panax ginseng C.A. Meyer) on toxicity caused by overdosed acetaminophen

Fan, Yao; Wang, Xinxiang; Cao, Xinxin; Zhang, Kangqing; Sun, Jing; Li, Yuanhang; Sui, Jinling

doi:10.1016/j.biopha.2021.112177

Cited by 10 publications

(9 citation statements)

References 53 publications

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“…Animal models provide an important tool for exploring the pathways of drug-induced liver injury and therapeutic activities of hepatoprotective drugs [ 7 ]. Over the last 50 or so years, several researchers have focused on the mechanisms underlying hepatotoxicity of ARHI [ 7 , 8 ]. Here, we introduced a high-throughput and rapid metabonomics approach to clarify the pathways of hepatotoxicity of acetaminophen and protective effects of PSM.…”

Section: Introductionmentioning

confidence: 99%

Hepatoprotection of Paederia scandens (Lour.) Merr. on Acetaminophen-Related Hepatic Injury Rats by 1H-NMR-Based Metabonomics Coupled with Network Pharmacology

Tang

Ma²,

Sun

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Background. Acetaminophen-related hepatic injury (ARHI) is a kind of acute hepatic injury caused by overdosing acetaminophen, which is mainly related to toxic metabolite production, oxidative stress, and mitochondrial dysfunction. The extract of Paederia scandens (Lour.) Merr. (PSM) has the abilities of anti-inflammatory, antivirus, and antioxidation. Research studies showed that PSM could improve acute or chronic hepatic injury, while the mechanism of which is still indistinct. Methods. Here, the authors applied the approach based on serum metabonomics combined with network pharmacology to study the protection of PSM on ARHI rats. Results. 10 serum potential biomarkers were found to be closely related to ARHI by metabonomics, while 3 compounds (L-ascorbyl 2,6-dipalmitate, squalene, and tributyl O-acetylcitrate) and 3 targets (NOS2, MAOB, and PDE3A) were found that might be the potential active components and active site of PSM on treating ARHI by network pharmacology analysis. Furthermore, molecular biology strategy was performed to validate whether iNOS/NF-κB signaling pathway is the potential mechanism of PSM treating ARHI. Conclusions. This study indicated that PSM could ameliorate ARHI by iNOS/NF-κB signaling pathway. During ARHI treatment by PSM, L-ascorbyl 2, 6-dipalmitate, squalene, and tributyl O-acetylcitrate might be the potential active components, while the possible active site might be NOS2, MAOB, and PDE3A.

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Section: Introductionmentioning

confidence: 99%

Hepatoprotection of Paederia scandens (Lour.) Merr. on Acetaminophen-Related Hepatic Injury Rats by 1H-NMR-Based Metabonomics Coupled with Network Pharmacology

Tang

Ma²,

Sun

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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“…There were numerous evidences that the marked increase in bile acid levels was one of the main pathophysiology of drug-induced liver injury, which could destruct cholesterol homeostasis, promote liver inflammatory response, and produce toxicity. [30][31][32] There may be a connection between bile acid metabolism and the regulation of DWYG in the inflammatory response.…”

Section: Discussionmentioning

confidence: 99%

Integrated Serum Metabolomics and Network Pharmacology Approach to Reveal the Potential Mechanisms of Diwuyanggan Prescription in the Prevention of Acute Liver Injury

Feng

Lin

et al. 2023

Natural Product Communications

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Objective: Acute liver injury (ALI) has become a major reason for emergency liver transplantation mortality worldwide. Diwuyanggan (DWYG), a hospital preparation of traditional chinese medicine, does a satisfactory job of treating liver disease, but its pharmacological mechanisms should be further investigated. Thus, we aimed to unravel the mechanisms of DWYG against ALI through a comprehensive approach integrating metabolomics and network pharmacology analysis in this study. Methods: An untargeted metabolomics based on ultra-high pressure liquid chromatography together with quadrupole time of flight mass spectrometry was applied to identify differential metabolites between normal mice and thioacetamide (TAA)-induced ALI mice. By utilizing network pharmacology, potential targets against ALI caused by TAA were excavated. Subsequently, the key targets were validated by real-time polymerase chain reaction assays. Results: DWYG alleviated TAA-induced ALI. Furthermore, 28 differential metabolites were identified with an association between ALI pathological processes and DWYG effects. The pathways involved in bile acid, glycerophospholipid, fatty acid, sphingolipid, tryptophan, and tyrosine metabolism. Then, we found 127 active compounds in DWYG and 26 hub genes associated with the treatment of ALI according to network pharmacology. Besides, according to Kyoto Encyclopedia of Genes and Genome analysis, sphingolipid signaling pathway was deemed as one of the main signaling pathways involved in DWYG anti-ALI, which was in agreement with the metabolomics findings. Further, a combined analysis was performed focusing on 7 key targets, including mitogen-activated protein kinase 1, mitogen-activated protein kinase 8, caspase 3, peroxisome proliferator-activated receptor gamma, albumin, carboxylesterase 1 and glucocerebrosidase, along with their related core metabolites and pathways. Confirmatory experiment further showed that DWYG could reverse the abnormal mRNA expression of these targets in TAA mice. Conclusion: This study revealed direct evidence for the preventive effect of DWYG against ALI and the related pharmacological mechanisms.

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“…Yao et al used liver metabolomics to explore the liver-protecting effect of steamed shoot extracts of ginseng ( Panax ginseng C.A. Meyer) [ 13 ]. The fecal metabolomics analysis showed that Phyllanthus emblica extracts restored the disturbed metabolites in NAFLD mice [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Investigation of the Therapeutic Effect of Total Alkaloids of Corydalis saxicola Bunting on CCl4-Induced Liver Fibrosis in Rats by LC/MS-Based Metabolomics Analysis and Network Pharmacology

Wang

Luo

et al. 2022

Metabolites

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: Liver fibrosis is a pathological result of liver injury that usually leads to a pathophysiological wound healing response. The total alkaloids of Corydalis saxicola Bunting (TACS) have been used for hepatoprotective effects on the liver. However, its exact therapeutic mechanisms of liver fibrosis are not yet well understood. To explore the potential anti-fibrosis mechanism of TACS, metabolomics coupled with network pharmacology were applied to reveal the underlying mechanisms. Ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) combined with multivariate statistical analyses were performed to estimate changes in metabolic profiles. As a result, a total of 23 metabolites in rats with liver fibrosis were altered; of these, 11 had been downregulated and 12 had been upregulated compared with the control group. After TACS treatment, the levels of 13 metabolites were significantly restored compared with the CCl4-treated group, of which 4 metabolites were up-regulated and 9 metabolites were down-regulated. Many of these metabolites are involved in the bile acid metabolism, glutathione metabolism, tryptophan metabolism and purine metabolism. Then, three key targets, including cytochrome P450 family1 subfamily A member 1 (CYP1A1), ornithine decarboxylase 1 (OCD1) and monoamine oxidase Type B (MAOB) were predicted as potential therapeutic targets of TACS against liver fibrosis through network pharmacology analysis. Finally, palmatine, tetrahydropalmatine and dehydrocavidine were screened as potential active compounds responsible for the anti-fibrosis effect of TACS by molecular docking analysis. This study reveals that TACS exerted anti-fibrosis effects by regulating the liver metabolic pathway with multiple components and multiple targets, which is helpful to further clarify the hepatoprotective mechanisms of natural plant extracts.

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Integration of transcriptomics and metabolomics confirmed hepatoprotective effects of steamed shoot extracts of ginseng (Panax ginseng C.A. Meyer) on toxicity caused by overdosed acetaminophen

Cited by 10 publications

References 53 publications

Hepatoprotection of Paederia scandens (Lour.) Merr. on Acetaminophen-Related Hepatic Injury Rats by 1H-NMR-Based Metabonomics Coupled with Network Pharmacology

Hepatoprotection of Paederia scandens (Lour.) Merr. on Acetaminophen-Related Hepatic Injury Rats by 1H-NMR-Based Metabonomics Coupled with Network Pharmacology

Integrated Serum Metabolomics and Network Pharmacology Approach to Reveal the Potential Mechanisms of Diwuyanggan Prescription in the Prevention of Acute Liver Injury

Investigation of the Therapeutic Effect of Total Alkaloids of Corydalis saxicola Bunting on CCl4-Induced Liver Fibrosis in Rats by LC/MS-Based Metabolomics Analysis and Network Pharmacology

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