Comprehensive analysis of transcriptomics and metabolomics to understand triptolide-induced liver injury in mice

Zhao, Jie; Xie, Cen; Wang, Kanglong; Takahashi, Shogo; Krausz, Kristopher W.; Lu, Dasheng; Wang, Qiong; Gong, Xianqiong; Mu, Xiyan; Wang, Qiao; Su, Suwen; Gonzalez, Frank J.

doi:10.1016/j.toxlet.2020.08.007

Cited by 56 publications

(24 citation statements)

References 42 publications

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“…Some drugs may cause an increase in pyrimidine metabolites in the blood or urine, thus causing disorders of pyrimidine metabolism. − In this study, we found that two metabolites of pyrimidine metabolism, namely, uridine 5′-monophosphate and thymidine, were disturbed in the emodin group. Uridine 5′-monophosphate, a pyrimidine mononucleotide, is involved in several metabolic disorders, some of which include dihydropyrimidinase deficiency, UMP synthase deficiency, and β-ureidopropionase deficiency.…”

Section: Discussionmentioning

confidence: 63%

UPLC-Q-TOF/MS-Based Metabolomics Approach to Reveal the Hepatotoxicity of Emodin and Detoxification of Dihydromyricetin

Gao

Shi²,

Guo³

et al. 2021

ACS Omega

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Dihydromyricetin (DMY), an important flavanone found in Ampelopsis grossedentata, plays a protective role in liver injury. Our previous research found that DMY protected L02 cells against hepatotoxicity caused by emodin. In this study, serum, urine, and liver samples from rats were systematically used for biochemical analysis, pathological observation, and nontargeted metabolomics to evaluate the toxicity of emodin and DMY intervention. After oral administration of DMY, DMY may alleviate liver injury by improving liver metabolism. Approximately, 8 of 15 metabolites in rat urine and serum were significantly regulated by DMY. Metabolic pathway analysis showed that glutathione metabolism, pyrimidine metabolism, and tryptophan metabolism were the most affected pathways, and 18 proteins were predicted to be potential targets of DMY during the alleviation of liver injury induced by emodin. This research is of great significance in confirming the liver-protective effect of DMY, especially during acute liver injury caused by traditional Chinese medicine.

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Section: Discussionmentioning

confidence: 63%

UPLC-Q-TOF/MS-Based Metabolomics Approach to Reveal the Hepatotoxicity of Emodin and Detoxification of Dihydromyricetin

Gao

Shi²,

Guo³

et al. 2021

ACS Omega

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“…[ 34 ] and Zhao, et al . [ 35 ]. In the PCA analysis, the 2 replications of medium-dose group were separated from others, we hypothesized that the deviation may come from biological differences between replications because all experiments were performed using exactly same protocols and conditions.…”

Section: Discussionmentioning

confidence: 99%

Metabolomics reveal alterations in arachidonic acid metabolism in Schistosoma mekongi after exposure to praziquantel

et al. 2021

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Background Mekong schistosomiasis is a parasitic disease caused by the blood-dwelling fluke Schistosoma mekongi. This disease contributes to human morbidity and mortality in the Mekong region, posing a public health threat to people in the area. Currently, praziquantel (PZQ) is the drug of choice for the treatment of Mekong schistosomiasis. However, the molecular mechanisms of PZQ action remain unclear, and Schistosoma PZQ resistance has been reported occasionally. Through this research, we aimed to use a metabolomic approach to identify the potentially altered metabolic pathways in S. mekongi associated with PZQ treatment. Methodology/Principal findings Adult stage S. mekongi were treated with 0, 20, 40, or 100 μg/mL PZQ in vitro. After an hour of exposure to PZQ, schistosome metabolites were extracted and studied with mass spectrometry. The metabolomic data for the treatment groups were analyzed with the XCMS online platform and compared with data for the no treatment group. After low, medium (IC50), and high doses of PZQ, we found changes in 1,007 metabolites, of which phosphatidylserine and anandamide were the major differential metabolites by multivariate and pairwise analysis. In the pathway analysis, arachidonic acid metabolism was found to be altered following PZQ treatment, indicating that this pathway may be affected by the drug and potentially considered as a novel target for anti-schistosomiasis drug development. Conclusions/Significance Our findings suggest that arachidonic acid metabolism is a possible target in the parasiticidal effects of PZQ against S. mekongi. Identifying potential targets of the effective drug PZQ provides an interesting viewpoint for the discovery and development of new agents that could enhance the prevention and treatment of schistosomiasis.

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“…Metabolomics was analyzed using Ultra-performance liquid chromatography equipped with quadrupole time-of-flight mass spectroscopy (UPLC-Xevo G2-XS QTof, Waters, United States) as previously described ( Zhao et al, 2020 ). Approximately 50 mg liver tissue was homogenized with 500 μl lysis buffer (acetonitrile: methanol: extra-pure water = 2:2:1) at 4°C for 20 s and centrifuged at 12,000 g for 10 min at 4°C.…”

Section: Methodsmentioning

confidence: 99%

“…Metabolomics analysis can provide the global metabolic profile and identify the differently expressed metabolites. The integrative analysis of transcriptome and metabolome has been increasingly used to investigate the complicated mechanisms of liver diseases ( Zhao et al, 2020 ; Tang et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Tormentic Acid Ameliorates Hepatic Fibrosis in vivo by Inhibiting Glycerophospholipids Metabolism and PI3K/Akt/mTOR and NF-κB Pathways: Based on Transcriptomics and Metabolomics

Lin

Wei

et al. 2022

Front. Pharmacol.

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This study aimed to investigate the effects and underlying mechanisms of tormentic acid (TA) on carbon tetrachloride (CCl4)-induced liver fibrosis in rats. The rats were intragastrically administered with 50% CCl4 for 9 weeks to induce hepatic fibrosis, followed by various agents for 6 weeks. Transcriptomic analysis was carried out to predict the potential targets, and then multiple examinations were performed to verify the prediction. The results showed that TA significantly alleviated liver injury and fibrosis, as evidenced by the ameliorative pathological tissue, low transaminase activity, and decreased collagen accumulation. Besides, TA markedly reduced hepatocyte apoptosis by regulating the expression of caspase-3 and Bcl-2 families. The transcriptomic analysis revealed 2,173 differentially expressed genes (DEGs) between the TA and model groups, which could be enriched in the metabolic pathways and the PI3K/Akt and NF-κB signaling pathways. The metabolomics analysis showed that TA could regulate the glycerophospholipid metabolism pathway by regulating the synthesis of phosphatidylserines, phosphatidylethanolamines and phosphatidylcholines. Moreover, the integrative analysis of the transcriptomics and metabolomics data indicated that TA inhibited the glycerophospholipid metabolism pathway by inhibiting the expression of LPCAT4, PTDSS2, PLA2G2A and CEPT1. In addition, the relevant signaling pathways analysis confirmed that TA inhibited HSCs activation by blocking the PI3K/Akt/mTOR pathway and ameliorated inflammatory injury by inhibiting the NF-κB pathway. In conclusion, TA significantly alleviates liver fibrosis in vivo by inhibiting the glycerophospholipid metabolism pathway and the PI3K/Akt/mTOR and NF-κB signaling pathways.

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Comprehensive analysis of transcriptomics and metabolomics to understand triptolide-induced liver injury in mice

Cited by 56 publications

References 42 publications

UPLC-Q-TOF/MS-Based Metabolomics Approach to Reveal the Hepatotoxicity of Emodin and Detoxification of Dihydromyricetin

UPLC-Q-TOF/MS-Based Metabolomics Approach to Reveal the Hepatotoxicity of Emodin and Detoxification of Dihydromyricetin

Metabolomics reveal alterations in arachidonic acid metabolism in Schistosoma mekongi after exposure to praziquantel

Tormentic Acid Ameliorates Hepatic Fibrosis in vivo by Inhibiting Glycerophospholipids Metabolism and PI3K/Akt/mTOR and NF-κB Pathways: Based on Transcriptomics and Metabolomics

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