A new perspective of triptolide-associated hepatotoxicity: the relevance of NF- B and NF- B-mediated cellular FLICE-inhibitory protein

Yuan, Ziqiao; Yuan, Zihang; Hasnat, Muhammad; Zhang, Haoran; Liang, Peishi; Sun, Lixin; Jiang, Zhenzhou; Zhang, Luyong

doi:10.1016/j.apsb.2020.02.009

Cited by 30 publications

(38 citation statements)

References 68 publications

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“…It has been previously reported that the alleviation of TP-induced hepatotoxicity was involved in the inactivation of the NF-κB pathway (Wei et al, 2017). Besides, TP treatment might disrupt immune homeostasis and induce liver hypersensitivity through the regulation of NF-κB-dependent pro-survival genes (Yuan et al, 2020). These shreds of evidence support the close correlation among unbalanced expression of Nrf2, NK-κB, and hepatotoxicity.…”

Section: Triptolide (Tp)-induced Liver Injurymentioning

confidence: 52%

Dissecting the Crosstalk Between Nrf2 and NF-κB Response Pathways in Drug-Induced Toxicity

Gao

Guo

Yang

et al. 2022

Front. Cell Dev. Biol.

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Nrf2 and NF-κB are important regulators of the response to oxidative stress and inflammation in the body. Previous pharmacological and genetic studies have confirmed crosstalk between the two. The deficiency of Nrf2 elevates the expression of NF-κB, leading to increased production of inflammatory factors, while NF-κB can affect the expression of downstream target genes by regulating the transcription and activity of Nrf2. At the same time, many therapeutic drug-induced organ toxicities, including hepatotoxicity, nephrotoxicity, cardiotoxicity, pulmonary toxicity, dermal toxicity, and neurotoxicity, have received increasing attention from researchers in clinical practice. Drug-induced organ injury can destroy body function, reduce the patients’ quality of life, and even threaten the lives of patients. Therefore, it is urgent to find protective drugs to ameliorate drug-induced injury. There is substantial evidence that protective medications can alleviate drug-induced organ toxicity by modulating both Nrf2 and NF-κB signaling pathways. Thus, it has become increasingly important to explore the crosstalk mechanism between Nrf2 and NF-κB in drug-induced toxicity. In this review, we summarize the potential molecular mechanisms of Nrf2 and NF-κB pathways and the important effects on adverse effects including toxic reactions and look forward to finding protective drugs that can target the crosstalk between the two.

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Section: Triptolide (Tp)-induced Liver Injurymentioning

confidence: 52%

Dissecting the Crosstalk Between Nrf2 and NF-κB Response Pathways in Drug-Induced Toxicity

Gao

Guo

Yang

et al. 2022

Front. Cell Dev. Biol.

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“…After the treatment with wogonin, the accumulation of MDA in liver was significantly ameliorated, together with the increased activity of SOD (Figure 3A,B), indicating the potent anti‐oxidative capacity of wogonin in vivo. Previous reports have revealed that the exposure to LPS combined with TNF‐α mimics the stressful condition accounting for liver inflammatory response and liver injury in sepsis 36‐39 . We cultured AML12 hepatocytes in vitro and stimulated them with LPS combined with TNF‐α, which induced significant increase of MDA and decrease of SOD activity (Figure 3C,D).…”

Section: Resultsmentioning

confidence: 86%

Wogonin alleviates liver injury in sepsis through Nrf2‐mediated NF‐κB signalling suppression

Dai

Guo

Tan

et al. 2021

J Cellular Molecular Medi

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Sepsis is a life‐threatening organ dysfunction syndrome, and liver is a susceptible target organ in sepsis, because the activation of inflammatory pathways contributes to septic liver injury. Oxidative stress has been documented to participate in septic liver injury, because it not only directly induces oxidative genotoxicity, but also exacerbates inflammatory pathways to potentiate damage of liver. Therefore, to ameliorate oxidative stress is promising for protecting liver in sepsis. Wogonin is the compound extracted from the medicinal plant Scutellaria baicalensis Geogi and was found to exert therapeutic effects in multiple inflammatory diseases via alleviation of oxidative stress. However, whether wogonin is able to mitigate septic liver injury remains unknown. Herein, we firstly proved that wogonin treatment could improve survival of mice with lipopolysaccharide (LPS)‐ or caecal ligation and puncture (CLP)‐induced sepsis, together with restoration of reduced body temperature and respiratory rate, and suppression of several pro‐inflammatory cytokines in circulation. Then, we found that wogonin effectively alleviated liver injury via potentiation of the anti‐oxidative capacity. To be specific, wogonin activated Nrf2 thereby promoting expressions of anti‐oxidative enzymes including NQO‐1, GST, HO‐1, SOD1 and SOD2 in hepatocytes. Moreover, wogonin‐induced Nrf2 activation could suppress NF‐κB‐regulated up‐regulation of pro‐inflammatory cytokines. Ultimately, we provided in vivo evidence that wogonin activated Nrf2 signalling, potentiated anti‐oxidative enzymes and inhibited NF‐κB‐regulated pro‐inflammatory signalling. Taken together, this study demonstrates that wogonin can be the potential therapeutic agent for alleviating liver injury in sepsis by simultaneously ameliorating oxidative stress and inflammatory response through the activation of Nrf2.

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“…C20:4n6-related inflammatory metabolic pathway was regulated by phospholipase A2 (PLA2), the activity of which was positively correlated with Ca 2+ concentration in the hepatic cell. The significant elevated level of Ca 2+ in hepatocyte was determined in TP-induced liver-injured rats [ 24 , 25 ]. Therefore, we speculated that overdose TP could induce C20:4n6-related inflammatory metabolic pathway, resulting in the significant decreased level of C20:4n6 in the liver.…”

Section: Discussionmentioning

confidence: 99%

Metabolic profiling of fatty acids in Tripterygium wilfordii multiglucoside- and triptolide-induced liver-injured rats

Liu

et al. 2021

Open Life Sciences

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Tripterygium wilfordii multiglucoside (TWM) is a fat-soluble extract from a Chinese herb T. wilfordii, that’s used in treating rheumatoid arthritis, nephrotic syndrome and other skin diseases. Triptolide (TP) is a major active component in TWM. However, clinical applications of TWM are limited by its various toxicities especially hepatotoxicity. In recent studies, it has been reported that drug-induced liver injury (DILI) could induce the disorder of lipid metabolism in animals. Hence, this study focuses on the metabolic profile of fatty acids in TWM- and TP-induced liver-injured rats. In serum and liver tissue, 16 free and 16 esterified fatty acids were measured by gas chromatography coupled with mass spectrometry. Metabolic profile of serum fatty acids in rats with liver injury was identified by multivariate statistical analysis. The fatty acid levels in the serum of TWM- and TP-treated rats significantly decreased, whereas those in the liver tissue of TWM- and TP-treated rats obviously increased when compared with the vehicle-treated rats. Four free fatty acids were identified as candidate biomarkers of TWM- and TP-induced liver injury. Therefore, the targeted metabolomic method may be used as a complementary approach for DILI diagnosis in clinic.

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A new perspective of triptolide-associated hepatotoxicity: the relevance of NF- B and NF- B-mediated cellular FLICE-inhibitory protein

Cited by 30 publications

References 68 publications

Dissecting the Crosstalk Between Nrf2 and NF-κB Response Pathways in Drug-Induced Toxicity

Dissecting the Crosstalk Between Nrf2 and NF-κB Response Pathways in Drug-Induced Toxicity

Wogonin alleviates liver injury in sepsis through Nrf2‐mediated NF‐κB signalling suppression

Metabolic profiling of fatty acids in Tripterygium wilfordii multiglucoside- and triptolide-induced liver-injured rats

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