Arctiin Antagonizes Triptolide-Induced Hepatotoxicity via Activation of Nrf2 Pathway

Zhou, Yuyan; Li, Xia; Yao, Weichao; Han, Jun Hyun; Wang, Guodong

doi:10.1155/2020/2508952

Cited by 24 publications

(16 citation statements)

References 39 publications

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“…Nrf2 or HO-1 inhibition abrogated the antiin ammatory effects exerted by various bioactive agents [55,56]. A recent study has revealed that arctiin prevented triptolide-induced acute live damage through activation of Nrf2 signaling [57]. Likewise, our ndings showed that the blockade of HO-1 reversed the suppression effect of arctiin on H9N2 viruselevated proin ammatory mediators (IL-6, TNF-α, COX-2, and PGE 2 ).…”

Section: Discussionsupporting

confidence: 54%

Arctiin Suppresses H9N2 Avian Influenza Virus-Mediated Inflammation Via Activation of Nrf2/HO-1 Signaling

Zhou

Wang²,

Liang

et al. 2021

Preprint

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Background: H9N2 avian influenza viruses (AIVs) infect avian and mammalian hosts and provide internal genes for new emerging highly pathogenic avian viruses that cause severe pneumonia with high mortality, for which few medications are available. Arctiin, a bioactive lignan glycoside, has been reported to possess multiple pharmacological properties. However, the effect of arctiin on H9N2 virus infection is unclear. In the current study, we analyzed the effect of arctiin on H9N2 virus infection and the underlying molecular mechanism in vitro. Methods: The antiviral effect against H9N2 virus was determined by plaque reduction assay (PRA) and progeny virus reduction assay. We employed MTT assay, qRT-PCR, ELISA, immunofluorescence and Western blotting to better understand the anti-inflammatory effect and corresponding mechanism of arctiin on H9N2 virus-infected cells.Results: The results showed that arctiin had antiviral activity against H9N2 virus. Arctiin treatment reduced H9N2 virus-triggered proinflammatory cytokines, such as IL-6, and TNF-α. Moreover, arctiin significantly suppressed H9N2 virus-mediated expression of COX-2 and PGE2. Furthermore, we found that arctiin inhibited H9N2 virus-mediated activation of RIG-I/JNK MAPK signaling. Interestingly, arctiin treatment obviously reversed H9N2 virus-induced reduction of Nrf2, increased the nuclear translocation of Nrf2, and upregulated Nrf2 signaling target genes (HO-1 and SOD2). Zinc protoporphyrin (Znpp)—an HO-1 inhibitor—weakened the inhibitory effect of arctiin on H9N2 virus-induced RIG-I/JNK MAPK and proinflammatory mediators. Conclusion: Taken together, these results suggested that the anti-inflammatory effects of arctiin on H9N2 virus infection may be due to the activation of Nrf2/HO-1 and blocked RIG-I/JNK MAPK signaling; thus, arctiin may be a promising agent for prevention and treatment of H9N2 virus infections.

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Section: Discussionsupporting

confidence: 54%

Arctiin Suppresses H9N2 Avian Influenza Virus-Mediated Inflammation Via Activation of Nrf2/HO-1 Signaling

Zhou

Wang²,

Liang

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…Nrf2 or HO-1 inhibition abrogated the anti-inflammatory effects exerted by various bioactive agents [ 58 , 59 ]. A recent study has revealed that arctiin prevented triptolide-induced acute live damage through activation of Nrf2 signaling [ 60 ]. Likewise, our findings showed that the blockade of HO-1 reversed the suppression effect of arctiin on H9N2 virus-elevated proinflammatory mediators (IL-6, TNF-α, COX-2, and PGE 2 ).…”

Section: Discussionmentioning

confidence: 99%

Arctiin suppresses H9N2 avian influenza virus-mediated inflammation via activation of Nrf2/HO-1 signaling

Zhou

Wang²,

Liang

et al. 2021

BMC Complement Med Ther

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Background H9N2 avian influenza viruses (AIVs) infect avian and mammalian hosts and provide internal genes for new emerging highly pathogenic avian viruses that cause severe pneumonia with high mortality, for which few medications are available. Arctiin, a bioactive lignan glycoside, has been reported to possess multiple pharmacological properties. However, the effect of arctiin on H9N2 virus infection is unclear. In the current study, we analyzed the effect of arctiin on H9N2 virus infection and the underlying molecular mechanism in vitro. Methods The antiviral effect against H9N2 virus was determined by plaque reduction assay (PRA) and progeny virus reduction assay. We employed MTT assay, qRT-PCR, ELISA, immunofluorescence and Western blotting to better understand the anti-inflammatory effect and corresponding mechanism of arctiin on H9N2 virus-infected cells. Results The results showed that arctiin had antiviral activity against H9N2 virus. Arctiin treatment reduced H9N2 virus-triggered proinflammatory cytokines, such as IL-6, and TNF-α. Moreover, arctiin significantly suppressed H9N2 virus-mediated expression of COX-2 and PGE2. Furthermore, we found that arctiin inhibited H9N2 virus-mediated activation of RIG-I/JNK MAPK signaling. Interestingly, arctiin treatment obviously reversed H9N2 virus-induced reduction of Nrf2, increased the nuclear translocation of Nrf2, and upregulated Nrf2 signaling target genes (HO-1 and SOD2). Zinc protoporphyrin (Znpp)—an HO-1 inhibitor—weakened the inhibitory effect of arctiin on H9N2 virus-induced RIG-I/JNK MAPK and proinflammatory mediators. Conclusion Taken together, these results suggested that the anti-inflammatory effects of arctiin on H9N2 virus infection may be due to the activation of Nrf2/HO-1 and blocked RIG-I/JNK MAPK signaling; thus, arctiin may be a promising agent for prevention and treatment of H9N2 virus infections.

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“…MiR155, a regulator of the Nrf2 antioxidant pathway, was significantly activated and then inhibited the activity of the Nrf2 pathway in TP-induced hepatotoxicity (Li et al, 2021a). TP indeed decreased the protein expressions of the Nrf2 pathway including HO-1, NQO1, and Nrf2 associated with the oxidative stress pathway (Zhou et al, 2020). And a study found that TP-induced oxidative stress and cell damage in HepG2 cells could be aggravated by Nrf2 knockdown or counteracted by overexpression of Nrf2 (Li et al, 2014b).…”

Section: Triptolide (Tp)-induced Liver Injurymentioning

confidence: 98%

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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Arctiin Antagonizes Triptolide-Induced Hepatotoxicity via Activation of Nrf2 Pathway

Cited by 24 publications

References 39 publications

Arctiin Suppresses H9N2 Avian Influenza Virus-Mediated Inflammation Via Activation of Nrf2/HO-1 Signaling

Arctiin Suppresses H9N2 Avian Influenza Virus-Mediated Inflammation Via Activation of Nrf2/HO-1 Signaling

Arctiin suppresses H9N2 avian influenza virus-mediated inflammation via activation of Nrf2/HO-1 signaling

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

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