International immunopharmacology, 2020-07, Vol.84, p.106539-106539, Article 106539
2020
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Details
- Autor(en) / Beteiligte
- Titel
- Arctigenin exhibits hepatoprotective activity in Toxoplasma gondii-infected host through HMGB1/TLR4/NF-κB pathway
- Ist Teil von
- International immunopharmacology, 2020-07, Vol.84, p.106539-106539, Article 106539
- Ort / Verlag
- Netherlands: Elsevier B.V
- Erscheinungsjahr
- 2020
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- •Arctigenin ameliorates T. gondii infection-induced liver injury.•Arctigenin attenuates the overexpression of HMGB1 and iNOS.•Arctigenin down-regulates the TLR4/NF-κB signaling pathways. Toxoplasmosis is a parasitic zoonosis with the highest incidence in humans. Severe lesions due to acute toxoplasmosis have been recorded in the visceral organs including the liver, where hepatocytes and Kupffer cells are important innate immune cells. Arctigenin (AG) is a bioactive ingredient of Arctium lappa L. and increasing evidence suggests that AG exhibits anti-oxidant, anti-inflammatory and anti-Toxoplasma gondii (T. gondii) effects. However, the role of AG in acute liver damage induced by T. gondii infection remains unclear. In this study, we analyzed the effects of AG against T. gondii-induced liver damage by establishing an in vitro infection model using a murine liver cell line (NCTC-1469 cells) and an in vivo mouse model with acute T. gondii infection of virulent RH strain. In the current study, AG effectively attenuated hepatocytes apoptosis and inhibited the reproduction of T. gondii. The results of in vitro and in vivo studies showed that AG significantly reduced alanine aminotransferase/aspartate aminotransferase activities and lessened pathological damage of liver. Moreover, AG suppressed T. gondii-induced inducible nitric oxide synthase production. AG also attenuated liver inflammation by inhibiting T. gondii-induced activation of the high-mobility group box1/toll-like receptor 4/nuclear factor-kappa B (HMGB1/TLR4/NF-κB) signaling pathway. These findings demonstrated that AG exhibited prominent hepatoprotective activities in toxoplasmic liver injury with anti-inflammatory effects by inhibiting the HMGB1/TLR4/NF-κB signaling axis. Thus, this study provides the basis for the development of new drugs to treat toxoplasmic hepatitis.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1567-5769eISSN: 1878-1705DOI: 10.1016/j.intimp.2020.106539Titel-ID: cdi_proquest_miscellaneous_2398155069
- Format
- –
- Schlagworte
- Alanine, Alanine transaminase, Alanine Transaminase - blood, Animals, Antioxidants, Apoptosis, Arctigenin, Aspartate aminotransferase, Aspartate Aminotransferases - blood, Cell Line, Damage, Drug development, Female, Furans - pharmacology, Furans - therapeutic use, Hepatitis, Hepatocytes, HMGB1, HMGB1 protein, HMGB1 Protein - immunology, Immune system, Immunosuppressive agents, In vivo methods and tests, Infections, Inflammation, Kupffer cells, Lignans - pharmacology, Lignans - therapeutic use, Liver, Liver - drug effects, Liver - immunology, Liver injury, Mice, Inbred BALB C, NF-kappa B - immunology, NF-κB, NF-κB protein, Nitric oxide, Nitric-oxide synthase, Organs, Oxidants, Oxidizing agents, Protective Agents - pharmacology, Protective Agents - therapeutic use, Protozoa, Rodents, Signal transduction, Signal Transduction - drug effects, Signaling, TLR4 protein, TLR4/MyD88, Toll-Like Receptor 4 - immunology, Toll-like receptors, Toxoplasma, Toxoplasma gondii, Toxoplasmosis, Toxoplasmosis - drug therapy, Toxoplasmosis - immunology