ReferenceID 2170
Upregulation of Nrf2 signaling and suppression of ferroptosis and NF-κB pathway by leonurine attenuate iron overload-induced hepatotoxicity
Chem Biol Interact
Hepatotoxicity is a major health concern that associates the iron overload diseases including hemochromatosis, sickle cell anemia, and thalassemia. Induction of ferroptosis, oxidative stress, and inflammation substantial
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- Reference Id
- 2170
- Evidence Id
- 18760
- Core Evidence Id
- 18760
- Source Reference Id
- 4391
- Herb2 Reference Id
- HBREF005188
- Subject Paper Key
- HBIN032907_35247364
- Pubmed Id
- 35247364
- Doi
- 10.1016/j.cbi.2022.109875
- Paper Title
- Upregulation of Nrf2 signaling and suppression of ferroptosis and NF-κB pathway by leonurine attenuate iron overload-induced hepatotoxicity
- Paper Abstract
- Hepatotoxicity is a major health concern that associates the iron overload diseases including hemochromatosis, sickle cell anemia, and thalassemia. Induction of ferroptosis, oxidative stress, and inflammation substantially mediates the iron-evoked hepatotoxicity. The current work investigated the potential protective effect of the natural alkaloid leonurine against the iron-induced hepatotoxicity and elucidated the underlining molecular mechanisms. Male Wistar rats were treated with iron only (30 mg/kg every other day over a ten-day period via intraperitoneal injection) or with iron and leonurine (leonurine: 100 mg/kg/day per oral via gastric gavage for 10 days) to establish the iron-overload model. Liver and blood specimens were then collected and subjected to molecular, biochemical, and histopathological investigations. The results revealed the ability of leonurine to suppress the iron-induced ferroptosis as reflected by modulation of the ferroptotic biomarkers glutathione peroxidase 4, cyclooxygenase-2, liver iron content, lipid hydroperoxides, and the leakage of the liver intracellular enzymes. Leonurine alleviated the iron-induced oxidative damage and inflammatory response in the liver tissues as indicated by decreased levels of DNA oxidation, lipid peroxidation, and the pro-inflammatory cytokines. In the same context, it improved the antioxidant potential of the liver tissues and ameliorated the iorn-induced histopathological abnormalities. Mechanistically, leonurine enhanced nuclear translocation of the antioxidant transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) and increased protein levels of its downstream targets NAD(P)H-quinone oxidoreductase 1 and heme oxygenase-1. Additionally, it suppressed the nuclear translocation of the inflammatory transcription factor nuclear factor kappa B (NF-κB) and downregulated its downstream pro-inflammatory cytokines tumor necrosis factor-alpha and interleukin-1 beta. The study highlights the hepatoprotective activity of leonurine against the iron-evoked hepatotoxicity that is potentially mediated through modulation of Nrf2 and NF-κB signaling.
- Journal
- Chem Biol Interact
- Publish Year
- 2022
- Experiment Subject
- rat
- Experiment Type
- Animal Experiment
- Phenotype Related
- Thalassemia; Iorn-induced Histopathological Abnormalities; Hepatotoxicity; Iron Overload Diseases; Sickle Cell Anemia; Iron-overload; Hemochromatosis
- Paper Title Cn
- Paper Title En
- Upregulation of Nrf2 signaling and suppression of ferroptosis and NF-κB pathway by leonurine attenuate iron overload-induced hepatotoxicity
- Bilingual Status
- semi_complete