ArticleInternational journal of biological sciences2024
The PI3K/Akt-Nrf2 Signaling Pathway and Mitophagy Synergistically Mediate Hydroxytyrosol to Alleviate Intestinal Oxidative Damage.
Article in International journal of biological sciences, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed.
- Rewiring redox defense: Nrf2-driven antioxidant signaling as a gateway to programmed cell death activation in colorectal cancer.Genes & diseases · 2027Review
- A novel curcumin analog sAc15 alleviates LPS-induced acute lung injury by activating the PI3K/AKT/Nrf2 pathway in pulmonary epithelial cells.Redox report : communications in free radical research · 2026Article
- Divergent metabolic shifts of lactic acid bacteria strains shape the quality and predicted antioxidant mechanisms of a fermented fish-rice matrix (Yucha).Food chemistry: X · 2026Article
- Naringenin ameliorates postmenopausal osteoporosis by inhibiting BMSC oxidative stress via the PI3K/AKT/NRF2 pathway.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Hydroxytyrosol and Olive-Derived Hydroxytyrosol-Rich Products for Skin Health and Prevention of Skin Ageing: Current Evidence and Future Perspectives.Antioxidants (Basel, Switzerland) · 2026Review
- Liver-Directed Cyp2e1 RNA Interference Attenuates Hepatotoxicity Induced by Triptolide, a Bioactive Diterpenoid fromPharmaceuticals (Basel, Switzerland) · 2026Article
- Review
- Olive Oil as a Modulator of Gut Microbiota and Intestinal Health: A Narrative Review from Microbial Metabolism to Host Responses.Nutrients · 2026Review
- Microbial-enzymatic co-fermentation of feather meal for bioactive peptide production and its multi-pathway synergistic regulation of intestinal health in broilers.Poultry science · 2026Article
- The Fly Maggot Antioxidant Peptide (FMP) Alleviates Oxidative Damage in the Intestines of Weaned Piglets by Enhancing Mitochondrial Autophagy Through Activation of the Nrf2 Signaling Pathway.Antioxidants (Basel, Switzerland) · 2026Article
- Smart immunomodulatory polysaccharide hydrogels promote diabetic bone regeneration by regulating the inflammation-angiogenesis-osteogenesis axis.Materials today. Bio · 2026Article
- Rutin alleviates heat stress-induced intestinal oxidative damage in broilers via AMPK/PINK1-Parkin signaling pathway.Poultry science · 2026Article
- Integrated fabrication of a shape-adaptable, antioxidative composite stent for effective closure and biological repair of enteroatmospheric fistula.Bioactive materials · 2026Article
- Systems metabolic engineering for hydroxytyrosol production inApplied and environmental microbiology · 2026Article
- Targeting the Apelin-APJ Axis: A Promising Strategy to Mitigate Anthracycline-Induced Cardiotoxicity.Cardiovascular toxicology · 2026Review
- Mitochondrial Network Dynamics in Aging: Cellular Mechanisms, Intercellular Communication, and Their Impact on Tissue Adaptability.International journal of molecular sciences · 2026Review
- Pre-treatment with baicalein alleviates the diquat-induced microglial pyroptosis through gut microbiota-derived indole-3-propionic acid and DDX3X/G3BP1 pathway.Cell biology and toxicology · 2026Article
- Oxidative stress affects intestinal health by inhibiting the differentiation of porcine intestinal epithelial cells through producing arachidonic acid.Science China. Life sciences · 2026Article
- Identification of Ellagic Acid as a Natural GPR35 Agonist for Ulcerative Colitis Therapy.Biomolecules · 2026Article
- Maternal supplementation with rumen-protected arginine reshapes the ileal microbiome and enhances neonatal lamb growth.Animal microbiome · 2026Article
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oxidative stress is a major pathogenic factor in many intestinal diseases, such as inflammatory bowel disease (IBD) and colorectal cancer (CRC). The Nrf2 signaling pathway and mitophagy can reduce reactive oxygen species (ROS) and alleviate oxidative stress, but their relationship is unclear. Hydroxytyrosol (HT), a polyphenolic compound abundant in olive oil, has strong antioxidant activity and may help treat these diseases. We used pigs as a model to investigate HT's effect on intestinal oxidative damage and its mechanisms. Diquat (DQ) induced oxidative stress and impaired intestinal barrier function, which HT mitigated. Mechanistic studies in IPEC-J2 cells showed that HT protected against oxidative damage by activating the PI3K/Akt-Nrf2 signaling pathway and promoting mitophagy. Our study highlighted the synergistic relationship between Nrf2 and mitophagy in mediating HT's antioxidant effects. Inhibition studies confirmed that disrupting either pathway compromised HT's protective effects. Maintaining redox balance through Nrf2 and mitophagy is important for eliminating excess ROS. Nrf2 increases antioxidant enzymes to clear existing ROS, while mitophagy removes damaged mitochondria and reduces ROS generation. This study demonstrates that these pathways collaboratively modulate the antioxidant effects of HT, with neither being dispensable. Targeting Nrf2 and mitophagy could be a promising strategy for treating oxidative stress-related intestinal diseases, with HT as a potential treatment.
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