ArticleNutrients2022
The Citrus Flavonoid Hesperetin Encounters Diabetes-Mediated Alzheimer-Type Neuropathologic Changes through Relieving Advanced Glycation End-Products Inducing Endoplasmic Reticulum Stress.
Article in Nutrients, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 33 citations in OpenAlex.
- A probioticGut microbes · 2026Article
- Hesperetin, Acting Through Inhibition of c-Jun Signaling, Mitigates Hypomyelinating Disease-Associated Stop-Loss Claudin-11-Induced Defective Morphogenesis in Oligodendroglial FBD-102b Cells.International journal of molecular sciences · 2026Article
- Hesperetin reduces neuronal death in an SHSY5Y Alzheimer's model by inhibiting inflammation and apoptosis and pyroptosis cell death pathways.Scientific reports · 2025Article
- Tirzepatide: a novel therapeutic approach for Alzheimer's disease.Metabolic brain disease · 2025Review
- Hesperetin-Enhanced Metformin to Alleviate Cognitive Impairment via Gut-Brain Axis in Type 2 Diabetes Rats.International journal of molecular sciences · 2025Article
- Hesperidin alleviated D-GalN/LPS induced acute liver injury in mice: insights into gut microbiota and the Nrf2/Keap1 pathway.Frontiers in microbiology · 2025Article
- Nobiletin restores HFD-induced enteric nerve injury by regulating enteric glial activation and the GDNF/AKT/FOXO3a/P21 pathway.Molecular medicine (Cambridge, Mass.) · 2024Article
- Hesperetin Alleviated Experimental Colitis via Regulating Ferroptosis and Gut Microbiota.Nutrients · 2024Article
- Computational and Experimental Approaches Exploring the Role of Hesperetin in Improving Autophagy in Rat Diabetic Retinopathy.Biomedicines · 2024Article
- The Role of Ion-Transporting Proteins in Human Disease.International journal of molecular sciences · 2024Article
- Oxidative stress, the blood-brain barrier and neurodegenerative diseases: The critical beneficial role of dietary antioxidants.Acta pharmaceutica Sinica. B · 2023Review
- Review
- Advanced Glycation End-Products and Diabetic Neuropathy of the Retina.International journal of molecular sciences · 2023Review
- Neuroprotective Potentials of Flavonoids: Experimental Studies and Mechanisms of Action.Antioxidants (Basel, Switzerland) · 2023Review
- Protective effect of Huangpu Tongqiao capsule against Alzheimer's disease through inhibiting the apoptosis pathway mediated by endoplasmic reticulum stressSaudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2022Article
- Nutritional intervention for diabetes mellitus with Alzheimer's disease.Frontiers in nutrition · 2022Review
- The Correlation between the Level of Skin Advanced Glycation End Products in Type 2 Diabetes Mellitus and the Stages of Diabetic Retinopathy and the Types of Traditional Chinese Medicine Syndrome.Evidence-based complementary and alternative medicine : eCAM · 2022Article
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Authors and funding
4 authors at 2 institutions in 1 country.
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Abstract
The present study investigates whether hesperetin, a citrus flavonoid, can encounter advanced glycation end-product (AGE)-induced Alzheimer's disease-like pathophysiological changes with the underlying mechanisms. SH-SY5Y cells pretreated with hesperetin before stimulation with AGEs (200 μg/mL) were assessed in the following experiments. Hesperetin (40 μmol/L) elevated the reduced cell viability induced by AGEs. Hesperetin ameliorated reactive oxygen species overproduction and the downregulation of superoxide dismutase, glutathione peroxidase, and catalase, triggered by AGEs. Amyloid precursor protein upregulation, accompanied by the increased production of Aβ, caused by AGEs, was reversed by hesperetin. However, hesperetin lowered β-site APP-cleaving enzyme 1 expression, inducing insulin-degrading and neprilysin expression. In addition, hesperetin downregulated the expressions of the AGEs-induced endoplasmic reticulum (ER) stress proteins, including 78-kDa glucose-regulated protein and C/EBP homologous protein, and lowered the phosphorylation of protein kinase R-like ER kinase and activating transcription factor 4. Hesperetin-pretreated cells had a minor apoptotic DNA fragmentation. Hesperetin is able to upregulate Bcl-2 protein expression, downregulate Bax expression, and decrease caspase-12/-9/-3 activity as well, indicating that it inhibits ER stress-mediated neuronal apoptosis. There is a similar effect between hesperetin and positive rosiglitazone control against Aβ aggravation of SH-SY5Y cell injury induced by AGEs. Thus, hesperetin might be a potential agent for treating glycation-induced Aβ neurotoxicity.
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