ArticleFrontiers in pharmacology2020
The Antidepressant-Like Effects of Hesperidin in Streptozotocin-Induced Diabetic Rats by Activating Nrf2/ARE/Glyoxalase 1 Pathway.
Article in Frontiers in pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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31 citing papers in PubMed, 60 citations in OpenAlex.
- Polyphenol-based modulation of the Glo1-Nrf2-RAGE axis in diabetes and neurodegeneration: mechanistic evidence, translational constraints, and critical appraisal.Frontiers in pharmacology · 2026Review
- A classic traditional chinese medicine formula for depression: mechanistic insights from phytochemical constituents and multitarget pathways.Psychopharmacology · 2025Article
- Therapeutic potential of hesperidin in diabetes mellitus-induced erectile dysfunction through Nrf2-mediated ferroptosis and oxidative stress.Andrology · 2025Article
- Medicine-food homology bioactives in Parkinson's disease: multi-target oxidative-stress modulation and translation to dietary supplements.Frontiers in nutrition · 2025Review
- Pharmacological mechanism of natural antidepressants: the role of epigenetic modifications.Frontiers in pharmacology · 2025Review
- Protocatechualdehyde attenuates oxidative stress in diabetic cataract via GLO1-mediated inhibition of AGE/RAGE glycosylation.Frontiers in pharmacology · 2025Article
- Sinisan ameliorates early-life stress-induced depressive-like behaviors by repairing DRN synaptic damage through CaSR.Frontiers in pharmacology · 2025Article
- Vitamin K2 Ameliorates Diabetes-Associated Cognitive Decline by Reducing Oxidative Stress and Neuroinflammation.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2024Article
- Development of chitosan lipid nanoparticles to alleviate the pharmacological activity of piperine in the management of cognitive deficit in diabetic rats.Scientific reports · 2024Article
- Neurological and metabolic related pathophysiologies and treatment of comorbid diabetes with depression.CNS neuroscience & therapeutics · 2024Review
- Review
- Citrate synthase lysine K215 hypoacetylation contributes to microglial citrate accumulation and pro-inflammatory functions after traumatic brain injury.CNS neuroscience & therapeutics · 2024Article
- Potential antidepressant effects of Traditional Chinese botanical drug formula Chaihu-Shugan-San and its active ingredients.Frontiers in pharmacology · 2024Review
- Flavonoids against depression: a comprehensive review of literature.Frontiers in pharmacology · 2024Review
- The Antidiabetic Mechanisms of Hesperidin: Hesperidin Nanocarriers as Promising Therapeutic Options for Diabetes.Current molecular medicine · 2024Review
- The Nrf2 Pathway in Depressive Disorders: A Systematic Review of Animal and Human Studies.Antioxidants (Basel, Switzerland) · 2023Review
- Neuroprotective Potentials of Flavonoids: Experimental Studies and Mechanisms of Action.Antioxidants (Basel, Switzerland) · 2023Review
- Glucosyl hesperidin exhibits more potent anxiolytic activity than hesperidin accompanied by the attenuation of noradrenaline induction in a zebrafish model.Frontiers in pharmacology · 2023Article
- Promising influences of hesperidin and hesperetin against diabetes and its complications: a systematic review of molecular, cellular, and metabolic effects.EXCLI journal · 2023Review
- Neurotrophic basis to the pathogenesis of depression and phytotherapy.Frontiers in pharmacology · 2023Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The co-occurrence of diabetes and depression is a challenging and underrecognized clinical problem. Alpha-carbonyl aldehydes and their detoxifying enzyme glyoxalase 1 (Glo-1) play vital roles in the pathogenesis of diabetic complications, including depression. Hesperidin, a naturally occurring flavanone glycoside, possesses numerous pharmacological properties, but neuroprotection by hesperidin in depression-like behaviors in diabetes was not observed. This study aimed to investigate the mechanisms and signaling pathways by which hesperidin regulates depression-like behaviors in diabetic rats and to identify potential targets of hesperidin. Rats with streptozotocin-induced diabetes were treated orally with hesperidin (50 and 150 mg/kg) or the nuclear factor erythroid 2-related factor 2 (Nrf2) inducer tert-butylhydroquinone (TBHQ, 25 mg/kg) for 10 weeks. After behavioral test, the brains were collected to evaluate the effects of hesperidin on Glo-1, Nrf2, protein glycation, and oxidative stress. Hesperidin showed antidepressant and anxiolytic effects in diabetic rats, as evidenced by the decreased immobility time in the forced swimming test, increased time spent in the center area of the open field test, and increased percentage of open-arm entries and time spent in the open arms in the elevated plus maze, as well as by the enhancement of Glo-1 and the inhibition of the AGEs/RAGE axis and oxidative stress in the brain. In addition, hesperidin caused significant increases in the Nrf2 levels and upregulated γ-glutamylcysteine synthetase, a well-known target gene of Nrf2/ARE signaling.
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