ArticleNutrients2019
Leucine-Histidine Dipeptide Attenuates Microglial Activation and Emotional Disturbances Induced by Brain Inflammation and Repeated Social Defeat Stress.
Article in Nutrients, 2019. 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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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
- Correlation Between Lactic Acid Bacteria Beverage Intake and Stress Resilience.The Kobe journal of medical sciences · 2021Trial
- Human placental extract, melsmon, suppresses stress-induced neuroinflammation and peripheral inflammation in a mouse model of depression.Frontiers in pharmacology · 2026Article
- Peptidomics-based identification of endogenous free peptides fromFrontiers in pharmacology · 2026Article
- Canagliflozin Reprograms the Aging Hippocampus in Genetically Diverse UM-HET3 Mice and Attenuates Alzheimer's-Like Pathology.Aging cell · 2025Article
- Associations Between Stress Level, Environment, and Emotional and Behavioral Characteristics in Service Sector Employees.International journal of environmental research and public health · 2025Article
- Enhancement of memory and emotional functions by long-term ingestion of protease-treated porcine liver extract in mice.Scientific reports · 2025Article
- Downregulation of Gbp2 Attenuates LPS-Induced Inflammation in BV2 Microglia Cells Through Inhibition of STAT1.Journal of inflammation research · 2025Article
- Impact of Peptide Transport and Memory Function in the Brain.Nutrients · 2024Review
- Review
- Effect of melatonin on gut microbiome and metabolomics in diabetic cognitive impairment.Frontiers in pharmacology · 2024Article
- Relationship between dairy product intake and sense of coherence among middle and high school students in Japan.PloS one · 2022Article
- Regional Brain Analysis of Modified Amino Acids and Dipeptides during the Sleep/Wake Cycle.Metabolites · 2021Article
- 919 Syrup Alleviates Postpartum Depression by Modulating the Structure and Metabolism of Gut Microbes and Affecting the Function of the Hippocampal GABA/Glutamate System.Frontiers in cellular and infection microbiology · 2021Article
- Comprehensive Dipeptide Analysis Revealed Cancer-Specific Profile in the Liver of Patients with Hepatocellular Carcinoma and Hepatitis.Metabolites · 2020Article
- Comprehensive Circulatory Metabolomics in ME/CFS Reveals Disrupted Metabolism of Acyl Lipids and Steroids.Metabolites · 2020Article
- Brain-transportable soy dipeptide, Tyr-Pro, attenuates amyloid β peptideNPJ science of food · 2020Article
- Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The number of patients with mental illnesses is rapidly increasing, and daily lifestyle is closely associated with the development of symptoms. It is suggested that inflammatory molecules derived from microglia play crucial roles for the pathophysiology of depression. In the present study, we discovered that leucine-histidine (LH) dipeptide suppressed activation of primary microglia. The effects of LH dipeptide orally administered were measured using tail suspension test (TST) in mice injected with lipopolysaccharide and social interaction test in mice received social defeat stress. LH dipeptide reduced pro-inflammatory cytokines upon stimulation in microglia. Orally administered LH dipeptide was delivered to the brain and suppressed the production of pro-inflammatory cytokines in the brain and concomitant depression-like behavior in the TST. Moreover, oral administration of LH dipeptide suppressed the induction of depression- and anxiety-like behaviors induced by repeated social defeat stress. These results indicate that LH dipeptide suppressed the activation of microglia and ameliorated depression-associated emotional disturbances. Further, we found that LH dipeptide was abundant in various fermented products. Together with previous epidemiological reports that daily intake of these fermented foods is negatively associated with the incidence of psychiatric diseases, our findings suggest that food rich in LH dipeptide may improve mental health.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.