Indole‐3‐propionic acid attenuates neuronal damage and oxidative stress in the ischemic hippocampus
Abstract
Tryptophan‐derived indole compounds have been widely investigated as antioxidants and as free‐radical scavengers. Indole‐3‐propionic acid (IPA), one of these compounds, is a deamination product of tryptophan. In the present study, we used Mongolian gerbils to investigate IPA's neuroprotective effects against ischemic damage and its antioxidative effects in the hippocampal CA1 region (CA1) after 5 min of transient forebrain ischemia. The repeated oral administration of IPA (10 mg/kg) for 15 days before ischemic surgery protected neurons from ischemic damage. In this group, the percentage of cresyl violet–positive neurons in the CA1 was 56.8% compared with that in the sham group. In the vehicle‐treated group, glial fibrillary acidic protein (GFAP)‐, S‐100‐, and vimentin‐immunoreactive astrocytes and ionized calcium‐binding adapter molecule 1 (Iba‐1)– and isolectin B4 (IB4)–immunoreactive microglia were activated 4 days after ischemia/reperfusion, whereas in the IPA‐treated ischemic group, GFAP, S‐100, Iba‐1, and IB4, but not vimentin, immunoreactivity was distinctly lower than that in the vehicle‐treated ischemic groups. The administration of IPA significantly decreased the level of 4‐hydroxy‐2‐nonenal, a marker of lipid peroxidation, in ischemic hippocampal homogenates compared with that in the vehicle‐treated ischemic groups at various times after ischemia/reperfusion. In addition, immunostaining for 8‐hydroxy‐2′‐deoxyguanosine showed DNA damage in pyramidal neurons in the ischemic CA1 was significantly lower in the IPA‐treated ischemic groups than in the vehicle‐treated ischemic groups. These results suggest that IPA protects neurons from ischemia‐induced neuronal damage by reducing DNA damage and lipid peroxidation. © 2009 Wiley‐Liss, Inc.
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IPA can inhibit neuronal death induced by endoplasmic reticulum stress.
“Previous studies have demonstrated that IPA can cross the blood-brain barrier (30) and modulate astrocyte activation and neuroinflammation; it can also inhibit neuronal death induced by endoplasmic reticulum stress (31).”
From Sepsis-Induced Gut Dysbiosis Mediates the Susceptibility to Sepsis-Associated Encephalopathy in Mice (2022) · cites this paper as [31]
IPA has a protective effect against neuronal inflammation.
“These studies indicate the protective effect of IPA against neuronal inflammation, which prompted us to select IPA from the metabolites enriched in SER feces as a possible protective substance against SAE.”
From Sepsis-Induced Gut Dysbiosis Mediates the Susceptibility to Sepsis-Associated Encephalopathy in Mice (2022) · cites this paper as [31]
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“Previous studies have demonstrated that IPA can cross the blood-brain barrier (30) and modulate astrocyte activation and neuroinflammation; it can also inhibit neuronal death induced by endoplasmic reticulum stress (31).”
BackgroundXie, Y., Zou, X., Han, J., Zhang, Z., Feng, Z., Ouyang, Q., Hua, S., Liu, Z., Li, C., Cai, Y., et al. (2022) · Experimental Neurology · doi:10.1016/j.expneurol.2022.114081 · Cited by 80 · see citing works
- Authors
- Hwang, I. K., Yoo, K., Li, H., Park, O. K., Lee, C. H., Choi, J. H., Jeong, Y., Lee, Y. L., Kim, Y., Kwon, Y., & Won, M.
- Affiliations
- Seoul National University (KR)
- Hallym University (KR)
- Konyang University (KR)
- Kangwon National University (KR)
- Yonsei University (KR)
- Corresponding author
- Won, Moo‐Ho
- ORCID
- Venue
- Journal of Neuroscience Research
- Publisher
- Wiley
- Published
- 2009-02-23
- Volume
- 87
- Issue
- 9
- Pages
- 2126-2137
- ISSN
- 0360-4012 (ISSN-L)
- 1097-4547
- OpenAlex
- W2115015582
- Cited by
- 186
- References
- 58
- Citations by year
- 2026: 11 · 2025: 23 · 2024: 26 · 2023: 23 · 2022: 18 · 2021: 12 · 2020: 18 · 2019: 7 · 2018: 4 · 2017: 10 · 2016: 6 · 2015: 3 · 2014: 5 · 2013: 2 · 2012: 3
- FWCI
- 3.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuroscience Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Hallym University
- Topics
- Life Sciences › Neuroscience › Neurology › Neurological Disorders and Treatments
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- indole-3-propionic acid, tryptophan metabolites, neuroprotection, cerebral ischemia, hippocampal CA1, oxidative stress, lipid peroxidation, 4-hydroxynonenal, DNA damage, 8-hydroxy-2'-deoxyguanosine, astrocyte activation, microglial activation, ischemia-reperfusion
- MeSH terms
- Administration, Oral, Animals, Astrocytes, Disease Models, Animal, DNA Damage, Gerbillinae, Gliosis, Hippocampus, Indoles, Male, Nerve Degeneration, Neurons, Lipid Peroxidation, Biomarkers, Treatment Outcome, Microglia, Oxidative Stress, Neuroprotective Agents, Hypoxia-Ischemia, Brain
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