A DKP cyclo(L-Phe-L-Phe) found in chicken essence is a dual inhibitor of the serotonin transporter and acetylcholinesterase.
Diketopiperazines (DKPs) are naturally-occurring cyclic dipeptides with a small structure and are found in many organisms and in large amounts in some foods and beverages. We found that a chicken essence beverage, which is popular among Southeast Asians as a traditional remedy and a rich source of D...
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| Format: | Article |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3509069?pdf=render |
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| author | Nobuo Tsuruoka Yoshinori Beppu Hirofumi Koda Nobutaka Doe Hiroshi Watanabe Keiichi Abe |
| author_facet | Nobuo Tsuruoka Yoshinori Beppu Hirofumi Koda Nobutaka Doe Hiroshi Watanabe Keiichi Abe |
| author_sort | Nobuo Tsuruoka |
| collection | DOAJ |
| description | Diketopiperazines (DKPs) are naturally-occurring cyclic dipeptides with a small structure and are found in many organisms and in large amounts in some foods and beverages. We found that a chicken essence beverage, which is popular among Southeast Asians as a traditional remedy and a rich source of DKPs, inhibited the serotonin transporter (SERT) and suppressed serotonin uptake from rat brain synaptosomes, which prompted us to isolate and identify the active substance(s). We purified a SERT inhibitor from the chicken essence beverage and identified it as the DKP cyclo(L-Phe-L-Phe). Interestingly, it was a naturally occurring dual inhibitor that inhibited both SERT and acetylcholinesterase (AChE) in vitro. The DKP increased extracellular levels of the cerebral monoamines serotonin, norepinephrine, and dopamine in the medial prefrontal cortex and acetylcholine in the ventral hippocampus of freely moving rats when administered orally. Moreover, cyclo(L-Phe-L-Phe) significantly shortened escape latency in the water maze test in depressed mice previously subjected to a repeated open-space swimming task, which induces a depression-like state. Cyclo(L-Phe-L-Phe) also significantly improved accuracy rates in a radial maze test in rats and increased step-through latencies in a passive avoidance test in mice with scopolamine-induced amnesia. These animal test results suggest that cyclo(L-Phe-L-Phe), which is present abundantly in some foods such as chicken essence, may abrogate the onset of depression and, thus, contribute to preventing the development of Alzheimer's disease and other dementia, because senile depression is a risk factor for dementia. |
| first_indexed | 2024-12-13T04:26:20Z |
| format | Article |
| id | doaj.art-c233e9696e094fbdad2fd1b65ab12b21 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T04:26:20Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-c233e9696e094fbdad2fd1b65ab12b212022-12-21T23:59:41ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01711e5082410.1371/journal.pone.0050824A DKP cyclo(L-Phe-L-Phe) found in chicken essence is a dual inhibitor of the serotonin transporter and acetylcholinesterase.Nobuo TsuruokaYoshinori BeppuHirofumi KodaNobutaka DoeHiroshi WatanabeKeiichi AbeDiketopiperazines (DKPs) are naturally-occurring cyclic dipeptides with a small structure and are found in many organisms and in large amounts in some foods and beverages. We found that a chicken essence beverage, which is popular among Southeast Asians as a traditional remedy and a rich source of DKPs, inhibited the serotonin transporter (SERT) and suppressed serotonin uptake from rat brain synaptosomes, which prompted us to isolate and identify the active substance(s). We purified a SERT inhibitor from the chicken essence beverage and identified it as the DKP cyclo(L-Phe-L-Phe). Interestingly, it was a naturally occurring dual inhibitor that inhibited both SERT and acetylcholinesterase (AChE) in vitro. The DKP increased extracellular levels of the cerebral monoamines serotonin, norepinephrine, and dopamine in the medial prefrontal cortex and acetylcholine in the ventral hippocampus of freely moving rats when administered orally. Moreover, cyclo(L-Phe-L-Phe) significantly shortened escape latency in the water maze test in depressed mice previously subjected to a repeated open-space swimming task, which induces a depression-like state. Cyclo(L-Phe-L-Phe) also significantly improved accuracy rates in a radial maze test in rats and increased step-through latencies in a passive avoidance test in mice with scopolamine-induced amnesia. These animal test results suggest that cyclo(L-Phe-L-Phe), which is present abundantly in some foods such as chicken essence, may abrogate the onset of depression and, thus, contribute to preventing the development of Alzheimer's disease and other dementia, because senile depression is a risk factor for dementia.http://europepmc.org/articles/PMC3509069?pdf=render |
| spellingShingle | Nobuo Tsuruoka Yoshinori Beppu Hirofumi Koda Nobutaka Doe Hiroshi Watanabe Keiichi Abe A DKP cyclo(L-Phe-L-Phe) found in chicken essence is a dual inhibitor of the serotonin transporter and acetylcholinesterase. PLoS ONE |
| title | A DKP cyclo(L-Phe-L-Phe) found in chicken essence is a dual inhibitor of the serotonin transporter and acetylcholinesterase. |
| title_full | A DKP cyclo(L-Phe-L-Phe) found in chicken essence is a dual inhibitor of the serotonin transporter and acetylcholinesterase. |
| title_fullStr | A DKP cyclo(L-Phe-L-Phe) found in chicken essence is a dual inhibitor of the serotonin transporter and acetylcholinesterase. |
| title_full_unstemmed | A DKP cyclo(L-Phe-L-Phe) found in chicken essence is a dual inhibitor of the serotonin transporter and acetylcholinesterase. |
| title_short | A DKP cyclo(L-Phe-L-Phe) found in chicken essence is a dual inhibitor of the serotonin transporter and acetylcholinesterase. |
| title_sort | dkp cyclo l phe l phe found in chicken essence is a dual inhibitor of the serotonin transporter and acetylcholinesterase |
| url | http://europepmc.org/articles/PMC3509069?pdf=render |
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