Neuroprotective Effect of Cyclo-(L-Pro-L-Phe) Isolated from the Jellyfish-Derived Fungus <i>Aspergillus flavus</i>
Peroxisome proliferator-activated receptor (PPAR) expression has been implicated in pathological states such as cancer, inflammation, diabetes, and neurodegeneration. We isolated natural PPAR agonists—eight 2,5-diketopiperazines—from the jellyfish-derived fungus <i>Aspergillus flavus</i>...
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MDPI AG
2021-07-01
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| Online Access: | https://www.mdpi.com/1660-3397/19/8/417 |
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| author | Dan-dan Li Ying Wang Eun La Kim Jongki Hong Jee H. Jung |
| author_facet | Dan-dan Li Ying Wang Eun La Kim Jongki Hong Jee H. Jung |
| author_sort | Dan-dan Li |
| collection | DOAJ |
| description | Peroxisome proliferator-activated receptor (PPAR) expression has been implicated in pathological states such as cancer, inflammation, diabetes, and neurodegeneration. We isolated natural PPAR agonists—eight 2,5-diketopiperazines—from the jellyfish-derived fungus <i>Aspergillus flavus</i>. Cyclo-(L-Pro-L-Phe) was the most potent PPAR-γ activator among the eight 2,5-DKPs identified. Cyclo-(L-Pro-L-Phe) activated PPAR-γ in Ac2F rat liver cells and SH-SY5Y human neuroblastoma cells. The neuroprotective effect of this partial PPAR-γ agonist was examined using the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, lactate dehydrogenase release, and the Hoechst 33342 staining assay in SH-SY5Y cells. Our findings revealed that cyclo-(L-Pro-L-Phe) reduced hydrogen peroxide-induced apoptosis as well as the generation of reactive oxygen species. Rhodamine 123 staining and western blotting revealed that cyclo-(L-Pro-L-Phe) prevented the loss of mitochondrial membrane potential and inhibited the activation of mitochondria-related apoptotic proteins, such as caspase 3 and poly (ADP-ribose) polymerase. Moreover, cyclo-(L-Pro-L-Phe) inhibited the activation and translocation of nuclear factor-kappa B. Thus, the partial PPAR-γ agonist cyclo-(L-Pro-L-Phe) demonstrated potential neuroprotective activity against oxidative stress-induced neurodegeneration in SH-SY5Y cells. |
| first_indexed | 2024-03-10T08:38:39Z |
| format | Article |
| id | doaj.art-0303618d71c54fe78a2c00beb0c666e5 |
| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-03-10T08:38:39Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-0303618d71c54fe78a2c00beb0c666e52023-11-22T08:25:21ZengMDPI AGMarine Drugs1660-33972021-07-0119841710.3390/md19080417Neuroprotective Effect of Cyclo-(L-Pro-L-Phe) Isolated from the Jellyfish-Derived Fungus <i>Aspergillus flavus</i>Dan-dan Li0Ying Wang1Eun La Kim2Jongki Hong3Jee H. Jung4College of Pharmacy, Pusan National University, Busan 46241, KoreaCollege of Pharmacy, Pusan National University, Busan 46241, KoreaCollege of Pharmacy, Pusan National University, Busan 46241, KoreaCollege of Pharmacy, Kyung Hee University, Seoul 02447, KoreaCollege of Pharmacy, Pusan National University, Busan 46241, KoreaPeroxisome proliferator-activated receptor (PPAR) expression has been implicated in pathological states such as cancer, inflammation, diabetes, and neurodegeneration. We isolated natural PPAR agonists—eight 2,5-diketopiperazines—from the jellyfish-derived fungus <i>Aspergillus flavus</i>. Cyclo-(L-Pro-L-Phe) was the most potent PPAR-γ activator among the eight 2,5-DKPs identified. Cyclo-(L-Pro-L-Phe) activated PPAR-γ in Ac2F rat liver cells and SH-SY5Y human neuroblastoma cells. The neuroprotective effect of this partial PPAR-γ agonist was examined using the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, lactate dehydrogenase release, and the Hoechst 33342 staining assay in SH-SY5Y cells. Our findings revealed that cyclo-(L-Pro-L-Phe) reduced hydrogen peroxide-induced apoptosis as well as the generation of reactive oxygen species. Rhodamine 123 staining and western blotting revealed that cyclo-(L-Pro-L-Phe) prevented the loss of mitochondrial membrane potential and inhibited the activation of mitochondria-related apoptotic proteins, such as caspase 3 and poly (ADP-ribose) polymerase. Moreover, cyclo-(L-Pro-L-Phe) inhibited the activation and translocation of nuclear factor-kappa B. Thus, the partial PPAR-γ agonist cyclo-(L-Pro-L-Phe) demonstrated potential neuroprotective activity against oxidative stress-induced neurodegeneration in SH-SY5Y cells.https://www.mdpi.com/1660-3397/19/8/417PPAR2,5-diketopiperazinescyclo-(L-Pro-L-Phe)neuroprotectionoxidative stress |
| spellingShingle | Dan-dan Li Ying Wang Eun La Kim Jongki Hong Jee H. Jung Neuroprotective Effect of Cyclo-(L-Pro-L-Phe) Isolated from the Jellyfish-Derived Fungus <i>Aspergillus flavus</i> Marine Drugs PPAR 2,5-diketopiperazines cyclo-(L-Pro-L-Phe) neuroprotection oxidative stress |
| title | Neuroprotective Effect of Cyclo-(L-Pro-L-Phe) Isolated from the Jellyfish-Derived Fungus <i>Aspergillus flavus</i> |
| title_full | Neuroprotective Effect of Cyclo-(L-Pro-L-Phe) Isolated from the Jellyfish-Derived Fungus <i>Aspergillus flavus</i> |
| title_fullStr | Neuroprotective Effect of Cyclo-(L-Pro-L-Phe) Isolated from the Jellyfish-Derived Fungus <i>Aspergillus flavus</i> |
| title_full_unstemmed | Neuroprotective Effect of Cyclo-(L-Pro-L-Phe) Isolated from the Jellyfish-Derived Fungus <i>Aspergillus flavus</i> |
| title_short | Neuroprotective Effect of Cyclo-(L-Pro-L-Phe) Isolated from the Jellyfish-Derived Fungus <i>Aspergillus flavus</i> |
| title_sort | neuroprotective effect of cyclo l pro l phe isolated from the jellyfish derived fungus i aspergillus flavus i |
| topic | PPAR 2,5-diketopiperazines cyclo-(L-Pro-L-Phe) neuroprotection oxidative stress |
| url | https://www.mdpi.com/1660-3397/19/8/417 |
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