Neuroprotective Effect of Cyclo-(L-Pro-L-Phe) Isolated from the Jellyfish-Derived Fungus Aspergillus flavus
| Autor: | Dan-Dan Li, Ying Wang, Jongki Hong, Eun La Kim, Jee H. Jung |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Agonist Aquatic Organisms Scyphozoa QH301-705.5 medicine.drug_class Pharmaceutical Science Caspase 3 Diketopiperazines medicine.disease_cause PPAR Rhodamine 123 Article 2 5-diketopiperazines Cell Line Neuroblastoma 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cell Line Tumor Lactate dehydrogenase Drug Discovery medicine oxidative stress Animals Humans Biology (General) Pharmacology Toxicology and Pharmaceutics (miscellaneous) chemistry.chemical_classification Reactive oxygen species Activator (genetics) Molecular biology Rats Neuroprotective Agents 030104 developmental biology cyclo-(L-Pro-L-Phe) chemistry Apoptosis neuroprotection lipids (amino acids peptides and proteins) 030217 neurology & neurosurgery Oxidative stress Aspergillus flavus |
| Zdroj: | Marine Drugs Marine Drugs, Vol 19, Iss 417, p 417 (2021) Volume 19 Issue 8 |
| ISSN: | 1660-3397 |
| Popis: | 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 Aspergillus flavus. 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. |
| Databáze: | OpenAIRE |
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