Neuroprotective Effect of Cyclo-(L-Pro-L-Phe) Isolated from the Jellyfish-Derived Fungus Aspergillus flavus |
| |
Authors: | Dan-dan Li Ying Wang Eun La Kim Jongki Hong Jee H Jung |
| |
Institution: | 1.College of Pharmacy, Pusan National University, Busan 46241, Korea; (D.-d.L.); (Y.W.); (E.L.K.);2.College of Pharmacy, Kyung Hee University, Seoul 02447, Korea; |
| |
Abstract: | 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. |
| |
Keywords: | PPAR 2 5-diketopiperazines cyclo-(L-Pro-L-Phe) neuroprotection oxidative stress |
|
|