Indole Diterpenes from Mangrove Sediment-Derived Fungus Penicillium sp. UJNMF0740 Protect PC12 Cells against 6-OHDA-Induced Neurotoxicity via Regulating the PI3K/Akt Pathway

In our chemical investigation into Penicillium sp. UJNMF0740 derived from mangrove sediment, fourteen indole diterpene analogs, including four new ones, are purified by multiple chromatographic separation methods, with their structures being elucidated by the analyses of NMR, HR-ESIMS, and ECD data....

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Published inMarine drugs Vol. 21; no. 11; p. 593
Main Authors Wang, Xin-Xin, Chen, Ze-Long, Zhang, Jun-Sheng, Liu, Hai-Shan, Ma, Ruo-Ping, Liu, Xin-Ping, Li, Ming-Yue, Ge, Di, Bao, Jie, Zhang, Hua
Format Journal Article
LanguageEnglish
Published Basel MDPI AG 01.11.2023
Subjects
1-Phosphatidylinositol 3-kinase
6-Hydroxydopamine
AKT protein
Antibacterial activity
Antibiotics
Apoptosis
Diterpenes
Fungi
indole diterpenes
Indoles
Mangroves
Metabolites
Neuroprotection
Neuroprotective agents
Neurotoxicity
NMR
Nuclear magnetic resonance
Penicillium
Penicillium sp
Pheochromocytoma cells
Phosphorylation
PI3K/Akt pathway
Reactive oxygen species
Sediment
Signal transduction
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Summary:In our chemical investigation into Penicillium sp. UJNMF0740 derived from mangrove sediment, fourteen indole diterpene analogs, including four new ones, are purified by multiple chromatographic separation methods, with their structures being elucidated by the analyses of NMR, HR-ESIMS, and ECD data. The antibacterial and neuroprotective effects of these isolates were examined, and only compounds 6 and 9 exhibited weak antibacterial activity, while compounds 5, 8, and 10 showed protective effects against the injury of PC12 cells induced by 6-hydroxydopamine (6-OHDA). Additionally, compound 5 could suppress the apoptosis and production of reactive oxygen species (ROS) in 6-OHDA-stimulated PC12 cells as well as trigger the phosphorylation of PI3K and Akt. Taken together, our work enriches the structural diversity of indole diterpenes and hints that compounds of this skeleton can repress the 6-OHDA-induced apoptosis of PC12 cells via regulating the PI3K/Akt signaling pathway, which provides evidence for the future utilization of this fascinating class of molecules as potential neuroprotective agents.
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ISSN:1660-3397
1660-3397
DOI:10.3390/md21110593