Indole Diterpenes from Mangrove Sediment-Derived Fungus Penicillium sp. UJNMF0740 Protect PC12 Cells against 6-OHDA-Induced Neurotoxicity via Regulating the PI3K/Akt Pathway
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Published:2023-11-14
Issue:11
Volume:21
Page:593
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ISSN:1660-3397
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Container-title:Marine Drugs
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language:en
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Short-container-title:Marine Drugs
Author:
Wang Xin-Xin1, Chen Ze-Long1, Zhang Jun-Sheng1, Liu Hai-Shan1, Ma Ruo-Ping1, Liu Xin-Ping1, Li Ming-Yue1, Ge Di1, Bao Jie1, Zhang Hua1ORCID
Affiliation:
1. School of Biological Science and Technology, University of Jinan, 336 West Road of Nan Xinzhuang, Jinan 250022, China
Abstract
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.
Funder
Project of Shandong Province Higher Educational Youth Innovation Science and Technology Program Natural Science Foundation of Shandong Province, China
Subject
Drug Discovery,Pharmacology, Toxicology and Pharmaceutics (miscellaneous),Pharmaceutical Science
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