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Ganoderma resinaceum, as a traditional edible mushroom, has been widely reported to improve neurodegenerative diseases characterized by oxidative stress and inflammation. In this study, five new terpenoids, including four lanostane triterpenoids, named ganoresinoid A-D (1-4) and one meroterpenoid, named ganoresinoid E (5), along with 27 known compounds (6-32), were isolated from the fruiting bodies of edible mushroom G. resinaceum. These structures were identified by NMR, HRESIMS data analysis. All metabolites were evaluated for anti-inflammatory, antioxidative and anti-apoptosis activities. Among them, ganoresinoid A showed notably restrained nitric oxide (NO), IL-1β, IL-6 and TNF-α levels in LPS-activated BV-2 microglial cells via suppressing TLR-4/ NF-κB and MAPK signaling pathway. Simultaneously, ganoresinoid A remarkably alleviated LPS-induced apoptosis by means of the decrease of mitochondrial membrane potential (MMP) and reactive oxygen species (ROS). In addition, ganoresinoid A demonstrated antioxidant effects in H 2 O 2 -induced SH-SY5Y cells by activating the Akt/GSK-3β/Nrf2 signaling pathway. Taken together, these results may provide a stronger theoretical basis for ganoresinoid A from G. resinaceum as nutrition intervention to alleviate neurodegenerative diseases., (Copyright © 2022 Elsevier Inc. All rights reserved.)