Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, Yangling 712100, Shaanxi, People's Republic of China.
College of Food Science and Technology, Northwest University, Xi'an 710069, Shaanxi, People's Republic of China.
Bioorg Chem. 2022 Apr;121:105689. doi: 10.1016/j.bioorg.2022.105689. Epub 2022 Feb 21.
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 HO-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.
灵芝,作为一种传统的食用蘑菇,已被广泛报道可改善氧化应激和炎症特征的神经退行性疾病。在这项研究中,从可食用蘑菇灵芝的子实体中分离得到了五种新的三萜类化合物,包括四种羊毛甾烷三萜类化合物,命名为 ganoresinoid A-D(1-4)和一种 meroterpenoid,命名为 ganoresinoid E(5),以及 27 种已知化合物(6-32)。这些结构通过 NMR、HRESIMS 数据分析进行鉴定。所有代谢物均评估了抗炎、抗氧化和抗细胞凋亡活性。其中,ganoresinoid A 通过抑制 TLR-4/NF-κB 和 MAPK 信号通路,显著抑制 LPS 激活的 BV-2 小胶质细胞中的一氧化氮(NO)、IL-1β、IL-6 和 TNF-α 水平。同时,ganoresinoid A 通过降低线粒体膜电位(MMP)和活性氧(ROS)显著减轻 LPS 诱导的细胞凋亡。此外,ganoresinoid A 通过激活 Akt/GSK-3β/Nrf2 信号通路,在 HO 诱导的 SH-SY5Y 细胞中表现出抗氧化作用。总之,这些结果可能为灵芝中的 ganoresinoid A 作为营养干预缓解神经退行性疾病提供更强的理论依据。