ABSTRACT
Six ionone glycosides (1-3 and 5-7), including three new ones, named capitsesqsides A-C (1-3), together with an eudesmane sesquiterpenoid glycoside (4) and three known triterpenoid saponins (8-10) were isolated from Rhododendron capitatum. The structures of these compounds were determined by extensive spectroscopic techniques (MS, UV, 1D-NMR, and 2D-NMR) and comparison with data reported in the literature. The absolute configurations were determined by comparison of the experimental and theoretically calculated ECD curves and LC-MS analyses after acid hydrolysis and derivatization. The anti-inflammatory activities of these compounds were evaluated in the LPS-induced RAW264.7 cells. Molecular docking demonstrated that 2 has a favorable affinity for NLRP3 and iNOS.
Subject(s)
Glycosides , Rhododendron , Rhododendron/chemistry , Mice , Glycosides/chemistry , Glycosides/pharmacology , Glycosides/isolation & purification , RAW 264.7 Cells , Animals , Molecular Docking Simulation , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/isolation & purification , Norisoprenoids/chemistry , Norisoprenoids/pharmacology , Norisoprenoids/isolation & purification , Molecular Structure , Nitric Oxide Synthase Type II/metabolism , Nitric Oxide Synthase Type II/antagonists & inhibitors , Lipopolysaccharides/pharmacology , Plant Extracts/chemistry , Plant Extracts/pharmacologyABSTRACT
Inonotus obliquus (Fr.) Pilat is an edible mushroom which is used to produce tea and syrup due to its medicinal properties. In this study, 10 secondary metabolites (1-10), including a new lanostane triterpenoid named 2α-hydroxy-inotodiol (2α-HI, 1), were identified from the edible mushroom I. obliquus through high-resolution electrospray ionization mass spectrometry (HRESIMS) and nuclear magnetic resonance spectroscopy (NMR) data analysis. The neuroprotective function of all steroidal metabolites in H2O2-induced SH-SY5Y cells was investigated. The results showed that 2α-HI exhibited the most remarkable neuroprotective activity. In the meantime, 2α-HI significantly ameliorated oxidative stress damage, reactive oxygen species (ROS) accumulation and mitochondrial damage induced by H2O2 in SH-SY5Y cells. The Nrf2 siRNA and inhibitors transfected the SH-SY5Y cells, indicating the Nrf2 and BDNF/TrkB/ERK/CREB pathway mediated the neuroprotective effects of 2α-HI against the H2O2-stimulated oxidative stress and apoptosis. Moreover, the neuroprotection of 2α-HI was preliminarily verified in zebrafish. In conclusion, this research was the first to confirm that 2α-HI could effectively protect SH-SY5Y cells against H2O2-induced oxidative stress and apoptosis via the Nrf2 and BDNF/TrkB/ERK/CREB signaling pathway. Hence, this mushroom could be a potential dietary supplement to ameliorate neurodegenerative diseases.
Subject(s)
Agaricales , Neuroblastoma , Neuroprotective Agents , Triterpenes , Animals , Humans , Agaricales/metabolism , Apoptosis , Brain-Derived Neurotrophic Factor/genetics , Brain-Derived Neurotrophic Factor/metabolism , Cell Line, Tumor , Hydrogen Peroxide/toxicity , Neuroprotective Agents/pharmacology , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism , Oxidative Stress , Reactive Oxygen Species/metabolism , Signal Transduction , Triterpenes/pharmacology , Zebrafish/metabolismABSTRACT
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-1ß, 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 H2O2-induced SH-SY5Y cells by activating the Akt/GSK-3ß/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.