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源自子实体的神经保护萜类化合物:分离、结构解析及作用机制洞察

Neuroprotective Terpenoids Derived from Fruiting Bodies: Isolation, Structural Elucidation, and Mechanistic Insights.

作者信息

Cao Ying, Wang Qiaona, Li Lu, Jiang Haitao, Zhang Bianjiang, Wu Yulong, Zhou Feng, Hua Chun, Huo Guangming, Li Shengjie, Li Jianmei

机构信息

School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing 210023, China.

School of Food Science, Nanjing Xiaozhuang University, Nanjing 211171, China.

出版信息

Int J Mol Sci. 2025 Jul 10;26(14):6606. doi: 10.3390/ijms26146606.

Abstract

, a medicinal macrofungus, is renowned for its potential neuroprotective benefits. Here, we isolated and characterized secondary metabolites from fruiting bodies and explored their neuroprotective effects and primary mechanisms of action. A novel terpenoid (4) and four known compounds (, , , and ) were identified. Their chemical structures were determined using nuclear magnetic resonance (NMR), high-resolution mass spectrometry (HRMS), and x-ray diffraction (XRD). Bioactivity screening using PC12 cells indicated that (3R,4R)-4-acetyl-3,4-dihydro-6,8-dihydroxy-3-methoxy-5-methyl-1H-2-benzopyran (3) and the terpenoid, (1R,4S,8aS)-1,4-dihydroxy-2,5,5,8a-tetramethyl-1,4,4a,5,6,7,8,8a-octahydronaphthalene-1-carbaldehyde (4), demonstrated protective properties against hydrogen peroxide (HO)-induced damage. Transcriptomics, network pharmacology, and molecular docking showed that compound counteracted HO-induced oxidative stress and inflammation by substantially attenuating pro-inflammatory cytokine (IL-1β, IL-6) expression, downregulating pro-oxidant factors (Aoc3, Dusp3), and decreasing reactive oxygen species levels, while boosting superoxide dismutase activity. Compound exerted neuroprotective effects via the NF-κB pathway. represents a valuable natural reservoir of bioactive compounds for treating and preventing neurodegenerative diseases.

摘要

[某种药用大型真菌]以其潜在的神经保护益处而闻名。在此,我们从[该真菌]子实体中分离并鉴定了次生代谢产物,并探讨了它们的神经保护作用及其主要作用机制。鉴定出一种新型萜类化合物(4)和四种已知化合物([化合物名称1]、[化合物名称2]、[化合物名称3]和[化合物名称4])。使用核磁共振(NMR)、高分辨率质谱(HRMS)和X射线衍射(XRD)确定了它们的化学结构。使用PC12细胞进行的生物活性筛选表明,(3R,4R)-4-乙酰基-3,4-二氢-6,8-二羟基-3-甲氧基-5-甲基-1H-2-苯并吡喃(3)和萜类化合物(1R,4S,8aS)-1,4-二羟基-2,5,5,8a-四甲基-1,4,4a,5,6,7,8,8a-八氢萘-1-甲醛(4)对过氧化氢(HO)诱导的损伤具有保护特性。转录组学、网络药理学和分子对接表明,化合物[3]通过大幅减弱促炎细胞因子(IL-1β、IL-6)的表达、下调促氧化因子(Aoc3、Dusp3)并降低活性氧水平,同时增强超氧化物歧化酶活性,来对抗HO诱导的氧化应激和炎症。化合物[3]通过NF-κB途径发挥神经保护作用。[该真菌]是用于治疗和预防神经退行性疾病的生物活性化合物的宝贵天然来源。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c80/12294627/d153f00003f4/ijms-26-06606-g001.jpg

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