Ganoderterpene A, a New Triterpenoid from Ganoderma lucidum, Attenuates LPS-Induced Inflammation and Apoptosis via Suppressing MAPK and TLR-4/NF-κB Pathways in BV-2 Cells,Journal of Agricultural and Food Chemistry

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Ganoderterpene A, a New Triterpenoid from Ganoderma lucidum, Attenuates LPS-Induced Inflammation and Apoptosis via Suppressing MAPK and TLR-4/NF-κB Pathways in BV-2 Cells
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2021-10-20 , DOI: 10.1021/acs.jafc.1c04905
Rong-Wei Kou ₁ , Yu-Qi Gao ₁ , Bing Xia ₂ , Jia-Yun Wang ₁ , Xiao-Ning Liu ₂ , Jiang-Jiang Tang ₁ , Xia Yin ₁ , Jin-Ming Gao ₁

Affiliation

An investigation of the fruiting bodies of edible mushroom Ganoderma lucidum produced 13 steroids, containing one new lanostane-type triterpene compound, named ganoderterpene A (1). Nuclear magnetic resonance and high-resolution electrospray ionization mass spectrometry data were used to deduce these structures. All the isolates were evaluated for their ability to suppress NO generation in BV-2 microglial cells treated with lipopolysaccharide (LPS) and exhibited moderate to strong inhibition effects, with IC₅₀ values in the range 7.15–36.88 μM. Among the tested compounds, compound 1 exhibited the most marked activity with an IC₅₀ value of 7.15 μM, and the structure–activity relationships were studied. This study showed that compound 1 significantly suppressed the activation of MAPK and TLR-4/NF-κB signaling pathways, as evidenced by an immunofluorescence assay and a molecular docking experiment. Furthermore, compound 1 effectively improved the LPS-induced mitochondrial membrane potential and apoptosis. These findings suggest that ganoderterpene A could exert protective effects in microglial cells from apoptosis by restraining the inflammatory response. Hence, G. lucidum could be used as a novel preventative agent for neurodegenerative disorders.

中文翻译：

Ganoderterpene A，一种来自灵芝的新三萜，通过抑制 BV-2 细胞中的 MAPK 和 TLR-4/NF-κB 通路减弱 LPS 诱导的炎症和细胞凋亡

一项对食用菌灵芝子实体的研究产生了 13 种类固醇，其中含有一种新的羊毛脂烷型三萜化合物，命名为灵芝 A ( 1 )。核磁共振和高分辨率电喷雾电离质谱数据用于推断这些结构。评估了所有分离株抑制脂多糖 (LPS) 处理的 BV-2 小胶质细胞中 NO 生成的能力，并表现出中到强的抑制作用，IC ₅₀值在 7.15–36.88 μ M范围内。在测试的化合物中，化合物1表现出最显着的活性，IC ₅₀值为 7.15 μM，并研究了构效关系。这项研究表明，化合物1显着抑制了 MAPK 和 TLR-4/NF-κB 信号通路的激活，免疫荧光测定和分子对接实验证明了这一点。此外，化合物1有效地改善了LPS诱导的线粒体膜电位和细胞凋亡。这些发现表明，灵芝萜烯 A 可以通过抑制炎症反应对小胶质细胞发挥保护作用，使其免于凋亡。因此，灵芝可用作神经退行性疾病的新型预防剂。

更新日期：2021-11-03

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