State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Science, Kunming 650201, People's Republic of China.
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Science, Kunming 650201, People's Republic of China; University of the Chinese Academy of Science, Beijing 100049, People's Republic of China.
Bioorg Chem. 2021 Nov;116:105338. doi: 10.1016/j.bioorg.2021.105338. Epub 2021 Sep 8.
Four pairs of novel meroterpenoid dimers, (±)-applandimeric acids A-D (1-4) with an unprecedented spiro[furo[3,2-b]benzofuran-3,2'-indene] core were isolated from the fruiting bodies of Ganoderma applanatum. Their planar structures were unambiguously determined via extensive spectroscopic analysis. Their relative and absolute configurations were confirmed through calculated internuclear distance, coupling constant, C NMR with DP4 + analysis and electronic circular dichroism (ECD). Furthermore, the molecular docking-based method was used to evaluate their interaction with formyl peptide receptor 2 (FPR2) associated with inflammation. Interestingly, (±)-applandimeric acid D (4) can bond with FPR2 by some key hydrogen bonds. Furthermore, an in vitro bioassay verified that 4 can inhibit the expression of FPR2 with IC value of 7.93 μM. In addition, compared to the positive control LiCl (20 mM), 4 showed comparable anti-lipogenesis activity at the concentration of 20 μM. Meanwhile, 4 can suppress the protein levels of peroxisome proliferators-activated receptor-γ (PPAR-γ), CCAAT/enhancer-binding protein-β (C/EBP-β), adipocyte fatty acid-binding protein 4 (FABP4), and fatty acid synthase (FAS) through activating AMP-activated protein kinase (AMPK) signaling pathway. Thus, our findings indicate that compound 4 could be a lead compound to treat obesity and obesity-related diseases by inhibiting lipid accumulation in adipocyte and alleviating inflammation.
四对新型倍半萜二聚体（±）-applandimeric 酸 A-D（1-4），具有前所未有的螺[furo[3,2-b]苯并呋喃-3,2'-茚]核心，从灵芝的子实体中分离出来。通过广泛的光谱分析，明确确定了它们的平面结构。通过计算核间距离、耦合常数、C NMR 与 DP4+分析和电子圆二色性（ECD），确定了它们的相对和绝对构型。此外，还使用基于分子对接的方法评估了它们与与炎症相关的甲酰肽受体 2（FPR2）的相互作用。有趣的是，（±）-applandimeric 酸 D（4）可以通过一些关键氢键与 FPR2 结合。此外，体外生物测定证实，4 可以通过抑制 FPR2 的表达来抑制炎症，IC 值为 7.93μM。此外，与阳性对照 LiCl（20mM）相比，4 在 20μM 浓度下表现出相当的抗脂肪生成活性。同时，4 通过激活 AMP 激活蛋白激酶（AMPK）信号通路，可抑制过氧化物酶体增殖物激活受体-γ（PPAR-γ）、CCAAT/增强子结合蛋白-β（C/EBP-β）、脂肪细胞脂肪酸结合蛋白 4（FABP4）和脂肪酸合成酶（FAS）的蛋白水平。因此，我们的研究结果表明，化合物 4 可能通过抑制脂肪细胞中脂质积累和减轻炎症来治疗肥胖症和肥胖相关疾病。
