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Pyranochromones with Anti-Inflammatory Activities in Arthritis from Calophyllum membranaceum
Journal of Natural Products ( IF 3.3 ) Pub Date : 2022-05-03 , DOI: 10.1021/acs.jnatprod.2c00157 Wei Shen 1 , Xiao-Long Hu 1 , Si-Yuan Li 1 , Lun Li 1 , Xiao-Wei Dong 1 , Hao Liu 1 , Jia-Min Cui 1 , Zhe Song 2 , Xiao-Qi Zhang 3 , Wen-Cai Ye 3 , Hao Wang 1
Journal of Natural Products ( IF 3.3 ) Pub Date : 2022-05-03 , DOI: 10.1021/acs.jnatprod.2c00157 Wei Shen 1 , Xiao-Long Hu 1 , Si-Yuan Li 1 , Lun Li 1 , Xiao-Wei Dong 1 , Hao Liu 1 , Jia-Min Cui 1 , Zhe Song 2 , Xiao-Qi Zhang 3 , Wen-Cai Ye 3 , Hao Wang 1
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Eleven new pyranochromones, calomembranone A–K (1–11), two new pyranocoumarins, calopolyanolide E and F (12 and 13), together with six known analogues (14–19) were isolated from the leaves of Calophyllum membranaceum. Their structures and absolute configurations were elucidated by analysis of spectroscopic data, computational calculations, as well as X-ray crystallography of 4 and 9. The anti-inflammatory activities of all the isolates were evaluated by measuring their NO inhibitory effects in LPS-stimulated RAW 264.7 cells. Structure–activity relationships are also discussed. Compound 7 showed the strongest NO inhibition (IC50 = 0.92 μM). Oral administration of 7 dose-dependently reduced the paw swelling and downregulated neutrophil-to-lymphocyte ratio in the carrageenan-induced acute arthritis mice model. Molecular dynamics simulation and cellular thermal shift assay results indicated that 7 participated in a robust and stable interaction with the active site of TLR4. Compound 7 also suppressed the inflammation in arthritis through the regulation of TLR4 mediated signal transduction via IKK/NF-κB signaling pathway and the consequent reduction of IL-2, IL-4, and IL-5.
中文翻译：
黄花菜中具有抗炎活性的吡喃色酮类化合物
十一种新的吡喃色酮，calomembranone A-K ( 1-11 ) ，两种新的吡喃香豆素，calopolyanolide E 和 F ( 12和13 )，以及六种已知的类似物 ( 14-19 )从Calophyllum membranaceum的叶子中分离出来。通过光谱数据分析、计算计算以及4和9的 X 射线晶体学，阐明了它们的结构和绝对构型。通过测量它们在 LPS 刺激的 RAW 264.7 细胞中的 NO 抑制作用来评估所有分离物的抗炎活性。还讨论了结构-活性关系。化合物7显示出最强的 NO 抑制作用 (IC 50 = 0.92 μM)。在角叉菜胶诱导的急性关节炎小鼠模型中，口服7剂量依赖性地减少爪肿胀并下调中性粒细胞与淋巴细胞的比例。分子动力学模拟和细胞热位移测定结果表明，7参与了与 TLR4 活性位点的稳健和稳定的相互作用。化合物7还通过 IKK/NF-κB 信号通路调节 TLR4 介导的信号转导和随后的 IL-2、IL-4 和 IL-5 减少来抑制关节炎中的炎症。
更新日期：2022-05-03
中文翻译：
黄花菜中具有抗炎活性的吡喃色酮类化合物
十一种新的吡喃色酮，calomembranone A-K ( 1-11 ) ，两种新的吡喃香豆素，calopolyanolide E 和 F ( 12和13 )，以及六种已知的类似物 ( 14-19 )从Calophyllum membranaceum的叶子中分离出来。通过光谱数据分析、计算计算以及4和9的 X 射线晶体学，阐明了它们的结构和绝对构型。通过测量它们在 LPS 刺激的 RAW 264.7 细胞中的 NO 抑制作用来评估所有分离物的抗炎活性。还讨论了结构-活性关系。化合物7显示出最强的 NO 抑制作用 (IC 50 = 0.92 μM)。在角叉菜胶诱导的急性关节炎小鼠模型中，口服7剂量依赖性地减少爪肿胀并下调中性粒细胞与淋巴细胞的比例。分子动力学模拟和细胞热位移测定结果表明，7参与了与 TLR4 活性位点的稳健和稳定的相互作用。化合物7还通过 IKK/NF-κB 信号通路调节 TLR4 介导的信号转导和随后的 IL-2、IL-4 和 IL-5 减少来抑制关节炎中的炎症。
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