通过 LCMS/MS 从 Colebrookea oppositifolia 中快速鉴定和分离新型抗炎类黄酮的基于去复制的策略,ACS Omega

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通过 LCMS/MS 从 Colebrookea oppositifolia 中快速鉴定和分离新型抗炎类黄酮的基于去复制的策略
ACS Omega ( IF 3.7 ) Pub Date : 2021-11-02 , DOI: 10.1021/acsomega.1c01837
Neha Sharma ₁ , Vidushi Khajuria _{2,

3} , Shilpa Gupta _{2,

3} , Chetan Kumar ₁ , Anjana Sharma _{3,

4} , Nazir Ahmad Lone _{3,

4} , Satya Paul ₅ , Siya Ram Meena ₆ , Zabeer Ahmed _{2,

3} , Naresh Kumar Satti ₁ , Mahendra Kumar Verma ₁

Affiliation

Colebrookea oppositifolia是一种民间药用植物，以其巨大的药用特性而闻名，例如治疗癫痫、溃疡和泌尿问题。本研究的目的是将去复制策略应用于具有强效抗炎活性的C. oppositifolia乙醇提取物，以快速鉴定和分离新型生物活性分子，以帮助药物发现过程。使用液相色谱-质谱联用 (LCMS) 和制备型高效液相色谱 (HPLC) 的综合方法从C. oppositifolia的抗炎提取物中分离有效分子。化合物的纯度 (>98.5%) 通过 HPLC 确定，并通过 NMR 和 ESI-MS 进行鉴定。5,6,7-Trihydroxyflavone-3- O -glucuronidemethylester （化合物 III）从C. oppositifolia中分离出来，被广泛研究在脂多糖 (LPS) 刺激的 RAW 264.7 细胞和小鼠模型中的抗炎潜力。化合物 III 显着抑制各种促炎介质并上调抗炎细胞因子 IL-10 的释放。当研究吞噬指数、角叉菜胶诱导的小鼠爪水肿和对器官重量的影响等参数时，化合物 III 减轻了炎症。它在体外和体内都以剂量依赖的方式减少炎症. 对该研究的进一步分子洞察表明，化合物 III 可阻断 Iκb 激酶 α/β (IKKα/β)、IκBα 和核因子 kB p65 (NF-κBp65) 的磷酸化，后者是炎症的关键控制因子，从而显示出抗- 炎症潜能。因此，该研究允许进一步研究开发化合物 III 作为抗炎药。

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Dereplication Based Strategy for Rapid Identification and Isolation of a Novel Anti-inflammatory Flavonoid by LCMS/MS from Colebrookea oppositifolia

Colebrookea oppositifolia is a folkloric medicinal plant, well known for its tremendous medicinal properties such as curing epilepsy, ulcers, and urinary problems. The aim of the present study was to apply the dereplication strategy on the ethanol extract of C. oppositifolia with potent anti-inflammatory activity for the rapid identification and isolation of novel bioactive molecules to aid the drug discovery process. An integrated approach using liquid chromatography–mass spectrometry (LCMS) followed by preparative high-performance liquid chromatography (HPLC) was used for the isolation of potent molecules from the anti-inflammatory extract of C. oppositifolia. Purity of the compounds (>98.5%) was established by HPLC, and identification was carried out by NMR and ESI-MS. 5,6,7-Trihydroxyflavone-3-O-glucuronide methyl ester (compound III) isolated from C. oppositifolia was extensively studied for anti-inflammatory potential in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and the mice model. Compound III significantly repressed various proinflammatory mediators and upregulated the release of anti-inflammatory cytokine IL-10. Compound III reduced inflammation when studied for parameters such as the phagocytic index, carrageenan-induced paw edema in mice, and effect on organ weight. It reduced inflammation in a dose-dependent manner both in vitro and in vivo. Further molecular insights into the study revealed that compound III blocks the phosphorylation of I kappa b kinase α/β (IKKα/β), IκBα, and nuclear factor kB p65 (NF-κBp65) which is a key controller of inflammation, thereby showing anti-inflammatory potential. Hence, this study permits further investigation to develop compound III as an anti-inflammatory drug.

更新日期：2021-11-16

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