迷迭香中抑制NLRP3炎症小体活性成分的发现

Discovery of Bioactive Ingredients in Rosemary officinalis Inhibiting NLRP3 Inflammasome

摘要:

迷迭香的抗炎活性成分已有多篇文献报道归结于其中所含的鼠尾草酸、鼠尾草酚和熊果酸等，但将迷迭香乙醇提取物除去上述3种含量较多的成分后，剩余组分仍显示出较好的抗炎活性，提示迷迭香中存在没被发现的抗炎活性成分。在体外抑制NLRP3炎症小体抗炎活性的筛选结果指导下，利用各种色谱技术和波谱学方法，从上述抗炎活性组分中，分离分析鉴定了3个黄酮类化合物： 4′，5-二羟基-7-甲氧基黄酮（1）、 5-羟基-7，4′-二甲氧基黄酮（2）和5-羟基-7，8，4′-三甲氧基黄酮（3）。对分离得到的3个化合物进行体外抑制NLRP3炎症小体的验证，均显示一定的抑制活性。其中化合物1的抑制活性最强，与阳性对照MCC950（炎症小体抑制剂）相当。化合物3是首次从迷迭香属植物中分离得到。

Abstract:

The anti-inflammatory active ingredients of rosemary have been reported in many literatures, including carnosic acid, carnosol and ursolic acid. However, the rosemary ethanol extract still showed good anti-inflammatory activity after removal of the above three large-content components, suggesting that there were undiscovered anti-inflammatory ingredients in rosemary in addition to the reported active ingredients. Under the guidance of inhibiting the anti-inflammatory activity of NLRP3 inflammasome in vitro, three flavonoids were isolated and identified from the above-mentioned anti-inflammatory components by various chromatographic techniques and spectroscopy methods including 4′,5-dihydroxy-7-methoxyflavone (1), 5-dydroxy-7, 4′-dimethoxy flavone (2) and 5-hydroxy-7, 8, 4′-trimethoxyflavone (3). The three isolated compounds were confirmed to possess inhibitory effect on NLRP3 inflammasome in vitro. Among them, compound 1 had the strongest inhibitory activity, comparable to the positive control MCC950 (inflammatory inhibitor). Compound 3 was isolated from Rosmarinus for the first time.