Xu Qingxia, Lv Qian, Liu Lu, Zhang Yingtao, Yang Xiuwei
State Key Laboratory of Natural and Biomimetic Drugs, Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University Health Science Center, Peking University, No. 38, Xueyuan Road, Haidian District, Beijing, 100191, China.
Chin Med. 2021 Oct 7;16(1):98. doi: 10.1186/s13020-021-00499-y.
Dried fruits of Psoralea corylifolia L. (Psoraleae Fructus) is one of the most popular traditional Chinese medicine with treatment for nephritis, spermatorrhea, pollakiuria, asthma, and various inflammatory diseases. Bakuchiol is main meroterpenoid with bioactive diversity from Psoraleae Fructus. This study was designed to seek structural diverse bakuchiol derivants with anti-inflammatory activities from this plant.
Various column chromatography methods were used for isolation experiment. Structures and configurations of these compounds were determined by spectroscopic methods and single-crystal X-ray diffraction. Their inhibition on nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages were evaluated by the Griess reaction.
Twelve unpresented bakuchiol dimmers, bisbakuchiols M-U (1-9) and bisbakuchiol ethers A-C (10-12), along with five known compounds (13-17), were isolated from the fruits of Psoralea corylifolia L. Compounds 1-3, 10-12, 16 and 17 exhibited inhibitory activities against LPS-induced NO production in RAW264.7 macrophages, and the inhibition of compound 1 (half maximal inhibitory concentration (IC) value = 11.47 ± 1.57 μM) was equal to that of L-N(6)-(1-iminoethyl)-lysine (IC = 10.29 ± 1.10 μM) as a positive control.
Some compounds exhibited inhibitory activities against NO production, and the study of structure-activity relationship suggested that uncyclized compounds with oxygen substitution at C-12/12' showed strong inhibitory activities, and carbonyl units contributed to enhanced activities.
补骨脂（Psoralea corylifolia L.）的干燥果实是最常用的传统中药之一，可用于治疗肾炎、遗精、尿频、哮喘和各种炎症性疾病。补骨脂酚是补骨脂果实中具有多种生物活性的主要半萜类化合物。本研究旨在从该植物中寻找具有抗炎活性的结构多样的补骨脂酚衍生物。
采用多种柱色谱方法进行分离实验。通过光谱方法和单晶X射线衍射确定这些化合物的结构和构型。采用Griess反应评估它们对脂多糖（LPS）刺激的RAW264.7巨噬细胞中一氧化氮（NO）产生的抑制作用。
从补骨脂果实中分离出12个未见报道的补骨脂酚二聚体，双补骨脂酚M-U（1-9）和双补骨脂酚醚A-C（10-12），以及五个已知化合物（13-17）。化合物1-3、10-12、16和17对LPS诱导的RAW264.7巨噬细胞中NO的产生具有抑制活性，化合物1的抑制作用（半数最大抑制浓度（IC）值=11.47±1.57μM）与作为阳性对照的L-N(6)-(1-亚氨基乙基)-赖氨酸（IC=10.29±1.10μM）相当。
一些化合物对NO的产生具有抑制活性，构效关系研究表明，在C-12/12'处有含氧取代的开环化合物具有较强的抑制活性，羰基单元有助于增强活性。
