咖啡酸代谢物的抗肾炎活性分析

Biotechnological Analysis of Caffeic Acid Metabolites Possessing Potent Anti-nephritic Activity

在研究治疗肾功能紊乱植物的细胞培养时,建立了一个Eritrichium sericeum的E-4愈伤组织株系,发现此株系可产生大量的咖啡酸代谢物、(–)-rabdosiin(1.8%干重)和迷迭香酸(4.6%干重),通过诱导(–)-rabdosiin的含量提高至4.1%(干重)。将E-4愈伤组织喂服Masugi肾炎大鼠,结果发现,与对照组(未喂服E-4愈伤组织的Masugi肾炎大鼠)相比,处理组(喂服E-4愈伤组织)中的大鼠出现如下症状:尿多、排泄物中肌氨酸酐降低、尿蛋白水平降低;当对照组中所有大鼠都出现疼痛症状时,处理组中仍有约/4的大鼠表现出健康状况良好。以上结果表明,E-4株系具有缓解肾炎症状的潜在功能。此外,利用富含多酚的rolC转基因的细胞株系,研究了愈伤组织中咖啡酸代谢物的诱导合成机制。结果发现,在rloC转基因的E.sericeum愈伤组织中,咖啡酸代谢物的高产与迷迭香酸生物合成中的关键基因CYP98A3的高表达有关。

During an investigation of plant cell cultures which may be useful for the treatment of renal disorders, we established a well-growing E-4 callus culture of Eritrichium sericeum that produced high amounts of caffeic acid metabolites, （-）-rabdosiin （1.8% dry wt） and rosmarinic acid （4.6% dry wt）. Elicitation of the calli induced an increase in （-）-rabdosiin production by as much as 4.1% dry wt. Oral administration of E-4 callus biomass to rats with induced Masugi-nephritis caused an increase of diuresis, lowered creatinine excretion and proteinuria levels, compared with Masugi-nephritis untreated rats. While all of the Masugi-nephritis untreated rats began to ache, near a quarter of the E-4 treated rats remained in good health. This result indicates that the E-4 culture has a potential to alleviate symptoms associated with nephritis. A mechanism by which production of caffeic acid metabolites could be activated in the calli was studied using a high polyphenol-producing cell cultures transformed with the rolC gene. We established that the increase of caffeic acid metabolites production in rolC-transgenic E. sericeum calli positively correlated with high expression of the CYP98A3 gene, a key gene for rosmarinic acid biosynthesis.