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

Abstract:

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.