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During an investigation of plant cell cultures that might be useful in the treatment of renal disorders, we established a vigorously-growing E-4 callus culture of Eritrichium sericeum that produced large amounts of caffeic acid metabolites, (-)-rabdosiin (1.8% dry wt) and rosmarinic acid (4.6% dry wt). Elicitation of the calli by methyl jasmonate induced a 38% increase in total polyphenol production. The most efficient method of eliciting (-)-rabdosiin biosynthesis was through the treatment of E-4 calli with cuprum glycerate, which induced an increase in (-)-rabdosiin production of as much as 4.1% dry wt. Oral administration of E-4 callus biomass (100 mg/kg/d for 30 d) to rats with induced Masugi-nephritis caused an increase in diuresis and lowered creatinine excretion and proteinuria levels as compared with Masugi-nephritis untreated rats. While all of the Masugi-nephritis untreated rats began to suffer, near a quarter of the E-4 treated rats remained in good health. This result indicates that the E-4 culture has the potential to alleviate the symptoms associated with nephritis.

Rabdosiin and related caffeic acid metabolites have been proposed as active pharmacological agents demonstrating potent anti-HIV and antiallergic activities. We transformed Eritrichium sericeum and Lithospermum erythrorhizon seedlings by the rolC gene, which has been recently described as an activator of plant secondary metabolism. Surprisingly, the rolC-transformed cell cultures of both plants yielded two- to threefold less levels of rabdosiin and rosmarinic acid (RA) than respective control cultures. This result establishes an interesting precedent when the secondary metabolites are differently regulated by a single gene. We show that the rolC gene affects production of rabdosiin and RA irrespective of the methyl jasmonate (MeJA)-mediated and the Ca(2+)-dependent NADPH oxidase pathways. Cantharidin, an inhibitor of serine/threonine phosphatases, partly diminishes the rolC-gene inhibitory effect that indicates involvement of the rolC-gene-mediated signal in plant regulatory controls, mediated by protein phosphatases. We also show that the control MeJA-stimulated E. sericeum root culture produces (-)-rabdosiin up to 3.41% dry weight, representing the highest level of this substance for plant cell cultures reported so far.

Eritrichium sericeum (Boraginaceae) callus and root cultures were established and analyzed for caffeic acid metabolite (CAM) production. Two substances, (-)-rabdosiin and rosmarinic acid, were identified as main CAMs produced by these cultures. The E. sericeum Er-1 root culture accumulated up to 1.5 % and 4.5 % DW of (-)-rabdosiin and rosmarinic acid, respectively. Rabdosiin in the Lithospermum erythrorhizon callus cultures was produced exclusively as the (+)-enantiomer while in both Eritrichium cultures it occurred as the (-)-enantiomer. The E. sericeum Er-1 culture accumulated 3-fold higher levels of CAMs than the L. erythrorhizon culture. A new compound, named eritrichin, was isolated from the cultured E. sericeum cells. The structure of this compound was established as (2R)-3-(3,4-dihydroxyphenyl)-2-[4-(3,4-dihydroxyphenyl)-6,7-dihydroxy-2-naphthoyloxy]propanoic acid on the basis of spectral data.