Leopersin E and further labdane typ diterpenes from Leonurus cardiaca L.

Following the development of primary and refined antiarrhythmic extracts of Leonurus cardiaca L. [1] our main task was to search for possible cardioactive or cardiotoxic single constituents. In this context the paper attendant is focused on the group of lipophilic labdane type diterpenes. Via combination of normal and reversed phase column chromatography, it was possible to isolate three furanolabdanes from Leonurus cardiaca L., the structures of those have been determined mainly by 1d/2d ¹H/¹³C NMR spectroscopic experiments. Leopersine E, which has been only once reported in Leonurus persicus [2], could be found as a major diterpene for the first time in Leonurus cardiaca L. Furthermore the occurrence of leosibiricine and preleosibirine in Leonurus cardiaca L. could be confirmed mainly by NMR spectroscopy. In accordance to Knöss et al. [5, 6] the postulated presence of leocardine [3, 4] as a major reference substance of Leonurus cardiaca L. could not be confirmed. In view of the above mentioned search for possible cardioactive constituents, the similarity of leosibiricine to e.g. premarrubeine and marrubenol from the closely related Marrubium vulgare L. might be an important hint at a possible cardioactive property, particularly since those have been evaluated as calcium channel blocking agents.

During our survey we discovered a complete rearrangement of leosibiricine to leopersine E, which shows us the importance of leopersine E as an important marker substance of this Leonurus cardiaca fraction.

This can be demonstrated by orientating HPLC and NMR experiments of fresh and dried plant material, an enriched cc-fraction as well as NMR-samples.

References: [1] Ritter M, Rauwald HW, Dhein S. Cardiac and electrophysiological effects of primary and refined extracts from Leonurus cardiaca L. (Ph.Eur). Planta Med 2010; 76: 572–582

[2] Tasdemir D, Wright AD, Sticher O. New furanoid and seco-labdanoid diterpenes from Leonurus persicus. J Nat Prod 1996; 59: 131–134

[3] Brieskorn CH, Hofmann R. Labiatengerbstoffe: Ein Clerodanderivat aus Leonurus cardiaca L. Tetrahedron Letters 1979; 27; 2511–2512

[4] Malakov P, Papanov G, Jakupovic J. The structure of leocardin, two epimers of a diterpenoid from Leonurus cardiaca L. Phytochemistry 1985; 24: 2341–2343

[5] Knöss W. Establishment of callus, cell suspension, and shoot cultures of Leonurus cardiaca L. and diterpene analysis. Plant Cell Reports 1995; 14: 790–793

[6] Knöss W, Zapp J. Accumulation of furanic labdane diterpenes in Marrubium vulgare and Leonurus cardiaca L. Planta Med 1998; 64: 357–361

[7] El Bardai S, Morel N, Wibo M. The vasorelaxant activity of marrubenol and marrubiin from Marrubium vulgare. Planta Med 2003; 69: 75–77