Triterpene alcohols from Calendula officinalis L. flowers and in vitro studies on their wound healing activity

Skin wound healing is a well organized process to restore tissue integrity and can be divided into three overlapping phases; inflammation, new tissue formation and remodelling. Complications in the wound healing process are a high physiological and psychological interface for patients and a tremendous socio- economic problem [1]. Calendula officinalis L. (marigold) flower extracts are recommended for the treatment of wounds by the Pharm. Eur., the ESCOP, the WHO and the EMA. Despite some studies for the wound healing activity the active components are still a matter of debate. In addition to polysaccharides, carotenoids and triterpene saponins, free and esterified triterpenes are major constituents of Calendula officinalis L. flowers with proven anti-inflammatory activity in the Croton oil ear test [2]. Previously Fronza et al. observed remarkable effects for the myristic and palmitic acid ester of faradiol, the major triterpene in Calendula officinalis L. flowers, in the scratch assay using 3T3-mouse fibroblasts [3]. Here we report on phytochemical studies of the hexane extract which afforded the isolation of 6 triterpene alcohols from the psi-taraxene, taraxene, oleanene, lupene and dammarane type, of which 3 are described for Calendula officinalis L. flowers for the first time. Some of the isolated triterpenes were studied for their effect on the migration and proliferation of keratinocytes in the scratch assay and first structure-activity-relationships are drawn. Studies are in progress to gain further insights in the complex wound healing mechanism of preparations from Calendula officinalis L. flowers.

Acknowledgements: We are grateful to S. Ferlaino, Department for Pharmaceutical and Medical Chemistry, for measuring the NMR spectra as well as to Dr. J. Wörth and C. Warth, Department for Organic Chemistry, for taking the mass spectra, all University of Freiburg, Germany and to Dr. Junghanns for providing us with Calendula officinalis flowers.

Keywords: Calendula, triterpenes, wound healing

References:

1. Gurtner GC, Werner S, Barrandon Y, Longaker MT. Wound repair and regeneration. Nature 2008; 453: 314 – 321; 2. Della Loggia R, Tubaro A, Sosa S, Becker H, Saar S, Isaac O. The role of triterpenoids in the topical anti-inflammatory activity of Calendula officinalis flowers. Planta Med. 1994; 60: 516 – 520; 3. Fronza M, Heinzmann B, Hamburger M, Laufer S, Merfort I. Determination of the wound healing effect of Calendula extracts using the scratch assay with 3T3 fibroblasts. J. Ethnopharmacol 2009; 126: 463 – 467