Studies on the chemical stability of umbelliprenin, the active principle of Ferula spp.

7-Oxyprenylated coumarins are among the most notable examples of biologically active oxyprenylated plant secondary metabolites occurring in nature, mainly in plants belonging to Rutaceae and Apiaceae families. Umbelliprenin (UMP) is a farnesyloxy- umbelliferon derivative that has been found in several edible fruits and vegetables including celery, coriander, angelica, lemon, and Ferula spp. It has been isolated in the 60's but only recently the phytochemical and biological profile has been detailed [1]. Umbelliprenin was shown to exert valuable and promising anti-cancer, anti-inflammatory, anti-oxidant, and anti-protozoal effects. Despite its effectiveness as pharmacological tool, studies on the chemical stability of this active principle have never been reported in the literature. In this talk data obtained from a simple, economic, and selective HPLC method for the forced degradation of umbelliprenin indicating its chemical stability upon exposure to oxidation, heat, sun, and UV light will be discussed. Forced degradation studies provide insights into degradation pathways and side-products formation from the candidate drug substance, help in the elucidation of the structure of the degradation products, and allow to better set-up formulation and package. In our studies a C-18 reversed-phase packed column, was employed for the separation, and the column was thermostated at 25 ± 1 °C using a cool pocket chiller. UV detector with excitation and emission wavelength of 323nm was used for determination of umbelliprenin. Empower v.2 Software (Waters Spa, Milford, MA, USA) was used for data acquisition and elaboration. The flow rate was set at 1.2 mL/min., chromatographic separation was carried out using gradient eluition. Samples (20µL) were injected by means of a Rheodyne injector fitted with a 20-µL loop. The method was validated for accuracy, precision, reproducibility, specificity, robustness, and detection and quantification limits, in accordance with ICH guidelines. Results obtained are summarized in Figures 1 (UMP in the solid state) and 2 (UMP inEtOH solution). The protective effect of several natural and synthetic antioxidants on umbelliprenin degradation will be also discussed.

Acknowledgements: Financial support to this research from University “G. d'Annunzio” of Chieti-Pescara is gratefully acknowledged.

Keywords: Antioxidant activity, chemical stability, oxyprenylated coumarins, umbelliprenin.

Fig. 1: Degradation of UMP in the solid state

Fig. 2: Degradation of UMP in ethanolic solution

References:

[1] Shakeri A, Iranshahy M, Inrashahi M. Biological properties and molecular targets of umbelliprenin – a minireview. J As Nat Prod Res 2014; 8: 884 – 889