Planta Med 2015; 81 - PM_114
DOI: 10.1055/s-0035-1565491

LC-MS-based phytochemical characterization of an antiproliferative Daphne altaica stem bark extract

M Kizaibek 1, EM Pferschy-Wenzig 2, N Kretschmer 2, M Hamburger 3, R Bauer 2
  • 1Traditional Kazakh Medicine Research Institute of Ili Kazakh Autonomous Prefecture, Yining, Xinjiang, China
  • 2University of Graz, Institute of Pharmaceutical Sciences, Department of Pharmacognosy, Graz, Austria
  • 3University of Basel, Department of Pharmaceutical Sciences, Pharmaceutical Biology, Basel, Switzerland

Daphne altaica Pall. (Thymelaeaceae) is a deciduous shrub native to central Asia. The plant has long been used in traditional Kazakh Medicine to treat different types of cancer and ailments like rheumatism, common cold and sore throat. In a previous study, D. altaica stem bark extracts have been shown to possess antiproliferative activity in human esophageal squamous cell carcinoma, gastric carcinoma, hepatoma and cervical carcinoma cells [1]. In the current investigation, D. altaica stem bark was submitted to sequential extraction with n-hexane, dichloromethane (CH2Cl2) and methanol, and the extracts were tested for antiproliferative activity in human CCRF-CEM leukemia and MDA-MB-231 breast cancer cells. The most active CH2Cl2 extract was analyzed by LC-DAD-MSn and by LC-DAD-HRESIMS in positive mode. This allowed the unambiguous identification of the four diterpene orthoesters daphnetoxin,1,2-dihydrodaphnetoxin, gnidicin and excoecariatoxin, of the bis-coumarin daphnoretin (Fig. 1), and the tentative identification of 9 further diterpene orthoesters. All compounds were identified in D. altaica for the first time. Daphnane-type diterpene orthoesters are characteristic of the Thymelaceae family. For daphnetoxin, gnidicin, excoecariatoxin and some of the tentatively identified diterpene orthoesters, anticancer activity has been described [2, 3]. We found that 1,2-dihydrodaphnetoxin was moderately active in CCRF-CEM and MDA-MB-231 cells. Also, daphnoretin is known to possess anticancer effects in vitro [4, 5]. Therefore, it can be assumed that the identified constituents are of high relevance for the antiproliferative activity of the D. altaica CH2Cl2 extract.

Fig. 1: Constituents unambiguously identified from D. altaica CH2Cl2 extract

Acknowledgements: M. Kizaibek thanks Austrian Exchange Service (OeAD) for supporting his stay in Austria (Ernst Mach-Nachbetreuungsstipendium, EZA), and National Science Foundation of China for financial support (Grant 81360499). We thank K. Jensen (NAWI Graz Central Lab "Environmental, Plant & Microbial Metabolomics") for support with the LC-HRMS instrument.

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