This study was aimed at identifying new efficient antioxidant juniper species and their metabolites, which are responsible for this activity. About 30 juniper representatives were assayed for antioxidant activity (DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS (2,2′-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) radical scavenging) and total polyphenol content (TPC). The most active species were identified, and their most abundant polyphenols were quantified by the LC-electrospray ionization (ESI)-MS/MS-multiple reaction monitoring (MRM) method. In the group of studied species, J. ashei (mountain cedar) leaf extract was outlined as the best antioxidant with the highest TPC. Catechin was revealed as the most abundant polyphenol in the J. ashei extract, contributing to its superior antioxidant properties. An in-depth analysis of antioxidant capacity was also performed. The higher metal-chelating activity was observed in the case of J. sibirica (0.83 mg DE/mL), whereas the lowest was observed for J. communis (3.2 mg dry extract (DE)/mL) extracts. All efficient antioxidant extracts were also able to inhibit lipoxygenase. EC50 values ranged from 1.77 to 2.44 mg DE/mL. The most effective inhibitors were J. ashei and J. formozana extracts, which acted as uncompetitive lipoxygenase (LOX) inhibitors. The presented results have potential application in the pharmacy and cosmetics for the generation of antioxidant compositions based on naturally derived lead compounds for the prevention of oxidative-stress associated organ-degenerative diseases, cancer, or other free radical-induced disorders.

Juniper representatives are natural sources of plenty of bioactive metabolites and have been used since ancient times as folk remedies against tapeworms, warts, cancer, etc. The antiproliferative activities of junipers are attributed to podophyllotoxin (PPT), which is a precursor for the synthesis of efficient anticancer drugs. However, the natural sources of PPT, Sinopodophyllum hexandrum (Royle) T. S. Ying and Podophyllum peltatum L., are already endangered species because of their intensive industrial exploitation. Therefore, identification of other sources of PPT is necessary. This study is a broad comparative investigation of junipers, for which original sources have been accessed from different continents of the world. The present research is aimed at the identification of species, producing PPT and other lignans at concentrations that are sufficient for the high antiproliferative activity of the corresponding extracts. Cytotoxic juniper leaf extracts demonstrated a broad spectrum of activity on a panel of cancer cell lines. The antiproliferative properties of junipers were attributed to the combined activity of great diversity of lignans (podophyllotoxin, deoxypodophyllotoxin, β-peltatin, yatein, matairesinol, anhydropodorhizol, etc.), detected by UHPLC-HRMS and LC-ESI-MS/MS in the corresponding extracts. Several species of the genus Juniperus L. were outlined as perspective sources of drug precursors with potential pharmaceutical applications.

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