Juniper berry oil is stated to possess a wide spectrum of pharmacological activities and its monographs are included in some National Pharmacopoeias. The antibacterial and antifungal activity of the oil was reported by some authors. In our study we estimated the antibacterial and antifungal activity of three different juniper berry oils and their main components. All the micro-organisms used in this experiment were isolated from patients of Regional Hospital of Gdańsk and some of them showed resistance against commonly used antibiotics. Only one of the oils (labelled A) revealed good antimicrobial properties. None of the single oil components was a stronger antibacterial and antifungal inhibitor than the oil A itself. Our data suggest that the antimicrobial activity of juniper oil A is the result of either the specific composition of the oil A (highest concentration of (-)-alpha-pinene, p-cymene and beta-pinene) or activity of a single non-identified compound. The presence of an adulterant in the oil was excluded.
Background
Most studies on regenerative medicine focus on cell-based therapies and transplantations. Small-molecule therapeutics, though proved effective in different medical conditions, have not been extensively investigated in regenerative research. It is known that healing potential decreases with development and developmental changes are driven by epigenetic mechanisms, which suggests epigenetic repression of regenerative capacity.
Methods
We applied zebularine, a nucleoside inhibitor of DNA methyltransferases, to stimulate the regenerative response in a model of ear pinna injury in mice.
Findings
We observed the regeneration of complex tissue that was manifested as improved ear hole repair in mice that received intraperitoneal injections of zebularine. Six weeks after injury, the mean hole area decreased by 83.2 ± 9.4% in zebularine-treated and by 43.6 ± 15.4% in control mice (p < 10
−30
). Combined delivery of zebularine and retinoic acid potentiated and accelerated this effect, resulting in complete ear hole closure within three weeks after injury. We found a decrease in DNA methylation and transcriptional activation of neurodevelopmental and pluripotency genes in the regenerating tissues.
Interpretation
This study is the first to demonstrate an effective induction of complex tissue regeneration in adult mammals using zebularine. We showed that the synergistic action of an epigenetic drug (zebularine) and a transcriptional activator (retinoic acid) could be effectively utilized to induce the regenerative response, thus delineating a novel pharmacological strategy for regeneration. The strategy was effective in the model of ear pinna regeneration in mice, but zebularine acts on different cell types, therefore, a similar approach can be tested in other tissues and organs.
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