Seasonal changes in the composition of the essential oil extract of East Mediterranean sage (Salvia libanotica) and its toxicity in mice.

Sage (Salvia libanotica) is an East Mediterranean plant, the extract of which is used for the treatment of colds, coughs, and stomach ache. Experimental studies on the toxicity of its oil are scarce despite its wide use in traditional medicine. This study aims to provide data on its acute toxicity and to investigate the relationship between seasonal changes in oil composition and toxicity. The composition of the oil extract from the leaves of this plant was determined at four different times of the year; August (summer), October (fall), January (winter) and April (spring). The toxicity of each fraction was investigated following intraperitoneal (i.p.) injection into mice. Distillations of oils from plants and GC analyses revealed that the main constituent of sage oil is 1,8-cineole. Other components included ketones such as camphor and alpha,beta-thujone, terpenes such as limonene and alpha,beta-pinene, and alcohols such as borneol and linalool. Major seasonal changes were found in the composition of the oil. Essential oil extracted from plants collected in the winter season (January) contained higher levels of camphor (12.3%), alpha,beta-thujone (1.9%), and camphene (4.8%). The winter extract was found to be the most toxic, (LD(50): 839 mg/kg body weight) and exhibited powerful convulsant properties. This indicates a strong correlation between the contents of camphor, thujones and camphene and the oils' toxicity. The spring extract was the least toxic (LD(50): 1200 mg/kg body weight) and contained lower levels of camphor (7.7%), alpha,beta-thujone (1.3%) and camphene (3.1%). Thus, we recommend that oil extracts of sage marketed for use in certain unconventional medicines be prepared from spring plants.

Chemopreventive effects of sage oil on skin papillomas in mice.

Salvia libanotica (sage) extract is a popular plant remedy used by Middle Eastern people to treat common complaints such as colds and abdominal pain. In this study, the chemopreventive effects of sage oil on 7,12 dimethylbenz[a]anthracene (DMBA)-initiated and 12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted skin papillomas was investigated. Furthermore, its growth inhibitory and cytotoxic effects on a mouse papilloma-derived cell line (SP-1) were studied using 3H-thymidine incorporation, cell count and trypan blue dye exclusion assays. Sage oil was either applied topically to mouse skin at concentrations of 5, 50 and 100% in acetone, injected intraperitoneally at concentrations of 4 (37 mg/ml) and 8% (75 mg/ml) in saline or given by gavage at 100% twice per week for 20 weeks, 20 minutes prior to each promotion treatment with TPA. The topically applied 100% oil extract delayed tumor appearance by 4 weeks and inhibited tumor incidence and yield by 19 and 61%, respectively, at week 20. Topical application of 50% and 5% sage oil inhibited tumor yield by 41% at week 20. Tumor weight was decreased by 75% and 80% following treatment of mouse skin with 50% and 100% oil, respectively. Intraperitoneal injections and gavage treatments failed to inhibit the promotion of tumors in mouse skin, but significantly decreased tumor weight and volume. Sage oil displayed strong growth inhibitory effects on the SP-1 papilloma derived cell line following 24 hrs of treatment with estimated IC50 of 50 microg/ml. This observed growth inhibition was due to cytostatic and not cytotoxic effects. Our results suggest that the oil extract of the sage plant has potent suppressive activities against tumor promotion in mouse skin and thus could be an effective chemopreventive agent against skin cancer.