Antinociceptive and anxiolytic-like effects of a neo-clerodane diterpene from Salvia semiatrata aerial parts

Context: Salvia semiatrata Zucc. (Lamiaceae) is a species used as a tranquilizer and to relieve pain in folk medicine in Santiago Huauclilla, Oaxaca, Mexico.

Objective: To evaluate the antinociceptive and anxiolytic-like effects of S. semiatrata extracts and identify a bioactive metabolite.

Materials and methods: The extracts were obtained by maceration of S. semiatrata aerial parts using solvents in increasing polarity (hexane, ethyl acetate and methanol). A neo-clerodane diterpene was extracted from the ethyl acetate fraction using open column chromatography. Identification of this metabolite was performed by crystallography, ¹H NMR, ¹³C NMR, ATR-IR, ECD, MS and elemental analysis. The antinociceptive activity was explored using the writhing and formalin tests. Whereas, the anxiolytic-like responses were analysed in the open-field, hole-board and plus-maze tests. All the treatments were administered using oral gavage in male CD1 mice and explored 30 min after administration of the individual extracts (300 mg/kg) or the compound 1 (0.1, 1 or 10 mg/kg).

Results: All the extracts produced significant reduction in the nociceptive and anxiety-like behaviour compared to mice treated with the vehicle (0.5% tween 80 in saline solution). The spectroscopic analysis corroborated the presence of the neo-clerodane diterpene 7-keto-neoclerodan-3,13-dien-18,19:15,16-diolide (1), as partial responsible of the antinociceptive and anxiolytic-like effects, which produced a dose-dependent response in the writhing test with an ED₅₀=4.15 mg/kg. Discussion and conclusions: These results reinforce the medicinal properties of S. semiatrata in folk medicine, where participation of a neo-clerodane diterpene was evidenced in the inhibitory central nervous system activity of this species.

Keywords: Anxiety; Lamiaceae; neoclerodanes terpenoids; nociception; salvias; traditional medicine.