Anti-inflammatory and antinociceptive effects of tilifodiolide, isolated from Salvia tiliifolia Vahl (Lamiaceae)
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Salvia tiliifolia Vahl (Lamiaceae) is used for the empirical treatment of pain and inflammation. The diterpenoid tilifodiolide (TFD) was isolated from Salvia tiliifolia. The in vitro anti-inflammatory effects of TFD (0.1–200 µM) were assessed using murine macrophages stimulated with LPS and estimating the levels of pro-inflammatory mediators for 48 h. The in vivo anti-inflammatory activity of TFD was assessed using the carrageenan-induced paw edema test for 6 h. The antinociceptive effects of TFD were evaluated using the formalin test and the acetic acid induced-writhing test. The effects of TFD on locomotor activity were assessed using the open field test and the rotarod test. TFD inhibited the production of TNF-α (IC50 = 5.66 µM) and IL-6 (IC50 = 1.21 µM) in macrophages. TFD (200 mg/kg) showed anti-inflammatory effects with similar activity compared to 10 mg/kg indomethacin. The administration of TFD induced antinociception in the phase 1 (ED50 = 48.2 mg/kg) and the phase 2 (ED50 = 28.9 mg/kg) of the formalin test. In the acetic acid assay, TFD showed antinociceptive effects (ED50 = 32.3 mg/kg) with similar potency compared to naproxen (ED50 = 36.2 mg/kg). In the presence of different inhibitors in the acetic acid assay, only the co-administration of TFD and naloxone reverted the antinociceptive activity shown by TFD alone. TFD did not affect locomotor activity in mice. TFD exerts in vitro and in vivo anti-inflammatory activity and in vivo antinociceptive effects. © 2018 Wiley Periodicals, Inc.
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anti-inflammatory; antinociceptive; Salvia tiliifolia; tilifodiolide 1h 1,2,4 oxadiazolo[4,3 a]quinoxalin 1 one; antiinflammatory agent; antinociceptive agent; clonazepam; diterpenoid; glibenclamide; indometacin; interleukin 6; n(g) nitroarginine methyl ester; naloxone; naproxen; tilifodiolide; tumor necrosis factor; unclassified drug; yohimbine; analgesic agent; antiinflammatory agent; indometacin; interleukin 6; naloxone; naproxen; tumor necrosis factor; animal cell; animal experiment; animal model; antiinflammatory activity; antinociception; Article; carrageenan-induced paw edema; controlled study; drug potency; ED50; formalin test; hot plate test; IC50; in vitro study; in vivo study; locomotion; motor coordination; mouse; nonhuman; open field test; peritoneum macrophage; phagocytosis; rotarod test; Salvia; Salvia tiliifolia; TPA-induced ear edema; writhing test; animal; chemistry; dose response; drug effect; macrophage; male; metabolism; motor activity; pain measurement; Salvia; Analgesics; Animals; Anti-Inflammatory Agents; Dose-Response Relationship, Drug; Indomethacin; Interleukin-6; Macrophages; Male; Mice; Motor Activity; Naloxone; Naproxen; Pain Measurement; Rotarod Performance Test; Salvia; Tumor Necrosis Factor-alpha
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