Department of Pharmacy, Division of Natural and Exact Sciences, University of Guanajuato, Guanajuato, Mexico.
School of Chemistry, Autonomous University of Yucatan, Merida, Mexico.
Drug Dev Res. 2019 Nov;80(7):981-991. doi: 10.1002/ddr.21578. Epub 2019 Jul 25.
Salvia tiliifolia is used in folk medicine as a relaxant agent and for the treatment of diarrhea and neurodegenerative diseases. Tilifodiolide (TFD) is a diterpene obtained from this plant. The purpose of this work was to evaluate the antidiarrheal, vasorelaxant, and neuropharmacological actions of TFD. These effects were selected based on the folk medicinal use of S. tiliifolia. The antidiarrheal activity of 1-50 mg/kg p.o. TFD was assessed with the castor oil related tests. The vasorelaxant effect of TFD (0.9-298 μM) was performed with smooth muscle tissues from rats, and its mechanism of action was evaluated using different inhibitors. The sedative, anxiolytic, and antidepressant effects of 1-100 mg/kg TFD were assessed. The possible mechanisms of action of the anxiolytic and antidepressant effects of TFD were evaluated using inhibitors. TFD exhibited antidiarrheal (ED = 10.62 mg/kg) and vasorelaxant (EC = 48 ± 3.51 μM) effects. The coadministration of TFD with N(ω)-nitro-L-arginine methyl ester (L-NAME) or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), reverted the vasorelaxant action showed by TFD alone. TFD exerted anxiolytic actions (ED = 20 mg/kg) in the cylinder exploratory test, whereas TFD (50 mg/kg) showed antidepressant actions in the tail suspension test by 44%. The pretreatment with 2 mg/kg flumazenil partially reverted the anxiolytic actions of TFD, whereas the pretreatment with 1 mg/kg yohimbine abolished the antidepressant effects of TFD. In summary, TFD exerted antidiarrheal activity by decreasing the intestinal fluid accumulation and vasorelaxant effects mediated by nitric oxide and cyclic guanosine monophosphate. TFD showed anxiolytic and antidepressant effects by the partial involvement of gamma-Aminobutyric acid (GABA) receptors and the possible participation of α2-adrenoreceptors, respectively.
透骨草被民间医学用作松弛剂，用于治疗腹泻和神经退行性疾病。Tilifodiolide (TFD) 是从这种植物中提取的二萜。本工作旨在评价 TFD 的抗腹泻、血管舒张和神经药理学作用。这些作用是基于透骨草的民间药用选择的。通过蓖麻油相关试验评估了 1-50mg/kg 口服 TFD 的抗腹泻活性。用大鼠平滑肌组织进行 TFD（0.9-298μM）的血管舒张作用，并使用不同的抑制剂评估其作用机制。评价了 1-100mg/kg TFD 的镇静、抗焦虑和抗抑郁作用。使用抑制剂评价了 TFD 抗焦虑和抗抑郁作用的可能作用机制。TFD 表现出抗腹泻（ED = 10.62mg/kg）和血管舒张（EC = 48±3.51μM）作用。TFD 与 N（ω）-硝基-L-精氨酸甲酯（L-NAME）或 1H-[1,2,4]恶二唑并[4,3-a]喹喔啉-1-酮（ODQ）共同给药，可逆转 TFD 单独作用引起的血管舒张作用。TFD 在圆筒探索试验中表现出抗焦虑作用（ED = 20mg/kg），而 TFD（50mg/kg）在悬尾试验中表现出 44%的抗抑郁作用。2mg/kg 氟马西尼预处理部分逆转了 TFD 的抗焦虑作用，而 1mg/kg 育亨宾预处理则消除了 TFD 的抗抑郁作用。总之，TFD 通过减少肠道液体积累和一氧化氮和环鸟苷单磷酸介导的血管舒张作用发挥抗腹泻活性。TFD 通过部分涉及γ-氨基丁酸（GABA）受体和可能涉及α2-肾上腺素受体分别表现出抗焦虑和抗抑郁作用。
