Objective:To determine the depressant-like effects and the possible mechanism of action of tilianin isolated from active methanol extract of Agastache mexicana(A.mexicana).Also,to establish the pharmacophoric requirem...Objective:To determine the depressant-like effects and the possible mechanism of action of tilianin isolated from active methanol extract of Agastache mexicana(A.mexicana).Also,to establish the pharmacophoric requirements of tilianin,as a possible ligand of GABA_A/BZD receptor,by the alignment of diazepam.CGS-9896 and diindole,using a previously described pharmacophoric model.Methods:Tilianin(30 to 300 mg/kg.ip.and 300 mg/kg,pa.) and methanol crude extract(10 to 300 mg/kg,ip.and 300 mg/kg po.) from A.mexicana were evaluated for potential sedative and anxiolytic-like response drugs by using open-field,hole-board,cylinder of exploration,plus-maze and sodium pentobarbital-induced hypnosis mice methods.Results:Methanol extract and tilianin showed anxiolytic-like activity from a dosage of 30 mg/kg,ip.or 300 mg/kg,po.and were less potent than diazepam 0.1 mg/kg.a reference anxiolytic drug used.Moreover,depressant activity of both potentiates sodium pentobarbital(SP)-induced sleeping time.The anxiolytic-like effect of 30 mg/kg ip.observed for the extract and tilianin,by using the plus-maze model,was partially prevented in the presence of flumazenil(a GABA_A/BZD antagonist,5 mg/kg ip.) but not in the presence of WAY100635(a selective 5-HT_(1A) receptor antagonist,0.32 mg/kg.ip.).Pharmacophoric modeling alignments of three agonist of GABA_A/BZD allow identify seven chemical features.Tilianin contains six of the seven features previously determined.Conclusions:Results indicate that tilianin is one of the bioactive metabolites in the anxiolytic-like activity of 4.mexicana.reinforcing its central nervous system uses,where GABA_A/BZD,but not 5-HT_(1A),receptors are partially involved.展开更多
OBJECTIVE:To investigate the efficacy of tilianin extracted from Xiangqinglan(Herba Dracocephali Moldovicae)on apoptosis of H9c2 cell after oxygenglucose deprivation/reoxygenation(OGD/R)and the mechanism.METHODS:Tilia...OBJECTIVE:To investigate the efficacy of tilianin extracted from Xiangqinglan(Herba Dracocephali Moldovicae)on apoptosis of H9c2 cell after oxygenglucose deprivation/reoxygenation(OGD/R)and the mechanism.METHODS:Tilianin was obtained from Beijing Inluck Science and Technology Development Co.Ltd.,with purity≥98%.The OGD/R model was established in H9c2 cells.Flow cytometry detected the mitochondrial membrane potential,apoptosis rates,mitochondrial reactive oxygen species(ROS)and calcium ion concentration.Succinate dehydrogenase(SDH)activity,succinate content and levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and interleukin-1β(IL-1β)were detected with enzyme-linked immunosorbent assay.Western blot measured protein levels.RESULTS:Tilianin significantly reduced the apoptotic rates,ROS levels,calcium ion concentration,succinate content,and,levels of TNF-α,IL-6 and IL-1βof OGD/R cells,while significantly increased the membrane potential and SDH activity in mitochondria.Western blot analysis showed that tilianin significantly up-regulated pCalmodulin-dependent protein kinaseⅡand voltagedependent anion selective channel levels in OGD/R cells,while significantly down-regulated p-protein kinase B,Bcl-2-associated X,and dynamin-related protein 1 levels related to apoptosis in the mitochondrial pathway.Moreover,tilianin significantly up-regulated B-cell lymphoma-2 and mitochondrial protein 2 related to the inhibition of apoptosis.Furthermore,tilianin downregulated phosphorylated-apoptosis signal-regulated kinase 1,phosphorylated-p38 and C/EBP homologous protein related to endoplasmic reticulum stress.CONCLUSIONS:Tilianin may inhibit OGD/R-induced H9c2 cell apoptosis mediated by mitochondrial pathway and endoplasmic reticulum stress,thus protecting cardiomyocytes.展开更多
基金partially supported by CONACYT 80811.NC123280 grantFaculty of Pharmacy Budgets(FECES 2011 and 2012)
文摘Objective:To determine the depressant-like effects and the possible mechanism of action of tilianin isolated from active methanol extract of Agastache mexicana(A.mexicana).Also,to establish the pharmacophoric requirements of tilianin,as a possible ligand of GABA_A/BZD receptor,by the alignment of diazepam.CGS-9896 and diindole,using a previously described pharmacophoric model.Methods:Tilianin(30 to 300 mg/kg.ip.and 300 mg/kg,pa.) and methanol crude extract(10 to 300 mg/kg,ip.and 300 mg/kg po.) from A.mexicana were evaluated for potential sedative and anxiolytic-like response drugs by using open-field,hole-board,cylinder of exploration,plus-maze and sodium pentobarbital-induced hypnosis mice methods.Results:Methanol extract and tilianin showed anxiolytic-like activity from a dosage of 30 mg/kg,ip.or 300 mg/kg,po.and were less potent than diazepam 0.1 mg/kg.a reference anxiolytic drug used.Moreover,depressant activity of both potentiates sodium pentobarbital(SP)-induced sleeping time.The anxiolytic-like effect of 30 mg/kg ip.observed for the extract and tilianin,by using the plus-maze model,was partially prevented in the presence of flumazenil(a GABA_A/BZD antagonist,5 mg/kg ip.) but not in the presence of WAY100635(a selective 5-HT_(1A) receptor antagonist,0.32 mg/kg.ip.).Pharmacophoric modeling alignments of three agonist of GABA_A/BZD allow identify seven chemical features.Tilianin contains six of the seven features previously determined.Conclusions:Results indicate that tilianin is one of the bioactive metabolites in the anxiolytic-like activity of 4.mexicana.reinforcing its central nervous system uses,where GABA_A/BZD,but not 5-HT_(1A),receptors are partially involved.
基金Supported by the National Natural Science Foundation:Mechanisms of the Protective Effects of Tilianin Against Myocardium Ischemia/Reperfusion Injury Through Ox-CaMKII-mediated Mitochondrial Regulating Pathway(No.81760045)the Xinjiang Uygur Natural Science Foundation of Autonomous Region:Study on the Mechanism of Tilianin Anti-atherosclerosis Effect of Tealis via the Reverse Cholesterol Transport Pathway(No.2018D01C317)the Chinese Medical Association Clinical Pharmacy Branch-Wu Jieping Medical Foundation:Study on the Mechanism of Tilianin Mediate Mitochondrial Function to Regulate Endoplasmic Reticulum Stress and Participate in Anti-myocardial Ischemia/Reperfusion Injury(No.320.6750.2020-04-32)。
文摘OBJECTIVE:To investigate the efficacy of tilianin extracted from Xiangqinglan(Herba Dracocephali Moldovicae)on apoptosis of H9c2 cell after oxygenglucose deprivation/reoxygenation(OGD/R)and the mechanism.METHODS:Tilianin was obtained from Beijing Inluck Science and Technology Development Co.Ltd.,with purity≥98%.The OGD/R model was established in H9c2 cells.Flow cytometry detected the mitochondrial membrane potential,apoptosis rates,mitochondrial reactive oxygen species(ROS)and calcium ion concentration.Succinate dehydrogenase(SDH)activity,succinate content and levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and interleukin-1β(IL-1β)were detected with enzyme-linked immunosorbent assay.Western blot measured protein levels.RESULTS:Tilianin significantly reduced the apoptotic rates,ROS levels,calcium ion concentration,succinate content,and,levels of TNF-α,IL-6 and IL-1βof OGD/R cells,while significantly increased the membrane potential and SDH activity in mitochondria.Western blot analysis showed that tilianin significantly up-regulated pCalmodulin-dependent protein kinaseⅡand voltagedependent anion selective channel levels in OGD/R cells,while significantly down-regulated p-protein kinase B,Bcl-2-associated X,and dynamin-related protein 1 levels related to apoptosis in the mitochondrial pathway.Moreover,tilianin significantly up-regulated B-cell lymphoma-2 and mitochondrial protein 2 related to the inhibition of apoptosis.Furthermore,tilianin downregulated phosphorylated-apoptosis signal-regulated kinase 1,phosphorylated-p38 and C/EBP homologous protein related to endoplasmic reticulum stress.CONCLUSIONS:Tilianin may inhibit OGD/R-induced H9c2 cell apoptosis mediated by mitochondrial pathway and endoplasmic reticulum stress,thus protecting cardiomyocytes.
