The current study aimed to assess the effect of timosaponin AⅢ(T-AⅢ)on drug-metabolizing enzymes during anticancer therapy.The in vivo experiments were conducted on nude and ICR mice.Following a 24-day administratio...The current study aimed to assess the effect of timosaponin AⅢ(T-AⅢ)on drug-metabolizing enzymes during anticancer therapy.The in vivo experiments were conducted on nude and ICR mice.Following a 24-day administration of T-AⅢ,the nude mice exhibited an induction of CYP2B10,MDR1,and CYP3A11 expression in the liver tissues.In the ICR mice,the expression levels of CYP2B10 and MDR1 increased after a three-day T-AⅢ administration.The in vitro assessments with HepG2 cells revealed that T-AⅢ induced the expression of CYP2B6,MDR1,and CYP3A4,along with constitutive androstane receptor(CAR)activation.Treatment with CAR siRNA reversed the T-AⅢ-induced increases in CYP2B6 and CYP3A4 expression.Furthermore,other CAR target genes also showed a significant increase in the expression.The up-regulation of murine CAR was observed in the liver tissues of both nude and ICR mice.Subsequent findings demonstrated that T-AⅢ activated CAR by inhibiting ERK1/2 phosphorylation,with this effect being partially reversed by the ERK activator t-BHQ.Inhibition of the ERK1/2 signaling pathway was also observed in vivo.Additionally,T-AⅢ inhibited the phosphorylation of EGFR at Tyr1173 and Tyr845,and suppressed EGF-induced phosphorylation of EGFR,ERK,and CAR.In the nude mice,T-AⅢ also inhibited EGFR phosphorylation.These results collectively indicate that T-AⅢ is a novel CAR activator through inhibition of the EGFR pathway.展开更多
Objective:To study the preventive effect of Timosaponin BII(T-BII)-loaded temperature/ion-sensitive nasal in situ hydrogels(ISGs)on Alzheimer's disease(AD),its preparation technology,characteristics and in vivo ef...Objective:To study the preventive effect of Timosaponin BII(T-BII)-loaded temperature/ion-sensitive nasal in situ hydrogels(ISGs)on Alzheimer's disease(AD),its preparation technology,characteristics and in vivo effects were evaluated.Methods:The morphological and rheological properties were evaluated.The preventive effects of T-BII ISG on scopolamine-induced AD in mice were determined with the index of muscarinicreceptor 1(M1)expression and pathological changes.Results:Results revealed that T-BII ISG significantly increased the content of M1 choline receptors in the hippocampus of mice and ameliorated the damage incurred to the hippocampal cornu ammonis 1(CA1)area.Conclusion:T-BII ISGs is a reasonable and convenient method of exerting an obvious preventive effect on mice with AD induced by scopolamine.This,thereby,lays forth a new treatment option for preventing AD.展开更多
Two new saponins 3-O-β-d-glucopyranosyl (1 → 2)-β-d-mannopyranosyl sarsasapogenin, named timosaponin A IV(1) and (5β, 25S)-26-O-β-d-glucopyranosyl-furost-20(22)-en-3,26-diol-3-O-β-d-glucopyranosyl (1 → 4) gluco...Two new saponins 3-O-β-d-glucopyranosyl (1 → 2)-β-d-mannopyranosyl sarsasapogenin, named timosaponin A IV(1) and (5β, 25S)-26-O-β-d-glucopyranosyl-furost-20(22)-en-3,26-diol-3-O-β-d-glucopyranosyl (1 → 4) glucopyranosyl (1 → 2)-β-d-galacopyranoside, named timosaponin B IV(2), were isolated by silica gel column chromatography and preparative HPLC from Anemarrhena asphodeloides Bge. Their structures were elucidated by chemical characters and spectroscopic analysis.展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.82073934,81872937,and 81673513).
文摘The current study aimed to assess the effect of timosaponin AⅢ(T-AⅢ)on drug-metabolizing enzymes during anticancer therapy.The in vivo experiments were conducted on nude and ICR mice.Following a 24-day administration of T-AⅢ,the nude mice exhibited an induction of CYP2B10,MDR1,and CYP3A11 expression in the liver tissues.In the ICR mice,the expression levels of CYP2B10 and MDR1 increased after a three-day T-AⅢ administration.The in vitro assessments with HepG2 cells revealed that T-AⅢ induced the expression of CYP2B6,MDR1,and CYP3A4,along with constitutive androstane receptor(CAR)activation.Treatment with CAR siRNA reversed the T-AⅢ-induced increases in CYP2B6 and CYP3A4 expression.Furthermore,other CAR target genes also showed a significant increase in the expression.The up-regulation of murine CAR was observed in the liver tissues of both nude and ICR mice.Subsequent findings demonstrated that T-AⅢ activated CAR by inhibiting ERK1/2 phosphorylation,with this effect being partially reversed by the ERK activator t-BHQ.Inhibition of the ERK1/2 signaling pathway was also observed in vivo.Additionally,T-AⅢ inhibited the phosphorylation of EGFR at Tyr1173 and Tyr845,and suppressed EGF-induced phosphorylation of EGFR,ERK,and CAR.In the nude mice,T-AⅢ also inhibited EGFR phosphorylation.These results collectively indicate that T-AⅢ is a novel CAR activator through inhibition of the EGFR pathway.
基金This study was funded by the Beijing Natural Science Foundation(7202147).
文摘Objective:To study the preventive effect of Timosaponin BII(T-BII)-loaded temperature/ion-sensitive nasal in situ hydrogels(ISGs)on Alzheimer's disease(AD),its preparation technology,characteristics and in vivo effects were evaluated.Methods:The morphological and rheological properties were evaluated.The preventive effects of T-BII ISG on scopolamine-induced AD in mice were determined with the index of muscarinicreceptor 1(M1)expression and pathological changes.Results:Results revealed that T-BII ISG significantly increased the content of M1 choline receptors in the hippocampus of mice and ameliorated the damage incurred to the hippocampal cornu ammonis 1(CA1)area.Conclusion:T-BII ISGs is a reasonable and convenient method of exerting an obvious preventive effect on mice with AD induced by scopolamine.This,thereby,lays forth a new treatment option for preventing AD.
文摘Two new saponins 3-O-β-d-glucopyranosyl (1 → 2)-β-d-mannopyranosyl sarsasapogenin, named timosaponin A IV(1) and (5β, 25S)-26-O-β-d-glucopyranosyl-furost-20(22)-en-3,26-diol-3-O-β-d-glucopyranosyl (1 → 4) glucopyranosyl (1 → 2)-β-d-galacopyranoside, named timosaponin B IV(2), were isolated by silica gel column chromatography and preparative HPLC from Anemarrhena asphodeloides Bge. Their structures were elucidated by chemical characters and spectroscopic analysis.
