Dehydroevodiamine (DHED) is a major bioactive quinazoline alkaloid isolated from Evodiae Fructus, and has an antiarrhythmic effect in guinea-pig ventricular myocytes[3]. Dehydroevodiamine (0-50 μM; 2 hours) inhibits iNOS and COX-2 expression and prevents degradation of IκB-α in LPS induced RAW 264.7 macrophages[4]. Similarly to the cholinesterase inhibitor, physostigmine (0.03--0.3 mg/kg, i.p.), dehydroevodiamine (0.75--12.0 mg/kg, i.p.) administered 30 min before the training trial, immediately after the training trial, and 30 min before the retention test significantly improved scopolamine- and beta-amyloid peptide-(25--35)-induced amnesia[5]. DHED (10 mg/kg, p.o.) and Donepezil (1 mg/kg, p.o.) ameliorated the spatial memory impairment in the scopolamine-induced amnestic rats[6]. DHED could suppress the overactivation of GSK-3 (glycogen synthase kinase-3) and improve tau hyperphosphorylation and spatial memory deficit of the rats[7]. DHED (Pre-incubation of the brain slices with DHED) can attenuate CA(calyculin A)-induced tau hyperphosphorylation at multiple AD-related sites in metabolically active rat brain slices[8].
Dehydroevodiamine/去氢吴茱萸碱 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Hepa-1c1c7 cells
5 μM
12 h
To confirm whether RUT, EOD, and DHED activate the AHR. Results showed that at 5 μM, RUT, EOD, and DHED induced luciferase activity by 23.6-, 2.14-, and 10.8-fold, respectively.
Drug Metab Dispos. 2018 Jul;46(7):1030-1040
HepG2 cells
5 μM
12 h
To confirm whether RUT, EOD, and DHED activate the AHR. Results showed that at 5 μM, RUT, EOD, and DHED induced luciferase activity by 20.4-, 2.43-, and 6.60-fold, respectively.
Drug Metab Dispos. 2018 Jul;46(7):1030-1040
Mouse primary hepatocytes
5 μM
24 h
To investigate whether RUT, EOD, and DHED could directly activate the AHR. Results showed that Cyp1a1 mRNA was significantly upregulated by RUT, EOD, and DHED, with induction of 665-, 12.5-, and 20.6-fold, respectively, with an efficacy order of RUT > DHED > EOD.
Drug Metab Dispos. 2018 Jul;46(7):1030-1040
Dehydroevodiamine/去氢吴茱萸碱 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
C57BL/6N mice
Wild-type and Ahr-/- mice
Gavage
80 mg/kg
Once daily for 3, 12, and 21 days
To determine whether RUT, EOD, and DHED possess AHR activity in vivo. Results showed that RUT and DHED significantly induced the expression of Cyp1a1, Cyp1a2, and Cyp1b1 mRNAs in Ahr+/+ mice but not in Ahr-/- mice. EOD failed to activate AHR in vivo. Additionally, RUT and DHED disrupted bile acid homeostasis via an AHR-dependent mechanism.
Drug Metab Dispos. 2018 Jul;46(7):1030-1040
SD rats
DSS-induced ulcerative colitis model
Gavage
20 mg/kg and 40 mg/kg
7 consecutive days
Significantly alleviated DSS-induced colitis symptoms, suppressed inflammatory and oxidative stress responses, repaired colonic barrier injury, inhibited apoptosis, modulated gut microbes and serum metabolites, and inhibited the PI3K/AKT/NF-κB signaling pathway by targeting AKT1
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