Protective effect of dehydroevodiamine on gastric mucosa of rats with experimental gastric ulcer and its mechanism / 中草药

Objective: To investigate the protective effect and mechanism of dehydroevodiamine on gastric mucosa of rats with experimental gastric ulcer and its mechanism, so as to provide objective data for clinical application. Methods: Male SD rats were selected and the gastric ulcer model was established by acetic acid cauterization. Forty model rats were randomly divided into model group, dehydroevodiamine low-dose (6.25 mg/kg) group, dehydroevodiamine high-dose (12.5 mg/kg) group, and positive control (omeprazole 10 mg/kg) group. Another 10 healthy rats were selected as the sham group. The rats in each group were ig the corresponding dose of drugs, while the rats in the sham group and the model group were given the same amount of normal saline. After the end of experiment for 14 d, the area and inhibition ratio of gastric ulcer, repair factor of gastric mucosa, serum oxidative stress factor, inflammatory factor, and gastric tissue-related protein levels were compared. Results: Compared with the model group, dehydroevodiamine could decrease the area of gastric ulcer significantly (P < 0.05, 0.01), and increase the inhibition ratio of gastric ulcer significantly. Dehydroevodiamine could increase the trefoil factor family 1 (TFF1) and stomach tissue epidermal growth factor (EGF) significantly (P < 0.05, 0.01), and could decrease the serum malondialdehyde (MDA), cyclooxygenase 2 (COX-2), tumor necrosis factor (TNF-α) and IL-6. Dehydroevodiamine could increase the activity of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) (P < 0.05, 0.01), and could decrease the expression levels of Rho, ROCK1, ROCK2 and NF-κB in gastric tissues (P < 0.05, 0.01). Conclusion: Dehydroevodiamine can significantly improve gastric ulcer in rats through anti-oxidative stress and anti-inflammatory factors, and its potential mechanism may be related to the regulation of Rho/NF-κB signaling pathway.

Dehydroevodiamine·HCl enhances cognitive function in memory-impaired rat models

Progressive memory impairment such as that associated with depression, stroke, and Alzheimer's disease (AD) can interfere with daily life. In particular, AD, which is a progressive neurodegenerative disorder, prominently features a memory and learning impairment that is related to changes in acetylcholine and abnormal β-amyloid (Aβ) deposition in the brain. In the present study, we investigated the effects of dehydroevodiamine·HCl (DHED) on cognitive improvement and the related mechanism in memory-impaired rat models, namely, a scopolamine-induced amnesia model and a Aβ₁₋₄₂-infused model. The cognitive effects of DHED were measured using a water maze test and a passive avoidance test in the memory-impaired rat models. The results demonstrate that DHED (10 mg/kg, p.o.) and Donepezil (1 mg/kg, p.o.) ameliorated the spatial memory impairment in the scopolamine-induced amnestic rats. Moreover, DHED significantly improved learning and memory in the Aβ₁₋₄₂-infused rat model. Furthermore, the mechanism of these behavioral effects of DHED was investigated using a cell viability assay, reactive oxygen species (ROS) measurement, and intracellular calcium measurement in primary cortical neurons. DHED reduced neurotoxicity and the production of Aβ-induced ROS in primary cortical neurons. In addition, similar to the effect of MK801, DHED decreased intracellular calcium levels in primary cortical neurons. Our results suggest that DHED has strong protective effects against cognitive impairments through its antioxidant activity and inhibition of neurotoxicity and intracellular calcium. Thus, DHED may be an important therapeutic agent for memory-impaired symptoms.

Simultaneous Analysis of Thirteen Bioactive Components in Evodia rutaecarpa and Its Varieties by HPLC-DAD-MS / 中草药·英文版

Objective To control the quality of Evodia rutaecarpa better. Methods An HPLC-DAD-MS/MS method was established for the rapid and efficient identification of bioactive constituents and for simultaneous quantitative analysis of four bioactive ingredients including evodiamine, rutaecarpine, dehydroevodiamine, and evodin in E.rutaecarpa, which was applied to evaluating eight samples of E. rutaecarpa and its varieties from different areas.Results Thirteen potentially bioactive constituents including one flavonoid glycoside, one limonin, four indoloquinazoline alkaloids, and seven quinolone alkaloids were identified in all samples and the contents of dehydroevodiamine, evodine, evodiamine, and rutaecarpine varied widely from 0.10% to 0.51%, 0.49% to 3.12%,0.07% to 1.56%, and 0.10% to 0.69%, respectively. Conclusion This method is found to be convenient, fast,accurate, and it is facilitated to improve the quality control standard of E. rutaecarpa and related products.

Pharmacokinetics of Dehydroevodiamine Following Intravenous Administration in Rats

Dehydroevodiamine (DHED) is one of the bioactive components of the Chinese herbal medicine Wu-chu-yu-tang that has been shown to produce various pharmacological effects. In the present study, we investigated the pharmacokinetics of DHED after intravenous administration of two doses (2.5 and 5 mg/kg) in anesthetized rats. The plasma concentration of DHED was measured by reverse-phase high-performance liquid chromatography with UV detection. The mean area under the curve of the time-concentration profile was 21.9 and 53.9 microgram-min/ml after the 2.5- and 5-mg/kg doses, respectively, and the volume of distribution was 1584.9 and 1580.6 ml following 2.5- and 5-mg/kg doses, respectively. Plasma concentration profiles versus time were compatible with a two-compartment model and first-order kinetics. The terminal elimination half-life was 91.8+/-16.6 min and 78.7+/-11.9 min in the dose of 2.5 and 5 mg/kg, respectively. This is the first report to study the pharmacokinetics of DHED in animals.