RESUMEN
Alzheimer's Disease (AD) is one of the commonest neural degeneration in aging population, and has become a global health challenge. 2-(2-benzofuranyl)-2-imidazoline (2-BFI) was reported to effectively improved the damage of patients with neuropathological disorders. In the present study, we investigated the effect of 2-BFI on the improvement of antioxidative, inflammation, and apoptosis in AD rats. Sprague-Dawley rats (2 months old, n=40) were used in this study and after injection of Aß1-42 into hippocampal CA1 (Cornu Ammonis) region, the rats were given high, moderate and low dose of 2-BFI though intraperitoneal (i.p.) injection. Then spatial memory and navigation ability were analyzed by Morrize Water Maze. For the molecular testing, chemical colorimetry, ELISA and immunoblotting were performed to measure the activities of antioxidative enzymes, the abundance of immune cytokines and expression of apoptotic proteins, respectively. Hematoxylin and Eosin staining was used to analyze the pathological changes. We observed that 2-BFI significantly ameliorated the learning and memory abilities in rat models with AD by dosage treatment, as demonstrated by the shorten learning latency and greater times of travel across the platform quadrant. Additionally, reactive oxygen species (ROS) and malondialdehyde (MDA), were decreased after treatment of 2-BFI with dosage dependency, while the activities of superoxidase dismutase (SOD) and (GPX) Glutathione peroxidase were in turn enhanced, suggesting that 2-BFI could protect the antioxidative enzymes and reduce the oxidative stress in the hippocampus. Moreover, the expression of inflammatory factors including TNF-a and IL-1ß were decreased after 2-BFI treatment. Additionally, the neuronal apoptosis was also attenuated, as shown by Western blot results. Taken together, the cognitive impairment in AD rats could be significantly improved by 2-BFI in a dose-dependent manner through suppressing oxidants accumulation, inhibiting of inflammatory response, as well as enhancing the neural viability.
Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Apoptosis/efectos de los fármacos , Benzofuranos/farmacología , Imidazoles/farmacología , Inflamación/tratamiento farmacológico , Fármacos Neuroprotectores/farmacología , Estrés Oxidativo/efectos de los fármacos , Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/fisiopatología , Péptidos beta-Amiloides , Animales , Antiinflamatorios no Esteroideos/farmacología , Apoptosis/fisiología , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Hipocampo/patología , Inflamación/patología , Inflamación/fisiopatología , Aprendizaje por Laberinto/efectos de los fármacos , Aprendizaje por Laberinto/fisiología , Nootrópicos/farmacología , Estrés Oxidativo/fisiología , Fragmentos de Péptidos , Distribución Aleatoria , Ratas Sprague-Dawley , Memoria Espacial/efectos de los fármacos , Memoria Espacial/fisiología , Navegación Espacial/efectos de los fármacos , Navegación Espacial/fisiologíaRESUMEN
BACKGROUND: Most studies on Guhong injection have involved a single center with a small sample size, and the level of clinical evidence is low. AIM: To assess the safety and efficacy of Guhong injection for mild ischemic stroke (IS). METHODS: A total of 399 IS patients treated at six hospitals from August 2018 to August 2019 were retrospectively analyzed. The patients were given Guhong injection (experimental group) or Butylphthalide and Sodium Chloride Injection (control group). Changes in National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) scores were observed before treatment and at 1, 2, and 3 wk after treatment in each group. The efficacy and safety of Guhong injection for IS were assessed. Other medications taken by the patients were confounding factors for efficacy assessment. These factors were controlled by propensity score matching, and the results were further analyzed based on the matching. RESULTS: The marked response rates at three follow-up visits were 64.64%, 74.7%, and 66.7% in the experimental group, and 48.26%, 45.4%, and 22.2% in the control group. The marked response rates increased significantly in the experimental group compared with the control group (P < 0.05). The overall response rate at the first visit (days 7 ± 2) did not differ significantly between the two groups, but differed significantly at the second (days 14 ± 2) and third visits (days 21 ± 3) (P < 0.05). The proportion of patients without any symptoms in the experimental group was significant different at the first visit (P < 0.05), but not significantly different at the second visit. The two groups showed no significant difference in the baseline distribution of mRS scores. At the first and second visits, the change in mRS scores was -2 and -1 in the experimental and control groups, respectively, which were significantly different (P < 0.05). After propensity score matching, the overall response rate and marked response rate were 97.29% and 100% in the experimental group (P > 0.05) and 64.0% and 47.7% in the control group (P < 0.05) at the first visit, respectively. The decreased NIHSS scores in the two groups were significant different (P < 0.05). The overall response rate and marked response rate differed significantly between the two groups at the second visit (P < 0.05). There was no significant difference in the incidence of adverse events between the two groups. No severe adverse events occurred in either group. CONCLUSION: Guhong injection is safe and more effective than Butylphthalide and Sodium Chloride Injection for treatment of IS.