phenanthrenes and Dementia--Vascular

To investigate the effect of triptolide on cognitive dysfunction in vascular dementia rats and its effect on SIRT1/NF-κB pathway,fifty healthy male Sprague-Dawley rats were randomly divided into 5 groups: Sham operation group( Sham group),vascular dementia model group( 2 VO group),triptolide intraperitoneal injection group( TR group),triptolide intraperitoneal injection + EX527 intracerebroventricular administration group( T+E group),EX527 intracerebroventricular administration group( EX527 group). After 4 weeks of modeling,Morris water maze test and object recognition test were used to evaluate the learning and memory ability of rats. The morphological changes of hippocampus in each group were observed in brain tissue. The chemical colorimetry was used to detect the activities of SOD and MDA in hippocampus. IL-6 and TNF-α levels were detected by ELISA. Western blot was used to detect the expression of SIRT1,NF-κB,IκBα and caspase 3 in hippocampus. The results showed that compared with the Sham group,the learning and memory ability of the vascular dementia model rats was reduced,the SOD activity in the hippocampus was decreased,the MDA activity and IL-6 level were increased,the neuronal degeneration changed significantly,the expression of SIRT1 and IκBα was decreased and the expression of caspase 3 and NF-κB was significantly increased. After intervention by triptolide,the level of oxidative stress and the degenerative changes in hippocampus were significantly slowed down. The expression of SIRT1 and IκBα protein was increased and the expression of caspase 3 and NF-κB was significantly decreased. While,after intervention by triptolide and EX527,the expression of SIRT1 was decreased,the levels of oxidative stress and neuronal degeneration in the hippocampus were aggravated,and the learning and memory ability was reduced. The results showed that triptolide could improve cognitive impairment in vascular dementia rats and its mechanism may be related to SIRT1/NF-κB signaling pathway.

Topics: Animals; Cognitive Dysfunction; Dementia, Vascular; Diterpenes; Epoxy Compounds; Hippocampus; Male; NF-kappa B; Oxidative Stress; Phenanthrenes; Random Allocation; Rats; Rats, Sprague-Dawley; Signal Transduction; Sirtuin 1

Tripterygium Wilfordii Hook F has been exploited as a treatment for several diseases due to its neuroprotective, anti-tumor, and anti-inflammatory effects. Triptolide is one of its key bioactive compounds. Currently, the role of triptolide in cognitive dysfunction remains unclear. Here, the role of triptolide on cognitive dysfunction was investigated using chronic cerebral hypoperfusion-induced vascular dementia (VD) rat model. SD rats were administrated with Triptolide (5 μg/kg) for 6 weeks after undergoing permanent bilateral common carotid artery occlusion. The results show that triptolide treatment conferred neuroprotective effects in VD rats. Intraperitoneal injection of triptolide attenuated oxidative stress, learning and memory deficits, and neuronal apoptosis in the hippocampi. Moreover, triptolide enhanced the expression of SIRT1, PGC-1α, ZO-1, Claudin-5, and decreased the serum levels of NSE and S100B significantly. It also improved CCH-induced learning and memory deficits, and this is attributed to its capacity to promote SIRT1/PGC-1α signaling, confer antioxidant effects, and inhibit neuronal apoptosis. These findings indicate that triptolide may be an effective therapeutic agent for vascular cognitive dysfunction.

Topics: Animals; Apoptosis; Blood-Brain Barrier; Claudin-5; Dementia, Vascular; Diterpenes; Epoxy Compounds; Hippocampus; Male; Maze Learning; Neuroprotective Agents; Nootropic Agents; Oxidative Stress; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Phenanthrenes; Rats, Sprague-Dawley; Signal Transduction; Sirtuin 1; Spatial Memory; Zonula Occludens-1 Protein

To investigate the underlying neuroprotective mechanisms of Tanshinone II A (TSA) on rat cerebral ischemia in vivo.. Study of TSA on rat cerebral ischemia in vivo: Male SD rats were divided into four groups (sham-operated, ischemic and treated group (lower dose and higher dose). Chronic cerebral ischemmia after permanent bilateral carotid artery ligation was introduced as an in vivo ischemic model. After ischemia impairment, TSA (2, 4 mg x kg(-1) x d(-1)) was administrated by ip for 30 days in treated group. We used Morris water maze to investigate the learning and memory. Levels of malondialdehyde (MDA), activity of superoxide dismetase (SOD) and glutathione peroxidase (GPX) in brain tissue were detected by spectrophotometer. High-performance liquid chromatography (HPLC) with fluorescence detection was applied to measure the contents of glutamate and gamma-aminobutyric acid (GABA) in cortex and hippocampus.. TSA can improve learning and memory deficits in vascular dementia. An elevation of SOD and GPX activity and decrease of MDA level were shown in TSA treated group after brain ischemia. Decreased glutamate and gamma-aminobutyric acid induced by chronic brain ischemia were markedly inhibited by TSA pretreatment.. The neuroprotective effect of TSA are partly due to its functions as follow: anti-free radical injury; regulating the content of glutamate and gamma-aminobutyric acid.

Topics: Abietanes; Animals; Dementia, Vascular; Disease Models, Animal; Drugs, Chinese Herbal; Humans; Male; Malondialdehyde; Maze Learning; Memory; Neuroprotective Agents; Phenanthrenes; Random Allocation; Rats; Rats, Sprague-Dawley