Gypenoside attenuates white matter lesions induced by chronic cerebral hypoperfusion in rats
Institute for Functional Neurosurgery P.L.A and Institute for Functional Brain Disorders, Tang Du Hospital, The Fourth Military Medical University, Xi'an 710038, PR China. Pharmacology Biochemistry and Behavior
(Impact Factor: 2.78).
03/2011; 99(1):42-51. DOI: 10.1016/j.pbb.2011.03.019
Cerebral white matter lesions (WMLs) are frequently observed in vascular dementia and Alzheimer's disease and are believed to be responsible for cognitive dysfunction. The cerebral WMLs are most likely caused by chronic cerebral hypoperfusion and can be experimentally induced by permanent bilateral common carotid artery occlusion (BCCAO) in rats. Previous studies found the involvement of oxidative stress and astrocytic activation in the cerebral WMLs of BCCAO rats. Gypenoside (GP), a pure component extracted from the Gyrostemma pentaphyllum Makino, a widely reputed medicinal plants in China, has been reported to have some neuroprotective effects via anti-oxidative stress and anti-inflammatory mechanisms. In the present study, we investigated the protective effect of GP against cerebral WMLs and the underlying mechanisms for its inhibition of cognitive decline in BCCAO rats. Adult male Sprague-Dawley rats were orally administered daily doses of 200 and 400mg/kg GP for 33 days after BCCAO, and spatial learning and memory were assessed using the Morris water maze. Following behavioral testing, oxygen free radical levels and antioxidative capability were measured biochemically. The levels of lipid peroxidation and oxidative DNA damage were also assessed by immunohistochemical staining for 4-hydroxynonenal and 8-hydroxy-2'-deoxyguanosine, respectively. Activated astrocytes were also assessed by immunohistochemical staining and Western blotting with GFAP antibodies. The morphological changes were stained with Klüver-Barrera. Rats receiving 400mg/kg GP per day performed significantly better in tests for spatial learning and memory than saline-treated rats. GP 400mg/kg per day were found to markedly scavenge oxygen free radicals, enhance antioxidant abilities, decrease lipid peroxide production and oxidative DNA damage, and inhibit the astrocytic activation in corpus callosum and optic tract in BCCAO rats. However, GP 200mg/kg per day had no significant effects. GP may have therapeutic potential for treating dementia induced by chronic cerebral hypoperfusion and further evaluation is warranted.
Available from: Giancarlo Zito
- "and oxidative DNA damage have been observed in 2VO rats treated with gypenoside, a pure component extracted from the Chinese medicinal plant Gyrostemma pentaphyllum . This outcome seems be due to the suppression of oxidative stress and astrocytic activation. "
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ABSTRACT: Vascular dementia (VaD) is the second most common form of dementia. Different studies have indicated that patients with VaD have increased levels of local and systemic oxidative stress markers. Furthermore, in vivo and clinical experiments have demonstrated that the administration of antioxidants via foods and/or supplementation therapies significantly reduces the pathological features of VaD, including cognitive
decline. Here, we provide a survey of studies about the role of oxidative stress and antioxidants in VaD pathogenesis. Moreover, we suggest the potential approach that caregivers might use to verify the effectiveness of antioxidants to prevent VaD or treat VaD patients.
Keywords: cerebrovascular disorders, oxidative stress, neurodegenerative diseases, Antioxidants, diet.
Available from: Yanfeng Wang
- "The bioactivity of GP, including anti-inflammatory, anti-oxidative and anti-tumor activity, has been investigated in numerous studies (6,11,12). However, its anti-oxidative capacity is the significant function. "
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ABSTRACT: Gynostemma pentaphyllum is a traditional Chinese medicine that has previously been used for the treatment of chronic inflammation, hyperlipidemia and liver disease. Gypenoside (GP), the predominant component of Gynostemma pentaphyllum, exhibits a therapeutic effect on chronic hepatic injury, fibrosis and fatty liver disease via its anti-inflammatory and anti-oxidant activity. However, the effect of GP on ischemia/reperfusion (I/R)-induced hepatic injury has, to the best of our knowledge, not previously been investigated. In the present study, a hepatic I/R-injury model was successfully established using C57BL/6 mice. In the treatment group, 50 mg/kg GP was administered orally 1 h prior to ischemia. Following hepatic I/R, the levels of hepatic lipid peroxidation and serum alanine aminotransferase increased, while the ratio of hepatic glutathione (GSH):oxidized GSH was reduced, which was effectively attenuated by pretreatment with GP. Furthermore, an increased protein expression of heme oxygenase-1 in the liver tissues of the I/R mice was attenuated by the administration of GP. In addition, the present study indicated that treatment with GP suppressed the I/R-induced increase in the pro-apoptotic protein levels of Bax and cytochrome c and the activity of caspase-3/8, as well as the I/R-induced decrease in the levels of anti-apoptotic protein Bcl-2. In conclusion, the present study indicated that GP effectively protected against I/R-induced hepatic injury via its anti-oxidative and anti-apoptotic bioactivity.
Available from: Costantino Iadecola
- " damage . Accordingly , scavenging of free radicals or approaches to suppress inflammation counteract white matter damage and behavioral deficits in rodent models of cerebral hypoperfusion ( Dong et al . , 2011 ; Kim et al . , 2008a ; Maki et al . , 2011 ; Ueno et al . , 2009 ; Wakita et al . , 2008 ; Wang et al . , 2010 ; Washida et al . , 2010 ; Zhang et al . , 2011 ) . NADPH oxidase , a multiunit enzyme particularly enriched in cerebral blood vessels ( Miller et al . , 2005 ) , has emerges as an important source in vascular oxidative stress in aging , hypertension , hyperlipidemia and dia - betes ( Faraci et al . , 2011 ) , and inhibition or genetic inactivation of this enzyme has been shown to am"
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ABSTRACT: Vascular cognitive impairment defines alterations in cognition, ranging from subtle deficits to full-blown dementia, attributable to cerebrovascular causes. Often coexisting with Alzheimer's disease, mixed vascular and neurodegenerative dementia has emerged as the leading cause of age-related cognitive impairment. Central to the disease mechanism is the crucial role that cerebral blood vessels play in brain health, not only for the delivery of oxygen and nutrients, but also for the trophic signaling that inextricably links the well-being of neurons and glia to that of cerebrovascular cells. This review will examine how vascular damage disrupts these vital homeostatic interactions, focusing on the hemispheric white matter, a region at heightened risk for vascular damage, and on the interplay between vascular factors and Alzheimer's disease. Finally, preventative and therapeutic prospects will be examined, highlighting the importance of midlife vascular risk factor control in the prevention of late-life dementia.
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