Gypenosides improve cognitive impairment induced by chronic cerebral hypoperfusion in rats by suppressing oxidative stress and astrocytic activation

Abstract

Gypenosides (GP), the saponin extract derived from the Gynostemma pentaphyllum Makino, a widely reputed medicinal plant in China, has been reported to have some neuroprotective effects. We used a rat model of chronic cerebral hypoperfusion to investigate the protective effects of GP on the cortex and hippocampal CA1 region and the underlying mechanisms for its inhibition of cognitive decline. Daily doses of 100 and 200 mg/kg GP were orally administered to adult male Sprague-Dawley rats for 61 days after inducing cerebral hypoperfusion experimentally, and spatial learning and memory were assessed using the Morris water maze. Antioxidative capability was measured biochemically. The levels of lipid peroxidation and oxidative DNA damage were assessed by immunohistochemical staining for 4-hydroxynonenal and 8-hydroxy-2'-deoxyguanosine, respectively. Activated astrocytes were assessed by immunohistochemical staining and western blotting with GFAP antibodies. Rats receiving 200 mg/kg GP had better spatial learning and memory than saline-treated rats. GP 200 mg/kg/day were found to markedly enhance antioxidant abilities, decrease lipid peroxide products and oxidative DNA damage, and reduce the activation of inflammatory astrocytes. However, GP 100 mg/kg had no significant effects. GP may have therapeutic potential for the treatment of dementia induced by chronic cerebral hypoperfusion and further evaluation is warranted.

Environmental enrichment prevents behavioral deficits and oxidative stress caused by chronic cerebral hypoperfusion in the rat

“…However, a previous study reported that chronic cerebral hypoperfusion causes learning impairments in the water maze without marked histological alterations in the hippocampus and striatum (Cechetti et al, 2010;Murakami et al, 2005). Several authors have shown that the long-lasting learning deficits observed in these rats are at least partially attributable to damage to the white matter (Zhang et al, 2011). Cho et al (2006) identified that the main areas affected are corpus callosum, optic tract, and internal capsule in rats with chronic cerebral hypoperfusion.…”

“…Recent studies designed a mouse model of chronic cerebral hypoperfusion by placing microcoils bilaterally to the common carotid arteries, where the visual pathway is preserved since blood flow in the common carotid arteries albeit reduced is maintained, but still develops working memory (Shibata et al, 2007) as well as reference memory impairments (Nishio et al, 2010)". In addition, several authors describe damage to white matter in the standard model of two vessels, unlike the modified model (Cho et al, 2006;Farkas et al 2007;Zhang et al, 2011).…”

“…The same occurred with Gypenosides (GP), the saponin extract derived from the Gynostemma pentaphyllum Makino, by increasing antioxidant abilities, decreasing lipid peroxide products and oxidative DNA damage, and reducing the activation of inflammatory astrocytes. Thus, attenuating the oxidative stress and suppressing the activation of inflammatory glial cells are potential approaches for treating cerebral white matter damage and alleviating the cognitive impairment (Zhang et al, 2011).…”

Minocycline improves postoperative cognitive impairment in aged mice by inhibiting astrocytic activation

“…Preliminary animal research found that inhibiting astrocytic activation improved cognitive impairment induced by chronic cerebral hypoperfusion [4].…”

Research progress on natural products from traditional Chinese medicine in treatment of Alzheimer's disease

“…Gypenosides are a series of saponins isolated from Gynostemma pentaphyllum (95). They exhibit strong antioxidative properties manifesting as scavenging free radicals and increasing the levels of SOD in brain tissues.…”