Asiatic acid, a pentacyclic triterpene from Centella asiatica, is neuroprotective in a mouse model of focal cerebral ischemia

Abstract

Asiatic acid, a triterpenoid derivative from Centella asiatica, has shown biological effects such as antioxidant, antiinflammatory, and protection against glutamate-or β-amyloid-induced neurotoxicity. We investigated the neuroprotective effect of asiatic acid in a mouse model of permanent cerebral ischemia. Various doses of asiatic acid (30, 75, or 165 mg/kg) were administered orally at 1 hr pre-and 3, 10, and 20 hr postischemia, and infarct volume and behavioral deficits were evaluated at day 1 or 7 postischemia. IgG (blood-brain barrier integrity) and cytochrome c (apoptosis) immunostaining was carried out at 24 hr postischemia. The effect of asiatic acid on stress-induced cytochrome c release was examined in isolated mitochondrial fractions. Furthermore, its effects on cell viability and mitochondrial membrane potential were studied in HT-22 cells exposed to oxygenglucose deprivation. Asiatic acid significantly reduced the infarct volume by 60% at day 1 and by 26% at day 7 postischemia and improved neurological outcome at 24 hr postischemia. Our studies also showed that the neuroprotective properties of asiatic acid might be mediated in part through decreased blood-brain barrier permeability and reduction in mitochondrial injury. The present study suggests that asiatic acid may be useful in the treatment of cerebral ischemia.Keywords infarct volume; blood-brain barrier; oxygen-glucose deprivation; mitochondria; apoptosis Although the molecular mechanisms involved in ischemic brain injury are not fully understood, much progress has been made in identifying some pathogenic pathways, such as inflammation, excitotoxicity, mitochondrial dysfunction, and oxidative stress, that might be involved in ischemic neuronal death (Durukan and Tatlisumak, 2007 Centella asiatica is a herbaceous plant that might also have medicinal value. It is being used in Ayurvedic preparations to improve learning and memory (Zheng and Qin, 2007). Published data suggest that the plant extract has nootropic effects (Rao et al., 2005), protects the brain from age-related oxidative damage (Subathra et al., 2005), and promotes nerve growth and neuronal dendritic arborization (Mohandas et al., 2006).Asiatic acid (AA), a pentacyclic triterpene derivative from Centella asiatica, has been shown to display neuroprotective properties both in vitro and in vivo (Bonfill et al., 2006). In cellular systems, AA was reported to offer protection against β-amyloid-induced cell death in the neuroblastoma B103 cell line (Mook-Jung et al., 1999;Jew et al., 2000). It also reduced H 2 O 2 -related cell death and decreased intracellular free radical concentration (Mook-Jung et al., 1999). Furthermore, AA derivatives were effective at rescuing primary rat cortical cells from glutamate-induced toxicity through activation of the cellular oxidative defense pathway (Lee et al., 2000).Because AA exhibits numerous pharmacological activities that might be beneficial to the ischemic brain, and given that no significant toxicity was observed following subcutaneous o...

Asiatic acid, a pentacyclic triterpene in Centella asiatica, attenuates glutamate-induced cognitive deficits in mice and apoptosis in SH-SY5Y cells

“…In our experiments, AA attenuated the decline of the MMP induced by Glu. Our data corroborate the results of a previous study, which reported that AA prevents the collapse of the MMP in rotenone-induced neuronal damage [14] and in the oxygenglucose deprivation (OGD) cell culture model of ischemia [17] .…”

“…The animals were divided into four experimental groups: control, MSG, MSG+50 mg/kg AA and MSG+100 mg/kg AA. The AA doses used in this study were chosen on the basis of previously published experiments [17] . AA was administered after MSG treatment on PD 14 and daily thereafter for 30 d. The mice then performed the Morris water maze.…”

“…AA also showed protective effects against Glu-and Aβ-induced neurotoxicity [15,16] . Moreover, AA may be an effective agent for treating cerebral ischemia [17] . Therefore, AA is interesting as a candidate for potential application in the treatment of neurodegenerative diseases.…”

Retraction: Asiatic Acid from <i>Potentilla chinensis</i> Attenuate Ethanol-Induced Hepatic Injury <i>via</i> Suppression of Oxidative Stress and Kupffer Cell Activation

“…Previous studies have shown that Asiatic acid has a variety of pharmacological effects on anti-inflammation, 8,9) anti-tumor, 10) neuroprotection. 11) In particular, Asiatic acid has been shown to be a hepatoprotective agent. A number of studies demonstrated that Asiatic acid can protect liver from injury via mechanisms underlying antimitochondrial stress and cellular antioxidant system in cultured hepatocytes and Kupffer cells, and in a mouse model induced by D-galactosamine and lipopolysaccharides.…”

Efficiency of an eastern traditional medicine- asiatic acid on traumatic spinal cord injury: an experimental study

“…Some reports stated that AA is a promising agent in the treatment of stroke. AA exerts neuroprotection by maintaining the stability of the blood brain barrier and by protecting the mitochondrial functions (10,12,13,20).…”