An antioxidant phytotherapy to rescue neuronal oxidative stress

Abstract

Oxidative stress is involved in the pathogenesis of ischemic neuronal injury. A Chinese herbal formula composed of Poria cocos (Chinese name: Fu Ling), Atractylodes macrocephala (Chinese name: Bai Zhu) and Angelica sinensis (Chinese names: Danggui, Dong quai, Donggui; Korean name: Danggwi) (FBD), has been proved to be beneficial in the treatment of cerebral ischemia/reperfusion (I/R).This study was carried out to evaluate the protective effect of FBD against neuronal oxidative stress in vivo and in vitro. Rat I/R were established by middle cerebral artery occlusion (MCAO) for 1 h, followed by 24 h reperfusion. MCAO led to significant depletion in superoxide dismutase and glutathione and rise in lipid peroxidation (LPO) and nitric oxide in brain. The neurological deficit and brain infarction were also significantly elevated by MCAO as compared with sham-operated group. All the brain oxidative stress and damage were significantly attenuated by 7 days pretreatment with the aqueous extract of FBD (250 mg kg(-1), p.o.). Moreover, cerebrospinal fluid sampled from FBD-pretreated rats protected PC12 cells against oxidative insult induced by 0.2 mM hydrogen peroxide, in a concentration and time-dependent manner (IC(50) 10.6%, ET(50) 1.2 h). However, aqueous extract of FBD just slightly scavenged superoxide anion radical generated in xanthine-xanthine oxidase system (IC(50) 2.4 mg ml(-1)) and hydroxyl radical generated in Fenton reaction system (IC(50) 3.6 mg ml(-1)). In conclusion, FBD was a distinct antioxidant phytotherapy to rescue neuronal oxidative stress, through blocking LPO, restoring endogenous antioxidant system, but not scavenging free radicals.

Figure 1

Effects of aqueous extract of FBD on neurological score and brain infarction in rats subject to MCAO. Each column represents the mean ± SD of 10–12 rats. Significance was evaluated with one-way ANOVA following by two-sided Dunnett's t-test. _* P < .05, _** P < .01 versus the vehicle-pretreated MCAO group.

Figure 2

Effect of rat CSF-FBD on PC12 cells induced by hydrogen peroxide. All the data were shown as the mean ± SD, n = 6. Significance was evaluated with one-way ANOVA following by two-sided Dunnett's t-test. *P < .05, _** P < .1, _*** P < .001 versus blank CSF.

Figure 3

Scavenging activities of aqueous extract of FBD against superoxide anion radical generated in xanthine-XO system and hydroxyl radical generated in Fe²⁺/H₂O₂ Fenton reaction system with ascorbic acid as a positive control. Values were means ± SD, n = 6.