Anticonvulsant and neuroprotective effects of ginsenosides in rats
Introduction
The possibility that ginseng may have anticonvulsant activity was first suggested by Lee et al. (2002). Although there are many possible active components in the plant, the ginsenosides are believed to have the most biological activity (Attele et al., 1999). Over 28 ginsenosides have been isolated from American (Panax quinquefolius) and Asian ginseng (Panax ginseng). They have been divided into two major groups based on structure. The panaxadiols (Rb1, Rb2, Rc, Rd, Rg3, Rh2 and Rh3) are sometimes referred to as the Rb group and are thought to have ‘cooler’ actions or calming influences. The panaxatriols (Re, Rf, Rg1, Rg2 and Rh1) are dominated by the presence of Rg1, which is thought to have ‘warmer’ or stimulant activity (Li and Fitzloff, 2002). The study by Lee et al. (2002), suggesting an anticonvulsant effect, used a mixture of ginsenosides, including the panaxadiols and panaxatriols.
An extract from the leaves and stems of American ginseng has recently been shown to have an anticonvulsant effect in several animal models of seizures (Lian et al., 2005a). This extract consisted of 25% Rb1, 46% Rb3 and 13% Rd. One hypothesis is that Rb1 is the ginsenoside with anticonvulsant activity. However, it is possible that only the mixture of ginsenosides has activity. With herbal products, purification often results in loss of activity. However, a neuroprotective effect has been reported with purified Rb1, suggesting that individual ginsenosides have activity in the central nervous system. Pretreatment with Rb1 reduces the loss of neurons in the hippocampus in gerbils after bilateral occlusion of the carotid arteries (Wen et al., 1996, Zhang and Liu, 1996). Rb1 also protects against excitotoxicity in neuronal cultures (Kim et al., 1998, Liao et al., 2002) and has been shown to have anxiolytic activity (Churchill et al., 2002). In contrast, Rd has no effect on pyramidal cell death in mice treated with kainic acid (Lee et al., 2003). The goal of the current study was to determine the contribution of the individual ginsenosides to the anticonvulsant activity of the ginseng extract previously shown to be effective (Lian et al., 2005a). To facilitate comparison between experimental groups, the individual ginsenosides were tested in the same animal models of seizures as in the previous study. This data can then be used to develop preliminary guidelines for purification of additional extract for clinical testing.
Section snippets
Seizure induction and treatment with the ginseng products
All animal experiments were carried out in accordance with the National Institutes of Health guide for the care and use of laboratory animals (NIH publication 8023, revised 1996) and with the approval of the local Animal Use Committee. Adult male Sprague–Dawley rats weighing 200–250 g were used throughout this study. Animals were housed in a room with controlled temperature (22 ± 1 °C) and humidity (50 ± 5%).
Kainic acid (KA; Ocean Produce Int., Shelburne, Nova Scotia, Canada), pentylenetetrazole
Effects of ginsenosides on kainic acid-induced seizures
Status epilepticus was induced by intraperitoneal injection of 10 mg/kg KA (Fig. 1). Seven out of eight animals (87.5%) pretreated with normal saline had stage 4–5 motor seizures. The remaining one (12.5%) had stage 2 seizures intermittently for several hours. The mean seizure score for the entire group was 4.1 ± 0.35 (mean ± S.E.M., n = 8), the mean weight loss was 14.8 ± 1.3%, and the mean latency to the first wet dog shake was 38 ± 3 min. All these parameters are consistent with those in our previous
Discussion
Previously, we found that a partially purified ginseng extract (Rb extract), which concentrates the panaxadiols (Rb1, Rb3 and Rd), has anticonvulsant activity in three models of seizures in rats (Lian et al., 2005a). The present study demonstrates that the individual ginsenosides all contribute to this anticonvulsant activity. No one individual ginsenoside accounted for all of the activity of the Rb fraction previously reported. By contrast, the mixture of Rb1, Rb3 and Rd had the same
Acknowledgement
This study was supported by the New Therapies Program of The Epilepsy Research Foundation.
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