The antistress effect of ginseng total saponin and ginsenoside Rg3 and Rb1 evaluated by brain polyamine level under immobilization stress

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Abstract

The present study aims to demonstrate the ability of ginseng total saponin (GTS), ginsenosides Rg3 and Rb1 to reduce brain polyamine levels in immobilization-stressed gerbil mice. A previous study reported that ginsenosides had an anti-stress property. So, we tested the anti-stress effect of ginseng by investigating the brain level of polyamine, a well-known stress stimuli marker. We determined the brain polyamine levels under 30-min immobilization stress in pretreating GTS (100 mg kg−1, oral), ginsenosides Rg3 and Rb1 (10 mg kg−1, oral, respectively). Then, we compared polyamine levels between the non-stressed mouse and the stressed mouse which had taken saline orally to check the placebo effect. Putrescine (PUT) levels were significantly increased (P < 0.01) in the stressed condition, but it was reduced in pretreatment of GTS, ginsenosides Rg3 (P < 0.01, respectively) and Rb1 (P < 0.001) under 30-min immobilization stressed-mouse. However, other polyamine levels did not change regardless of stressed condition or GTS-, ginsenosides Rg3- and Rb1-treated stressed condition. These results mean that only PUT could be a marker for stress and GTS, ginsenosides Rg3 and Rb1 administration lead to an anti-stress effect. Thus, our studies indicate that GTS, ginsenosides Rg3 and Rb1 may play a neuroprotective role in the immobilization-stressed brain.

Introduction

Putrescine (PUT), spermidine (SPD), and spermine (SP) are endogenous polyamines which are essential for cellular growth, proliferation, regeneration, and differentiation [1]. The metabolism and catabolism of polyamines is highly regulated by the concerted action of six enzymes [2], [3], such as ornithine decarboxylase (ODC), S-adenosyl-l-methionine decarboxylase (AdoMetDC), spermidine synthases, spermine synthases, spermidine/spermine N1-acetyltransferase (SSAT), and polyamine oxidase (PAO). Various forms of stresses result in the alteration of polyamine metabolism [4], [5]. The ODC has particularly been considered as a biochemical hallmark of brain damage. The ODC or SSAT activity is particularly increased in the stressed condition, and it leads to the accumulation of putrescine levels [1], [6]. Therefore, inhibiting the activity of ODC or SSAT could result in an anti-stress effect against stressed brain damage.

Panax ginseng C.A. Mayer (Araliaceae), one of the most popular herbal medicines, has been widely used for the therapy of stress disorders [7]. There are eight major ginsenosides in ginseng. Rb1 is the most abundant ginsenoside in ginseng, and reportedly, it has a neuroprotective effect against ischemia [8], glutamate neurotoxicity [9], [10], seizures [11], motor impairment, and cell loss in the striatum [12]. Rg3 is well known as a potent ginsenoside which has a neuroprotective effect in fermented red-ginseng [13] and an anti-stress effect [14].

Therefore, the present study was investigated whether or not the administration of ginseng total saponin (GTS) and ginsenosides Rg3 and Rb1 can attenuate polyamine levels in brain damage after an experience with immobilization stress.

Section snippets

Animals and immobilization stress

Male Mongolian gerbils (60–80 g) were housed in a temperature-controlled environment under 12-h dark:12-h light cycle under condition where food and water were freely available. All experiments conformed to the animal care guidelines of the Korean Academy of Medical Sciences, and all efforts were made to minimize their suffering. Stress procedures were approved and monitored by the ethical committee of Kyung Hee University. For stress experiments, gerbils were immobilized for 30 min in tightly

Results

To confirm the optimal stressed condition, we measured the corticosterone levels in mouse plasma following immobilization stress at 30 min points. In the present study, the corticosterone level was markedly increased (457.06 ± 34.02 ng mL−1, P < 0.01) at 30-min immobilization stress stage when compared to the levels of the control groups (201.17 ± 98.12 ng mL−1).

We examined the changes in brain polyamine levels before and after immobilization stress (Table 1). The PUT was significantly elevated (P < 0.01),

Discussion

Several researchers examined the changes in brain polyamine levels after stress [4], [19]. Acute stress causes neurotransmitter maximum increase at early time (within 30 min) [20], [21]. These results agree with our preliminary data, according to these data we set up stress model to give 30-min immobilization stress to gerbil. In this study, the PUT level was significantly elevated (P < 0.01), whereas the spermidine and spermine levels showed no significant changes in immobilization-stressed

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    In previous reports, some of the ginsenosides, especially Rb1 and Rg3, were studied for their effects on stress-related changes [57–59]. When Rb1 was administered orally, immobilization-stressed animals showed recovery from decreased brain-derived neurotrophic factor (BDNF) levels in the hippocampus and from increased levels of polyamine, which is a known stress stimuli marker in the brain [57,58]. In addition, Rg3 displayed an anxiolytic effect on chronic unpredictable stress by normalizing the serotonergic system [59].

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