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ADAPTOGENIC (MODULATES STRESS RESPONSE)
Siberian ginseng appears to alter the levels of different neurotransmitters and hormones involved in the stress response, chiefly at the HPA axis. It degrades the enzyme (catechol-O-methyl transferase), and increases levels of noradrenaline and serotonin in the brain and adrenaline in the adrenal glands, according to animal studies. Eleutherosides have also been reported to bind to receptor sites for progestin, oestrogen, mineralocorticoids and glucocorticoids in vitro and therefore may theoretically exert numerous pharmacological actions important for the body’s stress response.
Owing to such actions, herbalists and naturopaths describe the herb’s overall action as ‘adaptogenic’, whereby the body is better able to adapt to change and homeostasis is more efficiently restored. More recently, the term ‘allostasis’ is being adopted in the medical arena to describe ‘the ability to achieve stability through change’.
Although the mechanism of action responsible is still unclear, several theories have been proposed to explain the effect of Siberian ginseng on allostatic systems, largely based on the pharmacological actions observed in test-tube and animal studies.
Siberian ginseng increases levels of noradrenaline, serotonin, adrenaline and cortisol that are able to induce both positive and negative feedback responses. Therefore, for example, if allostatic load is such that responses have become inadequate, then the resulting increase in hormone levels would theoretically induce a more efficient response. Alternatively, situations of chronic overactivity, also due to allostatic load, would respond to Siberian ginseng in a different way, with negative feedback systems being triggered to inactivate the stress response. As a result, Siberian ginseng could theoretically induce quite different effects, largely dependent on whether allostatic responses were underactive or overwhelmed.
Siberian ginseng appears to exert an immunomodulatory rather than just an immunosuppressive or stimulating action; however, evidence for the immune enhancing effects of Siberian ginseng is contradictory. Clinical studies in vitro and in vivo have revealed stimulation of general non-specific resistance and an influence on T-lymphocytes, NK cells and cytokines, although other studies suggest that Siberian ginseng does not significantly stimulate the innate macrophage immune functions that influence cellular immune responses. Alternatively, another in vitro study has demonstrated that activation of macrophages and NK cells does occur and may be responsible for inhibiting tumor metastasis both prophylactically and therapeutically.
The main constituents responsible appear to be lignans (seamin, syringin) and polysaccharides such as glycans, which demonstrate immunostimulant effects in vitro. Additionally, effects on the HPA axis will influence immune responses.
It has been suggested that eleutheroside E may be responsible for the improved recovery from reduced NK activity and the inhibition of corticosterone elevation induced by forced swimming in mice and may contribute to the antifatigue action.
Siberian ginseng extracts have been reported to provide better usage of glycogen and high energy phosphorus compounds and improve the metabolism of lactic and pyruvic acids. Additionally, preliminary evidence of possible anabolic effects makes this herb a popular treatment among athletes in the belief that endurance, performance and power may improve with its use.
While initial animal studies showed promise for improving weight gain and increasing organ and muscle weight, clinical studies confirming whether anabolic effects occur also in humans could not be located.
ANTICOAGULANT AND ANTIPLATELET EFFECTS
A controlled trial using Siberian ginseng tincture for 20 days in 20 athletes detected a decrease in the blood coagulation potential and activity of the blood coagulation factors that are normally induced by intensive training of the athletes. Whether the effects also occur in non-athletes is unknown. The 3, 4-dihydroxybenzoic acid constituent of Siberian ginseng has demonstrated antiplatelet activity in vivo.
In vitro studies have demonstrated vasorelaxant effects for Siberian ginseng. The effect is thought to be endothelium-dependent and mediated by NO and/or endothelium-derived hyperpolarising factor, depending on the size of the blood vessel. Other vasorelaxation pathways may also be involved.
In vitro studies demonstrate that Siberian ginseng has anti-allergic properties in mast-cell-mediated allergic reactions.
Animal studies have found that administration of Siberian ginseng prior to a lethal dose of radiation produced an 80% survival rate in mice. This result suggests that Siberian ginseng may protect against radiation toxicity.
Preliminary animal studies have suggested possible neuroprotective effects in transient middle cerebral artery occlusion in Sprague-Dawley rats. Infarct volume was reduced by 36.6% by inhibiting inflammation and microglial activation in brain ischaemia after intraperitoneal injection of a water extract of Siberian ginseng. Similarly, intraperitoneal injection of Siberian ginseng was found to relieve damage to neurons following hippocampal ischaemia hypoxia and improve the learning and memory of rats with experimentally induced vascular dementia. Thesaponins present in Siberian ginseng have also been shown to protect against cortical neuron injury induced by anoxia/ reoxygenation by inhibiting the release of NO and neuron apoptosis in vitro.
Animal studies have demonstrated that an intravenous extract of Siberian ginseng decreased thioacetamide-induced liver toxicity when given before and after thioacetamide administration. More recently oral administration of aqueous extract and polysaccharide was found to attenuate fulminant hepatic failure induced by D-galactosamine/lipopolysaccharide in mice, reducing serum AST, ALT and TNF-alpha levels. The protective effect is thought to be due to the water-soluble polysaccharides.
Animal studies have demonstrated that the inclusion of Siberian ginseng attenuated the ‘weight gain, serum LDL-cholesterol concentration and liver triglycerides accumulation in mice with obesity induced by high-fat diets’.
GLYCAEMIC CONTROL AND INSULIN-SENSITISING EFFECT
Animal studies have indicated a potential for hypoglycaemic effects when used intravenously. Eleutherens A-G exert marked hypoglycaemic effects in normal and alloxan-induced hyperglycaemic mice and eleutherosides show an insulin-like action in diabetic rats. However, these effects have not been borne out in human studies and may not relate to oral dosages of Siberian ginseng.
A small, double-blind, randomised, multiple-crossover study using 12 healthy participants actually showed an increase in postprandial plasma glucose at 90 and 120 minutes when 3 g Siberian ginseng was given orally 40 minutes before a 75-g oral glucose tolerance test. More recently, oral administration of an aqueous extract of Siberian ginseng was shown to improve insulin sensitivity and delay the development of insulin resistance in rats. As a result further trials in people with impaired glucose tolerance and/or insulin resistance are warranted.