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Chapter: Basic & Clinical Pharmacology : Dietary Supplements & Herbal Medications

Botanical Substances: Ginseng

Ginseng may be derived from any of several species of the genus Panax. Of these, crude preparations or extracts of Panax ginseng,the Chinese or Korean variety, and P quinquefolium, the American variety.

GINSENG

Chemistry

 

Ginseng may be derived from any of several species of the genus Panax. Of these, crude preparations or extracts of Panax ginseng,the Chinese or Korean variety, and P quinquefolium, the American variety, are most often available to consumers in the United States. The active principles appear to be the triterpenoid saponin glyco-sides called ginsenosides or panaxosides, of which there are approximately 30 different types. It is recommended that com-mercial P ginseng formulations be standardized to contain 4–10% ginsenosides.

 

Other plant materials are commonly sold under the name ginseng but are not from Panax species. These include Siberian ginseng (Eleutherococcus senticosus) and Brazilian ginseng (Pfaffiapaniculata). Of these, Siberian ginseng is more widely available inthe USA. Siberian ginseng contains eleutherosides but no ginseno-sides. Currently, there is no recommended standardization for eleutheroside content in Siberian ginseng products.

 

Pharmacology

 

An extensive literature exists on the potential pharmacologic effects of ginsenosides. Unfortunately, the studies differ widely in the species of Panax used, the ginsenosides studied, the degree of purification applied to the extracts, the animal species studied, and the measurements used to evaluate the responses. A remark-able list of reported beneficial pharmacologic effects include modulation of immune function (induced mRNA expression for interleukins-2 and -1α, interferon-γ, and granulocyte-macrophage colony-stimulating factor; activated B and T cells, natural killer cells, and macrophages); central nervous system effects (increased proliferating ability of neural progenitors; increased central levels of acetylcholine, serotonin, norepinephrine, and dopamine in thecerebral cortex); antioxidant activity; anti-inflammatory effects (inhibition of TNF-α, interleukin-1β, and vascular and intracel-lular cell adhesion molecules); antistress activity (ie, stimulation of pituitary-adreno-cortical system, agonist at glucocorticoid receptor); analgesia (inhibition of substance P); vasoregulatory effects (increased endothelial nitric oxide and inhibition of prostacyclin production); cardioprotective activity (reduced ventricular remod-eling and cardiac hypertrophy in animal models of myocardial ischemia); antiplatelet activity; improved glucose homeostasis (increased insulin release, number of insulin receptors, and insulin sensitivity); and anticancer properties (reduced tumor angiogene-sis, increased tumor cell apoptosis).

 

Clinical Trials

 

Ginseng is most often claimed to help improve physical and men-tal performance or to function as an “adaptogen,” an agent that helps the body to return to normal when exposed to stressful or noxious stimuli. Unfortunately, the clinical trials evaluating gin-seng for these indications have shown few if any benefits. Some randomized controlled trials evaluating “quality of life” have claimed significant benefits in some subscale measures of quality of life but rarely in overall composite scores using P ginseng. Better results have been observed with P quinquefolium and P ginseng in lowering postprandial glucose indices in subjects with and without diabetes. This was the subject of a recent systematic review in which 15 studies (13 randomized and 2 nonrandomized) were evaluated. Nine of the studies reported significant reductions in blood glucose. Newer randomized, placebo-controlled trials have reported some immunomodulating benefits of P quinquefolium (four trials) and P ginseng (one trial) in preventing upper respira-tory tract infections. Use of ginseng for 2–4 months in healthy seniors may reduce the incidence of acquiring the common cold as well as the duration of symptoms. Because of heterogeneity in these trials, however, these findings are insufficient to war-rant recommending the use of ginseng for this indication at this time. Two case-control studies, a cohort study and one randomized, double-blind, placebo-controlled study, also suggest a non-organ-specific cancer preventative effect with long-term administration of P ginseng. In summary, the strongest support for use of P ginsengor P quinquefolium currently relates to its effects in coldprevention, lowering postprandial glucose, and nonspecific cancer prevention.

 

Adverse Effects

 

Vaginal bleeding and mastalgia have been described in case reports. Central nervous system stimulation (eg, insomnia, nervousness) and hypertension have been reported in patients using high doses (more than 3 g/d) of P ginseng. Methylxanthines found in the ginseng plant may contribute to this effect. Vasoregulatory effects of ginseng are unlikely to be clinically significant.

 

Drug Interactions & Precautions

 

Irritability, sleeplessness, and manic behavior have been reported in psychiatric patients using ginseng in combination with other medications (phenelzine, lithium, neuroleptics). Ginseng should be used cautiously in patients taking any psychiatric, estrogenic, or hypoglycemic medications. Ginseng has antiplatelet properties and should not be used in combination with warfarin. Cytokine stimulation has been claimed for both P ginseng and P quinquefo-lium in vitro and in animal models. In a randomized, double-blind, placebo-controlled study, P ginseng significantly increased natural killer cell activity versus placebo with 8 and 12 weeks of use. Immunocompromised individuals, those taking immune stimulants, and those with autoimmune disorders should use ginseng products with caution.

 

Dosing

 

One to two grams of the crude P ginseng root or its equivalent is considered standard dosing. Two hundred milligrams of standard-ized P ginseng extract is equivalent to 1 g of the crude root. Ginsana has been used as a standardized extract in some clinical trials and is available in the USA.

 

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