What is ginseng tea

Ginseng applies to various herbs that commonly refers to species within the Panax genus in the family Araliaceae (Table 1). The two main species used in herbal medicines are Asian or Korean ginseng (Panax ginseng) and American ginseng (Panax quinquefolius). Asian ginseng (Panax ginseng C.A. Meyer) is one of several types of true ginseng; another is American ginseng (Panax quinquefolius). A herb called Siberian ginseng or eleuthero (Eleutherococcus senticosus) is not a true ginseng. Asian ginseng (Panax ginseng), which is native to China, Korea, and Russia, has been an important herbal remedy in traditional Chinese medicine for at least 2,000 years. Ginseng has been traditionally used as a panacea to promote longevity, and as a treatment for weakness and fatigue. It restores the balance between Yin and Yang, stabilizes the dynamic equilibrium of the five elements towards physiological processes, revitalizes and aids recovery from illness ¹⁾. Asian ginseng is one of several types of ginseng see Table 1 for more details. Ginseng is classified as fresh ginseng (raw ginseng less than four years old), white ginseng (four to six years old and dried after peeling), red ginseng (harvested when six years old, steamed and dried), fermented ginseng and cultured ginseng depending on how it is processed ²⁾. Ginseng consists of 60% carbohydrate, 8–15% crude protein, 1–3% lipid, 4–6% ash, 3–7% crude saponin, and other chemicals, including phenolic and volatile compounds ³⁾.

Ginseng that is produced in the United States and Canada (Panax quinquefolius) is particularly prized in Chinese societies ⁴⁾. According to folk legend, American Ginseng root is more Yin (shadow, cold, negative, female). It is believed to promote Yin energy, clean excess Yang in the body, and restore the dynamic equilibrium of Yin and Yang ⁵⁾. According to traditional Chinese medicine, for example, diabetes mellitus is defined as Yin deficiency (fatigue, weakness, lethargy, pale complexion), and American ginseng that is believed to promote Yin energy can be used to treat diabetes mellitus ⁶⁾. The reason it has been claimed that American ginseng (Panax quinquefolius) promotes Yin (shadow, cold, negative, female) while East Asian ginseng (Panax ginseng) promotes Yang (sunshine, hot, positive, male) is that, according to traditional Korean medicine, things living in cold places are strong in Yang and vice versa, so that the two are balanced. Chinese/Korean ginseng grows in northeast China and Korea, the coldest area known to many Koreans in traditional times. Thus, ginseng from there is supposed to be very Yang. Originally, American ginseng (Panax quinquefolius) was imported into China via subtropical Guangzhou, the seaport next to Hong Kong, so traditional Chinese medicine practitioners believed that American ginseng must be good for Yin, because it came from a hot area. However they did not know that American ginseng can only grow in cold regions ⁷⁾.

The main active ingredients of the ginseng (Panax genus) are the so-called “ginsenosides” or “panaxosides”, which belong to the chemical class of triterpene saponins that are thought to contribute to the herb’s claimed health-related properties. Other substances like some sugars and polysaccharides are also active agents.

The chemical composition of ginseng is affected by the following factors: the species, the habitat in which it grows, the maturity of the plant and the geographical origin of cultivation. In addition, harvesting, storage and post-harvest processing can affect the bioactive compound of ginseng ⁸⁾. Researchers have shown that the pharmaceutical and medicinal effects of ginseng can vary according to the species. Panax ginseng has a ‘warm’ (Yang) property and is known to refill the ‘vital energy’, but Panax quinquefolius has a ‘cooling’ (Yin) effect and is used mainly to reduce the ‘internal heat’ and uphold the secretion of body fluids ⁹⁾. In addition, the distribution of the main bioactive compounds in ginseng－ginsenosides or ginseng saponins－varies with the species ¹⁰⁾. When ginseng is used properly, it appears to be safe. In many countries, it is considered a supplement food, not a drug, and most documented side effects are related to inappropriate use. Nevertheless, reported side effects include hypertension, diarrhoea, sleeplessness, mastalgia, skin eruptions and vaginal bleeding ¹¹⁾. Ginseng is generally safe, but it may affect glucose levels and also be unsafe for people with blood pressure disorders. Some experts recommend that women who are pregnant or breastfeeding not use ginseng.

Ginseng has been popularly referred to as an “adaptogen” in much of the alternative medicine literature. The term “adaptogen” implies a substance that increases resistance to physical, chemical, and biological stress and builds up general vitality including physical and mental capacity. Panax ginseng has been used for centuries as an important component of many Chinese prescriptions to treat disease and combat aging. Its medicinal efficacy was first documented in Shengnong Bencao Jing and was later summarised by Li Shizhen in Bencao Gangmu and Zhongyao Zhi (Chinese Materia Medica). More recently, ginseng has received much attention as a treatment claimed to enhance cognitive performance and well-being.

In traditional Chinese medicine, Asian ginseng was used as a tonic that was believed to replenish energy. Today, Asian ginseng root is used as a dietary supplement to improve general well-being, physical stamina, and concentration; stimulate immune function; slow the aging process; and relieve various health problems such as respiratory disorders, cardiovascular disorders, depression, anxiety, erectile dysfunction, and menopausal hot flashes.

There have been many studies of Asian ginseng in people, but few have been high quality. Therefore, our understanding of Asian ginseng’s health effects is limited. However, there’s currently no conclusive evidence supporting any health benefits of Asian ginseng ¹²⁾.

The fresh ginseng root, after peeled, can be directly chewed, or soaked in various wines for a period of time before drink and chewing ¹³⁾. Ginseng is most often available in dried form, either in whole or sliced form. Ginseng leaf, although not as highly prized, is also used; as with the root it is most often available in dried form ¹⁴⁾. The correct and efficient cooking processes for the dried ginseng are as following: washing the dried roots with running water, immersing the dried roots in boiled water and maintaining the water hot for at least 3 hours or overnight, taking the soaked and hence soft roots out of water and slicing the roots with a knife as small as possible, and finally stewing the sliced roots slowly and gently in the water in a closed vessel before drinking the liquid ¹⁵⁾. Ginseng is usually sliced and simmered in hot water to make a decoction. Ginseng ingredient may also be found in some popular energy drinks, ginseng tea varieties, or functional foods. Ginseng root is often sliced and steamed with chicken meat as a soup in China (including Taiwan), and Korea. Usually ginseng is used at subclinical doses for a short period and as such, it does not produce measurable medicinal effects.

Table 1. Species of Ginseng belonging to the genus Panax

English Name	Latin Name
Asian ginseng Asiatic ginseng Chinese ginseng Ginseng Korean ginseng Manchurian ginseng Oriental ginseng Red ginseng (steamed & dried peeled roots) White ginseng (sun-dried roots)	Panax ginseng
American ginseng Ginseng (USA) Wild American ginseng Occidental ginseng	Panax quinquefolius
Japanese ginseng	Panax japonicus
Narrow-leaved Japanese ginseng	Panax japonicus
Notoginseng Sanchi ginseng (USA) San-qi ginseng (USA) South China ginseng Tien-qi ginseng Yunnan ginseng	Panax notoginseng
False ginseng Nepal ginseng Himalayan ginseng Pseudoginseng	Panax pseudoginseng
Elegant pseudoginseng Pearl ginseng	Panax pseudoginseng
Pearl ginseng	Panax pseudoginseng
Pingpien ginseng	Panax stipuleanatus
Dwarf ginseng Groundnut (USA)	Panax trifolius
Bamboo ginseng Vietnamese ginseng	Panax vietnamensis
Narrow-leaved pseudoginseng	Panax wangianus
Ginger ginseng Ginger-like pseudo-ginseng	Panax zingiberensis

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Ginseng tea benefits

Ginsenosides or “panaxosides” are the most studied active components in ginseng ¹⁷⁾. About 40 types of ginsenosides are contained in ginseng along with non-saponin compounds like acidic polysaccharides and polyacetylenes ¹⁸⁾, ¹⁹⁾. More than 10 phenolic compounds in fresh and/or processed ginseng have previously been reported as follows: salicylic acid, vanillic acid, ascorbic acid, p-coumaric acid, ferulic acid, caffeic acid, gentisic acid, p-hydroxybenzoic acid, maltol, cinnamic acid, protocatechuic acid, syringic acid, and quercetin ²⁰⁾. Among these phenolic compounds, ferulic acid is considered a phenolic compound with anticancer properties. Maltol, which is found in processed ginseng, shows strong scavenging activity against reactive oxygen species ²¹⁾. Korean ginseng usually contains more phenolic compounds than Chinese ginseng; therefore, Korean ginseng has more health benefits than other ginseng species ²²⁾. This study ²³⁾ showed that chlorogenic acid, gentisic acid, p- and m-coumaric acid, and rutin were the main phenolic compounds in 3–6-yr-old ginseng fruit, leaves, and roots. In contrast, gallic acid, myricetin, and biochanin A were not found in 3–6-yr-old ginseng fruit, leaves, and roots. Much basic research on the range of efficacies of ginseng, including its immune-enhancing, anti-fatigue, and anti-cancer functions and improvements to cardiovascular function, is ongoing, along with numerous studies on its mechanisms ²⁴⁾.

In general, ginseng fruit and leaves are less attractive to consumers compared with the ginseng roots; in fact, the fruit and leaves are usually discarded ²⁵⁾. Therefore, information on the phenolic compounds present in the ginseng fruit or leaves is very limited to date. Traditionally, ginseng leaves have been used as a form of tea. In addition, the leaves of hydroponically grown ginseng have been recently used as salad ²⁶⁾. Furthermore, American ginseng berries have been reported to inhibit the growth of colorectal cancer both in vitro and in vivo ²⁷⁾.

Ginsenosides have been isolated and evaluated for pharmacological effects and on the basis of their chemical structure are classified into three groups: the Panaxadiol group (Rb1, Rb2, Rb3, Rc, etc.), the Panaxatriol group (Re, Rf, Rg1, Rg2, Rh1) and the oleanolic acid group (e.g. Ro) ²⁸⁾. These ginsenosides have varying concentrations in ginseng species as a result of the different processing methods that affect deacetylation of enzymes within the raw plant. It has been well documented that the polysaccharides contained within ginseng possess various antitumour activities, including preventive and inhibitory effects against tumours, as well as enhancing immunological functions ²⁹⁾.

Ginseng products are popularly referred to as “tonics,” a term that has been replaced by “adaptogen” in much of the alternative medicine literature. The term “adaptogen” connotes an agent that purportedly increases resistance to physical, chemical, and biological stress and builds up general vitality, including the physical and mental capacity for work. Both American and Panax (Asian) ginseng roots are taken orally as adaptogens, aphrodisiacs, nourishing stimulants, and in the treatment of sexual dysfunction in men ³⁰⁾.

Figure 1. Main structures of ginsenosides

[Source ³¹⁾]

What is ginseng tea good for?

Asian ginseng (Panax ginseng C.A. Meyer) is a common herb with many purported health benefits. However, there is no conclusive evidence supporting its use in the treatment of any particular disease. The therapeutic effects of ginseng are very diverse, and the evidence for its efficacy in treating several conditions such as cardiovascular disease ³²⁾, Alzheimer’s disease ³³⁾, common cold ³⁴⁾ and hypertension ³⁵⁾, has been evaluated. Ginseng has also been used to improve general conditions relevant to quality of life and athletic performance in the healthy population ³⁶⁾. Current evidence does not support the use of ginseng to treat cardiovascular risk factors ³⁷⁾. Some studies suggest a small reduction in blood pressure. Despite some evidence showing that ginseng lowers blood glucose and improves lipid profiles, well-designed, randomized, controlled trials evaluating its effects are lacking ³⁸⁾. A systematic review on ginseng as a treatment for Alzheimer’s disease, the evidence for ginseng as a treatment of Alzheimer’s disease is scarce and inconclusive and Further research is needed. ³⁹⁾. Athletes use ginseng for its alleged performance-enhancing attributes ⁴⁰⁾. However, many studies examining the pharmacological effects of ginseng on physical performance have not employed sound scientific design and methodology ⁴¹⁾. This review authors concluded that many of the same methodological shortcomings observed in earlier studies persist ⁴²⁾. Enhanced physical performance after ginseng administration in well-designed investigations remains to be demonstrated ⁴³⁾. Currently, there is insufficient evidence to support the use of North American ginseng extracts in the prevention of common colds ⁴⁴⁾.

A 2013 systematic review ⁴⁵⁾ to evaluate randomized controlled trials evaluating Panax ginseng in patients with any type of disease or in healthy individuals. The authors assessed the quality of studies using the Cochrane risk of bias tool. Of the 475 potentially relevant studies, 65 met the inclusion criteria. These studies examined Panax ginseng’s effects on psychomotor performance (17 studies), physical performance (ten), circulatory system (eight), glucose metabolism (six), the respiratory system (five), erectile dysfunction (four), immunomodulation (four), quality of life/mood (four), antioxidant function (two), cancer (two), menopausal symptoms (two) and dry mouth (one). The risk of bias was unclear in most studies. The authors evaluated adverse events in 40 studies, with 135 minor events and no serious adverse events reported. Panax ginseng shows promising results for improving glucose metabolism and moderating the immune response ⁴⁶⁾. This may have implications for several diseases including type 2 diabetes and chronic respiratory conditions. Further studies are needed to explore Panax ginseng’s potential as an effective treatment for these and other health conditions.

Ginseng for cognition

Despite ginseng appearing to have some beneficial effects on cognition, behavior and quality of life in small trials ⁴⁷⁾, there is currently a lack of convincing evidence to show a cognitive enhancing effect of Panax ginseng in healthy participants and no high quality evidence about ginseng efficacy in patients with dementia ⁴⁸⁾. Randomized, double-blind, placebo-controlled, parallel group trials with large sample sizes are needed to further investigate the effect of ginseng on cognition in different populations, including dementia patients.

Ginseng and diabetes

Vuksan et al. ⁴⁹⁾ demonstrated that American ginseng (Panax quinquefolius Linn) reduced postprandial glycemia in nondiabetic subjects and subjects with type 2 diabetes mellitus. In addition, Sotaniemi et al. ⁵⁰⁾ showed that treatment of newly diagnosed type 2 diabetes mellitus patients with ginseng (100 or 200 mg) or placebo for 8 weeks elevated mood, improved psychophysical performance, and reduced fasting blood glucose and body weight. The 200-mg dose of ginseng improved glycated hemoglobin, serum PIIINP, and physical activity. Placebo reduced body weight and altered the serum lipid profile but did not alter fasting blood glucose.

Sievenpiper’s study ⁵¹⁾ used a randomized, double-blind, multiple-crossover, double-placebo controlled design. Each participant received 10 single-dose treatments in random order: 3 g of ground whole root of American (Panax quinquefolius L.), American-wild (wild Panax quinquefolius L), Asian (Panax ginseng C.A. Meyer), Asian-red (steam treated Panax ginseng C.A. Meyer), Vietnamese-wild (Panax vietnemensis), Siberian (Eleutherococcus senticosus), Japanese-ginseng (Panax Japonicus C.A. Meyer), and Sanchi (Panax notoginseng) ginsengs and two identical placebos. The two placebos were then mixed and treated as one for all comparisons to increase the probability of obtaining a true control for comparisons with the eight ginseng types. The studies showed decreasing, null and increasing effects of the 8 types of ginseng on acute postprandial glycemic indices in healthy humans. The experience with ginseng suggests that although reproducible efficacy may be achieved using an acute postprandial clinical screening model to select an efficacious ginseng batch, dose, and time of administration, there is a need to develop a basis for standardization that ties the composition of herbs to efficacy. In absence of such standardization, the use of herbs in diabetes must be approached cautiously.

Ginseng as aphrodisiac

The effects of ginseng on the sexual performance appear to be mediated by the release and/or modification of release of nitric oxide (NO) from endothelial cells and perivascular nerves. Nitric oxide (NO) was named “The Molecule of the Year” in 1992 by the journal Science ⁵²⁾, but it took another 6 years for those who discovered it to win the 1998 Nobel Prize for Physiology and Medicine, including Dr. Robert Furchgott ⁵³⁾.

Ginseng has a long reputation in traditional Chinese medicine for treatment of sexual impotence. Recent studies in laboratory animals have shown that both Asian and American forms of ginseng enhance libido and copulatory performance ⁵⁴⁾. There is some evidence that ginsenosides can facilitate penile erection by directly inducing the vasodilatation and relaxation of penile corpus cavernosum. Treatment with American ginseng also affects the central nervous system and has been shown to significantly alter the activity of hypothalamic catecholamines involved in the facilitation of copulatory behavior and hormone secretion ⁵⁵⁾. Consistently with these findings, Choi et al. ⁵⁶⁾ confirmed in a clinical study the efficacy of Korean red ginseng for erectile dysfunction in 30 patients. In 2002, another double-blind, crossover study of Korean red ginseng’s effects on impotence reported that ginseng can be an effective alternative for treating male erectile dysfunction ⁵⁷⁾.

The effect of ginseng on the sexual performance may partially be due to changes in hormone secretion, and partially to its (or ginsenosides’) effects on the central nervous system, gonadal tissues, and production of nitric oxide (NO). Panax ginseng produced a dose-related increase in serum testosterone levels and American ginseng reduced the plasma level of prolactin hormone in rats ⁵⁸⁾. Testosterone might mediate the heightened copulatory behavior in ginseng-treated animals, while prolactin altered it. These results suggest that both ginseng species may have direct actions on the anterior pituitary gland and/or on the hypothalamic dopaminergic mechanisms ⁵⁹⁾. Recent findings that ginseng treatment decreased prolactin secretion also suggested a direct nitric oxide-mediated effect of ginseng at the level of the anterior pituitary ⁶⁰⁾. Thus, animal studies lend growing support for the use of ginseng in the treatment of sexual dysfunction and provide increasing evidence for a role of nitric oxide in the mechanism of ginsenoside action. Several recent studies have suggested that the antioxidant and organ-protective actions of ginseng are linked to enhance NO synthesis in endothelium of lung, heart, and kidney and in the corpus cavernosum ⁶¹⁾. Enhanced production and function of NO synthase by ginseng thus could contribute to ginseng-associated vasodilatation and perhaps also to an aphrodisiac action of the root. Ginsenoside Re was demonstrated ⁶²⁾ to release NO via a membrane sex steroid receptors resulting in K(Ca) channel activation in vascular smooth muscle cells and promoting vasodilation. Korean ginseng is well known as a treatment for sexual dysfunction ⁶³⁾ because of its ‘Yang’ effect as mentioned above. Korean red ginseng is usually not peeled, but steamed, or heated, and subsequently dried. As a consequence, the process causes an increase in saponin content ⁶⁴⁾. Traditionally red ginseng has been used to restore and enhance normal well-being, and is often referred to as an adaptogenic. Kim et al. ⁶⁵⁾ recently showed that water extract of Korean red ginseng (1–20 mg/ml) produced relaxation response up to 85% in isolated female rabbit vaginal tissue in a dose-dependent manner. Similarly, Choi et al. ⁶⁶⁾ used male rabbit cavernosal muscle strips (precontracted with phenylephrine) to investigate effect of Korean red ginseng on penile erectile tissue and erectile response. After 3 months of oral administration of 50 mg/kg of Korean red ginseng to both rabbits and rats, relaxation effects were significant as measured in both the male rabbit cavernosal muscle strips and the cavernosal pressures after the stimulation of pelvic nerves innervating rat corpus cavernosum. These effects might be mediated partly through the NO pathway and hyperpolarization via Ca(2+)-activated K(+) channels, or mediated by endothelium-derived relaxing factor, which was later demonstrated to be NO ⁶⁷⁾ and peripheral neurophysiologic enhancement.

Cardiovascular effects of ginseng

Ginseng has been shown to produce a number of actions on the cardiovascular system. Intravenous administration of ginseng to anesthetized dogs resulted in reduction, followed by an increase in blood pressure, and transient vasodilatation ⁶⁸⁾. Recent studies found close relationship between ginseng’s effects and NO production pathway, including regulation of cGMP and cAMP levels [76]. For instance, in rats and rabbits, Lei and Chiou ⁶⁹⁾ and Kim et al. ⁷⁰⁾ found that extracts of Panax notoginseng decreased systemic blood pressure and ginsenosides exerted relaxing effects in rings of rat and rabbit aorta, respectively. This relaxing effect of ginseng and its active constituents on the cardiovascular system is partially due to the release of endothelial NO. Researchers have reported that chronic feeding of rabbits with ginsenosides may enhance indirectly vasodilatation by preventing NO degradation by oxygen radicals such as superoxide anions ⁷¹⁾. Ginsenosides have depressant action on cardiomyocyte (heart muscle) contraction which may be mediated, in part, through increased NO production ⁷²⁾. Korean red ginseng can improve the vascular endothelial dysfunction in patients with hypertension possibly through increasing NO ⁷³⁾. In addition to endothelium-derived NO release, Li et al. ⁷⁴⁾ reported that ginsenoside-induced vasorelaxation involves Ca2+ activated K+ channels in vascular smooth muscle cells. It has also been reported that crude saponin fractions from Korean red ginseng enhanced cerebral blood flow in rats ⁷⁵⁾ and ginsenosides reduced plasma cholesterol levels and the formation of atheroma in the aorta of rabbits fed on a high cholesterol diet ⁷⁶⁾. This antiatherosclerotic action of ginseng components is apparently due to the correction in the balance between prostacyclin and thromboxane ⁷⁷⁾, inhibition of 5-hydroxytryptamine (5-HT) release, and adrenaline and thrombin-induced aggregation of platelets ⁷⁸⁾, regulation of cGMP and cAMP levels, and prolongation of the time interval between conversion of fibrinogen to fibrin ⁷⁹⁾. Also, ginsenosides have been shown to be relatively potent platelet activating factor antagonists ⁸⁰⁾.

In parallel with these findings, Nakajima et al. ⁸¹⁾ concluded that red ginseng was found to promote the proliferation of vascular endothelial cells, to inhibit the production of endothelin (that is known to constrict blood vessels and result in raising blood pressure), and to increase the production of IL-1β, which suppresses the formation of thrombin in blood coagulation. In the same direction, Yuan et al. ⁸²⁾ used cultured human umbilical vein endothelial cells to conclude that panax quinquefolium extracts significantly decreased endothelin (an NO antagonist) concentration in a dose and time dependent manner after thrombin treatment. The role of ginseng in angiogenesis has also been reported. For instance, Kim et al. ⁸³⁾ demonstrated that water extract of Korean red ginseng stimulated in vitro and in vivo angiogenesis via activation of phosphorylation of ERK1/2, phosphatidylinositol 3-kinase (Akt), and endothelial nitric oxide synthase (eNOS) resulting in an increase in NO production ⁸⁴⁾. Ginsenoside Rg1 promoted functional neovascularization into a polymer scaffold in animal and tubulogenesis by endothelial cells in test tube study ⁸⁵⁾.

Ginseng and Parkinson’s disease

A number of studies have recently described the beneficial effect of ginseng and its main components, ginsenosides, on some neurodegenerative disease models. Special interest has been paid to Parkinson’s disease models either in animal or in test tube study. In an in animal model, Van Kampen et al. ⁸⁶⁾ reported that prolonged oral administration of ginseng extract G115 significantly protected against neurotoxic effects of parkinsonism inducing agents such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its active metabolite 1-methyl-4-phenylpyridinium (MPP+) in rodents. The authors found that ginseng-treated animals sustained less damage and TH+ neuronal loss in substantia nigra pars compacta (SNpc) after MPP+ exposure. Likewise, reduction of TH immunoreactivity in the striatum was effectively diminished as a result of ginseng treatment compared to MPP+-exposed animals. Similarly, striatal dopamine transporter was significantly preserved due to ginseng treatment. In vitro studies showed that ginseng saponins enhanced neurite growth of dopaminergic SK-N-SH neuroblastoma cells ⁸⁷⁾.

Although the processes and mechanisms underlying the neuroprotective effects of ginseng upon dopaminergic neurons remain to be elucidated, several reports demonstrated the inhibition of ginseng on MPP+ uptake in dopaminergic neurons, the suppression of oxidative stress induced by auto-oxidation of dopamine, the attenuation of MPP+-induced apoptosis, and the potentiation of nerve growth factor. It has been shown that certain ginsenosides inhibit dopamine uptake into rat synaptosomes, and consequently, provide protection against MPP+ through blockade of its uptake by dopaminergic neurons ⁸⁸⁾. Ginsenoside Rg1 was shown to interrupt dopamine-induced elevation of reactive oxygen species (ROS) or NO generation in pheochromocytoma cells. Ginseng radix attenuated MPP+-induced apoptosis as it decreased the intensity of MPP+-induced DNA laddering in pheochromocytoma cells and ginsenoside Rg1 had protective effects against MPTP-induced apoptosis in the mouse substantia nigra. These anti-apoptotic effects of ginseng may be attributed to the enhanced expression of Bcl-2 and Bcl-xl, reduced expression of bax and nitric oxide synthase (NOS), and inhibited activation of caspase-3. Ginseng may also reverse the neurotoxic effects of MPP+ through elevation of NGF mRNA expression ⁸⁹⁾. In accordance, ginsenosides Rb1 and Rg1 elevated NGF mRNA expression in rat brain and potentiated NGF-induced neurite outgrowth in cell culture. Furthermore, it has been reported that ginsenosides Rb1, Rg1, Rc, and Re inhibited tyrosine hydroxylase activity and exhibited anti-dopaminergic action since they reduced the availability of dopamine at presynaptic dopamine receptors ⁹⁰⁾. Ginseng and its components prevent neuronal loss in amyotrophic lateral sclerosis models, and Ginseng radix has also been used for treatment of Alzheimer’s disease.

In addition to interactions of ginseng with the opioid systems, recent reports have demonstrated that the Korean ginseng product (ginseng total san, also called GTS) attenuates cocaine- or amphetamine-induced behavioral activity such as hyperactivity and conditioned place preference ⁹¹⁾. Using real-time measurements of the extracellular DA concentrations in slices of rat brain nucleus accumbens, Nah et al. ⁹²⁾ showed the ginseng total san attenuated both the release enhancement and the rebound increase during cocaine application and withdrawal, respectively.

Ginseng and cancer

 

To date, clinical research results on ginseng are not conclusive enough to prove health claims associated with the herb and only a handful of large clinical trials on ginseng have been conducted. Some claims for health benefits are based only on studies conducted in animals ⁹³⁾. During active cancer therapy, ginseng should generally be evaluated in combination with chemotherapy and radiation. In this role, it acts as biological response modifiers and adaptogens to synergistically enhance efficacy of the conventional therapy ⁹⁴⁾. It can improve immune system activity of patients and their appetite, and functions as a supplementary agent of chemotherapy. For instance, Xing et al. ⁹⁵⁾ treated 35 rectal cancer patients with retention enema containing 85% ginsenoside for 4–6 h per day for 6–8 consecutive days before surgical operation. The control group (n=15) received retention enema containing saline in the same way. They reported that after ginsenoside treatment symptoms such as frequent defecation, hematochezia and tenesmus were palliated in most patients (25 out of 35), and abdominal pain was relieved in 7 patients with incomplete intestinal obstruction. Electron microscopic examination showed apoptosis in 23 treated patients. In comparison, the above-mentioned changes were not observed in the control group. Preclinical studies have showed some immune-stimulating activity of ginseng and ginsenosides ⁹⁶⁾.

The recent studies have shown effects of ginsenosides on angiogenesis under many pathological conditions including tumor progression and cardiovascular dysfunctions ⁹⁷⁾. Angiogenesis in human body is regulated by two counteracting factors, angiogenic stimulators and inhibitors. Intriguingly, existing literature reports both wound-healing and antitumor effects of ginseng extract through opposing activities on the vascular system. The ‘Yin and Yang’ action of ginseng on angiomodulation is evidenced in parallel by the experimental data showing that the angiogenic effects of ginseng may be related to the compositional ratio of ginsenoside Rg1 to Rb1 ⁹⁸⁾. Rb1 inhibits the earliest steps of angiogenesis and chemoinvasion of endothelial cells. By contrast, Rg1 promotes functional neovascularization in animal study and endothelial proliferation, chemoinvasion and tubulogenesis in test tube study, as well as the effects mediated through expression of nitric oxide synthase and phosphatidylinositol-3 kinase→Akt pathway. In addition, the anti-tumor and anti-angiogenic effects of ginsenosides (e.g. Rg3 and Rh2) have been demonstrated in various models of tumor and endothelial cells, indicating that different ginsenosides may have opposing activities in regulating the ‘Yin and Yang’ balance ⁹⁹⁾. Chronic inflammation is associated with a high cancer risk. Ginseng’s anti-inflammatory effect may help to prevent the progression of reactive oxygen species (ROS) related inflammation to cancer sequence ¹⁰⁰⁾.

Recent in test tube experimental studies have showed anti-cancer effects of various ginsenosides. However, we have to point out that these in vitro studies, although inexpensive to carry out, should only serve as an adequate screening mechanism, or help us understand the mechanisms of actions of ginsenosides. In addition, the concentrations of ginsenosides applied in some in vitro experiments are as high as 100 μM level in order to produce some biological effects. This fact suggests that the observed biological effects of ginsenosides be non-specific to a particular pathway. Therefore, we propose that when a difference arises between in test tube and in animal findings, the in animal results should always take precedence over in vitro studies.

Zhao et al. ¹⁰¹⁾ recently characterized a new chemical entity 20(S)-25-methoxyl-dammarane-3beta, 12beta, 20-triol, and found that this molecule exhibits apoptosis and cell cycle arrest in the G1 phase of many cancer cell lines including breast and prostate cancer lines at IC50 of low micromolar levels ¹⁰²⁾. Recently it has been shown that American ginseng can both prevent and treat mouse colitis ¹⁰³⁾, which is associated with a high colon cancer risk.

Ginsenosides could specifically induce apoptosis in HL-60 cells. The results provide an experimental basis for treating leukemia with ginsenosides as a supplementary agent in chemotherapy ¹⁰⁴⁾. Some ginsenosides have the effects to induce apoptosis in rectal cancer patients ¹⁰⁵⁾. Ginsenoside Rh2 induced apoptosis in various tumor cells by different pathways. Rh2 interfered with B-cell lymphocyte/leukemia-2 (Bcl-2) family proteins related apoptosis and activated protein kinase Caspase-3 to cause cell apoptosis ¹⁰⁶⁾. Rh2 induced apoptosis of rat C6Bu-1 glioma cells and human SK-N-BE(2) neuroblastoma cells through protein kinase C pathway ¹⁰⁷⁾. Ginsenoside Rh2 also induced apoptosis in human malignant melanoma, which was partially dependent on caspase-8 and caspase-3 ¹⁰⁸⁾. Ginsenoside Rh2 induced apoptosis and inhibited cell growth in C6 glioma cells, human lung adenocarcinoma A549 cells, and various ovarian cancer cell lines ¹⁰⁹⁾. Mediating G1 growth arrest and apoptosis in human lung adenocarcinoma A549 cells appeared to be the molecular mechanisms of ginsenoside Rh2 ¹¹⁰⁾. Rh2 inhibited human hepatoma Bel-7404 cell lines via arresting cell cycle, up-regulating Bax protein expression and down-regulating mutated p53 protein expression ¹¹¹⁾. Rh2 inhibited the growth of MCF-7 cells by inducing p21 protein expression and reducing cyclin D levels. As a result, cyclin/Cdk complex kinase activity, pRb phosphorylation, and E2F release could be inhibited ¹¹²⁾.

Rg3 is one of the most effective cytostasis ginsenosides separated from ginseng. Rg3 inhibits human prostate cancer cells and other androgen dependent cells from proliferating ¹¹³⁾. The mechanisms of actions of Rg3 include (1) decreasing genetic expression of 5α-reductase; (2) inhibiting cell cycle evolution genes such as proliferating cell nuclear antigen gene and cell cycle protease D1 gene that would stop cells from proliferating; (3) increasing cyclinase suppressor gene such as p21and p27 so as to make cells settle down at G1 stage; (4) down-regulating Bcl-2 (the anti-induction apoptosis gene); and (5) activating caspase-3 (the induction apoptosis gene) to induce the cells to delete. Rg3 inhibited tumor cell proliferation and induced cell apoptosis in mice with induced liver cancer ¹¹⁴⁾. In addition, Rg3 can affect the differential expression of cell signaling genes and other related genes in human lung adenocarcinoma cell line A549, and induce apoptosis in the A549 tumor cells and HUVEC 304 cell lines. It was showed that Rg3 and Rg5 had significant inhibition on benzo(a)pyrene-induced adenocarcinoma ¹¹⁵⁾ and dimethylbenz(a)anthracene-induced lung tumor in mice ¹¹⁶⁾. The ginsenosides had strong inhibitory effects on the development of rat mammary adenocarcinoma induced by methyl-N-nitrosourea and N-ethyl-N-nitrosourea administration, as well as on DMBA-induced uterine and vaginal tumors ¹¹⁷⁾. Using athymic mice transplanted with ovarian SKOV-3 cancer cells, Xu et al. ¹¹⁸⁾ showed that intraperitoneal injection of ginsenoside Rg3 alone, or Rg3 combined with cyclophosphamide to the mice for 10 days improved life quality and survival of the mice, and reduced tumor weight in the mice in comparison to the control untreated mice. Chen et al. ¹¹⁹⁾ reported that Rg3 produced apoptosis in human bladder transitional cell carcinoma cell line EJ at IC50 125.5 μg/ml after 48 h of incubation. When treated with 150 μg/ml of Rg3 for 24 h and 48 h, the cells showed significant DNA ladders and apoptotic morphological characteristics including the condensed chromatin, the nuclear fragmentation, the apoptotic body and bright fluorescent granules as well as a higher caspase-3 expression. When the cells were treated with 75 μg/ml of Rg3 for 24 h and 48 h, or 150 μg/ml of Rg3 for 48 h, the percentage of cells in S phase and G2/M phase was increased, whereas the percentage of cells in G0-G1 was decreased.

Another ginsenoside, i.e., Compound K (or IH901), was shown to induce apoptosis in human hepatoblastoma HepG2 cells ¹²⁰⁾, and KMS-11 cells ¹²¹⁾ through a cytochrome C-mediated activation of caspase-3 and caspase-8 proteases and inhibition of the fibroblast growth factor receptor 3 (FGFR3) expression ¹²²⁾. Incubation of archeo-marrow leukemic cells HL260 with Compound-K produced apoptosis in the cells in a concentration- and time-dependent manner with morphous changes in chromatic agglutination, atrophy, and nuclear fragmentation ¹²³⁾. Compound-K suppressed melanoma cell proliferation in BI6-BL6 mice by activating the protein kinase caspase-3 and releasing cytochrome C in mitochondria into cytoplasm ¹²⁴⁾. Western blot test revealed that Compound-K could elevate p27Kipl expression, degrade expression of c-Myc and cyclin D1, and induce cell LLC apoptosis through activating caspase-3 protein kinase at the same time ¹²⁵⁾. Recently, IH-901 has been reported to induce both G1 arrest and apoptosis, and the apoptosis could be inhibited by COX-2 induction ¹²⁶⁾.

Ginsenoside Rg1 ¹²⁷⁾ has been reported to induce the apoptosis of melanoma cells implanted in mice. Inducing morphological change of the tumor cells seems to be the main mechanism of Rg1. Wakabayashi et al. ¹²⁸⁾ reported ginsenoside M, the intestinal bacterium metabolite of protopanoxadiol saponins, could induce apoptosis in melanoma cell B16-BL6 through up-regulating the expression p27kipl and down-regulating the expression of gene c-myc that promotes cell proliferation.

Park et al. ¹²⁹⁾ discovered that ginsenosides Rg3, Rg5, Rk1, Rs5 and Rs4 were toxic to the human hepatoma carcinoma cell Sk-Hep-1. Rg5 and Rs4 could induce apoptosis by selectively elevating protein levels of p53 and p21WAF (the inhibitor of periodicity-replying protein kinase) and down-regulating the activity of protein kinase in cell cycle E and A, ¹³⁰⁾.

Ginseng tea side effects

Short-term use of Asian ginseng in recommended amounts appears to be safe for most people. However, questions have been raised about its long-term safety, and some experts recommend against its use by infants, children, and women who are pregnant or breastfeeding.

The most common side effects of ginseng are headaches, dizziness, sleep problems (insomnia), diarrhea, constipation, vomiting, gastric complaints, and dermatitis or eczema ¹³¹⁾. Other reported side effects that occurred in some individuals include high blood pressure, restlessness, anxiety, euphoria, nosebleed, breast pain and vaginal bleeding ¹³²⁾. Some evidence suggests that Asian ginseng might affect blood sugar and blood pressure. If you have diabetes or high blood pressure, consult your health care provider before using Asian ginseng. Siberian ginseng may cause nervousness and restlessness in some individuals. In rare cases, Siberian ginseng may cause mild diarrhea. Siberian ginseng is not recommended for individuals with very high blood pressure. It may cause insomnia in some people if taken too close to bedtime. If symptoms like breathing problems, tightness in the throat or chest, chest pain, skin hives, rash, or itchy or swollen skin develop, the use of Siberian ginseng should stop.

In mice, a lethal oral dose of purified ginseng was determined to be higher than 5 g/kg body weight, the highest dose that can be orally given to a mouse and considered good practice at the maximal dose volumes without violating animal welfare. That level is equivalent to about 0.4 g/kg of oral ginseng given to an adult man ¹³³⁾. In a 2-year human study, 14 out of a total of 133 subjects were reported to experience side effects attributed to long-term exposure of ginseng when consumed at levels up to 15 g/day ¹³⁴⁾. The long-term side effects of ginseng are characterized by hypertension, nervousness, sleeplessness, skin rash, diarrhea, confusion, depression, or depersonalization. The effects were described as “ginseng abuse syndrome”. This level of ginseng consumption far exceeds the recommended daily intake of 1–2 g/day of Asian ginseng, in which 4–5% are ginsenosides ¹³⁵⁾. Consuming six of 500-mg ginseng capsules daily was reported to produce side effects such as hypertension, gastrointestinal disturbances, insomnia and nervousness. The validity of these observations is difficult to evaluate quantitatively. Moreover, as is the case in many studies with ginseng, the ginsenoside content of ginseng consumed was not determined ¹³⁶⁾.

The risk of interactions between ginseng and medications is believed to be low, but there are uncertainties about whether ginseng might interact with certain medications, such as the anticoagulant (blood thinner) warfarin (Coumadin) and phenelzine (a monoamine oxidase inhibitor) ¹³⁷⁾. If you’re taking medication, consult your health care provider before using Asian ginseng.

In conclusion, the most common side effects of ginseng resulted from its overdose are nervousness and excitability. These side effects usually decrease after the first few days. In inappropriate uses, the most common side-effects are the inability to sleep and high blood pressure. Other side-effects include nausea, diarrhea, euphoria, headaches, epistaxis, mastalgia, eruptions, and vaginal bleeding ¹³⁸⁾. Ginseng may lower levels of blood sugar; this effect may be seen more in people with diabetes. Therefore, diabetic patients who are taking anti-diabetic medicine should be cautious with Asian ginseng and monitor their blood sugar levels closely. Because ginseng has an estrogen-like effect, women who are pregnant or breastfeeding should take it at recommended doses. Occasionally, there have been reports of more serious side effects, such as asthma attacks, increased blood pressure, palpitations, and, in postmenopausal women, uterine bleeding ¹³⁹⁾.