American Ginseng (Panax quinquefolium L.) as a Source of Bioactive Phytochemicals with Pro-Health Properties

Introduction

For centuries, phytochemicals have played a significant role in human health protection and treatment of many diseases. These plant-derived substances are reported to display anti-cancer, antimicrobial and anti-diabetic activity [1]. They were also reported to diminish the risk of several disorders such as cardiovascular and neurodegenerative diseases [2].

Panax quinquefolium L. (American Ginseng, AG) is an example of a plant rich in bioactive phytochemicals. Its active compounds—ginsenosides—have been documented to exert a wide range of different biological activities resulting in hypoglycemic, anti-inflammatory, cardio protective, and anti-tumor effects [3,4]. A therapeutic potential of AG in chronic obstructive pulmonary disease has been also suggested [5]. It can also act as an agent diminishing unpleasant menopause symptoms [6].

By now, reviews of AG focused mostly on its chemical analysis and ecological aspects of its use and health-related activities were mainly limited to nervous and cardiovascular systems [7,8,9]. Recently, some reviews addressing molecular targets in pharmacological activities of AG components were published [10,11,12].

The review updates information on general properties of AG and focuses on its anti-diabetic, anti-obesity, anti-cancer, anti-aging, and antimicrobial activities. Special attention is paid to the metabolism of ginsenosides by intestinal microbiota and the action of AG in nervous, cardiovascular, and gastrointestinal systems is briefly discussed.

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Conclusions and Perspectives

AG has been applied for centuries as a diet supplement due to a chemical composition rich in active compounds: ginsenosides. These saponins belonging to a group of glycosides are responsible for wide range of health-beneficial activities of the plant and may allow to distinguish AG from other Panax species. AG is also rich in unsaturated fatty acids, linoleic and linolenic, which are important for proper function of the human organism. Different parts of the plant, the leaves, stem, flowers, berries and primarily roots (raw or thermally processed), can be a raw material for production of extracts. There are many commercial products containing AG extracts, including shredded slices, drinks, alcoholic beverages and dried sugar coated roots. Also, AG is used in cosmetics such as shower gels, hair conditioners, lotions, and shampoos [28].

This review highlights the most important characteristics and possible applications of AG. Among numerous studies AG was documented to exert beneficial activity towards nervous system. It boosts memory, increases calmness, and enhances cognitive performance [68]. It has therapeutic potential in treatment of Alzheimer disease and anxiety [64,66]. It also affects cardiovascular system—changes cardiac structure in hypertension, reduces heart rate, inhibits hypertrophy and heart failure [79,81,128,170]. Furthermore, AG prevents oesophageal damage resulted from reflux oesophagitis and formation of ulcer in gastric mucosa [84,85]. Apart from that, it displays antimicrobial activity against different pathogenic strains of bacteria including resistant to antibiotics S. aureus strain [159]. AG is extensively investigated in terms of anti-cancer activity. It promotes apoptosis of cancer cells and alters many different signalling pathways important for cancer transformation [92,93,94,95,96,97,98,171]. It also protects normal cells from unwanted side effects of anti-cancer drugs and diminishes cancer-related fatigue [100,110]. However, the mechanisms underlying beneficial activity of AG in cancer is not fully understood. Administration of AG may be beneficial for individuals suffering from obesity and diabetes. It enhances sensitivity of tissues to insulin and inhibits formation of adipose tissue. Also, polysaccharides of AG were reported to display pro-health effects by stimulating the immune system. Assinewe et al. observed that polysaccharide of AG extract containing glucose, galactose, arabinose, rhamnose, and mannose displayed cytokine-stimulating activity on macrophages. In this study, aqueous extracts of AG roots (1–100 μg/mL) stimulated the release of immunoreactive TNF, contributing to the activation of macrophages [172]. Yu et al. also showed immunostimulatory effect of the fraction of polysaccharide present in AG extract (50–400 μg/mL). AG extract application led to enhancement of splenic lymphocyte proliferation, macrophage phagocytosis and nitric oxide production [173]. AG extract (125 mg/kg for 3–6 days) stimulated alveolar macrophages in rats associated with increased level of NO, TNF-α and IL-6 in plasma [174]. These results were in agreement with those obtained by Azike. Similarly, AdG water extract (125 mg/kg) administered to rats for 3–6 days upregulated nitric oxide, TNF-α and IL-6. Within in vitro study macrophages were incubated with different concentrations of AG. A dose-dependent immunostimulatory activity of aqueous and alcohol extracts of AG (50–200 μg/mL) in rat macrophages was observed and an in vitro effect was more pronounced than corresponding in vivo result due to relatively low bioavailability of the extract administrated orally [175]. As the methodology of AG separation is poorly developed, it is a promising direction for the future research.

Although many health beneficial pharmaceutical effects have been attributed to AG, molecular mechanisms underlying these effects are poorly known. Usually, studies showing a biological/medical effect of AG or its component, suggest more than only one molecular target. This follows from the fact that pharmaceutical effects of AG may be underlined by several mechanisms of its action with many possible molecular targets linked with each of the mode of action. Therefore, we have not attempted to comprehensively address the problem of identifying molecular targets of AG as the length of this review is limited. Excellent reviews on this subject can be found elsewhere [9,10,11,12,176,177].

Most health effects of AG are mainly due to its strong antioxidant properties. In general, AG is frequently considered to have a greater capacity for free radicals scavenging and inhibit lipid peroxidation than its Asian counterpart [178]. To investigate mechanisms beyond antioxidant activity of AG, Kitts et al. showed that its extract containing main ginsenosides was able to scavenge DPPH (2,2-diphenyl-1-picrylhydrazyl)-stable free radical as well as and peroxyl (LOO•) and hydroxyl (•OH) free radicals [179]. Moreover, the extract efficiently chelated transition metals, preventing their involvement in the Fenton reaction, which was confirmed by inhibition of the induction of DNA strand breaks and suppression of protein oxidation. Additionally, the extract displayed protective action against lipid peroxidation in a metal-free solution. This important study shows the potential of AG to exert an antioxidant action by scavenging free radicals, chelating Fenton metals and preventing lipid peroxidation to further investigations in biological systems. These results were confirmed in a significant range in V79-4 Chinese hamster fibroblast-like cell line incubated with steamed root (red ginseng) of AG [26].

In spite of wide range of beneficial activities towards human organism, AG is not recommended for women during pregnancy and lactation period, because its teratogenic effects in rats and mice embryos as well as its not reported safety in breast-feeding women [180,181]. Because it has a cooling effect on the body, it is recommended to be consumed in summer [167]. Overdose of AG extract may lead to appearance of side effects such as insomnia, nervousness, gastrointestinal track disorders and symptoms of depression [27]. Components of AG extract may demonstrate antagonistic activity on drugs, such as anticoagulants, prescribed for chronic atrial fibrillation, mechanical valves, deep vein thrombosis and recurrent stroke [171]. It is difficult to determine the effective preventive and therapeutic concentrations of AG, because different units (e.g., mg/kg bw, mg/mL, mg) and time of application (e.g., 4 times in 2 h interval; twice in 4 h interval; for 12 h; for 2, 10, 12, 14, 30 or 33 days; for 10 or 24 weeks; for 3 months) are used in different studies. For this reason, it is not possible to make a comprehensive summary of effective preventive and therapeutic doses of AG, and it needs standardisation.

Currently, AG is a promising source of health beneficial phytochemicals. In view of its foregoing pro-health activity, possible mechanisms responsible for its mode of action and potential of application in different branches of medicine are worth further investigation. There are very few studies on AG interactions with probiotics in terms of its stimulatory or inhibitory activity on growth of certain strains of these beneficial microorganisms [165]. Apart from that, there is not much information about AG interactions with normal human microbiota, its influence on ginsenosides transformation, and their biological activity in the human body [165,166,167]. The antibiotic effect of AG towards pathogenic strains also requires more extensive investigation [159,160,161,162,163]. American Ginseng still has great potential to be explored in both basal research and clinical medicine.

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