By Ron Teeguarden
The diversity of highly desirable physiological effects of ginseng has intrigued scientists for years. There is extensive literature on the beneficial effects of ginseng. The pharmacological, regulating and nurturing effects of ginseng have been demonstrated to affect the central nervous system, cardiovascular system, various endocrine functions and secretions, immune functions, metabolic functions, biomodulating actions, anti-stress functions, and anti-aging functions that help maintain active health.
Ginseng products are usually used as general tonic and adaptogen to help the body to resist the adverse influences of a wide range of physical, chemical and biological factors and to restore homeostasis. These tonic and adaptogenic effects of ginseng are believed to enhance physical performance (including sexual function) and general vitality in healthy individuals, to increase the body’s ability to fight stress in stressful circumstances and to support resistance to diseases by strengthening normal body function as well as to reduce the detrimental effects of the aging processes.
Most studies indicate that the pharmacological effects of ginseng are attributed to its bioactive constituents such as ginsenosides, saponins, phytosterols, peptides, polysaccharides, fatty acids, polyacetylenes, vitamins and minerals, of which the ginsenosides are considered to be the major active constituents of ginseng.
In general, antioxidant, anti-inflammatory, anti-apoptotic and immunostimulant activities are mostly underlying the possible ginseng-mediated protective mechanisms. Ginseng ginsenosides can play a highly beneficial role in regulating nitric oxide (NO), scavenging of free radicals and counteracting excitotoxicity.
The National Center for Complementary and Alternative Medicine (NCCAM; www.nccam.nih.gov), one of the Centers of the National Institutes of Health, USA, is supporting research studies to better understand the use of Asian ginseng, including its interaction with other herbs and drugs, its potential to treat Alzheimer’s disease (PD), and its uses to improve the health of people recovering from illness, increase a sense of well-being and stamina, improve both mental and physical performance, treat erectile dysfunction, hepatitis C, and symptoms related to menopause, and lower blood glucose and control blood pressure. The NCCAM also funds projects to study the effects of American ginseng on colitis and colon cancer associated with colitis. [None of the tests support the use of ginseng as a drug to treat, cure, prevent any disease. Ginseng is a dietary supplement]
In Chinese medicine, ginseng (Panax ginseng C.A. Meyer) has long been used as a general tonic or an adaptogen to promote longevity and enhance bodily functions. It has also been claimed to be effective in combating stress, fatigue and pro-oxidants. In general, most of ginseng’s pharmacological actions have been attributed to a group of triterpenoid saponins called ginsenosides.
The ginsenosides have demonstrated an ability to target different types of tissues, producing an array of pharmacological responses. Since ginsenosides may produce effects that are different from one another, and single ginsenosides and/or their metabolized products may initiate multiple actions in the same tissue, the overall pharmacology of ginseng and ginseng products is very complex.
The most used ginseng roots in dietary supplements are those from Panax quinquefolium (American ginseng) and Panax ginseng (Asian ginseng). The ginsenoside profiles of these species can be distinguished by the presence or absence of a chemical constituent known as ginsenoside Rf. Ginsenoside Rf is detectable in Panax ginseng but not in Panax quinquefolium.
The pharmacological effects of ginseng and ginseng preparations and hence their quality are clearly dependent on their content of ginsenosides.
Ginsenosides are a unique group of compounds that have demonstrated a multiple of pharmacological effects including immunostimulatory, blood pressure regulating, and insulin regulating effects, as well as effects on the CNS and on stress response. Though the ginsenosides are being investigated for their potential therapeutic applications (that’s the main interest of most medical researchers), the research is clearly demonstrating why ginseng can be used as a regularly consumed dietary supplement (tonic) to help maintain homeostasis in a wide range of physiological functions.
The content of total and individual ginsenosides varies between plant species and the various plant parts. The content of ginsenosides in ginseng roots also depends on growing conditions, age of the roots, and internal root size (root hairs, lateral roots, and main roots).
Studies show that Asian ginseng has a higher ratio of Rg1: Rb1, while American ginseng has a lower ratio. These findings are consistent with the traditional attributes of ‘hot’ (i.e. stimulating) properties of Asian ginseng and ‘cool’ (i.e. calming) properties of American ginseng.
The pharmacological and therapeutic effects of ginseng have been demonstrated to affect the central nervous system (CNS), cardiovascular system, endocrine secretion, immune function, metabolism, biomodulating action, anti-stress, and anti-aging . Recently, there have been controversies concerning the usefulness of ginseng in cancer therapy.
The modulatory effects of ginseng or probably ginsenosides have been extensively investigated. Recently, it has been found that ginsenosides can act as functional ligands to activate different steroid hormone receptors. Through such mechanisms, ginseng can exert its effects on the human body by acting in a similar way as the steroid hormones, though they are not in fact steroids. The interaction between ginsenosides and various nuclear steroid hormone receptors may explain the diverse activities of ginseng. Thus the various pharmacological effects of ginsenosides may also be due to their resemblance in chemical structure/nature with triterpenoid steroid hormones.
Ginsenosides also have an amphiphilic nature being able to insert themselves into plasma membranes. This amphiphilic properties of ginsenosides can lead to changes in the membrane fluidity, and thus affect membrane function and elicit a cellular response. This amphiphilic nature is possibly of great importance and I’ll discuss it more in the Biofilm section below.
Ginsenosides hey are lipid-soluble signaling molecules that can traverse the plasma membrane and interact with membrane anchored receptors and ion channels, as well as nuclear receptors, initiating genomic effects.
Pharmacokinetic studies have confirmed that ginsenosides are bioavailable and that to some extent they are metabolized in the gastrointestinal tract to ginsenoside metabolites whose ability to traverse membranes are even better than intact ginsenosides, which further adds to the multifunctional pharmacological activities of the ginsenosides. The ginsenosides are largely metabolized by intestinal microbes, which produce many additional, highly beneficial ginsenoside metabolites.
One researcher summed up the knowledge of ginsenosides as follows: “The diversity in ginsenoside structures, including structural isomerism, contributes to the multifunctional pharmacological effects of ginsenosides. The demonstration of the health effects of ginseng and ginseng preparations in epidemiological and cohort studies and the fact that ginsenosides are bioavailable and can initiate effects at the plasma membrane by interacting with multireceptor systems and that ginsenosides are able to traverse the membrane and produce genomic effects clearly indicates that ginsenosides have potential health effects in humans.”
The pharmacological effects of ginseng and ginseng preparations and hence their quality are clearly dependent on their content of ginsenosides. So far, more than 150 naturally occurring ginsenosides have been isolated from roots, leaves/stems, fruits, and/or flower heads of the major varieties of ginseng.
In general, the contents of ginsenosides vary widely ranging from 2 to 20% depending on the species, age and part of ginseng, and even vary with the preservation or extraction method. More than 150 ginsenosides have been isolated, and characterized from various Panax species. In terms of their chemical structural characteristics, ginsenosides can be classified into three major categories, namely protopanaxadiols (PPD) (e.g. Rb1, Rb2, Rc, Rd, Rg3, Rh2), protopanaxatriols (PPT) (e.g. Re, Rf, Rg1, Rg2, Rh1) and the oleanolic acid derivatives.
Ginsenosides have a steroid-like skeleton consisting of four trans-rings, with modifications from each other depending the type (e.g. glucose, maltose and fructose), number of sugar moieties and the sites of attachment of the hydroxyl group (e.g. C-3, C-6, or C-20).
Scientific studies have shown that the ginsenoside content varies with different Panax species; other factors can also change the quality of ginseng’s products, including growing conditions such as soil conditions, sunlight, rainfall, temperature, time of harvest, age and life cycle stage of ginseng at harvest, time of year when it is harvested, method of drying, storage conditions and duration of storage, processing procedures, the plant age, the part of the plant, and the extraction method. All these can result in deviation in amount of active ingredients of ginseng and the related pharmacological effects. This is why Di Tao is so important and using wild roots guaranties ginsenoside abundance and activity.
Summary of Important Effects and Possible Actions on Different Body Systems
|Subject||Ginseng’s effect(s)||Possible action(s)|
|Whole body||General tonic and adaptogen||· Resistance against adverse conditions (physical, chemical and biological factors)· Restores body’s homeostasis· Anti-aging effects|
|Central Nervous system||Neuroprotection either in vivo or in vitro||· Potentiates nerve growth factor· Anti-oxidative and anti-apoptotic mechanisms· Reduces lipid peroxidation· Inhibits excitotoxicity and Ca2+ over-influx into neurons· Maintains cellular ATP levels· Preserves structural integrity of neurons|
|Glial cells||· Prevents astroglial swelling· Inhibits microglial respiratory burst activity and NO production by activated microglia|
|Increasing cognitive performance (learning & memory)||· Modulates neurotransmission· Direct effect on hippocampal neurons|
|Cardiovascular system||Antihypertensive||· Relaxes vascular smooth muscle cells through NO and Ca2+ mediated mechanisms· Inhibits production of endothelin which plays a role in blood vessel constriction|
|Anti-atherosclerotic effect||· Prevents platelet aggregation· Shows antagonistic action for platelet activity factor· Suppresses thrombin formation|
|Acceleration of wound healing||· Promotes functional neo-vascularization through endothelial proliferation|
|Inflammation and allergy||Anti-inflammatory and anti-allergic effects||· Inhibits cytokine production such as IL-1β, IL-6 and TNF-α· Abrogates cyclooxygenase -2 gene expression· Suppresses histamine and leukotrienes release from mast cells· Stabilizes inflammatory cells such as neutrophils and lymphocytes· Antifibroblastic activity|
|Immune system||Immunostimulant||· Enhances interferon induction, phagocytosis, natural killer cells, and B and T cells|
|Carcinogenesis||Anti-carcinogenic effect||· Suppresses malignant transformation· Inhibits proliferation of tumor cells· Inhibits tumor invasiveness, metastasis and angiogenesis|
|Aphrodisiac effect||Enhancement of male copulatory behavior||· Relaxes corpus cavernosum smooth muscles via NO mediated processes· Increases serum testosterone levels and reduces plasma levels of prolactin hormone· Direct effects on anterior pituitary and hypothalamic dopaminergic mechanisms|
|Hyperglycemia||Antihyperglycemic activity||· Increases plasma insulin levels, the number of insulin receptors and insulin sensitivity|