The term Ginsenoside was conceived to describe a class of many molecules that are found in Ginseng; the term refers to steroidal saponins structures with a dammarane steroid backbone, which is a chemical designation of structure; not to be confused with anabolic steroids and are given a designation of R x ; the X being in reference to their movement on a TLC plate in vitro with A being most polar and H being least polar. Despite the fact that there are well over Ginsenosides in existence,  they all belong to four classes.
The Protopanaxa diol class, which has a dammarane backbone and includes Ginsenosides Ra and Rb; more than 30 Ginsenosides belong to the Rb series. The Protopanaxa triol class, with an additional hydroxyl group on C6 which turns 'di'ol into 'tri'ol and includes Ginseosides Re, Rf, and Rg1. Oleanolic Acid type Ginsenosides Including Ginsenoside Ro which have a pentacyclic triterpenoid base rather than dammarane. Ocotillol type Ginsenosides, which have a 5-membered epoxy ring at C20; the prototypical Ocotillol-type Ginseoside is actually Makonoside R2 from Vietnamese Ginseng .
The or so Ginsenosides are, for the most part, glycosides of the above classes. Various sugar molecules are bound to differing areas of the above four molecular backbones to create unique molecules and thus a unique Ginsenoside designation. Panax Ginseng contains a variety of active components called 'Ginsenosides', which are steroid-like saponins that are unique to the Ginseng species in regards to the chemical structure; not anabolic properties ; well over Ginsenosides exist,  and the following list contains the major ones:. Other compounds that are found in Ginseng that are non-caloric phytochemicals and not under the umbrella term of Ginsenoside include:.
Polyynes compounds with alternating single and triple bonds including falcarinol, falcarintriol, acetic acid and linolenic acid . Some MicroRNAs .
With caloric components included in the root itself, and may be processed out of a capsule constaining Panax Ginseng as they contain calories such as proteins and carbohydrates include:. The Polysaccharide 'Ginsan', which appears to be an immune system modulator . Shorter oligosaccharides  and beta-glucans .
Polysaccharides that may possess anti-cancer effects,  may be classified as either neutral or acidic, with the latter having more biological relevance. Ginsenoside Rg 2 at 0. Panaxadione at 0. Saringosteryl and its glycoside . Daucosterol and 5a,6b-dihydroxydaucosterol . The indole alkaloid Ginsenine . Total Ginsenosides in the berries can reach 9. Ginseng plants are typically grown for years before harvested for medicinal purposes as opposed to consumption as a food product, where fresh ginseng can be harvested after two years  ; levels of total ginsenosides tend to decrease after the fifth year of life.
There are methods to discriminate between 'True' Panax Ginseng and American Ginseng Panax quinquefolius despite carrying many of the same bioactives. The Ginsenoside Rf is unique to Panax Ginseng while the Pseudoginsenoside F 11 is unique to American; the ratio of the two found in any given commerical product can be used to determine source of Ginseng.
Similar to how various forms of Tea from Camellia Sinensis green, white, black are distinguished due to processing yet are the same plant, the difference between Panax Ginseng and Korean Red Ginseng is merely processing; they are the same plant. When looking at total Ginsenoside content, one study noted that KRG had equal to or higher levels of the main ginsenosides when compared to Panax Ginseng, which varied by source KRG rivaling 'Wild ginseng' from Shangshen, outperforming cultivated ginseng but this may not be the standard.
Additionally, via Amadori rearrangements there can be formations of unique compounds during fermentation called arginyl-fructose and arginyl-fructosyl-glucose also known as maltulosyl arginine ;   these compounds show some promise in inhibiting carbohydrate uptake from the diet. White Ginseng is a term used to refer to Panax Ginseng that has been cultivated and then air dried, as opposed to a steam drying to form Red Ginseng.
One study specifically breaking down the component Ginsenosides noted that G had 1. Ginsenosides are able to metabolize from one to another, and the paths of metabolism diverge based on which of the four basic groups the Ginsenoside belongs to structurally protopanaxadiol, protopanaxotril, etc; mentioned in the structures section. Protopanaxadiol compounds such as Rb1, Rb2, and Rc tend to be metabolized to an active molecule called Compound K, with the elongated name of O-b-D-glucopyranosyl S -protopanaxadiol. Ginsenoside Re protopanaxatriol has been proposed to be metabolized into Rg1 and Rg2 two different pathways by colonic bacterial fermentation; both Rg1 and Rg2 can further metabolize into Rh1, but only Rg1 can metabolize into F1 with both Rh1 and F1 the second stages of metabolism being finally converted into the basic protopanaxatriol skeleton to be excreted via the urine.
One study done in mice who were primed to be either cold lower caloric intake, cold water swimming until fatigue or feel warm excess of dietary protein noted that the addition the Panax Ginseng root was able to confer a warming effect on both groups, as assessed by less time spent on a warming pad located near the mice. Ginseng is one of few herbs that has traditionally been used as an appetite stimulant for anorexia appetite-loss and cancer-related cachexia to stimulate appetite,  alongside the vertical root of Astragalus Membranaceus.
Ginsenoside-enriched fragments of Panax Ginseng at A study in young healthy adults using or mg acutely noted increased reaction time associated with mg, but not mg, 2. Interestingly, mg led to slightly but significantly slower reaction times on the first day of tested, which may have been secondary to an induction of calmess. Another study by the same researchers tested mg and mg of G in healthy young adults found improved performance on the serial sevens subtraction task,  a test for intellectual efficiency.
Alertness and relaxation specifically have also been noted with a Ginseng multi-nutrient combination supplement when taken over a period of 12 weeks, when compared to baseline values. Anti-depressive effects have been noted in mice given Ginsenosides as well, suggesting both main components of Ginseng are active regarding depression.
Red Ginseng also appears to be effective, with either hydrolysis of Red Ginseng or acetate fermentation fermented Korean Red Ginseng being significantly more effective at exerting anti-depressive effects in mice relative to normal Red Ginseng. In regards to stress, a possible mechanism may be altering genetic transcription of some enzymes.
When looking at Ginsenoside Rb1 in isolation, it appears to be responsible for enhanced learning rats in the hippocampus.
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In studies assessing learning deficits cognitive decline associated with toxins or aging, Ginseng appears to be somewhat effective at reducing the rate of learning deficits. One study in humans assessing Panax Ginseng ingestion at either mg or mg acutely in healthy young adults noted that mg was able to reduce a fall in mood associated with prolonged 4 hour psychological testing and mg induced a state of calmness. A systemic review of Cerebrovascular effects of Ginseng only found two studies, the aforementioned study and one other that is not indexed online.
One study using and mg Panax Ginseng found increased calmness in a relatively dose-dependent manner after acute ingestion in healthy adults. Another study using a lower dose of mg or mg found that, over the course of 8 weeks, mood was improved in type II diabetics; this may be secondary to a bettering of the glycemic profile.
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One study that used a Ginseng multi-nutrient formulation that noted statistically significant improvements across the board on alertness and relaxation placebo and ginseng both improved, significantly better effects in ginseng though noted that when the results were controlled for only the persons in the lowest quintile of scores on the Visual Analogue Scale at baseline a psychometric test that there were also significant improvements in depressive scores and vitality, giving some evidence that the effects of Panax may be more pronounced in those more deviant from 'normal' baseline values.
Interestingly, an increase in quality of life is seen with multivitamins containing 40mg Panax Ginseng as G extract more-so than using standard multivitamins without the Ginseng, suggesting low dose Panax Ginseng may be valuable to add into a multivitamin formulation. This study was comparative with no placebo control, and thus the improvements seen in both groups could be attributed to placebo. Benefits with Ginseng-containing multinutrient formulations are not always present, with trends towards improvement that are not statistically significant being seen  and sometimes benefits only seen with the subject's dietary habits are deemed as 'poor'.
Compounds formed during amadori rearrangements in Red Ginseng fermentation arginyl-fructose and arginyl-fructosyl-glucose appear to have minor inhibitory potential on carbohydrate digestive enzymes, intestinal glucosidases and pancreatic alpha-amylase in vitro. These mechanisms in muscle cells appear to extend to other Ginsenosides such as Rb1  and Rb2,  the former of which is the precursor ginsenoside from which Rg 3 is formed from. AMPK activation also occurs in liver cells and by Ginsenoside Re, and may contribute to lesser glucose levels circulating. Type I Diabetes is insulin-dependent, usually caused by genetics and tied in to immunology; this is not the more common diet-induced form of diabetes Type II although there are interactions with the diet in disease pathology.
Korean Red Ginseng for 2 weeks in mice later injected with streptozotocin to induce Type I diabetes was associated with better glucose levels in the mice at rest, possibly secondary to protective effects on the pancreas and a trend to normalize insulin levels. Hepatic gluconeogenesis production of glucose in the liver , a major source of circulating glucose, appears to also be suppressing in animal models in response to Ginsenosides,  particularily Rg2.
One systemic review on human studies, however,  using Cochrane evaluation criteria and searching 14 databases found four randomized trials in humans of good quality with three comparing Red Ginseng against placebo, only one of which is indexed in Medline. Studies in healthy subjects with normal testicular function both human and rodent are uncommon for Panax Ginseng.
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For those with impaired testicular function, one study conducted in men with infertility oligoasthenospermia found that supplementation with Panax Ginseng raised testosterone relative to baseline, suggesting that Panax has the ability to normalize testosterone levels. There variability in this sample made the results not statistically significant. Other studies note that Ginseng has 5a-reductase inhibitory potential, being able to reduce the conversion of testosterone to dihydrotestosterone DHT , which is attributed to Ginsenoside Ro IC 50 of Ginsenoside Rg 3 was later investigated for its potent 5-AR inhibitory potential, and found that injections of a water extract of Red Ginseng Extract were highly effective in suppressing prostate growth induced by testosterone.
When investigating direct androgen receptor effects, Rh1 failed to exert any effect on the androgen receptor at concentrations of 50uM, a dose sufficient to cause estrogen-like effects. Several ginsenosides have been found to be agonists activators of the estrogen receptor in vitro , such as Rg1,  Rb1,  Rh1,  and Ginsenoside Re vicariously through its metabolite Rh1.
Efficacy of Ginseng Supplements on Fatigue and Physical Performance: a Meta-analysis
When looking at Rg1, the aglycone ginsenoside without carbohydrates was found to not significantly influence estrogenic signalling as assessed by thymidine uptake into breast cancer cells. A study in persons with congestive heart failure CHF given one course of ginseng injections of 2g red ginseng diluted to 10mL in addition to standard therapy of cardiotonics and diuretics noted that, relative to standard therapy alone, there was a statistically insignificant increase in benefits on standard symptoms and signs yet the benefits on thyroid hormones increase in T3 and T4 with a decrease in rT3 seen with standard therapy were increased further with the addition of red ginseng.
General testicular protective effects also appear to exist, and may help normalize testicular function in the state of type II diabetes when taken over the course of 90 days. When tested in human interventions, Panax Ginseng appears to increase spermatogenesis and sperm motility in men who suffer from infertiltiy. In the treatment of erectile dysfunction ED , one pilot study using 60 patients with mild to moderate ED were given 3g of Korean Red Ginseng in three daily doses of 1g with meals for 12 weeks.
Korean Red Ginseng appeared to be effective, with A systemic review conducted on Korean Red Ginseng  assessing seven randomized controlled trials found consistent benefits associated with Red Ginseng Extract, with doses ranging from mg taken thrice a day totaling 1,mg in four studies two cited here   or mg taken thrice daily totaling 2,mg in two studies one cited here.
Ginseng has been reported before as being a 'vaccine adjuvant', being able to amplify the efficacy of vaccines when Ginseng is in circulation when the vaccine is administered.
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Additionally, Red ginseng polysaccharides have been demonstrated to increase Natural Killer NK Cell activity  which seems to also apply to the polysaccharide Ginsan not exclusive to Red Ginseng. Acidic polysaccharides from Korean Red Ginseng appear to activate Nitric Oxide NO signalling in macrophages when administered via injection or incubated. Other polysaccharides isolated from Korean Red Ginseng known as acidic polysaccharides also appear to influence the immune system and more-so when paired with pidotimod, a compound structurally similar to Piracetam.
The aforementioned augmentation of vaccines was demonstrated with isolated Ginsenosides Rg1 and Re that were able to enhance immune cell proliferation and cytokine secretion from macrophages, but not in mice with a defective TLR4 receptor;  Rg1 appears to act by another mechanism as well though, since abolishing the receptor did not fully prevent Rg1's activity like it did Re.