Panax Ginseng

Last Updated: November 15 2022

Panax ginseng is commonly referred to as “true Ginseng”. It appears to be effective for mood, immunity, and cognition, but is subpar for erectile function, testosterone, and exercise performance.

Panax Ginseng is most often used for.



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1.

Sources and Composition

1.1

Source

Panax Ginseng (of the family Araliaceae[1]), with synonyms of Korean Ginseng, Mountain Ginseng, True Ginseng, and Asian Ginseng (although this latter term refers to a few 'Ginsengs'), is a plant that has been used in Traditional Chinese Medicine historically for a wide range of preventative purposes. It bears yellow-red berries (depending on cultivar[2]) although the root is typically used in a powdered form for medicinal purposes.

Up to thirteen plants belong to the Panax genera, with only five of them used medicinally in traditional medicine. These include Panax Ginseng (this article) as well as American Ginseng (Panax quinquefolius, aka Xiyangshen) Vietnamese Ginseng (Panax vietnamensis) Japanese Ginseng (Panax Japonicus) and Pseudoginseng (Panax Notoginseng).[3] Of these five, Panax Ginseng is the most commonly used species medicinally, being used in 16.6% of the 3,944 prescriptions in the Korean Clinical Pharmacopoeia written in 1610 AD.[3]

Panax Ginseng is a herb with the Species of 'Panax' and the Genera of 'Ginseng', and is the most commonly used medicinal Ginseng in this Genera (with 4 others being used medicinally, and 8 other plants in the Genera of 'Panax' not being used medicinally)

The term 'Panax' is derived from the Greek words for 'all-healing' (not panacea actually, but 'pan' for all and 'axos' for cure).[4][5] 'Ginseng' has less complimenting origins, being an English translation of the chinese word rénshen meaning 'man root', although supposedly this was a reference to the roots of the plants looking like a man's legs; therefore, a literal translation of Panax Ginseng into English is All-healing Man Root.[5] The surface of the root is wrinkled and furrowed, and its taste is sweetish at first, with a somewhat bitter aftertaste.[5]

Panax Ginseng,[6] as well as American Ginseng,[7] can be heat treated to form 'Red' Ginsengs. These are slightly different in composition to the untreated plants and confer some unique bioactives, but originate from the same plant sources.

Panax Ginseng derives its names from All-Cure (Panax) and Man Root (Ginseng, a translation from rénshen) which reference the way the root looks, like two legs of a human; the prefix of 'Red' (Red Ginseng, Red Panax Ginseng, etc.) refers to a process of heat treatment which alters the coloration

'Korean Red Ginseng', therefore, is heat-treated Panax Ginseng (as Korean Ginseng is a synonym for Panax Ginseng)

1.2

Disambiguation of 'Ginseng'

The term 'Ginseng' appears to have dual meanings, one of which is botanical in nature and the other social. The botanical term of 'Ginseng' refers to the species of Panax Ginseng and is therefore unique to this plant or different variants and chemotypes (chemical differences of the same plant species, seem with Cat's Claw in particular). The social word of 'Ginseng' appears to have been derived from how Panax Ginseng was used to increase vitality and prevent disease, and appears to have been applied to other herbs unrelated to Panax Ginseng that also have historical usage of increasing vitality or preventing disease.

'Ginseng' is both a botanical term, in reference to the species, and a social name, in regard to the ability of a plant to supposedly bolster vitality and prevent disease

As mentioned before, the plants that are still within the genera of Panax and have colloquiolly been given the name of 'Ginseng' despite not being the same species include Panax quinquefolius (American Ginseng or Xiyangshen), Panax vietnamensis (Vietnamese Ginseng), Panax Japonicus (Japanese Ginseng) and Panax Notoginseng (Pseudoginseng).

Herbs outside of the Araliaceae family bestowed the status of Ginseng include Eurycoma Longifolia Jack (Tongkat Ali or Malaysian Ginseng), Lepidium Meyenii (Maca root or Peruvian Ginseng), Gynostemma Pentaphyllum (Southern or 'Cheap' Ginseng), Pfaffia paniculata (Suma Root or Brazilian Ginseng), Eleutherococcus senticosus (Siberian Ginseng), Trichopus Zeylanicus (Kerala Ginseng), Kaempferia Parviflora (Thai Ginseng), Dracaena angustifolia (Nam Ginseng[8]) and Withania Somnifera (Ashwagandha or Indian Ginseng).

Additionally, the herb Codonopsis Pilosula has traditionally been used as a cheap substitute for Panax Ginseng and, in some texts, it appears that the Codonopsis Pilosula plant may be falsely called Panax Ginseng.[9] Codonopsis Pilosula, per se, does not have Ginseng status although it is tied into the history of Panax Ginseng being expensive and having other herbs used in place of it to cut cost; Panax Ginseng being historically expensive and limited in supply (seen also with Ganoderma Lucidum, the Reishi mushroom) appears to also have influenced Gynostemma Pentaphyllum, which shares many of the saponins, being referred to as 'Cheap Ginseng' as it appears to be a cheap substitute.

The above list comprises plants and supplements associated with the term or history of Panax Ginseng

1.3

'Ginsenoside' overview

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.[10][11] Ginsenosides tend to be amphipathic as they inherently have a hydroxyl group on their backbone (polar) yet the backbone itself is non-polar.[5]

Despite the fact that there are well over 100 Ginsenosides in existence,[5] they all belong to four classes.

  • The Protopanaxadiol class, which has a dammarane backbone and includes Ginsenosides Ra1-3 and Rb1-2; more than 30 Ginsenosides belong to the Rb series
  • The Protopanaxatriol 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[12]

The 100 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).

All 'Ginsenosides' are just one of four molecules that have varying sugar attachments to the molecule, slightly altering their shape. Despite there being over 100 Ginsenosides in Panax Ginseng, they can be narrowed down to one of four classes based on the molecule the sugars are modifying

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1.4

Composition

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 100 Ginsenosides exist,[5] and the following list contains the major ones:

  • Ginsenoside Ro at 20.1+/-0.4 (rhizome) and 2.2+/-0.4 (root) in mg/g ethanolic extract
  • Ginsenoside Rb(1) 14.6+/-0.2 (rhizome) and 4.8+/-0.1 (root) in mg/g ethanolic extract
  • Ginsenoside Rb(2) 5.5+/-0.1 (rhizome) and 2.0+/-0.4 (root) in mg/g ethanolic extract
  • Ginsenoside Rc 7.1+/-0.5 (rhizome) and 2.6+/-0.2 (root) in mg/g ethanolic extract
  • Ginsenoside Rd 2.5+/-0.2 (rhizome) and 0.2+/-0.2 (root) in mg/g ethanolic extract
  • Ginsenoside Re 10.8+/-0.2 (rhizome) and 2.6+/-0.3 (root) in mg/g ethanolic extract
  • Ginsenoside Rf 1.9+/-0.1 (rhizome) and 1.3+/-0.1 (root) in mg/g ethanolic extract
  • Ginsenoside Rg(1) 7.1+/-0.5 (rhizome) and 2.6+/-0.2 (root) in mg/g ethanolic extract

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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[4]
  • Some MicroRNAs[13]

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[14]
  • Shorter oligosaccharides[15] and beta-glucans[16]
  • Polysaccharides that may possess anti-cancer effects,[17] may be classified as either neutral or acidic, with the latter having more biological relevance
  • L-Arginine[18] and GABA as amino acids[18]

For the most part, the unique properties of Panax Ginseng are related to the Ginsenoside content (which is, for the most part, unique; Gynostemma Pentaphyllum and America Ginseng share many of the Ginsenosides); the polysaccharides in the root itself may have some unique properties, with most other compounds being unremarkable. The above is in reference to the root only, which is by far the most used part of the plant

The seeds of Panax Ginseng include:

  • Ginsenoside Rg2 at 0.0012-0.0025%, Re at 0.0028%, Rd at 0.0011%[19]
  • Panaxadione at 0.00043% dry weight, 20(S)-protopanaxatriol (0.00052%), 3-keto-20(S)-protopanaxatriol (0.001%), [19]
  • Dencichine, aka beta-N-oxalyl-L-alpha,beta-diaminopropionic acid (beta-ODAP) at 0.43% of total seed weight and 70% of total amino acids in the seeds, with content declining with age of the plant[18]
  • Saringosteryl and its glycoside[19]
  • Daucosterol and 5a,6b-dihydroxydaucosterol[19]

The seeds of Panax Ginseng do not have as much of a Ginsenoside content, relative to the roots; they tend to be a subpar supplemental option

The fruits of Panax Ginseng include:

  • High yields of Ginsenoside Re (up to 6% dry weight[2][20]) up to 28-fold higher than the Re content of the roots
  • Ginsenosides Rb1 (0.2%), Rc (0.1%), Rd (0.1%), Rg1 (0.04%)
  • The indole alkaloid Ginsenine[21]

Total Ginsenosides in the berries can reach 9.09% dry weight, which is up to 4.8-fold higher than the roots on a dry weight basis;[20][22]

Berries have substantially more Ginsenoside Re content than do root extracts, and would be preferable if the biological effects of Panax Ginseng desired are due to the Re content

Ginseng plants are typically grown for 4-6 years before harvested for medicinal purposes (as opposed to consumption as a food product, where fresh ginseng can be harvested after two years[3]); levels of total ginsenosides tend to decrease after the fifth year of life.[23]

When selecting ginseng products, the rhizome (thick vertical root aspect) appears to have more ginsenosides on a weight basis than do the roots, although both of them possess Ginsenosides; supplements that standardize to a certain total ginsenoside content may not need differentiation due to standardization. The fruits tend to have much more Re, so if you want that particular Ginsenoside for any particular reason then the fruits are the way to go

Although the Ginsenosides are seen as the active ingredients, for immune system related and immunological purposes the polysaccharides cannot be forgotten about (if doubting the potency of polysaccharides, please refer to Ganoderma Lucidum)

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 F11 is unique to American; the ratio of the two found in any given commerical product can be used to determine source of Ginseng.[24][25]

As for the differences between American and Asian (Panax) Ginseng, the collection of Ginsenosides Rb1, Rb2, Rc, Rd, Re, and Rg1 comprise over 90% of the total Ginsenosides in Panax Ginseng, with most or all of the bioactive effects being traced back to these six Ginsenosides.[26][27] When looking for the major bioactive Ginsenosides that make up 70% of American Ginseng, five of the six are similar yet Rb2 is seemingly absent and replaced with Rb3.[28] Rf is also in higher quantities in American rather than Asian Ginseng.[28][5]

American Ginseng and Asian Ginseng (the latter being true Panax Ginseng) are similar plants with a lot of the exact same bioactives, just in different amounts; however, these 'differing amounts' may make the actual effects of the ginseng different if the molecules actually possess different effects. Common effects of Ginsenosides in general may be the same between the two plants

2.

Types and Forms of Panax Ginseng

2.1

Korean Red 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.

Korean Red Ginseng (KRG) is Panax Ginseng that is steamed and then dried, which appears to change some of the bioactive compounds. While Panax Ginseng tends to have Ginsenoside Rb1, Ro, and Re as the main components KRG touts Ginsenoside Rb(3) as the main bioactive.[6] The latter can be metabolized to Ginsenoside Rb(2) (not unique to KRG) by intestinal bacteria, and KRG also possesses an Rg(3) content which is unique to KRG.[29] Rb(3) and Rg(3) are seen as the main active ingredients of KRG, and the steaming and fermentation process favorably alters the Ginsenoside profile to favor these two.[30] Further fermentation of already steamed/dried Red Ginseng, resulting in fermented Red Ginseng, further enhances the anti-inflammatory and anti-nocireceptive (pain-dulling) effects of it.[31]

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.[32] In general, compounds sold commercially (Korean market) seem to vary from 0.5-1.1% ginsenosides by weight[30] which tends to be lower than the averages for fresh ginseng (and especially the research standards of G115 and NAGE, Panax Ginseng at 4% and 10% total ginsenosides, respectively).

In general, biotransformation of Ginsenosides in Panax Ginseng when it becomes 'red' from steaming and fermentation mimics colonic metabolism. Not too many unique products are formed (although some are) and many are metabolized to their bioactive forms, which may enhance the effects of Panax Ginseng or at least make them more reliable from one person to another

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);[33][34] these compounds show some promise in inhibiting carbohydrate uptake from the diet.[35] These compounds also appear to bind to minerals (particularly copper) and exert anti-oxidative properties,[34] and at least Arginyl-Fructose can be absorbed after oral administration to rats, with the other Amadori product possibly losing its glucose molecule and becoming Arginyl-Fructose.[36] The total content of amadori products in Korean Red Ginseng is quite variable and dependent on steaming, and a study measuring 8 commerical products obtained in Korea noted between 0.85-2.51% for arginyl-fructose and 0.25-2.64% with arginyl-fructosyl-glucose

Some unique products to Korean Red Ginseng that are not related to the Ginsenosides, two Amadori rearrangement products common to the fermentation and steaming process. Fructose binding to the amino acid L-Arginine or Maltose binding to the same amino acid, may be bioactive

2.2

White Ginseng

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.[4] The process of air drying follows peeling of the root and drying until the moisture content is below 12%, and turns the root into a yellow-ish white color.[4][3] Some of the bioactives may be lost during this process.

2.3

G115 and NAGE

G115 is a patented extraction of Panax Ginseng patented by Pharmaton, Switzerland that contains 4% ginsenosides by total weight[37][38] while NAGE is a standardized extract from the same company containing 10% ginensosides by weight.[38] Both extracts tend to be used in research to ensure quality standards and control for total amount of Ginsenosides, with one study noting that purity of the extracts ranged from 95.9-100% as assessed by HPLC; both extracts are rich in Rb1 and Re, and fairly reflective of what ginseng (naturally occurring, noted in the opening section) should contain when looking at the ratios between ginsenosides.[38]

One study specifically breaking down the component Ginsenosides noted that G115 had 1.07% (Rb1), 0.66% (Rb2), 0.67% (Rc), 0.46% (Rd), 0.56% (Re) 0.14% (Rf) and 0.44% (Rg1) while NAGE had 4.56% (Rb1), 0.31% (Rb2), 1.09% (Rc), 1.43% (Rd), 2.36% (Re), and 0.24% (Rg1) with no Rf detected.[38]

Simply standardized vessels for Panax Ginseng, with fairly high validity of being 4% Ginsenosides (G115) and 10% Ginsenosides (NAGE), used in research not because they are somehow better than the Ginseng plant, but because their contents are reliable

3.

Pharmacology

3.1

Metabolism

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 20-O-b-D-glucopyranosyl-20(S)-protopanaxadiol.[39] Oral administraiton of Rb1 in isolation can cause blood increases in Compound K in rats[40][41] and urinary increases, despite Rb1 not being detected in the urine.[42]

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.[39] This general metabolic chain was proposed earlier, although without the intermediates.[43]

General metabolism of the Ginsenosides appears to be related to the protopanaxa-diol annd -triol backbones, with interconversion of metabolites in vivo

3.2

Enzymatic Interactions

An In vitro study assessing the interactions of ginsenosides found that Panax Ginseng was able to reduce the catalytic activity of CYP1A1 and CYP1A2 (two variants of Aromatase) and CYP1B1 in a dose-dependent manner that correlated with Ginsenoside content.[38] The inhibition appeared to be competitive for CYP1A1 and mixed for the other two, with CYP1A2 being more susceptable. When the ginsenosides Rb1, Rb2, Rc, Rd, Re, Rf, and Rg1 were tested in isolation all ginsenosides failed to inhibit these three enzymes nor did they inhibit 7-ethoxyresorufin O-dealkylation (EROD) activity when they were added to the same concentration previously used with whole Panax, and regained inhibitory potential when the concentration was elevated to 50uM with more potency seen with Rc (75% inhibition of CYP1A2) and none from Re.[38] This suggests that total ginsenoside content may be more relevant than an individual ginsenoside, as the inhibition seems to occur with most ginsenosides.[38]

4.

Skeletal Muscle and Physical Performance

4.1

Fatigue and Endurance

A study in mice using a forced swim test noted that the polysaccharide content of Panax Ginseng may offer benefits to endurance via reducing fatigue, as administration of polysaccharides at 50, 100, and 200mg/kg bodyweight for 15 days noted that 1 hour after the last dose that only 200mg/kg bodyweight significantly improved performance.[44] When the neutral polysaccharide fragment (40, 100, 160, and 200mg/kg) were compared against the acidic polysaccharide fragment, it was found that all doses of the acidic polysaccharides significantly improved performance and were the active ingredients (although the highest dose only of neutral polysaccharides also showed benefit).[44] The acid fragment was more effective at enhancing circulating glucose, suppressing circulating TGs, and increased SOD expression relative to both the neutral fragment and unsupplemented control.[44]

Another study using 1, 10, and 100mg/kg in mice (10% Ginsenosides) failed to demonstrate a statistically significant improvement in forced swim time after 7 days of supplementation in mice (although trended towards significance).[45]

4.2

Hormonal Indices

One study using 2g of Panax Ginseng 60% ethanolic extract in endurance trained athletes (minimum 2 years experience with 5 hours exercise weekly) for 6 weeks failed to notice any significant changes in testosterone, cortisol, or their ratio associated with Panax Ginseng.[46]

4.3

Exercise Immunology

A study on 30 male endurance runners failed to establish any altered immune cell count or receptor (CD3+, CD4+, CD8+, CD20+) expression after 6 weeks of having 2g of 60% ethanolic extract of Panax Ginseng alongside their running regimens.[46]

4.4

Temperature

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.[47]

5.

Neurology

5.1

Appetite

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,[48] alongside the vertical root of Astragalus Membranaceus.[49] Studies looking into the appetite enhancing effet of Panax Ginseng are lacking, with a study which injected isolated Ginsenoside Rb1 and found no influence on appetite per se, but a prevention of heat and surgery induced reduction of appetite; in accordance with traditional claims.[50] One other rat study merely measuring food intake as an outcome parameter noted increases of 37.7% and 50% in normal chow and high-fat chow with 3% Red Ginseng, respectively, without significant differences in weight gain observed with the added calories (which was attributed to decreasing fat absorption from the diet, due to in vitro lipase testing and fecal analysis).[51] This study used male Balb/c mice 8 weeks of age with no health abnormalities.[51]

Ginsenoside-enriched fragments of Panax Ginseng at 12.5-25mg/kg (relatively low dose to anti-obesity doses) appear to somewhat attenuate radiation-induced pica (appetite for non-food products) in rats[52] and the berries may have the same effect at a slightly higher dose of 50-150mg/kg.[53]

Actual studies done on the subject matter note a reduction in food intake in obese mice possibly secondary to regulation of NPY in the hypothalamus (possibly secondary to IL-1b modulation[54]), using an isolated Ginsenoside mixture at 200mg/kg bodyweight and suppressing intake by 12.4-21.2% that also affected lean mice over 3 weeks.[55] Another study using Panax Ginseng berries found that 150mg/kg bodyweight was able to suppress food intake by 16% of the control group in diet-induced obese mice, and this was demonstrated to not occur with isolated ginsenoside Re at 20mg/kg bodyweight; this study tested lean mice, but did not report food intake alterations,[56] food intake suppression may be more related to Rb1[57] or protopanaxadiols in general, including Rb1-3 and Ra1-3 (amongst others) which have been shown to reduce food intake by 16.3% in high-fat fed mice given 50mg/kg.[58]

It is possible that Red Ginseng ginsenosides (also applies to Panax Ginseng in general) may help regulate abnormal feeding patterns with no influence on normal feeding patterns, but surprisingly little research has been done on appetite stimulation for which Ginseng is traditionally said to do. No human studies directed to answer this topic either, but potent and acute suppression of intake is seen in obese mice that overeat with mixed results in lean mice

5.2

General Cognition

A study in young healthy adults using 200 or 400mg acutely noted increased reaction time associated with 400mg, but not 200mg, 2.5 hours after ingestion. Interestingly, 200mg led to slightly but significantly slower reaction times on the first day of tested, which may have been secondary to an induction of calmess.[59] These improvements in reaction time have been replicated with 400mg of 4% Ginsenoside extract (G115) in regards to spatial reaction time at the same time after ingestion, but only when combined with Ginkgo Biloba did they reach statistical significance at 4 hours post ingestion for simple reaction time.[60] A third test measuring reaction time noted some significant improvements, but most results were statistically insignificane; the results of this test may be secondary to anti-fatigue.[61] The addition of Ginseng to Ginkgo appears to improve the parameters related to accuracy, and the 'relaxing' reports of Ginseng may reduce frequency of errors in cognitive tests.[60]

Another study by the same researchers tested 200mg and 400mg of G115 in healthy young adults found improved performance on the serial sevens subtraction task,[61] a test for intellectual efficiency.[62] Lesser inconsistent benefits were acheived on serial threes and on a reduction of errors in serial 3s, but little benefit was seen in reduction of errors in serial sevens.[61]

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.[63]

Panax ginseng might improve reaction speed and accuracy, but by currently unknown mechanisms and relative potency to other herbs; it doesn't reach statistical significance all the time, so it may be unreliable as well.

Many of the general cognitive benefits may be secondary to the anti-fatigue effects of Ginsenosides and Polysaccharides, paired with persistance causing differences from the fatigued placebo

5.3

Depression, Anxiety, Stress

In mice, 100mg/kg of the acidic polysaccharide fragment of Ginseng was able to decrease depressive symptoms in mice while improving social interactions and reducing aggression.[64] 200mg/kg appeared to not be significantly effective on these parameters. Anti-depressive effects have been noted in mice given Ginsenosides as well, suggesting both main components of Ginseng are active regarding depression.[65]

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.[66]

In regards to stress, a possible mechanism may be altering genetic transcription of some enzymes.[67] This study used pure saponin extracts in vitro at 10ug/mL and orally to rats at 200mg/kg noted that the mRNA levels of Tyrosine Hydroxylase and dopamine β-hydroxylase that was increased with stimuli was attenuated with Ginseng by 35.6 and 48.2% in adrenal glands (induced by stress) and 57.2% and 48.9% in neurons (induced by nicotine), respectively.[67]

5.4

Memory and Learning

When looking at Ginsenoside Rb1 in isolation, it appears to be responsible for enhanced learning rats in the hippocampus. It can enhance NGF-induced neurite growth in the ganglia of chicks,[68] and when fed orally to rats at 2mg/kg daily for 30 days showed a decrease in acquisition phase of learning, suggesting that the enhanced memory seen later was secondary to better learning.[69] This latter study failed to note any significant influence on motivation despite the enhanced learning, and after 30 days there was no significant difference in immunostaining of the hippocampus suggesting that no significant neurogenesis occurred.[69]

5.5

Neuroprotection

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.[70][71][72]

Oral administration of the Korean Red Ginseng compound Ginsenoside Rg3 has shown protective effects against cerebral ischemia-induced injury in animals,[73] and in transient focal cerebral ischemia where 5, 10, and 20mg/kg Rg3 was given in feed found that 10mg/kg was as effective as 1mg/kg active control Nimodipine in reducing the cognitive deficit induced by ischemia, and 20mg/kg appeared to be more protective but not significantly so.[74] The percentage of infarct volume in the hippocampus was reduced to a similar degree in both 20mg/kg and Nimodipine, at about 20.1+/-2.8%, suggesting the potential to improve mitochondrial activity after brain injury with Rg3; and other measures of neurodegradation (TUNEL positive cells, Calpain-1 or Capsase-3 positive cells) were equally reduced by 10-20mg/kg Rg3 and Nimopidine.[74] The mechanism by which Ginseng may protect from Ischemia can be through deregulating the expected sequence of hypoxia,[75] as the incubation of ginsenosides from Korean Red Ginseng (KRG) appear to reduce the activity of a protein (Hypoxia-Inducible factor-1; HIF1) on the nucleus at the post-transcriptional level, but incubation with ginsenosides appears to actually increase HIF1 activity despite lesser actions.[75] This appears to be since HIF1 needs to bind to the nuclear factor ARNT to induce its effects, and incubation with Korean Red Ginesng prevents this.[75]

5.6

Fatigue

One study in humans assessing Panax Ginseng ingestion at either 200mg or 400mg acutely in healthy young adults noted that 200mg was able to reduce a fall in mood associated with prolonged (4 hour) psychological testing and 400mg induced a state of calmness.[59] There were no significantly different effects when comparing the first dose against the 8th consecutive daily dose, suggesting no tolerance nor build-up effect.

Another study replicated this reduction of fatigue with 200mg of the G115 extract (4% Ginsenosides) where a 10 minute neural test was performed, followed by 50 minutes rest, and then the same test 6 times in immediate succession.[61] 400mg was still effective, but less so than 200mg.

5.7

Cerebrovascular Function

A study done in humans assessing blood flow to the brain after Ginseng ingestion in healthy persons where 200mg G115 extract noted significantly reduced P300 latency (not amplitude) in all five tested cerebral lobes (main four, but left and right temporal tested independently) with significantly reduced beta and theta waveband power (in mV2/Hz) while alpha was reduced only in the frontal lobe, where beta and theta were more potent.[76] No significant differneces were seen between placebo and Ginseng in regards to CNV data, and the above differences were seen with eyes closed, with no significant differences on any parameter with eyes open.

A systemic review of Cerebrovascular effects of Ginseng only found two studies, the aforementioned study and one other that is not indexed online.[77] The aforementioned study[76] was rated high quality on the Jadad scale, with the other of low quality; their combination constituted moderate evidence, but both showed similar results.

5.8

Mood and Quality of Life

One study using 200 and 400mg Panax Ginseng found increased calmness in a relatively dose-dependent manner after acute ingestion in healthy adults.[59] These same doses and product were used in another trial on young adults over a period of 60 days in another trial, which failed to note any significant changes in any mood parameter measured.[78] Interesting, a study conducted over a period of 8 weeks with a measurement at the 4 week marker found significant improvements in mental health and function as well as social function (assessed by the Short Form-36 Health Survey v.2) at 4 weeks, but the benefits associated with 200mg Ginseng became not significantly different than placebo at 8 weeks.[79] One of the studies on mood and cognition that measured reactions to the initial dose and reactions to the 8th dose (when a once daily dose was taken) found that some parameters were less potent than baseline, but none of these trends of attenuation reached statistical significance.[59]

It is possible that the mo

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