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APPALACHIAN PLANT MONOGRAPHS

Prepared by Tai Sophia Institute

For

Appalachian Center for Ethnobotanical Studies

September 2011

Panax quinquefolius L. American ginseng

Ch ie f Au t h o r a n d Ed it o r : An d r ew Pen ge lly Ph D, AHG, FNHAA

Assis t a n t Au t h o r : Ka t h leen Ben n e t t

Ed it o r ia l Tea m : Ja m es Sn o w AHG

Bevin Cla r e MS, AHG

No r a Zie t z

Deb o r a h Mizu r

Lin d sa y Klu ge

Mim i He r n a n d ez , MS, RH (AHG)

Citation Instruction: Pengelly, A., & Bennett, K.,(2011). Appalachian plant monographs: Panax quinquefolius L., American ginseng. Retrieved from http://www.frostburg.edu/aces/appalachian-plants/

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American Ginseng – Panax quinquefolius L.

1. Taxonomy Panax quinquefolius L.

Family: Araliaceae

Common names: American ginseng, five finger root, sang, tartar root, redberry, man‟s health,

root of life, dwarf groundnut, garantogen, jinshard, ninsin, little man, garent-oquen.

Synonyms: Panax quinquefolium (L.) Alph.Wood, Aralia quinquefolia (L.)Decne. & Planch.,

Ginseng quinquefolium (L.) Alph.Wood, Panax americanus (Raf.) Raf., Panax cuneatus Raf..

Two species of Panax (P. quinquefolius and P. trifolius L.) are native to North America. The

latter species is much smaller and rarely used for medicinal purposes. There are 11 species

globally, several of which are Asian, most notably P. ginseng C.A.Mey. known as Korean or

Asian ginseng.

2. Botany and distribution P. quinquefolius is a slender deciduous perennial growing to a height of 2 feet and bearing

palmate-compound, serrated leaves at the apex of the stem. Individual leaflets range from lance

Figure 1. Image from Applied and

Economic Botany by Henry

Kraemer. Published by author,

1914.

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shape to oblong. Leaves from young plants may consist of only three leaflets. As the plant

matures, more sets of these leaves appear, but it is rare to see plants with four or more compound

leaves or „prongs‟ as they are known. As the stem („sympodium‟) dies back each fall it leaves a

bud scar on the root collar or rhizome - these are used as a means of assessing the plant‟s age

(Rural Action Inc., 2005). Adventitious roots may form from these nodes in older plants (Van

Der Voort, Bailey, Samuel, & McGraw, 2003).

Small whitish flowers appear in the summer, born on a simple umbel in the main leaf axis. These

are followed by red berry-like fruit containing up to three seeds. Seeds remain dormant for well

over a year, germinating in the second spring season (Schlag & McIntosh, 2004). P.

quinquefolius also has the ability to remain in a dormant state for a year or several years when

weather conditions are adverse (Taylor, 2006).

Ginseng roots are fleshy white or light colored tap roots, and variably branched. As the plant

ages it sometimes puts out an auxiliary root that may act as a „spare‟ if the main root is damaged

(Elliot, 1976)

The preferred habitat for P. quinquefolius is in the shady understory of deciduous hardwood

forests in Eastern USA and Canada. It was once quite prevalent in the Appalachian region

though now its distribution is quite patchy (Case, Flinn, Jancaitis, Alley, & Paxton, 2007;

McGraw, Sanders, & Voort, 2003) and gene flow between populations is restricted (Assinewe,

Baum, Gagnon, & Arnason, 2003; Cruse-Sanders & Hamrick, 2004). It likes well-drained,

humus-rich soil and prefers east-facing slopes (Foster & Johnson, 2006).

Parts Used

The dried root, harvested from plants at least 6 years old, in late summer and fall.

Research indicates the leaves and fruit are also pharmacologically active.

3. Traditional Uses

Traditional use in Appalachia

P. quinquefolius has traditionally been administered as a tea for general tonic purposes and as an

aphrodisiac. It is used to dispel a cough and promote perspiration in colds, driving out the force

of illness from within (Crellin & Philpott, 1990). It is cultivated and revered in central and

eastern North America by tribal and Appalachian cultures for its longevity-promoting effects,

although differentiation between Chinese and American ginseng uses has often been blurred

(Duke, 1986; Millspaugh, 1974). P. quinquefolius has also been used as a poultice for boils and

decoctions of the roots have been taken to relieve headaches and “female troubles” (Banks,

2004). It is said that the root of P. quinquefolius ceased unpleasant dreams in children and infants

and remedied issues relating to flatulence and colic (Howell, 2006).

P. quinquefolius has been traded interstate and overseas for hundreds of years, and it remains an

integral part of the Appalachian economy (Cavender, 2003).

Traditional use - general

European interest in P. quinquefolius can be dated back to the early 18th

century when a French

Jesuit, Joseph-Francois Lafitau, spent many years amongst the Canadian Mohawk Nation

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searching for an American equivalent to Asian ginseng. His quest was so successful that a

ginseng industry was quickly established, and within a few years large quantities were being

exported to China (Taylor, 2006).

Native American

Before Lafitau‟s discovery of the similarity between Asian and American ginseng, P.

quinquefolius was already a medicinal agent in native traditions (Taylor, 2006). The Iroquois

Indians used ginseng for a variety of disorders including upset stomach, sore eyes and tape

worm, but also as an article “to give thanks and for preventative health care” (Taylor, 2006).

Other recorded Native American uses of this herb included applications as an analgesic,

anticonvulsive, expectorant, digestive tonic, gynecological aid, & general tonic (Moerman,

1998). It was sometimes used as a remedy for headaches and colic.

Folklore & Home

The main home use of American ginseng was as a digestive stimulant particularly for the

weakened or uneasy stomach. It was also used to treat a sluggish nervous system and strengthen

the circulation (Harding, 1936).

Physiomedical

P. quinquefolius was said to have sedating and relaxing effects, and was used to address

dyspepsia as well as nervous sensitiveness with debility (Cook, 1869). Its main action was a

nervine tonic and relaxant to the whole body, with a particular affinity for the brain.

Eclectic

Felter (1922) and Scudder (1870) report that the root of P. quinquefolius required long-term use

to be effective. It was used as a nervous system sedative, having the greatest effects on calming

nervous dyspepsia as well as “mental and other forms of nervous exhaustion from overwork.”

Felter noted its use as a long term, building tonic for patients with depleted resources,

particularly cerebral anemia (Felter, 1898).

Regulars

Allopathic physicians found little use for P. quinquefolius except as a demulcent and as a

flavorful root to chew (Remington & Wood, 1918). Many believed that ginseng‟s medicinal

qualities were a myth of the Chinese and had little use for it in this country as an effective

medicine (Wood & Bache, 1858). Nevertheless P. quinquefolius was official in the United

States Pharmacopoeia (USP) from 1842 until 1882 (Blumenthal, 2003).

China

P. quinquefolius is used in Traditional Chinese Medicine to treat “deficiency” conditions

associated with symptoms such as fatigue, irritability, thirst and dryness of the mouth or

respiratory tract (Chen & Chen, 2004)

4. Scientific Research

Phytochemistry

The most significant group of active constituents in P quinquefolius and P. ginseng are a group

of triterpenoid saponins known as ginsenosides. Ginsenosides are glycosides whose aglycones

have dammarane-type structures. A rare ocotillo-type saponin known as 24-R-

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pseudoginsenoside is found only in P. quinquefolius (Leung & Wong, 2010). Another class of

dammarane-type triperpene oligoglycosides (quinquenosides I-V) are also found in the species

(Yoshikawa et al., 1998).

A wide range of extraction, separation and detection methods have been applied for the

determination of ginsenoside structures and levels in different plant sections. These methods

include high-performance liquid chromatography (HPLC), mass spectroscopy (MS), diode-array

detectors (DAD), infra-red (IR) spectroscopy and evaporative light scattering detection (ELSD)

(Ferreira, Ebbs, Murphy, & Corbit, 2005; Jia, Zhao, & Liang, 2009; Orsat & Dai, 2010; Qi,

Wang, & Yuan, 2011; Wan, Li, Chen, & Wang, 2007; Yat et al., 1998). The United States

Monograph (USP, 2004) includes TLC and HPLC methods for ginsenoside evaluation, with the

acceptable total content being no less than 4% of the dried roots (USP, 2004). Modifications to

the USP methods have been recommended, in an attempt to overcome inconsistent results

observed from the use of different HPLC columns (Li, Chen, Chou, Want, & Hu, 2004). For

identity of pseudoginsenoside F11, HPLC was coupled with ELSD (Li & Fitzloff, 2001).

Using ultra-performance LC linked with MS for separation and identification, G. Xie et al (2008)

further analyzed five ginseng species by principal component analysis and found that P.

quinquefolius was readily discriminated from the other four species tested.

Gene sequencing experiments have also led to an understanding of the biosynthesis of

ginsenosides; the genes encoding enzymes identified include 150 cytochrome P450 and 235

glycosyltransferase sequences unique to P. quinquefolius (Sun et al., 2010).

Ginsenosides are classified into two main groups known as protopanaxadiol (PPD) and

protopanaxatriol (PPT), based on the hydroxylation pattern at C6 and attachment of sugar

moieties (Table 1). Phytochemically Panax species are distinguished by the ratio between these

groups (Hall, Lu, Yat, Fitzloff, et al. 2001). For example P. ginseng ginsenosides are mainly of

the PPD group, while PPTs are more prominent in P. quinquefolius although Rf is entirely

absent. Further differentiation may be made by the ratios of Rg1/Rb1 and Rb2/Rb1 which tend to

be higher in P. ginseng (Yuan, Wang, Wicks, & Qi, 2010) although some wild populations of P.

quinquefolius have been found to have high Rg1/Rb1 ratios (Schlag & McIntosh, 2006). As a

generalization the most prominent P. quinquefolius constituents are Rb1 and Re (Assinewe et al.,

2003). However North America P. quinquefolius populations have been further differentiated

according to their Rg1/Re ratio (Schlag & McIntosh, 2006; McIntyre et al. 2011). The variation

in chemotypes is not only significant for identification purposes - they also have clinical

implications as discussed below under metabolism. The main ginsenosides in P. quinquefolius

are listed in Table 2.

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Table 1. Classification of ginsenosides in Panax spp. (Leung & Wong, 2010).

Compounds are named according to a decreasing polarity scale (i.e.water solubility). Generally

the PPT group is more polar due to the extra hydroxyl group e.g. Re, while the less polar PPDs

tend to be lower in the alphabet eg. Rb.

Protopanaxadiol group

(PPD)

Protopanaxatriol group

(PPT)

Others

Rb1, Rb2, Rb3 Re F11 ocotillo

saponin (P.

quinquefolius only)

Rc Rf (P. ginseng only) Oleanane saponins

Rd Rg1, Rg2 Quinquenosides

Rg3 Rh1

Rh2

Rs1

Table 2: Main ginsenosides and ratios typical of P. quinquefolius

Ginsenosides and their ratios

Rb1

Rg1

Rg1 / Rb1 < 1 (see text for clarification)

Re

F11 ocotillo saponin - 24R-pseudoginsenoside

Rf / F11 ratio =0.1

Ginsenoside content will also vary as a consequence of increased temperatures. P. quinquefolius

grown at high temperatures tends to accumulate less biomass and develop smaller roots, leading

to a reduction in total ginsenoside content (though not concentration) in plants subjected to a 5°C

increase in growth temperatures in comparison to controls (Jochum, Mudge, & Thomas, 2007).

Preferential selection of larger roots for analysis of ginsenosides and polyacetylenes did not

influence the concentrations of either group of constituents (Christensen & Jensen, 2008).

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Ginsenoside levels are not influenced by root shape or section harvested, although root “fibre”

has higher concentrations - though not of Rb1 (Roy, Grohs, & Reeleder, 2003). Other factors

that may act as predictors of ginsenoside concentration are age and stage of plant development,

soil pH, light concentration (Schlag, 2004) and understory light levels including the effect of sun

flecks (Fourniera et al, 2003), while variation may also be found between cultivated, wild and

wild-simulated plant material – this in turn is influenced by the seed source (Schlag, 2004).

Exposure of the roots to soil-borne heavy metals such as lead and arsenic can also influence

ginsenoside production in ginseng roots (Corbit, Ebbs, King, & Murphy, 2006).

In a surprise finding, J.-T. Xie et al (2004) revealed that for Wisconsin cultivated P.

quinquefolius the leaves contain far higher levels of ginsenosides (15.3%) compared to the

berries (10.8%) and root (5.5%), and the ratio of the leaf components also differed, with

particularly high concentrations of Rd and Re. By contrast Assinewe et al (2003) found the

leaves of seven wild populations to contain only 3.33% ginsenosides compared with 5.78% for

root.

Huge variability exists between different ginseng commercial products, partly due the number of

species marketed as ginseng, as well as differences within products from the same species

(Harkey, Henderson, Gershwin, Stern, & Hackman, 2001). In an attempt to identify mislabeled

and adulterated products marketed as ginseng in North America, and to develop a set of

standardized tests for identity and quality, the American Botanical Council initiated the Ginseng

Evaluation Program in collaboration with the Universities of Ottawa and Chicago (Hall, Lu,

Fitzloff, Arnason, Awang, Fong, & Blumenthal, 2001).

Pharmacokinetics There have been few pharmacokinetic investigations into P. quinquefolius. Those available are

based around the ginsenosides, which are found to be of low bioavailability (Jia et al., 2009;

Reeds et al., 2011). This is partly a result of the first-pass metabolism that occurs, leading to

formation of metabolites which may in fact be more potent that the ginsenoside „pro-drugs‟ from

which they derive (Bae et al., 2004).

Ginseng saponins appear to be readily degraded under mild acid conditions such as found in the

human stomach. For example ginsenosides Rg1, Re and Rb1 were shown to yield their

prosapogenins under such conditions (Han et al., 1982). In further studies Bae, Han, Choo, Park,

and Kim (2002) demonstrated the formation of ginsenoside Rg3 following mild acid treatment.

This Rg3 metabolite was further transformed by human intestinal bacteria to Rh2, which showed

increased cytotoxicity against tumor cells and Heliobacter pylori in vitro. Ginsenoside Rb1

occurs in both an acid form (malonyl-Rb1) and the neutral form, which in cultivated P.

quinquefolius are in approximately equal proportions (Awang, 2000). The acidic form can be

converted to neutral Rb1 by steaming or by digestion in the stomach, after which it is further

converted by anerobic bacterial enzymes to a more polar and more active metabolite - Rd ( Kim,

Lee, & Lee, 2005). Removal of glucose units from Rd by intestinal bacteria leads to formation

of Intestinal Bacterial Metabolite (IBM) also called compound K – this unit can be absorbed into

the bloodstream (Awang, 2000). Ginsenosides Rb2, Rc and Rd follow a similar route.

Ginseng metabolites have also been shown to have more significant cytochrome P450 influence

compared to the natural saponins (Liu et al., 2006). These studies provide further evidence that

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ginsenosides actually act as pro-drugs, which depend on transformation by stomach acid and

intestinal bacteria to release their active constituents (Bae, Han, Kim, & Kim, 2004). For a flow

chart that displays the stages of biotransformation of the various ginsenosides by intestinal

microflora to their metabolites, see Leung & Wong (2010).

In addition to first pass effect, ginsenoside profiles may also be influenced by steaming ginseng –

a common tradition in Asia. HPLC profile comparisons between steamed and unsteamed P.

quinquefolius roots have been published (Qi, Wang, & Yuan, 2010). When berries were steamed

in a separate study, the overall level of ginsenosides was reduced however there was significant

augmentation of Rg3, a recognized anticancer agent (Wang et al., 2006). Rg3 has also been

identified in heat-processed P. ginseng (Bae, et al. 2002).

Polyacetylenes

Polyacetylenes are small lipid soluble molecules of limited distribution in plants. The major

such compounds in P. quinquefolius roots are the alcohols falcarinol and panaxydol

(Christensen, Jensen, & Kidmose, 2006), while others include PQ-1→ PQ-8 (all previously

unknown), panaxytriol, acetylpanaxydol and ginsenoyne G (Fujimoto, Satoh, Takeuchi, &

Kirisawa, 1991; Fujimoto, Wang, Kirisawa, Satoh, & Takeuchi, 1992; Fujimoto, Wang, Satoh, &

Takeuchi, 1994; Satoh et al., 2007) and a recently discovered compound 3-oxy-PQ-1 (Satoh et

al., 2007). The main analytical methods for identification and quantification of polyacetylenes in

P. quinquefolius roots are HPLC, MS and C/H-NMR, while Christensen et al. (2006) have

developed an HPLC method for simultaneous analysis of ginsenosides and polyacetylenes.

Polysaccharides

Numerous polysaccharides as well as oligosaccharides and monosaccharides have been extracted

from P. quinquefolius. Assinewe, Amason, Aubry, Mullin, & Lemaire (2002) extracted a linear

polysaccharide fraction which, upon acid hydrolysis, was found to yield mainly glucose with

small amounts of galactose and arabinose and a 9% uronic residue. A commercial extract

standardized to polysaccharide content has been developed by CT Technologies. CVT-E002

(COLD-fx® ) is comprised of poly-furanosyl-pyranosyl-saccharides that have been shown to

stimulate the immune system (Shan, Rodgers, Lai, & Sutherland, 2007).

Other constituents

Apart from saponins P. quinquefolius contains phenolic compounds, amino acids, flavonoids,

volatile oils, vitamins and minerals (Schlag, 2004; Jia et al, 2009; Qi, Wang, & Yuan, 2011).

Pharmacology

Pharmacology of ginsenosides As mentioned above, individual ginsenosides provide significantly different pharmacological

effects, hence the interest in ascertaining specific levels and ratios. This is exemplified by the

two major ginsenosides – Rb1 and Rg1 – characteristic of P. quinquefolius and P. ginseng

respectively. Rb1 tends to be more of a depressant (more “yin”, eg inhibiting angiogenesis) while

Rg1 is a mild stimulant (more “yang”, eg. promoting angiogenesis) (Harkey et al., 2001;

Sengupta et al., 2004). Further correlations between individual ginsenosides and their activities

are listed in Table 3.

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Table 3. Some pharmacological effects of ginsenosides

Compound Pharmacological action Reference

Rb1 Estrogen-like activity

Anti-diabetic, insulin sensitizing

Antiobesity

Angiogenesis inhibitor

Neurotropic, neuroprotective

Benishin, Lee, Wang, &

Liu, 1991; Duda et al.,

1996; Papapetropoulos,

2007; Radad et al.,

2004; Rudakewich, Ba,

& Benishin, 2001;

Sengupta et al., 2004;

Shang et al., 2007;

Shang et al. 2008;

Xiong et al., 2010

Rc Inhibit proliferation of breast

cancer cells

Murphy, 2002

Re Anti-diabetic

Antioxidant, cardioprotective

Attele et al., 2002; Yuan

et al., 2010

Rg1 Neurotropic, neuroprotective

Ligand for glucocorticoid

receptor

Suppresses oxidative stress

Promotes angiogenesis

Chen, Chen, Zhu, Fang,

& Chen, 2002; Chen et

al., 2003; Lee et al.,

1997; Radad et al.,

2004; Rudakewich et

al., 2001; Radad et al.,

2004; Sengupta et al.,

2004

Rg2 Neuronal Ach inhibitor Sala et al., 2002

Rg3 Inhibits proliferation of prostate

cancer cells

H-S Kim et al., 2004

Rh1 Activates estrogen receptor Lee et al., 2003

Rh2 Cytotoxic, inhibits breast cancer

cell proliferation

Inhibits proliferation of prostate

cancer cells

H-S Kim et al. 2004;

Murphy, 2002

F11 Assists memory improvement

Neuroprotective

Z. Li, Guo, Wu, Li, &

Wang, 1999; Wu et al.,

2003

Effects on blood sugar and metabolism

Numerous studies indicate that P. quinquefolius reduces postprandial glycemia in diabetic and

non-diabetic human subjects in doses as low as 1g, suggesting a possible role for this species in

complementing existing diabetic treatment (Vuksan et al., 2000a; Vuksan et al, 2000b; Vuksan et

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al, 2001). However, in one case when a different batch of P. quinquefolius from the same

supplier - but with a much lower ginsenoside profile - was tested, no such effect was observed

(Sievenpiper, Arnason, Leiter, & Vuksan, 2003). In a separate study using P. ginseng no

hypoglycemic effects were shown, rather there was a tendency towards elevated glucose

(Sievenpiper et al., 2003). This finding was confirmed in a subsequent study of several species

and types of ginseng in which the ginsenoside ratio (PPD:PPT) is posited as a significant factor

in the variable glycemic response (Sievenpiper, Arnason, Leiter, & Vuksan, 2004). Yet in a

recent study using five batches of Ontario-grown P. quinquefolius reduced postprandial glycemia

and insulinemia were shown for three of the batches but not for the other two, and variations in

ginsenoside content did not correlate with these differences (Dascalu et al, 2007). Studies in

animals using P. quinquefolius leaves with high ginsenoside levels (referred to above) also

demonstrated marked anti-hyperglycemic activity (J.-T. Xie et al., 2004), and similar results

have been obtained using berry extracts of both P. quinquefolius and P. ginseng (Attele et al.,

2002; J-T Xie, Mehendale, & Yuan, 2005). In a recent in vivo antidiabetic screening study of

ninety botanical species, all three P. quinquefolius products (rhizome, leaf, berry) tested positive

for lipogenic activity, however P. ginseng did not (Babish et al, 2010). Lipogenesis improves

insulin sensitivity as new adipocytes take up more glucose and secrete fewer detrimental

cytokines compared to the larger adipocytes they replace (Babish et al., 2010). Ginsenoside E

has been identified as a specific hypoglycemic agent (Attele et al., 2002) although to date studies

in humans do not support this effect (Reeds et al., 2011).

Ginsenoside Rb1 also suppressed food intake and body weight gain in obese rats, while

improving glucose homeostasis. Modulation of associated signaling pathways and neuropeptides

in the hypothalamus was observed (Xiong et al., 2010). Further studies with mice treated with

polysaccharides extracted from the fruit suggest the polysaccharides are another potential

component associated with anti-hyperglycemic activity for P. quinquefolius (Xie et al. 2004).

Molecular studies based on P. ginseng indicate ginsenosides suppress gene expression associated

with the nuclear hormone receptors peroxisome proliferator-activated receptors (PPAR) in vitro

and in vivo (Yoon et al., 2003; Banz et al., 2007). Furthermore, a specific ginsenoside Rb1 has

been found to activate PPARγ - a transcription factor in adipogenesis - and increase expression

of glucose transporters (GLUT) 1 and 4 in vitro. PPAR regulation has been linked to improved

insulin sensitivity and reductions of lipid accumulation in muscle and liver (Banz et al., 2007)

PPARs are also molecular targets for the anti-diabetic drugs known as TZDs (Kyu et al., 2006).

In sum these studies confirm a marked benefit on glycemic profiles at low doses for P.

quinquefolius but the benefits for P. ginseng species are less consistent. While differences in

ginsenoside levels and their ratios may influence the efficacy of P. quinquefolius it would appear

that other components may also be involved (Sievenpiper et al., 2004).

Diabetic renal damage

Animal studies suggest that heat-processed P. quinquefolius (H-AG) extracts may have

beneficial effects on renal damage associated with diabetic nephropathy. H-AG

significantly decreased elevated urinary protein levels in streptozotocin (STZ)-induced diabetic

rats, increased creatinine clearance and significantly reduced accumulation of advanced

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glycation endproducts (AGE) - a weaker effect on AGE was found with the unprocessed P.

quinquefolius extract (H. Y. Kim, Kang, Yamabe, Nagai, & Yokozawa, 2007).

Cardiovascular effects

Preliminary studies on rats have demonstrated potential cardioprotective, anti-ischemic,

antioxidant, calcium channel blocking and platelet aggregate moderating effects of P.

quinquefolius (Yuan et al., 2010). Four months of dietary supplementation decreased oxidation

damage to heart and muscle fibres with P. quinquefolius powder in rats (Fu & Ji, 2003).

Promotion of angiogenesis to infarcted or ischemic regions by an extract high in saponins was

shown to provide cardioprotection in vivo (Wang, Shi, & Yin, 2007). Ginseng species have

ambiguous effects on angiogenesis – promoting wound healing on the one hand (dependent on

angiogenesis) and inhibiting tumor growth via an antiangiogenic action on the other (Sengupta et

al., 2004). These contrasting properties have been linked to specific ginsenosides (Rb1 as

inhibitor and Rg1 as inducer of angiogenesis respectively). Rb1 angiogenesis inhibition has been

linked to agonistic effect on estrogen receptor β (Papapetropoulos, 2007).

Memory and cognition

In contrast to the mild central nervous system (CNS) stimulant effects of P. ginseng, P.

quinquefolius has a calming influence on the CNS (Yuan et al., 2010). There is a great deal of

evidence demonstrating that ginseng species in general and specific ginsenosides have multiple

effects in the CNS, an affinity for a wide range of receptors in the CNS (Yuan et al., 2010) and

specific influence on hippocampal neurons (Rausch, Liu, Gille, & Radad, 2006; Jia et al., 2009) .

Animal studies show cognitive enhancing and neuroprotective actions for P. quinquefolius, and

specifically for ginsenosides Rb1 and Rg1 – though possibly via different mechanisms (Benishin

et al., 1991; Rudakewich et al., 2001). Rb1 facilitated release of acetylcholine from the

hippocampus and increased choline in nerve endings (Benishin et al., 1991). Rb1, and to a less

extent Rg1, extended the survival time of dopaminergic neurons against a selective neurotoxin

(Radad et al., 2004). There is a particular focus on the use of ginseng products for prevention

and treatment of degenerative brain disorders such as Parkinson‟s and Alzheimer‟s diseases (Jia

et al., 2009; Radad et al., 2006; Rausch et al., 2006).

Common cold and immunity

Polysaccharide-rich extracts have been found to increase proliferation of spleen cells and

macrophage activity in cell cultures as well as stimulate immunoglobulin G (IgG) in vivo and

tumor necrosis factor (TNF) production from macrophages (Assinewe et al, 2002; Wang et al.,

2001). Increased TNF- production also occurred in blood samples of three human volunteers

following intake of P. quinquefolius (Zhou & Kitts 2002). CVT-E002– a water soluble extract

standardized for polysaccharides, is marketed under the patented name COLD-fX for the

treatment of upper respiratory tract infections (Wang et al., 2004) and has been subjected to

several clinical investigations (see „Clinical Studies' section below).

Mechanisms of anti-inflammatory activity have also been studied. Treating murine macrophages

with P. quinquefolius extract quantified to contain 10% ginsenosides, LPS-induced nitrous oxide

(iNOS) expression was inhibited, apparently by suppression of signal transducer and activator of

transcription (STAT) cascade (Ichikawa et al., 2009).

Cancer

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There has been considerable interest in the potential use of ginseng in cancer for many decades.

Initially this interest focused mainly on using P. ginseng as an adjuvant to enhance efficacy and

reduce side-effects of active cancer therapies such as chemotherapy and radiotherapy – based on

the herb's reputation as an „adaptogenic‟ agent (Jia et al., 2009). During the last decade there

have been numerous investigations into the potential for P. quinquefolius to assist in the

prevention and treatment of various forms of cancer.

Qi et al (2010) have explored potential structure-function relationships of ginsenosides in P.

quinquefolius, identifying a number of possible cancer-prevention mechanisms including cell

cycle modification, induction of apoptosis, and inhibition of angiogenesis and pro-inflammatory

pathways. For a comprehensive review of studies and mechanisms involving ginseng and cancer

see Jia et al. (2009).

Breast cancer

Using the standardized extract CNT-2000, studies on ER positive breast cancer cells showed

dose-dependent decreases in cell and paradoxically an ability to induce expression of the

estrogen-related gene pS2. There was no interference with the estrogen antagonist drug

Tamoxifen when used concurrently, suggesting the possibility for synergistic interactions with

conventional breast cancer agents (Duda et al., 1999). In a subsequent study the CNT-2000

extract was found to be an inducer of the p21 protein, a universal cell cycle inhibitor, in estrogen

sensitive and insensitive breast cancer cell lines, suggesting a molecular mechanism of action for

inhibition of breast cancer (Duda, Kang, Archer, Meng, & Hodin, 2001). Rice and Murphy

confirmed in vitro inhibition of breast cancer cells, and further identified potent inhibition by a

combination of ginsenosides Rc and Rh2. The two compounds appear to act via different

mechanisms, Rc inhibiting progression of the cell cycle and Rh2 showing cytotoxic activity

(Murphy, 2002). Further in vitro studies have elicited other potential molecular mechanisms,

including induction of apoptosis through activation of a protease, and via protein kinase

signaling pathways in cancer cells (King & Murphy, 2007).

Other cancers

Polyacetylenes in P. quinquefolius are cytotoxic to leukemia cells (Fujimoto et al., 1992).

Ginsenosides Rg3 and Rh2 have been shown to inhibit DNA synthesis in prostate cancer cells, to

induce cell detachment and to modulate protein kinases (H.-S. Kim et al., 2004). Rg3 can also

inhibit metastasis of ovarian cancer cells in vitro (Xu et al., 2008). Miller, Delorme, and Shan

(2009) conducted studies on mice with viral-induced tumors (erythroleukemia). Mice that were

given 40mg/d of the CNT-2000 extract survived up to 50% longer compared to controls. When

human colon cancer cells were exposed to P. quinquefolius extracts, cell proliferation and cell

cycle progression was inhibited, an effect which was associated with both ginsenosides and

polysaccharides (King, & Murphy, 2010).

Endocrine effects

The effect of ginseng on human hormones has long been a source of controversy. Laboratory

investigations indicate ginsenoside Rb1 is an estrogen receptor agonist (Papapetropoulos, 2007);

Leung et al., 2006). P. quinquefolius extract has also been shown to activate estrogen receptors

however the effect was shown to depend on the extraction solvent used – aqueous extractions

1 3

(which are polysaccharide rich) provide no estrogenic activity (King, Adler, & Murphy , 2006).

Rg1 activates glucocorticoid receptors (Lee et al., 1997) however this does not necessarily imply

the ginsenoside acts like a steroid hormone (Leung & Wong, 2010).

Clinical Trials

Common cold

McElhaney et al. (2004) found that when COLD-fx was taken early in the “cold and flu” season

the relative risk and duration of the common cold in a group of 43 elderly subjects was reduced

compared to placebo by 48% and 55% respectively. In a larger trial of 323 subjects aged 18-65

years, the mean number of colds in the ginseng group was significantly reduced compared to the

placebo group; severity of symptoms was reduced and the duration was also reduced by 2.4 days

– these results are comparable to those of common antiviral drugs used for treatment of influenza

(Predy et al., 2005).

Recently in a systemic review of five randomized clinical trials (four using COLD-fx, one

Ginsana G-115- P. ginseng), the authors noted a consistent trend towards a lower risk of

developing the common cold and evidence in two trials (both COLD-fx) that duration of colds

and other acute respiratory infections was reduced by an average of six days. They concluded

however that there is insufficient evidence to recommend ginseng extracts for prevention of the

common cold (Seida, Durec, & Kuhle, 2009).

Memory and cognition

Recently an acute randomized double-blinded clinical study of 32 healthy young adults

demonstrated significant improvement in working memory and other cognitive measures

following ingestion of varying doses of P. quinquefolius extract (CereboostTM

) standardized to

11.65% ginsenosides (Scholey et al., 2010).

Cancer A randomized double-blind pilot study was conducted on 290 adult patients with a history of

cancer-related fatigue, who were given ascending doses of 4-year old Wisconsin grown P.

quinquefolius over eight weeks. The groups who received doses of 1,000 and 2000 mg daily

appeared to have less fatigue compared to the group taking a placebo, as assessed by various

validated scales (Barton et al., 2009). By contrast a randomized controlled crossover trial of ten

healthy males given 1,125mg of CNT-2000 (a proprietary extract also known as North American

Ginseng Extract (NAGE) containing 10% ginsenosides daily for five weeks failed to show

significant effects on immune response as assessed by changes to white blood cell levels,

lymphocyte proliferation or neutrophil oxidative burst (Biondo et al., 2008).

5 . Mo d e rn Ph y to th erap y

Ginseng species are adaptogens – agents that increase general capacities to withstand situations

of stress. P. quinquefolius is a noted adaptogen, inducing a reduction in stress and increase in

physical performance over a period of time (Keville, 2000; Yarnell & Hooper, 2003). These

adaptogenic effects are thought to assist in stress reduction via an influence on the hypothalamic-

pituitary-adrenal (HPA) axis (Braun & Cohen 2010). Modern clinical applications include

1 4

hormone modulation for menopausal women, reduction and prevention of tumors in breast

cancer patients and overall support for people living with HIV (Yarnell & Hooper, 2003).

Additional uses include improving cerebral circulation, reducing fatigue and supporting healthy

heart function (Keville, 2000; Yarnell & Hooper, 2003).

The main therapeutic actions and clinical indications for P. quinquefolius are listed in Table 4.

Table 4. Modern phytotherapeutic uses of P. quinquefolius.

ACTIONS

Adaptogen Antioxidant

Sedative Mild stimulant

Hypoglycemic Hepatoprotective

Immunomodulatory Stomachic

Tonic Aphrodisiac

THERAPEUTIC INDICATIONS

Weakness, deficient vitality, lethargy, convalescence

Anxiety, depression, improve memory and concentration

Physical and mental effects of ageing, sexual inadequacy

Menopausal symptoms

1 5

Adjuvant for patients on cancer therapies, HIV

Type II diabetes, hypoglycemia

Anorexia

Increase resistance to infections

Orthostatic hypertension

(Blumenthal, 2003; Green, 1991; Keville, 2000; Mills & Bone, 2000; Mitchell, 2003; Yarnell,

Abascal, & Hooper 2003).

Combinations

With Rehmannia glutinosa (Gaertn.) DC. and Astragalus membranaceus Moench for debility,

low grade fever and convalescence.

With Turnera diffusa Willd. Ex Schult. and Serenoa serrulata (Michx.) Hook.f. ex B.D.Jacks.

for sexual inadequacy in males (Green, 1991).

With Avena sativa L. for nervous exhaustion

Contraindications

Avoid in conditions manifested by acute inflammation or high fever or irritability.

Preparations and Dosage (Blumenthal, 2003; Keville, 2000; Yarnell et al., 2003).

Powder: 0.30-10.0 grams, three times daily.

Decoction: 3-6g dried root simmered in 750-1000mL water.

Tincture: 2-4ml 3x a day

Standardized extract (5:1) – CNT2000: 2-300mg, 2-3 caps daily

TCM dose: 1-9g (Bensky & Gamble, 1993).

Safety and toxicity

P. quinquefolius is generally regarded as a safe herb, and is categorized as Class 1: “herbs that

can be safely consumed when used appropriately” by the Botanical Safety Handbook (McGuffin,

Hobbs, Upton, & Goldberg, 1997). Most of the literature concerning ginseng and safety is based

on P. ginseng which is not a reliable predictor given known phytochemical differences between

the two species (Kitts & Hu, 2000). The National Toxicological Program performed short-term

toxicity, long term carcinogenicity and genetic toxicology in vivo studies on ginseng species and

1 6

found no evidence of toxicity (National Toxicology Program [NTP], 2004). In a Phase II clinical

trial of 75 children with existing respiratory tract infections, safety data was generated and no

significant adverse events were reported (Vohra et al., 2008). Charrios (2006) warns that the

elderly may be at risk of exacerbating existing hypoglycaemia, and that diabetic subjects taking

P. quinquefolius should monitor blood glucose more frequently. She also refers to potential

„severe effects‟ of ginseng in general, but cites no examples or evidence (Charrios 2006). High

doses do have the potential to cause nervousness or insomnia with both species (Jia et al., 2009).

P. quinquefolius does not appear to significantly affect cytochrome P450 enzymes, hence the risk

of negative drug-herb reactions is relatively low. An in vitro study indicated inhibition of

CYP3A4 was dependent on overall ginsenoside levels, however there was no such correlation

with CYP2C9 (Luu, Foster, McIntyre, Tam, & Arnason, 2011). In one study on healthy human

volunteers, a P. quinquefolius extract was combined with the HIV protease inhibitor drug

Indinavir; there was no evidence of any pharmacokinetic interaction (Andriana et al., 2008).

Regulatory Status

P. quinquefolius is regulated in the U.S.A. as a Dietary Supplement. In Canada it is regulated as

Food, if no therapeutic claims are made, and New Drug if claims are made.

6. Sustainability

Ecological status-RTE status

On a global scale, P. quinquefolius is listed as G3-G4. States vary in their assessment of the

status of ginseng and not all states have up-to-date plant surveys. Connecticut, Minnesota,

Massachussets, and North Carolina list P. quinquefolius as of "special concern”, Pennsylvania as

vulnerable, Michigan and New Hampshire as threatened and Rhode Island as endangered.

Tennessee lists P. quinquefolius as commercially exploited and does not include P. quinquefolius

in its standard environmental review process. Landowners are advised that harvest is not

sustainable (Tennessee Natural Heritage Program, 2008)

The Massachusetts DNR (n.d.) notes that across the nation, P quinquefolius is considered to be a

locally threatened species because of over-harvesting, primarily for export to China. (See

Appendix-1)

Harvesting & Collection regulations

The collection, cultivation and trade of P. quinquefolius is governed at the county, state and

federal level. The export of P. quinquefolius roots is regulated by the Convention on

International Trade in Endangered Species of Wild Fauna and Flora (CITES) as an Appendix II

species. Under the terms of CITES, the interstate and international trade is strictly controlled by

the U.S. Fish and Wildlife Service. Interstate and international commerce records are required by

the US Fish and Wildlife Service when permits are granted. These permits are limited to states

that demonstrate adequate monitoring programs (U.S. Fish and Wildlife, 2011).

Continued approval for export from individual states is based on a determination by the U.S.

Fish and Wildlife Service that exports will not be detrimental to the survival of the species.

Table 5. Harvesting regulations by state.

1 7

Licensing required Fee Harvesting

Time

Restrictions

All

states

USFWS requires state

agreement for any export

PA

1. Vulnerable Plant license

Required for harvesting &

for cultivation except when

gathered for personal use,

pleasure or direct to the

consumer via farmers market

2. Harvester Certificate

3. PA Export Certificate

4. Dealer-Quarterly Reports

5. March 31- Weight slip for

any unsold ginseng

$50 Sept.1-Nov.

30

Only plants with at least three leaves having five

leaflets each may be harvested and only if all berries

are red. Berries must be planted at that site. April 1

to September 1 no one in PA shall possess green

harvested ginseng roots (Burkhart & Jacobson,

2004).

As of May 2002, individual State Forest Districts

stopped issuing collection permits for ginseng and

goldenseal. To determine if ginseng/goldenseal

collection is permitted on State Forest land, contact

the District Office in which collection is desired.

NC 1. Dealers Permit

a) Resident unlimited

b) Resident limited

(<100lbs)

c) non-resident

2. Annual Dealer Reports

3. Export certificate & fee

4. Import certificate with

state of origin

5. Certificate of cultivated

ginseng

$100

$50

$500

---

$3/lb.

Buying

season

Sept 1- Mar

31

Harvest

Sept 1-

Dec 1

Dealers permit from the Plant Industry Division

Ginseng may not be sold outside the season, no

exceptions ( the Statement indicating legal

collection of ginseng from one's own land is no

longer accepted)

The certificate for cultivated ginseng - allows a

grower to dig and sell ginseng at any time.

The NCNFS (2005) sets the price per pound, offers

permits from Sept 1 to Sept 30 which are good for

30 days only. Each permit allows a maximum of 3

pounds per person.

The following states all have restrictions, licensing and permits which can be accessed on a state by state

basis

MA Protected from take (picking, collecting, killing...)

and sale under the Massachusetts Endangered

Species Act

MN Sept1-

Dec31

Ginseng harvest regulated under Minnesota Rules,

Chapter 6282. Seeds are required to be planted,

plants must have 3 prongs.

KY license Aug 15-

Dec1

HB 362, the "Ginseng bill went into effect June 8,

2011 There is $1,000 fine for buying ginseng from

an unlicensed seller. Plants must have 3 prongs &

seeds must be replanted.

AL permit Sept 1-

Dec13

Minimum age-3 prongs, seeds must be planted at

site

AR Sept 1- Dec

1

No harvesting on state lands, minimum age 5 years,

3 prongs, seeds must be planted at the site

GA Aug 15-Dec

31

No harvesting on state lands, must have 3 prongs,

seeds must be planted at the site

IL 1st Sat in

Sept- Nov 1

No harvesting on state lands, minimum age 10

years, 4 leafed, planting encouraged at the site.

1 8

IN Sept 1-

Dec31

Does not require seeds to be replanted, plants must

have

1. 3 prongs, 2. a flowering or fruiting stalk or 3. 4

internodes on root. Note: allows harvesting during

flowering.

IA Sept 1-Oct

31

Requires seeds to be replanted, plants must have 3

prongs

Allows harvesting state forests, but not in state parks

or preserves.

MD Aug 20-Dec

1

Harvesting allowed in state forests, not in parks,

Plants must be 5 years old with 3 prongs.

MO Sept1-Dec

31

Seeds must be replanted, plants must have 3 prongs

or fruiting stems

NY Sept1-Nov

30

Seeds must be replanted, plants must have 3 prongs

OH Sept 1-

Dec31

Seeds must be replanted, plants must have 3 prongs

TN Aug 15-Dec

31

Seeds must be replanted, plants must have be 5

years old with 3 prongs.

VT Aug 20-

Oct10

Seeds must be replanted, plants must have be 5

years old with 3 prongs.

VA Aug 15-

Dec31

Seeds are not required to be re-planted and plants

must have a minimum of 3 prongs

WV Sept 1-

Nov 30

Seeds must be replanted, harvesting is limited to

plants with 3 prongs

WI Sept 1-

Nov 1

Plants must have 3 prongs & mature fruit before

they can be harvested, seeds must be replanted.

Export is currently regulated under the Convention on International Trade in Endangered Species

of Wild Fauna & Flora Agreement.

Plants can only be exported if they are shown to be legally obtained in a fashion not detrimental

to the survival of the species. States are given control over the management and certification for

export of P. quinquefolius within their boundaries and are required to develop and implement a

ginseng management program. They are required to submit specific export findings on a 3-year

schedule (Michigan State University [MSU] Board of Trustees, 2004).

P. quinquefolius is on the United Plant Savers „at risk' list and no wild harvest is recommended

(Gladstar & Hirsch, 2000).

Market Data - Harvesting Impact, Tonnage Surveys

Current 2011 market reports are available for a fee at Research and Markets

http://www.researchandmarkets.com/reports/1330243/the_2011_import_and_export_market_for

_ginseng

The following data is from the American Herbal Products Association.

1 9

In 2008 roots gathered in the wild were being sold for as much as $1,000/pound of dried root or

about $4/root (Janiskee, 2008).

Cultivation

Habitat: Prefers rich hardwood forest with nutrient rich soils (Maine Department of Natural

Resources [DNR], n.d.). Ginseng often occurs at the base of rock outcrops or on upland hill

slopes where nutrient-rich soil has collected. Ginseng's medicinal and economic value varies

according to how it has grown (Hertzog, 2010).

Cultivation: habitat

1. Wild Grown - These are plants that are naturally wild. They are considered to be the most

valuable.

Plant habitats are easily disturbed and plants may be damaged by campers, hikers or gatherers.

2. Wild-simulated- Seeds and rootlets are planted in a suitable habitat in its natural range.

3. Woods-grown- Seeds and rootlets are grown in woods similar in habitat to wild.

4. Field Cultivated - Seeds and rootlets are grown in fields with artificial shade. According to

Herzog (2010) once ginseng has been grown and harvested from a field, it cannot be grown in

that field again.

Table 6. Comparison chart (WildGrown.com, 2011)

Wild Grown Wild-Simulated Woods-Grown Field Cultivated

Origin Occurs naturally Seeds & Rootlets

planted

Seeds & rootlets

planted

Seeds & rootlets planted

2 0

Habitat Natural range in

natural habitat

Within its natural

range in suitable

ginseng habitat

grown in woods

similar to natural

habitat

Grown in fields with

artificial shade

Cultivation None planting seeds &

rootlets only

Raised beds built for

drainage

Intensive human

cultivation

Fungicide none none extensive extensive

Harvest

Method

Dug by hand Dug by hand Dug by machine Dug by machine

Price/grade highest high medium low

problems Selective harvests

required to maintain

population.

may need to remove

some forest canopy

Pesticides &

fertilizers. Not

organic

High labor costs

Pesticides, fungicides,

fertilizers

subject to mold

Organic Organic Not Organic Not organic

Cultivation: Seeds

Ginseng begins to produce berries (each with two seeds) in the third year. These should be cold

stratified and some sources suggest storing in damp sand for a year before planting. The law

may require that seeds from wild-gathered plants be planted immediately in the area surrounding

the original plants. Gathered seeds may be planted from the end of September until the end of

February, and will germinate April/May.

Plant seeds about 1/2" deep.

Cultivation: Roots

Ginseng does not reproduce vegetatively. Two-year old roots will produce berries the following

fall.

Plant the roots about 1 1/2 inches deep, with the roots placed longways across the soil. Do not

plant vertically. Cover the bed with mulch or rotten leaves.

Cultivation: Crop Treatments

Canada maintains a list of chemicals that are approved for use with ginseng.

1. "Glyphosate application is usually recommended in the first few weeks of April. For

glyphosate to work properly, the weeds should be green and actively growing. However,

it is important to ensure that no ginseng has emerged above the soil, or it could be

damaged. There have also been reports in the past that glyphosate residues on the straw

can damage ginseng if it emerges into the straw shortly after application. Closely examine

the stage of ginseng emergence before applying glyphosate products" (Ontario Ministry

of Agriculture, Food and Rural Affairs (OMAFRA), 2011.

2. "Quadris can be applied at any time and should be applied before ginseng begins to

emerge for maximum protection from Rhizoctonia. Quadris can be extremely toxic to

some varieties of apple and crabapple. Do not apply where there is the possibility of drift

onto apple trees. Application before a rainfall will improve penetration of the product to

the root zone" (OMAFRA, 2011).

3. "The first application of Bravo should be applied when the ginseng has 20% emerged.

2 1

For more information on ginseng pest management, consult OMAFRA Publication 610 –

Production Recommendations for Ginseng" (OMAFRA, 2011)

4. OMFRA (2011) also lists the following as approved for 2011:

1) Switch 62.5 WG Fungicide for the control of Botrytis blight (Botrytis cinerea)

and Alternaria leaf blight (Alternaria panax) on ginseng in Canada. Restrictions

include: A maximum of two (2) applications per season can be made at an interval

of 7 – 10 days if conditions remain favourable for disease development. In

general begin applications prior to or at the onset of disease. Do not apply within

7 days of harvest for ginseng.

2) Beleaf 50 SG Insecticide for the control of aphids. Allow a minimum of 7 days

between applications. Do not apply more than 3 times per year.

Harvesting

Roots should be dug in the fall after the above-ground parts die back. Take care to dig the entire

root with all of its branches. Wash as soon as possible, but do not scrub.

Grower's Associations

Appalachian Ginseng Foundation - http://www.a-spi.org/AGF/agfnl25.htm

Northwest Ginseng Growers Association- http://www.nwginseng.org/home.html

Ontario Ginseng Growers Association (OGGA)- http://www.ginsengontario.com/

Websites

Ginsengfaq - http://www.ginsengfaq.com/Ginseng/GinsengPrices.php

Wildgrown - http://www.wildgrown.com/index.php/Buying-Selling-Ginseng/

7. Summary – some possibilities moving forward

More than any other herbal species, P. quinquefolius plays a significant role in the history,

culture and economy of the Appalachian community. Until recently, research into therapeutic

applications has been focused on the Asian counterpart (P. ginseng), however the last decade has

seen a dramatic rise in the number of peer-reviewed publications investigating the biology,

phytochemistry, pharmacology of the indigenous species, as well as clinic effects on humans.

Initiatives such as the American Botanical Council‟s Ginseng Evaluation Program (Hall et al.,

2001) which help to set standards for ginseng products are increasingly likely to focus on P.

quinquefolius.

To date investigators have tended to focus on ginsenoside levels and their ratios in determining

herb quality, and linking different ginsenosides to certain biological activities. It seems likely

that levels of other constituents such as polyacetylenes and polysaccharides also influence

quality and efficacy of P. quinquefolius, and that more focus should be placed on the use of

whole root preparations, as well as of other plant sections. Now that a body of evidence is

accumulating from laboratory and animal studies including safety data, there is a need for more

human studies focusing on the potential benefits for cognition and memory, metabolic

impairment, stress, fatigue and immune deficient disorders.

2 2

Finally, any research on the benefits to human health of P. quinquefolius needs to be paralleled

by research on sustainable cultivation of this valuable Appalachian resource as well as policies

that ensure the maintenance and growth of wild populations and native habitat.

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Ap p en d ix 1 . Endangered, threatened, rare status

Global G3-G4 Michigan Natural Features Inventory. 1999. Michigan's special plants (20

October 2002). Michigan Department of Natural Resources, Michigan. Updated

list (April 9, 2009)

US federal

CT Sc special

concern Endangered, threatened & special concern plants (10 July, 2010). State of

Connecticut, Connecticut.

http://www.ct.gov/dep/cwp/view.asp?a=2702&q=323482&depNav_GID=1628

MI threatened

S2S3 Michigan Natural Features Inventory. 1999. Michigan's special plants (20

October 2002). Michigan Department of Natural Resources, Michigan. Updated

list (April 9, 2009)

3 5

NY S3-S4 New York, Department of Environmental Conservation. (2010) 2010 New York

Rare Plant Status Lists.

http://www.dec.ny.gov/docs/fish_marine_pdf/2010rareplantstatus.pdf

New York notes that they do not have a current count for ginseng and need such.

Maine S3 Maine Department of Conservation, Natural Areas Program, Rare Plants.

P. Quinquefolius last observation date: 2002

RI SE Rhode Island, one extant population. SE, G4, Rhode ISland Rare PLants

(2007) http://www.rinhs.org/wp-content/uploads/ri_rare_plants_2007.pdf

one extant population

NH S2

threatened New Hampshire Natural Heritage Inventory. 2011. Rare plant list for New

Hampshire Concord, NH: New Hampshire Heritage Bureau, Division of Forests

and Lands. Accessed online at

http://www.nhdfl.org/library/pdf/Natural%20Heritage/TrackingList-

PlantGeneral.pdf

NC special concern Plant Industry -Plant Conservation ( 2011) Ginseng Raleigh, NS: North Carolina

Department of Agriculture and Consumer Services. Accessed at

http://www.ncagr.gov/plantindustry/plant/plantconserve/ginseng.htm

MA special concern Natural Heritage and Endangered Species Program. 2008. Massachusetts list of

endangered, threatened, and special concern species. Westborough, MA:

Massachusetts Division of Fisheries and Wildlife accessed at

http://www.mass.gov/dfwele/dfw/nhesp/species_info/mesa_list/mesa_list.htm

PA vulnerable Thompson, S.A. 1997 (20 October 2002). Department of Conservation and Natural

Resources, Pennsylvania.

PA DNR. (2011) Vulnerable plants in Pennsylvania. Accessed at

http://www.dcnr.state.pa.us/forestry/wildplant/vulnerable_plants.aspx

TN commercially

exploited

S-CE

S3S4

Tennessee Natural Heritage Program. 2008. Rare plant list Nashville, Tennessee:

Department of Environment and Conservation, Division of Natural Areas.

Accessed at http://www.state.tn.us/environment/na/pdf/plant_list.pdf.