Islamset-Medicinal Plants-Radix Ginseng

Radix Ginseng

Definiton
Radix Ginseng is the dried root of panax ginseng C.A. Meyer (Araliaceae)

Synonyms
Panax schinseng Nees.
Other Panax species, including P. quinquefolius L. (American ginseng), P. notoginseng Burk. (San-chi ginseng), P. pseudoginseng Wall. ssp. japonicus Hara = P. japonicus C.A. Meyer (Japanese chikutsu ginseng) and P. notoginseng ssp. himalaicus (Himalayan ginseng) have also been referred to as "ginseng" and used medically. However, scientific documentaiton of these species is insufficient to justify the preparation of amonograph at this time.

Selected vernacular names
Chosen ninjin, ginseng, Ginsengwurzel, hakusan, hakushan, higeninjin, hongshen, hungseng, hungshen, hunseng, jenseng, jenshen, jinpi, kao-li-seng, korean ginseng, minjin, nhan sam, ninjin, ninzin, niuhuan, Oriental ginseng, otane ninjin, renshen, san-pi, shanshen, sheng-sai-seng, shenshaishanshen, shengshaishen, t'ang-seng, tyosenninzin, yakuyo ninjin, yakuyo ninzin, yeh-sahn-seng, yuan-seng, yaunshen.

Description
A perennial herb with characteristic branched roots extending from the middle of the main root in the form of a human figure. Stem erect, simple, and not branching. Leaves verticillate, compound, digitate, leaflets 5, with the 3 terminal leaflets larger than the lateral ones, elliptical or slightyly obovate, 4-15 cm long by 2-6.5cm wide; apex acuminate; base cuneate; margin serrulate or finely bidentate. In general, 1 leaf in the first year with 1 leaflet added annually until the sixth year. Inflorescence a small terminal umbel, hemispherical in early summer. Flowers polygamous, pink. Calyx vaguely 5-toothed. Petals 5, stamens 5. Fruit a small berry, nearly drupaceous, and red when ripe in autumn.

Plant material of interest: dried root
General appearance
The main root is fusiform or cylindrical, 2.5-20 cm long by 0.5-3.0cm in diameter; externally greyish yellow; upper part or entire root exhibiting sparse, shallow, interrupted, and coarse transverse striations and distinct longitudinal wrinkles; lower part beating 2-5 branching lateral root sand numerous slender rootlets with inconspicuous minute tubercles. Rhizomes 1-4cm long by 0.3-1.5cm in diameter, mostly constricted and curved, bearing adventitious roots and sparse depressed circular stem scars. Texture relatively hard, fracture yellowish white, cambium ring brownish yellow, strachy.

Geographical distribution
Mountain regions of China (Manchria), the Democratic People's Republic of Korea, Japan, the Republic of Korea, and the Russian Federation (eastern Siberia). It is commercially produced mainly by cultivation.

General identity tests
Macrosopic and microscopic examinations, microchemical tests, and thin-layer chromatographic analysis.

Chemical assays
Microchemical, thin-layer chromatographic, and spectrophoometric methods are used for the qualitative and quantitative analysis of ginsenosides. High performance liquid chromatography and liquid chromatography-mass spectrometry methods are also available.

Characterstic saponins known as ginsenosides, not less than 1.5% calculated as ginsenoside Rg1 (D-glucopytanosyl-6B-glucopyranosyl-20S-rpotopanaxatiol, relative molecular mass 800).

Major chemical constituents
The major chemical constituents are triterpene saponins. More than 30 are based on the dammarane structure, and one (ginsenoside Ro) is derived from oleanolic acid. The dammarane saponins are drivatives of either protopanaxadiol or protopanaxatriol. Members of the former group include ginsenoside Ra1-3, Rb1-3, Rc, Rc2, Rd, Rd2, and Rh2; (20S)-ginsenoside Rg3; and malonyl ginsenosides Rb1, Rb2, Rc, and Rd. Examples of protopanaxtriol saponins are ginsenosides Re2, Re3, Rf, Rg1, Rg2 and Rh1; 20-gluco-ginsenoside Rf; and (20R)- ginsenosides Rg2 and Rh1. Those considered most important are ginsenosides Rb1, Rb2, Rc, Rd, Rf, Rg1, and Rg2; Rb1, Rb2, and Rg1 are the most abundant. Representative structures are presented below.

Intrapenritoneal administration to rats of ginseng saponin fractions or the ginsenosides Rb1, Rb2, Rc, Rd, and Re elevated serum levels of adrenocorticotropic hormone (ACTH) and corticosterone. Pretreatment with dexamethasone, which blocks hypothalamus and pituitary functions, prevented ginseng saponin-mediated release of a CTH an dcorticosterone, and thereby demonstrated that the increase in serum corticosterone by ginseng occurs indirectly thrugh release of ACTH from the pituitary.

The immunomodulatory activity of ginseng appears to be at least partly responsible for its adaptogenic effect. Alcohol extracts of Radix Ginseng Stimulated phagocytosis in vitro, were mitogenic in cultured human lymphocytes, stimulated the production of interferon, and enhanced the activity of natural killer cells. Intraperitoneal administration of an extract of the drug to mice stimulate cell-meidated immunity against Semliki Foirest virus, elevated antibody levels against sheep red blood cells and natural killer cells, and stimulated the production of interferon.

Improvement in physical and mental performance has been observed in mice and rats after oral or intraperitoneal administration of the drug. Oral administration of ginseng saponin fractions to mice increased endurance and prolonged swimming time in swimming tests. However, two studies concluded that ginseng had no positive effects on the physical performance in mice and rats. The adaptogenic effects of Radix Ginseng are generally attributed to the ginsenosides. The ginsenosides have been shown to alter mechanisms of fueld homeostasis during prolonged exercise, by increasing the capacity of skeletal muscle to oxidize free fatty acids in preferenc to glucose for cellular energy production. Other constituents of Radix Ginseng, such as vanillic an dsalicylic acid, have also been reported to have "anti-fatigue" activity in rats. Furthermore, the antioxidant activity of ginseng was associated with both the ginsenosides and th eflavonoid constituents. The ginsenosides protected pulmonary vascular endothelium against free-radical-induced injury.

Mice given ginseng extract or ginsenosides Rb1 and Rg2 orally during passiveavoidance response tests showed an improvement in learning ability which was negtively influenced by stress, and rats showed improved retention of learned behaviour. Ginsenosides Rg1 and Rb1 are the active nootropic constituents of the drug, an dimprove memory and learning in normal as well as cognition-impaired animals. The mode of action involves an increase in the synthesis and release of acetylcholine, and a decreasse of brain serotonin levels. In cerebral and coronary blood vessels, extracts of Radix Ginseng produced vasodilatation, which improved brain and coronary blood flow. The vasodilatory activity of the ginsenosides appears to be primarily due to relaxation of vascular smooth muscles. The ginsenosides block the contricting effects of norepinephrine in isolated aorta strips, and inhibit the uptake of 45 Ca2+ in the membrane and sarcolemma of rabbit heart tissue. Inhibition of Ca2+ uptake in the muscle membrane contributes to the mechanism of vasodilatation.

A number of polypeptide and glycans isolated from Radix Ginseng, named GP and panaxans A-E, respectively, have demonstrated hypoglycaemic panaxans A and B, have been shown to stimulate hepatic glucose utilization by increasing the activity of glucose-6-phosphate 1-dehydrogenase, phosphorylase a, and phosphofructokinase. Panaxan A did not affect plasma insulin levels or insulin sensitivity, but panaxan B elevated the plasma insulin level by stimulating insulin secretion from pancreatic islets, and further enhanced inslulin sensitivity by increasing insulin binding to receptors. The panaxans are not activce after oral administration. Administration of GP (intravenously or subcutaneously) to mice or rats decreased blood glucose and liver glycogen levels. Radix Ginseng also contains a number of other constituents with hypoglycaemic activity. denosine, isolated from a water extract of Radix ginseng, enhanced lipogensesis and cyclic AMP accumulation of adipocytes, and some of the ginsenoosides inhibited ACTH-induced lipolysis, suppressed insulin-stimulated lipogenesis, and stimulated the release of insulin from cultured islets.

Subcutaneous administration of a ginseng extract enhanced the mating behaviour of male rats. The drug further stimulated spermatogenesis in rat, and rabbit testes, and increased the motility and survival of rabbit sperm outside the body.

Intragastric or intradermal administration of an ethanol extract of the drug to rats decreased histamine-, pentagastrin-, carbachol- and vagal stimulation- induced gastric secretion, and inhibited gastric ulcers induced by stress or by pyloric ligation.

Liver-protectant activity of ginseng has been demonstrated in in vitro and in vivo. Intraperitoneal administration of Radix Ginseng extracts to normal and dexamethasone-treated rats did not influence the blood chemistry of normal rats, but it decreased aspartate aminotransferase and alanine aminotransferase levels in dexamethasone-treated animals, thereby demonstrating a liver-protectant effects. However, another study demonstrated that an intraperitoneal injection of a methanol extract of Radix Ginseng had no protective activity against carbon tetrachloride-induced hepatotoxicity in rats.

Clinical pharmacology
Antifatigue activity
The results of clinical studies measuring increased performance and antifatigue effects of ginseng extracts are conflicting and, in general, most studes suffer from poor methodology, lack of proper controls, and no standardization of the ginseng extracts used. The influence of chronic Radix Ginseng administration (2g/day orally for 4 weeks) on substrate utilization, hormone production, endurance, metabolism, and perception of effort during consecutive days of exhaustive exercise in 11 naval cadets was reported. No significant differences were observed between the control group receiving the ginseng supplementation. Another clinical trial with eight participants reported no significant difference between placebo and ginseng adminsitration during exhaustive exercise after 7 days of treatment. A randomized, double-blind, cross-over study sought the effects of ginseng on circulatory, respiratory, and metabolic functions during maximal exercise in 50 men (21-47 years old). Total tolerated workload and maximal oxygen uptake were signifcantly higher following ginseng administration than with placebo. At the sam eworkload, oxygen consumption, plasma lactate levels, ventilation, carbon dioxide production, and heart rate during exercise were all lower in the ginseng treatment group. The results indicated that the ginseng preparations effectively increased the work capacity of the participants by improving oxygen utilization. A placebo-controlled, cross-over study determined the effects of ginseng on the physical fitness of 43 male triathletes. The participants received 200 mg of a ginseng preparation twice daily for two consecutive training periods of 10 weeks. No significant changes were observed during the first 10-week period, but ginseng appeared to prevent the loss of physical fitness (as measured by oxygen uptake and oxygen pulse) during the second 10-week period. Two further studies with athletes given 100 mg of a standardized ginseng extract twice daily for 9 weeks reported significant improvement in aerobic capacity and reduction in blood lactate and heart rates, but placebos or controls were not used in either of the two studies. Further extension of these studies using placebo-controlled, double-blind trials demonstratedsiginificant improvement in the ginseng group as compared with the placebo group. Similar results were reported in another study on athletes, and the differences between the ginseng and placebo groups lasted for approximately 3 weeks after the last ginseng dose. The effects of 1200mg of Radix Ginseng in a placebo-controlled, double-blind cross-over study in fatigued night nurses were assessed and th eresults were compared with placebo and with effects on nurses engaged in daytime work. Ginseng restored ratings on tests of mood, competence, and general performacne, and the study concluded that ginseng had anti-fatigue activity.

Aqueous and standardized ginseng extracts were tested in a placebo-controlled, double-blind study for immunomodulatory actions. Sixty healthy volunteers were divided into three groups of 20 each and were given either a placebo or 100mg of aqueous ginseng extract or 100mg of standardized ginseng extract, every 12 hours for 8 weeks. Blood samples drawn from the volunteers revealed an increase in chemotaxis of polymorphonuclear leukocytes, the phagocytic index, and the total number of T3 and T4 lymphocytes after 4 and 8 weeks of ginseng therapy, as compared with the placebo group0. The group receiving the standardized extract also increased their T4:T8 ratio and the activity of natural killer cells. The conclusion of this study was that ginseng extract stimulated the immune system in humans, and that the standardized extract was more effective than the aqueous extract.

Psychomotor activity
Adouble-blind, placebo-controlled clinical study assessed the effect of standardized ginseng extract (100 mg twice daily for 12 weeks) on ppsychomotor performance in 16 healthy individuals. Various tests psychomotor peformance found a favourable effect on attention, processing, integrated sensory-motor function, an dauditory reaction time. The study concluded that the drug was superior to the placebo in improving certain psychomotor functions in healthy subjects.

Antidiabetic activity
Radix Ginseng has been shown in clinical studies to have beneficial effects in both insulin-depenedent and non-insulin-dependent diabetic patients. Oral administration of ginseng tablets (200mg daily for 8 weeks) to 36 non-insulin-dependent patients elevated mood, improved physical performance, reduced fasting blood glucose and serum aminoterminal propeptide of type III procollagen concentrations, and lowered glycated haemoglobin.

Impotence
Ginseng extracts improved sperm production in men and may have some usefulness in treating impotence. The ginsenosides, which appear to be the active components, are thought to depress blood prolactin levels, thereby increasing libido. In one clinical study, 90 patients with erectile dysfunction were treated with ginseng saponins (600mg orally perday). Treatment improved rigidity, tumescence, and libido, but not the frequency of coitus.

Contraindications
None.

Warnings
No information available.

Precautions
General
Diabetic patients should consult a physician prior to taking Radix Ginseng, as ginseng intake may slightyly reduce blood glucose levels.

Drug interactions
There are two reports of an interaction between Radix Ginseng and phenelzine, a monoamine oxidase inhibitor. The clinical significance of this interaction has not been evaluated.

Drug and laboratory test interactions
None reported

Carcinogenesis, mutagenesis, impairment of fertility
Radix Ginseng is not carcinogenic or mutagenic in vitro, and does not have any effect on fertility.

Pregnancy: teratogenic effects
Radix Ginseng is not teratogenic in vivo.

Pregnancy: non-teratogenic effects
The safety of Radix Ginseng for use in pregnancy has not been established.

Nursing mothers
The safety and efficacy of Radix Ginseng use in children have not been established.

Adverse reactions
Various researchers who studied Radix Ginseng extracts using conventional toxicological methods in five different animal models reported no acute or chronic toxicity of the extract.

On the basis of Radix Ginseng's long use, and the relative unfrequency of significant demonstrable side-effects, it has been concluded that the use of Radix Ginseng is not associated with serious adverse effects if taken at the recommended dose. However, in Siegel's open study of 133 patients ingesting large quantities, ginseng was reported to result in hypertension, nervousness, irritability, diarrhoea, skin eruptions, and insomnia, which were collectively called ginseng abuse syndrome (GAS). Critical analysis of this report has shown that there were no controls or analyses to determine the type of giseng being ingested or the constituents of the preparation taken, and that some of the amounts ingested were clearly excessive (as much as 15g per day, where the recommended daily dose is 0.5-2g). When the dose was decreased to 1.7g/day the symptoms of the "syndrome" were rare. Thus the only conclusion that can be validly extracted from the Siegel study is that the excessive and uncontrolled intake of ginseng products hsould be avoided. One case of gisneng-associated cerebral arteritis has been reported in a patient consuming a high dose of an ethanol extract of ginseng root (approximately 6g in one dose). HOwever, again the type an dquantity of ginseng extract were not reported. Two cases of mydriasis and distrubance in accommodation, as well as dizziness have been reported after ingestion of large doses (3-9g) of an unspecified type of ginseng preparation.

Estrogenic-like side-effects have been reported in both premenopausal and postmenopausal women following th euse of ginseng. Seven cases of mastalgia and one caseof vaginal bleeding in a postmenopausal woman were reported after ingestion of unspecified ginseng products. An increased libido in premenopausal women has also been reported. Specific studies on the possible hormonal side-effects of gisneng have been carried out with a standardized ginseng extract. Under physiological conditions, there is no interaction of the gineng extract with either cytosolic estrogen receptors isolated from mature rat uterus or progesterone receptors from human myometrium. Furthermore, clinical studies have demonstrated that a standardized ginseng extract does not cause a change in male and female hormonal status.

Posology
Unless otherwise prescribed, daily dose (taken in the morning): dried root o.5-2g by decoction; doses of other preparations hsould be calculated accordingly.