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2006 The Japanese Pharmacological Society Use of Ginseng in Medicine With Emphasis on Neurodegenerative Disorders Khaled Radad1,*, Gabriele Gille2, Linlin Liu3, and Wolf-Dieter Rausch41Department of Pathology and Clinical Pathology, Faculty of Veterinary Medicine, Assiut University, Assiut, Egypt2Department of Neurology, Technical University, D-01307 Dresden, Germany3Jilin University, Changchun 130012, China4Institute for Medical Chemistry, Veterinary Medical University, A-1210 Vienna, Austria Received November 17, 2005; Accepted January 27, 2006 Ginseng, the root of Panax species, is a well-known herbal medicine. It has been used as a traditional medicine in China, Korea, and Japan for thousands of years and is now apopular and worldwide used natural medicine. The active ingredients of ginseng are ginsenosideswhich are also called ginseng saponins. Recently, there is increasing evidence in the literature onthe pharmacological and physiological actions of ginseng. However, ginseng has been usedprimarily as a tonic to invigorate week bodies and help the restoration of homeostasis. Currentin vivo and in vitro studies have shown its beneficial effects in a wide range of pathologicalconditions such as cardiovascular diseases, cancer, immune deficiency, and hepatotoxicity.
Moreover, recent research has suggested that some of ginseng’s active ingredients also exertbeneficial effects on aging, central nervous system (CNS) disorders, and neurodegenerativediseases. In general, antioxidant, anti-inflammatory, anti-apoptotic, and immune-stimulatoryactivities are mostly underlying the possible ginseng-mediated protective mechanisms. Next toanimal studies, data from neural cell cultures contribute to the understanding of these mecha-nisms that involve decreasing nitric oxide (NO), scavenging of free radicals, and counteractingexcitotoxicity. In this review, we focus on recently reported medicinal effects of ginseng andsummarize the current knowledge of its effects on CNS disorders and neurodegenerativediseases.
Keywords: ginseng, ginsenoside, central nervous system, herbal medicine, Chinese herb which means “human” as ginseng roots resemble thehuman body (1). In China, ginseng roots are harvested Ginseng refers to the root of several species in the when the plant is 3 – 6-year-old, and then the roots are plant genus Panax (C.A. MEYER Araliaceae). Among submitted to air drying (white ginseng) or are steamed them, Panax ginseng is the most widely used ginseng (red ginseng). Interestingly, after these two ways of and is indigenous to the Far East countries (most notably treatment, the roots differ in their content of saponins (1) China and Korea). Panax ginseng was first cultivated and this may be the reason for the variable actions of around 11 BC and has a medical history of more than different ginseng products. Other species of the genus five thousand years. The genus name of Panax ginseng Panax include Panax quinquefolius (found in southern “Panax” was given by the Russian botanist C.A.
Canada and in the United States), Panax japonicus Meyer, and it is derived from the Greek words “pan” (grown in Japan), and less frequently, Panax notogin- meaning all and “axos” meaning cure. The species name seng (grown in China), Panax pseudoginseng (grown in “ginseng” comes from the Chinese word “rensheng” Nepal and eastern Himalayas), and Panax vietnamensis(grown in Vietnam) (2).
Ginseng is a widespread herbal medicine (3) and it Published online in J-STAGE: March 4, 2006 has served as an important component of many Chinese prescriptions since thousands of years (4, 5). Today it well as to reduce the detrimental effects of the aging still occupies a permanent and prominent position in the herbal (best-sellers) list and is considered the mostwidely taken herbal product in the world (6). Moreover, it is estimated that more than six million Americans areregularly consuming ginseng products (7). Ginseng is Ginseng rescues neuronal cells either in vivo or in vitro believed not only to engender physical benefits, but also Recently, it has been shown that ginseng and its to have positive effects on cognitive performance and components, ginsenosides, have a wide range of actions in the CNS (21). These effects include increased cell Ginsenosides or ginseng saponins are the principle survival, extension of neurite growth, and rescuing of active ingredients in ginseng and more than thirty neurons from death in consequence of different insults different ginsenosides have been identified (8, 9).
either in vivo or in vitro. Sugaya et al. (22), Himi et al.
Ginsenosides are unique to Panax species, many of (4), and Mizumaki et al. (23) reported that ginseng roots which exist in minute amounts and are believed to be appeared to facilitate survival and neurite extension of responsible for most of ginseng’s actions (10 – 13).
cultured cortical neurons, and Kim et al. (24) showed Additionally, ginsenosides operate by many mecha- that ginsenosides Rb1 and Rg3 protected neurons from nisms and it was suggested that each ginsenoside may glutamate-induced neurotoxicity. Following forebrain have its own specific tissue-dependent effects (14). The ischemia in gerbils, Wen et al. (5) and Lim et al. (25) basic structure of ginsenosides is similar. They consist of demonstrated that central infusion of ginsenoside Rb1 a gonane steroid nucleus with 17 carbon atoms arranged rescued the hippocampal CA1 neurons against lethal in four rings. The characteristic biological responses damage of cellular hypoxia. Using a spinal neuron for each ginsenoside are attributed to the differences in model, ginsenosides Rb1 and Rg1 proved to be poten- the type, position, and number of sugar moieties tially effective therapeutic agents for spinal cord injuries attached by the glycosidic bond at C-3 and C-6 (15).
as they protected spinal neurons from excitotoxicity Based on their structural differences, they can be induced by glutamate and kainic acid and oxidative classified into three categories: the panaxadiol group stress induced by hydrogen peroxide (26).
(e.g., Rb1, Rb2, Rb3, Rc, Rd, Rg3, Rh2, Rs1), thepanaxatriol group (e.g., Re, Rf, Rg1, Rg2, Rh1), and the Ginseng’s role in Parkinson’s disease models oleanolic acid group (e.g., Ro) (5, 16). The ginsenoside A number of studies have recently described the content of ginseng is varying depending on the Panax beneficial effect of ginseng and its main components, species, the plant age, the part of the plant, the preserva- ginsenosides, on some neurodegenerative disease models.
tion method, the season of harvest, and the extraction Special interest has been paid on Parkinson’s disease (PD) models either in vivo or in vitro. In an in vivo Nowadays, herbal medicine has received much model, Van Kampen et al. (21) reported that prolonged attention and is recommended as a natural alternative oral administration of ginseng extract G115 significantly to maintain one’s health. Therefore, we try in this protected against neurotoxic effects of parkinsonism- review to focus on the recently reported medicinal inducing agents such as 1-methyl-4-phenyl-1,2,3,6- effects of ginseng and to summarize the results of tetrahydropyridine (MPTP) and its active metabolite 1- different scientific studies using ginseng particularly in methyl-4-phenylpyridinium (MPP+) in rodents. He central nervous system (CNS) disorders.
found that ginseng-treated animals sustained lessdamage and TH+ neuronal loss in substantia nigra pars compacta (SNpc) after MPP+ exposure. Likewise,reduction of TH immunoreactivity in the striatum was Ginseng products are usually used as a general tonic effectively diminished as a result of ginseng treatment and adaptogen to help the body to resist the adverse compared to MPP+-exposed animals. Similarly, striatal influences of a wide range of physical, chemical, and dopamine transporter (DAT) was significantly preserved biological factors and to restore homeostasis (1, 19).
due to ginseng treatment. In vitro studies showed that These tonic and adaptogenic effects of ginseng are ginseng saponins enhanced neurite growth of dopamin- believed to enhance physical performance (including ergic SK-N-SH neuroblastoma cells (27). Recently, we sexual function) and general vitality in healthy indi- demonstrated that ginsenosides Rb1 and Rg1 increased viduals, to increase the body’s ability to fight stress in the survival of primary cultured dopaminergic cells and stressful circumstances, and to support resistance to promoted their neuritic growth after exposure to either diseases by strengthening normal body function as MPP+ or glutamate (28, 29). Interestingly, Tanner and Ben-Schlomo (30) speculated that geographic variations General mechanisms and processes underlying neuro- in PD prevalence might reflect ginseng consumption as in North America, PD occurs in approximately 200 cases In addition to the mechanisms involved in neuro- per 100,000 persons compared to only 44 cases per protection of dopaminergic neurons, there exist addi- 100,000 in China. On the other hand, this variation in tional data demonstrating the protective potential of PD prevalence in different populations may strengthen ginseng against various neuronal insults. Potentiation the familial theory of PD rather than consumption of of NGF by ginseng is also involved in other neuronal models. Nishiyama et al. (40) and Liao et al. (26) Although the processes and mechanisms underlying reported that ginsenosides increased neuronal survival the neuroprotective effects of ginseng upon dopaminergic and promoted neurite outgrowth of cultured chick neurons remain to be elucidated, several reports demon- embryonic dorsal root ganglia and cultured spinal cord strate the inhibitory role of ginseng on MPP+ uptake in neurons, respectively. Moreover, ginsenosides alleviated dopaminergic neurons, the suppression of oxidative oxidative stress by scavenging of free radicals, inhibiting stress induced by autooxidation of dopamine, the of NO production which usually accompanies glutamate attenuation of MPP+-induced apoptosis, and the excitotoxicity, inducing superoxide dismutase (SOD1) potentiation of nerve growth factor (NGF). It has been and catalase genes and reducing lipid peroxidation (24, shown that certain ginsenosides inhibit dopamine uptake 41 – 43). Also, it has been suggested that ginseng, in into rat synaptosomes (31) and consequently ginseng particular ginsenoside Rg3, inhibits both N-methyl-D- could potentially provide protection against MPP+ aspartate (NMDA) and non-NMDA glutamate receptors through blockade of its uptake by dopaminergic neurons (44, 45) which contribute significantly to many neuro- (21). Ginsenoside Rg1 was shown to interrupt logical disorders particularly brain ischemia, trauma, dopamine-induced elevation of reactive oxygen species stroke, and seizures (46 – 48). Inhibition of NMDA (ROS) or NO generation in pheochromocytoma cells and non-NMDA receptors by ginsenosides resulted in (PC12) (32). Kim et al. (33) and Chen et al. (34) a reduction of Ca2+ over-influx into neurons and thus reported that Ginseng radix attenuated MPP+-induced protected cells from neurodegenerative processes apoptosis as it decreased the intensity of MPP+-induced evoked by Ca2+ overload (26, 49). These findings are DNA laddering in PC12 cells and ginsenoside Rg1 had in line with our recent results since we found that protective effects against MPTP-induced apoptosis in ginsenosides Rb1 and Rg1 increased the red / green the mouse substantia nigra. These anti-apoptotic effects fluorescence ratio of mitochondrial JC-1 staining in of ginseng may be attributed to enhanced expression of primary dopaminergic cell culture after glutamate treat- Bcl-2 and Bcl-xl, reduced expression of bax and nitric ment, indicating the possible role of both ginsenosides oxide synthase (NOS), and inhibited activation of in attenuating mitochondrial depolarization induced by caspase-3. Ginseng may also reverse the neurotoxic glutamate excitotoxicity and subsequent Ca2+ over- effects of MPP+ through elevation of NGF mRNA influx into mitochondria (28). Additionally, inhibition expression (21). In accordance, Salim et al. (35) showed of Na+ channels (50) and improved energy metabolism that ginsenosides Rb1 and Rg1 elevate NGF mRNA by retarding ATP breakdown in cultured neurons are expression in rat brain and Rudakewich et al. (36) also involved (51). Furthermore, some reports showed concluded that both ginsenosides potentiate NGF- that neuroprotection by ginseng may be, in part, due to induced neurite outgrowth in cell culture. Furthermore, its effect on glial cell populations. In this respect, it it has been reported that ginsenosides Rb1, Rg1, Rc, and has been reported that ginseng total saponins prevented Re inhibited tyrosine hydroxylase activity and exhibited astrocytic swelling induced by glutamate (52) and anti-dopaminergic action since they reduced the avail- ginsenoside Rg1 inhibited microglial respiratory burst ability of dopamine at presynaptic dopamine receptors activity and decreased the accumulation of NO produced There are few reports concerning the effect of ginseng on other neurodegenerative diseases. For example, Jiang Modulatory effect of ginseng on neurotransmission et al. (38) and Lee et al. (39) reported that ginseng and its A number of studies have shown that some ginseno- components prevent neuronal loss in amyotrophic lateral sides can modulate neurotransmission in the brain.
sclerosis models and Ginseng radix has also been used Ginsenosides Rb1 and Rg1, the most abundant ginseno- for treatment of Alzheimer’s disease.
sides in ginseng root, can modulate acetylcholine releaseand re-uptake and the number of choline uptake sites,especially in the hippocampus (54). They also increasecholine acetyltransferase levels in rodent brains (35, 55).
These results suggested that these compounds may finding of Sorensen and Sonne (78) who reported that improve central cholinergic function in humans and may ginseng intake did not enhance memory functions.
be used to treat memory deficit (36). It has also beenreported that ginsenosides increased dopamine and norepinephrine in the cerebral cortex (56), which mayexplain the favorable effects of ginseng extract upon Ginseng has been shown to produce a number of attention, cognitive processing, integrated sensory- actions on the cardiovascular system. Intravenous motor function, and auditory reaction time in healthy administration of ginseng to anesthetized dogs resulted subjects (57). Additionally, it has been shown that in reduction, followed by an increase in blood pressure, ginseng total saponins can modulate dopaminergic and transient vasodilatation (79). In rats and rabbits, activity at both pre-synaptic and post-synaptic receptors Lei and Chiou (80) and Kim et al. (81) found that (58); and they can block behavioral sensitization extracts of Panax notoginseng decreased systemic blood induced by psychostimulants such as morphine (59), pressure and ginsenosides exerted relaxing effects in cocaine (58), methamphetamines (60), and nicotine rings of rat and rabbit aorta, respectively. This relaxing (61 – 63). Furthermore, it was found that ginseng effect of ginseng and its active constituents on the increased serotonin in the cortex (64), ginseng saponins cardiovascular system is partially due to the release of raised the levels of biogenic amines in normal rat brain endothelial NO. Researchers have reported that chronic (65), ginsenoside Rg2 directly interacted with nicotinic feeding of rabbits with ginsenosides may enhance receptor subtypes (66), and ginseng administration lead indirectly vasodilatation by preventing NO degradation to regulation of GABAergic transmission in animals by oxygen radicals such as superoxide anions (82).
Ginsenosides have depressant action on cardiomyocytecontraction which may be mediated, in part, through increased NO production (83). Korean red ginseng can The use of herbal medicine, particularly ginseng, for improve the vascular endothelial dysfunction in patients improving cognitive performance has become increas- with hypertension possibly through increasing NO (84).
ingly popular during recent years and some studies have In addition to endothelium-derived NO release, Li et al.
shown its enhancing effects on learning and memory (85) reported that ginsenoside-induced vasorelaxation either in aged and / or brain damaged rodents (69, 70).
also involves Ca2+ activated K+ channels in vascular For example, significant improvement in learning and memory has been observed in aged and brain-damaged It has also been reported that crude saponin fractions rats after local administration of ginseng powder (71 – of Korean red ginseng enhanced cerebral blood flow in 73). In humans, Terasawa et al. (74) and D’Angelo et al.
rats (86) and ginsenosides reduced plasma cholesterol (57) have shown that ginseng or ginseng extract had levels and the formation of atheroma in the aorta of significant effects on neurological and psychiatric rabbits fed on a high cholesterol diet (82). This anti- symptoms in aged humans and psychomotor functions in atherosclerotic action of ginseng components is appar- healthy subjects, respectively. This positive effect of ently due to the correction in the balance between ginseng on cognition performance is due to the direct prostacyclin and thromboxane (87), inhibition of 5- action of ginseng on the hippocampus (75). Consistent hydroxytryptamine (5-HT) release from, and adrenaline with the study of Kurimoto et al. (75), Wen et al. (5) and thrombin-induced aggregation of platelets (88), demonstrated that red ginseng, ginseng powder, and regulation of cGMP and cAMP levels, and prolongation ginsenoside Rb1 administration for seven days prior to of the time interval between conversion of fibrinogen to ischemia rescued the hippocampal CA1 pyramidal fibrin (89). Also, ginsenosides have been shown to be neurons and subsequently ameliorated learning deficits relatively potent platelet activating factor antagonists in gerbils. Moreover, Shen and Zhang (76) suggested (90). In parallel with these findings, Nakajima et al. (91) that the influence of ginsenoside Rg1 on the proliferat- concluded that red ginseng was found to promote the ing ability of neuronal progenitor cells may serve as an proliferation of vascular endothelial cells, to inhibit the important mechanism underlying its nootropic and anti- production of endothelin which is known to constrict aging effects particularly on learning and memory.
blood vessels resulting in raising blood pressure, and On the other hand, Persson et al. (77) have reported in to increase the production of IL-1β, which suppresses a more recent study that regular use of ginseng during the formation of thrombin in blood coagulation. In the long periods of time (up to 2 years) by healthy partici- same direction, Yuan et al. (92) used cultured human pants did not provide any quantifiable beneficial effects umbilical vein endothelial cells to conclude that on memory performance. This result coincides with the American ginseng, Panax quinquefolium L. extracts, significantly decreased endothelin concentration in a inhibited tumor angiogenesis and metastasis (112), dose and time dependent manner after thrombin treat- while ginsenoside Rh1 inhibited proliferation of the NIH 3T3 mouse fibroblast cell line (113).
The role of ginseng in angiogenesis has also been Some of the mechanisms and processes underlying reported. Ginsenoside Rg1 promoted functional neo- the above cited beneficial effects of ginseng against vascularization into a polymer scaffold in vivo and cancer have been stated by Surh et al. (114) and others.
tubulogenesis by endothelial cells in vitro (93). There- Using both in vivo and in vitro models, Surh et al. (114) fore, ginsenoside Rg1 might be useful in wound healing reported that ginsenoside Rg3 treatment caused marked as it can induce therapeutic angiogenesis.
suppression of TPA-induced cyclooxygenase-2 (COX-2) expression in mouse skin and in human breast Anti-inflammatory and anti-allergic effects of ginseng epithelial cells (MCF-10A). Also, he observed the samesuppressive effect on NF-κB in mouse skin and extra- More recently, the role of ginseng in modulation of cellular regulated protein kinases (ERK) activation in inflammatory and allergic processes has been docu- TPA-stimulated MCF-10A cells. Consistent with the mented by some researchers. For example, Ginseng root results of Surh et al. (114), Keum et al. (115) reported saponins exerted an inhibitory effect on IL-1β and IL-6 that topical application of ginseng extract prior to each gene expression in a chronic inflammation model of topical dose of the tumor promoter TPA markedly aged rats, ginsenosides Rb1 and Rg1 decreased TNF-α lowered the papilloma formation in mouse skin and production by murine macrophages, pretreatment with caused substantial reduction in epidermal ornithine ginsenoside Rg3 abrogated cyclooxygenase-2 expres- decarboxylase (ODC) activity and suppressed the sion in response to 12-O-tetradecanoylphorbol-13- expression of its mRNA. All of the above mentioned acetate (TPA) in mouse skin, and ginsenosides Rb1 and enzymes and factors are, in part, involved in tumoro- Rc suppressed histamine and leukotriene release during genesis. COX-2 was upregulated in transformed cells the activation of guinea-pig lung mast cells in vitro and in various forms of cancer. Its overexpression (94 – 97). An additional anti-inflammatory action by inhibited apoptosis and increased the invasiveness of ginseng has been mentioned by Li and Li (98). They tumor cells (116). ODC is a rate-limiting enzyme in the reported that total saponins of Sanchi (Panax pseudo- biosynthesis of polyamines that play a pivotal role in cell ginseng notoginseng) reduced the level of the intra- proliferation and tumor promotion (117). The mitogen- cellular Ca2+ concentration in neutrophils and Kim et al.
activated protein kinase (MAPK) cascade is responsible, (99) found that ginseng had radioprotective effects in part, for upregulation of COX-2 as specific inhibitors against γ-ray-induced DNA double strand breaks in of the corresponding MAPK abolish the induction of cultured murine spleen lymphocytes. Furthermore, it COX-2 and result in production of prostaglandin E2 was found that ginseng promoted the apoptosis of renal (114). NF-κB is a ubiquitous eukaryotic transcription interstitial fibroblasts and thus affected renal interstitial factor implicated in cellular proliferation and malignant fibrosis (100). Ginseng also has immunostimulant transformation. Its activation by oncogenic Ras is an effects as it enhances interferon induction, phagocytosis, essential early event prior to malignant transformation natural killer (NK) cells, and B and T cells in various animal species including mice and guinea pigs and alsoin humans (101 – 104). Hu et al. (105) reported that ginseng stimulated the immune system of dairy cows asit activated the innate immunity of cows and contributed Ginseng effects on male sex behavior have been to the cow’s recovery from mastitis.
discussed recently by Murphy et al. (119), Nocerinoet al. (1), and Murphy and Lee (14). In brief, it has been shown that ginseng is an essential constituent in tradi-tional Chinese medicine for treatment of sexual impo- With respect to its anti-carcinogenic effects, it was tence (1), and Panax ginseng and Panax quinquefolium reported that chronic intake of Panax ginseng C.A.
enhanced male copulatory behavior in rats (119, 120).
MEYER decreased the incidence of cancers such as lung, Consistently with these finding, Choi et al. (121) con- gastric, liver, and colorectal tumors (106, 107). Ginseno- firmed in a clinical study the efficacy of Korean red side Rh2 has been shown to suppress proliferation in a ginseng for erectile dysfunction in 30 patients. These number of human cancer cells including breast, prostate, positive aphrodisiac effects of ginseng may be attributed hepatic, and intestinal cancer, but also in animal cell to the enhancement of nitric oxide release from endo- lines (108 – 111). Ginsenosides Rb1, Rb2, and Rc thelial cells of penile corpus cavernosum and consequent relaxation (122). Furthermore, Fahim et al. (123) and ginseng polysaccharides compared to patients not Bahrke and Morgan (124) reported that Panax ginseng receiving ginseng polysaccharides. Moreover, one of produced a dose-related increase in serum testosterone the future promising effects of ginseng is treatment of levels and American ginseng reduced the plasma level of the irritable bowel syndrome (IBS) since it was shown prolactin hormone in rats. Testosterone might mediate that protopanaxatriol (PT) ginsenosides attenuated the the heightened copulatory behavior in ginseng-treated experimentally-induced visceral hypersensitivity (130).
animals, while prolactin altered it. Taken together, these Sparsely, ginseng has been reported to possess positive results suggest that both ginseng species may have direct effects against herpes simplex type-II infections and actions on the anterior pituitary gland and / or on the diabetes mellitus, common cold symptom complex, hypothalamic dopaminergic mechanisms (14).
ethanol-induced gastric lesion, and aspirin-inducedgastric ulcers (131). Another study showed that ginseng helped postmenopausal women to alleviate climactericsyndromes, particularly fatigue, insomnia, and depres- Based on the medical history and experimentally- promising results of ginseng, ginseng and its compo-nents have recently been introduced into the clinic. It has been used as a curative substance to enhance the generalperformance, immunity, and mood of patients, parti- Ginseng and its constituents, ginsenosides, have a cularly post-operatively. The relevant clinical trials number of other pharmacological actions including regarding the effect of ginseng on cardiovascular dis- antipyretic activity, increase of gastro-intestinal tract eases are managing hypertension and improving cardio- motility, and acceleration of glycolysis and cholesterol vascular function (125). It could also improve cardiac synthesis as well as increased synthesis of serum pro- function in patients suffering from congestive heart teins (36). Another important biological effect reported failure (126). The authors have observed that the levels for Panax ginseng or its saponins is hypoglycemic and of serum cardiac troponin T (cTnT), a specific marker antihyperglycemic activity (133, 134). It has been shown reflecting myocardial injury, was effectively reduced that ginsenoside Rg1 increased the number of insulin after treatment with the ginseng-containing Shenmai receptors (135) and panaxan B, the main constituent of injection in congestive heart failure patients (126).
Panax ginseng for hypoglycemic activity, increased the Some current studies have shown the role of ginseng plasma insulin level and enhanced insulin sensitivity in reducing the side effects of either chemo- or radio- (133). Ginseng also shows anti-stress activities against therapy in cancer patients. For example, ginseng could physical (i), chemical (ii), and biological (iii) stressful inhibit the recurrence of American Joint Committee on circumstances. For instance, i) it was shown that Cancer (AJCC) stage III gastric tumor and showed treatment with root saponins partially prevented the immunomodulatory activities during post-operative rectal temperature decline in normal rats exposed to cold chemotherapy. Moreover, red ginseng also increased stress (136), extracts of Panax ginseng had radio- the overall survival of patients during post-operative protective effects or prolonged the survival time of chemotherapy in comparison with the matched control irradiated mice (137, 138), and accelerated the (127). Additionally, Li (128) has reported that the hematological recovery of mice after x-ray irradiation ginseng-containing Shen-Qi injection could reduce the (139) as well as reduced DNA damage in normal cells toxic effects produced by chemical agents in patients (140); ii) ginseng can moderate chemical stress as it suffering from digestive tract tumors. This effect seemed decreased damage to rat liver and inhibited the elevation to be mediated by increasing the cellular immunologic of serum glutamic pyruvic transaminase in carbon function as assessed by phagocytic index, percentage tetrachloride or thioacetamide-intoxicated mice (141, of phagocytes, T lymphocyte transformation rate, and 142); and iii) Panax ginseng saponins-treated mice esterase staining (128). Regarding the toxic effect of were found to be more resistant to infections by radiotherapy, it has been reported that ginseng poly- Staphylococcus aureus, Escherichia coli, and Salmo- saccharides have certain effects on improvement of nella typhi (143). Saponins attenuated the process of immune function in nasopharyngeal carcinoma patients trypanosomiasis, prolonged the life span of the treated during radiotherapy treatment (129). It was further mice and delayed the appearance of trypanosomes in reported that the activity of natural killer cells and their blood (144). They also prevented the development lymphocyte-activated killer cells was significantly of fever induced by typhoid and paratyphoid vaccines.
increased in the peripheral blood of patients undergoing Moreover, the aqueous extract of ginseng radix pro- radiotherapy with simultaneous administration of duced beneficial effects against gastritis and ginsenoside Rb1 had an anti-ulcer effect through increasing mucus tension, diarrhea, sleeplessness, mastalgia, eruptions, and vaginal bleeding (124, 148). Additionally, Siegel(149) described the term “ginseng abuse syndrome” Adverse effects and drug interaction of ginseng after studying 133 users in Los Angeles. The authorshowed that the long term effects of the use of ginseng is The root of Panax ginseng appeared nontoxic to characterized by hypertension, nervousness, sleepless- rats, dogs, and humans (146, 147). In inappropriate use, ness, skin rash, diarrhea, confusion, depression, or the most commonly experienced symptoms are hyper- depersonalization. Possible drug interactions have Table 1. Important ginseng effects and its possible actions on different body systems - Resistance against adverse conditions (physical, chemical, - Restores body’s homeostasis- Anti-aging effects - Neuroprotection either in vivo or in vitro - Potentiates nerve growth factor- Anti-oxidative and anti-apoptotic mechanisms- Reduces lipid peroxidation- Inhibits excitotoxicity and Ca2+ over-influx into neurons- Maintains cellular ATP levels- Preserves structural integrity of neurons - Prevents astroglial swelling- Inhibits microglial respiratory burst activity and NO production - Relaxes vascular smooth muscle cells through NO and Ca2+ - Inhibits production of endothelin which plays a role in blood - Prevents platelet aggregation- Shows antagonistic action for platelet activity factor- Suppresses thrombin formation - Promotes functional neovascularization through endothelial - Anti-inflammatory and anti-allergic effects - Inhibits cytokine production such as IL-1β, IL-6, and TNF-α- Abrogates cyclooxygenase-2 gene expression- Suppresses histamine and leukotrienes release from mast cells- Stabilizes inflammatory cells such as neutrophils and lymphocytes- Antifibroblastic activity - Enhances interferon induction, phagocytosis, natural killer cells, - Suppresses malignant transformation- Inhibits proliferation of tumor cells- Inhibits tumor invasiveness, metastasis, and angiogenesis - Enhancement of male copulatory behavior - Relaxes corpus cavernosum smooth muscles via NO mediated - Increases serum testosterone levels and reduces plasma levels - Direct effects on anterior pituitary and hypothalamic dopaminergic - Increases plasma insulin levels, number of insulin receptors been reported between Panax ginseng and warfarin, 13 Wakabayashi C, Hasegawa H, Murata J, Saiki I. In vivo anti- metastatic action of ginseng protopanaxadiol saponins is basedon their intestinal bacterial metabolism after oral administration.
Oncol Res. 1997;9:411–417.
14 Murphy LL, Lee TJ. Ginseng, sex behavior and nitric oxide. Ann To our understanding, the worldwide use of ginseng 15 Byun BH, Shin I, Yoon YS, Kim SI, Joe CO. Modulation of as a medical herb and its intake by many healthy indi- protein kinase C activity in NIH 3T3 cells by plant glycosides viduals to invigorate their body functions (e.g., perfor- from Panax ginseng. Planta Med. 1997;63:389–392.
mance) are based primarily on i) its empirical history in 16 Tackikawa E, Kudo K, Harada K, Kashimoto T, Miyate M, contributing to recovery from a wide range of disease Kakizaki A. Effects of ginseng saponins on responses inducedby various receptor stimuli. Eur J Pharmacol. 1999;369:23–32.
conditions particularly in Far East countries and ii) the 17 Liberti LE, Der Mardersian A. Evaluation of commercial results of recent experimental research that reported ginseng products. J Pharm Sci. 1978;10:1487–1489.
some of its beneficial effects in experimental animals.
18 Phillipson JD, Anderson LA. Ginseng-quality safety and To date, there is a shortage of literature concerning efficacy? Pharm J. 1984;232:161–165.
clinical studies and the clinical use of ginseng to treat 19 Brekhman I, Dardymov I. New substances of plant origin which specific diseases in patients. Also, further research has to increase non specific resistance. Ann Rev Pharmacol. 1969;9: be considered to elucidate the definite pharmacological actions of ginseng and its constituents. In Table 1, the 20 O’Hara M, Kiefer D, Farrell K, Kemper K. A review of 12 commonly used medicinal herbs. Arch Fam Med. 1998;7:523– important effects of ginseng on different body systems and its possible actions are briefly summarized.
21 Van Kampen J, Robertson H, Hagg T, Drobitch R. Neuro- protective actions of the ginseng extract G115 in two rodent models of Parkinson’s disease. Exp Neurol. 2003;184:21–29.
22 Sugaya A, Yuzurihara M, Tsuda T, Yasuda K, Kajiwara K, 1 Nocerino E, Amato M, Izzo AA. The aphrodisiac and adapto- Sugaya AE. Proliferative effect of ginseng saponin on neurite genic properties of ginseng. Fitoterapia. 2000;71:1–5.
extension of primary cultured neurons of the rat cerebral cortex.
2 Yun TK. Brief introduction of Panax ginseng C.A. Meyer. J J Ethnopharmacol. 1988;22:173–181.
23 Mizumaki Y, Kurimoto M, Hirashima Y, Nishijima M, 3 Rhim H, Kim H, Lee DY, Oh TH, Nah SY. Ginseng and ginse- Kamiyama H, Nagai S, et al. Lipophilic fraction of Panax noside Rg3, a newly identical active ingredient of ginseng, ginseng induces neuronal differentiation of PC12 cells and modulate Ca2+ channel currents in rat sensory neurons. Eur J promotes neuronal survival of rat cortical neurons by protein kinase C dependent manner. Brain Res. 2002;20:254–260.
4 Himi T, Saito H, Nishiyama N. Effects of ginseng saponins on 24 Kim YC, Kim SR, Markelonis GJ, Oh TH. Ginsenosides Rb1 the survival of cerebral cortex neurons in cell cultures. Chem and Rg3 protect cultured rat cortical cells from glutamate- Pharm Bull (Tokyo). 1989;37:481–484.
induced neurodegeneration. J Neurosci Res. 1998;4:426–432.
5 Wen TC, Yoshimura H, Matsuda S, Lim JH, Sakanaka M.
25 Lim JH, Wen TC, Matsuda S, Tanaka J, Maeda N, Peng H, et al.
Ginseng root prevents learning disability and neuronal loss in Protection of ischaemic hippocampal neurons by ginsenosides gerbils with 5-minute forebrain ischaemia. Acta Neuropathol.
Rb1, a main ingredient of ginseng root. Neurosci Res.
6 Blumenthal M. Asian ginseng: potential therapeutic uses. Adv 26 Liao B, Newmark H, Zhou R. Neuroprotective effects of ginseng total saponin and ginsenosides Rb1 and Rg1 on spinal cord 7 Smolinski AT, Pestka JJ. Modulation of lipopolysacchride- neurons in vitro. Exp Neurol. 2002;173:224–234.
induced proinflammatory cytokine production in vitro and in 27 Tohda C, Matsumoto N, Zou K, Meselhy MR, Komatsu K.
vivo by the herbal constituents apigenin (chamomile), ginseno- Axonal and dendritic extension by protopanaxadiol-type saponins side Rb1 (ginseng) and parthenolide. Food Chem Toxicol.
from ginseng drugs in SK-N-SH cells. Jpn J Pharmacol.
8 Liu CX, Xiao PG. Recent advances on ginseng research in 28 Radad K, Gille G, Moldzio R, Saito H, Rausch WD. Ginseno- China. J Ethnopharmacol. 1992;36:27–38.
sides Rb1 and Rg1 effects on mesencephalic dopaminergic cells 9 Back NI, Kim DS, Lee YH, Park JD, Lee CB, Kim SI. Ginseno- stressed with glutamate. Brain Res. 2004;17:41–53.
side Rh4, a genuine dammarane glycoside from korean red 29 Radad K, Gille G, Moldzio R, Saito H, Ishige K, Rausch WD.
ginseng. Planta Med. 1996;62:86–87.
Ginsenosides Rb1 and Rg1 effects on survival and neurite 10 Attele AS, Wu JA, Yuan CS. Ginseng pharmacology: multiple growth of MPP+-affected mesencephalic dopaminergic cells.
constituents and multiple actions. Biochem Pahrmacol.
30 Tanner CM, Ben-Schlomo Y. Epidemiology of Parkinson’s 11 Fleming T. Physician desk references for herbal medicine. 1st disease. Adv Neurol. 1999;80:153–159.
ed. Montvale, NJ: Medical Economics Company; 1998.
31 Tsang D, Yeung HW, Tso WW, Peck H. Ginseng saponins: 12 Tyler VE. The honest herbal-A sensible guide to the use of herbs influence on neurotransmitter uptake in rat brain synaptosomes.
and related remedies. 3rd ed. New York: Haworth Press; 1993.
32 Chun CX, Gui ZY, An ZL, Chun H, Ying C, Min CL, et al.
dependent inhibition of brain Na+ channels by American Ginsenoside Rg1 attenuates dopamine-induced apoptosis in ginseng. Eur J Pharmacol. 2001;413:47–54.
PC12 cells by suppressing oxidative stress. Eur J Pharmacol.
51 Jiang KY, Qian ZN. Effects of Panax notoginseng saponins on posthypoxic cell damage of neurons in vitro. Zhongguo Yao Li 33 Kim EH, Jang MH, Shin MC, Shin MS, Kim CJ. Protective effect of aqueous extract of Ginseng radix against 1-methyl-4- 52 Seong YH, Shin CS, Kim HS, Baba A. Inhibitory effect of phenylpyridinium-induced apoptosis in PC12 cells. Biol Pharm ginseng total saponins on glutamate-induced swelling of cultured astrocytes. Biol Pharm Bull. 1995;18:1776–1778.
34 Chen XC, Chen Y, Zhu YG, Fang F, Chen LM. Protective effect 53 Gong YS, Zhang JT. Effect of 17-beta-estradiol and ginsenoside of ginsenoside Rg1 against MPTP-induced apoptosis in mouse Rg1 on reactive microglia induced by beta-amyloid peptides.
substantia nigra neurons. Acta Pharmacol Sin. 2002;23:829–834.
J Asian Nat Prod Res. 1999;1:153–161.
35 Salim KN, McEven BS, Choa HM. Ginsenoside Rb1 regulates 54 Benishin CG. Actions of ginsenoside Rb1 on choline uptake in ChAT, NGF and trkA mRNA expression in the rat brain. Brain central cholinergic nerve endings. Neurochem Int. 1992;21:1–5.
Res Mol Brain Res. 1997;47:177–182.
55 Zhang JT, Qu ZW, Liu Y, Deng HL. Preliminary study on 36 Rudakewich M, Ba F, Benishin CG. Neurotrophic and neuro- antiamnestic mechanism of ginsenosides Rb1 and Rg1. Chin protective actions of ginsenosides Rb1 and Rg1. Planta Med.
56 Itoh T, Zang YF, Murai S, Saito H. Effects of Panax ginseng 37 Kim HS, Zhang YH, Fang LH, Lee MK. Effects of ginsenosides root on the vertical and horizontal motor activities and on on bovine adrenal tyrosine hydroxylase. J Ethnopharmacol.
brain monoamine-related substances in mice. Planta Med.
38 Jiang F, DeSilva S, Turnbull J. Beneficial effect of ginseng 57 D’Angelo L, Grimaldi R, Caravaggi M, Marcoli M, Perucca E, root in SOD-1 (G93A) transgenic mice. J Neurol Sci.
Lecchini S, et al. A double-blind, placebo-controlled clinical study on the effect of a standardized ginseng extract on psycho- 39 Lee TF, Shiao YJ, Chen CF, Wang LC. Effect of ginseng motor performance in healthy volunteers. J Ethnopharmacol.
saponins on beta-amyloid-suppressed acetylcholine release from rat hippocampal slices. Planta Med. 2001;67:634–637.
58 Kim HS, Kang JG, Seong YH, Nam KY, Oh KW. Blockade by 40 Nishiyama N, Cho SI, Kitagawa I, Saito H. Malonylginsenoside ginseng total saponins of the development of cocaine induced Rb1 potentiates nerve growth factor (NGF)-induced neurite reverse tolerance and dopamine receptor supersensitivity in outgrowth of cultured chick embryonic dorsal root ganglia. Biol mice. Pharmacol Biochem Behav. 1995;50:23–27.
59 Kim HS, Kang JG, Oh KW. Inhibition by ginseng total saponins 41 Braughler JM, Chase RL, Neff GL, Yonkers PA, Day JS, of the development of morphine reverse tolerance and dopamine Hall ED, et al. A new 21-aminosteroid antioxidant lacking receptor supersensitivity in mice. Gen Pharmacol. 1995;26: glucocorticoid activity stimulates adrenocorticotropin secretion and blocks arachidonic acid release from mouse pituitary tumor 60 Kim HS, Hong YT, Oh KW, Seong YH, Rheu HM, Cho DH.
(AtT-20) cells. J Pharmacol Exp Ther. 1988;244:423–427.
Inhibition by ginsenosides Rb1 and Rg1 of methamphetamine- 42 Chu GX, Chen X. Anti-lipid peroxidation and protection of induced hypersensitivity, conditioned place preference and ginsenosides against cerebral ischemia-reperfusion injuries in postsynaptic dopamine receptor supersensitivity on mice. Gen rats. Zhongguo Yao Li Xue Bao. 1990;11:119–123.
43 Chang MS, Lee SG, Rho HM. Transcriptional activation of 61 Kim HS, Kim K, Oh K. Ginseng total saponins inhibits nicotine Cu / Zn superoxide dismutase and catalase genes by panaxadiol induced hyperactivity and conditioned place preference in mice.
ginsenosides extracted from Panax ginseng. Phytother Res.
62 Kim ND, Kang SY, Park JH, Schini-Kerth VB. Ginsenoside 44 Kim S, Ahn K, Oh TH, Nah SY, Rhim H. Inhibitory effect of Rg3 mediates endothelium-dependent relaxation in response to ginsenosides on NMDA receptor-mediated signals in rat ginsenoside in rat aorta: role of K+ channels. Eur J Pharmacol.
hippocampal neurons. Biochem Biophys Res Commun. 2002; 63 Shim I, Won J, Song J, Kim SE, Huh S. Modulatory effect of 45 Kim S, Rhim H. Ginsenosides inhibit NMDA receptor-mediated ginseng total saponins on dopamine release and tyrosine epileptic discharges in cultured hippocampal neurons. Arch hydroxylase gene expression induced by nicotine in the mouse.
J Ethnopharmacol. 2000;70:161–169.
46 Coyle JT, Puttfarcken P. Oxidative stress, glutamate, and neuro- 64 Petkov V. Effect of ginseng on the brain biogenic monoamines degenerative disorders. Science. 1993;262:689–695.
and 3',5'-AMP system. Experiments on rats. Arzneimittelfors- 47 Choi DW, Rothman SM. The role of glutamate neurotoxicity in hypoxic-ischemic neuronal death. Annu Rev Neurosci. 1990;13: 65 Wang A, Cao Y, Wang Y, Zhao R, Liu C. [Effects of Chinese ginseng root and stem-leaf saponins on learning, memory and 48 Sattler R, Tymianski M. Molecular mechanisms of calcium- biogenic monoamines of brain in rats]. Zhongguo Zhong Yao Za dependent excitotoxicity. J Mol Med. 2000;78:3–13.
Zhi 1995;20:493–495. (text in Chinese with English abstract) 49 Liu M, Zhang J. Effects of ginsenoside Rb1 and Rg1 on 66 Sala F, Mulet J, Choi S, Jung SY, Nah SY, Rhim H, et al. Effects synaptosomal free calcium level, ATPase and calmodulin in of ginsenoside Rg2 on human neuronal nicotinic acetylcholine rat hippocampus. Chin Med J. 1995;108:544–547.
receptors. J Pharmacol Exp Ther. 2002;301:1052–1059.
50 Liu D, Li B, Liu Y, Attele AS, Kyle JW, Yuan CS. Voltage- 67 Kimura T, Saunders PA, Kim HS, Rheu HM, Oh KW, Ho IK.
Interactions of ginsenosides with ligand-bindings of GABA(A) 87 Shi L, Fan PS, Wu L, Fang JX, Han ZX. Effects of total saponins and GABA(B) receptors. Gen Pharmacol. 1994;25:193–199.
of Panax notoginseng on increasing PGI2 in carotid artery and 68 Choi SE, Choi S, Lee JH, Whiting PJ, Lee SM, Nah SY. Effects decreasing TXA2 in blood platelets. Zhongguo Yao Li Xue of ginsenosides on GABA(A) receptor channels expressed in Xenopus oocytes. Arch Pharm Res. 2003;26:28–33.
88 Kimura Y, Okuda H, Arichi S. Effects of various ginseng 69 Yamaguchi Y, Higashi M, Kobayashi H. Effects of ginsenosides saponins on 5-hydroxytryptamine release and aggregation in on impaired performance caused by scopolamine in rats. Eur J human platelets. J Pharm Pharmacol. 1988;40:838–843.
89 Park HJ, Lee JH, Song YB, Park KH. Effects of dietary 70 Mook-Jung I, Hong HS, Boo JH, Lee KH, Yun SH, Cheong MY, supplementation of lipophilic fraction from Panax ginseng on et al. Ginsenoside Rb1 and Rg1 improve spatial learning and cGMP and cAMP in rat platelets and on blood coagulation.
increase hippocampal synaptophysin level in mice. J Neurosci Biol Pharm Bull. 1996;19:1434–1439.
90 Jung KY, Kim DS, Oh SR, Lee IS, Lee JJ, Park JD, et al. Platelet 71 Zhao R, McDaniel WF. Ginseng improves strategic learning by activating factor antagonist activity of ginsenosides. Biol Pharm normal and brain-damaged rats. Neuroreport. 1998;11:1619– 91 Nakajima S, Uchiyama Y, Yoshida K, Mizukawa H, Haruki E.
72 Zhong YM, Nishijo H, Uwano T, Tamura R, Kawanishi K, Ono The effect of ginseng radius rubra on human vascular endothelial T. Red ginseng ameliorated place navigation deficits in young cells. Am J Chin Med. 1998;26:365–373.
rats with hippocampal lesions and aged rats. Physiol Behav.
92 Yuan CS, Attele AS, Wu JA, Lowell TK, Gu Z, Lin Y. Panax quinquefolium L. Inhibits thrombin-induced endothelin release 73 Kennedy DO, Scholey AB. Ginseng: potential for the enhance- in vitro. Am J Chin Med. 1999;27:331–338.
ment of cognitive performance and mood. Pharmacol Biochem 93 Sengupta S, Toh SA, Sellers LA, Skepper JN, Koolwijk P, Leung HW, et al. Modulating angiogenesis: the yin and the yang 74 Terasawa K, Shimada Y, Kita T. Choto-san in the treatment of in ginseng. Circulation. 2004;7:1219–1225.
vascular dementia: a double blind, placeb-controlled study.
94 Yu SC, Li XY. Effect of ginsenoside on IL-1 beta and IL-6 mRNA expression in hippocampal neurons in chronic inflam- 75 Kurimoto H, Nishijo H, Uwano T, Yamaguchi H, Zhong YM, mation model of aged rats. Acta Pharmacol Sin. 2000;21:915– Kawanishi K, et al. Effects of nonsaponin fraction of red ginseng on learning deficits in aged rats. Physiol Behav. 2004;82:345– 95 Cho JY, Park J, Yoo ES, Baik KU, Park MH. Effect of ginseng saponin on tumor necrosis factor-α production and T cell 76 Shen L, Zhang J. Ginsenoside Rg1 increases ischemia-induced proliferation. Yakhak Hoeji. 1998;43:296–301.
cell proliferation and survival in the dentate gyrus of adult 96 Keum YS, Han SS, Chun KS, Park KK, Park JH, Lee SK, et al.
gerbils. Neurosci Lett. 2003;344:1–4.
Inhibitory effects of the ginsenoside Rg3 on phorbol ester- 77 Persson J, Bringlov E, Nilsson LG, Nyberg L. The memory- induced cyclooxygenase-2 expression, NF-kappaB activation enhancing effects of Ginseng and Ginkgo biloba in healthy and tumor promotion. Mutat Res. 2003;523–524:75–85.
volunteers. Psychopharmacology. 2004;172:430–434.
97 Ro JY, Ahn YS, Kim KH. Inhibitory effect of ginsenoside on 78 Sorensen H, Sonne J. A double-masked study of the effect of the mediator release in the guinea pig lung mast cells activated ginseng on memory functions. Curr Ther Res. 1996;57:959–968.
by specific antigen-antibody reactions. Int J Immunopharmacol.
79 Wood WB, Roh BL, White RP. Cardiovascular actions of Panax ginseng in dogs. Jpn J Pharmacol. 1964;14:284–294.
98 Li X, Li SH. Effect of total saponins of Sanchi (Panax pseudo- 80 Lei XL, Chiou GC. Cardiovascular pharmacology of Panax ginseng notoginseng) on TNF, No and its mechanisms. Zhong notoginseng. Am J Chin Med. 1986;14:145–152.
cao yao: Chin Tradit Herbal Drugs. 1999;30:514–517.
81 Kim ND, Kang SY, Schini VB. Ginsenosides evoke endo- 99 Kim TH, Lee YS, Cho CK, Park S, Choi SY, Yool SY.
thelium-dependent vascular relaxation in rat aorta. Gen Protective effect of ginseng on radiation-induced DNA double strand breaks and repair in murine lymphocytes. Cancer Biother 82 Kang SY, Kim SH, Schini VB, Kim ND. Dietary ginsenosides improve endothelium-dependent relaxation in the thoracic aorta 100 Zhang GQ, Ye RG, Kong QY, Yang NS, Zhang JL, Guan WM, of hypercholesterolemic rabbit. Gen Pharmacol. 1995;26:483– et al. Panax notoginseng saponins induced of human renal interstitial fibroblast and its mechanisms. Chin J Nephrology.
83 Scott GI, Colligan PB, Ren BH, Ren J. Ginsenosides Rb1 and Re decrease cardiac contraction in adult rat ventricular myocytes: 101 Matsuda H, Kubo M, Tani T, Kitagawa I, Mizuno M.
role of nitric oxide. Br J Pharmacol. 2001;134:1159–1165.
[Pharmacological study of Panax ginseng C. A. Meyer (IX).
84 Sung J, Han KH, Zo JH, Park HJ, Kim CH, Oh BH. Effects of Protective effect of red ginseng on interferon (2) on phagocytic red ginseng upon vascular endothelial function in patients with activity of mouse reticuloendothelial cells system]. Shoyaku- essential hypertension. Am J Chin Med. 2000;28:205–216.
gaku Zasshi. 1987;41:135–141. (text in Japanese with English 85 Li Z, Chen X, Niwa Y, Sakamoto S, Nakaya Y. Involvement of Ca2+-activated K+ channels in ginsenosides-induced aortic 102 Ahn YK, Kim YK, Chang JG, Kim JH, Goo JD. The effect of relaxation in rats. J Cardiovasc Pharmacol. 2001;37:41–47.
Korean ginseng on the immunotoxicity of mitomycin C. Yakhak 86 Kim CS, Park JB, Kim KJ, Chang SJ, Ryoo SW, Jeon BH. Effect of Korea red ginseng on cerebral blood flow and superoxide 103 Park HW, Kim SC, Jung NP. The effect of ginseng saponin production. Acta Pharmacol Sin. 2002;23:1152–1156.
fractions on humoral immunity of mice. Korean J Ginseng Sci.
104 Ohtani K, Mizutani K, Kasai R, Hirose K, Kishi K, Tanaka O, 122 Chen X, Lee TJ. Ginsenosides-induced a nitric oxide-mediated et al. Reticuloendothelial system activating polysaccharides relaxation of the rabbit corpus cavernosum. Br J Pharmacol.
from Panax spp – Panax-notoginseng, Panax-ginseng and Panax- japonicus. J Pharmacobiodyn. 1987;10:S63.
123 Fahim MS, Fahim Z, Harman JM. Effect of Panax ginseng on 105 Hu S, Concha C, Johannisson A, Meglia G, Waller KP. Effect of testosterone level and prostate in male rats. Arch Androl.
subcutaneous injection of ginseng on cows with subclinical Staphylococcus aureus mastitis. J Vet Med B Infect Dis Vet 124 Bahrke MS, Morgan WP. Evaluation of the ergogenic properties of ginseng. Sports Med. 1994;18:229–248.
106 Yun TK. Experimental and epidemiologic evidence of cancer 125 Zhou W, Chai H, Lin PH, Lumsden AB, Yao Q, Chen CJ.
preventive effects of Panax ginseng C.A. Meyer. Nutr Rev.
Molecular mechanisms and clinical applications of ginseng root for cardiovascular disease. Med Sci Monit. 2004;10:187–192.
107 Yun TK. Panax ginseng- a non-organ-specific cancer preven- 126 Long MZ, Wang DB, Yang JM. [Clinical study on effect of Shenmai injection in treating congestive heart failure].
108 Lee YN, Lee HY, Chung HY, Kim SI, Lee SK, Park BC, et al.
Zhongguo Zhong Xi Yi Jie He Za Zhi. 2003;23:808–810. (text in In vitro induction of differentiation by ginsenoides in F9 teratocarcinoma cells. Eur J Cancer. 1996;32:1420–1428.
127 Suh SO, Kroh M, Kim NR, Joh YG, Cho MY. Effects of red 109 Park J, Lee KY, Oh YJ, Kim KW, Lee SK. Activation of ginseng upon postoperative immunity and survival in patients caspase-3 protease via a Bcl-2-insensitive pathway during the with stage III gastric cancer. Am J Chin Med. 2002;30:483–494.
process of ginsenoside Rh2-induced apoptosis. Cancer Lett.
128 Li NQ. [Clinical and experimental study on shen-qi injection with chemotherapy in the treatment of malignant tumor of diges- 110 Oh M, Choi YH, Choi S, Chung H, Kim K, Kim SI, et al. Anti- tive tract]. Zhongguo Zhong Xi Yi Jie He Za Zhi. 1992;12:588– proliferating effects of ginsenoside Rh2 on MCF-7 human breast 592. (text in Chinese with English abstract) cancer cells. Int J Oncol. 1999;14:869–875.
129 Xie FY, Zeng ZF, Huang HY. [Clinical observation on 111 Kim HE, Oh JH, Lee SK, Oh YJ. Ginsenoside Rh2 induces nasopharyngeal carcinoma treated with combined therapy of apoptotic cell death in rat C6 glioma via a reactive oxygen- radiotherapy and ginseng polysaccharide injection]. Zhongguo and caspase-dependent but Bcl-X(L)-independent pathway. Life Zhong Xi Yi Jie He Za Zhi. 2001;21:332–334. (text in Chinese 112 Mochizuki M, Yoo YC, Matsuzawa K, Sato K, Saiki I, Tono- 130 Kim JH, Lee JH, Jeong SM, Lee BH, Yoon IS, Lee JH, et al.
oka S, et al. Inhibitory effect of tumor metastasis in mice by Effect of ginseng saponins on a rat visceral hypersensitivity saponins, ginsenoside-Rb2, 20(R)- and 20(S)-ginsenoside-Rg3, model. Biol Pharm Bull. 2005;28:2120–2124.
of red ginseng. Biol Pharm Bull. 1995;18:1197–1202.
131 Kaneko H, Nakanishi K. Proof of the mysterious efficacy of 113 Byun BH, Shin I, Yoon YS, Kim SI, Joe CO. Modulation of ginseng: basic and clinical trials: clinical effects of medical protein kinase C activity in NIH 3T3 cells by plant glycosides ginseng, korean red ginseng: specifically, its anti-stress action from Panax ginseng. Planta Med. 1997;63:389–392.
for prevention of disease. J Pharmacol Sci. 2004;95:158–162.
114 Surh YJ, Na HK, Lee JY, Keum YS. Molecular mechanisms 132 Tode T, Kikuchi Y, Hirata J, Kita T, Nakata H, Nagata I. Effect underlying anti-tumor promoting activities of heat-processed of Korean red ginseng on psychological functions in patients Panax ginseng C.A. Meyer. J Korean Med Sci. 2001;16:38–41.
with severe climacteric syndromes. Int J Gynaecol Obstet.
115 Keum YS, Park KK, Lee JM, Chun KS, Park JH, Lee SK, et al.
Antioxidant and anti-tumor promoting activities of the methanol 133 Suzuki Y, Hikino H. Mechanisms of hypoglycaemic activity of extract of heat-processed ginseng. Cancer Lett. 2000;150:41–48.
panaxans A and B, glycans of Panax ginseng roots: effects on 116 Subbaramaiah K, Telang N, Ramonetti JT, Araki R, DeVito B, plasma level, secretion, sensitivity and binding of insulin in Weksler BB, et al. Transcription of cyclooxygenase-2 is mice. Phytother Res. 1989;3:20–24.
enhanced in transformed mammary epithelial cells. Cancer 134 Ng TB, Yeung HW. Hypoglycemic constituents of Panax ginseng. Gen Pharmacol. 1985;16:549–552.
117 O’Brien TG. The induction of ornithine decarboxylase as an 135 Tchilian EZ, Zhelezarov IE, Hadjiivanova CI. Effect of ginseno- early, possibly obligatory event in mouse skin carcinogenesis.
side Rg1 on insulin binding in mice liver and membranes.
118 Mayo MW, Wang CY, Congswell PC, Rogers-Graham KS, 136 Wang LC, Lee TF. Effect of ginseng saponins on cold tolerance Lowe SW, Der CJ, et al. Requirement of NF-κB activation to in young and elderly rats. Planta Med. 2000;66:144–147.
suppress p53-independent apoptosis induced by oncogenic Ras.
137 Park DL. Effect of Panax ginseng on x-ray irradiation and synergetic study on nitromin. Insam Munhun Teukjip. 1964;2: 119 Murphy LL, Cadena RS, Chavez D, Ferraro JS. Effect of American ginseng (Panax quinquefolium) on male copulatory 138 Pande S, Dumar M, Kumar A. Evaluation of radimodyfing behaviour in the rat. Physiol Behav. 1998;64:445–450.
effect of root extract of Panax ginseng. Phytother Res.
120 Kim C, Choi H, Kim CC, Kim JK, Kim MS, Ahn BT, et al.
Influence of ginseng on mating behaviour of male rats. Am J 139 Yonezawa M, Takeda A, katoh N. Restoration of radiation injury by ginseng extract. Proceeding of the Third International 121 Choi HK, Seong DH, Rha KH. Clinical efficacy of Korean red Ginseng Symposium, Soul, Republic of Korea. 1980:17–20.
ginseng for erectile dysfunction. Int J Impot Res. 1995;7:181– 140 Kim C, Choi JE. Effect of radioprotective ginseng protein on UV-induced sister chromatid exchanges. Arch Pharm Res.
organism activity. Acta Pharm Sin. 1966;13:106–111.
145 Jeong CS, Hyun JE, Kim YS. Ginsenoside Rb1: the anti-ulcer 141 Wang B, Cui J, Liu A. Effect of saponins isolated from stems constituent from the head of Panax ginseng. Arch Pharm Res.
and leaves of ginseng (SSLG) on experimental liver injury. Acta 146 Wang BX, Cui JC, Liu AJ. [The action of ginsenosides extracted 142 Hikino H, Kiso Y, Kinouchi J, Sanada S, Shoji J. Validity of from the stems and leaves of Panax ginseng in promoting animal the oriental medicines. 73 Liver-protective drugs. 18 Anti- growth]. Yao Xue Xue Bao. 1982;17:899–904. (in Chinese) hepatotoxic actions of ginsenosides from Panax ginseng roots.
147 Hess FG Jr, Parent RA, Stevens KR, Cox GE, Becci PJ. Effects of subchronic feeding of ginseng extract G115 in beagle dogs.
143 Wang BX, Cui JC, Liu AJ. The effect of ginseng on immune responses. In: Chang HM, Yeung HW, Tso W-W, Koo A, 148 Coon JT, Ernst E. Panax ginseng: a systematic review of adverse editors. Advance in Chinese medicinal materials research.
effects and drug interactions. Drug Saf. 2002;25:323–344.
Singapore/Philadelphia: World Scientific Publishing; 1985.
149 Siegel RK. Ginseng abuse syndrome-problems with the panacea.
144 Chang PH. The effect of ginseng (Panax ginseng C.A. Meyer) on

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