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PubMed2003

Discovery of genes for ginsenoside biosynthesis by analysis of ginseng expressed sequence tags.

Expressed sequence tags (ESTs) provide a valuable tool that can be used to identify genes in secondary metabolite biosynthesis. Ginseng (Panax ginseng C.A Meyer) is a medicinal plant that accumulates ginsenosides in roots. We sequenced 11,636 ESTs from five ginseng libraries in order to create a gene resource for biosynthesis of ginsenosides, which are thought to be the major active component in roots. Only 59% of the ginseng ESTs exhibited significant homology to previously known polypeptide sequences. Stress- and pathogen-response proteins were most abundant in 4-year-old ginseng roots. ESTs involved in ginsenoside biosynthesis were identified by a keyword search of BLASTX results and a domain search of ginseng ESTs. We identified 4 oxidosqualene cyclase candidates involved in the cyclization reaction of 2,3-oxidosqualene, 9 nine cytochrome P450 and 12 glycosyltransferse candidates, which may be involved in modification of the triterpene backbone.

DNA, Plant↗
PubMed2004

Construction of a BAC library of Korean ginseng and initial analysis of BAC-end sequences.

We estimated the genome size of Korean ginseng (Panax ginseng C.A. Meyer), a medicinal herb, constructed a HindIII BAC library, and analyzed BAC-end sequences to provide an initial characterization of the library. The 1C nuclear DNA content of Korean ginseng was estimated to be 3.33 pg (3.12 x 10(3) Mb). The BAC library consists of 106,368 clones with an average size of 98.61 kb, amounting to 3.34 genome equivalents. Sequencing of 2167 BAC clones generated 2492 BAC-end sequences with an average length of 400 bp. Analysis using BLAST and motif searches revealed that 10.2%, 20.9% and 3.8% of the BAC-end sequences contained protein-coding regions, transposable elements and microsatellites, respectively. A comparison of the functional categories represented by the protein-coding regions found in BAC-end sequences with those of Arabidopsis revealed that proteins pertaining to energy metabolism, subcellular localization, cofactor requirement and transport facilitation were more highly represented in the P. ginseng sample. In addition, a sequence encoding a glucosyltransferase-like protein implicated in the ginsenoside biosynthesis pathway was also found. The majority of the transposable element sequences found belonged to the gypsy type (67.6%), followed by copia (11.7%) and LINE (8.0%) retrotransposons, whereas DNA transposons accounted for only 2.1% of the total in our sequence sample. Higher levels of transposable elements than protein-coding regions suggest that mobile elements have played an important role in the evolution of the genome of Korean ginseng, and contributed significantly to its complexity. We also identified 103 microsatellites with 3-38 repeats in their motifs. The BAC library and BAC-end sequences will serve as a useful resource for physical mapping, positional cloning and genome sequencing of P. ginseng.

Chromosomes, Artificial, Bacterial↗
PubMed1988

Psychotropic effects of ginseng saponins on agonistic behavior between resident and intruder mice.

The psychotropic actions of crude ginseng saponins, pure ginsenoside Rb1 (GS-Rb1) and ginsenoside Rg1 (GS-Rg1) obtained from the root of Panax ginseng, were evaluated from their effects on agonistic behavior in mice. A resident-intruder test situation was used. When the resident mouse was treated with crude ginseng saponins (25, 50 and 100 mg/kg i.p.), aggressive episodes (offensive sideways posture and attack bite) were significantly suppressed in a dose-dependent manner. However, the agonistic behavior was not altered when the intruder was treated with crude ginseng saponins. GS-Rb1 (2.5, 5 ad 10 mg/kg i.p.) also significantly suppressed aggressive episodes when given to the resident, whereas GS-Rg1 (2.5, 5 and 10 mg/kg i.p.) was ineffective. Neither GS-Rb1 nor GS-Rg1 given to the intruder caused any significant changes in the behavior of the resident. Although the highest dose of crude ginseng saponins suppressed locomotion frequency, it appears that both crude ginseng saponins and GS-Rb1 possess a specific psychotropic action on agonistic behavior.

Aggression↗
PubMed1994

Ginseng root extract inhibits calcium channels in rat sensory neurons through a similar path, but different receptor, as mu-type opioids.

The effect of Panax ginseng root extract on Ca2+ current of adult rat trigeminal ganglion neurons was investigated using whole-cell patch-clamp methods. The application of P. ginseng root extract (100 micrograms/ml) produced rapid, reversible reduction of the Ca2+ current by 22 +/- 4%. Treatment with pertussis toxin (250 ng/ml) for 16 h reduced the inhibition to 4 +/- 1%. The continual presence of 1 microM DAGO, a selective mu-opioid agonist that inhibits Ca2+ channels, occluded further inhibition of Ca2+ current by P. ginseng root extract. Yohimbine, phaclofen, atropine, and naloxone--antagonists of alpha 2-adrenergic, GABAB, muscarinic, and opiate receptors, respectively--did not block the inhibitory effect on Ca2+ current of P. ginseng root extract. Thus, P. ginseng root extract acts on sensory neurons through a similar pathway as mu-type opioids: both inhibit Ca2+ channels through pertussis toxin-sensitive GTP-binding proteins. However, the receptor for P. ginseng root extract is not an alpha 2-adrenergic, GABAB, muscarinic, or opioid receptor.

Animals↗
PubMed1999

Ginseng pharmacology: multiple constituents and multiple actions.

Ginseng is a highly valued herb in the Far East and has gained popularity in the West during the last decade. There is extensive literature on the beneficial effects of ginseng and its constituents. The major active components of ginseng are ginsenosides, a diverse group of steroidal saponins, which demonstrate the ability to target a myriad of tissues, producing an array of pharmacological responses. However, many mechanisms of ginsenoside activity still remain unknown. Since ginsenosides and other constituents of ginseng produce effects that are different from one another, and a single ginsenoside initiates multiple actions in the same tissue, the overall pharmacology of ginseng is complex. The ability of ginsenosides to independently target multireceptor systems at the plasma membrane, as well as to activate intracellular steroid receptors, may explain some pharmacological effects. This commentary aims to review selected effects of ginseng and ginsenosides and describe their possible modes of action. Structural variability of ginsenosides, structural and functional relationship to steroids, and potential targets of action are discussed.

Adjuvants, Immunologic↗
PubMed2003

Electrophysiological effects of ginseng and ginsenoside Re in guinea pig ventricular myocytes.

Panax ginseng is a folk medicine with various cardiovascular actions; however, its underlying mechanisms of action are not well known. In the present study, we examined the effects of ginseng and its main component, ginsenoside Re, on action potentials and membrane currents recorded from isolated guinea pig ventricular myocytes with the whole-cell patch clamp technique. Ginseng (1 mg/ml) shortened the action potential duration in a rate-dependent manner. Ginseng depressed the L-type Ca2+ current (I(Ca-L)) in a mode of both tonic block and use-dependent block, and enhanced the slowly activating component of the delayed rectifier K+ current (I(Ks)). Ginsenoside Re 3 microM exhibited similar electrophysiological effects to those of 1 mg/ml ginseng, but of slightly smaller magnitude. Inhibition of I(Ca,L) and enhancement of I(Ks) by ginsenoside Re appear to be one of the main electrophysiological actions of ginseng in the heart, although contributions from other ingredients should be considered.

Action Potentials↗
PubMed1999

Effects of ginseng on ethanol induced sedation in mice.

The effects of ginseng, ginsenosides, coffee, and caffeine on 75% ethanol induced sleeping in mice were examined. Mice treated with ethanol lost their righting reflex within 30 min and this lasted for about 4 h. The onset time of lose of righting reflex (LR) in mice pre-treated with ginseng, ginsenosides, coffee or caffeine 10 min before ethanol was significantly delayed; whereas the duration of sleep was not affected by all treatments. Administration of these agents 10 min after ethanol was ineffective in counteracting the LR effect of ethanol. Coffee and caffeine produced central stimulation and increased locomotor activity. Ginseng and ginsenosides were found to enhance exercise endurance and reduced the plasma level of ethanol. Gastric emptying was slowed by ginseng, ginsenosides or ethanol administration. An additive effect was observed when the mice were pre-treated with ginseng or ginsenosides 10 min before ethanol administration. It is suggested that ginseng decreased plasma ethanol concentration by delaying gastric emptying and this may be partly due to the effect of the ginsenosides.

Animals↗
PubMed2003

Components of Panax ginseng that improve accelerated small intestinal transit.

We previously clarified that Dai-kenchu-to, a Chinese prescription, was useful for improving carbachol-induced hyperperistalsis of the small intestine in vivo, and the efficacy of Ginseng Radix, a crude drug component of Dai-kenchu-to, was also confirmed. Ginseng Radix, the root of Panax ginseng C.A. Meyer, showed significant ameliorative effects on both the carbachol-induced and the BaCl(2)-induced accelerated small intestinal transit model in mice, suggesting that both an inhibitory effect on the cholinergic nervous system and direct suppressive effect on muscles were involved in the ameliorative effect of Ginseng Radix on the accelerated small intestinal transit. Ginsenoside Rb1 (4) and ginsenoside Rd (7), major components of Ginseng Radix, improved both animal models. These results suggest that ginsenoside Rb1 (4) and ginsenoside Rd (7) were representative compounds of Ginseng Radix for improving the accelerated movement of the small intestine and that these compounds partly contribute to the action of Dai-kenchu-to on small intestinal transit.

Animals↗
PubMed2006

Saponins composition in American ginseng leaf and berry assayed by high-performance liquid chromatography.

The root of American ginseng is a commonly used herbal medicine in the United States. However, the compositions of American ginseng leaves and berries are not clear to date. In this study, we improved a method for the analysis of 12 ginsenosides based on solid phase extraction and high-performance liquid chromatography-ultraviolet. Good resolution was obtained for all tested ginsenosides: Rb1, Rb2, Rb3, Rc, Rd, Re, Rg1, Rg2, 20(R)-Rg2, Rg3, Rh1, and Rh2. Ginsenosides Rh1, Rg2, and 20(R)-Rg2 were easily separated with this column. The modified gradient elution program resulted in satisfactory linearity and precision. Solid phase extraction made the analysis accurate and efficient. Other investigators recently observed that ginsenoside Rb3 is a potent neuroprotective compound; it can promote learning and memory. In this report, we found that the major ginsenoside in American ginseng leaves and berries was ginsenoside Rb3, while Rb3 only had limited amounts in the root of American ginseng and other species of the Panax genus. Ginsenoside Rb3 was quantified as 4.71% in American ginseng leaves and 5.35% in berries, suggesting that American ginseng leaves and berries are new sources of ginsenoside Rb3.

Chromatography, High Pressure Liquid↗
PubMed2000

Steaming of ginseng at high temperature enhances biological activity.

The present study was performed to evaluate the effect of steaming ginseng at a temperature over 100 degrees C on its chemical constituents and biological activities. Raw ginseng was steamed at 100, 110, and 120 degrees C for 2 h using an autoclave. The ginseng steamed at 120 degrees C was more potent in its ability to induce endothelium-dependent relaxation. Steaming the raw ginseng at 120 degrees C also remarkably increased the radical-scavenging activity. Ginsenosides F(4), Rg(3), and Rg(5), which were not present in raw ginseng, were produced after steaming. Ginsenosides Rg(3) and Rg(5) were the most abundant ginsenosides in the ginseng steamed at 120 degrees C, accounting for 39% and 19% of all ginsenosides, respectively.

Chromatography, High Pressure Liquid↗
PubMed1993

Effect of ginseng on plasma levels of ethanol in the rat.

The effect of red ginseng extract on the disposition of ethanol was studied in male Fischer 344 rats. Blood was drawn from the tail vein before and at 0.5, 1, 2, 3, 4, and 5 hours after dosing rats orally with aqueous ginseng (200 mg/kg), or an equivalent volume of water, followed immediately by 50% ethanol orally (3.2 g/kg) or intraperitoneally (1.5 g/kg). When the ethanol was administered orally, the mean area under the plasma concentration-time curve (0-->5 h) of ethanol was 21.0% less in the ginseng-treated rats than in the control rats. When the ethanol was administered intraperitoneally, there was no significant difference between ginseng-treated and control rats in area under the plasma concentration-time curve. The results show that plasma levels of ethanol are lower when the ethanol is administered orally with ginseng than when it is administered alone, but that orally administered ginseng has no effect on plasma levels of ethanol administered intraperitoneally.

Animals↗
PubMed2002

Gerimax ginseng regulates both humoral and cellular immunity during chronic Pseudomonas aeruginosa lung infection.

BACKGROUND: Chronic lung infection among patients with cystic fibrosis (CF), diffused panbronchiolitis, and chronic obstructive bronchiecteisis is often because of Pseudomonas aeruginosa. High morbidity and mortality in patients with CF are because of P. aeuruginosa that undergoes genotypic and phenotypic changes during prolonged stay in the lung resulting in increased antibiotic resistance, necessitating a search for alternative or supplement drugs. OBJECTIVE: In this study we compared the therapeutical effect of Gerimax (Dansk Droge A/S, Ishøj, Denmark) ginseng with placebo control by using a rat model of chronic P. aeruginosa lung infection mimicking that in patients with CF. METHODS AND INTERVENTIONS: The animals were challenged intratracheally with the prototypic P. aeruginosa PAO1 in alginate beads (1 x 10(9) colony-forming units per milliliter [CFU/mL]) followed by subcutaneous injection of ginseng extract (150 mg/kg body weight once per day) and examined on days 7 and 21. RESULTS: The day 7 analyses show that ginseng treatment resulted in lowering serum immunoglobulin M (IgM) and lung interleukin-4 (IL-4) levels compared to the control group. On day 21, higher lung IgA, upregulated serum IgG2a, stronger lung responses of interferon-gamma, IL-4, and tumor necrosis factor-alpha with milder lung pathology and enhanced lung bacteriology were detected in the ginseng-treated group when compared to those of the control group. CONCLUSION: These results suggest that the Gerimax ginseng treatment can modulate the immune system in favor of clearing the infection with P. aeruginosa in the lungs of rats. Thus, ginseng might be a promising alternative supplement for the treatment of chronic P. aeruginosa lung infection in patients with CF.

Animals↗
PubMed1996

Protective effect of ginseng on radiation-induced DNA double strand breaks and repair in murine lymphocytes.

We have examined the effects of ginseng on the induction and repair of gamma-ray-induced DNA double strand breaks (dsb) using neutral filter elution technique at pH 9.6 in cultured murine spleen lymphocytes. Ginseng water extract 500 micrograms/ml was added to the culture medium either for 48 hours prior to irradiation. Ginseng extract showed protective effect against the formation of dsb when it was treated for 48 hours before 100 Gy gamma-ray-irradiation. While repair was almost completed until 220.2 minutes after irradiation, DNA repair of irradiated cells in the presence of ginseng extract was did not return to the corresponding control levels even after 621.8 minutes. From these data, it could be calculated that ginseng reduced the relative strand scission factor (RSSF) by about 2. Therefore, it could be concluded that ginseng has radioprotective effect against gamma-ray induced DNA dsb and repair in cultured mouse lymphocytes.

Animals↗
PubMed2004

Menometrorrhagia and tachyarrhythmia after using oral and topical ginseng.

Widespread and uncontrolled use of ginseng has raised the question of its side effects and drug interactions. A 39-year-old female patient experienced menometrorrhagia. Her complaints had started 5 months earlier. The laboratory tests revealed follicle-stimulating hormone (FSH) and estradiol levels to be 10 mIU and 90 mIU, respectively. Endometrial biopsy was planned for the diagnosis of abnormal uterine bleeding. During the preoperative evaluation, the patient stated that she had been using both oral and topical ginseng for cosmetic reasons. The ECG revealed sinus tachycardia with occasional atrial premature beats. The procedure was postponed for 2 weeks so that the patient would stop taking ginseng, smoking, and drinking coffee. Arrhythmia stopped 10 days later. Tachycardia continued during the procedure but did not require treatment, as it did not cause any hemodynamic instability. An endometrial biopsy specimen showed a disordered proliferative pattern. The patient was advised to stop using oral and topical ginseng. During a follow-up visit, she had no sign of menometrorrhagia or tachyarrhythmia and her hemoglobin levels were in the normal range. Smoking and coffee consumption, along with ginseng use, can be responsible for arrhythmogenic effects. Abnormal uterine bleeding can cause tachycardia secondary to anemia. The clinical progress of this patient is consistent with our hypothesis that ginseng is responsible for menometrorrhagia, although this could be coincidental. Patients should always be asked prior to surgery if they use herbal medications, food supplements, or cosmetics as well as prescription drugs. This is of great importance for both diagnosis and avoidance of drug interactions and side effects during anesthesia.

Adult↗
PubMed2006

Expression and RNA interference-induced silencing of the dammarenediol synthase gene in Panax ginseng.

Panax ginseng is one of the most highly valued herbal medicines in the Orient, where it has gained an almost magical reputation for being able to maintain the quality of life. The root of ginseng contains noble tetracyclic triterpenenoid saponins, which are thought to be the major effective ingredients in P. ginseng. The first committed step in ginsenoside synthesis is the cyclization of 2,3-oxidosqualene to dammarenediol II by oxidosqualene cyclase, dammarenediol synthase (DDS). The gene encoding DDS has been characterized. Here, we investigated the expression of the DDS gene together with the genes involved in ginsenoside biosynthesis (SS, SE, PNX, PNY, PNY2 and PNZ). Expression of DDS mRNA was higher in flower buds compared with root, leaf and petiole of ginseng plants. Elicitor (methyl jasmonate) treatment up-regulated the expression of DDS mRNA. Ectopic expression of DDS in a yeast mutant (erg7) lacking lanosterol synthase resulted in the production of dammarenediol and hydroxydammarenone which were confirmed by liquid chromatography-atmospheric pressure chemical ionization mass spectrometry (LC/APCIMS). RNA interference (RNAi) of DDS in transgenic P. ginseng resulted in silencing of DDS expression which leads to a reduction of ginsenoside production to 84.5% in roots. These results indicate that expression of DDS played a vital role in the biosynthesis of ginsenosides in P. ginseng.

Acetates↗
PubMed1999

Ginseng treatment improves psychomotor performance at rest and during graded exercise in young athletes.

This study was designed to determine the effect of ginseng treatment on multiple choice reaction time (RT) during exercise. Fifteen soccer players (age 19.07 +/- 0.62 yrs) were placed in a double-blind manner into one of two groups: ginseng (n = 7), receiving 350 mg of ginseng daily for 6 weeks, or placebo (n = 8), receiving a placebo daily for 6 weeks. Before and after the treatment all the subjects performed an incremental bicycle ergometer exercise with intensity increasing 50 W every 3 min until volitional exhaustion. RT was measured before exercise, and then in the last 2 min of each exercise load. Maximal oxygen uptake (VO2max) and lactate threshold (LAT) were also determined from the exercise test. Ginseng treatment was found to shorten RT at rest and during exercise, shifting the exercise load associated with the shortest RT toward higher exercise loads. Neither ginseng nor placebo influenced VO2 max and LAT. In conclusion, ginseng extract does improve psychomotor performance during exercise without affecting exercise capacity.

Adult↗
PubMed2004

Lack of evidence for induction of CYP2B1, CYP3A23, and CYP1A2 gene expression by Panax ginseng and Panax quinquefolius extracts in adult rats and primary cultures of rat hepatocytes.

Treatment of rats with a single oral dose (10-30 mg/kg) of a crude Panax ginseng extract of unknown ginsenoside content has been reported to modestly increase hepatic microsomal cytochrome P450-mediated aminopyrine N-demethylation activity. In the present study, we compared the effect of P. ginseng and Panax quinquefolius extracts on rat hepatic CYP2B1, CYP3A23, and CYP1A2 gene expression. Adult male Sprague-Dawley rats (250-275 g) received, by oral gavage or i.p., P. ginseng extract [4% (w/w) total ginsenosides; 30 or 100 mg/kg/day for 1 or 4 days], P. quinquefolius extract [10% (w/w) total ginsenosides; 100 or 400 mg/kg/day for 21 consecutive days), or an equivalent volume (2 ml/kg) of the vehicle (0.9% NaCl or 0.3% carboxymethylcellulose) and were terminated 1 day after the last dose. P. ginseng and P. quinquefolius extracts did not affect body weight gain, absolute or relative liver weight, hepatic CYP2B1, CYP3A23, or CYP1A2 mRNA expression, or microsomal CYP2B-mediated 7-benzyloxyresorufin O-dealkylation (BROD) or CYP1A-mediated 7-ethoxyresorufin O-dealkylation (EROD) activity. In contrast, results from positive control experiments indicated that phenobarbital increased CYP2B1 mRNA and BROD activity, dexamethasone increased CYP3A23 mRNA, and beta-naphthoflavone increased CYP1A2 mRNA and EROD activity levels. Treatment of primary cultures of rat hepatocytes with either of the ginseng extracts (0.1-1000 microg/ml for 2 days) also did not affect CYP2B1 or CYP3A23 mRNA expression. Overall, our data indicate that P. ginseng and P. quinquefolius extracts do not increase rat hepatic CYP2B1, CYP3A23, or CYP1A2 gene expression.

Animals↗
PubMed2006

Long-term intake of North American ginseng has no effect on 24-hour blood pressure and renal function.

Ginseng is consumed by 10% to 20% of adults in Asia and by up to 5% in Western countries. Despite observational evidence suggesting a link between its intake and the development of hypertension, there remains no long-term scrutiny for its effect on blood pressure (BP). We therefore undertook a randomized, placebo-controlled, double-blinded, crossover trial in 52 hypertensive individuals to determine the effect of 12-week North American ginseng intake on 24-hour BP; we also measured serum cystatin C as a marker of renal function. After a 4-week placebo run-in, we randomly assigned 52 participants to 3 g/day of ginseng or placebo for 12 weeks. This was followed by an 8-week washout and a subsequent 12-week period in which the opposite treatment was administered. At run-in and at weeks 0 and 12 of each treatment period, participants were fitted with an ambulatory BP monitor to assess 24-hour BP. The primary outcome was the treatment difference at week 12 in mean 24-hour systolic BP. Secondary outcomes were treatment differences at week 12 in other ambulatory BP parameters and serum cystatin C. Forty participants (77%) completed the trial, with 3 removed from main analysis (n=2, antihypertensive drug changes; n=1, incomplete ambulatory monitoring). In the remaining 37, 12-week ginseng treatment was associated with a neutral effect on all ambulatory BP parameters compared with placebo; an intention-to-treat analysis supported this. Ginseng did not affect serum cystatin C level. Overall, long-term ginseng use had no effect on 24-hour BP and renal function in hypertensive individuals.

Blood Pressure↗