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The main active components of Panax ginseng are ginsenosides. Ginsenoside Rb1 and Rg1 are accepted as marker substances for quality control worldwide. The analytical methods currently used to detect these two compounds unfairly penalize steamed and dried (red) P. ginseng preparations, because it has a lower content of those ginsenosides than white ginseng. To manufacture red ginseng products from fresh ginseng, the ginseng roots are exposed to high temperatures for many hours. This heating process converts the naturally occurring ginsenoside Rb1 and Rg1 into artifact ginsenosides such as ginsenoside Rg3, Rg5, Rh1, and Rh2, among others. This study highlights the absurdity of the current analytical practice by investigating the time-dependent changes in the crude saponin and the major natural and artifact ginsenosides contents during simmering. The results lead us to recommend (20S)- and (20R)-ginsenoside Rg3 as new reference materials to complement the current P. ginseng preparation reference materials ginsenoside Rb1 and Rg1. An attempt has also been made to establish validated qualitative and quantitative analytical procedures for these four compounds that meet International Conference of Harmonization (ICH) guidelines for specificity, linearity, range, accuracy, precision, detection limit, quantitation limit, robustness and system suitability. Based on these results, we suggest a validated analytical procedure which conforms to ICH guidelines and equally values the contents of ginsenosides in white and red ginseng preparations.

Red ginseng saponin fraction-A (RGSF-A) contains a high percentage of panaxadiol saponins that were isolated from Korean red ginseng by ultrafiltration. The aim of this study was to elucidate the effects of RGSF-A on the porcine distal left anterior descending (LAD) coronary artery. The relaxant responses to RGSF-A were examined during contractions induced by 100 nM U46619 (9,11-dideoxy-9a,11a-methanoepoxy-prostaglandin F2a), a stable analogue of thromboxane A2. RGSF-A dose-dependently induced biphasic (fast- and slow-) relaxation in the distal LAD coronary artery in the presence of an intact endothelium. The fast-relaxation was quickly achieved in a minute, and then the slow-relaxation was slowly developed and sustained for more than thirty minutes after the administration of RGSF-A. The slow-relaxation had a tendency to be bigger than the fast-relaxation. Fast relaxation induced by RGSF-A was almost blocked by N ω -Nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase synthase inhibitor and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), a guanylate cyclase inhibitor. However slow relaxation induced by RGSF-A was only partially inhibited by L-NAME and ODQ. In the endothelium-removed ring, RGSF-A evoked only slow-relaxation to a certain extent. These data suggest that RGSF-A induced both endothelium dependent fast- and slow-relaxation and endothelium independent slow-relaxation in the porcine distal LAD coronary artery. The endothelium dependent fast-relaxation is mediated by the nitric oxide (NO)-cGMP pathway, and the endothelium dependent slow-relaxation is at least partially mediated by the NO-cGMP pathway. However, the endothelium-independent slow-relaxation remains to be elucidated.

We reported previously that the administration of Korean red ginseng water extract (KRG-WE) protected the guinea pig testis against damage induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (a potent endocrine disruptor). We also found that crude saponin from ginseng was the active ingredient responsible for this protection. Here, we examined the biological role of KRGWE in an animal model of age-induced dysfunction of spermatogenesis. Twenty-four male Sprague-Dawley (six 2-monthold and eighteen 12-month-old) rats were used. The young and old control groups received only vehicle. The ginseng saponin (GS)- and KRG-WE-treated groups received GS (40 ㎎/㎏ body weight/day) and KRG-WE (200 ㎎/㎏ body weight/day), respectively, for 4 months. The number of cells, Sertoli cell index, Johnsen’ score, and sex hormone levels decreased significantly with age. However, the administration of KRG-WE and GS markedly improved the number of germ cells, seminiferous tubular size, and Johnsen’ score in the old rats. Ginseng produced a distinct testicular histological improvement in old rats. KRG-WE and GS elevated testosterone levels, while attenuating the aberrant increase in follicle stimulating hormone and luteinizing hormone levels. Sperm kinematics evaluated by a computer-assisted sperm analyzer demonstrated improvement in the percentage of motile sperm, progressive sperm motility, and curvilinear velocity associated with sperm quality, supporting the beneficial role of red ginseng in senile spermatogenesis. Overall, the total water extract had a more potent effect than the corresponding saponin fraction. In conclusion, Korean red ginseng rejuvenated age-induced testicular dysfunction. Additionally, the total water extract was more potent than the corresponding saponin fraction.

In the present study, we synthesized a diglyceride (CLA-DG) from glycerol and conjugated linoleic acid (CLA). CLA-DG contained about 66% CLA as fatty acids. The safety of CLA-DG was assessed in acute and subchronic studies and in genotoxicity assays. In a single-dose acute study of CLA-DG, male and female rats were administered 5000 mg/kg body weight. CLA-DG caused no adverse effects and body weight gain and food consumption were within the normal range, thus the LD50 of CLA-DG was determined to be greater than 5000 mg/kg. In a 90-day subchronic study (500, 1000, and 2000 mg/kg b.w./day, oral via gavage) in male and female rats, no significant adverse effects in food consumption, body weight, mortality, clinical chemistry, hematology, gross pathology, and histopathology were observed. CLA-DG did not show any potential to induce gene mutations in reverse mutation tests using Salmonella typhimurium TA98, TA100, TA1535, TA1537, and Escherichia coli WP2uvrA strains. CLA-DG did not induce chromosomal aberrations in cultured Chinese hamster lung cells. The results from these studies support the safety of CLA-DG.

Compound K (CK), a protopanaxadiol ginsenoside metabolite, was previously shown to have immunomodulatory effects. In this study, we isolated the CK rich fractions (CKRF) from Korean Red Ginseng and investigated the regulation of CKRF-mediated inflammatory signaling during Toll-like receptor (TLR)-mediated cellular activation. Among various TLR ligands, CKRF considerably abrogated TLR4- or TLR9-induced inflammatory signaling. Both LPS and CpG-containing oligodeoxynucleotides (CpG-ODN) stimulation rapidly activates mitogen-activated protein kinases [MAPKs; extracellular signal-regulated kinases 1/2 and p38], NF-, and expression of pro-inflammatory cytokines tumor necrosis factor-, and interleukin-6 in murine bone marrow-derived macrophages (BMDMs) in a time- and dose-dependent manner. Of interest, pre-treatment of CKRF in either LPS/TLR4- or CpG-ODN/TLR9-stimulated macrophages substantially attenuated the LPS-induced inflammatory cytokine production and mRNA expressions, as well as MAPK and NF- activation. To our knowledge, this is the first description of the inhibitory roles for CKRF in TLR4- or TLR9-associated signaling in BMDMs. Collectively, these results demonstrate that CKRF specifically modulates distinct TLR4 and TLR9-mediated inflammatory responses, and further studies are urgently needed for their in vivo roles for potential therapeutic uses, such as in systemic inflammatory syndromes.

Korean red ginseng has broad efficacious effects against hypertension, diabetes, nociception, and cancer, and it counteracts weakness. It has been reported that Korean red ginseng is able to normalize blood pressure, improve cholesterol and lower blood glucose levels. We have recently reported that Korean red ginseng extract (KRGE) significantly prevented rat carotid arterial thrombosis in vivo, and inhibited platelet aggregation ex vivo and in vitro in a dose-dependent manner. The purpose of this study was to examine the effects of KRGE on blood circulation in human by measuring ex vivo platelet aggregation, plasma coagulation and serum lipid profiles in healthy volunteers. Subjects were randomly divided into three groups (placebo-group, KRGE-low dose group, KRGE-high dose group). Administration of KRGE to subjects significantly inhibited ADP-induced platelet aggregations both in KRGE-low dose group from to (p=0.0009), and in KRGE-high dose group from to (p=0.0039), respectively. Administration of KRGE to subjects also significantly inhibited collagen-induced platelet aggregations both in KRGE-low dose group from to (p=0.0916), and in KRGE-high dose group from to (p=0.0565), respectively. Whereas, KRGE has no significant effects on coagulation system, such as prothrombin time (PT) and activated partial thromboplastin time (APTT), and serum lipid profiles, such as total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol and triglyceride. KRGE also has no significant effects on hematological and serum biochemical profiles. These results suggest that KRGE has a potential to improve blood circulation through antiplatelet activity in human, and KRGE intake may be beneficial for the individuals with high risks of thrombotic and cardiovascular diseases.

To develop a new functional food material, edible crude saponin was isolated from soybean cake using HP-20 resin and its anticancer effect and immune-activity were investigated. The saponin significantly inhibited the growth of cancer cells such as A549, MCF-7 and SW480 at a concentration of 1,000 g/mL. Morphological changes was observed in the AS49 cells surface treated with the saponin of 1,000 g/mL concentration. The proliferation of mouse spleen cells treated with saponin was increased in a dose-dependent manner compared with untreated control cells until the concentration of 1 g/mL but decreased at higher concentrations than that. The NO production in marcrophage cell lines (RAW 264.7) treated with saponin was increased in a dosedependent manner compared with untreated control cells.

The aims of this study were to investigate the antioxidative and antitumor effects of crude polysaccharide fraction from Pleurtus eryngii (CPPE). CPPE inhibited autoxidation of linoleic acid at 1,000 g/mL concentration, and the inhibitory rates of lipid peroxidation in rat liver microsome were 5.28, 9.40, and 32.5% at 10, 100, and 1,000 g/mL concentrations, respectively. After treatment with CPPE for 72 hours, the inhibitory rates against MCF-7, A549 and AGS cell lines showed 42.3, 33.4 and 26.7% at concentration of 1,000 g/mL, respectively. Results of CPPE treatment at 100 and 300 mg/kg/day for 7 days in sarcoma-180 bearing-mice showed survival rates of 70 and 90%, respectively. Body weights of mice treated with CPPE were significantly decreased when compared with the control.

Previously we have reported that administration of Korean red ginseng water extract (KRG-WE) plays both preventive and therapeutic roles in testicular toxicity of guinea pigs exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Further study was carried out to verify the beneficial role of Korean red ginseng in TCDD-induced testicular toxicity with different animal species by different route of administration. Korean red ginseng crude saponin (KRG-CS) was prepared by Diaion HP-20 adsorption chromatography. One hundred twenty rats (Sprauge Dawley, 200±10 g) were divided into 6 groups. The normal control group (NC) received vehicle (i.p.) and saline (p.o.). Predetermined dosage of TCDD (40 μg/kg b.w., i.p.) was administered to single TCDD-treated (TT) and test (CS) groups. KRG-CS was administered (p.o.) at daily doses of 5 (CS5), 10 (CS10), 20 (CS20) and/or 40 mg/kg b.w. (CS40) for 5 weeks, starting 1 week before the TCDD-exposure. Body weight gain, organ weights, and sperm quality were investigated. Decrease in body weight gain induced by TCDD was greatly attenuated by KRG-CS in a dose-dependent manner. Testicular weight, sperm head counts and ratio of sperm with progressive movement in TT group decreased significantly but those parameters were improved by the treatment of KRG-CS in a dose-dependent manner. This result led us to conclude that crude saponin might be the active ingredient of Korean red ginseng that attenuates the testicular toxicity induced by TCDD.

Ginseng polysaccharide has been known to have multiple immunomodulatory effects. In this study, we investigated whether Panax ginseng polysaccharide (GP) would have a preventive effect on influenza infection. Administration of mice with GP prior to infection was found to confer a survival benefit against infection with H1N1 (A/PR/8/34) and H3N2 (A/Philippines/82) influenza viruses. Mice infected with the 2009 H1N1 virus suspended in GP solution showed moderately enhanced survival rates and lower levels of lung viral titers and the inflammatory cytokine (IL-6). Daily treatment of vaccinated mice with GP improved their survival against heterosubtypic lethal challenge. This study demonstrates the first evidence that GP can be used as a remedy against influenza viral infection.

In an ongoing study, rat and human urine have been examined for the presence of malondialdehyde (MDA) derivatives as indicators of the nature of lipid peroxidative damage caused by this compoundin vivo. MDA in urine was found to be present mainly in the form of two lysine adducts, one acetylated and the other unacetylated, reflectingin vivo reactions with tissue proteins. Two minor metabolites were identified as adducts with the phospholipid bases serine and ethanolamine and a third one as an adduct with the nucleic acid base guanine. The identification of an MDA adduct with deoxyguanosine (dG-MDA) among the products of hydrolysis of rat liver DNA suggested the possible occurrence of this compound in urine. In the present study dG-MDA was identified in rat and in human urine, and a high-performance liquid chromatographic method utilizing fluorescence detection was developed for its estimation. The method is sensitive to 1 pmol of dG-MDA and requires a minimum of 1 mL of rat urine or 5 mL of human urine. Its rate of excretion by five-week-old rats (28.54±2.28 nmol/kg/24 h) (mean±SEM) was higher than that for nine-week-old rats (6.29±1.02) and much higher than that for adult humans (0.40±0.05). The results indicate that, as reported for 8-hydroxy-deoxyguanosine, dG-MDA excretion is related to metabolic rate. Excretion of dG-MDA by the rat, like the excretion of total MDA, declines during growth on a body weight basis at a rate similar to the decrease in resting energy metabolism. In contrast to other MDA derivatives excreted in rat urine, vitamin E deficiency had no effect on the excretion of dG-MDA. Together with evidence that the dG-MDA content of rat liver DNA likewise is unaffected by vitamin E depletion or by administration of catalysts ofin vivo lipid peroxidation, these findings indicate that DNA is protected from lipid peroxidative damage, possibly through conservation of the vitamin E associated with the lipids of the nuclear membrane.

The major bioactive components of P. ginseng are the ginsenosides, a group of saponins with dammarane triterpenoid structure (Huang 1999). Almost 50 ginsenosides have been isolated from P. ginseng root (white and red ginsengs), and novel structures continue to be identified, particularly from Panax quinquefolius (American ginseng) and Panax japonica (Japanese ginseng) as well as their berries (Gillis 1997; Yoshikawa et al. 1998; Attele et al. 2002; Christensen 2009). In this chapter, we review the structural and pharmacological properties of ginseng, and its active constituents, including ginsenosides, polysaccharides, and polyacetylenic alcohols. The pharmacological and clinical usages of ginseng, particularly ginsenosides, are discussed in relation to its anticancer, antidiabetes, immunomodulatory functions, and improving CNS functions including learning, memory, and neurodegenerative diseases.

The antiplatelet and antithrombotic activities of Korean Red Ginseng (KRG) were examined on rat carotid artery thrombosis in vivo, and platelet aggregation in vitro and ex vivo. Administration of KRG to rats not only prevented carotid artery thrombosis in vivo in a dose-dependent manner, but also significantly inhibited ADP- and collagen-induced platelet aggregation ex vivo, while failed to prolong coagulation times such as activated partial thromboplastin time (APTT) and prothrombin time (PT), indicating the antithrombotic effect of KRG might be due to its antiplatelet aggregation rather than anticoagulation effect. In line with the above observations, KRG inhibited U46619-, arachidonic acid-, collagen- and thrombin-induced rabbit platelet aggregation in vitro in a concentration-dependent manner, with IC50 values of 620 +/- 12, 823 +/- 22, 722 + 21 and 650 +/- 14 microg/mL, respectively. Accordingly, KRG also inhibited various agonists-induced platelet serotonin secretions as it suppressed platelet aggregation. These results suggest that KRG has a potent antithrombotic effect in vivo, which may be due to antiplatelet rather than anticoagulation activity, and KRG intake may be beneficial to the individuals with high risks of thrombotic and cardiovascular diseases.

This study was carried out to develop a cost-, labor- and efficiency-effective elimination method of pesticide residues in ginseng extract. A two-phase partition method between soybean oil and distilled water or aqueous ginseng extract was employed for the elimination of pesticide residues. Content of the pesticides was determined by gas chromatography with electron capture or nitrogen phosphorus detector. A total of 15 pesticides representing four categories (organochlorine, organophosphorus, carbamate, pyrethroid) were spiked (ca. 2 ppm) to 2 ml soybean oil in a test tube and the oil was mixed with 6 ml distilled water or 10% aqueous ginseng extract. The test tubes were then vortexed (2 min) and centrifuged at 3000 rpm for 15 min to separate the oil and aqueous layers. Each layer was harvested and subjected to quantitative analysis of pesticides. The average distribution ratio of the pesticides to the oil layer was 94.4 +/- 6.7% in the mixture of the oil and distilled water, and 105.5 +/- 6.6% in the mixture of the oil and ginseng extract. No significant qualitative and quantitative change of ginsenosides, the active ingredients of Panax ginseng, was observed in the ginseng extract before and after the oil treatment. These results suggest that two-phase partition chromatography between soybean oil and the aqueous phase is a cost-, labor- and efficiency-effective reliable method for the elimination of pesticide residues in ginseng extract.

The effect of age and peroxidative stress on the concentration of a deoxyguanosine malondialdehyde adduct (dG-MDA) in rat tissues was investigated. Vitamin E deficiency had not effect on the dG-MDA content of liver DNA in rats fed a diet containing 10% corn oil. When 2% cod liver oil was added to this diet, the dG-MDA content of liver DNA doubled in the positive controls fed a high level of vitamin E (100 ppm dl-α-tocopherol), and there was a further increase when vitamin E was deleted. Neither iron nitrilotriacetate administration nor choline deficiency had any effect on the dG-MDA content of liver DNA. Carbon tetrachloride had a lowering effect. The failure of iron or carbon tetrachloride administration and of vitamin E deficiency to increase liver dG-MDA is consistent with their failure in previous experiments to affect the urinary excretion of dG-MDA. In contrast, these forms of peroxidative stress produce large increments in the urinary excretion of MDA adducts with lysine, reflecting increased formation and degradation of MDA-modified proteins. DNA appears to be protected from modification by MDA produced at extranuclear sites. The frequency of dG-MDA in different tissues of 4-month-old rats varied markedly: brain ≫ liver > kidneys and testes. Higher concentrations of dG-MDA were found in the liver and kidneys, but not the testes, of 25-month-old rats. The determinants of the concentration of dG-MDA in DNA merit further investigation.

The effects of the subchronic administration of Panax ginseng extracts were examined on the hepatic cytochrome P450-dependent monooxygenase system of guinea pigs pre-exposed to 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD). Panax ginseng extracts were intraperitoneally administered to guinea pigs at 100 mg/kg/day for 14 days from 1 week after a single intraperitoneal injection of 1 μg of TCDD/kg of body weight. TCDD treatment increased the total cytochrome P450 content 2.86-fold, and this was remarkably inhibited by the administration of Panax ginseng extracts. Treatment with ginseng extract alone also decreased the contents of cytochrome P450 by 33%, but both TCDD and ginseng extracts had no effect on cytochrome b 5 content. The administration of TCDD resulted in a 1.73-fold increase in microsomal NADPH-cytochrome P450 reductase activity in the guinea pig liver, and this was significantly inhibited by ginseng extracts, but treatment with ginseng extracts alone had no effect on its activity, and no statistical changes in the activity of NADPH-cytochrome b 5 reductase were observed in guinea pig liver due to TCDD and/or ginseng extract administration. Compared to the control, ECOD activity remarkably (1.76-fold) increased after TCDD administration, but this increase was completely inhibited by treatment with ginseng extract. Treatment with ginseng extract alone resulted in a 50% reduction of ECOD activity. TCDD administration remarkably induced benzphetamine demethylation (BPDM) activity, while ginseng extract also slightly increased the enzyme’s activity, but the induction attributed to ginseng extracts was not statistically significant. Even though administration of ginseng extracts slightly inhibited TCDD-induced BPDM activity, the inhibition was not statistically significant. These results indicate that ginseng extract exerts different effect on the induction of P450 isozymes. From these results, we suggest that Panax ginseng extracts may act as an inhibitor of CYP1A rather than that of CYP2B.

From the ether soluble alkaloidal fraction ofPanax ginseng, 4-methyl-5-thiazoleethanol, norharman and harman were isolated. 4-Methyl-5-thiazoleethanol was isolated for the first time from natural resources.

Two alkaloids were isolated from an ether-soluble alkaloidal fraction ofPanax ginseng. They were identified as 1-carbobutoxy-β-carboline and 1-carbomethoxy-β-carboline.