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Jin-Hee Lee, Hae-June Lee, Miyoung Yang, , Jong-Choon Kim, Chun-Sik Bae, Sung-Kee Jo, Jong-Sik Jang, Sung-Ho Kim
Published: 15 October 2013
Journal of Ginseng Research, Volume 37, pp 435-441; https://doi.org/10.5142/jgr.2013.37.435

Abstract:
This study investigated the effects of Korean Red Ginseng (KRG) on radiation-induced bone loss in C3H/HeN mice. C3H/HeN mice were divided into sham and irradiation (3 Gy, gamma-ray) groups. The irradiated mice were treated for 12 wk with vehicle, KRG (per os, p.o.) or KRG (intraperitoneal). Serum alkaline phosphatase (ALP), tartrate-resistant acid phosphatase, estradiol level, and biomechanical properties were measured. Tibiae were analyzed using micro-computed tomography. Treatment of KRG (p.o., 250 mg/kg of body weight/d) significantly preserved trabecular bone volume, trabecular number, structure model index, and bone mineral density of proximal tibia metaphysic, but did not alter the uterus weight of the mice. Serum ALP level was slightly reduced by KRG treatment. However, grip strength, mechanical property, and cortical bone architecture did not differ among the experimental groups. The results indicate that KRG can prevent radiation-induced bone loss in mice.
Published: 15 October 2013
Journal of Ginseng Research, Volume 37, pp 451-456; https://doi.org/10.5142/jgr.2013.37.451

Abstract:
Compound K is a major metabolite of ginsenoside Rb1, which has various pharmacological activities in vivo and in vitro. However, previous studies have focused on the pharmacokinetics of a single metabolite or the parent compound and have not described the pharmacokinetics of both compounds in humans. To investigate the pharmacokinetics of ginsenoside Rb1 and compound K, we performed an open-label, single-oral dose pharmacokinetic study using Korean Red Ginseng extract. We enrolled 10 healthy Korean male volunteers in this study. Serial blood samples were collected during 36 h after Korean Red Ginseng extract administration to determine plasma concentrations of ginsenoside Rb1 and compound K. The mean maximum plasma concentration of compound K was 8.35±3.19 ng/mL, which was significantly higher than that of ginsenoside Rb1 (3.94±1.97 ng/mL). The half-life of compound K was 7 times shorter than that of ginsenoside Rb1. These results suggest that the pharmacokinetics, especially absorption, of compound K are not influenced by the pharmacokinetics of its parent compound, except the time to reach the maximum plasma concentration The delayed absorption of compound K support the evidence that the intestinal microflora play an important role in the transformation of ginsenoside Rb1 to compound K.
, Jungyeob Ham, Young-Joo Kim, Jeong Hill Park, Eun-Ju Cho, Noriko Yamabe
Published: 15 October 2013
Journal of Ginseng Research, Volume 37, pp 379-388; https://doi.org/10.5142/jgr.2013.37.379

Abstract:
Diabetic nephropathy is one of the serious complications in patients with either type 1 or 2 diabetes mellitus but current treatments remain unsatisfactory. Results of clinical research studies demonstrate that Panax ginseng can help adjust blood pressure and reduce blood sugar and may be advantageous in the treatment of tuberculosis and kidney damage in people with diabetes. The heat-processing method to strengthen the efficacy of P. ginseng has been well-defined based on a long history of ethnopharmacological evidence. The protective effects of P. ginseng on pathological conditions and renal damage associated with diabetic nephropathy in the animal models were markedly improved by heat-processing. The concentrations of less-polar ginsenosides (20(S)-Rg3, 20(R)-Rg3, Rg5, and Rk1) and maltol in P. ginseng were significantly increased in a heat-processing temperature-dependent manner. Based on researches in animal models of diabetes, ginsenoside 20(S)-Rg3 and maltol were evaluated to have therapeutic potential against diabetic renal damage. These effects were achieved through the inhibition of inflammatory pathway activated by oxidative stress and advanced glycation endproducts. These findings indicate that ginsenoside 20(S)-Rg3 and maltol are important bioactive constituents of heat-processed ginseng in the control of pathological conditions associated with diabetic nephropathy.
Hyun Myung Ko, So Hyun Joo, Pitna Kim, Jin Hee Park, Hee Jin Kim, Geon Ho Bahn, Hahn Young Kim, , Seol-Heui Han, , et al.
Published: 15 October 2013
Journal of Ginseng Research, Volume 37, pp 401-412; https://doi.org/10.5142/jgr.2013.37.401

Abstract:
Korean Red Ginseng (KRG) is an oriental herbal preparation obtained from Panax ginseng Meyer (Araliaceae). To expand our understanding of the action of KRG on central nervous system (CNS) function, we examined the effects of KRG on tissue plasminogen activator (tPA)/plasminogen activator inhibitor-1 (PAI-1) expression in rat primary astrocytes. KRG extract was treated in cultured rat primary astrocytes and neuron in a concentration range of 0.1 to 1.0 mg/mL and the expression of functional tPA/PAI-1 was examined by casein zymography, Western blot and reverse transcription-polymerase chain reaction. KRG extracts increased PAI-1 expression in rat primary astrocytes in a concentration dependent manner (0.1 to 1.0 mg/mL) without affecting the expression of tPA itself. Treatment of 1.0 mg/mL KRG increased PAI-1 protein expression in rat primary astrocytes to 319.3±65.9% as compared with control. The increased PAI-1 expression mediated the overall decrease in tPA activity in rat primary astrocytes. Due to the lack of PAI-1 expression in neuron, KRG did not affect tPA activity in neuron. KRG treatment induced a concentration dependent activation of PI3K, p38, ERK1/2, and JNK in rat primary astrocytes and treatment of PI3K or MAPK inhibitors such as LY294002, U0126, SB203580, and SP600125 (10 μM each), significantly inhibited 1.0 mg/mL KRG-induced expression of PAI- 1 and down-regulation of tPA activity in rat primary astrocytes. Furthermore, compound K but not other ginsenosides such as Rb1 and Rg1 induced PAI-1 expression. KRG-induced up-regulation of PAI-1 in astrocytes may play important role in the regulation of overall tPA activity in brain, which might underlie some of the beneficial effects of KRG on CNS such as neuroprotection in ischemia and brain damaging condition as well as prevention or recovery from addiction.
Sang-Hyun Sohn, Si-Kwan Kim, Young-Ock Kim, Hyung-Don Kim, Yu-Su Shin, Seung-Ok Yang, Seung-Yu Kim,
Published: 15 October 2013
Journal of Ginseng Research, Volume 37, pp 442-450; https://doi.org/10.5142/jgr.2013.37.442

Abstract:
The aim of this study was to determine and compare the preventive effect of Korean White Ginseng and Red Ginseng on oxidative stress in H2O2-treated HepG2 cells. The roots of ginseng were extracted with 70% methanol and partitioned with butanol to obtain saponin fractions, which have been known as bioactive constituents of ginseng. 2',7'-Dichlorofluorescein diacetate (DCF-DA) assay and malondialdehyde (MDA) content were measured for evaluating intracellular reactive oxygen species (ROS) generation. Also, mRNA expressions and activities of antioxidant enzymes were analyzed to determine the antioxidant activity of saponin or non-saponin fractions of ginsengs. According to DCF-DA assay, H2O2-induced MDA release and ROS generation were significantly reduced by treatment with saponin fractions of white and red ginseng roots. Also, saponin fractions increased effectively intracellular antioxidant enzyme activities including catalase, glutathione peroxidase and superoxide dismutase in H2O2- treated HepG2 hepatoma cells. In general, red ginseng was more effective than white ginseng for reducing oxidative stress. These results indicate that administration of red ginseng may certainly contribute relatively stronger than white ginseng to prevent from damaging liver function by oxidative stress.
Myung-Hee Lee, Sung-Soo Kim, Chang-Won Cho, Sang-Yoon Choi, Gyo In, Kyung-Tack Kim
Published: 15 October 2013
Journal of Ginseng Research, Volume 37, pp 468-474; https://doi.org/10.5142/jgr.2013.37.468

Abstract:
Ginseng seed oil was prepared using compressed, solvent, and supercritical fluid extraction methods of ginseng seeds, and the extraction yield, color, phenolic compounds, fatty acid contents, and phytosterol contents of the ginseng seed oil were analyzed. Yields were different depending on the roasting pretreatment and extraction method. Among the extraction methods, the yield of ginseng seed oil from supercritical fluid extraction under the conditions of 500 bar and 65℃ was the highest, at 17.48%. Color was not different based on the extraction method, but the b-value increased as the roasting time for compression extraction was increased. The b-values of ginseng seed oil following supercritical fluid extraction were 3.54 to 15.6 and those following compression extraction after roasting treatment at 200℃ for 30 min, were 20.49, which was the highest value. The result of the phenolic compounds composition showed the presence of gentisic acid, vanillic acid, ferulic acid, and cinnamic acid in the ginseng seed oil. No differences were detected in phenolic acid levels in ginseng seed oil extracted by compression extraction or solvent extraction, but vanillic acid tended to decrease as extraction pressure and temperature were increased for seed oil extracted by a supercritical fluid extraction method. The fatty acid composition of ginseng seed oil was not different based on the extraction method, and unsaturated fatty acids were >90% of all fatty acids, among which, oleic acid was the highest at 80%. Phytosterol analysis showed that β-sitosterol and stigmasterol were detected. The phytosterol content of ginseng seed oil following supercritical fluid extraction was 100.4 to 135.5 mg/100 g, and the phytosterol content following compression extraction and solvent extraction was 71.8 to 80.9 mg/100 g.
Jae-Jun Ahn, Kashif Akram, Mi-Seon Jeong, Ji-Young Kwak, Eun-Joo Park,
Published: 15 October 2013
Journal of Ginseng Research, Volume 37, pp 483-490; https://doi.org/10.5142/jgr.2013.37.483

Abstract:
Gamma-irradiation (0-7 kGy) of ginseng is permitted in Korea for the purpose of microbial decontamination; with strict labeling, traceability and monitoring requirements. An identification study was conducted to determine the photostimulated-luminescence (PSL) and thermoluminescence (TL) properties of gamma-irradiated fresh and white ginsengs cultivated in different areas. Dosedependent PSL-based screening was possible for white ginseng samples; however, inappropriate results from non-irradiated fresh ginseng samples were obtained, showing intermediate (700 to 5,000) or positive (T2 >5,000, irradiated) PSL counts due to the abundance of minerals on the surfaces of the samples. TL analysis of separated minerals from all non-irradiated samples gave TL glow curves of low intensity with a maximum peak after 300℃. However, well-defined irradiation-specific (high intensity with a maximum peak at about 200℃) glow curves were observed for all the irradiated samples, regardless of their type and origins. TL ratios (first glow curve /second glow curve) were also determined to confirm the irradiated (>0.1) and non-irradiated (<0.1) results. SEM-EDX (scanning electron microscope-energy dispersive X-ray) and XRD (X-ray diffraction) spectroscopic analyses showed that feldspar and quartz minerals were the main source for the typical radiation-specific luminescence properties.
Chang Taek Oh, Jong Il Park, Yi Ra Jung, Yeon Ah Joo, Dong Ha Shin, Hyoung Joo Cho, Soo Mi Ahn, Young-Ho Lim, Chae Kyu Park,
Published: 15 October 2013
Journal of Ginseng Research, Volume 37, pp 389-400; https://doi.org/10.5142/jgr.2013.37.389

Abstract:
Korean Red Ginseng (KRG) has been reported to exert anticancer, anti-oxidant, and anti-inflammatory effects. However, there has been no report on the effect of KRG on skin pigmentation. In this study, we investigated the inhibitory effect of KRG on melanocyte proliferation. KRG extract (KRGE) at different concentrations had no effect on melanin synthesis in melan-A melanocytes. Saponin of KRG (SKRG) inhibited melanin content to 80% of the control at 100 ppm. Keratinocyte-derived factors induced by UV-irradiation were reported to stimulate melanogenesis, differentiation, proliferation, and dendrite formation. In this study, treatment of melan-A melanocytes with conditioned media from UV-irradiated SP-1 keratinocytes increased melanocyte proliferation. When UV-irradiated SP-1 keratinocytes were treated with KRGE or SKRG, the increase of melanocyte proliferation by the conditioned media was blocked. Granulocyte-macrophage colony-stimulating factor (GM-CSF) was produced and released from UV-irradiated keratinocytes. This factor has been reported to be involved in regulating the proliferation and differentiation of epidermal melanocytes. In this study, GM-CSF was significantly increased in SP-1 keratinocytes by UVB irradiation (30 mJ/cm2), and the proliferation of melan-A melanocytes increased significantly by GM-CSF treatment. In addition, the proliferative effect of keratinocyte-conditioned media on melan-A melanocytes was blocked by anti-GM-CSF treatment. KRGE or SKRG treatment decreased the expression of GM-CSF in SP-1 keratinocytes induced by UVB irradiation. These results demonstrate that UV irradiation induced GM-CSF expression in keratinocytes and KRGE or SKRG inhibited its expression. Therefore, KRG could be a good candidate for regulating UV-induced melanocyte proliferation.
, Jung Hwan Kim, Hyuk Min Kwon, Dong Heon Lee, Moo-Ho Won, Young-Guen Kwon
Published: 15 October 2013
Journal of Ginseng Research, Volume 37, pp 413-424; https://doi.org/10.5142/jgr.2013.37.413

Abstract:
Korean Red Ginseng extract (KRGE) is a traditional herbal medicine utilized to prevent endothelium dysfunction in the cardiovascular system; however, its underlying mechanism has not been clearly elucidated. We here examined the pharmacological effect and molecular mechanism of KRGE on apoptosis of human umbilical vein endothelial cells (HUVECs) in a serum-deprived apoptosis model. KRGE protected HUVECs from serum-deprived apoptosis by inhibiting mitochondrial cytochrome c release and caspase-9/-3 activation. This protective effect was significantly higher than that of American ginseng extract. KRGE treatment increased antiapoptotic Bcl-2 and Bcl-XL protein expression and Akt-dependent Bad phosphorylation. Moreover, KRGE prevented serum deprivation-induced subcellular redistribution of these proteins between the mitochondrion and the cytosol, resulting in suppression of mitochondrial cytochrome c release. In addition, KRGE increased nitric oxide (NO) production via Akt-dependent activation of endothelial NO synthase (eNOS), as well as inhibited caspase-9/-3 activities. These increases were reversed by co-treatment of cells with inhibitors of eNOS and phosphoinositide 3-kinase (PI3K) and pre-incubation of cell lysates in dithiothreitol, indicating KRGE induces NO-mediated caspase modification. Indeed, KRGE inhibited caspase-3 activity via S-nitrosylation. These findings suggest that KRGE prevents serum deprivation-induced HUVEC apoptosis via increased Bcl-2 and Bcl-XL protein expression, PI3K/Akt-dependent Bad phosphorylation, and eNOS/NO-mediated S-nitrosylation of caspases. The cytoprotective property of KRGE may be valuable for developing new pharmaceutical means that limit endothelial cell death induced during the pathogenesis of vascular diseases.
Eunson Hwang, , Taek Hwan Lee, Heon-Sub Shin, Sang-Yong Park, Don-Gil Lee, Byung-Goo Cho, Hyunjoo Sohn, Oh Wook Kwon, Sun Yeou Kim, et al.
Published: 15 October 2013
Journal of Ginseng Research, Volume 37, pp 425-434; https://doi.org/10.5142/jgr.2013.37.425

Abstract:
UV irradiation is the main factor contributing to skin damages that are associated with an excessive production of matrix-degrading metalloproteinase (MMP)-1 and a deficient expression of collagens. To date, red ginseng has been revealed to possess many biomedical effects, such as anti-aging, anti-oxidation, and anti-inflammatory. In this study, we prepared the Korean Red Ginseng extracts treated with enzyme (KRGE) and investigated the effects of dietary KRGE on the formation of wrinkles generated by UVB irradiation in hairless mice. It was found that KRGE inhibited the UVB-induced formation of wrinkles, epidermal thickness, and skin dryness in hairless mice. Further results also showed that KRGE attenuated UVB-induced MMP-1 level, while accelerated procollagen type I, transforming growth factor-β1 secretion. Interestingly, the expression of profilaggrin and filaggrin in both the epidermis and dermis were decreased due to UVB exposure and reversed by KRGE. The KRGE 0.06% was prior to KRGE 0.24%. In view of these results, which indicated that KRGE protected skin from UVB-induced photodamages, which may not only mediated by regulating of MMP-1 and procollagen type I, but also by increasing the production of profilaggrin and filaggrin. In conclusion, our results suggest that KRGE may be a promising agent for the treatment of skin photodamages. The challenge of KRGE will be expected as cosmeceuticals and nutraceuticals in order to intervene in aging-related degenerative skin changes.
Hee-Won Park, Gyo In, Sung-Tai Han, Myoung-Woo Lee, So-Young Kim, Kyung-Tack Kim, Byung-Goo Cho, Gyeong-Ho Han, Il-Moo Chang
Published: 15 October 2013
Journal of Ginseng Research, Volume 37, pp 457-467; https://doi.org/10.5142/jgr.2013.37.457

Abstract:
A quick and simple method for simultaneous determination of the 30 ginsenosides (ginsenoside Ro, Rb1, Rb2, Rc, Rd, Re, Rf, Rg1, 20(S)-Rg2, 20(R)-Rg2, 20(S)-Rg3, 20(R)-Rg3, 20(S)-Rh1, 20(S)-Rh2, 20(R)-Rh2, F1, F2, F4, Ra1, Rg6, Rh4, Rk3, Rg5, Rk1, Rb3, Rk2, Rh3, compound Y, compound K, and notoginsenoside R1) in Panax ginseng preparations was developed and validated by an ultra performance liquid chromatography photo diode array detector. The separation of the 30 ginsenosides was efficiently undertaken on the Acquity BEH C-18 column with gradient elution with phosphoric acids. Especially the chromatogram of the ginsenoside Ro was dramatically enhanced by adding phosphoric acid. Under optimized conditions, the detection limits were 0.4 to 1.7 mg/L and the calibration curves of the peak areas for the 30 ginsenosides were linear over three orders of magnitude with a correlation coefficients greater than 0.999. The accuracy of the method was tested by a recovery measurement of the spiked samples which yielded good results of 89% to 118%. From these overall results, the proposed method may be helpful in the development and quality of P. ginseng preparations because of its wide range of applications due to the simultaneous analysis of many kinds of ginsenosides.
Il-Woung Kim, Kyu-Min Cha, Jae Joon Wee, Michael B. Ye,
Published: 15 October 2013
Journal of Ginseng Research, Volume 37, pp 475-482; https://doi.org/10.5142/jgr.2013.37.475

Abstract:
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.
Mu Sup Beon, Jun Ho Park, Hag Mo Kang, Sung Jong Cho, Hyun Kim
Published: 15 October 2013
Journal of Ginseng Research, Volume 37, pp 491-495; https://doi.org/10.5142/jgr.2013.37.491

Abstract:
Wood-cultivated ginseng, including roots in its dried form, is produced in forest land without using artificial facilities such as light barriers. To identify suitable sites for the propagation of wood-cultivated ginseng, factor combination technique (FCT) and linear combination technique (LCT) were used with geographic information system and the results were superimposed onto an actual wood-cultivated ginseng plantation. The LCT more extensively searched for suitable sites of cultivation than that by the FCT; further, the LCT probed wide areas considering the predominance of precipitous mountains in Korea. In addition, the LCT showed the much higher degree of overlap with the actual cultivation sites; therefore, the LCT more comprehensively reflects the cultivator's intention for site selection. On the other hand, the inclusion of additional factors for the selection of suitable cultivation sites and experts' opinions may enhance the effectiveness and accuracy of the LCT for site application.
Muhammad Hanif Siddiqi, Sungeun Ahn, Sera Kang, Yeon-Ju Kim, Natarajan Sathishkumar, Dong-Uk Yang,
Published: 15 July 2013
Journal of Ginseng Research, Volume 37, pp 261-268; https://doi.org/10.5142/jgr.2013.37.261

Abstract:
The ginseng plant (Panax ginseng Meyer) has a large number of active ingredients including steroidal saponins with a dammarane skeleton as well as protopanaxadiol and protopanaxatriol, commonly known as ginsenosides, which have antioxidant, anticancer, antidiabetic, anti-adipocyte, and sexual enhancing effects. Though several discoveries have demonstrated that ginseng saponins (ginsenosides) as the most important therapeutic agent for the treatment of osteoporosis, yet the molecular mechanism of its active metabolites is unknown. In this review, we summarize the evidence supporting the therapeutic properties of ginsenosides both in vivo and in vitro, with an emphasis on the different molecular agents comprising receptor activator of nuclear factor kappa-B ligand, receptor activator of nuclear factor kappa-B, and matrix metallopeptidase-9, as well as the bone morphogenetic protein-2 and Smad signaling pathways.
Mi Ra Lee, Byung Chan Kim, Ran Kim, Hyun In Oh, Hyun Kyoung Kim, Kang Ju Choi,
Published: 15 July 2013
Journal of Ginseng Research, Volume 37, pp 308-314; https://doi.org/10.5142/jgr.2013.37.308

Abstract:
Black ginseng is produced by a repeated steaming process. The aim of this study was to investigate the anti-obesity effects of black ginseng ethanol extract (BG-EE) in high fat (HF) diet-fed mice. Two groups were fed either a normal control (NC) diet or a HF diet (45% kcal fat). The other three groups were given a HF diet supplemented with 1% BG-EE, 3% BG-EE, and 5% BG-EE for 12 wk. The anti-obesity effects of the BG-EE supplement on body weight, the development of fat mass, and lipid mechanisms were assessed in obese mice. HF-induced hyperlipidemia, fat accumulation in the liver, and white adipose tissues were reduced after BG-EE supplementation. Total fecal weight and the amount of fecal fat excretion also were increased after BG-EE supplementation. These results suggest that BG-EE may be useful to ameliorate HF-induced obesity through the strong inhibition of fat digestion.
Dong Sub Kim, Mira Song, Sun-Hee Kim, Duk-Soo Jang, Jin-Baek Kim, Bo-Keun Ha, Sang Hoon Kim, Kyung Jun Lee, Si-Yong Kang, Il Yun Jeong
Published: 15 July 2013
Journal of Ginseng Research, Volume 37, pp 332-340; https://doi.org/10.5142/jgr.2013.37.332

Abstract:
In this study, gamma rays were used to irradiate embryogenic calli induced from cotyledon explants of Panax ginseng Meyer. After the embryogenic calli were irradiated, they were transferred to adventitious roots using an induction medium; next, mutated adventitious root (MAR) lines with a high frequency of adventitious root formations were selected. Two MAR lines (MAR 5-2 and MAR 5-9) from the calli treated with 50 Gy of gamma rays were cultured on an NH4NO3-free Murashige and Skoog medium with indole-3-butyric acid 3 mg/L. The expression of genes related to ginsenoside biosynthesis was analyzed using reverse transcription polymerase chain reaction with RNA prepared from native ginseng (NG), non-irradiated adventitious root (NAR) and 2 MAR lines. The expression of the squalene epoxidase and dammarenediol synthase genes was increased in the MAR 5-2 line, whereas the phytosterol synthase was increased in the MAR 5-9 line. The content and pattern of major ginsenosides (Rb1, Rb2, Rc, Rd, Re, Rf, and Rg1) were analyzed in the NG, NAR, and 2 MAR lines (MAR 5-2 and MAR 5-9) using TLC and HPLC. In the TLC analysis, the ginsenoside patterns in the NG, NAR, and 2 MAR lines were similar; in contrast, the MAR 5-9 line showed strong bands of primary ginsenosides. In the HPLC analysis, compared with the NG, one new type of ginsenoside was observed in the NAR and 2 MAR lines, and another new type of ginsenoside was observed in the 2 MAR lines irradiated with gamma rays. The ginsenoside content of the MAR 5-9 line was significantly greater in comparison to the NG.
Ru Zhang, Jie Zhu, Hong-Zhe Cao, Xiao-Lei Xie, Jing-Jia Huang, Xiang-Hui Chen, Zhi-Yong Luo
Published: 15 July 2013
Journal of Ginseng Research, Volume 37, pp 361-370; https://doi.org/10.5142/jgr.2013.37.361

Abstract:
A lysine histidine transporter (LHT) cDNA was isolated and characterized from the roots of Panax ginseng, designated PgLHT. The cDNA is 1,865 bp with an open reading frame that codes for a protein with 449 amino acids and a calculated molecular mass of 50.6 kDa with a predicted isoelectric point of 8.87. Hydropathy analysis shows that PgLHT is an integral membrane protein with 9 putative membrane-spanning domains. Multiple sequence alignments show that PgLHT shares a high homology with other plant LHTs. The expression profile of the gene was investigated by real-time quantitative polymerase chain reaction during various chemical treatments. PgLHT was up-regulated in the presence of abscisic acid, salicylic acid, methyl jasmonate, NaCl, and amino acids. To further explore the function of PgLHT gene, full-length cDNA of PgLHT was introduced into P. ginseng by Agrobacterium rhizogenes A4. The overexpression of PgLHT in the hairy roots led to an obviously increase of biomass compared to the controls, and after addition of the amino acids, the overexpressed-PgLHT hairy roots grew more rapidly than untreated controls during early stage of the culture cycle. The results suggested that the PgLHT isolated from ginseng might have role in the environmental stresses and growth response.
Hyun-Jin Kim, Chang-Won Cho, Jin-Taek Hwang, Nari Son, Ji Hea Choi, Gun-Sub Shim,
Published: 15 July 2013
Journal of Ginseng Research, Volume 37, pp 371-378; https://doi.org/10.5142/jgr.2013.37.371

Abstract:
Serum and liver metabolites in rats fed red ginseng (RG) were analyzed by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. The mass data were analyzed by partial least squares-discriminant analysis (PLS-DA) to discriminate between control and RG groups and identify metabolites contributing to this discrimination. The RG group was clearly separated from the control group on PLS-DA scores plot for serum samples, but not liver samples. The major metabolites contributing to the discrimination included lipid metabolites (lysophosphatidylcholine, acyl-carnitine, and sphingosine), isoleucine, nicotinamide, and corticosterone in the serum; the blood levels of all but isoleucine were reduced by RG administration. Not all metabolites were positively correlated with the health benefits of RG. However, the blood levels of lysophosphatidylcholine, which stimulate various diseases, and long-chain acylcarnitines and corticosterone, which activate the stress response, were reduced by RG, suggesting long-term RG might relieve stress and prevent physiological and biological problems.
Kyu Hee Lim, Dae-Jun Lim,
Published: 15 July 2013
Journal of Ginseng Research, Volume 37, pp 283-292; https://doi.org/10.5142/jgr.2013.37.283

Abstract:
Ginsenosides are divided into two groups based on the types of the panaxadiol group (e.g., ginsenoside-Rb1 and -Rc) and the panaxatriol group (e.g., ginsenoside-Rg1 and -Re). Among them, ginsenoside-Re (G-Re) is one of the compounds with the highest content in Panax ginseng and is responsible for pharmacological effects. However, it is not yet well reported if G-Re increases the hemodynamics functions on ischemia (30 min)/reperfusion (120 min) (I/R) induction. Therefore, in the present study, we investigated whether treatment of G-Re facilitated the recovery of hemodynamic parameters (heart rate, perfusion pressure, aortic flow, coronary flow, and cardiac output) and left ventricular developed pressure (±dp/dtmax). This research is designed to study the effects of G-Re by studying electrocardiographic changes such as QRS interval, QT interval and R-R interval, and inflammatory marker such as tissue necrosis factor-α (TNF-α) in heart tissue in I/R-induced heart. From the results, I/R induction gave a significant increase in QRS interval, QT interval and R-R interval, but showed decrease in all hemodynamic parameters. I/R induction resulted in increased TNF-α level. Treatment of G-Re at 30 and 100 μM doses before I/R induction significantly prevented the decrease in hemodynamic parameters, ameliorated the electrocardiographic abnormality, and inhibited TNF-α level. In this study, G-Re at 100 μM dose exerted more beneficial effects on cardiac function and preservation of myocardium in I/R injury than 30 μM. Collectively, these results indicate that G-Re has distinct cardioprotectective effects in I/R induced rat heart.
Mi-Yeon Kim,
Published: 15 July 2013
Journal of Ginseng Research, Volume 37, pp 293-299; https://doi.org/10.5142/jgr.2013.37.293

Abstract:
20S-dihydroprotopanaxadiol (2H-PPD) is a derivative of protopanaxadiol, a glycone of ginsenosides prepared from Panax ginseng. Although ginsenosides and acidic polysaccharides are known to be major active ingredients in ginseng, the immunopharmacological activities of their metabolites and derivatives have not been fully explored. In this study, we aimed to elucidate the regulatory action of 2H-PPD on the function of monocytes and macrophages in innate immune responses. 2H-PPD was able to boost the phagocytic uptake of fluorescein isothiocyanate-dextran in macrophages and enhance the generation of radicals (reactive oxygen species) in sodium nitroprusside-treated RAW264.7 cells. The surface levels of the costimulatory molecules such as CD80 and CD86 were also increased during 2H-PPD treatment. In addition, this compound boosted U937 cellcell aggregation induced by CD29 and CD43 antibodies, but not by cell-extracellular matrix (fibronectin) adhesion. Similarly, the surface levels of CD29 and CD43 were increased by 2H-PPD exposure. Therefore, our results strongly suggest that 2H-PPD has the pharmacological capability to upregulate the functional role of macrophages/monocytes in innate immunity.
Mi-Yeon Kim,
Published: 15 July 2013
Journal of Ginseng Research, Volume 37, pp 300-307; https://doi.org/10.5142/jgr.2013.37.300

Abstract:
20S-dihydroprotopanaxatriol (2H-PPT) is a derivative of protopanaxatrol from ginseng. Unlike other components from Panax ginseng, the pharmacological activity of this compound has not been fully elucidated. In this study, we investigated the modulatory activity of 2H-PPT on the cellular responses of monocytes and macrophages to understand its immunoregulatory actions. 2H-PPT strongly upregulated the release of radicals in sodium nitroprusside-treated RAW264.7 cells and the surface levels of costimulatory molecule CD86. More importantly, this compound remarkably suppressed nitric oxide production, morphological changes, phagocytic uptake, cell-cell aggregation, and cell-matrix adhesion in RAW264.7 and U937 cells in the presence or absence of lipopolysaccharide, anti-CD43 antibody, fibronectin, and phorbal 12-myristate 13-acetate. Therefore, our results suggest that 2H-PPT can be applied as a novel functional immunoregulator of macrophages and monocytes.
Eun-Hye Kim, In-Hye Kim, Jung-Ah Ha, Kwang-Tae Choi, Suhkneung Pyo,
Published: 15 July 2013
Journal of Ginseng Research, Volume 37, pp 315-323; https://doi.org/10.5142/jgr.2013.37.315

Abstract:
Ginseng is known to have antistress effects. Previously, red ginseng (RG) was shown to repress stress-induced peptidyl arginine deiminase type IV (PADI4) via estrogen receptor β (ERβ) in the brain, thus inhibiting brain cell apoptosis. Moreover, tumor necrosis factor (TNF)-α plays a critical role in immobilization (IMO) stress. However, the signaling pathway of RG-mediated repressesion of inflammation is not completely understood. In this study, we determined how RG modulated gene expression in stressed brain cells. Since secretion of TNF-α is modulated via TNF-α converting enzyme (TACE) and nuclear factor (NF)-κB, we examined the inflammatory pathway in stressed brain cells. Immunohistochemistry revealed that TACE was induced by IMO stress, but RG repressed TACE induction. Moreover, PADI4 siRNA repressed TACE expression compared to the mock transfected control suggesting that PADI4 was required for TACE expression. A reporter assay also revealed that H2O2 oxidative stress induced NF-κB in neuroblastoma SK-N-SH cells, however, RG pretreatment repressed NF-κB induction. These findings were supported by significant induction of nitric oxide and reactive oxygen species (ROS) by oxidative stress, which could be repressed by RG administration. Taken together, RG appeared to repress stress-induced PADI4 via TACE and NF-κB in brain cells thus preventing production of ROS and subsequently protecting brain cells from apoptosis.
Chang-Won Cho, Young-Chan Kim, Jin-Hee Kang, Young Kyoung Rhee, Sang Yoon Choi, Kyung-Tack Kim, Young-Chul Lee, Hee-Do Hong
Published: 15 July 2013
Journal of Ginseng Research, Volume 37, pp 349-354; https://doi.org/10.5142/jgr.2013.37.349

Abstract:
Dried ginseng (DG) is in fact the representing ginseng product in the worldwide market. Although it is made in various packages depending on the processing method, size and age of DG, basic scientific data reporting the chemical components are limited. In this study, 4-year-old curved ginseng (CG), one of the domestic DG products, was selected for further investigation. Eighty-six samples of 30 and 50 piece-grade CG, which are the most widely distributed in the market, were collected for 5 yr. Their major components, such as moisture, total sugar, acidic polysaccharides, total phenolic compounds, and saponins, were analyzed to figure out the standard quality characteristics. The moisture content of all CG samples was less than 15%. The total water-soluble sugar contents were 22.9% to 47.8% and 23.2% to 49.5% in the 30 and 50 piece-grade CG, respectively. The acidic polysaccharide contents were 3.6% to 6.7% and 2.9% to 6.9% in the 30 and 50 piece-grade CG, respectively. The total phenolic compound content was 0.4% to 0.5% in CG, regardless of the piece-grade. The crude saponin content, which represents the active component of ginseng, was over 2% in all samples. In 30 piece-grade CG samples, the contents of major ginsenosides, Rb1, Rf, and Rg1, were 2.2 to 4.7 mg/g, 0.4 to 1.3 mg/g, and 1.6 to 4.0 mg/g, respectively. The ginsenoside contents in 50 piece-grade CG samples were 2.1 to 3.9 mg/g (Rb1), 0.5 to 1.2 mg/g (Rf), and 1.3 to 3.4 mg/g (Rg1). Overall, since there were relatively high standard deviation and coefficient of variation in all the chemical component contents that were assessed, we found some difficulties in showing the CG standard chemical component characteristics by average, standard deviation, and other statistical analysis factors.
Shin-Jung Kim, ,
Published: 15 July 2013
Journal of Ginseng Research, Volume 37, pp 269-272; https://doi.org/10.5142/jgr.2013.37.269

Abstract:
MGB-20 findings show that the ginseng berry extracts that had been processed with microwave and vinegar for 20 min peaked in the level of ginsenoside Rg2 (2.28%) and Rh1 (1.28%). MGB-1 peaked in the level of ginsenoside Rg3 (1.13%) in the ginseng berry extract processed with microwave and vinegar for 1 min.
Kyu Hee Lim, Dukhwan Ko,
Published: 15 July 2013
Journal of Ginseng Research, Volume 37, pp 273-282; https://doi.org/10.5142/jgr.2013.37.273

Abstract:
The present study was designed to investigate the cardioprotective effects of Korean Red Ginseng extract (KRG) on isoproterenol (ISO)-induced cardiac injury in rats, particularly in regards to electrocardiographic changes, hemodynamics, cardiac function, serum cardiac enzymes, components of the myocardial antioxidant defense system, as well as inflammatory markers and histopathological changes in heart tissue. ISO (150 mg/kg, subcutaneous, two doses administered at 24-hour intervals) treatment induced significant decreases in P waves and QRS complexes (p0.05). Our results suggest that KRG significantly protects against cardiac injury and ISO-induced cardiac infarction by bolstering antioxidant action in myocardial tissue.
Sun-Hye Choi, Byung-Hwan Lee, Hyeon-Joong Kim, Seok-Won Jung, Sung-Hee Hwang,
Published: 15 July 2013
Journal of Ginseng Research, Volume 37, pp 324-331; https://doi.org/10.5142/jgr.2013.37.324

Abstract:
Channels formed by the co-assembly of the KCNQ1 subunit and the mink (KCNE1) subunit underline the slowly activating delayed rectifier K(+) channels (IKs ) in the heart. This K(+) channel is one of the main pharmacological targets for the development of drugs against cardiovascular disease. Panax ginseng has been shown to exhibit beneficial cardiovascular effects. In a previous study, we showed that ginsenoside Rg3 activates human KCNQ1 K(+) channel currents through interactions with the K318 and V319 residues. However, little is known about the effects of ginsenoside metabolites on KCNQ1 K(+) alone or the KCNQ1 + KCNE1 K(+) (IKs ) channels. In the present study, we examined the effect of protopanaxatriol (PPT) and compound K (CK) on KCNQ1 K(+) and IKs channel activity expressed in Xenopus oocytes. PPT more strongly inhibited the IKs channel currents than the currents of KCNQ1 K(+) alone in concentration- and voltage-dependent manners. The IC50 values on IKs and KCNQ1 alone currents for PPT were 5.18±0.13 and 10.04±0.17 μM, respectively. PPT caused a leftward shift in the activation curve of IKs channel activity, but minimally affected KCNQ1 alone. CK exhibited slight inhibition on IKs and KCNQ1 alone K(+) channel currents. These results indicate that ginsenoside metabolites show limited effects on IKs channel activity, depending on the structure of the ginsenoside metabolites.
Hyuk-Hwan Song, Doo-Young Kim, Soyeun Woo, Hyeong-Kyu Lee,
Published: 15 July 2013
Journal of Ginseng Research, Volume 37, pp 341-348; https://doi.org/10.5142/jgr.2013.37.341

Abstract:
Identification of the origins of Panax ginseng has been issued in Korea scientifically and economically. We describe a metabolomics approach used for discrimination and prediction of ginseng roots from different origins in Korea. The fresh ginseng roots from six ginseng cooperative associations (Gangwon, Gaeseong, Punggi, Chungbuk, Jeonbuk, and Anseong) were analyzed by UPLC-MS-based approach combined with orthogonal projections to latent structure-discriminant analysis multivariate analysis. The ginsengs from Gangwon and Gaeseong were easily differentiated. We further analyzed the metabolomics results in subgroups. Punggi, Chungbuk, Jeonbuk, and Anseong ginseng could be easily differentiated by the first two orthogonal components. As a validation of the discrimination model, we performed blind prediction tests of sample origins using an external test set. Our model predicted their geographical origins as 99.7% probability. The robust discriminatory power and statistical validity of our method suggest its general applicability for determining the origins of P. ginseng samples.
Hong-Yan Pan, Yang Qu, Jian-Kui Zhang, Ting-Guo Kang,
Published: 15 July 2013
Journal of Ginseng Research, Volume 37, pp 355-360; https://doi.org/10.5142/jgr.2013.37.355

Abstract:
Ginseng cultivated and grown naturally under mountainous forest is formally called "Lin-Xia-Shan-Shen" (LXSS) and grown in manual condition is called garden ginseng (GG) according to Chinese pharmacopoeia (2010 edition). Usually the growing condition of LXSS is similar to wild ginseng and mostly used in Chinese folks in ancient times. The antioxidant properties of LXSS with different growing years were evaluated by their inhibitions of thiobarbituric acid-reactive substance (TBA-RS) formation in liver homogenate and 2, 2-diphenyl-1-picrylhydrazyl (DPPH)-radical scavenging activity comparing with those of GG. The inhibitions of different polar extracts (n-butanol and water) of LXSS and GG on TBA-RS formation were also evaluated. The results showed that the antioxidant effects of LXSS were higher than those of GG and the TBARS formation inhibition of LXSS with longer growing years were stronger than those with shorter growing years, while the DPPH-radical scavenging activity of LXSS did not show significant difference with the change of the growing year. The results indicated that the inhibitory effect of TBA-RS formation and the DPPH-radical scavenging of LXSS were correlated with the contents of ginsenosides. In adddition, the starch contents of LXSS and GG were determined by micro-amount method with spectrophotometer. It showed that the starch content in GG was higher than that of LXSS whose starch decreased gradually with the growing year.
Sergiy Oliynyk, Seikwan Oh
Published: 15 April 2013
Journal of Ginseng Research, Volume 37, pp 144-166; https://doi.org/10.5142/jgr.2013.37.144

Abstract:
Actoprotectors are preparations that increase the mental performance and enhance body stability against physical loads without increasing oxygen consumption. Actoprotectors are regarded as a subclass of adaptogens that hold a significant capacity to increase physical performance. The focus of this article is studying adaptogen herbs of genus Panax (P. ginseng in particular) and their capabilities as actoprotectors. Some animal experiments and human studies about actoprotective properties of genus Panax attest that P. ginseng (administered as an extract) significantly increased the physical and intellectual work capacities, and the data provided suggests that ginseng is a natural source of actoprotectors. Preparations of ginseng can be regarded as potential actoprotectors which give way to further research of its influence on physical and mental work capacity, endurance and restoration after exhaustive physical loads while compared with reference actoprotectors.
Joo Hyun Jung, Il Gyu Kang, , You Jin Hwang, Seon Tae Kim
Published: 15 April 2013
Journal of Ginseng Research, Volume 37, pp 167-175; https://doi.org/10.5142/jgr.2013.37.167

Abstract:
Korean red ginseng (KRG) is reported to have anti-allergic properties, including beneficial effects on asthma and atopic dermatitis. However, its effect on allergic rhinitis has not been studied extensively. This study examined how KRG affected allergic inflammation of the nasal cavity in an allergic mouse model. A total of 40 Balb/c female mice were divided into four experimental groups according to treatment and allergic state: group 1 (G1), saline only; group 2 (G2), ovalbumin (OVA); group 3 (G3), OVA+KRG; and group 4 (G4), OVA+dexamethasone. Serum IgE levels were significantly lower in the KRG treatment group (G3) than in the allergic group (G2). However, serum IgG1 levels did not differ between G2 and G3. In the nasal lavage fluid, IL-4 and IL-5 levels were significantly lower in G3 than in G2 (p<0.05). H&E and Luna staining revealed that the eosinophil count was lower in G3 and G4 than in G2 (p<0.05). Immunohistochemical staining revealed that there were fewer IL-4-, IL- 5-, and MUC5AC-positive cells in G3 and G4 than in G2 (p<0.05). These results indicate that KRG reduces the nasal allergic inflammatory reaction in an allergic murine model by reducing Th2 cytokines.
Su-Jeong Seo, Jae Youl Cho, Yeon Ho Jeong,
Published: 15 April 2013
Journal of Ginseng Research, Volume 37, pp 194-200; https://doi.org/10.5142/jgr.2013.37.194

Abstract:
Korean red ginseng (KRG) is prepared by the process of steaming the roots of Panax ginseng. In this study, the feeding effects of KRG-water extract (KRGE) on ethanol-induced liver damage were elucidated by measuring serum biomarkers in rats. Serum γ-glutamyltranspeptidase (γ-GT) activity and the concentration of malondialdehyde (MDA) were significantly increased by short-term and long-term ethanol treatment in rats, whereas the activities of serum glutamate pyruvate transaminase (GPT) and glutamate oxaloacetate transaminase (GOT) did not respond. Pretreatment with KRGE maintained the activity of serum GPT, and the MDA concentration induced by short-term ethanol ingestion remained within the normal range. However, co-feeding of KRGE to rats decreased the concentration of MDA but failed to modulate the serum γ-GT activity induced by long-term ethanol treatment. Our studies suggest that in rats, it appears that KRGE does not sufficiently reverse the physiological response evoked by long-term ethanol ingestion to maintain normal conditions, in view of the serum biomarker γ-GT, regardless of KRGE's favorable antioxidant activity.
Byung Joo Kim
Published: 15 April 2013
Journal of Ginseng Research, Volume 37, pp 201-209; https://doi.org/10.5142/jgr.2013.37.201

Abstract:
Ginsenoside, one of the active ingredients of Panax ginseng, has a variety of physiologic and pharmacologic effects. The purpose of this study was to explore the effects of ginsenoside Rd (G-Rd) on melastatin type transient receptor potential 7 (TRPM7) channels with respect to the proliferation and survival of AGS and MCF-7 cells (a gastric and a breast cancer cell line, respectively). AGS and MCF-7 cells were treated with different concentrations of G-Rd, and caspase-3 activities, mitochondrial depolarizations, and sub-G1 fractions were analyzed to determine if cell death occurred by apoptosis. In addition, human embryonic kidney (HEK) 293 cells overexpressing TRPM7 channels were used to confirm the role of TRPM7 channels. G-Rd inhibited the proliferation and survival of AGS and MCF-7 cells and enhanced caspase-3 activity, mitochondrial depolarization, and sub-G1 populations. In addition, G-Rd inhibited TRPM7-like currents in AGS and MCF-7 cells and in TRPM7 channel overexpressing HEK 293 cells, as determined by whole cell voltage-clamp recordings. Furthermore, TRPM7 overexpression in HEK 293 cells promoted G-Rd induced cell death. These findings suggest that G-Rd inhibits the proliferation and survival of gastric and breast cancer cells by inhibiting TRPM7 channel activity.
Ying Gui,
Published: 15 April 2013
Journal of Ginseng Research, Volume 37, pp 219-226; https://doi.org/10.5142/jgr.2013.37.219

Abstract:
This study was conducted to investigate the effect of extrusion conditions (moisture content 20% and 30%, screw speed 200 and 250 rpm, barrel temperature 115℃ and 130℃) on the acidic polysaccharide, ginsenoside contents and antioxidant properties of extruded Korean red ginseng (KRG). Extruded KRGs showed relatively higher amounts of acidic polysaccharide (6.80% to 9.34%) than nonextruded KRG (4.34%). Increased barrel temperature and screw speed significantly increased the content of acidic polysaccharide. The major ginsenosides (Rb1, Rb2, Rc, Rd, Re, Rf, Rg2s, Rg3s, Rh1, and Rg3r) of KRG increased through extrusion, while the ginsenoside (Rg1) decreased. The EX8 (moisture 30%, screw speed 250 rpm, and temperature 130℃) had more total phenolics and had a better scavenging effect on 2,2-diphenyl-1-picrylhydrazyl radicals than those of extruded KRG samples. The extrusion cooking showed a significant increase (6.8% to 20.9%) in reducing power. Increased barrel temperature significantly increased the values of reducing power, the highest value was 1.152 obtained from EX4 (feed moisture 20%, screw speed 250 rpm, and temperature 130℃). These results suggest that extrusion conditions can be optimized to retain the health promoting compounds in KRG products.
Dong-Ha Lee, Hyun-Jeong Cho, Hyun-Hong Kim, , Jin-Hyeob Ryu, Hwa-Jin Park
Published: 15 April 2013
Journal of Ginseng Research, Volume 37, pp 176-186; https://doi.org/10.5142/jgr.2013.37.176

Abstract:
In this study, we have investigated the effects of total saponin from Korean red ginseng (TSKRG) on thrombin-induced platelet aggregation. TSKRG dose-dependently inhibited thrombin-induced platelet aggregation with IC50 value of about 81.1 μg/mL. In addition, TSKRG dose-dependently decreased thrombin-elevated the level of cytosolic-free Ca(2+) ([Ca(2+)]i), one of aggregation-inducing molecules. Of two Ca(2+)-antagonistic cyclic nucleotides as aggregation-inhibiting molecules, cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), TSKRG significantly dose-dependently elevated intracellular level of cAMP, but not cGMP. In addition, TSKRG dose-dependently inhibited thrombin-elevated adenosine triphosphate (ATP) release from platelets. These results suggest that the suppression of [Ca(2+)]i elevation, and of ATP release by TSKRG are associated with upregulation of cAMP. TSKRG elevated the phosphorylation of vasodilator-stimulated phosphoprotein (VASP)-Ser(157), a cAMP-dependent protein kinase (A-kinase) substrate, but not the phosphorylation of VASP-Ser(239), a cGMPdependent protein kinase substrate, in thrombin-activated platelets. We demonstrate that TSKRG involves in increase of cAMP level and subsequent elevation of VASP-Ser(157) phosphorylation through A-kinase activation to inhibit [Ca(2+)]i mobilization and ATP release in thrombin-induced platelet aggregation. These results strongly indicate that TSKRG is a beneficial herbal substance elevating cAMP level in thrombin-platelet interaction, which may result in preventing of platelet aggregation-mediated thrombotic diseases.
Hai Yan Quan, Do Yeon Kim,
Published: 15 April 2013
Journal of Ginseng Research, Volume 37, pp 187-193; https://doi.org/10.5142/jgr.2013.37.187

Abstract:
The effect of Korean red ginseng (KRG) on diabetic renal damage was investigated using streptozotocin (STZ)-induced diabetic rats. The diabetic rats showed loss of body weight gain, and increases in kidney weight and urine volume, whereas the oral administration of KRG at a dose of 100 or 250 mg/kg of body weight per day for 28 d prevented these diabetes-induced physiological abnormalities. Among the kidney function parameters, elevated plasma levels of urea nitrogen and creatinine in diabetic control rats tended to be lowered in KRG-treated rats. In addition, administration of KRG at a dose of 100 mg/kg body weight in the diabetic rats showed significant decreases in serum glucose and tumor necrosis factor-α (TNF-α), implying that KRG might prevent the pathogenesis of diabetic complications caused by impaired glucose metabolism and oxidative stress. KRG also significantly reduced advanced glycation end product (AGE) formation and secretion from kidney of diabetic rats. Furthermore, KRG decreased the levels of N-(carboxymethyl) lysine and expression of AGE receptor. KRG also reduced the overexpression of cyclooxygenase-2 and inducible nitric oxide synthase in the kidney via deactivation of nuclear factor-kappa B. We also found that KRG prevented STZ-induced destruction of glomerular structure and significantly suppressed high glucose-induced fibronectin production. Taken together, KRG ameliorates abnormalities associated with diabetic nephropathy through suppression of inflammatory pathways activated by TNF-α and AGEs. These findings indicate that KRG has a beneficial effect on pathological conditions associated with diabetic nephropathy.
Seung-Ok Yang, Sang Won Lee, Young Ock Kim, Sang-Hyun Sohn, Dong Yoon Hyun, Yoon Pyo Hong, Yu Su Shin
Published: 15 April 2013
Journal of Ginseng Research, Volume 37, pp 248-253; https://doi.org/10.5142/jgr.2013.37.248

Abstract:
Leaves from Panax ginseng Meyer (Korean origin and Chinese origin of Korean ginseng) and P. quinquefolius (American ginseng) were harvested in Haenam province, Korea, and were analyzed to investigate patterns in major metabolites using HPLC-based metabolic profiling. Partial least squares discriminant analysis (PLS-DA) was used to analyze the HPLC chromatogram data. There was a clear separation between Panax species and/or origins from different countries in the PLS-DA score plots. The ginsenoside compounds of Rg1, Re, Rg2, Rb2, Rb3, and Rd in Korean leaves were higher than in Chinese and American ginseng leaves, and the Rb1 level in P. quinquefolius leaves was higher than in P. ginseng (Korean origin or Chinese origin). HPLC chromatogram data coupled with multivariate statistical analysis can be used to profile the metabolite content and undertake quality control of Panax products.
Ara Cho, Yoon Seok Roh, Erdenebileg Uyangaa, Surim Park, Jong Won Kim, Kyu Hee Lim, Jungkee Kwon, Seong Kug Eo, Chae Woong Lim, Bumseok Kim
Published: 15 April 2013
Journal of Ginseng Research, Volume 37, pp 210-218; https://doi.org/10.5142/jgr.2013.37.210

Abstract:
Numerous studies have suggested that Korean red ginseng (KRG) extract has various immune modulatory activities both in vivo and in vitro. In this study, we used a mouse model to examine the effects of orally administered KRG extract on immunity against herpes simplex virus (HSV). Balb/c mice were administered with 100, 200, and 400 mg/kg oral doses of KRG extract for 10 d and then vaginally infected with HSV. We found that KRG extract rendered recipients more resistant against HSV vaginal infection and further systemic infection, including decreased clinical severity, increased survival rate, and accelerated viral clearance. Such results appeared to be mediated by increased vaginal IFN-γ secretion. Moreover, increased mRNA expression of IFN-γ, granzyme B, and Fas-ligand was identified in the iliac lymph node and vaginal tracts of KRG extract treated groups (200 and 400 mg/kg). These results suggest that the activities of local natural killer cells were promoted by KRG extract consumption and that KRG may be an attractive immune stimulator for helping hosts overcome HSV infection.
Ramya Mathiyalagan, Sathiyamoorthy Subramaniyam, , Yeon Ju Kim, Myung Suk Sun, Se Young Kim, Yu-Jin Kim,
Published: 15 April 2013
Journal of Ginseng Research, Volume 37, pp 227-247; https://doi.org/10.5142/jgr.2013.37.227

Abstract:
MicroRNAs (miRNAs) are a class of recently discovered non-coding small RNA molecules, on average approximately 21 nucleotides in length, which underlie numerous important biological roles in gene regulation in various organisms. The miRNA database (release 18) has 18,226 miRNAs, which have been deposited from different species. Although miRNAs have been identified and validated in many plant species, no studies have been reported on discovering miRNAs in Panax ginseng Meyer, which is a traditionally known medicinal plant in oriental medicine, also known as Korean ginseng. It has triterpene ginseng saponins called ginsenosides, which are responsible for its various pharmacological activities. Predicting conserved miRNAs by homology-based analysis with available expressed sequence tag (EST) sequences can be powerful, if the species lacks whole genome sequence information. In this study by using the EST based computational approach, 69 conserved miRNAs belonging to 44 miRNA families were identified in Korean ginseng. The digital gene expression patterns of predicted conserved miRNAs were analyzed by deep sequencing using small RNA sequences of flower buds, leaves, and lateral roots. We have found that many of the identified miRNAs showed tissue specific expressions. Using the insilico method, 346 potential targets were identified for the predicted 69 conserved miRNAs by searching the ginseng EST database, and the predicted targets were mainly involved in secondary metabolic processes, responses to biotic and abiotic stress, and transcription regulator activities, as well as a variety of other metabolic processes.
John T. A. Proctor, J. Alan Sullivan
Published: 15 April 2013
Journal of Ginseng Research, Volume 37, pp 254-260; https://doi.org/10.5142/jgr.2013.37.254

Abstract:
Greenhouse and field experiments with American ginseng (Panax quinquefolius L.) stratified seed sown at depths of 10 to 100 mm were carried out to determine effects of seeding depth on seedling emergence, growth and development and to calculate optimum seeding depth. The time to 50% seedling emergence (E50) in the field increased linearly from 17 d at 20 mm seeding depth to 42.5 d at 80 mm. Seedling emergence and root weight (economic yield) at the end of the first year each increased quadratically with the increase of seeding depth. Maximum emergence and root yields were produced at sowing depths of 26.9 and 30.6 mm respectively. In a greenhouse pot experiment, increasing seeding depth from 10 to 100 mm increased partitioning of dry matter to leaves from 23.6% to 26.1%, to stems from 6.9% to 14.2%, and decreased dry matter to roots from 69.5% to 59.7%. Optimum seeding depth was 31.1 mm for a corresponding maximum root weight of 119.9 mg. A predictor equation [X (seeding depth, mm)=Y (seed weight, mg)/9.1+20.96] for seeding depth for ginseng, based on data for ten vegetable crops, their seed weights and suggested seeding depths, predicted a seeding depth of 28.3 mm for ginseng similar to that reported above for most pot and field experiments.
Joonki Kim, Sung Hun Kim, Deuk-Sik Lee, Dong-Jin Lee, Soo-Hyun Kim, Sungkwon Chung,
Published: 15 January 2013
Journal of Ginseng Research, Volume 37, pp 100-107; https://doi.org/10.5142/jgr.2013.37.100

Abstract:
This study examined the effect of fermented ginseng (FG) on memory impairment and β-amyloid (Aβ) reduction in models of Alzheimer's disease (AD) in vitro and in vivo. FG extract was prepared by steaming and fermenting ginseng. In vitro assessment measured soluble Aβ42 levels in HeLa cells, which stably express the Swedish mutant form of amyloid precursor protein. After 8 h incubation with the FG extract, the level of soluble Aβ42 was reduced. For behavioral assessments, the passive avoidance test was used for the scopolamine-injected ICR mouse model, and the Morris water maze was used for a transgenic (TG) mouse model, which exhibits impaired memory function and increased Aβ42 level in the brain. FG extract was treated for 2 wk or 4 mo on ICR and TG mice, respectively. FG extract treatment resulted in a significant recovery of memory function in both animal models. Brain soluble Aβ42 levels measured from the cerebral cortex of TG mice were significantly reduced by the FG extract treatment. These findings extract was prepared by steaming and fermenting ginseng. of Aβ42 protein, which results in enhanced behavioral memory function, thus, suggesting that FG extract may be an effective preventive or treatment for AD.
Jae-Joon Kim,
Published: 15 January 2013
Journal of Ginseng Research, Volume 37, pp 117-123; https://doi.org/10.5142/jgr.2013.37.117

Abstract:
Polyphenol oxidase (PPO) was purified from fresh ginseng roots using acetone precipitation, carboxymethyl (CM)-Sepharose chromatography, and phenyl-Sepharose chromatography. Two isoenzymes (PPO 1 and PPO 2) were separated using an ion-exchange column with CM-Sepharose. PPO 1 was purified up to 13.2-fold with a 22.6% yield. PPO 2 bound to CM-Sepharose, eluted with NaCl, and was purified up to 22.5-fold with a 17.4% yield. PPO 2 was further chromatographed on phenyl-Sepharose. The molecular weight of the purified PPO 2 from fresh ginseng was determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and was about 40 kDa. The optimum temperature and pH were 20℃ and 7.0, respectively, using catechol as a substrate. Pyrogallol showed the highest substrate specificity. The effect of a PPO inhibitor showed that its activity increased slightly in the presence of a low concentration of citric acid. High concentrations of acidic compounds and sulfite agents significantly inhibited purified ginseng PPO 2.
, Jin-Seok Lee, Ji-Young Choi, Hye-Young Park
Published: 15 January 2013
Journal of Ginseng Research, Volume 37, pp 94-99; https://doi.org/10.5142/jgr.2013.37.94

Abstract:
Proteinuric conditions demonstrate structural and compositional changes of the foot processes and slit diaphragms between podocytes. p130Cas in podocytes serves as an adapter protein anchoring glomerular basement membrane to actin filaments of podocyte cytoskeleton. To investigate the effect of ginseng total saponin (GTS) on the pathologic changes of podocyte p130Cas induced by diabetic conditions, we cultured mouse podocytes under: 1) normal glucose (5 mM, control); 2) high glucose (HG, 30 mM); 3) advanced glycosylation endproducts (AGE)-added; or 4) HG plus AGE-added conditions and treated with GTS. In confocal imaging, p130Cas colocalized with zonula occludens-1 and synaptopodin connecting to F-actin. However, diabetic conditions relocalized p130Cas molecules at perinuclear cytoplasmic area and reduced the intensity of p130Cas. In Western blotting, diabetic conditions, especially HG plus AGE-added condition, decreased cellular p130Cas protein levels at 24 and 48 h. GTS improved such quantitative and qualitative changes. These findings imply that HG and AGE have an influence on the redistribution and amount of p130Cas of podocytes, which can be reversed by GTS.
Eun Jin Kim, Hyun-A Oh, Hyuck Jai Choi, Jeong Hill Park, Dong-Hyun Kim,
Published: 15 January 2013
Journal of Ginseng Research, Volume 37, pp 87-93; https://doi.org/10.5142/jgr.2013.37.87

Abstract:
To evaluate the effect of the saponin of heat-processed ginseng (Sun ginseng, SG), we investigated the protective effect of SG total saponin fraction against adenine-induced chronic renal failure in rats. SG saponin significantly decreased the levels of urea nitrogen and creatinine in the serum, but increased the urinary excretion of urea nitrogen and creatinine, indicating an improvement of renal function. SG saponin also inhibited adenine-induced kidney hypertrophy and edema. SG saponin reduced serum glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and lactate dehydrogenase activities increased by adenine. Based on these findings, the ameliorating effect of SG on chronic renal failure may result from its saponin.
Jae Sik Ryu, Hyun Jung Lee, Song Hwan Bae, Sun Young Kim, Yooheon Park, , Yoon Hwa Jeong
Published: 15 January 2013
Journal of Ginseng Research, Volume 37, pp 108-116; https://doi.org/10.5142/jgr.2013.37.108

Abstract:
For the improvement of ginsenoside bioavailability, the ginsenosides of fermented red ginseng by Phellinus linteus (FRG) were examined with respect to bioavailability and physiological activity. The polyphenol content of FRG (19.14±0.50 mg/g) was significantly higher (p<0.05) compared with that of non-fermented red ginseng (NFRG, 11.31±1.15 mg/g). The antioxidant activities in FRG, such as 2,2'-diphenyl-1-picrylhydrazyl, 2,2-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid, and ferric reducing antioxidant power, were significantly higher (p<0.05) than those in NFRG. The HPLC analysis results showed that the FRG had a high level of ginsenoside metabolites. The total ginsenoside contents in NFRG and FRG were 41.65±1.53 mg/g and 50.12±1.43 mg/g, respectively. However, FRG had a significantly higher content (33.90±0.97 mg/g) of ginsenoside metabolites (Rg3, Rg5, Rk1, compound K, Rh1, F2, and Rg2) compared with NFRG (14.75±0.46 mg/g). The skin permeability of FRG was higher than that of NFRG using Franz diffusion cell models. In particular, after 3 h, the skin permeability of FRG was significantly higher (p<0.05) than that of NFRG. Using a rat everted intestinal sac model, FRG showed a high transport level compared with NFRG after 1 h. FRG had dramatically improved bioavailability compared with NFRG as indicated by skin permeation and intestinal permeability. The significantly greater bioavailability of FRG may have been due to the transformation of its ginsenosides by fermentation to more easily absorbable forms (ginsenoside metabolites).
Myung-Sunny Kim, Hyun-Ja Lim, Hye Jeong Yang, , Byung-Cheul Shin, Edzard Ernst
Published: 15 January 2013
Journal of Ginseng Research, Volume 37, pp 30-36; https://doi.org/10.5142/jgr.2013.37.30

Abstract:
The aim of this review was to assess the effectiveness of ginseng as a treatment option for managing menopause symptoms. We searched the literature using 11 databases from their inception to 26 September 2012 and included all randomized clinical trials (RCTs) that compared any type of ginseng to a placebo controls in postmenopausal women. The methodological quality of all studies was assessed using a Cochrane risk of bias tool. Four RCTs met our inclusion criteria. Most RCTs had high risk of bias. One RCT showed that Korean red ginseng (KRG) significantly improved sexual arousal and global health compared with placebo. Another RCT reported the superiority of KRG over placebo for treating menopause symptoms on Kupperman’s index and menopausal rating score. The third RCT failed to show a significant effect of KRG on hot flash frequency compared to placebo. The fourth RCT found beneficial effects of ginseng compared to placebo on depression and well-being. In conclusion, the evidence on ginseng as an effective treatment for managing menopause symptoms is limited. Most of the RCTs are burdened with a high risk of bias. Thus firm conclusions cannot be drawn. Rigorous studies seem warranted.
Sook Jahr Park, Jong Rok Lee, Mi Jeong Jo, Sang Mi Park, Sae Kwang Ku,
Published: 15 January 2013
Journal of Ginseng Research, Volume 37, pp 37-44; https://doi.org/10.5142/jgr.2013.37.37

Abstract:
Korean red ginseng is known to regulate the immune system and help the body struggle infection and disease. Cadmium is widely distributed in the environment due to its use in industry. Exposure to cadmium is problematic causing organ dysfunction. This study was conducted to evaluate the protective effect of Korean red ginseng extract (RGE) against cadmium-induced hepatotoxicity in rats. In experiments, animals were orally administrated with RGE (25, 50 mg/kg) for 7 d and then intravenously injected with cadmium (CdCl2, 4 mg/kg) to induce acute hepatotoxicity. Cadmium caused the elevated levels of alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase in serum. In contrast, pretreatment with RGE significantly reduced those serum indexes related with liver damage. In histopathological analysis, RGE decreased the centrilobular necrosis around central veins and the peripheral hemorrhage around portal triads. Moreover, RGE restored the deficit in hepatic glutathione level resulting from cadmium treatment. RGE also inhibited the increase in the expression of Bad, a representative apoptosis marker protein, induced by cadmium treatment. Collectively, these results demonstrate that RGE can reduce the cadmium-induced hepatic toxicity, partly via anti-oxidative and anti-apoptotic process.
Sung Hwan Ki, Ji Hye Yang, Sae Kwang Ku, Sang Chan Kim, , Il Je Cho
Published: 15 January 2013
Journal of Ginseng Research, Volume 37, pp 45-53; https://doi.org/10.5142/jgr.2013.37.45

Abstract:
Korean red ginseng, the processed root of Panax ginseng Meyer, has been frequently used for various therapeutic purposes in oriental medicine. The present study investigated the possible effect of Korean red ginseng extract (RGE) for the treatment of liver fibrosis in mice injected with carbon tetrachloride (CCl4) for 4 wk. Liver injuries were assessed by blood biochemistry and histopathology in mice treated with CCl4 alone or CCl4+ RGE (30, 100, and 300 mg/kg). Concomitant treatment with RGE and CCl4 (three times/wk for 4 wk) effectively inhibited liver fibrosis as evidenced by decreases in plasma alanine and aspartate aminotransferases, as well as by the percentages of degenerative regions, numbers of degenerative hepatocytes, and collagen accumulation in hepatic parenchyma. Treatment with CCl4 for 4 wk increased mRNA levels of transforming growth factor β1 and plasminogen activator inhibitor 1 in fibrogenic liver, whereas RGE (30, 100, and 300 mg/kg) significantly blocked the induction of fibrogenic genes by CCl4. Similarly, RGE also prevented transforming growth factor β1-mediated induction of fibrogenic genes in human hepatic stellate cell lines. More importantly, RGE markedly reduced the number of α-smooth muscle actin-positive cells in liver tissue. This study implies that RGE efficaciously protects against the liver fibrosis induced by chronic CCl4 treatment, and may therefore have potential to treat liver disease.
Dae Hyun Kim, , Ji Sung Yoon, Young Mi Ha, Sungjin Bae, Eun Kyeong Lee, Kyung Jin Jung, Min Sun Kim, You Jung Kim, Mi Kyung Kim, et al.
Published: 15 January 2013
Journal of Ginseng Research, Volume 37, pp 54-63; https://doi.org/10.5142/jgr.2013.37.54

Abstract:
Ginsenoside Rd is a primary constituent of the ginseng rhizome and has been shown to participate in the regulation of diabetes and in tumor formation. Reports also show that ginsenoside Rd exerts anti-oxidative effects by activating anti-oxidant enzymes. Treatment with ginsenoside Rd decreased nitric oxide and prostaglandin E2 (PGE2) in lipopolysaccharides (LPS)-challenged RAW264.7 cells and in ICR mouse livers (5 mg/kg LPS; LPS + ginsenoside Rd [2, 10, and 50 mg/kg]). Furthermore, these decreases were associated with the down-regulations of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 and of nuclear factor (NF)-κB activity in vitro and in vivo. Our results indicate that ginsenoside Rd treatment decreases; 1) nitric oxide production (40% inhibition); 2) PGE2 synthesis (69% to 93% inhibition); 3) NF-κB activity; and 4) the NF-κB-regulated expressions of iNOS and COX-2. Taken together, our results suggest that the anti-inflammatory effects of ginsenoside Rd are due to the down-regulation of NF-κB and the consequent expressional suppressions of iNOS and COX-2.
Woosung Shin, Jeongyeon Yoon, Goo Taeg Oh, Sungwoo Ryoo
Published: 15 January 2013
Journal of Ginseng Research, Volume 37, pp 64-73; https://doi.org/10.5142/jgr.2013.37.64

Abstract:
Korean red ginseng water extract (KG-WE) has known beneficial effects on the cardiovascular system via inducting nitric oxide (NO) production in endothelium. Endothelial arginase inhibits the activity of endothelial nitric oxide synthase (eNOS) by substrate depletion, thereby reducing NO bioavailability and contributing to vascular diseases including hypertension, aging, and atherosclerosis. In the present study, we demonstrate that KG-WE inhibits arginase activity and negatively regulates NO production and reactive oxygen species generation in endothelium. This is associated with increased dimerization of eNOS without affecting the protein expression levels of either arginase or eNOS. In a vascular tension assay, when aortas isolated from wild type mice were incubated with KG-WE, NO-dependent enhanced vasorelaxation was observed. Furthermore, KG-WE administered via by drinking water to atherogenic model mice being fed high cholesterol diet improved impaired vascular function. Taken together, these results suggest that KG-WE may exert vasoprotective effects through augmentation of NO signaling by inhibiting arginase. Therefore, KG-WE may be useful in the treatment of vascular diseases derived from endothelial dysfunction, such as atherosclerosis.
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