• Journal of the Korea Academia-Industrial cooperation Society
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• v.18 no.12
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• pp.521-528
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• 2017

Excessive alcohol consumption is one of the leading causes of many neurological diseases, such as dementia and Alzheimer's disease, and many efforts are under way to solve them. Red ginseng is known to enhance neuronal survival, inhibit apoptosis, and promote nerve regeneration of nerve cells. This study examined whether Rg3-enriched Korean red ginseng extract (KRG) inhibits the apoptosis of PC12 cells caused by alcohol-induced neurotoxicity and how KRG regulates several factors related to the caspase mediated pathway. In this way, the cell survival rate and apoptosis rate of PC12 cells were measured using an EZ-Cytox cell viability assay kit and flow cytometry, respectively. The expression of the apoptosis-related proteins (Bcl-2, Bid, Bax and caspase-3) were analyzed by western blotting, and the significance of the measured results was confirmed using the ANOVA method. As a result, KRG increased the expression of Bcl-2; inhibited the expression of Bid, Bax, and caspase-3; and inhibited the apoptosis of alcohol-induced PC12 cells. These results mean that the KRG-induced increase in Bcl-2 expression and down-regulation of Bid and Bax expression down-regulate caspase-3 expression, which in turn inhibits the mitochondrial apoptotic pathways. This study suggests that KRG is worth developing as a neuroprotective agent candidate.

• Journal of Ginseng Research
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• v.42 no.4
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• pp.571-576
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• 2018

Background: Korean Red Ginseng (KRG) has been used in Asia for its various biological effects, but no studies have investigated the safety of its long-term intake. Therefore, the present study evaluated the safety of KRG intake for 24 weeks. Methods: We randomized 1,000 participants in a 1:1 ratio into two groups, which were treated daily with 2 g of KRG or a placebo for 24 weeks. The primary endpoint was all adverse events and adverse drug reactions (ADRs) that occurred after KRG or placebo administration, which were reported at week 4, 12, and 24 after the baseline visit. Results: In total, 192 and 211 participants experienced adverse events in the KRG and placebo groups (39.2% and 42.0%, respectively; p = 0.361), and 59 and 57 KRG- and placebo-treated individuals reported ADRs (12.0% and 11.4%, respectively; p = 0.737). The frequently occurring ADRs were pruritus (2.0%), headache (1.6%), diarrhea (1.4%), and dizziness (1.2%) in the KRG group and pruritus (2.0%), headache (1.8%), dizziness (1.6%), rash (1.4%), and diarrhea (1.2%) in the placebo group. Discontinuation of drug administration due to ADRs was reported in 13 participants, six (1.2%) and seven (1.4%) in the KRG and placebo groups, respectively (p = 0.814). No significant abnormal changes were revealed by anthropometric, laboratory, and vital sign measurements in the KRG group compared with those in the placebo group. Conclusion: The present study confirms the safety and tolerability of daily intake of 2 g of KRG for 24 weeks by healthy adults.

• Journal of Life Science
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• v.22 no.8
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• pp.991-998
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• 2012

Ginseng is one of the most commonly used herbal medicines and health foods. Korean red ginseng (KRG; Panax ginseng C.A. Meyer) extract is known to have potential therapeutic activities, such as anti-viral effects, the amelioration of food allergies, anti-oxidant effects, and obesity reduction. Nevertheless, no reports have been issued the modulatory effects of KRG extract on the activity of cytochrome P450 (CYP). In the present study, we investigated the modulatory effect of KRG extract in vitro and in vivo by using pooled human liver microsomes and male ICR mice. When human liver microsomes were incubated with KRG extract at 0.01-10 mg/ml, CYP1A2, 2B6, 2C19, 2D6, and 3A were not significantly inhibited by KRG extract, although CYP2B6 was slightly inhibited. Mice were orally administered KRG extract at 50, 250, or 500 mg/kg daily for 3, 7, or 14 days. However, the activities of CYPs in mouse livers were not significantly different from those of vehicle-treated controls. In conclusion, no significant ginseng-drug interaction was observed. KRG extract did not significantly modulate the activities of CYPs in vitro or in vivo.

• Journal of Ginseng Research
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• v.47 no.3
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• pp.385-389
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• 2023

Background: Ginseng has been used as a traditional medicine for treatment of many diseases and for general health maintenance. Previously, we showed that ginseng did not demonstrate estrogenic property in ovariectomized mouse model. However, it is still possible that disruption of steroidogenesis leading to indirect hormonal activity. Methods: The hormonal activities were examined in compliance with OECD guidelines for detecting endocrine disrupting chemicals: test guideline (TG) No. 456 (an in vitro assay method for detecting steroidogenesis property) and TG No. 440 (an in vivo short-term screening method for chemicals with uterotrophic property). Results: Korean Red Ginseng (KRG) and ginsenosides Rb1, Rg1, and Rg3 did not interfere with estrogen and testosterone hormone synthesis as examined in H295 cells according to TG 456. KRG treatment to ovariectomized mice did not show a significant change in uterine weight. In addition, serum estrogen and testosterone levels were not change by KRG intake. Conclusion: These results clearly demonstrate that there is no steroidogenic activity associated with KRG and no disruption of the hypothalamic-pituitary-gonadal axis by KRG. Additional tests will be performed in pursuit of cellular molecular targets of ginseng to manifest mode of action.

• Journal of Ginseng Research
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• v.37 no.3
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• pp.273-282
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• 2013

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 (p<0.01), as well as a significant increase in ST segments. Moreover, ISO-treated rats exhibited decreases in left-ventricular systolic pressure, maximal rate of developed left ventricular pressure ($+dP/dt_{max}$) and minimal rate of developed left ventricular pressure ($-dP/dt_{max}$), in addition to significant increases in lactate dehydrogenase, aspartate transaminase, alanine transaminase and creatine kinase activity. Heart rate, however, was not significantly altered. And the activities of superoxide dismutase, catalase and glutathione peroxidase were decreased, whereas the activity of malondialdehyde was increased in the ISO-treated group. ISO-treated group also showed increased caspase-3 level, release of inflammatory markers and neutrophil infiltration in heart tissue. KRG pretreatment (250 and 500 mg/kg, respectively) significantly ameliorated almost all of the parameters of heart failure and myocardial injury induced by ISO. The protective effect of KRG on ISO-induced cardiac injury was further confirmed by histopathological study. In this regard, ISO treatment induced fewer morphological changes in rats pretreated with 250 or 500 mg/kg of KRG. Compared with the control group, all indexes in rats administered KRG (500 mg/kg) alone were unaltered (p>0.05). Our results suggest that KRG significantly protects against cardiac injury and ISO-induced cardiac infarction by bolstering antioxidant action in myocardial tissue.

• Journal of Ginseng Research
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• v.35 no.3
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• pp.352-359
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• 2011

Korean red ginseng (KRG) is used worldwide as a popular traditional herbal medicine. KRG has shown beneficial effects on cardiovascular diseases, such as atherosclerosis, diabetes, and hypertension. Up-regulation of a cytoprotective protein, heme oxygenase (HO)-1, is considered to augment the cellular defense against various agents that may induce cytotoxic injury. In the present study, we demonstrate that KRG water extract induces HO-1 expression in human umbilical vein endothelial cells (HUVECs) and possible involvement of the anti-oxidant transcription factor nuclear factor-eythroid 2-related factor 2 (Nrf2). KRG-induced HO-1 expression was examined by western blots, reverse transcriptase polymerase chain reaction and immunofluorescence staining. Specific silencing of Nrf2 genes with Nrf2-siRNA in HUVECs abolished HO-1 expression. In addition, the HO inhibitor zinc protoporphyrin blunted the preventive effect of KRG on $H_2O_2$-induced cell death, as demonstrated by terminal transferase dUTP nick end labeling assay. Taken together, these results suggest that KRG may exert a vasculoprotective effect through Nrf2-mediated HO-1 induction in human endothelial cell by inhibition of cell death.

• Journal of Ginseng Research
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• v.34 no.3
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• pp.212-218
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• 2010

Korean red ginseng (KRG) has been shown to enhance endothelium-dependent vasorelaxation in experimental animals; however, little is known about its pharmacological effects on vascular stiffness in patients with coronary artery disease (CAD). This randomized, double-blind, placebo-controlled crossover trial was carried out to determine whether KRG has beneficial effects on arterial stiffness, cardiovascular risk factors such as plasma lipid profiles and blood pressure (BP), and Rho-associated kinase (ROCK) activity. Twenty patients (mean age, 62.5 years) with stable angina pectoris were given KRG (2.7 g/day) and a placebo alternatively for 10 weeks. Blood biochemical analysis and pulse wave velocity (PWV) recording were performed on day 0 and after the completion of each treatment. ROCK activity was assessed based on the level of phospho-$Thr^{853}$ in the myosin-binding subunit of myosin light chain phosphatase, determined by Western blot analysis of peripheral blood mononuclear cells. KRG significantly decreased the systolic BP, brachial ankle PWV, and heart femoral PWV in the patients (all p<0.05), but did not significantly alter the serum lipid profiles, including triglycerides and total, high-density lipoprotein, and low-density lipoprotein cholesterol levels. The ROCK activity tended to decrease (p=0.068) following KRG treatment. The placebo did not significantly alter any of the variables. In conclusion, KRG decreased systolic BP and arterial stiffness, probably via the inhibition of ROCK activity, in patients with CAD, but had a neutral effect on serum lipid profiles. Our data suggest that KRG has a therapeutic effect on CAD.

• Journal of Ginseng Research
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• v.39 no.2
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• pp.148-154
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• 2015

Background: Ginseng is known to have antiapoptotic, anti-inflammatory, and antioxidant effects. The present study investigated a possible role of Korean Red Ginseng (KRG) in suppressing dopaminergic neuronal cell death and the cleavage of p35 to p25 in the substantia nigra (SN) and striatum (ST) using a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease mouse model. Methods: Ten-week-old male C57BL/6 mice were injected intraperitoneally with 30 mg/kg of MPTP at 24-h intervals for 5 d, and then administered KRG (1 mg/kg, 10 mg/kg, or 100 mg/kg) once a day for 12 consecutive days from the first injection. Pole tests were performed to assess the motor function of the mice, dopaminergic neuronal survival in the SN and ST was evaluated using tyrosine hydroxylase-immunohistochemistry, and the expressions of cyclin-dependent kinase 5 (Cdk5), p35, and p25 in the SN and ST were measured using Western blotting. Results: MPTP administration caused behavioral impairment, dopaminergic neuronal death, increased Cdk5 and p25 expression, and decreased p35 expression in the nigrostriatal system of mice, whereas KRG dose-dependently alleviated these MPTP-induced changes. Conclusion: These results indicate that KRG can inhibit MPTP-induced dopaminergic neuronal death and suppress the cleavage of p35 to p25 in the SN and the ST, suggesting a possible role for KRG in the treatment of Parkinson's disease.

• Journal of Ginseng Research
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• v.41 no.3
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• pp.284-289
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• 2017

Background: Compound FK506 is an immunosuppressant agent that is frequently used to prevent rejection of solid organs upon transplant. However, nephrotoxicity due to apoptosis and inflammatory response mediated by FK506 limit its usefulness. In this study, the protective effect of Korean Red Ginseng (KRG) against FK506-induced damage in LLC-PK1 pig kidney epithelial cells was investigated. Methods: LLC-PK1 cells were exposed to FK506 with KRG and cell viability was measured. Western blotting and RT-PCR analyses evaluated protein expression of MAPKs, caspase-3, and KIM-1. TLR-4 gene expression was assessed. Caspase-3 activities were also determined. The number of apoptotic cells was measured using an image-based cytometric assay. Results: The reduction in LLC-PK1 cell viability by $60{\mu}M$ FK506 was recovered by KRG cotreatment in a dose-dependent manner. The phosphorylation of p38, p44/42 MAPKs (ERK), KIM-1, cleaved caspase-3, and TLR-4 mRNA expression was increased markedly in LLC-PK1 cells treated with $60{\mu}M$ FK506. However, with the exception of p-ERK, elevated levels of p-p38, KIM-1, cleaved caspase-3, and TLR-4 mRNA expression were significantly decreased after cotreatment with KRG. Activity level of caspase-3 was also attenuated by KRG cotreatment. Moreover, image-based cytometric assay showed that apoptotic cell death was increased by $60{\mu}M$ FK506 treatment, whereas it was decreased after cotreatment with KRG. Conclusion: Taken together, these results suggest that the molecular mechanism of KRG in the FK506-induced nephrotoxicity may lead to the development of an adjuvant for the inhibition of adverse effect FK506 in the kidney.

• Journal of Ginseng Research
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• v.45 no.3
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• pp.380-389
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• 2021

Metabolic syndrome (MS) refers to a clustering of at least three of the following medical conditions: high blood pressure, abdominal obesity, hyperglycemia, low high-density lipoprotein level, and high serum triglycerides. MS is related to a wide range of diseases which includes obesity, diabetes, insulin resistance, cardiovascular disease, dyslipidemia, or non-alcoholic fatty liver disease. There remains an ongoing need for improved treatment strategies for MS. The most important risk factors are dietary pattern, genetics, old age, lack of exercise, disrupted biology, medication usage, and excessive alcohol consumption, but pathophysiology of MS has not been completely identified. Korean Red Ginseng (KRG) refers to steamed/dried ginseng, traditionally associated with beneficial effects such as anti-inflammation, anti-fatigue, anti-obesity, anti-oxidant, and anti-cancer effects. KRG has been often used in traditional medicine to treat multiple metabolic conditions. This paper summarizes the effects of KRG in MS and related diseases such as obesity, cardiovascular disease, insulin resistance, diabetes, dyslipidemia, or non-alcoholic fatty liver disease based on experimental research and clinical studies.