• Journal of Ginseng Research
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• v.47 no.1
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• pp.123-132
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• 2023

Background: Pseudotyped virus systems that incorporate viral proteins have been widely employed for the rapid determination of the effectiveness and neutralizing activity of drug and vaccine candidates in biosafety level 2 facilities. We report an efficient method for producing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pseudovirus with dual luciferase and fluorescent protein reporters. Moreover, using the established method, we also aimed to investigate whether Korean Red Ginseng (KRG), a valuable Korean herbal medicine, can attenuate infectivity of the pseudotyped virus. Methods: A pseudovirus of SARS-CoV-2 (SARS-2pv) was constructed and efficiently produced using lentivirus vector systems available in the public domain by the introduction of critical mutations in the cytoplasmic tail of the spike protein. KRG extract was dose-dependently treated to Calu-3 cells during SARS2-pv treatment to evaluate the protective activity against SARS-CoV-2. Results: The use of Calu-3 cells or the expression of angiotensin-converting enzyme 2 (ACE2) in HEK293T cells enabled SARS-2pv infection of host cells. Coexpression of transmembrane protease serine subtype 2 (TMPRSS2), which is the activator of spike protein, with ACE2 dramatically elevated luciferase activity, confirming the importance of the TMPRSS2-mediated pathway during SARS-CoV-2 entry. Our pseudovirus assay also revealed that KRG elicited resistance to SARS-CoV-2 infection in lung cells, suggesting its beneficial health effect. Conclusion: The method demonstrated the production of SARS-2pv for the analysis of vaccine or drug candidates. When KRG was assessed by the method, it protected host cells from coronavirus infection. Further studies will be followed for demonstrating this potential benefit.

• Journal of Ginseng Research
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• v.48 no.3
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• pp.333-340
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• 2024

Background: Korean red ginseng (KRG) is a product from ginseng roots, which is enriched with ginsenosides and has been utilized for a long time as an adaptogen to alleviate various physiological or disease conditions. While KRG is generally considered safe, conducting a thorough toxicological assessment of the spray-dried powder G1899 during the juvenile period is essential to establish its safety profile. This study aimed to assess the safety of G1899 during the juvenile period using Sprague-Dawley rats. Methods: Two studies were conducted separately: a juvenile toxicity study and a uterotrophic bioassay. To assess the potential toxicity at systemic, postnatal developmental, and reproductive levels, G1899 was orally gavaged once a day in post-weaning juvenile Sprague-Dawley (SD) rats at 0, 1250, 2500, or 5000 mg/kg/day. Estrogenicity was assessed by orally gavaging G1899 in immature female SD rats at 0, 2500, or 5000 mg/kg/day on postnatal days (PND) 19-21, followed by a uterotrophic bioassay. These studies were conducted in accordance with the Good Laboratory Practice (GLP) regulations and regulatory test guidelines. Results: Regarding juvenile toxicity, no abnormalities related to the G1899 treatment were observed in any group during the experiment. Moreover, no uterotrophic responses were observed in the dosed female group. Based on these results, the no observed adverse effect level (NOAEL) of G1899 was determined to be at least 5000 mg/kg/day for general systemic function, developmental/reproductive function, and estrogenic activity. Conclusion: Our results suggest that G1899 is not toxic to juveniles at doses of up to 5000 mg/kg/day.

• Journal of Ginseng Research
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• v.23 no.4
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• pp.222-229
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• 1999

Histopathological study has been carried out to elucidate the protective effect of Korean red ginseng water extract (KRG-WE) on 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced acute toxicity in male guinea pigs. Forty male guinea pigs ($200{\pm}20g$) were divided into 4 groups: normal controls (group 1) received vehicle and saline; group 2 (single TCDD-treated) received TCDD (5 ${\mu}g/kg$, single dose) and saline; group 3 received KRG-WE (200 mg/kg, i.p.) for 2 weeks starting 1 week before TCDD-exposure; group 4 received same dose of KRG-WE for 7 days from the day of TCDD-exposure. Weights of liver, testis, kidney, spleen and lung of the TCDD-exposed guinea pigs were significantly decreased. Thymus was severely shrunken, thereby could not be distinguished from adipose tissue in group 2 animals. Focal interstitial inflammation and fibrosis were observed from the lung parenchyma of group 2 animals. Furthermore, moderate swelling of hepatocyte, diffused aggregates of hemosiderin-laden macrophages from the Prussian blue stained spleen, marked decrease in spermatogenesis, and pyknotic and degenerative changes in the renal tubules were observed from intestinal organs of group 2 animals. On the other hand, histopathological damage was moderately to markedly alleviated in groups 3 and 4, but pretreatment of KRG-WE was more effective than the simultaneous treatment. In particular, TCDD-induced testicular atrophy was significantly attenuated by KRG-WE (p<0.01). From these results, it could be suggested that Korean red ginseng might be a useful herb that prevented TCDD-induced toxicity on liver, testis, kidney and spleen.

• Journal of Ginseng Research
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• v.33 no.2
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• pp.104-110
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• 2009

It is well known that the saponin of Korean red ginseng (KRG) has an anti-oxidant effect and could suppress the accumulation of lipid peroxidation. The aim of the present study was to observe the inhibitory effect of KRG on mice with noise-induced hearing loss, and to determine its optimal dose. BALB/c mice with a normal hearing level and normal Preyer's reflexes were used in the study. The mice in the permanent-threshold-shift (PTS) group were exposed to noise (120-dB SPL, white noise band) in a noise booth for 3 h a day, for three consecutive days. The mice in the experimental group were given heat-processed red-ginseng extract (50 mg/kg, 100 mg/kg, and 200 mg/kg), and those in the control group were given normal saline alone during their noise exposure. The mice in the temporary-threshold-shift (TTS) group were exposed to noise (120 dBSPL, white noise band) in a noise booth for 3 h. The mice in the experimental group were given heat-processed red-ginseng extract (50 mg/kg, 100 mg/kg, and 200 mg/kg), and those in the control group were given normal saline alone before their noise exposure. The hearing levels of the mice were measured through auditory brainstem response (ABR) immediately and I, 3, 5, 7, and 14 days after their noise exposure. Cochleae were removed from the mice 14 days after their noise exposure. lmmunochemical and immunofluorescent staining were performed to observe the expression of 8-oxoG in cochlea. In the PTS group, the hearing function of the mice in all the groups was not recovered after their noise exposure. In the TTS group, however, the hearing function of the mice in all the groups was recovered within 14 days. Reduced hearing impairment and early recovery were observed in the mice that were given 200 mg/kg KRG, and early recovery was observed in the mice that were given 100 mg/kg KRG The immunopositive staining of 8-oxoG was detected in the stria vascularis in the control group but was diminished in the mice that were given 200 mg/kg KRG The ingestion of more than 100 mg/kg KRG demonstrated a protection and recovery effect on the noiseinduced-TTS group. Since KRG has been reported to be a safe compound even up to hundreds of mg/kg, a higher concentration of it may effectively protect and recover TTS.

• The Journal of Korean Medicine
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• v.26 no.3 s.63
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• pp.228-238
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• 2005

Objectives : We conducted a randomized, double-blinded clinical trial to assess the anti-hypertensive effect of Ginseng and to know the difference of the effect according to it's growing districts md species by 24-hour ambulatory blood pressure measurement (ABPM). Methods : We allocated 96 hypertensive patients enrolled in this trial to Korean ginseng(KG), American ginseng (AG), Chinese ginseng (CG), and Korean red ginseng (KRG) groups by randomization. Each subject was administered 4.5mg/day of encapsulated ginseng for 4 weeks. We assessed anti-hypertensive effect, blood pressure variability using ABPM and toxicity by blood chemistry before and after treatment. We also evaluated changes of symptoms due to hypertension and adverse effect in all groups at the first visit, 2 weeks later and 4 weeks later. Results : Blood pressure after treatments showed significant decrease of systolic blood pressure (sBP) in the CG-group (p<0,05) and diastolic blood pressure (dBP) in the KRG-group (p<0.05). However, there were no significant changes of sBP (or dBP) after treatment in the other groups and no significant difference in changes of BP between before and after treatment among the 4 groups. Blood pressure variability in the CG-group showed significant decrease after treatment but not in the KRG-group. Symptoms such as headache or neck stiffness and heating sensation due to hypertension improved significantly in all groups, especially in the KRG-group. A3l patients had no adverse effect after treatment and there was no liver or kidney toxicity. Conclusions : CG and KRG seem to have anti-hypertensive effects, but there was no significantly different effect depending on growing district and species of Ginseng.

• Journal of Ginseng Research
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• v.47 no.2
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• pp.302-310
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• 2023

Background: The most common type of dementia, Alzheimer's disease (AD), is marked by the formation of extracellular amyloid beta (Aβ) plaques. The impairments of axons and synapses appear in the process of Aβ plaques formation, and this damage could cause neurodegeneration. We previously reported that non-saponin fraction with rich polysaccharide (NFP) from Korean Red Ginseng (KRG) showed neuroprotective effects in AD. However, precise molecular mechanism of the therapeutic effects of NFP from KRG in AD still remains elusive. Methods: To investigate the therapeutic mechanisms of NFP from KRG on AD, we conducted proteomic analysis for frontal cortex from vehicle-treated wild-type, vehicle-treated 5XFAD mice, and NFP-treated 5XFAD mice by using nano-LC-ESI-MS/MS. Metabolic network analysis was additionally performed as the effects of NFP appeared to be associated with metabolism according to the proteome analysis. Results: Starting from 5,470 proteins, 2,636 proteins were selected for hierarchical clustering analysis, and finally 111 proteins were further selected for protein-protein interaction network analysis. A series of these analyses revealed that proteins associated with synapse and mitochondria might be linked to the therapeutic mechanism of NFP. Subsequent metabolic network analysis via genome-scale metabolic models that represent the three mouse groups showed that there were significant changes in metabolic fluxes of mitochondrial carnitine shuttle pathway and mitochondrial beta-oxidation of polyunsaturated fatty acids. Conclusion: Our results suggested that the therapeutic effects of NFP on AD were associated with synaptic- and mitochondrial-related pathways, and they provided targets for further rigorous studies on precise understanding of the molecular mechanism of NFP.

• The Journal of Korean Medicine
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• v.33 no.3
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• pp.1-9
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• 2012

Objectives: This research was aimed 1) to find out various subjective symptoms cancer patients had, 2) to find out the quantitative difference of symptoms occurring according to the area of cancer, current treatment methods, and relapse of the cancer and 3) to analyze the relationship between the occurrence of symptoms. Methods: This study was a survey about the various subjective symptoms cancer patients had. The subjects were 48 cancer patients in a double-blinded randomized controlled trial about the effectiveness of Korean Red Ginseng (KRG) treatments. Surveys were examined before Korean Red Ginseng (KRG) treatments. The questionnaire consisted of demographic research, patient history and accompanying symptoms. The symptoms part consisted of 4 questions on general symptoms (vertigo, hot flush, rash, insomnia), 2 questions on digestion symptoms (anorexia, dyspepsia), 2 questions on excretions (diarrhea, constipation), and 5 questions on symptoms in different body parts (headache, dryness of lips, chest pain, aphthous ulcer, nose bleeding). The questionnaire was used to research presence of symptoms and relationships between the occurrence of symptoms. Results: A total of 48 patients took part in this survey. Dizziness was the most frequent subjective symptom patients had (64.58%), followed by dry mouth (43.75%), headache (43.75%), insomnia (41.67%), anorexia (37.5%) and chest discomfort (37.5%). The presence of these subjective symptoms was partially related to the patient's history details - type of cancer, method of cancer treatment (chemotherapy, radiotherapy), termination of treatment, presence of pain, fatigue and recurrence, etc. Factor analysis was conducted to analyze the relationship between the occurrence of symptoms. It suggested 5 factors as a result, but there was a limitation that only a low level of correlation was shown among them. Conclusions: We were able to analyze the occurrences and the relationships among them for accompanying subjective symptoms in cancer patients. However the results of the study are limited in that only 48 patients participated. The symptoms in cancer patients showed a tendency for clustering, occurring simultaneously or continuously rather than occurring alone. The study of these symptom clusters is worth further study, for it is similar to the Symptom Differentiation System in Traditional Korean Medicine. For effective approach to the treatment of cancer in Traditional Korean Medicine, further research on the Korean traditional view of cancer patients should be done based on this research, regarding various symptoms and those relationships on a larger scale.

• Journal of Ginseng Research
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• v.19 no.1
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• pp.17-21
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• 1995

A study was designed to investigate the effectiveness of Korean Red Ginseng (ERG) as an oral agent for erectile dysfunction (EF), which was compared to that of placebo and trazodone. Patients who were believed to have EF of mild or non-organic etiologies, randomized into 3 groups to receive 600 mg KRG 3 times daily (group A), placebo (group B) and 25mg trazodone once a day after evening (group C). All agents were given orally. Ninety patients, composed of 30 in each group, were included and analyzed only when clinical follow-up could be achieved at the end of the study for at least 3 months. There were no significant differences(p>0.05) between each group in mean age (43.7 years), duration of EF (5.8 years), the state of marriage (married : 80 patients) and duration of marriage (18.2 years). In group A, the parameters such as rigidity and tumescence on erection, early detumescence, libido and patient's satisfaction were significantly more effective than that of other group (p<0.05). But there were no significant differences in the parameters such as the frequency of coitus, premature ejaculation and morning erection between 3 groups (p>0.05). The efficacy achieved with KGR (60%) was significantly higher (p<0.05) than that of placebo (30%) and trazodone (30%). There were no significant changes on level of serum testosterone and type of AVS-penogram in group A. No side effect was demonstrated in all patients.

• Journal of Ginseng Research
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• v.42 no.4
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• pp.562-570
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• 2018

Background: Lung cancer is the leading cause of cancer-related death worldwide. In this study, we used a bioactivity-guided isolation technique to identify constituents of Korean Red Ginseng (KRG) with antiproliferative activity against human lung adenocarcinoma cells. Methods: Bioactivity-guided fractionation and preparative/semipreparative HPLC purification were used with LC/MS analysis to separate the bioactive constituents. Cell viability and apoptosis in human lung cancer cell lines (A549, H1264, H1299, and Calu-6) after treatment with KRG extract fractions and constituents thereof were assessed using the water-soluble tetrazolium salt (WST-1) assay and terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, respectively. Caspase activation was assessed by detecting its surrogate marker, cleaved poly adenosine diphosphate (ADP-ribose) polymerase, using an immunoblot assay. The expression and subcellular localization of apoptosis-inducing factor were assessed using immunoblotting and immunofluorescence, respectively. Results and conclusion: Bioactivity-guided fractionation of the KRG extract revealed that its ethyl acetate-soluble fraction exerts significant cytotoxic activity against all human lung cancer cell lines tested by inducing apoptosis. Chemical investigation of the ethyl acetatesoluble fraction led to the isolation of six ginsenosides, including ginsenoside Rb1 (1), ginsenoside Rb2 (2), ginsenoside Rc (3), ginsenoside Rd (4), ginsenoside Rg1 (5), and ginsenoside Rg3 (6). Among the isolated ginsenosides, ginsenoside Rg3 exhibited the most cytotoxic activity against all human lung cancer cell lines examined, with $IC_{50}$ values ranging from $161.1{\mu}M$ to $264.6{\mu}M$. The cytotoxicity of ginsenoside Rg3 was found to be mediated by induction of apoptosis in a caspase-independent manner. These findings provide experimental evidence for a novel biological activity of ginsenoside Rg3 against human lung cancer cells.

• Journal of Ginseng Research
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• v.44 no.6
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• pp.790-798
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• 2020

Background: Beneficial effects of Korean Red Ginseng (KRG) on polycystic ovarian syndrome (PCOS) remains unclear. Methods: We examined whether pretreatment (daily from 2 hours before PCOS induction) with KRG extract in water (KRGE; 75 and 150 mg/kg/day, p.o.) could exert a favorable effect in a dehydroepian-drosterone (DHEA)-induced PCOS rat model. Results: Pretreatment with KRGE significantly inhibited the elevation of body and ovary weights, the increase in number and size of ovarian cysts, and the elevation of serum testosterone and estradiol levels induced by DHEA. Pretreatment with KRGE also inhibited macrophage infiltration and enhanced mRNA expression levels of chemokines [interleukin (IL)-8, monocyte chemoattractant protein-1), proinflammatory cytokines (IL-1β, IL-6), and inducible nitric oxide synthase in ovaries induced by DHEA. It also prevented the reduction in mRNA expression of growth factors (epidermal growth factor, transforming growth factor-beta (EGF, TGF-β)) related to inhibition of the nuclear factor kappa-light-chain-enhancer of activated B cell pathway and stimulation of the nuclear factor erythroid-derived 2-related factor 2 pathway. Interestingly, KRGE or representative ginsenosides (Rb1, Rg1, and Rg3(s)) inhibited the activity of inflammatory enzymes cyclooxygenase-2 and iNOS, cytosolic p-IκB, and nuclear p-nuclear factor kappa-light-chain-enhancer of activated B in lipopolysaccharide-induced RAW264.7 cells, whereas they increased nuclear factor erythroid-derived 2-related factor 2 nuclear translocation. Conclusion: These results provide that KRGE could prevent DHEA-induced PCOS via antiinflammatory and antioxidant activities. Thus, KRGE may be used in preventive and therapeutic strategies for PCOS-like symptoms.