Effects Of Korean Red Ginseng Research Articles

Evaluation of the effectiveness and safety of Korean red ginseng extract as immune-enhancer in Vietnamese adults: A randomized placebo-controlled trial

Purpose: To investigate the safety and immune-enhancing effect of Korean red ginseng (KRG) extract in Vietnamese adults. Methods: Participants in this randomized, placebo-controlled double-blinded study were administered either 960 mg of KRG extract (n = 51) or placebo capsules (n = 50) for 12 weeks at Hanoi Medical University, Vietnam. The KRG extract was standardized to contain 5.27 mg of 3 ginsenosides (Rg1, Rb1, and Rg3) per gram. Blood samples for assessment of treatment effectiveness were collected from the subjects on days 21 and 84. Immune cytokines were quantified using enzyme-linked immunosorbent assay (ELISA). Blood samples for safety assessment, hematological and biochemical variables, and urinalysis were performed at the beginning and end of the intervention (days 21 and 84, respectively). Results: The KRG group showed a significant increase in lymph T cell % at the end of the 12-week intervention (p < 0.001). There were significant decreases in numbers of white blood cells (WBC) and natural killer (NK) cells in both groups. However, there were no significant differences in populations of WBC and NK cells between the 2 groups. Serum concentrations of cytokines, i.e., TNF-α, β, γ; IFN- α, γ; IL-1β and 4β were decreased in the KRG group when compared to baseline values. There were no probable or definite adverse events (AEs) related to KRG. A total of 9 participants (4 in KRG group and 5 in placebo group) tested positive for COVID-19 during the trial. Conclusion: The KRG extract-induced increase in population of T-cells and reductions in cytokine levels following a 12-week exposure may be beneficial for COVID-19 patients.

Effects of Korean red ginseng on auditory, cognitive, and liver functions in a naturally aged mouse model

BackgroundKorean Red Ginseng and ginsenosides have been studied for their efficacy against various diseases, including those related to aging. However, most aging studies use D-galactose to induce aging, which often does not accurately represent natural aging. This study aimed to verify improvements in auditory, cognitive, and liver function through administering red ginseng to an 18-month-old naturally aging mouse model. MethodsAuditory function was assessed using Auditory Brainstem Response (ABR) and Auditory Middle Latency Response (AMLR). Cognitive function was evaluated electrophysiologically with P300 and mismatch negativity (MMN), and behaviorally using the Y-maze. Additionally, biochemical tests and histological analysis were conducted to assess liver function. The effects of red ginseng on gene expression regulation were also examined in the cochlea, auditory cortex, and liver, focusing on age-related disease processes. ResultsRed ginseng significantly decreased hearing thresholds and improved central auditory function. It also enhanced cognitive behavior and function in response to external stimulation. Furthermore, red ginseng regulated alkaline phosphatase (ALP), albumin (Alb), and total protein (TP) levels, notably decreasing aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. Hematoxylin and eosin (H&E) staining of liver tissue showed significant improvement in fat droplets. These effects appear to be mediated by the regulation of aging-related genes Dec, c-Jun, Stat5b, and Lims2. ConclusionThese results suggest that red ginseng improves auditory, cognitive, and liver functions in a naturally aged mouse model.

Effect of Korean Red Ginseng on the stress-derived plasma hormone and lipid levels and oxidative stress in mice

Effect of Korean Red Ginseng on the stress-derived plasma hormone and lipid levels and oxidative stress in mice

The synergistic effects of Korean Red Ginseng and Cervi Parvum Cornu ameliorating FeCl3-induced arterial thrombosis by downregulating ICAM-1 and VCAM-1

In this study, we compared antithrombotic activities of Korean Red Ginseng (KRG) and Cervi Parvum Cornu (CPC) on rats with induced thrombosis. Results indicate that KRG and CPC suppressed the arterial occlusion and the combination of KRG and CPC (KRG + CPC) treatment exhibited a synergistic effect with maximum reduction in thrombosis.

Effect of Korean Red Ginseng on the motor performance and ataxia

This study presents a preliminary exploration into the effect of Korean Red Ginseng (KRG) on the cerebellum in individuals with cerebellar atrophy. Over a three month-long period, nine subjects received a 4.5g of KRG daily, with assessments including the ARS, ADAS-Cog, and FDG-PET/CT scans. Results revealed a notable improvement in ataxia and cognitive function without a significant correlation between them. PET/CT scans and SUVR analyses supported these findings, showing an increase in cerebellar glucose uptake after KRG intake. These outcomes suggest a potential pleiotropic effect of KRG on cerebellar function.

Protective Effects of Korean Red Ginseng Against Oxidative Stress-Induced Damage in Human Hair

Protective Effects of Korean Red Ginseng Against Oxidative Stress-Induced Damage in Human Hair

Correction: Kang et al. Anticolon Cancer Effect of Korean Red Ginseng via Autophagy- and Apoptosis-Mediated Cell Death. Nutrients 2022, 14, 3558

In the original publication [...]

Korean Red Ginseng suppresses emphysematous lesions induced by cigarette smoke condensate through inhibition of macrophage-driven apoptosis pathways

BackgroundCigarette smoke is generally accepted as a major contributor to chronic obstructive pulmonary disease (COPD), which is characterized by emphysematous lesions. In this study, we investigated the protective effects of Korean Red Ginseng (KRG) against cigarette smoke condensate (CSC)-induced emphysema. MethodsMice were instilled with 50 mg/kg of CSC intranasally once a week for 4 weeks, KRG was administered to the mice once daily for 4 weeks at doses of 100 or 300 mg/kg, and dexamethasone (DEX, positive control) was administered to the mice once daily for 2 weeks at 3 mg/kg. ResultsKRG markedly decreased the macrophage population in bronchoalveolar lavage fluid and reduced emphysematous lesions in the lung tissues. KRG suppressed CSC-induced apoptosis as revealed by terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling staining and Caspase 3 immunohistochemistry. Additionally, KRG effectively inhibited CSC-mediated activation of Bcl-2-associated X protein/Caspase 3 signaling, followed by the induction of cell survival signaling, including vascular endothelial growth factor/phosphoinositide 3-kinase/protein kinase B in vivo and in vitro. The DEX group also showed similar improved results in vivo and in vitro. ConclusionTaken together, KRG effectively inhibits macrophage-mediated emphysema induced by CSC exposure, possibly via the suppression of pro-apoptotic signaling, which results in cell survival pathway activation. These findings suggest that KRG has therapeutic potential for the prevention of emphysema in COPD patients.

Effects of Korean red ginseng on T-cell repopulation after autologous hematopoietic stem cell transplantation in childhood cancer patients

BackgroundAlthough the survival outcomes of childhood cancer patients have improved, childhood cancer survivors suffer from various degrees of immune dysfunction or delayed immune reconstitution. This study aimed to investigate the effect of Korean Red Ginseng (KRG) on T cell recovery in childhood cancer patients who underwent autologous hematopoietic stem cell transplantation (ASCT) from the perspective of inflammatory and senescent phenotypes. MethodsThis was a single-arm exploratory trial. The KRG group (n = 15) received KRG powder from month 1 to month 12 post-ASCT. We compared the results of the KRG group with those of the control group (n = 23). The proportions of T cell populations, senescent phenotypes, and cytokine production profiles were analyzed at 1, 3, 6, and 12 months post-ASCT using peripheral blood samples. ResultsAll patients in the KRG group completed the treatment without any safety issues and showed a comparable T cell repopulation pattern to that in the control group. In particular, KRG administration influenced the repopulation of CD4+ T cells via T cell expansion and differentiation into effector memory cell re-expressing CD45RA (EMRA) cells. Although the KRG group showed an increase in the number of CD4+ EMRA cells, the expression of senescent and exhausted markers in these cells decreased, and the capacity for senescence-related cytokine production in the senescent CD28- subset was ameliorated. ConclusionsThese findings suggest that KRG promotes the repopulation of CD4+ EMRA T cells and regulates phenotypical and functional senescent changes after ASCT in pediatric patients with cancer.

Korean Red Ginseng Prevents the Deterioration of Lung and Brain Function in Chronic PM2.5-Exposed Mice by Regulating Systemic Inflammation.

This study was conducted to confirm the effects of Korean red ginseng on lung and brain dysfunction in a BALB/c mice model exposed to particulate matter (PM)2.5 for 12 weeks. Learning and cognitive abilities were assessed with Y-maze, passive avoidance, and Morris water maze tests. To evaluate the ameliorating effect of red ginseng extract (RGE), the antioxidant system and mitochondrial function were investigated. The administration of RGE protected lung and brain impairment by regulating the antioxidant system and mitochondrial functions damaged by PM2.5-induced toxicity. Moreover, RGE prevented pulmonary fibrosis by regulating the transforming growth factor beta 1 (TGF-β1) pathway. RGE attenuated PM2.5-induced pulmonary and cognitive dysfunction by regulating systemic inflammation and apoptosis via the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)/c-Jun N-terminal kinases (JNK) pathway. In conclusion, RGE might be a potential material that can regulate chronic PM2.5-induced lung and brain cognitive dysfunction.

The effects of Korean Red Ginseng on stress-related neurotransmitters and gene expression: A randomized, double-blind, placebo-controlled trial

BackgroundKorean Red Ginseng (KRG) is an effective anti-stress treatment. In this study, we investigated the therapeutic potential effects of KRG on relieving stress in a general population using transcriptome analysis. MethodsWe conducted an 8-week clinical pilot study on 90 healthy men who reported stress. The study was completed by 43 participants in the KRG group and 44 participants in the placebo group. Participants were randomized 1:1 to the KRG and placebo groups. We evaluated the stress by stress response inventory (SRI) at baseline and 8 weeks. The main outcomes were changes in the levels of neurotransmitters (NTs) and NT-related gene expression. NTs were analyzed using automated (GC) content, and levels of gene expression were measured by reads per kilobase of transcript per million mapped reads (RPKM). ResultsThe KRG group showed significantly preserved epinephrine decrease compared with placebo group at 8 weeks (changes in epinephrine, KRG vs. placebo; −1623.2 ± 46101.5 vs. −35116.3 ± 86288.2, p = 0012). Among subjects who higher SRI score, meaning stress increased compared to baseline, the KRG group showed a smaller decrease in serotonin than the placebo group (changes in serotonin, KRG vs. placebo; −2627.5 ± 5859.1 vs, −8087.4 ± 7162.4, p = 0.005) and a smaller increase in cortisol than the placebo group (changes in cortisol, KRG vs. placebo; 1912.7 ± 10097.75 vs. 8046.2 ± 8050.6 , p = 0.019) in subgroup analysis. Transcriptome findings indicated that KRG intake affects gene expression related with metabolism of choline, adrenalin, and monoamine. ConclusionThese findings suggest that KRG has beneficial effects on the amelioration of stress response in NTs, and this effect is more prominent in stressful situations. Further clinical studies are required to confirm the anti-stress effect of KRG.

Korean Red Ginseng Potentially Improves Maintaining Antibodies after COVID-19 Vaccination: A 24-Week Longitudinal Study.

Despite the effectiveness and safety of COVID-19 vaccines, vaccine-induced responses decline over time; thus, booster vaccines have been approved globally. In addition, interest in natural compounds capable of improving host immunity has increased. This study aimed to examine the effect of Korean Red Ginseng (KRG) on virus-specific antibodies after COVID-19 vaccination. We conducted a 24 week clinical pilot study of 350 healthy subjects who received two doses of the COVID-19 vaccine and a booster vaccination (third dose). These subjects were randomized 1:2 to the KRG and control groups. We evaluated antibody response five times: just before the second dose (baseline), 2 weeks, 4 weeks, 12 weeks after the second dose, and 4 weeks after the third dose. The primary endpoints were changes in COVID-19 spike antibody titers and neutralizing antibody titers. The antibody formation rate of the KRG group was sustained higher than that of the control group for 12 weeks after the second dose. This trend was prominently observed in those above 50 years old. We found that KRG can help to increase and maintain vaccine response, highlighting that KRG could potentially be used as an immunomodulator with COVID-19 vaccines.

Antitumor Effect of Korean Red Ginseng through Blockade of PD-1/PD-L1 Interaction in a Humanized PD-L1 Knock-In MC38 Cancer Mouse Model

Blocking immune checkpoints, programmed death-1 (PD-1) and its ligand PD-L1, has proven a promising anticancer strategy for enhancing cytotoxic T cell activity. Although we previously demonstrated that ginsenoside Rg3, Rh2, and compound K block the interaction of PD-1 and PD-L1, the antitumor effect through blockade of this interaction by Korean Red Ginseng alone is unknown. Therefore, we determined the effects of Korean Red Ginseng extract (RGE) on the PD-1/PD-L1 interaction and its antitumor effects using a humanized PD-1/PD-L1-expressing colorectal cancer (CRC) mouse model. RGE significantly blocked the interaction between human PD-1 and PD-L1 in a competitive ELISA. The CD8+ T cell-mediated tumor cell killing effect of RGE was evaluated using murine hPD-L1-expressing MC38 cells and tumor-infiltrating hPD-1-expressing CD8+ T cells isolated from hPD-L1 MC38 tumor-bearing hPD-1 mice. RGE also reduced the survival of hPD-L1 MC38 cells in a cell co-culture system using tumor-infiltrating CD8+ T cells as effector cells combined with hPD-L1 MC38 target cells. RGE or Keytruda (positive control) treatment markedly suppressed the growth of hPD-L1 MC38 allograft tumors, increased CD8+ T cell infiltration into tumors, and enhanced the production of Granzyme B. RGE exhibits anticancer effects through the PD-1/PD-L1 blockade, which warrants its further development as an immunotherapy.

Korean Red Ginseng Relieves Inflammation and Modulates Immune Response Induced by Pseudo-Type SARS-CoV-2.

Few studies have reported the therapeutic effects of Korean red ginseng (KRG) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the positive effects of KRG on other viruses have been reported and the effects of KRG on pulmonary inflammatory diseases have also been studied. Therefore, this study investigated the therapeutic effects of KRG-water extract (KRG-WE) in a pseudo-type SARS-CoV-2 (PSV)-induced lung injury model. Constructing the pseudovirus, human angiotensin-converting enzyme 2 (hACE2) transgenic mice were infected via intranasal injection that had been orally administered with KRG-WE for six weeks. After 7-days post infection (dpi), the antiviral effects of KRG-WE were confirmed, followed by real-time polymerase chain reaction (PCR), western blot analysis, flow cytometric analysis, and an enzyme-linked immunoassay (ELISA). KRG-WE significantly inhibited an increase in immunoglobulin caused by PSV. Furthermore, KRG-WE effectively suppressed alveolar macrophages (AMs) inside the lungs and helped normalize the population of other immune cells. In addition, virus-induced gene expression and inflammatory signals such as nuclear factor-kappa B and other upstream molecules were downregulated. Moreover, KRG-WE also normalized gene expression and protein activity in the spleen. In conclusion, KRG-WE reduced AMs, normalized the immune response, and decreased the expression of inflammatory genes and activation of signaling pathway phosphorylation, thereby exhibiting anti-inflammatory effects and attenuating lung damage.

The antitussive effects of Korean red ginseng on citric acid-induced cough in Guinea pigs

The antitussive effects of Korean red ginseng on citric acid-induced cough in Guinea pigs

Long-term evaluation of safety and biological effects of Korean Red Ginseng (Panax Ginseng): a long-term in vivo study

BackgroundAlthough Korean Red Ginseng (KRG) is safe, this finding was only evaluated in 3-mo-long studies. Its safety was verified through a 6-mo KRG administration clinical study, but long-term studies beyond 6 mo are insufficient. This study investigated the safety and efficacy of 12-mo KRG administration.MethodsIn this study, 300 mg/kg of KRG was administered to male and female Sprague Dawley rats for 4, 8, and 12 mo to evaluate its efficacy and safety. Clinical signs, including pathological examination and haematological analyses, were observed. Flow cytometric analyses were utilised to analyse spleen and thymus immune cell counts after 12 mo. Proteomic analysis of the sera was performed using a nanospray-interfaced mass spectrometer with an 11-plex Tandem Mass Tag (TMT) labelling system. Bioinformatic analysis was then performed using Ingenuity Pathway Analysis and PANTHER. Data are available via ProteomeXchange with identifier PXD032036.ResultsNo significant body and organ weight changes were observed, and haematological and serum biochemical analyses did not show clinical significance. The effectiveness of long-term KRG administration was confirmed through increased immune cell distribution and activity. Changes in proteins correlated with viral infection reduction were confirmed through proteomic analysis.ConclusionThe results suggested that 12-mo KRG intake is safe, improves immune system activity, and reduces viral infections with no significant changes in toxicological aspects.

Antiviral effects of Korean Red Ginseng on human coronavirus OC43

BackgroundPanax ginseng Meyer is a medicinal plant well-known for its antiviral activities against various viruses, but its antiviral effect on coronavirus has not yet been studied thoroughly. The antiviral activity of Korean Red Ginseng (KRG) and ten ginsenosides against Human coronavirus OC43 (HCoV-OC43) was investigated in vitro. MethodsThe antiviral response and mechanism of action of KRG extract and ginsenoside Rc, Re, Rf, Rg1, Rg2-20 (R) and −20 (S), Rg3-20 (R) and −20 (S), and Rh2-20 (R) and −20 (S), against the human coronavirus strain OC43 were investigated by using plaque assay, time of addition assay, real-time PCR, and FACS analysis. ResultsVirus plaque formation was reduced in KRG extract-treated and HCoV-OC43-infected HCT-8 cells. KRG extract decreased the viral proteins (Nucleocapsid protein and Spike protein) and mRNA (N and M gene) expression, while increased the expression of interferon genes. ConclusionKRG extract exhibits antiviral activity by enhancing the expression of interferons and can be used in treating infections caused by HCoV-OC43.

Korean Red Ginseng extract treatment prevents post-antibiotic dysbiosis-induced bone loss in mice

BackgroundThe intestinal microbiota is an important regulator of bone health. In previous studies we have shown that intestinal microbiota dysbiosis, induced by treatment with broad spectrum antibiotics (ABX) followed by natural repopulation, results in gut barrier dysfunction and bone loss. We have also shown that treatment with probiotics or a gut barrier enhancer can inhibit dysbiosis-induced bone loss. The overall goal of this project was to test the effect of Korean Red Ginseng (KRG) extract on bone and gut health using antibiotics (ABX) dysbiosis-induced bone loss model in mice. MethodsAdult male mice (Balb/C, 12-week old) were administered broad spectrum antibiotics (ampicillin and neomycin) for 2 weeks followed by 4 weeks of natural repopulation. During this 4-week period, mice were treated with vehicle (water) or KRG extract. Other controls included mice that did not receive either antibiotics or KRG extract and mice that received only KRG extract. At the end of the experiments, we assessed various parameters to assess bone, microbiota and in vivo intestinal permeability. ResultsConsistent with our previous results, post-ABX- dysbiosis led to significant bone loss. Importantly, this was associated with a decrease in gut microbiota alpha diversity and an increase in intestinal permeability. All these effects including bone loss were prevented by KRG extract treatment. Furthermore, our studies identified multiple genera including Lactobacillus and rc4-4 as well as Alistipes finegoldii to be potentially linked to the effect of KRG extract on gut-bone axis. ConclusionTogether, our results demonstrate that KRG extract regulates the gut-bone axis and is effective at preventing dysbiosis-induced bone loss in mice.

Anticolon Cancer Effect of Korean Red Ginseng via Autophagy- and Apoptosis-Mediated Cell Death.

Ginseng (Panax ginseng Meyer) has been used in East Asian traditional medicine for a long time. Korean red ginseng (KRG) is effective against several disorders, including cancer. The cytotoxic effects of KRG extract in terms of autophagy- and apoptosis-mediated cell death and its mechanisms were investigated using human colorectal cancer lines. KRG induced autophagy-mediated cell death with enhanced expression of Atg5, Beclin-1, and LC3, and formed characteristic vacuoles in HCT-116 and SNU-1033 cells. An autophagy inhibitor prevented cell death induced by KRG. KRG generated mitochondrial reactive oxygen species (ROS); antioxidant countered this effect and decreased autophagy. KRG caused apoptotic cell death by increasing apoptotic cells and sub-G1 cells, and by activating caspases. A caspase inhibitor suppressed cell death induced by KRG. KRG increased phospho-Bcl-2 expression, but decreased Bcl-2 expression. Moreover, interaction of Bcl-2 with Beclin-1 was attenuated by KRG. Ginsenoside Rg2 was the most effective ginsenoside responsible for KRG-induced autophagy- and apoptosis-mediated cell death. KRG induced autophagy- and apoptosis-mediated cell death via mitochondrial ROS generation, and thus its administration may inhibit colon carcinogenesis.

Anxiolytic effect of Korean Red Ginseng through upregulation of serotonin and GABA transmission and BDNF expression in immobilized mice

BackgroundAnxiolytic properties of Korean Red Ginseng (KRG) have been previously reported. However, the exact mechanism(s) of action remains to be elucidated. The present study investigated the effect of KRG on immobilization-induced anxiety-like behaviors in mice and explored the involvement of the serotonin and GABA systems and BDNF in the anxiolytic action. MethodsMice were orally administered with KRG (200 mg/kg/day) for 4 weeks and immobilized once daily for 2 h. p-Chlorophenylalanine (p-CPA) was intraperitoneally injected on day 22-28, and flumazenil or bicuculline was injected on day 25-28. After behavioral evaluations, brains were dissected for biochemical analyses. ResultsKRG improved immobilization-induced anxiety-like behaviors in mice, as assessed by the elevated plus maze (EPM) and marble burying tests (MBT). The anxiolytic effect of KRG was comparable to that of fluoxetine, a reference drug clinically used for anxiety disorders. A serotonin synthesis inhibitor, p-CPA, blocked the effect of KRG in the EPM and MBT, indicating the requirement of serotonin synthesis for anxiolytic action. In addition, the anxiolytic effect of KRG was inhibited by bicuculline (a GABAA antagonist) in MBT, implying the involvement of GABA transmission. Western blotting analyses revealed that KRG upregulated the expression of tryptophan hydroxylase and GABAA receptor in the brain, which was blocked by p-CPA. Enhanced BDNF expression by KRG in the hippocampus was also indicated to mediate the anxiolytic action of KRG in immobilized mice. ConclusionKRG exhibited the anxiolytic effect in immobilized mice by multiple mechanisms of action, involving enhanced serotonin and GABA transmissions and BDNF expression.