• Journal of Ginseng Research
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• v.45 no.2
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• pp.316-324
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• 2021

Background: Korea Red Ginseng (KRG) has been used as remedies with hepato-protective effects in liver-related condition. Microbiota related gut-liver axis plays key roles in the pathogenesis of chronic liver disease. We evaluated the effect of KRG on gut-liver axis in patients with nonalcoholic statohepatitis by the modulation of gut-microbiota. Methods: A total of 94 patients (KRG: 45 and placebo: 49) were prospectively randomized to receive KRG (2,000 mg/day, ginsenoside Rg1+Rb1+Rg3 4.5mg/g) or placebo during 30 days. Liver function test, cytokeraton 18, and fatigue score were measured. Gut microbiota was analyzed by MiSeq systems based on 16S rRNA genes. Results: In KRG group, the mean levels (before vs. after) of aspartate aminotransferase (53 ± 19 vs. 45 ± 23 IU/L), alanine aminotransferase (75 ± 40 vs. 64 ± 39 IU/L) and fatigue score (33 ± 13 vs. 26 ± 13) were improved (p < 0.05). In placebo group, only fatigue score (34 ± 13 vs. 31 ± 15) was ameliorated (p < 0.05). The changes of phyla were not statistically significant on both groups. In KRG group, increased abundance of Lactobacillus was related with improved alanine aminotransferase level and increased abundance of Clostridium and Intestinibacter was associated with no improvement after KRG supplementation. In placebo group, increased abundance of Lachnospiraceae could be related with aggravation of liver enzyme (p < 0.05). Conclusion: KRG effectively improved liver enzymes and fatigue score by modulating gut-microbiota in patients with fatty liver disease. Further studies are needed to understand the mechanism of improvement of nonalcoholic steatohepatitis. ClnicalTrials.gov: NCT03945123 (www.ClinicalTrials.gov).

• Journal of the Korea Academia-Industrial cooperation Society
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• v.15 no.9
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• pp.5708-5715
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• 2014

The effects of korean red ginseng (KRG) extracts on orifacial pain control in terms of the systemic inflammatory response and pharmacological effects as health supplements were investigated. The experimental group were divided into three groups, the control group (n=6), formalin (5%, $50{\mu}{\ell}$) injection group (n=6), and formalin (5%, $50{\mu}{\ell}$) injection added KRG administrated group (4.5 ml/kg, n=6). The KRG administrated group prior to the formalin injection significantly attenuated the behavioral response compared to that of the control group. Pain reduction was suppressed mainly from 15 min to 30 min. The KRG administrated rats showed significantly reduced p38 MAPK, iNOS and Nrf2 expression in the brain and medulla oblongata according to Western blot analysis. These findings suggest that KRE may have a useful effect on orificial pain control functions by preventing the p38 MAPK pathway.

• Journal of Ginseng Research
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• v.48 no.1
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• pp.1-11
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• 2024

Fresh ginseng is prone to spoilage due to its high moisture content. For long-term storage, most fresh ginsengs are dried to white ginseng (WG) or steamed for hours at high temperature/pressure and dried to form Korean Red ginseng (KRG). They are further processed for ginseng products when subjected to hot water extraction/concentration under pressure. These WG or KRG preparation processes affect ginsenoside compositions and also other ginseng components, probably during treatments like steaming and drying, to form diverse bioactive phospholipids. It is known that ginseng contains high amounts of gintonin lysophosphatidic acids (LPAs). LPAs are simple lipid-derived growth factors in animals and humans and act as exogenous ligands of six GTP-binding-protein coupled LPA receptor subtypes. LPAs play diverse roles ranging from brain development to hair growth in animals and humans. LPA-mediated signaling pathways involve various GTP-binding proteins to regulate downstream pathways like [Ca²⁺]_i transient induction. Recent studies have shown that gintonin exhibits anti-Alzheimer's disease and antiarthritis effects in vitro and in vivo mediated by gintonin LPAs, the active ingredients of gintonin, a ginseng-derived neurotrophin. However, little is known about how gintonin LPAs are formed in high amounts in ginseng compared to other herbs. This review introduces atypical or non-enzymatic pathways under the conversion of ginseng phospholipids into gintonin LPAs during steaming and extraction/concentration processes, which exert beneficial effects against degenerative diseases, including Alzheimer's disease and arthritis in animals and humans via LPA receptors.

• Archives of Pharmacal Research
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• v.29 no.10
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• pp.898-903
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• 2006

The antiplatelet and antithrombotic activities of Korean Red Ginseng (KRG) were examined on rat carotid artery thrombosis in vivo, and platelet aggregation in vitro and ex vivo. Administration of KRG to rats not only prevented carotid artery thrombosis in vivo in a dose-dependent manner, but also significantly inhibited ADP- and collagen-induced platelet aggregation ex vivo, while failed to prolong coagulation times such as activated partial thromboplastin time (APTT) and prothrombin time (PT), indicating the antithrombotic effect of KRG might be due to its anti platelet aggregation rather than anticoagulation effect. In line with the above observations, KRG inhibited U46619-, arachidonic acid-, collagen- and thrombin-induced rabbit platelet aggregation in vitro in a concentration-dependent manner, with $IC_{50}$ values of $620{\pm}12$, $823{\pm}22$, $722{\pm}21$ and $650{\pm}14\;{\mu}g/mL$, respectively. Accordingly, KRG also inhibited various agonists-induced platelet serotonin secretions as it suppressed platelet aggregation. These results suggest that KRG has a potent antithrombotic effect in vivo, which may be due to antiplatelet rather than anticoagulation activity, and KRG intake may be beneficial to the individuals with high risks of thrombotic and cardiovascular diseases.

• Journal of Ginseng Research
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• v.23 no.1 s.53
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• pp.13-20
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• 1999

We previously reported that Korean red ginseng (KRG) has a relaxation effect on the smooth muscles of corpus cavernosum via nitric oxide (NO) pathway and calcium and potassium channels. However, it is suggested that the active ingredients of KRG might be different depending on the sources of preparation, and there might be differences in actions for different compositions. We first investigated the composition of KRG saponins according to the extractions of the various sources of KRG, then with these extractions the relaxation effects were evaluated in vitro and hemodynamical in vivo using New Zealand white rabbit and rat corpus cavernosum. The total compositions of ginsenoside $(G-Rb_1,\;-Rb_2,\;-Rc,\;-Rd,\;G-Re,\;-Rf,\;-Rg_1)$ in fractionated KRG saponin designated as TS-1, TS-2, TS-3 were $41\%,\;40\%,\;and\;62\%,$ respectively, and the ratios of PD saponin and PT saponin (PD/PT) were 1,55, 1.72, 2.25, and 2.61, the values of which were statistically significant. In vitro studies using the rabbit corpus cavernosal muscle strips, the KRG saponin relaxed cavernosal strips in a dose-dependent manner, and same results were observed in in vivo studies, that KRG saponin increased the intracavernosal pressure in the rat. There was difference in the efficacy according to fractionation techniques. The differences in the total contents of ginsenosides did not affect relaxation, rather PT saponin content was statistically related to the degree of cavernosal relaxation, and this action presumed to be mediated by NO pathway and calcium and potassium channels. In conclusion, KRG exerts relaxation which is a key step in erection via combination of effects on NO system or calcium and potassium channels. The efficacy of this action is different to the sources of ginseng, which is affected by the different composition of ginsenosides $(G-Rb_1,\;-Rb_2,\;-Rc,\;-Rd,\;G-Re,\;-Rf,\;-Rg_1).$ Thus the further studies on the active ingredients such as minor ginsenosides and non-saponin components of red ginseng with maximum potency should be sought.

• Journal of Ginseng Research
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• v.46 no.4
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• pp.585-591
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• 2022

Background: Korean Red Ginseng (KRG) extract has been shown to have beneficial effects in patients with atherosclerosis, suggesting that KRG extract may be effective in preventing subsequent ischemic stroke in patients with severe atherosclerosis. Methods: This double-blind, placebo-controlled trial randomized patients with severe atherosclerosis in major intracranial arteries or extracranial carotid artery, to ginseng group and placebo group. They were given two 500-mg KRG tablets or identical placebo tablets twice daily for 12 months according to randomization. The primary endpoint was the composite of cerebral ischemic stroke and transient ischemic attack during 12 months after randomization. The secondary endpoints were change in volumetric blood flow of the intracranial vessels and the incidence of newly developed asymptomatic ischemic lesions. Any adverse events were monitored. Results: Fifty-eight patients were randomized from June 2016 to June 2017, 29 to ginseng and 29 to placebo, and 52 (28 and 24, respectively) completed the study. One patient in the placebo group, but none in the ginseng group, experienced ischemic symptoms (p = 0.46). Changes in volumetric blood flow and the presence of ischemic brain lesions did not differ significantly in the two groups, and none of these patients experienced adverse drug reactions. Conclusion: Ginseng was well tolerated by patients with severe atherosclerosis, with these patients showing good compliance with ginseng dosing. Ginseng did not show significant effects compared with placebo, although none of the ginseng-treated patients experienced ischemic events. Long-term studies in larger patient populations are required to test the effect of ginseng.

• 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.46 no.3
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• pp.489-495
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• 2022

Background: Although ginsenosides and saponins in Korea red ginseng (KRG) shows various pharmacological roles, their roles in the inflammatory response are little known. This study investigated the anti-inflammatory role of ginsenosides identified from KRG saponin fraction (RGSF) and the potential mechanism in macrophages. Methods: The ginsenoside composition of RGSF was identified by high-performance liquid chromatography (HPLC) analysis. An anti-inflammatory effect of RGSF and its mechanisms were studied using nitric oxide (NO) and prostaglandin E₂ (PGE₂) production assays, mRNA expression analyses of inflammatory genes and cytokines, luciferase reporter gene assays of transcription factors, and Western blot analyses of inflammatory signaling pathways using the lipopolysaccharide (LPS)-treated RAW264.7 cells. Results: HPLC analysis identified the types and amounts of various panaxadiol ginsenosides in RGSF. RGSF reduced the generation of inflammatory molecules and mRNA levels of inflammatory enzymes and cytokines in LPS-treated RAW264.7 cells. Additionally, RGSF inhibited the signaling pathways of NF-κB and AP-1 by suppressing both transcriptional factors and signaling molecules in LPS-treated RAW264.7 cells. Conclusion: RGSF contains ginsenosides that have anti-inflammatory action via restraining the NF-κB and AP-1 signaling pathways in macrophages during inflammatory responses.

• Journal of Ginseng Research
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• v.34 no.4
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• pp.342-347
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• 2010

Ginseng is one of the most-widely used herbal remedies. This systematic review evaluates the current evidence for its use in the reducing blood pressure (BP) in patients with hypertension. Systematic searches of 12 electronic databases were conducted without language restrictions. All randomized clinical trials (RCTs) of ginseng as a treatment for hypertension were candidates for inclusion. Methodological quality was assessed using the Cochrane risk of bias. Five RCTs met the inclusion criteria. The risk of bias was low in most of the trials. Four of the included RCTs compared the effectiveness of ginseng to placebo. The meta-analysis of these data failed to show a statistically significant acute effect on systolic BP (SBP) or diastolic BP (DBP). However, subgroup analyses showed beneficial effects of Korean red ginseng (KRG) on both SBP (n=54, mean difference [MD], -6.52; 95% confidence interval [CI], -9.99 to -3.04; p=0.0002) and DBP (n=54, MD, -5.21; 95% CI, -7.90 to -2.51; p=0.0001). Two RCTs tested the long-term effects of ginseng for BP for 24hours. One of these trials failed to show any benefits of KRG compared to no treatment, and the other failed to show superior effects of North American ginseng compared to placebo. Adverse events with ginseng were none in one trial or not assessed. Collectively, these RCTs provide limited evidence for the acute effectiveness of KRG in the treatment of high BP. The total number of RCTs included in the analysis and the total sample size were insufficient to draw definitive conclusions. More rigorous studies are warranted.

• 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.