• Journal of Ginseng Research
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• v.44 no.4
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• pp.655-663
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• 2020

Background: Korean Red Ginseng is known to exhibit immune-enhancing and anti-inflammatory properties. The immune-enhancing effects of the nonsaponin fraction (NSF) of Korean Red Ginseng have been studied in many reports. However, the gastroprotective effect of this fraction is not fully understood. In this study, we demonstrate the activities of NSF for gastrointestinal protection and its related critical factor. Methods: The in vitro and in vivo regulatory functions of NSF on cyclooxygenase-1 (COX-1) messenger RNA and protein levels were examined by reverse transcription polymerase chain reaction and immunoblotting analyses. Gastroprotective effects of NSF were investigated by histological score, gastric juice pH, and myeloperoxidase activity on indomethacin-induced, cold stress-induced, and acetylsalicylic acid-induced gastritis and dextran sulfate sodium-induced colitis in in vivo mouse models. Results: NSF did not show cytotoxicity, and it increased COX-1 messenger RNA expression and protein levels in RAW264.7 cells. This upregulation was also observed in colitis and gastritis in vivo models. In addition, NSF treatment in mice ameliorated the symptoms of gastrointestinal inflammation, including histological score, colon length, gastric juice pH, gastric wall thickness, and myeloperoxidase activity. Conclusion: These results suggest that NSF has gastroprotective effects on gastritis and colitis in in vivo mouse models through COX-1 upregulation.

• Journal of Ginseng Research
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• v.43 no.1
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• pp.49-57
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• 2019

Background: Korean Red Ginseng (KRG; Panax ginseng Meyer) is a widely used medicinal herb known to exert various immune modulatory functions. KRG and one of its purified components, ginsenoside Rg3, are known to possess anti-inflammatory activities. How they impact helper T cell-mediated responses is not fully explored. In this study, we attempted to evaluate the effect of KRG extract (KRGE) and ginsenoside Rg3 on Th1 cell responses. Methods: Using well-characterized T cell in vitro differentiation systems, we examined the effects of KRGE or enhanced Rg3 on the Th1-inducing cytokine production from dendritic cells (DC) and the naïve $CD4^+$ T cells differentiation to Th1 cells. Furthermore, we examined the change of Th1 cell population in the intestine after treatment of enhanced Rg3. The influence of KRGE or enhanced Rg3 on Th1 cell differentiation was evaluated by fluorescence-activated cell sorting, enzyme-linked immunosorbent assay, and quantitative real-time polymerase chain reaction. Results: KRGE significantly inhibited the production level of IL-12 from DCs and subsequent Th1 cell differentiation. Similarly, enhanced Rg3 significantly suppressed the expression of interferon gamma ($IFN{\gamma}$) and T-bet in T cells under Th1-skewing condition. Consistent with these effects in vitro, oral administration of enhanced Rg3 suppressed the frequency of Th1 cells in the Peyer's patch and lamina propria cells in vivo. Conclusion: Enhanced Rg3 negatively regulates the differentiation of Th1 cell in vitro and Th1 cell responses in the gut in vivo, providing fundamental basis for the use of this agent to treat Th1-related diseases.

• Analytical Science and Technology
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• v.30 no.3
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• pp.146-153
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• 2017

In this study, we isolated ginseng crude saponin (GCS) from Korean red ginseng (KRG) and determined the ginsenoside content in it to investigate the physiological and pathological effects of GCS on acute pulmonary inflammation induced by intratracheal instillation of cigarette smoke condensates (CSC) and lipopolysaccharide (LPS) solution in BALB/c mice. GCS was orally administered at doses of 10 mg/kg and 25 mg/kg for 3 weeks. The recovery rate of GCS from KRG was 6.5 % and total ginsenosides from GCS was 1.13 %, and the content of Rb1 was the highest among them. Total inflammatory cells in the lung homogenates and bronchoalveolar lavage fluid (BALF) increased following intratracheal administration of CSC and LPS. However, GCS administration impaired this increase. Furthermore, it inhibited the increase in leukocytes in the blood, considerably decreased neutrophils in BALF, and declined infiltration of inflammatory cells and deposition of collagen in the tracheal and alveolar tissue. In this study, GCS was found to have a protective effect against acute pulmonary inflammation and it may be beneficial in preventing various respiratory diseases.

• Biomedical Science Letters
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• v.23 no.4
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• pp.310-320
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• 2017

Ginseng has been widely used for traditional medicine in eastern Asia and is known to have inhibitory effects on cardiovascular disease (CVD) such as thrombosis, atherosclerosis, and myocardial infarction. Because, platelet is a crucial mediator of CVD, many studies are focusing on inhibitory mechanism of platelet functions. Among platelet activating molecules, thromboxane $A_2$ ($TXA_2$) and P-selectin play a central role in CVD. $TXA_2$ leads to intracellular signaling cascades and P-selectin plays an important role in platelet-neutrophil and platelet-monocyte interactions leading to the inflammatory response. In this study, we investigated the inhibitory mechanisms of total saponin fraction from Korean red ginseng (KRG-TS) on $TXA_2$ production and P-selectin expression. Thrombin-elevated $TXA_2$ production and arachidonic acid release were decreased by KRG-TS dose (25 to $150{\mu}g/mL$)-dependently via down regulation of microsomal cyclooxygenase-1 (COX-1), $TXA_2$ synthase (TXAS) activity and dephosphorylation of cytosolic phospholipase $A_2$ ($cPLA_2$). In addition, KRG-TS suppressed thrombin-activated P-selectin expression, an indicator of granule release via dephosphorylation of mitogen-activated protein kinases (MAPK). Taken together, we revealed that KRG-TS is a beneficial novel compound inhibiting $TXA_2$ production and P-selectin expression, which may prevent platelet aggregation-mediated thrombotic disease.

• 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.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.43 no.1
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• pp.135-142
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• 2019

Background: Panax ginseng Meyer, known as Korean Red Ginseng (KRG), is one of the important age-old traditional herbs used in boosting libido and improving male fertility. In this study, the effects of Rg3-enriched KRG extract (KGC04P) on heat stress-induced testicular damage in experimental rats was evaluated. Methods: Male rats (Sprague-Dawley) were divided into four groups (n = 10): normal control (NC), heat-stressed control (HC), heat-stressed plus KGC04P-100 mg/kg (HK100), and heat-stressed plus KGC04P-200 mg/kg (HK200) groups. Starting 1 week prior to heat stress, animals were administered orally with KGC04P (100 and 200 mg/kg) mixed with a regular pellet diet and continued for 25 weeks. Heat stress was induced to HC, HK100, and HK200 groups by intermittently exposing the animals to high temperatures ($32{\pm}1^{\circ}C$, 2 h/day). After 6 months, animals were euthanized under general anesthesia with carbon dioxide and evaluated for various parameters in serum and testicular tissue by using Western blotting, biochemical kits, and reverse transcription-polymerase chain reaction. Results: Significant (p < 0.05) alterations in several parameters, such as body/organ weight, sperm kinematics, and lipid metabolism marker levels, in the serum and testis of rats were observed. Further, the expression of testicular antioxidant enzymes, inflammatory cytokines, sex hormonal receptors, and spermatogenesis-related genes were also affected significantly (p < 0.05) in the heat-stressed group. However, KGC04P prevented the heat stress-induced changes in rats significantly (p < 0.05) at both concentrations. Conclusion: KGC04P attenuated heat stress-induced testicular damage by a multifunctional approach and can be developed as an excellent therapeutic agent for hyperthermia-mediated male infertility.

• The Journal of Korean Medicine
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• v.27 no.3 s.67
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• pp.38-50
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• 2006

Objectives: The aim of this study was to evaluate the effects of Korean ginseng (KG), Korean red ginseng (KRG) and fermented Korean red ginseng (FKRG) extracts on cerebral hemodynamics and to compare distinction of each extract. Methods: Ten healthy male volunteers $(26.0{\pm}1.8yrs)$ participated in the study according to double-blind and cross-over protocols. Each volunteer was blindly administered 500mg of KG, KRG, FKRG extract or placebo (Dextrin). Blinded researchers measured changes of hyperventilation-induced cerebrovascular reactivity (CVR), mean blood flow velocity (MBFV) of middle cerebral arteries (MCAs) and corrected blood flow velocity at $P_{ETCO2}=40mmHg$ (CV40) using transcranial Doppler ultrasound (DWL Co., Germany). Researchers also observed changes of mean blood pressure (MBP), pulse rate (PR) and expiratory $CO_2$ using S/5 Collector (Datex-Ohmeda Co., Finland). The evaluation was performed at basal condition, and repeated at 1, 2, 3, 4 and 5 hours after administration. Results: MBFV and CV40 in the KRG group tended to rise at I hour after administration, while those of the FKRG group tended to rise at 2 hours after administration. CVR increased significantly after 1 hour in the KRG group (p=0.009) and after 2 hours in the FKRG group (p=0.035), respectively. The KG group showed increasing tendency at 4 hours after administration. No group showed significant difference from the placebo in changes of MBP and PR. Conclusions: It is suggested that KG, KRG and FKRG extracts have effects of enhancing CVR and thus of increasing cerebral blood flow in human subjects.

• Journal of Ginseng Research
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• v.47 no.5
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• pp.672-680
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• 2023

Background: Korean Red Ginseng (KRG), the steamed root of Panax ginseng, has pharmacological activities for immunological and neurodegenerative disorders. But, the role of KRGE in multiple sclerosis (MS) remains unclear. Purpose: To determine whether KRG extract (KRGE) could inhibit demyelination in corpus callosum (CC) of cuprizone (CPZ)-induced murine model of MS Methods: Male adult mice were fed with a standard chow diet or a chow diet supplemented with 0.2% (w/w) CPZ ad libitum for six weeks to induce demyelination while were simultaneously administered with distilled water (DW) alone or KRGE-DW (0.004%, 0.02 and 0.1% of KRGE) by drinking. Results: Administration with KRGE-DW alleviated demyelination and oligodendrocyte degeneration associated with inhibition of infiltration and activation of resident microglia and monocyte-derived macrophages as well as downregulation of proinflammatory mediators in the CC of CPZ-fed mice. KRGE-DW also attenuated the level of infiltration of Th1 and Th17) cells, in line with inhibited Mrna expression of IFN-γ and IL-17, respectively, in the CC. These positive effects of KRGE-DW mitigated behavioral dysfunction based on elevated plus maze and the rotarod tests. Conclusion: The results strongly suggest that KRGE-DW may inhibit CPZ-induced demyelination due to its oligodendroglial protective and anti-inflammatory activities by inhibiting infiltration/activation of immune cells. Thus, KRGE might have potential in therapeutic intervention for MS.

• Journal of Ginseng Research
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• v.36 no.1
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• pp.47-54
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• 2012

Korean red ginseng (KRG) has been used worldwide as a traditional medicine for the treatment of various reproductive diseases. Gonadotropin releasing hormone (GnRH) neurons are the fundamental regulators of pulsatile release of gonadotropin required for fertility. In this study, an extract of KRG (KRGE) was applied to GnRH neurons to identify the receptors activated by KRGE. The brain slice patch clamp technique in whole cell and perforated patch was used to clarify the effect of KRGE on the membrane currents and membrane potentials of GnRH neurons. Application of KRGE (3 ${\mu}g$/${\mu}L$) under whole cell patch induced remarkable inward currents (56.17${\pm}$7.45 pA, n=25) and depolarization (12.91${\pm}$3.80 mV, n=4) in GnRH neurons under high $Cl^-$ pipette solution condition. These inward currents were not only reproducible, but also concentration dependent. In addition, inward currents and depolarization induced by KRGE persisted in the presence of the voltage gated $Na^+$ channel blocker tetrodotoxin (TTX), suggesting that the responses by KRGE were postsynaptic events. Application of KRGE under the gramicidin perforated patch induced depolarization in the presence of TTX suggesting its physiological significance on GnRH response. Further, the KRGE-induced inward currents were partially blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; non-NMDA glutamate receptor antagonist, 10 ${\mu}M$) or picrotoxin (PIC; $GABA_A$ receptor antagonist, 50 ${\mu}M$), and almost blocked by PIC and CNQX mixture. Taken together, these results suggest that KRGE contains ingredients with possible GABA and non-NMDA glutamate receptor mimetic activity, and may play an important role in the endocrine function of reproductive physiology, via activation of $GABA_A$ and non-NMDA glutamate receptors in GnRH neurons.