Korean Red Ginseng Extract Research Articles

Dual Effects of Korean Red Ginseng on Astrocytes and Neural Stem Cells in Traumatic Brain Injury: The HO-1-Tom20 Axis as a Putative Target for Mitochondrial Function.

Astrocytes display regenerative potential in pathophysiologic conditions. In our previous study, heme oxygenase-1 (HO-1) promoted astrocytic mitochondrial functions in mice via the peroxisome-proliferator-activating receptor-γ coactivator-1α (PGC-1α) pathway on administering Korean red ginseng extract (KRGE) after traumatic brain injury (TBI). In this study, KRGE promoted astrocytic mitochondrial functions, assessed with oxygen consumption and adenosine triphosphate (ATP) production, which could be regulated by the translocase of the outer membrane of mitochondria 20 (Tom20) pathway with a PGC-1α-independent pathway. The HO-1–Tom20 axis induced an increase in mitochondrial functions, detected with cytochrome c oxidase subunit 2 and cytochrome c. HO-1 crosstalk with nicotinamide phosphoribosyltransferase was concomitant with the upregulated nicotinamide adenine dinucleotide (NAD)/NADH ratio, thereby upregulating NAD-dependent class I sirtuins. In adult neural stem cells (NSCs), KRGE-treated, astrocyte-conditioned media increased oxygen consumption and Tom20 levels through astrocyte-derived HO-1. HO inactivation by Sn(IV) protoporphyrin IX dichloride in TBI mice administered KRGE decreased neuronal markers, together with Tom20. Thus, astrocytic HO-1 induced astrocytic mitochondrial functions. HO-1-related, astrocyte-derived factors may also induce neuronal differentiation and mitochondrial functions of adult NSCs after TBI. KRGE-mediated astrocytic HO-1 induction may have a key role in repairing neurovascular function post-TBI in peri-injured regions by boosting astrocytic and NSC mitochondrial functions.

Korean Red Ginseng Extract Inhibits IL-8 Expression via Nrf2 Activation in Helicobacter pylori-Infected Gastric Epithelial Cells.

Helicobacter pylori (H. pylori) causes gastric diseases by increasing reactive oxygen species (ROS) and interleukin (IL)-8 expression in gastric epithelial cells. ROS and inflammatory responses are regulated by the activation of nuclear factor erythroid-2-related factor 2 (Nrf2) and the expression of Nrf2 target genes, superoxide dismutase (SOD) and heme oxygenase-1 (HO-1). We previously demonstrated that Korean red ginseng extract (RGE) decreases H. pylori-induced increases in ROS and monocyte chemoattractant protein 1 in gastric epithelial cells. We determined whether RGE suppresses the expression of IL-8 via Nrf2 activation and the expression of SOD and HO-1 in H. pylori-infected gastric epithelial AGS cells. H. pylori-infected cells were treated with RGE with or without ML385, an Nrf2 inhibitor, or zinc protoporphyrin (ZnPP), a HO-1 inhibitor. Levels of ROS and IL-8 expression; abundance of Keap1, HO-1, and SOD; levels of total, nuclear, and phosphorylated Nrf2; indices of mitochondrial dysfunction (reduction in mitochondrial membrane potential and ATP level); and SOD activity were determined. As a result, RGE disturbed Nrf2–Keap1 interactions and increased nuclear Nrf2 levels in uninfected cells. H. pylori infection decreased the protein levels of SOD-1 and HO-1, as well as SOD activity, which was reversed by RGE treatment. RGE reduced H. pylori-induced increases in ROS and IL-8 levels as well as mitochondrial dysfunction. ML385 or ZnPP reversed the inhibitory effect of RGE on the alterations caused by H. pylori. In conclusion, RGE suppressed IL-8 expression and mitochondrial dysfunction via Nrf2 activation, induction of SOD-1 and HO-1, and reduction of ROS in H. pylori-infected cells.

Synergistic Effects of Korean Red Ginseng Extract and the Conventional Systemic Therapeutics of Atopic Dermatitis in a Murine Model.

The synergistic effects of Korean Red ginseng (KRG, Panax ginseng C.A. Mey.) on conventional systemic therapeutics of atopic dermatitis (AD) have not been studied yet. To analyze the synergistic effects of KRG extract and the conventional systemic therapeutics of AD in TNCB-induced AD mouse model, we determined the change in modified scoring of index, the transepidermal water loss, the skin pathology, serum IgE, and the expression of various cytokines after combination treatment to the five-week-old NC/Nga female mice. The severity of AD was significantly decreased in the KRG + hydroxyzine (AH) group than AH group, and in the KRG + evening primrose oil (EPO) group than EPO group. A significant decrease in dermal inflammation was observed in the KRG + AH group than that in the AH group, and in the KRG + EPO group than that in the EPO group (p = 0.008), respectively. A decrease in CD1a expression was observed in the KRG + AH group when compared to the AH group (p = 0.008), and KRG + EPO group when compared to the EPO group. Compared to the CS group, the KRG + CS group showed a significant decrease in IL-17 expression. A combination of KRG and conventional systemic therapeutics can safely and effectively manage the AD.

Korean Red Ginseng Improves Astrocytic Mitochondrial Function by Upregulating HO-1-Mediated AMPKα-PGC-1α-ERRα Circuit after Traumatic Brain Injury.

Heme oxygenase-1 (HO-1) exerts beneficial effects, including angiogenesis and energy metabolism via the peroxisome proliferator-activating receptor-γ coactivator-1α (PGC-1α)–estrogen-related receptor α (ERRα) pathway in astrocytes. However, the role of Korean red ginseng extract (KRGE) in HO-1-mediated mitochondrial function in traumatic brain injury (TBI) is not well-elucidated. We found that HO-1 was upregulated in astrocytes located in peri-injured brain regions after a TBI, following exposure to KRGE. Experiments with pharmacological inhibitors and target-specific siRNAs revealed that HO-1 levels highly correlated with increased AMP-activated protein kinase α (AMPKα) activation, which led to the PGC-1α-ERRα axis-induced increases in mitochondrial functions (detected based on expression of cytochrome c oxidase subunit 2 (MTCO2) and cytochrome c as well as O2 consumption and ATP production). Knockdown of ERRα significantly reduced the p-AMPKα/AMPKα ratio and PGC-1α expression, leading to AMPKα–PGC-1α–ERRα circuit formation. Inactivation of HO by injecting the HO inhibitor Sn(IV) protoporphyrin IX dichloride diminished the expression of p-AMPKα, PGC-1α, ERRα, MTCO2, and cytochrome c in the KRGE-administered peri-injured region of a brain subjected to TBI. These data suggest that KRGE enhanced astrocytic mitochondrial function via a HO-1-mediated AMPKα–PGC-1α–ERRα circuit and consequent oxidative phosphorylation, O2 consumption, and ATP production. This circuit may play an important role in repairing neurovascular function after TBI in the peri-injured region by stimulating astrocytic mitochondrial biogenesis.

Korean red ginseng extract exploits NF-κB to promote wound repair and protein expression in keratinocytes

Korean red ginseng extract exploits NF-κB to promote wound repair and protein expression in keratinocytes

Synergistic effect of Korean red ginseng extract and GABA mixture on the IgE production in mice via Th1/Th2 cell balance.

It has been recently reported that the immune system has been linked to the nervous system. This study was conducted to investigate the effect of administration of two components, gamma-aminobutyric acid (GABA) and Panax ginseng Meyer (GIN), on the production of IgE and Th1-Th2 dominant cytokines. Antibody and inflammatory mediator levels in serum, and the cytokines secreted to spleen cells of ovalbumin (OVA) immunized mice were analyzed. The group of GABA and GIN mixture significantly reduced IgE level and dramatically increased OVA-IgG2a antibody production. In addition, rising effect on IFN-gamma and GM-CSF levels related to Th1 cytokine was observed only in the group of GABA + GIN. The mixture alleviated allergic symptoms by reducing the level of histamine and prostaglandin. These studies suggest that GIN + GABA administration in the allergen-induced mouse model may regulate the Th1-Th2 balance by strongly acting on the immune response associated with Th1.

Effect of a combination of Korean red ginseng extract and probiotics on the prevention of atopic dermatitis in a murine model

Ethnopharmacological relevancePanax ginseng C.A.Mey. (Korea red ginseng) has been used in Asia to treat inflammatory skin diseases. Recently, Korea red ginseng (KRG) is emerging as a good candidate for treating atopic dermatitis (AD) because of its anti-allergic and anti-inflammatory effects. Aim of the studyDespite much effort, no systemic prevention strategy has been established for AD currently. Therefore, the aim of this study was to determine the preventive effect of a combination of KRG extract and probiotics on AD-like skin lesions of mice. Materials and methodsForty NC/Nga mice were randomly divided into eight groups: Sham, AD control, Cyclosporine, KRG, Duolac ATP® (ATP), BYO Plant Origin Skin Probiotics (BYO), KRG + ATP, and KRG + BYO. Mice were administered orally with KRG and/or other agents using a gastric tube for 5 days prior to challenge with 1-chloro-2,4-dinitrobenzene (DNCB). AD-like skin lesions were induced by percutaneous challenge with DNCB on ears and backs of NC/Nga mice. Effects of each treatment were evaluated based on the following: Clinical severity score, ear thickness, transepidermal water loss (TEWL), total serum Immunoglobulin E (IgE) level, mRNA expression levels and immunohistochemistry analysis of IFN-γ, IL-4, and TSLP in cutaneous lesions. ResultsTEWL, serum IgE level, and expression of immunohistopathologic markers were more improved in the group using KRG combined with probiotics than in the group using KRG or probiotics alone. ATP, KRG + ATP, and KRG + BYO groups showed reduced TEWL increase (ΔTEWL) at 48 h (p < 0.005). KRG + ATP showed a preventive effect on the increase of serum IgE level (p = 0.009). In immunohistopathologic analysis, KRG, ATP, BYO, KRG + ATP, and KRG + BYO groups showed significantly reduced expression levels of IFN-γ at 1 h, 6 h, and 48 h (all p < 0.05). KRG, ATP, BYO, and KRG + BYO groups showed reduced expression levels of IL-4 compared to the AD control group at 6 h and 24 h. KRG, ATP, BYO, KRG + ATP, and KRG + BYP groups showed significantly lower expression levels of TSLP than the AD control group at 1 h and 24 h. ConclusionKRG can suppress increases of allergic and inflammatory cytokines and increase of TEWL. A combination of KRG and probiotics might have better effects than KRG or probiotics alone for preventing an AD flare-up.

Restorative effects of Rg3-enriched Korean Red Ginseng and Persicaria tinctoria extract on oxazolone-induced ulcerative colitis in mice

BackgroundUlcerative colitis (UC) is the large intestine disease that results in chronic inflammation and ulcers in the colon. Rg3-enriched Korean Red Ginseng extract (Rg3-RGE) is known for its pharmacological activities. Persicaria tinctoria (PT) is also used in the treatment of various inflammatory diseases. The aim of this study is to investigate the attenuating effects of Rg3-RGE with PT on oxazolone (OXA)-induced UC in mice. MethodsA total of six groups of mice including control group, OXA (as model group, 1.5%) group, sulfasalazine (75 mg/kg) group, Rg3-RGE (20 mg/kg) group, PT (300 mg/kg) group, and Rg3-RGE (10 mg/kg) with PT (150 mg/kg) group. Data on the colon length, body weight, disease activity index (DAI), histological changes, nitric oxide (NO) assay, Real-time PCR of inflammatory factors, ELISA of inflammatory factors, Western blot, and flow cytometry analysis were obtained. ResultsOverall, the combination treatment of Rg3-RGE and PT significantly improved the colon length and body weight and decreased the DAI in mice compared with the treatment with OXA. Additionally, the histological injury was also reduced by the combination treatment. Moreover, the NO production level and inflammatory mediators and cytokines were significantly downregulated in the Rg3-RGE with the PT group compared with the model group. Also, NLR family pyrin domain containing 3 (NLRP3) inflammasome and nuclear factor kappa B (NF-κB) were suppressed in the combination treatment group compared with the OXA group. Furthermore, the number of immune cell subtypes of CD4+ T-helper cells, CD19+ B-cells, and CD4+ and CD25+ regulatory T-cells (Tregs) was improved in the Rg3-RGE with the PT group compared with the OXA group. ConclusionOverall, the mixture of Rg3-RGE and PT is an effective therapeutic treatment for UC.

Improved Hygroscopicity and Bioavailability of Solid Dispersion of Red Ginseng Extract with Silicon Dioxide.

This study aims to develop a powder formulation for the Korean red ginseng extract (RGE) and to evaluate its in vitro and in vivo formulation characteristics. The solid dispersion of RGE was prepared with hydrophilic carriers using a freeze-drying method. After conducting the water sorption–desorption isothermogram (relative humidity between 30 and 70% RH), differential scanning calorimetry thermal behavior, dissolution test, and intestinal permeation study, a solid dispersion formulation of RGE and silicon dioxide (RGE-SiO2) was selected. RGE-SiO2 formulation increased intestinal permeability of ginsenoside Rb1 (GRb1), GRb2, GRc, and GRd by 1.6-fold in rat jejunal segments as measured by the Ussing chamber system. A 1.6- to 1.8-fold increase in plasma exposure of GRb1, GRb2, GRc, and GRd in rats was observed following oral administration of RGE-SiO2 (375 mg/kg as RGE). No significant difference was observed in the time to reach maximum concentration (Tmax) and half-life in comparison to those in RGE administered rats (375 mg/kg). In conclusion, formulating solid dispersion of RGE with amorphous SiO2, the powder formulation of RGE was successfully formulated with improved hygroscopicity, increased intestinal permeability, and enhanced oral bioavailability and is therefore suitable for processing solid formulations of RGE product.

Characterization of hyperglycemia due to sub-chronic administration of red ginseng extract via comparative global proteomic analysis

Ginseng (Panax ginseng Meyer) is commonly used as an herbal remedy worldwide. Few studies have explored the possible physiological changes in the liver although patients often self-medicate with ginseng preparations, which may lead to exceeding the recommended dose for long-term administration. Here, we analyzed changes in the hepatic proteins of mouse livers using quantitative proteomics after sub-chronic administration of Korean red ginseng (KRG) extract (control group and 0.5, 1.0, and 2.0 g/kg KRG) using tandem mass tag (TMT) 6‐plex technology. The 1.0 and 2.0 g/kg KRG groups exhibited signs of liver injury, including increased levels of aspartate transaminase (AST) and alanine aminotransferase (ALT) in the serum. Furthermore, serum glucose levels were significantly higher following KRG administration compared with the control group. Based on the upregulated proteins found in the proteomic analysis, we found that increased cystathionine beta-synthase (CBS) and cystathionine gamma-lyase (CSE) levels promoted greater hydrogen sulfide (H2S) synthesis in the liver. This investigation provides novel evidence that sub-chronic administration of KRG can elevate H2S production by increasing protein expression of CBS and CSE in the liver.

Inhibitory Effect of Korean Red Ginseng Extract on Interleukin-8 Expression in Helicobacter pylori-Infected Gastric Epithelial Cells

ObjectivesInfection of Helicobacter pylori (H. pylori), a gram-negative bacterium, leads to various gastric diseases, such as gastritis, peptic ulcer and gastric cancer. H. pylori increases cytokine release and activates inflammatory mediators in gastric mucosa. Particularly, H. pylori upregulates the inflammatory chemokine interleukin-8 (IL-8), which are activated by oxidative stress. IL-8 can cause severe inflammation of the stomach and gastric cancer. Korean red ginseng is the steamed root of 6-year-old Korean ginseng (Panax ginseng Meyer). Ginsenosides, triterpene glycosides, are the active components of Korean red ginseng. Ginsenosides have antioxidant, anti-inflammatory, and antitumor activities. The present study is aimed at determining whether Korean red ginseng extract inhibits H. pylori-induced IL-8 expression in gastric epithelial cells. MethodsThe human gastric epithelial cell line AGS was used. Gastric epithelial AGS cells were treated with Korean red ginseng extract, and infected with H. pylori (NCTC 11,637). Reactive oxygen species (ROS) levels were determined using dichlorofluorescein fluorescence. NADPH oxidase activity was measured using lucigenin chemiluminescence. IL-8 mRNA expression was measured by using real-time PCR. NADPH oxidase subunits were determined in cytosolic extract and membrane extract by using Western blotting. ResultsH. pylori increased NADPH oxidase activity, ROS levels, and upregulated IL-8 expression in gastric epithelial cells. Korean red ginseng extract inhibited IL-8 expression by suppressing NADPH oxidase activity and reducing ROS levels in gastric epithelial cells. H. pylori induced translocation of NADPH oxidase cytosolic subunits to membrane, which is a marker of NADPH oxidase activation, in AGS cells. Korean red ginseng extract inhibited translocation of cytosolic subunits of NADPH oxidase to membrane in AGS cells. ConclusionsKorean red ginseng may be beneficial for preventing H. pylori-associated gastric inflammation by inhibiting oxidative stress and IL-8 expression. Funding SourcesThis study was supported by a Brain Korea 21 FOUR Project, Yonsei University, Seoul, Republic of Korea.

Korean Red Ginseng inhibits methamphetamine addictive behaviors by regulating dopaminergic and NMDAergic system in rodents

BackgroundMethamphetamine (METH) is the most widely used psychostimulant and has been known to exhibit reinforcing effects even after long abstinence. We showed the inhibitory effect of Korean Red Ginseng extract (RGE) on METH-induced addictive behaviors in animal models mimicking the human drug-use pattern. MethodsWe first investigated the effect of RGE on the acquisition of METH-induced dependence using self-administration and conditioned place preference (CPP) tests. Additionally, further experiments such as METH-induced motivational behavior and seeking behavior were conducted. To study the underlying mechanism, dopamine receptor, dopamine transporter, and N-methyl-D-aspartate receptor were assessed through Western blot analysis. ResultsTreatment with RGE significantly reduced METH-induced self-administration on a fixed-ratio 1 schedule of reinforcement. It could be also decreased a progressive ratio schedule, and inhibited METH-primed reinstatement. In CPP, RGE significantly prevented the development of METH-induced CPP. Moreover, RGE not only shortened the withdrawal period clearly, but also prevented the reinstatement of CPP. RGE treatment also reversed METH-induced overexpression of dopamine transporter, dopamine receptor D1, and NMDA receptor in the nucleus accumbens. ConclusionOur findings reflect that RGE has therapeutic potential to suppress METH-induced addictive behaviors by regulating dopaminergic and NMDAergic system.

Korean red ginseng induces extrinsic and intrinsic apoptotic pathways in MCF-7 breast cancer cells and MCF-10A non-malignant breast cells.

Among non-hormonal treatments, herbal products are frequently used by women. Korean red ginseng (KRG) is one of the popular herbal medicines. KRG could be one option for relieving menopausal symptoms. However, there are still concerns about the safety for long-term use. In order to be used for alleviating menopausal symptoms, the safety of KRG on breast must be ensured. The purpose of this study was to investigate the effects of KRG on breast cells. MCF-7 and MCF-10A cells were treated with different concentrations of KRG extracts for 48 h. Cell viability was evaluated by MTT assay, and apoptosis by flow cytometry. The expression of apoptosis-related proteins was determined by western blot analysis and estrogen receptor (ER) affinity by ER binding assay. KRG extract inhibited growth and induced apoptosis of both MCF-7 and MCF-10A cells in dose-dependent manner. KRG extract increased the expression of pro-apoptotic proteins BAX, BAK, and BAD and decreased the expression of anti-apoptotic proteins Bcl-2 and Bcl-XL in both cells. The expressions of Fas and FasL were increased in lower doses, but decreased in higher doses in both cells. Activities of caspase-3, -8 and -9 increased in MCF-10A, while caspase-8 and -9 showed increase in MCF-7. Competition of KRG to E2 was significant in MCF-7 as KRG dose increased, whereas ER binding was hardly shown in MCF-10. KRG induced apoptosis via extrinsic and intrinsic pathway in MCF-7 breast cancer cells and MCF-10A non-malignant cells. KRG may be safely used with regard to breast cancer risk in postmenopausal women to reduce the vasomotor symptoms.

The effects of Korean Red Ginseng-derived components on oligodendrocyte lineage cells: Distinct facilitatory roles of the non-saponin and saponin fractions, and Rb1, in proliferation, differentiation and myelination

BackgroundAbnormalities of myelin, which increases the efficiency of action potential conduction, are found in neurological disorders. Korean Red Ginseng (KRG) demonstrates therapeutic efficacy against some of these conditions, however effects on oligodendrocyte (OL)s are not well known. Here, we examined the effects of KRG-derived components on development and protection of OL-lineage cells. MethodsPrimary OL precursor cell (OPC) cultures were prepared from neonatal mouse cortex. The protective efficacies of the KRG components were examined against inhibitors of mitochondrial respiratory chain activity. For in vivo function of Rb1 on myelination, after 10 days of oral gavage into adult male mice, forebrains were collected. OPC proliferation were assessed by BrdU incorporation, and differentiation and myelination were examined by qPCR, western blot and immunocytochemistry. ResultsThe non-saponin promoted OPC proliferation, while the saponin promoted differentiation. Both processes were mediated by AKT and extracellular regulated kinase (ERK) signaling. KRG extract, the saponin and non-saponin protected OPCs against oxidative stress, and both KRG extract and the saponin significantly increased the expression of the antioxidant enzyme. Among 11 major ginsenosides tested, Rb1 significantly increased OL membrane size in vitro. Moreover, Rb1 significantly increased myelin formation in adult mouse brain. ConclusionAll KRG components prevented OPC deaths under oxidative stress. While non-saponin promoted proliferation, saponin fraction increased differentiation and OL membrane size. Furthermore, among all the tested ginsenosides, Rb1 showed the biggest increase in the membrane size and significantly enhanced myelination in vivo. These results imply therapeutic potentials of KRG and Rb1 for myelin-related disorders.

Ovarian cysts disappear after 14-day oral regimen of Korean red ginseng extract in letrozole-induced polycystic ovarian syndrome.

ObjectiveHormonal and inflammatory mechanisms are involved in the pathogenesis of polycystic ovarian syndrome (PCOS), which is a prevalent metabolic disorder among women of reproductive age. We aimed to evaluate the comparative efficiency of short-term oral administration of Korean red ginseng extract (KRGE) and the standard treatment on PCOS by focusing on the histopathological parameters and serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, and nuclear factor kappa B (NF-κB).MethodsA PCOS rat model was established by oral gavage of letrozole (1 mg/kg) for 21 days. The serum levels of LH, FSH, testosterone, and NF-κB were measured, and the morphological features and differences of the ovaries were examined in each group using a light microscope before and after 14 days of treatment with oral regimens—KRGE, oral contraceptives (OCPs), KRGE+OCPs, and carboxymethyl cellulose (CMC).ResultsOCPs alone could not normalize the mean ovarian weights of PCOS rats despite the 14-day oral regimen, but they were more effective in reducing the number and size of cysts compared to others. KRGE alone and in combination with OCPs was effective in normalizing abnormal ovarian weights, decreasing LH serum levels, and dissipating the ovarian cysts in PCOS rats. However, when combined with the standard regimen, KRGE showed additional therapeutic effects by efficiently reducing serum testosterone and NF-κB levels.ConclusionOur necropsy and histopathological evidence suggests the efficacy of KRGE as a novel integrative medicine against abnormal multiple follicular cysts. However, antiandrogenic and anti-inflammatory effects were only seen in animals that were administered a combination of KRGE and the standard regimen.

Alleviation of Ulcerative Colitis Potentially through th1/th2 Cytokine Balance by a Mixture of Rg3-enriched Korean Red Ginseng Extract and Persicaria tinctoria.

Ginseng is a vastly used herbal supplement in Southeast Asian countries. Red ginseng extract enriched with Rg3 (Rg3-RGE) is a formula that has been extensively studied owing to its various biological properties. Persicaria tinctoria (PT), belonging to the Polygonaceae family, has also been reported for its anti-inflammatory properties. Ulcerative colitis (UC) is inflammation of the large intestine, particularly in the colon. This disease is increasingly common and has high probability of relapse. We investigated, separately and in combination, the effects of Rg3-RGE and PT using murine exemplary of UC induced by DSS (Dextran Sulfate Sodium). For in vitro and in vivo experiments, nitric oxide assay, qRT-Polymerase Chain Reaction (PCR), Western blot, ulcerative colitis introduced by DSS, Enzyme Linked Immunosorbent Assay (ELISA), and flow cytometry analysis were performed. The results obtained demonstrate that treatment with Rg3-RGE + PT showed synergism to suppress inflammation (in vitro) in RAW 264.7 cells via mitogen-activated protein kinase and nuclear factor κB pathways. Moreover, in C57BL/6 mice, this mixture exhibits strong anti-inflammatory effects in restoring colon length, histopathological damage, pro-inflammatory mediators, and cytokines amount, and decreasing levels of NLRP3 inflammasome (in vivo). Our results recommend that this mixture can be used for the prevention of UC as a prophylactic/therapeutic supplement.

Effect of Korean Red Ginseng on Early Vestibular Function Restoration after Unilateral Labyrinthectomy

Objectives: Vertigo is a common condition. Definitive treatment is to induce vestibular compensation. Currently, no medications have been discovered that enhance vestibular functional restoration. The current study was conducted to evaluate the ability of ordinary Korean red ginseng (KRG) to induce vestibular compensation. Methods: Twelve Sprague-Dawley rats were divided into two groups. Five rats (KRG group) were fed KRG extract (100 mg/kg) for 2 weeks before undergoing unilateral labyrinthectomy (ULx). The remaining seven rats (control group) were untreated before ULx. After surgery, all animals were housed in the same environment without being fed additional extract. To evaluate vestibular function, gain of the horizontal nystagmus to 0.2 Hz with a peak velocity of 100°/second sinusoidal rotation was compared and analyzed before ULx as well as 3 and 7 days after surgery. Results: Before the operation, gain of the control and KRG group were 0.81±0.05 and 0.88±0.08, respectively, with 0.2-Hz stimulation. This value decreased to 0.43±0.08 and 0.53±0.08, respectively on 3 days after operation (p=0.047), and it was 0.40±0.06 and 0.68±0.11, respectively on 7 days after surgery. The difference of gain between the two groups was statistically significant at each 3 and 7 days (p＜0.05). By confirming c-Fos protein expression in medial vestibular nuclei, the functional effect of KRG causing vestibular modulation was confirmed. Conclusions: Rats treated with KRG showed more rapid and complete recovery after acute vestibular loss compared to untreated animals. Therefore, KRG could be one of candidate for the useful medication of vestibular diseases. Keywords: Compensation; Ginseng; Vertigo; Vestibule 중심 단어: 보상, 홍삼, 어지럼, ì „ì •

Rg3-enriched Korean Red Ginseng extract inhibits blood-brain barrier disruption in an animal model of multiple sclerosis by modulating expression of NADPH oxidase 2 and 4

BackgroundMultiple sclerosis (MS) and its animal model, the experimental autoimmune encephalomyelitis (EAE), are primarily characterized as dysfunction of the blood-brain barrier (BBB). Ginsenoside-Rg3-enriched Korean Red Ginseng extract (Rg3-KRGE) is known to exert neuroprotective, anti-inflammatory, and anti-oxidative effects on neurological disorders. However, effects of Rg3-KRGE in EAE remain unclear. MethodsHere, we investigated whether Rg3-KRGE may improve the symptoms and pathological features of myelin oligodendroglial glycoprotein (MOG)35-55 peptide – induced chronic EAE mice through improving the integrity of the BBB. ResultsRg3-KRGE decreased EAE score and spinal demyelination. Rg3-KRGE inhibited Evan's blue dye leakage in spinal cord, suppressed increases of adhesion molecule platelet endothelial cell adhesion molecule-1, extracellular matrix proteins fibronection, and matrix metallopeptidase-9, and prevented decreases of tight junction proteins zonula occludens-1, claudin-3, and claudin-5 in spinal cord following EAE induction. Rg3-KRGE repressed increases of proinflammatory transcripts cyclooxygenase-2, inducible nitric oxide synthase, interleukin (IL)-1 beta, IL-6, and tumor necrosis factor-alpha, but enhanced expression levels of anti-inflammatory transcripts arginase-1 and IL-10 in the spinal cord following EAE induction. Rg3-KRGE inhibited the expression of oxidative stress markers (MitoSOX and 4-hydroxynonenal), the enhancement of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2) and NOX4, and NADPH activity in the spinal cord of chronic EAE mice. Furthermore, apocynin, a NOX inhibitor, mimicked beneficial effects of Rg3-KRGE in chronic EAE mice. ConclusionOur findings suggest that Rg3-KRGE might alleviate behavioral symptoms and pathological features of MS by improving BBB integrity through modulation of NOX2/4 expression.

Characterization of red ginseng-drug interaction by CYP3A activity increased in high dose administration in mice.

Ginseng (Panax ginseng Meyer) is a popular traditional herbal medicine used worldwide. Patients often take ginseng preparations with other medicines where the ginseng dose could exceed the recommended dose during long-term administration. However, ginseng-drug interactions at high doses of ginseng are poorly understood. This study showed the possibility of herb-drug interactions between the Korean red ginseng (KRG) extract and cytochrome P450 (CYP) substrates in higher administration in mice. The CYP activities were determined in vivo after oral administration of KRG extract doses of 0.5, 1.0, and 2.0 g/kg for 2 or 4 weeks by monitoring the concentration of five CYP substrates/metabolites in the blood. The area under the curve for OH-midazolam/midazolam catalysed by CYP3A was increased significantly by the administration of 2.0 g/kg KRG extract for 2 and 4 weeks. CYP3A-catalysed midazolam 1'-hydroxylation also increased significantly in a dose- and time-dependent manner in the S9 fraction of mouse liver which was not related to induction by transcription. Whereas CYP2D-catalysed dextromethorphan O-deethylation decreased in a dose- and time-dependent manner in vivo. In conclusion, interactions were observed between KRG extract and CYP2D and CYP3A substrates at subchronic-high doses of KRG administration in mice.

Red Ginseng Inhibits Tau Aggregation and Promotes Tau Dissociation In Vitro.

Tau, a microtubule-associated protein expressed in mature neurons, interacts with tubulin to promote the assembly and stabilization of microtubules. However, abnormally hyperphosphorylated tau dissociates from microtubules and self-aggregates. Tau aggregates, including paired helical filaments and neurofibrillary tangles, promote neuronal dysfunction and death and are the defining neuropathological feature of tauopathies. Therefore, suppressing tau aggregation or stimulating the dissociation of tau aggregates has been proposed as an effective strategy for treating neurodegenerative diseases associated with tau pathology such as Alzheimer's disease (AD) and frontotemporal dementia. Interestingly, ginsenosides extracted from Panax ginseng reduced the hippocampal and cortical expression of phosphorylated tau in a rat model of AD. However, no studies have been conducted into the effect of red ginseng (RG) and its components on tau pathology. Here, we evaluated the effect of Korean red ginseng extract (KRGE) and its components on the aggregation and disassociation of tau. Using the thioflavin T assay, we monitored the change in fluorescence produced by the aggregation or disassociation of tau K18, an aggregation-prone fragment of tau441 containing the microtubule-binding domain. Our analysis revealed that KRGE not only inhibited tau aggregation but also promoted the dissociation of tau aggregates. In addition, the KRGE fractions, such as saponin, nonsaponin, and nonsaponin fraction with rich polysaccharide, also inhibited tau aggregation and promoted the dissociation of tau aggregates. Our observations suggest that RG could be a potential therapeutic agent for the treatment of neurodegenerative diseases associated with tauopathy.