Rg3-enriched Korean Red Ginseng Research Articles

Rg3-enriched Korean red ginseng alleviates chloroquine-induced itch and dry skin pruritus in an MrgprA3-dependent manner in mice

BackgroundPrevious studies have found that Korean red ginseng extract (KRG) has antipruritic effects, which can be attributed to the presence of Rg3, one of the most potent ginsenosides. Therefore, Rg3-enriched KRG extract (Rg3EKRG) is anticipated to have enhanced antipruritic effects. The present study was conducted to examine the effects of Rg3EKRG in acute chloroquine (CQ)-induced and chronic dry skin pruritus. MethodsCalcium imaging technique was used in HE293T cells expressing MrgprA3 and TRPA1 (“MrgprA3/TRPA1”) and in primary cultures of mouse dorsal root ganglia (DRG) neurons. Mouse scratching behavior tests were performed on dry skin models. To verify the altered expression of itch-related genes, real-time RNA sequencing analysis and PCR were performed on DRG sections obtained from dry skin models. ResultsRg3EKRG suppressed CQ-induced intracellular calcium changes to a greater degree than KRG. Rg3EKRG dose-dependently inhibited CQ-induced responses in MrgprA3/TRPA1 cells. Rg3EKRG likely targeted MrgprA3 rather than TRPA1 to exert its inhibitory effect. Further, Rg3EKRG strongly inhibited the scratching behavior in mice induced by acute CQ injection. Importantly, DRG neurons obtained from dry skin mice models showed increased mRNA levels of MrgprA3, and treatment with Rg3EKRG alleviated chronic dry skin conditions and suppressed spontaneous scratching behaviors. ConclusionThe results of the present study imply that Rg3EKRG has a stronger antipruritic effect than KRG, inhibiting both acute CQ-induced and chronic dry skin pruritus in an MrgprA3-dependent manner. Therefore, Rg3EKRG is a potential antipruritic agent that can suppress acute and chronic itching at the peripheral sensory neuronal level.

Ginsenoside Rg3-enriched Korean Red Ginseng extract attenuates Non-Alcoholic Fatty Liver Disease by way of suppressed VCAM-1 expression in liver sinusoidal endothelium

BackgroundThe incidence and clinical importance of nonalcoholic fatty liver disease (NAFLD) has emerged. However, effective therapeutic strategies for NAFLD have yet to be found. Panax ginseng (P. ginseng) is a traditional herb in Eastern Asia with therapeutic effects in many chronic disorders. However, the precise effects of ginseng extract on NAFLD are currently unknown. In present study, the therapeutic effects of Rg3-enriched red ginseng extract (Rg3-RGE) on the progression of NAFLD were explored. MethodsTwelve-week-old C57BL/6 male mice were fed a chow or western diet supplemented with high sugar water solution with or without Rg3-RGE. Histopathology, immunohistochemistry, immunofluorescence, serum biochemistry, western blot analysis, and quantitative RT-PCR were used for in vivo experiment. Conditionally immortalized human glomerular endothelial cell (CiGEnC) and primary liver sinusoidal endothelial cells (LSECs) were used for in vitro experiments. ResultsEight weeks of Rg3-RGE treatment significantly attenuated the inflammatory lesions of NAFLD. Furthermore, Rg3-RGE inhibited the inflammatory infiltrate in liver parenchyma and the expression of adhesive molecules to LSECs. Moreover, the Rg3-RGE exhibited similar patterns on the in vitro assays. ConclusionThe results demonstrate that Rg3-RGE treatment ameliorates NAFLD progression by inhibiting chemotaxis activities in LSECs.

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.

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.

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.

Effect of coadministration of enriched Korean Red Ginseng (Panax ginseng) and American ginseng (Panax quinquefolius L) on cardiometabolic outcomes in type-2 diabetes: A randomized controlled trial

BackgroundDiabetes mellitus and hypertension often occur together, amplifying cardiovascular disease (CVD) risk and emphasizing the need for a multitargeted treatment approach. American ginseng (AG) and Korean Red Ginseng (KRG) species could improve glycemic control via complementary mechanisms. Additionally, a KRG-inherent component, ginsenoside Rg3, may moderate blood pressure (BP). Our objective was to investigate the therapeutic potential of coadministration of Rg3-enriched Korean Red Ginseng (Rg3-KRG) and AG, added to standard of care therapy, in the management of hypertension and cardiometabolic risk factors in type-2 diabetes. MethodsWithin a randomized controlled, parallel design of 80 participants with type-2 diabetes (HbA1c: 6.5–8%) and hypertension (systolic BP: 140–160 mmHg or treated), supplementation with either 2.25 g/day of combined Rg3-KRG + AG or wheat-bran control was assessed over a 12-wk intervention period. The primary endpoint was ambulatory 24-h systolic BP. Additional endpoints included further hemodynamic assessment, glycemic control, plasma lipids and safety monitoring. ResultsCombined ginseng intervention generated a mean ± SE decrease in primary endpoint of 24-h systolic BP (−3.98 ± 2.0 mmHg, p = 0.04). Additionally, there was a greater reduction in HbA1c (−0.35 ± 0.1% [–3.8 ± 1.1 mmol/mol], p = 0.02), and change in blood lipids: total cholesterol (−0.50 ± 0.2 mmol/l, p = 0.01), non-HDL-C (−0.54 ± 0.2 mmol/l, p = 0.01), triglycerides (−0.40 ± 0.2 mmol/l, p = 0.02) and LDL-C (−0.35 ± 0.2 mmol/l, p = 0.06) at 12 wks, relative to control. No adverse safety outcomes were observed. ConclusionCoadministration of Rg3-KRG + AG is an effective addon for improving BP along with attaining favorable cardiometabolic outcomes in individuals with type 2 diabetes. Ginseng derivatives may offer clinical utility when included in the polypharmacy and lifestyle treatment of diabetes. Clinical trial registrationClinicaltrials.gov identifier, NCT01578837;

Anti-Inflammatory Activity of Rg3-Enriched Korean Red Ginseng Extract in Murine Model of Sepsis.

Ginseng has therapeutic effects on various bodily disorders ranging from minor inflammation to major cardiovascular diseases. In our study, we explored the anti-inflammatory effects of Rg3-enriched red ginseng extract (Rg3-RGE), a ginsenoside belonging to the panaxadiol group. We employed nitric oxide assay (NO) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), western blot, and hematoxylin and eosin staining (H&E) to elucidate the anti-inflammatory activity of Rg3-RGE. Rg3-RGE potently suppressed NO production in the murine macrophage cell line, RAW 264.7 cells, without any cytotoxicity across dosages. Additionally, it inhibited the mRNA expression of proinflammatory mediators and cytokines like iNOS, COX-2, IL-1β, IL-6, and TNF-α. Moreover it also inhibited the levels of malondialdehyde levels in serum of septic shock mice. Immunoblot analysis showed that Rg3-RGE induced anti-inflammatory signal transduction via the NF-κB and MAPK pathways. A remarkable attenuation of inflammation by oral treatment with Rg3-RGE in mice was observed in the survival study. The in vivo study using a septic shock mouse model also showed similar results as the in vitro study. Our findings suggest that Rg3-RGE can potentially be a potent anti-inflammatory agent that likely mediates its anti-inflammatory effects via the NF-κB and MAPK pathways.

Efficacy and Safety of Oral Supplementation of Combined Rg3-Enriched Korean Red Ginseng (Panax Ginseng C.A. Meyer) and American Ginseng (Panax Quinquefolius) in the Management of Cardiovascular Risk F

Background and Objective: Diabetes mellitus is often concomitant with hypertension, which manifests a 3-fold greater risk for cardiovascular disease (CVD). Recent studies suggest the ability of American (AG) and Korean red ginseng (KRG) species to improve diabetes control via complementary mechanisms. Additionally, a KRG-inherent component, ginsenoside Rg3, may moderate blood pressure (BP). Our objective, therefore, is to investigate the therapeutic potential of co-administration of Rg3-enriched Korean Red Ginseng (Rg3-KRG) and AG, added to conventional treatment, in the management of hypertension and glycemic control in type 2 diabetes.

Neuroprotective effects of Rg3-enriched Korean Red Ginseng on alcohol-induced apoptosis in PC12 Cells

Neuroprotective effects of Rg3-enriched Korean Red Ginseng on alcohol-induced apoptosis in PC12 Cells

Rg3-enriched Korean Red Ginseng enhances blood pressure stability in spontaneously hypertensive rats

BackgroundKorean Red Ginseng (Panax ginseng) has been shown to exert antihypertensive effects. In particular, ginsenoside Rg3 is thought to be a potent modulator of vascular function. The present study was performed to examine the antihypertensive efficacy of Korean Red Ginseng (KRG) extract and Rg3-enriched KRG (REKRG) extract. MethodsSpontaneously hypertensive rats (SHRs) and Wistar–Kyoto rats (WKYs) were divided into six groups (WKY control, WKY-KRG, WKY-REKRG, SHR control, SHR-KRG, and SHR-REKRG), and systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured at the carotid artery, followed by injection of 3mg/kg KRG or 3mg/kg REKRG. ResultsREKRG treatment significantly decreased SBP and DBP 3hours post-treatment in the SHR group compared with SHR control group. However, SBP and DBP were not significantly different in KRG-treated SHRs compared with control SHRs. REKRG treatment did not significantly alter SBP or DBP 3hours post-treatment in the WKY group compared with WKY control group. Similarly, there were no differences in SBP or DBP with KRG treatment in the WKY group and WKY control group. Both KRG and REKRG increased endothelial nitric oxide synthase phosphorylation levels in the aorta, and the increases in endothelial nitric oxide synthase phosphorylation levels by REKRG treatment were higher than those with KRG treatment. Similarly, nitric oxide production in plasma from WKYs and SHRs was also increased by both KRG and REKRG. ConclusionThese results suggest that REKRG has a more beneficial effect on blood pressure control than KRG in SHRs.

Rg3-enriched Korean Red Ginseng improves vascular function in spontaneously hypertensive rats

BackgroundPanax ginseng has distinct and impressive health benefits, such as improved blood pressure and immune system functioning. Rg3-enriched Korean Red Ginseng (REKRG) isolated from Korean Red Ginseng contains a high percentage of Rg3. MethodsIn this study, we examined the effects of REKRG on endothelial cell nitric oxide synthase (eNOS) activation and adhesion molecules in endothelial cells and vascular function in rats. ResultsREKRG dose-dependently increased eNOS phosphorylation and nitric oxide (NO) production in endothelial cells. In addition, REKRG markedly inhibited the tumor necrosis factor-α (TNF-α)-mediated induction of intercellular adhesion molecule (ICAM)-1 and cyclooxygenase (COX)-2 expressions in endothelial cells. REKRG improved endothelium-dependent vasorelaxation in the Wistar-Kyoto (WKY) rat and spontaneously hypertensive rats (SHRs) compared with controls. Furthermore, REKRG treatment for 6 weeks increased serum NO levels and reduced the mean aortic intima-media thickness compared with controls. ConclusionTaken together, these results suggest that REKRG increased vascular function and improved immune system functioning. Therefore, REKRG is a very useful food for preventing or improving various cardiovascular diseases.

Effect of Rg3-enriched Korean red ginseng (Panax ginseng) on arterial stiffness and blood pressure in healthy individuals: a randomized controlled trial

Ginsenoside Rg3, present in steamed ginseng (Panax Ginseng C.A. Meyer), is thought to be a potent modulator of vascular function. Our objective was to clinically evaluate acute effects of ginsenoside Rg3–enriched Korean red ginseng (Rg3-KRG) on measures of arterial stiffness and peripheral and central blood pressure (BP) parameters in healthy volunteers. Using a double-blind, randomized, crossover design, 23 individuals (9 males:14 females; age, 25 ± 2 years; body mass index, 22 ± 0.6 kg/m2; systolic BP/diastolic BP, 113 ± 3/70 ± 2 mm Hg) were administered 400-mg Rg3-KRG extract or 400-mg wheat bran control on two separate visits with a 7-day washout period. Aortic augmentation index and central BP were measured using applanation tonometry by radial pulse wave analysis, and peripheral BP was evaluated oscillometrically. Measurements were taken at baseline and at 1, 2, and 3 hours after intervention. Compared with control, there were significant reductions in augmentation index (−4.3 ± 8.9%, P = .03), central (−4.8 ± 6.8 mm Hg, P = .01) and brachial mean arterial pressure (−4.4 ± 6.6 mm Hg, P = .01), central systolic (−5.0 ± 7.9 mm Hg, P = .01) and diastolic BP (−3.9 ± 6.6 mm Hg, P = .01), and brachial systolic (−4.4 ± 10.0 mm Hg, P = .048) and diastolic BP (−3.6 ± 6.4 mm Hg, P = .01) at 3 hours after intervention compared with control. This study is the first to demonstrate Rg3-KRG extract acutely lowers central and peripheral arterial pressures in healthy adults. Further clinical evaluation is desired to quantify efficacy in higher risk individuals and in long-term settings.

Efficacy of Rg3‐Enriched Korean Red Ginseng (Steamed Panax Ginseng C.A. Meyer) Extract on Arterial Stiffness and Blood Pressure in Healthy Volunteers

ObjectiveTo evaluate the acute effects of 10% Rg3‐enriched Korean Red Ginseng (KRG) on arterial stiffness and peripheral and central systolic (SBP) and diastolic blood pressure (DBP) in healthy adult volunteers.MethodsUsing a double‐blind, randomized, crossover design, 17 individuals (6M:11F; age 25±3; BMI 22±0.8; SBP 111±4, DBP 69±2mmHg) were administered 400mg 10% Rg3‐enriched KRG extract or 400mg corn starch placebo. Aortic augmentation index (AIx) and central BP were measured using applanation tonometry by radial pulse wave analysis and peripheral BP was evaluated oscillometrically. Measurements were taken at baseline and 1,2 and 3hrs post‐treatment.ResultsCompared to placebo, there was a significant reduction in peripheral mean arterial pressure (p=0.046), peripheral DBP (p=0.015), and central SBP (p=0.02) 3hrs post‐treatment. Central DBP and central mean arterial pressure were significantly lower at 1hr (p=0.035, 0.041) and 3hrs (p=0.025, 0.009) post‐treatment. AIx and peripheral SBP also decreased post‐treatment, but this only approached significance (p=0.053).ConclusionsThis study is the first to demonstrate that an Rg3 KRG extract acutely lowers central and peripheral mean arterial pressures in healthy young adults. Further clinical testing is still required as this extract may be more potent in higher‐risk subjects.Sponsor: Heart and Stroke Foundation of Canada