Administration Of Red Ginseng Extract Research Articles

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.

Concomitant Administration of Red Ginseng Extract with Lactic Acid Bacteria Increases the Plasma Concentration of Deglycosylated Ginsenosides in Healthy Human Subjects.

With the increased frequency of red ginseng extract (RGE) and lactic acid bacteria (LAB) co-administration, we aimed to investigate the interactions between RGE and LAB with regard to in vitro and in vivo deglycosylation metabolism and the pharmacokinetics of ginsenosides. As a proof-of-concept study, five healthy humans were administered RGE (104.1 mg of total ginsenosides/day) with or without co-administration of LAB (2 g, 1 billion CFU/day) for 2 weeks, and the plasma concentrations of ginsenosides in human plasma were monitored. The plasma exposure to compound K (CK), ginsenoside Rh2 (GRh2), protopanaxadiol (PPD), and protopanaxatriol (PPT) in the concomitant administration RGE and LAB groups increased by 2.7-, 2.1-, 1.6-, and 3.5-fold, respectively, compared to those in the RGE administration group, without a significant change in Tmax. The plasma concentrations of GRb1, GRb2, and GRc remained unchanged, whereas the AUC values of GRd and GRg3 significantly decreased in the concomitant administration RGE and LAB groups. To understand the underlying mechanism, the in vitro metabolic activity of ginsenosides was measured during the fermentation of RGE or individual ginsenosides in the presence of LAB for 1 week. Consistent with the in vivo results, co-incubation with RGE and LAB significantly increased the formation rate of GRh2, CK, PPD, and PPT. These results may be attributed to the facilitated deglycosylation of GRd and GRg3 and the increased production of GRh2, CK, PPD, and PPT by the co-administration of LAB and RGE. In conclusion, LAB supplementation increased the plasma concentrations of deglycosylated ginsenosides, such as GRh2, CK, PPD, and PPT, through facilitated deglycosylation metabolism of ginsenosides in the intestine.

Hair Growth-Promoting Mechanisms of Red Ginseng Extract through Stimulating Dermal Papilla Cell Proliferation and Enhancing Skin Health.

This study aimed to investigate the underlying mechanisms of red ginseng extract (RGE) on regulating hair growth and hair follicle development. Results from in vitro studies showed that RGE treatment simultaneously enhanced viability and inhibited apoptosis in human hair dermal papilla cells. Moreover, RGE administration promoted telogen-to-anagen transition, prolonged anagen in hair follicular cycling, and increased the size of hair follicles and skin thickness in a C57BL/6 mouse model. Furthermore, RGE treatment significantly upregulated the expression of β-catenin, phospho-glycogen synthase kinase 3β, cyclin D1, cyclin E, and Bcl-2, phospho-extracellular signal-regulated protein kinase, and phospho-Akt, which are associated with promoting hair growth. In addition, RGE enhanced skin health by activation of antiox-idant defense systems. Our data demonstrates that hair regenerative mechanisms of RGE may be mediated by stimulating dermal papilla cell proliferation and enhancing skin functions.

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.

Herb-Drug Interaction of Red Ginseng Extract and Ginsenoside Rc with Valsartan in Rats.

The purpose of this study was to investigate the herb–drug interactions involving red ginseng extract (RGE) or ginsenoside Rc with valsartan, a substrate for organic anion transporting polypeptide (OATP/Oatp) transporters. In HEK293 cells overexpressing drug transporters, the protopanaxadiol (PPD)-type ginsenosides- Rb1, Rb2, Rc, Rd, Rg3, compound K, and Rh2-inhibited human OATP1B1 and OATP1B3 transporters (IC50 values of 7.99–68.2 µM for OATP1B1; 1.36–30.8 µM for OATP1B3), suggesting the herb–drug interaction of PPD-type ginsenosides involving OATPs. Protopanaxatriol (PPT)-type ginsenosides-Re, Rg1, and Rh1-did not inhibit OATP1B1 and OATP1B3 and all ginsenosides tested didn’t inhibit OCT and OAT transporters. However, in rats, neither RGE nor Rc, a potent OATP inhibitor among PPD-type ginsenoside, changed in vivo pharmacokinetics of valsartan following repeated oral administration of RGE (1.5 g/kg/day for 7 days) or repeated intravenous injection of Rc (3 mg/kg for 5 days). The lack of in vivo herb–drug interaction between orally administered RGE and valsartan could be attributed to the low plasma concentration of PPD-type ginsenosides (5.3–48.4 nM). Even high plasma concentration of Rc did not effectively alter the pharmacokinetics of valsartan because of high protein binding and the limited liver distribution of Rc. The results, in conclusion, would provide useful information for herb–drug interaction between RGE or PPD-type ginsenosides and Oatp substrate drugs.

Detection of 13 Ginsenosides (Rb1, Rb2, Rc, Rd, Re, Rf, Rg1, Rg3, Rh2, F1, Compound K, 20(S)-Protopanaxadiol, and 20(S)-Protopanaxatriol) in Human Plasma and Application of the Analytical Method to Human Pharmacokinetic Studies Following Two Week-Repeated Administration of Red Ginseng Extract.

We aimed to develop a sensitive method for detecting 13 ginsenosides using liquid chromatography–tandem mass spectrometry and to apply this method to pharmacokinetic studies in human following repeated oral administration of red ginseng extract. The chromatograms of Rb1, Rb2, Rc, Rd, Re, Rf, Rg1, Rg3, Rh2, F1, compound K (CK), protopanaxadiol (PPD), and protopanaxatriol (PPT) in human plasma were well separated. The calibration curve range for 13 ginsenosides was 0.5–200 ng/mL and the lower limit of quantitation was 0.5 ng/mL for all ginsenosides. The inter- and intra-day accuracy, precision, and stability were less than 15%. Among the 13 ginsenosides tested, nine ginsenosides (Rb1, Rb2, Rc, Rd, Rg3, CK, Rh2, PPD, and PPT) were detected in the human plasma samples. The plasma concentrations of Rb1, Rb2, Rc, Rd, and Rg3 were correlated with the content in red ginseng extract; however, CK, Rh2, PPD, and PPT were detected although they are not present in red ginseng extract, suggesting the formation of these ginsenosides through the human metabolism. In conclusion, our analytical method could be effectively used to evaluate pharmacokinetic properties of ginsenosides, which would be useful for establishing the pharmacokinetic–pharmacodymic relationship of ginsenosides as well as ginsenoside metabolism in humans.

Enhanced Intestinal Permeability and Plasma Concentration of Metformin in Rats by the Repeated Administration of Red Ginseng Extract.

We aimed to assess the potential herb–drug interactions between Korean red ginseng extract (RGE) and metformin in rats in terms of the modulation of metformin transporters, such as organic cation transporter (Oct), multiple toxin and extrusion protein (Mate), and plasma membrane monoamine transporter (Pmat). Single treatment of RGE did not inhibit the in vitro transport activity of OCT1/2 up to 500 µg/mL and inhibited MATE1/2-K with high IC50 value (more than 147.8 µg/mL), suggesting that concomitant used of RGE did not directly inhibit OCT- and MATE-mediated metformin uptake. However, 1-week repeated administration of RGE (1.5 g/kg/day) (1WRA) to rats showed different alterations in mRNA levels of Oct1 depending on the tissue type. RGE increased intestinal Oct1 but decreased hepatic Oct1. However, neither renal Oct1/Oct2 nor Mate1/Pmat expression in duodenum, jejunum, ileum, liver, and kidney were changed in 1WRA rats. RGE repeated dose also increased the intestinal permeability of metformin; however, the permeability of 3-O-methyl-d-glucose and Lucifer yellow was not changed in 1WRA rats, suggesting that the increased permeability of metformin by multiple doses of RGE is substrate-specific. On pharmacokinetic analysis, plasma metformin concentrations following intravenous injection were not changed in 1WRA, consistent with no significant change in renal Oct1, Oct2, and mate1. Repeated doses of RGE for 1 week significantly increased the plasma concentration of metformin, with increased half-life and urinary excretion of metformin following oral administration of metformin (50 mg/kg), which could be attributed to the increased absorption of metformin. In conclusion, repeated administration of RGE showed in vivo pharmacokinetic herb–drug interaction with metformin, with regard to its plasma exposure and increased absorption in rats. These results were consistent with increased intestinal Oct1 and its functional consequence, therefore, the combined therapeutic efficacy needs further evaluation before the combination and repeated administration of RGE and metformin, an Oct1 substrate drug.

Effects of Red Ginseng Extract on the Pharmacokinetics and Elimination of Methotrexate via Mrp2 Regulation.

We aimed to investigate the effects of red ginseng extract (RGE) on the expression of efflux transporters and to study the pharmacokinetics of representative substrate. For this, rats received single or repeated administration of RGE (1.5 g/kg/day) for 1 and 2 weeks via oral gavage. mRNA and protein levels of multidrug resistance-associated protein2 (Mrp2), bile salt export pump (Bsep), and P-glycoprotein (P-gp) in the rat liver were measured via real-time polymerase chain reaction and Western blot analysis. Ginsenosides concentrations from the rat plasma were also monitored using a liquid chromatography–tandem mass spectrometry (LC–MS/MS) system. Plasma concentrations of ginsenoside Rb1, Rb2, Rc, and Rd following repeated administration of RGE for 1 and 2 weeks were comparable but significantly higher than those after single administration of RGE. These dosing regimens did not induce significant biochemical abnormalities in the liver, kidneys, and lipid homeostasis. In the RGE repeated oral administration groups, the mRNA and protein levels of Mrp2 significantly decreased. Accordingly, we investigated the changes in the pharmacokinetics of methotrexate, a probe substrate for Mrp2, following intravenous administration of 3 mg/kg methotrexate to rats in the RGE 1-week repeated oral administration group, compared to that in the control group. Biliary excretion, but not urinary excretion, of methotrexate decreased in the RGE repeated administration group, compared to that in the control group. Consequently, the plasma concentrations of methotrexate slightly increased in the RGE repeated administration group. In conclusion, repeated administration of RGE for 1 week resulted in a decrease in Mrp2 expression without inducing significant liver or kidney damage. Pharmacokinetic herb–drug interaction between RGE and methotrexate might occur owing to the decrease in the mRNA and protein levels of Mrp2.

Tolerability and pharmacokinetics of ginsenosides Rb1, Rb2, Rc, Rd, and compound K after single or multiple administration of red ginseng extract in human beings

BackgroundWe investigated the tolerability and pharmacokinetic properties of various ginsenosides, including Rb1, Rb2, Rc, Rd, and compound K, after single or multiple administrations of red ginseng extract in human beings. MethodsRed ginseng extract (dried ginseng > 60%) was administered once and repeatedly for 15 days to 15 healthy Korean people. After single and repeated administration of red ginsengextract, blood sample collection, measurement of blood pressure and body temperature, and routine laboratory test were conducted over 48-h test periods. ResultsRepeated administration of high-dose red ginseng for 15 days was well tolerated and did not produce significant changes in body temperature or blood pressure. The plasma concentrations of Rb1, Rb2, and Rc were stable and showed similar area under the plasma concentration-time curve (AUC) values after 15 days of repeated administration. Their AUC values after repeated administration of red ginseng extract for 15 days accumulated 4.5- to 6.7-fold compared with single-dose AUC. However, the plasma concentrations of Rd and compound K showed large interindividual variations but correlated well between AUC of Rd and compound K. Compound K did not accumulate after 15 days of repeated administration of red ginseng extract. ConclusionA good correlation between the AUC values of Rd and compound K might be the result of intestinal biotransformation of Rb1, Rb2, and Rc to Rd and subsequently to compound K, rather than the intestinal permeability of these ginsenosides. A strategy to increase biotransformation or reduce metabolic intersubject variability may increase the plasma concentrations of Rd and compound K.

Effect of red and black ginseng on cholinergic markers, presynaptic markers, and neurotrophins in the brain of aged mice.

This study investigated the effects of chronic administration of red ginseng extract (RGE) and black ginseng extract (BGE) on memory impairment in aged (18-month-old) mice. RGE and BGE (200mg/kg) were orally administered for 16weeks. Aging induced DNA damage; however, RGE and BGE protected DNA from damage and allowed for DNA recovery in blood lymphocytes. Choline acetyltransferase, vesicular acetylcholine transporter, growth-associated protein 43, synaptosomal-associated protein 25, nerve growth factor, and brain-derived neurotrophic factor protein expression were significantly increased after treatment with RGE and BGE. These data suggest that chronic administration of red ginseng and black ginseng may decrease the cognitive deficits associated with normal aging.

Oral Administration of Red Ginseng Extract Promotes Neurorestoration after Compressive Spinal Cord Injury in Rats.

Red ginseng and its active ingredients have been shown to decrease neuron death after brain ischemia in experimental animals. However, little is known about the effects of orally administered ginseng extract on spinal cord injury. We orally gave red ginseng extract (RGE) to rats with compressed spinal cord injury (SCI). Open-field locomotor scores were measured as indices of motor function. Histopathological changes and cytokine expressions in situ after SCI were evaluated. Compared to vehicle treatment, RGE treatment (350 mg/kg/day) significantly improved locomotor score up to levels close to those pre-SCI, prevented neuron loss, and facilitated the restoration of white matter in the spinal cord at 14 days after SCI. Treatment with RGE caused less aggregation of Iba-1-positive microglia in grey and white matter at 7 days after SCI, upregulated the expression levels of VEGF and Bcl-xL, and reduced IL-1β and TNFα expressions in the spinal cord at 7 and 14 days after SCI. We concluded that oral administration of RGE facilitates almost complete functional recovery from motor and behavioral abnormalities in rats with SCI and prevents neuron death in situ, possibly through inhibition of inflammation and upregulation of neuroprotective factors in the injured spinal cord.

The Effect of Red Ginseng Extract Intake on Ischemic Flaps

ABSTRACTRed ginseng is well known for its angiogenic effects and its effect of increasing expression of vascular endothelial growth factors (VEGFs), but little experimental evidence has been published. In this study, we examined the effect of red ginseng using an ischemic flap model. Twenty male Sprague-Dawley rats were divided into two groups of 10. One group drank red ginseng solution from 7 days prior to surgery to 7 days after, whereas the other group drank distilled water. We created a local flap on the back of each rat. We analyzed the surviving area of the flap for 10 days after surgery and measured the blood flow of the flap. Ten days after the operation, CD31-positive vessels and VEGF expression were examined by immunohistochemistry. The percentages of surviving areas of the flap were 76 ± 3% for the experimental group and 39 ± 5% for the control group (P = 0.0002). Blood flow in the experimental group increased for 10 days after the surgery. The number of newly generated capillaries in the experimental group was 14.0 ± 3.5, which was significantly higher than 5.7 ± 1.9 in the control group. The expression of VEGF in the experimental group was significantly higher than in the control group (p = 0.0003). Administration of red ginseng extract increases the survival of ischemic flaps via angiogenesis and elevated blood flow. Further clinical studies are warranted to apply the effect shown in this current investigation to various ischemic conditions.

Korean Red Ginseng attenuates ethanol-induced steatosis and oxidative stress via AMPK/Sirt1 activation

BackgroundAlcoholic steatosis is the earliest and most common liver disease, and may precede the onset of more severe forms of liver injury. MethodsThe effect of Korean Red Ginseng extract (RGE) was tested in two murine models of ethanol (EtOH)-feeding and EtOH-treated hepatocytes. ResultsBlood biochemistry analysis demonstrated that RGE treatment improved liver function. Histopathology and measurement of hepatic triglyceride content verified the ability of RGE to inhibit fat accumulation. Consistent with this, RGE administration downregulated hepatic lipogenic gene induction and restored hepatic lipolytic gene repression by EtOH. The role of oxidative stress in the pathogenesis of alcoholic liver diseases is well established. Treatment with RGE attenuated EtOH-induced cytochrome P450 2E1, 4-hydroxynonenal, and nitrotyrosine levels. Alcohol consumption also decreased phosphorylation of adenosine monophosphate-activated protein kinase, which was restored by RGE. Moreover, RGE markedly inhibited fat accumulation in EtOH-treated hepatocytes, which correlated with a decrease in sterol regulatory element-binding protein-1 and a commensurate increase in sirtuin 1 and peroxisome proliferator-activated receptor-α expression. Interestingly, the ginsenosides Rb2 and Rd, but not Rb1, significantly inhibited fat accumulation in hepatocytes. ConclusionThese results demonstrate that RGE and its ginsenoside components inhibit alcoholic steatosis and liver injury by adenosine monophosphate-activated protein kinase/sirtuin 1 activation both in vivo and in vitro, suggesting that RGE may have a potential to treat alcoholic liver disease.

Immunomodulatory Activity of Red Ginseng against Influenza A Virus Infection

Ginseng herbal medicine has been known to have beneficial effects on improving human health. We investigated whether red ginseng extract (RGE) has preventive effects on influenza A virus infection in vivo and in vitro. RGE was found to improve survival of human lung epithelial cells upon influenza virus infection. Also, RGE treatment reduced the expression of pro-inflammatory genes (IL-6, IL-8) probably in part through interference with the formation of reactive oxygen species by influenza A virus infection. Long-term oral administration of mice with RGE showed multiple immunomodulatory effects such as stimulating antiviral cytokine IFN-γ production after influenza A virus infection. In addition, RGE administration in mice inhibited the infiltration of inflammatory cells into the bronchial lumens. Therefore, RGE might have the potential beneficial effects on preventing influenza A virus infections via its multiple immunomodulatory functions.

Effects of red ginseng extract on sleeping behaviors in human volunteers

Ethnopharmacological relevenceThe ginseng root has been traditionally used as a sedative in oriental countries. However, the condition “ginseng abuse syndrome” (GAS), defined as hypertension, nervousness, sleeplessness, skin eruption, and morning diarrhea, was coined as a result of a study of people who had been using a variety of ginseng preparations. However, we reported that administration of RGE increased rapid eye movement (REM) and non rapid eye movement (NREM) sleep via GABAergic systems in animals. Therefore, this study was performed to investigate how red ginseng extract (RGE) affects sleeping behaviors in human volunteers. Materials and methodsRGE (1500mg) was orally administered to young male healthy volunteers (from 15 to 37 years old ages, n=15) three times a day for 7 days. Overnight polysomnographic (PSG) studies were performed two times, 1 day before and 7 days after RGE administration. We investigated differences in sleep architecture parameters such as total sleep time (TST), sleep efficacy (SE: total sleep time/time in bed), proportion of each sleep stage, and wakefulness after sleep onset (WASO) between baseline PSG and PSG after RGE administration. ResultsTotal wake time (TWT) was significantly reduced (P<0.05) and SE was increased (P<0.05), although slow wave sleep stage 1 (N1) was reduced (P<0.01) and non-rapid eye movement (REM) sleep was increased (P<0.03) after administration. ConclusionFrom these results, it is presumed that RGE intake would improve the quality of sleep, thus having beneficial effects on sleep disturbed subjects.

Antiobesity, antioxidant and antidiabetic activities of red Ginseng plant extract in obese diabetic rats

Aim: This study aimed to investigate the effects of red ginseng extract (RGE) on adiposity index, some serum biochemical parameters and tissue antioxidant activity in obese diabetic rats. Materials and Methods: Five groups of male Sprague-Dawley rats were used. Group (1) was negative control and the other 4 groups were fed on high fat-diet for 6 weeks to induce obesity. The obese rats were then rendered diabetic by intraperitoneal injection of alloxan for 5 days. Group (2) was kept obese diabetic (positive control) and the other 3 groups were orally given RGE at 100, 200 and 400 mg /kg /day, respectively, for 4 weeks. Blood samples were collected for biochemical analyses and kidneys were taken to assay of activities of antioxidant enzymes. Results: oral dosage of RGE to obese diabetic rats significantly (P < 0.05) reduced adiposity index; decreased serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma- glutamyl transpeptidase (GGT) enzymes, total cholesterol (TC), triglycerides (TG), and low density lipoproteins (LDL-c) and improved atherogenic index. Blood glucose and leptin hormone decreased, but insulin increased by administration of RGE. it increased activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) antioxidant enzymes in kidneys tissues. Conclusion: Red ginseng extract produces antiobesity, antioxidant, and antidiabetic activities in obese diabetic rats. The study suggests that red ginseng plant may be beneficial for the treatment of patients who suffer from obesity associated with diabetes.

Effects of Korean red ginseng extracts on neural tube defects and impairment of social interaction induced by prenatal exposure to valproic acid

Ginseng is one of the most widely used medicinal plants, which belongs to the genus Panax. Compared to uncured white ginseng, red ginseng has been generally regarded to produce superior pharmacological effects with lesser side/adverse effects, which made it popular in a variety of formulation from tea to oriental medicine. Using the prenatal valproic acid (VPA)-injection model of autism spectrum disorder (ASD) in rats, which produces social impairrment and altered seizure susceptibility as in human ASD patients as well as mild neural tube defects like crooked tail phenotype, we examined whether chronic administration of red ginseng extract may rescue the social impairment and crooked tail phenotype in prenatally VPA-exposed rat offspring. VPA-induced impairment in social interactions tested using sociability and social preference paradigms as well as crooked tail phenotypes were significantly improved by administration of Korean red ginseng (KRG) in a dose dependent manner. Rat offspring prenatally exposed to VPA showed higher sensitivity to electric shock seizure and increased locomotor activity in open-field test. KRG treatment reversed abnormal locomotor activity and sensitivity to electric shock to control level. These results suggest that KRG may modulate neurobehavioral and structural organization of nervous system adversely affected by prenatal exposure to VPA.

Alterations of Spontaneous Sleep Architecture and Cortical Electroencephalogram Power Spectra by Red Ginseng Extract via GABAAergic Systems

This study was undertaken to discover the effects and possible mechanisms of the effect of red ginseng extract (RGE) on spontaneous sleep. The effects of a low dose (10 mg/kg) and a high dose (200 mg/kg) of RGE were compared in rats. After recovery from a surgical operation enabling electroencephalograms recordings, rats were administered RGE orally. RGE was administered orally for 1 day or once per day for 5 days in either 10 or 200 mg/kg doses. Polygraphic signs were recorded for 12 h after oral administration of RGE. Both treatment with a large dose (200 mg/kg) of RGE for one day and treatment with either a large or a small dose for 5 days reduced the number of sleep.wake cycles. Daily treatment with RGE (either 10 or 200 mg/kg) for 5 days augmented NREM and total sleep, but reduced wakefulness. Delta wave activity recorded during non-REM (NREM) sleep and REM sleep was increased after one treatment with RGE (either 10 or 200 mg/kg). Delta wave activity during NREM was enhanced after daily treatment with RGE (either 10 or 200 mg/kg) for 5 days. Both alpha and beta subunits of the <TEX>$\gamma$</TEX>-aminobutyric acid <TEX>$(GABA)_A$</TEX> receptor were significantly over-expressed in the hypothalamus of the RGE-treated groups. Moreover, the expression of glutamic acid decarboxylase was also increased in the hypothalamus. These results demonstrate that RGE may regulate spontaneous sleep via <TEX>$GABA_A$</TEX>ergic systems.

Effects of Red Ginseng on Neonatal Hypoxia-induced Hyperacitivity Phenotype in Rats

Attention deficit hyperactivity disorder (ADHD) affects 4-12% of chool-age children worldwide and is characterized by three core symptoms: hyperactivity, inattention, and impulsivity. Although standard pharmacological treatments, such as methylphenidate and atomoxetine, are available, concerns about drug-induced psychological and cardiovascular problems, as well as growth retardation and sleep disturbances, highlight the continuing need for new therapeutic interventions. Using a neonatal hypoxia-induced hyperactivity model in rats, the potential positive role that oral administration of red ginseng extract may have in relation to the hyperactive phenotype was investigated. Hypoxia was induced in 2-day-old male Sprague-Dawley (SD) rat pups by placing them in a nitrogen chamber for 15 min. The neonatal hypoxia-induced rats showed a significant increase in hyperactivity phenotype, such as increased movement duration, movement distance, and rearing frequency, which was determined by monitoring their spontaneous locomotor activity using the Ethovision video tracking system. One week of oral treatment with red ginseng extract decreased the hyperactivity phenotype of the neonatal hypoxia-induced rats and increased the locomotor activity of the control rats. In the neonatal hypoxia-induced rats, expression of the norepinephrine transporter in the forebrain was increased, and red ginseng treatment partially prevented its up-regulation, while increasing its level in the control rats. Taken together, these results suggest that red ginseng extract decreased the neonatal hypoxia-induced hyperactivity phenotype, although it increased locomotor activity in normal animals.

Effects of Red Ginseng extract on ultraviolet B‐irradiated skin change in C57BL mice

Red Ginseng (the roots of Panax ginseng C.A. Meyer) is used clinically in China, Korea and Japan for various diseases, including atherosclerosis, hypertension and stress etc. Although Red Ginseng roots have traditionally been thought to have antiageing effects, the basis for this hearsay is unclear. This study examined the effects of Red Ginseng extract on ultraviolet B (UVB)-irradiated skin ageing in mice. Oral administration of Red Ginseng extract (20 or 60 mg/kg, twice daily) prevented UVB-irradiated skin damage (increases of skin thickness and pigmentation, and reduction of skin elasticity). Furthermore, Red Ginseng extract inhibited the increases of epidermis and corium thickness induced by UVB irradiation. Red Ginseng extract inhibited the increase of skin TGF-beta1 content induced by UVB irradiation. These findings suggest that the protective action of Red Ginseng extract against UVB-irradiated skin ageing may be due partly to an inhibition of the increase of skin TGF-beta1 induced by UVB irradiation. In conclusion, the oral administration of Red Ginseng extract may be useful as a health supplement for protection against photoageing.