Subacute oral toxicity and bacterial mutagenicity of a mixture of Puerariae radix and Hizikia fusiforme extracts.

The study aims to identify the safety profile of a mixed extract (KGC-02-PS) from two traditional medicinal herbs, Puerariae radix and Hizikia fusiforme. In a subacute oral toxicity study, KGC-02-PS was administered orally for 28 days by gavage to Sprague Dawley rats (both sexes) at a daily dose of 0, 500, 1000, and 2000 mg/kg body weight. Bodyweight, food consumption, and clinical signs were monitored during the experimental period. After administering the final dose, this study conducted hematology, serum biochemistry, and pathological evaluations. In addition, the study performed a bacterial reverse mutation test with varying concentrations of KGC-02-PS (312.5 µg - 5,000 µg/plate) following OECD guideline No. 471, before testing five bacterial strains (Salmonella typhimurium TA98, TA100, TA1535, TA1537, and Escherichia coli WP2) in the presence or absence of metabolic activation. The preclinical evaluation of KGC-02-PS's subacute oral toxicity yielded no associated toxicological effects or any changes in clinical signs, body weight, and food consumption. Moreover, examining KGC-02-PS's hematological and serum biochemical characteristics and pathology yielded no toxicological changes in terms of organ weight measurements and gross or histopathological findings. KGC-02-PS neither increased the number of revertant colonies in all bacterial strains used in the bacterial reverse mutation test, nor did it induce genotoxicity related to bacterial reverse mutations under the study's conditions. Also, KGC-02-PS's no-observed-adverse-effect level was greater than 2000 mg/kg.

Immune Activity of Polysaccharide Fractions Isolated from Korean Red Ginseng.

Korean red ginseng (KRG)'s pharmacological efficacy and popular immunomodulatory effects have already been proven in many studies; however, the component of KRG that is effective in immune activity has not been studied before. Therefore, this study extracted and separated KRG for an immune activity comparison. In the water fraction obtained by extracting KRG powder with water, a red ginseng neutral polysaccharide (RGNP) fraction and a red ginseng acidic polysaccharide (RGAP) fraction were obtained. Each fraction was orally administered for 10 days to mice with reduced immunity, and the number of IgM antibody-forming cells (AFCs) in splenocytes was measured to compare the immune activity of the water fractions. The results showed that the RGAP fraction has the greatest number of AFCs. To set the optimal dose of the RGAP fraction, which had the highest immune activity, the AFCs, macrophage activity, and splenocyte subtype in the mice were analyzed. As a result, the number of AFCs was significantly increased in the RGAP fraction compared to RGNP. The intraperitoneal macrophage phagocytosis activity and the number of T cells, B cells, and macrophages in the spleen increased significantly. It can, therefore, be confirmed that immune activity increases by a fraction containing higher RGAP content, and we hypothesize that RGAP activates immune activity.

Biological Effects of Korean Red Ginseng Polysaccharides in Aged Rat Using Global Proteomic Approach.

Much has been written on the physiological benefits of Korean Red Ginseng (KRG). Among its various components, ginsenosides have been widely investigated for their various pharmacological effects. However, polysaccharides are a major KRG component that has not received scrutiny similar to that of ginsenosides. The present study aims to fill that gap in the existing literature and to investigate the possible functions of polysaccharide in KRG. The researchers evaluated proteomic changes in non-saponin fractions with rich polysaccharides (NFP) in KRG. Based on the serum analysis, proteomics analysis of the liver and the spleen was additionally conducted to identify related functions. We validated the suggested functions of NFP with the galactosamine-induced liver injury model and the cyclophosphamide-induced immunosuppression model. Then, we evaluated the antimetastatic potential of NFP in the lungs. Further proteomics analysis of the spleen and liver after ingestion confirmed functions related to immunity, cancer, hepatoprotection, and others. Then, we validated the suggested corresponding functions of the NFP in vivo model. NFP showed immune-enhancing effects, inhibited melanoma cell metastasis in the lung, and decreased liver damage. The results show that using the proteomic approach uncovers the potential effects of polysaccharides in KRG, which include enhancing the immune system and protecting the liver.

Metabolomic Approach for Discrimination of Four- and Six-Year-Old Red Ginseng (Panax ginseng) Using UPLC-QToF-MS.

Panax ginseng C.A. MEYER is one of the most popular medicinal herbs in Asia and the chemical constituents are changed by processing methods such as steaming or sun drying. Metabolomic analysis was performed to distinguish age discrimination of four- and six-year-old red ginseng using ultra-performance liquid chromatography quadruple time of flight mass spectrometry (UPLC-QToF-MS) with multivariate statistical analysis. Principal component analysis (PCA) showed clear discrimination between extracts of red ginseng of different ages and suggest totally six discrimination markers (two for four-year-old and four for six-year-old red ginseng). Among these, one marker was isolated and the structure determined by NMR spectroscopic analysis was 13-cis-docosenamide (marker 6-1) from six-year-old red ginseng. This is the first report of a metabolomic study regarding the age differentiation of red ginseng using UPLC-QToF-MS and determination of the structure of the marker. These results will contribute to the quality control and standardization as well as provide a scientific basis for pharmacological research on red ginseng.

Sphingomonas kyungheensis sp. nov., a bacterium with ginsenoside-converting activity isolated from soil of a ginseng field.

A bacterial strain THG-B283(T), which has ß-glucosidase activity, was isolated from soil of a ginseng field. Cells were Gram-reaction-negative, oxidase- and catalase-positive, aerobic, motile with one polar flagellum and rod-shaped. The strain was subjected to a polyphasic taxonomic study. Strain THG-B283(T) grew optimally at around pH 7.0, at 25-28 °C and in the absence of NaCl on R2A agar. 16S rRNA gene sequence analysis revealed that strain THG-B283(T) belongs to the family Sphingomonadaceae and is closely related to Sphingomonas melonis DAPP-PG 224(T) (98.2 %), S. aquatilis JSS7(T) (98.1 %), S. insulae DS-28(T) (97.6 %), S. mali IFO 15500(T) (97.1 %) and S. pruni IFO 15498(T) (97.0 %). Strain THG-B283(T) contained Q-10 as the predominant ubiquinone. The major fatty acids included summed feature 3 (comprising C16 : 1ω7c and/or C16 : 1ω6c), C18 : 1ω7c, C14 : 0 2-OH and C16 : 0. The DNA G+C content was 72.2 mol%. The major component in the polyamine pattern was sym-homospermidine. The major polar lipids were phosphatidylglycerol, phosphatidylethanolamine, phosphatidyldimethylethanolamine, phosphatidylcholine, sphingoglycolipid, diphosphatidylglycerol, an unidentified glycolipid, unidentified aminolipids, an unidentified phospholipid and unidentified lipids. Genomic and chemotaxonomic data supported the affiliation of strain THG-B283(T) to the genus Sphingomonas. DNA-DNA relatedness between strain THG-B283(T) and its closest phylogenetic neighbours was below 23 %. On the basis of phenotypic, phylogenetic and genetic data, strain THG-B283(T) represents a novel species of genus Sphingomonas, for which the name Sphingomonas kyungheensis sp. nov. is proposed. The type strain is THG-B283(T) ( = KACC 16224(T) = LMG 26582(T)).

Dyella kyungheensis sp. nov., isolated from soil of a cornus fruit field.

A Gram-reaction-negative, aerobic, motile by one polar flagellum, yellow-pigmented, rod-shaped bacterium, designated strain THG-B117(T), was isolated from soil of a cornus fruit field of Hoengseong province in South Korea and its taxonomic position was investigated by a polyphasic study. Strain THG-B117(T) grew well at 25-30 °C and at pH 6.0-8.0 in the absence of NaCl on nutrient agar. On the basis of 16S rRNA gene sequence similarity, strain THG-B117(T) was shown to belong to the family Xanthomonadaceae and be related to Dyella japonica XD53(T) (98.7 % similarity), Dyella terrae JS14-6(T) (98.0 %), Dyella koreensis BB4(T) (96.9 %), Dyella soli JS12-10(T) (96.9 %) and Dyella thiooxydans ATSB10(T) (96.7 %). DNA-DNA hybridization experiments showed that DNA relatedness between strain THG-B117(T) and its phylogenetically closest neighbours was below 45.1 %. The G+C content of the genomic DNA of strain THG-B117(T) was 64.8 mol%. The major polar lipids were phosphatidylglycerol, phosphatidylethanolamine, diphosphatidylglycerol, unidentified aminolipids, unidentified aminophospholipids and unidentified phospholipids. Phenotypic and chemotaxonomic data (major ubiquinone was Q-8, and major fatty acids were iso-C15 : 0, iso-C16 : 0, iso-C17 : 0 and iso-C17 : 1ω9c) supported the affiliation of strain THG-B117(T) with the genus Dyella. The results of physiological and biochemical tests suggested that strain THG-B117(T) was different genotypically and phenotypically from recognized species of the genus Dyella, and represents a novel species of this genus. The name Dyella kyungheensis sp. nov. is proposed, with the type strain THG-B117(T) ( = KACC 16981(T) = JCM 18747(T)).

Inhibitory effects of epi-sesamin on endothelial protein C receptor shedding in vitro and in vivo.

OBJECTIVE AND DESIGN: Endothelial protein C receptor (EPCR) plays a pivotal role in augmenting Protein C activation by the thrombin-thrombomodulin complex. The activity of EPCR is markedly changed by ectodomain cleavage and release as the soluble protein (sEPCR). The EPCR shedding is mediated by the tumor necrosis factor-α converting enzyme (TACE). Epi-sesamin (ESM), from the roots of Asarum siebodlii, is known to exhibit anti-allergic and anti-fungal activities. However, little is known about the effects of ESM on EPCR shedding. METHODS: We investigated this issue by monitoring the effects of ESM on phorbol-12-myristate 13-acetate (PMA), tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and cecal ligation and puncture (CLP)-mediated EPCR shedding. RESULTS: Data showed that ESM induced potent inhibition of PMA, TNF-α, IL-1ß, and CLP-induced EPCR shedding, likely through suppression of TACE expression. In addition, treatment with ESM resulted in a reduction of PMA-stimulated phosphorylation of p38, extracellular regulated kinases (ERK) 1/2, and c-Jun N-terminal kinase (JNK). CONCLUSIONS: Given these results, ESM should be viewed as a candidate therapeutic agent for treatment of various severe vascular inflammatory diseases via inhibition of EPCR shedding.

Pharmacokinetics of hederacoside C, an active ingredient in AG NPP709, in rats.

1. Hederacoside C (HDC) is one of the active ingredients in Hedera helix leaf extract (Ivy Ex.) and AG NPP709, a new botanical drug to treat acute respiratory infection and chronic inflammatory bronchitis. However, information regarding its pharmacokinetic properties remains limited. 2. Here, we report the pharmacokinetics of HDC in rats after intravenous administration of HDC (3, 12.5, and 25 mg/kg) and after oral administration of HDC, Ivy Ex., and AG NPP709 (equivalent to 12.5, 25, and 50 mg/kg HDC). 3. Linear pharmacokinetics of HDC were identified upon its intravenous administration at doses of 3-25 mg/kg. Intravenous administration of HDC results in relatively slow clearance (1.46-2.08 mL/min/kg) and a small volume of distribution at steady state (138-222 mL/kg), while oral administration results in a low absolute oral bioavailability (F) of 0.118-0.250%. The extremely low F of HDC may be due to poor absorption of HDC from the gastrointestinal (GI) tract and/or its decomposition therein. 4. The oral pharmacokinetics of HDC did not differ significantly among pure HDC, Ivy Ex., and AG NPP709.

Biodistribution and pharmacokinetic evaluation of Korean Red Ginseng components using radioisotopes in a rat model.

Background: Although many studies have evaluated the efficacy and pharmacokinetics of Korean Red Ginseng (KRG) components (Rg1, Rb1, Rg3, Rd, etc.), few have examined the in vivo pharmacokinetics of the radiolabeled components. This study investigated the pharmacokinetics of ginsenosides and their metabolite compound K (CK), 20(s)-protopanaxadiol (PPD), and 20(s)-protopanaxatriol (PPT) using radioisotopes in rat oral administration. Methods: Sprague-Dawley rats were dosed orally once with 10 mg/kg of the tritium(3H) radiolabeled samples, and then the blood was collected from the tail vein after 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 96, and 168 h. Radioactivity in the organs, feces, urine, and carcass was determined using a liquid scintillation counter (LSC) and a bio-imaging analyzer system (BAS). Results and conclusion: After oral administration, as the 3H-labeled ginsenosides were converted to metabolites, Cmax and half-life increased, and Tmax decreased. Interestingly, Rb1 and CK showed similar values, and after a single oral administration of components, the cumulative excretion ratio of urine and feces was 88.9%-92.4%. Although most KRG components were excreted within 96-168 h of administration, small amounts of components were detected in almost all tissues and mainly distributed to the liver except for the digestive tract when observed through autoradiography. This study demonstrated that KRG components were distributed to various organs in the rats. Further studies could be conducted to prove the bioavailability and transmission of KRG components to confirm the mechanism of KRG efficacy.

Respiratory protective effects of Korean Red Ginseng in a mouse model of particulate matter 4-induced airway inflammation.

Background: Air pollution has led to an increased exposure of all living organisms to fine dust. Therefore, research efforts are being made to devise preventive and therapeutic remedies against fine dust-induced chronic diseases. Methods: Research of the respiratory protective effects of KRG extract in a particulate matter (PM; aerodynamic diameter of <4 µm) plus diesel exhaust particle (DEP) (PM4+D)-induced airway inflammation model. Nitric oxide production, expression of pro-inflammatory mediators and cytokines, and IRAK-1, TAK-1, and MAPK pathways were examined in PM4-stimulated MH-S cells. BALB/c mice exposed to PM4+D mixture by intranasal tracheal injection three times a day for 12 days at 3 day intervals and KRGE were administered orally for 12 days. Histological of lung and trachea, and immune cell subtype analyses were performed. Expression of pro-inflammatory mediators and cytokines in bronchoalveolar lavage fluid (BALF) and lung were measured. Immunohistofluorescence staining for IRAK-1 localization in lung were also evaluated. Results: KRGE inhibited the production of nitric oxide, the expression of pro-inflammatory mediators and cytokines, and expression and phosphorylation of all downstream factors of NF-κB, including IRAK-1 and MAPK/AP1 pathway in PM4-stimulated MH-S cells. KRGE suppressed inflammatory cell infiltration and number of immune cells, histopathologic damage, and inflammatory symptoms in the BALF and lungs induced by PM4+D; these included increased alveolar wall thickness, accumulation of collagen fibers, and TNF-α, MIP2, CXCL-1, IL-1α, and IL-17 cytokine release. Moreover, PM4 participates induce alveolar macrophage death and interleukin-1α release by associating with IRAK-1 localization was also potently inhibited by KRGE in the lungs of PM4+D-induced airway inflammation model. KRGE suppresses airway inflammatory responses, including granulocyte infiltration into the airway, by regulating the expression of chemokines and inflammatory cytokines via inhibition of IRAK-1 and MAPK pathway. Conclusion: Our results indicate the potential of KRGE to serve as an effective therapeutic agent against airway inflammation and respiratory diseases.

Korean Red Ginseng water extract inhibits cadmium-induced lung injury via suppressing MAPK/ERK1/2/AP-1 pathway.

Background: Few studies reported the therapeutic effect of Korean Red Ginseng (KRG) in lung inflammatory diseases. However, the anti-inflammatory role and underlying molecular in cadmium-induced lung injury have been poorly understood, directly linked to chronic lung diseases (CLDs): chronic obstructive pulmonary disease (COPD), cancer etc. Therefore, in this study we aim to investigate the therapeutic activities of water extract of KRG (KRG-WE) in mouse cadmium-induced lung injury model. Method: The anti-inflammatory roles and underlying mechanisms of KRG-WE were evaluated in vitro under cadmium-stimulated lung epithelial cells (A549) and HEK293T cell line and in vivo in cadmium-induced lung injury mouse model using semi-quantitative polymerase chain reaction (RT-PCR), quantitative real-time PCR (qPCR), luciferase assay, immunoblotting, and FACS. Results: KRG-WE strongly ameliorated the symptoms of CdSO4-induced lung injury in mice according to total cell number in bronchoalveolar lavage fluid (BALF) and severity scores as well as cytokine levels. KRG-WE significantly suppressed the upregulation of inflammatory signaling comprising mitogen-activated protein kinases (MAPK) and their upstream enzymes. In in vitro study, KRG-WE suppressed expression of interleukin (IL)-6, matrix metalloproteinase (MMP)-2, and IL-8 while promoting recovery in CdSO4-treated A549 cells. Similarly, KRG-WE reduced phosphorylation of MAPK and c-Jun/c-Fos in cadmium-exposed A549 cells. Conclusion: KRG-WE was found to attenuate symptoms of cadmium-induced lung injury and reduce the expression of inflammatory genes by suppression of MAPK/AP-1-mediated pathway.

Safety of red ginseng and herb extract complex (RHC) in menopausal women: A randomized, double-blind, placebo-controlled trial.

Background: Various treatments are used to relieve menopausal symptoms for women. However, herbal substances are frequently used as complementary and alternative therapies as other treatments can increase ovarian and breast cancer risk. While the herbal substances' therapeutic effect is essential, the safety of their use is considered more important. This study aims to confirm the safety of red ginseng and herb extract complex (RHC), which are used to relieve menopausal symptoms. Methods: This randomized, double-blind, placebo-controlled clinical study recruited and divided 120 women experiencing menopausal symptoms into the RHC and placebo groups (60 women per group). Subjects were administered with 2 g RHC or placebo daily for 12 wk. Adverse reactions, female hormonal changes, and uterine thickness were observed and recorded on wk 0, 6, and 12. Hematologic and blood chemistry tests were also conducted. Results: The reactions of the subjects who received RHC or placebo at least once were analyzed. A total of six adverse reactions occurred in the RHC group, while nine occurred in the placebo group; common reactions observed in both groups were genital, subcutaneous tissue, and vascular disorders. However, there was no statistically significant difference between the administration groups (p = 0.5695), and no severe adverse reactions occurred in both groups. Conclusion: This study confirms the safety of daily intake of 2 g of RHC for 12 wk by menopausal women.

Long-term evaluation of safety and biological effects of Korean Red Ginseng (Panax Ginseng): a long-term in vivo study.

BACKGROUND: Although Korean Red Ginseng (KRG) is safe, this finding was only evaluated in 3-mo-long studies. Its safety was verified through a 6-mo KRG administration clinical study, but long-term studies beyond 6 mo are insufficient. This study investigated the safety and efficacy of 12-mo KRG administration. METHODS: In this study, 300 mg/kg of KRG was administered to male and female Sprague Dawley rats for 4, 8, and 12 mo to evaluate its efficacy and safety. Clinical signs, including pathological examination and haematological analyses, were observed. Flow cytometric analyses were utilised to analyse spleen and thymus immune cell counts after 12 mo. Proteomic analysis of the sera was performed using a nanospray-interfaced mass spectrometer with an 11-plex Tandem Mass Tag (TMT) labelling system. Bioinformatic analysis was then performed using Ingenuity Pathway Analysis and PANTHER. Data are available via ProteomeXchange with identifier PXD032036. RESULTS: No significant body and organ weight changes were observed, and haematological and serum biochemical analyses did not show clinical significance. The effectiveness of long-term KRG administration was confirmed through increased immune cell distribution and activity. Changes in proteins correlated with viral infection reduction were confirmed through proteomic analysis. CONCLUSION: The results suggested that 12-mo KRG intake is safe, improves immune system activity, and reduces viral infections with no significant changes in toxicological aspects.

Adaptogenic effects of Panax ginseng on modulation of immune functions.

Traditional medicinal practices have used natural products such as adaptogens to treat inflammatory, autoimmune, neurodegenerative, bacterial, and viral diseases since the early days of civilization. Panax ginseng Myer is a common herb used in East Asian countries for millennia, especially in Korea, China, and Japan. Numerous studies indicate that ginseng can modulate the immune system and thereby prevent diseases. Although the human immune system comprises many different types of cells, multiple studies suggest that each type of immune cell can be controlled or stimulated by ginseng or its derivatives. Provisional lists of ginseng's potential for use against viruses, bacteria, and other microorganisms suggest it may prove to be a valuable pharmaceutical resource, particularly if higher-quality evidence can be found. Here, we reviewed the role of ginseng as an immune-modulating agent in attempt to provide a valuable starting point for future studies on the herb and the human immune system.

The antioxidant activities of Korean Red Ginseng (Panax ginseng) and ginsenosides: A systemic review through in vivo and clinical trials.

A wide range of studies have steadily pointed out the relation of oxidative stress to the primary and secondary causes of human disease and aging. As such, there have been multiple misconceptions about oxidative stress. Most of reactive oxygen species (ROS) generated from chronic diseases cause oxidative damage to cell membrane lipids and proteins. ROS production is increased by abnormal stimulation inside and outside in the body, and even though ROS are generated in cells in response to abnormal metabolic processes such as disease, it does not mean that they directly contribute to the pathogenesis of a disease. Therefore, the focus of treatment should not be on ROS production itself but on the prevention and treatment of diseases linked to ROS production, including types 1 and 2 diabetes, cancer, heart disease, schizophrenia, Parkinson's disease, and Alzheimer's disease. In this regard, Korean Red Ginseng (KRG) has been traditionally utilized to help prevent and treat diseases such as diabetes, cancer, inflammation, nervous system diseases, cardiovascular disease, and hyperlipidemia. Therefore, this review was intended to summarize in vivo animal and human clinical studies on the antioxidant activities of KRG and its components, ginsenosides.

Immuno-enhancement effects of Korean Red Ginseng in healthy adults: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Most clinical studies of immune responses activated by Korean Red Ginseng (KRG) have been conducted exclusively in patients. However, there is still a lack of clinical research on immune-boosting benefits of KRG for healthy persons. This study aims to confirm how KRG boosts the immune system of healthy subjects. METHODS: A total of 100 healthy adult subjects were randomly divided into two groups that took either a 2 g KRG tablet or a placebo per day for 8 weeks. The primary efficacy evaluation variables included changes in T cells, B cells, and white blood cells (WBCs) before and after eight weeks of KRG ingestion. Cytokines (TNF-α, INF-γ, IL-2 and IL-4), WBC differential count, and incidence of colds were measured in the secondary efficacy evaluation variables. Safety evaluation variables were used to identify changes in laboratory test results that incorporated adverse reactions, vital signs, hematological tests, blood chemistry tests, and urinalysis. RESULTS: Compared to the placebo group, the KRG intake group showed a significant increase in the number of T cells (CD3) and its subtypes (CD4 and CD8), B cells, and the WBC count before and after eight weeks of the intake. There were no clinically significant adverse reactions or other notable results in the safety evaluation factors observed. CONCLUSION: This study has proven through its eight-week intake test and subsequent analysis that KRG boosts the immune system through an increase in T cells, B cells, and WBCs, and that it is safe according to the study's safety evaluation.

Korean Red Ginseng exerts anti-inflammatory and autophagy-promoting activities in aged mice.

BACKGROUND: Korean Red Ginseng (KRG) is a traditional herb that has several beneficial properties including anti-aging, anti-inflammatory, and autophagy regulatory effects. However, the mechanisms of these effects are not well understood. In this report, the underlying mechanisms of anti-inflammatory and autophagy-promoting effects were investigated in aged mice treated with KRG-water extract (WE) over a long period. METHODS: The mechanisms of anti-inflammatory and autophagy-promoting activities of KRG-WE were evaluated in kidney, lung, liver, stomach, and colon of aged mice using semi-quantitative reverse transcription polymerase chain reaction (RT-PCR), quantitative RT-PCR (qRT-PCR), and western blot analysis. RESULTS: KRG-WE significantly suppressed the mRNA expression levels of inflammation-related genes such as interleukin (IL)-1ß, IL-8, tumor necrosis factor (TNF)-α, monocyte chemoattractant protein-1 (MCP-1), and IL-6 in kidney, lung, liver, stomach, and colon of the aged mice. Furthermore, KRG-WE downregulated the expression of transcription factors and their protein levels associated with inflammation in lung and kidney of aged mice. KRG-WE also increased the expression of autophagy-related genes and their protein levels in colon, liver, and stomach. CONCLUSION: The results suggest that KRG can suppress inflammatory responses and recover autophagy activity in aged mice.

Korean Red Ginseng aqueous extract improves markers of mucociliary clearance by stimulating chloride secretion.

BACKGROUND: Abnormal chloride (Cl-) transport has a detrimental impact on mucociliary clearance in both cystic fibrosis (CF) and non-CF chronic rhinosinusitis. Ginseng is a medicinal plant noted to have anti-inflammatory and antimicrobial properties. The present study aims to assess the capability of red ginseng aqueous extract (RGAE) to promote transepithelial Cl- secretion in nasal epithelium. METHODS: Primary murine nasal septal epithelial (MNSE) [wild-type (WT) and transgenic CFTR-/-], fisher-rat-thyroid (FRT) cells expressing human WT CFTR, and TMEM16A-expressing human embryonic kidney cultures were utilized for the present experiments. Ciliary beat frequency (CBF) and airway surface liquid (ASL) depth measurements were performed using micro-optical coherence tomography (µOCT). Mechanisms underlying transepithelial Cl- transport were determined using pharmacologic manipulation in Ussing chambers and whole-cell patch clamp analysis. RESULTS: RGAE (at 30µg/mL of ginsenosides) significantly increased Cl- transport [measured as change in short-circuit current (ΔISC = µA/cm2)] when compared with control in WT and CFTR-/- MNSE (WT vs control = 49.8±2.6 vs 0.1+/-0.2, CFTR-/- = 33.5±1.5 vs 0.2±0.3, p < 0.0001). In FRT cells, the CFTR-mediated ΔISC attributed to RGAE was small (6.8 ± 2.5 vs control, 0.03 ± 0.01, p < 0.05). In patch clamp, TMEM16A-mediated currents were markedly improved with co-administration of RGAE and uridine 5-triphosphate (8406.3 +/- 807.7 pA) over uridine 5-triphosphate (3524.1 +/- 292.4 pA) or RGAE alone (465.2 +/- 90.7 pA) (p < 0.0001). ASL and CBF were significantly greater with RGAE (6.2+/-0.3 µm vs control, 3.9+/-0.09 µm; 10.4+/-0.3 Hz vs control, 7.3 ± 0.2 Hz; p < 0.0001) in MNSE. CONCLUSION: RGAE augments ASL depth and CBF by stimulating Cl- secretion through CaCC, which suggests therapeutic potential in both CF and non-CF chronic rhinosinusitis.

Therapeutic effects of non-saponin fraction with rich polysaccharide from Korean red ginseng on aging and Alzheimer's disease.

Biological aging provokes morbidity and several functional declines, causing older adults more susceptible to a variety of diseases than younger adults. In particular, aging is a major risk factor contributing to non-communicable diseases, such as neurodegenerative disorders. Alzheimer's disease (AD) is an aging-related neurodegenerative disease that is characterized by cognitive deficits and the formation of amyloid plaques formed by the accumulation of amyloid-ß (Aß) peptides. Non-saponin fraction with rich polysaccharide (NFP) from red ginseng, the largest fraction of the components of red ginseng, perform many biological activities. However, it has not been clarified whether the NFP from Korean red ginseng (KRG) has beneficial effects in the aging and AD. First, proteomics analysis was performed in aged brain to identify the effect of NFP on protein changes, and we confirmed that NFP induced changes in proteins related to the neuroprotective- and neurogenic-effects. Next, we investigated (1) the effects of NFP on AD pathologies, such as Aß deposition, neuroinflammation, neurodegeneration, mitochondrial dysfunction, and impaired adult hippocampal neurogenesis (AHN), in 5XFAD transgenic mouse model of AD using immunostaining; (2) the effect of NFP on Aß-mediated mitochondrial respiration deficiency in HT22 mouse hippocampal neuronal cells (HT22) using Seahorse XFp analysis; (3) the effect of NFP on cell proliferation using WST-1 analysis; and (4) the effect of NFP on Aß-induced cognitive dysfunction in 5XFAD mouse model of AD using Y-maze test. Histological analysis indicated that NFP significantly alleviated the accumulation of Aß, neuroinflammation, neuronal loss, and mitochondrial dysfunction in the subiculum of 5XFAD mouse model of AD. In addition, NFP treatment ameliorated mitochondrial deficits in Aß-treated HT22 cells. Moreover, NFP treatment significantly increased the AHN and neuritogenesis of neural stem cells in both healthy and AD brains. Furthermore, NFP significantly increased cell proliferation in the HT22 cells. Finally, NFP administration significantly enhanced and restored the cognitive function of healthy and AD mice, respectively. Taken together, NFP treatment demonstrated changes in proteins involved in central nervous system organization/maintenance in aged brain and ameliorates AD pathology. Collectively, our findings suggest that NFP from KRG could be a potential therapeutic candidate for aging and AD treatments.

Adaptogenic effects of Panax ginseng on modulation of cardiovascular functions.

Cardiovascular diseases are a rapidly growing epidemic with high morbidity and mortality. There is an urgent need to develop nutraceutical-based therapy with minimum side effects to reduce cardiovascular risk. Panax ginseng occupies a prominent status in herbal medicine for its various therapeutic effects against inflammation, allergy, diabetes, cardiovascular diseases, and even cancer, with positive, beneficial, and restorative effects. The active components found in most P. ginseng varieties are known to include ginsenosides, polysaccharides, peptides, alkaloids, polyacetylene, and phenolic compounds, which are considered to be the main pharmacologically active constituents in ginseng. P. ginseng is an adaptogen. That is, it supports living organisms to maintain optimal homeostasis by exerting effects that counteract physiological changes caused by physical, chemical, or biological stressors. P. ginseng possesses immunomodulatory (including both immunostimulatory and immunosuppressive), neuromodulatory, and cardioprotective effects; suppresses anxiety; and balances vascular tone. P. ginseng has an antihypertensive effect that has been explained by its vasorelaxant action, and paradoxically, it is also known to increase blood pressure by vasoconstriction and help maintain cardiovascular health. Here, we discuss the potential adaptogenic effects of P. ginseng on the cardiovascular system and outline a future research perspective in this area.