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.

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.

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.

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.

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.

Effects of a herbal formulation, KGC3P, and its individual component, nepetin, on coal fly dust-induced airway inflammation.

Coal fly dust (CFD)-induced asthma model is used as an ambient particulate matter model of serious pulmonary damage. We aimed to evaluate the effects of a combination of ginseng and Salvia plebeia R. Br extract (KGC-03-PS; KG3P) and its individual components (hispidulin, nepetin and rosmarinic acid) in a CFD-induced mouse model of airway inflammation (asthma). We also evaluated signal transduction by KG3P and its individual components in the alveolar macrophage cell line, MH-S cells. In vitro, KG3P and its individual components inhibited nitric oxide production and expression of pro-inflammatory mediators and cytokines (iNOS, COX-2, IL-1ß, IL-6 and TNF-α) through the NF-κB and MAPK pathways in coal fly ash (CFA)-induced inflammation in MH-S cells. Moreover, in the CFD-induced asthma model in mice, KG3P and its predominant individual component, nepetin, inhibited Asymmetric Dimethyl arginine (ADMA) and Symmetric Dimethyl arginine (SDMA) in serum, and decreased the histopathologic score in the lungs. A significant reduction in the neutrophils and immune cells in BALF and lung tissue was demonstrated, with significant reduction in the expression of the pro-inflammatory cytokines. Finally, IRAK-1 localization was also potently inhibited by KG3P and nepetin. Thus, KG3P extract can be considered as a potent candidate for amelioration of airway inflammation.

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.

Physiological and pharmacological features of the non-saponin components in Korean Red Ginseng.

Panax ginseng, a medicinal plant, has been used as a blood-nourishing tonic for thousands of years in Asia, including Korea and China. P. ginseng exhibits adaptogen activity that maintains homeostasis by restoring general biological functions and non-specifically enhancing the body's resistance to external stress. Several P. ginseng effects have been reported. Korean Red Ginseng, in particular, has been reported in both basic and clinical studies to possess diverse effects such as enhanced immunity, fatigue relief, memory, blood circulation, and anti-oxidation. Moreover, it also protects against menopausal symptoms, cancer, cardiac diseases, and neurological disorders. The active components found in most Korean Red Ginseng varieties are known to include ginsenosides, polysaccharides, peptides, alkaloids, polyacetylene, and phenolic compounds. In this review, the identity and bioactivity of the non-saponin components of Korean Red Ginseng discovered to date are evaluated and the components are classified into polysaccharide and nitrogen compounds (protein, peptide, amino acid, nucleic acid, and alkaloid), as well as fat-soluble components such as polyacetylene, phenols, essential oils, and phytosterols. The distinct bioactivity of Korean Red Ginseng was found to originate from both saponin and non-saponin components rather than from only one or two specific components. Therefore, it is important to consider saponin and non-saponin elements together.

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.

KGC3P attenuates ovalbumin-induced airway inflammation through downregulation of p-PTEN in asthmatic mice.

BACKGROUND: The roots of Korean red ginseng (Panax ginseng C.A.Mey.; KGC) have been used as an herbal supplement to enhance vital energy and immune capacity. Salvia plebeia R.Br. has been used to treat inflammatory diseases. PURPOSE: The aim of this study was to examine the anti-asthmatic effects of a mixture of Korean red ginseng and Salvia plebeia R.Br. (KGC3P), its component nepetin, and their modes of action in alleviating ovalbumin (OVA)-induced asthma in mice. METHOD: BALB/c mice were sensitized with OVA then subjected to intratracheal, intraperitoneal, and aerosol challenges. KGC3P and nepetin were administered orally for four weeks. Airway hyperresponsiveness (AHR), OVA-specific IgE levels, and Th2 cytokine- and gene expression levels in bronchoalveolar lavage fluid (BALF) and splenocytes were measured. Histological and immune cell subtype analyses were performed. PTEN and Akt phosphorylation levels were also evaluated. RESULTS: KGC3P reduced OVA-induced AHR, serum IgE levels, histological changes, and eosinophils infiltration but also the absolute number of immune cell subtypes including CD3+/CD4+, CD3+/CD8+, CD4+/CD69+, and Gr-1+/CD11b+ in the lungs, BALF, and mesenteric lymph nodes (MLN). KGC3P also lowered the Th2 cytokines IL-4, IL-5, and IL-13 in the BALF and splenocytes and downregulated the IL-4, IL-13, IL-17, TNF-α, and MUC5AC genes in the lung. KGC3P upregulated the peroxisome proliferator-activated receptor (PPAR)γ gene but downregulated the p-Akt and p-PTEN phosphorylation. Similar results were obtained with nepetin treatment. CONCLUSION: KGC3P and nepetin are anti-asthmatic because they reduce various immune cells such as eosinophils and Th2 cell as well as Th2 cytokines. These mechanisms may be accompanied by the regulation of PPARγ expression and the PTEN pathway. Taken together, our results indicate that KGC3P and nepetin may potentially prevent and treat asthma.

In situ analysis of chemical components induced by steaming between fresh ginseng, steamed ginseng, and red ginseng.

BACKGROUND: The chemical constituents of Panax ginseng are changed by processing methods such as steaming or sun drying. In the present study, the chemical change of Panax ginseng induced by steaming was monitored in situ. METHODS: Samples were separated from the same ginseng root by incision during the steaming process, for in situ monitoring. Sampling was sequentially performed in three stages; FG (fresh ginseng) → SG (steamed ginseng) → RG (red ginseng) and 60 samples were prepared and freeze dried. The samples were then analyzed to determine 43 constituents among three stages of P. ginseng. RESULTS: The results showed that six malonyl-ginsenoside (Rg1, Rb1, Rb3, Rc, Rd, Rb2) and 15 amino acids were decreased in concentration during the steaming process. In contrast, ginsenoside-Rh1, 20(S)-Rg2, 20(S, R)-Rg3 and Maillard reaction product such as AF (arginine-fructose), AFG (arginine-fructose-glucose), and maltol were newly generated or their concentrations were increased. CONCLUSION: This study elucidates the dynamic changes in the chemical components of P. ginseng when the steaming process was induced. These results are thought to be helpful for quality control and standardization of herbal drugs using P. ginseng and they also provide a scientific basis for pharmacological research of processed ginseng (Red ginseng).

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.

Korean red ginseng extract rejuvenates testicular ineffectiveness and sperm maturation process in aged rats by regulating redox proteins and oxidative defense mechanisms.

Distortion of intracellular oxidant and antioxidant balances appears to be a common feature that underlies in age-related male sexual impairment. Therefore regulating oxidative defense mechanisms might be an ideal approach in improving male sexual dysfunctions. In the present study, the effect of Korean red ginseng aqueous extract (KRG) on age-induced testicular dysfunction in rats was investigated. KRG (200mg/kg) mixed with regular pellet diet was administered orally for six months and the morphological, spermatogenic and antioxidant enzyme status in testis of aged rats (18months) were evaluated. Data indicated a significant change in morphology and decrease in spermatogenesis-related parameters in aged rats (AC) compared with young rats (YC). Sperm number, germ cell count, Sertoli cell count and Sertoli cell index were significantly (p<0.05) restored in KRG-treated aged rat groups (G-AC). Further the increased lipid peroxidation as measured by malondialdehyde (p<0.05), and altered enzymatic (superoxide dismutase, glutathione peroxidase, glutathione S-transferase, glutathione reductase and catalase) and non-enzymatic (reduced glutathione, ascorbic acid and α-tocopherol) antioxidants (p<0.05) were attenuated by KRG treatment in aged rats to near normal levels as in YC groups. Furthermore, proteomic analysis demonstrated differential expression of selected proteins such as phosphatidylinositol transfer protein, fatty acid binding protein-9, triosephosphate isomerase-1 and aldehyde (aldose) reductase-1in aged rats was significantly (p<0.05) protected by KRG treatment. In conclusion, long-term administration of KRG restored aging-induced testicular ineffectiveness in rats by modulating redox proteins and oxidative defense mechanisms.

Safety Analysis of Panax Ginseng in Randomized Clinical Trials: A Systematic Review.

Background:Panax ginseng C.A. Meyer is one of the most frequently used herbs in the world. The roots of Panax ginseng have been used as a traditional tonic and medicine for thousands of years in Korea and China. Today, ginseng root is used as a dietary supplement and complementary medicine and for adjuvant therapeutics worldwide. The efficacy of ginseng has been studied in a wide range of basic research and clinical studies. However, it has been reported that the results from clinical studies are conflicting, and they depend on the parameters of the protocol design including the conditions of the participants and the types of ginseng used such as red ginseng, white ginseng, fermented ginseng and cultured ginseng. [...].

Antithrombotic activities of epi-sesamin in vitro and in vivo.

Sesamin (SM) and epi-sesamin (ESM) were isolated from Asarum sieboldii and their anticoagulant activities were examined by monitoring activated partial thromboplastin time (aPTT), prothrombin time (PT), and the activities of cell-based thrombin and activated factor X (FXa). In addition, the effects of SM and ESM on the expression of plasminogen activator inhibitor type 1 (PAI-1) and tissue-type plasminogen activator (t-PA) were tested in tumor necrosis factor-α (TNF-α) activated human umbilical vein endothelial cells (HUVECs). Treatment with ESM, but not SM, resulted in significantly prolonged aPTT and PT and inhibition of the activities of thrombin and FXa, and ESM inhibited production of thrombin and FXa in HUVECs; and ESM inhibited thrombin-catalyzed fibrin polymerization and platelet aggregation. In accordance with these anticoagulant activities, ESM elicited anticoagulant effects in mice. In addition, treatment with ESM, but not SM, resulted in the inhibition of TNF-α-induced production of PAI-1, and treatment with ESM resulted in a significant reduction of the PAI-1 to t-PA ratio. Of particular interest, inhibition of the anticoagulant activity by ESM was more potent than that by SM, likely due to differences between their three-dimensional structures. Collectively, ESM possesses antithrombotic activities and offers a basis for the development of a novel anticoagulant.

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)).

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.

SK-PC-B70M from Pulsatilla koreana improves scopolamine-induced impairments of memory consolidation and spatial working memory.

Previous studies have shown that hederacolchiside-E from Pulsatilla koreana has neuroprotective effects and cognition-enhancing effects. Subsequently, in the current study, we demonstrate that oral administrations of oleanolic-glycoside saponins enriched fraction from P. koreana, designated as SK-PC-B70M, improve impairments in memory consolidation and spatial working memory by systemic injection of scopolamine, a muscarinic cholinergic receptor antagonist. In a step-through avoidance task, when the rats stepped through a dark chamber in a shuttle box, an electric shock was given and then SK-PC-B70M was administered 30 min later. Twenty-four hours later, the rats were placed in an illuminated chamber. The rats with SK-PC-B70M treatments showed longer response latencies than rats with only scopolamine. Spatial working memory was measured with a trial-unique matching-to-place task in a water maze which assessed memory for place information over varying lengths of delays. Three delay lengths were used: 1 min, 5 min, and 3 h. In comparison with the control rats, the rats with scopolamine treatments took significantly longer to find the platform in the second trial with 1- and 5-min delays. The rats with both scopolamine and SK-PC-B70M had significantly less search error compared with the rats with scopolamine only. These findings indicate that SK-PC-B70M has effects on reversing impairments of memory consolidation and working memory impairments induced by scopolamine.

Cognition-enhancing and neuroprotective effects of hederacolchiside-E from Pulsatilla koreana.

The root extract of Pulsatilla koreana (Ranunculaceae) has been found to have prominent abilities to reverse scopolamine-induced cognitive impairment in rats, and to increase the viability of human neuroblastoma SK-N-SH cells incubated with amyloid-beta peptide (1 - 42) [A beta (1 - 42)]. In vivo and in vitro activity-guided fractionation studies using solvent-partitioning and subsequent chromatographic separations led to the isolation of hederacolchiside-E, an oleanolic glycoside, as an active ingredient. Administration of hederacolchiside-E (30 and 60 mg/kg body weight, P. O.) increased the step-through latency time in the passive avoidance test as efficiently as tacrine (30 mg/kg, P. O.). The neuroprotective effect of hederacolchiside-E on SK-N-SH cells against the toxicity of A beta (1 - 42) was comparable to that of catechin. These data suggest that hederacolchiside-E might be a good therapeutic candidate for the treatment of Alzheimer's disease.