Gintonin absorption in intestinal model systems Lee, Byung-Hwan; Choi, Sun-Hye; Kim, Hyeon-Joong ...
Journal of Ginseng Research/Journal of ginseng research,
01/2018, Volume:
42, Issue:
1
Journal Article
Peer reviewed
Open access
Recently, we identified a novel ginseng-derived lysophosphatidic acid receptor ligand, called gintonin. We showed that gintonin induces Ca2+i transient-mediated morphological changes, proliferation, ...and migration in cells expressing lysophosphatidic acid receptors and that oral administration of gintonin exhibits anti-Alzheimer disease effects in model mice. However, little is known about the intestinal absorption of gintonin. The aim of this study was to investigate gintonin absorption using two model systems.
Gintonin membrane permeation was examined using a parallel artificial membrane permeation assay, and gintonin absorption was evaluated in a mouse everted intestinal sac model.
The parallel artificial membrane permeation assay showed that gintonin could permeate an artificial membrane in a dose-dependent manner. In the everted sac model, gintonin absorption increased with incubation time (from 0 min to 60 min), followed by a decrease in absorption. Gintonin absorption into everted sacs was also dose dependent, with a nonlinear correlation between gintonin absorption and concentration at 0.1–3 mg/mL and saturation at 3–5 mg/mL. Gintonin absorption was inhibited by the Rho kinase inhibitor Y-27632 and the sodium–glucose transporter inhibitor phloridzin. Moreover, lipid extraction with methanol also attenuated gintonin absorption, suggesting the importance of the lipid portion of gintonin in absorption. This result shows that gintonin might be absorbed through passive diffusion, paracellular, and active transport pathways.
The present study shows that gintonin could be absorbed in the intestine through transcellular and paracellular diffusion, and active transport. In addition, the lipid component of gintonin might play a key role in its intestinal absorption.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Ginseng exhibits beneficial effects on GABAA receptor-related anxiety and sleep disorders. However, little is known regarding the cellular and molecular bases of the ginseng action on GABAA receptor. ...The present study was performed to elucidate the molecular mechanism of the ginseng effect on GABAA receptor. The effect of ginsenoside Rg3 (Rg3), one of the active ingredients of ginseng, on γ-aminobutyric acid (GABA)A receptor channel activity was examined in Xenopus oocytes using two-electrode voltage-clamp technique. Rg3 itself evoked an inward current in Xenopus oocytes expressing GABAA receptor subunits (α1β1γ2) and the Rg3 itself-elicited inward current was only selective to γ2 subunit expression ratio, since Rg3 alone had no effects in oocytes expressing other subunits such as γ1, γ3, δ, or ε. Co-treatment of Rg3 with GABA enhanced GABA receptor (α1β1γ2)-mediated inward currents (IGABA) but Rg3-mediated IGABA enhancement was independent on γ2. Rg3 itself-elicited inward current was blocked by GABAA receptor antagonist. The present results indicate that Rg3-induced GABAA receptor activation via the γ2 subunit and IGABA enhancement by Rg3 might be one of the molecular bases of ginseng effects on GABAA receptor.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
33.
Can Bassett’s ligament be removed? Yeo, Eui Dong; Rhyu, Im Joo; Kim, Hak Jun ...
Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA,
04/2016, Volume:
24, Issue:
4
Journal Article
Peer reviewed
Purpose
To investigate the functional characteristics of Bassett’s ligament in the ankle, focusing on mechanoreceptors and potential problems following resection of Bassett’s ligament.
Methods
...Bassett’s ligament, the anterior talofibular ligament (ATFL), and synovium were obtained from 20 ankles of 10 fresh-frozen cadavers. Histologically, mechanoreceptors were identified and classified as Ruffini (type I), Vater–Pacini (type II), Golgi–Mazzoni (type III) corpuscles, and free nerve endings (type IV). Differences in receptor densities were compared.
Results
Type I clusters were observed with three to six ramifications; type II mechanoreceptors were encapsulated in clusters of two to four with ovoid or cylindrical shape; type III were amorphous, long and wide, and fusiform- or spindle-shaped; and type IV were long and fine without a defined shape. Differences in the densities of the mechanoreceptors inside three soft tissues (Bassett’s ligament, ATFL, and synovium) were not significant.
Conclusion
There were no significant differences in the densities of the four types of mechanoreceptors among the soft tissues studied. In Bassett’s ligament, type I mechanoreceptors were present at significantly higher densities than the other receptors.
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EMUNI, FSPLJ, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UL, UM, UPUK, VKSCE, ZAGLJ
Gintonin is a newly discovered ingredient of ginseng and plays an exogenous ligand for G protein-coupled lysophosphatidic acid receptors. We previously showed that gintonin exhibits diverse effects ...from neurotransmitter release to improvement of Alzheimer's disease-related cognitive dysfunctions. However, previous studies did not show whether gintonin has protective effects against environmental heavy metal. We investigated the effects of gintonin-enriched fraction (GEF) on methylmercury (MeHg)-induced neurotoxicity and learning and memory dysfunction and on organ MeHg elimination. Using hippocampal neural progenitor cells (hNPCs) and mice we examined the effects of GEF on MeHg-induced hippocampal NPC neurotoxicity, on formation of reactive oxygen species (ROS), and on in vivo learning and memory functions after acute MeHg exposure. Treatment of GEF to hNPCs attenuated MeHg-induced neurotoxicity with concentration- and time-dependent manner. GEF treatment inhibited MeHg- and ROS inducer-induced ROS formations. Long-term treatment of GEF also improved MeHg-induced learning and memory dysfunctions. Oral administration of GEF decreased the concentrations of MeHg in blood, brain, liver, and kidney. This is the first report that GEF attenuated MeHg-induced in vitro and in vivo neurotoxicities through LPA (lysophosphatidic acids) receptor-independent manner and increased organ MeHg elimination. GEF-mediated neuroprotection might achieve via inhibition of ROS formation and facilitation of MeHg elimination from body.
Synthesizing facial wrinkles has been tackled either by a long process of manual sculpting on 3D models, or using automatic methods that do not allow for user interaction or artistic expression. In ...this paper, we propose a method that accepts interactive sketchy drawings depicting wrinkle patterns, and synthesizes realistic looking wrinkles on faces. The method inherits the simplicity of sketching, making it possible for artists as well as novice users to generate realistic facial detail very efficiently, allowing fast preview for physical makeup, or aging simulations for fun and professional applications. All strokes are used to infer the wrinkles, retaining the expressiveness of the sketches and realism of the final result at the same time. This is achieved by designing novel multi‐scale statistics tailored to the wrinkle geometry and coupled to the sketch interpretation method. The statistics capture the cross‐sectional profiles of wrinkles at different scales and parts of a face. The strokes are augmented with the statistics extracted from given example face models, and applied to an input face model interactively. The interface gives the user control over the shapes and scales of wrinkles via sketching while adding extra details required for realism automatically.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
The formation of biofilms on the enamel surface of teeth by
Streptococcus
mutans
is an important step in dental plaque formation,
demineralization, and early caries because the biofilm is where other ...bacteria
involved in dental caries attach, grow, and proliferate. The objectives of this
study were to determine the effect of phosvitin (PSV) on the biofilm formation,
exopolysaccharides (EPS) production, adherence activity of
S.
mutans
, and the expression of genes related to the compounds
essential for biofilm formation (quorum-sensing inducers and components of
biofilm matrix) by
S. mutans
. PSV significantly reduced the
biofilm-forming activity of
S. mutans
and increased the
degradation of preformed biofilms by
S. mutans
. PSV inhibited
the adherence activity of
S. mutans
by
31.9%–33.6%, and the production of EPS by
62%–65% depending upon the strains and the amount of PSV
added. The expressions of genes regulating the production of EPS and the
quorum-sensing-inducers (
gtfA, gtfD, ftf, relA, vicR, brpA
, and
comDE
) in all
S. mutans
strains were
down-regulated by PSV, but
gtfB
was down-regulated only in
S. mutans
KCTC 5316. Therefore, the anti-biofilm-forming
activity of PSV was accomplished through the inhibition of biofilm formation,
adherence activity, and the production of quorum-sensing inducers and EPS by
S. mutans
.
•Gαq/11 protein-coupled receptor-mediated Ca2+i transients of astrocytes are coupled to release of gliotransmitters.•Gintonin treatment to astrocytes activates Ca2+i transients pathway via LPA ...receptor activation.•Gintonin-mediated Ca2+i transients are coupled to release of ATP and glutamate.•Gintonin regulates gliotransmitter release via LPA receptor activation in primary astrocytes.
Lysophosphatidic acid (LPA) is a simple and minor phospholipid, but serves as a lipid-derived neurotransmitter via activation of G protein-coupled LPA receptors. Astrocytes abundantly express LPA receptors and contain gliotransmitters that modulate astrocyte-neuron interactions. Gintonin is a novel ginseng-derived G protein-coupled LPA receptor ligand. Gintonin induces Ca2+i transients in neuronal and non-neuronal cells via activation of LPA receptors, which regulate calcium-dependent ion channels and receptors. A line of evidence shows that neurotransmitter-mediated Ca2+i elevations in astrocytes are coupled with gliotransmitter release. However, little is known about whether gintonin-mediated Ca2+i transients are coupled to gliotransmitter release in astrocytes. In the present study, we examined the effects of gintonin on adenosine triphosphate (ATP) and glutamate release in mouse cortical primary astrocytes. Application of gintonin to astrocytes induced Ca2+i transients in a concentration-dependent and reversible manner. However, ginsenosides, other active ingredients in ginseng, had no effect on Ca2+i transients. The induction of gintonin-mediated Ca2+i transients was attenuated/blocked by the LPA1/3 receptor antagonist Ki16425, a phospholipase C inhibitor, an inositol 1,4,5-triphosphate receptor antagonist, and an intracellular Ca2+ chelator. Gintonin treatment on astrocytes increased ATP and glutamate release in a concentration- and time-dependent manner. BAPTA and Ki16425 attenuated gintonin-mediated ATP and glutamate release in astrocytes. The present study shows that gintonin-mediated Ca2+i transients are coupled to gliotransmitter release via LPA receptor activation. Finally, gintonin-mediated Ca2+i transients and gliotransmitter release from astrocytes via LPA receptor activation might explain one mechanism of gintonin-mediated neuromodulation in the central nervous system.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Ginseng has been used as a tonic for invigoration of the human body. In a previous report, we identified a novel candidate responsible for the tonic role of ginseng, designated gintonin. Gintonin ...induces Ca2+i transient in animal cells via lysophosphatidic acid receptor activation. Gintonin-mediated Ca2+i transient is linked to anti-Alzheimer's activity in transgenic Alzheimer's disease animal model. The previous method for gintonin preparation included multiple steps. The aim of this study is to develop a simple method of gintonin fraction with a high yield.
We developed a brief method to obtain gintonin using ethanol and water. We extracted ginseng with fermentation ethanol and fractionated the extract with water to obtain water-soluble and water-insoluble fractions. The water-insoluble precipitate, rather than the water-soluble supernatant, induced a large Ca2+i transient in primary astrocytes. We designated this fraction as gintonin-enriched fraction (GEF).
The yield of GEF was approximately 6-fold higher than that obtained in the previous gintonin preparation method. The apparent molecular weight of GEF, determined using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, was equivalent to that obtained in the previous gintonin preparation method. GEF induced Ca2+i transient in cortical astrocytes. The effective dose (ED50) was 0.3 ± 0.09 μg/mL. GEF used the same signal transduction pathway as gintonin during Ca2+i transient induction in mouse cortical astrocytes.
Because GEF can be prepared through water precipitation of ginseng ethanol extract and is easily reproducible with high yield, it could be commercially utilized for the development of gintonin-derived functional health food and natural medicine.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Ovotransferrin (OTF), an egg protein known as transferrin family protein, possess strong antimicrobial and antioxidant activity. This is because OTF has two iron binding sites, so it has a strong ...metal chelating ability. The present study aimed to evaluate the improved immune-enhancing activities of OTF hydrolysates produced using bromelain, pancreatin, and papain. The effects of OTF hydrolysates on the production and secretion of pro-inflammatory mediators in RAW 264.7 macrophages were confirmed. The production of nitric oxide (NO) was evaluated using Griess reagent and the expression of inducible nitric oxide synthase (iNOS) were evaluated using quantitative real-time polymerase chain reaction (PCR). And the production of pro-inflammatory cytokines (tumor necrosis factor TNF-α and interleukin IL-6) and the phagocytic activity of macrophages were evaluated using an ELISA assay and neutral red uptake assay, respectively. All OTF hydrolysates enhanced NO production by increasing iNOS mRNA expression. Treating RAW 264.7 macrophages with OTF hydrolysates increased the production of pro-inflammatory cytokines and the phagocytic activity. The production of NO and pro-inflammatory cytokines induced by OTF hydrolysates was inhibited by the addition of specific mitogen-activated protein kinase (MAPK) inhibitors. In conclusion, results indicated that all OTF hydrolysates activated RAW 264.7 macrophages by activating MAPK signaling pathway.
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