[Show abstract][Hide abstract] ABSTRACT: Ginseng has been used as a tonic for invigoration of 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 (LPA) receptor activation. Gintonin-mediated [Ca2+]i transient is linked to anti-Alzheimer’s disease 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.
Preview · Article · Jun 2015 · Journal of ginseng research
[Show abstract][Hide abstract] ABSTRACT: Objectives:
Fatigue is common in Parkinson's disease (PD), causing serious negative effects on quality of life. Despite its clinical importance, the nature of fatigue in PD is poorly understood because its underlying neurobiology is unknown. Fatigue can be more complicated in advanced PD because of its chronicity. In order to find features that are innate to fatigue in PD, it would be useful to conduct a study looking at de novo PD. Assessing fatigue in de novo patients allows excluding at least one confounding factor.
We prospectively investigated 87 drug-naïve PD patients. Thirty-nine patients (44.8%) were found to have fatigue around the time of diagnosis of PD.
We found that depression and difficulties with activities of daily living were independent risk factors for fatigue; however, motor dysfunction was not related. Clinically meaningful responses to dopaminergic medication were observed.
Our study determined that fatigue occurs in the early stages of PD. It can inform clinical decision-making to significantly benefit PD patients with fatigue.
No preview · Article · Jun 2013 · European Neurology
[Show abstract][Hide abstract] ABSTRACT: Ginseng has been used for cancer prevention. However, little is known about its active components and the molecular mechanisms underlying its effects. Recently, we isolated a unique lysophosphatidic acid (LPA) receptor ligand, gintonin. Gintonin contains approximately 9.5% LPA, mainly LPA C18:2. Autotaxin (ATX) is responsible for metastasis by overproducing LPA in cancers. However, LPA, particularly LPA C18:2, is a strong negative feedback ATX inhibitor. It is unknown whether gintonin inhibits ATX activity and whether gintonin‑induced ATX inhibition is coupled with antimetastatic activity. In this study, we examined whether gintonin and LPA C18:2 inhibit ATX activity and metastasis‑related cellular activities in melanoma cells. We found that gintonin and LPA C18:2 inhibited the purified and secreted ATX activity from melanoma cells in a concentration‑dependent manner. Gintonin also inhibited cell migration with a minimal inhibition of cell growth. The oral administration of gintonin or LPA C18:2 inhibited lung metastasis induced by tail‑vein inoculations of melanoma cells. Moreover, the oral administration of gintonin significantly suppressed the tumor growth induced by subcutaneous grafts of melanoma cells. A histological analysis showed that the oral administration of gintonin reduced tumor necrosis, the pleomorphism of tumor cells, tumor cell mitosis and angiogenesis. The present study demonstrates that the gintonin‑induced inhibition of ATX activity may be the molecular basis of ginseng‑induced antimetastatic and antitumor activities.
No preview · Article · Nov 2012 · International Journal of Oncology
[Show abstract][Hide abstract] ABSTRACT: Ginseng extracts show cognition-enhancing effects in Alzheimer's disease (AD) patients. However, little is known about the active components and molecular mechanisms of how ginseng exerts its effects. Recently, we isolated a novel lysophosphatidic acid (LPA) receptor-activating ligand from ginseng, gintonin. AD is caused by amyloid-β protein (Aβ) accumulation. Aβ is derived from amyloid-β protein precursors (AβPPs) through the amyloidogenic pathway. In contrast, non-amyloidogenic pathways produce beneficial, soluble AβPPα (sAβPPα). Here, we describe our investigations of the effect of gintonin on sAβPPα release, Aβ formation, Swedish-AβPP transfection-mediated neurotoxicity in SH-SY5Y neuroblastoma cells, and Aβ-induced neuropathy in mice. Gintonin promoted sAβPPα release in a concentration- and time-dependent manner. Gintonin action was also blocked by the Ca2+ chelator BAPTA, α-secretase inhibitor TAPI-2, and protein-trafficking inhibitor brefeldin. Gintonin decreased Aβ1-42 release and attenuated Aβ1-40-induced cytotoxicity in SH-SY5Y cells. Gintonin also rescued Aβ1-40-induced cognitive dysfunction in mice. Moreover, in a transgenic mouse AD model, long-term oral administration of gintonin attenuated amyloid plaque deposition as well as short- and long-term memory impairment. In the present study, we demonstrated that gintonin mediated the promotion of non-amyloidogenic processing to stimulate sAβPPα release to restore brain function in mice with AD. Gintonin could be a useful agent for AD prevention or therapy.
[Show abstract][Hide abstract] ABSTRACT: Central pontine myelinolysis (CPM) is rare demyelinating disorder characterized by loss of myelin in the center of the basis pontis. The clinical features of CPM vary depending on the involved areas. Diffusion-weighted imaging (DWI) is thought to be useful for early detection during the acute phase, but its utility in this context has not been investigated thoroughly. We report the case of a CPM patient with normal initial DWI findings even at 1 week after symptom onset. To the best of our knowledge, no such cases of CPM have previously been reported.
No preview · Article · Apr 2012 · The International journal of neuroscience
[Show abstract][Hide abstract] ABSTRACT: Recently, we isolated a subset of glycolipoproteins from Panax ginseng, that we designated gintonin, and demonstrated that it induced [Ca2+]i transients in cells via G protein-coupled receptor (GPCR) signaling pathway(s). However, active components responsible for Ca2+ mobilization and the corresponding receptor(s) were unknown. Active component(s) for [Ca2+]i transients of gintonin were analyzed by liquid chromatography-electrospray ionization-tandem mass spectrometry and ion-mobility mass spectrometry, respectively. The corresponding receptor(s)were investigated through gene expression assays. We found that gintonin contains LPA C18:2 and other LPAs. Proteomic analysis showed that ginseng major latex-like protein and ribonuclease-like storage proteins are protein components of gintonin. Gintonin induced [Ca2+]i transients in B103 rat neuroblastoma cells transfected with human LPA receptors with high affinity in order of LPA2 >LPA5 > LPA1 > LPA3 > LPA4. The LPA1/LPA3 receptor antagonist Ki16425 blocked gintonin action in cells expressing LPA1 or LPA3. Mutations of binding sites in the LPA3 receptor attenuated gintonin action. Gintonin acted via pertussis toxin (PTX)-sensitive and -insensitive G protein-phospholipase C (PLC)-inositol 1,4,5-trisphosphate (IP3)-Ca2+ pathways. However, gintonin had no effects on other receptors examined. In human umbilical vein endothelial cells (HUVECs) gintonin stimulated cell proliferation and migration. Gintonin stimulated ERK1/2 phosphorylation. PTX blocked gintonin-mediated migration and ERK1/2 phosphorylation. In PC12 cells gintonin induced morphological changes, which were blocked by Rho kinase inhibitorY-27632. Gintonin contains GPCR ligand LPAs in complexes with ginseng proteins and could be useful in the development of drugs targeting LPA receptors.
[Show abstract][Hide abstract] ABSTRACT: Ginseng, the root of Panax ginseng, is one of the oldest herbal medicines. It has a variety of physiological and pharmacological effects. Recently, we isolated a subset of glycolipoproteins that we designated gintonin, and demonstrated that it induced transient change in intracellular calcium concentration ([Ca(2+)]i) in cells via G-protein-coupled receptor signaling pathway(s). The previous method for gintonin isolation included multiple steps using methanol, butanol, and other organic solvents. In the present study, we developed a much simple method for the preparation of gintonin from ginseng root using 80% ethanol extraction. The extracted fraction was designated edible gintonin. This method produced a high yield of gintonin (0.20%). The chemical characteristics of gintonin such as molecular weight and the composition of the extract product were almost identical as the gintonin prepared using the previous extraction regimen involving various organic solvents. We also examined the physiological effects of edible gintonin on endogenous Ca(2+)-activated Cl(-) channel activity of Xenopus oocytes. The 50% effective dose was 1.03±0.3 μg/mL. Finally, since gintonin preparation through ethanol extraction is easily reproducible, gintonin could be commercially applied for ginseng-derived functional health food and/or drug following the confirmations of in vitro and in vivo physiological and pharmacological effects of gintonin.
Preview · Article · Nov 2011 · Journal of ginseng research
[Show abstract][Hide abstract] ABSTRACT: Numerous neck muscles are involved in neck movements, and so isolated neck weakness is extremely uncommon in cerebral infarction.
We report herein the case of a 65-year-old woman with hypertension and acute cortical infarction, presenting with ipsilateral head tilt and contralateral sensory changes in the neck and shoulder area, which has never been described before.
Transient neck weakness and sensory deficits can occur in acute cortical infarction. The motor representation of the neck muscles can be at the same level of the cortical sensory representation, near to the level of the trunk representation, which is in contrast to Penfield's findings. Several possible mechanisms for the ipsilateral tilt are described.
[Show abstract][Hide abstract] ABSTRACT: Ginseng has been used as a general tonic agent to invigorate the human body as an adaptogenic agent. In a previous report, we have shown that ginseng contains a novel glycolipoprotein called gintonin. The main function of gintonin is to transiently enhance intracellular free Ca(2+) [Ca(2+)]i levels in animal cells. The previous method for gintonin isolation included multiple steps using organic solvents. In the present report, we developed a simple method for the preparation of crude gintonin from ginseng root as well as stem and leaf, which produced a higher yield of gintonin than the previous one. The yield of gintonin was 0.20%, 0.29%, and 0.81% from ginseng root, stem, and leaf, respectively. The apparent molecular weight of gintonin isolated from stem and leaf through sodium dodecyl sulfate polyacrylamide gel electrophoresis was almost same as that from root but the compositions of amino acids, carbohydrates or lipids differed slightly between them. We also examined the effects of crude gintonin from ginseng root, stem, and leaf on endogenous Ca(2+)-activated Cl- channel (CaCC) activity of Xenopus oocytes through mobilization of [Ca(2+)]i. We found that the order of potency for the activation of CaCC was ginseng root > stem > leaf. The ED50 was 1.4±1.4, 4.5±5.9, and 3.9±1.1 μg/mL for root, stem and leaf, respectively. In the present study, we demonstrated for the first time that in addition to ginseng root, ginseng stem and leaf also contain gintonin. Gintonin can be prepared from a simple method with higher yield of gintonin from ginseng root, stem, and leaf. Finally, these results demonstrate the possibility that ginseng stem and leaf could also be utilized for ginstonin preparation after a simple procedure, rather than being discarded.
Preview · Article · Jun 2011 · Journal of ginseng research
[Show abstract][Hide abstract] ABSTRACT: Ginsenosides, active ingredients of Panax ginseng, are known to exhibit neuroprotective effects. Large-conductance Ca(2+)-activated K(+) (BK(Ca)) channels are key modulators of cellular excitability of neurons and vascular smooth muscle cells. In the present study, we examined the effects of ginsenosides on rat brain BK(Ca) (rSlo) channel activity heterologously expressed in Xenopus oocytes to elucidate the molecular mechanisms how ginsenoside regulates the BK(Ca) channel activity. Ginsenoside Rg(3) (Rg(3)) enhanced outward BK(Ca) channel currents. The Rg(3)-enhancement of outward BK(Ca) channel currents was concentration-dependent, voltage-dependent, and reversible. The EC(50) was 15.1 ± 3.1 μM. Rg(3) actions were not desensitized by repeated treatment. Tetraetylammonium (TEA), a K(+) channel blocker, inhibited BK(Ca) channel currents. We examined whether extracellular TEA treatment could alter the Rg(3) action and vice versa. TEA caused a rightward shift of the Rg(3) concentration-response curve (i.e., much higher concentration of Rg(3) is required for the activation of BK(Ca) channel compared to the absence of TEA), while Rg(3) caused a rightward shift of the TEA concentration-response curve in wild-type channels. Mutation of the extracellular TEA binding site Y360 to Y360I caused a rightward shift of the TEA concentration-response curve and almost abolished both the Rg(3) action and Rg(3)-induced rightward shift of TEA concentration-response curve. These results indicate that Tyr360 residue of BK(Ca) channel plays an important role in the Rg(3)-enhancement of BK(Ca) channel currents.
[Show abstract][Hide abstract] ABSTRACT: Short life expectancy influences decision-making when treating very old patients with acute ischemic stroke (AIS). We investigated mortality and survival duration in very old AIS patients (>or= 80 years) who received hospital care.
Mortality data were obtained from medical records, structured telephone inquiries, death certificates from the Korean National Statistical Office, and social security data 5+/-1.9 years after stroke onset. Age, gender, vascular risk factors, and functional outcomes from modified Rankin scales (MRS) at discharge were analyzed as predictors of mortality.
Among 134 patients, 92 (68.7%) died. On Kaplan-Meier analysis, duration of survival of patients aged 80-84 years was longer than those aged 85-89 or 90-94 (24+/-6.4, 8+/-7.3, 7+/-2.0 months, respectively, p=0.002). Duration of survival of patients discharged in a state of MRS 0-1 was longer than the remaining groups at 47+/-4.8 months (p<0.001). In Cox proportional hazard analysis, age and MRS at discharge were independent predictors of mortality.
Long-term outcomes of very old patients with AIS are not uniformly grave, therefore predictors of mortality and estimated duration of survival should be considered during decision-making for treatment.
Full-text · Article · Jun 2008 · Yonsei Medical Journal
[Show abstract][Hide abstract] ABSTRACT: Septo-optic dysplasia (SOD) is an uncommon developmental disorder involving variable midline brain structures, characterized by optic nerve hypoplasia, dysgenesis of septum pellucidum, and pituitary-hypothalamic dysfunction such as growth hormone deficiency. The phenotype is highly variable and the clinical presentation may be mild or extremely severe. Other distinct features, which occur especially when cerebral cortical abnormalities are also present (SOD-plus), consist of significant generalized developmental delay and/or spastic motor deficits. We report a case of SOD-plus with mild cortical dysplasia which was revealed to be thickening of bilateral insular cortex without schizencephaly by MRI, and there was no sign or symptom of cortical dysfunction except for one episode of brief seizure.
No preview · Article · Feb 2008 · Journal of the Neurological Sciences