Kyungha Shin

Nattokinase improves blood flow by inhibiting platelet aggregation and thrombus formation

The effects of nattokinase on the in vitro platelet aggregation and in vivo thrombosis were investigated in comparison with aspirin. Rabbit platelet-rich plasma was incubated with nattokinase and aggregation inducers collagen and thrombin, and the platelet aggregation rate was analyzed. Nattokinase significantly inhibited both the collagen- and thrombin-induced platelet aggregations. Nattokinase also reduced thromboxane B2 formation from collagen-activated platelets in a concentration-dependent manner. Rats were orally administered with nattokinase for 1 week, and their carotid arteries were exposed. Arterial thrombosis was induced by applying 35% FeCl3-soaked filter paper for 10 min, and the blood flow was monitored with a laser Doppler probe. Nattokinase delayed the FeCl3-induced arterial occlusion in a dose-dependent manner, doubling the occlusion time at 160 mg/kg. In addition, a high dose (500 mg/kg) of nattokinase fully prevented the occlusion, as achieved with aspirin (30 mg/kg). The results indicate that nattokinase extracted from fermented soybean inhibit platelet aggregation by blocking thromboxane formation, and thereby delay thrombosis following oxidative arterial wall injury. Therefore, it is suggested that nattokinase could be a good candidate without adverse effects for the improvement of blood flow.

Perilla oil improves blood flow through inhibition of platelet aggregation and thrombus formation.

The inhibitory effects of perilla oil on the platelet aggregation in vitro and thrombosis in vivo were investigated in comparison with aspirin, a well-known blood flow enhancer. Rabbit platelet-rich plasma was incubated with perilla oil and aggregation inducers collagen or thrombin, and the platelet aggregation rate was analyzed. Perilla oil significantly inhibited both the collagen- and thrombin-induced platelet aggregations, in which the thromboxane B2 formation from collagen-activated platelets were reduced in a concentration-dependent manner. Rats were administered once daily by gavage with perilla oil for 1 week, carotid arterial thrombosis was induced by applying 35% FeCl3-soaked filter paper for 10 min, and the blood flow was monitored with a laser Doppler probe. Perilla oil delayed the FeCl3-induced arterial occlusion in a dose-dependent manner, doubling the occlusion time at 0.5 mL/kg. In addition, a high dose (2 mL/kg) of perilla oil greatly prevented the occlusion, comparable to the effect of aspirin (30 mg/kg). The results indicate that perilla oil inhibit platelet aggregation by blocking thromboxane formation, and thereby delay thrombosis following oxidative arterial wall injury. Therefore, it is proposed that perilla oil could be a good candidate without adverse effects for the improvement of blood flow.

Health Span-Extending Activity of Human Amniotic Membrane- and Adipose Tissue-Derived Stem Cells in F344 Rats

Aging brings about the progressive decline in cognitive function and physical activity, along with losses of stem cell population and function. Although transplantation of muscle‐derived stem/progenitor cells extended the health span and life span of progeria mice, such effects in normal animals were not confirmed. Human amniotic membrane‐derived mesenchymal stem cells (AMMSCs) or adipose tissue‐derived mesenchymal stem cells (ADMSCs) (1 × 106 cells per rat) were intravenously transplanted to 10‐month‐old male F344 rats once a month throughout their lives. Transplantation of AMMSCs and ADMSCs improved cognitive and physical functions of naturally aging rats, extending life span by 23.4% and 31.3%, respectively. The stem cell therapy increased the concentration of acetylcholine and recovered neurotrophic factors in the brain and muscles, leading to restoration of microtubule‐associated protein 2, cholinergic and dopaminergic nervous systems, microvessels, muscle mass, and antioxidative capacity. The results indicate that repeated transplantation of AMMSCs and ADMSCs elongate both health span and life span, which could be a starting point for antiaging or rejuvenation effects of allogeneic or autologous stem cells with minimum immune rejection.

Comparative Effects of Human Neural Stem Cells and Oligodendrocyte Progenitor Cells on the Neurobehavioral Disorders of Experimental Autoimmune Encephalomyelitis Mice

Since multiple sclerosis (MS) is featured with widespread demyelination caused by autoimmune response, we investigated the recovery effects of F3.olig2 progenitors, established by transducing human neural stem cells (F3 NSCs) with Olig2 transcription factor, in myelin oligodendrocyte glycoprotein- (MOG-) induced experimental autoimmune encephalomyelitis (EAE) model mice. Six days after EAE induction, F3 or F3.olig2 cells (1 × 106/mouse) were intravenously transplanted. MOG-injected mice displayed severe neurobehavioral deficits which were remarkably attenuated and restored by cell transplantation, in which F3.olig2 cells were superior to its parental F3 cells. Transplanted cells migrated to the injured spinal cord, matured to oligodendrocytes, and produced myelin basic proteins (MBP). The F3.olig2 cells expressed growth and neurotrophic factors including brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), ciliary neurotrophic factor (CNTF), and leukemia inhibitory factor (LIF). In addition, the transplanted cells markedly attenuated inflammatory cell infiltration, reduced cytokine levels in the spinal cord and lymph nodes, and protected host myelins. The results indicate that F3.olig2 cells restore neurobehavioral symptoms of EAE mice by regulating autoimmune inflammatory responses as well as by stimulating remyelination and that F3.olig2 progenitors could be a candidate for the cell therapy of demyelinating diseases including MS.

Protective Effects of N-Acetyl-L-Cysteine in Human Oligodendrocyte Progenitor Cells and Restoration of Motor Function in Neonatal Rats with Hypoxic-Ischemic Encephalopathy

Objective. Since oligodendrocyte progenitor cells (OPCs) are the target cells of neonatal hypoxic-ischemic encephalopathy (HIE), the present study was aimed at investigating the protective effects of N-acetyl-l-cysteine (NAC), a well-known antioxidant and precursor of glutathione, in OPCs as well as in neonatal rats. Methods. In in vitro study, protective effects of NAC on KCN cytotoxicity in F3.Olig2 OPCs were investigated via MTT assay and apoptotic signal analysis. In in vivo study, NAC was administered to rats with HIE induced by hypoxia-ischemia surgery at postnatal day 7, and their motor functions and white matter demyelination were analyzed. Results. NAC decreased KCN cytotoxicity in F3.Olig2 cells and especially suppressed apoptosis by regulating Bcl2 and p-ERK. Administration of NAC recovered motor functions such as the using ratio of forelimb contralateral to the injured brain, locomotor activity, and rotarod performance of neonatal HIE animals. It was also confirmed that NAC attenuated demyelination in the corpus callosum, a white matter region vulnerable to HIE. Conclusion. The results indicate that NAC exerts neuroprotective effects in vitro and in vivo by preserving OPCs, via regulation of antiapoptotic signaling, and that F3.Olig2 human OPCs could be a good tool for screening of candidates for demyelinating diseases.

Effectiveness of the combinational treatment of Laminaria japonica and Cistanche tubulosa extracts in hair growth

Since scalp hair loss has increased recently even in young people, seriously affecting individuals quality of life, the hair growth-stimulating effects of Laminaria japonica extract (LJE) and Cistanche tubulosa extract (CTE) were investigated. After confirming anagen phase of follicles under shaving, male C57BL/6 mice were dermally applied with 3% Minoxidil or orally administered with the combinations of LJE and CTE for 21 days. Minoxidil promoted the hair regrowth and increased γ-glutamyl transpeptidase (γ-GTP) and alkaline phosphatase (ALP) activities. In addition, Minoxidil up-regulated epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) levels. Co-administration of LJE and CTE at 54 mg/kg LJE plus 162 mg/kg CTE exerted synergistic promoting effects on the hair regrowth, comparable to 3% Minoxidil. LJE preferentially enhanced ALP activity, while CTE increased both γ-GTP and ALP activities as well as EGF and VEGF expressions. In vivo air pouch inflammation model, carrageenan-induced vascular exudation and increased nitric oxide and prostaglandin E2 concentrations in the exudates were synergistically suppressed by co-administration of LJE and CTE. In addition, inflammatory cell infiltration was substantially inhibited by the combinational treatment. The results suggest that combinational oral treatment with LJE and CTE in appropriate doses and ratios prevent hair loss and improve alopecia, which might be in part mediated by their anti-inflammatory activities.

Anti-Helicobacter pylori activities of FEMY-R7 composed of fucoidan and evening primrose extract in mice and humans

Helicobacter pylori-eliminating effects of FEMY-R7, composed of fucoidan and evening primrose extract, were investigated in mice and humans. Male C57BL/6 mice were infected with the bacteria by intragastric inoculation (1×109 CFU/mouse) 3 times at 2-day intervals, and simultaneously, orally treated twice a day with 10 or 100 mg/kg FEMY-R7 for 2 weeks. In Campylobcter-like organism-detection test, FEMY-R7 markedly reduced the urease-positive reactivity. In a clinical sudy, human subjects, confirmed to be infected with Helicobacter pylori, were orally administered twice a day with a capsule containing 150 mg FEMY-R7 for 8 weeks. FEMY-R7 significantly decreased both the Delta over baseline-value in urea breath test and the serum pepsinogens I and II levels. The results indicate that FEMY-R7 not only eliminates H. pylori from gastric mucosa of animals and humans, but also improves gastric function.

In vitro and in vivo anti-Helicobacter pylori activities of FEMY-R7 composed of fucoidan and evening primrose extract

[This corrects the article on p. 28 in vol. 30, PMID: 24707302.].

Comparative effects of plant oils on the cerebral hemorrhage in stroke-prone spontaneously hypertensive rats

Objectives: Since oils and fats can induce metabolic syndrome, leading to cardiovascular and cerebrovascular diseases, the present study was performed to find out whether the plant oils affect the cerebral hemorrhage in stroke-prone spontaneously hypertensive (SHR-SP) rats. Methods: From 47 days of age, male SHR-SP rats were given drinking water containing 1% NaCl to induce hypertension, and simultaneously fed semi-purified diets containing 10% perilla oil, canola oil, or shortening. The onset time of convulsion following cerebral hemorrhage was recorded, and the areas of hemorrhage and infarction were analyzed in the stroke brains. Results: In comparison with 58-day survival of SHR-SP rats during feeding NaCl alone, perilla oil extended the survival time to 68.5 days, whereas canola oil shortened it to 45.7 days. Feeding perilla oil greatly reduced the total volume of cerebral hemorrhage from 17.27% in the control group to 4.53%, while shortening increased the lesions to 21.23%. In a microscopic analysis, perilla oil also markedly decreased the hemorrhagic and infarction lesions to 1/10 of those in control rats, in contrast to an exacerbating effect of shortening. In blood analyses, perilla oil reduced blood total cholesterol and low-density lipoproteins which were increased in SHR-SP, but canola oil further increased them and markedly lowered platelet counts. Discussion: Perilla oil delayed and attenuated cerebral hemorrhage by improving hyperlipidemia in hypertensive stroke animals, in contrast to the aggravating potential of canola oil and shortening. It is suggested that perilla oil should be the first choice oil for improving metabolic syndrome in hypertensive persons at risk of hemorrhagic stroke.

Extraction conditions of white rose petals for the inhibition of enzymes related to skin aging

In order to assess inhibitory potentials of white rose petal extracts (WRPE) on the activities of enzymes related to dermal aging according to the extraction conditions, three extraction methods were adopted. WRPE was prepared by extracting dried white rose (Rosa hybrida) petals with 50% ethanol (WRPE-EtOH), Pectinex® SMASH XXL enzyme (WRPE-enzyme) or high temperature-high pressure (WRPE-HTHP). In the inhibition of matrix metalloproteinase-1, although the enzyme activity was fully inhibited by all 3 extracts at 100 µg/mL in 60 min, partial inhibition (50-70%) was achieved only by WRPE-EtOH and WRPE-enzyme at 50 µg/mL. High concentrations (≥250 µg/mL) of all 3 extracts markedly inhibited the elastase activity. However, at low concentrations (15.6-125 µg/mL), only WRPE-EtOH inhibited the enzyme activity. Notably, WRPE-EtOH was superior to WRPE-enzyme and WRPE-HTHP in the inhibition of tyrosinase. WRPE-EtOH significantly inhibited the enzyme activity from 31.2 µM, reaching 80% inhibition at 125 µM. In addition to its strong antioxidative activity, the ethanol extract of white rose petals was confirmed to be effective in inhibiting skin aging-related enzymes. Therefore, it is suggested that WRPE-EtOH could be a good candidate for the improvement of skin aging such as wrinkle formation and pigmentation.