• 대한한방내과학회지
• /
• 제27권3호
• /
• pp.603-616
• /
• 2006

The water extract of Gamiyaengshinhwan (GYH), has been used in vitro tests for its beneficial effects on neuronal survival and neuroprotective functions, particularly in connection with CT105-related dementias and Alzheimer's disease(AD). CT105 derived from proteolytic processing of the $\beta$-amyloid precursor protein (APP), including the amyloid-$\beta$ peptide ($A{\beta}$), plays a critical role in the pathogenesis of Alzheimer's dementia. We determined that transfected overexpressing APP695 and $A{\beta}$ CT105 have a profound attenuation in the Increase in CT105 expressing neuro2A cells from GYH. Experimental evidence indicates that GYH protects against neuronal damage from cells, but its cellular and molecular mechanisms remain unknown. Using a neuroblastoma cell line stably expressing CT105-associated neuronal degeneration, we demonstrated that GYH inhibits formation of amyloid-$\beta$ fragment ($A{\beta}$ CT105). which are the characteristic, and possibly causative, features of AD. The decreased CT105 $A{\beta}$ in the presence of GYH was observed in the conditioned medium of this CT105-secreting cell line under in vitro. In the cells, GYH significantly attenuated mitochondrion-initiated apoptosis and decreased the activity of Bax, a key enzyme in the apoptosis cell-signaling cascade. These results suggest that neuronal damage in AD might be due to two factors: a direct CT05 toxicity and the apoptosis initiated by the mitochondria. Multiple cellular and molecular neuroprotective mechanisms, including attenuation of apoptosis and direct inhibition of CT105 aggregation, underlie the neuroprotective effects of GYH.

• Molecules and Cells
• /
• 제27권4호
• /
• pp.409-416
• /
• 2009

ADAP is an AP2-domain protein that interacts with ARIA, which, in turn, interacts with ABF2, a bZIP class transcription factor. ABF2 regulates various aspects of the abscisic acid (ABA) response by controlling the expression of a subset of ABA-responsive genes. Our expression analyses indicate that ADAP is expressed in roots, emerging young leaves, and flowers. We found that adap knockout mutant lines germinate more efficiently than wild-type plants and that the mutant seedlings grow faster. This suggests that ADAP is involved in the regulation of germination and seedling growth. Both germination and post-germination growth of the knockout mutants were partially insensitive to ABA, which indicates that ADAP is required for a full ABA response. The survival rates for mutants from which water was withheld were low compared with those for wild-type plants. The result shows that ADAP is necessary for the response to stress induced by water deprivation. Together, our data indicate that ADAP is a positive regulator of the ABA response and is also involved in regulating seedling growth. The role of ADAP is similar to that of ARIA, which is also a positive regulator of the ABA response. It appears that ADAP acts through the same ABA response pathway as ARIA.

• Animal cells and systems
• /
• 제16권3호
• /
• pp.190-197
• /
• 2012

Depression is one of the most prevalent diseases of alcohol abuse. Brain-derived neurotrophic factor (BDNF) plays a critical role in cell survival in the hippocampus. Phosphorylation of extracellular signal-regulated kinase 1/2 (p-ERK1/2) is induced by BDNF, and it regulates cell proliferation and differentiation in the brain. We investigated the effects of alcohol intake on depression-like behavior, cell proliferation, expressions of BDNF and its downstream molecules in the hippocampus using Mongolian gerbils. The gerbils were divided into four groups: control group, 0.5 g/kg alcohol-treated group, 1 g/kg alcohol-treated group, 2 g/kg alcohol-treated group. Each dose of alcohol was orally administered for 3 weeks. The present results demonstrated that alcohol intake induced depression-like behavior. Both 5-hydroxytryptamine synthesis and its synthesizing enzyme tryptophan hydroxylase expression in the dorsal raphe and cell proliferation in the hippocampal dentate gyrus were decreased by alcohol intake. Alcohol intake suppressed BDNF expression, and resulted in the decrease of its downstream molecules, pERK1/2 and Bcl-2, in the hippocampus. We showed that alcohol intake may lead to a depressed-like state with reduced hippocampal cell proliferation through inhibition of the BDNF-ERK signaling pathway.

• Journal of Ginseng Research
• /
• 제43권2호
• /
• pp.218-225
• /
• 2019

Background: Streptococcus pneumoniae, more than 90 serotypes of which exist, is recognized as an etiologic agent of pneumonia, meningitis, and sepsis associated with significant morbidity and mortality worldwide. Immunization with a pneumococcal pep27 mutant (${{\Delta}}pep27$) has been shown to confer comprehensive, long-term protection against even nontypeable strains. However, ${{\Delta}}pep27$ is effective as a vaccine only after at least three rounds of immunization. Therefore, treatments capable of enhancing the efficiency of ${{\Delta}}pep27$ immunization should be identified without delay. Panax ginseng Mayer has already been shown to have pharmacological and antioxidant effects. Here, the ability of Korean Red Ginseng (KRG) to enhance the efficacy of ${{\Delta}}pep27$ immunization was investigated. Methods: Mice were treated with KRG and immunized with ${{\Delta}}pep27$ before infection with the pathogenic S. pneumoniae strain D39. Total reactive oxygen species production was measured using lung homogenates, and inducible nitric oxide (NO) synthase and antiapoptotic protein expression was determined by immunoblotting. The phagocytic activity of peritoneal macrophages was also tested after KRG treatment. Results: Compared with the other treatments, KRG significantly increased survival rate after lethal challenge and resulted in faster bacterial clearance via increased phagocytosis. Moreover, KRG enhanced ${{\Delta}}pep27$ vaccine efficacy by inhibiting reactive oxygen species production, reducing extracellular signal-regulated kinase apoptosis signaling and inflammation. Conclusion: Taken together, our results suggest that KRG reduces the time required for immunization with the ${{\Delta}}pep27$ vaccine by enhancing its efficacy.

• 한국동물생명공학회지
• /
• 제36권4호
• /
• pp.203-211
• /
• 2021

Diabetic mellitus (DM) is a carbohydrate metabolic disorder that involves high blood sugar because insulin works abnormally. Type 2 diabetes accounts for most of them. However, diabetes treatments such as GLP-1 and DPP-4 inhibitors commonly caused side effects including gastrointestinal disorders. Grifola frondosa (G. frondosa) revealed various pharmacological effects in recent studies. It has a variety of anti-cancer polysaccharides through host-mediated mechanisms. D-fraction in G. frondosa has apoptotic effects, promoting myeloid cell proliferation and differentiation into granulocytes-macrophages. It has also been shown to reduce the survival rate of breast cancer cells. Though, no further study has been conducted on the specific effects of G. frondosa in the db/db mouse. Therefore, we would like to research the blood glucose improving effect of G. frondosa, a natural material, in type 2 diabetes model mouse, in this study. G. frondosa was administered to the disease model mouse (BKS.Cg-+Lepr^db/+Lepr^db/OlaHsd) for 8 weeks to monitor weight and blood glucose changes every week. And we evaluated anti-diabetes effects by checking biomarker changes shown through blood. Experiment did not show statistically significant weight differences, but control groups showed significantly higher weight gain than G. frondosa administered groups. We collected blood from the tail veins of the db/db mouse each week. As a result, the lowest blood sugar level was shown in the 500 mg/kg group of G. frondosa. Glucose in the blood was examined with HBA1c, and 7.8% was shown in the 500 mg/kg administration group, lower than in other groups. These results suggest the potential improvements of diabetes in G. frondosa.

• Journal of Nutrition and Health
• /
• 제55권1호
• /
• pp.47-58
• /
• 2022

Purpose: Obesity and a high-fat diet (HFD) are risk factors for colorectal cancer. We have previously shown that luteolin (LUT) supplementation in HFD-fed mice markedly inhibits tumor development in chemically induced colon carcinogenesis. In this study, we evaluated the anticancer effect of LUT in the inhibition of cell proliferation in HFD-fed obese mice and HT-29 human colorectal adenocarcinoma cells grown in an adipocyte-derived medium. Methods: C57BL/6 mice were fed a normal diet (ND, 11.69% fat out of total calories consumed, n = 10), HFD (40% fat out of total calories consumed, n = 10), HFD with 0.0025% LUT (n = 10), and HFD with 0.005% LUT (n = 10) and were subjected to azoxymethane-dextran sulfate sodium chemical colon carcinogenesis. All mice were fed the experimental diet for 11 weeks. 3T3-L1 preadipocytes and HT-29 cells were treated with various doses of LUT in an adipocyte-conditioned medium (Ad-CM). Results: The weekly body weight changes in the LUT groups were similar to those in the HFD group; however, the survival rates of the LUT group were higher than those of the HFD group. Impaired crypt integrity of the colonic mucosa in the HFD group was observed to be restored in the LUT group. The colonic expression of proliferating cell nuclear antigen and insulin-like growth factor 1 (IGF-1) receptors were suppressed by the LUT supplementation in the HFD-fed mice. The LUT treatment (10, 20, and 40 µM) inhibited the proliferation and migration of HT-29 cells cultured in Ad-CM in a dose-dependent manner, as well as the differentiation of 3T3-L1 preadipocytes. Conclusion: These results suggest that the anticancer effect of LUT is probably due to the inhibition of IGF-1 signaling and adipogenesis-related cell proliferation in colon cancer cells.

• 대한본초학회지
• /
• 제37권4호
• /
• pp.39-48
• /
• 2022

Objectives : In the present study, we assessed the effects of water extract of Ulmus davidiana(UED) on the learning and memory impairments induced by scopolamine in mice through its favorable acetylcholinesterase (AChE) activity and antioxidant effect. Methods : The memory and cognitive enhancing effect of the UDE was investigated using a passive avoidance test, the Morris water maze test and Y-maze test in mice. In addition, to examine the mechanism of UDE using acetylcholinesterase (AChE) and antioxidant activity. Results : The water extract of UDE (100, and 200 mg/kg) significantly reversed the scopolamine-induced cognitive impairments in the passive avoidance test (P < 0.05). Moreover, UDE (100, and 200 mg/kg) also improved escape latencies in training trials and increased swimming times and distances within the target zone of the Morris water maze (P < 0.05). On the Y-maze test, UDE (100, and 200 mg/kg) also significantly reversed scopolamine-induced cognitive impairments in mice (P < 0.05). In an in vitro study, UDE was found to inhibit acetylcholinesterase, changes in neurotrophic factor (CREB), and antioxidant activity in a dose-dependent manner. Conclusions : The water extract of UDE dramatically possesses the anti-amnestic and cognitive-enhancing activities related to the memory processes, and these activities were parallel to treatment duration and dependent on the learning models. These results suggest that the administration of UDE enhances learning and memory, and that this effect is partially mediated by ERK-CREB-BDNF signaling and the survival of immature neurons.

• Journal of Applied Biological Chemistry
• /
• 제65권4호
• /
• pp.387-396
• /
• 2022

골격근은 체중의 약 40-50%를 차지하며 자세 유지, 연조직 지지, 체온 유지, 호흡 등 다양한 기능을 수행하는 중요한 조직이다. 전 세계적으로 광범위하게 발생하는 암은 근위축을 동반한 암 악액질을 일으켜 항암제의 효과를 떨어뜨리고 암환자의 삶의 질과 생존율을 크게 떨어뜨린다. 따라서 암 악액질을 개선하기 위한 연구가 진행 중이지만 암과 근육 위축 사이의 연관성에 관한 연구는 거의 없다. 암 세포는 종양 관련 대식세포(TAM), 종양 관련 호중구(TAN) 및 Warburg 효과로 인한 인슐린 저항성을 포함하여 독특한 미세 환경 및 대사를 나타낸다. 따라서 암세포의 미세환경과 대사적 특성, 사이토카인과 인슐린 저항성에 의해 영향을 받을 수 있는 근육 위축의 분자적 기전을 정리하였다. 또한 이는 TAM, TAN, Warburg 효과에 영향을 미치는 물질의 암 악액질 개선 가능성을 시사한다. 본 논문에서는 또한 암 악액질을 개선할 수 있는 단일 화합물 및 이들에 의해 매개되는 신호 전달 경로를 통해 지금까지 확인된 메커니즘을 정리하였다.

• Biomolecules & Therapeutics
• /
• 제31권5호
• /
• pp.484-495
• /
• 2023

Idiopathic pulmonary fibrosis (IPF) can be defined as a progressive chronic pulmonary disease showing scarring in the lung parenchyma, thereby resulting in increase in mortality and decrease in the quality of life. The pathophysiologic mechanism of fibrosis in IPF is still unclear. Repetitive microinjuries to alveolar epithelium with genetical predisposition and an abnormal restorative reaction accompanied by excessive deposition of collagens are involved in the pathogenesis. Although the two FDA-approved drugs, pirfenidone and nintedanib, are under use for retarding the decline in lung function of patients suffered from IPF, they are not able to improve the survival rate or quality of life. Therefore, a novel therapeutic agent acting on the major steps of the pathogenesis of disease and/or, at least, managing the clinical symptoms of IPF should be developed for the effective regulation of this incurable disease. In the present review, we tried to find a potential of managing the clinical symptoms of IPF by natural products derived from medicinal plants used for controlling the pulmonary inflammatory diseases in traditional Asian medicine. A multitude of natural products have been reported to exert an antifibrotic effect in vitro and in vivo through acting on the epithelial-mesenchymal transition pathway, transforming growth factor (TGF)- β-induced intracellular signaling, and the deposition of extracellular matrix. However, clinical antifibrotic efficacy of these natural products on IPF have not been elucidated yet. Thus, those effects should be proven by further examinations including the randomized clinical trials, in order to develop the ideal and optimal candidate for the therapeutics of IPF.

• Journal of Korean Neurosurgical Society
• /
• 제66권4호
• /
• pp.400-408
• /
• 2023

Objective : Nicotinamide mononucleotide adenylyl transferase 2 (NMNAT2) is a crucial factor for the survival of neuron. The role of NMNAT2 in damage following traumatic brain injury (TBI) remains unknown. This study was designed to investigate the role of NMNAT2 in TBI-induced neuronal degeneration and neurological deficits in rats. Methods : The TBI model was established in Sprague-Dawley rats by a weight-dropping method. Real-time polymerase chain reaction, western blot, immunofluorescence, Fluoro-Jade C staining, and neurological score analyses were carried out. Results : NMNAT2 mRNA and protein levels were increased in the injured-side cortex at 6 hours and peaked 12 hours after TBI. Knocking down NMNAT2 with an injection of small interfering RNA in lateral ventricle significantly exacerbated neuronal degeneration and neurological deficits after TBI, which were accompanied by increased expression of BCL-2-associated X protein (Bax). Conclusion : NMNAT2 expression is increased and NMNAT2 exhibits neuroprotective activity in the early stages after TBI, and Bax signaling pathway may be involved in the process. Thus, NMNAT2 is likely to be an important target to prevent secondary damage following TBI.