Aster ageratoides Turcz. extract attenuates Alzheimer’s disease-associated cognitive deficits and vascular dementia-associated neuronal death / 대한해부학회지

Dementia is the common neurodegenerative disorder affecting the elderly, with a progressive cognitive decline and memory loss. Since Alzheimer’s disease (AD) and vascular dementia (VD) share key pathologies including oxidative damage, oral supplement of phytochemical medicines, which are well-known for their antioxidant properties, can be a viable therapy for both types of dementia. In this study, the therapeutic potential of the Aster ageratoides extract (AAE), an oriental drug with multiple medicinal properties, was tested on experimental rat models of AD and VD. After confirming the in vitro attenuation of neuronal excitotoxicity by AAE, rats were orally administered with AAE for 7 days and subsequently tested under 2 different experimental paradigms: efficacy screening against #1 AD and #2 VD. For paradigm #1, the rats received intraperitoneal scopolamine and subsequently underwent 3 different behavior tests i.e., the Y-maze, novel object recognition, and passive avoidance tests. For paradigm #2, the rats were operated with the 2-vessel occlusion and hypovolemia (2VO/H) technique, and at postoperative day 7, their hippocampal neuronal viability and the neuroinflammatory changes were quantified. The results showed that the scopolamine-induced impairment of memory performance was significantly improved by AAE intake. Furthermore, while the 2VO/H operation induced marked hippocampal neuronal death and microglial activation, both these effects were significantly attenuated by AAE supplements. Some of the aforementioned effects of AAE intake were dose-dependent. These results provided evidence that AAE supplements can exert anti-AD and -VD efficacies and suggested that AAE might be used as an edible phytotherapeutic for the 2 major types of dementia.

Aster ageratoides Turcz. extract attenuates Alzheimer’s disease-associated cognitive deficits and vascular dementia-associated neuronal death / 대한해부학회지

Dementia is the common neurodegenerative disorder affecting the elderly, with a progressive cognitive decline and memory loss. Since Alzheimer’s disease (AD) and vascular dementia (VD) share key pathologies including oxidative damage, oral supplement of phytochemical medicines, which are well-known for their antioxidant properties, can be a viable therapy for both types of dementia. In this study, the therapeutic potential of the Aster ageratoides extract (AAE), an oriental drug with multiple medicinal properties, was tested on experimental rat models of AD and VD. After confirming the in vitro attenuation of neuronal excitotoxicity by AAE, rats were orally administered with AAE for 7 days and subsequently tested under 2 different experimental paradigms: efficacy screening against #1 AD and #2 VD. For paradigm #1, the rats received intraperitoneal scopolamine and subsequently underwent 3 different behavior tests i.e., the Y-maze, novel object recognition, and passive avoidance tests. For paradigm #2, the rats were operated with the 2-vessel occlusion and hypovolemia (2VO/H) technique, and at postoperative day 7, their hippocampal neuronal viability and the neuroinflammatory changes were quantified. The results showed that the scopolamine-induced impairment of memory performance was significantly improved by AAE intake. Furthermore, while the 2VO/H operation induced marked hippocampal neuronal death and microglial activation, both these effects were significantly attenuated by AAE supplements. Some of the aforementioned effects of AAE intake were dose-dependent. These results provided evidence that AAE supplements can exert anti-AD and -VD efficacies and suggested that AAE might be used as an edible phytotherapeutic for the 2 major types of dementia.

Comparison of whitening effect of Rubus coreanus fruit according to maturity / 한국영양학회지

Purpose@#The Rubus coreanus fruit (RF) is an important traditional medicinal herb having antioxidant, anti-inflammatory, and immunoregulatory properties. These activities are known to change dramatically, depending on maturity of the RF. It is presumed that change of functional components, such as flavonoids, tannins, phenolic acids, triterpenoids and organic acids in RF, affect the various bioactivities. This study aimed to confirm changes in the anti-melanogenic effects of RF based on maturity, and to identify the bioactive compounds responsible. @*Methods@#The cell viability of mature RF (MRF) and immature RF (IRF) extracts was investigated using B16F10 cells. To compare the anti-melanogenic effect of MRF and IRF extracts, we first assessed the melanin content. High-performance liquid chromatography analysis was performed to evaluate changes in the level of ellagic acid according to maturity of the RF. In addition, tyrosinase inhibitory activity of both extracts was examined. @*Results@#MRF and IRF extracts (50–200 μg/mL) do not affect the cell viability of B16F10 melanoma cells. IRF extract more effectively inhibited melanin synthesis than MRF extract. The content of ellagic acid in IRF extract was higher than that obtained in MRF extract. Furthermore, greater inhibition of tyrosinase activity was observed after exposure to IRF extract than MRF extract. A positive correlation was determined between ellagic acid content and tyrosinase inhibitory activity, and a negative correlation was obtained between ellagic acid content and melanin content. Taken together, our results indicate that ellagic acid is one of the major bioactive compounds of RF that imparts a whitening effect. @*Conclusion@#Our results indicate that ellagic acid in MRF and IRF extracts affect the anti-melanogenesis effect through inhibition of tyrosinase activity. Therefore, the ellagic acid rich IRF has greater potential for application as a natural and functional cosmetic material.

Anti-oxidant and anti-adipocyte differentiation of Aster glehni and Aster yomena / 한국영양학회지

PURPOSE: Aster glehnii (AG) and Aster yomena (AY) are medicinal plants that belong to the family Compositea and grow widely in Korea. Plants in the genus Aster have been used to treat snakebite wounds or bruises in oriental medicine. This study compared the effects of anti-oxidants and anti-adipocyte differentiation according to the species (the aerial parts of AG and AY). METHODS: AG and AY were extracted using 70% ethanol (−E) and water (−W) at room temperature. The anti-oxidant activities were measured by total phenol contents (TPC), total flavonoid contents (TFC), DPPH and ABTS+ assay. In addition, correlation analysis was performed for the anti-oxidant compounds and effect. The level of anti-adipocyte differentiation was assessed using an oil red O assay on pre-adipocytes. RESULTS: AG-W showed higher TPC (6.92 µg/mL) and AG-E presented higher TFC (8.22 µg/mL) than the other extracts. Furthermore, AG-E exhibited higher radical scavenging activity in the DPPH and ABTS+ assay (IC50: 104.88 and 30.06 µg/mL). In the cytotoxicity assay, AG and AY extracts at concentrations less than 100µg/mL were non toxic. AG-W reduced the lipid accumulation of 3T3-L1 cells significantly after differentiation (70.49%) compared to the other extracts. CONCLUSION: These results show that the water extract of AG has anti-oxidant effects and reduces the differentiation of 3T3-L1 cells. Therefore, AG has utility as a functional food material for its anti-oxidant activities and ability to prevent lipid accumulation.

Cognition enhancing effect of panax ginseng in Korean volunteers with mild cognitive impairment: a randomized, double-blind, placebo-controlled clinical trial

This study aimed to investigate the cognition-enhancing effect of Panax ginseng. A randomized, double-blind, placebo-controlled clinical trial was conducted to address the cognition-enhancing effects of Panax ginseng. A total of 90 Korean volunteers with mild cognitive impairment participated in this study. All subjects were allocated randomly into ‘Ginseng’ group or ‘Placebo’ group. All subjects were administered 3g of Panax ginseng powder or starch (placebo) for 6 months. The Korean version of the Mini-Mental Status Examination (K-MMSE), Korean version of Instrumental Activities of Daily Living (K-IADL), and Seoul Neuropsychological Screening Battery (SNSB) were used to assess the changes in cognitive function at the end of the 6 month study period. The subjects of the ‘Ginseng’ group improved significantly on the Rey Complex Figure Test (RCFT) immediate recall (P = 0.0405 and P = 0.0342 in per-protocol (PP) and intention-to-treat (ITT) analysis, respectively) and on the RCFT 20-min delayed recall (P = 0.0396 and P = 0.0355 in PP and ITT analysis, respectively) compared with ‘placebo’ group throughout the 6 months of Panax ginseng administration. There were no serious adverse events. These results suggest that Panax ginseng has a cognition-enhancing effect.

Anti-quorum sensing and anti-biofilm formation activities of plant extracts from South Korea

Objective: To investigate anti-quorum sensing (anti-QS) and anti-biofilm formation (anti- BF) activities of the ethanol extracts of 388 plants. Methods: The anti-QS activity of the plant extracts was evaluated by disc-diffusion assays using the bio-reporter strain, Chromobacterium violaceum CV017. Pseudomonas aeruginosa PAO1, Yersinia enterocolitica ATCC 9610, and Agrobacterium tumefaciens C58, which possess QS systems, were used to evaluate the anti- BF activity of the plant extracts. Results: Among 388 plant extracts, the Cornus controversa (C. controversa) and Cynanchum wilfordii extracts exhibited the strongest anti-QS activity. The C. controversa extract exhibited anti-BF activity against Pseudomonas aeruginosa, Yersinia enterocolitica and Agrobacterium tumefaciens, whereas the Cynanchum wilfordii extract exhibited no anti-BF activity against Pseudomonas aeruginosa. In addition, the C. controversa extract suppressed soft rot of cabbage. Conclusions: The C. controversa extract inhibits bacterial QS and BF, and is capable of controlling soft rot. Therefore, this extract has potential for the prevention and treatment of bacterial infections and for the development of alternatives to antibiotics.

Patterns of Inhalant Allergen Sensitization and Geographical Variation in Korean Adults: A Multicenter Retrospective Study

PURPOSE: Inhalant allergen sensitization is one of the major factors involved in the pathogenesis of allergic respiratory diseases. However, the sensitization is determined by interactions between genetic and environmental factors. Thus, testing panels of inhalant allergens may differ among geographical areas. Here we aimed to determine 10 common inhalant allergens in Korean adult patients with suspected respiratory allergies and to examine the variation between different geographical locations. METHODS: A total of 28,954 patient records were retrieved for retrospective analysis, from 12 referral allergy clinics located in 9 different areas. Inclusion criteria were Korean adults (≥18 years old) who underwent the inhalant allergen skin prick test for suspected history of respiratory allergy. The primary outcome was inhalant allergen skin prick response. Demographic and clinical information were also collected. Positive skin prick responses to allergens were defined as allergen-to-histamine wheal ratio ≥1. Based on skin test results, the most prevalent aeroallergens were determined. RESULTS: The overall prevalence of allergic sensitization was 45.3%. Dermatophagoides farinae and Dermatophagoides pteronyssinus were the most commonly sensitized allergens. Other common inhalant allergens were cat epithelium (8.1%), birch (7.7%), mugwort (6.9%), alder (6.7%), hazel (6.7%), beech (6.7%), oak (6.6%), and Tyrophagus putres (6.2%), in decreasing order frequency. These 10 inhalant allergens explained 90% of inhalant allergen sensitization in the study participants. However, distinct patterns of the 10 inhalant sensitization were observed in patients living in Chungnam and Jeju. American cockroach, Gernam cockroach, and Trichophyton metagrophytes were unique in Chungnam. Orchard, Japanese cedar, and Velvet were unique in Jeju. CONCLUSIONS: The present analysis suggests a panel of 10 most common inhalant allergens in Korean adult patients with suspected respiratory allergies, which explained 90% of inhalant allergen sensitization. This panel can be utilized as a practical and convenient tool for primary practice and epidemiological surveys of respiratory allergic diseases.

AAV-Mediated Astrocyte-Specific Gene Expression under Human ALDH1L1 Promoter in Mouse Thalamus

Adeno-associated virus (AAV)-mediated gene delivery has been proposed to be an essential tool of gene therapy for various brain diseases. Among several cell types in the brain, astrocyte has become a promising therapeutic target for brain diseases, as more and more contribution of astrocytes in pathophysiology has been revealed. Until now, genetically targeting astrocytes has been possible by utilizing the glial fibrillary acidic protein (GFAP) promoter. In some brain areas including thalamus, however, the GFAP expression in astrocytes is reported to be low, making it difficult to genetically target astrocytes using GFAP promoter. To study the function of astrocytes in thalamus, which serves as a relay station, there is a great need for identifying an alternative astrocyte-specific promoter in thalamus. Recently, a new astrocyte-specific promoter of ALDH1L1 has been identified. However, it has not been examined in thalamus. Here we developed and characterized an AAV vector expressing Cre recombinase under the human ALDH1L1 promoter, AAV-hALDH1L1-Cre. To test the cell-type specific expression of AAV-hALDH1L1-Cre, AAV virus was injected into several brain regions of Ai14 (RCL-tdTomato) mouse, which reports Cre activity by tdTomato expression. In thalamus, we observed that tdTomato was found mostly in astrocytes (91.71%), with minimal occurrence in neurons (2.67%). In contrast, tdTomato signal was observed in both neurons and astrocytes of the amygdala (neuron: 68.13%, astrocyte: 28.35%) and hippocampus (neuron: 76.25%, astrocyte: 18.00%), which is consistent with the previous report showing neuronal gene expression under rat ALDH1L1 promoter. Unexpectedly, tdTomato was found mostly in neurons (91.98%) with minimal occurrence in astrocytes (6.66%) of the medial prefrontal cortex. In conclusion, hALDH1L1 promoter shows astrocyte-specificity in thalamus and may prove to be useful for targeting thalamic astrocytes in mouse.

Wernicke's encephalopathy after total parenteral nutrition in patients with Crohn's disease

Micronutrient deficiencies in Crohn's disease (CD) patients are not uncommon and usually result in a combination of reduced dietary intake, disease-related malabsorption, and a catabolic state. Decreased serum thiamine levels are often reported in patients with CD. Wernicke's encephalopathy (WE) is a severe form of thiamine deficiency that can cause serious neurologic complications. Although WE is known to occur frequently in alcoholics, a number of non-alcoholic causes have also been reported. Here, we report two cases of non-alcoholic WE that developed in two severely malnourished CD patients who were supported by prolonged total parenteral nutrition without thiamine supplementation. These patients complained of sudden-onset ophthalmopathy, cerebellar dysfunction, and confusion. Magnetic resonance imaging allowed definitive diagnosis for WE despite poor sensitivity. The intravenous administration of thiamine alleviated the symptoms of WE dramatically. We emphasize the importance of thiamine supplementation for malnourished patients even if they are not alcoholics, especially in those with CD.

Chios Gum Mastic Induces Cell Cycle Arrest and Apoptosis in Human Osteosarcoma Cells / 대한해부학회지

Chios gum mastic (CGM) is a resin produced from the stem and leaves of Pistiacia lentiscus L var chia, a plant which grows only on Chios Island in Greece. CGM has been used for many centuries as a dietary supplement and folk medicine for stomach and duodenal ulcers in many Mediterranean countries and is also known to induce cell cycle arrest and apoptosis in some cancer cells. This study was undertaken to investigate the alteration of the cell cycle and induction of apoptosis by CGM treatment on human osteosarcoma (HOS) cells. The viability and the growth inhibition of HOS cells were assessed by the MTT assay and clonogenic assay respectively. The hoechst staining, TUNEL assay and DNA electrophoresis were conducted to observe the HOS cells undergoing apoptosis. HOS cells were treated with CGM, and Western blotting, immunocytochemistry, confocal microscopy, FACScan flow cytometry, mitochondrial membrane potential change and proteasome activity were conducted. CGM treatment of HOS cells was found to result in a dose- and time-dependent decrease in cell viability, a dose-dependent inhibition of cell growth, and apoptotic cell death. Tested HOS cells also showed several lines of apoptotic manifestation and G1 arrest in cell cycle progression. In summary, this study clearly demonstrated that CGM induces G1 cell cycle arrest via the modulation of cell cycle-related proteins, and apoptosis via proteasome, mitochondrial and caspase cascades in HOS cells. Therefore, our data provide the possibility that a natural product, CGM could be considered as a novel therapeutic strategy for human osteosarcoma.

Chios Gum Mastic Induces Cell Cycle Arrest and Apoptosis in YD9 Human Oral Squamous Carcinoma Cells / 체질인류학회지

Chios gum mastic (CGM) is obtained from the stem and leaves of Pistacia lentiscus trees and has been extensively used for centuries in Mediterranean and Middle Eastern countries, both as a dietary supplement and herbal remedy. This study was undertaken to examine in vitro effects of cytotoxicity and growth inhibition, and the molecular mechanism underlying modulation of cell cycle and induction of apoptosis in YD9 human oral squamous carcinoma cell line treated with CGM. The viability of YD9 cells and human normal keratinocyes (HaCaT cells), and the growth inhibition of YD9 cells were assessed by the MTT assay and clonogenic assay respectively. The hoechst staining and DNA electrophoresis were conducted to observe the YD9 cells undergoing apoptosis. YD9 cells were treated with CGM, and Western blotting, immunocytochemistry, confocal microscopy and FACScan flow cytometry were conducted. Mitochondrial membrane potential change and proteasome activity were measured. CGM treatment on YD9 cells resulted in a does-dependent inhibition of cell growth and induced apoptotic cell death. And tested YD9 cells showed several lines of apoptotic manifestation. Flow cytometric analysis revealed that CGM resulted in G1 arrest in cell cycle progression which was associated with decrease in the protein expression of cyclin D1, cyclin D3, Cdk2 and Cdk4, and increase in the protein expression of p21(WAF1/CIP1) and p53. These results demonstrate that CGM induces G1 the cell cycle arrest via the modulation of cell cycle-related proteins, and apoptosis via mitochondria and caspase pathway in YD9 cells, suggesting that CGM can be considered as a novel therapeutic strategy for human oral squamous cell carcinoma from its strong cell cycle arrest and apoptosis-inducing activity.