Potential Phytotherapy of DSS-Induced Colitis: Ameliorating Reactive Oxygen Species-Mediated Necroptosis and Gut Dysbiosis with a New Crataegus pinnatifida Bunge Variety-Daehong.

Developing new plant varieties plays a crucial role in competitiveness in the agricultural and food industries and enhancing food security. Daehong (DH) is a new variety of Crataegus pinnatifida Bunge (CP); however, its physiological functions and potential as a nutraceutical ingredient remain unknown. Here, the efficacy of DH on inflammatory bowel disease (IBD) was investigated using dextran sulfate sodium (DSS)-induced colitis mice, and its relative pharmacological effects were analyzed against CP. DH improved colitis-induced weight loss, colon shortening, and inflammatory responses and reduced intestinal permeability. The reactive oxygen species (ROS)-mediated necroptotic signal that triggers enterocyte cell death in DSS-induced colitis was effectively controlled by DH, attributed to epicatechin. DSS-induced gut dysbiosis was recovered into a healthy gut microbiome environment by DH, increasing beneficial bacteria, like Akkermansia muciniphila, and changing harmful bacteria, including Bacteroides vulgatus and Peptostreptococcaceae. DH shows potential as a dietary or pharmaceutical ingredient to promote gut health and to prevent and treat IBD.

Arginine-fructose-glucose from red ginseng extract reduces stiffness of keratin fiber in corneocyte of skin.

PURPOSE: The moisture content of the stratum corneum of the skin changes depending on the external environment. The structure of keratinous fiber protein in corneocyte of the skin changes depending on the amount of moisture. As the moisture decreases, the population of the alpha-helix increases, the beta-sheet deceases, and the stiffness increases accordingly. Here, we investigated the effect of humectants from ginseng on the keratin structure. METHODS: Corneocyte was prepared from dry porcine skin with disc tape and measured through ATR-FT-IR. The signal from amide I of the keratin protein in corneocyte was detected, and the change in the ratio of alpha-helix and beta-sheet was calculated. The test samples were treated on the exfoliated corneocyte, and the degree of change was checked. RESULT: Arginine-fructose-glucose (AFG)-enriched extract of red ginseng was effective in changing the keratin structure and was superior to humectants such as glycerin. However, arginine, mono sugar were not effective, and the AFG form in which two sugars were bound to one amino acid could perform its function. CONCLUSION: The present study suggests that AFG, when applied to cosmetics, is expected to improve skin texture in a different way from existing moisturizers represented by glycerin by reducing the alpha-helix structure of corneocyte keratin.

A rare triad of appendiceal diverticula, appendiceal carcinoid, and colonic diverticula.

Appendiceal diverticulosis is a rare finding associated with appendiceal neoplasms. Both can masquerade as appendicitis in patients and are overlooked in differentials of right upper quadrant pain. A 37-year-old African American female presented with appendicitis-like symptoms to the emergency room with fever and leukocytosis. Appendectomy was performed with pathological evaluation revealing coexisting appendiceal diverticula and carcinoid of the appendix with lymphovascular invasion and mesoappendiceal involvement. In line with the National Comprehensive Cancer Network guidelines, right hemicolectomy with lymph node dissection was performed which was negative for neoplastic invasion but positive for colonic diverticulosis. While there have been many case reports of appendiceal diverticula with coexisting appendiceal carcinoid, a concurrent colonic diverticulum in the right hemicolectomy specimen during the oncologic resection of the appendiceal carcinoid has not been previously reported. We propose colonic diverticula as another possible feature that may be associated with appendiceal diverticula especially with an underlying appendiceal neoplasm.

Ambient Air Pollution and Kawasaki Disease in Korean Children: A Study of the National Health Insurance Claim Data.

Background Kawasaki disease (KD) is a systemic vasculitis of unknown etiology that primarily affects children under 5 years of age. Some researchers suggested a potential triggering effect of air pollution on KD, but the findings are inconsistent and limited by small sample size. We investigated the association between ambient air pollution and KD among the population of South Korea younger than 5 years using the National Health Insurance claim data between 2007 and 2019. Methods and Results We obtained the data regarding particulate matter ≤10 or 2.5 µm in diameter, nitrogen dioxide, sulfur dioxide, carbon monoxide, and ozone from 235 regulatory monitoring stations. Using a time-stratified case-crossover design, we performed conditional logistic regression to estimate odds ratios (OR) of KD according to interquartile range increases in each air pollutant concentration on the day of fever onset after adjusting for temperature and relative humidity. We identified 51 486 children treated for KD during the study period. An interquartile range increase (14.67 µg/m3) of particulate matter ≤2.5 µm was positively associated with KD at lag 1 (OR, 1.016; 95% CI, 1.004-1.029). An interquartile range increase (2.79 ppb) of sulfur dioxide concentration was associated with KD at all lag days (OR, 1.018; 95% CI, 1.002-1.034 at lag 0; OR, 1.022; 95% CI, 1.005-1.038 at lag 1; OR, 1.017; 95% CI, 1.001-1.033 at lag 2). Results were qualitatively similar in the second scenario of different fever onset, 2-pollutant model and sensitivity analyses. Conclusions In a KD-focused national cohort of children, exposure to particulate matter ≤2.5 µm and sulfur dioxide was positively associated with the risk of KD. This finding supports the triggering role of ambient air pollution in the development of KD.

Botanical formulation, TADIOS, alleviates lipopolysaccharide (LPS)-Induced acute lung injury in mice via modulation of the Nrf2-HO-1 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: TADIOS is an herbal formulation prepared from a mixture of Taraxacum officinale (L.) Weber ex F.H.Wigg, Dioscorea batatas Decaisne and Schizonepeta tenuifolia (Benth.) Briquet. These plants have traditionally been used in Asia to treat a variety of respiratory diseases. A bulk of literature on traditional Korean medicine describe their activities and functions for respiratory problems. Therefore, we hypothesized that the combination of these plants might be effective in alleviating respiratory symptoms. AIM OF THE STUDY: In this study, we investigated whether TADIOS ameliorates LPS-induced acute lung injury via regulation of the Nrf2-HO-1 signaling pathway. MATERIALS AND METHODS: The LPS-induced acute lung injury mouse model was used to determine the anti-inflammatory and anti-oxidative stress effects of TADIOS. The amount of marker compounds contained in TADIOS was quantified using high-performance liquid chromatography (HPLC) analysis. The protein level of pro-inflammatory cytokines in culture supernatant was measured by ELISA. Changes in the RNA level of pro-inflammatory cytokines in mice lungs and RAW264.7 cells were measured by quantitative RT-PCR. The relative amounts of reactive oxygen species (ROS) were measured by DCF-DA assay. Western blot analysis was used to evaluate expression of cellular proteins. Effects of TADIOS on antioxidant responsive elements (AREs) were determined by luciferase assay. The severity of acute lung injury was evaluated by Hematoxylin & Eosin (H&E) staining. To test the effects of TADIOS on LPS-induced oxidative stress, myeloperoxidase (MPO) activity and the total antioxidant capacity were measured. RESULTS: TADIOS was prepared by extraction of a blend of these three plants by ethanol, and quality control was performed through quantification of marker compounds by HPLC and measurement of bioactivities using cell-based bioassays. In the murine macrophage cell line RAW264.7, TADIOS effectively suppressed the production of pro-inflammatory cytokines such as IL-6 and IL-1ß, and also ROS induced by LPS. When RAW264.7 cells were transfected with a luciferase reporter plasmid containing nucleotide sequences for AREs, TADIOS treatment increased the level of relative luciferase units in a dose-dependent manner. In the LPS-induced acute lung injury mouse model, orally administered TADIOS alleviated lung damage and neutrophil infiltration induced by LPS. Consistent with the in vitro data, treatment with TADIOS inhibited the LPS-mediated expression of pro-inflammatory cytokines and oxidative stress, and activated the Nrf2-HO-1 axis. CONCLUSION: Our data suggest the potential for TADIOS to be developed as a safe and effective therapeutics for the treatment of acute respiratory distress syndrome.

Air Pollution and Incidence of Lung Cancer by Histological Type in Korean Adults: A Korean National Health Insurance Service Health Examinee Cohort Study.

: Studies have reported associations between long-term exposure to ambient air pollution and lung cancer. However, there have been inconsistent reports of such associations with lung cancer by histological type. Thus, the aim of this study was to assess the association of long-term exposure to particulate matter with an aerodynamic diameter up to 10 µm (PM10) and nitrogen dioxide (NO2) with lung cancer incidence by histological subtype in South Korea. This population-based cohort study included 6,567,909 cancer-free subjects from the Korean National Health Insurance Service (NHIS) database for 2006-2007. We linked population data to Korea Central Cancer Registry data to confirm lung cancer incidence for 2006-2013. Individual exposures to PM10 and NO2 were assessed as five-year average concentrations predicted at subjects' district-specific home addresses for 2002-2007. We divided these exposures into two categories based on the 75th percentile. Cox proportional hazards models were used to estimate hazard ratios (HRs) of lung cancer incidence for the upper 25% exposure compared to the low 75% by histological subtypes at diagnosis after adjusting for potential confounders. A total of 27,518 lung cancer were found between 2006 to 2013. The incidence of lung cancer was higher in males, smokers, drinkers and subjects with chronic obstructive pulmonary disease. Overall, we did not find an increased risk of lung cancer with higher exposure to PM10 or NO2. However, high exposure to PM10 was associated with increased risk of adenocarcinoma in comparison with lower exposure in males and current smokers (HR, 1.14; 95% CI, 1.03-1.25). This study showed that long-term air pollution exposures were associated with an elevated risk of lung adenocarcinoma in male smokers in Korea.

Memory-Enhancing Effects of Mangosteen Pericarp Water Extract through Antioxidative Neuroprotection and Anti-Apoptotic Action.

Mangosteen has long been utilized as a traditional medicine in Southeast Asia. Diverse extracts of mangosteen pericarp and its bioactive xanthones exhibit various bioactivities. However, the pharmacological potential of mangosteen pericarp water extract (MPW) has not been reported yet. This study used primary cultured rat cortical cells to investigate the effect of MPW on neurotoxicity. We found that MPW inhibited neurotoxicity and production of reactive oxygen species triggered by Aß(25-35) or excitatory amino acids. MPW inhibited caspase 3 activation and DNA fragmentation in Aß(25-35)- or N-methyl-D-aspartate-treated cells, suggesting an anti-apoptotic action. Additionally, MPW reduced lipid peroxidation and scavenged 1,1-diphenyl-2-picrylhydrazyl radicals, assuring its antioxidant property. Furthermore, MPW suppressed ß-secretase and acetylcholinesterase activities. These findings prompted us to evaluate its effect on memory dysfunction in scopolamine-treated mice using Morris water maze test. Oral administration of MPW at the dosage of 50, 100, or 300 mg/kg for four days significantly decreased the latency time to find the platform and markedly increased the swimming time in the target quadrant. Taken together, our results suggest that MPW exerts memory-enhancing effect through antioxidative neuroprotection and anti-apoptotic action. Accordingly, MPW may have a potential to prevent or treat memory impairment associated with Alzheimer's disease.

Improvement of the Bonding Properties of Mineral Trioxide Aggregate by Elastin-Like Polypeptide Supplementation.

INTRODUCTION: Elastin-like polypeptide (ELP) supplementation was previously reported to enhance the physical properties of mineral trioxide aggregate (MTA). The aim of this study was to investigate the effect of ELP supplementation on the bonding properties of MTA to dentin. METHODS: Two types of ELPs were synthesized and mixed with MTA in a 0.3 liquid/powder ratio. The push-out bond strength test and interfacial observation with scanning electron microscopy were performed for ELP-supplemented MTA. The porosity of MTA fillings in the cavity was observed with microcomputed tomography. The stickiness, flow rate, and contact angle were additionally measured for potential increased bonding properties. RESULTS: ELP supplementation improved the bond strength of MTA to dentin. MTA supplemented by a specific ELP exhibited a less porous structure, higher stickiness, and higher flow rate. ELPs also decreased the contact angle to dentin. CONCLUSIONS: This research data verifies that ELP improves the bonding properties of MTA to a tooth structure. The sticky and highly flowable characteristics of ELP-supplemented MTA may provide intimate contact with dentin and supply a less porous cement structure, which might improve the bonding properties of MTA.

Water-Soluble Extract from Actinidia arguta (Siebold & Zucc.) Planch. ex Miq. and Perilla frutescens (L.) Britton, ACTPER, Ameliorates a Dry Skin-Induced Itch in a Mice Model and Promotes Filaggrin Expression by Activating the AhR Signaling in HaCaT Cells.

With a complex etiology involving multiple factors, the condition known as itch is a primary symptom of many skin diseases. Current treatment methods are ineffective for addressing itches caused by dry skin, for example. We developed a botanical extract, ACTPER, made from a mixture of Actinidia arguta and Perilla frutescens, which have traditionally been used to treat itch. The quality of ACTPER as a research agent was controlled in our experiment by cell-based bioassays, as well as by high-performance liquid chromatography (HPLC), using two chemical markers. In the acetone-induced dry skin mice model, the oral administration of ACTPER alleviated dry skin-related skin properties and itching behavior. The RNA and protein expression of the filament aggregating protein (filaggrin) gene, a key factor involved in the regulation of skin barrier function, was significantly increased, as measured by quantitative reverse transcription polymerase chain reaction (RT-PCR) and immunofluorescence assay. To understand the underlying mechanism(s) at the molecular level, HaCaT cells, a human keratinocyte-derived cell line, were treated with various concentrations of ACTPER. We found that the protein expression of filaggrin was indeed upregulated by ACTPER in a dose dependent manner. Data from experiments involving the reporter plasmid containing the xenobiotic response element (XRE), and the chemical antagonist for the aryl hydrocarbon receptor (AhR), indicated that the ACTPER-mediated upregulation of filaggrin was controlled through the activation of the AhR signaling pathway. The molecular docking simulation study predicted that ACTPER might contain chemical compounds that bind directly to AhR. Taken together, our results suggest that ACTPER may provide the platform, based upon which a variety of safe and effective therapeutic agents can be developed to treat itch.

Inhibition of Oxidative Neurotoxicity and Scopolamine-Induced Memory Impairment by γ-Mangostin: In Vitro and In Vivo Evidence.

Among a series of xanthones identified from mangosteen, the fruit of Garcinia mangostana L. (Guttifereae), α- and γ-mangostins are known to be major constituents exhibiting diverse biological activities. However, the effects of γ-mangostin on oxidative neurotoxicity and impaired memory are yet to be elucidated. In the present study, the protective effect of γ-mangostin on oxidative stress-induced neuronal cell death and its underlying action mechanism(s) were investigated and compared to that of α-mangostin using primary cultured rat cortical cells. In addition, the effect of orally administered γ-mangostin on scopolamine-induced memory impairment was evaluated in mice. We found that γ-mangostin exhibited prominent protection against H2O2- or xanthine/xanthine oxidase-induced oxidative neuronal death and inhibited reactive oxygen species (ROS) generation triggered by these oxidative insults. In contrast, α-mangostin had no effects on the oxidative neuronal damage or associated ROS production. We also found that γ-mangostin, not α-mangostin, significantly inhibited H2O2-induced DNA fragmentation and activation of caspases 3 and 9, demonstrating its antiapoptotic action. In addition, only γ-mangostin was found to effectively inhibit lipid peroxidation and DPPH radical formation, while both mangostins inhibited ß-secretase activity. Furthermore, we observed that the oral administration of γ-mangostin at dosages of 10 and 30 mg/kg markedly improved scopolamine-induced memory impairment in mice. Collectively, these results provide both in vitro and in vivo evidences for the neuroprotective and memory enhancing effects of γ-mangostin. Multiple mechanisms underlying this neuroprotective action were suggested in this study. Based on our findings, γ-mangostin could serve as a potentially preferable candidate over α-mangostin in combatting oxidative stress-associated neurodegenerative diseases including Alzheimer's disease.

Subcutaneous Immunotherapy in Patients with Fagales Pollen-Induced Oral Allergy Syndrome.

Oral allergy syndrome (OAS) is the most common food allergy-related condition in adults. This study aimed to investigate whether subcutaneous immunotherapy (SCIT) with Fagales pollen-containing extracts can improve the clinical symptoms of OAS in Korea. In total, 56 OAS patients were included: 19 subjects treated with SCIT, which included Fagales pollen extracts, and 37 not treated with immunotherapy (IT). We reviewed the patients' medical records and administered a telephone questionnaire at one point to assess baseline OAS features and changes in the patients' OAS and allergic rhinoconjunctivitis (ARC) symptoms after treatment. Only 12 patients who received SCIT and 15 patients that did not receive SCIT could report on changes in OAS symptoms after treatment because the other patients practiced strict avoidance of their culprit fruits and vegetables, and they could not respond to the status of OAS. SCIT reduced the severity of OAS (p=0.005). Nine of the 12 patients (75%) that received SCIT reported a more than 50% reduction in OAS symptoms. In contrast, only three of the 15 patients (20%) that did not receive IT reported more than a 50% reduction in OAS symptoms. SCIT also reduced the severity of ARC symptoms (p<0.001). The results indicate that SCIT with Fagales pollen-containing extracts is associated with improved OAS symptoms in Korea.

PG102 Upregulates IL-37 through p38, ERK, and Smad3 Pathways in HaCaT Keratinocytes.

IL-37 is an immunomodulatory cytokine that suppresses inflammation in various cell types and disease models. However, its role in keratinocytes has not been clearly understood, and there has been no report on the agents that can increase the expression of IL-37 in keratinocytes. In this study, we investigated the effects of silencing IL37 in HaCaT keratinocytes and the molecular mechanisms involved in the upregulation of IL-37 by PG102, a water-soluble extract from Actinidia arguta. It was found that knockdown of IL37 resulted in the augmented expression of antimicrobial peptides (AMPs) in response to cytokine stimulation. PG102 increased the expression of IL-37 at both mRNA and protein levels presumably by enhancing the phosphorylation of Smad3, ERK, and p38. Indeed, when cells were treated with specific inhibitors for these signaling molecules, the expression level of IL-37 was reduced. PG102 also promoted colocalization of phospho-Smad3 and IL-37. Our results suggest that IL-37 inhibits the expression of AMPs and that PG102 upregulates IL-37 through p38, ERK, and Smad3 pathways in HaCaT cells.

Botanical Formulation HX109 Ameliorates TP-Induced Benign Prostate Hyperplasia in Rat Model and Inhibits Androgen Receptor Signaling by Upregulating Ca2+/CaMKKß and ATF3 in LNCaP Cells.

Benign prostatic hyperplasia (BPH) is a common disease in the elderly male population throughout the world. Among other factors, androgen dysregulation has been known to play major roles in its pathogenesis. HX109 is a botanical formulation prepared from a mixture of Taraxacum officinale, Cuscuta australis, and Nelumbo nucifera, which have traditionally been used-usually along with other plants-to treat urinary diseases. An ethanol extract was prepared from a mixture of these three plants, and its quality was controlled through cell-based bioassays and by quantification of several marker compounds by high-performance liquid chromatography (HPLC). In the testosterone propionate (TP)-induced prostate hyperplasia rat model, oral administration of HX109 ameliorated prostate enlargement and histological changes induced by TP. In LNCaP cells, a human prostate epithelial cell line, HX109 repressed AR-mediated cell proliferation and the induction of androgen receptor (AR) target genes at the transcriptional level without affecting the translocation or expression of AR. Such effects of HX109 on AR signaling were mediated through the control of activating transcriptional factor 3 (ATF3) expression, phosphorylation of calcium/calmodulin-dependent protein kinase kinase ß (CaMKKß), and increases in intracellular calcium, as evidenced by data from experiments involving ATF3-specific siRNA, CaMKKß inhibitor, and calcium chelator, respectively. Taken together, our data suggest that HX109 might be used as a starting point for developing therapeutic agents for the treatment of BPH.

A Water-Soluble Extract from Actinidia arguta Ameliorates Psoriasis-Like Skin Inflammation in Mice by Inhibition of Neutrophil Infiltration.

Psoriasis is a chronic inflammatory disease with complex etiology involving multiple factors. Current treatment methods are highly limited and there is a strong need for the development of safer and efficacious agents. We have previously shown that a water-soluble extract derived from hardy kiwifruit Actinidia arguta, called PG102, shows potent anti-inflammatory effects. Based on its reported biological activities, the effects of PG102 were examined on imiquimod-induced psoriasis-like skin inflammation. Our results showed that topical application of PG102 ameliorates clinical symptoms of psoriasis, reducing skin thickness and Interleukin (IL)-17A level in draining lymph nodes without causing any adverse effects. Treatment with PG102 on cytokine-stimulated HaCaT cells suppressed hyperproliferation and downregulated the expression of various chemokines and antimicrobial peptides known to induce neutrophil infiltration. These anti-inflammatory activities of PG102 were mediated via inhibition of NF-κB and signal transducer of activation (STAT) signaling. We also found decreased neutrophil chemotaxis both in vitro and in vivo. Taken together, PG102 has potential as a safe and effective reagent for the treatment of psoriasis.

Combined effects of four major geriatric syndromes on adverse outcomes based on Korean National Health Insurance claims data.

AIM: Geriatric syndromes are common among older individuals, and can affect their health and quality of life. The present study aimed to determine if combinations of geriatric syndromes affected adverse outcomes among older Koreans. METHODS: Korean national health insurance data were collected for a cohort of 5 058 720 individuals who were aged ≥65 years in 2008. The same data source was used to follow these individuals until 2015. Diagnostic codes were used to assess four major geriatric syndromes (delirium, fall-related fractures, incontinence and pressure ulcers) and adverse outcomes (mortality and nursing home institutionalization). RESULTS: The prevalence of geriatric syndromes was 0.3% for delirium, 3.49% for fall-related fractures, 1.08% for incontinence and 0.82% for pressure ulcers. All four geriatric syndromes were associated with increased risks of institutionalization (adjusted hazard ratio [aHR] 2.18, 95% CI 2.08-2.17 for delirium; aHR 1.59, 95% CI 1.58-1.60 for fall-related fractures; aHR 1.43, 95% CI 1.41-1.44 for incontinence; and aHR 2.51, 95% CI 2.47-2.55 for pressure ulcers) and increased risks of mortality (aHR 2.13, 95% CI 2.08-2.17 for delirium; aHR 1.41, 95% CI 1.40-1.42 for fall-related fractures; aHR 1.09, 95% CI 1.07-1.10 for incontinence; and aHR 3.23, 95% CI 3.20-3.27 for pressure ulcers). The aHR for institutionalization were 1.64 (95% CI 1.63-1.65) for one geriatric syndrome, 2.40 (95% CI 2.35-2.44) for two coexisting geriatric syndromes and 2.56 (95% CI 2.35-2.74) for three coexisting geriatric syndromes. The aHR for mortality were 1.52 (95% CI 1.51-1.53) for one geriatric syndrome, 2.36 (95% CI 2.32-2.40) for two coexisting geriatric syndromes and 2.90 (95% CI 2.72-3.09) for three coexisting geriatric syndromes. CONCLUSIONS: Delirium, fall-related fractures, incontinence and pressure ulcers were associated with increased risks of institutionalization and mortality. The magnitude of these risks increased with increasing numbers of coexisting geriatric syndromes. Geriatr Gerontol Int 2018; 18: 1463-1468.

PG201 protects mice from experimental autoimmune encephalomyelitis via suppression of effector T cell activation.

BACKGROUND: PG201 is a botanical formulation, approved as an ethical drug (ETC) phytomedicine for treatment of patients with osteoarthritis in Korea, following satisfactory phase II and phase III studies. This phytomedicine was previously been shown to possess significant anti-inflammatory activities, presumably via the control of Th1 and Th17 cells in animal models and in vitro cell culture systems. PURPOSE: In this study, the possibility of using PG201 to treat multiple sclerosis was explored. METHODS: In vitro, the effect of PG201 on the differentiation of CD4+ T cells was investigated. To test the effects of PG201 in vivo, a mouse experimental autoimmune encephalomyelitis (EAE) model was used. RESULTS: It was found that PG201 treatment decreased the frequency of both CD4+T-bet+ and CD4+RORγt+T cells. In addition, the production of interferon- gamma (IFN-γ) and interleukin-17 (IL-17) from respective Th cells was highly reduced. The data from western blots showed that the amount of phosphorylated c-Jun, but not that of p65, was decreased by PG201. Consistently, the level of luciferase activity was downregulated by PG201 in activator protein 1 (AP-1) reporter plasmid assays. In mice pretreated with PG201, the day of onset was delayed and clinical symptoms of EAE were significantly improved in a dose-dependent manner. Consistent with these results, the number of infiltrated cells and the expression level of pro-inflammatory molecules were decreased. CONCLUSION: These findings indicate that PG201 may exert strong immunomodulatory effects in the EAE model via suppression of T cell activation, and that PG201 is a therapeutic reagent for the treatment of multiple sclerosis.

Euodia daniellii Hemsl. (Bee-Bee Tree) Oil Attenuates Palmitate-Induced Lipid Accumulation and Apoptosis in Hepatocytes.

Hepatic lipid accumulation and apoptosis is elevated in patients with non-alcoholic steatohepatitis and is closely associated with severity. Saturated fatty acid palmitate stimulates lipid accumulation and apoptosis in hepatocytes. In the present study, we examined bee-bee tree oil (BO)-mediated protective effects on palmitate-induced lipid accumulation and apoptosis in mouse primary hepatocytes. Cells were cultured in a control media or the same media containing 150 or 300 µmol/L of albumin-bound palmitate for 24 h. BO concentrations used were 0, 0.1, 0.2, or 0.5%. Palmitate induced lipid accumulation and mRNA expression of lipogenic genes such as SREBP1c and SCD1. However, BO prevented these changes. Furthermore, palmitate stimulated caspase-3 activity and decreased cell viability in the absence of BO. BO reduced palmitate-induced activation of caspase-3 and cell death in a dose-dependent manner. AMP-activated protein kinase inhibitors abolished the effects of BO. Furthermore, BO suppressed palmitate-induced c-Jun N-terminal kinase (JNK) phosphorylation through the 5' adenosine monophosphate-activated protein kinase (AMPK)-dependent pathway. In conclusion, BO attenuated palmitate-induced hepatic steatosis and apoptosis through AMPK-mediated suppression of JNK signaling. These data suggest that BO is an important determinant of saturated fatty acid-induced lipid accumulation and apoptosis, and may be an effective therapeutic strategy for treatment of obesity-mediated liver diseases.

Improvement of physical properties of calcium phosphate cement by elastin-like polypeptide supplementation.

Calcium phosphate cements (CPCs) are synthetic bioactive cements widely used as hard tissue substitutes. Critical limitations of use include their poor mechanical properties and poor anti-washout behaviour. To address those limitations, we combined CPC with genetically engineered elastin-like polypeptides (ELPs). We investigated the effect of the ELPs on the physical properties and biocompatibility of CPC by testing ELP/CPC composites with various liquid/powder ratios. Our results show that the addition of ELPs improved the mechanical properties of the CPC, including the microhardness, compressive strength, and washout resistance. The biocompatibility of ELP/CPC composites was also comparable to that of the CPC alone. However, supplementing CPC with ELPs functionalized with octaglutamate as a hydroxyapatite binding peptide increased the setting time of the cement. With further design and modification of our biomolecules and composites, our research will lead to products with diverse applications in biology and medicine.

Comparative studies of bioactive organosulphur compounds and antioxidant activities in garlic (Allium sativum L.), elephant garlic (Allium ampeloprasum L.) and onion (Allium cepa L.).

We evaluated organosulphur compounds in Allium vegetables, including garlic, elephant garlic and onion, using high-performance liquid chromatography. Among organosulphur compounds, elephant garlic had considerable γ-glutamyl peptides, and garlic had the highest alliin content. Onion had low level of organosulphur compounds than did elephant garlic and garlic. In addition, antioxidant capacities were evaluated by oxygen radical absorbance capacity (ORAC) values and 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) radical scavenging assay. The results showed that garlic had the highest antioxidant capacity, followed by elephant garlic and onion. Furthermore, a positive correlation was observed between antioxidant activities and organosulphur compounds (R > 0.77). Therefore, our results indicate that there was a close relationship between antioxidant capacity and organosulphur compounds in Allium vegetables.

Anti-cancer Effect of Cyanidin-3-glucoside from Mulberry via Caspase-3 Cleavage and DNA Fragmentation in vitro and in vivo.

BACKGROUND: Fruits of Morus alba L. (mulberry) have various bioactive compounds such as polyphenols and anthocyanins and used as a herbal medicine. However, the anti-cancer effects and molecular basis have not been elucidated. METHODS: We isolated the cyanidin-3-glucoside in various cultivar of mulberry by acidified-methanol extraction methods. This molecule were compared mass spectroscopic properties by LC-MS/MS and analyzed by 1H and 13C NMR. We examined the anti-cancer effect with molecular mechanisms of the cyanidin-3-glucoside on MDA-MB-453 human breast cancer cells and xenograft animal model. RESULTS: The treatment with the mulberry cyanidin-3-glucoside decreased cell viability in a dose-dependent manner with alteration of apoptotic protein contents, and DNA fragmentation, suggesting that cells undergo apoptosis. Supporting the observations, Treatment with the cyanidin-3-glucoside showed active apoptosis by caspase-3 cleavage and DNA fragmentation through Bcl-2 and Bax pathway. Indeed, cyanidin-3-glucoside inhibits tumor growth in MDA-MB-453 cells-inoculated nude mice. Tumor growth of xenograft nude mouse was significantly reduced compared to the control group by the cyanidin-3-glucoside. CONCLUSION: The data demonstrate that cyanidin-3-glucoside isolated from mulberry induced apoptosis in breast cancer (MDA-MB-453) cells, and therefore, has a potential as an anti-cancer agent. These results show that mulberry cyanidin-3-glucoside inhibit the proliferation and growth in vitro and in vivo model and, indicating the inhibition of tumor progression.