Decursinol Angelate Inhibits LPS-Induced Macrophage Polarization through Modulation of the NFκB and MAPK Signaling Pathways.

Inflammation is considered the root cause of various inflammatory diseases, including cancers. Decursinol angelate (DA), a pyranocoumarin compound obtained from the roots of Angelica gigas, has been reported to exhibit potent anti-inflammatory effects. In this study, the anti-inflammatory effects of DA on the MAP kinase and NFκB signaling pathways and the expression of pro-inflammatory cytokines were investigated in phorbol 12-myristate 13-acetate (PMA)-activated human promyelocytic leukemia (HL-60) and lipopolysaccharide (LPS)-stimulated macrophage (Raw 264.7) cell lines. PMA induced the activation of the MAP kinase-NFκB pathway and the production of pro-inflammatory cytokines in differentiated monocytes. Treatment with DA inhibited the activation of MAP kinases and the translocation of NFκB, and decreased the expression and exogenous secretion of IL-1ß and IL-6. Furthermore, LPS-stimulated Raw 264.7 cells were found to have increased expression of M1 macrophage-associated markers, such as NADPH oxidase (NOX) and inducible nitric oxide synthase (iNOS), and the M2 macrophage-associated marker CD11b. LPS also activated pro-inflammatory cytokines and Erk-NFκB. Treatment with DA suppressed LPS-induced macrophage polarization and the inflammatory response by blocking Raf-ERK and the translocation of NFκB in Raw 264.7 cells. Treatment with DA also inhibited the expression of pro-inflammatory cytokines, such as IL-1ß and IL-6, NOX, and iNOS in Raw 264.7 cells. These results suggest that DA has the potential to inhibit macrophage polarization and inflammation by blocking the activation of pro-inflammatory signals. These anti-inflammatory effects of DA may contribute to its potential use as a therapeutic strategy against various inflammation-induced cancers.

The Effect of Asthma Clinical Guideline for Adults on Inhaled Corticosteroids PrescriptionTrend: A Quasi-Experimental Study.

In order to increase inhaled corticosteroid (ICS) use and to reduce hospitalization, emergency department visits and ultimately the economic burden of asthma, "Korean Asthma Management Guideline for Adults 2007" was developed. To assess the guideline effects on physician's ICS prescription for asthma, we conducted segmented regression and multilevel logistic regression using National Health Insurance claims database of outpatient visits from 2003 to 2010. We set each quarter of a year as a time unit and compared ICS prescription between before and after guideline dissemination. A total of 624,309 quarterly visits for asthma was observed. The ICS prescription rate before and after guideline dissemination was 13.3% and 16.4% respectively (P < 0.001). In the segmented regression, there was no significant guideline effect on overall ICS prescription rate. In multilevel logistic regression analyses, the effect of guideline on overall ICS prescription was not significant (odds ratio, 1.03; 95% CI, 1.00-1.06). In subgroup analysis, ICS prescription increased in secondary care hospitals (odds ratio, 1.15; 95% CI, 1.02-1.30) and in general hospitals (odds ratio, 1.10; 95% CI, 1.04-1.16). However, in primary clinics, which covered 81.7% of asthma cases, there was no significant change (odds ratio, 0.98; 95% CI, 0.94-1.02). From the in-depth interview, we could identify that the reimbursement criteria of the Health Insurance Review and Assessment Service and patient's preference for oral drug were barriers for the ICS prescription. The domestic asthma clinical guideline have no significant effect on ICS prescription, especially in primary clinics.

Effect of the fragrance inhalation of essential oil from Asarum heterotropoides on depression-like behaviors in mice.

BACKGROUND: Psychological stressors may cause affective disorders, such as depression and anxiety, by altering expressions of corticotropin releasing factor (CRF), serotonin (5-HT), and tyrosine hydroxylase (TH) in the brain. This study investigated the effects of essential oil from Asarum heterotropoides (EOAH) on depression-like behaviors and brain expressions of CRF, 5-HT, and TH in mice challenged with stress. METHODS: Male ICR mice received fragrance inhalation of EOAH (0.25, 0.5, 1.0, and 2.0 g) for 3 h in the special cage capped with a filter paper before start of the forced swimming test (FST) and tail suspension test (TST). The duration of immobility was measured for the determination of depression-like behavior in the FST and TST. The selective serotonin reuptake inhibitor fluoxetine as positive control was administered at a dose of 15 mg/kg (i.p.) 30 min before start of behavioral testing. Immunoreactivities of CRF, 5-HT, and TH in the brain were also measured using separate groups of mice subjected to the FST. RESULTS: EOAH at higher doses (1.0 and 2.0 g) reduced immobility time in the FST and TST. In addition, EOAH at a dose of 1.0 g significantly reduced the expected increases in the expression of CRF positive neurons in the paraventricular nucleus and the expression of TH positive neurons in the locus coeruleus, and the expected decreases of the 5-HT positive neurons in the dorsal raphe nucleus. CONCLUSION: These results provide strong evidence that EOAH effectively inhibits depression-like behavioral responses, brain CRF and TH expression increases, and brain 5-HT expression decreases in mice challenged with stress.

Angelica keiskei ameliorates scopolamine-induced memory impairments in mice.

Memory impairment is the most common symptom in patients with Alzheimer's disease (AD). Angelica keiskei (AK) has traditionally been used as a diuretic, laxative, analeptic and galactagogue. However, the anti-amnesic effects of AK and its molecular mechanisms have yet to be clearly elucidated. The aim of the present study is to evaluate the effects of AK on scopolamine-induced memory impairments in mice. The regulatory effect of AK on memory impairment was investigated using passive avoidance, Y-maze and the Morris water maze tasks. Acetylcholinesterase (AChE) activity assay was performed to investigate the cholinergic antagonistic effect of AK in the hippocampus. The effect of AK on phosphorylation of cAMP response element-binding protein (CREB) and expression of brain-derived neurotrophic factor (BDNF) were evaluated by Western blot assays and immunohistochemistry. The findings showed that AK significantly attenuated scopolamine-induced cognitive impairment in mice. Increase of AChE activity caused by scopolamine was significantly attenuated by AK. Additionally, AK significantly recovered the phosphorylation of CREB and expression of BDNF reduced by scopolamine in the hippocampus. Taken together, these results provide experimental evidence that AK might be a useful agent in preventing deficit of learning and memory caused by AD and aging.

The ameliorative effect of sophoricoside on mast cell-mediated allergic inflammation in vivo and in vitro.

Sophoricoside exhibits numerous pharmacological effects, including anti- inflammatory and anti-cancer actions, yet the exact mechanism that accounts for the anti-allergic effects of sophoricoside is not completely understood. The aim of the present study was to elucidate whether and how sophoricoside modulates the mast cell-mediated allergic inflammation in vitro and in vivo. We investigated the pharmacological effects of sophoricoside on both compound 48/80 or histamine-induced scratching behaviors and 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis in mice. Additionally, to find a possible explanation for the anti-inflammatory effects of sophoricoside, we evaluated the effects of sophoricoside on the production of histamine and inflammatory cytokines and activation of nuclear factor-κB (NF-κB) and caspase-1 in phorbol 12-myristate 13-acetate plus calcium ionophore A23187 (PMACI)-stimulated human mast cells (HMC-1). The finding of this study demonstrated that sophoricoside reduced compound 48/80 or histamine-induced scratching behaviors and DNCB-induced atopic dermatitis in mice. Additionally, sophoricoside inhibited the production of inflammatory cytokines as well as the activation of NF-κB and caspase-1 in stimulated HMC-1. Collectively, the findings of this study provide us with novel insights into the pharmacological actions of sophoricoside as a potential molecule for use in the treatment of allergic inflammation diseases.

Anti-Obesity Effects of Petasites japonicus (Meowi) Ethanol Extract on RAW 264.7 Macrophages and 3T3-L1 Adipocytes and Its Characterization of Polyphenolic Compounds.

Koreans have been consuming Petasites Japonicus (PJ) as food. Although the therapeutic effect of PJ on allergic or inflammatory reactions associated with asthma has been proven, its effect on obesity is unclear. Therefore, the present study was aimed to assess the obesity related anti-inflammatory and anti-adipogenic effects of ethanol extract PJ (EPJ) on the inflammatory response in RAW 264.7 macrophages and on differentiation in 3T3-L1 adipocytes. In addition, the polyphenolic compound was quantitatively characterized from the EPJ using ultra performance liquid chromatography coupled with diode array detector, quadrupole time-of-flight-mass spectrometry (UPLC-DAD-QToF-MS). In RAW 264.7 or 3T3-L1, reduction of nitric oxide (in macrophages) production as well as monocyte chemoattractant protein-1 and tumor necrosis factor-α were observed. Treatment of EPJ in adipocyte differentiation showed an improvement in adiponectin and lipid accumulation and a significant reduction of PPARγ and FABP-4 mRNA expression levels. On the other hand, mRNA expression of UCP-1, PPARα, and ACO increased in the EPJ treated group. In addition, a total of 26 polyphenolic compounds were detected and of which 12 are reported for the first time from PJ. The higher content of diverse polyphenolic compounds presented in EPJ might be responsible for the observed anti-inflammatory and anti-adipogenic effect. These results suggest that PJ is valuable in improving obesity-related inflammatory responses.

Decursin and decursinol angelate inhibit VEGF-induced angiogenesis via suppression of the VEGFR-2-signaling pathway.

Inhibition of angiogenesis is an attractive approach for the treatment of angiogenic diseases, such as cancer. Vascular endothelial growth factor (VEGF) is one of the most important activators of angiogenesis and interacts with the high-affinity tyrosine kinase receptors, VEGFR-1 and VEGFR-2. The pyranocoumarin compounds decursin and decursinol angelate isolated from the herb, Angelica gigas, are known to possess potent anti-inflammatory activities. However, little is known about their antiangiogenic activity or their underlying mechanisms. Here, we show the antiangiogenic effects of decursin and decursinol angelate using in vitro assays and in vivo animal experiments. Decursin and decursinol angelate inhibited VEGF-induced angiogenic processes in vitro, including proliferation, migration and tube formation of human umbilical vein endothelial cells. Decursin and decursinol angelate significantly suppressed neovessel formation in chick chorioallantoic membrane and tumor growth in a mouse model. The microvessel density in tumors treated with decursin for 14 days was significantly decreased compared with a vehicle control group. Decursin and decursinol angelate inhibited VEGF-induced phosphorylation of VEGFR-2, extracellular signal-regulated kinases and c-Jun N-terminal kinase mitogen-activated protein kinases. Taken together, these results demonstrate that decursin and decursinol angelate are novel candidates for inhibition of VEGF-induced angiogenesis.

Decursin inhibits retinal neovascularization via suppression of VEGFR-2 activation.

PURPOSE: Pathologic angiogenesis in the retina leads to the catastrophic loss of vision. Retinopathy of prematurity (ROP), a vasoproliferative retinopathy, is a leading cause of blindness in children. We evaluated the inhibitory effect of decursin on retinal neovascularization. METHODS: Anti-angiogenic activity of decursin was evaluated by vascular endothelial growth factor (VEGF)-induced proliferation, migration, and in vitro tube formation assay of human retinal microvascular endothelial cells (HRMECs). We also used western blot analysis to assess inhibition of vascular endothelial growth factor receptor-2 (VEGFR-2) phosphorylation by decursin. After intravitreal injection of decursin in a mouse model of ROP, retinal neovascularization was examined by fluorescence angiography and vessel counting in cross-sections. The toxicity of decursin was evaluated through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in HRMECs as well as histologic and immunohistochemistry examination for glial fibrillary acidic protein in the retina. RESULTS: Decursin significantly inhibited VEGF-induced proliferation, migration, and the formation of capillary-like networks of retinal endothelial cells in a dose-dependent manner. Decursin inhibited VEGF-induced phosphorylation of VEGFR-2, blocking the VEGFR-2 signaling pathway. When intravitreously injected, decursin dramatically suppressed retinal neovascularization in a mouse model of ROP. Even in a high concentration, decursin never induced any structural or inflammatory changes to cells in retinal or vitreous layers. Moreover, the upregulation of glial fibrillary acidic protein expression was not detected in Mueller cells. CONCLUSIONS: Our data suggest that decursin may be a potent anti-angiogenic agent targeting the VEGFR-2 signaling pathway, which significantly inhibits retinal neovascularization without retinal toxicity and may be applicable in various other vasoproliferative retinopathies as well.

Regulation of type IV collagen alpha chains of glomerular epithelial cells in diabetic conditions.

An early feature of diabetic nephropathy is the alteration of the glomerular basement membrane (GBM), which may result in microalbuminuria, subsequent macroproteinuria, and eventual chronic renal failure. Although type IV collagen is the main component of thickened GBM in diabetic nephropathy, cellular metabolism of each alpha chains of type IV collagen has not been well studied. To investigate the regulation of alpha(IV) chains in diabetic conditions, we examined whether glucose and advanced glycosylation endproduct (AGE) regulate the metabolism of each alpha(IV) chains in the diabetic tissue and glomerular epithelial cells (GEpC). Glomerular collagen alpha3(IV) and alpha5(IV) chains protein were higher and more intense in immunofluorescence staining according to diabetic durations compared to controls. In vitro, mainly high glucose and partly AGE usually increased total collagen protein of GEpC by [(3)H]-proline incorporation assay and each alpha(IV) chain proteins including alpha1(IV), alpha3(IV), and alpha5(IV) in time-dependent and subchain-specific manners. However, the changes of each alpha(IV) chains mRNA expression was not well correlated to the those of each chain proteins. The present findings suggest that the metabolism of individual alpha(IV) chains of GBM is differentially regulated in diabetic conditions and those changes might be induced not only by transcriptional level but also by post-translational modifications.

The ameliorative effect of Protaetia brevitarsis Larvae in HFD-induced obese mice.

Protaetia brevitarsis Lewis (P. brevitarsis) larvae, edible insect, traditionally is consumed for various health benefits. However, little information is available with respect to its direct anti-obesity effects. Thus, the present study was designed to investigate the regulatory effect of P. brevitarsis against high-fat diet (HFD)-induced obese mice. HFD-fed mice showed an increase in the body weight and serum levels of total cholesterol as well as low-density lipoprotein-cholesterol, and triglycerides. The administration of P. brevitarsis to obese mice induced a reduction in their body weight, lipid accumulation in liver and serum lipid parameter compared with the HFD fed mice. P. brevitarsis also inhibited the expression of obesity-related genes such as CCAAT/enhancer-binding protein alpha and fatty acid synthesis in 3T3-L1 cells. Moreover, oleic acid was identified as predominant fatty acid of P. brevitarsis by gas chromatography analysis. Conclusively, these findings suggested that P. brevitarsis may help to prevent obesity and obesity-related metabolic diseases.

Evaluation of Community-based Hypertension Control Programme in South Korea.

INTRODUCTION: This study was conducted to provide an overview of the community-based hypertension and diabetes control programme of 19 cities in Korea and to evaluate its effectiveness in controlling hypertension at the community level. MATERIALS AND METHODS: In this longitudinal observational study, we analysed the data of 117,264 hypertensive patients aged ≥65 years old from the time of their first enrolment in July 2012 to October 2013 (up to their 2-year follow-up). RESULTS: The hypertension control rate of 72.5% at the time of enrolment increased to 81.3% and 82.4% at 1 and 2 years after enrolment. Treatment continuity, completion of hypertension self-management education, and longer enrolment duration in the programme contributed to improvements in hypertension control rate. CONCLUSION: This programme was characterised by a public health-clinical partnership at the community level. Despite its simplicity, the programme was evaluated as a successful attempt to control hypertension among patients aged >65 years at the community level.

Do Korean Doctors Think a Palliative Consultation Team Would Be Helpful to Their Terminal Cancer Patients?

PURPOSE: Hospice and palliative care services (HPC) are not commonly utilized in Korea; however, palliative care teams (PCTs) have been found to be effective at addressing the shortcomings in HPC. In this study, we attempted to outline unmet palliative care needs of terminal cancer patients and the potential benefits of PCTs as perceived by doctors in Korea. MATERIALS AND METHODS: We surveyed 474 doctors at 10 cancer-related academic conferences from June to November 2014 with a self-report questionnaire to assess their perceptions of end-of-life care needs and the expected effects of PCTs on caring for terminal cancer patients. Among those surveyed, 440 respondents who completed the entire questionnaire were analyzed. RESULTS: In all domains, fewer participants reported satisfaction with palliative care services than those reporting needs (p < 0.001). The surveyed participants also reported difficulties with a shortage of time for treatment, psychological burden, lack of knowledge regarding hospice care, lengths of stay, and palliative ward availability. Multivariate logistic regression analysis revealed that female doctors (odds ratio [OR], 2.672; 95% confidence interval [CI], 1.035 to 6.892), doctors who agreed that referring my patients to a HPC means I must give up on my patient (OR, 3.075; 95% CI, 1.324 to 7.127), and doctors who had no experience with HPC education (OR, 3.337; 95% CI, 1.600 to 7.125) were associated with higher expected effectiveness of PCT activities. CONCLUSION: The PCT activities were expected to fill the doctor's perceived unmet HPC needs of terminal cancer patients and difficulties in communications.

Cytotoxic and ACAT-inhibitory sesquiterpene lactones from the root of Ixeris dentata forma albiflora.

Ixeris dentata forma albiflora was extracted with 80% aqueous MeOH, and the concentrated extract was partitioned with EtOAc, n-BuOH and H2O. Eight sesquiterpenes were isolated through repeated silica gel and octadecyl silica gel (C18, ODS) column chromatography of the EtOAc and n-BuOH fractions. Physicochemical analysis using NMR, MS and IR revealed the chemical structures of the sesquiterpenes, which were zaluzanin (1), 9a-hydroxyguaian-4(15),10(14),11(13)-triene-6,12-olide (2), 3beta-O-beta-D-glucopyranosyl-8beta-hydroxyguaian-4(15),10(14)-diene-6,12-olide (3), 3-O-beta-D-glucopyranosyl-8beta-hydroxyguauan-10(14)-ene-6,12-olide (4), ixerin M (5), glucozaluzanin C (6), crepiside I (7), and ixerin D (8). This is the first time that these sesquiterpene lactones have been isolated from this plant. Compounds 1, 2 and 7 revealed relatively high cytotoxicities on human colon carcinoma cell and lung adenocarcinoma cell, while compounds 5 and 7 showed acyl-CoA: cholesterol acyltransferase (ACAT) inhibitory activity.

Decursinol angelate inhibits PGE2-induced survival of the human leukemia HL-60 cell line via regulation of the EP2 receptor and NFκB pathway.

Decursinol angelate (DA), an active pyranocoumarin compound from the roots of Angelica gigas, has been reported to possess anti-inflammatory and anti-cancer activities. In a previous study, we demonstrated that prostaglandin E2 (PGE2) plays a survival role in HL-60 cells by protecting them from the induction of apoptosis via oxidative stress. Flow cytometry and Hoechst staining revealed that PGE2 suppresses menadione-induced apoptosis, cell shrinkage, and chromatin condensation, by blocking the generation of reactive oxygen species. Treatment of DA was found to reverse the survival effect of PGE2 as well as restoring the menadione-mediated cleavage of caspase-3, lamin B, and PARP. DA blocked PGE2-induced activation of the EP2 receptor signaling pathway, including the activation of PKA and the phosphorylation of CREB. DA also inhibited PGE2-induced expression of cyclooxygenase-2 and the activation of the Ras/Raf/ Erk pathway, which activates downstream targets for cell survival. Finally, DA greatly reduced the PGE2-induced activation of NF-κB p50 and p65 subunits. These results elucidate a novel mechanism for the regulation of cell survival and apoptosis, and open a gateway for further development and combinatory treatments that can inhibit PGE2 in cancer cells.

Prevalence and Associated Factors of Anxiety and Depressive Symptoms Among Bereaved Family Members of Cancer Patients in Korea: A Nation-Wide Cross-Sectional Study.

Bereaved family members of cancer patient are at risk of having psychological problems such as anxiety and depression. However, prevalence and associated factors of anxiety and depressive symptoms among this population have not been explored in Korea.We conducted a nation-wide cross-sectional questionnaire survey of 3522 bereaved family members of cancer patients who died at 44 hospice palliative care unit (HPCU) in Korea in 2012. The questionnaire comprised the Hospital Anxiety and Depression Scale (HADS) and Good Death Inventory (GDI). Deceased patient's age, sex, primary site of cancer, duration of stay at HPCU, awareness of terminal status, bereaved family member's age, sex, and relation to the deceased were collected from Korean Terminal Cancer Patients Information System.1121 returned questionnaires were analyzed (response rate, 31.8%). Using a cut-off value of 8 for HADS subscale, the prevalence of anxiety and depressive symptoms was 48.0% and 57.6%, respectively. Mean scores for HADS-A and HADS-D were 7.88 ±â€Š4.87 and 8.91 ±â€Š4.82, respectively. Among the bereaved, older age, being a spouse to the deceased, family members of younger patient, and negative score for a few GDI items were significantly associated with an increased risk of having anxiety or depressive symptoms in the multivariate logistic analysis.In conclusion, we noted the high prevalence of anxiety and depressive symptoms among the bereaved of cancer patients and identified associated factors for these psychological morbidities. Systematic efforts are needed to improve the mental health of the bereaved family members of cancer patients.

Triterpenoids from the flower of Campsis grandiflora K. Schum. as human acyl-CoA: cholesterol acyltransferase inhibitors.

The flower of Campsis grandiflora K. Schum. was extracted with 80% aqueous MeOH, and the concentrated extract was partitioned with EtOAc, n-BuOH and H2O. From the EtOAc fraction, seven triterpenoids were isolated through the repeated silica gel, ODS column chromatographies and preparative HPLC. From the result of physico-chemical data including NMR, MS and IR, the chemical structures of the compounds were determined as 3beta-hydroxyolean-12-en-28-oic acid (oleanolic acid, 1), 3beta-hydroxyurs-12-en-28-oic acid (ursolic acid, 2), 3beta-hydroxyurs-12-en-28-al (ursolic aldehyde, 3), 2alpha,3beta-dihydroxyolean-12-en-28-oic acid (maslinic acid, 4), 2alpha,3beta-dihydroxyurs-12-en-28-oic acid (corosolic acid, 5), 3beta,23-dihydroxyurs-12-en-28-oic acid (23-hydroxyursolic acid, 6) and 2alpha,3beta,23-trihydroxyolean-12-en-28-oic acid (arjunolic acid, 7). These teriterpenoids were isolated for the first time from this plant. Also, compounds 4, 5, 6, and 7 revealed relatively high hACAT-1 inhibitory activity with the value of 46.2+/-1.1, 46.7+/-0.9, 41.5+/-1.3 and 60.8+/-1.1% at the concentration of 100 microg/mL, respectively.

Angelica keiskei Koidzumi extracts improve some markers of liver function in habitual alcohol drinkers: a randomized double-blind clinical trial.

Alcohol induces oxidative stress and inflammatory response, which can lead to hepatitis and cirrhosis. Previous studies reported that the extracts of Angelica keiskei Koidzumi (AKE) have antioxidant and anti-inflammatory properties, suggesting that AKE could improve abnormalities associated with alcoholic liver disease. In this study, the effectiveness of AKE supplementation was assessed in 82 habitual alcohol drinkers (male: more than 14 units per week, female: more than 7 units per week) with abnormal liver biochemistry in a placebo-controlled, randomized double-blind trial over 12 weeks. Among the subjects, 65% (n=43) were heavy drinkers consuming more than 35 units per week. Among heavy drinkers, gamma-glutamyl transferase levels of 19 subjects per AKE-treated group were significantly decreased (21.16±37.63, P=.016) with significant differences observed compared to the 24 subjects per placebo group (P=.046). However, no significant differences were observed in aspartate aminotransferase and alanine aminotransferase levels between the AKE- and placebo-treated groups. These results suggest that AKE supplementation might improve liver function in heavy drinkers.

Recovery effect of phenylpropanoid glycosides from Magnolia obovata fruit on alloxan-induced pancreatic islet damage in zebrafish (Danio rerio).

Investigation of phytochemicals from Magnolia obovata fruit led to the isolation of three novel phenylpropanoid glycosides: obovatoside A-C (1-3) and two known phenylpropanoids, syringin (4) and pavonisol (5). The structures of 1-5 were determined by NMR, HRMS, IR and CD spectroscopic analyses. All compounds were evaluated for their effects on recovery from alloxan-induced pancreatic islet damage in zebrafish. All compounds increased the size of the injured pancreatic islet from 0.60- to 1.14-fold. Compounds 1 and 3-5 significantly increased glucose absorption in zebrafish.

Protection against beta-amyloid peptide-induced memory impairment with long-term administration of extract of Angelica gigas or decursinol in mice.

We investigated the effect of long-term oral administration of ethanolic extract of Angelica gigas Nakai (Umbelliferae) (EAG) or decursinol, a coumarin isolated from A. gigas, on beta-amyloid peptide 1-42 (Abeta(1-42))-induced memory impairment in mice. Mice were allowed free access to drinking water (control) or water containing different concentrations of EAG. After 4 weeks, Abeta(1-42) (410 pmol) was administered via intracerebroventricular injection. Pretreatment of mice with EAG (0.1%) for 4 weeks significantly blocked the Abeta(1-42)-induced impairment in passive avoidance performance. Next, mice were fed with chow mixed with various doses of decursinol for 4 weeks before intracerebroventricular injection of Abeta(1-42) (410 pmol). Pretreatment of mice with decursinol (0.001%, 0.002%, and 0.004%) for 4 weeks significantly attenuated the Abeta(1-42)-induced impairment in passive avoidance performance. Decursinol (0.004%) also significantly blunted the Abeta(1-42)-induced decrease in alternation behavior (spatial working memory) in the Y-maze test without change in general locomotor activity. These findings suggest that EAG or decursinol may have preventive effect against memory impairment related with Abeta of Alzheimer's disease.

Prenylated flavonoids from Moghania philippinensis.

Five prenylated flavonoids, 8-(1,1-dimethylallyl)genistein (1), 5,7,3',4'-tetrahydroxy-2',5'-di(3-methylbut-2-enyl)isoflavone (2), 5,7,3'-trihydroxy-2'-(3-methylbut-2-enyl)-4',5'-(3,3-dimethylpyrano)isoflavone (3), (2R)-5,2',4'-trihydroxy-8,5'-di(3-methylbut-2-enyl)-6,7-(3,3-dimethylpyrano)flavanone (4a) and (2S)-5, 2', 4'-trihydroxy-8,5'-di(3-methylbut-2-enyl)-6,7-(3,3-dimethylpyrano)flavanone (4b), were isolated from the roots of Moghania philippinensis. The structures of these compounds were determined on the basis of spectroscopic and chemical means.