Fourteen compounds were isolated from the stem of Angelica polymorpha. On the basis of spectral data, these compounds were identified as isoimperatorin (1), phellopterin (2), bergapten (3), xanthyletin (4), cnidilin (5), geijerine (6), (−)-3'-acetyl hamaudol (7), 7-demethylsuberosine (8), dehydrogeijerin (9), (−)-hamaudol (10), (+)-visamminol (11), divaricatol (12), scopoletin (13), and decursidate (14), respectively. Among them, compounds 4 - 6, 8, 9, 13, and 14 were isolated for the first time from A. polymorpha. Dehydrogeijerin (6) and geijerin (9) were isolated for the first time from genus Angelica. All isolates tested for inhibitory activity against acetylcholinesterae. Compounds 1 to 13 showed acetylcholinesterase inhibitory activity with IC₅₀ values ranging from 1.4 to 37.5 µM.
Acetylcholinesterase* ; Angelica* ; Cholinesterase Inhibitors* ; Chromones ; Coumarins ; Scopoletin

OBJECTIVE: Depending on genetic or environmental effects over adolescent development, typical behavioral responses come out in adolescence. Also, alteration of nitric oxide (NO) levels in the brain has been associated with modifications of stress related behavior. Present study was designed to investigate the possible influence of chronic stress from restraint on the generation of depression in adolescent mice, and also to evaluate whether NO has modulatory roles in the behavioral and biological reactions. METHODS: ICR mice exposed to stressful restraint, 2 h per day, was treated with NG-nitro L-arginine methyl ester (L-NAME) (10 mg/kg), a non-selective NO synthase (NOS) inhibitor. To evaluate depression-like behavior in the mice, forced swim test and open field test were performed after the last restraint. To investigate stress-induced changes in the expression level of glial cell-derived neurotrophic factor (GDNF), free-floating immunohistochemistry was performed. RESULTS: The results showed that stressed group has longer immobility time and less crossing number in forced swimming and open field test, and that these stress responses were significantly prevented by L-NAME. Furthermore, decreased GDNF expression in the hippocampus by stress was prevented to that of controls within the L-NAME treated group. CONCLUSION: The results suggest that stress and NO signaling could be involved in generation of depression in adolescence. It also suggested that GDNF might contribute to prevent stress-related behaviors.
Adolescent ; Adolescent Development ; Animals ; Arginine ; Brain ; Depression ; Glial Cell Line-Derived Neurotrophic Factor ; Hippocampus ; Humans ; Immunohistochemistry ; Mice ; Mice, Inbred ICR ; NG-Nitroarginine Methyl Ester ; Nitric Oxide ; Nitric Oxide Synthase ; Swimming

A new stereoisomeric monoterpene glycoside and five already-known compounds were isolated from the n-BuOH soluble fraction of Clematis heracleifolia leaves. On the basis of spectral data, the structures of the isolated compounds were identified as protocatechuic acid (1), ferulic acid (2), caffeic acid (3), aesculin (4), (6Z)-9-hydroxylinaloyl glucoside (5), and 9-hydroxylinaloyl glucoside (6) and these were isolated for the first time from this plant. Among these compounds, (6Z)-9-hydroxylinaloyl glucoside (5) is a newly isolated from plant source.
Clematis* ; Esculin ; Plants ; Stereoisomerism*

Neurofi brillary tangles (NFTs) of microtubule-associated protein tau are a pathological hallmark of Alzheimer's disease (AD). Endoplasmic reticulum (ER) stress has been known to be involved in the pathogenesis of AD. However, the exact role of ER stress in tau pathology has not yet been clearly elucidated. In present study, the possible relationship between tau pathology and ER stress was examined in terms of sorcin, which is a calcium binding protein and plays an important role in calcium homeostasis. Our previous yeast two hybrid study showed that sorcin is a novel tau interacting protein. Caspase-3-cleaved tau (T4C3) showed significantly increased tau-sorcin interaction compared to wild type tau (T4). Thapsigargin-induced ER stress and co-expression of constitutively active GSK3β (GSK3β-S9A) also exhibited significantly increased tau-sorcin interactions. T4C3-expressing cells showed potentiated thapsigargin-induced apoptosis and disruption of intracellular calcium homeostasis compared to T4-expressing cells. Overexpression of sorcin signifi cantly attenuated thapsigargin-induced apoptosis and disruption of calcium homeostasis. In contrary, siRNA-mediated knock-down of sorcin showed significantly increased thapsigargin-induced apoptosis and disruption of calcium homeostasis. These data strongly suggest that sequestration of sorcin by aberrant forms of tau compromises the function of sorcin, such as calcium homeostasis and cellular resistance by ER stress, which may consequently result in the contribution to the progression of AD.
Alzheimer Disease ; Apoptosis ; Calcium* ; Carrier Proteins ; Endoplasmic Reticulum ; Endoplasmic Reticulum Stress ; Homeostasis* ; Pathology ; Thapsigargin ; Yeasts

PURPOSE: Rheumatoid arthritis (RA) is a common, chronic inflammatory arthritis that develops most often in women. Gonadal hormones may account for the sexual dimorphism in the immune response and for the greater incidence of autoimmune disease in females. Gonadotrophin-releasing hormone (GnRH), one of the gonadal hormones, plays an important role in immune system modulation. This study examined the effects of single nucleotide polymorphisms (SNP) in GnRH on gender differences in the pathophysiology of RA. MATERIALS AND METHODS: The presence of SNPs rs2659590, rs2321248, rs6186, rs6185, and rs2321049 in the human GnRH1 gene was confirmed in Korean RA patients by Taqman(R) SNP genotyping assays. A total of 153 unrelated female, Korean RA patients and 96 female Korean controls participated. RESULTS: There were no significant associations between GnRH1 polymorphisms and RA. However, we found that the rs2659590, rs6185 and rs2321248 polymorphism might be associated with a susceptibility to aberrantly high erythrocyte sedimentation rates in female RA patients. CONCLUSION: Additional studies, with a larger number of patients and in different populations will be required to assess whether GnRH1 polymorphisms and these haplotypes could be used as susceptibility or resistance markers in RA. To our knowledge, this study is the first to analyze associations between SNPs of GnRH1 and RA.
Arthritis ; Arthritis, Rheumatoid ; Autoimmune Diseases ; Blood Sedimentation ; Female ; Gonadal Hormones ; Gonadotropin-Releasing Hormone ; Haplotypes ; Humans ; Immune System ; Incidence ; Polymorphism, Single Nucleotide

OBJECTIVE: In our previous study, it has been reported that valproic acid (VPA) effects gliogenesis and increases the number of glial precursor cells during the early postnatal period. However there is no specific report that whether this process is going on up to the age of mature brain development and the consequence effect of this ongoing gliogenesis process. METHODS: As an ongoing study, using Immunoblotting analysis, we checked the level of glial protein and glial-derived factor markers in the frontal cortex of a rat brain at postnatal day (PND) 21. RESULTS: The finding of the study suggests that, in the VPA group (p < 0.05), early exposure elicited significantly to increase the expression level of glial protein cells at PND 21 in the frontal cortex of rat brain. CONCLUSION: Therefore we suggest that, alter gliogenesis and abnormal number of glial cells modulate the neurobiological dysfunction and induces the risk of neurodevelopmental disorders.
Animals ; Astrocytes* ; Brain ; Frontal Lobe* ; Immunoblotting ; Neurodevelopmental Disorders ; Neuroglia ; Rats* ; Valproic Acid*

A new phenolic compound and three known flavonoids isolated from the MeOH extracts of Lespedeza tomentosa. Based on spectral data, the isolated compounds were identified as methyl 4,5-dihydroxy-3-methoxy-2-(3-methylbut-2-en-1-yl)benzoate (1), 1-methoxylespeflorin G11 (2), farrerol (3) and 1-methoxylespeflorin I2 (4). Methyl 4,5- dihydroxy-3-methoxy-2-(3-methylbut-2-en-1-yl)benzoate (1) is newly isolated from plant source.

A new phenolic compound and three known flavonoids isolated from the MeOH extracts of Lespedeza tomentosa. Based on spectral data, the isolated compounds were identified as methyl 4,5-dihydroxy-3-methoxy-2-(3-methylbut-2-en-1-yl)benzoate (1), 1-methoxylespeflorin G11 (2), farrerol (3) and 1-methoxylespeflorin I2 (4). Methyl 4,5- dihydroxy-3-methoxy-2-(3-methylbut-2-en-1-yl)benzoate (1) is newly isolated from plant source.

N-(p-Coumaryol) tryptamine (CT), a phenolic amide, has been reported to exhibit anti-oxidant and anti-inflammatory activities. However, the underlying mechanism by which CT exerts its pharmacological properties has not been clearly demonstrated. The objective of this study is to elucidate the anti-inflammatory mechanism of CT in lipopolysaccharide (LPS)-challenged RAW264.7 macrophage cells. CT significantly inhibited LPS-induced extracellular secretion of pro-inflammatory mediators such as nitric oxide (NO) and PGE2, and protein expressions of iNOS and COX-2. In addition, CT significantly suppressed LPS-induced secretion of pro-inflammatory cytokines such as TNF-alpha and IL-1beta. To elucidate the underlying anti-inflammatory mechanism of CT, involvement of MAPK and Akt signaling pathways was examined. CT significantly attenuated LPS-induced activation of JNK/c-Jun, but not ERK and p38, in a concentration-dependent manner. Interestingly, CT appeared to suppress LPS-induced Akt phosphorylation. However, JNK inhibition, but not Akt inhibition, resulted in the suppression of LPS-induced responses, suggesting that JNK/c-Jun signaling pathway significantly contributes to LPS-induced inflammatory responses and that LPS-induced Akt phosphorylation might be a compensatory response to a stress condition. Taken together, the present study clearly demonstrates CT exerts anti-inflammatory activity through the suppression of JNK/c-Jun signaling pathway in LPS-challenged RAW264.7 macrophage cells.
Cytokines ; Dinoprostone ; Macrophages ; Nitric Oxide ; Phenol ; Phosphorylation ; Tumor Necrosis Factor-alpha

In the present study, neuroprotective property of celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, and its underlying mechanism were examined in the animal model of kainic acid (KA)-induced excitotoxicity. KA, administered intracerebroventricularly (i.c.v.), induced marked neuronal cell death with concurrent microglial activation and subsequent induction of inducible nitric oxide synthase (iNOS) in the hippocampus. Histopathological analysis demonstrated that celecoxib (100 mg/kg), pre-treated 1 hr before or post-treated 2 hr after KA i.c.v. injection, significantly attenuated KA-induced death of pyramidal neurons in CA3 region. Celecoxib obviously suppressed KA-induced microglial activation and subsequent iNOS expression. KA- induced phosphorylation of c-Jun N-terminal kinases (JNK) was attenuated with celecoxib treatments. The results of the present study demonstrate that suppression of JNK phosphorylation by celecoxib contributes to its neuroprotective action against KA-induced excitotoxicity suggesting that celecoxib may be a potentially valuable in the treatment of acute brain pathologies associated with excitotoxic neuronal damage such as epilepsy, stroke, and traumatic brain injury.
Brain ; Brain Injuries ; Cell Death ; Cyclooxygenase 2 ; Epilepsy ; Hippocampus ; JNK Mitogen-Activated Protein Kinases ; Kainic Acid ; Microglia ; Models, Animal ; Neurons ; Nitric Oxide Synthase Type II ; Phosphorylation ; Phosphotransferases ; Pyrazoles ; Stroke ; Sulfonamides ; Celecoxib