Effect of Mollusca shell extracts on inhibition of kimchi over-acidification.

Mollusca species shell such as oyster shell (OS) and snail shell (SS), are discarded after taking the meat, and the discarded shell causes the environmental problems. Therefore, recycling shell waste could potentially eliminate the environmental problems. This study aimed to evaluate the potential of OS and SS as natural calcium resources. The minerals, calcium, magnesium, potassium, phosphorus and sodium were analyzed in OS and SS extracts. Among them, the calcium content was the highest: 36.87 (%) and 33.42 (%) in the OS and SS extracts, respectively. Further, the content of ionized bioavailable form of calcium in OS and SS was higher than that of CaCO3 under simulated gastrointestinal digestion conditions. Additionally, OS and SS were added to kimchi, and their inhibitory effect on kimchi acidification was evaluated by assessing pH, titratable acidity and microbial analysis. As the results indicated that the addition of OS and SS had little effect on inhibiting the growth of lactic acid bacteria. However, it was confirmed that calcium neutralizes the organic acids produced during fermentation. Overall, the results of this study provide preliminary information on the re-use of OS and SS extracts as ionized natural calcium supplements and fermentation retardants.

Gintonin mitigates experimental autoimmune encephalomyelitis by stabilization of Nrf2 signaling via stimulation of lysophosphatidic acid receptors.

Gintonin (GT), a glycolipoprotein fraction isolated from ginseng, exerts neuroprotective effects in models of neurodegenerative diseases such as Alzheimer's disease. However, the in vivo role of GT in multiple sclerosis (MS) has not been clearly resolved. We investigated the effect of GT in myelin oligodendrocyte glycoprotein (MOG35-55)-induced experimental autoimmune encephalomyelitis (EAE), an animal model of MS. GT alleviated behavioral symptoms of EAE associated with reduced demyelination, diminished infiltration and activation of immune cells (microglia and macrophage), and decreased expression of inflammatory mediators in the spinal cord of the EAE group compared to that of the sham group. GT reduced the percentages of CD4+/IFN-γ+ (Th1) and CD4+/IL-17+ (Th17) cells but increased the population of CD4+/CD25+/Foxp3+ (Treg) cells in the spinal cord, in agreement with altered mRNA expression of IFN-γ, IL-17, and TGF-ß in the spinal cord in concordance with mitigated blood-brain barrier disruption. The underlying mechanism is related to inhibition of the ERK and p38 mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB) pathways and the stabilization of nuclear factor erythroid 2-related factor 2 (Nrf2) via increased expression of lysophosphatidic acid receptor (LPAR) 1-3. Impressively, these beneficial effects of GT were completely neutralized by inhibiting LPARs with Ki16425, a LPAR1/3 antagonist. Our results strongly suggest that GT may be able to alleviate EAE due to its anti-inflammatory and antioxidant activities through LPARs. Therefore, GT is a potential therapeutic option for treating autoimmune disorders including MS.

Antioxidant activity and calcium bioaccessibility of Moringa oleifera leaf hydrolysate, as a potential calcium supplement in food.

Moringa oleifera leaf (ML) is rich in vitamins and minerals, specially abundant calcium, therefore it is widely used as a calcium supplement for food. This study aimed to investigate the antioxidant activity and calcium bioaccessibility of M. oleifera leaf hydrolysate (MLH) as a calcium supplement for kimchi. MLH was prepared under three different proteases, two different protease contents, and three different incubation times. Total phenol content (TPC), total flavonoid content (TFC), and antioxidant activities were investigated. Cellular activity and calcium bioaccessibility were also investigated. The highest calcium level of MLH was observed in 3% Protamex treatment for 4 h. TPC, TFC, and antioxidant activities of MLH in Protamex and Alcalase treatments were higher than those in Flavourzyme treatment (p < 0.05). Moreover, high cell viability and alkaline phosphatase activity were also observed in C2C12 cells. Kimchi containing MLH showed high calcium accessibility compared to kimchi alone. Taken together, the application of MLH could have potential as a calcium supplement for kimchi production.

Valeriana fauriei Exerts Antidepressant-Like Effects Through Anti-inflammatory and Antioxidant Activities by Inhibiting Brain-Derived Neurotrophic Factor Associated with Chronic Restraint Stress.

Although depression is the most common psychiatric disorder, its pharmacological properties are not well known yet. It has been reported that Valeriana fauriei (VF) extract is beneficial for several neurological diseases. However, little information is available regarding its antidepressant activity. Therefore, the objective of this study was to determine antidepressant activity of VF and the underlying mechanism involved in its effect on chronic restraint stress (CRS)-induced depression using a mouse model. Oral treatment of VF extract for 14 days significantly ameliorated depression-like behavior (immobility time) in forced swimming and tail suspension tests following CRS induction, in accordance with decreased levels of serum corticosterone. VF extract ameliorated c-Fos expression, microglial activation, phosphorylated p38 expression, and inflammatory response (protein expression levels of cyclooxygenase-2 and inducible nitric oxide) in the prefrontal cortex, hippocampus, and amygdala of mice after CRS induction. However, VF extract enhanced the stimulation of nuclear factor erythroid 2-related factor 2 pathways, in accordance with upregulation in protein expression of brain-derived neurotrophic factor (BDNF). Collectively, our findings demonstrate that VF extract has antidepressant-like activity against CRS-induced depression through its anti-inflammatory and antioxidant effects by inhibiting BDNF expression. Further studies are warranted to investigate VF extract's fraction and components to develop possible antidepressants.

Allium hookeri Root Extract Inhibits Adipogenesis by Promoting Lipolysis in High Fat Diet-Induced Obese Mice.

Allium hookeri (AH) is widely consumed as a herbal medicine. It possesses biological activity against metabolic diseases. The objective of this study was to investigate effects of AH root water extract (AHR) on adipogenesis in 3T3-L1 cells and in high-fat diet (HFD)-induced obese mice. AHR inhibited lipid accumulation during adipocyte differentiation by downregulation of gene expression, such as hormone sensitive lipase (HSL), lipoprotein lipase (LPL) and an adipogenic gene, CCAAT/enhancer binding protein-α in 3T3-L1 preadipocytes. Oral administration of AHR significantly suppressed body weight gain, adipose tissue weight, serum leptin levels, and adipocyte cell size in HFD-induced obese mice. Moreover, AHR significantly decreased hepatic mRNA expression levels of cholesterol synthesis genes, such as 3-hydroxy-3-methylglutaryl CoA reductase, sterol regulatory element-binding transcription factor (SREBP)-2, and low-density lipoprotein receptor, as well as fatty acid synthesis genes, such as SREBP-1c and fatty acid synthase. Serum triglyceride levels were also lowered by AHR, likely as a result of the upregulating gene involved in fatty acid ß-oxidation, carnitine palmitoyltransferase 1a, in the liver. AHR treatment activated gene expression of peroxisome proliferator-activated receptor-γ, which might have promoted HSL and LPL-medicated lipolysis, thereby reducing white adipose tissue weight. In conclusion, AHR treatment can improve metabolic alterations induced by HFD in mice by modifying expression levels of genes involved in adipogenesis, lipogenesis, and lipolysis in the white adipose tissue and liver.

Acupuncture for Histamine-Induced Itch: Association With Increased Parasympathetic Tone and Connectivity of Putamen-Midcingulate Cortex.

Previous studies have suggested that acupuncture is effective for ameliorating itch intensity. However, factors associated with the antipruritic effects of acupuncture have yet to be clarified. In a randomized, sham-controlled, crossover trial, we investigated the antipruritic effects of acupuncture against histamine-induced itch in healthy volunteers. Autonomic changes using heart rate variability (HRV) and brain connectivity using functional magnetic resonance imaging (fMRI) were also assessed to identify physiological factors associated with the acupuncture response. Acupuncture significantly reduced itch intensity and skin blood perfusion as assessed by laser Doppler perfusion imaging compared to sham control, indicating the antipruritic effects of acupuncture. In responder and non-responder analysis, the power of normalized high frequency (HF norm) was significantly higher, while the power of normalized low frequency (LF norm) and LF/HF ratio were significantly lower in responders compared to non-responders, suggesting the acupuncture response involved parasympathetic activation. In fMRI analysis, the putamen and the posterior part of the midcingulate cortex (pMCC) were positively connected to itch and negatively correlated with itch intensity in responders. These results suggest that parasympathetic activity and functional connectivity of the putamen and pMCC could be associated with antipruritic response to acupuncture.

A pilot study: Horticulture-related activities significantly reduce stress levels and salivary cortisol concentration of maladjusted elementary school children.

The effects of three horticulture-related activities (HRAs), including floral arranging, planting, and flower pressing were compared to see if they influenced changes on a stress scale and on salivary cortisol concentrations (SCC) in maladjusted elementary school children. Twenty maladjusted elementary school children were randomly assigned either to an experimental or control group. The control group carried out individual favorite indoor activities under the supervision of a teacher. Simultaneously, the ten children in the experimental group participated in a HRA program consisting of flower arrangement (FA), planting (P), and flower pressing (PF) activities, in which the other ten children in the control group did not take part. During nine sessions, the activities were completed as follows: FA-FA-FA, P-P-P, and PF-PF-PF; each session lasted 40 min and took place once a week. For the quantitative analysis of salivary cortisol, saliva was collected from the experimental group one week before the HRAs and immediately after the activities for 9 consecutive weeks at the same time each session. In the experimental group, stress scores of interpersonal relationship, school life, personal problems, and home life decreased after the HRAs by 1.3, 1.8, 4.2, and 1.3 points, respectively. In particular, the stress score of school life was significantly reduced (P < 0.01). In addition, from the investigation of the SCCs for the children before and after repeating HRAs three times, it was found that flower arrangement, planting, and flower pressing activities reduced the SCCs by ≥37% compared to the SCCs prior to taking part in the HRAs. These results indicate that HRAs are associated with a reduction in the stress levels of maladjusted elementary school children.

Review of Natural Product-Derived Compounds as Potent Antiglioblastoma Drugs.

Common care for glioblastoma multiforme (GBM) is a surgical resection followed by radiotherapy and temozolomide- (TMZ-) based chemotherapy. Unfortunately, these therapies remain inadequate involving severe mortality and recurrence. Recently, new approaches discovering combinations of multiple inhibitors have been proposed along with the identification of key driver mutations that are specific to each patient. To date, this approach is still limited by the lack of effective therapy. Hopefully, novel compounds derived from natural products are suggested as potential solutions. Inhibitory effects of natural products on angiogenesis and metastasis and cancer suppressive effect of altering miRNA expression are provident discoveries. Angelica sinensis accelerates apoptosis by their key substances influencing factors of apoptosis pathways. Brazilin displays antitumor features by making influence on reactive oxygen species (ROS) intensity. Sargassum serratifolium, flavonoids, and so on have antimetastasis effect. Ficus carica controls miRNA that inhibits translation of certain secretory pathway proteins during the UPR. Serratia marcescens and patupilone (EPO 906) are physically assessed materials through clinical trials related to GBM progression. Consequently, our review puts emphasis on the potential of natural products in GBM treatment by regulating multiple malignant cancer-related pathway solving pending problem such as reducing toxicity and side effect.

Phase I and Preliminary Phase II Study of TRC105 in Combination with Sorafenib in Hepatocellular Carcinoma.

Purpose: Endoglin (CD105) is an endothelial cell membrane receptor highly expressed on proliferating tumor vasculature, including that of hepatocellular carcinoma (HCC), and is associated with poor prognosis. Endoglin is essential for angiogenesis, and its expression is induced by hypoxia and VEGF pathway inhibition. TRC105 is a chimeric IgG1 CD105 mAb that inhibits angiogenesis and causes antibody-dependent cellular cytotoxicity and apoptosis of proliferating endothelium.Experimental Design: Patients with HCC (Child-Pugh A/B7), ECOG 0/1, were enrolled in a phase I study of TRC105 at 3, 6, 10, and 15 mg/kg every 2 weeks given with sorafenib 400 mg twice daily. Correlative biomarkers included DCE-MRI and plasma levels of angiogenic factors, including soluble endoglin. Pharmacokinetics were assessed in serum.Results: Twenty-six patients were enrolled, of whom 25 received treatment, 15 with cirrhosis. Hep B/C: 3/15; M:F 19:6; mean age of 60 (range, 18-76); 1 DLT (grade 3 AST) occurred at 10 mg/kg. The most frequent toxicity was low-grade epistaxis, a known toxicity of TRC105. One patient experienced an infusion reaction and was replaced. One patient with coronary stenosis developed a fatal myocardial infarction, and one patient developed G3 cerebral tumor hemorrhage. MTD was not established and DL4 (15 mg/kg) was expanded. The overall response rate in 24 evaluable patients at all 4 dose levels was 21% [95% confidence interval (CI), 7.1-42.2], and 25% (95% CI, 8.7-49.1) in patients with measureable disease. Four patients had confirmed stable disease, one of whom was treated for 22 months. Median progression-free survival (PFS) for 24 patients evaluable for PFS was 3.8 months (95% CI, 3.2-5.6 months); median overall survival was 15.5 months (95% CI, 8.5-26.3 months).Conclusions: TRC105 combined with sorafenib was well tolerated at the recommended single agent doses of both drugs. Encouraging evidence of activity to date (PR rate 25%) was observed, and the study is now continuing to recruit in the phase II stage as a multicenter study to confirm activity of the combination. Clin Cancer Res; 23(16); 4633-41. ©2017 AACR.

Allium hookeri root extract exerts anti-inflammatory effects by nuclear factor-κB down-regulation in lipopolysaccharide-induced RAW264.7 cells.

BACKGROUND: Allium hookeri (AH) is widely consumed as a vegetable and herbal medicine in southeastern Asia. AH has been reported antioxidant, antimicrobial, improvement of bone health and antidiabetic effects. In the present study, we investigated the inhibitory effect of a methanol extract of AH root (AHE) on inflammatory response in lipopolysaccharide (LPS)-induced RAW264.7 cells. METHODS: Initially, characterization of organic sulfur compounds in AHE was determined using high performance liquid chromatography-electrospray ionization-mass spectrometry (HPLC-ESI-MS). Cells were incubated with LPS and AHE for 24 h. The productions of nitric oxide (NO), reactive oxygen species (ROS), and inflammation-related cytokines were examined. Gene and protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were assessed by polymerase chain reaction and Western blotting. Key factor, nuclear factor kappa B (NF-κB) was also determined. RESULTS: AHE contained organosulfur compounds such as alliin and S-allylcysteine by HPLC-ESI-MS. AHE significantly inhibited NO, ROS, and cytokines production in LPS-induced RAW264.7 cells. In addition, AHE treatment inhibited iNOS and COX-2 mRNA and protein levels, leading to a decrease in iNOS-derived NO level. Furthermore, NF-κB activation was, at least in part, suppressed by AHE treatment. CONCLUSION: Our data suggest that AHE treatment inhibits the inflammation condition through suppression of iNOS and COX-2 expression via NF-κB down-regulation.

Immunogenic cancer cell death selectively induced by near infrared photoimmunotherapy initiates host tumor immunity.

Immunogenic cell death (ICD) is a form of cell death that activates an adaptive immune response against dead-cell-associated antigens. Cancer cells killed via ICD can elicit antitumor immunity. ICD is efficiently induced by near-infrared photo-immunotherapy (NIR-PIT) that selectively kills target-cells on which antibody-photoabsorber conjugates bind and are activated by NIR light exposure. Advanced live cell microscopies showed that NIR-PIT caused rapid and irreversible damage to the cell membrane function leading to swelling and bursting, releasing intracellular components due to the influx of water into the cell. The process also induces relocation of ICD bio markers including calreticulin, Hsp70 and Hsp90 to the cell surface and the rapid release of immunogenic signals including ATP and HMGB1 followed by maturation of immature dendritic cells. Thus, NIR-PIT is a therapy that kills tumor cells by ICD, eliciting a host immune response against tumor.

Effects of Oriental Medicine Kyung-Ok-Ko on Uterine Abnormality in Hyperandrogenized Rats.

A traditional herbal prescription Kyung-Ok-Ko (KOK), composed of Rehmannia glutinosa Liboschitz var. purpurae, Lycium chinense, Aquilaria agallocha, Poria cocos, Panax ginseng, and honey, has been widely used in Oriental medicine as an invigorant for age-related diseases, such as amnesia and stroke. However, the beneficial value of KOK on uterine dysfunction related to hyperandrogenism is largely unknown. We investigated the effect of KOK (2.0 g/kg/day, per os) on endometrial abnormalities in a dehydroepiandrosterone (DHEA, subcutaneous)-induced polycystic ovary syndrome (PCOS) rat model. Preadministration of KOK significantly (p<0.05) decreased the elevated body weight, uterus weight, and endometrial thickness by PCOS induction, corresponding to reduced apoptosis and the infiltration of immune cells (CD4+ T cells, CD8+ T cells, and macrophages) in the endometrium. These results were associated with reduced mRNA expression of interleukin (IL)-1ß, IL-6, IL-8, and matrix metalloproteinase-3 and increased mRNA expression of IGF-ß1, transforming growth factor (TGF)-ß, TGF-ß1, and vascular endothelial growth factor in the uterus after DHEA injection. These multiple effects of KOK may synergistically prevent the development of endometrial abnormalities in DHEA-induced hyperandrogenism via anti-inflammatory action, indicating that KOK has preventive and therapeutic potential for suppressing PCOS.

Korean Red Ginseng and Ginsenoside-Rb1/-Rg1 Alleviate Experimental Autoimmune Encephalomyelitis by Suppressing Th1 and Th17 Cells and Upregulating Regulatory T Cells.

The effects of Korean red ginseng extract (KRGE) on autoimmune disorders of the nervous system are not clear. We investigated whether KRGE has a beneficial effect on acute and chronic experimental autoimmune encephalomyelitis (EAE). Pretreatment (daily from 10 days before immunization with myelin basic protein peptide) with KRGE significantly attenuated clinical signs and loss of body weight and was associated with the suppression of spinal demyelination and glial activation in acute EAE rats, while onset treatment (daily after the appearance of clinical symptoms) did not. The suppressive effect of KRGE corresponded to the messenger RNA (mRNA) expression of proinflammatory cytokines (tumor necrosis factor-α [TNF-α] and interleukin [IL]-1ß), chemokines (RANTES, monocyte chemotactic protein-1 [MCP-1], and macrophage inflammatory protein-1α [MIP-1α]), adhesion molecules (intercellular adhesion molecule-1 [ICAM-1], vascular cell adhesion molecule-1 [VCAM-1], and platelet endothelial cell adhesion molecule [PECAM-1]), and inducible nitric oxide synthase in the spinal cord after immunization. Interestingly, in acute EAE rats, pretreatment with KRGE significantly reduced the population of CD4(+), CD4(+)/IFN-γ(+), and CD4(+)/IL-17(+) T cells in the spinal cord and lymph nodes, corresponding to the downregulation of mRNA expression of IFN-γ, IL-17, and IL-23 in the spinal cord. On the other hand, KRGE pretreatment increased the population of CD4(+)/Foxp3(+) T cells in the spinal cord and lymph nodes of these rats, corresponding to the upregulation of mRNA expression of Foxp3 in the spinal cord. Interestingly, intrathecal pretreatment of rats with ginsenosides (Rg1 and Rb1) significantly decreased behavioral impairment. These results strongly indicate that KRGE has a beneficial effect on the development and progression of EAE by suppressing T helper 1 (Th1) and Th17 T cells and upregulating regulatory T cells. Additionally, pre- and onset treatment with KRGE alleviated neurological impairment of myelin oligodendrocyte glycoprotein(35-55)-induced mouse model of chronic EAE. These results warrant further investigation of KRGE as preventive or therapeutic strategies for autoimmune disorders, such as multiple sclerosis.

Bee Venom Acupuncture Alleviates Experimental Autoimmune Encephalomyelitis by Upregulating Regulatory T Cells and Suppressing Th1 and Th17 Responses.

The protective and therapeutic mechanism of bee venom acupuncture (BVA) in neurodegenerative disorders is not clear. We investigated whether treatment with BVA (0.25 and 0.8 mg/kg) at the Zusanli (ST36) acupoints, located lateral from the anterior border of the tibia, has a beneficial effect in a myelin basic protein (MBP)(68-82)-induced acute experimental autoimmune encephalomyelitis (EAE) rat model. Pretreatment (every 3 days from 1 h before immunization) with BVA was more effective than posttreatment (daily after immunization) with BVA with respect to clinical signs (neurological impairment and loss of body weight) of acute EAE rats. Treatment with BVA at the ST36 acupoint in normal rats did not induce the clinical signs. Pretreatment with BVA suppressed demyelination, glial activation, expression of cytokines [interferon (IFN)-γ, IL-17, IL-17A, tumor necrosis factor-alpha (TNF-α), and IL-1ß], chemokines [RANTES, monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein (MIP)-1α], and inducible nitric oxide synthase (iNOS), and activation of p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB (p65 and phospho-IκBα) signaling pathways in the spinal cord of acute EAE rats. Pretreatment with BVA decreased the number of CD4(+), CD4(+)/IFN-γ(+), and CD4(+)/IL-17(+) T cells, but increased the number of CD4(+)/Foxp3(+) T cells in the spinal cord and lymph nodes of acute EAE rats. Treatment with BVA at six placebo acupoints (SP9, GB39, and four non-acupoints) did not have a positive effect in acute EAE rats. Interestingly, onset and posttreatment with BVA at the ST36 acupoint markedly attenuated neurological impairment in myelin oligodendrocyte glycoprotein (MOG)(35-55)-induced chronic EAE mice compared to treatment with BVA at six placebo acupoints. Our findings strongly suggest that treatment with BVA with ST36 acupoint could delay or attenuate the development and progression of EAE by upregulating regulatory T cells and suppressing T-helper (Th) 17 and Th1 responses. These results warrant further investigation of BVA as a treatment for autoimmune disorders of the central nervous system.

An Oriental Medicine, Hyungbangpaedok-San Attenuates Motor Paralysis in an Experimental Model of Multiple Sclerosis by Regulating the T Cell Response.

The preventive and therapeutic mechanisms in multiple sclerosis are not clearly understood. We investigated whether Hyungbangpaedok-san (HBPDS), a traditional herbal medicine, has a beneficial effect in experimental autoimmune encephalomyelitis (EAE) mice immunized with myelin oligodendrocyte glycoprotein peptide (MOG 35-55). Onset-treatment with 4 types of HBPDS (extracted using distilled water and 30%/70%/100% ethanol as the solvent) alleviated neurological signs, and HBPDS extracted within 30% ethanol (henceforth called HBPDS) was more effective. Onset-treatment with HBPDS reduced demyelination and the recruitment/infiltration and activation of microglia/macrophages in the spinal cord of EAE mice, which corresponded to the reduced mRNA expression of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1ß), iNOS, and chemokines (MCP-1, MIP-1α, and RANTES) in the spinal cord. Onset-treatment with HBPDS inhibited changes in the components of the blood-brain barrier such as astrocytes, adhesion molecules (ICAM-1 and VCAM-1), and junctional molecules (claudin-3, claudin-5, and zona occludens-1) in the spinal cord of EAE mice. Onset-treatment with HBPDS reduced the elevated population of CD4+, CD4+/IFN-γ+, and CD4+/IL-17+ T cells in the spinal cord of EAE mice but it further increased the elevated population of CD4+/CD25+/Foxp3+ and CD4+/Foxp3+/Helios+ T cells. Pre-, onset-, post-, but not peak-treatment, with HBPDS had a beneficial effect on behavioral impairment in EAE mice. Taken together, HBPDS could alleviate the development/progression of EAE by regulating the recruitment/infiltration and activation of microglia and peripheral immune cells (macrophages, Th1, Th17, and Treg cells) in the spinal cord. These findings could help to develop protective strategies using HBPDS in the treatment of autoimmune disorders including multiple sclerosis.

Oriental medicine Kyung-Ok-Ko prevents and alleviates dehydroepiandrosterone-induced polycystic ovarian syndrome in rats.

Kyung-Ok-Ko (KOK), a traditional herbal prescription composed of Rehmannia glutinosa Liboschitz var. purpurae, Lycium chinense, Aquillaria agallocha, Poria cocos, Panax ginseng, and honey, has been widely used in traditional Oriental medicine as a vitalizing medicine or as the prescription for patients with age-associated disorders such as amnesia and stroke. However, the potential protective value of KOK for the treatment of polycystic ovarian syndrome (PCOS) is largely unknown. We investigated whether pre-administration (daily from 2 hours before PCOS induction) and post-administration (daily after induction of PCOS) of KOK (0.5, 1.0, and 2.0 g/kg/day, p.o.) could have a protective effect in a dehydroepiandrosterone (DHEA, s.c.)-induced PCOS rat model. Pre-administration of KOK significantly decreased the elevated body weight and ovary weight, elevated size and number of follicular cysts, elevated level of serum glucose, and estradiol after DHEA injection. KOK reduced the elevated percentage of CD8 (+) T lymphocytes in lymph nodes, the elevated mRNA expression of CD11b and CD3 in ovaries, and infiltration of macrophages in ovarian tissue with PCOS. KOK diminished the increased mRNA expression of pro-inflammatory cytokines (IL-1ß, IL-6, TNF-α), chemokines (IL-8, MCP-1), and iNOS in the ovaries, and increased the reduced mRNA expression of growth factors (EGF, TGF-ß) by DHEA injection. Post-administration of KOK also improved the DHEA-induced PCOS-like symptoms, generally similar to those evident from pre-administration of KOK. KOK may effectively prevent and improve DHEA-induced PCOS via anti-inflammatory action, indicating its preventive and therapeutic potential for suppressing PCOS.

Live bee acupuncture (Bong-Chim) dermatitis: dermatitis due to live bee acupuncture therapy in Korea.

Live bee acupuncture (Bong-Chim) dermatitis is an iatrogenic disease induced by so-called live bee acupuncture therapy, which applies the honeybee (Apis cerana) stinger directly into the lesion to treat various diseases in Korea. We present two cases of live bee acupuncture dermatitis and review previously published articles about this disease. We classify this entity into three stages: acute, subacute, and chronic. The acute stage is an inflammatory reaction, such as anaphylaxis or urticaria. In the chronic stage, a foreign body granuloma may develop from the remaining stingers, similar to that of a bee sting reaction. However, in the subacute stage, unlike bee stings, we see the characteristic histological "flame" figures resulting from eosinophilic stimulation induced by excessive bee venom exposure. We consider this stage to be different from the adverse skin reaction of accidental bee sting.

Korean Red Ginseng Extract Attenuates 3-Nitropropionic Acid-Induced Huntington's-Like Symptoms.

Korean red ginseng (KRG) possesses neuroprotective activity. However, the potential neuroprotective value of KRG for the striatal toxicity is largely unknown. We investigated whether KRG extract (KRGE) could have a neuroprotective effect in a 3-nitropropionic acid- (3-NP) induced (i.p.) Huntington's disease (HD) model. KRGE (50, 100, and 250 mg/kg/day, p.o.) was administrated 10 days before 3-NP injection (pre-administration), from the same time with 3-NP injection (co-administration), or from the peak point of neurological impairment by 3-NP injection (post-administration). Pre-administration of KRGE produced the greatest neuroprotective effect in this model. Pre-administration of KRGE significantly decreased 3-NP-induced neurological impairment, lethality, lesion area, and neuronal loss in the 3-NP-injected striatum. KRGE attenuated microglial activation and phosphorylation of mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB) signal pathway. KRGE also reduced the level of mRNA expression of tumor necrosis factor-alpha, interleukin- (IL-) 1ß, IL-6, inducible nitric oxide synthase, and OX-42. Interestingly, the intrathecal administration of SB203580 (a p38 inhibitor) or PD98059 (an inhibitor of MAPK Kinase, MEK) increased the survival rate in the 3-NP-induced HD model. Pre-administration of KRGE may effectively inhibit 3-NP-induced striatal toxicity via the inhibition of the phosphorylation of MAPKs and NF-κB pathways, indicating its therapeutic potential for suppressing Huntington's-like symptoms.

Effects of Angelica acutiloba on mast cell-mediated allergic reactions in vitro and in vivo.

The root of Angelica acutiloba is a widely used herbal medicine which has been used as a typical therapeutic for allergic diseases in traditional medicine. This study was aimed to investigate the effects of A. acutiloba on allergic reactions in in vitro and in vivo models and its mechanism of action. A. acutiloba was extracted by maceration with 80% ethanol (AAE) and standardized by high-performance liquid chromatography. We investigated the effect of AAE on phorbol-12-myristate-13-acetate plus calcium ionophore A23187 (PMACI)-induced cytokine release; phosphorylation of JNK, ERK, and p38 in human mast cell-1 (HMC-1); and compound 48/80-induced release of histamine in rat peritoneal mast cells (RPMCs). We also investigated the effects on Evans blue (EB) extravasation induced by anti-DNP IgE in rats. Treatment with 1, 10 and 100 µg/ml AAE concentration-dependently inhibited the release of cytokines (tumor necrosis factor-α, interleukin (IL) -6, and IL-8) and phosphorylation of ERK and JNK induced by PMACI in HMC-1 cells, but it did not inhibit the phosphorylation of p38. It also inhibited compound 48/80-induced histamine release in RPMCs. Oral administration of 271 mg/kg AAE inhibited EB extravasation in a passive cutaneous anaphylaxis rat model. In conclusion, AAE inhibited mast cell-derived allergic reactions by inhibiting the release of histamine, the production of pro-inflammatory cytokines, and the phosphorylation of ERK and JNK.