Artemisia Iwayomogi Research Articles

A Carbohydrate Fraction, AIP1, fromArtemisia IwayomogiReduces the Action Potential Duration by Activation of Rapidly Activating Delayed Rectifier K+Channels in Rabbit Ventricular Myocytes

We investigated the effects of a hot-water extract of Artemisia iwayomogi, a plant belonging to family Compositae, on cardiac ventricular delayed rectifier K(+) current (I(K)) using the patch clamp technique. The carbohydrate fraction AIP1 dose-dependently increased the heart rate with an apparent EC(50) value of 56.1+/-5.5 microg/ml. Application of AIP1 reduced the action potential duration (APD) in concentration-dependent fashion by activating I(K) without significantly altering the resting membrane potential (IC(50) value of APD(50): 54.80+/-2.24, IC(50) value of APD(90): 57.45+/-3.47 microg/ml). Based on the results, all experiments were performed with 50 microg/ml of AIP1. Pre-treatment with the rapidly activating delayed rectifier K(+) current (I(Kr)) inhibitor, E-4031 prolonged APD. However, additional application of AIP1 did not reduce APD. The inhibition of slowly activating delayed rectifier K(+) current (I(Ks)) by chromanol 293B did not change the effect of AIP1. AIP1 did not significantly affect coronary arterial tone or ion channels, even at the highest concentration of AIP1. In summary, AIP1 reduces APD by activating I(Kr) but not I(Ks). These results suggest that the natural product AIP1 may provide an adjunctive therapy of long QT syndrome.

Phenolic Compounds from Artemisia iwayomogi and Their Effects on Osteoblastic MC3T3-E1 Cells

One new (4) and twelve known phenolic compounds (1-3, 5-13) were isolated from a 70% MeOH extract of the aerial parts of Artemisia iwayomogi. The new compound was identified as 7,8-dimethoxy-coumarin-9-O-(6'-O-(E)-coumaroyl)-beta-D-glucopyranoside (4) and named iwayomin. The effects of compounds 1-13 on the function of osteoblastic MC3T3-E1 cells were examined by evaluating cell viability, alkaline phosphatase (ALP) activity, collagen synthesis, and mineralization in the presence of each compound. Compounds 3, 4, 7, and 9 showed potential in stimulating osteoblastic bone formation and may be useful for the prevention and/or treatment of osteoporosis.

국화과 식물의 섭취가 Streptozotocin 유발 당뇨 흰쥐의 혈당과 지질 수준에 미치는 영향

Dept. of Food and Nutrition, Duksung Women's University, Seoul 132-714, KoreaAbstractThis study was designed to examine the effects of Compositae plants on plasma glucose and lipid levels in streptozotocin (STZ) induced diabetic rats. Sprague-Dawley rats were randomly assigned to 5 groups: normal, STZ-control and three experimental groups [Artemisia iwayomogi (A. iwayomogi), Atractylodes lancea (A. lancea), and Taraxacum mongolicum (T. mongolicum)]. Normal and STZ-control group were fed an AIN-93 diet and three experimental groups were each fed a modified diet containing 10% compositae powder for 4 weeks. The plasma glucose levels at 4 weeks of A. iwayomogi, A. lancea, and T. mongolicum groups were significantly lower than STZ-control group. The A. iwayomogi and A. lancea groups had significantly suppressed hypertrophy of liver and kidney. The hematocrit levels of A. lancea and T. mongolicum group were significantly lower than STZ-control groups. The total cholesterol and triglyceride levels and atherogenic index (AI) of A. lancea group were significantly lower than STZ-control group. Intake of Compositae plants may be effective in anti- hyperglycemia by lowering blood glucose levels. The A. iwayomogi, A. lancea, and T. mongolicum can be beneficial for the diabetic complications and damage from the lipid peroxidation.Key words: Compositae plants, diabetic rats, hypoglycemic effect

MAPK activation is necessary to the apoptotic death of KB cells induced by the essential oil isolated from Artemisia iwayomogi

Aim of the study Artemisia iwayomogi is a perennial small herbal plant that has long been used as a chemopreventive agent in traditional Korean medicine. Previously, the purified essential oil was isolated from Artemisia iwayomogi, herein named AIEO, and found to contain the active components responsible for the chemopreventive potential of the herb. Materials and methods This study examined whether or not AIEO has potential chemopreventative effects against cancer using the human oral epidermoid carcinoma cell line, KB cells. The possible mechanism of AIEO-induced apoptosis was also examined. Results The results showed that AIEO induces the apoptotic death of KB cells, which is mediated by mitogen-activated protein kinases (MAPKs). In addition, AIEO not only induced an imbalance between the mitochondrial Bcl-2 and Bax levels with the concomitant release of Cytochrome c into the cytosol but also induced the activation of caspases and the cleavage of PARP. This induction was significantly suppressed by MAPK inhibitors. Moreover, pretreating the cells with each of the caspase or MAPK-specific inhibitors apparently inhibited AIEO-induced cytotoxicity of KB cells. Conclusions These results strongly suggest that AIEO might have cancer chemopreventive and therapeutic potential, which is closely related to its ability to activate the MAPK-mediated signaling pathways with the subsequent induction of a mitochondria- and caspase-dependent mechanism.

Phytotoxicity and Volatile Monoterpenes of Leaves from Artemisia capillaris and Artemisia iwayomogi Used as Korean Herbal Injin

Artemisia capillaris and Artemisia iwayomogi are weeds used as medicinal plants in Korea under the name Injin. I collected leaves of A. capillaris and A. iwayomogi, examined them for phytotoxic effects from volatile substances and determined the composition of monoterpenes in the leaves. The effects of volatile substances from each species on seed germination and radicle elongation in each of the two Artemisia species were assessed. The volatile substances of A. capillaris did not negatively affect the seed germination of A. capillaris, but they did inhibit radicle elongation. Rates of seed germination of A. iwayomogi decreased when the seeds were exposed to high concentration of A. capillaris volatile substances. The inhibition of seed germination and radicle elongation by volatile substances from both Artemisia species was stronger for A. iwayomogi than for A. capillaris. I identified the monoterpenoids from the leaves with a gas chromatograph-mass spectrometer (GC-MS). The main constituents of A. capillaris were acenaphthylene (37.91%), -pinene (12.08%), 4-carene (10.61%) and -curcumene (9.92%), while those of A. iwayomogi were germacrene- (32.15%), borneol (21.24%), camphor (20.45%) and trans-caryophyllene (7.75%).

AIP1, a carbohydrate fraction from Artemisia iwayomogi, modulates the functional differentiation of bone marrow-derived dendritic cells

Dendritic cells (DCs) are the most potent antigen-presenting cells (APC) particularly important in the initiation of primary T cell-mediated immune responses. Thus, inhibition of the differentiation and function of DC could lead to the suppression of immunological hyperresponsiveness. Artemisia iwayomogi, a member of the Compositae, is a perennial herb easily found in Korea and has been used as a traditional anti-inflammatory medicine. We investigated suppressive effects of carbohydrate fraction 1 from the water extracts of A. iwayomogi (AIP1) on the differentiation and function of bone marrow-derived dendritic cells. Bone marrow cells were cultured in the presence of granulocyte monocyte-colony stimulating factor (GM-CSF) and interleukin (IL)-4 for 6–7 days. Then, non-adherent cells were harvested for subsequent analyses. Percentage(s) of CD11c+ MHC II+ cell population(s) mostly composed of immature or mature DC and the allogeneic T cell stimulating ability of the cells were reduced by AIP1. Proteomic analyses along with RT-PCR revealed that expressions of several proteins including TNF receptor-associated factor (TRAF) 5-like protein, pyruvate kinase M2 (PKM2), and coactosin-like protein 1 (CLP1) were down-regulated upon AIP1 treatment.

A carbohydrate fraction, AIP1 from Artemisia iwayomogi suppresses pulmonary eosinophilia and Th2-type cytokine production in an ovalbumin-induced allergic asthma. Down-regulation of TNF-α expression in the lung

Asthma is a chronic inflammatory disease of the airways characterized by reversible airway obstruction, airway hyperreactivity, and remodeling of the airways. The incidence of asthma is on the rise despite ongoing intensive asthma research. Artemisia iwayomogi, a member of the Compositae, is a perennial herb easily found around Korea and has been used as a traditional anti-inflammatory medicine in liver diseases. We investigated suppressive effects of AIP1, a water-soluble carbohydrate fraction from A. iwayomogi on ovalbumin-induced allergic asthma in BALB/c mice and studied the possible mechanisms of its anti-allergic action. AIP1 significantly reduced pulmonary eosinophilia and Th2 cytokine expression in the lungs as well as serum IgE levels. Flow cytometric analysis of lung-infiltrating cells showed that the surface levels of CD11c and MHC II in CD11c+MHC II+ cells, potent dendritic cells, decreased in animals treated with AIP1. Expression of TNF-α, one of several proinflammatory cytokines released into the airway during episodes of asthma, was down-regulated by AIP1 injection, suggesting that reduced expression of TNF-α could account for the suppression of pulmonary eosinophilia and Th2-type cytokine production by AIP1.

Regulation of obesity and lipid disorders by herbal extracts from Morus alba, Melissa officinalis, and Artemisia capillaris in high-fat diet-induced obese mice

Melissa officinalis L. (Labiatae), Morus alba L. (Moraceae), and Artemisia capillaris Thunb. (Compositae) are suggested to be involved in the regulation of hyperlipidemia. We hypothesized that Ob-X, a mixture of three herbs, Morus alba, Melissa officinalis and Artemisia iwayomogi, improves lipid metabolism, body weight gain and adiposity and that peroxisome proliferator-activated receptor α (PPARα) is associated with these events. Mice fed a high-fat diet for 12 weeks exhibited increases in body weight gain and adipose tissue mass compared with mice fed a low fat diet. However, feeding a high-fat diet supplemented with Ob-X significantly reduced these effects. Ob-X treatment also decreased the circulating levels of triglycerides and total cholesterol, and inhibited hepatic lipid accumulation. Ob-X supplementation was found to increase the hepatic mRNA levels of PPARα target enzymes responsible for fatty acid β-oxidation. Moreover, Ob-X elevated the endogenous expression of a luciferase reporter gene containing three copies of a PPAR response element (PPRE) in NMu2Li liver cells. These data demonstrate that Ob-X regulates body weight gain, adipose tissue mass, and lipid metabolism in part through changes in the expression of hepatic PPARα target genes.

Chemical Composition and Antibacterial Activity Against Oral Bacteria by the Essential Oil of Artemisia iwayomogi

The aerial part of Artemisia iwayomogi KITAMURA has traditionally been used for antitumour, immunomodulating, antimutagenic, antioxidant, antibacterial, antifungal, antipyretic, diuretic, liver protective effect, and choleretic purposes in Korea. The chemical composition of the essential oil obtained from A. iwayomogi was analyzed by GC/MS. The essential oil and its major compounds were tested for antibacterial activities against 15 different genera of oral bacteria. The essential oil of A. iwayomogi was rich in camphor (17.96%), 1,8-cineole (14.79%), terpinen-4-ol (3.28%), α-terpineol (17.60%), and β-caryophyllene (4.05%). The essential oil of A. iwayomogi exhibited considerable inhibitory effects against all obligate anaerobic bacteria (MICs, 0.05 to 0.2 mg/ml; MBCs, 0.1 to 0.4 mg/ml) tested, while its major compounds demonstrated various degrees of growth inhibition.

Anti-inflammatory effects of water-soluble fractions from Artemisia species using the LPS-induced inflammatory response in primary rat astrocyte cultures

Water-soluble fractions have been purified from the crude aqueous extracts of Artemisia species, especially from Artemisia folum (AVF3) and Artemisia iwayomogi Kitam. (AIP1). The herbs are traditionally used as the medicinal plant to prevent or treat a number of liver diseases in Asia [1]. The AIP1 fraction has been shown to have diverse immuno-modulating activities including, anti-apoptosis and anti-cancer effects in our previous works [2, 3]. In this study, we have investigated the anti-inflammatory activity of the fractions using the LPS-induced inflammation model with primary rat astrocyte cultures. The treatment of the astrocyte culture either with AVF3 or AIP1 resulted in the suppression of the NO production by the LPS treatment, which was comparable to that of the dexamethasone treatment. Quantitative real-time PCR analysis revealed that the expression of iNOS gene was significantly suppressed by the samples, indicating that the inhibition of NO production could result from an inhibitory effect on iNOS gene transcription. The treatment also suppressed the up-regulation of the pro-inflammatory IL-6 and MIP-1β genes as the dexamethasone treatment. These results clearly demonstrate that the water-soluble fractions from Artemisia species might modulate the inflammatory response in brain astrocytes. Since NO production in brain astrocytes is important in the pathogenesis of a number of brain inflammatory diseases such as multiple sclerosis and Alzheimer's disease, the anti-inflammatory effect of the fraction could have considerable value for the protection or the treatment of the neurodegenerative diseases.

Artemisia iwayomogi Inhibits Immediate-Type Allergic Reaction and Inflammatory Cytokine Secretion

The immediate-type allergic reaction is involved in many allergic diseases such as asthma and allergic rhinitis. The discovery of drugs for the treatment of immediate-type allergic diseases is a very important subject in human health. In this study, we investigated the effect of Artemisia iwayomogi (AIAE) on mast cell-mediated allergic reaction and inflammatory cytokine secretion. AIAE inhibited compound 48/80-induced systemic reactions in mice. AIAE decreased the passive cutaneous anaphylaxis (PCA) reaction activated by antidinitrophenyl (anti-DNP) IgE antibody. AIAE dose-dependently reduced histamine release from rat peritoneal mast cells activated by compound 48/80 or anti-DNP IgE. Furthermore, AIAE attenuated the phorbol 12‐myristate 13-acetate plus calcium ionophore A23187-stimulated tumor necrosis factor-α and interleukin-6 secretion in human mast cells. These results provide evidence that AIAE may be beneficial in the treatment of allergic diseases.

Inhibitory effect on proliferation of vascular smooth muscle cells and protective effect on CCl 4-induced hepatic damage of HEAI extract

The effects of methanol extract from Hericium erinaceus cultivated with Artemisia iwayomogi (HEAI) on proliferation of vascular smooth muscle cells and CCl 4-induced hepatic damage were evaluated. HEAI was shown to have a potent inhibitory effect on the proliferation of vascular smooth muscle cells (VSMCs). Interestingly, a methanol extract of Hericium erinaceus showed no inhibitory effect on the proliferation of VSMCs, while a methanol extract of Artemisia iwayomogi possessed strong inhibitory effects on the proliferation of VSMCs. Therefore, the inhibitory effects of HEAI may be caused by the changes of chemical components in the culture broth after the addition of Artemisia iwayomogi in the HEAI growth media. HEAI also had a strong protective effect on CCl 4-induced hepatic damage in rats. The activity was evaluated using biochemical parameters such as glutamic oxalacetic transaminase (GOT), glutamic pyruvic transaminase (GPT) and alkaline phosphatase (ALP). HEAI treatment caused a significant reduction in the activity of GOT but not of GPT and ALP in comparison with CCl 4 treatment alone. Histopathological studies showed that liver samples treated with HEAI were significantly different when compared to non-treated animals after CCl 4 exposure.

Anti-Allergic Effects of Artemisia iwayomogi on Mast Cell-Mediated Allergy Model

The discovery of drugs for the treatment of allergic disease is an important subject in human health. The Artemisia iwayomogi (Compositae) (AIE) has been used as a traditional medicine in Korea and is known to have an anti-inflammatory effect. However, its specific mechanism of action is still unknown. In this report, we investigated the effect of AIE on the mast cell-mediated allergy model and studied the possible mechanism of action. AIE inhibited compound 48/80-induced systemic reactions and plasma histamine release in mice. AIE decreased immunoglobulin E (IgE)-mediated local allergic reaction, passive cutaneous anaphylaxis (PCA) reaction. AIE dose dependently attenuated histamine release from rat peritoneal mast cells activated by compound 48/80 or IgE. AIE decreased the compound 48/80-induced intracellular Ca(2+). Furthermore, AIE decreased the phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187-stimulated tumor necrosis factor-alpha and interleukin-6 gene expression and production in human mast cells. The inhibitory effect of AIE on the proinflammatory cytokine was p38 mitogen-activated protein kinase (MAPK) and nuclear factor-kappaB (NF-kappaB) dependent. AIE attenuated PMA plus A23187-induced degradation of IkappaBalpha and nuclear translocation of NF-kappaB and specifically blocked activation of p38 MAPK but not that of c-jun N-terminal kinase and extracellular signal-regulated kinase. Our findings provide evidence that AIE inhibits mast cell-derived immediate-type allergic reactions and involvement of intracellular Ca(2+), proinflammatory cytokines, p38 MAPK, and NF-kappaB in these effects.

Genetic identification of internal transcribed spacers sequence in rDNA of Artemisis iwayomogi Kitam. and other two Artemisia species

To make an useful identification method for the molecule of DNA on 3 herbs of Artemisia genus and compare the differences of the genes of Korean and Chinese species of Artemisia. Sequence of 3 herbs (Artemisia sacrorum Ledeb., Artemisia iwayomogi Kitam. and Artemisia capillaris Thunb.) was determined by PCR sequence system. DNA was extracted from rDNA/ITS (internal transcribed spacers) and 5.8 s. The analysis was based on the amplification through DNA sequence system. There were profound differences between the Korean Artemisia and Artemisia sacrorum L. These 2 herbs had a difference in the PCR amplifications of the agarose gel electrophoresis. There was a slight difference in the analysis of the DNA sequence system, and the substitution percentage for ITS gene fragments sequence was 3.96%. Analytic identification method on sequence system of ITS in rDNA is effective for these 3 herbs.

Active components from Artemisia iwayomogi displaying ONOO(-) scavenging activity.

Peroxynitrite (ONOO(-)) is one of cytotoxic species produced by the reaction between superoxide (*O(2) (-)) and nitric oxide (NO). The main aim of this study was to identify ONOO(-) scavenging constituents from herbs. Methanolic extracts derived from one hundred thirty eight herbs were screened out for their ONOO(-) scavenging activities. Twenty herbs showed excellent ONOO(-) scavenging activity in a dose dependent manner. Of them, Artemisia iwayomogi, which showed the highest activity, was fractioned with several solvents. The ONOO(-) scavenging activity of fractions was in order of ethyl acetate (EtOAc) > n-butanol (BuOH) > dichloromethane (CH(2)Cl(2)) > water (H(2)O) fraction. The EtOAc and the n-BuOH fractions were further purified to isolate active principles by column chromatography. Apigenin 7-methylether (genkwanin), apigenin 7,4'-di-O methylether, jaceosidin, and scopoletin from the EtOAc fraction and chlorogenic acid, 2,4-dihydroxy 6-methoxy acetophenone 4-O-beta-D-glucoside, quebrachitol, and scopolin from the n-BuOH fraction were identified. The scavenging activities of chlorogenic acid (IC(50) = 0.52 +/- 0.04 microM), genkwanin (IC(50) = 1.01 +/- 0.10 microM), and scopoletin (IC(50) = 1.03 +/- 0.15 micro M) were higher than or comparable to a well-known ONOO(-) scavenger, penicillamine (IC(50) = 1.76 +/- 0.18 microM), suggesting that those compounds might be developed as effective ONOO(-) scavengers for, prevention of the ONOO(-)-involved diseases.

Inhibitory activity of plant extracts on nitric oxide synthesis in LPS-activated macrophages.

Nitric oxide (NO) produced in large amounts by inducible nitric oxide synthase (iNOS) is known to be responsible for the vasodilation and hypotension observed in septic shock and inflammation. Inhibitors of iNOS, thus, may be useful candidates for the treatment of inflammatory diseases accompanied by overproduction of NO. We prepared alcoholic extracts of woody plants and screened the inhibitory activity of NO production in lipopolysaccharide (LPS)-activated macrophages after the treatment of these extracts. Among 83 kinds of plant extracts, 23 kinds of extracts showed potent inhibitory activity of NO production above 60% at the concentration of 80 micro g/ml. Some of potent extracts showed dose dependent inhibition of NO production of LPS-activated macrophages at the concentration of 80, 40, 20 micro g/ml. Especially, Artemisia iwayomogi, Machilus thunbergii, Populus davidiana and Populus maximowiczii showed the most potent inhibition (above 70%) at the concentration of 40 micro g/ml. Inhibitory activity of NO production was concentrated to nonpolar solvent fractions (ethyl ether and/or ethyl acetate soluble fractions) of Artemisia iwayomogi, Machilus thunbergii and Morus bombycis. These plants are promising candidates for the study of the activity-guided purification of active compounds and would be useful for the treatment of inflammatory diseases and endotoxemia accompanying overproduction of NO.

Eudesman-12,8β-olides and other terpenes from Artemisia species

The aerial parts of Artemisia iwayomogi afforded, in addition to already known terpenes, eleven new cudesmanolides whereas four new guaianolides were found in A. gmelinii. No sesquiterpene lactones were detected in the aerial parts of A. santolinifolia which afforded two new nerolidol derivatives besides several other already known compounds. From A. caerulescens var. cretacea six eudesmanolides were isolated, one of which has not been reported previously. The structures were elucidated by high field 1H NMR spectroscopy and chemical transformations. The chemotaxonomic significance of sesquiterpene lactones within the section Abrotanum and the subgenus Seriphidium is briefly discussed.