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ABSTRACT: Artemisinin can be isolated from Artemisia annua L. In addition to its well-known anti-malarial activity, artemisinin has antitumor and anti-microbial effects. In this study, we investigated the effect of artemisinin on the production of IL-12p40, which is important in the generation of T helper 1 responses. Artemisinin significantly induced IL-12p40 production in LPS-stimulated RAW264.7 macrophage cells. To elucidate the signaling molecules regulated by artemisinin in induced IL-12p40 production, the DNA-binding activity of several transcription factors and activation of mitogen-activated protein kinase (MAPK)s were investigated. The band intensities of NF-κB, AP-1, and SP1, and the activation of p38 MAPK and ERK were not changed by artemisinin. However, the induced phosphorylation of JNK was significantly decreased by artemisinin, and inhibition of the JNK signaling pathway further increased IL-12p40 production in LPS-stimulated RAW264.7 macrophage cells. Taken together, these data suggest that artemisinin induces the production of IL-12p40 in LPS-stimulated macrophage cells by inhibiting JNK activity.
Archives of Pharmacal Research 11/2012; 35(11):1961-8. · 1.59 Impact Factor
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ABSTRACT: Activity profiling of the n-BuOH extract from Cimicifuga heracleifolia rhizomes led to the identification of three cytotoxic caffeic acid derivatives, carboxymethyl isoferulate (2), cimicifugic acid A (3), and cimicifugic acid B (4) together with a series of structurally related inactive compounds. The extract was separated by time-based fractionation in a gradient HPLC condition, and cytotoxicity of each fraction was evaluated using HCT116 colon cancer cells in vitro. HPLChyphenated spectroscopy including LC/NMR and LC/PDA/MS provided structural information for phenolic compounds contained in the extract, and further preparative isolation of active compounds 2-4 was achieved by semi-preparative HPLC. Compounds 2-4 showed cytotoxic activity against cancer cells in a dose-dependent manner at the concentrations of 2.5-40 μM, and western blotting analysis showed that these compounds increased expression of cleaved poly ADP ribose polymerase (PARP), a critical apoptosis marker.
Archives of Pharmacal Research 09/2012; 35(9):1559-65. · 1.59 Impact Factor
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The Journal of Antibiotics 08/2012; 65(8):437-40. · 1.65 Impact Factor
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ABSTRACT: Two triterpenoids, 24-methylene-3, 4-seco-cycloart-4(28)-en-3-oic acid (1) and 3-oxo-9ß-lanosta-7, 22Z, 24-trien-26, 23-olide
(6) were isolated fromAbies koreana, together with ß-sitosterol (2), maltol (3), ß-sitosterol-O-ß-D-glucoside (4), and hexacosylferulate (5). The structures
of the compounds were established based on the spectroscopic data. The cytotoxic activities of triterpenoids have been evaluated
using the sulforhodamine B (SRB) method. Compound 1 showed moderate cytotoxicities against human lung carcinoma (A549), ovarian
carcinoma (SK-OV-3), malignant melanoma (SK-MEL-2), and colon carcinoma (HCT-15) cell lines.
Archives of Pharmacal Research 04/2012; 24(6):527-531. · 1.59 Impact Factor
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ABSTRACT: Three diterpenes (1, 8, and9), three triterpenes (3, 4, and7), one saponin (11), four sterols (2, 5, 6, and12), and one cerebroside (10) were isolated from the EtOH extract of the aerial parts ofAralia cordata by repeated silica gel column chromatography. Their chemical structures were identified by comparing their physicochemical
and spectral data with those published in literatures. All isolated compounds were evaluated for their cytotoxicity against
L 1210, K562, and LLC tumor cell lines using MTT assay. Of which, 3β, 5α-dihydroxy-6β-methoxyergosta-7,22-diene (6) showed a potent cytotoxicity against all cell lines with IC50 values of 11.7, 11.9, and 15.1 μM, respectively, while compounds1, 5, and11 showed a moderate or weak cytotoxicity. These isolates were also examined for their inhibitory activity against COX-1 and
COX-2. Although most compounds, except for2, 10, and12, showed a strong inhibitory activity against COX-1, they exhibited a moderate or weak inhibitory activity against COX-2.
Archives of Pharmacal Research 04/2012; 29(7):548-555. · 1.59 Impact Factor
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ABSTRACT: Chronic inflammatory response in the brain is a characteristic etiopathology of various neurodegenerative diseases; consequently increasing the intrinsic anti-inflammatory potency could be an especially desirable strategy to prevent inflammation-related neuronal injuries. Transcription factor NF-E2-related factor-2 (Nrf2)-mediated control of redox homeostasis may participate in the modulation of microglial responses by regulating expression of important antioxidant and phase II detoxification genes. In our present work, we show that artesunate, a semi-synthetic derivative of anti-malarial agent artemisinin, attenuates LPS-induced inflammatory responses in microglial BV2 cells. Artesunate activates Nrf2-ARE system, and leads to an increase in the level of downstream heme oxygenase-1. Artesunate also activates PI3K/Akt, ERK, and JNK MAPKs signaling, but artesunate-induced activation of Nrf2 signaling and up-regulation of heme oxygenase-1 are ERK pathway-dependent. Collectively, this study demonstrates that artesunate is a potential activator of the Nrf2/ARE-dependent pathway and is therapeutically relevant to inflammatory responses of microglial cells.
Neuroscience Letters 02/2012; 509(1):17-21. · 2.11 Impact Factor
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Hue Thi My Van,
Daulat Bikram Khadka,
Su Hui Yang,
Thanh Nguyen Le,
Suk Hee Cho,
Chao Zhao, Ik-Soo Lee,
Youngjoo Kwon,
Kyung-Tae Lee,
Yong-Chul Kim,
Won-Jea Cho
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ABSTRACT: Benzo[3,4]azepino[1,2-b]isoquinolinones were designed and developed as constraint forms of 3-arylisquinolines with an aim to inhibit topoisomerase I (topo I). Ring closing metathesis (RCM) of 3-arylisoquinolines with suitable diene moiety provided seven membered azepine rings of benzoazepinoisoquinolinones. Spectral analyses of these heterocyclic compounds demonstrated that the methylene protons of the azepine rings are nonequivalent. The shielding environment experienced by these geminal hydrogens differs unusually by 2.21ppm. As expected, benzoazepinoisoquinolinones displayed potent cytotoxicity. However, cytotoxic effects of the compounds were not related to topo I inhibition which is explained by non-planar conformation of the rigid compounds incapable of intercalating between DNA base pairs. In contrast, flexible 3-arylisoquinoline 8d attains active conformation at drug target site to exhibit topo I inhibition identical to cytotoxic alkaloid, camptothecin (CPT).
Bioorganic & medicinal chemistry 08/2011; 19(18):5311-20. · 2.82 Impact Factor
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The Journal of Antibiotics 06/2011; 64(8):587-9. · 1.65 Impact Factor
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ABSTRACT: Xanthohumol (2',4',4-trihydroxy-6'-methoxy-3'-prenylchalcone) is a major chalcone derivative isolated from hop (Humulus lupulus L.) commonly used in brewing due to its bitter flavors. Xanthohumol has anti-carcinogenic, free radical-scavenging, and anti-inflammatory activities, but its precise mechanisms are not clarified yet. The basic leucine zipper (bZIP) protein NRF2 is a key transcription factor mediating the antioxidant and anti-inflammatory responses in animals. Therefore, we tested whether xanthohumol exerts anti-inflammatory activity in mouse microglial BV2 cells via NRF2 signaling. Xanthohumol significantly inhibited the excessive production of inflammatory mediators NO, IL-1β, and TNF-α, and the activation of NF-κB signaling in LPS-induced stimulated BV2 cells. Xanthohumol up-regulated the transcription of NAD(P)H:quinone oxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1), and increased the level of the endogenous antioxidant GSH. In addition, xanthohumol induced nuclear translocation of NRF2 and further activation of ARE promoter-related transcription. The anti-inflammatory response of xanthohumol was attenuated by transfection with NRF2 siRNA and in the presence of the HO-1 inhibitor, ZnPP, but not the NQO1 inhibitor, dicoumarol. Taken together, our study suggests that xanthohumol exerts anti-inflammatory activity through NRF2-ARE signaling and up-regulation of downstream HO-1, and could be an attractive candidate for the regulation of inflammatory responses in the brain.
Neurochemistry International 02/2011; 58(2):153-60. · 2.86 Impact Factor
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ABSTRACT: In an ongoing investigation of compounds from natural products that exhibit anti-aging properties, hydroxyhibiscone A (1), a new furanosesquiterpenoid, together with hibiscone D (2), was isolated from the root bark of Hibiscus syriacus. Utilizing UV, IR, NMR, and MS spectroscopic analyses, these chemical structures were revealed. Compounds 1 and 2 were found to possess significant anti-aging properties on the human neutrophil elastase (HNE) assay, exhibiting HNE inhibitory activities with IC50 values of 5.2 and 4.6 micronM, respectively.
Journal of Microbiology and Biotechnology 08/2010; 20(8):1189-91. · 1.38 Impact Factor
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Ik-Soo Lee,
Hong-Jin Kim,
Ui-Jung Youn,
Quan-Cheng Chen,
Jin-Pyo Kim,
Do Thi Ha,
Tran Minh Ngoc,
Byung-Sun Min,
Sang-Myung Lee,
Hyun-Ju Jung,
Min-Kyun Na,
Ki-Hwan Bae
Helvetica Chimica Acta 02/2010; 93(2):272 - 276. · 1.48 Impact Factor
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ABSTRACT: Xanthohumol (XN) and its related compounds were evaluated for their effects on modulating the production of interleukin (IL)-12, the most important factor driving T helper 1 immune responses. XN showed the strongest inhibitory effect on IL-12 production in macrophages stimulated by lipopolysaccharide (LPS) or LPS/interferon-gamma. Xanthohumol 4'-O-beta-D-glucopyranoside (XNG) inhibited IL-12 production less effectively than XN. Isoxanthohumol and 8-prenylnaringenin showed comparatively lower inhibitory effects on IL-12 production than XNG. (2S)-5-methoxy-8-prenylnaringenin 7-O-beta-D-glucopyranoside did not exert any effect on IL-12 production. We then tested how these compounds affected NF-kappaB binding activity to the kappaB site in the nucleus. The compounds inhibited kappaB binding in macrophages with the same potency order as IL-12 inhibition. Furthermore, we investigated whether XN, which showed the most effective reduction of IL-12 production, attenuated skin inflammation. Chronic allergic contact dermatitis, an experimental model for psoriasis, was used to determine the anti-inflammatory effects of XN in vivo. XN treatment reduced the degree of ear thickening induced by oxazolone. Taken together, XN might be effective as an anti-inflammatory agent to reduce skin inflammation by inhibiting IL-12 production.
International immunopharmacology 02/2010; 10(5):556-61. · 2.21 Impact Factor
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Helvetica Chimica Acta 10/2009; 92(10):2058 - 2062. · 1.48 Impact Factor
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ABSTRACT: The present study investigated an ethanol extract of the aerial part of Aralia cordata Thunb. (Araliaceae) for possible neuroprotective effects on neurotoxicity induced by amyloid beta (Abeta) protein (25 - 35) in cultured rat cortical neurons and antidementia activity in mice. Exposure of cultured cortical neurons to 10 muM Abeta(25 - 35) for 36 h induced neuronal apoptotic death. At 1 - 10 mug/ml, A. cordata inhibited neuronal death, elevation of intracellular calcium ([Ca(2+)](i)), glutamate release into the medium, and generation of reactive oxygen species (ROS) induced by Abeta(25-35) in primary cultures of rat cortical neurons. Memory loss induced by intracerebroventricular injection of ICR mice with 15 nmol Abeta(25-35) was inhibited by chronic treatment with A. cordata (50 and 100 mg/kg, p.o. for 7 days) as measured by a passive avoidance test, and corresponding reductions were observed in brain cholinesterase activity and neuronal death measured histologically in the hippocampal region. Oleanolic acid isolated from A. cordata also inhibited neuronal death, elevation of [Ca(2+)](i), glutamate release, and generation of ROS induced by Abeta(25-35) in cultured rat cortical neurons, suggesting that the neuroprotective effect of A. cordata may be, at least in part, attributable to this compound. From these results, we suggest that the antidementia effect of A. cordata is due to its neuroprotective effect against Abeta(25-35)-induced neurotoxicity and that A. cordata may have a therapeutic role in preventing the progression of Alzheimer's disease.
Journal of Pharmacological Sciences 09/2009; 111(1):22-32. · 2.08 Impact Factor
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ABSTRACT: Aralia has been reported to exhibit various pharmacological properties, including anti-inflammatory, antidiabetic and antioxidant activities. We performed in vitro and in vivo analyses on the neuroprotective effects of an ethanolic extract of the aerial parts of Aralia cordata Thunb. (Araliaceae). In cultured cortical neurons from rats, A. cordata (5-20 microg/mL) inhibited 100 muM hydrogen peroxide (H(2)O(2))-induced apoptotic neuronal death, elevation of intracellular calcium concentration ([Ca(2+)](i)) and generation of reactive oxygen species (ROS). Since oleanolic acid isolated from A. cordata also inhibited H(2)O(2)-induced neuronal death, increase in [Ca(2+)](i) and ROS generation in cultured cortical neurons, some of the neuroprotective effects of A. cordata might be attributable to this compound. In rats, A. cordata prevented cerebral ischemic injury induced by 3 h of middle cerebral artery occlusion, followed by 24 h of reperfusion. Ischemic infarct and edema volumes were significantly reduced in rats that received A. cordata (50 mg/kg, orally). These animals exhibited a corresponding improvement in neurological function and a reduction of neuronal death, as determined histologically from the cortex and hippocampal regions. It is possible that the anti-oxidative properties of A. cordata may be responsible for its neuroprotective effects against focal cerebral ischemic injury. In future, A. cordata might play a therapeutic role in the prevention and treatment of neurodegeneration in stroke.
Archives of Pharmacal Research 07/2009; 32(6):923-32. · 1.59 Impact Factor
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ABSTRACT: Gardeniae Fructus is a traditional medicine used for the treatment of contusion such as ankle sprain. Geniposide is one of the main components of Gardeniae Fructus with diverse biological activities. In order to gain further insight into the therapeutic action of Gardeniae Fructus extract (GFE) and geniposide on ligament injuries, a new in vitro model was developed in the present study. Rat hind ankle ligament fibroblasts (RHALFs) derived from Sprague-Dawley rats were cultured, and the cell proliferation and collagen content were examined by MTT and a Sirius Red-based colorimetric assay after stimulating with each drug. The cell growth of RHALFs was promoted by culturing with 37.5-150 microg/mL of GFE and 25-200 microM of geniposide. The content of collagen in the RHALFs was significantly increased up to 131.4% and 124.2% of the control value by culturing with the GFE and geniposide, respectively. By contrast, both cell growth and collagen content were impaired by adding 25-200 microM of diclofenac, one of the common medications for ligament injuries. The findings suggest that GFE and geniposide may ameliorate the treatment of ligament injuries by proliferating ligament fibroblasts and promoting the synthesis of collagen. However, the use of diclofenac to treat acute ligament injuries should be reassessed although it possesses a potential effect on relieving symptoms.
Phytotherapy Research 06/2009; 24 Suppl 1:S1-5. · 2.09 Impact Factor
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Hong Jin Kim, Ik Soo Lee,
UiJoung Youn,
Quan Cheng Chen,
Tran Minh Ngoc,
Do Thi Ha,
Hongguang Liu,
Byung Sun Min,
Jin Yong Lee,
Rack Seon Seong,
KiHwan Bae
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ABSTRACT: Two new biphenylquinolizidine alkaloids, 5-epi-dihydrolyfoline (1) and its stereoisomer, dihydrolyfoline (2), along with lagerine (3) were isolated from the aerial parts of Lagerstroemia indica. The structures of compounds 1-3 were elucidated by extensive spectroscopic techniques.
Journal of Natural Products 04/2009; 72(4):749-52. · 3.13 Impact Factor
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ABSTRACT: Xanthohumol (XN) is a major chalcone found in hop, which is used to add bitterness and flavor to beer. In this study, we investigated the effects of XN on the production of interlukin-2 (IL-2), a potent T cell growth factor. Treatment with XN significantly increased IL-2 production in mouse EL-4 T cells activated with phorbol 12-myristate 13-acetate (PMA) plus ionomycin (Io) in a dose-dependent manner. To further characterize its regulatory mechanism of XN on increased IL-2 production, the effects of XN on IL-2 promoter activity and the activity of several transcription factors modulating IL-2 expression were analyzed. XN enhanced activity of the IL-2 promoter, which contains distal and proximal regulatory elements in PMA/Io-activated EL-4 T cells. Furthermore, the activity of NF-AT and AP-1 was enhanced but NF-kappaB activity was not influenced by XN in PMA/Io-activated EL-4 T cells. These results suggest that XN increased IL-2 production at the transcriptional levels via the up-regulation of NF-AT and AP-1 in PMA/Io-activated EL-4 T cells.
International Immunopharmacology 12/2008; 9(1):103-7. · 2.38 Impact Factor
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ABSTRACT: Microbial metabolism studies of the phyto-estrogen (+/-)-8-prenylnaringenin (8-PN) (1) has led to the isolation of three pairs of metabolites (2-4). The structures of these compounds were identified as 5,4'-dihydroxy-7,8-[2-(1-hydroxy-1-methylethyl)-2,3-dihydrofurano]flavanones (2), 8-prenylnaringenin 7-O-beta-D-glucopyranosides (3), and 8-prenylnaringenin 7-O-beta-D-(6'''-O-alpha-hydroxypropionyl)-glucopyranosides (4) on the basis of the spectroscopic analysis.
Archives of Pharmacal Research 11/2008; 31(10):1241-6. · 1.59 Impact Factor
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ABSTRACT: Macrophages are the main cells responsible for the innate immunity, and their activation by lipopolysaccharide (LPS) from Gram-negative bacteria or interferon (IFN)-gamma from host immune cells is important for controlling infections. However, the overwhelming activation of macrophages can cause a severe inflammatory state. This study investigated the inhibitory mechanism of xanthohumol (XN) against the inflammatory effectors (IL-1beta, TNF-alpha, and iNOS) in activated RAW264.7 macrophages by using different stimuli such as LPS, IFN-gamma, or LPS plus IFN-gamma. XN is a major prenylated chalcone found in hops, which is used to add bitterness and flavor to beer. XN reduced the expression of the LPS receptor components such as TLR4 and MD2 resulting in the suppression of NF-kappaB activation in LPS-activated RAW264.7 cells. In the IFN-gamma stimulated RAW264.7 cells, the binding activity of STAT-1alpha and IRF-1 was inhibited by XN. This suggests that differential signaling pathways are used by XN for the inhibition of excess inflammatory mediators depending on the stimuli in macrophages.
International Immunopharmacology 05/2008; 8(4):567-73. · 2.38 Impact Factor
