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Se Eun Byeon, Tao Yu,
Yanyan Yang,
Yong Gyu Lee,
Ji Hye Kim,
Jueun Oh,
Hye Yoon Jeong,
Suntaek Hong,
Byong Chul Yoo,
Won-Jea Cho,
Sungyoul Hong,
Jae Youl Cho
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ABSTRACT: The hydroxylated benzene metabolite hydroquinone (HQ) is mainly generated from benzene, an important industrial chemical, and is also a common dietary component. Although numerous papers have addressed the potential role of HQ in tumorigenic responses, the immunosuppressive and anti-inflammatory effects of hydroquinone have also been considered. In this study, we characterized the mechanism of the induction of hemeoxygenase (HO)-1 and other phase 2 enzymes by HQ and its derivatives. HQ upregulated the mRNA and protein levels of HO-1 by increasing the ARE-dependent transcriptional activation of NRF-2. Src knockdown or deficiency induced via siRNA treatment and infection with a retrovirus expressing shRNA targeting Src as well as exposure to PP2, a Src kinase inhibitor, strongly abrogated HO-1 expression. Interestingly, HQ directly targeted and bound to the sulfhydryl group of Cysteine-483 (C483) and C400 residues of Src, potentially leading to disruption of intracellular disulfide bonds. Src kinase activity was dramatically enhanced by mutation of these Cysteine sites, implying that these sites may play an important role in the regulation of Src kinase activity. Therefore, our data suggest that Src and, particularly, its C483 target site can be considered as prime molecular targets of the HQ-mediated induction of phase 2 enzymes, which is potentially linked to HO-1-mediated cellular responses such as immunosuppressive and anti-inflammatory actions.
Free radical biology & medicine 01/2013; · 5.42 Impact Factor
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Tao Yu,
Sang Hyun Moh,
Sang-Bom Kim,
Yanyan Yang,
Eunji Kim,
Yeon-Weol Lee,
Chong-Kwan Cho,
Kyung-Hee Kim,
Byong Chul Yoo,
Jae Youl Cho,
Hwa-Seung Yoo
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ABSTRACT: Abstract HangAmDan-B (HAD-B) is a powdered mixture of eight ethnopharmacologically characterized folk medicines that is prescribed for solid masses and cancers in Korea. In view of the finding that macrophage-mediated inflammation is a pathophysiologically important phenomenon, we investigated whether HAD-B modulates inflammatory responses and explored the associated molecular mechanisms. The immunomodulatory activity of HAD-B in toll-like receptor-activated macrophages induced by lipopolysaccharide (LPS) was assessed by measuring nitric oxide (NO) and prostaglandin E(2) (PGE(2)) levels. To identify the specific transcription factors (such as nuclear factor [NF]-κB and signaling enzymes) targeted by HAD-B, biochemical approaches, including kinase assays and immunoblot analysis, were additionally employed. HAD-B suppressed the production of PGE(2) and NO in LPS-activated macrophages in a dose-dependent manner. Furthermore, the extract ameliorated HCl/EtOH-induced gastritis symptoms. Moreover, HAD-B significantly inhibited LPS-induced mRNA expression of inducible NO synthase and cyclooxygenase (COX)-2. Interestingly, marked inhibition of NF-κB and activating transcription factor was observed in the presence of HAD-B. Data from direct kinase assays and immunoblot analysis showed that HAD-B suppresses activation of the upstream signaling cascade involving spleen tyrosine kinase, Src, p38, c-Jun N-terminal kinase, and transforming growth factor β-activated kinase 1. Finally, kaempferol, but not quercetin or resveratrol was identified as a bioactive compound in HAD-B. Therefore, our results suggest that HAD-B possesses anti-inflammatory activity that contributes to its anticancer property.
Journal of medicinal food 12/2012; · 1.39 Impact Factor
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Yanyan Yang, Tao Yu,
Yong Gyu Lee,
Woo Seok Yang,
Jueun Oh,
Deok Jeong,
Sukchan Lee,
Tae Woong Kim,
Yung Chul Park,
Gi-Ho Sung,
Jae Youl Cho
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ABSTRACT: ETHNOPHARMACOLOGICAL RELEVANCE: Hopea odorata Roxb. (Dipterocarpaceae) is a representative Thai ethnopharmacological herbal plant used in the treatment of various inflammation-related diseases. In spite of its traditional use, systematic studies of its anti-inflammatory action have not been performed. MATERIALS AND METHODS: The inhibitory activities of a Hopea odorata methanol extract (Ho-ME) on the production of nitric oxide (NO), tumour necrosis factor (TNF)-α, and prostaglandin E(2) (PGE(2)) in RAW264.7 cells and peritoneal macrophages were investigated. The effects of Ho-ME on the gastritis symptoms induced by HCl/EtOH and on ear oedemas induced by arachidonic acid were also examined. Furthermore, to identify the immunopharmacological targets of this extract, nuclear fractionation, a reporter gene assay, immunoprecipitation, immunoblot analysis, and a kinase assay were employed. RESULTS: Ho-ME strongly inhibited the release of NO, PGE(2), and TNF-α in RAW264.7 cells and peritoneal macrophages stimulated by lipopolysaccharide (LPS). Ho-ME also clearly suppressed the gene expression of pro-inflammatory cytokines and chemokines, such as interferon (IFN)-β, interleukin (IL)-12, and monocyte chemotactic protein-1 (MCP-1). By analysing the inhibited target molecules, Syk and Src were found to be suppressed in the inhibition of nuclear factor (NF)-κB pathway. In addition, the observed downregulation of activator protein (AP)-1 and cAMP response element-binding (CREB) was due to the direct inhibition of interleukin-1 receptor-associated kinase (IRAK)1 and IRAK4, which was also linked to the suppression of c-Jun N-terminal kinase (JNK) and p38. In agreement with the in vitro observations, this extract also ameliorated the inflammatory symptoms in EtOH/HCl-induced gastritis and arachidonic acid-induced ear oedemas in mice. CONCLUSION: Ho-ME has potential as a functional herbal remedy targeting Syk- and Src-mediated anti-inflammatory mechanisms. Future pre-clinical studies will be needed to investigate this possibility.
Journal of ethnopharmacology 12/2012; · 2.32 Impact Factor
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ABSTRACT: ETHNOPHARMACOLOGICAL RELEVANCE: Dryopteris crassirhizoma Nakai (Aspiadaceae) has been traditionally used as an herbal medicine for treating various inflammatory and infectious diseases such as tapeworm infestation, colds, and viral diseases. However, no systematic studies on the anti-inflammatory actions of D. crassirhizoma and its inhibitory mechanisms have been reported. We therefore aimed at exploring the anti-inflammatory effects of 95% ethanol extracts (Dc-EE) of this plant. MATERIALS AND METHODS: The anti-inflammatory effect of Dc-EE on the production of inflammatory mediators in RAW264.7 cells and HCl/EtOH-induced gastritis was examined. Inhibitory mechanisms were also evaluated by exploring activation of transcription factors, their upstream signalling, and target enzyme activities. Finally, the active components from this extract were also identified using HPLC system. RESULTS: Dc-EE diminished the production of nitric oxide (NO) and prostaglandin (PG)E(2) in lipopolysaccharide (LPS)-stimulated RAW264.7 cells in a dose-dependent manner. Dc-EE also downregulated the levels of mRNA expression of pro-inflammatory genes such as inducible NO synthase (iNOS), cyclooxygenase (COX)-2, and TNF-α by inhibiting the activation of activator protein (AP-1) and IRF3. Indeed, the extract strongly blocked the activities of their upstream kinases ERK1 and TBK1. This extract also strongly ameliorated gastritis symptoms stimulated by HCl/EtOH in mice. According to HPLC fingerprinting, resveratrol, quercetin, and kampferol were identified from Dc-EE. CONCLUSION: Dc-EE displays strong anti-inflammatory activity by suppressing ERK/AP-1 and TBK1/IRF3 pathways, which contribute to its major ethno-pharmacological role as an anti-inflammatory and anti-infectious disease remedy.
Journal of ethnopharmacology 11/2012; · 2.32 Impact Factor
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ABSTRACT: Osbeckia stellata Buch.-Ham. ex D.Don is traditionally prescribed to treat various inflammatory diseases. However, how this plant is able to modulate inflammatory responses is unknown. This study explored the anti-inflammatory effects of 99% methanol extracts of O. stellata (Os-ME).
The anti-inflammatory effect of Os-ME was evaluated by measuring the levels of nitric oxide (NO) and prostaglandin E(2) (PGE(2)) in lipopolysaccharide (LPS)-treated RAW264.7 macrophage cells and by determining gastric inflammatory lesions in mice induced by HCl/ethanol (EtOH). The molecular mechanisms of the inhibitions were elucidated by analyzing the activation of transcription factors, upstream signaling cascade, and the kinase activities of target enzymes.
Os-ME dose-dependently diminished the release of NO and PGE(2), and suppressed the expression of inducible NO synthase and cyclooxygenase-2 in LPS-treated RAW264.7 cells. Os-ME clearly inhibited the translocation of c-Rel, a subunit of nuclear factor κB (NF-κB), and c-Fos, a subunit of activator protein-1 (AP-1), and their regulatory upstream enzymes including Src, Syk, and IRAK1. Interestingly, orally administered Os-ME ameliorated acute inflammatory symptoms and suppressed the activation of Src, Syk, and IKAK1 induced by HCl/EtOH treatment in mouse stomach.
Os-ME can be considered as an orally available anti-inflammatory herbal remedy with Src/Syk/NF-κB and IRAK1/AP-1 inhibitory properties.
Journal of ethnopharmacology 08/2012; 143(3):876-83. · 2.32 Impact Factor
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Hye Yoon Jeong,
Sang Hyun Moh,
Yanyan Yang, Tao Yu,
Jueun Oh,
Deok Jeong,
Deok Hyo Yoon,
Ki Myun Park,
Sukchan Lee,
Tae Woong Kim,
Sungyoul Hong,
Sun Young Kim,
Jae Youl Cho
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ABSTRACT: Aralia continentalis Kitagawa (Araliaceae) is a representative ethnomedicinal herbal plant traditionally prescribed in Korea to relieve various inflammatory symptoms. However, the exact molecular mechanism of its anti-inflammatory activity has not been fully investigated.
The effect of the ethanol extract from the roots of this plant (Ac-EE) on the production of the inflammatory mediator nitric oxide (NO) was studied in RAW264.7 cells. Its effect on inflammatory symptoms (gastritis and hepatitis) in mice was also examined. In particular, the molecular inhibitory mechanism was analysed by measuring the activation of transcription factors and their upstream signalling and the kinase activity of target enzymes.
Ac-EE dose-dependently suppressed NO production in lipopolysaccharide (LPS)-activated RAW264.7 cells. This extract also displayed curative activity against EtOH/HCl-induced gastritis and LPS-induced hepatitis in mice. Ac-EE-mediated anti-inflammatory activity was found to be at the transcriptional level, as it blocked the activation of the nuclear factor (NF)-κB pathway composed of Syk and Src, according to immunoblotting and immunoprecipitation analyses and a kinase assay with whole and nucleus lysates from RAW264.7 cells and mice.
Ac-EE may be developed as a functional herbal remedy targeting Syk- and Src-mediated anti-inflammatory mechanisms. Future work using pre-clinical studies will be needed to investigate this possibility.
Journal of ethnopharmacology 08/2012; 143(2):746-53. · 2.32 Impact Factor
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Yongwoo Jung,
Se Eun Byeon,
Dae Sung Yoo,
Yong Gyu Lee, Tao Yu,
Yanyan Yang,
Ji Hye Kim,
Eunji Kim,
Deok Jeong,
Man Hee Rhee,
Eui Su Choung,
Sungyoul Hong,
Jae Youl Cho
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ABSTRACT: The macrophage-mediated inflammatory response may contribute to the development of cancer, diabetes, atherosclerosis and septic shock. This study was to characterize several new compounds to suppress macrophage-mediated inflammation.
Peritoneal macrophages from C57BL/6 male mice and RAW264.7 cells were examined. Anti-inflammatory activity was evaluated in the cells exposed to lipopolysaccharide (LPS). The mechanisms of the anti-inflammatory activity were investigated via measuring transcription factor activation in response to specific signals and via assaying the activities of the target kinases.
Of 7 candidate compounds tested, 8-(tosylamino)quinoline (8-TQ, compound 7) exhibited the strongest activities in suppressing the production of NO, TNF-α, and PGE(2) in LPS-activated RAW264.7 cells and peritoneal macrophages (the IC(50) values=1-5 μmol/L). This compound (1.25-20 μmol/L) dose-dependently suppressed the expression of the pro-inflammatory genes for iNOS, COX-2, TNF-α, and the cytokines IL-1β and IL-6 at the level of transcription in LPS-activated RAW264.7 cells. 8-TQ (20 μmol/L) significantly suppressed the activation of NF-κB and its upstream signaling elements, including inhibitor of κB (IκBα), IκBα kinase (IKK) and Akt in LPS-activated RAW264.7 cells. In in vivo experiments, oral administration of 20 and 40 mg/kg 8-TQ for 3 d significantly alleviated the signs of LPS-induced hepatitis and HCl/EtOH-induced gastritis, respectively, in ICR mice.
8-TQ (compound 7) exerts significant anti-inflammatory activity through the inhibition of the Akt/NF-κB pathway, thus may be developed as a novel anti-inflammatory drug.
Acta Pharmacologica Sinica 07/2012; 33(8):1037-46. · 1.95 Impact Factor
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ABSTRACT: Inflammation is a complex biological response of tissues to harmful stimuli such as pathogens, cell damage, or irritants. Inflammation is considered to be a major cause of most chronic diseases, especially in more than 100 types of inflammatory diseases which include Alzheimer's disease, rheumatoid arthritis, asthma, atherosclerosis, Crohn's disease, colitis, dermatitis, hepatitis, and Parkinson's disease. Recently, an increasing number of studies have focused on inflammatory diseases. TBK1 is a serine/threonine-protein kinase which regulates antiviral defense, host-virus interaction, and immunity. It is ubiquitously expressed in mouse stomach, colon, thymus, and liver. Interestingly, high levels of active TBK1 have also been found to be associated with inflammatory diseases, indicating that TBK1 is closely related to inflammatory responses. Even though relatively few studies have addressed the functional roles of TBK1 relating to inflammation, this paper discusses some recent findings that support the critical role of TBK1 in inflammatory diseases and underlie the necessity of trials to develop useful remedies or therapeutics that target TBK1 for the treatment of inflammatory diseases.
Mediators of Inflammation 01/2012; 2012:979105. · 3.26 Impact Factor
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Yanyan Yang, Tao Yu,
Hyun-Jae Jang,
Se Eun Byeon,
Song-Yi Song,
Byoung-Hee Lee,
Man Hee Rhee,
Tae Woong Kim,
Jaehwi Lee,
Sungyoul Hong,
Jae Youl Cho
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ABSTRACT: Polygonum hydropiper L. (Polygonaceae) has been traditionally used to treat various inflammatory diseases such as rheumatoid arthritis. However, no systematic studies on the anti-inflammatory actions of Polygonum hydropiper and its inhibitory mechanisms have been reported. This study is therefore aimed at exploring the anti-inflammatory effects of 99% methanol extracts (Ph-ME) of this plant.
The effects of Ph-ME on the production of inflammatory mediators in RAW264.7 cells and peritoneal macrophages were investigated. Molecular mechanisms underlying the effects, especially inhibitory effects, were elucidated by analyzing the activation of transcription factors and their upstream signalling, and by evaluating the kinase activities of target enzymes. Additionally, a dextran sulphate sodium (DSS)-induced colitis model was employed to see whether this extract can be used as an orally available drug.
Ph-ME dose-dependently suppressed the release of nitric oxide (NO), tumour necrosis factor (TNF)-α, and prostaglandin (PG)E(2), in RAW264.7 cells and peritoneal macrophages stimulated by lipopolysaccharide (LPS). Ph-ME inhibited mRNA expression of pro-inflammatory genes such as inducible NO synthase (iNOS), cyclooxygenase (COX)-2, and TNF-α by suppressing the activation of nuclear factor (NF)-κB, activator protein (AP-1), and cAMP responsive element binding protein (CREB), and simultaneously inhibited its upstream inflammatory signalling cascades, including cascades involving Syk, Src, and IRAK1. Consistent with these findings, the extract strongly suppressed the kinase activities of Src and Syk. Based on HPLC analysis, quercetin, which inhibits NO and PGE(2) activities, was found as one of the active ingredients in Ph-ME.
Ph-ME exerts strong anti-inflammatory activity by suppressing Src/Syk/NF-κB and IRAK/AP-1/CREB pathways, which contribute to its major ethno-pharmacological role as an anti-gastritis remedy.
Journal of ethnopharmacology 12/2011; 139(2):616-25. · 2.32 Impact Factor
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ABSTRACT: Cinnamomum cassia Blume (Aceraceae) has been traditionally used to treat various inflammatory diseases such as gastritis. However, the anti-inflammatory mechanism of Cinnamomum cassia has not been fully elucidated. This study examined the anti-inflammatory mechanism of 95% ethanol extract (Cc-EE) of Cinnamomum cassia.
The effect of Cc-EE on the production of inflammatory mediators in RAW264.7 cells and peritoneal macrophages was investigated. Molecular mechanisms underlying the effects, especially inhibitory effects, was elucidated by analyzing the activation of transcription factors and their upstream signaling, and by evaluating the kinase activity of target enzymes.
Cc-EE of Cinnamomum cassia diminished the production of nitric oxide (NO), tumor necrosis factor (TNF)-α, and prostaglandin (PG)E(2), in lipopolysaccharide (LPS)-activated RAW264.7 cells and peritoneal macrophages in a dose-dependent manner. Cc-EE also blocked mRNA expression of inducible NO synthase (iNOS), cyclooxygenase (COX)-2, and TNF-α by suppressing the activation of nuclear factor (NF)-κB, and simultaneously inhibited its upstream inflammatory signaling cascades, including spleen tyrosine kinase (Syk) and Src. Consistent with these findings, the extract directly blocked the kinase activities of Src and Syk.
Cc-EE exerts strong anti-inflammatory activity by suppressing Src/Syk-mediated NF-κB activation, which contributes to its major ethno-pharmacological role as an anti-gastritis remedy. Future work will be focused on determining whether the extract can be further developed as an anti-inflammatory drug.
Journal of ethnopharmacology 12/2011; 139(2):566-73. · 2.32 Impact Factor
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ABSTRACT: Sanguisorba officinalis, a well known and valuable medicinal plant in Korea, China and Japan has been used traditionally for the treatment of inflammatory and metabolic diseases such as diarrhea, chronic intestinal infections, duodenal ulcers, and bleeding. We studied the anti-hyperlipidemic effects of a chemically modified triterpenoid glycoside (ZYM-201 sodium succinate) isolated from Sanguisorba officinalis in rats in which hyperlipidemia had been induced by dietary administration of cholesterol and cholic acid. Oral administration of ZYM-201 sodium succinate (1 to 10 mg/kg) dose-dependently attenuated the diet-induced increases in body and liver weights. At 10 mg/kg, this compound also reversed the enhancement of serum levels of triglycerides (TG) and total cholesterol back to normal levels. In addition, imbalances in both serum and hepatic values of high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL) were prevented. Finally, this compound both blocked the generation of lipid peroxide and hydroxyl radicals and enhanced the activity of superoxide dismutase (SOD) in liver. Therefore, our data strongly suggest that ZYM-201 sodium succinate could play a role in modulating hyperlipidemic conditions, which could be used as a valuable remedy for the treatment of relevant disorders such as atherosclerosis and vascular diseases.
Pharmazie 10/2011; 66(10):791-7. · 1.01 Impact Factor
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Tao Yu,
Hyo Min Ahn,
Ting Shen,
Keejung Yoon,
Hyun-Jae Jang,
Yong Jin Lee,
Hyun Mo Yang,
Jae Hun Kim,
Changhyuk Kim,
Moon Hi Han,
Sang-Hun Cha,
Tae Wong Kim,
Sun Young Kim,
Jaehwi Lee,
Jae Youl Cho
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ABSTRACT: Phaseolus angularis Wight (adzuki bean) is an ethnopharmacologically well-known folk medicine that is prescribed for infection, edema, and inflammation of the joints, appendix, kidney and bladder in Korea, China and Japan.
The anti-inflammatory effect of this plant and its associated molecular mechanisms will be investigated.
The immunomodulatory activity of Phaseolus angularis ethanol extract (Pa-EE) in toll like receptor (TLR)-activated macrophages induced by ligands such as lipopolysaccharide (LPS), Poly (I:C), and pam3CSK was investigated by assessing nitric oxide (NO) and prostaglandin (PG)E(2) levels. To identify which transcription factors such as nuclear factor (NF)-κB and their signaling enzymes can be targeted to Pa-EE, biochemical approaches including reporter gene assays, immunoprecipitation, kinase assays, and immunoblot analyses were also employed. Finally, whether Pa-EE was orally available, ethanol (EtOH)/hydrochloric acid (HCl)-induced gastritis model in mice was used.
Pa-EE dose-dependently suppressed the release of PGE(2) and NO in LPS-, Poly(I:C)-, and pam3CSK-activated macrophages. Pa-EE strongly down-regulated LPS-induced mRNA expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2. Interestingly, Pa-EE markedly inhibited NF-κB, activator protein (AP)-1, and cAMP response element binding protein (CREB) activation; further, according to direct kinase assays and immunoblot analyses, Pa-EE blocked the activation of the upstream signaling molecules spleen tyrosine kinase (Syk), p38, and transforming growth factor β-activated kinase 1 (TAK1). Finally, orally administered Pa-EE clearly ameliorated EtOH/HCl-induced gastritis in mice.
Our results suggest that Pa-EE can be further developed as a promising anti-inflammatory remedy because it targets multiple inflammatory signaling enzymes and transcription factors.
Journal of ethnopharmacology 08/2011; 137(3):1197-206. · 2.32 Impact Factor
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Tao Yu,
Yong Jin Lee,
Hyun Mo Yang,
Soryu Han,
Jae Hun Kim,
Yoonsuk Lee,
Changhyuk Kim,
Moon Hi Han,
Mi-Yeon Kim,
Jaehwi Lee,
Jae Youl Cho
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ABSTRACT: Sanguisorba officinalis, a well known valuable medicinal plant in Korea, China and Japan used traditionally for the treatment of inflammatory and metabolic diseases such as diarrhea, chronic intestinal infections, duodenal ulcers, and bleeding. Recent studies have revealed that its aqueous or ethanolic extracts exhibit a variety of pharmacological activities such as anti-oxidative, anti-cancer, anti-lipid peroxidation, anti-atherogenic, and vasorelaxant effects. Systematic studies on the anti-inflammatory effect of this plant and its molecular mechanisms have not yet been fully investigated. Ethanol extract of Sanguisorba officinalis (So-EE) the lipopolysaccharide (LPS)-stimulated macrophages and production of inflammatory mediators were employed to assess these properties.
So-EE significantly suppressed the production of nitric oxide (NO) and prostaglandin (PG) E(2) from LPS-activated RAW264.7 cells and peritoneal macrophages in a dose-dependent manner. This extract effectively diminished the mRNA levels of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2, implying that the blockade is generated at the transcriptional level. So-EE strongly blocked the activation and translocation of NF-κB and AP-1 by suppressing the upstream kinases including inhibitor of κBα (IκBα), IκBα kinase (IKK), Akt (protein kinase B), phosphoinositide-dependent kinase 1 (PDK1), p85/phosphoinositide-3-kinase (PI3K), and mitogen activated protein kinase (MAPK) such as extracellular signal-regulated kinase (ERK), p38, and c-Jun N-terminal kinase (JNK). Moreover, So-EE suppressed the phosphorylation of Src, its kinase activity, and complex formation between Src and p85.
This study suggests that So-EE has a potent anti-inflammatory activity mediated by NF-κB, and AP-1 inhibitory properties linked to the suppression of Src and MAPK activation.
Journal of ethnopharmacology 03/2011; 134(1):11-7. · 2.32 Impact Factor
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ABSTRACT: Sorbus commixta Hedl. (Rosaceae) is a well known traditionally valuable medicinal plant in Korea, China and Japan. This plant has been prescribed for long time for various inflammatory symptoms such as asthma, bronchitis, gastritis and dropsy.
Although a number of pharmacological properties have already been demonstrated, the anti-inflammatory effect of this plant and its associated molecular mechanisms has not yet been fully investigated.
In order to address the anti-inflammatory activity of S. commixta water extract (Sc-WE), lipopolysaccharide (LPS)-stimulated macrophages were employed and production of inflammatory mediators by these cells were evaluated.
Sc-WE significantly suppressed the production of nitric oxide (NO) and prostaglandin (PG)E(2) in a dose-dependent manner and blocked ear edema formation induced by arachidonic acid in mouse. In addition, this extract effectively diminished the mRNA levels of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2, indicating that the inhibition occurs at the transcriptional level. Interestingly, Sc-WE remarkably blocked NF-κB translocation and its upstream signaling events by inhibition of κBα (IκBα), IκBα kinase (IKK), Akt (protein kinase B), phosphoinositide-dependent kinase 1 (PDK1), p85/phosphoinositide-3-kinase (PI3K), as per the results obtained from the reporter gene assay and immunoblotting analysis. More intriguingly, Sc-WE suppressed activities of Src and Syk kinases as well as their phosphorylation levels without altering molecular complex formation between them and toll like receptor (TLR)4 or MyD88, an adaptor protein of TLR4-mediated signaling.
Therefore, our results suggest that Sc-WE can be developed as a potent anti-inflammatory remedy, acting by suppressing the inflammatory signaling cascade composed of Src, Syk, and NF-κB.
Journal of ethnopharmacology 12/2010; 134(2):493-500. · 2.32 Impact Factor
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ABSTRACT: Acer tegmentosum has been traditionally used for folk medicine to treat hepatic disorders such as hepatitis, hepatic cancer, and hepatic cirrhosis. In this study, we demonstrate the ethno-pharmacological activity of Acer tegmentosum in in vitro and in vivo inflammatory conditions.
The 70% ethanol extract (At-EE) of Acer tegmentosum dose-dependently diminished the production of nitric oxide (NO), tumour necrosis factor (TNF)-alpha, and prostaglandin (PG)E(2), in lipopolysaccharide (LPS)-activated RAW264.7 cells and peritoneal macrophages, by a transcriptional mechanism. At-EE also suppressed the activation of nuclear factor (NF)-kappaB, activator protein (AP)-1, and cAMP-responsive element binding (CREB), and simultaneously blocked their upstream inflammatory signalling cascades, including Akt, p38, and JNK. Furthermore, At-EE protected against LPS-induced cell death induced by reactive oxygen species (ROS) and reactive nitrogen species (RNS) and neutralized reactive species generation. In agreement with the in vitro results, orally administered At-EE strongly ameliorated ear oedema formation induced by arachidonic acid.
At-EE displays strong anti-inflammatory activities in vitro and in vivo, contributing to its major ethno-pharmacological role such as anti-hepatitis remedy and may be applicable to novel anti-inflammatory therapeutics.
Journal of ethnopharmacology 03/2010; 128(1):139-47. · 2.32 Impact Factor
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ABSTRACT: The paper is supported by Project supported by the Chinese Defence Advance Research Program of Science and Technology, China (DPC, KJSX0601)
02/2010; , ISBN: 978-953-7619-97-8
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ABSTRACT: Sorbus commixta has been known as enthopharmacologically valuable plant in Korea, China and Japan. This plant has been reported to display numerous pharmacological activities such as anti-oxidative, anti-ice nucleation, anti-vascular inflammation, anti-lipid peroxidation, anti-atherogenic, and vasorelaxant effects. Although numerous pharmacological potentials have been demonstrated, immunomodulatory effect of this plant has not been fully elucidated yet. To evaluate its anti-inflammatory activity, macrophages activated by lipopolysaccharide (LPS) were employed and the production of inflammatory mediators was explored in terms of understanding its molecular inhibitory mechanism. 70% ethanol extract (Sc-EE) from S. commixta strongly suppressed the production of nitric oxide (NO) and prostaglandin (PG) E 2 but not tumor necrosis factor (TNF)-. The extract also clearly diminished the mRNA levels of inducible NO synthase (iNOS) and cyclo-oxygenase (COX)-2, implying that the inhibition occurs at the transcriptional level. Indeed, Western blot analysis and luciferase activity assay revealed that Sc-EE remarkably suppressed AP-1 translocation and its activity, respectively. In agreement, this extract strongly suppressed the phosphorylation of JNK, a prime enzyme responsible for AP-1 translocation. Therefore, our results suggest that Sc-EE can be applied as an anti-inflammatory herbal medicine. To prove this possibility, in vivo efficacy test will be further continued in the following project.
Journal of Medicinal Plants Research. 09/2009; 3:600-607.
