The Experts below are selected from a list of 294 Experts worldwide ranked by ideXlab platform
Yangmee Kim - One of the best experts on this subject based on the ideXlab platform.
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target proteins of Phloretin for its anti inflammatory and antibacterial activities against propionibacterium acnes induced skin infection
Molecules, 2019Co-Authors: Dasom Cheon, Jieun Kim, Dasom Jeon, Hangcheol Shin, Yangmee KimAbstract:Phloretin is a natural chalcone with antibacterial and anti-inflammatory effects. This study investigated the anti-acne activity of Phloretin against Propionibacterium acnes-induced skin infection and the potential target proteins of its anti-inflammatory and antibacterial effects. Phloretin potently inhibited the growth of P. acnes and P. acnes-induced Toll-like receptor (TLR) 2-mediated inflammatory signaling in human keratinocytes. Secreted embryonic alkaline phosphatase assay confirmed that the anti-inflammatory activity of Phloretin is associated with the P. acnes-stimulated TLR2-mediated NF-κB signaling pathway. Phloretin significantly decreased the level of phosphorylated c-Jun N-terminal kinase (JNK), showing a binding affinity of 1.184 × 10-5 M-1. We also found that Phloretin binds with micromolar affinity to P. acnes β-ketoacyl acyl carrier protein (ACP) synthase III (KAS III), an enzyme involved in fatty acid synthesis. Conformation-sensitive native polyacrylamide gel electrophoresis showed that Phloretin reduced KAS III-mediated 3-ketoacyl ACP production by over 66%. A docking study revealed that Phloretin interacts with the active sites of JNK1 and KAS III, suggesting their involvement in P. acnes-induced inflammation and their potential as targets for the antibacterial activity of Phloretin. These results demonstrate that Phloretin may be useful in the prevention or treatment of P. acnes infection.
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Phloretin as a Potent Natural TLR2/1 Inhibitor Suppresses TLR2-Induced Inflammation.
Nutrients, 2018Co-Authors: Jieun Kim, Prasannavenkatesh Durai, Dasom Jeon, In Duk Jung, Seung Jun Lee, Yeong-min Park, Yangmee KimAbstract:Toll-like receptor 2 (TLR2) responses are involved in various inflammatory immune disorders. Phloretin is a naturally occurring dietary flavonoid that is abundant in fruit. Here, we investigated whether the anti-inflammatory activity of Phloretin is mediated through TLR2 pathways, and whether Phloretin acts as an inhibitor of TLR2/1 heterodimerization using the TLR2/1 agonist Pam3CSK4. We tested the effects of Phloretin on tumor necrosis factor (TNF)-α production induced by various TLRs using known TLR-specific agonists. Phloretin significantly inhibited Pam3CSK4-induced TRL2/1 signaling in Raw264.7 cells compared to TLR signaling induced by the other agonists tested. Therefore, we further tested the effects of Phloretin in human embryonic kidney (HEK) 293-hTLR2 cells induced by Pam3CSK4, and confirmed that Phloretin has comparable inhibition of TLR2/1 heterodimerization to that induced by the known TLR2 inhibitor CU-CPT22. Moreover, Phloretin reduced the secretion of the inflammatory cytokines TNF-α and interleukin (IL)-8 in Pam3CSK4-induced HEK293-hTLR2 cells, whereas it did not significantly reduce these cytokines under Pam2CSK4-induced activation. Western blot results showed that Phloretin significantly suppressed Pam3CSK4-induced TLR2 and NF-κB p65 expression. The molecular interactions between Phloretin and TLR2 were investigated using bio-layer interferometry and in silico docking. Phloretin bound to TLR2 with micromolar binding affinity, and we proposed a binding model of Phloretin at the TLR2–TLR1 interface. Overall, we confirmed that Phloretin inhibits the heterodimerization of TLR2/1, highlighting TLR2 signaling as a therapeutic target for treating TLR2-mediated inflammatory immune diseases.
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Phloretin as a potent natural tlr2 1 inhibitor suppresses tlr2 induced inflammation
Nutrients, 2018Co-Authors: Jieun Kim, Prasannavenkatesh Durai, Dasom Jeon, In Duk Jung, Seung Jun Lee, Yeong-min Park, Yangmee KimAbstract:Toll-like receptor 2 (TLR2) responses are involved in various inflammatory immune disorders. Phloretin is a naturally occurring dietary flavonoid that is abundant in fruit. Here, we investigated whether the anti-inflammatory activity of Phloretin is mediated through TLR2 pathways, and whether Phloretin acts as an inhibitor of TLR2/1 heterodimerization using the TLR2/1 agonist Pam3CSK4. We tested the effects of Phloretin on tumor necrosis factor (TNF)-α production induced by various TLRs using known TLR-specific agonists. Phloretin significantly inhibited Pam3CSK4-induced TRL2/1 signaling in Raw264.7 cells compared to TLR signaling induced by the other agonists tested. Therefore, we further tested the effects of Phloretin in human embryonic kidney (HEK) 293-hTLR2 cells induced by Pam3CSK4, and confirmed that Phloretin has comparable inhibition of TLR2/1 heterodimerization to that induced by the known TLR2 inhibitor CU-CPT22. Moreover, Phloretin reduced the secretion of the inflammatory cytokines TNF-α and interleukin (IL)-8 in Pam3CSK4-induced HEK293-hTLR2 cells, whereas it did not significantly reduce these cytokines under Pam2CSK4-induced activation. Western blot results showed that Phloretin significantly suppressed Pam3CSK4-induced TLR2 and NF-κB p65 expression. The molecular interactions between Phloretin and TLR2 were investigated using bio-layer interferometry and in silico docking. Phloretin bound to TLR2 with micromolar binding affinity, and we proposed a binding model of Phloretin at the TLR2–TLR1 interface. Overall, we confirmed that Phloretin inhibits the heterodimerization of TLR2/1, highlighting TLR2 signaling as a therapeutic target for treating TLR2-mediated inflammatory immune diseases.
Younghee Kang - One of the best experts on this subject based on the ideXlab platform.
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dietary phlorizin enhances osteoblastogenic bone formation through enhancing β catenin activity via gsk 3β inhibition in a model of senile osteoporosis
Journal of Nutritional Biochemistry, 2017Co-Authors: Lucia Dwi Antika, Eunjung Lee, Yunho Kim, Minkyung Kang, Sinhye Park, Dong Yeon Kim, Yeanjung Choi, Younghee KangAbstract:Osteoporosis is one of the most prevalent forms of age-related bone diseases. Increased bone loss with advancing age has become a grave public health concern. This study examined whether phlorizin and Phloretin, dihydrochalcones in apple peels, inhibited senile osteoporosis through enhancing osteoblastogenic bone formation in cell-based and aged mouse models. Submicromolar Phloretin and phlorizin markedly stimulated osteoblast differentiation of MC3T3-E1 cells with increased transcription of Runx2 and osteocalcin. Senescence-accelerated resistant mouse strain prone-6 (SAMP6) mice were orally supplemented with 10 mg/kg phlorizin and Phloretin daily for 12 weeks. Male senescence-accelerated resistant mouse strain R1 mice were employed as a nonosteoporotic age-matched control. Oral administration of ploretin and phorizin boosted bone mineralization in all the bones of femur, tibia and vertebra of SAMP6. In particular, phlorizin reduced serum RANKL/OPG ratio and diminished TRAP-positive osteoclasts in trabecular bones of SAMP6. Additionally, treating phlorizin to SAMP6 inhibited the osteoporotic resorption in distal femoral bones through up-regulating expression of BMP-2 and collagen-1 and decreasing production of matrix-degrading cathepsin K and MMP-9. Finally, phlorizin and Phloretin antagonized GSK-3β induction and β-catenin phosphorylation in osteoblasts and aged mouse bones. Therefore, phlorizin and Phloretin were potential therapeutic agents encumbering senile osteoporosis through promoting bone-forming osteoblastogenesis via modulation of GSK-3β/β-catenin-dependent signaling.
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Inhibition of osteoclast activation by Phloretin through disturbing αvβ3 integrin-c-Src pathway.
BioMed research international, 2015Co-Authors: Eunjung Lee, Sinhye Park, Jung-lye Kim, Ju-hyun Gong, Younghee KangAbstract:This study was to explore the sequential signaling of disorganization of the actin cytoskeletal architecture by Phloretin. RAW 264.7 macrophages were incubated with 1–20 M Phloretin for 5 days in the presence of RANKL. C57BL/6 mice were ovariectomized (OVX) and orally treated with 10 mg/kg Phloretin once a day for 8 weeks. Phloretin allayed RANKL stimulated formation of actin podosomes with the concomitant retardation of the vinculin activation. Oral administration of Phloretin suppressed the induction of femoral gelsolin and vinculin in OVX mice. The RANK-RANKL interaction resulted in the αv3 integrin induction, which was demoted by Phloretin. The RANKL induction of actin rings and vacuolar-type H
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Phloretin promotes osteoclast apoptosis in murine macrophages and inhibits estrogen deficiency induced osteoporosis in mice
Phytomedicine, 2014Co-Authors: Eunjung Lee, Yunho Kim, Minkyung Kang, Jung-lye Kim, Ju-hyun Gong, Younghee KangAbstract:Bone-remodeling imbalance induced by increased osteoclast formation and bone resorption is known to cause skeletal diseases such as osteoporosis. The reduction of estrogen levels at menopause is one of the strongest risk factors developing postmenopausal osteoporosis. This study investigated osteoprotective effects of the dihydrochalcone Phloretin found in apple tree leaves on bone loss in ovariectomized (OVX) C57BL/6 female mice as a model for postmenopausal osteoporosis. OVX demoted bone mineral density (BMD) of mouse femurs, reduced serum 17β-estradiol level and enhanced serum receptor activator of NF-κB ligand (RANKL)/osteoprotegerin ratio with uterine atrophy. Oral administration of 10 mg/kg Phloretin to OVX mice for 8 weeks improved such effects, compared to sham-operated mice. Phloretin attenuated TRAP activity and cellular expression of β3 integrin and carbonic anhydrase II augmented in femoral bone tissues of OVX mice. This study further examined that osteogenic activity of Phloretin in RANKL-differentiated Raw 264.7 macrophages into mature osteoclasts. Phloretin at 1-20 μM stimulated Smac expression and capase-3 activation concurrently with nuclear fragmentation of multi-nucleated osteoclasts, indicating that this compound promoted osteoclast apoptosis. Consistently, Phloretin enhanced bcl-2 induction but diminished bax expression. Furthermore, Phloretin activated ASK-1-diverged JNK and p38 MAPK signaling pathways in mature osteoclasts, whereas it dose-dependently inhibited the RANKL-stimulated activation of ERK. Therefore, Phloretin manipulated ASK-1-MAPK signal transduction leading to transcription of apoptotic genes. Phloretin was effective in preventing estrogen deficiency-induced osteoclastogenic resorption.
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Phloretin suppresses thrombin mediated leukocyte platelet endothelial interactions
Molecular Nutrition & Food Research, 2014Co-Authors: Min Soo Kim, Eunjung Lee, Yunho Kim, Sinhye Park, Seon-young Han, Jung Han Yoon Park, Younghee KangAbstract:Scope Thrombin playing a pivotal role in coagulation cascade may influence the onset and progression of atherosclerosis as a pro-inflammatory mediator. This study investigated whether Phloretin found in apple tree leaves, severed a linkage between thrombosis and atherosclerosis by thrombin. Methods and results Human endothelial cells were pre-treated with 1–20 μM Phloretin and stimulated with 10 U/mL thrombin. Phloretin attenuated adhesion of THP-1 monocytes and platelets to thrombin-inflamed endothelial cells with concurrent inhibition of protease-activated receptor (PAR-1) induction. The thrombin induction of endothelial CD40, endothelial integrin β3 and P-selectin, and monocytic CD40L was dampened by Phloretin. Additionally, Phloretin inhibited monocyte secretion of MCP-1, IL-6 and IL-8 responsible for pro-inflammatory activity of thrombin inducing endothelial CD40. The monocyte COX-2 induction and PGE2 secretion due to thrombin were down-regulated by Phloretin, deterring endothelial CD40 expression. Thrombin promoted production of PAI-1 and tissue factor in monocytes was attenuated by Phloretin through blocking PAR-1 and CD40. Thrombin up-regulated the induction of endothelial connective tissue growth factor independent of PAR-1 activation, which was reversed by Phloretin. Conclusion Phloretin disturbed tethering and stable adhesion of monocytes and platelets onto endothelium during increased thrombosis by thrombin. Phloretin would be a potent agent preventing thrombosis and atherosclerosis.
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Phloretin suppresses thrombin‐mediated leukocyte‐platelet‐endothelial interactions
Molecular nutrition & food research, 2013Co-Authors: Min Soo Kim, Eunjung Lee, Yunho Kim, Sinhye Park, Seon-young Han, Jung Han Yoon Park, Younghee KangAbstract:Scope Thrombin playing a pivotal role in coagulation cascade may influence the onset and progression of atherosclerosis as a pro-inflammatory mediator. This study investigated whether Phloretin found in apple tree leaves, severed a linkage between thrombosis and atherosclerosis by thrombin. Methods and results Human endothelial cells were pre-treated with 1–20 μM Phloretin and stimulated with 10 U/mL thrombin. Phloretin attenuated adhesion of THP-1 monocytes and platelets to thrombin-inflamed endothelial cells with concurrent inhibition of protease-activated receptor (PAR-1) induction. The thrombin induction of endothelial CD40, endothelial integrin β3 and P-selectin, and monocytic CD40L was dampened by Phloretin. Additionally, Phloretin inhibited monocyte secretion of MCP-1, IL-6 and IL-8 responsible for pro-inflammatory activity of thrombin inducing endothelial CD40. The monocyte COX-2 induction and PGE2 secretion due to thrombin were down-regulated by Phloretin, deterring endothelial CD40 expression. Thrombin promoted production of PAI-1 and tissue factor in monocytes was attenuated by Phloretin through blocking PAR-1 and CD40. Thrombin up-regulated the induction of endothelial connective tissue growth factor independent of PAR-1 activation, which was reversed by Phloretin. Conclusion Phloretin disturbed tethering and stable adhesion of monocytes and platelets onto endothelium during increased thrombosis by thrombin. Phloretin would be a potent agent preventing thrombosis and atherosclerosis.
Chian-jiun Liou - One of the best experts on this subject based on the ideXlab platform.
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Phloretin ameliorates hepatic steatosis through regulation of lipogenesis and Sirt1/AMPK signaling in obese mice.
Cell & bioscience, 2020Co-Authors: Chian-jiun Liou, Szu-chuan Shen, Li-chen Chen, Ya-ling Chen, Wen-chung HuangAbstract:Phloretin is isolated from apple trees and could increase lipolysis in 3T3-L1 adipocytes. Previous studies have found that Phloretin could prevent obesity in mice. In this study, we investigated whether Phloretin ameliorates non-alcoholic fatty liver disease (NAFLD) in high-fat diet (HFD)-induced obese mice, and evaluated the regulation of lipid metabolism in hepatocytes. HepG2 cells were treated with 0.5 mM oleic acid to induce lipid accumulation, and then treated with Phloretin to evaluate the molecular mechanism of lipogenesis. In another experiment, male C57BL/6 mice were fed normal diet or HFD (60% fat, w/w) for 16 weeks. After the fourth week, mice were treated with or without Phloretin by intraperitoneal injection for 12 weeks. Phloretin significantly reduced excessive lipid accumulation and decreased sterol regulatory element-binding protein 1c, blocking the expression of fatty acid synthase in oleic acid-induced HepG2 cells. Phloretin increased Sirt1, and phosphorylation of AMP activated protein kinase to suppress acetyl-CoA carboxylase expression, reducing fatty acid synthesis in hepatocytes. Phloretin also reduced body weight and fat weight compared to untreated HFD-fed mice. Phloretin also reduced liver weight and liver lipid accumulation and improved hepatocyte steatosis in obese mice. In liver tissue from obese mice, Phloretin suppressed transcription factors of lipogenesis and fatty acid synthase, and increased lipolysis and fatty acid β-oxidation. Furthermore, Phloretin regulated serum leptin, adiponectin, triglyceride, low-density lipoprotein, and free fatty acid levels in obese mice. These findings suggest that Phloretin improves hepatic steatosis by regulating lipogenesis and the Sirt-1/AMPK pathway in the liver.
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Phloretin Attenuates Allergic Airway Inflammation and Oxidative Stress in Asthmatic Mice.
Frontiers in immunology, 2017Co-Authors: Wen-chung Huang, Li-wen Fang, Chian-jiun LiouAbstract:Phloretin, isolated from the apple tree, was previously demonstrated to have anti-oxidative and anti-inflammatory effects in macrophages and anti-adiposity effects in adipocytes. Inflammatory immune cells generate high levels of reactive oxygen species for stimulated severe airway hyperresponsiveness (AHR) and airway inflammation. In this study, we investigated whether Phloretin could reduce oxidative stress, airway inflammation, and eosinophil infiltration in asthmatic mice, and ameliorate oxidative and inflammatory responses in tracheal epithelial cells. BALB/c mice were sensitized with ovalbumin (OVA) to induce asthma symptoms. Mice were randomly assigned to the five experimental groups: normal controls; OVA-induced asthmatic mice; and OVA-induced mice injected intraperitoneally with one of the three Phloretin doses (5 mg/kg, 10 mg/kg, or 20 mg/kg). In addition, we treated inflammatory human tracheal epithelial cells (BEAS-2B cells) with Phloretin to assess oxidative responses and the levels of proinflammatory cytokines and chemokines. We found that Phloretin significantly reduced goblet cell hyperplasia and eosinophil infiltration, which decreased AHR, inflammation, and oxidative responses in the lungs of OVA-sensitized mice. Phloretin also decreased malondialdehyde levels in the lung, and reduced Th2 cytokine production in bronchoalveolar lavage fluids. Furthermore, Phloretin reduced reactive oxygen species, proinflammatory cytokines, and eotaxin production in BEAS-2B cells. Phloretin also suppressed monocyte cell adherence to inflammatory BEAS-2B cells. These findings suggested that Phloretin alleviated pathological changes, inflammation, and oxidative stress by inhibiting Th2 cytokine production in asthmatic mice. Phloretin showed therapeutic potential for ameliorating asthma symptoms in the future.
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Phloretin attenuates lps induced acute lung injury in mice via modulation of the nf κb and mapk pathways
International Immunopharmacology, 2016Co-Authors: Wen-chung Huang, Chian-jiun Liou, Chinglong Lai, Yuanting Liang, Huichih Hung, Huichia LiuAbstract:Phloretin, which can be isolated from apple trees, has demonstrable anti-inflammatory and anti-oxidant effects in macrophages. We previously reported that Phloretin could inhibit the inflammatory response and reduce intercellular adhesion molecule 1 (ICAM-1) expression in interleukin (IL)-1β-activated human lung epithelial cells. In the present study we now evaluate whether Phloretin exposure could ameliorate lipopolysaccharide (LPS)-induced acute lung injury in mice. Intra-peritoneal injections of Phloretin were administered to mice for 7 consecutive days, prior to the induction of lung injury by intra-tracheal administration of LPS. Our subsequent analyses demonstrated that Phloretin could significantly suppress LPS-induced neutrophil infiltration of lung tissue, and reduce the levels of IL-6 and tumor necrosis factor (TNF)-α in serum and bronchoalveolar lavage fluid. We also found that Phloretin modulated myeloperoxidase activity and superoxide dismutase activity, with decreased gene expression levels for chemokines, proinflammatory cytokines, and ICAM-1 in inflamed lung tissue. Phloretin also significantly reduced the phosphorylation of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK), thus limiting the inflammatory response, while promoting expression of heme oxygenase (HO)-1 and nuclear factor erythroid 2-related factor 2, both of which are cytoprotective. Our findings suggest that, mechanistically, Phloretin attenuates the inflammatory and oxidative stress pathways that accompany lung injury in mice via blockade of the NF-κB and MAPK pathways.
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Phloretin ameliorates chemokines and icam 1 expression via blocking of the nf κb pathway in the tnf α induced hacat human keratinocytes
International Immunopharmacology, 2015Co-Authors: Wen-chung Huang, Yiwen Dai, Huiling Peng, Chiaowei Kang, Chunyu Kuo, Chian-jiun LiouAbstract:Previous studies found that Phloretin had anti-oxidant, anti-inflammatory, and anti-tumor properties. In this study, we investigated whether Phloretin could suppress the production of the intercellular adhesion molecule (ICAM)-1 and chemokines through downregulation of the nuclear transcription factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways in TNF-α-stimulated HaCaT human keratinocytes. HaCaT cells were treated with Phloretin and then the cells were stimulated by TNF-α. Phloretin treatment decreased the production of IL-6, IL-8, CCL5, MDC, and TARC. Phloretin decreased ICAM-1 protein and mRNA expression, and also suppressed the adhesion of monocyte THP-1 cells to inflammatory HaCaT cells. Phloretin inhibited NF-κB translocation into the nucleus and also suppressed the phosphorylation of Akt and MAPK signal. In addition, Phloretin increased heme oxygenase-1 production in a concentration-dependent manner. These results demonstrated that Phloretin has anti-inflammatory effects to inhibit chemokines and ICAM-1 expressions through suppression of the NF-κB and MAPK pathways in human keratinocytes.
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Phloretin inhibits interleukin 1β induced cox 2 and icam 1 expression through inhibition of mapk akt and nf κb signaling in human lung epithelial cells
Food & Function, 2015Co-Authors: Wen-chung Huang, Yourong Lai, Chian-jiun LiouAbstract:Phloretin, a flavonoid isolated from the apple tree, is reported to have anti-inflammatory, anti-oxidant, and anti-adiposity effects. In this study, we evaluated the suppressive effects of Phloretin on intercellular adhesion molecule 1 (ICAM-1) and cyclooxygenase (COX)-2 expression in IL-1β-stimulated human lung epithelial A549 cells. The cells were pretreated with various concentrations of Phloretin (3–100 μM), followed by induced inflammation by IL-1β. Phloretin inhibited levels of prostaglandin E2, decreased COX-2 expression, and suppressed IL-8, monocyte chemotactic protein 1, and IL-6 production. It also decreased ICAM-1 gene and protein expression and suppressed monocyte adhesion to inflammatory A549 cells. Phloretin also significantly inhibited Akt and mitogen-activated protein kinase (MAPK) phosphorylation and decreased nuclear transcription factor kappa-B (NF-κB) subunit p65 protein translocation into the nucleus. In addition, ICAM-1 and COX-2 expression was suppressed by pretreatment with both MAPK inhibitors and Phloretin in inflammatory A549 cells. However, phlorizin, a derivative of Phloretin, did not suppress the inflammatory response in IL-1β-stimulated A549 cells. These results suggest that Phloretin might have an anti-inflammatory effect by inhibiting proinflammatory cytokine, COX-2, and ICAM-1 expression via blocked NF-κB and MAPK signaling pathways.
Jieun Kim - One of the best experts on this subject based on the ideXlab platform.
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target proteins of Phloretin for its anti inflammatory and antibacterial activities against propionibacterium acnes induced skin infection
Molecules, 2019Co-Authors: Dasom Cheon, Jieun Kim, Dasom Jeon, Hangcheol Shin, Yangmee KimAbstract:Phloretin is a natural chalcone with antibacterial and anti-inflammatory effects. This study investigated the anti-acne activity of Phloretin against Propionibacterium acnes-induced skin infection and the potential target proteins of its anti-inflammatory and antibacterial effects. Phloretin potently inhibited the growth of P. acnes and P. acnes-induced Toll-like receptor (TLR) 2-mediated inflammatory signaling in human keratinocytes. Secreted embryonic alkaline phosphatase assay confirmed that the anti-inflammatory activity of Phloretin is associated with the P. acnes-stimulated TLR2-mediated NF-κB signaling pathway. Phloretin significantly decreased the level of phosphorylated c-Jun N-terminal kinase (JNK), showing a binding affinity of 1.184 × 10-5 M-1. We also found that Phloretin binds with micromolar affinity to P. acnes β-ketoacyl acyl carrier protein (ACP) synthase III (KAS III), an enzyme involved in fatty acid synthesis. Conformation-sensitive native polyacrylamide gel electrophoresis showed that Phloretin reduced KAS III-mediated 3-ketoacyl ACP production by over 66%. A docking study revealed that Phloretin interacts with the active sites of JNK1 and KAS III, suggesting their involvement in P. acnes-induced inflammation and their potential as targets for the antibacterial activity of Phloretin. These results demonstrate that Phloretin may be useful in the prevention or treatment of P. acnes infection.
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Phloretin as a Potent Natural TLR2/1 Inhibitor Suppresses TLR2-Induced Inflammation.
Nutrients, 2018Co-Authors: Jieun Kim, Prasannavenkatesh Durai, Dasom Jeon, In Duk Jung, Seung Jun Lee, Yeong-min Park, Yangmee KimAbstract:Toll-like receptor 2 (TLR2) responses are involved in various inflammatory immune disorders. Phloretin is a naturally occurring dietary flavonoid that is abundant in fruit. Here, we investigated whether the anti-inflammatory activity of Phloretin is mediated through TLR2 pathways, and whether Phloretin acts as an inhibitor of TLR2/1 heterodimerization using the TLR2/1 agonist Pam3CSK4. We tested the effects of Phloretin on tumor necrosis factor (TNF)-α production induced by various TLRs using known TLR-specific agonists. Phloretin significantly inhibited Pam3CSK4-induced TRL2/1 signaling in Raw264.7 cells compared to TLR signaling induced by the other agonists tested. Therefore, we further tested the effects of Phloretin in human embryonic kidney (HEK) 293-hTLR2 cells induced by Pam3CSK4, and confirmed that Phloretin has comparable inhibition of TLR2/1 heterodimerization to that induced by the known TLR2 inhibitor CU-CPT22. Moreover, Phloretin reduced the secretion of the inflammatory cytokines TNF-α and interleukin (IL)-8 in Pam3CSK4-induced HEK293-hTLR2 cells, whereas it did not significantly reduce these cytokines under Pam2CSK4-induced activation. Western blot results showed that Phloretin significantly suppressed Pam3CSK4-induced TLR2 and NF-κB p65 expression. The molecular interactions between Phloretin and TLR2 were investigated using bio-layer interferometry and in silico docking. Phloretin bound to TLR2 with micromolar binding affinity, and we proposed a binding model of Phloretin at the TLR2–TLR1 interface. Overall, we confirmed that Phloretin inhibits the heterodimerization of TLR2/1, highlighting TLR2 signaling as a therapeutic target for treating TLR2-mediated inflammatory immune diseases.
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Phloretin as a potent natural tlr2 1 inhibitor suppresses tlr2 induced inflammation
Nutrients, 2018Co-Authors: Jieun Kim, Prasannavenkatesh Durai, Dasom Jeon, In Duk Jung, Seung Jun Lee, Yeong-min Park, Yangmee KimAbstract:Toll-like receptor 2 (TLR2) responses are involved in various inflammatory immune disorders. Phloretin is a naturally occurring dietary flavonoid that is abundant in fruit. Here, we investigated whether the anti-inflammatory activity of Phloretin is mediated through TLR2 pathways, and whether Phloretin acts as an inhibitor of TLR2/1 heterodimerization using the TLR2/1 agonist Pam3CSK4. We tested the effects of Phloretin on tumor necrosis factor (TNF)-α production induced by various TLRs using known TLR-specific agonists. Phloretin significantly inhibited Pam3CSK4-induced TRL2/1 signaling in Raw264.7 cells compared to TLR signaling induced by the other agonists tested. Therefore, we further tested the effects of Phloretin in human embryonic kidney (HEK) 293-hTLR2 cells induced by Pam3CSK4, and confirmed that Phloretin has comparable inhibition of TLR2/1 heterodimerization to that induced by the known TLR2 inhibitor CU-CPT22. Moreover, Phloretin reduced the secretion of the inflammatory cytokines TNF-α and interleukin (IL)-8 in Pam3CSK4-induced HEK293-hTLR2 cells, whereas it did not significantly reduce these cytokines under Pam2CSK4-induced activation. Western blot results showed that Phloretin significantly suppressed Pam3CSK4-induced TLR2 and NF-κB p65 expression. The molecular interactions between Phloretin and TLR2 were investigated using bio-layer interferometry and in silico docking. Phloretin bound to TLR2 with micromolar binding affinity, and we proposed a binding model of Phloretin at the TLR2–TLR1 interface. Overall, we confirmed that Phloretin inhibits the heterodimerization of TLR2/1, highlighting TLR2 signaling as a therapeutic target for treating TLR2-mediated inflammatory immune diseases.
Dasom Jeon - One of the best experts on this subject based on the ideXlab platform.
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target proteins of Phloretin for its anti inflammatory and antibacterial activities against propionibacterium acnes induced skin infection
Molecules, 2019Co-Authors: Dasom Cheon, Jieun Kim, Dasom Jeon, Hangcheol Shin, Yangmee KimAbstract:Phloretin is a natural chalcone with antibacterial and anti-inflammatory effects. This study investigated the anti-acne activity of Phloretin against Propionibacterium acnes-induced skin infection and the potential target proteins of its anti-inflammatory and antibacterial effects. Phloretin potently inhibited the growth of P. acnes and P. acnes-induced Toll-like receptor (TLR) 2-mediated inflammatory signaling in human keratinocytes. Secreted embryonic alkaline phosphatase assay confirmed that the anti-inflammatory activity of Phloretin is associated with the P. acnes-stimulated TLR2-mediated NF-κB signaling pathway. Phloretin significantly decreased the level of phosphorylated c-Jun N-terminal kinase (JNK), showing a binding affinity of 1.184 × 10-5 M-1. We also found that Phloretin binds with micromolar affinity to P. acnes β-ketoacyl acyl carrier protein (ACP) synthase III (KAS III), an enzyme involved in fatty acid synthesis. Conformation-sensitive native polyacrylamide gel electrophoresis showed that Phloretin reduced KAS III-mediated 3-ketoacyl ACP production by over 66%. A docking study revealed that Phloretin interacts with the active sites of JNK1 and KAS III, suggesting their involvement in P. acnes-induced inflammation and their potential as targets for the antibacterial activity of Phloretin. These results demonstrate that Phloretin may be useful in the prevention or treatment of P. acnes infection.
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Phloretin as a Potent Natural TLR2/1 Inhibitor Suppresses TLR2-Induced Inflammation.
Nutrients, 2018Co-Authors: Jieun Kim, Prasannavenkatesh Durai, Dasom Jeon, In Duk Jung, Seung Jun Lee, Yeong-min Park, Yangmee KimAbstract:Toll-like receptor 2 (TLR2) responses are involved in various inflammatory immune disorders. Phloretin is a naturally occurring dietary flavonoid that is abundant in fruit. Here, we investigated whether the anti-inflammatory activity of Phloretin is mediated through TLR2 pathways, and whether Phloretin acts as an inhibitor of TLR2/1 heterodimerization using the TLR2/1 agonist Pam3CSK4. We tested the effects of Phloretin on tumor necrosis factor (TNF)-α production induced by various TLRs using known TLR-specific agonists. Phloretin significantly inhibited Pam3CSK4-induced TRL2/1 signaling in Raw264.7 cells compared to TLR signaling induced by the other agonists tested. Therefore, we further tested the effects of Phloretin in human embryonic kidney (HEK) 293-hTLR2 cells induced by Pam3CSK4, and confirmed that Phloretin has comparable inhibition of TLR2/1 heterodimerization to that induced by the known TLR2 inhibitor CU-CPT22. Moreover, Phloretin reduced the secretion of the inflammatory cytokines TNF-α and interleukin (IL)-8 in Pam3CSK4-induced HEK293-hTLR2 cells, whereas it did not significantly reduce these cytokines under Pam2CSK4-induced activation. Western blot results showed that Phloretin significantly suppressed Pam3CSK4-induced TLR2 and NF-κB p65 expression. The molecular interactions between Phloretin and TLR2 were investigated using bio-layer interferometry and in silico docking. Phloretin bound to TLR2 with micromolar binding affinity, and we proposed a binding model of Phloretin at the TLR2–TLR1 interface. Overall, we confirmed that Phloretin inhibits the heterodimerization of TLR2/1, highlighting TLR2 signaling as a therapeutic target for treating TLR2-mediated inflammatory immune diseases.
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Phloretin as a potent natural tlr2 1 inhibitor suppresses tlr2 induced inflammation
Nutrients, 2018Co-Authors: Jieun Kim, Prasannavenkatesh Durai, Dasom Jeon, In Duk Jung, Seung Jun Lee, Yeong-min Park, Yangmee KimAbstract:Toll-like receptor 2 (TLR2) responses are involved in various inflammatory immune disorders. Phloretin is a naturally occurring dietary flavonoid that is abundant in fruit. Here, we investigated whether the anti-inflammatory activity of Phloretin is mediated through TLR2 pathways, and whether Phloretin acts as an inhibitor of TLR2/1 heterodimerization using the TLR2/1 agonist Pam3CSK4. We tested the effects of Phloretin on tumor necrosis factor (TNF)-α production induced by various TLRs using known TLR-specific agonists. Phloretin significantly inhibited Pam3CSK4-induced TRL2/1 signaling in Raw264.7 cells compared to TLR signaling induced by the other agonists tested. Therefore, we further tested the effects of Phloretin in human embryonic kidney (HEK) 293-hTLR2 cells induced by Pam3CSK4, and confirmed that Phloretin has comparable inhibition of TLR2/1 heterodimerization to that induced by the known TLR2 inhibitor CU-CPT22. Moreover, Phloretin reduced the secretion of the inflammatory cytokines TNF-α and interleukin (IL)-8 in Pam3CSK4-induced HEK293-hTLR2 cells, whereas it did not significantly reduce these cytokines under Pam2CSK4-induced activation. Western blot results showed that Phloretin significantly suppressed Pam3CSK4-induced TLR2 and NF-κB p65 expression. The molecular interactions between Phloretin and TLR2 were investigated using bio-layer interferometry and in silico docking. Phloretin bound to TLR2 with micromolar binding affinity, and we proposed a binding model of Phloretin at the TLR2–TLR1 interface. Overall, we confirmed that Phloretin inhibits the heterodimerization of TLR2/1, highlighting TLR2 signaling as a therapeutic target for treating TLR2-mediated inflammatory immune diseases.
