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Xiuwei Yang - One of the best experts on this subject based on the ideXlab platform.
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the efflux of flavonoids Morin isorhamnetin 3 o rutinoside and diosmetin 7 o β d xylopyranosyl 1 6 β d glucopyranoside in the human intestinal cell line caco 2
Pharmaceutical Research, 2006Co-Authors: Xiaojuan Tian, Xiaoda Yang, Kui Wang, Xiuwei YangAbstract:PURPOSE In this study, we chose three of the flavonoids isorhamnetin-3-O-rutinoside(IRR) diosmetin-7-O-beta-D-xylopyranosyl-(1-6)-beta-D-glucopyranoside(DXG) and Morin, which showed obvious efflux, to test the hypothesis that a specific efflux transporter is responsible for their transportation. METHODS The intestinal epithelial membrane transport of the flavonoids were examined using the monolayer of the human Caco-2 cell line grown in Transwells, a common model of intestinal absorption. The flavonoids were measured by high performance liquid chromatography with UV detector. RESULT The efflux of Morin, IRR and DXG, across Caco-2 cell monolayers was examined over the concentration range from 2 to 200 microM and showed a saturable process. The depletion of the cellular ATP stores with 5 mM iodoacetamide led to a significant inhibition of the efflux. Fifty micromolar verapamil, a chemical inhibitor of P-glycoprotein, had no effect on the transport of the three flavonoids, while the presence of 50 microM MK-571 and 1 mM probenecid, MRP inhibitors, resulted in an obvious reduction in the efflux. Moreover, inhibition of Morin transport by MK-571 demonstrated concentration dependence. The transportation of the three flavonoids was compared with apigenin. CONCLUSION These data support a role for MRPs in the intestinal transcellular efflux of Morin, IRR, DXG and possibly other hydrophilic flavonoid aglycons and glycosides.
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the efflux of flavonoids Morin isorhamnetin 3 o rutinoside and diosmetin 7 o β d xylopyranosyl 1 6 β d glucopyranoside in the human intestinal cell line caco 2
Pharmaceutical Research, 2006Co-Authors: Xiaojuan Tian, Xiaoda Yang, Kui Wang, Xiuwei YangAbstract:In this study, we chose three of the flavonoids isorhamnetin-3-O-rutinoside(IRR) diosmetin-7-O-β-d-xylopyranosyl-(1-6)-β-d-glucopyranoside(DXG) and Morin, which showed obvious efflux, to test the hypothesis that a specific efflux transporter is responsible for their transportation. The intestinal epithelial membrane transport of the flavonoids were examined using the monolayer of the human Caco-2 cell line grown in Transwells, a common model of intestinal absorption. The flavonoids were measured by high performance liquid chromatography with UV detector. The efflux of Morin, IRR and DXG, across Caco-2 cell monolayers was examined over the concentration range from 2 to 200 μM and showed a saturable process. The depletion of the cellular ATP stores with 5 mM iodoacetamide led to a significant inhibition of the efflux. Fifty micromolar verapamil, a chemical inhibitor of P-glycoprotein, had no effect on the transport of the three flavonoids, while the presence of 50 μM MK-571 and 1 mM probenecid, MRP inhibitors, resulted in an obvious reduction in the efflux. Moreover, inhibition of Morin transport by MK-571 demonstrated concentration dependence. The transportation of the three flavonoids was compared with apigenin. These data support a role for MRPs in the intestinal transcellular efflux of Morin, IRR, DXG and possibly other hydrophilic flavonoid aglycons and glycosides.
Mahaboobkhan Rasool - One of the best experts on this subject based on the ideXlab platform.
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Morin a dietary bioflavonol suppresses monosodium urate crystal induced inflammation in an animal model of acute gouty arthritis with reference to nlrp3 inflammasome hypo xanthine phospho ribosyl transferase and inflammatory mediators
European Journal of Pharmacology, 2016Co-Authors: Chitra Dhanasekar, Mahaboobkhan RasoolAbstract:The anti-inflammatory effect of Morin, a dietary bioflavanol was explored on monosodium urate (MSU) crystal-induced inflammation in rats, an experimental model for acute gouty arthritis. Morin treatment (30mg/kg b.wt) significantly attenuated the ankle swelling and the levels of lipid peroxidation, nitric oxide, serum pro-inflammatory cytokines (tumor necrosis factor (TNF) -α, interleukin (IL)-1β, and IL-6), monocyte chemoattractant protein (MCP)-1, vascular endothelial growth factor (VEGF), prostaglandin E2 (PGE2), and articular elastase along with an increased anti-oxidant status (catalase (CAT) and superoxide dismutase (SOD)) in the joint homogenate of MSU crystal-induced rats. Histological assessment revealed that Morin limited the diffusion of joint space, synovial hyperplasia, and inflammatory cell infiltrations. The mRNA expression of NLRP3 (nucleotide oligomerization domain (NOD)-like receptor family, pyrin domain containing 3) inflammasome, caspase-1, pro-inflammatory cytokines, MCP-1, inflammatory enzymes (inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2)), and nuclear factor-kappa B (NF-κB) p65 was found downregulated and HPRT (hypo-xanthine phospho-ribosyl transferase) mRNA expression was upregulated in Morin treated MSU crystal-induced rats. In addition, Morin treatment reduced the protein expression of NF-κB p65, p-NF-κB p65, iNOS, COX-2, and TNF-α. The results clearly demonstrated that Morin exert a potent anti-inflammatory effect on MSU crystal-induced inflammation in rats.
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Morin a bioflavonoid suppresses monosodium urate crystal induced inflammatory immune response in raw 264 7 macrophages through the inhibition of inflammatory mediators intracellular ros levels and nf κb activation
PLOS ONE, 2015Co-Authors: Chitra Dhanasekar, Sowmiya Kalaiselvan, Mahaboobkhan RasoolAbstract:Our previous studies had reported that Morin, a bioflavanoid exhibited potent anti-inflammatory effect against adjuvant-induced arthritic rats. In this current study, we investigated the anti-inflammatory mechanism of Morin against monosodium urate crystal (MSU)-induced inflammation in RAW 264.7 macrophage cells, an in vitro model for acute gouty arthritis. For comparison purpose, colchicine was used as a reference drug. We have observed that Morin (100-300 μM) treatment significantly suppressed the levels of inflammatory cytokines (TNF-α, IL-1β, IL-6, MCP-1 and VEGF), inflammatory mediators (NO and PEG2), and lysosomal enzymes (acid phosphatase, β-galactosidase, N-acetyl glucosamindase and cathepsin D) in MSU-crystals stimulated macrophage cells. The mRNA expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, and MCP-1), inflammatory enzymes (iNOS and COX-2), and NF-κBp65 was found downregulated in MSU crystal stimulated macrophage cells by Morin treatment, however, the mRNA expression of hypoxanthine phospho ribosyl transferse (HPRT) was found to be increased. The flow cytometry analysis revealed that Morin treatment decreased intracellular reactive oxygen species levels in MSU crystal stimulated macrophage cells. The western blot analysis clearly showed that Morin mainly exerts its anti-inflammatory effects by inhibiting the MSU crystal-induced COX-2 and TNF-α protein expression through the inactivation of NF-κB signaling pathway in RAW 264.7 macrophage cells similar to that of BAY 11-7082 (IκB kinase inhibitor). Our results collectively suggest that Morin can be a potential therapeutic agent for inflammatory disorders like acute gouty arthritis.
Lingdong Kong - One of the best experts on this subject based on the ideXlab platform.
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fructose downregulates mir 330 to induce renal inflammatory response and insulin signaling impairment attenuation by Morin
Molecular Nutrition & Food Research, 2017Co-Authors: Lin Song, Xing Wang, Dongmei Zhang, Xiaoqin Ding, Tianyu Chen, Xiaojuan Zhao, Yanzi Yang, Ying Pan, Lingdong KongAbstract:cope Fructose induces insulin resistance with kidney inflammation and injury. MicroRNAs are emerged as key regulators of insulin signaling. Morin has insulin-mimetic effect with the improvement of insulin resistance and kidney injury. This study investigated the protective mechanisms of Morin against fructose-induced kidney injury, with particular focus on miR-330 expression change, inflammatory response, and insulin signaling impairment. Methods and results miR-330, sphingosine kinase 1 (SphK1)/sphingosine-1-phosphate (S1P)/S1P receptor (S1PR)1/3 signaling, nuclear factor-κB (NF-κB)/NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome, and insulin signaling were detected in kidney cortex of fructose-fed rats and fructose-exposed HK-2 cells, respectively. Whether miR-330 mediated inflammatory response to affect insulin signaling was examined using SphK1 inhibitor, S1PR1/3 short interfering RNA, or miR-330 mimic/inhibitor, respectively. Fructose was found to downregulate miR-330 expression to increase SphK1/S1P/S1PR1/3 signaling, and then activate NF-κB/NLRP3 inflammasome to produce IL-1β, causing insulin signaling impairment. Moreover, Morin upregulated miR-330 and partly attenuated inflammatory response and insulin signaling impairment to alleviate kidney injury. Conclusion These findings suggest that Morin protects against fructose-induced kidney insulin signaling impairment by upregulating miR-330 to reduce inflammatory response. Morin may be a potential therapeutic agent for the treatment of kidney injury associated with fructose-induced inflammation and insulin signaling impairment.
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Morin Improves Urate Excretion and Kidney Function through Regulation of Renal Organic Ion Transporters in Hyperuricemic Mice
2016Co-Authors: Cai-ping Wang, Xing Wang, Xian Zhang, Yun-wei Shi, Lei Liu, Lingdong KongAbstract:effects on hyperuricemia and renal dysfunction in animals. Since the decreased renal excretion of uric acid is the hallmark of hyperuricemia, here we studied the effects of oral Morin administration on renal organic ion transporters in potassium oxonate-induced hyperuricemic mice. Methods. Hyperuricemia in mice was induced by potassium oxonate. Uric acid and creatinine concentrations in urine and serum, and fractional excretion of uric acid (FEUA) were performed to evaluate renal urate handling. Changes in expression levels of renal organic ion transporters were detected by Western blotting and semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) methods. Results. Morin treatment significantly increased urinary uric acid/creatinine ratio and FEUA, resulting in reduction of serum uric acid levels in hyperuricemic mice. And kidney conditions were also improved after Morin treatment in this model. Protein and mRNA levels of glucose transporter 9 (mGLUT9) and urate transporter 1 (mURAT1) were significantly decreased, and of organic anion transporter 1 (mOAT1) were remarkably increased in the kidney of Morin-treated hyperuricemic mice. Morin treatment also blocked down-regulations of renal organic cation and carnitine transporters (mOCT1, mOCT2, mOCTN1 and mOCTN2) in hyperuricemic mice. Conclusion. These results suggest that Morin exhibits the uricosuric effects via suppressing urate reabsorption and promoting urate secretion in the kidney of hyperuricemic mice and may help to attenuate deleterious effects of hyperuricemia with renal dysfunction
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Morin reduces hepatic inflammation associated lipid accumulation in high fructose fed rats via inhibiting sphingosine kinase 1 sphingosine 1 phosphate signaling pathway
Biochemical Pharmacology, 2013Co-Authors: Xing Wang, Yun-wei Shi, Dongmei Zhang, Xiaoqin Ding, Chenyu Fan, Qin Zhu, Ye Hong, Lingdong KongAbstract:Abstract SphK1/S1P signaling pathway is involved in the development of hepatic inflammation and injury. But its role in high fructose-induced NAFLD has not yet been reported. The aim of this study was to elucidate the crucial role of SphK1/S1P signaling pathway in high fructose-induced hepatic inflammation and lipid accumulation in rats. Moreover, the hepatoprotective effects of Morin, a flavonoid with anti-inflammatory and anti-hyperlipedimic activities, on these hepatic changes in rats were investigated. High fructose-fed rats were orally treated with Morin (30 and 60 mg/kg) and pioglitazone (4 mg/kg) for 8 weeks, respectively. Fructose feeding induced hyperlipidemia, and activated SphK1/S1P signaling pathway characterized by the elevation of SphK1 activity, S1P production as well as SphK1, S1PR1 and S1PR3 protein levels, which in turn caused NF-κB signaling activation to produce IL-1β, IL-6 and TNF-α and inflammation in the liver of rats. Subsequently, hepatic insulin and leptin signaling impairment and lipid metabolic disorder were observed in this animal model, resulting in liver lipid accumulation. Morin restored high fructose-induced the activation of hepatic SphK1/S1P signaling pathway in rats. Subsequently, the reduced NF-κB signaling activation by Morin decreased inflammatory cytokine production, recovered insulin and leptin signaling impairment to reduce lipid accumulation and injury in the rat liver. These effects of Morin were confirmed in Buffalo rat liver (BRL3A) cell model stimulated with 5 mM fructose. Thus, the inhibition of hepatic SphK1/S1P signaling pathway may be a novel mechanism by which Morin exerts hepatoprotection in high fructose-fed rats, possibly involving liver inflammation inhibition and lipid accumulation recovery.
Bharat B Aggarwal - One of the best experts on this subject based on the ideXlab platform.
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Morin inhibits stat3 tyrosine 705 phosphorylation in tumor cells through activation of protein tyrosine phosphatase shp1
Biochemical Pharmacology, 2013Co-Authors: Subash C Gupta, Kanokkarn Phromnoi, Bharat B AggarwalAbstract:The major goal of cancer drug discovery is to find an agent that is safe and affordable, yet effective against cancer. Here we show that Morin (3,5,7,2',4'-pentahydroxyflavone) has potential against cancer cells through suppression of the signal transducer and activator of transcription 3 (STAT3) pathway, which is closely linked to the transformation, survival, proliferation, and metastasis of cancer. We found that Morin completely suppressed inducible and constitutively activated STAT3 and blocked the nuclear translocation of STAT3 and its DNA binding in multiple myeloma and head and neck squamous carcinoma cells. Morin inhibited activated Src, JAK-1, and JAK-2, all of which are linked to STAT3 activation, while up-regulating a protein inhibitor of activated STAT3, PIAS3. Pervanadate reversed the effects of Morin on STAT3 phosphorylation, indicating the role of a protein tyrosine phosphatase. Furthermore, Morin induced SHP1 expression at both the mRNA and protein levels, and silencing of SHP1 abrogated the effect of Morin on STAT3 phosphorylation, indicating that Morin mediates its effects on STAT3 through SHP1. Suppression of STAT3 correlated with the down-regulation of various gene products linked to tumor survival, proliferation, and angiogenesis and led to sensitization of tumor cells to thalidomide and bortezomib. Comparing the activities of Morin with those of four structurally related flavonols demonstrated the importance of hydroxyl groups in the B ring in inhibiting STAT3 activation. These findings suggest that Morin suppresses the STAT3 pathway, leading to the down-regulation of STAT3-dependent gene expression and chemosensitization of tumor cells.
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Morin 3 5 7 2 4 pentahydroxyflavone abolishes nuclear factor κb activation induced by various carcinogens and inflammatory stimuli leading to suppression of nuclear factor κb regulated gene expression and up regulation of apoptosis
Clinical Cancer Research, 2007Co-Authors: Sunil K Manna, Bharat B Aggarwal, Rishi S Aggarwal, Gautam Sethi, Govindarajan T RameshAbstract:Purpose: Morin is a flavone that exhibits antiproliferative, antitumor, and anti-inflammatory effects through a mechanism that is not well understood. Because of the role of transcription factor nuclear factor-κB (NF-κB) in the control of cell survival, proliferation, tumorigenesis, and inflammation, we postulated that Morin mediates its effects by modulating NF-κB activation. Experimental Design: We investigated the effect of Morin on NF-κB pathway activated by inflammatory agents, carcinogens, and tumor promoters. The effect of this flavone on expression of NF-κB–regulated gene products involved in cell survival, proliferation, and invasion was also examined. Results: We showed by DNA-binding assay that NF-κB activation induced by tumor necrosis factor (TNF), phorbol 12-myristate 13-acetate, lipopolysaccharide, ceramide, interleukin-1, and H 2 O 2 was suppressed by Morin; the suppression was not cell type specific. The suppression of NF-κB by Morin was mediated through inhibition of IκBα (inhibitory subunit of NF-κB) kinase, leading to suppression of phosphorylation and degradation of IκBα and consequent p65 nuclear translocation. Morin also inhibited the NF-κB–dependent reporter gene expression activated by TNF, TNF receptor (TNFR) 1, TNFR1-associated death domain, TNFR-associated factor 2, NF-κB–inducing kinase, IκB kinase, and the p65 subunit of NF-κB. NF-κB–regulated gene products involved in cell survival [inhibitor of apoptosis (IAP) 1, IAP2, X chromosome-linked IAP, Bcl-xL, and survivin], proliferation (cyclin D1 and cyclooxygenase-2), and invasion (matrix metalloproteinase-9) were down-regulated by Morin. These effects correlated with enhancement of apoptosis induced by TNF and chemotherapeutic agents. Conclusion: Overall, our results indicate that Morin suppresses the activation of NF-κB and NF-κB–regulated gene expression, leading to enhancement of apoptosis. This may provide the molecular basis for the ability of Morin to act as an anticancer and anti-inflammatory agent.
Xiaojuan Tian - One of the best experts on this subject based on the ideXlab platform.
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the efflux of flavonoids Morin isorhamnetin 3 o rutinoside and diosmetin 7 o β d xylopyranosyl 1 6 β d glucopyranoside in the human intestinal cell line caco 2
Pharmaceutical Research, 2006Co-Authors: Xiaojuan Tian, Xiaoda Yang, Kui Wang, Xiuwei YangAbstract:PURPOSE In this study, we chose three of the flavonoids isorhamnetin-3-O-rutinoside(IRR) diosmetin-7-O-beta-D-xylopyranosyl-(1-6)-beta-D-glucopyranoside(DXG) and Morin, which showed obvious efflux, to test the hypothesis that a specific efflux transporter is responsible for their transportation. METHODS The intestinal epithelial membrane transport of the flavonoids were examined using the monolayer of the human Caco-2 cell line grown in Transwells, a common model of intestinal absorption. The flavonoids were measured by high performance liquid chromatography with UV detector. RESULT The efflux of Morin, IRR and DXG, across Caco-2 cell monolayers was examined over the concentration range from 2 to 200 microM and showed a saturable process. The depletion of the cellular ATP stores with 5 mM iodoacetamide led to a significant inhibition of the efflux. Fifty micromolar verapamil, a chemical inhibitor of P-glycoprotein, had no effect on the transport of the three flavonoids, while the presence of 50 microM MK-571 and 1 mM probenecid, MRP inhibitors, resulted in an obvious reduction in the efflux. Moreover, inhibition of Morin transport by MK-571 demonstrated concentration dependence. The transportation of the three flavonoids was compared with apigenin. CONCLUSION These data support a role for MRPs in the intestinal transcellular efflux of Morin, IRR, DXG and possibly other hydrophilic flavonoid aglycons and glycosides.
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the efflux of flavonoids Morin isorhamnetin 3 o rutinoside and diosmetin 7 o β d xylopyranosyl 1 6 β d glucopyranoside in the human intestinal cell line caco 2
Pharmaceutical Research, 2006Co-Authors: Xiaojuan Tian, Xiaoda Yang, Kui Wang, Xiuwei YangAbstract:In this study, we chose three of the flavonoids isorhamnetin-3-O-rutinoside(IRR) diosmetin-7-O-β-d-xylopyranosyl-(1-6)-β-d-glucopyranoside(DXG) and Morin, which showed obvious efflux, to test the hypothesis that a specific efflux transporter is responsible for their transportation. The intestinal epithelial membrane transport of the flavonoids were examined using the monolayer of the human Caco-2 cell line grown in Transwells, a common model of intestinal absorption. The flavonoids were measured by high performance liquid chromatography with UV detector. The efflux of Morin, IRR and DXG, across Caco-2 cell monolayers was examined over the concentration range from 2 to 200 μM and showed a saturable process. The depletion of the cellular ATP stores with 5 mM iodoacetamide led to a significant inhibition of the efflux. Fifty micromolar verapamil, a chemical inhibitor of P-glycoprotein, had no effect on the transport of the three flavonoids, while the presence of 50 μM MK-571 and 1 mM probenecid, MRP inhibitors, resulted in an obvious reduction in the efflux. Moreover, inhibition of Morin transport by MK-571 demonstrated concentration dependence. The transportation of the three flavonoids was compared with apigenin. These data support a role for MRPs in the intestinal transcellular efflux of Morin, IRR, DXG and possibly other hydrophilic flavonoid aglycons and glycosides.