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Yao Zhang - One of the best experts on this subject based on the ideXlab platform.
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Inhibition of ROS-mediated activation Src-MAPK/AKT signaling by Orientin alleviates H 2 O 2-induced apoptosis in PC12 cells
Drug design development and therapy, 2018Co-Authors: Zunyong Feng, Yao ZhangAbstract:Purpose Reactive oxygen species (ROS) are considered a direct cause of neurodegenerative diseases (NDDs). Drugs developed to target ROS are effective for the treatment of NDDs. Orientin is a pyrone glucoside extracted from Polygonum orientale, and it exhibits many pharmacological activities. In this study, we aimed to determine whether Orientin could relieve hydrogen peroxide (H2O2)-induced neuronal apoptosis and to investigate the specific target of Orientin. Materials and methods In this study, the neuroprotective effect and its possible mechanisms of Orientin in mouse pheochromocytoma cell line (PC12) cells stimulated by H2O2, establishing an oxidative stress model, were investigated. And we further tested the role of ROS in the neuroprotective effects of Orientin. Results Orientin (5-100 µg/mL) did not cause toxicity in PC12 cells but significantly decreased H2O2-induced reduction in PC12 cell viability, cell apoptosis rates, and nuclear condensation. It also inhibited the activation of caspase-3 and degradation of poly(ADP-ribose) polymerase (PARP). Under the stimulation of H2O2, MAPKs (ERK, JNK, and p38), AKT, and Src signaling proteins in PC12 cells were activated in a time-dependent manner. The application of inhibitors that were specific for MAPKs, AKT, and Src effectively alleviated H2O2-induced cell apoptosis. In addition, the Src inhibitor decreased the activation of MAPKs and AKT signaling. More importantly, Orientin effectively decreased H2O2-induced phosphorylation of MAPKs, AKT, and Src signaling proteins. Finally, we confirmed that Orientin effectively inhibited H2O2-induced accumulation of ROS in cells. In addition, ROS inhibitors blocked the Src-MAPKs/AKT signaling pathway-dependent cell apoptosis stimulated by H2O2. Conclusion These results indicate that alleviation of H2O2-induced cell apoptosis by Orientin is Src-MAPKs/AKT dependent. Overall, our study confirms that Orientin alleviates H2O2-induced cell apoptosis by inhibiting the ROS-mediated activation of Src-MAPKs/AKT signaling.
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inhibition of ros mediated activation src mapk akt signaling by Orientin alleviates h 2 o 2 induced apoptosis in pc12 cells
Drug Design Development and Therapy, 2018Co-Authors: Zunyong Feng, Yao ZhangAbstract:Purpose Reactive oxygen species (ROS) are considered a direct cause of neurodegenerative diseases (NDDs). Drugs developed to target ROS are effective for the treatment of NDDs. Orientin is a pyrone glucoside extracted from Polygonum orientale, and it exhibits many pharmacological activities. In this study, we aimed to determine whether Orientin could relieve hydrogen peroxide (H2O2)-induced neuronal apoptosis and to investigate the specific target of Orientin. Materials and methods In this study, the neuroprotective effect and its possible mechanisms of Orientin in mouse pheochromocytoma cell line (PC12) cells stimulated by H2O2, establishing an oxidative stress model, were investigated. And we further tested the role of ROS in the neuroprotective effects of Orientin. Results Orientin (5-100 µg/mL) did not cause toxicity in PC12 cells but significantly decreased H2O2-induced reduction in PC12 cell viability, cell apoptosis rates, and nuclear condensation. It also inhibited the activation of caspase-3 and degradation of poly(ADP-ribose) polymerase (PARP). Under the stimulation of H2O2, MAPKs (ERK, JNK, and p38), AKT, and Src signaling proteins in PC12 cells were activated in a time-dependent manner. The application of inhibitors that were specific for MAPKs, AKT, and Src effectively alleviated H2O2-induced cell apoptosis. In addition, the Src inhibitor decreased the activation of MAPKs and AKT signaling. More importantly, Orientin effectively decreased H2O2-induced phosphorylation of MAPKs, AKT, and Src signaling proteins. Finally, we confirmed that Orientin effectively inhibited H2O2-induced accumulation of ROS in cells. In addition, ROS inhibitors blocked the Src-MAPKs/AKT signaling pathway-dependent cell apoptosis stimulated by H2O2. Conclusion These results indicate that alleviation of H2O2-induced cell apoptosis by Orientin is Src-MAPKs/AKT dependent. Overall, our study confirms that Orientin alleviates H2O2-induced cell apoptosis by inhibiting the ROS-mediated activation of Src-MAPKs/AKT signaling.
Do-young Yoon - One of the best experts on this subject based on the ideXlab platform.
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Orientin inhibits invasion by suppressing mmp 9 and il 8 expression via the pkcα erk ap 1 stat3 mediated signaling pathways in tpa treated mcf 7 breast cancer cells
Phytomedicine, 2018Co-Authors: Soo Jin Kim, Thu-huyen Pham, Yesol Bak, Hyung-won Ryu, Do-young YoonAbstract:Abstract Background Orientin (luteolin 8-C-β-D-glucopyranoside), a glycosyl dietary flavonoid, has therapeutic effects such as anti-inflammation and antiadipogenesis. However, there is little known about the antimigratory and anti-invasive effects of Orientin. Thus, we demonstrate the anti-invasive effects of Orientin compared with well-known anticancer flavonoid, luteolin and luteolin 8-C-β-fucopyranoside (LU8C-FP). Purpose We investigated whether Orientin would inhibit the migration and invasion of 12-O-tetradecanoyl phorbol-13-acetate (TPA) induced MCF-7 breast cancer cells. Methods We investigated the anti-invasive mechanism of Orientin by using wound-healing assay, Matrigel invasion assay, gelatin zymography, qRT-PCR, ELISA, western blotting, nuclear, membrane and cytosolic fractionations, and immunofluorescence staining in MCF-7 cell line. Results We demonstrated the antimigratory and anti-invasive effects of Orientin in TPA-treated MCF-7 cells. TPA-induced membrane translocation of protein kinase C alpha (PKCα), phosphorylation of extracellular signal regulated kinase (ERK), and nuclear translocations of activator protein-1 (AP-1) and signal transducer and activator of transcription 3 (STAT3) were downregulated by Orientin. In addition, Orientin also inhibited matrix metalloproteinase-9 (MMP-9) and interleukin-8 (IL-8) expression. Conclusion Orientin inhibits migratory and invasive responses by suppressing MMP-9 and IL-8 expression through mitigation of TPA-induced PKCα and ERK activation, as well as the nuclear translocation of AP-1 and STAT3. Therefore, Orientin prevents tumor invasion and could be applied as a possible therapeutic agent for the treatment of cancer metastasis.
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Orientin inhibits invasion by suppressing MMP-9 and IL-8 expression via the PKCα/ ERK/AP-1/STAT3-mediated signaling pathways in TPA-treated MCF-7 breast cancer cells
Phytomedicine : international journal of phytotherapy and phytopharmacology, 2018Co-Authors: Soo Jin Kim, Thu-huyen Pham, Yesol Bak, Hyung-won Ryu, Do-young YoonAbstract:Abstract Background Orientin (luteolin 8-C-β-D-glucopyranoside), a glycosyl dietary flavonoid, has therapeutic effects such as anti-inflammation and antiadipogenesis. However, there is little known about the antimigratory and anti-invasive effects of Orientin. Thus, we demonstrate the anti-invasive effects of Orientin compared with well-known anticancer flavonoid, luteolin and luteolin 8-C-β-fucopyranoside (LU8C-FP). Purpose We investigated whether Orientin would inhibit the migration and invasion of 12-O-tetradecanoyl phorbol-13-acetate (TPA) induced MCF-7 breast cancer cells. Methods We investigated the anti-invasive mechanism of Orientin by using wound-healing assay, Matrigel invasion assay, gelatin zymography, qRT-PCR, ELISA, western blotting, nuclear, membrane and cytosolic fractionations, and immunofluorescence staining in MCF-7 cell line. Results We demonstrated the antimigratory and anti-invasive effects of Orientin in TPA-treated MCF-7 cells. TPA-induced membrane translocation of protein kinase C alpha (PKCα), phosphorylation of extracellular signal regulated kinase (ERK), and nuclear translocations of activator protein-1 (AP-1) and signal transducer and activator of transcription 3 (STAT3) were downregulated by Orientin. In addition, Orientin also inhibited matrix metalloproteinase-9 (MMP-9) and interleukin-8 (IL-8) expression. Conclusion Orientin inhibits migratory and invasive responses by suppressing MMP-9 and IL-8 expression through mitigation of TPA-induced PKCα and ERK activation, as well as the nuclear translocation of AP-1 and STAT3. Therefore, Orientin prevents tumor invasion and could be applied as a possible therapeutic agent for the treatment of cancer metastasis.
Zunyong Feng - One of the best experts on this subject based on the ideXlab platform.
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Inhibition of ROS-mediated activation Src-MAPK/AKT signaling by Orientin alleviates H 2 O 2-induced apoptosis in PC12 cells
Drug design development and therapy, 2018Co-Authors: Zunyong Feng, Yao ZhangAbstract:Purpose Reactive oxygen species (ROS) are considered a direct cause of neurodegenerative diseases (NDDs). Drugs developed to target ROS are effective for the treatment of NDDs. Orientin is a pyrone glucoside extracted from Polygonum orientale, and it exhibits many pharmacological activities. In this study, we aimed to determine whether Orientin could relieve hydrogen peroxide (H2O2)-induced neuronal apoptosis and to investigate the specific target of Orientin. Materials and methods In this study, the neuroprotective effect and its possible mechanisms of Orientin in mouse pheochromocytoma cell line (PC12) cells stimulated by H2O2, establishing an oxidative stress model, were investigated. And we further tested the role of ROS in the neuroprotective effects of Orientin. Results Orientin (5-100 µg/mL) did not cause toxicity in PC12 cells but significantly decreased H2O2-induced reduction in PC12 cell viability, cell apoptosis rates, and nuclear condensation. It also inhibited the activation of caspase-3 and degradation of poly(ADP-ribose) polymerase (PARP). Under the stimulation of H2O2, MAPKs (ERK, JNK, and p38), AKT, and Src signaling proteins in PC12 cells were activated in a time-dependent manner. The application of inhibitors that were specific for MAPKs, AKT, and Src effectively alleviated H2O2-induced cell apoptosis. In addition, the Src inhibitor decreased the activation of MAPKs and AKT signaling. More importantly, Orientin effectively decreased H2O2-induced phosphorylation of MAPKs, AKT, and Src signaling proteins. Finally, we confirmed that Orientin effectively inhibited H2O2-induced accumulation of ROS in cells. In addition, ROS inhibitors blocked the Src-MAPKs/AKT signaling pathway-dependent cell apoptosis stimulated by H2O2. Conclusion These results indicate that alleviation of H2O2-induced cell apoptosis by Orientin is Src-MAPKs/AKT dependent. Overall, our study confirms that Orientin alleviates H2O2-induced cell apoptosis by inhibiting the ROS-mediated activation of Src-MAPKs/AKT signaling.
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inhibition of ros mediated activation src mapk akt signaling by Orientin alleviates h 2 o 2 induced apoptosis in pc12 cells
Drug Design Development and Therapy, 2018Co-Authors: Zunyong Feng, Yao ZhangAbstract:Purpose Reactive oxygen species (ROS) are considered a direct cause of neurodegenerative diseases (NDDs). Drugs developed to target ROS are effective for the treatment of NDDs. Orientin is a pyrone glucoside extracted from Polygonum orientale, and it exhibits many pharmacological activities. In this study, we aimed to determine whether Orientin could relieve hydrogen peroxide (H2O2)-induced neuronal apoptosis and to investigate the specific target of Orientin. Materials and methods In this study, the neuroprotective effect and its possible mechanisms of Orientin in mouse pheochromocytoma cell line (PC12) cells stimulated by H2O2, establishing an oxidative stress model, were investigated. And we further tested the role of ROS in the neuroprotective effects of Orientin. Results Orientin (5-100 µg/mL) did not cause toxicity in PC12 cells but significantly decreased H2O2-induced reduction in PC12 cell viability, cell apoptosis rates, and nuclear condensation. It also inhibited the activation of caspase-3 and degradation of poly(ADP-ribose) polymerase (PARP). Under the stimulation of H2O2, MAPKs (ERK, JNK, and p38), AKT, and Src signaling proteins in PC12 cells were activated in a time-dependent manner. The application of inhibitors that were specific for MAPKs, AKT, and Src effectively alleviated H2O2-induced cell apoptosis. In addition, the Src inhibitor decreased the activation of MAPKs and AKT signaling. More importantly, Orientin effectively decreased H2O2-induced phosphorylation of MAPKs, AKT, and Src signaling proteins. Finally, we confirmed that Orientin effectively inhibited H2O2-induced accumulation of ROS in cells. In addition, ROS inhibitors blocked the Src-MAPKs/AKT signaling pathway-dependent cell apoptosis stimulated by H2O2. Conclusion These results indicate that alleviation of H2O2-induced cell apoptosis by Orientin is Src-MAPKs/AKT dependent. Overall, our study confirms that Orientin alleviates H2O2-induced cell apoptosis by inhibiting the ROS-mediated activation of Src-MAPKs/AKT signaling.
Soo Jin Kim - One of the best experts on this subject based on the ideXlab platform.
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Orientin inhibits invasion by suppressing mmp 9 and il 8 expression via the pkcα erk ap 1 stat3 mediated signaling pathways in tpa treated mcf 7 breast cancer cells
Phytomedicine, 2018Co-Authors: Soo Jin Kim, Thu-huyen Pham, Yesol Bak, Hyung-won Ryu, Do-young YoonAbstract:Abstract Background Orientin (luteolin 8-C-β-D-glucopyranoside), a glycosyl dietary flavonoid, has therapeutic effects such as anti-inflammation and antiadipogenesis. However, there is little known about the antimigratory and anti-invasive effects of Orientin. Thus, we demonstrate the anti-invasive effects of Orientin compared with well-known anticancer flavonoid, luteolin and luteolin 8-C-β-fucopyranoside (LU8C-FP). Purpose We investigated whether Orientin would inhibit the migration and invasion of 12-O-tetradecanoyl phorbol-13-acetate (TPA) induced MCF-7 breast cancer cells. Methods We investigated the anti-invasive mechanism of Orientin by using wound-healing assay, Matrigel invasion assay, gelatin zymography, qRT-PCR, ELISA, western blotting, nuclear, membrane and cytosolic fractionations, and immunofluorescence staining in MCF-7 cell line. Results We demonstrated the antimigratory and anti-invasive effects of Orientin in TPA-treated MCF-7 cells. TPA-induced membrane translocation of protein kinase C alpha (PKCα), phosphorylation of extracellular signal regulated kinase (ERK), and nuclear translocations of activator protein-1 (AP-1) and signal transducer and activator of transcription 3 (STAT3) were downregulated by Orientin. In addition, Orientin also inhibited matrix metalloproteinase-9 (MMP-9) and interleukin-8 (IL-8) expression. Conclusion Orientin inhibits migratory and invasive responses by suppressing MMP-9 and IL-8 expression through mitigation of TPA-induced PKCα and ERK activation, as well as the nuclear translocation of AP-1 and STAT3. Therefore, Orientin prevents tumor invasion and could be applied as a possible therapeutic agent for the treatment of cancer metastasis.
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Orientin inhibits invasion by suppressing MMP-9 and IL-8 expression via the PKCα/ ERK/AP-1/STAT3-mediated signaling pathways in TPA-treated MCF-7 breast cancer cells
Phytomedicine : international journal of phytotherapy and phytopharmacology, 2018Co-Authors: Soo Jin Kim, Thu-huyen Pham, Yesol Bak, Hyung-won Ryu, Do-young YoonAbstract:Abstract Background Orientin (luteolin 8-C-β-D-glucopyranoside), a glycosyl dietary flavonoid, has therapeutic effects such as anti-inflammation and antiadipogenesis. However, there is little known about the antimigratory and anti-invasive effects of Orientin. Thus, we demonstrate the anti-invasive effects of Orientin compared with well-known anticancer flavonoid, luteolin and luteolin 8-C-β-fucopyranoside (LU8C-FP). Purpose We investigated whether Orientin would inhibit the migration and invasion of 12-O-tetradecanoyl phorbol-13-acetate (TPA) induced MCF-7 breast cancer cells. Methods We investigated the anti-invasive mechanism of Orientin by using wound-healing assay, Matrigel invasion assay, gelatin zymography, qRT-PCR, ELISA, western blotting, nuclear, membrane and cytosolic fractionations, and immunofluorescence staining in MCF-7 cell line. Results We demonstrated the antimigratory and anti-invasive effects of Orientin in TPA-treated MCF-7 cells. TPA-induced membrane translocation of protein kinase C alpha (PKCα), phosphorylation of extracellular signal regulated kinase (ERK), and nuclear translocations of activator protein-1 (AP-1) and signal transducer and activator of transcription 3 (STAT3) were downregulated by Orientin. In addition, Orientin also inhibited matrix metalloproteinase-9 (MMP-9) and interleukin-8 (IL-8) expression. Conclusion Orientin inhibits migratory and invasive responses by suppressing MMP-9 and IL-8 expression through mitigation of TPA-induced PKCα and ERK activation, as well as the nuclear translocation of AP-1 and STAT3. Therefore, Orientin prevents tumor invasion and could be applied as a possible therapeutic agent for the treatment of cancer metastasis.
Jong-sup Bae - One of the best experts on this subject based on the ideXlab platform.
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Inhibitory Effect of Orientin on Secretory Group IIA Phospholipase A2.
Inflammation, 2015Co-Authors: Jong-sup BaeAbstract:It is well known that the expression level of secretory group IIA phospholipase A2 (sPLA2-IIA) is elevated in inflammatory diseases and lipopolysaccharide (LPS) upregulates the expression of sPLA2-IIA in human umbilical vein endothelial cells (HUVECs). Orientin, a C-glycosyl flavonoid, is known to have anxiolytic, anti-oxidative, and anti-inflammatory activity. Here, Orientin was examined for its effects on the expression and activity of sPLA2-IIA in HUVECs and mouse. Prior treatment of cells or mouse with Orientin inhibited LPS-induced expression and activity of sPLA2-IIA. And Orientin suppressed the activation of cytosolic phospholipase A2 (cPLA2) and extracellular signal-regulated kinase (ERK) 1/2 by LPS. Therefore, these results suggest that Orientin may inhibit LPS-mediated expression of sPLA2-IIA by suppression of cPLA2 and ERK 1/2.
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Antithrombotic and antiplatelet activities of Orientin in vitro and in vivo
Journal of Functional Foods, 2015Co-Authors: Wonhwa Lee, Jong-sup BaeAbstract:Abstract Vaccinium bracteatum Thunb. is commonly used in staining and cooking rice. However, there are limited data regarding its active components and pharmacological effects that underlie its traditional use. Two flavonoid C -glycosyl compounds (Orientin and isoOrientin) found in V. bracteatum Thunb. are known for their antioxidant activity. Here, the anticoagulant activity of Orientin and isoOrientin was examined by monitoring the activated partial thromboplastin time (aPTT), prothrombin time (PT), and the thrombin and activated factor X (FXa) activity. Treatment with Orientin and isoOrientin prolonged the aPTT and PT and inhibited the thrombin and FXa activity and production in human umbilical vein endothelial cells (HUVECs). Furthermore, Orientin and isoOrientin inhibited thrombin-catalyzed fibrin polymerization and platelet aggregation. In exploring the mechanism underlying anti-platelet aggregation, we found that Orientin and isoOrientin specifically prevented protein kinase C (PKC) activation and calcium mobilization. Orientin and isoOrientin also elicited anticoagulant effects in mice. In addition, treatment with Orientin and isoOrientin significantly decreased the plasminogen activator inhibitor-1 (PAI-1) to tissue plasminogen activator (t-PA) ratio. Collectively, foods containing Orientin and isoOrientin possess antithrombotic activity and may be used in preventing thrombus formation and improving blood circulation.
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Orientin Inhibits High Glucose-Induced Vascular Inflammation In Vitro and In Vivo
Inflammation, 2014Co-Authors: Soyoung Kwak, Jong-sup BaeAbstract:Vascular inflammation plays a key role in the initiation and progression of atherosclerosis, a major complication of diabetes mellitus. Orientin, a C -glycosyl flavonoid, is known to have anxiolytic and antioxidative activity. In this study, we assessed whether Orientin can suppress vascular inflammation induced by high glucose (HG) in human umbilical vein endothelial cells (HUVECs) and mice. Our data indicate that HG markedly increased vascular permeability, monocyte adhesion, the expression of cell adhesion molecules (CAMs), the formation of reactive oxygen species (ROS), and the activation of nuclear factor kappa B (NF-κB). Remarkably, the vascular inflammatory effects of HG were attenuated by pretreatment with Orientin. Since vascular inflammation induced by HG is critical in the development of diabetic complications, our results suggest that Orientin may have significant benefits in the treatment of diabetic complications and atherosclerosis.
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Orientin Inhibits HMGB1-Induced Inflammatory Responses in HUVECs and in Murine Polymicrobial Sepsis
Inflammation, 2014Co-Authors: Hayoung Yoo, Taeho Lee, Jong-sup BaeAbstract:High mobility group box-1 (HMGB1) protein acts as a late mediator of severe vascular inflammatory conditions. Orientin has been known to have anxiolytic and antioxidative activities. However, the effect of Orientin on HMGB1-induced inflammatory response has not been studied. We assessed this question by monitoring the effects of post-treatment Orientin and its derivatives on lipopolysaccharide (LPS) and cecal ligation and puncture (CLP)-mediated release of HMGB1 and HMGB1-mediated regulation of pro-inflammatory responses in human umbilical vein endothelial cells (HUVECs) and septic mice. Post-treatment Orientin was found to suppress LPS-mediated release of HMGB1 and HMGB1-mediated cytoskeletal rearrangements. Orientin inhibited HMGB1-mediated hyperpermeability and leukocyte migration in septic mice. Orientin also induced down-regulation of CLP-induced release of HMGB1 and mortality. Collectively, these results suggest that Orientin may be regarded as a candidate therapeutic agent for treatment of vascular inflammatory diseases via inhibition of the HMGB1 signaling pathway.
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Vascular barrier protective effects of Orientin and isoOrientin in LPS-induced inflammation in vitro and in vivo.
Vascular pharmacology, 2014Co-Authors: Wonhwa Lee, Jong-sup BaeAbstract:Endothelial cell protein C receptor (EPCR) can be shed from the cell surface, and this process is mediated by tumor necrosis factor-α converting enzyme (TACE), and high levels of soluble EPCR are involved in vascular inflammation. Orientin, one of the C-glycosyl flavonoids, has been known to have anxiolytic and antioxidative activities. However, the effect of Orientin on lipopolysaccharide (LPS)-induced inflammatory response has not been studied. Here we investigated the barrier protective effects of Orientin against pro-inflammatory responses induced by LPS and the associated signaling pathways. We found that Orientin inhibited LPS-induced barrier disruption, expression of cell adhesion molecules (CAMs), and adhesion/transendothelial migration of monocytes to human endothelial cells. Orientin induced potent inhibition of phorbol-12-myristate 13-acetate (PMA) and LPS-induced EPCR shedding. Orientin also suppressed LPS-induced hyperpermeability and leukocyte migration in vivo. Furthermore, Orientin suppressed the production of tumor necrosis factor-α (TNF-α) or Interleukin (IL)-6 and the activation of nuclear factor-κB (NF-κB) or extracellular regulated kinases (ERK) 1/2 by LPS. Moreover, treatment with Orientin resulted in reduced LPS-induced lethal endotoxemia. These results suggest that Orientin protects vascular barrier integrity by inhibiting hyperpermeability, expression of CAMs, and adhesion and migration of leukocytes, thereby endorsing its usefulness as a therapy for vascular inflammatory diseases.