The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Zubaidah Haji Abdul Rahim - One of the best experts on this subject based on the ideXlab platform.
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antioxidant and Cytoprotective activities of piper betle areca catechu uncaria gambir and betel quid with and without calcium hydroxide
BMC Complementary and Alternative Medicine, 2013Co-Authors: Nordin Nur Sazwi, Thurairajah Nalina, Zubaidah Haji Abdul RahimAbstract:Betel quid chewing is a popular habit in Southeast Asia. It is believed that chewing betel quid could reduce stress, strengthen teeth and maintain oral hygiene. The aim of this study was to investigate the antioxidant and Cytoprotective activities of each of the ingredients of betel quid and compared with betel quid itself (with and without calcium hydroxide). The correlation of their Cytoprotective and antioxidant activities with phenolic content was also determined. Five samples (betel leaf, areca nut, gambir, betel quid and betel quid containing calcium hydroxide) were extracted in deionized distilled water for 12 hours at 37°C. Antioxidant activities were evaluated for radical scavenging activity using DPPH assay, ferric reducing activity using FRAP assay and lipid peroxidation inhibition activity using FTC assay. Total phenolic content (TPC) was determined using Folin-Ciocalteu procedure. Phenolic composition was analyzed using LC-MS/MS. Cytoprotective activity towards human gingival fibroblast cells was examined using MTT assay. Among the ingredients of betel quid, gambir demonstrated the highest antioxidant (DPPH - IC50 = 6.4 ± 0.8 μg/mL, FRAP - 5717.8 ± 537.6 μmol Fe(II)/mg), total phenolic content (TPC - 1142.5 ± 106.8 μg TAE/mg) and Cytoprotective (100.1 ± 4.6%) activities. Betel quid when compared with betel quid containing calcium hydroxide has higher antioxidant (DPPH - IC50 =59.4 ± 4.4 μg/mL, FRAP - 1022.2 ± 235.7 μmol Fe(II)/mg), total phenolic content (TPC - 140.0 ± 22.3 μg TAE/mg), and Cytoprotective (113.5 ± 15.9%) activities. However, all of the five samples showed good lipid peroxidation inhibition compared to vitamin E. LC-MS/MS analysis revealed the presence of quinic acid as the major compound of gambir and betel quid. A positive correlation was observed between TPC and radical scavenging (r = 0.972), reducing power (r = 0.981) and Cytoprotective activity (r = 0.682). The betel quid has higher TPC, and antioxidant and Cytoprotective activities than betel quid with calcium hydroxide. The quinic acid in betel quid may play an important role in the oral health protection.
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antioxidant and Cytoprotective activities of piper betle areca catechu uncaria gambir and betel quid with and without calcium hydroxide
BMC Complementary and Alternative Medicine, 2013Co-Authors: Nordin Nur Sazwi, Thurairajah Nalina, Zubaidah Haji Abdul RahimAbstract:Betel quid chewing is a popular habit in Southeast Asia. It is believed that chewing betel quid could reduce stress, strengthen teeth and maintain oral hygiene. The aim of this study was to investigate the antioxidant and Cytoprotective activities of each of the ingredients of betel quid and compared with betel quid itself (with and without calcium hydroxide). The correlation of their Cytoprotective and antioxidant activities with phenolic content was also determined. Five samples (betel leaf, areca nut, gambir, betel quid and betel quid containing calcium hydroxide) were extracted in deionized distilled water for 12 hours at 37°C. Antioxidant activities were evaluated for radical scavenging activity using DPPH assay, ferric reducing activity using FRAP assay and lipid peroxidation inhibition activity using FTC assay. Total phenolic content (TPC) was determined using Folin-Ciocalteu procedure. Phenolic composition was analyzed using LC-MS/MS. Cytoprotective activity towards human gingival fibroblast cells was examined using MTT assay. Among the ingredients of betel quid, gambir demonstrated the highest antioxidant (DPPH - IC50 = 6.4 ± 0.8 μg/mL, FRAP - 5717.8 ± 537.6 μmol Fe(II)/mg), total phenolic content (TPC - 1142.5 ± 106.8 μg TAE/mg) and Cytoprotective (100.1 ± 4.6%) activities. Betel quid when compared with betel quid containing calcium hydroxide has higher antioxidant (DPPH - IC50 =59.4 ± 4.4 μg/mL, FRAP - 1022.2 ± 235.7 μmol Fe(II)/mg), total phenolic content (TPC - 140.0 ± 22.3 μg TAE/mg), and Cytoprotective (113.5 ± 15.9%) activities. However, all of the five samples showed good lipid peroxidation inhibition compared to vitamin E. LC-MS/MS analysis revealed the presence of quinic acid as the major compound of gambir and betel quid. A positive correlation was observed between TPC and radical scavenging (r = 0.972), reducing power (r = 0.981) and Cytoprotective activity (r = 0.682). The betel quid has higher TPC, and antioxidant and Cytoprotective activities than betel quid with calcium hydroxide. The quinic acid in betel quid may play an important role in the oral health protection.
Laurent O Mosnier - One of the best experts on this subject based on the ideXlab platform.
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c terminal residues of activated protein c light chain contribute to its anticoagulant and Cytoprotective activities
Journal of Thrombosis and Haemostasis, 2020Co-Authors: Atsuki Yamashita, John H. Griffin, Yuqi Zhang, Michel F Sanner, Laurent O MosnierAbstract:BACKGROUND Activated protein C (APC) is an important homeostatic blood coagulation protease that conveys anticoagulant and Cytoprotective activities. Proteolytic inactivation of factors Va and VIIIa facilitated by cofactor protein S is responsible for APC's anticoagulant effects, whereas Cytoprotective effects of APC involve primarily the endothelial protein C receptor (EPCR), protease activated receptor (PAR)1 and PAR3. OBJECTIVE To date, several binding exosites in the protease domain of APC have been identified that contribute to APC's interaction with its substrates but potential contributions of the C-terminus of the light chain have not been studied in detail. METHODS Site-directed Ala-scanning mutagenesis of six positively charged residues within G142-L155 was used to characterize their contributions to APC's anticoagulant and Cytoprotective activities. RESULTS AND CONCLUSIONS K151 was involved in protein S dependent-anticoagulant activity of APC with some contribution of K150. 3D structural analysis supported that these two residues were exposed in an extended protein S binding site on one face of APC. Both K150 and K151 were important for PAR1 and PAR3 cleavage by APC, suggesting that this region may also mediate interactions with PARs. Accordingly, APC's Cytoprotective activity as determined by endothelial barrier protection was impaired by Ala substitutions of these residues. Thus, both K150 and K151 are involved in APC's anticoagulant and Cytoprotective activities. The differential contribution of K150 relative to K151 for protein S-dependent anticoagulant activity and PAR cleavage highlights that binding exosites for protein S binding and for PAR cleavage in the C-terminal region of APC's light chain overlap.
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neurotoxicity of the anticoagulant selective e149a activated protein c variant after focal ischemic stroke in mice
Blood Cells Molecules and Diseases, 2013Co-Authors: Yaoming Wang, John H. Griffin, Laurent O Mosnier, Ranjeet Kumar Sinha, Berislav V ZlokovicAbstract:Abstract Wild type (WT) activated protein C (APC) and Cytoprotective-selective APC variants such as 3K3A-APC ( 3-fold increased anticoagulant activity but defective Cytoprotective activities) to those of the Cytoprotective-selective 5A-APC variant ( P P P
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mechanisms of anticoagulant and Cytoprotective actions of the protein c pathway
Journal of Thrombosis and Haemostasis, 2013Co-Authors: Eveline A Bouwens, Fabian Stavenuiter, Laurent O MosnierAbstract:The protein C pathway provides multiple important functions to maintain a regulated balance between hemostasis and host defense systems in response to vascular and inflammatory injury. The anticoagulant protein C pathway is designed to regulate coagulation, maintain the fluidity of blood within the vasculature, and prevent thrombosis, whereas the Cytoprotective protein C pathway prevents vascular damage and stress. The Cytoprotective activities of activated protein C (APC) include anti-apoptotic activity, anti-inflammatory activity, beneficial alterations of gene expression profiles, and endothelial barrier stabilization. These Cytoprotective activities of APC, which require the endothelial protein C receptor (EPCR) and protease-activated receptor-1 (PAR1), have been a major research focus. Recent insights, such as non-canonical activation of PAR1 at Arg46 by APC and biased PAR1 signaling, provided better understanding of the molecular mechanisms by which APC elicits Cytoprotective signaling through cleavage of PAR1. The discovery and development of anticoagulant-selective and Cytoprotective-selective APC mutants provided unique opportunities for preclinical research that has been and may continue to be translated to clinical research. New mechanisms for the regulation of EPCR functionality, such as modulation of EPCR-bound lipids that affect APC's Cytoprotective activities, may provide new research directions to improve the efficacy of APC to convey its Cytoprotective activities to cells. Moreover, emerging novel functions for EPCR expand the roles of EPCR beyond mediating protein C activation and APC-induced PAR1 cleavage. These discoveries increasingly develop our understanding of the protein C pathway, which will conceivably expand its physiological implications to many areas in the future.
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Protein C anticoagulant and Cytoprotective pathways
International Journal of Hematology, 2012Co-Authors: John H. Griffin, Berislav V Zlokovic, Laurent O MosnierAbstract:Plasma protein C is a serine protease zymogen that is transformed into the active, trypsin-like protease, activated protein C (APC), which can exert multiple activities. For its anticoagulant action, APC causes inactivation of the procoagulant cofactors, factors Va and VIIIa, by limited proteolysis, and APC’s anticoagulant activity is promoted by protein S, various lipids, high-density lipoprotein, and factor V. Hereditary heterozygous deficiency of protein C or protein S is linked to moderately increased risk for venous thrombosis, while a severe or total deficiency of either protein is linked to neonatal purpura fulminans. In recent years, the beneficial direct effects of APC on cells which are mediated by several specific receptors have become the focus of much attention. APC-induced signaling can promote multiple Cytoprotective actions which can minimize injuries in various preclinical animal injury models. Remarkably, pharmacologic therapy using APC demonstrates substantial neuroprotective effects in various murine injury models, including ischemic stroke. This review summarizes the molecules that are central to the protein C pathways, the relationship of pathway deficiencies to venous thrombosis risk, and mechanisms for the beneficial effects of APC.
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activated protein c mutant with minimal anticoagulant activity normal Cytoprotective activity and preservation of thrombin activable fibrinolysis inhibitor dependent Cytoprotective functions
Journal of Biological Chemistry, 2007Co-Authors: Laurent O Mosnier, Xia V Yang, John H. GriffinAbstract:Abstract Activated protein C (APC) reduces mortality in severe sepsis patients and exhibits beneficial effects in multiple animal injury models. APC anticoagulant activity involves inactivation of factors Va and VIIIa, whereas APC Cytoprotective activities involve the endothelial protein C receptor and protease-activated receptor-1 (PAR-1). The relative importance of the anticoagulant activity of APC versus the direct Cytoprotective effects of APC on cells for the in vivo benefits is unclear. To distinguish Cytoprotective from the anticoagulant activities of APC, a protease domain mutant, 5A-APC (RR229/230AA and KKK191-193AAA), was made and compared with recombinant wild-type (rwt)-APC. This mutant had minimal anticoagulant activity but normal Cytoprotective activities that were dependent on endothelial protein C receptor and protease-activated receptor-1. Whereas anticoagulantly active rwt-APC inhibited secondary-extended thrombin generation and concomitant thrombin-dependent activation of thrombin activable fibrinolysis inhibitor (TAFI) in plasma, secondary-extended thrombin generation and the activation of TAFI were essentially unopposed by 5A-APC due to its low anticoagulant activity. Compared with rwt-APC, 5A-APC had minimal profibrinolytic activity and preserved TAFI-mediated anti-inflammatory carboxypeptidase activities toward bradykinin and presumably toward the anaphlatoxins, C3a and C5a, which are well known pathological mediators in sepsis. Thus, genetic engineering can selectively alter the multiple activities of APC and provide APC mutants that retain the beneficial Cytoprotective effects of APC while diminishing bleeding risk due to reduction in APC's anticoagulant and APC-dependent profibrinolytic activities.
Nordin Nur Sazwi - One of the best experts on this subject based on the ideXlab platform.
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antioxidant and Cytoprotective activities of piper betle areca catechu uncaria gambir and betel quid with and without calcium hydroxide
BMC Complementary and Alternative Medicine, 2013Co-Authors: Nordin Nur Sazwi, Thurairajah Nalina, Zubaidah Haji Abdul RahimAbstract:Betel quid chewing is a popular habit in Southeast Asia. It is believed that chewing betel quid could reduce stress, strengthen teeth and maintain oral hygiene. The aim of this study was to investigate the antioxidant and Cytoprotective activities of each of the ingredients of betel quid and compared with betel quid itself (with and without calcium hydroxide). The correlation of their Cytoprotective and antioxidant activities with phenolic content was also determined. Five samples (betel leaf, areca nut, gambir, betel quid and betel quid containing calcium hydroxide) were extracted in deionized distilled water for 12 hours at 37°C. Antioxidant activities were evaluated for radical scavenging activity using DPPH assay, ferric reducing activity using FRAP assay and lipid peroxidation inhibition activity using FTC assay. Total phenolic content (TPC) was determined using Folin-Ciocalteu procedure. Phenolic composition was analyzed using LC-MS/MS. Cytoprotective activity towards human gingival fibroblast cells was examined using MTT assay. Among the ingredients of betel quid, gambir demonstrated the highest antioxidant (DPPH - IC50 = 6.4 ± 0.8 μg/mL, FRAP - 5717.8 ± 537.6 μmol Fe(II)/mg), total phenolic content (TPC - 1142.5 ± 106.8 μg TAE/mg) and Cytoprotective (100.1 ± 4.6%) activities. Betel quid when compared with betel quid containing calcium hydroxide has higher antioxidant (DPPH - IC50 =59.4 ± 4.4 μg/mL, FRAP - 1022.2 ± 235.7 μmol Fe(II)/mg), total phenolic content (TPC - 140.0 ± 22.3 μg TAE/mg), and Cytoprotective (113.5 ± 15.9%) activities. However, all of the five samples showed good lipid peroxidation inhibition compared to vitamin E. LC-MS/MS analysis revealed the presence of quinic acid as the major compound of gambir and betel quid. A positive correlation was observed between TPC and radical scavenging (r = 0.972), reducing power (r = 0.981) and Cytoprotective activity (r = 0.682). The betel quid has higher TPC, and antioxidant and Cytoprotective activities than betel quid with calcium hydroxide. The quinic acid in betel quid may play an important role in the oral health protection.
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antioxidant and Cytoprotective activities of piper betle areca catechu uncaria gambir and betel quid with and without calcium hydroxide
BMC Complementary and Alternative Medicine, 2013Co-Authors: Nordin Nur Sazwi, Thurairajah Nalina, Zubaidah Haji Abdul RahimAbstract:Betel quid chewing is a popular habit in Southeast Asia. It is believed that chewing betel quid could reduce stress, strengthen teeth and maintain oral hygiene. The aim of this study was to investigate the antioxidant and Cytoprotective activities of each of the ingredients of betel quid and compared with betel quid itself (with and without calcium hydroxide). The correlation of their Cytoprotective and antioxidant activities with phenolic content was also determined. Five samples (betel leaf, areca nut, gambir, betel quid and betel quid containing calcium hydroxide) were extracted in deionized distilled water for 12 hours at 37°C. Antioxidant activities were evaluated for radical scavenging activity using DPPH assay, ferric reducing activity using FRAP assay and lipid peroxidation inhibition activity using FTC assay. Total phenolic content (TPC) was determined using Folin-Ciocalteu procedure. Phenolic composition was analyzed using LC-MS/MS. Cytoprotective activity towards human gingival fibroblast cells was examined using MTT assay. Among the ingredients of betel quid, gambir demonstrated the highest antioxidant (DPPH - IC50 = 6.4 ± 0.8 μg/mL, FRAP - 5717.8 ± 537.6 μmol Fe(II)/mg), total phenolic content (TPC - 1142.5 ± 106.8 μg TAE/mg) and Cytoprotective (100.1 ± 4.6%) activities. Betel quid when compared with betel quid containing calcium hydroxide has higher antioxidant (DPPH - IC50 =59.4 ± 4.4 μg/mL, FRAP - 1022.2 ± 235.7 μmol Fe(II)/mg), total phenolic content (TPC - 140.0 ± 22.3 μg TAE/mg), and Cytoprotective (113.5 ± 15.9%) activities. However, all of the five samples showed good lipid peroxidation inhibition compared to vitamin E. LC-MS/MS analysis revealed the presence of quinic acid as the major compound of gambir and betel quid. A positive correlation was observed between TPC and radical scavenging (r = 0.972), reducing power (r = 0.981) and Cytoprotective activity (r = 0.682). The betel quid has higher TPC, and antioxidant and Cytoprotective activities than betel quid with calcium hydroxide. The quinic acid in betel quid may play an important role in the oral health protection.
John H. Griffin - One of the best experts on this subject based on the ideXlab platform.
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c terminal residues of activated protein c light chain contribute to its anticoagulant and Cytoprotective activities
Journal of Thrombosis and Haemostasis, 2020Co-Authors: Atsuki Yamashita, John H. Griffin, Yuqi Zhang, Michel F Sanner, Laurent O MosnierAbstract:BACKGROUND Activated protein C (APC) is an important homeostatic blood coagulation protease that conveys anticoagulant and Cytoprotective activities. Proteolytic inactivation of factors Va and VIIIa facilitated by cofactor protein S is responsible for APC's anticoagulant effects, whereas Cytoprotective effects of APC involve primarily the endothelial protein C receptor (EPCR), protease activated receptor (PAR)1 and PAR3. OBJECTIVE To date, several binding exosites in the protease domain of APC have been identified that contribute to APC's interaction with its substrates but potential contributions of the C-terminus of the light chain have not been studied in detail. METHODS Site-directed Ala-scanning mutagenesis of six positively charged residues within G142-L155 was used to characterize their contributions to APC's anticoagulant and Cytoprotective activities. RESULTS AND CONCLUSIONS K151 was involved in protein S dependent-anticoagulant activity of APC with some contribution of K150. 3D structural analysis supported that these two residues were exposed in an extended protein S binding site on one face of APC. Both K150 and K151 were important for PAR1 and PAR3 cleavage by APC, suggesting that this region may also mediate interactions with PARs. Accordingly, APC's Cytoprotective activity as determined by endothelial barrier protection was impaired by Ala substitutions of these residues. Thus, both K150 and K151 are involved in APC's anticoagulant and Cytoprotective activities. The differential contribution of K150 relative to K151 for protein S-dependent anticoagulant activity and PAR cleavage highlights that binding exosites for protein S binding and for PAR cleavage in the C-terminal region of APC's light chain overlap.
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neurotoxicity of the anticoagulant selective e149a activated protein c variant after focal ischemic stroke in mice
Blood Cells Molecules and Diseases, 2013Co-Authors: Yaoming Wang, John H. Griffin, Laurent O Mosnier, Ranjeet Kumar Sinha, Berislav V ZlokovicAbstract:Abstract Wild type (WT) activated protein C (APC) and Cytoprotective-selective APC variants such as 3K3A-APC ( 3-fold increased anticoagulant activity but defective Cytoprotective activities) to those of the Cytoprotective-selective 5A-APC variant ( P P P
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Protein C anticoagulant and Cytoprotective pathways
International Journal of Hematology, 2012Co-Authors: John H. Griffin, Berislav V Zlokovic, Laurent O MosnierAbstract:Plasma protein C is a serine protease zymogen that is transformed into the active, trypsin-like protease, activated protein C (APC), which can exert multiple activities. For its anticoagulant action, APC causes inactivation of the procoagulant cofactors, factors Va and VIIIa, by limited proteolysis, and APC’s anticoagulant activity is promoted by protein S, various lipids, high-density lipoprotein, and factor V. Hereditary heterozygous deficiency of protein C or protein S is linked to moderately increased risk for venous thrombosis, while a severe or total deficiency of either protein is linked to neonatal purpura fulminans. In recent years, the beneficial direct effects of APC on cells which are mediated by several specific receptors have become the focus of much attention. APC-induced signaling can promote multiple Cytoprotective actions which can minimize injuries in various preclinical animal injury models. Remarkably, pharmacologic therapy using APC demonstrates substantial neuroprotective effects in various murine injury models, including ischemic stroke. This review summarizes the molecules that are central to the protein C pathways, the relationship of pathway deficiencies to venous thrombosis risk, and mechanisms for the beneficial effects of APC.
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activated protein c mutant with minimal anticoagulant activity normal Cytoprotective activity and preservation of thrombin activable fibrinolysis inhibitor dependent Cytoprotective functions
Journal of Biological Chemistry, 2007Co-Authors: Laurent O Mosnier, Xia V Yang, John H. GriffinAbstract:Abstract Activated protein C (APC) reduces mortality in severe sepsis patients and exhibits beneficial effects in multiple animal injury models. APC anticoagulant activity involves inactivation of factors Va and VIIIa, whereas APC Cytoprotective activities involve the endothelial protein C receptor and protease-activated receptor-1 (PAR-1). The relative importance of the anticoagulant activity of APC versus the direct Cytoprotective effects of APC on cells for the in vivo benefits is unclear. To distinguish Cytoprotective from the anticoagulant activities of APC, a protease domain mutant, 5A-APC (RR229/230AA and KKK191-193AAA), was made and compared with recombinant wild-type (rwt)-APC. This mutant had minimal anticoagulant activity but normal Cytoprotective activities that were dependent on endothelial protein C receptor and protease-activated receptor-1. Whereas anticoagulantly active rwt-APC inhibited secondary-extended thrombin generation and concomitant thrombin-dependent activation of thrombin activable fibrinolysis inhibitor (TAFI) in plasma, secondary-extended thrombin generation and the activation of TAFI were essentially unopposed by 5A-APC due to its low anticoagulant activity. Compared with rwt-APC, 5A-APC had minimal profibrinolytic activity and preserved TAFI-mediated anti-inflammatory carboxypeptidase activities toward bradykinin and presumably toward the anaphlatoxins, C3a and C5a, which are well known pathological mediators in sepsis. Thus, genetic engineering can selectively alter the multiple activities of APC and provide APC mutants that retain the beneficial Cytoprotective effects of APC while diminishing bleeding risk due to reduction in APC's anticoagulant and APC-dependent profibrinolytic activities.
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activated protein c
Journal of Thrombosis and Haemostasis, 2007Co-Authors: John H. Griffin, José A. Fernández, Andrew J Gale, Laurent O MosnierAbstract:Summary. Protein C is a vitamin K-dependent plasma protein zymogen whose genetic mild or severe deficiencies are linked with risk for venous thrombosis or neonatal purpura fulminans, respectively. Studies over past decades showed that activated protein C (APC) inactivates factors (F) Va and VIIIa to down-regulate thrombin generation. More recent basic and preclinical research on APC has characterized the direct Cytoprotective effects of APC that involve gene expression profile alterations, anti-inflammatory and anti-apoptotic activities and endothelial barrier stabilization. These actions generally require endothelial cell protein C receptor (EPCR) and protease activated receptor-1. Because of these direct Cytoprotective actions, APC reduces mortality in murine endotoxemia and severe sepsis models and provides neuroprotective benefits in murine ischemic stroke models. Furthermore, APC reduces mortality in patients with severe sepsis (PROWESS clinical trial). Although much remains to be clarified about mechanisms for APC’s direct effects on various cell types, it is clear that APC’s molecular features that determine its antithrombotic action are partially distinct from those providing Cytoprotective actions because we have engineered recombinant APC variants with selective reduction or retention of either anticoagulant or Cytoprotective activities. Such APC variants can provide relatively enhanced levels of either Cytoprotective or anticoagulant activities for various therapeutic applications. We speculate that APC variants with reduced anticoagulant action but normal Cytoprotective actions hold the promise of reducing bleeding risk because of attenuated anticoagulant activity while reducing mortality based on direct Cytoprotective effects on cells.
Thurairajah Nalina - One of the best experts on this subject based on the ideXlab platform.
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antioxidant and Cytoprotective activities of piper betle areca catechu uncaria gambir and betel quid with and without calcium hydroxide
BMC Complementary and Alternative Medicine, 2013Co-Authors: Nordin Nur Sazwi, Thurairajah Nalina, Zubaidah Haji Abdul RahimAbstract:Betel quid chewing is a popular habit in Southeast Asia. It is believed that chewing betel quid could reduce stress, strengthen teeth and maintain oral hygiene. The aim of this study was to investigate the antioxidant and Cytoprotective activities of each of the ingredients of betel quid and compared with betel quid itself (with and without calcium hydroxide). The correlation of their Cytoprotective and antioxidant activities with phenolic content was also determined. Five samples (betel leaf, areca nut, gambir, betel quid and betel quid containing calcium hydroxide) were extracted in deionized distilled water for 12 hours at 37°C. Antioxidant activities were evaluated for radical scavenging activity using DPPH assay, ferric reducing activity using FRAP assay and lipid peroxidation inhibition activity using FTC assay. Total phenolic content (TPC) was determined using Folin-Ciocalteu procedure. Phenolic composition was analyzed using LC-MS/MS. Cytoprotective activity towards human gingival fibroblast cells was examined using MTT assay. Among the ingredients of betel quid, gambir demonstrated the highest antioxidant (DPPH - IC50 = 6.4 ± 0.8 μg/mL, FRAP - 5717.8 ± 537.6 μmol Fe(II)/mg), total phenolic content (TPC - 1142.5 ± 106.8 μg TAE/mg) and Cytoprotective (100.1 ± 4.6%) activities. Betel quid when compared with betel quid containing calcium hydroxide has higher antioxidant (DPPH - IC50 =59.4 ± 4.4 μg/mL, FRAP - 1022.2 ± 235.7 μmol Fe(II)/mg), total phenolic content (TPC - 140.0 ± 22.3 μg TAE/mg), and Cytoprotective (113.5 ± 15.9%) activities. However, all of the five samples showed good lipid peroxidation inhibition compared to vitamin E. LC-MS/MS analysis revealed the presence of quinic acid as the major compound of gambir and betel quid. A positive correlation was observed between TPC and radical scavenging (r = 0.972), reducing power (r = 0.981) and Cytoprotective activity (r = 0.682). The betel quid has higher TPC, and antioxidant and Cytoprotective activities than betel quid with calcium hydroxide. The quinic acid in betel quid may play an important role in the oral health protection.
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antioxidant and Cytoprotective activities of piper betle areca catechu uncaria gambir and betel quid with and without calcium hydroxide
BMC Complementary and Alternative Medicine, 2013Co-Authors: Nordin Nur Sazwi, Thurairajah Nalina, Zubaidah Haji Abdul RahimAbstract:Betel quid chewing is a popular habit in Southeast Asia. It is believed that chewing betel quid could reduce stress, strengthen teeth and maintain oral hygiene. The aim of this study was to investigate the antioxidant and Cytoprotective activities of each of the ingredients of betel quid and compared with betel quid itself (with and without calcium hydroxide). The correlation of their Cytoprotective and antioxidant activities with phenolic content was also determined. Five samples (betel leaf, areca nut, gambir, betel quid and betel quid containing calcium hydroxide) were extracted in deionized distilled water for 12 hours at 37°C. Antioxidant activities were evaluated for radical scavenging activity using DPPH assay, ferric reducing activity using FRAP assay and lipid peroxidation inhibition activity using FTC assay. Total phenolic content (TPC) was determined using Folin-Ciocalteu procedure. Phenolic composition was analyzed using LC-MS/MS. Cytoprotective activity towards human gingival fibroblast cells was examined using MTT assay. Among the ingredients of betel quid, gambir demonstrated the highest antioxidant (DPPH - IC50 = 6.4 ± 0.8 μg/mL, FRAP - 5717.8 ± 537.6 μmol Fe(II)/mg), total phenolic content (TPC - 1142.5 ± 106.8 μg TAE/mg) and Cytoprotective (100.1 ± 4.6%) activities. Betel quid when compared with betel quid containing calcium hydroxide has higher antioxidant (DPPH - IC50 =59.4 ± 4.4 μg/mL, FRAP - 1022.2 ± 235.7 μmol Fe(II)/mg), total phenolic content (TPC - 140.0 ± 22.3 μg TAE/mg), and Cytoprotective (113.5 ± 15.9%) activities. However, all of the five samples showed good lipid peroxidation inhibition compared to vitamin E. LC-MS/MS analysis revealed the presence of quinic acid as the major compound of gambir and betel quid. A positive correlation was observed between TPC and radical scavenging (r = 0.972), reducing power (r = 0.981) and Cytoprotective activity (r = 0.682). The betel quid has higher TPC, and antioxidant and Cytoprotective activities than betel quid with calcium hydroxide. The quinic acid in betel quid may play an important role in the oral health protection.
