||Nothofagin has antioxidant, and antithrombotic activities, it possesses anti-inflammatory activity by inhibiting hyperpermeability, expression of CAMs, and adhesion and migration of leukocytes, thereby endorsing its usefulness as a therapy for vascular inflammatory diseases. Nothofagin may have significant benefits in the treatment of diabetic complications. Nothofagin has potential to as an anti-sendothelial cell protein C receptor shedding reagent against phorbol-12-myristate 13-acetate and cecal ligation and puncture -mediated endothelial cell protein C receptor shedding. |
|Fitoterapia. 2015 Jan;100:179-86. |
|Aspalathin and nothofagin from rooibos (Aspalathus linearis) inhibit endothelial protein C receptor shedding in vitro and in vivo.[Pubmed: 25510322]|
|Aspalathin (Asp) and Nothofagin (Not) are two major active dihydrochalcones found in green rooibos, which have been reported for their anti-oxidant activity.
METHODS AND RESULTS:
Increasing evidence has demonstrated that beyond its role in the activation of protein C, endothelial cell protein C receptor (EPCR) is also involved in vascular inflammation. EPCR activity is markedly changed by ectodomain cleavage and its release as the soluble EPCR. EPCR can be shed from the cell surface, which is mediated by tumor necrosis factor-α converting enzyme (TACE). However, little is known about the effects of Asp and Nothofagin on EPCR shedding. Our results demonstrated that Asp and Nothofagin induced potent inhibition of phorbol-12-myristate 13-acetate (PMA)-, tumor necrosis factor (TNF)-α-, interleukin (IL)-1β, and cecal ligation and puncture (CLP)-induced EPCR shedding. Asp and Nothofagin also inhibited the expression and activity of PMA-induced TACE in endothelial cells. Asp and Nothofagin also suppressed CLP-induced protein C decrease in mice and thrombin generation in HUVECs. In addition, treatment with Asp and Nothofagin resulted in reduced PMA-stimulated phosphorylation of p38, extracellular regulated kinase (ERK) 1/2, and c-Jun N-terminal kinase (JNK).
These results demonstrate the potential of Asp and Nothofagin as an anti-sEPCR shedding reagent against PMA and CLP-mediated EPCR shedding.
|Inflammation. 2015 Feb;38(1):445-55. |
|Aspalathin and Nothofagin from Rooibos (Aspalathus linearis) inhibits high glucose-induced inflammation in vitro and in vivo.[Pubmed: 25338943]|
|Vascular inflammation plays a key role in the initiation and progression of atherosclerosis, a major complication of diabetes mellitus. Aspalathin (Asp) and Nothofagin (Not) are two major active dihydrochalcones found in green rooibos, which have been reported for their antioxidant activity.
METHODS AND RESULTS:
In this study, we assessed whether Asp or Nothofagin can suppress vascular inflammation induced by high glucose (HG) in human umbilical vein endothelial cells (HUVECs) and mice. We monitored the effects of Asp or Nothofagin on HG-induced vascular hyperpermeability, expression of cell adhesion molecules (CAMs), formation of reactive oxygen species (ROS), and activation of nuclear factor (NF)-κB in vitro and in vivo.
Our data indicate that HG markedly increased vascular permeability, monocyte adhesion, expression of CAMs, formation of ROS, and activation of NF-κB. Remarkably, treatment of Asp or Nothofagin inhibited HG-mediated vascular hyperpermeability, adhesion of monocytes toward HUVECs, and expression of CAMs. In addition, Asp or Nothofagin suppressed the formation of ROS and the activation of NF-κB.
Since vascular inflammation induced by HG is critical in the development of diabetic complications, our results suggest that Asp or Nothofagin may have significant benefits in the treatment of diabetic complications.
|Arch Pharm Res. 2014 Oct 18. |
|Antithrombotic activities of aspalathin and nothofagin via inhibiting platelet aggregation and FIIa/FXa.[Pubmed: 25325928]|
|Aspalathin (Asp) and Nothofagin (Not) are two major active dihydrochalcones found in green rooibos tea (Aspalathus linearis; family, Fabaceae; tribe, Crotalarieae), which have been reported for their anti-oxidant activity.
METHODS AND RESULTS:
Here, the anticoagulant activities of Asp and Nothofagin were examined by monitoring activated partial thromboplastin time (aPTT), prothrombin time (PT), and the activities of thrombin (Factor IIa, FIIa) and activated factor X (FXa). And, the effects of Asp and Nothofagin on expression of plasminogen activator inhibitor type 1 (PAI-1) and tissue-type plasminogen activator (t-PA) were evaluated in tumor necrosis factor (TNF)-α activated human umbilical vein endothelial cells (HUVECs). Treatment with Asp and Nothofagin resulted in prolonged aPTT and PT and inhibition of the activities of thrombin and FXa, as well as inhibited production of thrombin and FXa in HUVECs. In addition, Asp and Nothofagin inhibited thrombin-catalyzed fibrin polymerization and platelet aggregation. Asp and Nothofagin also elicited anticoagulant effects in mice. In addition, treatment with Asp and Nothofagin resulted in significant reduction of the PAI-1 to t-PA ratio.
Collectively, Asp and Nothofagin possesses antithrombotic activities and offers a basis for development of a novel anticoagulant.