ABSTRACT
We investigate the protective effect of Carthamus tinctorius L. (CTL, also known as Honghua in China or Safflower) on cerebral ischemia-reperfusion and explored the possible mechanisms on regulating apoptosis and matrix metalloproteinases (MMPs). High-performance liquid chromatography method with diode array detection analysis was established to analyze the components of CTL. Middle cerebral artery occlusion rats model was established to evaluate Neurological Function Score and hematoxylin-eosin staining, as well as triphenyltetrazolium was used to examine the infarction area ratio. Transferase-mediated dUTP nick-end labeling was performed for the apoptosis. Apoptosis-related factors, including B-cell lymphoma-2 (Bcl-2), Bax and Caspase3, and MMPs-related MMP2, MMP9, tissue inhibitor of metalloproteinases 1 (TIMP1) in ischemic brain, were assayed by Western blot, reverse transcription polymerase chain reaction, and immunohistochemistry. The data showed that CTL (2, 4 g crude drug/kg/d) treatment could significantly reduce the ischemic damage in brain tissue and improve a significant neurological function score. In addition, CTL could also attenuate apoptosis degree of brain tissues and regulate Bcl-2, Bax, and Caspase 3 and also have a significant decrease on MMP-9 expression, followed by a significant increase of TIMP1 protein expression. These findings indicated that regulation of CTL on apoptosis and MMPs contributed to its protective effect on ischemia/reperfusion injury.
Subject(s)
Apoptosis/drug effects , Brain/drug effects , Carthamus tinctorius , Infarction, Middle Cerebral Artery/drug therapy , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Neuroprotective Agents/pharmacology , Plant Extracts/pharmacology , Reperfusion Injury/prevention & control , Animals , Apoptosis Regulatory Proteins/metabolism , Brain/enzymology , Brain/pathology , Carthamus tinctorius/chemistry , Disease Models, Animal , Infarction, Middle Cerebral Artery/enzymology , Infarction, Middle Cerebral Artery/pathology , Male , Neuroprotective Agents/isolation & purification , Plant Extracts/isolation & purification , Rats, Sprague-Dawley , Reperfusion Injury/enzymology , Reperfusion Injury/pathology , Signal Transduction , Tissue Inhibitor of Metalloproteinase-1/metabolismABSTRACT
The acute kidney injury(AKI) caused by nephrotoxic drugs contributes to inflammation and oxidative injury in podocytes. Wedelolactone (WED), a natural compound, is found with activities as anti-inflammation, anti-oxidative, anti-free radical,and etc. In this present study, MPC-5 cells were exposed to the nephrotoxic drugs doxorubicin (DOX). The results showed that WED significantly increased the SOD activity, CAT and GSH-Px levels, while significantly decreased the MDA content and ROS levels in DOX-induced MPC-5 cells. WED could also significantly decrease the levels of cytokines IL-6, MCP-1, TNF-α, and TGF-ß1. Additionally, the activation and phosphorylation of IκKα, IκBα and NF-κB p65 was inhibited by WED. The co-treatment of PDTC (NF-κB inhibitor) and WED significantly reduced NF-κB p65 phosphorylation. These findings suggested that WED alleviated inflammation and oxidative stress of doxorubicin-induced MPC-5 cells through IκK/IκB/NF-κB signaling pathway.
