Carthamus tinctorius L. Extract ameliorates cerebral ischemia-reperfusion injury in rats by regulating matrix metalloproteinases and apoptosis

Indian J Pharmacol. 2020 Mar-Apr;52(2):108-116. doi: 10.4103/ijp.IJP_400_18. Epub 2020 Jun 3.

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.

Keywords: Apoptosis; Carthamus tinctorius L.; cerebral ischemia-reperfusion; matrix metalloprotein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins / metabolism
  • Brain / drug effects*
  • Brain / enzymology
  • Brain / pathology
  • Carthamus tinctorius* / chemistry
  • Disease Models, Animal
  • Infarction, Middle Cerebral Artery / drug therapy*
  • Infarction, Middle Cerebral Artery / enzymology
  • Infarction, Middle Cerebral Artery / pathology
  • Male
  • Matrix Metalloproteinase 2 / metabolism*
  • Matrix Metalloproteinase 9 / metabolism*
  • Neuroprotective Agents / isolation & purification
  • Neuroprotective Agents / pharmacology*
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Rats, Sprague-Dawley
  • Reperfusion Injury / enzymology
  • Reperfusion Injury / pathology
  • Reperfusion Injury / prevention & control*
  • Signal Transduction
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism

Substances

  • Apoptosis Regulatory Proteins
  • Neuroprotective Agents
  • Plant Extracts
  • TIMP1 protein, rat
  • Tissue Inhibitor of Metalloproteinase-1
  • Matrix Metalloproteinase 2
  • Mmp2 protein, rat
  • Matrix Metalloproteinase 9
  • Mmp9 protein, rat