The intranasal administration of Carthamus tinctorius L. extract/phospholipid complex in the treatment of cerebral infarction via the TNF-α/MAPK pathway

Biomed Pharmacother. 2020 Oct:130:110563. doi: 10.1016/j.biopha.2020.110563. Epub 2020 Jul 31.

Abstract

Carthamus tinctorius L.(Safflower), a herbal formula from Traditional Chinese Medicine (TCM), has been widely used for the treatment of cardio-cerebrovascular diseases, particularly cerebral infarction (CI) or cerebral ischemia-reperfusion injury. However, we know very little about the specific mechanisms associated with the therapeutic effect of Safflower on CI. In this study, we used a network pharmacology-based approach, together with rat model of CI, to gain more insight into of such mechanisms. Our analysis showed that Safflower contains 52 active compounds that target 247 genes, which were also cross-referenced with 299 genes associated with CI. Consequently, we identified 52 target genes in Safflower that were associated with CI. These 52 target genes were analyzed by gene ontology (GO) enrichment analysis, leading to the identification of 1491 biological process items, 90 molecular function items and 19 cell assembly items. Eighty-nine pathways were generated by KEGG enrichment (P < 0.05). Next, we investigated the effect of the extract of safflower (ES) and Safflower extract phospholipid complex (ESPC), delivered via the nasal route, on an animal model of the middle cerebral artery occlusion (MCAO). Our data confirmed that Safflower was able to treat CI by the regulating the TNF-α/MAPK pathway via CASP3. The therapeutic effect of ES and ESPC on CI acts by improving the circulation of blood in the central nervous system, reducing the inflammatory reaction, inhibiting apoptosis, and by protecting brain nerve cells from injury.

Keywords: Carthamus tinctorius L.; Cerebral infarction; Network pharmacology; Safflower extract phospholipid complex; TNF-α/MAPK pathway.

MeSH terms

  • Administration, Intranasal
  • Animals
  • Apoptosis / drug effects
  • Carthamus tinctorius / chemistry*
  • Cell Survival / drug effects
  • Cerebral Infarction / drug therapy*
  • Cerebral Infarction / genetics*
  • Cerebral Infarction / mortality
  • Encephalitis / drug therapy
  • Infarction, Middle Cerebral Artery / drug therapy
  • Infarction, Middle Cerebral Artery / genetics
  • Infarction, Middle Cerebral Artery / mortality
  • Male
  • Medicine, Chinese Traditional
  • Mitogen-Activated Protein Kinase Kinases / genetics*
  • Neurons / drug effects
  • Phospholipids / chemistry
  • Plant Extracts / administration & dosage
  • Plant Extracts / therapeutic use*
  • Psychomotor Performance / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects*
  • Signal Transduction / genetics
  • Tumor Necrosis Factor-alpha / genetics*

Substances

  • Phospholipids
  • Plant Extracts
  • Tumor Necrosis Factor-alpha
  • Mitogen-Activated Protein Kinase Kinases