Synthetic ruthenium complex TQ-6 potently recovers cerebral ischemic stroke: Attenuation of microglia and platelet activation

Chih Wei Hsia, Thanasekaran Jayakumar, Joen Rong Sheu, Chih Wei Hsia, Wei Chieh Huang, Marappan Velusamy, Li Ming Lien

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)


Activated microglia are crucial in the regulation of neuronal homeostasis and neuroinflammation. They also contribute to neuropathological processes after ischemic stroke. Thus, finding new approaches for reducing neuroinflammation has gained considerable attention. The metal ruthenium has gained notable attention because of its ability to form new complexes that can be used in disease treatment. [Ru(η6-cymene)2-(1H-benzoimidazol-2-yl)-quinoline Cl]BF4 (TQ-6), a potent ruthenium (II)-derived compound, was used in this study to investigate its neuroprotective action against microglia activation, middle cerebral artery occlusion (MCAO)-induced embolic stroke, and platelet activation, respectively. TQ-6 (2 μM) potently diminished inflammatory mediators (nitric oxide/inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2)) expression, nuclear factor kappa B (NF-κB) p65 phosphorylation, nuclear translocation, and hydroxyl radical (OH) formation in LPS-stimulated microglia. Conversely, TQ-6 increased the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). Moreover, it significantly reduced brain infarct volume and edema in MCAO mice. Additionally, it drastically inhibited platelet aggregation and OH production in mice platelets. This study confirmed that TQ-6 exerts an anti-neuroinflammatory effect on microglia activation through neuroprotection, antiplatelet activation, and free radical scavenging. The authors propose that TQ-6 might mitigate neurodegenerative pathology by inhibiting the NF-κB-mediated downstream pathway (iNOS and COX-2) and enhancing Nrf2/HO-1 signaling molecules in microglia.

Original languageEnglish
Article number996
JournalJournal of Clinical Medicine
Issue number4
Publication statusPublished - Apr 2020


  • Brain infarct/edema
  • BV2 microglia
  • Neuroinflammation
  • NF-κB
  • Nrf2/HO-1
  • Platelets
  • Ruthenium complex

ASJC Scopus subject areas

  • Medicine(all)


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