Anti-inflammatory and anti-apoptotic effects of the combination of Ligusticum chuanxiong and Radix Paeoniae against focal cerebral ischaemia via TLR4/MyD88/MAPK/NF-κB signalling pathway in MCAO rats

J Pharm Pharmacol. 2018 Feb;70(2):268-277. doi: 10.1111/jphp.12841. Epub 2017 Nov 28.

Abstract

Objective: This study was performed to assess the anti-inflammatory and anti-apoptotic effects of the combination of Ligusticum chuanxiong and Radix Paeoniae (XS) on focal cerebral ischaemic stroke.

Methods: MCAO rats were used to evaluate the effect of XS on stroke. Cerebral water content was measured, and the levels of IFN-γ, IL-1β, IL-6 and IL-12 in serum and brain were assessed by ELISA kits. Protein expressions including p-p38, p-38, TLR-4, p-ERK, ERK, TLR-5, NF-κBp65, Myd88, Caspase-3 and Caspase-12 were examined by WB and IHC. Q-PCR was applied to examine IL-1β and IL-6 mRNA levels in the rat brain of each group.

Key findings: XS treatment remarkedly decreased the levels of IFN-γ, IL-1β, IL-6 and IL-12 in serum and brain tissues of MCAO rats. In the ischaemic brain, the expressions of TLR-4, TLR-5, p-p38, p-ERK, Myd88, NF-κBp65, Caspase-3 and Caspase-12 were increased significantly, while the treatment attenuated the activated expressions by MCAO. XS also downregulated Caspase-3 and Caspase-12 expressions. IL-1β and IL-6 mRNA levels in MCAO brain tissue were decreased by XS treatment.

Conclusions: XS could protect MCAO rats by anti-inflammation and anti-apoptosis through TLR4/MyD88/MAPK/NF-κB signalling pathway. Furthermore, the combination has a more meaningful improvement on focal cerebral ischaemic stroke.

Keywords: TLR4/NF-κB signalling pathway; combination of Ligusticum chuanxiong-Radix Paeoniae; inflammation; stroke.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / isolation & purification
  • Anti-Inflammatory Agents / pharmacology*
  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins / metabolism
  • Brain / drug effects*
  • Brain / enzymology
  • Brain / pathology
  • Cytokines / genetics
  • Cytokines / metabolism
  • Disease Models, Animal
  • Drug Therapy, Combination
  • Infarction, Middle Cerebral Artery / drug therapy*
  • Infarction, Middle Cerebral Artery / enzymology
  • Infarction, Middle Cerebral Artery / genetics
  • Infarction, Middle Cerebral Artery / pathology
  • Inflammation Mediators / metabolism
  • Ligusticum* / chemistry
  • Male
  • Mitogen-Activated Protein Kinases / metabolism*
  • Myeloid Differentiation Factor 88 / metabolism*
  • NF-kappa B / metabolism*
  • Paeonia* / chemistry
  • Phytotherapy
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Plants, Medicinal
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects
  • Toll-Like Receptor 4 / metabolism*

Substances

  • Anti-Inflammatory Agents
  • Apoptosis Regulatory Proteins
  • Cytokines
  • Inflammation Mediators
  • Myd88 protein, rat
  • Myeloid Differentiation Factor 88
  • NF-kappa B
  • Plant Extracts
  • Tlr4 protein, rat
  • Toll-Like Receptor 4
  • Mitogen-Activated Protein Kinases