Cardiotonic pill attenuates white matter and hippocampal damage via inhibiting microglial activation and downregulating ERK and p38 MAPK signaling in chronic cerebral hypoperfused rat

BMC Complement Altern Med. 2013 Nov 26:13:334. doi: 10.1186/1472-6882-13-334.

Abstract

Background: The cardiotonic pill (CP) is a herbal medicine composed of Salvia miltiorrhiza (SM), Panax notoginseng (PN), and Dryobalanops aromatica Gaertner (DAG) that is widely used to treat cardiovascular diseases. The present experiment was conducted to examine the effects of CP on white matter and hippocampal damage induced by chronic cerebral hypoperfusion.

Methods: Chronic cerebral hypoperfusion was induced in male Wistar rats by permanent bilateral common carotid artery occlusion (BCCAo). Daily oral administration of CP (200 mg/kg) began 21 days after BCCAo and continued for 42 days. The levels of microglial activation and myelin basic protein (MBP) were measured in the white matter and hippocampus of rats with chronic BCCAo, and the expression levels of mitogen-activated protein kinases (MAPKs) and inflammatory markers such as cyclooxygenase-2, interleukin-1β, and interleukin-6 were examined.

Results: MBP expression was reduced in the white matter and hippocampal regions of rats that received BCCAo. In contrast, reduced levels of MBP were not observed in BCCAo rats given CP treatments. The administration of CP alleviated microglial activation, the alteration of ERK and p38 MAPK signaling, and inflammatory mediator expression in rats with chronic BCCAo.

Conclusion: These results suggest that CP may have protective effects against chronic BCCAo-induced white matter and hippocampal damage by inhibiting inflammatory processes including microglial activation and proinflammatory mediator expression, and downreguating the hyperphosphorylation of ERK and p38 MAPK signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Cardiotonic Agents / pharmacology*
  • Carotid Stenosis / drug therapy*
  • Carotid Stenosis / metabolism
  • Carotid Stenosis / physiopathology
  • Cyclooxygenase 2 / metabolism
  • Dipterocarpaceae
  • Drugs, Chinese Herbal / pharmacology*
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Interleukin-1beta / metabolism
  • Interleukin-6 / metabolism
  • MAP Kinase Signaling System / drug effects*
  • Male
  • Microglia / drug effects
  • Mitogen-Activated Protein Kinases / metabolism*
  • Myelin Basic Protein / metabolism
  • Panax notoginseng
  • Phosphorylation / drug effects
  • Rats
  • Rats, Wistar
  • Salvia miltiorrhiza
  • p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

  • Cardiotonic Agents
  • Drugs, Chinese Herbal
  • Interleukin-1beta
  • Interleukin-6
  • Myelin Basic Protein
  • Cyclooxygenase 2
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases