Abstract

BackgroundThe 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.MethodsChronic 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.ResultsMBP 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.ConclusionThese 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.

Highlights

  • 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

  • We examined the effects of CP on chronic bilateral common carotid artery occlusion (BCCAo)-induced myelin basic protein (MBP) breakdown in the medial septum, corpus callosum, fimbria, fornix of the white matter, and hippocampus

  • The reduced level of MBP was not observed in the chronic BCCAo rats administered CP, implying that CP treatment could ameliorate the degradation of the myelin sheath induced by chronic cerebral hypoperfusion

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Summary

Introduction

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. A chronic reduction in cerebral blood flow may lead to vascular cognitive impairment [1]. Decreased cerebral blood flow is observed in patients with Alzheimer’s disease (AD) or vascular dementia (VaD) [2,3]. One pathological feature in the brains of chronic BCCAo rats is white matter lesions, which are frequently observed in the brains of patients with VaD [6]. BCCAo rats show cognitive impairments and altered signaling in brain structures, including the hippocampus [4,7]. It has been reported that neuroinflammation is associated with the development of white matter lesions and hippocampal damage in BCCAo rats [8,9]. Microglial activation may aggravate damage to these structures through the excessive production of reactive oxygen species and proinflammatory cytokines as well as through the activation of MAPK signaling [4,10,11]

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