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Open Access Research article

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

Ki Mo Lee1, Ji Hye Bang1, Jung-Soo Han2, Bu Yeo Kim1, In Sun Lee1, Hyung Won Kang3 and Won Kyung Jeon1*

Author Affiliations

1 KM-Based Herbal Drug Development Group, Korea Institute of Oriental Medicine, Daejeon 305-811, Republic of Korea

2 Department of Biological Sciences, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul 143-701, Republic of Korea

3 Department of Neuropsychiatry, College of Oriental Medicine, Won-Kwang University, Iksan 570-749, Republic of Korea

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BMC Complementary and Alternative Medicine 2013, 13:334  doi:10.1186/1472-6882-13-334

Published: 26 November 2013



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.


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.


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.


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.

Cardiotonic pill; Permanent bilateral common carotid artery occlusion; Inflammation; Microglia; White matter; Hippocampus