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Scutellarin as a Potential Therapeutic Agent for Microglia-Mediated Neuroinflammation in Cerebral Ischemia

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Abstract

The cerebral ischemia is one of the most common diseases in the central nervous system that causes progressive disability or even death. In this connection, the inflammatory response mediated by the activated microglia is believed to play a central role in this pathogenesis. In the event of brain injury, activated microglia can clear the cellular debris and invading pathogens, release neurotrophic factors, etc., but in chronic activation microglia may cause neuronal death through the release of excessive inflammatory mediators. Therefore, suppression of microglial over-reaction and microglia-mediated neuroinflammation is deemed to be a therapeutic strategy of choice for cerebral ischemic damage. In the search for potential herbal extracts that are endowed with the property in suppressing the microglial activation and amelioration of neuroinflammation, attention has recently been drawn to scutellarin, a Chinese herbal extract. Here, we review the roles of activated microglia and the effects of scutellarin on activated microglia in pathological conditions especially in ischemic stroke. We have further extended the investigation with special reference to the effects of scutellarin on Notch signaling, one of the several signaling pathways known to be involved in microglial activation. Furthermore, in light of our recent experimental evidence that activated microglia can regulate astrogliosis, an interglial “cross-talk” that was amplified by scutellarin, it is suggested that in designing of a more effective therapeutic strategy for clinical management of cerebral ischemia both glial types should be considered collectively.

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Abbreviations

Aβ:

β-amyloid peptide

AD:

Alzheimer’s disease

BBB:

Blood–brain barrier

CNS:

Central nervous system

DAPT:

N-[N-(3,5-difluorophenacetyl)-1-alany1]-S-phenyglycine t-butyl ester

GFAP:

Glial fibrillary acidic protein

Hes-1:

Transcription factor hairy and enhancer of split-1

IL-1β:

Interleukin-1β

Inos:

Inducible nitric oxide synthase

LPS:

Lipopolysaccharide

MCAO:

Middle cerebral artery occlusion

NF-κB:

Nuclear factor κ-light-chain-enhancer of activated B cells

NICD:

Notch intracellular domain

NO:

Nitric oxide

RBP-JK:

Recombining binding protein suppressor of hairless

ROS:

Reactive oxygen species

TNF-α:

Tumor necrosis factor-α

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Acknowledgments

This study was supported by National Natural Science Foundation of China (Project Number 31260254, C-Y Wu), Applied Basic Research Program Key Projects of Yunnan Province (Project Number 2015FA020, C-Y Wu), and National University of Singapore (NUS R181-000-140-592, E-A Ling).

Author’s contributions

Eng-Ang Ling and Chunyun Wu conceptualized this review. Yun Yuan and Ming Fang conducted the experiments mentioned in this review. Yun Yuan led to write the manuscript, and Ming Fang was responsible for submitting the final manuscript. All authors read, discussed, and approved the final manuscript.

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    Authors and Affiliations

    1. Department of Anatomy and Histology/Embryology, Faculty of Basic Medical Sciences, Kunming Medical University, 1168 West Chunrong Road, Kunming, 650500, People’s Republic of China

      Yun Yuan & Chun-Yun Wu

    2. Department of Emergency and Critical Care, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China

      Ming Fang

    3. Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, 4 Medical Drive, MD10, Singapore, 117594, Singapore

      Eng-Ang Ling

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    1. Yun Yuan
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    Correspondence to Chun-Yun Wu or Eng-Ang Ling.

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    The authors declare that they have no conflict of interest. All authors have read and approved the manuscript.

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    Yun Yuan and Ming Fang have contributed equally to this work.

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    Yuan, Y., Fang, M., Wu, CY. et al. Scutellarin as a Potential Therapeutic Agent for Microglia-Mediated Neuroinflammation in Cerebral Ischemia. Neuromol Med 18, 264–273 (2016). https://doi.org/10.1007/s12017-016-8394-x

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