Effects of Flower Buds Extract of Tussilago farfara on Focal Cerebral Ischemia in Rats and Inflammatory Response in BV2 Microglia

Ji Hye Hwang; Vinoth R. Kumar; Seok Yong Kang; Hyo Won Jung; Yong-Ki Park

doi:10.1007/s11655-018-2936-4

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Effects of Flower Buds Extract of Tussilago farfara on Focal Cerebral Ischemia in Rats and Inflammatory Response in BV2 Microglia

Updated：2021-08-27

- Effects of Flower Buds Extract of Tussilago farfara on Focal Cerebral Ischemia in Rats and Inflammatory Response in BV2 Microglia
- Chinese Journal of Integrative Medicine Vol. 24, Issue 11, Pages: 844-852(2018)
- Affiliations：
  
  1. Department of Acupuncture and Moxibustion Medicine, College of Korean Medicine, Gachon University, Seongnam, Republic of Korea
  2. Department of Herbology, College of Korean Medicine, Dongguk University, Gyeongju, Republic of Korea
- Author bio：
- Funds：
  
  Supported by the grant from Ministry of Food and Drug Safety in 2014 (No. 12172MFDS989), Republic of Korea
- DOI：10.1007/s11655-018-2936-4
  CLC：
- Published：2018，
  
  Published Online：8 August 2018，
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Hwang, J.H., Kumar, V.R., Kang, S.Y. et al. Effects of Flower Buds Extract of Tussilago farfara on Focal Cerebral Ischemia in Rats and Inflammatory Response in BV2 Microglia., Chin. J. Integr. Med. 24, 844–852 (2018). https://doi.org/10.1007/s11655-018-2936-4

Ji Hye Hwang, Vinoth R. Kumar, Seok Yong Kang, et al. Effects of Flower Buds Extract of Tussilago farfara on Focal Cerebral Ischemia in Rats and Inflammatory Response in BV2 Microglia. [J]. Chinese Journal of Integrative Medicine 24(11):844-852(2018)
Hwang, J.H., Kumar, V.R., Kang, S.Y. et al. Effects of Flower Buds Extract of Tussilago farfara on Focal Cerebral Ischemia in Rats and Inflammatory Response in BV2 Microglia., Chin. J. Integr. Med. 24, 844–852 (2018). https://doi.org/10.1007/s11655-018-2936-4 DOI：

Ji Hye Hwang, Vinoth R. Kumar, Seok Yong Kang, et al. Effects of Flower Buds Extract of Tussilago farfara on Focal Cerebral Ischemia in Rats and Inflammatory Response in BV2 Microglia. [J]. Chinese Journal of Integrative Medicine 24(11):844-852(2018) DOI： 10.1007/s11655-018-2936-4.

摘要

To investigate the effects of the flower buds extract of Tussilago farfara Linné (Farfarae Flos; FF) on focal cerebral ischemia through regulation of inflammatory responses in activated microglia. Brain ischemia was induced in Sprague-Dawley rats by a transient middle cerebral artery occlusion (tMCAO) for 90 min and reperfusion for 24 h. Twenty rats were randomly divided into 4 groups (n=5 per group): normal

tMCAO-induced ischemic control

tMCAO plus FF extract 300 mg/kg-treated

and tMCAO plus MK-801 1 mg/kg-treated as reference drug. FF extract (300 mg/kg

p.o.) or MK-801 (1 mg/kg

i.p.) was administered after reperfusion. Brain infarction was measured by 2

-triphenyltetrazolium chloride staining. Neuronal damage was observed by haematoxylin eosin

Nissl staining and immunohistochemistry using anti-neuronal nuclei (NeuN)

anti-glial fibrillary acidic protein (GFAP)

and anti-CD11b/c (OX42) antibodies in ischemic brain. The expressions of inducible nitric oxide synthase (iNOS)

tumor necrosis factor (TNF-α)

and hypoxia-inducible factor-1a (HIF-1α) were determined by Western blot. BV2 microglial cells were treated with FF extract or its main bioactive compound

tussilagone with or without lipopolysaccharide (LPS). Nitric oxide (NO) production was measured in culture medium by Griess assay. The expressions of iNOS

COX-2 and pro-inflammatory cytokines mRNA were analyzed by reverse transcription-polymerase chain reaction. The expression of iNOS

and COX-2 proteins

the phosphorylation of ERK1/2

JNK

and p38 MAPK and the nuclear expression of NF-κB p65 in BV2 cells were determined by Western blot. FF extract significantly decreased brain infarctions in ischemic rats (P<0.01). The neuronal death and the microglia/astrocytes activation in ischemic brains were inhibited by FF extract. FF extract also suppressed iNOS

TNF-α

and HIF-1α expression in ischemic brains. FF extract (0.2 and 0.5 mg/mL

P<0.01) and tussilagone 20 and 50 μmol/L

P<0.01) significantly decreased LPS-induced NO production in BV2 microglia through downregulation of iNOS mRNA and protein expression. FF extract and tussilagone significantly inhibited LPS-induced expression of TNF-α

IL-1β

and IL-6 mRNA

and also suppressed the phosphorylation of ERK1/2

JNK and p38 MAPK and the nuclear expression of NF-κB in a dose-dependent manner. FF extract has a neuroprotective effect in ischemic stroke by the decrease of brain infarction

and the inhibition of neuronal death and microglial activation-mediated inflammatory responses.

Abstract

tMCAO-induced ischemic control

tMCAO plus FF extract 300 mg/kg-treated

and tMCAO plus MK-801 1 mg/kg-treated as reference drug. FF extract (300 mg/kg

p.o.) or MK-801 (1 mg/kg

i.p.) was administered after reperfusion. Brain infarction was measured by 2

-triphenyltetrazolium chloride staining. Neuronal damage was observed by haematoxylin eosin

Nissl staining and immunohistochemistry using anti-neuronal nuclei (NeuN)

anti-glial fibrillary acidic protein (GFAP)

and anti-CD11b/c (OX42) antibodies in ischemic brain. The expressions of inducible nitric oxide synthase (iNOS)

tumor necrosis factor (TNF-α)

and hypoxia-inducible factor-1a (HIF-1α) were determined by Western blot. BV2 microglial cells were treated with FF extract or its main bioactive compound

tussilagone with or without lipopolysaccharide (LPS). Nitric oxide (NO) production was measured in culture medium by Griess assay. The expressions of iNOS

COX-2 and pro-inflammatory cytokines mRNA were analyzed by reverse transcription-polymerase chain reaction. The expression of iNOS

and COX-2 proteins

the phosphorylation of ERK1/2

JNK

TNF-α

and HIF-1α expression in ischemic brains. FF extract (0.2 and 0.5 mg/mL

P<0.01) and tussilagone 20 and 50 μmol/L

IL-1β

and IL-6 mRNA

and also suppressed the phosphorylation of ERK1/2

JNK and p38 MAPK and the nuclear expression of NF-κB in a dose-dependent manner. FF extract has a neuroprotective effect in ischemic stroke by the decrease of brain infarction

and the inhibition of neuronal death and microglial activation-mediated inflammatory responses.

关键词

Tussilago farfaraFocal Cerebral Ischemiainflammationmicrogliatussilagone

Keywords

Tussilago farfaraFocal Cerebral Ischemiainflammationmicrogliatussilagone

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Key Laboratory of Chinese Medicine Pharmacology, Tianjin University of Traditional Chinese Medicine

Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine

Department of Anesthesiology, The Second Affiliated Hospital of Wenzhou Medical College

Xiyuan Hospital, China Academy of Chinese Medical Sciences

Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine (Ministry of Education), Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College

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