A novel bioactivity of andrographolide from Andrographis paniculata on cerebral ischemia/reperfusion-induced brain injury through induction of cerebral endothelial cell apoptosis

Ting Lin Yen, Wen Hsien Hsu, Steven Kuan Hua Huang, Wan-Jung Lu, Chao Chien Chang, Li Ming Lien, George Hsiao, Joen Rong Sheu, Kuan Hung Lin

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Context: Andrographolide, extracted from the leaves of Andrographis paniculata (Burm. f.) Nees (Acanthaceae), is a labdane diterpene lactone. It is widely reported to possess anti-inflammatory and antitumorigenic activities. Cerebral endothelial cells (CECs) play a crucial role in supporting the integrity and the function of the blood-brain barrier (BBB). However, no data are available concerning the effects of andrographolide in CECs. The aim of this study was to examine the detailed mechanisms of andrographolide on CECs. Objective: This study investigated a novel bioactivity of andrographolide on cerebral ischemia/reperfusion-induced brain injury. Materials and methods: CECs were treated with andrographolide (20-100 μM) for the indicated times (0-24 h). After the reactions, cell survival rate and cytotoxicity were tested by the MTT assay and the lactate dehydrogenase (LDH) test, respectively. Western blotting was used to detect caspase-3 expression. In addition, analysis of cell cycle and apoptosis using PI staining and annexin V-FITC/PI labeling, respectively, was performed by flow cytometry. We also investigated the effect of andrographolide on middle cerebral artery occlusion (MCAO)/reperfusion- induced brain injury in a rat model. Results: In the present study, we found that andrographolide (50-100 μM) markedly inhibited CEC growth according to an MTT assay and caused CEC damage according to a LDH test. Our data also revealed that andrographolide (50 μM) induced CEC apoptosis and caspase-3 activation as respectively detected by PI/annexin-V double staining and western blotting. Moreover, andrographolide arrested the CEC cell cycle at the G0/G1 phase by PI staining. In addition, andrographolide (5 mg/kg) caused deterioration of MCAO/reperfusion-induced brain injury in a rat model. Conclusions: These data suggest that andrographolide may disrupt BBB integrity, thereby deteriorating MCAO/reperfusion-induced brain injury, which are, in part, associated with its capacity to arrest cell-cycle and induce CEC apoptosis.

Original languageEnglish
Pages (from-to)1150-1157
Number of pages8
JournalPharmaceutical Biology
Volume51
Issue number9
DOIs
Publication statusPublished - Sep 2013

Fingerprint

Andrographis
Brain Ischemia
Brain Injuries
Reperfusion
Endothelial Cells
Apoptosis
Middle Cerebral Artery Infarction
Annexin A5
Staining and Labeling
Blood-Brain Barrier
L-Lactate Dehydrogenase
Caspase 3
Cell Cycle
andrographolide
Acanthaceae
Western Blotting
Cell Cycle Resting Phase
Fluorescein-5-isothiocyanate
Diterpenes
G1 Phase

Keywords

  • Caspase-3
  • CECs
  • Cell cycle
  • MCAO

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology
  • Pharmaceutical Science
  • Complementary and alternative medicine
  • Molecular Medicine

Cite this

A novel bioactivity of andrographolide from Andrographis paniculata on cerebral ischemia/reperfusion-induced brain injury through induction of cerebral endothelial cell apoptosis. / Yen, Ting Lin; Hsu, Wen Hsien; Huang, Steven Kuan Hua; Lu, Wan-Jung; Chang, Chao Chien; Lien, Li Ming; Hsiao, George; Sheu, Joen Rong; Lin, Kuan Hung.

In: Pharmaceutical Biology, Vol. 51, No. 9, 09.2013, p. 1150-1157.

Research output: Contribution to journalArticle

@article{9d261b3db31b4f20a8d19c4a1fff3ecc,
title = "A novel bioactivity of andrographolide from Andrographis paniculata on cerebral ischemia/reperfusion-induced brain injury through induction of cerebral endothelial cell apoptosis",
abstract = "Context: Andrographolide, extracted from the leaves of Andrographis paniculata (Burm. f.) Nees (Acanthaceae), is a labdane diterpene lactone. It is widely reported to possess anti-inflammatory and antitumorigenic activities. Cerebral endothelial cells (CECs) play a crucial role in supporting the integrity and the function of the blood-brain barrier (BBB). However, no data are available concerning the effects of andrographolide in CECs. The aim of this study was to examine the detailed mechanisms of andrographolide on CECs. Objective: This study investigated a novel bioactivity of andrographolide on cerebral ischemia/reperfusion-induced brain injury. Materials and methods: CECs were treated with andrographolide (20-100 μM) for the indicated times (0-24 h). After the reactions, cell survival rate and cytotoxicity were tested by the MTT assay and the lactate dehydrogenase (LDH) test, respectively. Western blotting was used to detect caspase-3 expression. In addition, analysis of cell cycle and apoptosis using PI staining and annexin V-FITC/PI labeling, respectively, was performed by flow cytometry. We also investigated the effect of andrographolide on middle cerebral artery occlusion (MCAO)/reperfusion- induced brain injury in a rat model. Results: In the present study, we found that andrographolide (50-100 μM) markedly inhibited CEC growth according to an MTT assay and caused CEC damage according to a LDH test. Our data also revealed that andrographolide (50 μM) induced CEC apoptosis and caspase-3 activation as respectively detected by PI/annexin-V double staining and western blotting. Moreover, andrographolide arrested the CEC cell cycle at the G0/G1 phase by PI staining. In addition, andrographolide (5 mg/kg) caused deterioration of MCAO/reperfusion-induced brain injury in a rat model. Conclusions: These data suggest that andrographolide may disrupt BBB integrity, thereby deteriorating MCAO/reperfusion-induced brain injury, which are, in part, associated with its capacity to arrest cell-cycle and induce CEC apoptosis.",
keywords = "Caspase-3, CECs, Cell cycle, MCAO",
author = "Yen, {Ting Lin} and Hsu, {Wen Hsien} and Huang, {Steven Kuan Hua} and Wan-Jung Lu and Chang, {Chao Chien} and Lien, {Li Ming} and George Hsiao and Sheu, {Joen Rong} and Lin, {Kuan Hung}",
year = "2013",
month = "9",
doi = "10.3109/13880209.2013.782051",
language = "English",
volume = "51",
pages = "1150--1157",
journal = "Pharmaceutical Biology",
issn = "1388-0209",
publisher = "Informa Healthcare",
number = "9",

}

TY - JOUR

T1 - A novel bioactivity of andrographolide from Andrographis paniculata on cerebral ischemia/reperfusion-induced brain injury through induction of cerebral endothelial cell apoptosis

AU - Yen, Ting Lin

AU - Hsu, Wen Hsien

AU - Huang, Steven Kuan Hua

AU - Lu, Wan-Jung

AU - Chang, Chao Chien

AU - Lien, Li Ming

AU - Hsiao, George

AU - Sheu, Joen Rong

AU - Lin, Kuan Hung

PY - 2013/9

Y1 - 2013/9

N2 - Context: Andrographolide, extracted from the leaves of Andrographis paniculata (Burm. f.) Nees (Acanthaceae), is a labdane diterpene lactone. It is widely reported to possess anti-inflammatory and antitumorigenic activities. Cerebral endothelial cells (CECs) play a crucial role in supporting the integrity and the function of the blood-brain barrier (BBB). However, no data are available concerning the effects of andrographolide in CECs. The aim of this study was to examine the detailed mechanisms of andrographolide on CECs. Objective: This study investigated a novel bioactivity of andrographolide on cerebral ischemia/reperfusion-induced brain injury. Materials and methods: CECs were treated with andrographolide (20-100 μM) for the indicated times (0-24 h). After the reactions, cell survival rate and cytotoxicity were tested by the MTT assay and the lactate dehydrogenase (LDH) test, respectively. Western blotting was used to detect caspase-3 expression. In addition, analysis of cell cycle and apoptosis using PI staining and annexin V-FITC/PI labeling, respectively, was performed by flow cytometry. We also investigated the effect of andrographolide on middle cerebral artery occlusion (MCAO)/reperfusion- induced brain injury in a rat model. Results: In the present study, we found that andrographolide (50-100 μM) markedly inhibited CEC growth according to an MTT assay and caused CEC damage according to a LDH test. Our data also revealed that andrographolide (50 μM) induced CEC apoptosis and caspase-3 activation as respectively detected by PI/annexin-V double staining and western blotting. Moreover, andrographolide arrested the CEC cell cycle at the G0/G1 phase by PI staining. In addition, andrographolide (5 mg/kg) caused deterioration of MCAO/reperfusion-induced brain injury in a rat model. Conclusions: These data suggest that andrographolide may disrupt BBB integrity, thereby deteriorating MCAO/reperfusion-induced brain injury, which are, in part, associated with its capacity to arrest cell-cycle and induce CEC apoptosis.

AB - Context: Andrographolide, extracted from the leaves of Andrographis paniculata (Burm. f.) Nees (Acanthaceae), is a labdane diterpene lactone. It is widely reported to possess anti-inflammatory and antitumorigenic activities. Cerebral endothelial cells (CECs) play a crucial role in supporting the integrity and the function of the blood-brain barrier (BBB). However, no data are available concerning the effects of andrographolide in CECs. The aim of this study was to examine the detailed mechanisms of andrographolide on CECs. Objective: This study investigated a novel bioactivity of andrographolide on cerebral ischemia/reperfusion-induced brain injury. Materials and methods: CECs were treated with andrographolide (20-100 μM) for the indicated times (0-24 h). After the reactions, cell survival rate and cytotoxicity were tested by the MTT assay and the lactate dehydrogenase (LDH) test, respectively. Western blotting was used to detect caspase-3 expression. In addition, analysis of cell cycle and apoptosis using PI staining and annexin V-FITC/PI labeling, respectively, was performed by flow cytometry. We also investigated the effect of andrographolide on middle cerebral artery occlusion (MCAO)/reperfusion- induced brain injury in a rat model. Results: In the present study, we found that andrographolide (50-100 μM) markedly inhibited CEC growth according to an MTT assay and caused CEC damage according to a LDH test. Our data also revealed that andrographolide (50 μM) induced CEC apoptosis and caspase-3 activation as respectively detected by PI/annexin-V double staining and western blotting. Moreover, andrographolide arrested the CEC cell cycle at the G0/G1 phase by PI staining. In addition, andrographolide (5 mg/kg) caused deterioration of MCAO/reperfusion-induced brain injury in a rat model. Conclusions: These data suggest that andrographolide may disrupt BBB integrity, thereby deteriorating MCAO/reperfusion-induced brain injury, which are, in part, associated with its capacity to arrest cell-cycle and induce CEC apoptosis.

KW - Caspase-3

KW - CECs

KW - Cell cycle

KW - MCAO

UR - http://www.scopus.com/inward/record.url?scp=84882377986&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84882377986&partnerID=8YFLogxK

U2 - 10.3109/13880209.2013.782051

DO - 10.3109/13880209.2013.782051

M3 - Article

VL - 51

SP - 1150

EP - 1157

JO - Pharmaceutical Biology

JF - Pharmaceutical Biology

SN - 1388-0209

IS - 9

ER -