Abstract | ETHNOPHARMACOLOGICAL RELEVANCE:
Barakol, an anxiolytic agent isolated from Senna siamea leaves which has been traditionally used for producing natural sleep, has been described as toxic to patients. AIM OF THE STUDY: The aim of current study was to investigate the molecular mechanism of barakol-induced toxicity in mouse embryonal carcinoma P19 cell model. MATERIALS AND METHODS: RESULTS: Treatment with barakol decreased cell viability in a concentration- and time-dependent manner with an IC(50) value of 1.5mM in 24-h treated cells. A Hoechst 33342 assay revealed that barakol cytotoxicity was due to a significant increase in the number of apoptotic cells. Different scavengers to characterize ROS were utilized and revealed that hydroxyl radicals played a major role in ROS-induced apoptosis in barakol-treated cells. Western blot analysis demonstrated that barakol-induced apoptosis was mediated by the increase in expression ratio of Bax/Bcl-2. Furthermore, increase in caspase-9 activity after exposure to barakol for 24h was also observed. Pretreatment of cells with N-acetyl-l-cysteine (NAC) attenuated intracellular ROS generation, the Bax/Bcl-2 protein expression, and apoptosis. CONCLUSIONS: The mechanism of barakol-mediated toxicity in P19 cells is mainly associated with the ROS generation, followed by the imbalance of the Bax/Bcl-2 ratio, and caspase-9 activation leading to apoptotic cell death. Pretreatment of cells with NAC could antagonize the toxicity produced by barakol.
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Authors | Supim Wongtongtair, Pithi Chanvorachote, Pilaiwanwadee Hutamekalin, Chaiyo Chaichantipyuth, Vimolmas Lipipun, Pornthep Tiensiwakul, Duangdeun Meksuriyen |
Journal | Journal of ethnopharmacology
(J Ethnopharmacol)
Vol. 137
Issue 2
Pg. 971-8
(Sep 02 2011)
ISSN: 1872-7573 [Electronic] Ireland |
PMID | 21777666
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2011 Elsevier Ireland Ltd. All rights reserved. |
Chemical References |
- Anti-Anxiety Agents
- Bax protein, mouse
- Benzopyrans
- Phenalenes
- Proto-Oncogene Proteins c-bcl-2
- Reactive Oxygen Species
- bcl-2-Associated X Protein
- barakol
- Caspase 9
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Topics |
- Animals
- Anti-Anxiety Agents
(isolation & purification, toxicity)
- Apoptosis
(drug effects)
- Benzopyrans
(isolation & purification, toxicity)
- Blotting, Western
- Caspase 9
(metabolism)
- Cell Culture Techniques
- Cell Line, Tumor
- Cell Survival
(drug effects)
- Data Interpretation, Statistical
- Dose-Response Relationship, Drug
- Flow Cytometry
- Fluorometry
- Mice
- Phenalenes
(isolation & purification, toxicity)
- Plant Leaves
(chemistry)
- Proto-Oncogene Proteins c-bcl-2
(metabolism)
- Reactive Oxygen Species
(metabolism)
- Senna Plant
(chemistry)
- Time Factors
- bcl-2-Associated X Protein
(metabolism)
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