Abstract
Ethnopharmacological relevance: Gastrodia elata Blume (Fam. Orchidaceae) is a traditional Chinese herbal medicine for treating headaches, dizziness, tetanus, epilepsy, and numbness of the limbs, which suggests that it has neuroprotective effect. Aim of the study: To validate the neuroprotection of Gastrodia elata in preventing neurodegenerations, such as Huntington's disease (HD). Materials and methods: MTT assay was used to validate the protection of Gastrodia elata. In pheochromocytoma (PC12) cell. Transient transfection of mutant huntingtin (Htt) in PC12 cell was used as an in vitro model of HD. Filter retardation assay was used to measure Htt-induced protein aggregations. Proteasome activity was monitored by transfection of pZsProSensor-1 and imaged by a confocal laser scanning microscope. Results: This protection of Gastrodia elata could be blocked by an A 2A-R antagonist and a protein kinase A (PKA) inhibitor, indicating an A 2A-R signaling event. Gastrodia elata could reverse mutant Htt-induced protein aggregations and proteasome de-activation through A 2A-R signaling. In addition, activation of PKA tended to activate proteasome activity and reduce mutant Htt protein aggregations. The proteasome inhibitor, MG 132, blocked Gastrodia elata-mediated suppression of mutant Htt aggregations. Conclusion: Gastrodia elata prevented mutant Htt aggregations and increased proteasomal activity by targeting the A 2A-R through PKA-dependent pathway.
| Original language | English |
|---|---|
| Pages (from-to) | 162-168 |
| Number of pages | 7 |
| Journal | Journal of Ethnopharmacology |
| Volume | 138 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Oct 31 2011 |
| Externally published | Yes |
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Keywords
- Gastrodia elata
- Huntington's disease
- Polyglutamine
- Ubiquitin proteasome system
ASJC Scopus subject areas
- Pharmacology
- Drug Discovery
Cite this
Gastrodia elata prevents huntingtin aggregations through activation of the adenosine A 2A receptor and ubiquitin proteasome system. / Huang, Chuen Lin; Yang, Jung Mou; Wang, Kaw Chen; Lee, Yi Chao; Lin, Yun Lian; Yang, Ying Chen; Huang, Nai Kuei.
In: Journal of Ethnopharmacology, Vol. 138, No. 1, 31.10.2011, p. 162-168.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Gastrodia elata prevents huntingtin aggregations through activation of the adenosine A 2A receptor and ubiquitin proteasome system
AU - Huang, Chuen Lin
AU - Yang, Jung Mou
AU - Wang, Kaw Chen
AU - Lee, Yi Chao
AU - Lin, Yun Lian
AU - Yang, Ying Chen
AU - Huang, Nai Kuei
PY - 2011/10/31
Y1 - 2011/10/31
N2 - Ethnopharmacological relevance: Gastrodia elata Blume (Fam. Orchidaceae) is a traditional Chinese herbal medicine for treating headaches, dizziness, tetanus, epilepsy, and numbness of the limbs, which suggests that it has neuroprotective effect. Aim of the study: To validate the neuroprotection of Gastrodia elata in preventing neurodegenerations, such as Huntington's disease (HD). Materials and methods: MTT assay was used to validate the protection of Gastrodia elata. In pheochromocytoma (PC12) cell. Transient transfection of mutant huntingtin (Htt) in PC12 cell was used as an in vitro model of HD. Filter retardation assay was used to measure Htt-induced protein aggregations. Proteasome activity was monitored by transfection of pZsProSensor-1 and imaged by a confocal laser scanning microscope. Results: This protection of Gastrodia elata could be blocked by an A 2A-R antagonist and a protein kinase A (PKA) inhibitor, indicating an A 2A-R signaling event. Gastrodia elata could reverse mutant Htt-induced protein aggregations and proteasome de-activation through A 2A-R signaling. In addition, activation of PKA tended to activate proteasome activity and reduce mutant Htt protein aggregations. The proteasome inhibitor, MG 132, blocked Gastrodia elata-mediated suppression of mutant Htt aggregations. Conclusion: Gastrodia elata prevented mutant Htt aggregations and increased proteasomal activity by targeting the A 2A-R through PKA-dependent pathway.
AB - Ethnopharmacological relevance: Gastrodia elata Blume (Fam. Orchidaceae) is a traditional Chinese herbal medicine for treating headaches, dizziness, tetanus, epilepsy, and numbness of the limbs, which suggests that it has neuroprotective effect. Aim of the study: To validate the neuroprotection of Gastrodia elata in preventing neurodegenerations, such as Huntington's disease (HD). Materials and methods: MTT assay was used to validate the protection of Gastrodia elata. In pheochromocytoma (PC12) cell. Transient transfection of mutant huntingtin (Htt) in PC12 cell was used as an in vitro model of HD. Filter retardation assay was used to measure Htt-induced protein aggregations. Proteasome activity was monitored by transfection of pZsProSensor-1 and imaged by a confocal laser scanning microscope. Results: This protection of Gastrodia elata could be blocked by an A 2A-R antagonist and a protein kinase A (PKA) inhibitor, indicating an A 2A-R signaling event. Gastrodia elata could reverse mutant Htt-induced protein aggregations and proteasome de-activation through A 2A-R signaling. In addition, activation of PKA tended to activate proteasome activity and reduce mutant Htt protein aggregations. The proteasome inhibitor, MG 132, blocked Gastrodia elata-mediated suppression of mutant Htt aggregations. Conclusion: Gastrodia elata prevented mutant Htt aggregations and increased proteasomal activity by targeting the A 2A-R through PKA-dependent pathway.
KW - Gastrodia elata
KW - Huntington's disease
KW - Polyglutamine
KW - Ubiquitin proteasome system
UR - http://www.scopus.com/inward/record.url?scp=80255123778&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80255123778&partnerID=8YFLogxK
U2 - 10.1016/j.jep.2011.08.075
DO - 10.1016/j.jep.2011.08.075
M3 - Article
C2 - 21924340
AN - SCOPUS:80255123778
VL - 138
SP - 162
EP - 168
JO - Journal of Ethnopharmacology
JF - Journal of Ethnopharmacology
SN - 0378-8741
IS - 1
ER -