| Kinase Assay: |
| Biomed. Pharmacother.,2016 Oct;83:958-66. | | Bakkenolide A inhibits leukemia by regulation of HDAC3 and PI3K/Akt-related signaling pathways.[Pubmed: 27522258 ] |
Leukemia has been the third type of cancer killing many people across the world. Bakkenolide A (Bak), extracted from Petasites tricholobus, has been suggested to against cancer and display protective effects on inflammatory cytokines formation.
And increasing evidences suggest that histone deacetylase 3 (HDAC3) plays vital roles in cancer formation and persistence via cell death, apoptosis and inflammation. But the function of Bakkenolide A in regulating leukemia is not understood yet, particularly via HDAC3.
METHODS AND RESULTS:
Here, we found that HDAC3 is up-regulated in clinical samples of leukemia compared with adjacent normal tissues. Then the expression of HDAC3 was knocked down via RNA interference in K562 cells. And inhibition of HDAC3 expression is able to improve leukemia invasion, migration and proliferation. Further, we also found HDAC3 bound to IκBα, affecting subsequent inflammation response. Moreover, Bakkenolide A was found to inhibit inflammation, induce apoptosis and cell death in leukemia cells via PI3K-regulated signaling pathway, down-regulating IKKs expression and suppressing in proinflammatory cytokines of IL-1β, IL-18 and TNF-α. Up-regulation of Caspase3/7 was observed in cells of HDAC3-knockdown and Bakkenolide A treatment, inducing leukemia cell apoptosis. Also, the expression of Akt and GSK were activated by HDAC3-knockdown and Bakkenolide A-treatment.
CONCLUSIONS:
Thus, these results indicated that Bakkenolide A-mediated HDAC3 sensitization in leukemia cells seem to be associated with activation of effector IKKs, Akt/GSK, and caspases through induction of the PI3K pathway, leading to inflammation, cell death, and apoptosis. |
|
| Structure Identification: |
| J Mass Spectrom. 2012 Aug;47(8):962-8. | | Determination of bakkenolide A in rat plasma using liquid chromatography/tandem mass spectrometry and its application to a pharmacokinetic study.[Pubmed: 22899504] |
METHODS AND RESULTS:
A sensitive rapid analytical method was established and validated to determine the Bakkenolide A (BA) in rat plasma. This method was further applied to assess the pharmacokinetics of Bakkenolide A in rats receiving a single dose of Bakkenolide A. Intra- and inter-day accuracies for Bakkenolide A were 93-112% and 103-104%, respectively, and the inter-day precision was less than 15%. After a single oral dose of 20 mg/kg of Bakkenolide A, the mean peak plasma concentration (C(max) ) of Bakkenolide A was 234.7 ± 161 ng/mL at 0.25 h. The area under the plasma concentration-time curve (AUC(0-24 h) ) was 535.8 ± 223.7 h·ng/mL, and the elimination half-life (T(1/2) ) was 5.0 ± 0.36 h. In case of intravenous administration of Bakkenolide A at a dosage of 2 mg/kg, the area under the plasma concentration-time curve (AUC(0-24 h) ) was 342 ± 98 h⋅ng/mL, and the elimination half-life (T(1/2) ) was 5.8 ± 0.7 h.
CONCLUSIONS:
Based on the results, the oral bioavailability of Bakkenolide A in rats at 20 mg/kg is 15.7%. |
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