| Title |
Metabolic Profile of 3-Acetyl-11-Keto-β-Boswellic Acid and 11-Keto-β-Boswellic Acid in Human Preparations In Vitro, Species Differences, and Bioactivity Variation
|
|---|---|
| Published in |
The AAPS Journal, June 2016
|
| DOI | 10.1208/s12248-016-9945-7 |
| Pubmed ID | |
| Authors |
Yonglei Cui, Xiangge Tian, Jing Ning, Chao Wang, Zhenlong Yu, Yan Wang, Xiaokui Huo, Lingling Jin, Sa Deng, Baojing Zhang, Xiaochi Ma |
| Abstract |
3-Acetyl-11-keto-β-boswellic acid (AKBA) and 11-keto-β-boswellic acid (KBA) are widely used in the clinic as anti-inflammatory drugs. However, these drugs have the poor bioavailability, which may be caused by their extensive metabolism. In this study, we systemically characterized both phase I and II metabolism of AKBA and KBA in vitro. In total, four major metabolites were firstly biosynthesized and identified using 1D and 2D NMR spectroscopy. Among them, three metabolites were novel. The kinetic parameters (K m , V max , CL int, and K i ) were also analyzed systematically in various biological samples. Finally, the deacetylation of AKBA and hydroxylation of KBA were confirmed to be the major metabolic pathways based on their large CL int and the high amounts of KBA (46.7%) and hydroxylated KBA (50.8%) along with a low amount of AKBA (2.50%) in human primary hepatocytes. Carboxylesterase 2 (CE2) selectively catalyzed the deacetylation of AKBA to form KBA. Although CYP3A4, CYP3A5, and CYP3A7 catalyzed the metabolism of KBA, CYP3A4 played a predominant role in the hydroxylation reaction of KBA in human. Notably, deacetylation and regioselective hydroxylation exhibited considerable species differences. Deacetylation was only observed in human liver microsomes and primary human hepatocytes; 21- and 20-mono-hydroxylation of KBA were primarily observed in human, monkey, and dog; and 16- and 30-mono-hydroxylation were observed in other species. More importantly, all four mono-hydroxylation metabolites exhibited a moderate anti-inflammatory activity. The 21- and 20-hydroxylation metabolites inhibited the expression of iNOS, the LPS-induced activation of IkBα and p65 phosphorylation, and suppressed p65 nuclear translocation in RAW264.7 cells. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 13 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 13 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 4 | 31% |
| Researcher | 2 | 15% |
| Other | 1 | 8% |
| Student > Bachelor | 1 | 8% |
| Lecturer | 1 | 8% |
| Other | 2 | 15% |
| Unknown | 2 | 15% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 3 | 23% |
| Veterinary Science and Veterinary Medicine | 2 | 15% |
| Agricultural and Biological Sciences | 2 | 15% |
| Pharmacology, Toxicology and Pharmaceutical Science | 1 | 8% |
| Earth and Planetary Sciences | 1 | 8% |
| Other | 0 | 0% |
| Unknown | 4 | 31% |
Attention Score in Context
This research output has an Altmetric Attention Score of 10. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 02 August 2016.
All research outputs
#3,132,192
of 22,879,161 outputs
Outputs from The AAPS Journal
#134
of 1,287 outputs
Outputs of similar age
#58,434
of 353,105 outputs
Outputs of similar age from The AAPS Journal
#10
of 42 outputs
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