Identification of Toxic Pyrrolizidine Alkaloids and Their Common Hepatotoxicity Mechanism
Abstract
:1. Introduction
2. Results
2.1. Identifying the Potential Targets of PAs
2.2. Targets Enrichment of Toxic PAs
2.3. Molecular Interactions within PAs and GSTA1, GPX1
2.4. Importance of the GSTA1 and GPX1 in GSH Metabolism
3. Discussion
3.1. Toxicity Mechanism Analysis of Toxic PAs Based on GSTA1 and GPX1 Pattern
3.2. Limitations of Reverse Docking
4. Materials and Methods
4.1. Dataset
4.2. Identification of Potential Protein Targets of PAs
4.3. Targets Enrichment of Toxic PAs
4.4. Molecular Interactions within Toxic PAs and GSTA1, GPX1
4.5. Importance of the Targets Pattern in GSH Metabolism
5. Conclusions
Supplementary Materials
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Coefficients a | ||||||
---|---|---|---|---|---|---|
Model | Parameter | Unstandardized Coefficients | Standardized Coefficients | t | Sig. | |
B | Std. Error | Beta | ||||
1 | (Constant) | 8.47 × 10−17 | 0.100 | 0.000 | 1.000 | |
GSTA1 | 0.846 | 0.117 | 0.777 | 7.207 | 0.000 | |
2 | (Constant) | 0.119 | 0.079 | 1.516 | 0.139 | |
GSTA1 | 0.796 | 0.089 | 0.731 | 8.929 | 0.000 | |
GR | −0.597 | 0.115 | −0.423 | −5.171 | 0.000 | |
3 | (Constant) | −0.067 | 0.067 | −1.005 | 0.322 | |
GSTA1 | 0.471 | 0.088 | 0.433 | 5.340 | 0.000 | |
GR | −0.767 | 0.090 | −0.544 | −8.526 | 0.000 | |
GPX1 | 0.552 | 0.101 | 0.488 | 5.452 | 0.000 | |
4 | (Constant) | −0.078 | 0.063 | −1.234 | 0.227 | |
GSTA1 | 0.546 | 0.089 | 0.502 | 6.107 | 0.000 | |
GR | −0.962 | 0.121 | −0.683 | −7.964 | 0.000 | |
GPX1 | 0.858 | 0.166 | 0.697 | 5.183 | 0.000 | |
LAP3 | −0.364 | 0.161 | −0.334 | −2.261 | 0.031 |
Targets Pattern | Toxic Prediction Precision | Non-Toxic Predictive Precision | Total Prediction Precision |
---|---|---|---|
GSTA1 | 22/22 | 10/13 | 91.43% |
GPX1 | 22/22 | 7/13 | 82.86% |
LAP3 | 0/22 | 4/13 | 11.43% |
GR | 22/22 | 5/13 | 77.14% |
LAP3, GR | 0/22 | 2/13 | 5.71% |
GSTA1, GPX1 | 22/22 | 11/13 | 94.29% |
GSTA1, GPX1, GR | 22/22 | 0/13 | 62.86% |
GSTA1, GPX1, LAP3, GR | 0/22 | 0/13 | 0.00% |
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Yan, X.; Kang, H.; Feng, J.; Yang, Y.; Tang, K.; Zhu, R.; Yang, L.; Wang, Z.; Cao, Z. Identification of Toxic Pyrrolizidine Alkaloids and Their Common Hepatotoxicity Mechanism. Int. J. Mol. Sci. 2016, 17, 318. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms17030318
Yan X, Kang H, Feng J, Yang Y, Tang K, Zhu R, Yang L, Wang Z, Cao Z. Identification of Toxic Pyrrolizidine Alkaloids and Their Common Hepatotoxicity Mechanism. International Journal of Molecular Sciences. 2016; 17(3):318. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms17030318
Chicago/Turabian StyleYan, Xinmiao, Hong Kang, Jun Feng, Yiyan Yang, Kailin Tang, Ruixin Zhu, Li Yang, Zhengtao Wang, and Zhiwei Cao. 2016. "Identification of Toxic Pyrrolizidine Alkaloids and Their Common Hepatotoxicity Mechanism" International Journal of Molecular Sciences 17, no. 3: 318. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms17030318