| Title |
Influence of Nutritional Status on the Absorption of Polyphyllin I, an Anticancer Candidate from Paris polyphylla in Rats
|
|---|---|
| Published in |
European Journal of Drug Metabolism and Pharmacokinetics, March 2018
|
| DOI | 10.1007/s13318-018-0473-y |
| Pubmed ID | |
| Authors |
Feng-Ling Yu, Wei-Liang Gong, Fang-Jiang Xu, Jun-Wen Wu, Shailendra Shakya, He Zhu |
| Abstract |
Protein-calorie malnutrition (PCM) is one of the most suffered complications in cancer patients. Polyphyllin I (PPI), a saponin isolated from rhizome of Paris polyphylla, is a potential candidate in cancer therapy. In this study, the influence of nutritional status on the absorption of PPI in rats was explored after oral administration. PCM rats, namely mal-nourished (MN) rats, were induced from well-nourished (WN) rats by caloric restriction protocol. Intestinal absorption of PPI in WN and MN rats was evaluated by pharmacokinetic and intestinal perfusion methods. The potential mechanisms between two groups were investigated on the basis of intestinal permeability, intestinal efflux and PPI's depletions in vivo. The intestinal permeability was analyzed by determining the concentration of paracellular marker transport in serum and the expression of junction proteins in intestine. The intestinal efflux was evaluated through comparing the protein level of P-glycoprotein (P-gp) in intestine, and the depletions of PPI and/or generation of its metabolites in liver and intestines were analyzed by liquid chromatography triple quadrupole mass spectrometry (LC-MS/MS) method. Compared to WN rats, the oral systemic exposure of PPI was significantly increased in MN rats, evidenced by significant enhancement of maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC0-60h) by more than 2.51- and 3.71-folds as well as terminal elimination half-life (t1/2) prolonged from to 7.3 to 14.1 h. Further studies revealed that the potential mechanism might be associated with combined contribution of improved intestinal absorption and depressed deglycosylation of PPI in MN rats. Furthermore, enhanced intestinal absorption of PPI was benefited from increased intestinal permeability and decreased intestinal efflux in MN rats. Meanwhile, the former manifested as increased transport of paracellular marker and decreased junction proteins levels, while the later evidenced by reduced P-gp expression. The oral exposure of PPI was enhanced in MN rats, which suggested that nutritional status alters the absorption of PPI, and thus the dosage of PPI should be modified during the treatment of cancer patient with PCM. |
X Demographics
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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 15 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 15 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Master | 3 | 20% |
| Student > Bachelor | 2 | 13% |
| Student > Doctoral Student | 2 | 13% |
| Researcher | 1 | 7% |
| Unknown | 7 | 47% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 5 | 33% |
| Pharmacology, Toxicology and Pharmaceutical Science | 1 | 7% |
| Nursing and Health Professions | 1 | 7% |
| Environmental Science | 1 | 7% |
| Unknown | 7 | 47% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. 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 29 March 2018.
All research outputs
#20,472,403
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Outputs from European Journal of Drug Metabolism and Pharmacokinetics
#369
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Outputs of similar age from European Journal of Drug Metabolism and Pharmacokinetics
#8
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