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Influence of Nutritional Status on the Absorption of Polyphyllin I, an Anticancer Candidate from Paris polyphylla in Rats

  • Feng-Ling Yu
  • Wei-Liang Gong
  • Fang-Jiang Xu
  • Jun-Wen Wu
  • Shailendra Shakya
  • He Zhu
Original Research Article

Abstract

Background and Objectives

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.

Methods

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.

Results

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.

Conclusions

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.

Notes

Compliance with Ethical Standards

Funding

This study was financially supported by National Natural Science Foundation of China (no. 81503365) and Natural Science Foundation of Jiangsu Province, China (no. BK20151050).

Conflicts of interest

The authors declare no conflict of interest.

Ethics approval

The study was approved by the Animal Ethics Committee of Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, P.R. China.

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Linyi Central HospitalLinyiPeople’s Republic of China
  2. 2.Department of Pharmaceutical Analysis and MetabolomicsJiangsu Province Academy of Traditional Chinese Medicine and Jiangsu Branch of China Academy of Chinese Medical SciencesNanjingPeople’s Republic of China
  3. 3.Department of Pharmacy, School of ScienceKathmandu UniversityDhulikhelNepal
  4. 4.Novo Trial SMO Co., LtdBeijingPeople’s Republic of China

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