Bioguided Fraction and Isolation of the Antitumor Components from Phyllanthus niruri L

Abstract

Phyllanthus niruri L., a well-known medicinal plant, has been used as a folk antitumor remedy in the worldwide scale. However, the antitumor components in P. niruri have not been reported. In order to verify the antitumor components of P. niruri and the plants which have the high content of these components, we isolated the antitumor components with bioguided fraction and isolation, by different chromatographic methods from the ethyl acetate fraction of P. niruri., and identified them as ethyl brevifolincarboxylate and corilagin by ¹H-NMR, ¹³C-NMR, 2D-NMR, and mass spectrometric analyses. Cell cytotoxicity assays showed that corilagin has broad-spectrum antitumor activity, a better antitumor potential, and lower toxicity in normal cells. Besides, the coefficient of drug interaction (CDI) of 10 μM corilagin and 20 μM cDDP reached up to 0.77, which means corilagin can promote the antitumor activity of cDDP. Furthermore, by the extensive screening among 10 species of plants reported to contain corilagin, we found that Dimocarpus longan Lour. has the maximum content of corilagin. In conclusion, corilagin is the major active antitumor composition in P. niruri. L. on HCC cells and has high content in D. longan.

Figure 1

Scheme of bioguided fractionation and isolation of compounds from P. niruri.

Figure 2

Chemical structures of isolated constituents from P. niruri.

Figure 3

IC₅₀ value of two compounds and positive control cDDP on HCC cell lines.

Figure 4

IC₅₀ value of corilagin on different cancer cell lines.

Figure 5

The synergistic antitumor activity of corilagin combined with cDDP on SMMC7721 cells. CDI for the combination treatment of corilagin with cDDP on SMMC7721 cells. Data represent Means ± SE from 3 independent experiments.