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. 2019 Aug 17;24(16):2985.
doi: 10.3390/molecules24162985.

Inhibitory Effects of Ginsenoside Ro on the Growth of B16F10 Melanoma via Its Metabolites

Affiliations

Inhibitory Effects of Ginsenoside Ro on the Growth of B16F10 Melanoma via Its Metabolites

Si-Wen Zheng et al. Molecules. .

Abstract

Ginsenoside Ro (Ro), a major saponin derived and isolated from Panax ginseng C.A. Meyer, exerts multiple biological activities. However, the anti-tumour efficacy of Ro remains unclear because of its poor in vitro effects. In this study, we confirmed that Ro has no anti-tumour activity in vitro. We explored the anti-tumour activity of Ro in vivo in B16F10 tumour-bearing mice. The results revealed that Ro considerably suppressed tumour growth with no significant side effects on immune organs and body weight. Zingibroside R1, chikusetsusaponin IVa, and calenduloside E, three metabolites of Ro, were detected in the plasma of Ro-treated tumour-bearing mice and showed excellent anti-tumour effects as well as anti-angiogenic activity. The results suggest that the metabolites play important roles in the anti-tumour efficacy of Ro in vivo. Additionally, the haemolysis test demonstrated that Ro has good biocompatibility. Taken together, the findings of this study demonstrate that Ro markedly suppresses the tumour growth of B16F10-transplanted tumours in vivo, and its anti-tumour effects are based on the biological activity of its metabolites. The anti-tumour efficacy of these metabolites is due, at least in part, to its anti-angiogenic activity.

Keywords: B16F10; anti-tumour; ginsenoside Ro; metabolites.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Effects of Ro on tumour growth in B16F10 tumour-bearing mice. (A) Image of tumour masses. (B) Weight of tumour masses. (C) Tumour volume changes in B16F10 tumour xenograft mice. ** p < 0.01 vs. model group. CTX: cyclophosphamide.
Figure 2
Figure 2
Effects of Ro on B16F10 melanoma cell viability. The results of the control (0 µg/mL) were normalised to 100%, and the results from Ro-treated cells were expressed as % of the control.
Figure 3
Figure 3
Representative chromatograms of Ro and its metabolites in the plasma. The tumour-bearing mice were administered Ro for 15 successive days, after which they were sacrificed, and the plasma was collected and evaluated. (A) Extracted ion chromatogram (EIC) at m/z 955.5; (B) EIC at m/z 794.5; (C) EIC at m/z 631.5; (D) EIC at m/z 455.5; (E) chromatogram of standard oleanolic acid (OA) (45.2 ng/inj, EIC at m/z 455.5). (1) Ro: ginsenoside Ro; (2) IVa: chikusetsusaponin IVa; (3) R1: zingibroside R1; (4) E: calenduloside E.
Figure 4
Figure 4
Negative collision-induced dissociation (CID) spectrum of compounds 14. (1) Ro: ginsenoside Ro; (2) IVa: chikusetsusaponin IVa; (3) R1: zingibroside R1; (4) E: calenduloside E.
Figure 5
Figure 5
Structures of Ro, R1, IVa, and E.
Figure 6
Figure 6
Effects of IVa, R1, and E on B16F10 melanoma cells in vitro. The results of the control (0 µg/mL) were normalised to 100%, and the results from treated cells were expressed as % of the control (* p < 0.05, ** p < 0.01).
Figure 7
Figure 7
Effects of Ro metabolites on changes in tumour weight and tumour volume in B16F10 tumour xenograft mice. R1 (25 mg/kg), IVa (25 mg/kg), and E (5 mg/kg) were intraperitoneally injected into mice for 15 consecutive days. Values are expressed as the mean ± standard deviation (SD) of six mice.
Figure 8
Figure 8
Results of tube formation. (A) The human umbilical vein endothelial cells (HUVECs) tubular structures were imaged under a microscope at 100× magnification. (B) Tube networks were quantified using Image-Pro Plus 6.0 software (Media Cybernetics, Silver Spring, MD, USA). The tube length was calculated (* p < 0.05, ** p < 0.01).
Figure 9
Figure 9
Haemolysis test result of Ro.

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