Supplementation of Saponins from Leaves of Panax quinquefolius Mitigates Cisplatin-Evoked Cardiotoxicity via Inhibiting Oxidative Stress-Associated Inflammation and Apoptosis in Mice

Figure 1. (A) Fourteen saponins from leaves of P. quinquefolius are confirmed by HPLC analysis, chromatograms and chemical structures of these saponins mainly includes panaxadiol-type ginsenosides Rb1, Rc, Rb2, Rb3; Rd, 20(S)-ginsenoside Rg3, 20(R)-ginsenoside Rg3 and panaxatriol-type ginsenosides Rg1, Re, Rf, Rg6, F4, Rk3, and Rh4. (B) The structures of these fourteen saponins.

Figure 2. Effect of PQS on cisplatin-induced changes in heart tissues of mice (A). Cisplatin + PQS (125 mg/kg), Cisplatin + PQS (250 mg/kg) groups (H&E × 200). Effects of cisplatin and PQS on the serum levels of related markers CK (B), cTnT (C), viability of CK-MB (D), and concentration of CK-MB (E). All data were expressed as mean ± S.D. * p < 0.05 or ** p < 0.01 or *** p < 0.01 comparing with normal group. # p < 0.05 or ## p < 0.01 or ### p < 0.01 comparing with cisplatin group.

Figure 3. Effects of PQS on the levels of (A) MDA, (B) superoxide dismutase (SOD) and (C) glutathione (GSH). All data were expressed as mean ± S.D. * p < 0.05 or ** p < 0.01 comparing with normal group. # p < 0.05 or ## p < 0.01 comparing with cisplatin group.

Figure 4. Effect of PQS on cisplatin-induced changes in inflammatory markers in heart tissues of mice. (A) Tumor necrosis factor-a (TNF-α); (B) Interleukin-1β (IL-1β); (C) Myeloperoxidase (MPO) activity; (D) Lactate dehydrogenase (LDH); (E) ALT activity; (F) PQS exerted great changes on expression of COX-2 and iNOS in heart tissues, the expression levels of COX2 (Green) and iNOS (Red) in tissue section isolated from different groups were assessed by immunofluorescence. (G) Quantitative analysis of scanning densitometry for cleaved COX-2 (H) Quantitative analysis of scanning densitometry for cleaved iNOS. All data were expressed as mean ± S.D. ** p < 0.01 comparing with normal group. # p < 0.05 or ## p < 0.01 comparing with cisplatin group.

Figure 5. The expression of iNOS, COX-2, TNF-α and IL-1β were measured by western blotting analysis (A). Quantitative analysis of scanning densitometry for iNOS (B); COX-2 (C); IL-1β (D); TNF-α (E). All data were expressed as mean ± S.D. * p < 0.05 or ** p < 0.01 comparing with normal group. ## p < 0.01 comparing with cisplatin group.

Figure 6. (A). Quantitative analysis of scanning densitometry for p-NF-κB (B); p-IκBα (C); p-IKKα (D); p-IKKβ (E). All data were expressed as mean ± S.D. * p < 0.05 or ** p < 0.01 comparing with normal group. # p < 0.05 or ## p < 0.01 comparing with cisplatin group.

Figure 7. (A) The blots of Bax, Bcl-2, Bad, caspase 3, cleaved caspase 3, caspase 8, cleaved caspase 8 and caspase 9, cleaved caspase 9 were standardized to that of β-actin; Quantitative analysis of scanning densitometry for Bax (B), Bcl-2 (C), Caspase-3 (D), Caspase-8 (E), Caspase-9 (F). (G) Representative photomicrographs of cardiac immunohistochemically staining for Hoechst 33258, (H) Bax staining area. The percentage of apoptosis (I) and Bcl-2 staining area in indicated groups. Scale bars data were expressed as mean ± S.D. * p < 0.05 or ** p < 0.01 comparing with normal group. # p < 0.05 or ## p < 0.01 comparing with cisplatin group.

Figure 8. Mice pretreated with PQS or saline for 7days, given with or without cisplatin at day 7th, 9th, 11th and 13th. (A) Representative western blots depicting total and phosphorylated PI3K, Akt, GSK-3β. Quantitative analyses of the p-PI3K/PI3K, p-Akt/Akt, and p-GSK-3β/GSK-3β expression ratios are shown (B–D). All data were expressed as mean ± S.D. * p < 0.05, ** p < 0.01 comparing with normal group. # p < 0.05, ## p < 0.01 comparing with cisplatin group.

Figure 9. Scheme Summarizing the Inhibition of Cisplatin-Induced Cardiotoxicity by PQS via the Upregulation of PI3K/Akt/GSK-3β Mediated Inhibition of Oxidative Stress Inflammation and Apoptosis.

Figure 10. Experimental Flow Chart.