Screening of anti-heart failure active compounds from fangjihuangqi decoction in verapamil-induced zebrafish model by anti-heart failure index approach

Figures

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  FIGURE 1. Verapamil-induced heart failure model in zebrafish (A) Experimental scheme for heart failure model in zebrafish. (B) Representative images of vehicle-treated and verapamil-treated zebrafish heart. The heart of ES was shown in red line, and the heart of ED was shown in yellow line; ES: end systole, ED: end diastole (C–H) Quantification of cardiac function in Tg(cmlc2: eGFP) zebrafish larvae with verapamil. HR: heart rate, FAC: fractional area change, SV: stroke volume, FS: fractional shortening, EF: ejection fraction, CO: cardiac output. N ≥ 20. # p < 0.05 vs. Control, ## p < 0.01 vs. Control.

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  FIGURE 2. FJHQD alleviates cardiac function in verapamil-induced heart failure model (A) Experimental scheme for heart failure model in zebrafish. (B) Representative images of vehicle-treated and verapamil-treated zebrafish heart. The heart of ES was shown in red line, the heart of ED was shown in yellow line (C–H) Quantification of cardiac function in Tg(cmlc2: eGFP) zebrafish larvae treated with FJHQD. n ≥ 19. # p < 0.05 vs. Control, ## p < 0.01 vs. Control, * p < 0.05 vs. Model, ** p < 0.01 vs. Model.

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  FIGURE 3. The therapeutic effects of botanical drugs on verapamil-induced heart failure model in zebrafish. Representative images (A) and quantification (B–G) of cardiac function in Tg (cmlc2: eGFP) zebrafish larvae treated with botanical drugs. N ≥ 15. # p < 0.05 vs. Control, ## p < 0.01 vs. Control, * p < 0.05 vs. Model, ** p < 0.01 vs. Model.

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  FIGURE 4. FJHQD, STR and GRR inhibit oxidative damages in verapamil-induced heart failure zebrafish. Representative images (A) and quantification (B) of the fluorescence signals of DCFH-DA probe in control or verapamil treated larvae with or without botanical drugs extracts. N ≥ 11. # p < 0.05 vs. Control, ## p < 0.01 vs. Control, * p < 0.05 vs. Model, ** p < 0.01 vs. Model.

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  FIGURE 5. The therapeutic effects of the main components of botanical drugs on verapamil-induced heart failure model in zebrafish (A–C) Quantification of cardiac function in Tg(cmlc2: eGFP) zebrafish larvae treated with main components of STR, AR and GRR. N ≥ 10. # p < 0.05 vs. Control, ## p < 0.01 vs. Control, * p < 0.05 vs. Model, ** p < 0.01 vs. Model.

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  FIGURE 6. The therapeutic effects of main ingredients in active components on verapamil-induced heart failure model in zebrafish (A–F) Quantification of cardiac function in Tg(cmlc2: eGFP) zebrafish larvae treated with ingredients. (G) Quantification indicators of AHFI, the dotted line indicates an AHFI value of 0.6. N ≥ 6. # p < 0.05 vs. Control, ## p < 0.01 vs. Control, * p < 0.05 vs. Model, ** p < 0.01 vs. Model.

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  FIGURE 7. Glycyrrhizic acid, licochalcone A and calycosin inhibit oxidative damages in verapamil-induced heart failure zebrafish. Representative images (A) and quantification (B) of the fluorescence intensities of DCFH-DA probe in Control larvae or verapamil treated larvae with or without sample protection. N ≥ 15. # p < 0.05 vs. Control, ## p < 0.01 vs. Control, * p < 0.05 vs. Model, ** p < 0.01 vs. Model.

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  FIGURE 8. The mRNA relative expression of nppa, tnfa, il1b, il6, caspase 1 and caspase 3. N = 3. # p < 0.05 vs. Control, ## p < 0.01 vs. Control, * p < 0.05 vs. Model, ** p < 0.01 vs. Model.

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  FIGURE 9. FJHQD and its active ingredients may exert anti-heart failure activity through pathways related to inflammation and apoptosis.