FIGURE 1

GXNT restored blood circulation in PHZ-stimulated zebrafish thrombosis model. (A) Time line of drug protection and PHZ treatment. (B) Toxicity effects of different doses of GXNT on fish survival and general development. (C,D) Representative images (C) and quantification (D) of erythrocytes circulation in Tg (LCR:eGFP) fish embryos with different treatment. The concentration for the GXNT group was 1 mg/ml. Red triangles marked erythrocytes aggregation. #Compared with the control group; *compared with the model group; ## or **p < 0.01. (E) Comparison of the therapeutic effects in blood circulation between embryos treated with single herb and GXNT. Groups labeled without a common letter were significantly different (p < 0.05). The p-value of t-test comparing the observed effect with the additive effect is shown on (E).
FIGURE 2

GXNT restored platelet circulation and inhibited hemolysis in PHZ-stimulated zebrafish thrombosis model. (A,B) Representative images (A) and quantification (B) of platelets circulation in Tg (CD41:eGFP) fish embryos with different treatment. Red arrows marked circulating platelets. (C,D) Percentage of GFP labeled erythrocytes of Tg (LCR:eGFP) fish embryos with different treatment. #Compared with the control group; *compared with the model group; ## or **p < 0.01.
FIGURE 3

Characterization of the chemical composition in GXNT. (A) Molecular networking of GXNT, the main clusters consist of sugar, phenolic acid, terpene. GNPS library annotated nodes are represented in red. (B) HPLC chromatogram of GXNT, Salvia miltiorrhiza Bunge and Ligusticum striatum DC.
FIGURE 4

Cyptotanshinone and senkyunolide I showed synergistic anti-thrombotic effects in PHZ-stimulated zebrafish. (A) Quantification of erythrocytes circulation in Tg (LCR:eGFP) fish embryos treated with different compounds. #Compared with the control group; *compared with the model group; ## or **p < 0.01. (B,C) Representative images (C) and quantification (B) of erythrocytes circulation in Tg (LCR:eGFP) fish embryos with labeled treatment. Groups labeled without a common letter were significantly different (p < 0.05). The p-value of t-test comparing the observed effect with the additive effect is shown on (B).
FIGURE 5

GXNT and cryptotanshinone inhibits oxidative damages in PHZ-stimulated zebrafish. (A,B) Representative images (A) and quantification (B) of the fluorescence signals of DCFH-DA probe in 3.5 dpf control embryos or PHZ treated embryos with or without drug protection. (C) Concentration of MDA in embryos with different treatment. #Compared with the control group; *compared with the model group; *p < 0.05, ## or **p < 0.01.

FIGURE 6

Expression of representative factors in coagulation cascade and platelet activation in PHZ-stimulated zebrafish. (A) Expression of coagulation and platelet activation related factors with significant alterations in embryos with GXNT or compound treatment, compared with PHZ only stimulated group. (B) A proposed model showing the synergistic mechanism of GXNT and its major components in thrombosis regulation (created with BioRender.com).. The complete set of data are shown in Supplementary Figure S3. #Compared with the control group; *compared with the model group; # or *p < 0.05, ## or **p < 0.01.
Acknowledgments
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