Cichoric acid improves isoproterenol‐induced myocardial fibrosis via inhibition of HK1/NLRP3 inflammasome‐mediated signaling pathways by reducing oxidative stress, inflammation, and apoptosis

Figures

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  FIGURE 1. Chemical structure of cichoric acid.

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  FIGURE 2. Histopathological changes of the heart between the ISO group and CA treatment groups (scale bar = 50 μm, magnification: 400×). The results of H&E staining shown in (a–e) represent the Cont, ISO, CA‐L, CA‐H, and CA groups, respectively. Arrows indicate cell damage.

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  FIGURE 3. Masson's trichrome staining of the heart showing changes between the ISO group and CA treatment groups (scale bar = 50 μm, magnification: 400×). Arrow 1 shows the deposition of collagen fibers in the space between cardiomyocytes.

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  FIGURE 4. Changes in CK‐MB (a), LDH (b), and cTnI (c) expression are shown between the ISO group and CA treatment groups. Values are expressed as mean ± SD (n = 6; compared with the Cont group, ## p < .01; compared with the ISO group, **p < .01).

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  FIGURE 5. Changes in MDA (a), SOD (b), GSH (c), and CAT (d) expression are shown between the ISO group and CA treatment groups. Values are expressed as mean ± SD (n = 6; compared with the Cont group, ## p < .01; compared with the ISO group, **p < .01).

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  FIGURE 6. Changes in myocardial mitochondrion ultrastructure between the ISO group and CA treatment groups (scale bar = 2.0 μm, magnification: 7000×). (a–e) Cont, ISO, CA‐L, CA‐H, and CA groups, respectively.

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  FIGURE 7. Changes in ROS expression between the ISO group and CA treatment groups. Scale bar = 50 μm, magnification: 400×. (n=3, ## p < .01, compared to the Cont group; **p < .01, compared to the ISO group).

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  FIGURE 8. Changes in TNF‐α (a), IL‐1β (b), and IL‐18 (c) between the ISO group and CA treatment groups. Results are expressed as mean ± SD (n = 6; ## p < .01, compared to the Cont group; **p < .01, compared to the ISO group).

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  FIGURE 9. The effects of CA treatment on Bax, Bcl‐2, caspase‐3, and C‐caspase‐3 experessions as showns by western blotting (a). Changes in Bax (b), Bcl‐2 (c), caspase‐3 (d), and C‐caspase‐3 (e) protein expression between the ISO group and CA treatment groups. Results are expressed as mean ± SD (n = 3; ## p < .01, compared to the Cont group; *p < .05 **p < .01, compared to the ISO group).

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  FIGURE 10. The effects of CA treatment on collagen I, collagen III, HK1, α‐SMA, NLRP3, ASC, caspase‐1, and C‐caspase‐1 expressions as showns by western blotting (a). Changes in collagen I (b), collagen III (c), HK1 (d), α‐SMA (e), NLRP3 (f), ASC (g), caspase‐1 (h), and C‐caspase‐1 (I) protein expression between the ISO group and CA treatment groups. Results are expressed as mean ± SD (n = 3; # p < .05 and ## p < .01, compared to the Cont group; *p < .05, **p < .01 compared to the ISO group).

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  FIGURE 11. Mechanism for the protective effects of CA against ISO‐induced myocardial fibrosis.