Frontiers in pharmacology · 2026
Platycodin D alleviates cardiac hypertrophy in the treatment of heart failure by inhibiting p53-dependent BCL-2/Bax/caspase-3 signaling pathway.
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Li Yingrui, Li Heng, Liu Bin, Li Yu
Аннотация
INTRODUCTION: Cardiac hypertrophy drives heart failure progression, with cardiomyocyte apoptosis playing a central role. Platycodin D (PLD), a bioactive saponin derived from Platycodon grandiflorum, exhibits cardioprotective properties, but its therapeutic potential and mechanisms in heart failure remain poorly understood.
METHODS: In this study, we employed a mouse model of isoprenaline (ISO)-induced heart failure to investigate the therapeutic potential of PLD. Mice were administered PLD at doses of 12.5, 25, or 50 mg/kg/d for 4 weeks to evaluate its effects on cardiac function and hypertrophy. To elucidate the underlying mechanisms, we performed network pharmacology analysis, which identified p53 as a candidate target of PLD. The functional role of p53 was further assessed through pharmacological interventions, comparing the effects of PLD with those of the p53 inhibitor pifithrin-α (PFT-α) and examining whether p53 activation could abrogate PLD-mediated cardioprotection.
RESULTS: PLD dose-dependently improved cardiac function and attenuated cardiac hypertrophy in ISO-induced HF mice. Network pharmacology and molecular docking identified p53 as a direct binding partner of PLD. PLD alleviated the apoptosis of cardiomyocyte by inhibition p53 depended on Bcl-2/Bax/caspase-3 signaling pathway. The cardioprotective effects of PLD were comparable to those of the p53 inhibitor pifithrin-α (PFT-α). But, these benefits were abolished upon p53 activation.
CONCLUSION: This study demonstrates that PLD attenuates ISO-induced cardiac hypertrophy and heart failure by inhibiting the p53-mediated Bcl-2/Bax/caspase-3 apoptotic pathway. These findings establish PLD as a promising therapeutic candidate for heart failure.
METHODS: In this study, we employed a mouse model of isoprenaline (ISO)-induced heart failure to investigate the therapeutic potential of PLD. Mice were administered PLD at doses of 12.5, 25, or 50 mg/kg/d for 4 weeks to evaluate its effects on cardiac function and hypertrophy. To elucidate the underlying mechanisms, we performed network pharmacology analysis, which identified p53 as a candidate target of PLD. The functional role of p53 was further assessed through pharmacological interventions, comparing the effects of PLD with those of the p53 inhibitor pifithrin-α (PFT-α) and examining whether p53 activation could abrogate PLD-mediated cardioprotection.
RESULTS: PLD dose-dependently improved cardiac function and attenuated cardiac hypertrophy in ISO-induced HF mice. Network pharmacology and molecular docking identified p53 as a direct binding partner of PLD. PLD alleviated the apoptosis of cardiomyocyte by inhibition p53 depended on Bcl-2/Bax/caspase-3 signaling pathway. The cardioprotective effects of PLD were comparable to those of the p53 inhibitor pifithrin-α (PFT-α). But, these benefits were abolished upon p53 activation.
CONCLUSION: This study demonstrates that PLD attenuates ISO-induced cardiac hypertrophy and heart failure by inhibiting the p53-mediated Bcl-2/Bax/caspase-3 apoptotic pathway. These findings establish PLD as a promising therapeutic candidate for heart failure.