Key result
Tricholoma matsutake polypeptide improves LVEF ~21% in doxorubicin-treated rats by restoring metabolic flexibility.
Why the study?
Doxorubicin-induced cardiotoxicity triggers early senescence-like phenotypes and metabolic maladaptation without effective therapies, and the potential of Tricholoma matsutake polypeptide to modulate cardiac energy metabolism remained unexplored.
Does Tricholoma matsutake polypeptide prevent doxorubicin-induced cardiotoxicity and senescence in preclinical models?
Does Tricholoma matsutake polypeptide prevent doxorubicin-induced cardiotoxicity and senescence in preclinical models?
Absolute Event Rate: 81% vs 60%
p-value: p=<0.05
Tricholoma matsutake polypeptide protects against doxorubicin-induced cardiotoxicity by reprogramming energy metabolism and restoring autophagic flux, highlighting its potential as a cardioprotective adjuvant.
TMP may mitigate DIC via metabolic effects in rats; leaves open clinical translation.
Background Doxorubicin (Dox)-induced cardiotoxicity (DIC) is initiated by acute stress that triggers early senescence-like phenotypes and severe metabolic maladaptation, yet effective therapeutic interventions remain elusive. Tricholoma matsutake polypeptide (TMP), a bioactive component from a medicinal fungus, exhibits antioxidant properties, but its potential to modulate cardiac energy metabolism remains unexplored. Methods In vivo , Sprague-Dawley rats were administered Dox (20 mg/kg, i.p.) with or without TMP (200/400 mg/kg/day) for 7 days. Cardiac function was assessed via high-resolution echocardiography, and metabolic signatures were decoded using LC-MS/MS-based untargeted metabolomics. In vitro , H9c2 cardiomyocytes were co-treated with Dox (5 μM) and TMP (30 μg/mL). Senescence phenotypes (SA- β -gal), mitochondrial dynamics (JC-1/Fura-2AM), and energy metabolites (ATP/NAD+) were quantified. Mechanistic axes were interrogated via Western blotting. Results TMP significantly attenuated Dox-induced cardiac dysfunction, interstitial fibrosis, and inflammation. Metabolomics revealed that TMP mitigated the glycolysis-dominant metabolic reprogramming, restored phospholipid homeostasis, and preserved the nucleotide pool. In cardiomyocytes, TMP antagonized premature senescence and suppressed ROS generation without compromising Dox’s antitumor efficacy in MCF-7 cells. Mechanistically, TMP alleviated the Dox-induced blockade of autophagic flux (restoring Beclin1/p-Parkin) and reactivated the AMPK/Sirt1/PGC-1α energy-sensing pathway, thereby preserving the ATP/NAD + reserve. Conclusion TMP functions as a metabolic modulator that protects against DIC by reprogramming energy metabolism and restoring mitochondrial quality control. These findings highlight TMP as a promising adjuvant for preserving cardiovascular health in cancer survivors.
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Ye et al. (2026) studied Doxorubicin-induced cardiotoxicity (n=20). Tricholoma matsutake polypeptide vs. Doxorubicin alone was evaluated on Left Ventricular Ejection Fraction (LVEF) (p=<0.05). Tricholoma matsutake polypeptide significantly attenuated doxorubicin-induced cardiac dysfunction in rats, improving left ventricular ejection fraction from 60% to 81% (p<0.05) by restoring metabolic flexibility and autophagic flux.
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