Thymus quinquecostatus Celak., a member of the genus Thymus , is an edible medicinal plant rich in polyphenolic compounds (TCPRF). Although accumulating evidence suggests the beneficial effects of Thymus species, the underlying mechanisms of TCPRF in cardiovascular protection remain to be fully elucidated. Endoplasmic reticulum stress (ERS) has been implicated in the pathogenesis of myocardial ischemia/reperfusion injury (MIRI) and is considered a promising therapeutic target. In this study, network pharmacology prediction, GEO dataset validation, and molecular docking analysis were integrated to systematically investigate the potential molecular mechanisms of TCPRF against MIRI via ERS regulation, with HSPA5 identified as a key target. Furthermore, we aimed to experimentally validate the effects of TCPRF on ERS-mediated cardiomyocyte apoptosis in a rat model of MIRI. The results demonstrated that TCPRF treatment significantly ameliorated myocardial pathological alterations, reduced myocardial infarct size, and decreased serum levels of CK and LDH in MIRI rats. Moreover, TCPRF administration downregulated the expression of GRP78, ATF6, and CHOP, increased the Bcl-2/Bax ratio, and suppressed cardiomyocyte apoptosis in myocardial tissues. Treatment with TCPRF ameliorates endoplasmic reticulum stress-mediated cardiomyocyte apoptosis induced by myocardial ischemia-reperfusion injury, which provides an experimental basis for subsequent studies into the regulatory targets of TCPRF in the protection against myocardial ischemia-reperfusion injury. • Network pharmacology identifies candidate TCPRF targets against MIRI. • Molecular docking confirms the high affinity of TCPRF for GRP78. • TCPRF reduces myocardial injury, infarct size, CK and LDH levels in MIRI rats. • TCPRF inhibits ERS-mediated apoptosis in MIRI rats.
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Xie et al. (2026) studied this question.
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