Guanxinjing ameliorates coronary microvascular dysfunction in myocardial ischemia-reperfusion injury by alleviating inflammation and restoring endothelial function.

BACKGROUND

Coronary microvascular dysfunction (CMD) secondary to myocardial ischemia-reperfusion injury (MIRI) is characterized by profound inflammatory activation and endothelial impairment. Guanxinjing compound (GXJC) is a clinical drug widely used for coronary heart disease and angina pectoris closely associated with coronary microvascular function. Its efficacy and mechanisms against MIRI-induced CMD remain elusive.

METHODS

The chemical profiling of GXJC was performed via UHPLC-Q-Exactive HRMS. Network pharmacology analysis (NPA) screened the core targets and key pathways of GXJC. In vivo, C57BL/6 mice received 7-day GXJC pretreatment before MIRI modeling, followed by comprehensive evaluation using Evans blue/TTC staining, Hematoxylin and eosin staining (H&E), apoptosis assessment by TUNEL staining, immunofluorescence, Western blotting, and ELISA. For in vitro studies, a TNF-α-induced inflammatory injury model in HUVECs was established to dissect the underlying mechanisms.

RESULTS

UHPLC-Q-Exactive HRMS analysis identified 256 bioactive compounds in GXJC. NPA predicted the TNF signaling pathway as a potential key mechanism through which GXJC may ameliorate MIRI. In vivo, GXJC treatment reduced myocardial infarct size and cardiomyocyte apoptosis while downregulating pro-inflammatory factors. Mechanistically, GXJC suppressed vascular inflammation by inhibiting IL-6, IL-1β, and CCL2, attenuated endothelial contractile and diastolic dysfunction by modulating the eNOS/NO/ET-1 axis, and alleviated endothelial injury and thrombosis by lowering FGL2 and p-selectin levels.

CONCLUSION

Our study demonstrates that GXJC acts as a potential therapeutic agent for MIRI-induced myocardial injury and associated microvascular endothelial dysfunction through the dual modulation of inflammatory cascades and microvascular endothelial protection. These mechanistic insights support its future clinical development for microvascular complications following revascularization.