Zhigancao Decoction Attenuates Myocardial Ischemia–Reperfusion Injury in Rats in Association with Modulation of JAK2/STAT3/HIF-1α Signaling

Objective Zhigancao Decoction (ZGCD), a classic traditional Chinese formula, is widely used for cardiovascular disorders, but its role in myocardial ischemia–reperfusion injury (MIRI) is unclear. This study evaluated the cardioprotective effects of ZGCD in rats and investigated the association with JAK2/STAT3/HIF-1α signaling. Methods A left anterior descending coronary artery ligation–reperfusion model was established in rats, which were randomized to sham, MIRI, low- and high-dose ZGCD, JAK2 inhibitor, or JAK2 inhibitor + ZGCD groups. After 4 weeks of gavage, cardiac function and infarct size were assessed, and myocardial histology, inflammatory and oxidative stress markers, and JAK2/STAT3/HIF-1α protein expression were measured. Results ZGCD improved left ventricular ejection fraction and reduced infarct size, attenuated histological damage, decreased serum TNF-α, IL-1β, malondialdehyde and myocardial reactive oxygen species, and increased IL-10 and superoxide dismutase activity compared with MIRI alone. ZGCD also enhanced myocardial p-JAK2/JAK2 and p-STAT3/STAT3 ratios and HIF-1α expression, whereas the JAK2 inhibitor largely counteracted these functional and molecular benefits. Conclusion ZGCD attenuates MIRI in rats, which is accompanied by coordinated anti-inflammatory and antioxidant effects and enhanced JAK2/STAT3/HIF-1α signaling, supporting its potential as an adjunctive cardioprotective strategy.