Ginger-Processed American Ginseng Alleviates Myocardial Injury Induced by Acute Cold Exposure/Rewarming by Remodeling Gut Microbiota to Activate the AMPK/PGC-1α/PPARα Pathway.

Acute cold exposure/rewarming (ACE/R) disrupts cardiovascular homeostasis and causes severe myocardial injury, yet effective countermeasures are scarce. Ginger-processed American ginseng (GPAG), a medicine-food homologous herb, exerts anti-inflammatory, antioxidant, and metabolic-regulatory effects; however, its cardioprotective mechanisms against ACE/R remain unclear. An ACE/R rat model was established by exposing rats to -15 °C for 6 h followed by 24 °C rewarming for 12 h, with 7-day GPAG gavage (1 and 2 g/kg) prior to cold exposure. Integrated multiomics, fecal microbiota transplantation (FMT), and fecal metabolite-cardiomyocyte intervention assays were employed to elucidate the gut-heart axis mechanism. GPAG ameliorated hemorheological disorders, restored cardiac dysfunction, and attenuated myocardial lesions. Mechanistically, GPAG remodels gut microbiota to generate functional metabolites that activate the myocardial AMPK/PGC-1α/PPARα pathway via the gut-heart axis, thereby optimizing cardiac energy metabolism and restoring mitochondrial homeostasis to alleviate ACE/R-triggered myocardial damage.