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.
Feng S, Fu W, et al. • Journal of agricultural and food chemistry • 2026
Ginger-processed American ginseng alleviates acute cold exposure/rewarming-induced myocardial injury by remodeling 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.
Key Findings
Results
GPAG ameliorated hemorheological disorders and restored cardiac dysfunction induced by acute cold exposure/rewarming in rats.
The ACE/R model was established by exposing rats to -15°C for 6 hours followed by 24°C rewarming for 12 hours.
GPAG was administered by gavage for 7 days prior to cold exposure at doses of 1 g/kg and 2 g/kg.
GPAG treatment restored cardiac dysfunction and attenuated myocardial lesions induced by ACE/R.
Hemorheological disorders caused by ACE/R were ameliorated by GPAG pretreatment.
Results
GPAG remodeled gut microbiota composition in ACE/R-exposed rats.
Integrated multiomics approaches were employed to characterize gut microbiota changes.
Fecal microbiota transplantation (FMT) was used to confirm the causal role of gut microbiota remodeling in GPAG's cardioprotective effects.
GPAG-induced gut microbiota remodeling led to the generation of functional metabolites relevant to cardioprotection.
The gut-heart axis was identified as the mechanistic link between microbiota changes and cardiac outcomes.
Results
GPAG activated the myocardial AMPK/PGC-1α/PPARα pathway through gut microbiota-derived metabolites.
Fecal metabolite-cardiomyocyte intervention assays were used to demonstrate that gut-derived metabolites directly activate the AMPK/PGC-1α/PPARα pathway in cardiomyocytes.
Activation of this pathway was associated with optimization of cardiac energy metabolism.
The AMPK/PGC-1α/PPARα pathway activation was linked to restoration of mitochondrial homeostasis.
The mechanistic pathway connected gut microbiota remodeling to cardiac protection via specific metabolite signaling.
Results
GPAG restored mitochondrial homeostasis in myocardial tissue following ACE/R-induced injury.
Mitochondrial homeostasis disruption was identified as a key feature of ACE/R-induced myocardial damage.
GPAG treatment at 1 g/kg and 2 g/kg doses restored mitochondrial homeostasis.
Restoration of mitochondrial function was mechanistically downstream of AMPK/PGC-1α/PPARα pathway activation.
Optimized cardiac energy metabolism resulting from mitochondrial restoration contributed to alleviation of myocardial damage.
Results
Fecal microbiota transplantation confirmed that the gut microbiota remodeling by GPAG is causally responsible for its cardioprotective effects.
FMT was employed as one of the key experimental approaches alongside integrated multiomics.
This approach distinguished microbiota-mediated effects from direct pharmacological effects of GPAG.
The FMT data supported the conclusion that GPAG acts through remodeling gut microbiota rather than solely through direct cardiac effects.
Background
GPAG exerts anti-inflammatory, antioxidant, and metabolic-regulatory effects relevant to cardioprotection against ACE/R.
GPAG is a medicine-food homologous herb produced by processing American ginseng with ginger.
Prior literature established anti-inflammatory, antioxidant, and metabolic-regulatory properties of GPAG.
The cardioprotective mechanisms against ACE/R-induced injury were previously unclear prior to this study.
The current study established the gut-heart axis as the primary mechanistic framework for GPAG's cardioprotective action.
What This Means
This research suggests that ginger-processed American ginseng (GPAG), a traditional herbal preparation, can protect the heart from damage caused by sudden cold exposure followed by rewarming — a situation that can be dangerous for cardiovascular health. Using a rat model where animals were exposed to -15°C for 6 hours and then rewarmed, researchers found that giving rats GPAG orally for 7 days before cold exposure significantly reduced heart damage, improved blood flow properties, and restored normal heart function compared to untreated animals.
The study investigated how GPAG achieves these protective effects using a combination of advanced molecular analysis techniques and gut microbiota transplant experiments. The researchers discovered that GPAG works primarily by changing the composition of bacteria living in the gut, which in turn produces beneficial metabolites (chemical compounds) that travel to the heart and activate an important energy-regulating pathway called AMPK/PGC-1α/PPARα. This activation helps heart cells manage energy more efficiently and maintain healthy mitochondria — the energy-producing structures within cells — thereby protecting against cold-induced damage.
This research suggests that the gut microbiome plays a key role in how herbal medicines protect the heart, introducing what the authors call a 'gut-heart axis' mechanism. The findings are potentially relevant for people exposed to extreme cold conditions, such as outdoor workers or people living in cold climates, and highlight GPAG as a possible dietary or preventive strategy worth further investigation. The use of a natural food-medicine product that works through the gut microbiome rather than direct drug mechanisms may offer a different approach to cardiovascular protection, though further research in humans would be needed.
Feng S, Fu W, Xu H, Ma W, Zhang Z, Sui D, et al.. (2026). 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.. Journal of agricultural and food chemistry. https://doi.org/10.1021/acs.jafc.6c04969