The aim of this article is to introduce the roles and mechanisms of the JAK2/STAT3 pathway in various cardiovascular diseases, such as myocardial fibrosis, cardiac hypertrophy, atherosclerosis, myocardial infarction, and myocardial ischemiareperfusion. In addition, the effects of phytochemical ingredients and different natural plants, mainly traditional Chinese medicines, on the regulation of different cardiovascular diseases via the JAK2/STAT3 pathway are discussed. Surprisingly, the JAK2 pathway has dual roles in different cardiovascular diseases. Future research should focus on the dual regulatory effects of different phytochemical ingredients and natural plants on JAK2 to pave the way for their use in clinical trials.

Sepsis, a severe infectious disease causing multiple organ dysfunction, requires further exploration of its pathomechanisms and therapeutic options. Hydroxysafflor Yellow A (HYSA), extracted from Carthamus tinctorius L, has shown anti-inflammatory and antioxidant properties effective in treating sepsis, though its precise mechanism remains unclear. In this study, a cecum ligation puncture (CLP) model was used to evaluate HYSA’s effects on sepsis-induced organ injury. HYSA (300 mg/kg) was administered intraperitoneally 4 h post-CLP. Results showed that HYSA inhibited the inflammatory response and improved pathological scores in the liver, lungs, and kidneys. Metabolomics analysis identified key metabolites and pathways influenced by HYSA, including nicotinate and nicotinamide metabolism and glycine/serine metabolism. Network pharmacology and molecular docking identified JAK2/STAT1 as potential targets, with Western blotting confirmed that HYSA inhibits JAK2/STAT1 phosphorylation. These findings suggest that HYSA protects against sepsis-induced organ injury by regulating metabolic networks and modulating the JAK2/STAT1 pathway.

Mitochondria, the cell’s powerhouses, generate ATP to sustain essential biological functions. Dysfunctional mitochondria can lead to cell death and subsequent tissue damage. Mitochondrial impairment is a key driver of cellular dysfunction in cardiomyocytes, endothelial cells, and macrophages, contributing to cardiovascular diseases such as atherosclerosis, myocardial ischemia–reperfusion injury, and cardiac hypertrophy. The signal transducer and activator of transcription (STAT) family regulates immune responses, apoptosis, and cell proliferation. Despite evidence suggesting that STATs influence mitochondrial pathways in various cardiovascular conditions, their roles are often contradictory and context-dependent. This review examines the structural and functional dynamics of STATs, their upstream and downstream signaling networks, and therapeutic strategies targeting STAT3 (the most extensively studied isoform), with a particular focus on natural compounds and pharmacological inhibitors. By synthesizing current findings, this review offers valuable insights into STATs as potential therapeutic targets for mitochondrial dysfunction in cardiovascular diseases, while also highlighting directions for future research.