Doxorubicin (Dox)-induced cardiotoxicity (DIC) was characterized by severe myocardial damage that might progress to irreversible heart failure. There were limited options available for the prevention and treatment of DIC. Chicory (Cichorium intybus L.) has demonstrated notable cardioprotective effects. However, its potential to mitigate DIC remains unexplored. This study aimed to assess the therapeutic potential of chicory in alleviating DIC and elucidate its active ingredients and potential molecular mechanism. Male Sprague-Dawley (SD) rats were used to construct DIC models. The rats were prophylactically gavaged chicory to evaluate the therapeutic effect of chicory on DIC. The UPLC-QExactivePlus system was used for the subsequent analysis of heart tissue samples to reveal the potential active ingredients of chicory. The binding of chicory components to uncoupling protein 2 (UCP2) and NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) was validated using surface plasmon resonance (SPR). Highly binding ingredients were then utilized in an H9c2 cell model to validate underlying mechanisms. Chicory alleviated Dox-induced cardiac dysfunction and myocardial structural injury, and reversed mitochondrial damage. These protective effects may be attributed to its activation of UCP2 and inhibition of NLRP3 signaling, thereby attenuating Dox-induced cardiac oxidative damage and inflammatory infiltration. Additionally, a total of 15 chemical compositions of chicory into rat heart tissue were characterized. SPR validation demonstrated that nine compounds targeting UCP2 and NLRP3 increased survival rates in Dox-induced H9c2 cells, reduced oxidative and inflammatory levels, and improved mitochondrial function. Chicory could effectively alleviate DIC by reducing oxidative stress, inflammation, and preserving mitochondrial function. These findings offer a novel insight into chicory’s clinical relevance in DIC management. Targeting UCP2 to regulate the NLRP3 pathway highlights chicory as a promising therapeutic strategy for preventing and treating DIC.

Anthracycline’s clinical application is often hampered by severe life-threatening cardiotoxicity, which could result in death in approximately one-third of patients. Previous studies have found that during the anthracycline-induced cardiotoxicity (AIC), uric acid (UA) levels increase abnormally. However, the role of UA in AIC remains elusive. Here, we conducted a correlation analysis between UA and cardiac damage markers (NT-pro-BNP, hs-cTnT, LDH, CRP and hs-CRP) by using the National Health and Nutrition Examination Survey database (NHANES); the results revealed that the elevated UA levels showed significant positive associations with the levels of several cardiac damage markers. Secondly, molecular docking experiments suggested potential binding interactions between UA and BNP, cTnT, CRP, and LDH. Finally, animal experiments were performed to validate this correlation we explored and further validated the effect of UA on AIC by adding or lowering UA in animal models. We observed that under high uric acid (HUA) conditions, AIC not only manifested earlier but also progressed more severely. In contrast, AIC was alleviated under UA clearance conditions. Collectively, these results suggested that HUA might be an important contributing factor in the development and progression of AIC, supporting the further investigation of UA-lowering strategies for potential prevention. This work might offer new prevention and treatment strategies for AIC.

In traditional Chinese medicine (TCM), Gardeniae Fructus is classified as a “cold” herb, a property that is increasingly explained by modern research showing that it can alleviate related disorders through modulation of the central nervous and endocrine systems, energy metabolism, and gut microbiota. This study aimed to elucidate the material foundation and biological mechanisms underlying its cold property. Chemical components of Gardeniae Fructus were separated via multi-stage extraction and characterized by GC-MS and LC-MS, yielding four distinct fractions: aliphatic, iridoid, crocin, and polysaccharide. In a rat model of heat syndrome induced by levothyroxine sodium, administration of the total extract or individual fractions over 15 days modulated central nervous, endocrine, and energy metabolism indicators, with the iridoid, crocin, and polysaccharide fractions demonstrating significant cold properties. Gut microbiota analysis revealed that the total extract, polysaccharide, and iridoid fractions notably reshaped microbial structure, reducing Firmicutes and Lactobacillus abundance. These findings indicate that the iridoid, crocin, and polysaccharide fractions may be key material bases for the cold property of Gardeniae Fructus, with the iridoid fraction exhibiting the strongest effect.

Objective: This study aimed to evaluate the efficacy and safety of total glucosides of paeony (TGP) combined with conventional therapy in juvenile idiopathic arthritis (JIA) and explore the network regulatory mechanisms underlying TGP's synergistic enhancement and toxicity reduction effects. Method: We searched for randomized controlled trials (RCTs) on the efficacy of TGP combined with conventional therapy in JIA until 1 February 2026 (databases: PubMed, Embase, Web of Science, Cochrane Library, SinoMed, Chinese National Knowledge Infrastructure, Wanfang, and VIP). The outcome measures included overall effective rate, adverse reactions, inflammation indicators, autoantibody levels, and clinical symptoms. Subsequently, an integrative pharmacology approach was employed to construct a “drug target–efficacy/toxicity gene” interaction network, elucidating potential molecular mechanisms of TGP's synergistic and toxicity-reducing effects. Result: A total of 17 RCTs were included, involving 966 children with JIA. Compared with conventional Western medicine alone, TGP combination therapy significantly improved the overall response rate [risk ratio (RR) = 1.13, 95% confidence interval (CI) 1.07–1.19, P < 0.0001]and reduced the incidence of adverse events (RR = 0.63, 95% CI 0.43–0.91, P = 0.02), markedly ameliorating serum inflammatory indicators [interleukin (IL)-1, IL-17, tumor necrosis factor α , C-reactive protein, and erythrocyte sedimentation rate], autoantibody levels, and clinical symptoms in JIA patients. The “drug target–efficacy/toxicity gene” interaction network revealed that TGP exerts synergistic effects primarily by regulating energy metabolism, alleviating oxidative stress and inflammation, and suppressing synovitis and osteoclastogenesis. Its toxicity-reducing effects were mediated through the inhibition of hepatic inflammation, oxidative stress, and angiogenesis, as well as modulation of lipid and amino acid metabolism. Notably, oxidative stress and lipid metabolism emerged as potential common mechanisms for TGP enhancement and toxicity reduction. Conclusion: The therapy of TGP combined with conventional Western medicine could enhance clinical efficacy and reduce adverse events in JIA patients. The synergistic and toxicity-reducing mechanisms of TGP might be associated with multi-pathway regulation, particularly involving oxidative stress and lipid metabolism.