(Press-News.org) Coronary heart disease (CHD), characterized by atherosclerosis-induced myocardial ischemia, remains a leading cause of mortality in China. Safflower yellow pigments (SYPs), the primary bioactive components of Carthamus tinctorius L., consist mainly of quinochalcone C-glycosides, with hydroxysafflor yellow A (HSYA) and anhydrosafflor yellow B (AHSYB) as key constituents. This review synthesizes evidence on SYPs' mechanisms, therapeutic applications, and future directions in CHD management.
Chemical Composition and Pharmacokinetics
SYPs comprise over 20 identified compounds, including HSYA and AHSYB, which confer cardiovascular protection, anti-inflammatory, and antioxidant activities. Pharmacokinetic studies reveal poor oral bioavailability (HSYA: 1.2%; AHSYB: 0.3%) due to gastrointestinal hydrolysis, low membrane permeability, and hepatic first-pass effects. HSYA distributes widely across organs (kidney > liver > lung > heart) and is metabolized into phase I/II products, excreted via feces (oral) or urine (intravenous). Metabolic profiles differ between normal and disease models, impacting efficacy.
Advances in SYPs for CHD Treatment
1. Improving Myocardial Ischemia
Clinical trials demonstrate that safflower yellow injection (SYI) alleviates angina, improves cardiac function (ejection fraction), and normalizes hemorheology in CHD patients. Mechanistically, SYPs:
Inhibit inflammatory cytokines (IL-6, TNF-α, CRP).
Promote angiogenesis via HIF-1α/VEGF-A/CD31.
Reduce oxidative stress by activating Nrf2/HO-1.
Exhibit anticoagulant effects by prolonging PT/APTT.
2. Reducing Myocardial Ischemia-Reperfusion Injury (MIRI)
SYPs mitigate MIRI through:
Anti-inflammation: Suppressing TLR4/NF-κB signaling.
Antioxidant effects: Enhancing SOD, activating PI3K/Akt/Nrf2.
Anti-apoptosis: Regulating Bcl-2/Bax and miR-499.
Mitochondrial protection: Restoring ATP synthesis via Mdh1 and inhibiting permeability transition pore opening.
Novel pathways: Inhibiting ferroptosis (via HIF-1α/SLC7A11) and endoplasmic reticulum stress.
3. Alleviating Atherosclerotic Damage
SYPs reduce plaque formation and improve lipid profiles (↓TC, ↓LDL-C; ↑HDL-C) in clinical and animal studies. Key mechanisms include:
Inhibiting ox-LDL-induced endothelial damage and macrophage foam cell formation.
Suppressing vascular smooth muscle migration via SphK1/S1P/S1PR3.
Enhancing macrophage autophagy (via Atg13 demethylation) to stabilize plaques.
SYPs for CHD Risk Factors
SYPs ameliorate cardiometabolic comorbidities:
Obesity: Promote white fat browning, modulate gut microbiota (↑Akkermansia), and inhibit GIP/GIPR axis.
Hypertension: Activate KATP/BKCa channels, promote angiogenesis (Ang1/Tie-2), and inhibit vascular remodeling via NLRP3 inflammasome suppression.
Hyperlipidemia: Regulate AMPK/SREBP2/PCSK9/LDLR and inhibit platelet hyperactivation via miR-9a-5p/PLCγ2.
Diabetes: Improve insulin resistance (PI3K/Akt), protect β-cells from apoptosis (JNK/c-Jun inhibition), and reduce diabetic atherosclerosis via miR-429/SLC7A11.
Limitations and Future Perspectives
Challenges: Low oral bioavailability, short half-life, and limited large-scale clinical trials.
Solutions:
Develop advanced delivery systems (e.g., natural deep eutectic solvents) to enhance bioavailability.
Explore gut microbiota interactions (e.g., SCFAs, TMAO) in CHD pathogenesis.
Conduct multicenter, long-term trials to validate SYPs' efficacy and safety.
Conclusion
Safflower yellow pigments have demonstrated clear clinical efficacy in the treatment of coronary heart disease. Their pharmacological effects include anti-myocardial ischemia, mitigation of ischemia-reperfusion injury, anti-atherosclerosis, improvement of vascular injury, and reduction of coronary heart disease-related risk factors such as obesity, hypertension, hyperlipidemia, and diabetes. The mechanisms of action primarily involve inhibition of inflammatory responses, oxidative stress, and platelet aggregation, as well as reduction of endothelial cell damage and suppression of cardiomyocyte apoptosis. These effects illustrate the multi-target, multi-pathway, and multi-molecular characteristics of the therapeutic actions of safflower yellow pigments. However, the current understanding of coronary heart disease pathogenesis remains incomplete, and the mechanisms underlying the therapeutic effects of safflower yellow pigments require further elucidation. Future research priorities should focus on optimizing the drug delivery system to enhance the oral bioavailability of safflower yellow pigments, complemented by comprehensive safety and efficacy evaluations. Additionally, investigating how safflower yellow pigments regulate gut microbiota-derived metabolites such as short-chain fatty acids and trimethylamine N-oxide to influence coronary heart disease progression is crucial. Equally important are large-scale, multicenter, double-blind clinical trials to validate the long-term efficacy and safety of safflower yellow pigments in coronary heart disease management.
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The study was recently published in the Future Integrative Medicine.
Future Integrative Medicine (FIM) is the official scientific journal of the Capital Medical University. It is a prominent new journal that promotes future innovation in medicine.It publishes both basic and clinical research, including but not limited to randomized controlled trials, intervention studies, cohort studies, observational studies, qualitative and mixed method studies, animal studies, and systematic reviews.
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