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Current pharmaceutical biotechnology · 2026

Safflower Extract Mitigates MIRI in Rats by Modulating TLR-4/NF-κB Signaling Pathway, Demonstrating Protective Effects.

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Deng Mingling, Yang Jing, Julaiti Aimaiti, Dong Yue, Deng Yunfang, Wang Zhaoju

Аннотация

BACKGROUND: Myocardial ischemia-reperfusion injury (MIRI) exacerbates tissue damage following the restoration of coronary blood flow after ischemia. The TLR-4/NF-κB signaling pathway plays a crucial role in the pathogenesis of MIRI. This study investigated the therapeutic efficacy of safflower extract in mitigating MIRI and its modulation of TLR-4/NF-κB signaling in rats.

METHODS: Adult male Sprague-Dawley rats were subjected to 30 minutes of myocardial ischemia followed by 2 h of reperfusion. Safflower extract was administered intravenously at doses of 2, 4, and 8 mg/kg 15 minutes before ischemia and 1 minute before reperfusion. Infarct size was assessed using TTC staining. Serum levels of creatine kinase (CK) and lactate dehydrogenase (LDH) were measured. Pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) were quantified using ELISA. TLR-4 and NF-κB mRNA and protein expression were evaluated using qRT-PCR and western blotting, respectively. Histopathological changes were assessed using H&E staining.

RESULTS: Safflower extract effectively reduced myocardial infarct size in a dose-dependent manner, with the highest dose providing the greatest benefit. Treatment with safflower extract significantly lowered the elevated levels of serum CK and LDH caused by ischemia-reperfusion (I/R) injury, bringing these biochemical markers closer to normal values. In addition, safflower extract decreased the levels of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α in myocardial tissue, showing a clear dose-response relationship. Analysis through qRT-PCR and western blot confirmed that safflower extract downregulated the expression of TLR4 and NF-κB at both the transcriptional and protein levels. Histological studies further supported these findings, demonstrating that safflower extract improved myocardial tissue architecture, maintained cardiomyocyte structure, and reduced inflammatory cell infiltration.

CONCLUSION: Safflower extract provides significant cardioprotection against MIRI by modulating the TLR-4/NF-κB-mediated inflammatory response. These findings suggest that safflower extract may be a potential therapeutic agent for mitigating the effects of myocardial ischemiareperfusion injury.

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