Paeoniflorin attenuates cuproptosis and ameliorates left ventricular remodeling after AMI in hypobaric hypoxia environments

IF 2.5 4区 医学 Q3 CHEMISTRY, MEDICINAL Journal of Natural Medicines Pub Date : 2024-03-01 DOI:10.1007/s11418-024-01781-7
Xin Fang, Yaoxuan Ji, Shuang Li, Lei Wang, Bo He, Bo li, Boshen Liang, Hongke Yin, Haotian Chen, Duojie Dingda, Bing Wu, Fabao Gao
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Abstract

This study investigates the cardioprotective effects of Paeoniflorin (PF) on left ventricular remodeling following acute myocardial infarction (AMI) under conditions of hypobaric hypoxia. Left ventricular remodeling post-AMI plays a pivotal role in exacerbating heart failure, especially at high altitudes. Using a rat model of AMI, the study aimed to evaluate the cardioprotective potential of PF under hypobaric hypoxia. Ninety male rats were divided into four groups: sham-operated controls under normoxia/hypobaria, an AMI model group, and a PF treatment group. PF was administered for 4 weeks after AMI induction. Left ventricular function was assessed using cardiac magnetic resonance imaging. Biochemical assays of cuproptosis, oxidative stress, apoptosis, inflammation, and fibrosis were performed. Results demonstrated PF significantly improved left ventricular function and remodeling after AMI under hypobaric hypoxia. Mechanistically, PF decreased FDX1/DLAT expression and serum copper while increasing pyruvate. It also attenuated apoptosis, inflammation, and fibrosis by modulating Bcl-2, Bax, NLRP3, and oxidative stress markers. Thus, PF exhibits therapeutic potential for left ventricular remodeling post-AMI at high altitude by inhibiting cuproptosis, inflammation, apoptosis and fibrosis. Further studies are warranted to optimize dosage and duration and elucidate PF’s mechanisms of action.

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在低压缺氧环境中,芍药苷可减轻杯状突变并改善急性心肌梗死后的左心室重塑。
本研究探讨了在低压缺氧条件下,芍药苷(PF)对急性心肌梗死(AMI)后左心室重塑的心脏保护作用。急性心肌梗死后的左心室重塑在加重心力衰竭方面起着关键作用,尤其是在高海拔地区。该研究利用大鼠急性心肌梗死模型,旨在评估在低压缺氧条件下 PF 的心脏保护潜力。90 只雄性大鼠被分为四组:常氧/低氧条件下的假手术对照组、急性心肌梗死模型组和 PF 治疗组。在诱发急性心肌梗死后给大鼠服用 PF 4 周。使用心脏磁共振成像评估左心室功能。对杯突症、氧化应激、细胞凋亡、炎症和纤维化进行了生化检测。结果表明,在低压缺氧条件下,PF能明显改善急性心肌梗死后的左心室功能和重塑。从机制上讲,PF 降低了 FDX1/DLAT 的表达和血清铜,同时增加了丙酮酸。它还通过调节 Bcl-2、Bax、NLRP3 和氧化应激标记物来减轻细胞凋亡、炎症和纤维化。因此,通过抑制杯突、炎症、细胞凋亡和纤维化,PF 对高海拔地区急性心肌梗死后的左心室重塑具有治疗潜力。还需要进一步研究,以优化剂量和持续时间,并阐明 PF 的作用机制。
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来源期刊
CiteScore
6.90
自引率
3.00%
发文量
79
审稿时长
1.7 months
期刊介绍: The Journal of Natural Medicines is an international journal publishing original research in naturally occurring medicines and their related foods and cosmetics. It covers: -chemistry of natural products -biochemistry of medicinal plants -pharmacology of natural products and herbs, including Kampo formulas and traditional herbs -botanical anatomy -cultivation of medicinal plants. The journal accepts Original Papers, Notes, Rapid Communications and Natural Resource Letters. Reviews and Mini-Reviews are generally invited.
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