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豌豆皮提取物可减轻 DOX 诱导的氧化心肌损伤。

Pea (Pisum sativum) peel extract attenuates DOX-induced oxidative myocardial injury.

机构信息

Biology Department, College of Science, Taibah University, Saudi Arabia; Zoology Department, Faculty of Science, Ain Shams University, Cairo, Egypt.

Biology Department, College of Science, Taibah University, Saudi Arabia.

出版信息

Biomed Pharmacother. 2021 Nov;143:112120. doi: 10.1016/j.biopha.2021.112120. Epub 2021 Sep 28.

Abstract

The goal of this work aimed to evaluate the protective effects of pea (Pisum sativum) peels extract versus doxorubicin-induced oxidative myocardial injury in male mice. The mice were divided into seven groups (n = 7): (I) control group; (II) P. sativum 250 group; (III) P. sativum 500 group; (IV) DOX (3 times alternately of 2.5 mg/kg/week, i.p. for a continuous two-week period) group; (V) Vit. E 100 + DOX group; (VI) P. sativum 250 + DOX group, and (VII) P. sativum 500 + DOX group). Twenty polyphenolic compounds, mainly flavonoid glycosides such as quercetin, kaempferol apigenin, and phenolics compounds were characterized by LC-MS/MS analysis in the examined extract. DOX administration elevated the activities of serum biomarkers of myocardial dysfunction (ALT, AST, ALP, LDH, troponin, CPK, and CK-MB), lipid profile, and proinflammatory cytokines. Also, it decreased cardiac antioxidants (GSH, SOD, GPX, CAT) and increased myocardial markers of oxidative stress (NO and MDA) and inflammatory marker (MPO). As well as it downregulated and upregulated the Bcl-2 (anti-apoptotic gene) and the Bax (pro-apoptotic gene) expressions, respectively. Pre-treatment of DOX-exposed mice with P. sativum or vitamin E (as a reference protective antioxidant) alleviated the changes dose-dependently via DOX-induced cardiotoxicity. These data show that P. sativum has a cardio-protective impact against DOX-induced cardiomyocyte damage in mice via boosting endogenous antioxidants, decreasing inflammation, and regulating BcL-2 and Bax apoptosis pathway, which might be related to the presence of flavonoid glycosides. P. sativum peels are a by-product that could be suggested for further screening as a possible new candidate for therapeutic use.

摘要

本研究旨在评估豌豆皮提取物对雄性小鼠多柔比星诱导的氧化心肌损伤的保护作用。将小鼠分为七组(n=7):(I)对照组;(II)豌豆皮 250 组;(III)豌豆皮 500 组;(IV)DOX(3 次交替使用,每次 2.5mg/kg/周,腹腔注射连续两周)组;(V)Vit.E100+DOX 组;(VI)豌豆皮 250+DOX 组,和(VII)豌豆皮 500+DOX 组。采用 LC-MS/MS 分析方法对所检测的提取物中的 20 种多酚化合物进行了鉴定,主要为类黄酮糖苷,如槲皮素、山奈酚、芹菜素和酚类化合物。DOX 给药后,血清心肌功能障碍(ALT、AST、ALP、LDH、肌钙蛋白、CPK 和 CK-MB)、脂质谱和促炎细胞因子的生物标志物活性升高。此外,它降低了心脏抗氧化剂(GSH、SOD、GPX、CAT),增加了心肌氧化应激(NO 和 MDA)和炎症标志物(MPO)的水平。并且分别下调和上调了 Bcl-2(抗凋亡基因)和 Bax(促凋亡基因)的表达。用豌豆皮或维生素 E(作为参考保护抗氧化剂)预处理 DOX 暴露的小鼠,可通过 DOX 诱导的心脏毒性,呈剂量依赖性缓解变化。这些数据表明,豌豆皮通过增强内源性抗氧化剂、减少炎症以及调节 BcL-2 和 Bax 凋亡途径,对 DOX 诱导的小鼠心肌细胞损伤具有心脏保护作用,这可能与类黄酮糖苷的存在有关。豌豆皮是一种副产物,可以进一步筛选,作为治疗用途的潜在新候选药物。

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