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迷迭香酸通过抑制 NF-κB 炎症信号通路和 ROS 产生对心肌缺血/再灌注损伤的心脏保护作用在小鼠中。

Cardioprotective effect of rosmarinic acid against myocardial ischaemia/reperfusion injury via suppression of the NF-κB inflammatory signalling pathway and ROS production in mice.

机构信息

Xi'an Mental Health Center, School of Medicine, Xi'an Jiaotong University, Xi'an, China.

College of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang, China.

出版信息

Pharm Biol. 2021 Dec;59(1):222-231. doi: 10.1080/13880209.2021.1878236.

Abstract

CONTEXT

Rosmarinic acid (RosA), a natural poly-phenolic compound isolated from a variety of Labiatae herbs, has been reported to have a range of biological effects.

OBJECTIVE

To investigate the cardioprotective effects of RosA against myocardial ischaemia/reperfusion (I/R) injury.

MATERIALS AND METHODS

Male C57BL/6J mice were given RosA (100 mg/kg) via intragastric administration. After 1 week of administration, the mice were subjected to 30 min/24 h myocardial I/R injury. The mice were randomly subdivided into 4 groups: Vehicle, RosA, Vehicle + I/R, and RosA + I/R. Infarct size (IS), cardiac function (including EF, FS), histopathology, serum enzyme activities, ROS changes, cis aconitase (ACO) activity, and specific mRNA and protein levels were assessed . HL-1 cells were pre-treated with or without RosA (50 μM), followed by stimulation with 9 h/6 h of oxygen and glucose deprivation/re-oxygenation (OGD/R). The cells were randomly subdivided into 4 groups: Vehicle, RosA, Vehicle + OGD/R, and RosA + OGD/R. Lactate dehydrogenase (LDH) levels, ACO activity, ROS changes and protein levels were measured .

RESULTS

Treatment with RosA reduced the following indicators ( < 0.05): (1) IS (14.5%); (2) EF (-23.4%) and FS (-18.4%); (3) the myocardial injury enzymes CK-MB (20.8 ng/mL) and cTnI (7.7 ng/mL); (4) DHE-ROS: (94.1%); (5) ACO activity (-2.1 mU/mg protein); (6) mRNA level (122.9%); and (7) OGDH protein level (69.9%). Moreover, treatment with RosA attenuated the following indicators ( < 0.05): (1) LDH level (191 U/L); (2) DHE-ROS: (165.2%); (3) ACO activity (-3.2 mU/mg protein); (4) mRNA level (70.0%); and (5) OGDH (110.1%), p-IκB-a (56.8%), and p-NF-κB (57.7%) protein levels.

CONCLUSIONS

RosA has the potential to treat myocardial I/R injury with potential application in the clinic.

摘要

背景

迷迭香酸(RosA)是一种从多种唇形科草药中分离出来的天然多酚化合物,已被报道具有多种生物学效应。

目的

研究迷迭香酸(RosA)对心肌缺血/再灌注(I/R)损伤的心脏保护作用。

材料和方法

雄性 C57BL/6J 小鼠经灌胃给予 RosA(100mg/kg)。给药 1 周后,小鼠进行 30 分钟/24 小时心肌 I/R 损伤。将小鼠随机分为 4 组:载体组、RosA 组、载体+I/R 组和 RosA+I/R 组。评估梗死面积(IS)、心脏功能(包括 EF、FS)、组织病理学、血清酶活性、ROS 变化、顺乌头酸酶(ACO)活性以及特定的 mRNA 和蛋白水平。HL-1 细胞用或不用 RosA(50μM)预处理,然后进行 9 小时/6 小时的氧和葡萄糖剥夺/再氧合(OGD/R)刺激。将细胞随机分为 4 组:载体组、RosA 组、载体+OGD/R 组和 RosA+OGD/R 组。测量乳酸脱氢酶(LDH)水平、ACO 活性、ROS 变化和蛋白水平。

结果

RosA 治疗降低了以下指标 ( < 0.05):(1)IS(14.5%);(2)EF(-23.4%)和 FS(-18.4%);(3)心肌损伤酶 CK-MB(20.8ng/mL)和 cTnI(7.7ng/mL);(4)DHE-ROS:(94.1%);(5)ACO 活性(-2.1mU/mg 蛋白);(6)mRNA 水平(122.9%);和(7)OGDH 蛋白水平(69.9%)。此外,RosA 治疗降低了以下指标 ( < 0.05):(1)LDH 水平(191U/L);(2)DHE-ROS:(165.2%);(3)ACO 活性(-3.2mU/mg 蛋白);(4)mRNA 水平(70.0%);和(5)OGDH(110.1%)、p-IκB-a(56.8%)和 p-NF-κB(57.7%)蛋白水平。

结论

RosA 具有治疗心肌 I/R 损伤的潜力,有望在临床上应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a9a/7894452/588f30e351eb/IPHB_A_1878236_F0001_B.jpg

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