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诃子通过调节 NF-κB/PPAR-γ 介导的通路预防载脂蛋白 E 基因敲除小鼠的白细胞介素-18 诱导的动脉粥样硬化。

Terminalia arjuna prevents Interleukin-18-induced atherosclerosis via modulation of NF-κB/PPAR-γ-mediated pathway in Apo E-/- mice.

机构信息

Department of Pharmcology and Toxicology, Virginia Commonwealth University, Richmond, VA, USA.

Department of Histopathology, National Institute of Nutrition (NIN), Hyderabad, India.

出版信息

Inflammopharmacology. 2018 Apr;26(2):583-598. doi: 10.1007/s10787-017-0357-9. Epub 2017 May 25.

Abstract

AIM OF THE STUDY

Terminalia arjuna is a medicinal plant well known as a cardiotonic in Ayurvedic system of medicine. We hypothesized that aqueous stem bark extract of T. arjuna (TAE) may inhibit IL-18-induced atherosclerosis via NF-κB/PPAR-γ-mediated pathway in Apo E-/- mice.

MATERIALS AND METHODS

12-week-old, male Apo E-/- mice divided into four groups (n = 6/group) fed with normal chow-diet were employed: GP I: phosphate buffer saline (PBS) (2 month); GP II: rIL-18 (1 month) followed by PBS (1 month); GP III: rIL-18 (1 month) followed by TAE (1 month); GP IV: rIL-18 (1 month) followed by atorvastatin (1 month).

RESULTS

IL-18 treatment induced a significant increase (p < 0.001) in pro-inflammatory marker (IL-18) (170 ± 9.16 vs. 1178.66 ± 8.08, pg/ml), and downregulated cholesterol efflux gene (PPAR-γ) by ~0.6-fold vs. 1.00 in IL-18-treated mice as compared to the control animals, respectively. TAE treatment to both groups caused a significant reduction in IL-18 to 281.66 ± 9.60 vs. 1178.66 ± 8.08 (pg/ml), upregulated cholesterol efflux gene by ~1.5- vs. 0.6-fold in TAE-treated group, decreased atherogenic lipids, and percentage atherosclerotic lesion area, demonstrating comparable effects with atorvastatin.

CONCLUSION

Our data demonstrate that TAE protects against IL-18-induced atherosclerosis via NF-κB/PPAR-γ-mediated pathway.

摘要

研究目的

诃子是一种药用植物,在印度阿育吠陀医学体系中被广泛用作强心剂。我们假设诃子的水提茎皮提取物(TAE)可能通过 NF-κB/PPAR-γ 介导的途径抑制 IL-18 诱导的动脉粥样硬化。

材料和方法

12 周龄雄性 Apo E-/- 小鼠分为四组(每组 n=6),喂食正常饲料:GP I:磷酸盐缓冲盐水(PBS)(2 个月);GP II:rIL-18(1 个月)后 PBS(1 个月);GP III:rIL-18(1 个月)后 TAE(1 个月);GP IV:rIL-18(1 个月)后阿托伐他汀(1 个月)。

结果

IL-18 处理导致促炎标志物(IL-18)显著增加(p<0.001)(170±9.16 与 1178.66±8.08,pg/ml),并使胆固醇流出基因(PPAR-γ)下调约 0.6 倍与 IL-18 处理组相比,对照组动物分别为 1.00。TAE 处理两组均使 IL-18 显著降低至 281.66±9.60 与 1178.66±8.08(pg/ml),上调胆固醇流出基因约 1.5-与 TAE 处理组相比,0.6 倍,降低动脉粥样硬化脂质和动脉粥样硬化病变面积百分比,与阿托伐他汀的作用相当。

结论

我们的数据表明,TAE 通过 NF-κB/PPAR-γ 介导的途径保护免受 IL-18 诱导的动脉粥样硬化。

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