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川芎内酯可减轻血管炎症,激活 Nrf2/HO-1 诱导和 HUVECs 中的 NO 合成。

Ligustilide attenuates vascular inflammation and activates Nrf2/HO-1 induction and, NO synthesis in HUVECs.

机构信息

College of Oriental Medicine and Professional Graduate School of Oriental Medicine, Wonkwang University, 460 Iksandae-ro, Jeonbuk 54538, Republic of Korea; Hanbang Cardio-Renal Syndrome Research Center, Wonkwang University, 460 Iksandae-ro, Jeonbuk 54538, Republic of Korea.

College of Oriental Medicine and Professional Graduate School of Oriental Medicine, Wonkwang University, 460 Iksandae-ro, Jeonbuk 54538, Republic of Korea; Hanbang Cardio-Renal Syndrome Research Center, Wonkwang University, 460 Iksandae-ro, Jeonbuk 54538, Republic of Korea.

出版信息

Phytomedicine. 2018 Jan 1;38:12-23. doi: 10.1016/j.phymed.2017.09.022. Epub 2017 Oct 4.

Abstract

BACKGROUND

Ligustilide is a bioactive phthalide derivative isolated from Cnidii Rhizoma (Cnidium officinale, rhizome) and Angelicae Gigantis Radix (Angelica gigas Nakai, root) which are both medicinal herbs used to treat circulatory disorders. Vascular endothelium is a central spot in developing cardiovascular diseases and chronic vascular inflammation might result in atherosclerosis development.

PURPOSE

We previously found out that a traditional herbal formula, Samul-Tang (Si-Wu-Tang, containing Cnidii Rhizoma and Angelicae Gigantis Radix), attenuated vascular inflammation in human umbilical vein endothelial cells (HUVECs). However, which compound was responsible for vascular protective action remained unclear. Here, we investigated vascular protective potential of an isolated single compound, (Z)-ligustilide.

METHODS

MTT assay, western blotting, immunofluorescence, electrophoretic mobility shift assay was performed. BCECF-AM, CM-HDCFDA, DAF-FM diacetate were used as a fluorescent indicator.

RESULTS

Ligustilide suppressed HL-60 monocyte adhesion and CAMs (ICAM-1, VCAM-1, E-selectin) expression in HUVECs. Ligustilide significantly inhibited TNF-α-increased production of ROS and activated NF-κB signaling pathway. Also, ligustilide treated HUVECs exhibited significant HO-1 induction via Nrf2 nuclear translocation and endothelial NO synthesis.

CONCLUSION

Present study demonstrates that ligustilde attenuates vascular inflammation and activate defense system of endothelial cell. Ligustilide is a bioactive compound which might prevent cardiovascular complications such as thrombosis or atherosclerosis.

摘要

背景

藁本内酯是一种从川芎(Cnidium officinale,根茎)和当归(Angelica gigas Nakai,根)中分离得到的生物活性苯酞衍生物,这两种草药都被用于治疗循环系统疾病。血管内皮细胞是心血管疾病和慢性血管炎症发展的中心部位,可能导致动脉粥样硬化的发展。

目的

我们之前发现一种传统草药配方,四物汤(包含川芎和当归),可减轻人脐静脉内皮细胞(HUVEC)中的血管炎症。然而,哪种化合物负责血管保护作用仍不清楚。在这里,我们研究了一种分离的单一化合物(Z)-藁本内酯的血管保护潜力。

方法

进行 MTT 测定、western blot、免疫荧光、电泳迁移率变动分析。使用 BCECF-AM、CM-HDCFDA、DAF-FM 二乙酸酯作为荧光指示剂。

结果

藁本内酯抑制 HL-60 单核细胞黏附和 HUVECs 中细胞间黏附分子(ICAM-1、VCAM-1、E-选择素)的表达。藁本内酯显著抑制 TNF-α 增加的 ROS 产生,并激活 NF-κB 信号通路。此外,藁本内酯处理的 HUVECs 通过 Nrf2 核转位和内皮细胞一氧化氮合酶显著诱导 HO-1 的产生。

结论

本研究表明,藁本内酯可减轻血管炎症并激活内皮细胞的防御系统。藁本内酯是一种生物活性化合物,可预防血栓形成或动脉粥样硬化等心血管并发症。

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