10-Hydroxydec-2-enoic acid reduces vascular smooth muscle cell inflammation via interacting with Toll-like receptor 4

被引：0
作者：
Jia, Feng [1 ]
Wang, Yongqing [1 ]
Chen, Zhiqiang [1 ]
Jin, Jingxian [1 ]
Zeng, Lei [1 ]
Zhang, Li [1 ]
Tang, Huaijian [2 ]
Wang, Yanyan [2 ]
Fan, Pei [1 ]
机构：
[1] Henan Univ Technol, Sch Biol Engn, Zhengzhou 450001, Peoples R China
[2] Henan Univ Technol, Sch Food & Strateg Reserv, Zhengzhou 450001, Peoples R China
来源：
PHYTOMEDICINE | 2025年 / 140卷
关键词：
10-Hydroxydec-2-enoic acid; Vascular smooth muscle cell; Toll-like receptor 4; Inflammation; ANGIOTENSIN-II; OXIDATIVE STRESS; TRANSCRIPTION FACTOR; SIGNALING PATHWAY; ACTIVATION; DYSFUNCTION; EXPRESSION; KINASE; TLR4; SP1;
D O I：
10.1016/j.phymed.2025.156534
中图分类号：
Q94 [植物学];
学科分类号：
071001 ;
摘要：
Background: 10-Hydroxydec-2-enoic acid (10-HDA), a unique and marker compound in royal jelly, has a wide range of bio-activities. However, its role in regulating inflammation of vascular smooth muscle cell (VSMC), which is essential to a set of vascular diseases, is still unknown. Purpose: Our study aimed to investigate whether 10-HDA exerts effect on VSMC inflammation via interacting with toll-like receptor 4 (TLR4), a pivotal inflammatory initiator. Methods: A package of proteins, which might participate in TLR4-mediated signaling, influenced by 10-HDA were analyzed in mouse VSMCs with Angiotensin II(Ang II) or lipopolysaccharide (LPS) stimulation. Accordingly, proor anti-inflammatory cytokines, reactive oxygen species (ROS), and anti-oxidants that are closely relevant to inflammatory process were determined. The possible mode for 10-HDA interacting with TLR4 was also characterized. Moreover, involvement of a key miRNA in 10-HDA regulating VSMC inflammation was identified. Results: In the presence of Ang II, 10-HDA inhibited the TLR4 expression in a dose-dependent manner. In such occasion, 10-HDA hindered the up-regulation of specificity protein 1 (SP1) and serine/threonine-protein phosphatase 6 catalytic subunit (PPP6C), the phosphorylation of extracellular signal-regulated kinase 1/2, TGF beta-activated kinase 1, and nuclear factor-kappa B p56, as well as the enhancement of myeloid differentiation primary response gene 88. Apart from SP1 and PPP6C, the level change of these proteins by 10-HDA was similar with LPS stimulation. The effect might be resulted from 10-HDA blocking TLR4 through multiple atomic interactions. 10HDA mitigated the increase of pro-inflammatory cytokines tumor necrosis factor-alpha, interleukin-2 (IL-2), and IL-6, as well as increased the anti-inflammatory cytokine IL-10, in the Ang II- or LPS-induced VSMCs. Correspondingly, the level of ROS was attenuated and the anti-oxidants such as glutathione and superoxide dismutase were fortified. The data indicated the anti-inflammatory potential of 10-HDA in VSMCs, which was associated with 10-HDA's capability of relieving oxidative stress. Additionally, the expression of miR-17-5p was saved by 10-HDA from Ang II- or LPS-treated VSMCs, which might be relevant to SP1 and PPP6C targeting. Conclusion: The present work of 10-HDA, for the first time, revealed its ability to alleviate VSMC inflammation by targeting TLR4 and therefore modulate the downstream inflammatory participants. Our data will cast light on the utilization of 10-HDA in VSMC inflammation-related vascular disorders.
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页数：14
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