Marine-Derived Piericidin Diglycoside S18 Alleviates Inflammatory Responses in the Aortic Valve via Interaction with Interleukin 37

Calcific aortic valve disease (CAVD) is a valvular disease frequently in the elderly individuals that can lead to the valve dysfunction. Osteoblastic differentiation of human aortic valve interstitial cells (HAVICs) induced by inflammation play a crucial role in CAVD pathophysiological processes. To...

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Published in:Oxidative medicine and cellular longevity 2022, Vol.2022, p.6776050-18
Main Authors: Li, Shunyi, She, Jianglian, Zeng, Jingxin, Xie, Kaiji, Luo, Zichao, Su, Shuwen, Chen, Jun, Xian, Gaopeng, Cheng, Zhendong, Zhao, Jing, Li, Shaoping, Xu, Xingbo, Xu, Dingli, Tang, Lan, Zhou, Xuefeng, Zeng, Qingchun
Format: Article
Language:English
Subjects:
Animals
Aortic Valve - pathology
Aortic Valve Stenosis
Calcification
Calcinosis
Cells, Cultured
Chromatography
Cytokines
Disease
Glycosides - pharmacology
Humans
Inflammation
Interleukin-1 - metabolism
Interleukins
Lipopolysaccharides
Mice
NMR
Nuclear magnetic resonance
Oxidative stress
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Summary:Calcific aortic valve disease (CAVD) is a valvular disease frequently in the elderly individuals that can lead to the valve dysfunction. Osteoblastic differentiation of human aortic valve interstitial cells (HAVICs) induced by inflammation play a crucial role in CAVD pathophysiological processes. To date, no effective drugs for CAVD have been established, and new agents are urgently needed. Piericidin glycosides, obtained from a marine-derived Streptomyces strain, were revealed to have regulatory effects on mitochondria in previous studies. Here, we discovered that 13-hydroxypiericidin A 10-O-α-D-glucose (1→6)-β-D-glucoside (S18), a specific piericidin diglycoside, suppresses lipopolysaccharide- (LPS) induced inflammatory responses of HAVICs by alleviating mitochondrial stress in an interleukin (IL)-37-dependent manner. Knockdown of IL-37 by siRNA not only exaggerated LPS-induced HAVIC inflammation and mitochondrial stress but also abrogated the anti-inflammatory effect of S18 on HAVICs. Moreover, S18 alleviated aortic valve lesions in IL-37 transgenic mice of CAVD model. Microscale thermophoresis (MST) and docking analysis of five piericidin analogues suggested that diglycosides, but not monoglycosides, exert obvious IL-37-binding activity. These results indicate that S18 directly binds to IL-37 to alleviate inflammatory responses in HAVICs and aortic valve lesions in mice. Piericidin diglycoside S18 is a potential therapeutic agent to prevent the development of CAVD.
ISSN:1942-0900
1942-0994
DOI:10.1155/2022/6776050