Salidroside Decreases Atherosclerosis Plaque Formation via Inhibiting Endothelial Cell Pyroptosis

• Published in: Inflammation Vol. 43; no. 2; pp. 433 - 440
• Main Authors: Xing, Sha-Sha, Yang, Jin, Li, Wen-jing, Li, Jian, Chen, Lin, Yang, Yu-ting, Lei, Xia, Li, Jun, Wang, Kai, Liu, Xun
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.04.2020; Springer Nature B.V
• Subjects: Animals; Anti-inflammatory agents; Aorta; Apoptosis; Arteriosclerosis; Atherosclerosis; Atherosclerosis - drug therapy; Atherosclerosis - pathology; ATP; Biomedical and Life Sciences; Biomedicine; Caspase-1; Cell death; Dose-Response Relationship, Drug; Endothelial cells; Glucosides - pharmacology; Glucosides - therapeutic use; Human Umbilical Vein Endothelial Cells - drug effects; Human Umbilical Vein Endothelial Cells - pathology; Humans; IL-1β; Immunology; Inflammation; Internal Medicine; Lipopolysaccharides; Male; Mice; Mice, Knockout; Original Article; Pathology; Pharmacology/Toxicology; Phenols - pharmacology; Phenols - therapeutic use; Plaque, Atherosclerotic - drug therapy; Plaque, Atherosclerotic - pathology; Pyroptosis; Pyroptosis - drug effects; Pyroptosis - physiology; Rheumatology; Rhodiola; Umbilical vein; pyroptosis; salidroside; endothelial cells; GSDMD, atherosclerosis
• ISSN: 0360-3997; 1573-2576
• DOI: 10.1007/s10753-019-01106-x

Pyroptosis, a new pro-inflammatory programmed cell death, is linked to atherosclerosis (AS). Our previous studies suggested that salidroside (SAL) can alleviate AS and exert anti-oxidative and anti-inflammatory properties. However, the effect of SAL on atherosclerosis-related pyroptosis has not been studied. Here, we investigated the effect of SAL on pyroptosis to explain the underlying mechanisms of SAL on atherosclerosis-related inflammation. We established an atherosclerosis mouse model via western diet (HFD) to explore the protective effect of SAL. According to our results, administration of SAL for 12 weeks markedly reduced the atherosclerotic plaque in aorta. Meanwhile, SAL also alleviated the pyroptosis, as evidenced by inhibiting caspase-1 activation, interleukin-1β (IL-1β) release, and TUNEL-positive staining, and decreasing the expression of Gasdermin D (GSDMD). Furthermore, SAL also decreased the activation of caspase-1 and inhibited the release of IL-1β induced by lipopolysaccharide (LPS) and adenosine triphosphate (ATP) in human umbilical vein endothelial cell (HUVECs). Our data indicate that SAL inhibit NLRP3-related pyroptosis, which might be the underlying mechanism of SAL anti-inflammatory in atherosclerosis.