Hydroxysafflor Yellow A Inhibits Pyroptosis and Protecting HUVECs from OGD/R via NLRP3/Caspase-1/GSDMD Pathway

Fan Guo; Xiao Han; Yue You; Shu-Juan Xu; Ye-Hao Zhang; Yuan-Yuan Chen; Gao-Jie Xin; Zi-Xin Liu; Jun-Guo Ren; Ce Cao; Ling-Mei Li; Jian-Hua Fu

doi:10.1007/s11655-023-3716-y

Hydroxysafflor Yellow A Inhibits Pyroptosis and Protecting HUVECs from OGD/R via NLRP3/Caspase-1/GSDMD Pathway

Chin J Integr Med. 2024 Feb 6. doi: 10.1007/s11655-023-3716-y. Online ahead of print.

Authors

Fan Guo^{1

2}, Xiao Han^{1

2}, Yue You^{1

2}, Shu-Juan Xu^{1

2}, Ye-Hao Zhang^{1

2}, Yuan-Yuan Chen^{1

2}, Gao-Jie Xin^{1

2}, Zi-Xin Liu^{1

2}, Jun-Guo Ren^{1

2}, Ce Cao^{1

2}, Ling-Mei Li^{3

4

5}, Jian-Hua Fu^{1

2}

Affiliations

¹ Institute of Basic Medical Sciences of Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China.
² Beijing Key Laboratory of Chinese Materia Pharmacology, Beijing, 100091, China.
³ Institute of Basic Medical Sciences of Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China. lilingmei0018@126.com.
⁴ Beijing Key Laboratory of Chinese Materia Pharmacology, Beijing, 100091, China. lilingmei0018@126.com.
⁵ Department of Central Laboratory, Kunshan Hospital of Chinese Medicine, Kunshan, Jiangsu Province, 215300, China. lilingmei0018@126.com.

PMID: 38319525
DOI: 10.1007/s11655-023-3716-y

Abstract

Objective: To observe the protective effect and mechanism of hydroxyl safflower yellow A (HSYA) from myocardial ischemia-reperfusion injury on human umbilical vein endothelial cells (HUVECs).

Methods: HUVECs were treated with oxygen-glucose deprivation reperfusion (OGD/R) to simulate the ischemia reperfusion model, and cell counting kit-8 was used to detect the protective effect of different concentrations (1.25-160 µ mol/L) of HSYA on HUVECs after OGD/R. HSYA 80 µ mol/L was used for follow-up experiments. The contents of inflammatory cytokines interleukin (IL)-18, IL-1 β, monocyte chemotactic protein 1 (MCP-1), tumor necrosis factor α (TNF-α) and IL-6 before and after administration were measured by enzyme-linked immunosorbent assay. The protein expressions of toll-like receptor, NOD-like receptor containing pyrin domain 3 (NLRP3), gasdermin D (GSDMD) and GSDMD-N-terminal domain (GSDMD-N) before and after administration were detected by Western blot. NLRP3 inflammasome inhibitor cytokine release inhibitory drug 3 sodium salt (CRID3 sodium salt, also known as MCC950) and agonist were added, and the changes of NLRP3, cysteine-aspartic acid protease 1 (Caspase-1), GSDMD and GSDMD-N protein expressions were detected by Western blot.

Results: HSYA inhibited OGD/R-induced inflammation and significantly decreased the contents of inflammatory cytokines IL-18, IL-1 β, MCP-1, TNF-α and IL-6 (P<0.01 or P<0.05). At the same time, by inhibiting NLRP3/Caspase-1/GSDMD pathway, HSYA can reduce the occurrence of pyroptosis after OGD/R and reduce the expression of NLRP3, Caspase-1, GSDMD and GSDMD-N proteins (P<0.01).

Conclusions: The protective effect of HSYA on HUVECs after OGD/R is related to down-regulating the expression of NLRP3 inflammasome and inhibiting pyroptosis.

Keywords: Chinese medicine; NLRP3 inflammasome; human umbilical vein endothelial cells; hydroxysafflor yellow A; myocardial reperfusion injury; oxygen-glucose deprivation reperfusion; pyroptosis.