PMID- 38319525 OWN - NLM STAT- Publisher LR - 20240206 IS - 1993-0402 (Electronic) IS - 1672-0415 (Linking) DP - 2024 Feb 6 TI - Hydroxysafflor Yellow A Inhibits Pyroptosis and Protecting HUVECs from OGD/R via NLRP3/Caspase-1/GSDMD Pathway. LID - 10.1007/s11655-023-3716-y [doi] AB - 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 micro mol/L) of HSYA on HUVECs after OGD/R. HSYA 80 micro mol/L was used for follow-up experiments. The contents of inflammatory cytokines interleukin (IL)-18, IL-1 beta, monocyte chemotactic protein 1 (MCP-1), tumor necrosis factor alpha (TNF-alpha) 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 beta, MCP-1, TNF-alpha 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. CI - (c) 2023. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature. FAU - Guo, Fan AU - Guo F AD - Institute of Basic Medical Sciences of Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China. AD - Beijing Key Laboratory of Chinese Materia Pharmacology, Beijing, 100091, China. FAU - Han, Xiao AU - Han X AD - Institute of Basic Medical Sciences of Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China. AD - Beijing Key Laboratory of Chinese Materia Pharmacology, Beijing, 100091, China. FAU - You, Yue AU - You Y AD - Institute of Basic Medical Sciences of Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China. AD - Beijing Key Laboratory of Chinese Materia Pharmacology, Beijing, 100091, China. FAU - Xu, Shu-Juan AU - Xu SJ AD - Institute of Basic Medical Sciences of Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China. AD - Beijing Key Laboratory of Chinese Materia Pharmacology, Beijing, 100091, China. FAU - Zhang, Ye-Hao AU - Zhang YH AD - Institute of Basic Medical Sciences of Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China. AD - Beijing Key Laboratory of Chinese Materia Pharmacology, Beijing, 100091, China. FAU - Chen, Yuan-Yuan AU - Chen YY AD - Institute of Basic Medical Sciences of Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China. AD - Beijing Key Laboratory of Chinese Materia Pharmacology, Beijing, 100091, China. FAU - Xin, Gao-Jie AU - Xin GJ AD - Institute of Basic Medical Sciences of Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China. AD - Beijing Key Laboratory of Chinese Materia Pharmacology, Beijing, 100091, China. FAU - Liu, Zi-Xin AU - Liu ZX AD - Institute of Basic Medical Sciences of Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China. AD - Beijing Key Laboratory of Chinese Materia Pharmacology, Beijing, 100091, China. FAU - Ren, Jun-Guo AU - Ren JG AD - Institute of Basic Medical Sciences of Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China. AD - Beijing Key Laboratory of Chinese Materia Pharmacology, Beijing, 100091, China. FAU - Cao, Ce AU - Cao C AD - Institute of Basic Medical Sciences of Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China. AD - Beijing Key Laboratory of Chinese Materia Pharmacology, Beijing, 100091, China. FAU - Li, Ling-Mei AU - Li LM AD - Institute of Basic Medical Sciences of Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China. lilingmei0018@126.com. AD - Beijing Key Laboratory of Chinese Materia Pharmacology, Beijing, 100091, China. lilingmei0018@126.com. AD - Department of Central Laboratory, Kunshan Hospital of Chinese Medicine, Kunshan, Jiangsu Province, 215300, China. lilingmei0018@126.com. FAU - Fu, Jian-Hua AU - Fu JH AD - Institute of Basic Medical Sciences of Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China. AD - Beijing Key Laboratory of Chinese Materia Pharmacology, Beijing, 100091, China. LA - eng PT - Journal Article DEP - 20240206 PL - China TA - Chin J Integr Med JT - Chinese journal of integrative medicine JID - 101181180 SB - IM OTO - NOTNLM OT - Chinese medicine OT - NLRP3 inflammasome OT - human umbilical vein endothelial cells OT - hydroxysafflor yellow A OT - myocardial reperfusion injury OT - oxygen-glucose deprivation reperfusion OT - pyroptosis EDAT- 2024/02/06 13:42 MHDA- 2024/02/06 13:42 CRDT- 2024/02/06 11:12 PHST- 2023/07/03 00:00 [accepted] PHST- 2024/02/06 13:42 [medline] PHST- 2024/02/06 13:42 [pubmed] PHST- 2024/02/06 11:12 [entrez] AID - 10.1007/s11655-023-3716-y [pii] AID - 10.1007/s11655-023-3716-y [doi] PST - aheadofprint SO - Chin J Integr Med. 2024 Feb 6. doi: 10.1007/s11655-023-3716-y.