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Icariin, a flavonoid glycoside, is extracted from Epimedium. This study aimed to investigate the vascular protective effects of icariin in type 1 diabetic rats by inhibiting high-mobility group box 1 (HMGB1)-related inflammation and exploring its potential mechanisms. The impact of icariin on vascular dysfunction was assessed in streptozotocin (STZ)-induced diabetic rats through vascular reactivity studies. Western blotting and immunofluorescence assays were performed to measure the expressions of target proteins. The release of HMGB1 and pro-inflammation cytokines were measured by enzyme-linked immunosorbent assay (ELISA). The results revealed that icariin administration enhanced acetylcholine-induced vasodilation in the aortas of diabetic rats. It also notably reduced the release of pro-inflammatory cytokines, including interleukin-8 (IL-8), IL-6, IL-1β, and tumor necrosis factor-alpha (TNF-α) in diabetic rats and high glucose (HG)-induced human umbilical vein endothelial cells (HUVECs). The results also unveiled that the pro-inflammatory cytokines in the culture medium of HUVECs could be increased by rHMGB1. The increased release of HMGB1 and upregulated expressions of HMGB1-related inflammatory factors, including advanced glycation end products (RAGE), Toll-like receptor 4 (TLR4), and phosphorylated p65 (p-p65) in diabetic rats and HG-induced HUVECs, were remarkably suppressed by icariin. Notably, HMGB1 translocation from the nucleus to the cytoplasm in HUVECs under HG was inhibited by icariin. Meanwhile, icariin could activate G protein-coupled estrogen receptor (GPER) and sirt1. To explore the role of GPER and Sirt1 in the inhibitory effect of icariin on HMGB1 release and HMGB-induced inflammation, GPER inhibitor and Sirt1 inhibitor were used in this study. These inhibitors diminished the effects of icariin on HMGB1 release and HMGB1-induced inflammation. Specifically, the GPER inhibitor also negated the activation of Sirt1 by icariin. These findings suggest that icariin activates GPER and increases the expression of Sirt1, which in turn reduces HMGB1 translocation and release, thereby improving vascular endothelial function in type 1 diabetic rats by inhibiting inflammation.

Titel:	Icariin attenuates vascular endothelial dysfunction by inhibiting inflammation through GPER/Sirt1/HMGB1 signaling pathway in type 1 diabetic rats.
Autor/in / Beteiligte Person:	Yao, W ; Tao, R ; Wang, K ; Ding, X
Link:	Zum Volltext
Zeitschrift:	Chinese journal of natural medicines, Jg. 22 (2024-04-01), Heft 4, S. 293
Veröffentlichung:	<2009-> : Beijing : Science Press ; Elsevier ; <i>Original Publication</i>: Nanjing : Ke xue chu ban she, 2024
Medientyp:	academicJournal
ISSN:	1875-5364 (electronic)
DOI:	10.1016/S1875-5364(24)60618-7
Schlagwort:	Animals Rats Male Humans Human Umbilical Vein Endothelial Cells drug effects Inflammation drug therapy Inflammation metabolism Endothelium, Vascular drug effects Endothelium, Vascular metabolism Diabetes Mellitus, Type 1 drug therapy Diabetes Mellitus, Type 1 metabolism Cytokines metabolism Epimedium chemistry HMGB1 Protein metabolism HMGB1 Protein genetics Sirtuin 1 metabolism Sirtuin 1 genetics Flavonoids pharmacology Signal Transduction drug effects Diabetes Mellitus, Experimental drug therapy Diabetes Mellitus, Experimental metabolism Rats, Sprague-Dawley Receptors, G-Protein-Coupled metabolism Receptors, Cannabinoid
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [Chin J Nat Med] 2024 Apr; Vol. 22 (4), pp. 293-306. MeSH Terms: HMGB1 Protein* / metabolism ; HMGB1 Protein* / genetics ; Sirtuin 1* / metabolism ; Sirtuin 1* / genetics ; Flavonoids* / pharmacology ; Signal Transduction* / drug effects ; Diabetes Mellitus, Experimental* / drug therapy ; Diabetes Mellitus, Experimental* / metabolism ; Rats, Sprague-Dawley* ; Receptors, G-Protein-Coupled* / metabolism ; Receptors, Cannabinoid* ; Animals ; Rats ; Male ; Humans ; Human Umbilical Vein Endothelial Cells / drug effects ; Inflammation / drug therapy ; Inflammation / metabolism ; Endothelium, Vascular / drug effects ; Endothelium, Vascular / metabolism ; Diabetes Mellitus, Type 1 / drug therapy ; Diabetes Mellitus, Type 1 / metabolism ; Cytokines / metabolism ; Epimedium / chemistry Contributed Indexing: Keywords: Diabetes; GPER; HMGB1; Icariin; Inflammation; Vascular endothelial dysfunction Substance Nomenclature: VNM47R2QSQ (icariin) ; 0 (HMGB1 Protein) ; EC 3.5.1.- (Sirtuin 1) ; 0 (Flavonoids) ; 0 (Receptors, G-Protein-Coupled) ; 0 (Cytokines) ; 0 (GPR55 protein, human) ; EC 3.5.1.- (Sirt1 protein, rat) ; 0 (Receptors, Cannabinoid) Entry Date(s): Date Created: 20240424 Date Completed: 20240424 Latest Revision: 20240426 Update Code: 20240427

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Icariin attenuates vascular endothelial dysfunction by inhibiting inflammation through GPER/Sirt1/HMGB1 signaling pathway in type 1 diabetic rats.