Apigenin and apigenin-7, 4′-O-dioctanoate protect against acrolein-aggravated inflammation via inhibiting the activation of NLRP3 inflammasome and HMGB1/MYD88/NF-κB signaling pathway in Human umbilical vein endothelial cells (HUVEC). (October 2022)

• Record Type: Journal Article
• Authors: Yu, Jiangqiong; Jiang, Qingqing; Liu, Ning; Fan, Daming; Wang, Mingfu; Zhao, Yueliang
• Is Part Of: Food and chemical toxicology. Volume 168(2022)
• Publication Date: 2022-10
• Subjects: Acrolein -- Inflammation -- HUVEC -- Apigenin -- Apigenin-7 -- 4′-O-Dioctanoate; Toxicology -- Periodicals; Food poisoning -- Periodicals; Food Poisoning -- Periodicals; Toxicology -- Periodicals; Toxicologie -- Périodiques; Intoxications alimentaires -- Périodiques; Food poisoning; Toxicology; Periodicals; Electronic journals; 615.9
• DOI: 10.1016/j.fct.2022.113400
• Languages: English
• ISSNs: 0278-6915

Abstract

Abstract: Exposure to acrolein, one environmental and dietary pollutant, has been shown to cause inflammation. Here, we reported for the first time that acrolein aggravated lipopolysaccharide (LPS)-induced inflammation in Human umbilical vein endothelial cells (HUVEC) as evidenced by the further increased mRNA expression of three pro-inflammatory cytokines, including interleukin 1β (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor-alpha (TNF-α). Acrolein also further increased the generation of reactive oxygen species (ROS) and decreased the activity of glutathione peroxidase (GSH-Px) in LPS-pretreated HUVEC. Moreover, acrolein treatment further increased the nucleotide oligomerization domain-like receptor protein 3 (NLRP3) and apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) expression, caspase-1 cleavage, and downstream matures interleukin 18 (IL-18) and IL-1β level in LPS-pretreated HUVEC. Acrolein treatment also further increased the expressions of high-mobility group box 1 (HMGB1), toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and phospho–NF–κB P65 (P–P65) in the LPS pre-treated HUVEC. Thus, acrolein aggravated LPS-induced HUVEC inflammation through induction of oxidative stress, and activation of NLRP3 inflammasome and HMGB1/MYD88/NF-κB signaling pathway. In addition, apigenin and apigenin-7, 4′-O-dioctanoate attenuated acrolein-aggravated inflammation by targeting the above signaling pathways. Our findings could help to develop potential therapeutic strategies against acrolein-enhanced inflammation. Graphical abstract: Image 1 Highlights: Acrolein aggravated LPS-induced inflammation in HUVEC. Acrolein increased ROS generation and decreased the GSH-Px activity. Acrolein caused further activation of NLRP3 inflammasome. Acrolein activated the HMGB1/TLR4/MyD88/NF-κB signaling pathway. Apigenin-7, 4′-O-dioctanoate attenuated the acrolein-aggravated inflammation.