RT Journal Article T1 The Sponge-Derived Brominated Compound Aeroplysinin-1 Impairs the Endothelial Inflammatory Response through Inhibition of the NF-κB Pathway A1 Vidal-Valenzuela, Isabel A1 Castilla-Ruiz, Laura A1 Marrero-Capitán, Ana Dácil A1 Bravo-Ruiz, Inés A1 Bernal-Muñoz, Manuel A1 Manrique-Poyato, María Inmaculada A1 Rodríguez-Quesada, Ana María A1 Medina-Torres, Miguel Ángel A1 Martínez-Poveda, Beatriz Amparo A1 Vidal-Valenzuela, K1 Inflamación AB Aeroplysinin-1 (Apl-1) is a brominated compound isolated from the marine spongeAplysina aerophoba that exhibits pleiotropic bioactive effects, impairing cell growth in cancer cells,inhibiting angiogenesis in vitro and in vivo and modulating the redox status of different cell types,among other reported activities. In addition to the aforementioned effects, the anti-inflammatory po-tential of this natural compound was explored in previous work of our laboratory, but the mechanismof action underlying this effect was not described. In this work, we delve into the anti-inflammatoryeffect of Apl-1 in the context of vascular endothelial cells in vitro, providing new data regardingthe molecular mechanism underlying this activity. The characterization of the mechanism of actionpoints to an inhibitory effect of Apl-1 on the NF-κB pathway, one of the main axes involved inendothelial response during inflammatory events. Our results show that Apl-1 can inhibit the ex-pression of pro-inflammatory genes in tumor necrosis factor alpha (TNF-α)- and lipopolysaccharide(LPS)-stimulated human umbilical vein endothelial cells (HUVECs), targeting the nuclear factorkappa B subunit (NF-κB) pathway through a mechanism of action involving the inhibition of I kappaB kinase (IKK) complex phosphorylation and RelA/p65 nuclear import. In addition, Apl-1 preventedthe phosphorylation of Akt induced by TNF-α in HUVECs, probably supporting the inhibitory effectof this compound in the NF-κB pathway. Experimental evidence reported in this work opens the doorto the potential pharmacological use of this compound as an anti-inflammatory agent in diseases thatcourse with a pathological endothelial response to inflammation, such as atherosclerosis. PB MDPI YR 2022 FD 2022 LK https://hdl.handle.net/10630/33874 UL https://hdl.handle.net/10630/33874 LA eng NO Vidal, I.; Castilla, L.; Marrero, A.D.; Bravo-Ruiz, I.; Bernal, M.; Manrique, I.; R. Quesada, A.; Medina, M.Á.; Martínez-Poveda, B. The Sponge-Derived Brominated Compound Aeroplysinin-1 Impairs the Endothelial Inflammatory Response through Inhibition of the NF-κB Pathway. Mar. Drugs 2022, 20, 605. https://doi.org/10.3390/md20100605 NO This research was funded by grants PID2019-105010RB-I00 (MICINN and FEDER), UMA18-FEDERJA-220 and PY20_00257 (Andalusian Government and FEDER), and funds from groupBIO 267 (Andalusian Government). The “CIBER de Enfermedades Raras” and “CIBER de Enfer-medades Cardiovasculares” are initiatives from the ISCIII (Spain). M.B. is supported by “Juan dela Cierva—Incorporation Program” (IJC2018-037657-I; Spanish Ministry of Science and Innovation).The APC was funded by grant PID2019-105010RB-I00. DS RIUMA. Repositorio Institucional de la Universidad de Málaga RD 20 ene 2026