TABLE 3.

NF-κB and/or ER stress modulators in experimental atherosclerosis and associated disease models.

Category	Modulator	Disease	Model	Pharmacological effect	References
NF-κB inhibitors	BAY 11-7082	Cancer; inflammatory diseases; neurological diseases	LPS-stimulated RAW264.7 macrophages	Inhibition on the translocation of p65, AP-1, IRF3, and STAT-1; inhibition of the phosphorylation of ERK, p38, and JAK-2	(192)
			Imiquimod cream-induced rat model of psoriasis-like dermatitis	Reduction of pNF-κB, NLRP3, TNF-α, IL-6, IL-1β, IL-23, and phosphorylated STAT3	(193)
			In vitro and in vivo xenograft model of oral cancer	Reduction of OSCC cell viability and of NLRP3 inflammasome, caspase-1, IL-1β, and IL-18 expression; increase of Bax, Bad, and p53 expression; reduction of Bcl-2 expression	(194)
	Pyrrolidine dithiocarbamate (PDTC)	Inflammatory disease especially AS	Rat aortic SMCs	Activation of p38 MAPK and JNK; VSMC growth inhibition	(195)
			ApoE knock-out mice	Blockade of NF-κB; down-regulation of IL-18, IL-18Rα, CD36, and MMP-9; promotion of plaque instability	(196)
	IMD-0354	Cancer; inflammatory diseases; cardiovascular diseases	Organ culture of rat mesenteric arteries with removed endothelium	Inhibition on the up-regulated ET (B2) receptor expression and NF-κB activation	(197)
			Melanoma A375 cells and skin epidermoid carcinoma A431 cells	Inhibition of glutamine uptake; attenuation of mTOR signaling; modulator of cell cycle, DNA damage response and UPR/ATF4/CHOP	(198)
UPR inhibitors	Sirtuin 1 (SIRT1)	Cardiovascular diseases	Cardiomyocytes and adult-inducible Sirtuin 1 knock-out mice	Protection against ER stress-induced apoptosis; NAD+-dependent deacetylase, alleviating activation of the PERK/eIF2α branch of the UPR	(199)
	Irisin	Metabolic disorders and AS	OxLDL-induced RAW264.7 macrophages	Alleviation of the apoptosis by inhibiting the PERK/eIF2α/CHOP and ATF6/CHOP ER stress signaling pathways	(200)
	STF-083010 and 4μ8C	Metabolic disorders; AS; cancer	Tunicamycin-treated or high-fat diet fed BI-1 knock-out mice	Reduction of atherosclerotic plaque size; inhibition of IRE1α RNase activity, lipid-induced mtROS production, NLRP3 inflammasome activation, and consequent secretion of IL-1 and IL-18	(205)
ROS-interfering molecules	(E/Z)-BCI hydrochloride	Cancer; inflammatory diseases	LPS-activated macrophages	Inhibition on LPS-triggered inflammatory cytokine production; affecting macrophage polarization to an M1 phenotype; decrease of ROS production; inhibition on phosphorylation and nuclear expression of p65; elevation of Nrf2 levels	(206)
	Dihydrolipoic Acid	Inflammatory and neurological diseases	LPS-induced sickness behavior rat model	Increase of the expression of ERK, Nrf2, and HO-1; decrease of the ROS generation levels and the expression of NLRP3, caspase-1, and IL-1β	(207)
	LGH00168	Cancer	A549 human NSCLC xenograft mice	CHOP activator; induction of necroptosis via ROS-mediated ER stress and NF-κB inhibition	(177)
Natural compounds	Baicalin	Cardiovascular diseases; cancer	Neonatal rat cardiomyocytes	Protection from ER stress-induced apoptosis; targeting the CHOP/eNOS/NO pathway	(210)
	Quercetin	Cancer	Glucosamine- induced RAW264.7 macrophages	Prevention of apoptosis and lipid accumulation by inhibiting ER stress; decrease of CHOP and GRP78 expression; increase of ATF6 expression, activated JNK and caspase-12	(211)
	Resveratrol	Cancer; cardiovascular diseases; infection	Isoproterenol-induced rat cardiomyocytes	Inhibition of cardiomyocyte hypertrophy and apoptosis by suppressing ER stress; decrease of GRP78, GRP94, and CHOP expression; reversion of the expression of Bcl-2 and Bax	(215)
			Doxorubicin-induced H9c2 cells	Protection against ER stress; downregulation of the expression of ER stress marker proteins; ER stabilization through the activation of the SIRT1 pathway	(216)
	Parthenolide	Migraine; arthritis; AS; ischemic injury in brain; cancer	Jurkat cell	Promotion of plaque stability; decrease of NF-κB activation and FasL expression	(102)
			Permanent MCAO rat model	Downregulation of NF-κB, phosho-p38 MAPK, and caspase-1 expression	(220)
	Reticuline	Cardiovascular diseases and inflammatory diseases	Xylene-induced ear edema and carrageenan-induced paw edema in mice and rats	Inhibition on the expression of pro-inflammatory cytokines, such as TNF-α and IL-6; targeting JAK2/STAT3 and NF-κB pathway	(221)
	Sappanone A	Inflammatory diseases	LPS-stimulated RAW264.7 macrophages	Induction of HO-1 expression by activating Nrf2 through the p38 MAPK pathway	(222)
	Isoliquiritigenin	Cancer; infection; inflammatory and neurological diseases	Collagenase IV-induced intracerebral hemorrhage rat model	Suppression of ROS- and/or NF-κB-mediated NLRP3 inflammasome activation by promoting Nrf2 antioxidant pathway	(223)
NcRNAs	Mir-181a-5p/3p	Vascular inflammation and AS	ApoE knock-out mice	Alleviation of atherosclerotic plaque formation; decrease of proinflammatory gene expression; decrease of infiltration of macrophage, leukocyte and T cell into the lesions; targeting TAB2 and NEMO	(224)
	LncRNA VINAS	AS	LDLR knock-out mice	VINAS knockdown reduces atherosclerotic lesion formation and expression of key inflammatory markers and leukocyte adhesion molecules; targeting MAPK and NF-κB signaling pathway	(225)
	LncRNA NORAD	Cancer; AS	OxLDL-treated HUVECs and high-fat-diet ApoE knock-out mice	Increase of endothelial viability; targeting NF-κB, p53-p21 signaling pathways and IL-8	(226)
	Circ-Sirt1	Cardiovascular diseases	HUVECs, human and rat VSMCs	Inhibition on inflammatory phenotypic switching of VSMC and neointimal hyperplasia; impeding NF-κB translocation and its binding to DNA	(85)

ERK, extracellular signal-regulated kinase; JAK, Janus kinase; OSCC, oral squamous cell carcinoma; Bax, Bcl2-Associated X; Bad, Bcl-2 associated death promoter; Bcl-2, B-cell lymphoma 2; ET, endothelin; mTOR, mammalian target of rapamycin; BI-1, Bax inhibitor-1; NSCLC, non-small-cell lung cancer; HUVEC, human umbilical vein endothelial cell; eNOS, endothelial nitric oxide synthase; MCAO, middle cerebral artery occlusion.