Coumarins as Modulators of the Keap1/Nrf2/ARE Signaling Pathway

Table 2

Effect of coumarins on Nrf2 in in vitro studies.

Coumarin	Model/cells	Effects	Reference(s)
IMP	Arsenic trioxide-induced toxicity in H9c2 cells	IMP-attenuated ROS generation, cytotoxicity, and apoptosis triggered Nrf2 activation.	[76]
	IgE-mediated allergic responses in RBL-2H3 cells	IMP inhibited mast cell degranulation; suppressed NF-κB, p38, JNK, and ERK MAPKs; and increased Nrf2 nuclear translocation.	[77]
Urolithin B	LPS-induced BV2 microglial cells	Urolithin B reduced ROS production, NADPH oxidase expression, NF-κB, ERK, and JNK and increased AMPK phosphorylation, Nrf2, and HO-1.	[92]
Urolithin A	Senescent human skin fibroblasts	Urolithin A increased type I collagen expression, reduced intracellular ROS, abolished MMP-1 expression, and activated Nrf2/ARE signaling.	[103]
	LPS-induced Caco2 and HT-29 cells	Urolithin A activated aryl hydrocarbon receptor- (AhR-) Nrf2-dependent pathways.	[104]
Scopoletin	Rotenone-stimulated SH-SY5Y cells	Scopoletin prevented oxidative stress and apoptosis and activated Nrf2 signaling.	[122]
Daphnetin	Oleic acid-induced HepG2 cells	Daphnetin decreased CYP2E1 and CYP4A expression, promoted glucose uptake and insulin sensitivity, and enhanced PI3K/Akt and Nrf2 signaling.	[133]
	Arsenic-induced human lung epithelial cells	Daphnetin reduced ROS, JNK, ERK, Keap1, and apoptosis and activated Nrf2/ARE pathway.	[134]
	HG-induced human glomerular mesangial cells	Daphnetin reduced ROS production; attenuated the release of IL-1β, IL-6, and TNF-α via suppression of NF-κB pathway; inhibited the expression Keap1; and upregulated Nrf2.	[135]
	Oxygen-glucose deprivation/reoxygenation-induced hippocampal neurons	Daphnetin inhibited oxidative stress and cell apoptosis and enhanced the nuclear translocation of Nrf2 and HO-1 expression.	[136]
	t-BHP-induced RAW264.7 cells	Daphnetin suppressed ROS, inhibited cytochrome c release and NLRP3 inflammasome activation, and upregulated Nrf2 nuclear translocation along with Keap1 protein downregulation.	[137]
Esculin	EK 293 and RAW264.7 cells	Esculin suppressed ROS production and activated Nrf2/ARE signaling.	[148]
Esculetin	NB4 leukemia cells	Esculetin increased the nuclear translocation of Nrf2.	[164]
	HG-induced rat mesangial cell line HBZY-1	Esculetin suppressed ROS production and IL-6 expression and activated Nrf2.	[166]
	H2O2-induced C2C12 myoblasts	Esculetin suppressed ROS production and activated the Nrf2/NQO1 pathway.	[167]
	Pancreatic carcinoma cells (PANC-1)	Esculetin increased Nrf2 and NQO1 gene expression and Nrf2 nuclear accumulation.	[168]
	H2O2-induced HepG2 cells	Esculetin activated Nrf2/NQO1 pathway	[169]
UMB	HG-induced mesangial cells	UMB suppressed ROS production and activated Nrf2.	[166]
	MG-induced HepG2 cells	UMB abolished ROS generation and increased Nrf2 expression, effects inhibited by Nrf2 depletion.	[181]
Fraxetin	Vascular smooth muscle cells	Fraxetin increased the expression of HO-1 and Nrf2.	[195]
	HaCaT human keratinocytes	Fraxetin reduced ROS and upregulated Akt, AMPK, HO-1, and Nrf2.	[194]
Fraxin	t-BHP-induced HepG2 cells	Fraxin inhibited t-BHP-induced cytotoxicity and ROS generation through Nrf2-dependent HO-1 expression.	[198]
Wedelolactone	t-BHP-induced adrenal pheochromocytoma cells	A wedelolactone-rich extract prevented apoptosis and activated Nrf2/ARE pathway.	[219]
Osthole	LPS-stimulated BV2 mouse microglia	Osthole suppressed NF-κB, IL-1β, IL-6, and TNF-α and upregulated Nrf2/HO-1 signaling	[245]
	LPS-stimulated mesangial cells	Osthole inhibited ROS generation, MCP-1 secretion, and NF-κB activation and upregulated Nrf2.	[248]
Hydrangenol	LPS-stimulated BV2 microglial cells	Hydrangenol attenuated NO production and iNOS expression by inhibiting NF-κB activation and stimulated Nrf2/HO-1 signaling pathway.	[250]
Isoimperatorin	Aflatoxin B1-inducible cytotoxicity in H4IIE	Isoimperatorin activated Nrf2/ARE and GST-α and suppressed CYP1A expression.	[256]