Up-regulation of Nrf2/HO-1 and inhibition of TGF-β1/Smad2/3 signaling axis by daphnetin alleviates transverse aortic constriction-induced cardiac remodeling in mice

Carvacrol preserves antioxidant status and attenuates kidney fibrosis via modulation of TGF-β1/Smad signaling and inflammation

“…After 24 h, the cells were exposed to different concentrations of CVL (ranging from 0.39 to 50 μg ml −1 ) in serum-free media and incubated for 48 h. The cell viability was assessed by incubating cells with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) for 4 h as described in earlier literature. 22 The formazan crystals formed were solubilized in dimethyl sulfoxide (DMSO), and absorbance was read at 540 nm.…”

Natural Coumarin Derivatives Activating Nrf2 Signaling Pathway as Lead Compounds for the Design and Synthesis of Intestinal Anti-Inflammatory Drugs

“…control of allergic rhinitis induced by ovalbumin in C57BL/6 female mice after oral treatment with 5 mg/Kg alleviated nasal symptoms, inflammatory response, and oxidative stress, activating Nrf2/HO-1 and inactivating the NF-κB pathway through the reduction in Toll-like Receptor 4, NF-κB protein levels, and TNF-α and IL-5 production [89]. Modulation of Nrf2 associated with other signaling pathways has been reported as the molecular mechanism of protection against several diseases, including cardiac hypertrophy and fibrosis [90], diabetes, lipid metabolism, and insulin resistance [91,92], hepatotoxicity [93], inflammation [88], lung toxicity [94], and neuronal and renal damage [95][96][97]. Protective antioxidant properties of daphnetin upregulating the Nrf2/HO-1 pathway with simultaneous inhibition of transforming growth factor β1 (TGF-β1)/Smad2/3 signaling axis was demonstrated in rat cardiomyoblast H9c2 cells and transverse aortic constriction model in C57BL/6 mice, alleviating cardiac hypertrophy and fibrosis [90].…”

“…Modulation of Nrf2 associated with other signaling pathways has been reported as the molecular mechanism of protection against several diseases, including cardiac hypertrophy and fibrosis [90], diabetes, lipid metabolism, and insulin resistance [91,92], hepatotoxicity [93], inflammation [88], lung toxicity [94], and neuronal and renal damage [95][96][97]. Protective antioxidant properties of daphnetin upregulating the Nrf2/HO-1 pathway with simultaneous inhibition of transforming growth factor β1 (TGF-β1)/Smad2/3 signaling axis was demonstrated in rat cardiomyoblast H9c2 cells and transverse aortic constriction model in C57BL/6 mice, alleviating cardiac hypertrophy and fibrosis [90]. Hepatoprotective effects were reported on HepG2 cells and acute liver failure experimental models using C57BL/6 mice, in which daphnetin enhanced the Keap1/Nrf2 signaling, upregulating thioredoxin-1 expression, inactivating thioredoxin-interaction protein, and suppressing apoptosis signaling-regulating kinase/JNK pathways [93].…”

Induction of Cardiac Pathology: Endogenous versus Exogenous Nrf2 Upregulation

“…Of current controversy in cardiac research is the involvement of Nrf2 as a pro-hypertrophic, factor in progressive heart failure. On one side, numerous reports have linked Nrf2 deficiencies to ROS-mediated cardiac hypertrophy related to Angiotensin II, IL-6-mediated inflammation, aortic constriction (TGFβ1/SMAD2 signaling), and obesity-related stress [ 51 , 52 , 53 ]. Diverse other reports have detailed the role of Nrf2 in preventing cardiomyocyte necrosis, hypertrophy, and fibrosis of the myocardium due to ROS while antioxidant response proteins (e.g., NQO1, SOD1, GPX4) have been found at low expression levels under ischemic cardiomyopathy conditions [ 54 , 55 ]).…”