Nrf2 activator for the treatment of kidney diseases

Yamawaki, Kengo; Kanda, Hironori; Shimazaki, Ryutaro

doi:10.1016/j.taap.2018.09.030

Cited by 54 publications

(43 citation statements)

References 66 publications

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“…To further explore the mechanisms of SGF reduction of ROS accumulation in HEK-293 cells treated with Pb, we detected the effect of SGF on Nrf2 (a key regulator of redox homeostasis in cells). It has been reported that the Keap1/Nrf2/ARE signaling pathway plays an important part in ROS-induced oxidative stress ( Yamawaki et al., 2018 ; Upadhyaya et al., 2019 ). We measured expression of the proteins related to this pathway by western blotting.…”

Section: Resultsmentioning

confidence: 99%

Protective Effects of Smilax glabra Roxb. Against Lead-Induced Renal Oxidative Stress, Inflammation and Apoptosis in Weaning Rats and HEK-293 Cells

Shi

Tian

et al. 2020

Front. Pharmacol.

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Lead (Pb) is an important environmental pollutant. Oxidative stress and the inflammatory response have been postulated as mechanisms involved in lead-induced renal damage. Smilax glabra Roxb. has been used for treatment of heavy-metal poisoning in China for 500 years. We investigated S. glabra flavonoids extract (SGF) could attenuate lead acetate-induced nephrotoxicity in weaning rats and human embryonic kidney (HEK)-293 cells, and investigated the possible mechanisms. Compared with Pb exposed group of weaning rats, SGF could significantly promote lead excretion in the blood and kidney, and increase the content of the renal-function indicators blood urea nitrogen, serum uric acid, and serum creatinine. SGF could improve the glomerular filtration rate (GFR) and histologic changes in the kidneys of weaning rats exposed to Pb. SGF could also reduce lead-induced cytotoxicity, improve DNA damage-induced apoptosis and cleaved caspase-3-mediated apoptosis in HEK-293 cells stimulated with Pb. SGF significantly increased the activity of the antioxidant enzymes superoxide dismutase, glutathione peroxidase and catalase, and decreased excessive release of reactive oxygen species (ROS) and malondialdehyde in the kidneys of the weaning rats and in HEK-293 cells. The antioxidant mechanism of SGF related to activation of the Kelch-like ECH-associated protein 1/nuclear-factor-E2-related factor 2/hemeoxygenase-1(Keap1/Nrf2/HO-1) pathway. SGF could inhibit secretion of interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α induced by Pb in vivo and in vitro . The anti-inflammatory mechanism of SGF related to inhibition of ROS and pro-inflammatory cytokines triggered the nuclear factor-kappa B (NF-κB) pathway through blockade of inhibitors of I-κB degradation, phosphorylation of NF-κB p65, and nuclear translocation of p65. Our findings indicate that SGF could be a natural antioxidant and anti-inflammatory agent for treating lead-induced nephrotoxicity.

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Section: Resultsmentioning

confidence: 99%

Protective Effects of Smilax glabra Roxb. Against Lead-Induced Renal Oxidative Stress, Inflammation and Apoptosis in Weaning Rats and HEK-293 Cells

Shi

Tian

et al. 2020

Front. Pharmacol.

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“…17,18 Bardoxolone methyl is currently in clinical trials for Alport's Syndrome (CARDINAL, NCT03019185), IgA nephropathy, type 1 diabetic nephropathy, focal segmental glomerulosclerosis, and autosomal dominant polycystic kidney disease (PHOENIX, NCT03366337). An additional phase 3 study in patients with diabetic kidney disease is also being performed with a primary composite outcome as the time to onset of a 30% decline in eGFR or end-stage renal disease 19 (AYAME, NCT03550443). Supporters advocate for continued testing with careful monitoring and patient selection, 20 but long-term deleterious effects remain a concern.…”

Section: Introductionmentioning

confidence: 99%

Genetic or pharmacologic Nrf2 activation increases proteinuria in chronic kidney disease in mice

Rush

Bondi

Stocker

et al. 2021

Kidney International

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“…The Keap1-Nrf2 system gained the attention of many scholars in recent years due to its antioxidant and anti-in ammatory properties. Its pharmacological potential in treating kidney diseases has been extensively studied in nonclinical and clinical studies [23]. Activating Nrf2 might improve CKD progression by preventing oxidative stress and maintaining cellular redox homeostasis [24].…”

Section: Discussionmentioning

confidence: 99%

Extract of Corallodiscus Flabellata Attenuates Renal Fibrosis in Aging Mice via the Wnt/β-catenin/RAS Signaling Pathway

Cao

Zeng

et al. 2020

Preprint

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Abstract Background: Renal fibrosis is a common pathological feature of chronic kidney disease (CKD). Aging accelerates renal fibrosis and further aggravates the process of CKD. Corallodiscus flabellata B. L. Burtt (C. flabellata) is a commonly used botanical drug in the Chinese population. However, few studies have reported its physiological effects. This study aimed to explore the effect of C. flabellata extract on renal fibrosis in aging mice and identify potentially active compounds. Methods: Using Senescence-accelerated mouse-prone 8 (SAMP8) mice and β-galactosidase (β-gal)-induced normal rat kidney epithelial cells (NRK-52E cells) as a model, to explore the mechanism of C. flabellata extract on senescence-related renal fibrosis, and initially clarified the material basis of C. flabellata. Results: The C. flabellata extract reduced the senescence and fibrosis of the kidneys in SAMP8 mice by activating nuclear factor erythroid 2–related factor 2 (Nrf2) to balance oxidative stress and inflammation, and interrupting the fibrinogen signaling in the Wnt/β-catenin/renin–angiotensin system. Moreover, 3,4-dihydroxyphenylethanol (SDC-0-14, 16) and (3,4-dihydroxyphenylethanol-8-O-[4-O-trans-caffeoyl-β-D-apiofuranosyl-(1→3)-β-D-glucopyranosyl (1→6)]-β-D-glucopyranoside (SDC-1-8) were isolated compounds from C. flabellata, which reduced the senescence of NRK-52E cells, and maybe the material basis for the function of C. flabellata. Conclusion: Our experiments illuminated that the extract of C. flabellata may improve the aging-related renal fibrosis through the Wnt/β-catenin/RAS pathway, and the material basis of its function may be SDC-0-14, 16 and SDC-1- 8.

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Nrf2 activator for the treatment of kidney diseases

Cited by 54 publications

References 66 publications

Protective Effects of Smilax glabra Roxb. Against Lead-Induced Renal Oxidative Stress, Inflammation and Apoptosis in Weaning Rats and HEK-293 Cells

Protective Effects of Smilax glabra Roxb. Against Lead-Induced Renal Oxidative Stress, Inflammation and Apoptosis in Weaning Rats and HEK-293 Cells

Genetic or pharmacologic Nrf2 activation increases proteinuria in chronic kidney disease in mice

Extract of Corallodiscus Flabellata Attenuates Renal Fibrosis in Aging Mice via the Wnt/β-catenin/RAS Signaling Pathway

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