Carnosic acid improves diabetic nephropathy by activating Nrf2/ARE and inhibition of NF-κB pathway

Xie, Zhisheng; Zhong, Lingjun; Wu, Yanrao; Wan, Xiaomeng; Yang, Hua; Xu, Xiaojun; Li, Ping

doi:10.1016/j.phymed.2018.04.031

Cited by 46 publications

(21 citation statements)

References 49 publications

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“…With regards to the pathological progression in DN, Kuhad and Chopra ( 45 ) reported that suppression of the NF-κB pathway using NF-κB inhibitors protected renal functions via the suppression of the inflammatory response in diabetic rats. Xie et al ( 46 ) have also shown that Carnosic acid improved DN by inhibiting the NF-κB pathway in streptozotocin-induced diabetic mice. Moreover, Ohga et al ( 47 ) demonstrated that thiazolidinedione (a PPAR-γ agonist) treatment ameliorated renal injury in experimental diabetic rats via anti-inflammatory effects mediated by inhibiting NF-κB activation.…”

Section: Discussionmentioning

confidence: 96%

MicroRNA‑199a‑3p suppresses high glucose‑induced apoptosis and inflammation by regulating the IKKβ/NF‑κB signaling pathway in renal tubular epithelial cells

2020

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Renal tubular epithelial cells (RTEC) injury induced by hyperglycemia is considered a major contributor to the pathogenesis of diabetic nephropathy (DN). However, few studies have focused on the role of microRNAs (miRNAs/miRs) in RTEC injury. Therefore, the present study aimed to investigate the role and mechanisms of miRNAs in RTEC injury. In the study, miRNAs expression profiles were determined via microarray assay in the peripheral blood samples of patients with DN. High glucose (HG)-induced injury in HK-2 cells was used as a cell model to examine the potential role of miR-199a-3p in DN. The expression of miR-199a-3p was validated using reverse transcription-quantitative PCR. The expressions of TNF-α, IL-1β and IL-6, were detected via ELISA. The protein levels of apoptosis-related proteins were determined using western blotting. Cell apoptosis and caspase 3 activity were evaluated via flow cytometry analysis and caspase 3 activity assay, respectively. Luciferase reporter assay was used to confirm the interaction between miR-199a-3p and IKKβ. miR-199a-3p was found to be significantly downregulated in the peripheral blood samples, and there was a negative correlation between miR-199a-3p expression and proteinuria in patients with DN. It was identified that miR-199a-3p expression was time-dependently decreased in the HG-induced cell damage model. Moreover, miR-199a-3p overexpression significantly improved HG-induced cell injury, as evidenced by the decrease in cell apoptosis and inflammation. Subsequent analyses demonstrated that miR-199a-3p directly targeted IKKβ, whose expression was increased, and negatively correlated with miR-199a-3p expression in patients with DN. The protective effects of miR-199a-3p overexpression on HG-treated HK-2 cells were partially reversed by IKKβ overexpression. In addition, activation of the NF-κB pathway by HG was blocked by miR-199a-3p mimics transfection in HK-2 cells. Collectively, the present findings indicated that miR-199a-3p protected HK-2 cells against HG-induced injury via inactivation of the IKKβ/NF-κB pathway, suggesting enhanced expression of miR-199a-3p as a potential therapeutic strategy for patients with DN.

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Section: Discussionmentioning

confidence: 96%

MicroRNA‑199a‑3p suppresses high glucose‑induced apoptosis and inflammation by regulating the IKKβ/NF‑κB signaling pathway in renal tubular epithelial cells

2020

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“…upregulation) of Nrf2/HO-1 has been gaining popularity as a therapeutic approach. Several Nrf2 activating natural polyphenols have been reported to ameliorate DN in patients (Sun et al, 2017;Xie et al, 2018;Zhang et al, 2018). SA (3,5-dimethoxy-4-hydroxycinnamic acid), that can be found in berries, vegetables, cereals, and oilseed crops (Andreasen et al, 2001), is naturally phenolic compound that can be found in the plant such as fruits, vegetables, cereal grains, and oilseed crops.…”

Section: Introductionmentioning

confidence: 99%

Sinapic Acid Ameliorates the Progression of Streptozotocin (STZ)-Induced Diabetic Nephropathy in Rats via NRF2/HO-1 Mediated Pathways

Alaofi

2020

Front. Pharmacol.

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Diabetic neuropathy (DN) is a complicated inauspicious outcome of diabetes, like other abnormalities of diabetes the cause of DN is still vague and it may be the result of various pathological conditions leading up to end-stage renal failure. The present study examines the efficacy of sinapic acid (SA) in streptozotocin (STZ)-induced DN nephropathy and the linked pathway. Twenty-four rats were equally divided randomly into four categories: Normal control (NC), STZ, STZ + SA 20 mg/kg bw, and STZ + SA 40 mg/kg bw. After 8 weeks they were evaluated for ratio of renal index, the fasting blood glucose (FBG), blood urea nitrogen (BUN), 24 h urea protein, serum creatinine (SCr), reduced glutathione peroxidase (GPx), superoxide dismutase (SOD), lipid peroxidation (MDA), tumor necrosis factor a (TNFa), interleukin (IL)-6, as well as lipid profile total cholesterol (TC), total triglycerides (TG), very low density lipoprotein (VLDL), low density lipoprotein (LDL), and high density lipoprotein (HDL) levels. Additionally, histomorphology and ultrastructure of the kidneys were also assessed. Protein expression levels of transforming growth factor-b1 (TGF-b1), nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), IkBa protein (IkBa), anti-apoptotic protein BCl2, nuclear factor kappa B (NF-kB), and Bax were examined. We observed that SA 20 mg/kg bw and 40 mg/kg bw pretreatment significantly and dose-dependently upregulated the protein expression of HO-1, Nrf2, IKBa, and Bcl-2 but downregulated the protein expression of NF-kB, proposing that the nephroprotective mechanism of SA is due to its antioxidant and anti-inflammatory activity; SA prevents the release of cytokines and inflammatory markers (TNFa and IL-6), upregulates antioxidant defense enzymes, and reduces lipid peroxidation, as well as nitric oxide, and anti-apoptotic activity, which may be influenced by the regulation of TNF-a, IL-6, Bcl-2, NF-kB, and BaX via the Nrf2/HO-1 pathway in STZ induced DN. Thus, our results suggest that SA ameliorates the development of STZ-induced DN in rats via NRF2/HO-1 mediated pathways. Further comprehensive studies are required for complete elucidation of the fundamental mechanisms.

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“…Preceding experimental research has found that the production level of pro-inflammatory cytokines, for example, IL-1β and IL-6, TNF-α is increased in diabetic nephropathy [27,28]. Stimulating an increase in the expression of various pro-inflammatory cytokines goes through the stimulation of NF-κB pathway when the organism produces oxidative stress, thus damaging the renal tissue [29]. Foregone experimental studies have shown that pro-inflammatory cytokines affected renal function and renal damage in a few mechanistic pathways [20,30,34].…”

Section: Discussionmentioning

confidence: 99%

Raspberry ketone improves diabetic nephropathy in mice by inhibiting streptozotocin-induced oxidative stress and inflammation

Wang¹,

Chang²,

Wang³

et al. 2020

Preprint

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Background Oxidative stress and inflammation play important roles in the pathogenesis of diabetic nephropathy. Raspberry ketone (RK) is one of the main active substances in raspberry and has a variety of medicinal values. Nevertheless, its protective effect on streptozotocin (STZ)-induced diabetic nephropathy mice has not been reported. In this study, we researched if RK improves oxidative stress and inflammation of STZ-induced diabetic nephropathy mice. Methods The model of diabetic nephropathy mice was established by a single injection of STZ (130 mg/kg). Diabetic nephropathy mice were treated orally with 400 mg/kg/day raspberry ketone extract to eight weeks. The expression levels of serum creatinine (Scr), urine micro-albumin (mALB), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), interleukin 1β (IL-1β) and interleukin 6 (IL-6) were measured by Enzyme-linked immunosorbent (ELISA). Renal structural changes were investigated by using animal diagnostic ultrasound system. Results RK obviously ameliorated as observed in the visible decrease levels of serum creatinine (Scr), urine micro-albumin (mALB). Furthermore, RK improved expression levels of antioxidant enzyme markers (GSH-Px, SOD, CAT) and obviously reduced MDA, a product of lipid peroxidation, pro-inflammatory divisors (TNF-α, IL-6, IL-1β) in diabetic nephropathy mice. After treatment with RK, we observed that the size of the kidneys and the damage of renal interstitial of mice were obviously improved, as well as the loss of integrity of basement membrane and the renal interstitial edema in diabetic nephropathy mice by using animal diagnostic ultrasound system. Conclusion This study strongly indicates that raspberry ketone provides a protective effect against STZ-induced diabetic nephropathy in improving oxidative stress and inflammation.

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Carnosic acid improves diabetic nephropathy by activating Nrf2/ARE and inhibition of NF-κB pathway

Cited by 46 publications

References 49 publications

MicroRNA‑199a‑3p suppresses high glucose‑induced apoptosis and inflammation by regulating the IKKβ/NF‑κB signaling pathway in renal tubular epithelial cells

MicroRNA‑199a‑3p suppresses high glucose‑induced apoptosis and inflammation by regulating the IKKβ/NF‑κB signaling pathway in renal tubular epithelial cells

Sinapic Acid Ameliorates the Progression of Streptozotocin (STZ)-Induced Diabetic Nephropathy in Rats via NRF2/HO-1 Mediated Pathways

Raspberry ketone improves diabetic nephropathy in mice by inhibiting streptozotocin-induced oxidative stress and inflammation

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