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

Abstract

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.

Antidiabetic and Nephroprotective Effects of Polysaccharide Extract from the Seaweed Caulerpa racemosa in High Fructose-Streptozotocin Induced Diabetic Nephropathy

“…Urinary albumin, BUN and serum creatinine are markers for the progression of DN, indicating glomerular lesions that could trigger progressive glomerulosclerosis. 30 , 31 Glomerular basement membrane damage and the consequent glomerular filtration barrier dysfunction contribute to renal damage and urinary albumin. 32 Previous reports have shown albuminuria/proteinuria and decimated renal function in DN as well as characteristic renal lesions including, hypertrophy, tubule thickening, necrosis and epithelial desquamation.…”

“…Oxidative stress, which results from excess free radical production, is strongly implicated in DN as impaired antioxidant defence systems. 30 , 34 , 46 In an attempt to explore the possible antioxidant efficacy of natural agents, previous studies assessed antioxidant enzymes and lipid peroxidation in target organs. Similarly, we evaluated renal SOD, CAT, and GSH-Px activities, as well as MDA in the current investigation.…”

Pharmacotherapy against Oxidative Stress in Chronic Kidney Disease: Promising Small Molecule Natural Products Targeting Nrf2-HO-1 Signaling

“…These renoprotective activities of AST were attributed to its activation of Nrf2/ARE signaling [111]. Sinapic acid prevented STZ-induced DKD in rats by attenuating inflammation and OS through upregulating Nrf2/HO-1 signaling pathways [132]. Calycosin ameliorated kidney injury and dysfunction in HFD-fed/STZ-induced diabetic rats by inhibiting inflammation, and OS through modulating the IL33/ST2, NF-κB, and Nrf2 signaling pathways [114].…”

Sinapic Acid and Sinapate Esters in Brassica: Innate Accumulation, Biosynthesis, Accessibility via Chemical Synthesis or Recovery From Biomass, and Biological Activities

“…Many human health benefits of SinA and derivatives have been reported, and these include anti-inflammatory (Yun et al, 2008;Calabriso et al, 2019), anticancer (Raj Preeth et al, 2019Boeing et al, 2020), anti-diabetic (Cherng et al, 2013;Alaofi, 2020), and antihypertensive properties (Silambarasan et al, 2014) as well as their protections of the nervous, respiratory, and digestive systems (Sova and Saso, 2020). For further details on the health benefits of these metabolites, we highly recommend the reviews by Sova and Saso (Sova and Saso, 2020) and by Neelam et al (Neelam et al, 2020).…”