Dataset Information

Therapeutic potential of digitoflavone on diabetic nephropathy: nuclear factor erythroid 2-related factor 2-dependent anti-oxidant and anti-inflammatory effect.

ABSTRACT: Nuclear factor erythroid 2-related factor 2 (Nrf2) has emerged as a therapeutic target in many diseases, because it can induce antioxidant enzymes and other cytoprotective enzymes. Moreover, some Nrf2 activators have strong anti-inflammatory activities. Oxidative stress and inflammation are major components involved in the pathology of diabetic nephropathy. In the present study, we evaluated the Nrf2-dependent anti-oxidative and anti-inflammatory effects of digitoflavone in streptozotocin-induced diabetic nephropathy. The molecular mechanisms of digitoflavone were investigated in vitro using SV40-transformed mouse mesangial cells (SV40-Mes13). For the in vivo experiment, diabetes was induced in Nrf2+/+ and Nrf2-/- mice by STZ injection, and digitoflavone was administered 2 weeks after the STZ injection. Digitoflavone induced Nrf2 activation and decreased oxidative damage, inflammation, TGF-β1 expression, extracellular matrix protein expression, and mesangial cell hyperplasia in SV40-Mes13 cells. Digitoflavone-treated Nrf2+/+ mice, but not Nrf2-/- mice, showed attenuated common metabolic disorder symptoms, improved renal performance, minimized pathological alterations, and decreased oxidative damage, inflammatory gene expression, inflammatory cell infiltration, TGF-β1 expression, and extracellular matrix protein expression. Our results show that the anti-oxidative and anti-inflammatory effects of digitoflavone are mediated by Nrf2 activation and that digitoflavone can be used therapeutically to improve metabolic disorders and relieve renal damage induced by diabetes.

SUBMITTER: Yang Y

PROVIDER: S-EPMC4513300 | biostudies-other | 2015

REPOSITORIES: biostudies-other

ACCESS DATA

Similar Datasets

Project description:Potential probiotic bacteria can be used as a biotherapeutic agent and a sustainable alternative to antibiotics, as an anti-oxidative, anti-inflammatory, and anti-diabetic agent without causing any serious side effects. Mostly human-friendly Lactic acid bacteria (LAB) have been isolated from the animal-human origin to be used as biotherapeutic agents or to produce useful metabolites (nutraceutical). However, less information is known about the role of medicinal plants associated LAB as biotherapeutic agents. The isolation of 115 human-friendly Lactobacillus strains was done from the rhizosphere of the medicinal plants Ocimum tenuiflorum, Azadirachta indica, Ficus carica. The obtained bacteria were then tested for their safe status before being using it for a beneficial purpose. Out of 115 strains, 29 (25%) were negative for blood hemolytic activities. Among these 29 isolates, three isolates did not show a breakdown of gelatin and were recognized as safe. Antibiotic resistance assay showed resistance of two of them against antibiotics discs of Streptomycin (10 µg), Ciprofloxacin (20 µg), Vancomycin (30 µg), Metronidazole (10 µg), Ampicillin (5 µg), Chloramphenicol (30 µg), Kanamycin (30 µg), Erythromycin (15 µg), Penicillin (10 µg) and Tetracycline (30 µg). The bacterial isolate (T-2) was found safe that was identified as Lactobacillus agilis by sequence analysis of 16 s rRNA gene and processed in vitro as an anti-bacterial, anti-oxidant, anti-diabetic, and anti-inflammatory agent. Free radical scavenging activities and inhibition of α-amylase activities for Lactobacillus agilis were found relative to standard drug values as 68% and 73% and 51.3% and 65.3%, respectively. The in-vitro anti-inflammatory assay showed 61.6% (Lactobacillus agilis) while showed 69% (aspirin) activity for denaturation albumin protein. The results suggested that Lactobacillus agilis can be used as a potential probiotic strain as well as can be used to produce nutraceuticals.

Project description:Diabetic nephropathy (DN is a dreaded consequence of diabetes mellitus, accounting for about 40% of end-stage renal disease (ESRD). It is responsible for significant morbidity and mortality, both directly by causing ESRD and indirectly by increasing cardiovascular risk. Extensive research in this field has thrown light on multiple pathways that can be pharmacologically targeted, to control or reverse the process of DN. Glomerulocentric approach of DN still continues to produce favourable results as evidenced by the recent data on SGLT-2 (sodium glucose co-transporter type 2) inhibitors. Beyond the glomerular mechanisms, numerous novel pathways have been discovered in the last decade. Some of these pathways target inflammatory and oxidative damage, while the others target more specific mechanisms such as AGE-RAGE (advanced glycation end products-receptors for advanced glycation end products), ASK (apoptotic signal-regulating kinase), and endothelin-associated pathways. As a result of the research, a handful of clinically relevant drugs have made it to the human trials which have been elucidated in the following review, bearing in the mind that there are many more to come over the next few years. Ongoing research is expected to inform the clinicians regarding the use of the newer drugs in DN. Abbreviations: USFDA: Unites States Food and Drug Administration; SGLT-2: Sodium glucose transporter type 2; GLP-1: Glucagon-like peptide-1; DDP-4: Dipeptidyl peptidase-4; UACR: urinary albumin creatinine ratio; eGFR: Estimated glomerular filtration rate; CKD: Chronic kidney disease; DN: Diabetic nephropathy; TGF: Tubuloglomerular feedback; RAAS: Renin angiotensin aldosterone system; T1DM: Type 1 diabetes mellitus; T2DM: Type 2 diabetes mellitus; RCT: Randomized controlled trial; AGE-RAGE: Advanced glycation end products-receptors for advanced glycation end products; ASK-1: Apoptotic signal-regulating kinase-1; Nrf-2: Nuclear 1 factor [erythroid derived-2]-related factor 2; ml/min/1.73m2: Millilitre/minute/1.73 square meters of body surface area; ~: Approximately.

Dataset Information

Therapeutic potential of digitoflavone on diabetic nephropathy: nuclear factor erythroid 2-related factor 2-dependent anti-oxidant and anti-inflammatory effect.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets