ArticleDiabetes, metabolic syndrome and obesity : targets and therapy2019
Ursolic Acid Treatment Alleviates Diabetic Kidney Injury By Regulating The ARAP1/AT1R Signaling Pathway.
Article in Diabetes, metabolic syndrome and obesity : targets and therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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18 citing papers in PubMed, 38 citations in OpenAlex.
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- Insights into non-coding RNAS: biogenesis, function and their potential regulatory roles in acute kidney disease and chronic kidney disease.Molecular and cellular biochemistry · 2025Review
- Identification of promising dipeptidyl peptidase-4 and protein tyrosine phosphatase 1B inhibitors from selected terpenoids through molecular modeling.Bioinformatics advances · 2025Article
- The angiotensin II receptors type 1 and 2 modulate astrocytes and their crosstalk with microglia and neurons in an in vitro model of ischemic stroke.BMC neuroscience · 2024Article
- Oleanolic acid and its analogues: promising therapeutics for kidney disease.Chinese medicine · 2024Review
- Ursolic Acid Alleviates Mitotic Catastrophe in Podocyte by Inhibiting Autophagic P62 Accumulation in Diabetic Nephropathy.International journal of biological sciences · 2024Article
- A Review of Medicinal Plants with Renoprotective Activity in Diabetic Nephropathy Animal Models.Life (Basel, Switzerland) · 2023Review
- YY1-induced upregulation of LncRNA-ARAP1-AS2 and ARAP1 promotes diabetic kidney fibrosisFrontiers in pharmacology · 2023Article
- Protective mechanisms of loquat leaf extract and ursolic acid against diabetic pro-inflammation.Journal of molecular medicine (Berlin, Germany) · 2022Article
- Ursolic acid and SARS-CoV-2 infection: a new horizon and perspective.Inflammopharmacology · 2022Review
- Investigations of AGEs' inhibitory and nephroprotective potential of ursolic acid towards reduction of diabetic complications.Journal of natural medicines · 2022Article
- The possible role of ursolic acid in Covid-19: A real game changer.Clinical nutrition ESPEN · 2022Article
- The Use of Bioactive Compounds in Hyperglycemia- and Amyloid Fibrils-Induced Toxicity in Type 2 Diabetes and Alzheimer's Disease.Pharmaceutics · 2022Review
- Excessive Activation of Notch Signaling in Macrophages Promote Kidney Inflammation, Fibrosis, and Necroptosis.Frontiers in immunology · 2022Article
- Molecular Mechanistic Pathways Targeted by Natural Antioxidants in the Prevention and Treatment of Chronic Kidney Disease.Antioxidants (Basel, Switzerland) · 2021Review
- Ursolic acid treats renal tubular epithelial cell damage induced by calcium oxalate monohydrate via inhibiting oxidative stress and inflammation.Bioengineered · 2021Article
- Non-Coding RNAs in Kidney Diseases: The Long and Short of Them.International journal of molecular sciences · 2021Review
- Network Pharmacology-Based Prediction of Mechanism of Shenzhuo Formula for Application to DKD.Evidence-based complementary and alternative medicine : eCAM · 2021Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeThis study aimed to investigate whether ursolic acid (UA) mitigates renal inflammation, oxidative stress and fibrosis by regulating the angiotensin II type 1 receptor-associated protein (ARAP1)/angiotensin II type 1 receptor (AT1R) signaling pathway and subsequently alleviating renal damage.
methodsdb/db mice were divided randomly into a diabetic nephropathy (DN) group and a UA treatment group. Light microscopy and electron microscopy were used to observe pathological changes in renal tissues. Immunohistochemistry (IHC) was employed to examine changes in the expression of ARAP1, AT1R, 8-hydroxydeoxyguanosine (8-OHdG), NADPH oxidase 2 (NOX2), the extracellular matrix protein fibronectin (FN), IL-1β and IL-18 in renal tissues. Western blotting and RT-qPCR were used to detect the respective changes in the protein and mRNA levels of ARAP1, AT1R, NOX4, NOX2, transforming growth factor-β1 (TGF-β1), FN, collagen IV, IL-1β and IL-18 in renal tissues and mesangial cells. In addition, immunofluorescence staining was employed to examine changes in FN and NOX2 expression in mesangial cells.
resultsUA treatment effectively reduced the body weights and blood glucose levels of db/db mice (p<0.05) as well as the urinary albumin/creatinine ratio (p<0.05). In addition, the renal tissue lesions and glomerulosclerosis index of the db/db mice were significantly improved after treatment (p<0.01). Histochemical analysis results showed significantly lower expression levels of ARAP1, AT1R, FN, NOX2, 8-OHdG, IL-1β and IL-18 in renal tissues in the UA treatment group than in the DN group. Western blotting and RT-qPCR data also revealed UA-induced decreases in the renal levels of the ARAP1, AT1, NOX4, NOX2, TGF-β1, FN, collagen IV, IL-1β and IL-18 proteins in vivo and/or in vitro (p<0.01). ARAP1 knockdown effectively reduced the expression of NOX2 and FN in vitro.
conclusionUA alleviated renal damage in type 2 diabetic db/db mice by downregulating proteins in the ARAP1/AT1R signaling pathway to inhibit extracellular matrix accumulation, renal inflammation, fibrosis and oxidative stress.
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