ArticleBiological research2024
Renoprotective effect of a novel combination of 6-gingerol and metformin in high-fat diet/streptozotocin-induced diabetic nephropathy in rats via targeting miRNA-146a, miRNA-223, TLR4/TRAF6/NLRP3 inflammasome pathway and HIF-1α.
Article in Biological research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Research hotspots and future trends in lipid metabolism in chronic kidney disease: a bibliometric and visualization analysis from 2004 to 2023.Frontiers in pharmacology · 2024Pooled it
- Decoding miRNA‑146a: Mechanisms of action in cardiovascular diseases and endocrine metabolic disorders (Review).International journal of molecular medicine · 2026Review
- Silymarin attenuates diabetic nephropathy in rats via modulation of the miRNA-223/NLRP3/caspase-1/GSDMD axis and inflammasome-related pyroptotic signaling.Biology direct · 2026Article
- Integrated effects of dietary supplementation of Spirulina platensis in working dogs: nutritional, biochemical, antioxidant, immunological, gut-related microbial and nutrigenomic insights.BMC veterinary research · 2026Article
- 6-Gingerol ameliorates high-fat, high-sucrose diet-induced metabolic dysfunction and depressive-like behaviors by attenuating neuroinflammation and oxidative stress.Metabolic brain disease · 2026Article
- Natural Products as Potential Therapeutic Candidates for Diabetic Kidney Disease: Molecular Mechanisms, Translational Challenges, and Future Prospects.International journal of molecular sciences · 2025Review
- Carvedilol-loaded self-nanoemulsifying drug delivery system target diabetic nephropathy: preclinical evidence of antioxidant and antifibrotic effects.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Chinese ginger (Boesenbergia rotunda) mitigates diabetic nephropathy and cardiomyopathy by regulating oxidative inflammatory pathway.Journal of molecular histology · 2025Article
- MiR-183-5p modulates inflammatory response and apoptosis in diabetic nephropathy by targeting the TTP.American journal of translational research · 2025Article
- Preventive treatment of tripdiolide ameliorates kidney injury in diabetic mice by modulating the Nrf2/NF-κB pathway.Frontiers in pharmacology · 2025Article
- Advances in Understanding Diabetic Kidney Disease Progression and the Mechanisms of Acupuncture Intervention.International journal of general medicine · 2024Review
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3 authors.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundMiRNA-146a and miRNA-223 are key epigenetic regulators of toll-like receptor 4 (TLR4)/tumor necrosis factor-receptor-associated factor 6 (TRAF6)/NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome pathway, which is involved in diabetic nephropathy (DN) pathogenesis. The currently available oral anti-diabetic treatments have been insufficient to halt DN development and progression. Therefore, this work aimed to assess the renoprotective effect of the natural compound 6-gingerol (GR) either alone or in combination with metformin (MET) in high-fat diet/streptozotocin-induced DN in rats. The proposed molecular mechanisms were also investigated.
methodsOral gavage of 6-gingerol (100 mg/kg) and metformin (300 mg/kg) were administered to rats daily for eight weeks. MiRNA-146a, miRNA-223, TLR4, TRAF6, nuclear factor-kappa B (NF-κB) (p65), NLRP3, caspase-1, and hypoxia-inducible factor-1 alpha (HIF-1α) mRNA expressions were measured using real-time PCR. ELISA was used to measure TLR4, TRAF6, NLRP3, caspase-1, tumor necrosis factor-alpha (TNF-α), and interleukin-1-beta (IL-1β) renal tissue levels. Renal tissue histopathology and immunohistochemical examination of fibronectin and NF-κB (p65) were performed.
results6-Gingerol treatment significantly reduced kidney tissue damage and fibrosis. 6-Gingerol up-regulated miRNA-146a and miRNA-223 and reduced TLR4, TRAF6, NF-κB (p65), NLRP3, caspase-1, TNF-α, IL-1β, HIF-1α and fibronectin renal expressions. 6-Gingerol improved lipid profile and renal functions, attenuated renal hypertrophy, increased reduced glutathione, and decreased blood glucose and malondialdehyde levels. 6-Gingerol and metformin combination showed superior renoprotective effects than either alone.
conclusion6-Gingerol demonstrated a key protective role in DN by induction of miRNA-146a and miRNA-223 expression and inhibition of TLR4/TRAF6/NLRP3 inflammasome signaling. 6-Gingerol, a safe, affordable, and abundant natural compound, holds promise for use as an adjuvant therapy with metformin in diabetic patients to attenuate renal damage and stop the progression of DN.
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