Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011881 (diabetic nephropathy)
 10,836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although synergistic therapy for diabetes mellitus has displayed significant promise for the effective treatment of diabetic nephropathy (DN), developing a simple and effective strategy to construct multifunctional nanoparticles is still a huge challenge. Moreover, the complicated pathological mechanism of DN involves various pathway dysfunctions that limit the effectiveness of a single therapeutic approach. Herein, hollow mesoporous silica nanocomposite (HMSN) particles doped with trace cerium oxide that exhibit renoprotective activity have been designed, which not only have the ability to prevent ROS-associated DN pathogenesis but also have high drug loading capacity. Interestingly, the metformin (MET) loaded multifunctional nanoparticles (MET-HMSN-CeO2) with a special size exhibited significantly increased kidney accumulation over free MET. Moreover, the cyclic conversion between Ce3+ and Ce4+ of mixed-valence ceria in our system provides the possibility for long-term ROS-scavenging activity to achieve the antioxidative effect. Then, we investigated the renoprotective effect of these nanoparticles on the streptozotocin (STZ)-induced renal injury rat model and high-glucose induced NRK-52E cell damage model. As a result, our findings demonstrated that the nanoparticles could alleviate the DN symptoms by mitigating oxidative stress, suppressing cellular apoptosis and protecting renal injury both in vitro and in vivo. The kidney deficits of DN are significantly improved after treatment with MET-HMSN-CeO2. Overall, our studies indicated that the MET-HMSN-CeO2 multifunctional nanoparticles would be a promising therapeutic candidate for DN.
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PMID:A ROS-scavenging multifunctional nanoparticle for combinational therapy of diabetic nephropathy. 3321 Jun 70

Diabetic nephropathy (DN) as a global health concern is closely related to inflammation and oxidation. Isoliquiritigenin (ISL), a natural flavonoid compound, has been demonstrated to inhibit inflammation in macrophages. Herein, we investigated the effect of ISL in protecting against the injury in STZ-induced type 1 DN and in high glucose-induced NRK-52E cells. In this study, it was revealed that the administration of ISL not only ameliorated renal fibrosis and apoptosis, but also induced the deterioration of renal function in diabetic mice. Mediated by MAPKs and Nrf-2 signaling pathways, respectively, upstream inflammatory response and oxidative stress were neutralized by ISL in vitro and in vivo. Moreover, as further revealed by the results of molecular docking, sirtuin 1 (SIRT1) binds to ISL directly, and the involvement of SIRT1 in ISL-mediated renoprotective effects was confirmed by studies using in vitro models of SIRT1 overexpression and knockdown. In summary, by reducing inflammation and oxidative stress, ISL has a significant pharmacological effect on the deterioration of DN. The benefits of ISL are associated with the direct binding to SIRT1, the inhibition of MAPK activation, and the induction of Nrf-2 signaling, suggesting the potential of ISL for DN treatment.
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PMID:Isoliquiritigenin prevents hyperglycemia-induced renal injuries by inhibiting inflammation and oxidative stress via SIRT1-dependent mechanism. 3328 47


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