Quercetin liposomes ameliorate streptozotocin-induced diabetic nephropathy in diabetic rats

Abstract

The effects of quercetin liposomes (Q-PEGL) on streptozotocin (STZ)-induced diabetic nephropathy (DN) was investigated in rats. Male Sprague Dawley rats were used to establish a STZ induced DN model. DN rats randomly received one of the following treatments for 8 weeks: blank treatment (DN), free quercetin (Que), pegylated liposomes (PEGL) and pegylated quercetin liposomes (Q-PEGL). A group of healthy rats served as the normal control. The fasting blood glucose (FBG), body weights (BWs), renal hypertrophy index (rHI), serum and urine biochemistry, renal histopathology, oxidative stress and immunohistochemical measurements of AGEs were analyzed to compare the effect of different treatments. Que and Q-PEGL significantly improved DN biochemistry and pathological changes, although the treated rats still had some symptoms of DN. The therapeutic effect of Q-PEGL surpassed that of Que. Pegylated quercetin liposomes allow maintaining higher quercetin concentrations in plasma than non-encapsulated quercetin. In conclusion the use of quercetin liposomes allows to reduce disease symptoms in a rat model of DN.Diabetes mellitus (DM) is a metabolic disorder characterized by hyperglycemia due to impaired body's ability to produce or respond to the hormone insulin 1 . Diabetic nephropathy (DN) is a microvascular complication of DM and causes long-term or end-stage renal disease 2 . Multifactorial interaction between lipid disorders, oxidative stress, renal hemodynamic changes, polyol activation, inflammatory pathways, and mitogen-activated protein kinase signaling pathways are involved in the pathophysiology of DN 3,4,7 . Therefore, strong antioxidants could potentially serve as treatments to diabetes related diseases 5 Quercetin (C 15 H 10 O 7 ,3′,4′,5,7-pentahydroxyflavone) is a potent dietary bioflavonoid found in diverse fruits, seeds, and vegetables such as legumes, apples, and chili peppers 4-7 . Pharmacological studies in humans show that quercetin has multiple biological functions including circulation system protection, anti-allergic, anti-inflammatory, anti-cancer, anti-diabetes, and cataract prevention 7 . Another important attribution of quercetin is to reduce aldose reductase, which is an enzyme that converts glucose to sorbitol through polyol pathway 5 .Natural quercetin has poor water solubility, therefore, quercetin liposomes are laboratory-prepared to improve its solubility and in vivo absorbability 7-9 . Liposomes are the most studied particle carrier systems allowing sustained release, and have the potential of enhancing the oral bioavailability of proteins and peptides 10 . Liposomes are small spherical lipid vesicles, composed of phospholipids and cholesterol, characterized on size, number of lamellae, and inner/outer phases 11,12 . Liposomes have good cell compatibility, reduce drug toxicity, improve drug stability and function for a long time 13 , and have been used to deliver drugs including antibiotic, antifungal, and cytotoxic agents 14 . Coating inert biocompatible polymers, such as PEG, on the liposom...

Network Pharmacology Combined with Bioinformatics to Investigate the Mechanisms and Molecular Targets of Astragalus Radix-Panax notoginseng Herb Pair on Treating Diabetic Nephropathy

“…Quercetin, a natural flavonoid, is well known to possess multiple pharmacological functions, including but not limited to antioxidant, anti-inflammatory, anticancer, antidiabetic, neuroprotective, and antiobesity [ 51 , 52 ]. The use of quercetin contributes to a meaningful improvement in disease symptoms, renal hypertrophy index, renal histopathology, oxidative stress, and blood glucose in a rat model of DN [ 41 ]. Furthermore, quercetin treatment is beneficial to antioxidant capacity and vasoprotective effects against STZ-induced ER stress of diabetic rats via reducing the lipid peroxidation and increasing the expression of vascular endothelial growth factor (VEGF) and its receptor, VEGFR2, and nitric oxide (NO) [ 53 ].…”

“…Molecular docking, a method of analyzing the binding site and affinity between the conformation of molecules and macromolecular targets, has been considered a crucial technique for structure-based drug discovery [ 40 ]. The core DN-related genes targeted by the AR-PN herb pair bioactive components was identified according to the component-target-pathway network, which were further validated by molecular docking with the experimentally verified AR-PN herb pair bioactive components possessing renoprotective effects on DN, including quercetin [ 41 ], kaempferol [ 42 ], formononetin [ 43 ], and isorhamnetin [ 44 ]. First, the mol2 formats of these bioactive components were obtained from the TCMSP database and PubChem database, which were converted to the format of pdb and pdbqt via Pymol software and AutoDock Tools 1.5.6, respectively.…”

Network Pharmacology-Based Prediction of Mechanism of Shenzhuo Formula for Application to DKD

“…Interestingly, 3 of them had been proven to have kidney protection effect by experiments. For example, quercetin liposomes had renal protective effects of reducing oxidative stress, attenuating AGE expression, and delaying the progression of DKD [26]. Luteolin attenuated DKD mainly via suppression of inflammatory response and oxidative response [27].…”

A Study on the Mechanism of Milkvetch Root in the treatment of Diabetic Nephropathy based on Network Pharmacology

“…It also has anti-oxidant, hypoglycemic, hypolipidemic, tumor suppression, and anti-in ammatory effects [28.29.30]. One study showed that quercetin liposome or free quercetin can prevent weight loss, decrease kidney hypertrophy index, decrease blood glucose level and 24-hour urine protein in diabetic nephropathy model rat [31]. Kaempferol is a kind of natural peroxisome proliferator-activated receptor-γ(PPARγ) agonist, and PPARγ agonist has also become a common drug in the treatment of diabetes and its complications [32].…”