Nanoparticles Formulation Improves the Antifibrogenic Effect of Quercetin on an Adenine-Induced Model of Chronic Kidney Disease

Abstract

Renal fibrosis is the final stage of chronic kidney injury characterized by glomerulosclerosis and tubulointerstitial fibrosis with parenchymal destruction. Quercetin belongs to the most studied flavonoids with antioxidant, anti-inflammatory, antifibrogenic, and antitumor activity. It modifies the TGF-β/Smad signaling pathway, decreasing profibrogenic expression molecules and inducing the expression of antioxidant, anti-inflammatory, and antifibrogenic molecules. However, quercetin exhibits poor water solubility and low absorption and bioavailability. This limitation was solved by developing a nanoparticles formulation that improves the solubility and bioavailability of several bioactive compounds. Therefore, we aimed to investigate the in vivo antifibrogenic effect of a quercetin nanoparticles formulation. Male C57BL/6 mice were induced into chronic renal failure with 50 mg/kg of adenine for four weeks. The animals were randomly grouped and treated with 25, 50, or 100 mg/kg of quercetin, either macroparticles or nanoparticles formulation. We performed biochemical, histological, and molecular analyses to evaluate and compare the effect of macroparticles versus nanoparticles formulation on kidney damage. Here, we demonstrated that smaller doses of nanoparticles exhibited the same beneficial effect as larger doses of macroparticles on preventing kidney damage. This finding translates into less quercetin consumption reaching the desired therapeutic effect.

Protective Action Mechanisms of Launaea mucronata Extract and Its Nano-Formulation against Nephrotoxicity in Rats as Revealed via Biochemical, Histopathological, and UPLC-QTOF–MS/MS Analyses

“…Interestingly, our findings were in line with [ 79 ], who highlighted the promising antioxidant activity of the encapsulated apigenin for the treatment of hepatocellular carcinoma with an excellent stability and bioavailability. In the same context, the authors of [ 80 ] confirmed that the crystal structure of quercetin nanoparticles demonstrated a higher bioavailability than quercetin itself due to the increased surface area with a higher solubility. Notably, quercetin nanoparticles were able to inhibit the expression of profibrogenic genes.…”

Quercetin Alleviates Pulmonary Fibrosis in Silicotic Mice by Inhibiting Macrophage Transition and TGF-β-Smad2/3 Pathway

“…Quercetin effectively inhibited the TGF-β/Smad signaling pathway by promoting the expressions of antifibrogenic genes such as Smad6 and Smad7 while inhibiting the expressions of profibrogenic genes such as Col I, TGF-β, Smad3, and α-SMA. Quercetin may activate antifibrogenic and anti-inflammatory signaling pathways to inhibit the formation of an adenine-induced model of chronic kidney disease [ 28 ]. The study demonstrated that tripartite motif-containing 33 (TRIM33) is overexpressed in the lung during fibrotic conditions and plays a protective role against fibrogenesis by inhibiting the TGF-β1 pathway independently of inflammation.…”

The neuroprotective effect of quercetin nanoparticles in the therapy of neuronal damage stimulated by acrolein

“…Nanotechnology has made possible drug-loaded structures that can pass the blood–brain barrier, targeted medication delivery, and increased drug bioavailability ( Gao et al, 2018 ). When quercetin nanoparticles were utilized, the relative oral bioavailability rose by 523%, indicating the possibility of dosage reduction ( Sánchez-Jaramillo et al, 2022 ).…”