Apigenin-Loaded Solid Lipid Nanoparticle Attenuates Diabetic Nephropathy Induced by Streptozotocin Nicotinamide Through Nrf2/HO-1/NF-kB Signalling Pathway

Int J Nanomedicine. 2020 Nov 19:15:9115-9124. doi: 10.2147/IJN.S256494. eCollection 2020.

Abstract

Background: Apigenin is known to have a broad-spectrum efficacy in oxidative stress and conditions due to inflammation, although weak absorption, fast metabolic rate and a fast elimination (systemic) limit the pharmacological efficacy of this drug. Hence, we propose the usage of highly bioavailable Apigenin-solid lipid nanoparticles (SLNPs) to recognize such limitations. The defensive function of Apigenin-SLNPs on renal damage induced by streptozotocin (STZ) in animals was studied.

Materials and methods: We initially injected the rats with 35 mg kg-1 streptozocin intraperitoneally, and after 7 days, the rats were then injected 150 mg kg-1 of metformin intragastrically followed by a once-daily intragastric dose of Apigenin-SLNP (25 or 50 mg kg-1) for a continuous period of 30 days. We then measured the level of insulin and blood glucose, superoxide dismutase, catalase and malondialdehyde in the tissues of the kidney. We also observed messenger-RNA expression of Interleukin-1β, Interleukin-6 and Tumor Necrosis Factor-alpha in renal tissue through RT-PCR technique. Moreover, H&E staining and Western blotting observed the histopathological variations and protein expression of nuclear factor erythroid 2-related factor 2/heme oxygenase/Nuclear Factor-κB signaling pathway, respectively.

Results: An enhancement in the expressing of nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 and a suppression in the expression of Nuclear Factor-κB occurred due to Apigenin-SLNPs treatment, which was a result of the protective mechanism of Apigenin-SLNPs which is because of not only its anti-inflammatory function (by inhibition of release of inflammatory factors) but also their anti-oxidant activity (through reduction of lipid peroxidation production).

Conclusion: We found that a protective effect on diabetic nephropathy was shown due to Apigenin-SLNPs, in rats induced with streptozocin maybe through the pathway of nuclear factor erythroid 2-related factor 2/heme oxygenase-1/Nuclear Factor-κB.

Keywords: Apigenin-SLNPs; DN; HO-1; NF-κB; Nrf2.

Publication types

  • Retracted Publication

MeSH terms

  • Animals
  • Antioxidants / administration & dosage
  • Antioxidants / pharmacology
  • Apigenin / administration & dosage
  • Apigenin / pharmacology*
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Experimental / drug therapy
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetic Nephropathies / chemically induced
  • Diabetic Nephropathies / drug therapy*
  • Diabetic Nephropathies / metabolism
  • Drug Delivery Systems
  • Heme Oxygenase (Decyclizing) / metabolism*
  • Kidney / drug effects
  • Kidney / metabolism
  • Kidney / pathology
  • Lipids / chemistry
  • Male
  • Malondialdehyde / metabolism
  • NF-E2-Related Factor 2 / metabolism*
  • NF-kappa B / metabolism
  • Nanoparticles / administration & dosage*
  • Nanoparticles / chemistry
  • Oxidative Stress / drug effects
  • Rats
  • Signal Transduction / drug effects*
  • Streptozocin
  • Superoxide Dismutase / metabolism

Substances

  • Antioxidants
  • Lipids
  • NF-E2-Related Factor 2
  • NF-kappa B
  • Nfe2l2 protein, rat
  • Malondialdehyde
  • Streptozocin
  • Apigenin
  • Heme Oxygenase (Decyclizing)
  • Hmox1 protein, rat
  • Superoxide Dismutase