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

Abstract

Pingping Li,1 Syed Nasir Abbas Bukhari,2 Tahseen Khan,3 Renukaradhya Chitti,4 Davan B Bevoor,5 Anand R Hiremath,6 Nagaraja SreeHarsha,7 Yogendra Singh,8 Kumar Shiva Gubbiyappa9 1Department of Nephrology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou City, Henan Province 450007, People’s Republic of China; 2Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Sakaka, Aljouf 2014, Saudi Arabia; 3School of Pharmacy, Suresh Gyan Vihar University, Jaipur, India; 4Department of Pharmacy Practice, Sri Adichaunagiri College of Pharmacy, Adichunchanagiri University, Adichunchanagiri, Mandya, India; 5Department of Pharmacy Practice, SCS College of Pharmacy, Harapanahalli, Karnataka, India; 6Department of Pharmacology, Bapuji College of Pharmacy, Davanagere, Karnataka, India; 7Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al‐Ahsa, Saudi Arabia; 8Department of Pharmaceutical Sciences, Mahatma Gandhi College of Pharmaceutical Sciences, Jaipur, India; 9School of Pharmacy, GITAM University, Hyderabad, IndiaCorrespondence: Yogendra Singh Email [email protected]: 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, Nrf2, HO-1, NF-κB

Keywords

• apigenin-slnps
• diabetic nephropathy
• nrf2
• ho-1
• nf-κb