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

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Apigenin-Loaded Solid Lipid Nanoparticle Attenuates Diabetic Nephropathy Induced by Streptozotocin Nicotinamide Through Nrf2/ HO-1/NF-Kb Signalling Pathway International Journal of Nanomedicine Dovepress open access to scientific and medical research Open Access Full Text Article ORIGINAL RESEARCH Apigenin-Loaded Solid Lipid Nanoparticle Attenuates Diabetic Nephropathy Induced by Streptozotocin Nicotinamide Through Nrf2/ HO-1/NF-kB Signalling Pathway This article was published in the following Dove Press journal: International Journal of Nanomedicine Pingping Li1 Background: Apigenin is known to have a broad-spectrum efficacy in oxidative stress and Syed Nasir Abbas Bukhari 2 conditions due to inflammation, although weak absorption, fast metabolic rate and a fast Tahseen Khan 3 elimination (systemic) limit the pharmacological efficacy of this drug. Hence, we propose the Renukaradhya Chitti4 usage of highly bioavailable Apigenin-solid lipid nanoparticles (SLNPs) to recognize such Davan B Bevoor5 limitations. The defensive function of Apigenin-SLNPs on renal damage induced by strep­ 6 tozotocin (STZ) in animals was studied. Anand R Hiremath −1 7 Materials and Methods: We initially injected the rats with 35 mg kg streptozocin intraper­ Nagaraja SreeHarsha −1 8 itoneally, and after 7 days, the rats were then injected 150 mg kg of metformin intragastrically Yogendra Singh followed by a once-daily intragastric dose of Apigenin-SLNP (25 or 50 mg kg−1) for 9 Kumar Shiva Gubbiyappa a continuous period of 30 days. We then measured the level of insulin and blood glucose, 1Department of Nephrology, Zhengzhou superoxide dismutase, catalase and malondialdehyde in the tissues of the kidney. We also Central Hospital Affiliated to Zhengzhou observed messenger-RNA expression of Interleukin-1β, Interleukin-6 and Tumor Necrosis University, Zhengzhou City, Henan Province 450007, People’s Republic of Factor-alpha in renal tissue through RT-PCR technique. Moreover, H&E staining and Western China; 2Department of Pharmaceutical blotting observed the histopathological variations and protein expression of nuclear factor Chemistry, College of Pharmacy, Jouf erythroid 2-related factor 2/heme oxygenase/Nuclear Factor-κB signaling pathway, respectively. University, Sakaka, Aljouf 2014, Saudi Arabia; 3School of Pharmacy, Suresh Results: An enhancement in the expressing of nuclear factor erythroid 2-related factor 2 and Gyan Vihar University, Jaipur, India; heme oxygenase-1 and a suppression in the expression of Nuclear Factor-κB occurred due to 4Department of Pharmacy Practice, Sri Apigenin-SLNPs treatment, which was a result of the protective mechanism of Apigenin- Adichaunagiri College of Pharmacy, Adichunchanagiri University, SLNPs which is because of not only its anti-inflammatory function (by inhibition of release Adichunchanagiri, Mandya, India; of inflammatory factors) but also their anti-oxidant activity (through reduction of lipid 5Department of Pharmacy Practice, SCS College of Pharmacy, Harapanahalli, peroxidation production). Karnataka, India; 6Department of Conclusion: We found that a protective effect on diabetic nephropathy was shown due to Pharmacology, Bapuji College of Apigenin-SLNPs, in rats induced with streptozocin maybe through the pathway of nuclear Pharmacy, Davanagere, Karnataka, India; 7Department of Pharmaceutical Sciences, factor erythroid 2-related factor 2/heme oxygenase-1/Nuclear Factor-κB. College of Clinical Pharmacy, King Faisal Keywords: Apigenin-SLNPs, DN, Nrf2, HO-1, NF-κB University, Al-Ahsa, Saudi Arabia; 8Department of Pharmaceutical Sciences, Mahatma Gandhi College of Pharmaceutical Sciences, Jaipur, India; 9School of Pharmacy, GITAM University, Introduction Hyderabad, India Diabetes mellitus (DM) is a multi-dimensional metabolic disorder which is asso­ ciated with a deficit, wherein, the glucose utilization of the body and insulin homeostasis maintenance are affected. A chronic ruination, deterioration and an eventual breakdown of the organs mainly the eye, kidney, nerves and the cardio Correspondence: Yogendra Singh Email [email protected] vascular system is a result of a constant hyperglycaemia. Globally, there are submit your manuscript | www.dovepress.com International Journal of Nanomedicine 2020:15 9115–9124 9115 DovePress © 2020 Li et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php http://doi.org/10.2147/IJN.S256494 and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). Li et al Dovepress 366 million DM patients and the numbers of new cases are Materials and Methods 1 predicted to double up by the year 2030. Diabetic nephro­ Chemicals pathy (DN) is a common disorder that occurs because of We obtained Apigenin and STZ from Sigma. Glucose, UA, both type 1 and type 2 DM and affects DM-associated Creat. and commercial kits were provided by Jiancheng mortality drastically. It is also responsible for renal dys­ Bioengineering Institute. Rest of the chemicals and function in high-income countries. The clinical assessment reagents in use were of analytical grade. of DN is done through a five-stage criterion, wherein each stage features unique sets of functional and clinical altera­ tions along with alterations in the standard renal function Preparation of Apigenin-SLNPs markers.2 According to various studies, insulin resistance We used microemulsification method to prepare SLNPs. and the state of DM govern the production of oxidative We then briefly placed a mixture of 45.45% Tween 80, stress to a large extent. Recent studies have suggested DN 0.58% PLPC, and water in a beaker which was then to be an inflammatory process and the progression of subjected to heat to a temperature to attain the lipid- which can lead to implication of immune cells, even melting point. We also melted Lipid (7.27%) at though the heamodynamic and metabolic factors are a temperature of 82°C to 85°C separately. We then added most common causative factors of DN.3–5 Mesangial Apigenin (25 mg) aqueou phase containing Tween 80, expansion, alterations of extracellular matrix, tubulointer­ later we dropped the hot aqueousemulsifier mix into the stitial renal fibrosis, and glomerulosclerosis are the leading lipid melt all at once. This was done under magnetic pathological conditions of DN. This is due to the diverse stirring for obtaining a clear micro-emulsion. We then adverse effects caused by chronic use of hyperglycemic transferred hot microemulsion in cold water (~2°C) of an drugs, and hence, plant sources with negligible adverse equal amount. This process was carried out under mechan­ effects are now being considered in the development of ical stirring at a speed of 5000 rpm for a time period of 1.5 hyperglycemic drugs.6 Phytoconstituents with a persuasive hrs. The SLNPs are formed in aqueous medium by crystal­ antioxidant property have proved to be a breakthrough lization of the hot droplets of lipid that are present in the remedy against DM. Also, they have been highly consid­ microemulsion. The aqueous SLNP dispersion that was 13 ered as source of biologically active substance (antioxi­ prepared was refrigerated until further analysis. dants, anti-hyperglycemics and anti-hyperlipidaemics).7 Apigenin is a flavonoid naturally present in tea, berries, Characterization Studies of fruits, and vegetables. These have had various biological Apigenin-SLNPs functions, like antioxidant and anti-inflammatory activity.8 Nano-ZS ZEN 3600 measured the polydispersion (PDI), Apigenin was reported to be playing a protective role in zeta potential, mean size, and size distribution of oxidative-related disorders like CVD and neurology- Apigenin-SLNPs using the dynamic light scattering tech­ related diseases. Apigenin alleviates myocardial toxicity nique. We measured the scattering frequency at 90° and by modulating oxidative stress and inflammation in myo­ 25° angles. TEM investigated on the size of the Apigenin- cardial injury model reactive oxygen species (ROS) and SLNPs. We examined the morphology of the Apigenin- malondialdehyde (MDA) decreased significantly in rat SLNPs by using SEM. We then viewed SEM images of acrylonitrile-induced subchronic sperm injury.9–11 Apigenin-SLNPs by a Scanning Electron Microscope. Pharmacological studies have confirmed that Apigenin markedly inhibited glomerular mesangial cell prolifera­ tion, glomerulus hypertrophy, and extracellular matrix Evaluation of Apigenin-SLNPs development and aggregation in DN patients and mice. Encapsulation Efficiency Apigenin plays a multi-target role in DN treatment. Its We determined the nanoformulation encapsulation- low solubility, short half-life, low renal concentration, efficiencyas the percent of Apigenin trapped in the nanopar­ and minimal bioavailability hamper Apigenin uses.12 ticles. We then dissolved 25 mg of Apigenin nanoparticles Therefore, in laboratory animals, this research aimed to with 1 mL of 90% methanol, further subjected to sonication examine the attenuating effects of Apigenin-solid lipid for 5 mins in order to cause disruption of the nanoparticles nanoparticles(SLNPs) in diabetic nephropathy caused by and release encapsulated Apigenin. The resulting solution at streptozotocin (STZ) nicotinamide.
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