Therapeutic Potential of Naringenin Nanosuspension: In Vitro and In Vivo Anti-Osteoporotic Studies

Abstract

Naringenin (NRG) is a flavonoid and has been reported as an anti-osteoporotic agent. However, poor bioavailability may limit the anti-osteoporotic potential of the drug. The purpose of the study was to compare the anti-osteoporotic activity of naringenin nanosuspension (NRG-NS) with the NRG and standard therapeutic drug, raloxifene hydrochloride (RLX). Here, NRG-NS showed anti-osteoporotic activity in MG-63 cells by upregulating the osteocalcin levels. The in vivo anti-osteoporotic activity of NRG-NS was further investigated in an osteoporotic rat model to mimic the post-menopausal condition. The animals were randomized and separated into six groups. The animals were treated with RLX (p.o., 5.4 mg/kg), NRG (p.o., 20 mg/kg), NRG-NS (p.o., 20 mg/kg), and blank-NS for 60 days after completion of a 30-day post-surgery period and compared with control and ovariectomized (OVX) groups. After the treatment, body and uterine weights, biochemical estimation in serum (calcium, phosphorus, acid phosphatase, alkaline phosphatase, osteocalcin), bone parameters (length, diameter, dry weight, density, ash weight, bone mineral content) and bone microarchitecture by histopathology were determined. The results showed the protective effects of NRG-NS on osteoblast-like MG-63 cells. The biochemical estimations confirmed the normalization of parameters viz., alkaline phosphatase, calcium concentrations, and bone density with a decrease in levels of acid phosphatase and inorganic phosphorus with NRG-NS as compared to plain NRG. The results indicated that the oral administration of NRG-NS could be a potential therapeutic formulation for the treatment of osteoporosis.

Protective potential of naringenin and its nanoformulations in redox mechanisms of injury and disease

“…Results depicted that there was no considerable alteration in the proliferation with the NAR nanosuspension group as compared to the free NAR group except at 10 μg/mL concentration. In this concentration, the viability was more than 75 % in the presence of NAR nanosuspension, while it was less than 50 % in the presence of free NAR [ 125 ]. In the other study, the safety of free NAR and polylactic acid/polyvinyl alcohol-NAR NP was evaluated in Caco-2 cell lines by exposing the cells to different concentrations of the samples (5, 10, 20, 40, 60, 80, and 100 μg/mL of NAR).…”

Review on the Scale-Up Methods for the Preparation of Solid Lipid Nanoparticles

“…Polymeric nanomedicines have been extensively explored by the nanoprecipitation technique [62,63]. Nanomedicine is a broadly applied term for formulations such as liposomes [64], polymersomes [65,66], polymeric nanoparticles [67], inorganic nanocarriers [68], nanofibers [69,70] protein nanoparticles [71], nanosuspensions [72], and emulsions [73]. Using this technique, one can obtain smaller and more homogenous particles, so the selection of the solvent needs to have the attributes to diffuse into the water in less time and homogeneously [74].…”

The role of circadian rhythm in osteoporosis; a review

“…While in RAW264.7 cells, bisphosphonate zoledronate inhibits osteoclast migration, differentiation and bone resorption via the AMP-activated protein kinase (AMPK) pathway, suggesting this route could become a new target for disease treatment ( Dong et al, 2018 ). Although Wnt/Akt/MAPK/AMPK pathways exert important functions in bone homeostasis and bone related diseases, and new therapies are constantly emerging, the current therapeutic environment for osteoporosis is limited, therefore new side-effect free drugs and therapeutic targets are required ( Gera et al, 2022 ; Kobayakawa et al, 2022 ).…”