<p>Anti-osteoclastogenic effect of epigallocatechin gallate-functionalized gold nanoparticles in vitro and in vivo</p>

Abstract

Background: Epigallocatechin gallate (EGCG), the major anti-inflammatory compound in green tea, has been shown to suppress osteoclast (OC) differentiation. However, the low aqueous solubility of EGCG always leads to poor bioavailability, adverse effects, and several drawbacks for clinical applications. Purpose: In this study, we synthesized EGCG-capped gold nanoparticles (EGCG-GNPs) to solve the drawbacks for clinical uses of EGCG in bone destruction disorders by direct reduction of HAuCl 4 in EGCG aqueous solution. Methods and Results: The obtained EGCG-GNPs were negatively charged and spherical. Theoretical calculation results suggested that EGCG was released from GNPs in an acidic environment. Cellular uptake study showed an obviously large amount of intracellular EGCG-GNPs without cytotoxicity. EGCG-GNPs exhibited better effects in reducing intracellular reactive oxygen species levels than free EGCG. A more dramatic anti-osteoclastogenic effect induced by EGCG-GNPs than free EGCG was observed in lipopolysaccharide (LPS)-stimulated bone marrow macrophages, including decreased formation of TRAP-positive multinuclear cells and actin rings. Meanwhile, EGCG-GNPs not only suppressed the mRNA expression of genetic markers of OC differentiation but also inhibited MAPK signaling pathways. Furthermore, we confirmed that EGCG-GNPs greatly reversed bone resorption in the LPS-induced calvarial bone erosion model in vivo, which was more effective than applying free EGCG, specifically in inhibiting the number of OCs, improving bone density, and preventing bone loss. Conclusion: EGCG-GNPs showed better anti-osteoclastogenic effect than free EGCG in vitro and in vivo, indicating their potential in anti-bone resorption treatment strategy.

Monoalkylated Epigallocatechin-3-gallate (C18-EGCG) as Novel Lipophilic EGCG Derivative: Characterization and Antioxidant Evaluation

“…EGCG beneficial effects are however counteracted by its poor membrane permeability, rapid metabolism and chemical instability in physiological environment [10,11]. The stabilization of EGCG can be obtained by different approaches including the employment of reducing agents, structural modification and/or drug delivery systems [12][13][14]. Among these, the application of derivatization strategies designed to increase the molecule hydrophobicity and the interaction with cellular membrane [15][16][17][18][19][20] is considered as a feasible approach to improve the activity of bioactive molecules.…”

“…1 H NMR Chemical Shifts a . Chemical shifts are expressed in ppm downfield from the signals for TMS and coupling costants in Hertz are in parentheses 13. C NMR Chemical Shifts a .…”

Epigallocatechin-3-Gallate-Loaded Gold Nanoparticles: Preparation and Evaluation of Anticancer Efficacy in Ehrlich Tumor-Bearing Mice

“…A green synthesis approach was used for the preparation of EGCG-loaded GNPs where HAuCl 4 was reduced in aqueous solution using EGCG. This approach is eco-friendly, clean, simple, efficient, and avoids the use of hazardous man-made chemicals [25,32]. EGCG has eight orthophenolic hydroxyl groups, which form complexes with Au 3+ ions and facilitate their reduction to gold ions to form EGCG-capped GNPs [25].…”

“…Pharmaceuticals 2020, 13, x FOR PEER REVIEW 3 of 21 a stabilizing agent for GNPs due to the acidity of EGCG phenolic groups, which results in negative charge at pH 7.4 [25]. The color of the EGCG and HAuCl4 mixture changed from pale yellow to purple red within 15 min due to surface plasmon resonance (SPR) phenomenon confirming the formation of gold nanoparticles [34].…”

“…The literature shows several attempts to overcome these hurdles and enhance EGCG bioavailability and efficacy using several nanoparticle-based formulations such as gold nanoparticles, polymeric nanoparticles, and lipid-based nanoparticles [22][23][24][25][26][27][28]. Among these nanocarriers, gold nanoparticles (GNPs) showed excellent potential to maximize EGCG therapeutic effectiveness while minimizing its side effects.…”