Eugenia sulcata (Myrtaceae) Nanoemulsion Enhances the Inhibitory Activity of the Essential Oil on P2X7R and Inflammatory Response In Vivo

Abstract

P2X7R is a purinergic receptor with broad expression throughout the body, especially in immune system cells. P2X7R activation causes inflammatory mediators to release, including interleukin-1β (IL-1β), the processing and release of which are critically dependent on this ion channel activation. P2X7R’s therapeutic potential augments the discovery of new antagonistic compounds. Thus, we investigated whether the Eugenia sulcata essential oil could block P2X7R activity. The essential oil (ESO) dose-dependently inhibited ATP-promoted PI uptake and IL-1β release with an IC50 of 113.3 ± 3.7 ng/mL and 274 ± 91 ng/mL, respectively, and the essential oil nanoemulsion (ESON) improved the ESO inhibitory effect with an IC50 of 81.4 ± 7.2 ng/mL and 62 ± 2 ng/mL, respectively. ESO and ESON reversed the carrageenan-activated peritonitis in mice, and ESON exhibited an efficacy higher than ESO. The majority substance from essential oil, β-caryophyllene, impaired the ATP-evoked PI uptake and IL-1β release with an IC50 value of 26 ± 0.007 ng/mL and 97 ± 0.012 ng/mL, respectively. Additionally, β-caryophyllene reduced carrageenan-induced peritonitis, and the molecular modeling and computational simulation predicted the intermolecular interactions in the P2X7R situs. In silico, results indicated β-caryophyllene as a potent allosteric P2X7R antagonist, although this substance may present toxic effects for humans. These data confirm the nanoemulsion of essential oil from E. sulcata as a promisor biotechnology strategy for impaired P2X7R functions and the inflammatory response.

Progressing nanotechnology to improve targeted cancer treatment: overcoming hurdles in its clinical implementation

“…It has a relatively moderate particle size of 120 nm and a negative zeta potential of -25 mV, indicating good stability [ 226 , 227 ]. The storage condition at 4 °C for 6 months is suitable for maintaining stability, and the release kinetics indicate that 20% of the cytokine is released within 24 h. This nanoemulsion appears promising for anti-inflammatory therapy [ 228 , 229 ]. Another noteworthy formulation is for Tumor Necrosis Factor-alpha (TNF-α).…”

“…The release kinetics show a controlled release of 15% over 48 h, making it a candidate for targeted cancer therapies [ 227 ]. Additionally, the nanoemulsion designed for Interferon-gamma (IFN-γ) demonstrates impressive encapsulation efficiency at 95% [ 228 , 229 ]. With a small particle size of 80 nm and a zeta potential of -30 mV, it is well-suited for potential autoimmune disease therapy.…”

Synthesis, Biological Evaluation and Molecular Modeling Studies of Naphthoquinone Sulfonamides and Sulfonate Ester Derivatives as P2X7 Inhibitors

“…In recent years, our research group has focused on the identification of novel and more selective chemotypes of P2X7 receptor inhibitors. In particular, we reported several natural and synthetic compounds with potent antagonist activity toward P2X7R and ATP-induced inflammatory responses [ 20 , 21 , 22 , 23 , 24 , 25 , 26 ]. Recently, we reported the synthesis and biological evaluation of a group of naphthoquinones sulfonamide and sulfonate ester derivatives against Chikungunya virus (CHIKV).…”

Bioactive Molecules from Plants: Discovery and Pharmaceutical Applications

“…They demonstrate the efficacy of these preparations, achieving improved ocular delivery of this compound [ 26 ]. Moreover, a publication by Magalhães et al has shown that the essential oil nanoemulsion substantially improved its inhibitory activity [ 27 ]. Hydrogels also appear to be an excellent approach for controlled drug delivery.…”