Oral Administration of Nano-Emulsion Curcumin in Mice Suppresses Inflammatory-Induced NFκB Signaling and Macrophage Migration

Abstract

Despite the widespread use of curcumin for centuries in Eastern medicine as an anti-inflammatory agent, its molecular actions and therapeutic viability have only recently been explored. While curcumin does have potential therapeutic efficacy, both solubility and bioavailability must be improved before it can be more successfully translated to clinical care. We have previously reported a novel formulation of nano-emulsion curcumin (NEC) that achieves significantly greater plasma concentrations in mice after oral administration. Here, we confirm the immunosuppressive effects of NEC in vivo and further examine its molecular mechanisms to better understand therapeutic potential. Using transgenic mice harboring an NFκB-luciferase reporter gene, we demonstrate a novel application of this in vivo inflammatory model to test the efficacy of NEC administration by bioluminescent imaging and show that LPS-induced NFκB activity was suppressed with NEC compared to an equivalent amount of curcumin in aqueous suspension. Administration of NEC by oral gavage resulted in a reduction of blood monocytes, decreased levels of both TLR4 and RAGE expression, and inhibited secretion of MCP-1. Mechanistically, curcumin blocked LPS-induced phosphorylation of the p65 subunit of NFκB and IκBα in murine macrophages. In a mouse model of peritonitis, NEC significantly reduced macrophage recruitment, but not T-cell or B-cell levels. In addition, curcumin treatment of monocyte derived cell lines and primary human macrophages in vitro significantly inhibited cell migration. These data demonstrate that curcumin can suppress inflammation by inhibiting macrophage migration via NFκB and MCP-1 inhibition and establish that NEC is an effective therapeutic formulation to increase the bioavailability of curcumin in order to facilitate this response.

Recent trends in the development of nanophytobioactive compounds and delivery systems for their possible role in reducing oxidative stress in Parkinson’s disease models

“…30,122,153,154 Curcumin has multiple health benefits, including antioxidant, antimicrobial, anti-inflammatory, anti-aging, anti-Alzheimer, anti-Parkinson, and anticancer activities. 30,32,94,144,[153][154][155] A lower retention time in circulation leads to the lower therapeutic potential of this compound. 139,144 Reducing the size of the curcumin compound to the nanolevel and formulating it with polyesters leads to higher bioavailability in systemic circulation.…”

“…30,32,94,144,[153][154][155] A lower retention time in circulation leads to the lower therapeutic potential of this compound. 139,144 Reducing the size of the curcumin compound to the nanolevel and formulating it with polyesters leads to higher bioavailability in systemic circulation. 122,123,144,155 Many studies have confirmed that nanosizing curcumin enhances bioavailability and therapeutic efficiency for many diseases including PD.…”

“…139,144 Reducing the size of the curcumin compound to the nanolevel and formulating it with polyesters leads to higher bioavailability in systemic circulation. 122,123,144,155 Many studies have confirmed that nanosizing curcumin enhances bioavailability and therapeutic efficiency for many diseases including PD. 6,13,29,31,67,94,108,122,138,139 Nanocurcumin greatly reduces the oxidative stress and apoptosis in the brain of PD flies.…”

“…[141][142][143] A nanoemulsion is effective for encapsulating various bioactive compounds that are unstable under in vivo conditions for effective delivery to the brain. 144 Oral administration of nanoemulsified curcumin enhances bioavailability of curcumin in mice with reduced inflammation. 144 Similarly, a vitamin E-loaded resveratrol nanoemulsion with 102 nm particles was produced using the spontaneous emulsification technique and reduced brain-induced oxidative stress to treat PD.…”

“…144 Oral administration of nanoemulsified curcumin enhances bioavailability of curcumin in mice with reduced inflammation. 144 Similarly, a vitamin E-loaded resveratrol nanoemulsion with 102 nm particles was produced using the spontaneous emulsification technique and reduced brain-induced oxidative stress to treat PD. 145 A pomegranate seed oil nanoemulsion with 135 nm particles was produced using the sonication technique and reduced lipid peroxidation and neuronal loss with strong protective effects.…”