Ameliorative effects of epigallocatechin-3-gallate nanoparticles on 2,4-dinitrochlorobenzene induced atopic dermatitis: A potential mechanism of inflammation-related necroptosis

Abstract

Atopic dermatitis (AD) is a common autoimmune and chronic inflammatory cutaneous disease with a relapsing-remitting course. Necroptosis is a regulated necrotic cell death mediated by receptor-interacting protein 1 (RIP1), receptor-interacting protein 3 (RIP3), and mixed lineage kinase domain-like pseudokinase (MLKL), which is activated by tumor necrosis factor-α (TNF-α). However, the mechanism and the role of necroptosis have not been delineated in AD progression. (-)-Epigallocatechin-3-gallate (EGCG), the main biological activity of tea catechin, is well known for its beneficial effects in the treatment of skin diseases. Here, PEG-PLGA-EGCG nanoparticles (EGCG-NPs) were formulated to investigate the bioavailability of EGCG to rescue cellular injury following the inhibition of necroptosis after AD. 2,4-dinitrochlorobenzene (DNCB) was used to establish AD mouse models. As expected, topically applied EGCG-NPs elicited a significant amelioration of AD symptoms in skin lesions, including reductions in the ear and skin thickness, dermatitis score, and scratching behavior, which was accompanied by redox homeostasis restored early in the experiment. In addition, EGCG-NPs significantly decreased the expression of inflammatory cytokines like TNF-α, interferon-γ (IFN-γ), interleukin-4 (IL-4), interleukin-6 (IL-6), and interleukin-17A (IL-17A) in a time-dependent manner than those of in AD group. As a result, the overexpression of RIP1, RIP3, and MLKL in the entire epidermis layers was dramatically blocked by EGCG-NPs, as well as the expression ofphosphorylated p38 (p-p38), extracellular signal-regulated kinase 1 (ERK1), and extracellular signal-regulated kinase 2 (ERK2). These findings promote that EGCG-NPs formulation represents a promising drug-delivery strategy for the treatment of AD by maintaining the balance of Th1/Th2 inflammation response and targeting necroptosis.

EGCG-NPs inhibition HO-1-mediated reprogram iron metabolism against ferroptosis after subarachnoid hemorrhage

“…mPEG-PLGA (Poly lactiv- co -glycolic acid, 75:25, 45,000) was purchased from Daigang Biomaterial Co., Ltd (Jinan, China). EGCG-NPs was formulated in our lab based on the previous report [ 29 , 30 ]. Calcein-AM, FerroOrange, and Mito-FerroGreen were obtained from Thermo Fisher and Dongren Chemical Technology, respectively (Massachusetts, USA; Tokyo, Japan).…”

Modulating Inflammation-Mediated Diseases via Natural Phenolic Compounds Loaded in Nanocarrier Systems

“…Similarly, in dermatitis, the encapsulation of this catechin derivative in PEG-PLGA ameliorated the blockading of necroptosis (RIP 1, RIP 3, and MLKL expressions) in the 2,4 dinitrochlorobenzene (DNCB)-induced skin model, while the topical application resulted in noticeable downregulation of inflammatory cytokines releases. In the meantime, the synthesis of MAPK pathways (p-p38, ERK1, ERK2) in the epidermal layers of the dermatitis was also suppressed [ 114 ]. Co-loading of EGCG with Vit C in chitosan was established to quicken the wound healing of streptozocin-induced mice when administered intraperitoneally.…”

Nanotechnology-Based Topical Delivery of Natural Products for the Management of Atopic Dermatitis

“…Recently, Han et al [ 15 ] have created polyethylene glycol–PLGA–EGCG nanoparticles (EGCG-NPs) following the double emulsion methodology. The produced formulation presented an average size of 176.2 nm, the zeta potential was −33.3 mV, and the entrapment efficiency was 86% while PDI was 0.044.…”

“…To overcome some transdermal delivery problems, augment drug-to-site targeting, solve problems related to active compounds’ solubility, and increase efficacy of such natural ingredients in AD treatment, some nanotechnology-based solutions have been developed in recent years. As successful examples that are herein reviewed, investigators designed quercetin nanostructured lipid carriers [ 12 ], solid lipid nanoparticles loaded with capsaicin, curcurmin, and resveratrol [ 13 ], nanoparticles of epigallocatechin-3-gallate [ 14 , 15 ], transfersomes loaded with glycyrrhizic acid [ 16 ], innovative phytosomes with Centella asiatica (L.) Urban extracts [ 17 ], nanocapsule-based films of pomegranate seed oil [ 18 ], and ethosome-based cream of tea tree oil [ 19 ], and several other formulations presented throughout this paper.…”