BackgroundInhibition of the nuclear factor kappa beta (NF-κβ) pathway has been proposed as a therapeutic target due to its key role in the expression of pro-inflammatory genes, including pro-inflammatory cytokines, chemokines, and adhesion molecules. Caffeic acid phenethyl ester (CAPE) is a naturally occurring anti-inflammatory agent, found in propolis, and has been reported as a specific inhibitor of NF-κβ. However, the impact of CAPE on levels of myeloperoxidases (MPO) and pro-inflammatory cytokines during inflammation is not clear. The aims of this study were to investigate the protective efficacy of CAPE in the mouse model of colitis and determine its effect on MPO activity, pro-inflammatory cytokines levels, and intestinal permeability.MethodDextran sulphate sodium was administered in drinking water to induce colitis in C57/BL6 mice before treatment with intraperitoneal administration of CAPE (30 mg kg−1 day−1). Disease activity index (DAI) score, colon length and tissue histology levels of MPO, pro-inflammatory cytokines, and intestinal permeability were observed.ResultsCAPE-treated mice had lower DAI and tissue inflammation scores, with improved epithelial barrier protection and significant reduction in the level of MPO and pro-inflammatory cytokines.ConclusionOur results show that CAPE is effective in suppressing inflammation-triggered MPO activity and pro-inflammatory cytokines production while enhancing epithelial barrier function in experimental colitis. Thus, we conclude that CAPE could be a potential therapeutic agent for further clinical investigations for treatment of inflammatory bowel diseases in humans.Electronic supplementary materialThe online version of this article (doi:10.1007/s10787-017-0364-x) contains supplementary material, which is available to authorized users.

Piceatannol (PIC) is known to have anticancer activity, which has been attributed to its ability to block the proliferation of cancer cells via suppression of the NF-kB signaling pathway. However, its effect on hypoxia-inducible factor (HIF) is not well known in cancer. In this study, PIC was loaded into bovine serum albumin (BSA) by desolvation method as PIC–BSA nanoparticles (NPs). These PIC–BSA nanoparticles were assessed for in vitro cytotoxicity, migration, invasion, and colony formation studies and levels of p65 and HIF-1α. Our results indicate that PIC–BSA NPs were more effective in downregulating the expression of nuclear p65 and HIF-1α in colon cancer cells as compared to free PIC. We also observed a significant reduction in inflammation induced by chemical colitis in mice by PIC–BSA NPs. Furthermore, a significant reduction in tumor size and number of colon tumors was also observed in the murine model of colitis-associated colorectal cancer, when treated with PIC–BSA NPs as compared to free PIC. The overall results indicate that PIC, when formulated as PIC–BSA NPs, enhances its therapeutic potential. Our work could prompt further research in using natural anticancer agents as nanoparticels with possible human clinical trails. This could lead to the development of a new line of safe and effective therapeutics for cancer patients.

Our findings indicate that curcumin can effectively lower the elevated levels of HIF-1α and nuclear p65 (Rel A) in breast and lung cancer cells under an hypoxic tumour micro-environment when delivered in nanoparticulate form. This applied means of colloidal delivery could explain the improved anti-cancer efficacy of curcumin and has further potential applications in enhancing the activity of anti-cancer agents of low solubility.

Hypoxia inducible factor and nuclear factor-kappa beta pathways have been proposed as therapeutic targets for several inflammatory diseases. Caffeic acid phenethyl ester (CAPE) and piceatannol (PIC) are natural anti-inflammatory compounds; however, poor bioavailability and limited understanding of biomolecular mechanistic limits its clinical use. The aims of this study are to enhance bioavailability and investigate their impact on nuclear p65 and HIF-1α for the first time in experimental colitis.Dextran sulphate sodium was used to induce colitis in mice and effect of either free CAPE/PIC or CAPE/PIC loaded albumin nanoparticles treatment was observed on disease development and levels of cellular p65 and HIF-1α.Our results indicate that albumin nano-encapsulation of CAPE/PIC not only enhances its anti-inflammatory potential but also potentiates its ability to effectively modulate inflammation related biomolecular pathways. Hence, combining nanotechnology with natural compounds could result in development of new therapeutic options for IBD.Electronic supplementary materialThe online version of this article (10.1007/s13346-018-00597-9) contains supplementary material, which is available to authorized users.

Glaucoma is a group of optic neuropathies characterised by the degeneration of retinal ganglion cells, resulting in damage to the optic nerve head (ONH) and loss of vision in one or both eyes. Increased intraocular pressure (IOP) is one of the major aetiological risk factors in glaucoma, and is currently the only modifiable risk factor. However, 30–40% of glaucoma patients do not present with elevated IOP and still proceed to lose vision. The pathophysiology of glaucoma is therefore not completely understood, and there is a need for the development of IOP-independent neuroprotective therapies to preserve vision. Neuroinflammation has been shown to play a key role in glaucoma and, specifically, the NLRP3 inflammasome, a key driver of inflammation, has recently been implicated. The NLRP3 inflammasome is expressed in the eye and its activation is reported in pre-clinical studies of glaucoma. Activation of the NLRP3 inflammasome results in IL-1β processing. This pro inflammatory cytokine is elevated in the blood of glaucoma patients and is believed to drive neurotoxic inflammation, resulting in axon degeneration and the death of retinal ganglion cells (RGCs). This review discusses glaucoma as an inflammatory disease and evaluates targeting the NLRP3 inflammasome as a therapeutic strategy. A hypothetical mechanism for the action of the NLRP3 inflammasome in glaucoma is presented.