Curcumin and Heme Oxygenase: Neuroprotection and Beyond

Abstract

Curcumin is a natural polyphenol component of Curcuma longa Linn, which is currently considered one of the most effective nutritional antioxidants for counteracting free radical-related diseases. Several experimental data have highlighted the pleiotropic neuroprotective effects of curcumin, due to its activity in multiple antioxidant and anti-inflammatory pathways involved in neurodegeneration. Although its poor systemic bioavailability after oral administration and low plasma concentrations represent restrictive factors for curcumin therapeutic efficacy, innovative delivery formulations have been developed in order to overwhelm these limitations. This review provides a summary of the main findings involving the heme oxygenase/biliverdin reductase system as a valid target in mediating the potential neuroprotective properties of curcumin. Furthermore, pharmacokinetic properties and concerns about curcumin’s safety profile have been addressed.

Neuroprotective Effects of Necrostatin-1 Against Oxidative Stress–Induced Cell Damage: an Involvement of Cathepsin D Inhibition

“…As a positive control for the assay we used Ac-DEVD-CHO (20 μM), an inhibitor of caspase-3 which was given 30 min before the cell damaging factor Data were normalized to vehicle-treated cells (control) and are presented as the mean ± SEM from 3 separate experiments with 2 repetitions each **P<0.01 and ***P < 0.001 vs. vehicle-treated cells ### P < 0.001 vs. H 2 O 2 -treated cells curcumin in RA-SH-SY5Y cells against 6-OHDA-evoked cell damage, which is the cell death model connected rather with apoptotic than necrotic processes that are saturated after differentiation with RA (Cheung et al 2009;No et al 2010;Park et al 2014). Our results obtained in UN-SH-SY5Y cells confirmed previous findings on neuroprotective effect of curcumin which could be mediated by its antioxidant, antiapoptotic, and anti-inflammatory mechanisms (Mhillaj et al 2019;Sang et al 2018;Uğuz et al 2016).…”

“…In order to test a potential interplay between apoptosis and necroptosis in our models, we co-treated cells with the caspase-3 inhibitor, Ac-DEVD-CHO, and Nec-1. Since previous studies showed neuroprotective effects of curcumin in various types of neuronal cell damage (Mhillaj et al 2019;Szczepanowicz et al 2016) and the involvement of both apoptosis and necroptosis inhibition has been suggested to be associated with the curcuminmediated protection (Dai et al 2013;Wang et al 2017;Xu et al 2019), we studied a potential synergism in neuroprotective effects of Nec-1 and curcumin (Curc) in UN-and RA-SH-SY5Y cells. Next, we searched for putative mechanisms involved in neuroprotection mediated by Nec-1 by measuring the apoptotic markers (caspase-3 activity, AIF translocation), calpain activity (145 kDa cleavage product of spectrin α II) and lysosomal permeability (cathepsin D activity).…”

<p>Liposomal Encapsulated Curcumin Effectively Attenuates Neuroinflammatory and Reactive Astrogliosis Reactions in Glia Cells and Organotypic Brain Slices</p>

“…[8][9][10][11][12][13][14][15][16] These and other studies revealed that curcumin may influence several intracellular signaling cascades, yielding neuroprotective and anti-inflammatory microglia-attenuating effects. [17][18][19][20][21][22][23][24][25] In recent studies, curcumin has also been described to prevent glial scar formation in spinal cord and brain injuries. [26][27][28][29] In experimental studies on spinal cord injuries, curcumin could reduce in vitro and in vivo the production of pro-inflammatory mediators, the reactive expression of gliosis/fibrosis markers and the deposition of chondroitin sulfate proteoglycans, presumably by modulating several, partly diverging signaling pathways.…”

Optimization extraction and purification of biological activity curcumin from Curcuma longa L by high‐performance counter‐current chromatography

“…Turmeric, Curcuma longa L., is a well‐known herb of the Zingiberacea family and a natural colorant. As the main component of Curcuma longa L, curcuminoids have been explored in antiprotozoal [1], antioxidant [2], anticancer [3–5], preventing diabetic nephropathy [6], and preventing Alzheimer's disease [7]. Curcumin (CC), demethoxycurcumin (DMCC), and bisdemethoxycurcumin (BDMCC) are the three main curcuminoids (Figure 1A), and CC is the most important active component [8].…”