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Retinal degeneration is the major and principal cause behind many incurable blindness diseases. Several studies indicated the neuroprotective effect of Curcuma longa in eye pathologies, specifically retinopathy. However, the molecular mechanism behind its effect has not been completely elucidated. Using an ex vivo model of retinal degeneration obtained from an ex vivo optic nerve cut (ONC), we demonstrated that Curcuma extract (Cur) exerted a neuroprotective effect. Importantly, Cur was able to modulate apoptosis and MAPK signaling pathway activation and prevent retinal ganglion cell (RGC) loss. Other well-known neuroprotective pharmacological tools, including memantine (Mem), citicoline (Cit), and ginkgolic acid (GA), were used to compare the potential mechanisms of Cur. The antioxidant activity of retinas treated with Cur following optic nerve cut was significantly higher than control, but Cur failed to change the retina glutamate content. Considering the antioxidant effect of Cur and taking advantage of our recent findings on the crosstalk between oxidative stress and post-translational protein modifiers, in particular, small ubiquitin-related modifier (SUMO), we were interested in exploring the effect of Cur on SUMOylation. We found that Cur significantly prevented the increase of protein SUMOylation, confirming our previous in vitro data indicating the cytoprotective effect of curcumin through modulating the oxidative stress and SUMO-JNK axis. Altogether, these results suggest that Curcuma protects the retina from degeneration via antioxidant activity and targets SUMOylation. Therefore, it might be considered for the combination therapy with other neuroprotective agents with different mechanisms in preclinical studies on retinal degeneration., Competing Interests: The authors declare that they have no conflicts of interest regarding the publication of this paper., (Copyright © 2022 Kambiz Hassanzadeh et al.)

Among the extensive public and scientific interest in the use of phytochemicals to prevent or treat human diseases in recent years, natural compounds have been highly investigated to elucidate their therapeutic effect on chronic human diseases including cancer, cardiovascular disease, and neurodegenerative disease. Curcumin, an active principle of the perennial herb Curcuma longa , has attracted an increasing research interest over the last half-century due to its diversity of molecular targets, including transcription factors, enzymes, protein kinases, growth factors, inflammatory cytokines, receptors, and it's interesting pharmacological activities. Despite that, the clinical effectiveness of the native curcumin is weak, owing to its low bioavailability and rapid metabolism. Preclinical data obtained from animal models and phase I clinical studies done in human volunteers confirmed a small amount of intestinal absorption, hepatic first pass effect, and some degree of intestinal metabolism, might explain its poor systemic availability when it is given via the oral route. During the last decade, researchers have attempted with new pharmaceutical methods such as nanoparticles, liposomes, micelles, solid dispersions, emulsions, and microspheres to improve the bioavailability of curcumin. As a result, a significant number of bioavailable curcumin-based formulations were introduced with a varying range of enhanced bioavailability. This manuscript critically reviews the available scientific evidence on the basic and clinical effects and molecular targets of curcumin. We also discuss its pharmacokinetic and problems for marketing curcumin as a drug.

Oxidative stress is a toxic cellular condition, strictly related to inflammation and known to be a common feature of many neurodegenerative diseases. The imbalanced redox state modifies several molecular processes including protein SUMOylation, JNK and Tau protein activation, important actors in Alzheimer's disease. In this study, we showed a strong interaction among SUMO-1-JNK-Tau proteins and their molecular targets in an in vitro model (SHSY5Y cell line) of oxidative stress in which a significant reduction of cell viability and an augmented cell death was induced by increased doses of H2O2. The evoked oxidative stress led to a deficiency in the degradation system showing altered levels of Caspase-3, LC3BII/I and Ubiquitin. Curcumin, a natural compound with anti-oxidant and anti-inflammatory effects, demonstrated to tackle oxidative stress re-equilibrating SUMO-1, JNK and Tau functions. Importantly, 5 μM of curcumin induced an efficient recovery of cell viability, a reduction of cell death and a normalization of altered protein degradation marker levels. Interestingly, we found that H2O2 treatment induced a strong co-localization of SUMO-1-p-JNK-Tau proteins in nuclear bodies (NBs) and that curcumin was able to reduce these nuclear aggregates. These results highlight the SUMO-1-JNK-Tau axis key role in oxidative stress and the protective effect of curcumin against this pathological event, focusing on the importance of SUMO/deSUMOylation balance to regulate essential cellular processes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)