Intracellular ROS Protection Efficiency and Free Radical-Scavenging Activity of Curcumin

Curcumin has many pharmaceutical applications, many of which arise from its potent antioxidant properties. The present research examined the antioxidant activities of curcumin in polar solvents by a comparative study using ESR, reduction of ferric iron in aqueous medium and intracellular ROS/toxicity assays. ESR data indicated that the steric hindrance among adjacent big size groups within a galvinoxyl molecule limited the curcumin to scavenge galvinoxyl radicals effectively, while curcumin showed a powerful capacity for scavenging intracellular smaller oxidative molecules such as H2O2, HO•, ROO•. Cell viability and ROS assays demonstrated that curcumin was able to penetrate into the polar medium inside the cells and to protect them against the highly toxic and lethal effects of cumene hydroperoxide. Curcumin also showed good electron-transfer capability, with greater activity than trolox in aqueous solution. Curcumin can readily transfer electron or easily donate H-atom from two phenolic sites to scavenge free radicals. The excellent electron transfer capability of curcumin is because of its unique structure and different functional groups, including a β-diketone and several π electrons that have the capacity to conjugate between two phenyl rings. Therfore, since curcumin is inherently a lipophilic compound, because of its superb intracellular ROS scavenging activity, it can be used as an effective antioxidant for ROS protection within the polar cytoplasm

Anti-Viral Potential and Modulation of Nrf2 by Curcumin: Pharmacological Implications

Nuclear factor erythroid 2-related factor 2 (Nrf2) is an essential transcription factor that maintains the cell's redox balance state and reduces inflammation in different adverse stresses. Under the oxidative stress, Nrf2 is separated from Kelch-like ECH-associated protein 1 (Keap1), which is a key sensor of oxidative stress, translocated to the nucleus, interacts with the antioxidant response element (ARE) in the target gene, and then activates the transcriptional pathway to ameliorate the cellular redox condition. Curcumin is a yellow polyphenolic curcuminoid from Curcuma longa (turmeric) that has revealed a broad spectrum of bioactivities, including antioxidant, anti-inflammatory, anti-tumor, and anti-viral activities. Curcumin significantly increases the nuclear expression levels and promotes the biological effects of Nrf2 via the interaction with Cys151 in Keap1, which makes it a marvelous therapeutic candidate against a broad range of oxidative stress-related diseases, including type 2 diabetes (T2D), neurodegenerative diseases (NDs), cardiovascular diseases (CVDs), cancers, viral infections, and more recently SARS-CoV-2. Currently, the multifactorial property of the diseases and lack of adequate medical treatment, especially in viral diseases, result in developing new strategies to finding potential drugs. Curcumin potentially opens up new views as possible Nrf2 activator. However, its low bioavailability that is due to low solubility and low stability in the physiological conditions is a significant challenge in the field of its efficient and effective utilization in medicinal purposes. In this review, we summarized recent studies on the potential effect of curcumin to activate Nrf2 as the design of potential drugs for a viral infection like SARS-Cov2 and acute and chronic inflammation diseases in order to improve the cells' protection

Thermal Unfolding Pathway of PHD2 Catalytic Domain in Three Different PHD2 Species: Computational Approaches

Prolyl hydroxylase domain 2 containing protein (PHD2) is a key protein in regulation of angiogenesis and metastasis. In normoxic condition, PHD2 triggers the degradation of hypoxia-inducible factor 1 (HIF-1α) that induces the expression of hypoxia response genes. Therefore the correct function of PHD2 would inhibit angiogenesis and consequent metastasis of tumor cells in normoxic condition. PHD2 mutations were reported in some common cancers. However, high levels of HIF-1α protein were observed even in normoxic metastatic tumors with normal expression of wild type PHD2. PHD2 malfunctions due to protein misfolding may be the underlying reason of metastasis and invasion in such cases. In this study, we scrutinize the unfolding pathways of the PHD2 catalytic domain’s possible species and demonstrate the properties of their unfolding states by computational approaches. Our study introduces the possibility of aggregation disaster for the prominent species of PHD2 during its partial unfolding. This may justify PHD2 inability to regulate HIF-1α level in some normoxic tumor types

A Folding Pathway-Dependent Score to Recognize Membrane Proteins

While various approaches exist to study protein localization, it is still a challenge to predict where proteins localize. Here, we consider a mechanistic viewpoint for membrane localization. Taking into account the steps for the folding pathway of α-helical membrane proteins and relating biophysical parameters to each of these steps, we create a score capable of predicting the propensity for membrane localization and call it FP3mem. This score is driven from the principal component analysis (PCA) of the biophysical parameters related to membrane localization. FP3mem allows us to rationalize the colocalization of a number of channel proteins with the Cav1.2 channel by their fewer propensities for membrane localization

Evaluation of Gox^• scavenging rate by curcumin based on ESR results.

<p>The ESR spectra were followed after addition of different concentrations of curcumin (10 µM •; 20 µM ▪; 40 µM ▴). Inset: ESR spectra of 10 µM galvinoxyl radicals in different conditions. a) before addition of curcumin, b) 10 min after addition of 10 µM curcumin, c) 10 min after addition of 40 µM curcumin.</p

Effect of curcumin on viability of L-6 myoblasts exposed to cumene hydroperoxide (CHP).

<p>After a 30 min treatment of cells with different concentrations of curcumin (0, 1 and 5.0 µM) the cells were induced with 5 µl (1∶100) CHP. Viability was measured by the MTT assay.</p

In situ analysis of intracellular ROS.

<p>A) All samples were first incubated (30 min) with different concentration of curcumin (a, 0.0; b, 0.1; c, 0.25; d, 0.5; e, 1.0; f, 2.0; g, 4.0 µM), then the DCF fluorescence intensity changes were monitored by the addition of the ROS stimulating agent cumene hydroperoxide (CHP). In the absence of CHP, no change in DCF fluorescence intensity was seen with time; however, it started increasing in presence of CHP. B) The principle of the intracellular ROS protection activity of curcumin. Curcumin diffuses easily into the cells prevents ROS production, thereby preventing oxidation of DCFH₂ and the formation of the fluorescent DCF product.</p

The reaction of 5,5-dithiobis(2-nitrobenzoic acid) with bovine liver catalase with multiple reactive sulphydryl groups

Bull. Chem. Soc. Ethiop. 1995, 9(2), 101-106

Comparative physical properties of curcumin, trolox and α-tocopherol.

<p>*The parameters were obtained from ChemBank (<a href="http://chembank.broadinstitute.org/" target="_blank">http://chembank.broadinstitute.org/</a>).</p><p>a: total surface area (SA_tot), b: polar surface area (SA_pol), c: relative polar surface area (SA_pol/SA_tot).</p