Strategies for Improving Bioavailability, Bioactivity, and Physical-Chemical Behavior of Curcumin

Abstract

Curcumin (CCM) is one of the most frequently explored plant compounds with various biological actions such as antibacterial, antiviral, antifungal, antineoplastic, and antioxidant/anti-inflammatory properties. The laboratory data and clinical trials have demonstrated that the bioavailability and bioactivity of curcumin are influenced by the feature of the curcumin molecular complex types. Curcumin has a high capacity to form molecular complexes with proteins (such as whey proteins, bovine serum albumin, β-lactoglobulin), carbohydrates, lipids, and natural compounds (e.g., resveratrol, piperine, quercetin). These complexes increase the bioactivity and bioavailability of curcumin. The current review provides these derivatization strategies for curcumin in terms of biological and physico-chemical aspects with a strong focus on different type of proteins, characterization methods, and thermodynamic features of protein-curcumin complexes, and with the aim of evaluating the best performances. The current literature review offers, taking into consideration various biological effects of the CCM, a whole approach for CCM-biomolecules interactions such as CCM-proteins, CCM-nanomaterials, and CCM-natural compounds regarding molecular strategies to improve the bioactivity as well as the bioavailability of curcumin in biological systems.

Keywords: bioavailability; curcumin complexes; protein–curcumin interactions; therapeutic properties; whey proteins; β-lactoglobulin.

Figure 1

(A) Structure of curcumin (CCM), demethoxycurcumin (DMC), and bis-demethoxycurcumin (BMC) [20]. (B) The enol and keto forms of CCM [20].

Figure 6

The types of solid dispersions [89] and their disadvantages.

Figure 2

The therapeutical effects of CCM are reflected by a large spectrum of action, as reported by the literature. The antitumor action of CCM was extensively explored in clinical and experimental conditions [22,23,24,25,26,27,28,29,30,31,32,33] as well as the antioxidant [34], anti-inflammatory [35,36,37], antibacterial [38,39,40] and immunomodulatory effects [41].

Figure 3

Product decomposition of curcumin in alkaline condition [56,57].

Figure 4

The antioxidant and anti-inflammatory action of curcumin (CCM). (A) CCM-liposomes are internalized in the cell by three routes: (i) caveolin-mediated or (ii) clathrin-mediated endocytosis, and also (iii) macropinocytosis. CCM targets the PPARα/γ (peroxisome proliferator-activated receptor alpha/gamma) signaling and potentiates peroxisome activity by increasing peroxisomal enzymes (e.g., catalase, superoxide-dismutase). Increasing the activity of peroxisomal-derived antioxidant enzymes leads to a reduction in reactive oxidative species (ROS) and a decrease in oxidative stress. Additionally, CCM inhibits mRNA of CD31 (cluster of differentiation 31), IL-8 (interleukin 8), and VEGF (vascular endothelial growth factor) with anti-inflammatory effects in the cell. (B) Complexes of CCM-proteins act on the peroxisome by increasing peroxisomal enzymes, thus decreasing oxidative stress by their scavenging action on the ROS. Furthermore, like CCM internalized by caveolin/clathrin-mediated endocytosis, the CCM-protein complex inhibits mRNA of CD31, IL-8, and VEGF, thereby demonstrating anti-inflammatory activity due to CCM increased bioavailability.

Figure 5

The antitumor activity of CCM (A), of liposomes loaded with CCM (B), and of CCM complexes with silymarin (C). Strategy and pathway (A): CCM inhibits the proteasome by increasing miR-142–3p expression leading to negatively regulating PSMB5 (proteasome 20S subunit beta 5) leading to cell apoptosis; strategy and pathway (B): Liposomes loaded with CCM decrease the expression of CD31 (cluster of differentiation 31) and IL-8 (interleukin 8) leading to cell necrosis; strategy and pathway (C): CCM complexes with silymarin inhibit NF-κB (nuclear factor-κB) leading to cell apoptosis.

Figure 7

The structure of resveratrol, icariin, quercetin, piperine, and silybin as representative bioactive molecules.