Strong Anti-inflammatory Effect of Soluble Curcumin Shown at Cellular Level

This chapter aims to explore potentiality of a suitable drug molecule that can serve as an ideal candidate for exerting its therapeutic actions in order to cure or regulate pathological conditions at inflammatory levels. Inflammatory mechanisms have become one of the strongest underlying causative factors in most of the diseases. Atherosclerosis is one such inflammatory scenario wherein Endothelial cell (EC) activation and chronic inflammation can cause the initiation and progression of the disease. A promising candidate medicine with few negative effects is curcumin (CM). However, its therapeutic usage is constrained by poor water solubility, a lack of bioavailability, and significant hydrolytic breakdown. Conjugation of CM to Albumin (Alb) producing CM-Alb increases the solubility of the potential drug as well as targeted drug delivery with negligible adverse effects from the drug carrier. This study evaluates an albumin-CM conjugate for cellular uptake demonstrating bioavailability, determining the non-cytotoxic concentrations and anti-inflammatory response in human umbilical vein endothelial cells (HUVECs). The maximum tolerated biocompatible dose determined in HUVEC (EC) culture is 30µM; accordingly, this study evaluates an anti-inflammatory response at non-toxic concentrations. The experiments using fluorescence microscopy and flow cytometry confirmed the endocytosis of fluorescent-tagged CM-Alb and showed comparable cellular uptake of native albumin. Cytokine- induced activation of inflammation in EC culture was standardized as in vitro model for evaluating the response to CM-Alb. A significant increase in the expression of VCAM-1 in EC upon incubating with TNF- for a period of 24h gives a good model system to study the effect of the anti-inflammatory drug molecule. Further, the treatment of inflammation-induced ECs with CM-Alb conjugate at 5, 10, 20µM concentrations down-regulated the expression of VCAM-1 significantly compared to the TNF- treated cells. Expressions of markers at a protein level in cytokine-activated EC drop down to normalcy when treated with CM-Alb. In the inflammation-induced culture paradigm, the improved aqueous solubility and receptor-mediated absorption of the CM- Alb compound by ECs resulted in an anti-inflammatory response, suggesting the possibility for further research as an intravenous medicinal formulation.