Curcumin, demethoxycurcumin, bisdemethoxycurcumin, tetrahydrocurcumin and turmerones differentially regulate anti-inflammatory and anti-proliferative responses through a ROS-independent mechanism

Abstract

Curcumin, a component of turmeric (Curcuma longa), has been shown to exhibit chemopreventive activity. Whether analogs of curcumin (Cur), such as demethoxycurcumin (DMC), bisdemethoxycurcumin (BDMC), tetrahydrocurcumin (THC) and turmerones, modulate inflammatory signaling and cell proliferation signaling to same extent as curcumin was investigated. The results indicate that the relative potency for suppression of tumor necrosis factor (TNF)-induced nuclear factor-kappaB (NF-kappaB) activation was Cur > DMC > BDMC; thus suggesting the critical role of methoxy groups on the phenyl ring. THC, which lacks the conjugated bonds in the central seven-carbon chain, was completely inactive for suppression of the transcription factor. Turmerones also failed to inhibit TNF-induced NF-kappaB activation. The suppression of NF-kappaB activity correlated with inhibition of NF-kappaB reporter activity and with down-regulation of cyclooxygenase-2, cyclin D1 and vascular endothelial growth factor, all regulated by NF-kappaB. In contrast to NF-kappaB activity, the suppression of proliferation of various tumor cell lines by Cur, DMC and BDMC was found to be comparable; indicating the methoxy groups play minimum role in the growth-modulatory effects of curcumin. THC and turmerones were also found to be active in suppression of cell growth but to a much lesser extent than curcumin, DMC and BDMC. Whether suppression of NF-kappaB or cell proliferation, no relationship of any of the curcuminoid was found with reactive oxygen species (ROS) production. Overall, our results demonstrated that different analogs of curcumin present in turmeric exhibit variable anti-inflammatory and anti-proliferative activities, which do not correlate with their ability to modulate the ROS status.

A Kinetic Degradation Study of Curcumin in Its Free Form and Loaded in Polymeric Micelles

“…Interestingly, it has been reported that encapsulation of curcumin in the form of curcuminoid mixture in micelles or nanoparticles retards the degradation of curcumin (18)(19)(20)(21)(22)(23). In this present study, we focused on the curcuminoid mixture because the anticancer and antiinflammatory activities of this mixture were stronger than that of pure curcumin alone and because the curcuminoid mixture has been used in most clinical trials (5,24). The degradation of curcumin in the curcuminoid mixture in its free form was performed in mixture of water and methanol (varying volume fractions) and at different pH and temperatures to get insight into the mechanism of enhanced stability of curcumin in the form of curcuminoid mixture loaded in polymeric micelles.…”

“…Degradation of Curcumin (as Curcuminoid Mixture) Loaded in Micellar Formulations of mPEG-HPMA-Bz and Triton X-100 mPEG-HPMA-Bz polymer with a molecular weight of 28 kDa was synthesized by a free radical polymerization method and characterized by 1 H-NMR (24,25). Curcumin (in the form of the curcuminoid mixture) loaded mPEG-HPMA-Bz micelles were prepared by a nanoprecipitation method (25,26).…”

Curcumin as “Curecumin”: From kitchen to clinic

“…Although most studies indicate that curcumin glucuronides and THC are less active than curcumin [154,166], others suggest otherwise [20,21,89,[167][168][169][170][171][172]. The differences in results so far are most likely due to the assays employed.…”

Oxidative Stress and Cardiovascular Dysfunction Associated with Cadmium Exposure: Beneficial Effects of Curcumin and Tetrahydrocurcumin

“…Curcumin is a potent scavenger of ROS including O 2 •− , OH• and singlet oxygen. It has been suggested that a diketone group of curcumin can react with OH• and H 2 O 2 whereas the two phenyl methoxy groups of curcumin suppress NF-κB activation (Singh and Aggarwal 1995;Sandur et al 2007;Somparn et al 2007). Treatment with curcumin, a known activator of Nrf2-antioxidant response element (ARE) pathway, may suppress oxidant formation by up-regulation of antioxidant enzymes (Heiss et al 2009).…”

“…Moreover, tetrahydrocurcumin reduces amyloid-β-induced oxidative stress and neurotoxicity by regenerating the mitochondrial membrane potential and inhibiting ROS generation and casspase-3 activity in rat hippocampal and human neuronal cells (Mishra et al 2011). However, tetrahydrocurcumin was shown to be less effective than curcumin in TNF-induced NF-κB activation and COX2 expression (Sandur et al 2007). …”