The curcuminoids have been found to have a number of antioxidant activities, including scavenging of such reactive oxygen species as superoxide anions and hydrogen peroxide, inhibition of lipid peroxidation and inhibition of the oxidation of low-density lipoprotein (LDL). The reduced derivative of curcumin, tetrahydrocurcumin, has been found to have even stronger antioxidant activity. Tetrahydrocurcumin may be formed from curcumin following ingestion; however, this is unclear.
The possible anticarcinogenic activity of curcumin and the other curcuminoids may be accounted for by a few mechanisms. These include inhibition of angiogenesis, upregulation of apoptosis, interference with certain signal transduction pathways that are critical for cell growth and proliferation, inhibition of colonic mucosa cyclooxygenase (COX) and lipoxygenase (LOX) activities and inhibition of farnesyl protein transferase. In addition to its possible activity in preventing malignant transformation and inhibiting tumor growth, curcumin may have antimetastatic potential, as well. In this regard, curcumin has been found to inhibit matrix metalloproteinase-9 in a human hepatocellular carcinoma cell line. The possible anticarcinogenic activity of the curcuminoids may be attributed, at least in part, to their ability to inhibit activation of the transcription factors NF-KappaB and AP-1. Curcuminoids have also been found to target the fibroblast growth factor-2 (FGF-2) angiogenic signaling pathway and inhibit expression of gelatinase B in the angiogenic process.
In the final analysis, the curcuminoids' antioxidant activity may underlie many of the above mechanisms. Reactive oxygen species (ROS) can activate AP-1 and NF-KappaB. Further, FGF-2 induces AP-1 activation via ROS produced through NADPH oxidase. The curcuminoids, acting as antioxidants, may interfere with the ability of FGF-2 to stimulate AP-1, and they may generally inhibit the activation of NF-KappaB and AP-1.
The possible anti-inflammatory activity of the curcuminoids may also be accounted for by several mechanisms, including inhibition of COX and LOX, reduction of the release of ROS by stimulated neutrophils, inhibition of AP-1 and NF-KappaB, and inhibition of the activation of the pro-inflammatory cytokines TNF (tumor necrosis factor) -alpha and IL (interleukin)-1 beta.
Curcumin has modest anti HIV-1 activity. It has been found to inhibit HIV-1 and HIV-2 proteases, HIV-1 LTR (long terminal repeat)-directed gene expression, Tat-mediated transactivation of HIV-1-LTR and HIV-1 integrase. All of these actions have been demonstrated in vitro. There is no evidence that curcumin or the other curcuminoids significantly inhibit the replication of HIV-1 in vivo. The mechanism of the possible hypocholesterolemic effect of the curcuminoids is unclear.