Curcumin incorporates several functional groups. The aromatic ring systems, which are phenols, are connected by two α,β-unsaturated carbonyl groups. The diketones form stable enols and are readily deprotonated to form enolates; the α,β-unsaturated carbonyl group is a good Michael acceptor and undergoes nucleophilic addition. The structure was first identified in 1910 by J. Miłobędzka, Stanisław Kostanecki and Wiktor Lampe.^[3]

Although some preclinical studies suggest curcumin may be useful for the prevention and treatment of several diseases, the effectiveness of curcumin has neither been confirmed in sufficient preliminary research, nor has it been demonstrated in randomized, placebo-controlled, double-blind clinical trials.^[8]

In one preliminary study, a daily dose of 2 grams of curcumin extract was found to provide pain relief that was equivalent to ibuprofen for the relief of pain associated with osteoarthritis of the knee.^[9] A survey of the literature shows a number of other potential uses and that daily doses over a 3 month period of up to 12 grams proved safe.^[10] Some commercial capsules of curcumin contain piperine, a compound found in pepper which aids absorption of curcumin into the blood stream. However, as curcuma is known to inhibit blood clotting,^{[citation needed]} it should be avoided for a two-week period prior to major surgery and not used in conjunction with blood thinners.^{[citation needed]} Curcumin may also affect gallstone formation.^[11]

The effect of curcumin on amyloid beta plaque build up, a possible major cause for Alzheimer’s, has been studied in mice. According to theory, curcumin may provide anti-inflammatory effects in a neuro-inflammatory cascade in plaque pathogenesis. The study demonstrated that both low and high doses of curcumin reduced β-amyloid plaque buildup, an effect that may be similar to that of aspirin which suppressed development of β-amyloid plaque buildup in preliminary research.^[12]

Research in the latter half of the 20th century identified curcumin as the agent responsible for most of the biological activity of turmeric.^[13] In vitro and animal studies have suggested potential biological effects associated with curcumin. At present, these effects have not been confirmed in humans.

As of 2008, clinical trials in humans were underway, studying the effect of curcumin on various diseases, including multiple myeloma, pancreatic cancer,myelodysplastic syndromes, colon cancer, psoriasis, and Alzheimer's disease.^[14]

Several preliminary research studies have identified curcumin with potential biological effects:

• In both in vitro and animal studies, curcumin has shown antitumor,^[15][16][17] antioxidant, antiarthritic, antiamyloid, anti-ischemic,^[18] and anti-inflammatoryproperties.^[19]
• Anti-inflammatory properties may be due to inhibition of eicosanoid biosynthesis.^[20]
• In one study, curcumin protected mice from V. vulnificus-induced septicemia.^[21]
• A study found it hepatoprotective in combination with Absinthium in rats.^[22]
• A laboratory study found that low concentrations of curcumin interfere with Herpes simplex virus-1 (HSV-1) replication. It inhibited the recruitment of RNA polymerase II to viral DNA, thus inhibiting its transcription. This effect was independent of the effect on histone acetyltransferase activities of p300/CBP.^[23]
• One study found that curcumin may be associated with protection from infection by HSV-2 in animal models of intravaginal infections.^[24]
• A study in rats found that curcumin may act as a free radical scavenger and antioxidant, inhibiting lipid peroxidation and oxidative DNA damage, protecting against lead neurotoxicity.^[25]
• In rats, curcumin was shown to be effective in protecting against toxicity and spatial memory impairment induced by amyloid β-protein infusion.^[26]
• A study using a transgenic animal model indicated that curcumin diminished plaque burden and overall inflammation, but it also increased plaque-associated inflammatory cells suggesting enhanced clearance.^[27]
• A study found that curcumin shrank the size of plaques and reduced neurite dystrophy in an Alzheimer mouse model.^[28]
• A study found curcumin to have a synergistic effect with fish oil to protect against cognitive deficits in a transgenic rodent model.^[29]
• Preliminary studies indicate that curcumin may have a positive effect on neurogenesis in the hippocampus and may increase levels of brain-derived neurotrophic factor (BDNF) in rats.^[30][31][32]
• A curcumin pyrazole derivative was found to improve memory and was neuroprotective, stimulating BDNF in vitro and in vivo.^[33][34] The compound was found to be protective in animal models of brain trauma and stroke.^[35][36]
• In rats, curcumin may inhibit cardiac hypertrophy and affect cardiac health and repair through different mechanisms.^[37][38][39]
• In one preliminary human study, curcumin increased insulin secretion from the pancreas.^[40]

Preliminary cancer research

The potential anti-cancer effects of curcumin have been the subject of several preliminary studies:

• Its potential anticancer effects may stem from an ability to induce apoptosis in cancer cells without cytotoxic effects on healthy cells. Curcumin may interfere with activity of the transcription factor NF-κB, which has been linked to a number of inflammatory diseases such as cancer.^[41]
• One study suggested curcumin may inhibit a cancer-associated complex via mechanisms yet to be defined.^[42][43]
• An in vitro study in a human glioblastoma cell line reported that curcumin may inhibit tumor cell proliferation, migration and invasion, and that these effects may be mediated through interference with a signaling pathway.^[44]
• When 0.2% curcumin was added to the diet of rats or mice previously given a carcinogen, it reduced incidence of colon carcinogenesis.^[45]
• In one in vitro study curcumin had phyto-estrogenic activity that might affect onset of breast cancer.^[46]
• In immunodeficient mice with breast cancer, curcumin inhibited the formation of lung metastases,^[47] possibly through the regulation of cytokines.^[48][49]
• A study found that curcumin might affect kidney function by reducing lipopolysaccharide-induced renal inflammation.^[50]

Kawanishi et al. remarked that curcumin, like many antioxidants, can be a "double-edged sword" where, in the test tube, carcinogenic and pro-oxidant effects may be seen in addition to anticancer and antioxidant effects.^[54] Carcinogenic effects are inferred from interference with the p53 tumor suppressor pathway, an important factor in human colon cancer.^[55] In vitro and in vivo studies suggest that curcumin can have carcinogenic effects.^[56][57][58]

Clinical studies in humans with high doses (2–12 grams) of curcumin have shown few side effects, with some subjects reporting mild nausea or diarrhea.^[59] More recently, curcumin was found to alter iron metabolism by chelating iron and suppressing the protein hepcidin, potentially causing iron deficiency in susceptible patients.^[60] Further studies seem to be necessary to establish the benefit/risk profile of curcumin.^[56]

There is no or little evidence to suggest curcumin is either safe or unsafe for pregnant women. However, there is still some concern medicinal use of products containing curcumin could stimulate the uterus, which may lead to a miscarriage, although there is not much evidence to support this claim. According to experiments done on rats and guinea pigs, there is no obvious effect (neither positive, nor negative) on the pregnancy rate or number of live or dead embryos.^[61] Curcumin has embryotoxic and teratogenic effects on zebrafishes (Danio rerio) embryos.^[62]