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Page 14 of 36 Dave et al. J Cancer Metastasis Treat 2020;6:46 I http://dx.doi.org/10.20517/2394-4722.2020.106

carbon chains consisting of an α, β-unsaturated β-diketone component, and generally accounts for 60%-
70% of curcuminoid extracts [173,174] . The o-methoxyphenol rings are the primary domains for the antioxidant
activity of curcumin and the β-diketone component forms chelation complexes with metals rendering them
useful for the treatment of heavy metal poisoning [175] .

In a pre-clinical study, 500 mg/kg curcumin administered orally to rats gave a maximum plasma
concentration of approximately 0.06 µg/mL, reaching the peak by approximately 41 min; the half-life was
28 min, giving an oral bioavailability of about 1% [176] . As suggested by this poor bioavailability, the tolerance
for curcumin is very high for humans. In a dose escalation study, minimal adverse events were observed
which were unrelated to the dose after oral administration of 10,000 or 12,000 mg in healthy subjects. Still,
only traces were detected in serum [177] . At 10-12 g, the highest dose given to human subjects, the plasma
concentration of curcumin and its metabolites were in the range of 0.075-10 µg/mL [178] . Curcumin is
metabolized by the process of glucuronidation in the intestine and by the liver yielding metabolites such as
tetra-hydrocurcumin, and hexahydrocurcumin [179] .

Nevertheless, there are a vast number of studies conducted with curcumin to investigate anti-inflammatory,
antioxidant, anti-carcinogenic, antiviral, and anti-infection activities. Owing to its antibacterial, antioxidant,
anti-inflammatory, and antiseptic properties, curcumin has been proven useful in treating several skin
diseases, such as psoriasis, infection, acne, skin inflammation, and skin cancer [180] . Curcumin controlled the
in vitro growth of Staphylococcus aureus and Pseudomonas aeruginosa in an in vivo murine wound model,
and topical administration accelerated healing [181] . In a psoriasis keratin (K) 14-VEGF transgenic mouse
model, after oral curcumin administration, symptoms like ear redness, weight, thickness, and lymph node
weight were reduced significantly [182] .

There have been several conclusive in vitro, in vivo, and clinical studies conducted on the use and benefits
of curcumin in treating inflammatory diseases. Curcumin exhibited anti-inflammatory effects in adipose
tissue of C57BL/6 mice fed a high fat diet by down-regulating inflammatory transcription factors like
NF-κB and toll-like receptor-4 [183] . The clinical effectiveness of curcumin in treating inflammation was
studied in patients diagnosed with osteoarthritis, and significant reductions in myeloperoxidase, collagen
degradation activity, and C-reactive protein levels were observed; also, additional symptoms like pain and
effusion were reduced [184] . In 45 patients with active rheumatoid arthritis, curcumin (500 mg) was used
in combination with diclofenac sodium (50 mg) and there was a significant reduction in their disease
activity score compared with the group provided only with diclofenac sodium [185] . In yet another clinical
study, patients with acute rhinitis were administered 500 mg of curcumin orally. Symptoms like sneezing,
itching, and obstruction rhinorrhea were reduced significantly in patients treated with curcumin compared
to the placebo treatment, and inflammatory markers such as IL-4, TNF-α, IL-8, PEG were significantly
2
decreased [186] .

Curcumin as a chemopreventive and anticarcinogenic agent
Curcumin has been broadly studied for anti-cancer characteristics [Figure 6]. A pilot study conducted with
patients diagnosed with benign prostatic hyperplasia (BPH) and administered 500 mg of curcumin twice
a day along with the standard therapeutic regimen showed improved symptoms and improved quality of
life relative to the group administered the standard treatment only [187] . In another study, 85 patients with
prostate cancer were administered curcumin and soy isoflavones along with the standard treatment, and
elevated PSA levels were significantly decreased in patients treated with curcumin and soy isoflavones
compared with the group given the standard treatment [188] .

In other forms of cancer, like breast and cervical, curcumin has proved effective. In patients with advanced
metastatic breast cancer, curcumin reduced biomarkers like CEA with a maximum tolerated dose of 8000