Therapeutic roles of curcumin: lessons learned from clinical trials

Abstract

Extensive research over the past half century has shown that curcumin (diferuloylmethane), a component of the golden spice turmeric (Curcuma longa), can modulate multiple cell signaling pathways. Extensive clinical trials over the past quarter century have addressed the pharmacokinetics, safety, and efficacy of this nutraceutical against numerous diseases in humans. Some promising effects have been observed in patients with various pro-inflammatory diseases including cancer, cardiovascular disease, arthritis, uveitis, ulcerative proctitis, Crohn's disease, ulcerative colitis, irritable bowel disease, tropical pancreatitis, peptic ulcer, gastric ulcer, idiopathic orbital inflammatory pseudotumor, oral lichen planus, gastric inflammation, vitiligo, psoriasis, acute coronary syndrome, atherosclerosis, diabetes, diabetic nephropathy, diabetic microangiopathy, lupus nephritis, renal conditions, acquired immunodeficiency syndrome, β-thalassemia, biliary dyskinesia, Dejerine-Sottas disease, cholecystitis, and chronic bacterial prostatitis. Curcumin has also shown protection against hepatic conditions, chronic arsenic exposure, and alcohol intoxication. Dose-escalating studies have indicated the safety of curcumin at doses as high as 12 g/day over 3 months. Curcumin's pleiotropic activities emanate from its ability to modulate numerous signaling molecules such as pro-inflammatory cytokines, apoptotic proteins, NF-κB, cyclooxygenase-2, 5-LOX, STAT3, C-reactive protein, prostaglandin E(2), prostate-specific antigen, adhesion molecules, phosphorylase kinase, transforming growth factor-β, triglyceride, ET-1, creatinine, HO-1, AST, and ALT in human participants. In clinical trials, curcumin has been used either alone or in combination with other agents. Various formulations of curcumin, including nanoparticles, liposomal encapsulation, emulsions, capsules, tablets, and powder, have been examined. In this review, we discuss in detail the various human diseases in which the effect of curcumin has been investigated.

Figures

Fig. 1

a The interest in curcumin research in human participants has increased remarkably over the years. b Human diseases against which curcumin has exhibited activity

Fig. 2

a Effects of curcumin and quercetin on polyp number and polyp size in patients with familial adenomatous polyposis [reprinted from Clinical Gastroenterology and Hepatology, vol 4, Cruz–Correa et al., Combination treatment with curcumin and quercetin of adenomas in familial adenomatous polyposis, 1035–1038, copyright (2006), with permission from Elsevier (16)]. b MDA and GSH levels in patients with tropical pancreatitis after oral administration of curcumin for 6 weeks [reprinted by permission from Indian Journal of Medical Research, vol 122, issue 4, pages 315–318, Durgaprasad et al., copyright (2005) the IJMR (19)]. GSH, glutathione; MDA, malondialdehyde

Fig. 3

a Serum PSA levels at the baseline (pre) and after administration of isoflavones (40 mg/day) and curcumin (100 mg/day) supplements or placebo (post) for 6 months in participants with PSA < 10 or PSA ≥10 [reprinted with permission from Ide et al., (2010), Prostate, John Wiley and Sons (22)]. b Effects of turmeric extract, turmeric oil, and turmeric oleoresin on micronuclei formation in exfoliated buccal mucosal cells of patients with oral submucous fibrosis [reprinted from Cancer Letters, vol 116, Hastak et al., Effect of turmeric oil and turmeric oleoresin on cytogenetic damage in patients suffering from oral submucous fibrosis, pages 265–269, copyright (1997), with permission from Elsevier (27)]. PSA, prostate-specific antigen

Fig. 4

a Effects of curcumin on recurrence of disease in patients with ulcerative colitis [reprinted from Clinical Gastroenterology and Hepatology, vol 4, Hanai et al., Curcumin maintenance therapy for ulcerative colitis: randomized, multicenter, double-blind, placebo-controlled trial, pages 1502–1506, copyright (2006), with permission from Elsevier (33)]. b Levels of C-reactive protein in patients with active rheumatoid arthritis at baseline and after curcumin treatment [reprinted with permission from Chandran and Goel, (2012), Phytotherapy Research, John Wiley and Sons (39)]

Fig. 5

a Phosphorylase kinase values in curcumin- and vehicle-treated groups [reprinted with permission from Heng et al., (2000), British Journal of Dermatology, John Wiley and Sons (51)]. b Effects of curcumin on serum MDA and lipoproteins in human volunteers [reprinted from Soni and Kuttan, 1992, with permission of Executive Editor, Indian Journal of Physiology and Pharmacology (57)]. HDL, high density lipoprotein; MDA, malondialdehyde

Fig. 6

a Number of newly diagnosed diabetic subjects after treatment with curcumin [copyright 2012 American Diabetes Association From Diabetes Care(R), vol. 35, 2012, reprinted by permission of the American Diabetes Association (61)]. b Effects of C. longa and Tinospora formulation on liver aspartate transaminase, alanine transaminase, bilirubin, and body weight and erythrocyte sedimentation rate in tuberculosis patients [reprinted with permission from Adhvaryu et al., (2008), World Journal of Gastroenterology (71)]