Curcumin, the golden nutraceutical: multitargeting for multiple chronic diseases

Abstract

Curcumin, a yellow pigment in the Indian spice Turmeric (Curcuma longa), which is chemically known as diferuloylmethane, was first isolated exactly two centuries ago in 1815 by two German Scientists, Vogel and Pelletier. However, according to the pubmed database, the first study on its biological activity as an antibacterial agent was published in 1949 in Nature and the first clinical trial was reported in The Lancet in 1937. Although the current database indicates almost 9000 publications on curcumin, until 1990 there were less than 100 papers published on this nutraceutical. At the molecular level, this multitargeted agent has been shown to exhibit anti-inflammatory activity through the suppression of numerous cell signalling pathways including NF-κB, STAT3, Nrf2, ROS and COX-2. Numerous studies have indicated that curcumin is a highly potent antimicrobial agent and has been shown to be active against various chronic diseases including various types of cancers, diabetes, obesity, cardiovascular, pulmonary, neurological and autoimmune diseases. Furthermore, this compound has also been shown to be synergistic with other nutraceuticals such as resveratrol, piperine, catechins, quercetin and genistein. To date, over 100 different clinical trials have been completed with curcumin, which clearly show its safety, tolerability and its effectiveness against various chronic diseases in humans. However, more clinical trials in different populations are necessary to prove its potential against different chronic diseases in humans. This review's primary focus is on lessons learnt about curcumin from clinical trials.

Linked articles: This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc.

Figure 1

Molecular targets of curcumin. 5‐LOX, 5‐lipoxygenase; AAPK, autophosphorylation‐activated protein kinase; AATF‐1, arylamine N‐acetyltransferases‐1; AHR, aryl hydrocarbon receptor; AP‐1, activating protein‐1; AR, androgen receptor; Bcl‐2, beta‐cell lymphoma protein 2; Bcl‐xL, beta‐cell lymphoma extra large; Ca2+PK, Ca2+‐dependent protein kinase; CXCR4, chemokine (C‐X‐C motif) receptor 4; CREB‐BP, CREB‐binding protein; CTGF, connective tissue growth factor; DFF‐40, DNA fragmentation factor 40‐kd subunit; DR5, death receptor‐5; ELAM‐1, endothelial leukocyte adhesion molecule‐1; EPCR, endothelial protein C‐receptor; ERE, electrophile response element; ER‐α, estrogen receptor‐alpha; FAK, focal adhesion kinase; FPT, farnesyl protein transferase; FR, Fas receptor; GCL, glutamyl cysteine ligase; GST, gluthathione‐S‐transferase; H2R, histamine (2)‐receptor; HER‐2, human epidermal growth factor receptor‐2; HGF, hepatocyte growth factor; HIF‐1, hypoxia inducible factor‐1; HO, haem oxygenase 1; HSP‐70, heat‐shock protein 70; IAP‐1, inhibitory apoptosis protein‐1; ICAM‐1, intracellular adhesion molecule‐1; iNOS, inducible NOS; IR, integrin receptor; MaIP, macrophage inflammatory protein; MCP, monocyte chemoattractant protein; MDRP, multi‐drug resistance protein; MIP, migration inhibition protein; NGF, nerve growth factor; NQO‐1, NAD(P)H:quinoneoxidoreductase‐1; Nrf, nuclear factor 2‐related factor; ODC, ornithine decarboxylase; PAK, protamine kinase; PhpD, phospholipase D; Pp60c‐tk, pp60c‐src tyrosine kinase; PTK, protein tyrosine kinase; Src‐2, Src homology 2 domain‐containing tyrosine phosphatase 2; STAT, signal transducer and activator of transcription; TF, tissue factor; TMMP‐3, tissue inhibitor of metalloproteinase‐3; uPA, urokinase‐type plasminogen activator; VCAM‐1, vascular cell adhesion molecule‐1; WTG‐1, Wilms' tumour gene 1.

Figure 2

Activity of curcumin against different human diseases based on clinical findings.