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

Extensive research within the last several decades has revealed that the major risk factors for most chronic diseases are infections, obesity, alcohol, tobacco, radiation, environmental pollutants, and diet. It is now well established that these factors induce chronic diseases through induction of inflammation. However, inflammation could be either acute or chronic. Acute inflammation persists for a short duration and is the host defense against infections and allergens, whereas the chronic inflammation persists for a long time and leads to many chronic diseases including cancer, cardiovascular diseases, neurodegenerative diseases, respiratory diseases, etc. Numerous lines of evidence suggest that the aforementioned risk factors induced cancer through chronic inflammation. First, transcription factors NF-κB and STAT3 that regulate expression of inflammatory gene products, have been found to be constitutively active in most cancers; second, chronic inflammation such as pancreatitis, prostatitis, hepatitis etc. leads to cancers; third, activation of NF-κB and STAT3 leads to cancer cell proliferation, survival, invasion, angiogenesis and metastasis; fourth, activation of NF-κB and STAT3 leads to resistance to chemotherapy and radiation, and hypoxia and acidic conditions activate these transcription factors. Therefore, targeting these pathways may provide opportunities for both prevention and treatment of cancer and other chronic diseases. We will discuss in this review the potential of various dietary agents such as spices and its components in the suppression of inflammatory pathways and their roles in the prevention and therapy of cancer and other chronic diseases. In fact, epidemiological studies do indicate that cancer incidence in countries such as India where spices are consumed daily is much lower (94/100,000) than those where spices are not consumed such as United States (318/100,000), suggesting the potential role of spices in cancer prevention.

Curcumin, a component of a spice native to India, was first isolated in 1815 by Vogel and Pelletier from the rhizomes of Curcuma longa (turmeric) and, subsequently, the chemical structure of curcumin as diferuloylmethane was reported by Milobedzka et al. [(1910) 43., 2163-2170]. Since then, this polyphenol has been shown to exhibit antioxidant, anti-inflammatory, anticancer, antiviral, antibacterial, and antifungal activities. The current review primarily focuses on the anticancer potential of curcumin through the modulation of multiple cell signaling pathways. Curcumin modulates diverse transcription factors, inflammatory cytokines, enzymes, kinases, growth factors, receptors, and various other proteins with an affinity ranging from the pM to the mM range. Furthermore, curcumin effectively regulates tumor cell growth via modulation of numerous cell signaling pathways and potentiates the effect of chemotherapeutic agents and radiation against cancer. Curcumin can interact with most of the targets that are modulated by FDA-approved drugs for cancer therapy. The focus of this review is to discuss the molecular basis for the anticancer activities of curcumin based on preclinical and clinical findings.

Natural compounds, in recent years, have attracted significant attention for their use in the prevention and treatment of diverse chronic diseases as they are devoid of major toxicities. Boswellic acid (BA), a series of pentacyclic triterpene molecules, is isolated from the gum resin of Boswellia serrata and Boswellia carteri. It proved to be one such agent that has exhibited efficacy against various chronic diseases like arthritis, diabetes, asthma, cancer, inflammatory bowel disease, Parkinson’s disease, Alzheimer’s, etc. The molecular targets attributed to its wide range of biological activities include transcription factors, kinases, enzymes, receptors, growth factors, etc. The present review is an attempt to demonstrate the diverse pharmacological uses of BA, along with its underlying molecular mechanism of action against different ailments. Further, this review also discusses the roadblocks associated with the pharmacokinetics and bioavailability of this promising compound and strategies to overcome those limitations for developing it as an effective drug for the clinical management of chronic diseases.

ATP citrate lyase (ACLY), an important enzyme involved in lipid biogenesis linked with glucose metabolism, catalyzes the conversion of citrate to oxaloacetic acid (OAA) and acetyl-CoA. The obtained acetyl-CoA is required for lipid synthesis during membrane biogenesis, as well as for histone acetylation reactions to regulate the expression of certain proteins in aberrantly proliferating cancer cells. Studies have shown a role for ACLY in tumorigenesis whereby increased levels of the enzyme leads to increased metabolic activity via activation of Akt signaling. Increasing lines of evidence suggest that enzymes involved in lipid biogenesis play a significant role in cancer cell proliferation and progression. In many cancer types such as glioblastoma, colorectal cancer, breast cancer, non-small cell lung cancer, hepatocellular carcinoma etc., the level of ACLY has been found to be quite high as compared to normal cells. Cancer cell growth related to overexpression of ACLY can be inhibited by using chemical inhibitors or by the knockdown of ACLY gene. Inhibition of ACLY leads to changes in cancer cell metabolism that promotes tumor growth and proliferation. This review summarizes the role of ACLY in cancer development and its inhibitors in cancer treatment.