Current Pharmaceutical Design - Volume 19, Issue 11, 2013

Curcumin has been estimated as a potential agent for many diseases and attracted great attention owing to its various pharmacological activities, including anti-cancer, and anti-inflammatory. Now curcumin is being applied to a number of patients with breast cancer, rheumatoid arthritis, Alzheimer's disease, colorectal cancer, psoriatic, etc. Several clinical trials have stated that curcumin is safe enough and effective. The objective of this article was to summarize the clinical studies of curcumin, and give a reference for future studies.

A hydrophobic polyphenol compound extracted from turmeric, curcumin has been widely utilized as traditional medicines for centuries in China and India. Over the last decades, because of its low toxicity, extensive studies have been focused on its physicochemical properties and pharmacological activities on various diseases, such as cancer, cardio-vascular disease, inflammatory bowel, wound healing, Alzheimer's disease, rheumatoid arthritis, and diabetes. In particular, bioactivities of curcumin as an effective chemopreventive agent, chemo-/radio-sensitizer for tumor cells, and chemo-/radio-protector for normal organs, are of extraordinary research interests in the literature. Despite these advantages, applications of curcumin are limited in clinical trials because of its poor water solubility and low oral bioavailability. Nano-preparations as an emerging platform for the efficient delivery of anti-cancer drugs should overcome these problems. In this review, we at first briefly revisit important properties of curcumin as well as its uses in cancer treatments, and then overview various nano-preparations of curcumin for cancer therapy, including nanoparticles, liposomes, micelles, nanoemulsions, cyclodextrin complexes, nanodisks, nanofibres, solid lipid nanoparticles, and curcumin conjugates.

Cancer is the second leading cause of death in the United States. Conventional therapies cause widespread systemic toxicity and lead to serious side effects which prohibit their long term use. Additionally, in many circumstances tumor resistance and recurrence is commonly observed. Therefore, there is an urgent need to identify suitable anticancer therapies that are highly precise with minimal side effects. Curcumin is a natural polyphenol molecule derived from the Curcuma longa plant which exhibits anticancer, chemopreventive, chemo- and radio-sensitization properties. Curcumin’s widespread availability, safety, low cost and multiple cancer fighting functions justify its development as a drug for cancer treatment. However, various basic and clinical studies elucidate curcumin's limited efficacy due to its low solubility, high rate of metabolism, poor bioavailability and pharmacokinetics. A growing list of nanomedicine(s) using first line therapeutic drugs have been approved or are under consideration by the Food and Drug Administration (FDA) to improve human health. These nanotechnology strategies may help to overcome challenges and ease the translation of curcumin from bench to clinical application. Prominent research is reviewed which shows that advanced drug delivery of curcumin (curcumin nanoformulations or curcumin nanomedicine) is able to leverage therapeutic benefits by improving bioavailability and pharmacokinetics which in turn improves binding, internalization and targeting of tumor(s). Outcomes using these novel drug delivery systems have been discussed in detail. This review also describes the tumor-specific drug delivery system(s) that can be highly effective in destroying tumors. Such new approaches are expected to lead to clinical trials and to improve cancer therapeutics.

Curcumin is a natural polyphenol product derived from the rhizome of the Curcuma longa. In vivo and in vitro studies have uncovered many important bioactivities of curcumin, such as antioxidant activity, inducing cell apoptosis, inhibiting cell proliferation, anti-cell adhesion and motility, anti-angiogenesis and anti-microbe properties. Based on these functions, curcumin has been used in clinical trials on various inflammatory diseases and cancers. In the future, it will be necessary to focus attention partly on the clinical application of curcumin in neurodegenerative diseases, cardiovascular diseases and diabetes, because many experiments have clarified the potential value of curcumin in these areas. As a diet-derived agent, curcumin has no severe toxicity except for minor gastrointestinal side effects even up to the dosage of 8 grams for 3 months. However, curcumin has a low systemic bioavailability, so it is imperative to improve the bioavailability of curcumin in its clinical application. Many methods, such as adjuvant drug delivery system and structural modification have been demonstrated to have a potential effect.

There is a growing interest in herbal medicine. Scientific studies have demonstrated the beneficial pharmacological effects of curcumin. Curcumin is a bright yellow spice, derived from the rhizome of Curcuma longa Linn. It has been proven that curcumin is a highly pleiotropic molecule which can be a modulator of intracellular signaling pathways that control cell growth, inflammation, and apoptosis. Curcumin might be a potential candidate for the prevention and/or treatment of some diseases due to its anti-oxidant, antiinflammatory activities and an excellent safety profile. We present an updated concise review of currently available animal and clinical studies demonstrating the therapeutic effect of curcumin.

Curcumin is the active component of dried rhizome of Curcuma longa, a perennial herb belonging to ginger family, cultivated extensively in south and southeastern tropical Asia. It is widely consumed in the Indian subcontinent, south Asia and Japan in traditional food recipes. Extensive research over last few decades has shown that curcumin is a potent anti-inflammatory agent with powerful therapeutic potential against a variety of cancers. It suppresses proliferation and metastasis of human tumors through regulation of various transcription factors, growth factors, inflammatory cytokines, protein kinases and other enzymes. It induces apoptotic cell death and also inhibits proliferation of cancer cells by cell cycle arrest. Pharmacokinetic data has shown that curcumin undergoes rapid metabolism leading to glucuronidation and sulfation in the liver and excretion in the feces, which accounts for its poor systemic bioavailability. The compound has, therefore, been formulated and administered using different drug delivery systems such as liposomes, micelles, polysaccharides, phospholipid complexes and nanoparticles that can overcome the limitation of bioavailability to some extent. Attempts to avoid rapid metabolism of curcumin until now have been met with limited success. This has prompted researchers to look for new synthetic curcumin analogs in order to overcome the drawbacks of limited bioavailability and rapid metabolism, and gain efficacy with reduced toxicity. In this review we provide a summarized account of novel synthetic curcumin formulations and analogs, and the recent progress in the field of cancer prevention and treatment.

Curcumin, a yellow pigment extracted from the rhizome of Curcuma longa, commonly known as turmeric, is the most active agent of this herbal medicine. The therapeutic activities of curcumin are exemplified not only by its enhancement in wound healing but also in the treatment of inflammation, cystic fibrosis, Alzheimer’s disease and cancer. There are two critical issues involving low aqueous stability and solubility that limit the bioavailability and application of curcumin as a therapeutic agent. To address these issues, delivery systems of curcumin including surfactant micelles, liposomes, polymer nanoparticles, casein micelles, plasma proteins and cyclodextrins have been developed and characterized. From a biochemical perspective, the medicinal activities of curcumin are proposed to be related to an elevated level of transition metals including copper, zinc and iron in many disease sites, especially those in cancer and Alzheimer's disease. Previous studies have demonstrated the importance of copper(II)-curcumin complexes in DNA damage owing to the strong interaction between curcumin and copper(II). Curcumin, as an anti-oxidant, possesses the abilities to scavenge radicals and maintain the levels of anti-oxidant enzymes in the presence of copper. On the other hand, copper(II)-curcumin complexes show pro-oxidant effects by generating reactive oxygen species at a high free copper level in a reducing environment. This condition results in DNA damage and inhibition of vital signaling pathways in cancer cells, leading to apoptosis. In short, curcumin has dual roles as an anti-oxidant and a prooxidant in the presence of copper and these fascinating phenomena contribute greatly to its multiple medicinal effects.

Curcumin is a yellow pigment found in the spice turmeric and a main functional constituent of the rhizomes of Curcuma longa. The multi-functionality of curcumin has recently attracted much attention in various fields, including food, medicinal, and clinical industries. Three major curcuminoids, curcumin, demethoxycurcumin, and bis-demethoxycurcumin, are distributed in not only Curcuma, but also the Zingiber species; however, distribution of other curcuminoids is very limited in nature. The radical scavenging ability of curcumin, which is the basis of medicinal functionality, is its most important property. Herein, the structures of several rare curcuminoids that have been identified during the past four decades are summarized. Mechanistic studies of the radical trapping stage of curcumin are also comprehensively reviewed, and the studies on antioxidant effects derived from this radical trapping ability of curcuminoids are discussed. Various chemical reactions of curcumin, such as photo-oxidation, enzymatic oxidation, etc. are also summarized. In particular, antioxidation of curcumin in lipid media is introduced as a reaction unique to curcumin.

Curcumin, a polyphenolic natural product, exhibits therapeutic activity against a number of diseases, attributed mainly to its chemical structure and unique physical, chemical, and biological properties. It is a diferuloyl methane molecule [1,7-bis (4-hydroxy-3- methoxyphenyl)-1,6-heptadiene-3,5-dione)] containing two ferulic acid residues joined by a methylene bridge. It has three important functionalities: an aromatic o-methoxy phenolic group, α, β-unsaturated β-diketo moiety and a seven carbon linker. Extensive research in the last two decades has provided evidence for the role of these different functional groups in its crucial biological activities. A few highlights of chemical structural features associated with the biological activity of curcumin are: The o-methoxyphenol group and methylenic hydrogen are responsible for the antioxidant activity of curcumin, and curcumin donates an electron/ hydrogen atom to reactive oxygen species. Curcumin interacts with a number of biomolecules through non-covalent and covalent binding. The hydrogen bonding and hydrophobicity of curcumin, arising from the aromatic and tautomeric structures along with the flexibility of the linker group are responsible for the non-covalent interactions. The α, β-unsaturated β-diketone moiety covalently interacts with protein thiols, through Michael reaction. The β-diketo group forms chelates with transition metals, there by reducing the metal induced toxicity and some of the metal complexes exhibit improved antioxidant activity as enzyme mimics. New analogues with improved activity are being developed with modifications on specific functional groups of curcumin. The physico-chemical and structural features associated with some of the biological activities of curcumin and important analogues are summarized in this article.

Diabetes mellitus (DM) has reached pandemic status and shows no signs of abatement. It can severely impair people's quality of life and affects patients all over the world. Since it is a serious, chronic metabolic disease, it can bring about many kinds of complications, which can in turn increase mortality. In recent decades, more and more studies have shown that oxidative stress and inflammatory reactions play critical roles in the pathogenesis of DM. There is an increasing demand for natural antidiabetic medicines that do not have the same side effects as modern drugs. Curcumin, a phytochemical found in the spice turmeric, has been used in India for centuries, and it has no known side effects. It has been shown to have some beneficial effects against various chronic illnesses. Many of these therapeutic actions can be attributed to its potent anti-oxidant and anti-inflammatory activities. In view of the oxidative stress and inflammatory mechanisms of DM, curcumin can be considered suitable for the prevention and amelioration of diabetes. In this review, we summarize the nosogenesis of DM, giving primary focus to oxidative stress and inflammation. We discuss the anti-oxidant and anti-inflammatory activities of curcumin in DM and its ability to mitigate the effects on DM and its associated complications in detail.

Curcumin exhibits a surprisingly wide range of chemo-preventive and chemo-therapeutic activities. Curcumin has undergone more than 40 clinical trials for the treatment of inflammatory diseases and various human cancers. However, phase I/II clinical trials have shown that curcumin exhibit poor bioavailability in humans. Major reasons resulting in the low plasma and tissue levels of curcumin appear to be its poor absorption, fast metabolism, and rapid systemic elimination. It is suggested that the β-diketone moiety is responsible for the instability and weak pharmacokinetic profiles of curcumin. To attenuate the fast metabolism of curcumin, numerous approaches have been considered, including the adjuvant, the liposomal curcumin, curcumin nanoparticles and phospholipid complex, and structural modification to prepare the analogues without the β-diketone moiety. Particularly, the latter called mono-carbonyl analogs of curcumin (MACs) has been reported to has an enhanced stability in vitro and an improved pharmacokinetic profile in vivo. Thus, MACs have attracted a high attention for development of new curcumin-based agents with both enhanced bioactivities and pharmacokinetic profiles. A number of MACs have shown potential anticancer and anti-inflammatory activity in various models. Several of them have been studied intensively in order to develop novel agents. This review covers 607 MACs as well as their biological activities reported in the past two decades.