Glutathione (GSH) is a tripeptide, which has many biological roles including protection against reactive oxygen and nitrogen species. The primary goal of this paper is to characterize the principal mechanisms of the protective role of GSH against reactive species and electrophiles. The ancillary goals are to provide up-to-date knowledge of GSH biosynthesis, hydrolysis, and utilization; intracellular compartmentalization and interorgan transfer; elimination of endogenously produced toxicants; involvement in metal homeostasis; glutathione-related enzymes and their regulation; glutathionylation of sulfhydryls. Individual sections are devoted to the relationships between GSH homeostasis and pathologies as well as to developed research tools and pharmacological approaches to manipulating GSH levels. Special attention is paid to compounds mainly of a natural origin (phytochemicals) which affect GSH-related processes. The paper provides starting points for development of novel tools and provides a hypothesis for investigation of the physiology and biochemistry of glutathione with a focus on human and animal health.

https://downloads.hindawi.com/archive/2012/736837.pdf

Glutathione Homeostasis and Functions: Potential Targets forMedical Interventions

Turmeric is traditionally used as a spice and coloring in foods. It is an important ingredient in curry and gives curry powder its characteristic yellow color. As a consequence of its intense yellow color, turmeric, or curcumin (food additive E100), is used as a food coloring (e.g. mustard). Turmeric contains the curcuminoids curcumin, demethoxycurcumin, and bisdemethoxycurcumin. Recently, the health properties (neuroprotection, chemo-, and cancer prevention) of curcuminoids have gained increasing attention. Curcuminoids induce endogenous antioxidant defense mechanisms in the organism and have anti-inflammatory activity. Curcuminoids influence gene expression as well as epigenetic mechanisms. Synthetic curcumin analogues also exhibit biological activity. This Review describes the development of curcumin from a "traditional" spice and food coloring to a "modern" biological regulator.

Curcumin—From Molecule to Biological Function

Oxidative damage and inflammation have been pointed out in preclinical studies as the root cause of cancer and other chronic diseases such as diabetes, hypertension, Alzheimer's disease, etc. Epidemiological and clinical studies have suggested that cancer could be prevented or significantly reduced by treatment with anti-oxidant and anti-inflammatory drugs, therefore, curcumin, a principal component of turmeric (a curry spice) showing strong anti-oxidant and anti-inflammatory activities, might be a potential candidate for the prevention and/or treatment of cancer and other chronic diseases. However, curcumin, a highly pleiotropic molecule with an excellent safety profile targeting multiple diseases with strong evidence on the molecular level, could not achieve its optimum therapeutic outcome in past clinical trials, largely due to its low solubility and poor bioavailability. Curcumin can be developed as a therapeutic drug through improvement in formulation properties or delivery systems, enabling its enhanced absorption and cellular uptake. This review mainly focuses on the anti-inflammatory potential of curcumin and recent developments in dosage form and nanoparticulate delivery systems with the possibilities of therapeutic application of curcumin for the prevention and/or treatment of cancer.

/pdf/curcumin-an-anti-inflammatory-molecule-from-a-curry-spice-on-2s0wbyq64z.pdf

Curcumin: An Anti-Inflammatory Molecule from a Curry Spice on the Path to Cancer Treatment

Curcumin, a polyphenol extracted from Curcuma longa in 1815, has gained attention from scientists worldwide for its biological activities (e.g., antioxidant, anti-inflammatory, antimicrobial, antiviral), among which its anticancer potential has been the most described and still remains under investigation. The present review focuses on the cell signaling pathways involved in cancer development and proliferation, and which are targeted by curcumin. Curcumin has been reported to modulate growth factors, enzymes, transcription factors, kinase, inflammatory cytokines, and proapoptotic (by upregulation) and antiapoptotic (by downregulation) proteins. This polyphenol compound, alone or combined with other agents, could represent an effective drug for cancer therapy.

Curcumin and Cancer

Curcumin and its nano-formulation: the kinetics of tissue distribution and blood-brain barrier penetration.

Curcumin (diferuloylmethane), a derivative of turmeric is one of the most commonly used and highly researched phytochemicals. Abundant sources provide interesting insights into the multiple mechanisms by which curcumin may mediate chemotherapy and chemopreventive effects on cancer. The pleiotropic role of this dietary compound includes the inhibition of several cell signaling pathways at multiple levels, such as transcription factors (NF-κB and AP-1), enzymes (COX-2, MMPs), cell cycle arrest (cyclin D1), proliferation (EGFR and Akt), survival pathways (β-catenin and adhesion molecules), and TNF. Curcumin up-regulates caspase family proteins and down-regulates anti-apoptotic genes (Bcl-2 and Bcl-X(L)). In addition, cDNA microarrays analysis adds a new dimension for molecular responses of cancer cells to curcumin at the genomic level. Although, curcumin's poor absorption and low systemic bioavailability limits the access of adequate concentrations for pharmacological effects in certain tissues, active levels in the gastrointestinal tract have been found in animal and human pharmacokinetic studies. Currently, sufficient data has been shown to advocate phase II and phase III clinical trials of curcumin for a variety of cancer conditions including multiple myeloma, pancreatic, and colon cancer.

Curcumin in Cancer Chemoprevention: Molecular Targets, Pharmacokinetics, Bioavailability, and Clinical Trials

Background Natural phytochemicals and their derivatives have been used in medicine since prehistoric times. Natural phytochemicals have potential uses against various disorders, including cancers. However, due to low bioavailability, their success in clinical trials has not been reproduced. Nanotechnology has played a vital role in providing new directions for diagnosis, prevention, and treatment of different disorders, and of cancer in particular. Nanotechnology has demonstrated the capability to deliver conventional natural products with poor solubility or a short half-life to target specific sites in the body and regulate the release of drugs. Among the natural products, the phytoalexin resveratrol has demonstrated therapeutic effects, including antioxidant, antiinflammatory, and anti-proliferative effects, as well as the potential to inhibit the initiation and promotion of cancer. However, low water solubility and extensive first-pass metabolism lead to poor bioavailability of resveratrol, hindering its potential. Conventional dosage forms of resveratrol, such as tablets, capsules, dry powder, and injections, have met with limited success. Nanoformulations are now being investigated to improve the pharmacokinetic characteristics, as well as to enhance the bioavailability and targetability of resveratrol. Objectives This review details the therapeutic effectiveness, mode of action, and pharmacokinetic limitations of resveratrol, as well as discusses the successes and challenges of resveratrol nanoformulations. Modern nanotechnology techniques to enhance the encapsulation of resveratrol within nanoparticles and thereby enhance its therapeutic effects are emphasized. Conclusion To date, no resveratrol-based nanosystems are in clinical use, and this review would provide a new direction for further investigations on innovative nanodevices that could consolidate the anticancer potential of resveratrol.

Young Sup Lee

Papers

Curcumin in Cancer Chemoprevention: Molecular Targets, Pharmacokinetics, Bioavailability, and Clinical Trials

Curcumin in Cancer Chemoprevention: Molecular Targets, Pharmacokinetics, Bioavailability, and Clinical Trials

Switching from Conventional to Nano-natural Phytochemicals to Prevent and Treat Cancers: Special Emphasis on Resveratrol.

Improved methods for purification and assay of glycerol kinase from Escherichia coli