Curcumin, the bioactive pigment of turmeric which has polyphenolic‐hydrophobic components, has been used for the treatment of a variety of diseases. However, due to its insignificant intestinal‐liver ...metabolism, low stability, quick systemic elimination and its hydrophobic property with low solubility, curcumin has limited bioavailability. Exosomes are nanovesicles (30–100 nm) released from diverse cell types into extracellular and, ultimately, into bio‐fluids in a tightly regulated manner. Exosomes are capable of transferring lipids, proteins, RNAs and DNAs, both with and without direct cell‐to‐cell contact. Curcumin‐encapsulated exosomes are highly bioavailable, soluble and safe, and can reach high concentrations in the blood; they, therefore, have therapeutic potential without toxic effects and immune stimulation. Thus, curcumin‐encapsulated exosomes could be superior to other synthetic nanoparticles as a carrier of curcumin. The aim of the current review is to offer an overview of the in vitro, in vivo and clinical studies pertaining to the role of curcumin‐primed and curcumin‐encapsulated exosomes in the treatment of cancer, oxidative stress, brain disorders, cholesterol, and endothelial dysfunction.
Exosomes are capable of transferring lipids, proteins, RNAs and DNAs, both with and without direct cell‐to‐cell contact. Curcumin‐ encapsulated exosomes are highly bioavailable, soluble and safe, and can reach high concentrations in the blood; they, therefore, have therapeutic potential without toxic effects and immune stimulation; thus, curcumin‐encapsulated exosomes could be superior to other synthetic nanoparticles as a carrier of curcumin. The aim of the current review is to offer an overview of the in vitro, in vivo and clinical studies pertaining to the role of curcumin‐primed and curcumin‐encapsulated exosomes in the treatment of cancer, oxidative stress, brain disorders, cholesterol, and endothelial dysfunction.
Purpose
The optimal health benefits of curcumin are limited by its low solubility in water and corresponding poor intestinal absorption. Cyclodextrins (CD) can form inclusion complexes on a molecular ...basis with lipophilic compounds, thereby improving aqueous solubility, dispersibility, and absorption. In this study, we investigated the bioavailability of a new γ-cyclodextrin curcumin formulation (CW8). This formulation was compared to a standardized unformulated curcumin extract (StdC) and two commercially available formulations with purported increased bioavailability: a curcumin phytosome formulation (CSL) and a formulation of curcumin with essential oils of turmeric extracted from the rhizome (CEO).
Methods
Twelve healthy human volunteers participated in a double-blinded, cross-over study. The plasma concentrations of the individual curcuminoids that are present in turmeric (namely curcumin, demethoxycurcumin, and bisdemethoxycurcumin) were determined at baseline and at various intervals after oral administration over a 12-h period.
Results
CW8 showed the highest plasma concentrations of curcumin, demethoxycurcumin, and total curcuminoids, whereas CSL administration resulted in the highest levels of bisdemethoxycurcumin. CW8 (39-fold) showed significantly increased relative bioavailability of total curcuminoids (AUC
0−12
) in comparison with the unformulated StdC.
Conclusion
The data presented suggest that γ-cyclodextrin curcumin formulation (CW8) significantly improves the absorption of curcuminoids in healthy humans.
Curcumin (diferuloylmethane or 1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) is an interesting compound that is characterized by a special chemical structure with a diversified ...biological and pharmaceutical properties. A huge number of studies have explored the medicinal properties of curcumin, including antitumoral, antimicrobial, anti-inflammatory, antioxidant, antihepatotoxic, antihyperlipidemic, antiviral, and anti-Alzheimer's disease effects. Despite its range of reported pharmacological effects, it has poor bioavailability during oral administration and poor solubility and so, it is limited in its clinical applicability. Therefore, several strategies were developed to overcome this disadvantage, such as nanoparticle and formulations in liposomal, micellar or phospholipid complex. One of the most common strategies is the design and synthesis of new curcumin derivatives and analogues that have better therapeutic properties and bioavailability where great efforts have been made by scientists in this field. Thus, the scope of this review is to report the up-to-date synthesized derivatives, analogues and to classify them according to their chemical structure. The review sheds light on the most important and potent compounds where several effective moieties are introduced into different positions so as to be suitable for different biological activities. Additionally, an interesting class of curcumin hybrids and the synergy that would be expected based on their chemical structures are also covered in this review. Also, the structure-activity relationship of several analogues and some selected examples of patents on curcumin analogues were displayed.
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•Curcumin, the well-known traditional medicine, continues to inspire researchers.•This review covers the recent advances of curcumin analogues and their hybrids as multifunctional drugs.•The first part of the review classifies the newly synthesized curcumin analogues and focuses on the most important analogues.•The second part of the review provides efficient synthetic methods for curcumin hybrids and their biological properties.•Hybridization of curcumin with several bioactive molecules allowing synergy in many cases.
SCOPE: Curcumin revealed various health‐beneficial properties in numerous studies. However its bioavailability is low due to its limited intestinal uptake and rapid metabolism. The aim of our project ...was to develop novel curcumin formulations with improved oral bioavailability and to study their safety as well as potential sex‐differences. METHODS AND RESULTS: In this crossover study, healthy subjects (13 women, 10 men) took, in random order, a single oral dose of 500 mg curcuminoids as native powder, micronized powder, or liquid micelles. Blood and urine samples were collected for 24 h and total curcuminoids and safety parameters were quantified. Based on the area under the plasma concentration–time curve (AUC), the micronized curcumin was 14‐, 5‐, and 9‐fold and micellar curcumin 277‐, 114‐, and 185‐fold better bioavailable than native curcumin in women, men, and all subjects, respectively. Thus, women absorbed curcumin more efficiently than men. All safety parameters remained within the reference ranges following the consumption of all formulations. CONCLUSION: Both, the micronized powder and in particular the liquid micellar formulation of curcumin significantly improved its oral bioavailability without altering safety parameters and may thus be ideally suited to deliver curcumin in human intervention trials. The observed sex differences in curcumin absorption warrant further investigation.
Cancer is a life-threatening disease and is the second leading cause of death around the world. The increasing threats of drug-resistant cancers indicate that there is an urgent need for the ...improvement or development of more effective anticancer agents. Curcumin, a phenolic compound originally derived from turmeric plant (
L. (Zingiberaceae family)) widely known as a spice and a coloring agent for food have been reported to possess notable anticancer activity by inhibiting the proliferation and metastasis, and enhancing cell cycle arrest or apoptosis in various cancer cells. In spite of all these benefits, the therapeutic application of curcumin in clinical medicine and its bioavailability are still limited due to its poor absorption and rapid metabolism. Structural modification of curcumin through the synthesis of curcumin-based derivatives is a potential approach to overcome the above limitations. Curcumin derivatives can overcome the disadvantages of curcumin while enhancing the overall efficacy and hindering drug resistance. This article reports a review of published curcumin derivatives and their enhanced anticancer activities.
A series of structurally novel mono-carbonyl curcumin analogues have been synthesized and biologically evaluated to test their inhibitory potencies and the structure-activity relationship (SAR) on ...human and rat 11I2-hydroxysteroid dehydrogenase isoform (11I2-HSD1) activities. 11I2-HSD1 selective inhibitors have been discovered and compound A10 is discovered as a very potent with an IC50 value of 97 nM without inhibiting 11I2-HSD2.
The Essential Medicinal Chemistry of Curcumin Nelson, Kathryn M; Dahlin, Jayme L; Bisson, Jonathan ...
Journal of medicinal chemistry,
03/2017, Volume:
60, Issue:
5
Journal Article
Peer reviewed
Open access
Curcumin is a constituent (up to ∼5%) of the traditional medicine known as turmeric. Interest in the therapeutic use of turmeric and the relative ease of isolation of curcuminoids has led to their ...extensive investigation. Curcumin has recently been classified as both a PAINS (pan-assay interference compounds) and an IMPS (invalid metabolic panaceas) candidate. The likely false activity of curcumin in vitro and in vivo has resulted in >120 clinical trials of curcuminoids against several diseases. No double-blinded, placebo controlled clinical trial of curcumin has been successful. This manuscript reviews the essential medicinal chemistry of curcumin and provides evidence that curcumin is an unstable, reactive, nonbioavailable compound and, therefore, a highly improbable lead. On the basis of this in-depth evaluation, potential new directions for research on curcuminoids are discussed.
Curcumin, a natural polyphenolic and yellow pigment obtained from the spice turmeric, has strong antioxidative, anti‐inflammatory, and antibacterial properties. Due to these properties, curcumin has ...been used as a remedy for the prevention and treatment of skin aging and disorders such as psoriasis, infection, acne, skin inflammation, and skin cancer. Curcumin has protective effects against skin damage caused by chronic ultraviolet B radiation. One of the challenges in maximizing the therapeutic potential of curcumin is its low bioavailability, limited aqueous solubility, and chemical instability. In this regard, the present review is focused on recent studies concerning the use of curcumin for the treatment of skin diseases, as well as offering new and efficient strategies to optimize its pharmacokinetic profile and increase its bioavailability.
Curcumin, a natural polyphenolic and yellow pigment obtained from the spice turmeric, has strong antioxidative, anti‐inflammatory, and antibacterial properties; due to these properties, curcumin has been used as a remedy for the prevention and treatment of skin aging and disorders such as psoriasis, infection, acne, skin inflammation, and skin cancer and curcumin has protective effects against skin damage caused by chronic ultraviolet B radiation. One of the challenges in maximizing the therapeutic potential of curcumin is its low bioavailability, limited aqueous solubility, and chemical instability; in this regard, the present review is focused on recent studies concerning the use of curcumin for the treatment of skin diseases, as well as offering new and efficient strategies to optimize its pharmacokinetic profile and increase its bioavailability.
Comprehensive pharmacological screening of curcumin (CUR) has given the evidence that it is an excellent naturally occurring therapeutic moiety for cancer. It is very well tolerated with ...insignificant toxicity even after high doses of oral administration. Irrespective of its better quality as an anticancer agent, therapeutic application of CUR is hampered by its extremely low-aqueous solubility and poor bioavailability, rapid clearance and low-cellular uptake. A simple means of breaking up the restrictive factor of CUR is to perk-up its aqueous solubility, improve its bioavailability, protect it from degradation, and metabolism and potentiate its targeting capacity towards the cancer cell. The development in the field of nanomedicine has made excellent progresses toward enhancing the bioavailability of lipophilic drugs like CUR. Nanoparticles (NPs) are capable to deliver the CUR at specific area and thereby prevent it from physiological degradation and systemic clearance. In recent year, an assortment of nanomedicine-based novel drug delivery system has been designed to potentiate the bioavailability of CUR towards anticancer therapy. In this review, we discuss the recent development in the field of nanoCUR (NanoCur), including polymeric micelles, liposome, polymeric NPs, nanoemulsion, nanosuspension, solid lipid NPs (SLNPs), polymer conjugates, nanogel, etc. in anticancer application.
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