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    The Natural Product Curcumin as an Antibacterial Agent: Current Achievements and Problems
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    Abstract:
    The rapid spread of antibiotic resistance and lack of effective drugs for treating infections caused by multi-drug resistant bacteria in animal and human medicine have forced us to find new antibacterial strategies. Natural products have served as powerful therapeutics against bacterial infection and are still an important source for the discovery of novel antibacterial drugs. Curcumin, an important constituent of turmeric, is considered safe for oral consumption to treat bacterial infections. Many studies showed that curcumin exhibited antibacterial activities against Gram-negative and Gram-positive bacteria. The antibacterial action of curcumin involves the disruption of the bacterial membrane, inhibition of the production of bacterial virulence factors and biofilm formation, and the induction of oxidative stress. These characteristics also contribute to explain how curcumin acts a broad-spectrum antibacterial adjuvant, which was evidenced by the markedly additive or synergistical effects with various types of conventional antibiotics or non-antibiotic compounds. In this review, we summarize the antibacterial properties, underlying molecular mechanism of curcumin, and discuss its combination use, nano-formulations, safety, and current challenges towards development as an antibacterial agent. We hope that this review provides valuable insight, stimulates broader discussions, and spurs further developments around this promising natural product.
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    Natural product
    Abstract The spice curcumin and its metabolites have been linked to many beneficial health effects. These effects have, thus far, not been duplicated in independent research most likely due to low plasma concentrations of curcumin. Despite the many reports, the public’s interest in curcumin continues to grow and many people use curcumin in daily life. Moreover, companies seize the popularity of curcumin and claim that their formulations increase systemic expose of curcumin. In this independent study we determined the plasma concentration of curcumin after oral intake in daily life to determine if the systemic exposure is sufficient to achieve beneficial health effects. We used a validated HPLC-MS/MS assay to determine the plasma concentration of curcumin and its metabolites in 47 individuals (patient or healthy) using their own curcumin formulations. Through questionnaires, we assessed which other supplements and (self-)medication(s) were used. The concentrations of curcumin and its metabolites were analyzed in plasma samples collected just before and 1.5 h after curcumin intake. Each sample was pretreated with and without β-glucuronidase to determine the levels of conjugated and unconjugated curcumin. After oral intake of the curcumin supplement, plasma concentrations of curcumin, demethoxycurcumin, bisdemethoxycurcumin and tetrahydrocurcumin ranged between 2 and 4 nM. Use of adjuvants like piperine did not result in higher curcumin plasma concentrations. Adding β-glucuronidase to the plasma sample increased curcumin plasma levels from below LLQ to 25.3 ng/mL, however still below any plasma concentration to which a beneficial health effect can be expected. The observed plasma concentration of unchanged curcumin remained several orders below the concentration of 2-100 μg/mL used in in vitro studies. Therefore, our study confirms the low plasma levels of curcumin and indicates the need to be critical towards the claimed beneficial systemic health effects of current curcumin supplement use in daily life among patients and healthy individuals.
    Piperine
    Curcumin is a naturally occurring phytotherapeutic that has broad uses including the treatment of cancer and as a potent antimicrobial agent. Its dynamic ability to treat very different kinds of disease has spawned a significant increase in inquiry on how curcumin accomplishes these feats. Thousands of peer reviewed papers were published in the past few years regarding the various functions of curcumin. Unlike most pharmaceuticals, curcumin has a multi-range of different targets that it interacts with. Since curcumin's bioavailabilty is limited, methods of increasing curcumin's bioavailabilty are discussed. Mechanisms of action regarding curcumin's ability to effect cancer are discussed including upstream and downstream mechanisms starting with epigenetics to its effect on signal transduction pathways and apoptosis. Curcumin also works adjuvantly with chemotherapy to reduce resistance and enhance the mechanism of certain chemotherapeutic agents. Curcumin's antibacterial, antifungal, and antiviral capability is also discussed with regard to curcumin's dynamic ability to treat infections. Curcumin use in cancer adjunctive care and its anti-infectious capabilities make it a unique phytotherapeutic agent with promise.
    Citations (11)
    The major impediment towards the use of Curcumin for health benefits is its poor availability in the blood and tissues. This problem can be trounced by our innovative Curcumin preparation. The formulation treats curcumin as it occur inside the turmeric rhizome, where curcumin is more available in the blood. A human study conducted, where the innovative curcumin found to absorb ~15 times more as that of the normal curcumin. This Bio available curcumin was branded as “cureit” and its anti oxidant potential established. The study proves that “cureit” could be good source of natural antioxidant.
    Citations (5)
    Curcuma longa L. (Zingiberaceae family) and its polyphenolic compound curcumin have been subjected to a variety of antimicrobial investigations due to extensive traditional uses and low side effects. Antimicrobial activities for curcumin and rhizome extract of C. longa against different bacteria, viruses, fungi, and parasites have been reported. The promising results for antimicrobial activity of curcumin made it a good candidate to enhance the inhibitory effect of existing antimicrobial agents through synergism. Indeed, different investigations have been done to increase the antimicrobial activity of curcumin, including synthesis of different chemical derivatives to increase its water solubility as well ass cell up take of curcumin. This review aims to summarize previous antimicrobial studies of curcumin towards its application in the future studies as a natural antimicrobial agent.
    Zingiberaceae
    Citations (1,169)
    Curcumin, a non-nutritive yellow pigment derived from the rhizome of Curcuma longa (turmeric), is considered to be an established nutraceutical with anticancer activity. Turmeric contains three principal components, curcumin, demethoxycurcumin and bisdemethoxycurcumin, of which curcumin is most abundant and potent. The concurrence of a high consumption of turmeric and a low incidence of prostate cancer in Asian countries may suggest a role for curcumin in chemoprevention. Curcumin has been identified to exhibit anti-inflammatory, anti-oxidative and anticarcinogenic properties. Since the compound does not exhibit side effects, curcumin has been designated for several clinical trials as a treatment for human cancers. The pro-apototic, antioxidant and anti-inflammatory characteristics of curcumin are implicated in its anticancer activity, yet the mechanism of action of curcumin remains unknown. To achieve an effective pharmacological outcome, curcumin must reach and sustain appropriate levels at the site of action. However, the main disadvantage of curcumin is its high metabolic instability and poor aqueous solubility that limits its systemic bioavailability. To overcome this difficulty, the present study tested the anticancer activity of new curcumin-like compounds (E21cH and Q012095H). Also, the use of new medicaments requires an understanding of their pharmacokinetic profiles and targets. Thus, molecular modeling methods were used to identify the targets of curcumin and curcumin-like compounds compared with other anticancer drugs (Q012138 and Q012169AT), which were used as the controls. The present study identified several enzymes that are targeted by curcumin, aldo-keto reductase family 1 member B10 (AKR1B10), serine/threonine-protein kinase, protein kinase C, matrix metalloproteinase (MMP), cyclooxygenase and epidermal growth factor receptor, which were tested as targets for these anticancer chemicals. All the examined small compounds demonstrated anticancer activity in the in vitro experiments and may impact cancer cells by acting on AKR1B10, MMP-9 and their targets.
    Nutraceutical
    Citations (22)
    Curcumin (1,7‐bis (4‐hydroxy‐3‐methoxyphenyl)‐1,6‐heptadiene‐3,5‐dione) is a major yellow‐orange pigment found in turmeric, and has been used widely as a food ingredient. Curcumin has been associated with many health benefits, but its health‐promoting potential is limited by its poor bioavailability. This is due to the fact that curcumin is poorly absorbed, and absorbed curcumin is subject to extensive biotransformation. The detailed understanding of biotransformation of curcumin is needed to facilitate the elucidation of its biological significance. This study was aimed to establish the metabolic fate of curcumin in the gastrointestinal (GI) tract. The male CD‐1 mice were fed with curcumin in diet (0.05% w/w) for 5 weeks. The entire GI tract and its content were harvested for LC‐MS analysis. Our results demonstrated that curcumin underwent phase I metabolism in the small intestine to yield two major metabolites, namely hexahydro‐curcumin and octahydro‐curcumin. Curcumin, hexahydro‐curcumin and octahydro‐curcumin were all subject to phase II metabolism that converted them to their corresponding glucuronides and sulfates. The majority of curcumin, hexahydro‐curcumin and octahydro‐curcumin exist as phase II conjugates in the small intestine. However, due to the action of gut microbiota, curcumin, hexahydro‐curcumin and octahydro‐curcumin almost exclusively existed in the non‐conjugated forms in the cecum and colon. Furthermore, our results suggested that gut microbiota could break down curcumin, hexahydro‐curcumin and octahydro‐curcumin to produce different fission products. In summary, our results determined the metabolic fate of curcumin in the GI tract, which can help understand the biological effects of curcumin in the GI tract as well as other related organs. Support or Funding Information This study was partially supported by fund from USDA.
    Biotransformation
    Abstract Curcumin, a yellow pigment known to have various biological activities, was applied onto cotton as an antimicrobial agent. Curcumin could provide both color and antimicrobial activity to cotton and can be dyed using a batch or continuous process. However, curcumin and cotton have low affinity and therefore the ability of curcumin to impart durable antimicrobial activity on cotton needs to be studied. In this research, the ability of curcumin dyed onto cotton fabrics to inhibit the growth of Escherichia coli and Staphylococcus aureus was studied. Relationships that can predict the rate of inhibition based on the curcumin concentration or shade depth ( K / S values) were developed without the need for an antimicrobial test. Durability of antimicrobial activity to laundering and to light was also studied. Curcumin was more effective in inhibiting S. aureus than E. coli. The reduction of bacteria and durability of antimicrobial activity of curcumin to laundering was inferior on cotton fabrics compared with wool. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
    Citations (43)
    Curcumin is the major yellow pigment extracted from turmeric, a commonly used spice in Asian cuisine and extensively employed in ayurvedic herbal remedies. A number of studies have shown that curcumin can be a prevention and a chemotherapeutic agent for colon, skin, oral and intestinal cancers. Curcumin is also well known for its antiinflammatory and antioxidant properties, showing high reactivity towards peroxyl radicals, and thus acting as a free radical scavenger. Recently, experimental studies have demonstrated that curcumin might be used in the prevention and the cure of Alzheimer's disease. Indeed, curcumin injected peripherally in vivo into aged Tg mice crossed the blood-brain barrier and bound to amyloid plaques, reducing amyloid levels and plaque formation decisively. The present review will resume the most recent developments in the medicinal chemistry of curcumin and curcumin-like molecules. Keywords: Amyloid, anti-inflammatory molecules, antioxidant, cancer, curcumin, neuroprotective.
    Free radical scavenger
    Scavenger
    Curcumin is a polyphenolic compound with multiple beneficial effects in human health. It has shown a remarkable anti-inflammatory, antibacterial, antifungal, anticancer, and antioxidant effects. The limitations of curcumin are primarily in its bioavailability. Curcumin nanoparticles is suggested to reduce the limitation of bulk curcumin and probably enhance its desired effect. Curcumin was turned into nanoparticles by using simple wet-milling method. The characterization of curcumin nanoparticles indicated the presence of curcumin in size less than 100 nm. The effect of both curcumin and curcumin nanoparticles on wound healing was investigated in rabbits, in paraffin wax. Rabbits whom under curcumin and curcumin nanoparticles have shown faster healing from day 5 compared to control rabbits whom showed a proximate advancement after day 7. On day 14, rabbits whom treated with bulk and nanosized curcumin have shown a perfect healing with no sign of infection. Furthermore, both bulk and nanosized curcumin have shown a comparable antioxidant effect with ascorbic acid. Furthermore, curcumin nanoparticles were exhibited a slightly powerful antioxidant effect compared to curcumin.