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Mythri, R. B. and M. S. Bharath. 2012. Curcumin: A Potential Neuroprotective Agent in Parkinson's Disease. Curr Pharm Des. [Epub ahead of print].
Abstract: Parkinson's disease (PD) is an age-associated neurodegenerative disease clinically characterized as a movement disorder. The motor symptoms in PD arise due to selective degeneration of dopaminergic neurons in the substantia nigra of the ventral midbrain thereby depleting the dopamine levels in the striatum. Most of the current pharmacotherapeutic approaches in PD are aimed at replenishing the striatal dopamine. Although these drugs provide symptomatic relief during early PD, many patients develop motor complications with long-term treatment. Further, PD medications do not effectively tackle tremor, postural instability and cognitive deficits. Most importantly, most of these drugs do not exhibit neuroprotective effects in patients. Consequently, novel therapies involving natural antioxidants and plant products/molecules with neuroprotective properties are being exploited for adjunctive therapy. Curcumin is a polyphenol and an active component of turmeric (Curcuma longa), a dietary spice used in Indian cuisine and medicine. Curcumin exhibits antioxidant, anti-inflammatory and anti-cancer properties, crosses the blood-brain barrier and is neuroprotective in neurological disorders. Several studies in different experimental models of PD strongly support the clinical application of curcumin in PD. The current review explores the therapeutic potential of curcumin in PD.
.................................................................................. Dadhaniya, P., C. Patel, J. Muchhara, N. Bhadja, N. Mathuria, K. Vachhani and M. G. Soni. 2011. Safety assessment of a solid lipid curcumin particle preparation: acute and subchronic toxicity studies. Food Chem Toxicol. 49, 8: 1834-1342. Abstract: Curcumin, a polyphenol, is obtained from turmeric, the ground rhizomes of Curcuma longa L. Extensive research over the past half century has revealed several health benefits of curcumin. The objective of the present study was to investigate potential adverse effects, if any, of a novel solid lipid curcumin particle (SLCP) preparation in rats following acute and subchronic administration. The oral LD50 of the preparation in rats as well as in mice was found to be greater than 2000 mg/kg body weight (bw). In the subchronic toxicity study, Wistar rats (10/sex/group) were administered via oral gavage 0 (control), 180, 360, and 720 mg/kg bw/day of SLCP preparation for 90 days. Administration of the curcumin preparation did not result in any toxicologically significant treatment-related changes in clinical (including behavioral) observations, ophthalmic examinations, body weights, body weight gains, feed consumption, and organ weights. No adverse effects of the curcumin preparation were noted on the hematology, serum chemistry parameters, and urinalysis. Terminal necropsy did not reveal any treatment-related gross or histopathology findings. Based on the results of this study, the No Observed-Adverse-Effect Level (NOAEL) for this standardized novel curcumin preparation was determined as 720 mg/kg bw/day, the highest dose tested. ............................................................... Lin, T. Y., C. W. Lu, C. C. Wang, Y. C. Wang and S. J. Wang. 2011. Curcumin inhibits glutamate release in nerve terminals from rat prefrontal cortex: Possible relevance to its antidepressant mechanism. Prog Neuropsychopharmacol Biol Psychiatry. 35, 7: 1785-1793. Abstract: There is abundant evidence suggesting the relevance of glutamate to depression and antidepressant mechanisms. Curcumin, a major active compound of Curcuma longa, has been reported to have the biological function of antidepressant. The aim of the present study was to investigate the effect of curcumin on endogenous glutamate release in nerve terminals of rat prefrontal cortex and the underlying mechanisms. The results showed that curcumin inhibited the release of glutamate that was evoked by exposing synaptosomes to the K(+) channel blocker 4-aminopyridine (4-AP). This phenomenon was blocked by the chelating the extracellular Ca(2+) ions, and by the vesicular transporter inhibitor bafilomycin A1, but was insensitive to the glutamate transporter inhibitor DL-threo-β-benzyl-oxyaspartate (DL-TBOA). Further experiments demonstrated that curcumin decreased depolarization-induced increase in [Ca(2+)](C), whereas it did not alter the resting membrane potential or 4-AP-mediated depolarization. Furthermore, the inhibitory effect of curcumin on evoked glutamate release was prevented by blocking the Ca(v)2.2 (N-type) and Ca(v)2.1 (P/Q-type) channels, but not by blocking intracellular Ca(2+) release or Na(+)/Ca(2+) exchange. These results suggest that curcumin inhibits evoked glutamate release from rat prefrontocortical synaptosomes by the suppression of presynaptic Ca(v)2.2 and Ca(v)2.1 channels. Additionally, we also found that the inhibitory effect of curcumin on 4-AP-evoked glutamate release was completely abolished by the clinically effective antidepressant fluoxetine. This suggests that curcumin and fluoxetine use a common intracellular mechanism to inhibit glutamate release from rat prefrontal cortex nerve terminals. .......................................................................... Rasheed, A., G. Avinash Kumar Reddy, S. Mohanalakshmi and C. K. Ashok Kumar. 2011. Formulation and comparative evaluation of poly herbal anti-acne face wash gels. Pharm Biol 49, 8: 771-774. Abstract: Context: Rauvolfia serpentina (L). Benth. ex Kurz. (Apocynaceae) possessing antibacterial properties are widely used in modern herbal medicines. Curcuma longa L. (Zingiberaceae), a readily available antiseptic, possess antioxidant, antibacterial, blood purifying and antiinflammatory properties and used in various skin creams. Azadirachta indica A. Juss. (Meliaceae) possess astringent, antiviral, discutient, stimulant and antibacterial properties and works excellently well against acne and keeps the skin healthy. Objective: Acne is the common skin problem that 85% of the teenagers face today. In this study, poly herbal anti-acne face wash gels were prepared using two polymers Carbopol and hydroxy propyl methyl cellulose (HPMC) along with the extracts of plantsRauvolfia serpentina, Curcuma longa, and Azadiracta indica. Materials and methods: The gel formulations were prepared in four different concentrations of 50, 100, 200 mg/ml as Gel-CRB 100, Gel-HPMC 50, Gel-HPMC 100, Gel-HPMC 200, respectively. The formulations were tested for the anti-acne activity by turbidimetric method. Results: Results showed that the gels were non-irritant, stable and posses anti-acne activity. The efficacy when tested with a standard was almost same to that of Clindamycin gel. Discussion and conclusion: From this study, Gel-HPMC 100 was proved to be stable and considered as an effective herbal formulation for acne treatment. ...................................................................... Campos, H.C., M. D. da Rocha, F. P. Viegas, P. C. Nicastro, P. C. Fossaluzza, C. A. Fraga, E. J. Barreiro and C. Jr. Viegas. 2011.The Role of Natural Products in the Discovery of New Drug Candidates for the Treatment of Neurodegenative Disorders II: Alzheimer's Disease. CNS Neurol Disord Drug Targets 10, 2: 251-270. Abstract: The present review is part II in a series (part I focuses on Parkinson's Disease) that addresses the value of natural product chemistry in the discovery of medicines for the treatment of neurodegenerative disorders. Data reviewed document that a host of products from plant species and derivatives have neuroprotectant effects in vitro and in vivo. In addition, besides neuroprotection, natural products also demonstrate biological effects that target biochemical pathways underlying associated symptoms of neurdegnerative disorders that include cognitive impairments, energy/fatigue, mood, and anxiety. This part of the review series focuses specifically upon Alzheimer's Disease (AD). AD is postulated to result from extracellular formation of amyloid plaques and intracellular deposits of neurofibrilary tangles in the hippocampus, cerebral cortex and other areas of the brain essential for cognitive function. Plaques are formed mostly from the deposition -amyloid (A ), a peptide derived from the amyloid precursor protein (APP). Filamentous tangles are formed from paired helical filaments composed of neurofilament and hyperphosphorilated tau protein, a microtubule-associated protein. In addition, environmental factors can engender the production of cytokines that are closely related to the installation of an inflammatory process that contributes to neuronal death and the development and the progression of AD. In this review we focus on the recent main contribuitions of natural products chemistry to the discovery of new chemical entities usefull to the control and prevention of AD installation and progression. More than sixteen plant species, including Ginseng, Celastrus paniculatus, Centella asiatica, Curcuma longa, Ginkgo biloba, Huperzia serrata, Lycoris radiate, Galanthus nivalis, Magnolia officinalis, Polygala tenuifolia, Salvia lavandulaefolia, Salvia miltiorrhiza, Coptis chinensis, Crocus sativus, Evodia rutaecarpa, Sanguisorba officinalis, Veratrum grandiflorum and Picrorhiza kurvoa, are discussed as potential sources of active extracts. In addition, more than sixty secondary metabolites are under evaluation for their efficacy on controlling symptoms and to impede the development and progression of AD. ......................................................................................
Goel, A. and B. B. Aggarwal. 2010. Curcumin, the golden spice from Indian saffron, is a chemosensitizer and radiosensitizer for tumors and chemoprotector and radioprotector for normal organs. Nutr Cancer. 62, 7: 919-930.
Abstract: Curcumin (diferuloylmethane), the yellow pigment in Indian saffron (Curcuma longa; also called turmeric, haldi, or haridara in the East and curry powder in the West), has been consumed by people for centuries as a dietary component and for a variety of proinflammatory ailments. Extensive research within the last decade in cell culture and in rodents has revealed that curcumin can sensitize tumors to different chemotherapeutic agents including doxorubicin, 5-FU, paclitaxel, vincristine, melphalan, butyrate, cisplatin, celecoxib, vinorelbine, gemcitabine, oxaliplatin, etoposide, sulfinosine, thalidomide, and bortezomib. Chemosensitization has been observed in cancers of the breast, colon, pancreas, gastric, liver, blood, lung, prostate, bladder, cervix, ovary, head and neck, and brain and in multiple myeloma, leukemia, and lymphoma. Similar studies have also revealed that this agent can sensitize a variety of tumors to gamma radiation including glioma, neuroblastoma, cervical carcinoma, epidermal carcinoma, prostate cancer, and colon cancer. How curcumin acts as a chemosensitizer and radiosensitizer has also been studied extensively. For example, it downregulates various growth regulatory pathways and specific genetic targets including genes for NF-κB, STAT3, COX2, Akt, antiapoptotic proteins, growth factor receptors, and multidrug-resistance proteins. Although it acts as a chemosensitizer and radiosensitizer for tumors in some cases, curcumin has also been shown to protect normal organs such as liver, kidney, oral mucosa, and heart from chemotherapy and radiotherapy-induced toxicity. The protective effects of curcumin appear to be mediated through its ability to induce the activation of NRF2 and induce the expression of antioxidant enzymes (e.g., hemeoxygenase-1, glutathione peroxidase, modulatory subunit of gamma-glutamyl-cysteine ligase, and NAD(P)H:quinone oxidoreductase 1, increase glutathione (a product of the modulatory subunit of gamma-glutamyl-cysteine ligase), directly quench free radicals, and inhibit p300 HAT activity. These preclinical studies are expected to lead to clinical trials to prove the potential of this age-old golden spice for treating cancer patients. ...................................................................................... Wickenberg, J., S. L. Ingemansson and J. Hlebowicz. 2010. Effects of Curcuma longa (turmeric) on postprandial plasma glucose and insulin in healthy subjects. Nutr J. 12, 9: 43. Abstract:BACKGROUND: Previous animal studies have shown that Curcuma (C.) longa lowers plasma glucose.C. longa may thus be a promising ingredient in functional foods aimed at preventing type 2 diabetes. The purpose of the study is to study the effect of C. longa on postprandial plasma glucose, insulin levels and glycemic index (GI) in healthy subjects. METHODS: Fourteen healthy subjects were assessed in a crossover trial. A standard 75 g oral glucose tolerance test (OGTT) was administered together with capsules containing a placebo or C. longa. Finger-prick capillary and venous blood samples were collected before, and 15, 30, 45, 60, 90, and 120 min after the start of the OGTT to measure the glucose and insulin levels, respectively. RESULTS: The ingestion of 6 g C. longa had no significant effect on the glucose response. The change in insulin was significantly higher 30 min (P = 0.03) and 60 min (P = 0.041) after the OGTT including C. longa. The insulin AUCs were also significantly higher after the ingestion of C. longa, 15 (P = 0.048), 30 (P = 0.035), 90 (P = 0.03), and 120 (P = 0.02) minutes after the OGTT. CONCLUSIONS: The ingestion of 6 g C. longa increased postprandial serum insulin levels, but did not seem to affect plasma glucose levels or GI, in healthy subjects. The results indicate that C. longamay have an effect on insulin secretion. ......................................................................................
Bisht, S. et al. 2010. Systemic Administration of Polymeric Nanoparticle-Encapsulated Curcumin (NanoCurc) Blocks Tumor Growth and Metastases in Preclinical Models of Pancreatic Cancer. Mol Cancer Ther. 9, 8: 2255-2264.
Abstract: Curcumin or diferuloylmethane is a yellow polyphenol extracted from the rhizome of turmeric (Curcuma longa). A large volume (several hundreds) of published reports has established the anticancer and chemopreventative properties of curcumin in preclinical models of every known major cancer type. Nevertheless, the clinical translation of curcumin has been significantly hampered due to its poor systemic bioavailability, which mandates that patients consume up to 8 to 10 g of the free drug orally each day to achieve detectable levels in circulation. We have engineered a polymeric nanoparticle encapsulated curcumin formulation (NanoCurc) that shows remarkably higher systemic bioavailability in plasma and tissues compared with free curcumin upon parenteral administration. In xenograft models of human pancreatic cancer established in athymic mice, administration of parenteral NanoCurc significantly inhibits primary tumor growth in both subcutaneous and orthotopic settings. The combination of parenteral NanoCurc with gemcitabine results in enhanced tumor growth inhibition versus either single agent, suggesting an additive therapeutic influence in vivo. Furthermore, this combination completely abrogates systemic metastases in orthotopic pancreatic cancer xenograft models. Tumor growth inhibition is accompanied by significant reduction in activation of nuclear factor-kappaB, as well as significant reduction in expression of matrix metalloproteinase-9 and cyclin D1, in xenografts treated with NanoCurc and gemcitabine. NanoCurc is a promising new formulation that is able to overcome a major impediment for the clinical translation of curcumin to cancer patients by improving systemic bioavailability, and by extension, therapeutic efficacy. ..............................................................................
Kang, C. and E. Kim. 2010. Synergistic effect of curcumin and insulin on muscle cell glucose metabolism. Food Chem Toxicol. 48, 8-9: 2366-2373.
Abstract: Curcumin is a major phenolic compound of Curcuma longa, which has long been used in traditional Indian medicine. Recently, curcumin has been reported to have antihyperglycemic activity in animal models. However, the molecular basis of this action has not been adequately described. In the present study, curcumin was observed to contain a high level of polyphenols and strong antioxidant activity. Then, the antihyperglycemic effect of curcumin was examined for various signaling pathways using C2C12 mouse myoblast cells. From this, curcumin treatment strongly induced glucose uptake and the phosphorylation of AMPK (AMP-activated protein kinase)/ACC (acetyl-CoA carboxylase), but not PI3-kinase (phosphoinositide 3-kinase)/Akt. Interestingly, the co-treatment of insulin and curcumin produced a mutual synergistic activation of both AMPK/ACC and PI3-kinase/Akt pathways. On the other hand, the synergism could not be observed from the co-treatment of insulin and EGCG. It suggests that the two signaling pathways can crosstalk each other in a case-sensitive manner upon the treatment of antioxidant polyphenols. Further, these results were consistent with the findings of GLUT4 translocation to the cell surface. Our findings indicate that curcumin can promote AMPK activation and glucose uptake with increased insulin sensitivity in muscle cells as a potential anti-diabetic therapeutic agent. .......................................................................................
Yallapu, M. M., M. Jaggi and S. C.Chauhan. 2010. b-Cyclodextrin-curcumin self-assembly enhances curcumin delivery in prostate cancer cells. Colloids and Surfaces B: Biointerfaces 79, 1; 113-125.
Abstract: Curcumin, a hydrophobic polyphenolic compound derived from the rhizome of the herbCurcuma longa, possesses a wide range of biological applications including cancer therapy. However, its prominent application in cancer treatment is limited due to sub-optimal pharmacokinetics and poor bioavailability at the tumor site. In order to improve its hydrophilic and drug delivery characteristics, we havedeveloped a b-cyclodextrin (CD) mediated curcumin drug delivery system via encapsulation technique.Curcumin encapsulation into the CD cavity was achieved by inclusion complex mechanism. Curcuminencapsulation efficiency was improved by increasing the ratio of curcumin to CD. The formations of CD-curcumin complexes were characterized by Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), thermo-gravimetric analysis (TGA), scanning electron microscope (SEM), and transmission electron microscope (TEM) analyses. An optimized CD-curcumin complex (CD30) was evaluated for intracellular uptake and anti-cancer activity. Cell proliferation and clonogenic assays demonstrated that -cyclodextrin-curcumin self-assembly enhanced curcumin delivery and improved its therapeutic efficacy in prostate cancer cells compared to free curcumin. ................................................................................................ Koosirirat, C., S. Linpisarn, D. Changsom, K. Chawansuntati and J. Wipasa. 2010.Investigation of the anti-inflammatory effect of Curcuma longa in Helicobacter pylori-infected patients. International Immunopharmacology 10, 7: 815-818. Abstract: Helicobacter pylori infection of the lining of the stomach induces an array of inflammatory cytokine production leading to gastritis and peptic ulcer disease. The aim of this study was to investigate the effect of curcumin on the production of interleukin (IL)-8, IL-1β, tumor necrosis factor (TNF)-α and cyclooxygenase(COX)-2 in gastric mucosa from H. pylori-infected gastritis patients. Patients were randomly assigned to receive either OAM (Omeprazole, Amoxicillin and Metronidazole) treatment or a course of curcumin. Gastric biopsies were collected before and after treatment and were examined for the level of inflammatory cytokines mRNA by semi-quantitative reverse transcription polymerase chain reaction. The eradication rate of H. pylori in patients that received OAM treatment was significantly higher than the patients that received curcumin (78.9% versus 5.9%). The levels of IL-8 mRNA expression in the OAM group significantly decreased after treatment, but no changes of other cytokines were found. This emphasizes an important role of IL-8 in H. pylori infection. The decreases of cytokine production were not found in the curcumin group. We concluded that curcumin alone may have limited anti-bactericidal effect on H. pylori, and on the production of inflammatory cytokines. Nevertheless, other studies have reported that patients treated with curcumin had relieved symptoms. Further investigation should be carried out as the use of curcumin in combination with therapeutic regimens may be beneficial as an alternative treatment. ------------------------------------------------------------ Houssen, M. E., A. Ragab , A. Mesbah , A. Z. El-Samanoudy, G. Othman, A. Fathy and F. A. Badria. 2010. Natural anti-inflammatory products and leukotriene inhibitors as complementary therapy for bronchial asthma. Clinical Biochemistry. 43: 887–890. Abstract Objective: To assess the efficacy of a combination of Boswellia serrata, licorice root (Glycyrrhiza glabra) and turmeric root (Curcuma longa) as natural leukotriene inhibitor, antiinflammatory and antioxidant products respectively in controlling bronchial asthma. Subjects and methods: The study comprised 63 patients with bronchial asthma that are furthersubdivided into two groups .Group 1 receiving oral capsule (combined herb) in a soft-gelatin capsule 3 times daily for 4 weeks and group 2 receiving placebo. Plasma leukotriene C4 (LTC4), nitric oxide (NO) and malondialdehyde (MDA) levels were measured and pulmonary function was also assessed in all patients enrolled in the study. Results: There were a statistically significant decrease in the plasma levels of LTC4, (MDA), and NO in target therapy group when compared with placebo group. Conclusion: The used extract contained Boswellia serrata, Curcuma longa and Glycyrrhiza has apronounced effect in the management of bronchial asthma. .........................................................................................................................
GOTA, V. S., G. B. MARU, T. G. SONI, T. R. GANDHI, N. KOCHAR AND M. G. AGARWAL. 2010.Safety and Pharmacokinetics of a Solid Lipid Curcumin Particle Formulation in Osteosarcoma Patients and Healthy Volunteers. J. Agric. Food Chem. 58: 2095–2099. Abstract: Curcumin is the lipid-soluble antioxidant compound obtained from the rhizome of Curcuma longaLinn, also known as turmeric. Curcumin targets multiple chemotherapeutic and inflammatory pathways and has demonstrated safety and tolerability in humans, supporting its potential as a therapeutic agent; however, the clinical literature lacks conclusive evidence supporting its use as a therapeutic agent due to its low bioavailability in humans. The purpose of this study was to quantify plasma levels of free curcumin after dosing of a solid lipid curcumin particle (SLCP) formulation versus unformulated curcumin in healthy volunteers and to determine its tolerability and dose-plasma concentration relationship in late-stage osteosarcoma patients. Doses of 2, 3, and 4 g of SLCP were evaluated in 11 patients with osteosarcoma. Plasma curcumin levels were measured using a validated highperformance liquid chromatography method. The limit of detection of the assay was 1 ng/mL of curcumin. In healthy subjects, the mean peak concentration of curcumin achieved from dosing 650 mg of SLCP was 22.43 ng/mL, whereas plasma curcumin from dosing an equal quantity of unformulated 95% curcuminoids extract was not detected. In both healthy individuals and osteosarcoma patients, high interindividual variability in pharmacokinetics and nonlinear dose dependency was observed, suggesting potentially complex absorption kinetics. Overall, good tolerability was noted in both healthy and osteosarcoma groups. ............................................................................................................................................... Ringman,J. M., S. A. Frautschy, G. M. Cole, D. L. Masterman and J. L. Cummings. 2005. A Potential Role of the Curry Spice in AlZheimer's Disease. Curr Alzheimer Res 2, 2: 131-136. Abstract; There is substantial in-vitro data indicating that curcumin has antioxidant, anti-inflammatory, and anti-amyloid activity. In addition, studies in animal models of Alzheimer’s disease (AD) indicate a direct effect of curcumin in decreasing the amyloid pathology of AD. As the widespread use of curcumin as a food additive and relatively small short-term studies in humans suggest safety, curcumin is a promising agent in the treatment and/or prevention of AD. Nonetheless, important information regarding curcumin bioavailability, safety and tolerability, particularly in an elderly population is lacking. We are therefore performing a study of curcumin in patients with AD to gather this information in addition to data on the effect of curcumin on biomarkers of AD pathology. ................................................................................................................................Kelley, B. J., and D. S.Knopman, (2008). Alternative Medicine and Alzheimer's Disease. Neurologist 14, 5: 299-306. Abstract;
Background; Alternative medicine has an extensive worldwide history and is commonly used by older patients. A number of different alternative medicines are used by patients having Alzheimer's disease. It is both desirable and expected for clinicians to be acquainted with these medications.
Review Summary; This paper discusses the available clinical trial evidence regarding eight agents commonly used by people having Alzheimer's disease. We provide an overview of the history and basic scientific evidence available for each agent, followed by a critical analysis of the evidence available from clinical trials, including the number of participants, trial duration and specific outcomes evaluated.
Conclusion; While many of these compounds have been associated with interesting basic science, none has shown clear clinical benefit to date. Data available for some, such as Ginkgo biloba, curcumin and huperzine A, suggest that further evaluation is warranted. Familiarity with this literature will allow clinicians to provide meaningful recommendations to patients who wish to use these agents.
................................................................................................................................ Irfan Rahman. (2006). Antioxidant therapies in COPD. International Journal of COPD 1, 1: 15–29
Abstract: Oxidative stress is an important feature in the pathogenesis of COPD. Targeting oxidative stress with antioxidants or boosting the endogenous levels of antioxidants is likely to be benefi cial in the treatment of COPD. Antioxidant agents such as thiol molecules (glutathione and mucolytic drugs, such as N-acetyl-L-cysteine and N-acystelyn), dietarypolyphenols (curcumin, resveratrol, green tea, catechins/quercetin), erdosteine, and carbocysteine lysine salt, all have been reported to control nuclear factor-kappaB (NF-kB) activation, regulation of glutathione biosynthesis genes, chromatin remodeling, and hence inflammatory gene expression. Specific spin traps such as a-phenyl-N-tert-butyl nitrone, a catalytic antioxidant (ECSOD mimetic), porphyrins (AEOL 10150 and AEOL 10113), and a superoxide dismutase mimetic M40419 have also been reported to inhibit cigarette smoke-induced infl ammatory responses in vivo. Since a variety of oxidants, free radicals, and aldehydes are implicated in the pathogenesis of COPD, it is possible that therapeutic administration of multiple antioxidants will be effective in the treatment of COPD. Various approaches to enhance lung antioxidant capacity and clinical trials of antioxidant compounds in COPD are discussed.
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PATIL, B. S., G. K. JAYAPRAKASHA, K. N. C. MURTHY AND V. MAMIT. 2009. Bioactive Compounds: Historical Perspectives, Opportunities, and Challenges. Journal of Agricultural and Food Chemistry 57:8142–8160 Abstract: Mom’s conventional wisdom of eating fruits and vegetables to lead a healthy life has evolved with scientific, fact-finding research during the past four decades due to advances in science of “Foods for Health”. Epidemiological and prospective studies have demonstrated the vital role of fruits, vegetables, and nuts in reducing the risk of cancer and cardiovascular diseases. In recent years, several meta-analyses strongly suggested that by adding one serving of fruits and vegetables to daily diet, the risk of cardiovascular diseases will be decreased up to 7%. The multidisciplinary and partnership efforts of agriculture and medical scientists across the globe stimulated interest in establishing certain interdisciplinary centers and institutes focusing on “Foods for Health”. While theconsumption of various healthy foods continues, several questions about toxicity, bioavailability, and food-drug interactions of bioactive compounds are yet to be fully understood on the basis of scientific evidence. Recent research on elucidation of the molecular mechanisms to understand the “proof of the concept” will provide the perfect answer when consumers are ready for a “consumer-tofarm” rather than the current “farm-to-consumer” approach. The multidisciplinary research and educational efforts will address the role of healthy foods to improve eye, brain, and heart health while reducing the risk of cancer. Through this connection, this review is an attempt to provide insight and historical perspectives on some of the bioactive compounds from the day of discovery to their current status. The bioactive compounds discussed in this review are flavonoids, carotenoids, curcumin, ascorbic acid, and citrus limonoids. ................................................................................................................................
Garcea, G., D. P. Berry, D. J. L. Jones, R. Singh, A. R. Dennison, P. B. Farmer, R. A. Sharma, W. P.Steward and A. J. Gescher 2005. Consumption of the Putative Chemopreventive Agent Curcumin by Cancer Patients: Assessment of Curcumin Levels in the Colorectum and their Pharmacodynamic Consequences. Cancer Epidemiology, Biomarkers & Prevention 14, 1: 120-125.
Abstract; Curcumin, a constituent of the spice turmeric, has been shown to reduce the adenoma burden in rodent models of colorectal cancer accompanied by a reduction of levels of the oxidative DNA adduct 3-(2-deoxy-b-di-erythro-pentafuranosyl)-pyr[1,2-a]-purin-10(3H)one (M1G) and of expression of the enzyme cyclooxygenase-2 (COX-2). We tested the hypothesis that pharmacologically active levels of curcumin can be achieved in the colorectum of humans as measured by effects on levels of M1G and COX-2 protein. Patients with colorectal cancer ingested curcumin capsules (3,600, 1,800, or 450 mg daily) for 7 days. Biopsy samples of normal and malignant colorectal tissue, respectively, were obtained at diagnosis and at 6 to 7 hours after the last dose of curcumin. Blood was taken 1 hour after the last dose of curcumin. Curcumin and its metabolites were detected and quantitated by high-performance liquid chromatography with detection by UV spectrophotometry or mass spectrometry. M1G levels and COX-2 protein expression were measured by immunoslot blot and Western blotting, respectively. The concentrations of curcumin in normal and malignant colorectal tissue of patients receiving 3,600 mg of curcumin were 12.7 ± 5.7 and 7.7 ± 1.8 nmol/g, respectively. Curcumin sulfate and curcumin glucuronide were identified in the tissue of these patients. Trace levels of curcumin were found in the peripheral circulation. M1G levels were 2.5-fold higher in malignant tissue as compared with normal tissue (P < 0.05 by ANOVA). Administration of curcumin (3,600 mg) decreased M1G levels from 4.8 |
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