Curcumin, a polyphenol derived from turmeric, is an ancient therapeutic used in India for centuries to treat a wide array of ailments. Interest in curcumin has increased recently, with ongoing clinical trials exploring curcumin as an anticancer therapy and as a protectant against neurodegenerative diseases. In vitro, curcumin chelates metal ions. However, although diverse physiological effects have been documented for this compound, curcumin's mechanism of action on mammalian cells remains unclear. This study uses yeast as a model eukaryotic system to dissect the biological activity of curcumin. We found that yeast mutants lacking genes required for iron and copper homeostasis are hypersensitive to curcumin and that iron supplementation rescues this sensitivity. Curcumin penetrates yeast cells, concentrates in the endoplasmic reticulum (ER) membranes, and reduces the intracellular iron pool. Curcumin-treated, iron-starved cultures are enriched in unbudded cells, suggesting that the G1 phase of the cell cycle is lengthened. A delay in cell cycle progression could, in part, explain the antitumorigenic properties associated with curcumin. We also demonstrate that curcumin causes a growth lag in cultured human cells that is remediated by the addition of exogenous iron. These findings suggest that curcumin-induced iron starvation is conserved from yeast to humans and underlies curcumin's medicinal properties.
Curcumin is a polyphenolic compound derived from the plant Curcuma Long Lin that has been demonstrated to have antioxidant and anti-inflammatory effects as well as effects on reducing beta-amyloid aggregation. It reduces pathology in transgenic models of Alzheimer's disease (AD) and is a promising candidate for treating human AD. The purpose of the current study is to generate tolerability and preliminary clinical and biomarker efficacy data on curcumin in persons with AD.
We performed a 24-week randomized, double blind, placebo-controlled study of Curcumin C3 Complex® with an open-label extension to 48 weeks. Thirty-six persons with mild-to-moderate AD were randomized to receive placebo, 2 grams/day, or 4 grams/day of oral curcumin for 24 weeks. For weeks 24 through 48, subjects that were receiving curcumin continued with the same dose, while subjects previously receiving placebo were randomized in a 1:1 ratio to 2 grams/day or 4 grams/day. The primary outcome measures were incidence of adverse events, changes in clinical laboratory tests and the Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) at 24 weeks in those completing the study. Secondary outcome measures included the Neuropsychiatric Inventory (NPI), the Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) scale, levels of Aβ1-40 and Aβ1-42 in plasma and levels of Aβ1-42, t-tau, p-tau181 and F2-isoprostanes in cerebrospinal fluid. Plasma levels of curcumin and its metabolites up to four hours after drug administration were also measured.
Mean age of completers (n = 30) was 73.5 years and mean Mini-Mental Status Examination (MMSE) score was 22.5. One subject withdrew in the placebo (8%, worsened memory) and 5/24 subjects withdrew in the curcumin group (21%, 3 due to gastrointestinal symptoms). Curcumin C3 Complex® was associated with lowered hematocrit and increased glucose levels that were clinically insignificant. There were no differences between treatment groups in clinical or biomarker efficacy measures. The levels of native curcumin measured in plasma were low (7.32 ng/mL).
Curcumin was generally well-tolerated although three subjects on curcumin withdrew due to gastrointestinal symptoms. We were unable to demonstrate clinical or biochemical evidence of efficacy of Curcumin C3 Complex® in AD in this 24-week placebo-controlled trial although preliminary data suggest limited bioavailability of this compound.
ClinicalTrials.gov Identifier: NCT00099710.
Curcumin has shown considerable pharmacological activity, including anti-inflammatory, but its poor bioavailability and rapid metabolization have limited its application. The purpose of the present study was to formulate curcumin-solid lipid nanoparticles (curcumin-SLNs) to improve its therapeutic efficacy in an ovalbumin (OVA)-induced allergic rat model of asthma. A solvent injection method was used to prepare the curcumin-SLNs. Physiochemical properties of curcumin-SLNs were characterized, and release experiments were performed in vitro. The pharmacokinetics in tissue distribution was studied in mice, and the therapeutic effect of the formulation was evaluated in the model. The prepared formulation showed an average size of 190 nm with a zeta potential value of −20.7 mV and 75% drug entrapment efficiency. X-ray diffraction analysis revealed the amorphous nature of the encapsulated curcumin. The release profile of curcumin-SLNs was an initial burst followed by sustained release. The curcumin concentrations in plasma suspension were significantly higher than those obtained with curcumin alone. Following administration of the curcumin-SLNs, all the tissue concentrations of curcumin increased, especially in lung and liver. In the animal model of asthma, curcumin-SLNs effectively suppressed airway hyperresponsiveness and inflammatory cell infiltration and also significantly inhibited the expression of T-helper-2-type cytokines, such as interleukin-4 and interleukin-13, in bronchoalveolar lavage fluid compared to the asthma group and curcumin-treated group. These observations implied that curcumin-SLNs could be a promising candidate for asthma therapy.
airway hyperresponsiveness; pharmacokinetics; curcumin; solid lipid nanoparticles
Curcumin (diferuloylmethane) is found in the rhizomes of the turmeric plant (Curcuma longa L.) and has been used for centuries as a dietary spice and as a traditional Indian medicine used to treat different conditions. At the cellular level, curcumin modulates important molecular targets: transcription factors, enzymes, cell cycle proteins, cytokines, receptors and cell surface adhesion molecules. Because many of the curcumin targets mentioned above participate in the regulation of bone remodeling, curcumin may affect the skeletal system. Nitric oxide (NO) is a gaseous molecule generated from l-arginine during the catalization of nitric oxide synthase (NOS), and it plays crucial roles in catalization and in the nervous, cardiovascular and immune systems. Human osteoblasts have been shown to express NOS isoforms, and the exact mechanism(s) by which NO regulates bone formation remain unclear. Curcumin has been widely described to inhibit inducible nitric oxide synthase expression and nitric oxide production, at least in part via direct interference in NF-κB activation. In the present study, after exposure of human osteoblast-like cells (MG-63), we have observed that curcumin abrogated inducible NOS expression and decreased NO levels, inhibiting also cell prolifieration. This effect was prevented by the NO donor sodium nitroprusside. Under osteogenic conditions, curcumin also decreased the level of mineralization. Our results indicate that NO plays a role in the osteoblastic profile of MG-63 cells.
osteoblast; nitric oxide synthase; nitric oxide
The therapeutic effects of curcumin in treating Alzheimer’s disease (AD) depend on the ability to penetrate the blood–brain barrier. The latest nanoparticle technology can help to improve the bioavailability of curcumin, which is affected by the final particle size and stability. We developed a stable curcumin nanoparticle formulation to test in vitro and in AD model Tg2576 mice. Flash nanoprecipitation of curcumin, polyethylene glycol-polylactic acid co-block polymer, and polyvinylpyrrolidone in a multi-inlet vortex mixer, followed by freeze drying with β-cyclodextrin, produced dry nanocurcumin with mean particle size <80 nm. Nanocurcumin powder, unformulated curcumin, or placebo was orally administered to Tg2576 mice for 3 months. Before and after treatment, memory was measured by radial arm maze and contextual fear conditioning tests. Nanocurcumin produced significantly (p = 0.04) better cue memory in the contextual fear conditioning test than placebo and tendencies toward better working memory in the radial arm maze test than ordinary curcumin (p = 0.14) or placebo (p = 0.12). Amyloid plaque density, pharmacokinetics, and Madin–Darby canine kidney cell monolayer penetration were measured to further understand in vivo and in vitro mechanisms. Nanocurcumin produced significantly higher curcumin concentration in plasma and six times higher area under the curve and mean residence time in brain than ordinary curcumin. The Papp of curcumin and tetrahydrocurcumin were 1.8 × 10−6 and 1.6 × 10−5 cm/s, respectively, for nanocurcumin. Our novel nanocurcumin formulation produced highly stabilized nanoparticles with positive treatment effects in Tg2576 mice.
Electronic supplementary material
The online version of this article (doi:10.1208/s12248-012-9444-4) contains supplementary material, which is available to authorized users.
Alzheimer’s disease; behavior tests; nanocurcumin; oral route; pharmacokinetic
There has been a worldwide increase in allergy and asthma over the last few decades, particularly in industrially developed nations. This resulted in a renewed interest to understand the pathogenesis of allergy in recent years. The progress made in the pathogenesis of allergic disease has led to the exploration of novel alternative therapies, which include herbal medicines as well. Curcumin, present in turmeric, a frequently used spice in Asia has been shown to have anti-allergic and inflammatory potential.
We used a murine model of latex allergy to investigate the role of curcumin as an immunomodulator. BALB/c mice were exposed to latex allergens and developed latex allergy with a Th2 type of immune response. These animals were treated with curcumin and the immunological and inflammatory responses were evaluated.
Animals exposed to latex showed enhanced serum IgE, latex specific IgG1, IL-4, IL-5, IL-13, eosinophils and inflammation in the lungs. Intragastric treatment of latex-sensitized mice with curcumin demonstrated a diminished Th2 response with a concurrent reduction in lung inflammation. Eosinophilia in curcumin-treated mice was markedly reduced, co-stimulatory molecule expression (CD80, CD86, and OX40L) on antigen-presenting cells was decreased, and expression of MMP-9, OAT, and TSLP genes was also attenuated.
These results suggest that curcumin has potential therapeutic value for controlling allergic responses resulting from exposure to allergens.
Curcumin, the phytochemical component in turmeric, is used as a dietary spice and a topical ointment for the treatment of inflammation in India for centuries. Curcumin (diferuloylmethane) is relatively insoluble in water, but dissolves in acetone, dimethylsulphoxide, and ethanol. Commercial grade curcumin contains 10–20% curcuminoids, desmethoxycurcumin, and bisdesmethoxycurcumin and they are as effective as pure curcumin. Based on a number of clinical studies in carcinogenesis, a daily oral dose of 3.6 g curcumin has been efficacious for colorectal cancer and advocates its advancement into Phase II clinical studies. In addition to the anticancer effects, curcumin has been effective against a variety of disease conditions in both in vitro and in vivo preclinical studies. The present review highlights the importance of curcumin as an anti-inflammatory agent and suggests that the beneficial effect of curcumin is mediated by the upregulation of peroxisome proliferator-activated receptor-γ (PPAR-γ) activation.
To determine effects of curcumin on N-methyl-N-nitrosourea (MNU) and saturated sodium chloride (s-NaCl)-induced gastric cancer in rats. Male Wistar rats were divided into 5 groups: control (CO), control supplemented with 200 mg/kg curcumin (CC), MNU + s-NaCl, MNU + s-NaCl supplemented with 200 mg/kg curcumin daily for the first 3 weeks (MNU + s-NaCl + C3W), and MNU + s-NaCl supplemented with curcumin for 20 weeks (MNU + s-NaCl + C20W). To induce stomach cancer, rats except for CO and CC were orally treated with 100 mg/kg MNU on day 0 and 14, and s-NaCl twice-a-week for the first 3 weeks. The experiment was finished and rats were sacrificed at the end of 20 weeks. Cancers were found in forestomachs of all rats in MNU + s-NaCl. The expressions of phosphorylated inhibitor kappaB alpha (phospho-IκBα), 8-hydroxy-2′-deoxyguanosine (8-OHdG), and cyclin D1 significantly increased in MNU + s-NaCl compared with CO. Curcumin treatments for 3 and 20 weeks reduced the cancer incidence resulting in a decrease of phospho-IκBα expression in benign tumor-bearing rats compared with MNU + s-NaCl. Curcumin treatment for 20 weeks also decreased 8-OHdG expression in benign tumor-bearing rats compared with MNU + s-NaCl. Curcumin can attenuate cancer via a reduction of phospho-IκBα and 8-OHdG expressions, which may play a promising role in gastric carcinogenesis.
Allergic conjunctivitis (AC) from an allergen-driven T helper 2 (Th2) response is characterized by conjunctival eosinophilic infiltration. Because curcumin has shown anti-allergic activity in an asthma and contact dermatitis laboratory models, we examined whether administration of curcumin could affect the severity of AC and modify the immune response to ovalbumin (OVA) allergen in an experimental AC model.
Mice were challenged with two doses of topical OVA via the conjunctival sac after systemic sensitization with OVA in aluminum hydroxide (ALUM). Curcumin was administered 1 h before OVA challenge. Several indicators for allergy such as serum immunoglubulin E (IgE) antibodies production, eosinophil infiltration into the conjunctiva and Th2 cytokine production were evaluated in mice with or without curcumin treatment.
Mice challenged with OVA via the conjunctival sac following systemic sensitization with OVA in ALUM had severe AC. Curcumin administration markedly suppressed IgE-mediated and eosinophil-dependent conjunctival inflammation. In addition, mice administered curcumin had less interleukin-4 (IL-4) and interleukin-5 (IL-5) (Th2 type cytokine) production in conjunctiva, spleen, and cervical lymph nodes than mice in the non-curcumin-administered group. OVA challenge resulted in activation of the production of inducible nitric oxide (iNOS), and curcumin treatment inhibited iNOS production in the conjunctiva.
We believe our findings are the first to demonstrate that curcumin treatment suppresses allergic conjunctival inflammation in an experimental AC model.
Current therapy for allergic bronchopulmonary aspergillosis (ABPA) uses oral corticosteroids, exposing patients to the adverse effects of these agents. There are reports of the steroid-sparing effect of anti-IgE therapy with omalizumab for ABPA in patients with cystic fibrosis (CF), but there is little information on its efficacy against ABPA in patients with bronchial asthma without CF.
To examine the effects of omalizumab, measured by asthma control, blood eosinophilia, total serum immunoglobulin E (IgE), oral corticosteroid requirements, and forced expiratory volume spirometry in patients with ABPA and bronchial asthma.
A retrospective review of charts from 2004–2006 of patients treated with omalizumab at an academic allergy and immunology practice in the Bronx, New York were examined for systemic steroid and rescue inhaler usage, serum immunoglobulin E levels, blood eosinophil counts, and asthma symptoms, as measured by the Asthma Control Test (ACT).
A total of 21 charts were screened for the diagnosis of ABPA and bronchial asthma. Four patients with ABPA were identified; two of these patients were male. The median monthly systemic corticosteroid use at 6 months and 12 months decreased from baseline usage. Total serum IgE decreased in all patients at 12 months of therapy. Pre-bronchodilator forced expiratory vital capacity at one second (FEV1) was variable at 1 year of treatment. There was an improvement in Asthma Control Test (ACT) symptom scores for both daytime and nighttime symptoms.
Treatment with omalizumab creates a steroid-sparing effect, reduces systemic inflammatory markers, and results in improvement in ACT scores in patients with ABPA.
allergic bronchopulmonary aspergillosis; omalizumab; asthma
Anti IgE treatment with omalizumab is efficacious in the treatment of patients suffering from allergic asthma, improving asthma control and improving quality of life. Furthermore, this approach could be beneficial for patients with concomitant atopic dermatitis. We assessed quality of life and asthma control in atopic patients with allergic asthma and concomitant atopic dermatitis versus those with asthma and without atopic dermatitis treated with omalizumab.
A total of 22 patients with severe allergic asthma were treated with omalizumab for 12 months. 13 patients with allergic asthma without concomitant atopic dermatitis (IgE 212 ± 224 IU/ml) and 9 patients with concomitant allergic asthma and atopic dermatitis (IgE 3,528 ± 2,723 IU/ml) were included. Asthma-related quality of life (AQLQ), atopic dermatitis related quality of life (DLQI), and asthma-related treatment were compared between both groups at baseline and after initiating omalizumab treatment.
DLQI was significantly in favor of omalizumab after 2 months in the atopic dermatitis/asthma group (P = 0.01); AQLQ was improved after 6 months in the asthma group (P = 0.01), while no change was seen in AQLQ in the atopic dermatitis/asthma group (P = 0.12). Omalizumab controlled oral corticosteroid use more effective (P < 0.01) in patients with asthma and atopic dermatitis (in 9/9 cases) compared to patients with asthma alone (9/13). Baseline IgE as well as other factors do not predict response to omalizumab.
Omalizumab is effective in improving atopic dermatitis-related quality of life scores and modulates oral corticosteroid use in patients with concomitant asthma and atopic dermatitis in a positive fashion.
allergic asthma; anti-IgE; atopic dermatitis; omalizumab; quality of life
Common medications used to treat mild persistent asthma are glucocorticoids, leukotriene receptor antagonists and theophylline. The aim of the study was to evaluate monotherapy with either inhaled steroids, oral leukotriene receptor antagonist or theophylline in Egyptian children with mild persistent asthma by determining their clinical, laboratory and spirometric responses to treatment.
Material and methods
Thirty-nine mild asthmatic children between 8 and 13 years of age were included in the study. Patients were classified according to therapy received into four groups: oral leukotriene receptor antagonist (montelukast), inhaled corticosteroid (fluticasone propionate), sustained-release (SR) theophylline, and no treatment. Pulmonary function testing was performed at the start of therapy and 8 weeks later using spirometry. Eosinophil count and serum nitric oxide were estimated in the blood. Minitab statistical package was used for analysis of data.
Follow-up after 8 weeks revealed significant improvement in FEV1% in groups 1 (p < 0.01) and 3 (p < 0.05), significant improvement in PEFR in groups 1 (p < 0.05) and 2 (p < 0.01), significant decline in serum NO levels in groups 1 (p < 0.05) and 2 (p < 0.05), as well as significant improvement in eosinophil count in groups 1, 2 and 3 (p < 0.01, < 0.001, < 0.01 respectively). There was a statistically significant positive correlation between the decline in serum NO and the decline in blood eosinophil % in group 2 (p < 0.05).
Inhaled corticosteroids and montelukast have a significant role in controlling the pulmonary functions and the inflammatory process in children with mild persistent asthma, although inhaled corticosteroids seem to yield a better response. Children with mild persistent asthma should receive a controller medication, and SR theophylline may be a good cost-benefit alternative for low socio-economic groups of patients.
asthma; inhaled corticosteroids; montelukast; slow-release theophylline
The health beneficial effects of Resveratrol, Curcumin and Simvastatin have been demonstrated in various experimental models of inflammation. We investigated the potential anti-inflammatory and immunomodulatory mechanisms of the above mentioned compounds in a murine model of hyper-acute Th1-type ileitis following peroral infection with Toxoplasma gondii.
Here we show that after peroral administration of Resveratrol, Curcumin or Simvastatin, mice were protected from ileitis development and survived the acute phase of inflammation whereas all Placebo treated controls died. In particular, Resveratrol treatment resulted in longer-term survival. Resveratrol, Curcumin or Simvastatin treated animals displayed significantly increased numbers of regulatory T cells and augmented intestinal epithelial cell proliferation/regeneration in the ileum mucosa compared to placebo control animals. In contrast, mucosal T lymphocyte and neutrophilic granulocyte numbers in treated mice were reduced. In addition, levels of the anti-inflammatory cytokine IL-10 in ileum, mesenteric lymph nodes and spleen were increased whereas pro-inflammatory cytokine expression (IL-23p19, IFN-γ, TNF-α, IL-6, MCP-1) was found to be significantly lower in the ileum of treated animals as compared to Placebo controls. Furthermore, treated animals displayed not only fewer pro-inflammatory enterobacteria and enterococci but also higher anti-inflammatory lactobacilli and bifidobacteria loads. Most importantly, treatment with all three compounds preserved intestinal barrier functions as indicated by reduced bacterial translocation rates into spleen, liver, kidney and blood.
Oral treatment with Resveratrol, Curcumin or Simvastatin ameliorates acute small intestinal inflammation by down-regulating Th1-type immune responses and prevents bacterial translocation by maintaining gut barrier function. These findings provide novel and potential prophylaxis and treatment options of patients with inflammatory bowel diseases.
Curcumin has been successfully applied to treat inflammatory conditions in experimental research and in clinical trials. The purpose of our study is to evaluate the efficacy of an adjunctive-to-traditional treatment with Norflo tablets (curcumin-phosphatidylcholine complex; Meriva) administered twice a day in recurrent anterior uveitis of different etiologies. The study group consisted of 106 patients who completed a 12-month follow-up therapeutic period. We divided the patients into three main groups of different uveitis origin: group 1 (autoimmune uveitis), group 2 (herpetic uveitis), and group 3 (different etiologies of uveitis). The primary end point of our work was the evaluation of relapse frequency in all treated patients, before and after Norflo treatment, followed by the number of relapses in the three etiological groups. Wilcoxon signed-rank test showed a P < 0.001 in all groups. The secondary end points were the evaluation of relapse severity and of the overall quality of life. The results showed that Norflo was well tolerated and could reduce eye discomfort symptoms and signs after a few weeks of treatment in more than 80% of patients. In conclusion, our study is the first to report the potential therapeutic role of curcumin and its efficacy in eye relapsing diseases, such as anterior uveitis, and points out other promising curcumin-related benefits in eye inflammatory and degenerative conditions, such as dry eye, maculopathy, glaucoma, and diabetic retinopathy.
curcumin; anterior recurrent uveitis; phosphatidylcholine-bound-curcumin (Meriva)
Cystitis glandularis (CG) is a proliferative disorder in the urinary bladder. The outcome of current treatments in some patients is not satisfactory. Curcumin, a herbal medicine that has been used for centuries, has shown great potential in treating various diseases. Our pilot study aimed to explore the feasibility of an intravesical treatment for CG using curcumin. 14 patients diagnosed with CG that remained symptomatic after primary treatments were enrolled, underwent a 3-month curcumin intravesical treatment (50 mg/50 mL, 1 hour, once per week for first 4 weeks and once per month for next 2 months) and were followed up for 3 months. Efficacy of the treatment was evaluated using core lower urinary tract symptom score (CLSS) questionnaire. 10 patients demonstrated persistent improvement in symptoms up to the end of the 6-month study. Their CLSS decreased significantly after the 3-month treatment (6.0 ± 0.8; P < 0.01) from the baseline (10.5 ± 1.6) and maintained decreasing till the end of the study (6.2 ± 0.7; P < 0.01). 4 patients were classified as nonresponders. Our study suggests the feasibility of further randomized controlled trials on curcumin intravesical treatment in CG patients who remain symptomatic after primary treatments.
Curcumin can reduce inflammation and neurodegeneration, but its chemical instability and metabolism raise concerns, including whether the more stable metabolite tetrahydrocurcumin (TC) may mediate efficacy. We examined the antioxidant, anti-inflammatory, or anti-amyloidogenic effects of dietary curcumin and TC, either administered chronically to aged Tg2576 APPsw mice or acutely to lipopolysaccharide (LPS)-injected wild-type mice. Despite dramatically higher drug plasma levels after TC compared with curcumin gavage, resulting brain levels of parent compounds were similar, correlating with reduction in LPS-stimulated inducible nitric-oxide synthase, nitrotyrosine, F2 isoprostanes, and carbonyls. In both the acute (LPS) and chronic inflammation (Tg2576), TC and curcumin similarly reduced interleukin-1β. Despite these similarities, only curcumin was effective in reducing amyloid plaque burden, insoluble β-amyloid peptide (Aβ), and carbonyls. TC had no impact on plaques or insoluble Aβ, but both reduced Tris-buffered saline-soluble Aβ and phospho-c-Jun NH2-terminal kinase (JNK). Curcumin but not TC prevented Aβ aggregation. The TC metabolite was detected in brain and plasma from mice chronically fed the parent compound. These data indicate that the dienone bridge present in curcumin, but not in TC, is necessary to reduce plaque deposition and protein oxidation in an Alzheimer’s model. Nevertheless, TC did reduce neuroinflammation and soluble Aβ, effects that may be attributable to limiting JNK-mediated transcription. Because of its favorable safety profile and the involvement of misfolded proteins, oxidative damage, and inflammation in multiple chronic degenerative diseases, these data relating curcumin dosing to the blood and tissue levels required for efficacy should help translation efforts from multiple successful preclinical models.
Curcumin has been used in traditional Indian medicine for many centuries for its anti-inflammatory and anti-carcinogenic properties. There has been some promising research concerning curcumin as a safe therapeutic agent for many cancers, colorectal cancer being among them. This has been shown through research in cell cultures, animal models, and humans. At this time, it appears that curcumin’s anti-carcinogenic properties are most likely due to its effects on multiple molecular targets, such as nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) and activator protein 1 (AP-1). NF-κB and AP-1 are both major transcription factors that regulate inflammation and thus affect cell proliferation, differentiation and even apoptosis. Curcumin has also been shown to affect a variety of other key players involved in carcinogenesis, such as cyclooxygenase-2, matrix metallopeptidases 2 and 9 and tumor necrosis factor α induced vascular cell adhesion molecule, just to name a few. Although many molecular targets are involved, curcumin has been well tolerated in many studies: doses up to 8 g a day have been confirmed to be safe for humans. In this brief review, we will examine the current studies and literature and touch upon many molecular pathways affected by curcumin, and demonstrate the exciting possibility of curcumin as a chemopreventive agent for colorectal cancer.
Chemopreventive; Anti-inflammatory; Anti-carcinogenic; Curcumin; Turmeric; Cancer; Colorectal cancer
Curcumin, also known as diferuloylmethane, is derived from the plant Curcuma longa and is the active ingredient of the spice turmeric. The therapeutic activities of curcumin for a wide variety of diseases such as diabetes, allergies, arthritis and other chronic and inflammatory diseases have been known for a long time. More recently, curcumin’s therapeutic potential for preventing and treating various cancers is being recognized. As curcumin’s therapeutic promise is being explored more systematically in various diseases, it has become clear that, due to its increased bioavailability in the gastrointestinal tract, curcumin may be particularly suited to be developed to treat gastrointestinal diseases. This review summarizes some of the current literature of curcumin’s anti-inflammatory, anti-oxidant and anti-cancer potential in inflammatory bowel diseases, hepatic fibrosis and gastrointestinal cancers.
Curcumin; Inflammation; Cancer; Inflammatory bowel disease; Liver fibrosis; Gastrointestinal disease; Apoptosis
Allergic rhinitis is a common inflammatory condition affecting upper airways, nose, and eyes. Allergic rhinitis is a global health problem and is increasing in prevalence. Allergic rhinitis patients have often comorbidities asthma being one of the most common. Up to 40% of patients with allergic rhinitis have asthma and at least as many as 80% of asthma patients experience symptoms of allergic rhinitis. Patients with persistent allergic rhinitis should be evaluated for asthma, and patient with asthma should be properly evaluated for rhinitis. Allergic rhinitis and its impact on asthma update is proposing that treatments for one condition, one airway-one disease, may alleviate the coexisting conditions. Patients need early recognition, proper diagnosis, effective treatment, and follow-up. The treatment should be a combined strategy to treat the upper and lower airways for a good efficacy/safety ratio.
allergic rhinitis; ARIA; asthma; one airway; leukotriene receptor agonist
Curcumin is the active ingredient of the turmeric powder, a natural spice used for generations in traditional medicines. Curcumin’s broad spectrum of anti-oxidant, anti-carcinogenic, anti-mutagenic, and anti-inflammatory properties makes it particularly interesting for the development of pharmaceutical compounds. Due to curcumin’s various effects on the function of numerous unrelated membrane proteins, it has been suggested that it affects the properties of the bilayer itself. However, a detailed atomic-level study of the interaction of curcumin with membranes has not been attempted. A combination of solid-state NMR and differential scanning calorimetry experiments shows curcumin has a strong effect on membrane structure at low concentrations. Curcumin inserts deep into the membrane in a transbilayer orientation, anchored by hydrogen bonding to the phosphate group of lipids in a manner analogous to cholesterol. Like cholesterol, curcumin induces segmental ordering in the membrane. Analysis of the concentration dependence of the order parameter profile derived from NMR results suggests curcumin forms higher order oligomeric structures in the membrane that span and likely thin the bilayer. Curcumin promotes the formation of the highly curved inverted hexagonal phase which may influence exocytotic and membrane fusion processes within the cell. The experiments outlined here show promise for understanding the action of other drugs such as capsaicin in which drug-induced alterations of membrane structure have strong pharmacological effects.
Osteoporosis is a metabolic disease affecting both men and women especially in postmenopausal women. Curcumin possesses many medicinal properties. In this study, thirty two female Sprague-Dawley rats were used to determine the potential effect of curcumin in prevention of bone loss following ovariectomy. The animals were divided into Sham group, ovariectomised control, ovariectomised treated with curcumin 110 mg/kg and ovariectomised treated with Premarin 100 μg/kg. The treatments were given via daily oral gavages for 60 days. The structural parameters such as bone volume, trabecular number, trabecular thickness and trabecular separation were found to be deteriorated in ovariectomised rats compared to Sham group. Moreover, the reduced osteoblast count, the increased osteoclast count and increased eroded surface were found in ovariectomised groups. Treatment with curcumin was able to reverse all these ovariectomy-induced deteriorations. Curcumin treatment was as effective as Premarin in most parameters except the bone volume and eroded surface, which were better than Premarin. The high dose of curcumin treatment was not only able to reduce the osteoclast number but also increase the osteoblast count. Therefore, the potential effect of curcumin can be applied as an alternative to oestrogen for prevention of postmenopausal osteoporosis.
AIM: To investigate the signaling mechanism of anti-oxidative action by curcumin and its impact on glucose disposal.
METHODS: Male C57BL/6J mice were fed with either a normal diet (n = 10) or a high fat diet (HFD) (n = 20) to induce obesity and insulin resistance. After 16 wk, 10 HFD-fed mice were further treated with daily curcumin oral gavage at the dose of 50 mg/kg body weight (BW) (HFD + curcumin group). After 15 d of the curcumin supplementation, an intraperitoneal glucose tolerance test was performed. Fasting blood samples were also collected for insulin and glucose measurements. Insulin-sensitive tissues, including muscle, adipose tissue and the liver, were isolated for the assessments of malondialdehyde (MDA), reactive oxygen species (ROS) and nuclear factor erythroid-2-related factor-2 (Nrf2) signaling.
RESULTS: We show here that in a HFD mouse model, short-term curcumin gavage attenuated glucose intolerance without affecting HFD-induced BW gain. Curcumin also attenuated HFD-induced elevations of MDA and ROS in the skeletal muscle, particularly in its mitochondrial fraction, but it had no such an effect in either adipose tissue or the liver of HFD-fed mice. Correspondingly, in skeletal muscle, the levels of total or nuclear content of Nrf2, as well as its downstream target, heme oxygenase-1, were reduced by HFD-feeding. Curcumin intervention dramatically reversed these defects in Nrf2 signaling. Further analysis of the relationship of oxidative stress with glucose level by a regression analysis showed a positive and significant correlation between the area under the curve of a glucose tolerance test with MDA levels either in muscle or muscular mitochondria.
CONCLUSION: These findings suggest that the short-term treatment of curcumin in HFD-fed mice effectively ameliorates muscular oxidative stress by activating Nrf2 function that is a novel mechanism for its effect in improving glucose intolerance.
Oxidative stress; Insulin resistance; Glucose tolerance; Nuclear factor erythroid-2-related factor-2; Curcumin; Mitochondria
Bronchial asthma is recognized as a highly prevalent health problem in the developed and developing world with significant social and economic consequences. Increased asthma severity is not only associated with enhanced recurrent hospitalization and mortality but also with higher social costs. The pathogenetic background of allergic-atopic bronchial asthma is characterized by airway inflammation with infiltration of several cells (mast cells, basophils, eosinophils, monocytes, and T-helper (Th)2 lymphocytes). However, in atopic asthma the trigger factors for acute attacks and chronic worsening of bronchial inflammation are aeroallergens released by pollens, dermatophagoides, and pets, which are able to induce an immune response by interaction with IgE antibodies. Currently anti-inflammatory treatments are effective for most asthma patients, but there are asthmatic subjects whose disease is not completely controlled by inhaled or systemic corticosteroids and who account for a significant portion of the healthcare costs of asthma. A novel therapeutic approach to asthma and other allergic respiratory diseases involves interference in the action of IgE, and this antibody has been viewed as a target for novel immunological drug development in asthma. Omalizumab is a humanized recombinant monoclonal anti-IgE antibody approved for treatment of moderate to severe IgE-mediated (allergic) asthma. This non-anaphylactogenic anti-IgE antibody inhibits IgE functions, blocking free serum IgE and inhibiting their binding to cellular receptors. By reducing serum IgE levels and IgE receptor expression on inflammatory cells in the context of allergic cascade, omalizumab represents a new class of mast cells stabilizing drugs; it is a novel approach to the treatment of atopic asthma. Omalizumab therapy is well tolerated and significantly improves symptoms and disease control, reducing asthma exacerbations and the need to use high dosage of inhaled corticosteroids. Moreover, omalizumab improves quality of life of patients with severe persistent allergic asthma which is inadequately controlled by currently available asthma medications. In conclusion omalizumab may fulfil an important need in patients with moderate to severe asthma.
airway hyper-reactivity; asthma; allergic respiratory diseases; atopic respiratory diseases; anti-IgE therapy; hypersensitivity; monoclonal anti-IgE antibody; omalizumab
Sepsis, severe injury, and cancer are associated with loss of muscle mass. Muscle wasting in these conditions is mainly caused by increased proteolysis, at least in part regulated by NF-kB. Despite recent progress in the understanding of mediators and mechanisms involved in muscle wasting, effective and universally accepted treatments by which muscle atrophy can be prevented or reversed are still lacking. Here, we review recent evidence suggesting that curcumin (diferuloylmethane), a component of the spice turmeric, may prevent loss of muscle mass during sepsis and endotoxemia and may stimulate muscle regeneration after traumatic injury. Curcumin has been part of the traditional Asian medicine for centuries, mainly because of its anti-inflammatory properties. Studies suggest that inhibition of NF-kB is one of the mechanisms by which curcumin exerts its ant-inflammatory effects. Curcumin is easily accessible, inexpensive, and non-toxic even at high doses, and may therefore offer an important treatment modality in muscle wasting and injury. It should be noted, however, that the muscle-sparing effects of curcumin are not universally accepted, and more studies are therefore needed to further test the role of curcumin in the prevention and treatment of muscle wasting.
Muscle atrophy; proteolysis; NF-kB; catabolic
This paper discusses the effects of curcumin on patients with Alzheimer's disease (AD). Curcumin (Turmeric), an ancient Indian herb used in curry powder, has been extensively studied in modern medicine and Indian systems of medicine for the treatment of various medical conditions, including cystic fibrosis, haemorrhoids, gastric ulcer, colon cancer, breast cancer, atherosclerosis, liver diseases and arthritis. It has been used in various types of treatments for dementia and traumatic brain injury. Curcumin also has a potential role in the prevention and treatment of AD. Curcumin as an antioxidant, anti-inflammatory and lipophilic action improves the cognitive functions in patients with AD. A growing body of evidence indicates that oxidative stress, free radicals, beta amyloid, cerebral deregulation caused by bio-metal toxicity and abnormal inflammatory reactions contribute to the key event in Alzheimer's disease pathology. Due to various effects of curcumin, such as decreased Beta-amyloid plaques, delayed degradation of neurons, metal-chelation, anti-inflammatory, antioxidant and decreased microglia formation, the overall memory in patients with AD has improved. This paper reviews the various mechanisms of actions of curcumin in AD and pathology.
Alternative approach to Alzheimer's; beta amyloid plaques; curcumin; curcumin and dementia; epidemiology; turmeric