Turmeric (Curcuma longa) is a rhizomatic herbaceous plant belonging to the ginger family, Zingiberaceae. It is native to southwest India (also cultivated in Bangladesh, Pakistan, and most of Southeast Asia), where plants are gathered annually for their rhizomes and propagated from some of those same rhizomes in the following season.
When not used fresh (like ginger), the rhizomes are boiled for about 30–45 minutes then dried in hot ovens, after which they are ground into a deep-orange-yellow powder commonly used as a spice in various forms of curries, as a dye, and to impart color to mustard condiments.
One active ingredient in turmeric is curcumin (perhaps the most well-known as a result of the proliferation of curcumin supplements over the last two decades), which has an earthy, mildly bitter, and peppery flavor.
The most important chemical components of turmeric are a group of compounds called curcuminoids, which include curcumin (diferuloylmethane), demethoxycurcumin, and bisdemethoxycurcumin. The best-studied compound is curcumin, which constitutes between 3-6% (on average) of powdered turmeric. In addition, other important volatile oils include turmerone, atlantone, and zingiberene.
In India, turmeric has been used as a remedy for stomach and liver ailments, as well as topically to heal sores, basically for its supposed antimicrobial property.
The active compound curcumin is believed to have a wide range of biological effects including anti-inflammatory, antioxidant, antitumor, antibacterial, and antiviral activities, which have shown a lot of potential for use in clinical medicine.
In this review of the literature on curcumin, I am looking at the anti-inflammatory effects, diabetes prevention, anti-cancer effects, with a section devoted to prostate cancer, treatment and prevention of neurodegenerative disorders, and finally, its use of psychological disorders.
NOTE: One of the well-recognized issues with turmeric/curcumin as medicine is its poor bioavailability through oral administration. There is considerable effort dedicated to finding a way to make curcumin/turmeric more bioavailable, including lipid delivery systems, self-microemulsifying drug delivery system (SMEDDS), nanoparticulate delivery systems. and many others - see Advanced Drug Delivery Systems of Curcumin for Cancer Chemoprevention for a good overview.
If you choose to take turmeric/curcumin (traditionally, curcumin has been much more widely recognized, but newer research suggests the whole herb has more advantages), look for a product that contains piperine or Bioperine (black pepper extract), which inhibits the enzymes that break down most supplements and medicines in the gut.
Contents:
1. ANTI-INFLAMMATORY EFFECTS OF TURMERIC
2. TREATING AND/OR PREVENTING DIABETES
3. ANTI-CANCER USES FOR CURCUMIN
4. TURMERIC/CURCUMIN and PROSTATE CANCER
5. CURCUMIN FOR NEURODEGENERATIVE DISORDERS
6. CURCUMIN/TURMERIC AND PSYCHOLOGICAL DISORDERS
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The ability to reduce inflammation may one of the most widely studied actions of turmeric/curcumin.
Curcumin: An Anti-Inflammatory Molecule from a Curry Spice on the Path to Cancer Treatment
Purusotam Basnet and Natasa Skalko-Basnet
Molecules (2011): 16; 4567-4598; DOI: 10.3390/molecules16064567
Abstract: Oxidative damage and inflammation have been pointed out in preclinical studies as the root cause of cancer and other chronic diseases such as diabetes, hypertension, Alzheimer’s disease, etc. Epidemiological and clinical studies have suggested that cancer could be prevented or significantly reduced by treatment with anti-oxidant and anti-inflammatory drugs, therefore, curcumin, a principal component of turmeric (a curry spice) showing strong anti-oxidant and anti-inflammatory activities, might be a potential candidate for the prevention and/or treatment of cancer and other chronic diseases. However, curcumin, a highly pleiotropic molecule with an excellent safety profile targeting multiple diseases with strong evidence on the molecular level, could not achieve its optimum therapeutic outcome in past clinical trials, largely due to its low solubility and poor bioavailability. Curcumin can be developed as a therapeutic drug through improvement in formulation properties or delivery systems, enabling its enhanced absorption and cellular uptake. This review mainly focuses on the anti-inflammatory potential of curcumin and recent developments in dosage form and nanoparticulate delivery systems with the possibilities of therapeutic application of curcumin for the prevention and/or treatment of cancer.
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Antioxidant and Anti-Inflammatory Properties of Curcumin
Venugopal P. Menon and Adluri Ram Sudheer
Chapter: The Molecular Targets and Therapeutic Uses of Curcumin in Health and Disease
Volume 595 of the series Advances in Experimental Medicine and Biology; pp 105-125
Abstract: Curcumin, a yellow pigment from Curcuma longa, is a major component of turmeric and is commonly used as a spice and food-coloring agent. It is also used as a cosmetic and in some medical preparations. The desirable preventive or putative therapeutic properties of curcumin have also been considered to be associated with its antioxidant and anti-inflammatory properties. Because free-radical-mediated peroxidation of membrane lipids and oxidative damage of DNAand proteins are believed to be associated with a variety of chronic pathological complications such as cancer, atherosclerosis, and neurodegenerative diseases, curcumin is thought to play a vital role against these pathological conditions.
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Curcumin-free turmeric exhibits anti-inflammatory and anticancer activities: Identification of novel components of turmeric
Bharat B. Aggarwal, Wei Yuan, Shiyou Li, and Subash C. Gupta
Molecular nutrition & food research (2013): 57; 1529–1542. DOI: 10.1002/mnfr.201200838
Abstract: Turmeric, a dried powder derived from the rhizome of Curcuma longa, has been used for centuries in certain parts of the world and has been linked to numerous biological activities including antioxidant, anti-inflammatory, anticancer, antigrowth, anti-arthritic, anti-atherosclerotic, antidepressant, anti-aging, antidiabetic, antimicrobial, wound healing, andmemory-enhancing activities. One component of turmeric is curcumin, which has been extensively studied, as indicated bymore than 5600 citations,most of which have appeared within the past decade. Recent research has identified numerous chemical entities from turmeric other than curcumin. It is unclear whether all of the activities ascribed to turmeric are due to curcumin or whether other compounds in turmeric can manifest these activities uniquely, additively, or synergistically with curcumin. However, studies have indicated that turmeric oil, present in turmeric, can enhance the bioavailability of curcumin. Studies over the past decade have indicated that curcumin-free turmeric (CFT) components possess numerous biological activities including anti-inflammatory, anticancer, and antidiabetic activities. Elemene derived from turmeric is approved in China for the treatment of cancer. The current review focuses on the anticancer and anti-inflammatory activities exhibited by CFT and by some individual components of turmeric, including turmerin, turmerone, elemene, furanodiene, curdione, bisacurone, cyclocurcumin, calebin A, and germacrone.
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The effect of turmeric (Curcumin) supplementation on cytokine and inflammatory marker responses following 2 hours of endurance cycling
Joseph N Sciberras, Stuart DR Galloway, Anthony Fenech, Godfrey Grech, Claude Farrugia, Deborah Duca, and Janet Mifsud
Journal of the International Society of Sports Nutrition (2015); 12:5. DOI: 10.1186/s12970-014-0066-3
Abstract
Background: Endurance exercise induces IL-6 production from myocytes that is thought to impair intracellular defence mechanisms. Curcumin inhibits NF-κB and activator protein 1, responsible for cytokine transcription, in cell lines. The aim of this study was to investigate the effect of curcumin supplementation on the cytokine and stress responses following 2 h of cycling.
Methods: Eleven male recreational athletes (35.5 ± 5.7 years; Wmax 275 ± 6 W; 87.2 ± 10.3 kg) consuming a low carbohydrate diet of 2.3 ± 0.2 g/kg/day underwent three double blind trials with curcumin supplementation, placebo supplementation, and no supplementation (control) to observe the response of serum interleukins (IL-6, IL1-RA, IL-10), cortisol, c-reactive protein (CRP), and subjective assessment of training stress. Exercise was set at 95% lactate threshold (54 ± 7% Wmax) to ensure that all athletes completed the trial protocol.
Results: The trial protocol elicted a rise in IL-6 and IL1-RA, but not IL-10. The supplementation regimen failed to produce statistically significant results when compared to placebo and control. IL-6 serum concentrations one hour following exercise were (Median (IQR): 2.0 (1.8-3.6) Curcumin; 4.8 (2.1-7.3) Placebo; 3.5 (1.9-7.7) Control). Differences between supplementation and placebo failed to reach statistical significance (p = 0.18) with the median test. Repeated measures ANOVA time-trial interaction was at p = 0.06 between curcumin supplementation and placebo. A positive correlation (p = 0.02) between absolute exercise intensity and 1 h post-exercise for IL-6 concentration was observed. Participants reported “better than usual” scores in the subjective assessment of psychological stress when supplementing with curcumin, indicating that they felt less stressed during training days (p = 0.04) compared to placebo even though there was no difference in RPE during any of the training days or trials.
Conclusion: The limitations of the current regimen and trial involved a number of factors including sample size, mode of exercise, intensity of exercise, and dose of curcumin. Nevertheless these results provide insight for future studies with larger samples, and multiple curcumin dosages to investigate if different curcumin regimens can lead to statistically different interleukin levels when compared to a control and placebo.
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Effect on Pro-inflammatory and Antioxidant Genes and Bioavailable Distribution of Whole Turmeric vs Curcumin: Similar Root but Different Effects
Robert CG Martin, Harini S Aiyer, Daniel Malik, and Yan Li
Food Chemistry Toxicology (2012, Feb); 50(2): 227–231. Published online 2011 Nov 4. DOI: 10.1016/j.fct.2011.10.070
Abstract: Curcuma longa is a perennial member of the Zingiberaceae family, and cultivated mainly in India, and Southeast Asia. The hypothesis for this study is that turmeric will have distinctive effects from curcumin due to the presence of other bioactive compounds. Thirty Eight-week old Sprague-Dawley rats were separated into 3 oral feeding groups. Group 1, standard rat chow, Control diet - AIN 93M, group 2 Curcumin- 700 ppm or 0.7 g/kg diet, and group 3 - Turmeric -14,000 ppm or 14 g/kg diet for a total of 3 weeks. One group of rats were feed all three diets only and another group underwent esophagoduodenal anastomosis to evaluate the effects of bioavailability. Curcumin diet did not increase the transcription of mRNA of TNF-alpha, IL-6, iNOS and COX-2. The average fold change in the mRNAs level was not significant. Whereas turmeric diet increases the levels of IL-6 (1.9 fold, p=0.05) iNOS (4.39 fold, p=0.02), IL-8 (3.11 fold, p=0.04) and COX-2 (2.02 fold, p=0.05), suggesting that turmeric either was more bioavailabile or had more affect on pro-inflammatory genes compare to curcumin diet. We have demonstrated the molecular effects of curcumin and turmeric in the role as an anti-inflammatory therapy. However, significant bioavailable differences do occur and must be considered in further chemopreventative investigative trials the setting of reflux esophagitis, Barrett’s esophagus, and other upper gastrointestinal cancers.
Food Chemistry Toxicology (2012, Feb); 50(2): 227–231. Published online 2011 Nov 4. DOI: 10.1016/j.fct.2011.10.070
Abstract: Curcuma longa is a perennial member of the Zingiberaceae family, and cultivated mainly in India, and Southeast Asia. The hypothesis for this study is that turmeric will have distinctive effects from curcumin due to the presence of other bioactive compounds. Thirty Eight-week old Sprague-Dawley rats were separated into 3 oral feeding groups. Group 1, standard rat chow, Control diet - AIN 93M, group 2 Curcumin- 700 ppm or 0.7 g/kg diet, and group 3 - Turmeric -14,000 ppm or 14 g/kg diet for a total of 3 weeks. One group of rats were feed all three diets only and another group underwent esophagoduodenal anastomosis to evaluate the effects of bioavailability. Curcumin diet did not increase the transcription of mRNA of TNF-alpha, IL-6, iNOS and COX-2. The average fold change in the mRNAs level was not significant. Whereas turmeric diet increases the levels of IL-6 (1.9 fold, p=0.05) iNOS (4.39 fold, p=0.02), IL-8 (3.11 fold, p=0.04) and COX-2 (2.02 fold, p=0.05), suggesting that turmeric either was more bioavailabile or had more affect on pro-inflammatory genes compare to curcumin diet. We have demonstrated the molecular effects of curcumin and turmeric in the role as an anti-inflammatory therapy. However, significant bioavailable differences do occur and must be considered in further chemopreventative investigative trials the setting of reflux esophagitis, Barrett’s esophagus, and other upper gastrointestinal cancers.
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Anti-inflammatory and Anti-oxidant Properties of Curcuma longa (Turmeric) Versus Zingiber officinale (Ginger) Rhizomes in Rat Adjuvant-Induced Arthritis
Gamal Ramadan, Mohammed Ali Al-Kahtani, and Wael Mohamed El-Sayed
Inflammation (2011, Aug); 34(4); 291-301. DOI: 10.1007/s10753-010-9278-0
Anti-inflammatory and Anti-oxidant Properties of Curcuma longa (Turmeric) Versus Zingiber officinale (Ginger) Rhizomes in Rat Adjuvant-Induced Arthritis Gamal Ramadan,1,2,3 Mohammed Ali Al-Kahtani,1 and Wael Mohamed El-Sayed1,2 Abstract—Turmeric (rich in curcuminoids) and ginger (rich in gingerols and shogaols) rhizomes have been widely used as dietary spices and to treat different diseases in Ayurveda/Chinese medicine since antiquity. Here, we compared the anti-inflammatory/anti-oxidant activity of these two plants in rat adjuvant-induced arthritis (AIA). Both plants (at dose 200 mg/kg body weight) signi- ficantly suppressed (but with different degrees) the incidence and severity of arthritis by increasing/ decreasing the production of anti-inflammatory/pro-inflammatory cytokines, respectively, and activating the anti-oxidant defence system. The anti-arthritic activity of turmeric exceeded that of ginger and indomethacin (a non-steroidal anti-inflammatory drug), especially when the treatment started from the day of arthritis induction. The percentage of disease recovery was 4.6–8.3% and 10.2% more in turmeric compared with ginger and indomethacin (P<0.05), respectively. The present study proves the anti-inflammatory/anti-oxidant activity of turmeric over ginger and indomethacin, which may have beneficial effects against rheumatoid arthritis onset/progression as shown in AIA rat model.
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2. TREATING AND/OR PREVENTING DIABETES
One of the lesser known uses of turmeric/curcumin is in the treatment and prevention of diabetes.
Curcuminoids and Sesquiterpenoids in Turmeric (Curcuma longa L.) Suppress an Increase in Blood Glucose Level in Type 2 Diabetic KK-Ay Mice
Tozo Nishoyama, Tatsumasa Mae, Hideyuki Kishida, Misuzu Tsukagawa, Yoshihiro Mimaki, Minpei Kuroda, Yutaka Sashida, Kazuma Takahashi, Teruo Kawada, Kaku Nakagawa, and Mikio Kitahara
Journal of Agricultural Food Chemistry (2005): 53(4); 959−963. DOI: 10.1021/jf0483873
Abstract: Turmeric, the rhizome of Curcuma longa L., has a wide range of effects on human health. The chemistry includes curcuminoids and sesquiterpenoids as components, which are known to have antioxidative, anticarcinogenic, and antiinflammatory activities. In this study, we investigated the effects of three turmeric extracts on blood glucose levels in type 2 diabetic KK-Ay mice (6 weeks old, n ) 5/group). These turmeric extracts were obtained by ethanol extraction (E-ext) to yield both curcuminoids and sesquiterpenoids, hexane extraction (H-ext) to yield sesquiterpenoids, and ethanol extraction from hexane-extraction residue (HE-ext) to yield curcuminoids. The control group was fed a basal diet, while the other groups were fed a diet containing 0.1 or 0.5 g of H-ext or HE-ext/100 g of diet or 0.2 or 1.0 g of E-ext/100 g of diet for 4 weeks. Although blood glucose levels in the control group significantly increased (P < 0.01) after 4 weeks, feeding of 0.2 or 1.0 g of E-ext, 0.5 g of H-ext, and 0.5 g of HE-ext/100 g of diet suppressed the significant increase in blood glucose levels. Furthermore, E-ext stimulated human adipocyte differentiation, and these turmeric extracts had human peroxisome proliferator-activated receptor-γ (PPAR-γ) ligand-binding activity in a GAL4- PPAR-γ chimera assay. Also, curcumin, demethoxycurcumin, bisdemethoxycurcumin, and arturmerone had PPAR-γ ligand-binding activity. These results indicate that both curcuminoids and sesquiterpenoids in turmeric exhibit hypoglycemic effects via PPAR-γ activation as one of the mechanisms, and suggest that E-ext including curcuminoids and sesquiterpenoids has the additive or synergistic effects of both components.
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Turmerin, the antioxidant protein from turmeric (Curcuma longa) exhibits antihyperglycaemic effects
P.C. Lekshmi, Ranjith Arimboor, K.G. Raghu & A. Nirmala Menon
Natural Product Research (2012): 26(17); 1654-1658. DOI: 10.1080/14786419.2011.589386
Abstract: A wide range of proteinaceous inhibitors are present in plants to protect themselves from hydrolytic enzymes. In this study, turmerin, a water-soluble peptide in turmeric rhizomes, was evaluated for its inhibitory potential against glucosidase and its antioxidant (AO) capacity. Turmerin inhibited -amylase and -glucosidase activities with IC50 values 31 and 192 mg mL1, respectively. Under the experimental conditions, those values for a standard glucosidase inhibitor, acarbose, were 81 and 296 mg mL1, respectively. The AO capacity of turmerin was evaluated using in vitro assay systems. Turmerin showed good DPPH (IC50 ¼ 29 mg mL1 ) and superoxide (IC50 ¼ 48 mg mL1) and moderate ABTS (IC50 ¼ 83 mg mL1 ) radical scavenging and Fe(II) chelation (IC50 ¼ 101 mg mL1) capacities. The inhibitory potential showed by turmerin against enzymes linked to type 2 diabetes, as well as its moderate AO capacity, could rationalise the traditional usage of turmeric rhizome preparations against diabetes.
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Oral supplementation of turmeric attenuates proteinuria, transforming growth factor-b and interleukin-8 levels in patients with overt type 2 diabetic nephropathy: A randomized, double-blind and placebo-controlled study
Parviz Khajehdehi, Maryam Pakfetrat, Katayoun Javidnia, Fariborz Azadi, Leila Malekmakan, Mahshid Hashemi Nasab & Gholamreza Dehghanzadeh
Scandinavian Journal of Urology and Nephrology (2011); 45: 365–370. DOI: 10.3109/00365599.2011.585622
Abstract
Objective. End-stage renal disease (ESRD) due to type 2 diabetic nephropathy is a very common condition which is increasing in prevalence, and is associated with high global levels of mortality and morbidity. Both proteinuria and transforming growth factor-b (TGF-b) may contribute to the development of ESRD in patients with diabetic nephropathy. Experimental studies indicate that turmeric improves diabetic nephropathy by suppressing TGF-b. Therefore, this study investigated the effects of turmeric on serum and urinary TGF-b, interleukin-8 (IL-8) and tumour necrosis factor-a (TNF-a), as well as proteinuria, in patients with overt type 2 diabetic nephropathy.
Material and methods. A randomized, double-blind and placebocontrolled study was carried out in the Diabetes Clinic of the Outpatient Department of Shiraz University of Medical Sciences on 40 patients with overt type 2 diabetic nephropathy, randomized into a trial group (n = 20) and a control group (n = 20). Each patient in the trial group received one capsule with each meal containing 500 mg turmeric, of which 22.1 mg was the active ingredient curcumin (three capsules daily) for 2 months. The control group received three capsules identical in colour and size containing starch for the same 2 months.
Results. Serum levels of TGF-b and IL-8 and urinary protein excretion and IL-8 decreased significantly comparing the pre- and post-turmeric supplementation values. No adverse effects related to turmeric supplementation were observed during the trial.
Conclusion. Short-term turmeric supplementation can attenuate proteinuria, TGF-b and IL-8 in patients with overt type 2 diabetic nephropathy and can be administered as a safe adjuvant therapy for these patients.
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Curcumin, the Active Principle of Turmeric (Curcuma longa), Amerliorates Diabetic Nephropathy in Rats
Sameer Sharma, Shrinivas K Kulkarni and Kanwaljit Chopra
Clinical and Experimental Pharmacology and Physiology (2006); 33(10): 940–945. DOI: 10.1111/j.1440-1681.2006.04468.x
Summary
1. Chronic hyperglycaemia in diabetes leads to the overproduction of free radicals and evidence is increasing that these contribute to the development of diabetic nephropathy. Among the spices, turmeric (Curcuma longa) is used as a flavouring and colouring agent in the indian diet every day and is known to possess anti-oxidant properties. The present study was designed to examine the effect of curcumin, a yellow pigment of turmeric, on renal function and oxidative stress in streptozotocin (STZ)-induced diabetic rats.
2. Diabetes was induced by a single intraperitoneal injection of STZ (65 mg/kg) in rats. Four weeks after STZ injection, rats were divided into four groups, namely control rats, diabetic rats and diabetic rats treated with curcumin (15 and 30 mg/kg, p.o.) for 2 weeks. Renal function was assessed by creatinine, blood urea nitrogen, creatinine and urea clearance and urine albumin excretion. Oxidative stress was measured by renal malonaldehyde, reduced glutathione and the anti-oxidant enzymes superoxide dismutase and catalase.
3. Streptozotocin-injected rats showed significant increases in blood glucose, polyuria and a decrease in bodyweight compared with age-matched control rats. After 6 weeks, diabetic rats also exhibited renal dysfunction, as evidenced by reduced creatinine and urea clearance and proteinuria, along with a marked increase in oxidative stress, as determined by lipid peroxidation and activities of key anti-oxidant enzymes. Chronic treatment with curcumin significantly attenuated both renal dysfunction and oxidative stress in diabetic rats.
4. These results provide confirmatory evidence of oxidative stress in diabetic nephropathy and point towards the possible anti-oxidative mechanism being responsible for the nephroprotective action of curcumin.
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3. ANTI-CANCER USES FOR CURCUMIN
There has likely been more money invested in how curcumin/turmeric can combat various kinds of cancer than in any other research area. With good reason., as many of these studies show. I'm going to begin with some general studies, then move to the more specific, with a subjection here just for prostate cancer.
How Curcumin Protects Against Cancer
J. Everett Borger
Life Extension Magazine (2011, Mar)
Abstract:
According to the American Cancer Society [1], one out of every three women in the United
States risks developing some form of cancer over the course of their lives. For men, that
number rises to one in two. Since cancer is an age-related disease, the risk of diagnosis
increases the longer one lives, making it the second leading cause of death in this country [2,3].
These data underscore a stark reality. When it comes to cancer prevention, the medical
establishment and drug company profiteers remain grossly negligent in protecting the public.
The result is countless avoidable cancer deaths each year. There is an urgent need to provide
aging individuals with validated interventions to target cancer’s multiple causative factors before they take hold.
Among the most compelling and underrecognized of these is curcumin. In contrast to mainstream oncology’s focus on single agent toxic treatments, curcumin has emerged as a potent multimodal cancer-preventing agent, with 240 published studies appearing in the global scientific literature in the past year alone.
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Curcumin and Cancer Cells: How Many Ways Can Curry Kill Tumor Cells Selectively?
Jayaraj Ravindran, Sahdeo Prasad, and Bharat B. Aggarwal
The AAPS Journal (2009, Sep): 11(3); 495-510. DOI: 10.1208/s12248-009-9128-x
Abstract. Cancer is a hyperproliferative disorder that is usually treated by chemotherapeutic agents that are toxic not only to tumor cells but also to normal cells, so these agents produce major side effects. In addition, these agents are highly expensive and thus not affordable for most. Moreover, such agents cannot be used for cancer prevention. Traditional medicines are generally free of the deleterious side effects and usually inexpensive. Curcumin, a component of turmeric (Curcuma longa), is one such agent that is safe, affordable, and efficacious. How curcumin kills tumor cells is the focus of this review. We show that curcumin modulates growth of tumor cells through regulation of multiple cell signaling pathways including cell proliferation pathway (cyclin D1, c-myc), cell survival pathway (Bcl-2, Bcl-xL, cFLIP, XIAP, c-IAP1), caspase activation pathway (caspase-8, 3, 9), tumor suppressor pathway (p53, p21) death receptor pathway (DR4, DR5), mitochondrial pathways, and protein kinase pathway (JNK, Akt, and AMPK). How curcumin selectively kills tumor cells, and not normal cells, is also described in detail.
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Sita Aggarwal, Haruyo Ichikawa, Yasunari Takada, Santosh K. Sandur, Shishir Shishodia,
and Bharat B. Aggarwal
Molecular Pharmacology (2006): 69(1); 195–206. DOI: 10.1124/mol.105.017400
Abstract: Curcumin (diferuloylmethane), an anti-inflammatory agent used in traditional medicine, has been shown to suppress cellular transformation, proliferation, invasion, angiogenesis, and metastasis through a mechanism not fully understood. Because several genes that mediate these processes are regulated by nuclear factor- B (NF- B), we have postulated that curcumin mediates its activity by modulating NF- B activation. Indeed, our laboratory has shown previously that curcumin can suppress NF- B activation induced by a variety of agents (J Biol Chem 270:24995–50000, 1995) . In the present study, we investigated the mechanism by which curcumin manifests its effect on NF- B and NF- B-regulated gene expression. Screening of 20 different analogs of curcumin showed that curcumin was the most potent analog in suppressing the tumor necrosis factor (TNF)-induced NF- B activation. Curcumin inhibited TNF-induced NF- B-dependent reporter gene expression in a dose-dependent manner. Curcumin also suppressed NF- B reporter activity induced by tumor necrosis factor receptor (TNFR)1, TNFR2, NF- B-inducing kinase, I B kinase complex (IKK), and the p65 subunit of NF- B. Such TNFinduced NF- B-regulated gene products involved in cellular proliferation [cyclooxygenase-2 (COX-2), cyclin D1, and c-myc], antiapoptosis [inhibitor of apoptosis protein (IAP)1, IAP2, X-chromosome-linked IAP, Bcl-2, Bcl-xL, Bfl-1/A1, TNF receptor-associated factor 1, and cellular Fas-associated death domain protein-like interleukin-1 -converting enzyme inhibitory protein-like inhibitory protein], and metastasis (vascular endothelial growth factor, matrix metalloproteinase-9, and intercellular adhesion molecule-1) were also down-regulated by curcumin. COX-2 promoter activity induced by TNF was abrogated by curcumin. We found that curcumin suppressed TNFinduced nuclear translocation of p65, which corresponded with the sequential suppression of I B kinase activity, I B phosphorylation, I B degradation, p65 phosphorylation, p65 nuclear translocation, and p65 acetylation. Curcumin also inhibited TNF-induced Akt activation and its association with IKK. Glutathione and dithiothreitol reversed the effect of curcumin on TNF-induced NF- B activation. Overall, our results indicated that curcumin inhibits NF- B activation and NF- B-regulated gene expression through inhibition of IKK and Akt activation.
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Chemopreventive activity of turmeric essential oil and possible mechanisms of action.
Liju VB, Jeena K, Kuttan R.
Asian Pacific Journal of Cancer Prevention (2014): 15(16); 6575-6580.
Abstract: This study aimed to evaluate the antimutagenic and anticarcinogenic activity of turmeric essential oil as well as to establish biochemical mechanisms of action. Antimutagenicity testing was accomplished using strains and known mutagens with and without microsomal activation. Anticarcinogenic activity was assessed by topical application of 7, 12-dimethylbenz[a]anthracene (DMBA) as initiator and 1% croton oil as promoter for the induction of skin papillomas in mice. Inhibition of p450 enzymes by TEO was studied using various resorufins and aminopyrene as substrate. Turmeric essential oil (TEO) showed significant antimutagenic activity (p<0.001) against direct acting mutagens such as sodium azide (NaN3), 4-nitro-O-phenylenediamine (NPD) and N-methyl- N-nitro N'nitrosoguanine (MNNG). TEO was found to have significant antimutagenic effect (>90%) against mutagen needing metabolic activation such as 2-acetamidoflourene (2-AAF). The study also revealed that TEO significantly inhibited (p<0.001) the mutagenicity induced by tobacco extract to Salmonella TA 102 strain. DMBA and croton oil induced papilloma development in mice was found to be delayed and prevented significantly by TEO application. Moreover TEO significantly (P<0.001) inhibited isoforms of cytochrome p450 (CYP1A1, CYP1A2, CYP2B1/2, CYP2A, CYP2B and CYP3A) enzymes in vitro, which are involved in the activation of carcinogens. Results indicated that TEO is antimutagenic and anticarcinogenic and inhibition of enzymes (p450) involved in the activation of carcinogen is one of its mechanisms of action.
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Turmeric (Curcuma longa) inhibits inflammatory nuclear factor (NF)-κB and NF-κB-regulated gene products and induces death receptors leading to suppressed proliferation, induced chemosensitization, and suppressed osteoclastogenesis
Ji H. Kim, Subash C. Gupta, Byoungduck Park, Vivek R. Yadav, and Bharat B. Aggarwal
Molecular Nutrition & Food Research (2012, Mar): 56(3); 454–465. Published online 2011 Dec 7. DOI: 10.1002/mnfr.201100270
Abstract
Scope: The incidence of cancer is significantly lower in regions where turmeric is heavily consumed. Whether lower cancer incidence is due to turmeric was investigated by examining its effects on tumor cell proliferation, on pro-inflammatory transcription factors NF-κB and STAT3, and on associated gene products.
Methods and results: Cell proliferation and cell cytotoxicity were measured by the MTT method, NF-κB activity by EMSA, protein expression by Western blot analysis, ROS generation by FACS analysis, and osteoclastogenesis by TRAP assay. Turmeric inhibited NF-κB activation and down-regulated NF-κB-regulated gene products linked to survival (Bcl-2, cFLIP, XIAP, and cIAP1), proliferation (cyclin D1 and c-Myc), and metastasis (CXCR4) of cancer cells. The spice suppressed the activation of STAT3, and induced the death receptors (DR)4 and DR5. Turmeric enhanced the production of ROS, and suppressed the growth of tumor cell lines. Furthermore, turmeric sensitized the tumor cells to chemotherapeutic agents capecitabine and taxol. Turmeric was found to be more potent than pure curcumin for cell growth inhibition. Turmeric also inhibited NF-κB activation induced by RANKL that correlated with the suppression of osteoclastogenesis.
Conclusion: Our results indicate that turmeric can effectively block the proliferation of tumor cells through the suppression of NF-κB and STAT3 pathways.
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Bioactivity of Turmeric-Derived Curcuminoids and Related Metabolites in Breast Cancer
Laura E. Wright, Jen B. Frye, Bhavana Gorti, Barbara N. Timmermann, and Janet L. Funk
Current Pharmaceutical Design (2013): 19(34); 6218–6225.
Abstract: While the chemotherapeutic effect of curcumin, one of three major curcuminoids derived from turmeric, has been reported, largely unexplored are the effects of complex turmeric extracts more analogous to traditional medicinal preparations, as well as the relative importance of the three curcuminoids and their metabolites as anti-cancer agents. These studies document the pharmacodynamic effects of chemically-complex turmeric extracts relative to curcuminoids on human breast cancer cell growth and tumor cell secretion of parathyroid hormone-related protein (PTHrP), an important driver of cancer bone metastasis. Finally, relative effects of structurally-related metabolites of curcuminoids were assessed on the same endpoints. We report that 3 curcuminoid-containing turmeric extracts differing with respect to the inclusion of additional naturally occurring chemicals (essential oils and/or polar compounds) were equipotent in inhibiting human breast cancer MDA-MB-231 cell growth (IC50=10–16μg/mL) and secretion of osteolytic PTHrP (IC50=2–3μg/mL) when concentrations were normalized to curcuminoid content. Moreover, these effects were curcuminoid-specific, as botanically-related gingerol containing extracts had no effect. While curcumin and bis-demethoxycurcumin were equipotent to each other and to the naturally occurring curcuminoid mixture (IC50=58 μM), demethoxycurcumin was without effect on cell growth. However, each of the individual curcuminoids inhibited PTHrP secretion (IC50=22–31μM) to the same degree as the curcuminoid mixture (IC50=16 μM). Degradative curcuminoid metabolites (vanillin and ferulic acid) did not inhibit cell growth or PTHrP, while reduced metabolites (tetrahydrocurcuminoids) had inhibitory effects on cell growth and PTHrP secretion but only at concentrations ≥10-fold higher than the curcuminoids. These studies emphasize the structural and biological importance of curcuminoids in the anti-breast cancer effects of turmeric and contradict recent assertions that certain of the curcuminoid metabolites studied here mediate these anti-cancer effects.
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Curcumin Inhibition of Integrin (α6β4)-Dependent Breast Cancer Cell Motility and Invasion
Hong Im Kim, Huang Huang, Satish Cheepala, Shile Huang, and Jun Chung
Cancer Prevention Research (2008); 1: 385-391. Published online October 6, 2008. DOI: 10.1158/1940-6207.CAPR-08-0087
Abstract: Curcumin, a polyphenol natural product isolated from the rhizome of the plant Curcuma longa, has emerged as a promising anticancer therapeutic agent. However, the mechanism by which curcumin inhibits cancer cell functions such as cell growth, survival, and cell motility is largely unknown. We explored whether curcumin affects the function of integrin α6β4, a laminin adhesion receptor with an established role in invasion and migration of cancer cells. Here we show that curcumin significantly reduced α6β4-dependent breast cancer cell motility and invasion in a concentration-dependent manner without affecting apoptosis in MDA-MB-435/β4 (β4-integrin transfectants) and MDA-MB-231 breast cancer cell lines. Further, curcumin selectively reduced the basal phosphorylation of β4 integrin (Y1494), which has been reported to be essential in mediating α6β4-dependent phosphatidylinositol 3-kinase activation and cell motility. Consistent with this finding, curcumin also blocked α6β4-dependent Akt activation and expression of the cell motility–promoting factor ENPP2 in MDA-MB-435/β4 cell line. A multimodality approach using curcumin in combination with other pharmacologic inhibitors of α6β4 signaling pathways showed an additive effect to block breast cancer cell motility and invasion. Taken together, these findings show that curcumin inhibits breast cancer cell motility and invasion by directly inhibiting the function of α6β4 integrin, and suggest that curcumin can serve as an effective therapeutic agent in tumors that over-express α6β4.
[NOTE: This specific integrin is what the CressLab at the University of Arizona Comprehensive Cancer Center has been working on for the last 30 years in relation to prostate cancer. All integrins are comprised of an alpha unit and a beta unit, making 24 known combinations in humans. Integrins function as transmembrane receptors that are the bridges for cell-cell and cell-extracellular matrix (ECM) interactions. The α3, α6, and α7 subunits are laminin-binding integrins, which pair with either β1 or β4 to form heterodimers. The β4 subunit is unique in that it only pairs with the α6 subunit, but has recently been shown to have 5 variations: β4A. β4B, β4C (the "normal form" of β4, and the most widely studied), β4D, and β4E (a vary unique an relatively unknown form only recently investigated at the CressLab.]
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Curcumin Combined with Turmerones, Essential Oil Components of Turmeric, Abolishes Inflammation-Associated Mouse Colon Carcinogenesis
Akira Murakami, Ikuyo Furukawa, Shingo Miyamoto, Takuji Tanaka, and Hajime Ohigash
BioFactors (2013, MAr/Apr): 39(2); 221–232. DOI: 10.1002/biof.1054
Abstract: Curcumin (CUR), a yellow pigment in turmeric, has marked potential for preventing colon cancer. We recently reported that ar-turmerone (ATM) suppressed nitric oxide (NO) generation in macrophages. In the present study, we explored the molecular mechanisms by which ATM attenuates NO generation and examined the anti-carcinogenesis activity of turmerones (TUR, a mixture of 5 sesquiterpenes including ATM). Both CUR and ATM inhibited lipopolysaccharide (LPS)-induced expression of inducible forms of both nitric oxide synthase and cyclooxygenase (iNOS and COX-2, respectively). A chase experiment using actinomycin D revealed that ATM accelerated the decay of iNOS and COX-2 mRNA, suggesting a post-transcriptional mechanism. ATM prevented LPS-induced translocation of HuR, an AU-rich element-binding protein that determines mRNA stability of certain inflammatory genes. In a colitis model, oral administration of TUR significantly suppressed 2% dextran sulfate sodium (DSS)-induced shortening of the large bowel by 52–58%. We also evaluated the chemopreventive effects of oral feeding of TUR, CUR, and their combinations using a model of dimethylhydradine-initiated and DSS-promoted mouse colon carcinogenesis. At the low dose, TUR markedly suppressed adenoma multiplicity by 73%, while CUR at both doses suppressed adenocarcinoma multiplicity by 63–69%. Interestingly, the combination of CUR and TUR at both low and high doses abolished tumor formation. Collectively, our results led to our hypothesis that TUR is a novel candidate for colon cancer prevention. Furthermore, we consider that its use in combination with CUR may become a powerful method for prevention of inflammation-associated colon carcinogenesis.
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4. TURMERIC/CURCUMIN and PROSTATE CANCER
Chemopreventive potential of curcumin in prostate cancer
Marie-Helene Teiten, Francois Gaascht, Serge Eifes, Mario Dicato, Marc Diederich
Genes & Nutrition (2010); 5(1): 61–74. DOI 10.1007/s12263-009-0152-3
Abstract: The long latency and high incidence of prostate carcinogenesis provides the opportunity to intervene with chemoprevention in order to prevent or eradicate prostate malignancies. We present here an overview of the chemopreventive potential of curcumin (diferuloylmethane), a well-known natural compound that exhibits therapeutic promise for prostate cancer. In fact, it interferes with prostate cancer proliferation and metastasis development through the down-regulation of androgen receptor and epidermal growth factor receptor, but also through the induction of cell cycle arrest. It regulates the inflammatory response through the inhibition of pro-inflammatory mediators and the NF-jB signaling pathway. These results are consistent with this compound’s ability to up-induce pro-apoptotic proteins and to down-regulate the anti-apoptotic counterparts. Alone or in combination with TRAIL-mediated immunotherapy or radiotherapy, curcumin is also reported to be a good inducer of prostate cancer cell death by apoptosis. Curcumin appears thus as a non-toxic alternative for prostate cancer prevention, treatment or co-treatment.
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Curcumin Attenuates β-catenin Signaling in Prostate Cancer Cells through Activation of Protein Kinase D1
Vasudha Sundram, Subhash C. Chauhan, Mara Ebeling, Meena Jaggi
PLoS ONE (2012, Apr): 7(4); e35368. DOI: 10.1371/journal.pone.0035368
Abstract: Prostate cancer is the most commonly diagnosed cancer affecting 1 in 6 males in the US. Understanding the molecular basis of prostate cancer progression can serve as a tool for early diagnosis and development of novel treatment strategies for this disease. Protein Kinase D1 (PKD1) is a multifunctional kinase that is highly expressed in normal prostate. The decreased expression of PKD1 has been associated with the progression of prostate cancer. Therefore, synthetic or natural products that regulate this signaling pathway can serve as novel therapeutic modalities for prostate cancer prevention and treatment. Curcumin, the active ingredient of turmeric, has shown anti-cancer properties via modulation of a number of different molecular pathways. Herein, we have demonstrated that curcumin activates PKD1, resulting in changes in β-catenin signaling by inhibiting nuclear β-catenin transcription activity and enhancing the levels of membrane β-catenin in prostate cancer cells. Modulation of these cellular events by curcumin correlated with decreased cell proliferation, colony formation and cell motility and enhanced cell-cell aggregation in prostate cancer cells. In addition, we have also revealed that inhibition of cell motility by curcumin is mediated by decreasing the levels of active cofilin, a downstream target of PKD1. The potent anti-cancer effects of curcumin in vitro were also reflected in a prostate cancer xenograft mouse model. The in vivo inhibition of tumor growth also correlated with enhanced membrane localization of β-catenin. Overall, our findings herein have revealed a novel molecular mechanism of curcumin action via the activation of PKD1 in prostate cancer cells.
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Therapeutic potential of curcumin in human prostate cancer--I: Curcumin induces apoptosis in both androgen-dependent and androgen-independent prostate cancer cells
T Dorai, N Gehani & A Katz
Prostate Cancer and Prostatic Diseases (2000): 3(2); 84-93. DOI: 10.1038/sj.pcan.4500399
In an effort to find an alternative nontoxic means of inducing the apoptosis potential in both androgen-dependent and hormone refractory prostate cancer cells, attention was focused on curcumin (turmeric), traditionally used in medicine and cuisine in India and other south-east Asian countries. The results indicate that curcumin is a novel and potent inducer of apoptosis in both androgen-dependent and androgen-independent prostate cancer cells. This was accomplished by down-regulating apoptosis suppressor proteins and other crucial proteins such as the androgen receptor. It is concluded that curcumin may provide an alternative, nontoxic modality by which the clinician may prevent the progression of prostate cancer to its hormone refractory state or to treat advanced prostate cancer by forcing them to undergo apoptosis.
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Curcumin inhibits prostate cancer metastasis in vivo by targeting the inflammatory cytokines CXCL1 and -2
Peter H. Killian, Emanuel Kronski, Katharina M. Michalik, Ottavia Barbieri, Simonetta Astigiano,
Christian P. Sommerhoff, Ulrich Pfeffer, Andreas G. Nerlich, and Beatrice E. Bachmeier
Carcinogenesis (2012): 33(12); 2507-2519. DOI: 10.1093/carcin/bgs312
In America and Western Europe, prostate cancer is the second leading cause of death in men. Emerging evidence suggests that chronic inflammation is a major risk factor for the development and metastatic progression of prostate cancer. We previously reported that the chemopreventive polyphenol curcumin inhibits the expression of the proinflammatory cytokines CXCL1 and -2 leading to diminished formation of breast cancer metastases. In this study, we analyze the effects of curcumin on prostate carcinoma growth, apoptosis and metastasis. We show that curcumin inhibits translocation of NFκB to the nucleus through the inhibition of the IκB-kinase (IKKβ, leading to stabilization of the inhibitor of NFκB, IκBα, in PC-3 prostate carcinoma cells. Inhibition of NFκB activity reduces expression of CXCL1 and -2 and abolishes the autocrine/paracrine loop that links the two chemokines to NFκB. The combination of curcumin with the synthetic IKKβ inhibitor, SC-541, shows no additive or synergistic effects indicating that the two compounds share the target. Treatment of the cells with curcumin and siRNA-based knockdown of CXCL1 and -2 induce apoptosis, inhibit proliferation and down regulate several important metastasis-promoting factors like COX2, SPARC and EFEMP. In an orthotopic mouse model of hematogenous metastasis, treatment with curcumin inhibits statistically significantly formation of lung metastases. In conclusion, chronic inflammation can induce a metastasis prone phenotype in prostate cancer cells by maintaining a positive proinflammatory and prometastatic feedback loop between NFκB and CXCL1/-2. Curcumin disrupts this feedback loop by the inhibition of NFκB signaling leading to reduced metastasis formation in vivo.
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The effects of curcumin on the invasiveness of prostate cancer in vitro and in vivo
JH Hong, KS Ahn, E Bae, SS Jeon, and HY Choi
Prostate Cancer and Prostatic Diseases (2006): 9(2): 147–152. DOI: 10.1038/sj.pcan.4500856
Abstract: Curcumin has become a focus of interest with regard to its antitumor effects in prostate cancer; however, the effects of this agent on invasion and metastasis remain less well understood. Matrix metalloproteinases (MMPs) are important prerequisite for tumor invasion and metastasis. In this study, we evaluated the effects of curcumin on prostate cancer cells (DU-145) invasion in both in vitro and in vivo. We utilized zymography and ELISA in order to determine the MMP-2 and MMP-9 activity. Matrigel invasion assay was performed to assess cellular invasion. We developed a xenograft model to examine tumorigenicity. Curcumin treatment resulted not only in a significant reduction in the expression of MMP-2 and MMP-9, but also effected the inhibition of invasive ability in vitro. Curcumin was shown to induce a marked reduction of tumor volume, MMP-2, and MMP-9 activity in the tumor-bearing site. The metastatic nodules in vivo were significantly fewer in the curcumin treated group than untreated group. Curcumin appears to constitute a potential agent for the prevention of cancer progression, or at least of the initial phase of metastasis, in prostate cancer.
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Curcumin Inhibition of the Functional Interaction between Integrin α6β4 and the Epidermal Growth Factor Receptor
Young Hwa Soung and Jun Chung
Molecular Cancer Therapeuitics (2011): 10(5): 883-891. Published Online First March 9, 2011. DOI: 10.1158/1535-7163.MCT-10-1053
Abstract: The functional interaction between integrin α6β4 and growth factor receptors has been implicated in key signaling pathways important for cancer cell function. However, few attempts have been made to selectively target this interaction for therapeutic intervention. Previous studies showed that curcumin, a yellow pigment isolated from turmeric, inhibits integrin α6β4 signaling important for breast carcinoma cell motility and invasion, but the mechanism is not currently known. To address this issue, we tested the hypothesis that curcumin inhibits the functional interaction between α6β4 and the epidermal growth factor receptor (EGFR). In this study, we found that curcumin disrupts functional and physical interactions between α6β4 and EGFR, and blocks a6b4/EGFR-dependent functions of carcinoma cells expressing the signaling competent form of a6b4. We further showed that curcumin inhibits EGF-dependent mobilization of α6β4 from hemidesmosomes to the leading edges of migrating cells such as lammelipodia and filopodia, and thereby prevents α6β4 distribution to lipid rafts where functional interactions between α6β4 and EGFR occur. These data suggest a novel paradigm in which curcumin inhibits α6β4 signaling and functions by altering intracellular localization of α6β4, thus preventing its association with signaling receptors such as EGFR.
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5. CURCUMIN FOR NEURODEGENERATIVE DISORDERS
Probably the second largest research investment in turmeric/curcumin has been in the field of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington’s disease, and others.
Potential Therapeutic Effects of Curcumin, the Anti-inflammatory Agent, Against Neurodegenerative, Cardiovascular, Pulmonary, Metabolic, Autoimmune and Neoplastic Diseases
Bharat B. Aggarwal and Kuzhuvelil B. Harikumar
Abstract: Although safe in most cases, ancient treatments are ignored because neither their active component nor their molecular targets are well defined. This is not the case, however, with curcumin, a yellow-pigment substance and component of turmeric (Curcuma longa), which was identified more than a century ago. For centuries it has been known that turmeric exhibits anti-inflammatory activity, but extensive research performed within the past two decades has shown that this activity of turmeric is due to curcumin (diferuloylmethane). This agent has been shown to regulate numerous transcription factors, cytokines, protein kinases, adhesion molecules, redox status and enzymes that have been linked to inflammation. The process of inflammation has been shown to play a major role in most chronic illnesses, including neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. In the current review, we provide evidence for the potential role of curcumin in the prevention and treatment of various proinflammatory chronic diseases. These features, combined with the pharmacological safety and negligible cost, render curcumin an attractive agent to explore further.
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The effect of curcumin (turmeric) on Alzheimer's disease: An overview
Shrikant Mishra and Kalpana Palanivelu
Annals of Indian Academic Neurology (2008, Jan-Mar): 11(1); 13–19. DOI: 10.4103/0972-2327.40220
Abstract: 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.
Effects of turmeric on Alzheimer's disease with behavioral and psychological symptoms of dementia
AYU (An International Quarterly Journal of Research in Ayurveda) (2012, Oct/Nov): 33(4); 499-.
Abstract: We describe here three patients with the Alzheimer's Disease (AD) whose behavioral symptoms were improved remarkably as a result of the turmeric treatment, which is the traditional Indian medicine. Their cognitive decline and Behavioral and Psychological Symptoms of Dementia(BPSD) were very severe. All three patients exhibited irritability, agitation, anxiety, and apathy, two patients suffer from urinary incontinence and wonderings. They were prescribed turmeric powder capsules and started recovering from these symptoms without any adverse reaction in the clinical symptom and laboratory data. After 12 weeks of the treatment, total score of the Neuro-Psychiatric Inventory-brief questionnaire decreased significantly in both acuity of symptoms and burden of caregivers. In one case, the Mini-Mental State Examination (MMSE) score was up five points, from 12/30 to 17/30. In the other two cases, no significant change was seen in the MMSE; however, they came to recognize their family within 1 year treatment. All cases have been taking turmeric for more than 1 year, re-exacerbation of BPSD was not seen. The present cases suggest a significant improvement of the behavioral symptoms in the AD with the turmeric treatment, leading to probable benefit of the use of turmeric in individuals with the AD with BPSD.
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Effects of turmeric on Alzheimer's disease with behavioral and psychological symptoms of dementia
Nozomi Hishikawa, Yoriko Takahashi, Yoshinobu Amakusa, Yuhei Tanno, Yoshitake Tuji and Hisayoshi Niwa
AYU (An International Quarterly Journal of Research in Ayurveda) (2012, Oct/Nov): 33(4); 499-.
Abstract: We describe here three patients with the Alzheimer's Disease (AD) whose behavioral symptoms were improved remarkably as a result of the turmeric treatment, which is the traditional Indian medicine. Their cognitive decline and Behavioral and Psychological Symptoms of Dementia(BPSD) were very severe. All three patients exhibited irritability, agitation, anxiety, and apathy, two patients suffer from urinary incontinence and wonderings. They were prescribed turmeric powder capsules and started recovering from these symptoms without any adverse reaction in the clinical symptom and laboratory data. After 12 weeks of the treatment, total score of the Neuro-Psychiatric Inventory-brief questionnaire decreased significantly in both acuity of symptoms and burden of caregivers. In one case, the Mini-Mental State Examination (MMSE) score was up five points, from 12/30 to 17/30. In the other two cases, no significant change was seen in the MMSE; however, they came to recognize their family within 1 year treatment. All cases have been taking turmeric for more than 1 year, re-exacerbation of BPSD was not seen. The present cases suggest a significant improvement of the behavioral symptoms in the AD with the turmeric treatment, leading to probable benefit of the use of turmeric in individuals with the AD with BPSD.
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The Curry Spice Curcumin Reduces Oxidative Damage and Amyloid Pathology in an Alzheimer Transgenic Mouse
Giselle P. Lim, Teresa Chu, Fusheng Yang, Walter Beech, Sally A. Frautschy, and Greg M. Cole
Abstract: Inflammation in Alzheimer's disease (AD) patients is characterized by increased cytokines and activated microglia. Epidemiological studies suggest reduced AD risk associates with long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs). Whereas chronic ibuprofen suppressed inflammation and plaque-related pathology in an Alzheimer transgenic APPSw mouse model (Tg2576), excessive use of NSAIDs targeting cyclooxygenase I can cause gastrointestinal, liver, and renal toxicity. One alternative NSAID is curcumin, derived from the curry spice turmeric. Curcumin has an extensive history as a food additive and herbal medicine in India and is also a potent polyphenolic antioxidant. To evaluate whether it could affect Alzheimer-like pathology in the APPSw mice, we tested a low (160 ppm) and a high dose of dietary curcumin (5000 ppm) on inflammation, oxidative damage, and plaque pathology. Low and high doses of curcumin significantly lowered oxidized proteins and interleukin-1β, a proinflammatory cytokine elevated in the brains of these mice. With low-dose but not high-dose curcumin treatment, the astrocytic marker GFAP was reduced, and insoluble β-amyloid (Aβ), soluble Aβ, and plaque burden were significantly decreased by 43–50%. However, levels of amyloid precursor (APP) in the membrane fraction were not reduced. Microgliosis was also suppressed in neuronal layers but not adjacent to plaques. In view of its efficacy and apparent low toxicity, this Indian spice component shows promise for the prevention of Alzheimer's disease.
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Curcumin and neurodegenerative diseases: A perspective
Darvesh AS, Carroll RT, Bishayee A, Novotny NA, Geldenhuys WJ, Van der Schyf CJ
Expert Opinion on Investigational Drugs (2012, Aug): 21(8); 1123-40. DOI: 10.1517/13543784.2012.693479
Abstract
Introduction: Curcumin, a dietary polyphenol found in the curry spice turmeric, possesses potent antioxidant and anti-inflammatory properties and an ability to modulate multiple targets implicated in the pathogenesis of chronic illness. Curcumin has shown therapeutic potential for neurodegenerative diseases including Alzheimer's disease (AD) and Parkinson's disease (PD).
Areas Covered: This article highlights the background and epidemiological evidence of curcumin's health benefits and its pharmacodynamic and pharmacokinetic profile. Curcumin's ability to counteract oxidative stress and inflammation and its capacity to modulate several molecular targets is reviewed. We highlight the neuroprotective properties of curcumin including pre-clinical evidence for its pharmacological effects in experimental models of AD and PD. The bioavailability and safety of curcumin, the development of semi-synthetic curcuminoids as well as novel formulations of curcumin are addressed.
Expert Opinion: Curcumin possesses therapeutic potential in the amelioration of a host of neurodegenerative ailments as evidenced by its antioxidant, anti-inflammatory and anti-protein aggregation effects. However, issues such as limited bioavailability and a paucity of clinical studies examining its therapeutic effectiveness in illnesses such as AD and PD currently limit its therapeutic outreach. Considerable effort will be required to adapt curcumin as a neuroprotective agent to be used in the treatment of AD, PD and other neurodegenerative diseases.
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Curcumin: A potential neuroprotective agent in Parkinson's disease
Mythri RB & Bharath MM
Current Pharmaceutical Design (2012): 18(1); 91-9. DOI: 10.2174/138161212798918995
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.
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6. CURCUMIN/TURMERIC AND PSYCHOLOGICAL DISORDERS
This is one of the newer areas of research into the benefits of curcumin/turmeric. The majority of the studies seem to be focused on its potential as a natural antidepressant.
Curcumin reverses impaired hippocampal neurogenesis and increases serotonin receptor 1A mRNA and brain-derived neurotrophic factor expression in chronically stressed rats
Ying Xu, Baoshan Ku, Li Cui, Xuejun Li, Philip A. Barish, Thomas C. Foster, William O. Ogle
Brain Research (2007, Aug): 1162(8); 9–18. DOI: 10.1016/j.brainres.2007.05.071
Abstract: Curcuma longa is a major constituent of Xiaoyao-san, the traditional Chinese medicine, which has been used to effectively manage stress and depression-related disorders in China. As the active component of curcuma longa, curcumin possesses many therapeutic properties; we have previously described its antidepressant activity in our earlier studies using the chronic unpredictable stress model of depression in rats. Recent studies show that stress-induced damage to hippocampal neurons may contribute to the phathophysiology of depression. The aim of this study was to investigate the effects of curcumin on hippocampal neurogenesis in chronically stressed rats. We used an unpredictable chronic stress paradigm (20 days) to determine whether chronic curcumin treatment with the effective doses for behavioral responses (5, 10 and 20 mg/kg, p.o.), could alleviate or reverse the effects of stress on adult hippocampal neurogenesis. Our results suggested that curcumin administration (10 and 20 mg/kg, p.o.) increased hippocampal neurogenesis in chronically stressed rats, similar to classic antidepressant imipramine treatment (10 mg/kg, i.p.). Our results further demonstrated that these new cells mature and become neurons, as determined by triple labeling for BrdU and neuronal- or glial-specific markers. In addition, curcumin significantly prevented the stress-induced decrease in 5-HT1A mRNA and BDNF protein levels in the hippocampal subfields, two molecules involved in hippocampal neurogenesis. These results raise the possibility that increased cell proliferation and neuronal populations may be a mechanism by which curcumin treatment overcomes the stress-induced behavioral abnormalities and hippocampal neuronal damage. Moreover, curcumin treatment, via up-regulation of 5-HT1A receptors and BDNF, may reverse or protect hippocampal neurons from further damage in response to chronic stress, which may underlie the therapeutic actions of curcumin.
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Curcumin for the treatment of major depression: A randomised, double-blind, placebo controlled study
Adrian L Lopresti, Michael Maes, Garth L Maker, Sean D Hood, Peter D Drummond
Journal of Affective Disorders (2014, Jun): 167; 368-375. DOI: 10.1016/j.jad.2014.06.001
Abstract
Background: Curcumin, the principal curcuminoid derived from the spice turmeric, influences several biological mechanisms associated with major depression, namely those associated with monoaminergic activity, immune-inflammatory and oxidative and nitrosative stress pathways, hypothalamus-pituitary-adrenal (HPA) axis activity and neuroprogression. We hypothesised that curcumin would be effective for the treatment of depressive symptoms in individuals with major depressive disorder.
Methods: In a randomised, double-blind, placebo-controlled study, 56 individuals with major depressive disorder were treated with curcumin (500 mg twice daily) or placebo for 8 weeks. The primary measure was the Inventory of Depressive Symptomatology self-rated version (IDS-SR30). Secondary outcomes included IDS-SR30 factor scores and the Spielberger State-Trait Anxiety Inventory (STAI).
Results: From baseline to week 4, both curcumin and placebo were associated with improvements in IDS-SR30 total score and most secondary outcome measures. From weeks 4 to 8, curcumin was significantly more effective than placebo in improving several mood-related symptoms, demonstrated by a significant group x time interaction for IDS-SR30 total score (F1, 53=4.22, p=.045) and IDS-SR30 mood score (F1, 53=6.51, p=.014), and a non-significant trend for STAI trait score (F1, 48=2.86, p=.097). Greater efficacy from curcumin treatment was identified in a subgroup of individuals with atypical depression.
Conclusions: Partial support is provided for the antidepressant effects of curcumin in people with major depressive disorder, evidenced by benefits occurring 4 to 8 weeks after treatment.
Limitations: Investigations with larger sample sizes, over extended treatment periods, and with varying curcumin dosages are required.
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Curcumin reverses the effects of chronic stress on behavior, the HPA axis, BDNF expression and phosphorylation of CREB
Ying Xu, Baoshan Ku, Lu Tie, Haiyan Yao, Wengao Jiang, Xing Ma, Xuejun Li
Brain Research (2006, Nov): 1122(1); 56–64. DOI: 10.1016/j.brainres.2006.09.009
Abstract: Curcuma longa is a major constituent of the traditional Chinese medicine Xiaoyao-san, which has been used to effectively manage stress and depression-related disorders in China. Curcumin is the active component of curcuma longa, and its antidepressant effects were described in our prior studies in mouse models of behavioral despair. We hypothesized that curcumin may also alleviate stress-induced depressive-like behaviors and hypothalamic–pituitary–adrenal (HPA) axis dysfunction. Thus in present study we assessed whether curcumin treatment (2.5, 5 and 10 mg/kg, p.o.) affects behavior in a chronic unpredictable stress model of depression in rats and examined what its molecular targets may be. We found that subjecting animals to the chronic stress protocol for 20 days resulted in performance deficits in the shuttle-box task and several physiological effects, such as an abnormal adrenal gland weight to body weight (AG/B) ratio and increased thickness of the adrenal cortex as well as elevated serum corticosterone levels and reduced glucocorticoid receptor (GR) mRNA expression. These changes were reversed by chronic curcumin administration (5 or 10 mg/kg, p.o.). In addition, we also found that the chronic stress procedure induced a down-regulation of brain-derived neurotrophic factor (BDNF) protein levels and reduced the ratio of phosphorylated cAMP response element-binding protein (pCREB) to CREB levels (pCREB/CREB) in the hippocampus and frontal cortex of stressed rats. Furthermore, these stress-induced decreases in BDNF and pCREB/CREB were also blocked by chronic curcumin administration (5 or 10 mg/kg, p.o.). These results provide compelling evidence that the behavioral effects of curcumin in chronically stressed animals, and by extension humans, may be related to their modulating effects on the HPA axis and neurotrophin factor expressions.
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Is there a role for curcumin in the treatment of bipolar disorder?
Elisa Brietzke, Rodrigo B. Mansur, Andre Zugman, André F. Carvalho, Danielle S. Macêdo, Danielle S. Cha, Vanessa C. Abílio, and Roger S. McIntyre
Medical Hypotheses (2013, May): 80(5); 606–612. DOI: 10.1016/j.mehy.2013.02.001
Abstract: Curcumin is a polyphenolic nonflavonoid compound extracted from the rhizome of turmeric (Curcuma longa), a plant commonly used in Indian and Chinese traditional medicine to treat rheumatism, cough, inflammation and wounds. Curcumin putative targets, known based on studies of diverse central nervous system disorders other than bipolar disorders (BD) include several proteins currently implicated in the pathophysiology of BD. These targets include, but are not limited to, transcription factors activated by environmental stressors and pro-inflammatory cytokines, protein kinases (PKA, PKC), enzymes, growth factors, inflammatory mediators, and anti-apoptotic proteins (Bcl-XL). Herein, we review previous studies on the anti-inflammatory and anti-oxidant properties of curcumin and discuss its therapeutic potential in BD.
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An Overview of Curcumin in Neurological Disorders
S. K. Kulkarni and A. Dhir
Indian Journal Pharmaceutical Sciences (2010, Mar-Apr); 72(2); 149–154. DOI: 10.4103/0250-474X.65012
Abstract: Curcumin, the principal curcuminoid found in spice turmeric, has recently been studied for its active role in the treatment of various central nervous system disorders. Curcumin demonstrates neuroprotective action in Alzheimer's disease, tardive dyskinesia, major depression, epilepsy, and other related neurodegenerative and neuropsychiatric disorders. The mechanism of its neuroprotective action is not completely understood. However, it has been hypothesized to act majorly through its anti-inflammatory and antioxidant properties. Also, it is a potent inhibitor of reactive astrocyte expression and thus prevents cell death. Curcumin also modulates various neurotransmitter levels in the brain. The present review attempts to discuss some of the potential protective role of curcumin in animal models of major depression, tardive dyskinesia and diabetic neuropathy. These studies call for well planned clinical studies on curcumin for its potential use in neurological disorders.
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Multiple antidepressant potential modes of action of curcumin: A review of its anti-inflammatory, monoaminergic, antioxidant, immune-modulating and neuroprotective effects
Lopresti, A.L., Hood, S.D., and Drummond, P.D.
Journal of Psychopharmacology (2012, Dec): 26(12); 1512-1524. DOI: 10.1177/0269881112458732
Abstract: Curcumin is the principal curcuminoid of the popular Indian spice turmeric and has attracted increasing attention for the treatment of a range of conditions. Research into its potential as a treatment for depression is still in its infancy, although several potential antidepressant mechanisms of action have been identified. Research completed to date on the multiple effects of curcumin is reviewed in this paper, with a specific emphasis on the biological systems that are compromised in depression. The antidepressant effects of curcumin in animal models of depression are summarised, and its influence on neurotransmitters such as serotonin and dopamine is detailed. The effects of curcumin in moderating hypothalamus-pituitary-adrenal disturbances, lowering inflammation and protecting against oxidative stress, mitochondrial damage, neuroprogression and intestinal hyperpermeability, all of which are compromised in major depressive disorder, are also summarised. With increasing interest in natural treatments for depression, and efforts to enhance current treatment outcomes, curcumin is presented as a promising novel, adjunctive or stand-alone natural antidepressant.
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The CB1 Receptor-Mediated Endocannabinoid Signaling and NGF: The Novel Targets of Curcumin
Parichehr Hassanzadeh & Anna Hassanzadeh
Neurochemical Research (2012, May): 37(5); 1112-1120. DOI: 10.1007/s11064-012-0716-2
Abstract: Increasing interest has recently been attracted towards the identification of natural compounds including those with antidepressant properties. Curcumin has shown promising antidepressant effect, however, its molecular target(s) have not been well defined. Based on the interaction between the neurotrophins and endocannabinoid system as well as their contribution to the emotional reactivity and antidepressant action, here we show that 4-week treatment with curcumin, similar to the classical antidepressant amitriptyline, results in the sustained elevation of brain nerve growth factor (NGF) and endocannabinoids in dose-dependent and brain region-specific fashion. Pretreatment with cannabinoid CB1 receptor neutral antagonist AM4113, but not the CB2 antagonist SR144528, prevents the enhancement of brain NGF contents. AM4113 exerts no effect by itself. Our findings by presenting the CB1 receptor-mediated endocannabinoid signaling and NGF as novel targets for curcumin, suggest that more attention should be focused on the therapeutic potential of herbal medicines including curcumin.
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Anti-depressant like effect of curcumin and its combination with piperine in unpredictable chronic stress-induced behavioral, biochemical and neurochemical changes
Mohit Kumar Bhutani, Mahendra Bishnoi, and Shrinivas K. Kulkarni
Pharmacology Biochemistry and Behavior (2009, Mar): 92(1); 39–43. DOI: 10.1016/j.pbb.2008.10.007
Abstract: Curcumin, a yellow pigment extracted from rhizomes of the plant Curcuma longa (turmeric), has been widely used as food additive and also as a herbal medicine throughout Asia. The present study was designed to study the pharmacological, biochemical and neurochemical effects of daily administration of curcumin to rats subjected to chronic unpredictable stress. Curcumin treatment (20 and 40 mg/kg, i.p., 21 days) significantly reversed the chronic unpredictable stress-induced behavioral (increase immobility period), biochemical (increase monoamine oxidase activity) and neurochemical (depletion of brain monoamine levels) alterations. The combination ofpiperine (2.5 mg/kg, i.p., 21 days), a bioavailability enhancer, with curcumin (20 and 40 mg/kg, i.p., 21 days) showed significant potentiation of its anti-immobility,neurotransmitter enhancing (serotonin and dopamine) and monoamine oxidase inhibitory (MAO-A) effects as compared to curcumin effect per se. This study provided a scientific rationale for the use of curcumin and its co-administration with piperine in the treatment of depressive disorders
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