Henrotin, Y., F. Priem and A. Mobasheri. 2013. Curcumin: a new paradigm and therapeutic opportunity for the treatment of osteoarthritis: curcumin for osteoarthritis management. Springerplus. 2, 1: 56.
Abstract: The management of osteoarthritis represents a real challenge. This complex and multi-factorial disease evolves over decades and requires not only the alleviation of symptoms, i.e. pain and joint function but also the preservation of articular structure without side effects. Nutraceuticals are good candidates for the management of OA due to their safety profile and potential efficacy. However, they are not part of the treatment guidelines and published recommendations. Curcumin is the yellow pigment isolated from the rhizomes of Curcuma longa, commonly known as turmeric. Curcumin is a highly pleiotropic molecule with an excellent safety profile. Strong molecular evidence has been published for its potency to target multiple inflammatory diseases. However, naturally occurring curcumin cannot achieve its optimum therapeutic outcomes due to its low solubility and poor bioavailability. Nevertheless, curcumin presents great potential for treating OA and has been categorized as having preclinical evidence of efficacy. This review aimed at gathering most of the available information to document the potential efficacy of curcumin based on the results obtained in in vitro models of cartilage and osteoarthritis and in other diseases.
Chusri, S., S. Settharaksa, J. Chokpaisarn, S. Limsuwan and SP. Voravuthikunchai. 2013. Thai Herbal Formulas Used for Wound Treatment: A Study of Their
Antibacterial Potency, Anti-inflammatory, Antioxidant, and Cytotoxicity
Altern Complement Med. 19, 7: 671-676.
Abstract Aim: This present work was aimed to investigate wound
healing-related biologic activities of traditional herbal formulas used for
wound treatment in southern Thailand. Methods: Water and ethanol extracts of the
formulas (THR-SK004, THR-SK010, and THR-SK011) were tested for their
antibacterial potency against methicillin-resistant Staphylococcus aureus (MRSA)
and -susceptible S. aureus. Anti-inflammatory activities of the extracts were
assessed by detection of the inhibition of lipopolysaccharide-induced nitric
oxide production. Anti-oxidant activities and cytotoxicity of the extracts were
also measured. Results: Among the tested formulas, ethanol extract of THR-SK010
consisting of four herbs: Curcuma longa
L., Areca catechu L., Oryza sativa L., and Garcinia mangostana L., was found to
possess promising antibacterial activities with
MIC(90) of 4 μg mL(-1) against
MRSA isolates. This ethanol extract offered the highest anti-inflammatory
activity as well as DPPH and hydroxyl radical scavenging activities.
Conclusions: Remarkable antibacterial, anti-inflammatory, and antioxidant
activities as well as low toxicity on Vero cells of THR-SK010 ethanol extract
provide scientific information to support the topical use of the formula for
wound treatment. This information proposes the potential to develop a new
generation of phytopharmaceuticals based on traditional knowledge.
Madhu, K., K. Chanda and M. J. Saji. 2012. Safety and efficacy of Curcuma longa
extract in the treatment of painful knee osteoarthritis: a randomized
placebo-controlled trial. Inflammopharmacology. Inflammopharmacology. 21, 2: 129-136
Abstract; Curcuma longa Linn. is widely used for
the treatment of disorders associated with inflammation and was evaluated for
its safety and efficacy in the treatment of painful knee osteoarthritis (OA).
This was a randomized, single blind, placebo-controlled trial. Total of 120
patients (37 males and 83 females) with primary knee OA received either placebo
(400 mg twice daily) or NR-INF-02 (500 mg twice daily) or glucosamine sulphate
(GS) (750 mg twice daily) alone or combination of NR-INF-02 and GS for 42 days.
The efficacy was assessed during treatment period, on day 21 and day 42. The
decrease in severity of pain symptom and function of affected knee as primary
efficacy outcome measure was assessed by Visual Analog Scale (VAS) and Western
Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scale,
respectively. The clinical examination of affected joint was measured by an
orthopaedic specialist and using a Clinician Global Impression Change (CGIC)
scale. The analysis of post-treatment scores following administration of
NR-INF-02 using VAS, WOMAC, and CGIC at each clinical visit showed significant
decrease (p < 0.05) compared to placebo. NR-INF-02 treated group showed a
significant (p < 0.01) decrease in use of rescue medication, along with
clinical and subjective improvement compared to placebo. The tolerability and
acceptability profile of NR-INF-02 was better during the trial period. The study
demonstrates safety and efficacy of NR-INF-02 as a useful treatment option for
patients with primary painful knee OA.
Yallapu, M. M., M. Jaggi, S. C. Chauhan. 2012. Curcumin Nanomedicine : A Road to Cancer Therapeutics. Curr Pharm Des. 19, 11: 1994-2010.
Abstract: Cancer is the second leading cause of death in the United States.
Conventional therapies cause widespread systemic toxicity and lead to serious
side effects which prohibit their long term use. Additionally, in many
circumstances tumor resistance and recurrence is commonly observed. Therefore,
there is an urgent need to identify suitable anticancer therapies that are
highly precise with minimal side effects. Curcumin is a natural polyphenol
molecule derived from the Curcuma longa
plant which exhibits anticancer, chemo-preventive, chemo- and
radio-sensitization properties. Curcumin's widespread availability, safety, low
cost and multiple cancer fighting functions justify its development as a drug
for cancer treatment. However, various basic and clinical studies elucidate
curcumin's limited efficacy due to its low solubility, high rate of metabolism,
poor bioavailability and pharmacokinetics. A growing list of nanomedicine(s)
using first line therapeutic drugs have been approved or are under consideration
by the Food and Drug Administration (FDA) to improve human health. These
nanotechnology strategies may help to overcome challenges and ease the
translation of curcumin from bench to clinical application. Prominent research
is reviewed which shows that advanced drug delivery of curcumin (curcumin
nanoformulations or curcumin nanomedicine) is able to leverage therapeutic
benefits by improving bioavailability and pharmacokinetics which in turn
improves binding, internalization and targeting of tumor(s). Outcomes using
these novel drug delivery systems have been discussed in detail. This review
also describes the tumor-specific drug delivery system(s) that can be highly
effective in destroying tumors. Such new approaches are expected to lead to
clinical trials and to improve cancer therapeutics.
Fan, X., C. Zhang, D. B. Liu, J. Yan and H. P. Liang. 2012. The Clinical Applications of Curcumin: Current State and the Future. Curr
Pharm Des. 19, 11: 2011-2031.
Abstract: Curcumin is a natural polyphenol product derived from the rhizome of the
Curcuma longa. In vivo and in vitro
studies have uncovered many important bioactivities of curcumin, such as
antioxidant activity, inducing cell apoptosis, inhibiting cell proliferation,
anti-cell adhesion and motility, anti-angiogenesis and anti-microbe properties.
Based on these functions, curcumin has been used in clinical trials on various
inflammatory diseases and cancers. In the future, it will be necessary to focus
attention partly on the clinical application of curcumin in neurodegenerative
diseases, cardiovascular diseases and diabetes, because many experiments have
clarified the potential value of curcumin in these areas. As a diet-derived
agent, curcumin has no severe toxicity except for minor gastrointestinal side
effects even up to the dosage of 8 grams for 3 months. However, curcumin has a
low systemic bioavailability, so it is imperative to improve the bioavailability
of curcumin in its clinical application. Many methods, such as adjuvant drug
delivery system and structural modification have been demonstrated to have a
Ringman, J. M. et al. 2012. Oral curcumin for Alzheimer's disease: tolerability and efficacy in a 24-week randomized, double blind, placebo-controlled study. Alzheimers Res
Ther. 4, 5: 43.
INTRODUCTION: Curcumin is a polyphenolic compound derived from the plant
Curcuma Longa 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
METHODS: 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, 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 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 A1-40
and A1-42 in plasma and levels of A1-42, t-tau, p-tau181 and F2-isoprostanes in
cerebrospinal fluid. Plasma levels of curcumin and its metabolites up to 4 hours
after drug administration were also measured.
RESULTS: 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
CONCLUSIONS: Curcumin was generally well-tolerated though 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 though preliminary data suggest limited
bioavailability of this compound.
Gupta, S. C., S. Patchva and B. B. Aggarwal. 2012. AAPS J. 2012 Nov 10. Therapeutic Roles of Curcumin: Lessons Learned from Clinical Trials. AAPS J. 15, 1: 195-218.
Abstract: Extensive research over the past half century has shown that curcumin
(diferuloylmethane), a component of the golden spice turmeric (Curcuma longa), can modulate multiple cell signaling
pathways. Extensive clinical trials over the past quarter century have addressed
the pharmacokinetics, safety, and efficacy of this nutraceutical against
numerous diseases in humans. Some promising effects have been observed in
patients with various pro-inflammatory diseases including cancer, cardiovascular
disease, arthritis, uveitis, ulcerative proctitis, Crohn's disease, ulcerative
colitis, irritable bowel disease, tropical pancreatitis, peptic ulcer, gastric
ulcer, idiopathic orbital inflammatory pseudotumor, oral lichen planus, gastric
inflammation, vitiligo, psoriasis, acute coronary syndrome, atherosclerosis,
diabetes, diabetic nephropathy, diabetic microangiopathy, lupus nephritis, renal
conditions, acquired immunodeficiency syndrome, β-thalassemia, biliary
dyskinesia, Dejerine-Sottas disease, cholecystitis, and chronic bacterial
prostatitis. Curcumin has also shown protection against hepatic conditions,
chronic arsenic exposure, and alcohol intoxication. Dose-escalating studies have
indicated the safety of curcumin at doses as high as 12 g/day over 3 months.
Curcumin's pleiotropic activities emanate from its ability to modulate numerous
signaling molecules such as pro-inflammatory cytokines, apoptotic proteins,
NF-κB, cyclooxygenase-2, 5-LOX, STAT3, C-reactive protein, prostaglandin E(2),
prostate-specific antigen, adhesion molecules, phosphorylase kinase,
transforming growth factor-β, triglyceride, ET-1, creatinine, HO-1, AST, and ALT
in human participants. In clinical trials, curcumin has been used either alone
or in combination with other agents. Various formulations of curcumin, including
nanoparticles, liposomal encapsulation, emulsions, capsules, tablets, and
powder, have been examined. In this review, we discuss in detail the various
human diseases in which the effect of curcumin has been investigated.
Chaneiam, N., C. Changtam, T. Mungkongdee, U. Suthatvoravut, P. Winichagoon, J. Vadolas, A. Suksamrarn, S. Fucharoen S and S. Svasti. 2012. A reduced curcuminoid analog as a novel inducer of fetal hemoglobin. Ann
Hematol. 92, 3: 379-386.
Abstract: Thalassemia is an inherited disorder of hemoglobin molecules that is
characterized by an imbalance of α- and β-globin chain synthesis. Accumulation
of unbound α-globin chains in erythroid cells is the major cause of pathology in
β-thalassemia. Stimulation of γ-globin production can ameliorate disease
severity as it combines with the α-globin to form fetal hemoglobin. We examined
γ-globin-inducing effect of curcuminoids extracted from Curcuma longa L. and their metabolite reduced forms in
erythroid leukemia K562 and human primary erythroid precursor cells. The results
showed that curcuminoid compounds, especially bisdemethoxycurcumin are potential
γ-globin enhancers. We also demonstrated that its reduced analog,
hexahydrobisdemethoxycurcumin (HHBDMC), is most effective and leads to induction
of γ-globin mRNA and HbF in primary erythroid precursor cells for 3.6 ± 0.4- and
2.0 ± 0.4-folds, respectively. This suggested that HHBDMC is the potential agent
to be developed as a new therapeutic drug for β-thalassemia and related
Baliga, M. S., N. Joseph, M. V. Venkataranganna, A. Saxena, V. Ponemone and R. R. Fayad. 2012. Curcumin, an active component of turmeric in the prevention and treatment of
ulcerative colitis: preclinical and clinical observations. Food Funct. 3, 11: 1109-1117.
Abstract: Inflammatory bowel disease (IBD) comprising of ulcerative colitis (UC) and
Crohn's disease (CD) is a major ailment affecting the small and large bowel. In
clinics, IBD is treated using 5-amninosalicylates, antibiotics, the steroids and
immunomodulators. Unfortunately, the long term usages of these agents are
associated with undue side effects and compromise the therapeutic advantage.
Accordingly, there is a need for novel agents that are effective, acceptable and
non toxic to humans. Preclinical studies in experimental animals have shown that
curcumin, an active principle of the Indian spice turmeric (Curcuma longa Linn) is effective in preventing or
ameliorating UC and inflammation. Over the last few decades there has been
increasing interest in the possible role of curcumin in IBD and several studies
with various experimental models of IBD have shown it to be effective in
mediating the inhibitory effects by scavenging free radicals, increasing
antioxidants, influencing multiple signaling pathways, especially the kinases
(MAPK, ERK), inhibiting myeloperoxidase, COX-1, COX-2, LOX, TNF-α, IFN-γ, iNOS;
inhibiting the transcription factor NF-κB. Clinical studies have also shown that
co-administration of curcumin with conventional drugs was effective, to be
well-tolerated and treated as a safe medication for maintaining remission, to
prevent relapse and improve clinical activity index. Large randomized controlled
clinical investigations are required to fully understand the potential of oral
curcumin for treating IBD.
Ponnusamy, S., S. Zinjarde, S. Bhargava, P. R. Rajamohanan and A. Ravikumar. 2012. Discovering Bisdemethoxycurcumin from Curcuma
longa rhizome as a potent small molecule inhibitor of human pancreatic
α-amylase, a target for type-2 diabetes. Food Chem. 135, 4: 2638-2642.
Abstract: Curcuma longa rhizome is used
extensively in culinary preparations in Far East and South-East Asia. Health
benefits of curcuminoids from C. longa as
antioxidants, anti-cancer and anti-inflammatory molecules have been well
documented. We report here for the first time that Bisdemethoxycurcumin (BDMC)
from C. longa, acts as an inhibitor to
inactivate human pancreatic α-amylase, a therapeutic target for oral
hypoglycemic agents in type-2 diabetes. Bioactivity guided isolation of rhizome
isopropanol extract led to the identification by HPLC and NMR of BDMC as a lead
small molecule inhibitor of porcine and human pancreatic α-amylase with an
IC(50) value of 0.026 and 0.025mM, respectively. Kinetic analysis revealed that
using starch as the substrate, HPA exhibited an uncompetitive mode of inhibition
with an apparent K(i) of 3.0μM. The study gains importance as BDMC could be a
good drug candidate in development of new inhibitors of HPA and of functional
foods for controlling starch digestion in order to reduce post-prandial
Mythri, R. B. and M. S. Bharath. 2012. Curcumin: A Potential Neuroprotective Agent in Parkinson's Disease. Curr Pharm Des. 18, 1: 91-99.
Abstract: Parkinson's disease (PD) is an age-associated neurodegenerative disease clinically characterized as a movement disorder. The motor symptoms in PD arise due to selective degeneration of dopaminergic neurons in the substantia nigra of the ventral midbrain thereby depleting the dopamine levels in the striatum. Most of the current pharmacotherapeutic approaches in PD are aimed at replenishing the striatal dopamine. Although these drugs provide symptomatic relief during early PD, many patients develop motor complications with long-term treatment. Further, PD medications do not effectively tackle tremor, postural instability and cognitive deficits. Most importantly, most of these drugs do not exhibit neuroprotective effects in patients. Consequently, novel therapies involving natural antioxidants and plant products/molecules with neuroprotective properties are being exploited for adjunctive therapy. Curcumin is a polyphenol and an active component of turmeric (Curcuma longa), a dietary spice used in Indian cuisine and medicine. Curcumin exhibits antioxidant, anti-inflammatory and anti-cancer properties, crosses the blood-brain barrier and is neuroprotective in neurological disorders. Several studies in different experimental models of PD strongly support the clinical application of curcumin in PD. The current review explores the therapeutic potential of curcumin in PD.
Dadhaniya, P., C. Patel, J. Muchhara, N. Bhadja, N. Mathuria, K. Vachhani and M. G. Soni. 2011. Safety assessment of a solid lipid curcumin particle preparation: acute and subchronic toxicity studies. Food Chem Toxicol. 49, 8: 1834-1342.
Abstract: Curcumin, a polyphenol, is obtained from turmeric, the ground rhizomes of Curcuma longa L. Extensive research over the past half century has revealed several health benefits of curcumin. The objective of the present study was to investigate potential adverse effects, if any, of a novel solid lipid curcumin particle (SLCP) preparation in rats following acute and subchronic administration. The oral LD50 of the preparation in rats as well as in mice was found to be greater than 2000 mg/kg body weight (bw). In the subchronic toxicity study, Wistar rats (10/sex/group) were administered via oral gavage 0 (control), 180, 360, and 720 mg/kg bw/day of SLCP preparation for 90 days. Administration of the curcumin preparation did not result in any toxicologically significant treatment-related changes in clinical (including behavioral) observations, ophthalmic examinations, body weights, body weight gains, feed consumption, and organ weights. No adverse effects of the curcumin preparation were noted on the hematology, serum chemistry parameters, and urinalysis. Terminal necropsy did not reveal any treatment-related gross or histopathology findings. Based on the results of this study, the No Observed-Adverse-Effect Level (NOAEL) for this standardized novel curcumin preparation was determined as 720 mg/kg bw/day, the highest dose tested.
Lin, T. Y., C. W. Lu, C. C. Wang, Y. C. Wang and S. J. Wang. 2011. Curcumin inhibits glutamate release in nerve terminals from rat prefrontal cortex: Possible relevance to its antidepressant mechanism. Prog Neuropsychopharmacol Biol Psychiatry. 35, 7: 1785-1793.
Abstract: There is abundant evidence suggesting the relevance of glutamate to depression and antidepressant mechanisms. Curcumin, a major active compound of Curcuma longa, has been reported to have the biological function of antidepressant. The aim of the present study was to investigate the effect of curcumin on endogenous glutamate release in nerve terminals of rat prefrontal cortex and the underlying mechanisms. The results showed that curcumin inhibited the release of glutamate that was evoked by exposing synaptosomes to the K(+) channel blocker 4-aminopyridine (4-AP). This phenomenon was blocked by the chelating the extracellular Ca(2+) ions, and by the vesicular transporter inhibitor bafilomycin A1, but was insensitive to the glutamate transporter inhibitor DL-threo-β-benzyl-oxyaspartate (DL-TBOA). Further experiments demonstrated that curcumin decreased depolarization-induced increase in [Ca(2+)](C), whereas it did not alter the resting membrane potential or 4-AP-mediated depolarization. Furthermore, the inhibitory effect of curcumin on evoked glutamate release was prevented by blocking the Ca(v)2.2 (N-type) and Ca(v)2.1 (P/Q-type) channels, but not by blocking intracellular Ca(2+) release or Na(+)/Ca(2+) exchange. These results suggest that curcumin inhibits evoked glutamate release from rat prefrontocortical synaptosomes by the suppression of presynaptic Ca(v)2.2 and Ca(v)2.1 channels. Additionally, we also found that the inhibitory effect of curcumin on 4-AP-evoked glutamate release was completely abolished by the clinically effective antidepressant fluoxetine. This suggests that curcumin and fluoxetine use a common intracellular mechanism to inhibit glutamate release from rat prefrontal cortex nerve terminals.
Rasheed, A., G. Avinash Kumar Reddy, S. Mohanalakshmi and C. K. Ashok Kumar. 2011. Formulation and comparative evaluation of poly herbal anti-acne face wash gels. Pharm Biol 49, 8: 771-774.
Context: Rauvolfia serpentina (L). Benth. ex Kurz. (Apocynaceae) possessing antibacterial properties are widely used in modern herbal medicines. Curcuma longa L. (Zingiberaceae), a readily available antiseptic, possess antioxidant, antibacterial, blood purifying and antiinflammatory properties and used in various skin creams. Azadirachta indica A. Juss. (Meliaceae) possess astringent, antiviral, discutient, stimulant and antibacterial properties and works excellently well against acne and keeps the skin healthy. Objective: Acne is the common skin problem that 85% of the teenagers face today. In this study, poly herbal anti-acne face wash gels were prepared using two polymers Carbopol and hydroxy propyl methyl cellulose (HPMC) along with the extracts of plants Rauvolfia serpentina, Curcuma longa, and Azadiracta indica. Materials and methods: The gel formulations were prepared in four different concentrations of 50, 100, 200 mg/ml as Gel-CRB 100, Gel-HPMC 50, Gel-HPMC 100, Gel-HPMC 200, respectively. The formulations were tested for the anti-acne activity by turbidimetric method. Results: Results showed that the gels were non-irritant, stable and posses anti-acne activity. The efficacy when tested with a standard was almost same to that of Clindamycin gel. Discussion and conclusion: From this study, Gel-HPMC 100 was proved to be stable and considered as an effective herbal formulation for acne treatment.
Campos, H.C., M. D. da Rocha, F. P. Viegas, P. C. Nicastro, P. C. Fossaluzza, C. A. Fraga, E. J. Barreiro and C. Jr. Viegas. 2011.The Role of Natural Products in the Discovery of New Drug Candidates for the Treatment of Neurodegenative Disorders II: Alzheimer's Disease. CNS Neurol Disord Drug Targets 10, 2: 251-270.
Abstract: The present review is part II in a series (part I focuses on Parkinson's Disease) that addresses the value of natural product chemistry in the discovery of medicines for the treatment of neurodegenerative disorders. Data reviewed document that a host of products from plant species and derivatives have neuroprotectant effects in vitro and in vivo. In addition, besides neuroprotection, natural products also demonstrate biological effects that target biochemical pathways underlying associated symptoms of neurdegnerative disorders that include cognitive impairments, energy/fatigue, mood, and anxiety. This part of the review series focuses specifically upon Alzheimer's Disease (AD). AD is postulated to result from extracellular formation of amyloid plaques and intracellular deposits of neurofibrilary tangles in the hippocampus, cerebral cortex and other areas of the brain essential for cognitive function. Plaques are formed mostly from the deposition -amyloid (A ), a peptide derived from the amyloid precursor protein (APP). Filamentous tangles are formed from paired helical filaments composed of neurofilament and hyperphosphorilated tau protein, a microtubule-associated protein. In addition, environmental factors can engender the production of cytokines that are closely related to the installation of an inflammatory process that contributes to neuronal death and the development and the progression of AD. In this review we focus on the recent main contribuitions of natural products chemistry to the discovery of new chemical entities usefull to the control and prevention of AD installation and progression. More than sixteen plant species, including Ginseng, Celastrus paniculatus, Centella asiatica, Curcuma longa, Ginkgo biloba, Huperzia serrata, Lycoris radiate, Galanthus nivalis, Magnolia officinalis, Polygala tenuifolia, Salvia lavandulaefolia, Salvia miltiorrhiza, Coptis chinensis, Crocus sativus, Evodia rutaecarpa, Sanguisorba officinalis, Veratrum grandiflorum and Picrorhiza kurvoa, are discussed as potential sources of active extracts. In addition, more than sixty secondary metabolites are under evaluation for their efficacy on controlling symptoms and to impede the development and progression of AD.
Goel, A. and B. B. Aggarwal. 2010. Curcumin, the golden spice from Indian saffron, is a chemosensitizer and radiosensitizer for tumors and chemoprotector and radioprotector for normal organs. Nutr Cancer. 62, 7: 919-930.
Abstract: Curcumin (diferuloylmethane), the yellow pigment in Indian saffron (Curcuma longa; also called turmeric, haldi, or haridara in the East and curry powder in the West), has been consumed by people for centuries as a dietary component and for a variety of proinflammatory ailments. Extensive research within the last decade in cell culture and in rodents has revealed that curcumin can sensitize tumors to different chemotherapeutic agents including doxorubicin, 5-FU, paclitaxel, vincristine, melphalan, butyrate, cisplatin, celecoxib, vinorelbine, gemcitabine, oxaliplatin, etoposide, sulfinosine, thalidomide, and bortezomib. Chemosensitization has been observed in cancers of the breast, colon, pancreas, gastric, liver, blood, lung, prostate, bladder, cervix, ovary, head and neck, and brain and in multiple myeloma, leukemia, and lymphoma. Similar studies have also revealed that this agent can sensitize a variety of tumors to gamma radiation including glioma, neuroblastoma, cervical carcinoma, epidermal carcinoma, prostate cancer, and colon cancer. How curcumin acts as a chemosensitizer and radiosensitizer has also been studied extensively. For example, it downregulates various growth regulatory pathways and specific genetic targets including genes for NF-κB, STAT3, COX2, Akt, antiapoptotic proteins, growth factor receptors, and multidrug-resistance proteins. Although it acts as a chemosensitizer and radiosensitizer for tumors in some cases, curcumin has also been shown to protect normal organs such as liver, kidney, oral mucosa, and heart from chemotherapy and radiotherapy-induced toxicity. The protective effects of curcumin appear to be mediated through its ability to induce the activation of NRF2 and induce the expression of antioxidant enzymes (e.g., hemeoxygenase-1, glutathione peroxidase, modulatory subunit of gamma-glutamyl-cysteine ligase, and NAD(P)H:quinone oxidoreductase 1, increase glutathione (a product of the modulatory subunit of gamma-glutamyl-cysteine ligase), directly quench free radicals, and inhibit p300 HAT activity. These preclinical studies are expected to lead to clinical trials to prove the potential of this age-old golden spice for treating cancer patients.
Wickenberg, J., S. L. Ingemansson and J. Hlebowicz. 2010. Effects of Curcuma longa (turmeric) on postprandial plasma glucose and insulin in healthy subjects. Nutr J. 12, 9: 43.
BACKGROUND: Previous animal studies have shown that Curcuma (C.) longa lowers plasma glucose. C. longa may thus be a promising ingredient in functional foods aimed at preventing type 2 diabetes. The purpose of the study is to study the effect of C. longa on postprandial plasma glucose, insulin levels and glycemic index (GI) in healthy subjects.
METHODS: Fourteen healthy subjects were assessed in a crossover trial. A standard 75 g oral glucose tolerance test (OGTT) was administered together with capsules containing a placebo or C. longa. Finger-prick capillary and venous blood samples were collected before, and 15, 30, 45, 60, 90, and 120 min after the start of the OGTT to measure the glucose and insulin levels, respectively.
RESULTS: The ingestion of 6 g C. longa had no significant effect on the glucose response. The change in insulin was significantly higher 30 min (P = 0.03) and 60 min (P = 0.041) after the OGTT including C. longa. The insulin AUCs were also significantly higher after the ingestion of C. longa, 15 (P = 0.048), 30 (P = 0.035), 90 (P = 0.03), and 120 (P = 0.02) minutes after the OGTT.
CONCLUSIONS: The ingestion of 6 g C. longa increased postprandial serum insulin levels, but did not seem to affect plasma glucose levels or GI, in healthy subjects. The results indicate that C. longa may have an effect on insulin secretion.
Bisht, S. et al. 2010. Systemic Administration of Polymeric Nanoparticle-Encapsulated Curcumin (NanoCurc) Blocks Tumor Growth and Metastases in Preclinical Models of Pancreatic Cancer. Mol Cancer Ther. 9, 8: 2255-2264.
Abstract: Curcumin or diferuloylmethane is a yellow polyphenol extracted from the rhizome of turmeric (Curcuma longa). A large volume (several hundreds) of published reports has established the anticancer and chemopreventative properties of curcumin in preclinical models of every known major cancer type. Nevertheless, the clinical translation of curcumin has been significantly hampered due to its poor systemic bioavailability, which mandates that patients consume up to 8 to 10 g of the free drug orally each day to achieve detectable levels in circulation. We have engineered a polymeric nanoparticle encapsulated curcumin formulation (NanoCurc) that shows remarkably higher systemic bioavailability in plasma and tissues compared with free curcumin upon parenteral administration. In xenograft models of human pancreatic cancer established in athymic mice, administration of parenteral NanoCurc significantly inhibits primary tumor growth in both subcutaneous and orthotopic settings. The combination of parenteral NanoCurc with gemcitabine results in enhanced tumor growth inhibition versus either single agent, suggesting an additive therapeutic influence in vivo. Furthermore, this combination completely abrogates systemic metastases in orthotopic pancreatic cancer xenograft models. Tumor growth inhibition is accompanied by significant reduction in activation of nuclear factor-kappaB, as well as significant reduction in expression of matrix metalloproteinase-9 and cyclin D1, in xenografts treated with NanoCurc and gemcitabine. NanoCurc is a promising new formulation that is able to overcome a major impediment for the clinical translation of curcumin to cancer patients by improving systemic bioavailability, and by extension, therapeutic efficacy.
Kang, C. and E. Kim. 2010. Synergistic effect of curcumin and insulin on muscle cell glucose metabolism. Food Chem Toxicol. 48, 8-9: 2366-2373.
Abstract: Curcumin is a major phenolic compound of Curcuma longa, which has long been used in traditional Indian medicine. Recently, curcumin has been reported to have antihyperglycemic activity in animal models. However, the molecular basis of this action has not been adequately described. In the present study, curcumin was observed to contain a high level of polyphenols and strong antioxidant activity. Then, the antihyperglycemic effect of curcumin was examined for various signaling pathways using C2C12 mouse myoblast cells. From this, curcumin treatment strongly induced glucose uptake and the phosphorylation of AMPK (AMP-activated protein kinase)/ACC (acetyl-CoA carboxylase), but not PI3-kinase (phosphoinositide 3-kinase)/Akt. Interestingly, the co-treatment of insulin and curcumin produced a mutual synergistic activation of both AMPK/ACC and PI3-kinase/Akt pathways. On the other hand, the synergism could not be observed from the co-treatment of insulin and EGCG. It suggests that the two signaling pathways can crosstalk each other in a case-sensitive manner upon the treatment of antioxidant polyphenols. Further, these results were consistent with the findings of GLUT4 translocation to the cell surface. Our findings indicate that curcumin can promote AMPK activation and glucose uptake with increased insulin sensitivity in muscle cells as a potential anti-diabetic therapeutic agent.
Yallapu, M. M., M. Jaggi and S. C.Chauhan. 2010. b-Cyclodextrin-curcumin self-assembly enhances curcumin delivery in prostate cancer cells. Colloids and Surfaces B: Biointerfaces 79, 1; 113-125.
Abstract: Curcumin, a hydrophobic polyphenolic compound derived from the rhizome of the herb Curcuma longa, possesses a wide range of biological applications including cancer therapy. However, its prominent application in cancer treatment is limited due to sub-optimal pharmacokinetics and poor bioavailability at the tumor site. In order to improve its hydrophilic and drug delivery characteristics, we have developed a b-cyclodextrin (CD) mediated curcumin drug delivery system via encapsulation technique. Curcumin encapsulation into the CD cavity was achieved by inclusion complex mechanism. Curcumin encapsulation efficiency was improved by increasing the ratio of curcumin to CD. The formations of CD-curcumin complexes were characterized by Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), thermo-gravimetric analysis (TGA), scanning electron microscope (SEM), and transmission electron microscope (TEM) analyses. An optimized CD-curcumin complex (CD30) was evaluated for intracellular uptake and anti-cancer activity. Cell proliferation and clonogenic assays demonstrated that -cyclodextrin-curcumin self-assembly enhanced curcumin delivery and improved its therapeutic efficacy in prostate cancer cells compared to free curcumin.