Article

A Randomized, Pilot Study to Assess the Efficacy and Safety of Curcumin in Patients with Active Rheumatoid Arthritis

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Abstract

Curcumin is known to possess potent antiinflammatory and antiarthritic properties. This pilot clinical study evaluated the safety and effectiveness of curcumin alone, and in combination with diclofenac sodium in patients with active rheumatoid arthritis (RA). Forty-five patients diagnosed with RA were randomized into three groups with patients receiving curcumin (500 mg) and diclofenac sodium (50 mg) alone or their combination. The primary endpoints were reduction in Disease Activity Score (DAS) 28. The secondary endpoints included American College of Rheumatology (ACR) criteria for reduction in tenderness and swelling of joint scores. Patients in all three treatment groups showed statistically significant changes in their DAS scores. Interestingly, the curcumin group showed the highest percentage of improvement in overall DAS and ACR scores (ACR 20, 50 and 70) and these scores were significantly better than the patients in the diclofenac sodium group. More importantly, curcumin treatment was found to be safe and did not relate with any adverse events. Our study provides the first evidence for the safety and superiority of curcumin treatment in patients with active RA, and highlights the need for future large-scale trials to validate these findings in patients with RA and other arthritic conditions. Copyright © 2012 John Wiley & Sons, Ltd.

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... Combination therapy showed significantly higher therapeutic efficacy than simple treatment alone in patients with active RA and also in rats, by epigenetic regulation. [239][240][241][242][243][244][245] Autophagy inhibitors Activation of autophagy by inhibiting mTOR. [246,247] ...
... Curcumin (diferuloylmethane) is a natural polyphenolic compound found as a major component of turmeric (Curcuma Longa), which is used as a spice and has broad antiinflammatory activity and proven benefits in the treatment of autoimmune diseases, including RA [240,308]. Based on studies, curcumin has vigorous anti-inflammatory, antioxidant, and anti-carcinogenic properties [309][310][311][312][313][314][315][316] and is a natural inhibitor of the proinflammatory transcription factor NF-κB, which mediates the regulation of inflammatory cytokines and proteins during OA and RA [299,309,[317][318][319]. Curcumin has been reported to have consistently potent effects against RA as a multi-target agent. ...
... In fact, it has been reported that curcumin, a HAT-inhibitor, markedly diminishes histone H3 acetylation in the TNF-α-promoted IL-6 promoter, IL-6 mRNA, and IL-6 protein secretion in RA synovial fibroblasts [76]. In a pilot clinical trial, the overall efficacy and safety of curcumin in aggressive RA patients were evaluated, showing that curcumin significantly improved the American College of Rheumatology (ACR) Disease Activity Score (DAS) and was indeed well-established [240]. In addition, curcumin treatment has been shown to significantly reduce joint stiffness and swelling in patients with RA [320]. ...
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Rheumatoid arthritis (RA) is considered a chronic systemic, multi-factorial, inflammatory, and progressive autoimmune disease affecting many people worldwide. While patients show very individual courses of disease, with RA focusing on the musculoskeletal system, joints are often severely affected, leading to local inflammation, cartilage destruction, and bone erosion. To prevent joint damage and physical disability as one of many symptoms of RA, early diagnosis is critical. Auto-antibodies play a pivotal clinical role in patients with systemic RA. As biomarkers, they could help to make a more efficient diagnosis, prognosis, and treatment decision. Besides auto-antibodies, several other factors are involved in the progression of RA, such as epigenetic alterations, post-translational modifications, glycosylation, autophagy, and T-cells. Understanding the interplay between these factors would contribute to a deeper insight into the causes, mechanisms, progression, and treatment of the disease. In this review, the latest RA research findings are discussed to better understand the pathogenesis, and finally, treatment strategies for RA therapy are presented, including both conventional approaches and new methods that have been developed in recent years or are currently under investigation.
... The lack of information about the methodological characteristics of the studies evaluated in the present review made it difficult to classify the quality of evidence, as shown in Figure 2. Eight studies did not mention any method of randomization. [19][20][21][22][23][24][25][26] Among all the articles, five did not mention the allocation method. 18,19,22,23,27 Nine studies had a high risk of bias because the study participants were not blinded to either the intervention or the placebo groups. ...
... 18,19,22,23,27 Nine studies had a high risk of bias because the study participants were not blinded to either the intervention or the placebo groups. 20,21,24,25,29,30 In six studies, an imbalance in either the number of or the reasons for missing data, between the experimental and control groups, was observed. 18,20,25,26,28,30 Lastly, just four authors described all the outcomes targeted and measured. ...
... Shep et al. 22 Wong et al. 20 Schell et al. 18 Panahi et al. 33 Naderi et al. 27 Nakagawa et al. 32 Khojah et al. 23 Javadi et al. 19 Du et al. 28 Hussain et al. 21 Hänninen et al. 31 Chandran and Goel 24 Haroyan et al. 25 Henrotin et al. 17 Bitler et al. 29 Thimóteo et al. 26 Schumacher et al. 30 Low risk of bias Uncertain risk of bias Higher risk Figure 2. Assessment of the quality of randomized clinical trials selected to form part of the present review, 2020. ...
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Background: Rheumatic diseases (RDs) are a group of pathological conditions characterized by inflammation and functional disability. There is evidence suggesting that regular consumption of polyphenols has therapeutic effects capable of relieving RD symptoms. Objective: To synthesize data from randomized controlled trials on administration of polyphenols and their effects on RD activity. Design and setting: Systematic review conducted at Universidade Federal de Ouro Preto, Minas Gerais, Brazil. Methods: A systematic search was conducted in the databases PubMed (Medline), LILACS (BVS), IBECS (BVS), CUMED (BVS), BINACIS (BVS), EMBASE, Web of Science and Cochrane Library and in the grey literature. The present study followed a PRISMA-P checklist. Results: In total, 646 articles were considered potentially eligible, of which 33 were then subjected to complete reading. Out of these, 17 randomized controlled trials articles were selected to form the final sample. Among these 17 articles, 64.71% assessed osteoarthritis (n = 11), 23.53% rheumatoid arthritis (n = 4), 5.88% rheumatoid arthritis and fibromyalgia (n = 1) and 5.88% osteoarthritis and rheumatoid (n = 1). Intake of polyphenol showed positive effects in most of the studies assessed (94.12%): it improved pain (64.70%) and inflammation (58.82%). Conclusion: Polyphenols are potential allies for treating RD activity. However, the range of polyphenol sources administered was a limitation of this review, as also was the lack of information about the methodological characteristics of the studies evaluated. Thus, further primary studies are needed in order to evaluate the effects of polyphenol consumption for reducing RD activity. Systematic review register: PROSPERO - CRD42020145349.
... [15][16][17][18][19][20][21] Curcumin is the active ingredient of turmeric which its anti-inflammatory and antioxidant properties have been studied in patients with cardiovascular diseases and cancers. [22][23][24] Some studies indicated that curcumin decreased inflammatory markers, such as (Erythrocyte Sedimentation Rate) ESR and C-Reactive Protein (CRP), in patients with ADs, 25,26 but other studies failed to find such associations. 27 Inconsistent findings were also reported for the effects of curcumin supplementation on serum levels of interleukins and tumor necrosis factor-α. ...
... Overall, 438 participants of both genders, 212 in intervention and 226 in the placebo group, with a mean age ranging between 36 and 53.71 years, were included. Different types of curcumin, including turmeric matrix formulation (Acumin ™), 26 hydrogenated curcuminoids formulation (CuroWhite™), 32 curcumin nanomicelle, 33 and natural curcumin 25,29,34 were used as the intervention in included studies. Curcumin was administered daily, with doses ranging from 40 to 1500 mg in the included studies. ...
... Assessment of study quality by the predefined tool showed that half of the included studies in our meta-analysis had high quality (scores≥ 6), 29,33,34 whiles the others had a moderate methodological quality (scores between 3 and 6) 25,26,32 More detailed information about the quality assessment of the included studies is shown in Table 2. ...
Article
Background Although previous studies have examined the impact of curcumin supplementation on cytokine levels in patients with autoimmune disorders, we were unable to find a systematic review of the effect of curcumin supplementation on inflammatory biomarkers such as CRP and ESR in patients with rheumatoid arthritis or ulcerative colitis; therefore we conducted this systematic review and meta-analysis. Methods Relevant studies published from inception to December 2020 were systematically searched through the PubMed, SCOPUS, and google scholar databases. We conducted our systematic review and meta-analysis according to the 2020 PRISMA guidelines. The quality of the papers were assessed by using the Cochrane Collaboration's risk of bias tool. Included studies were randomized clinical trials on the effects of supplementation with curcumin or its derivative on inflammatory factors in patients with rheumatoid arthritis and ulcerative colitis. Pooled effect sizes were calculated using a random-effects model and reported as the weighted mean difference (WMD) and 95% CI. Results In all, six studies met the inclusion criteria for this study. Curcumin supplementation in doses of 250-1500 mg/day over 8-12 weeks was observed to be associated with decreases in CRP and ESR in adult patients with rheumatoid arthritis and ulcerative colitis in comparison with the control group (WMD: -0.42; 95% CI: -0.59, -0.26, I² = 94.3%; WMD: -55.96; 95% CI: -93.74, -18.17, I² = 99.7%, respectively). Significant findings were also observed based on subgroup analyses by the study sample size, duration, participants’ age, curcumin dosage, and type of disease. Conclusions Curcumin supplementation was associated with significant reductions in levels of CRP and ESR in patients with rheumatoid arthritis and ulcerative colitis. Earlier studies reported curcumin as a safe complementary therapy for several diseases. However, a handful of studies were found on the effect of curcumin on autoimmune diseases despite our comprehensive search. Further studies are therefore warranted in this area.
... Rheumatoid arthritis (RA) model: collagen-induced arthritis (CIA) rats [11] Inflammatory bowel disease model: DSS-induced mice 50 mg/kg [12] RA 250 or 500 mg/twice a day [13,14] Oral lichen planus 80 mg/d [15] Resveratrol Rheumatoid arthritis (RA) model: collageninduced arthritis (CIA) rats [11] Inflammatory bowel disease model: DSS-induced mice 50 mg/kg [12] RA 250 or 500 mg/twice a day [13,14] Oral lichen planus 80 mg/d [15] Resveratrol Polyphenolic Phytoalexin Autoimmune myocarditis model: Cardiay myosin immunized rats 50 mg/kg [16] RA model: BIICinduced rats 200 or 400 mg/kg [17] SLE model: pristine-induced mouse 25 or 50 mg/kg [18] RA 1 g/d [19] Quercetin Flavonoid RA model: Zymosan-induced mice [20] RA model: CIA mice 30 or 150 mg/kg [21,22] SLE model: chronic graft vs. ...
... Rheumatoid arthritis (RA) model: collagen-induced arthritis (CIA) rats [11] Inflammatory bowel disease model: DSS-induced mice 50 mg/kg [12] RA 250 or 500 mg/twice a day [13,14] Oral lichen planus 80 mg/d [15] Resveratrol Rheumatoid arthritis (RA) model: collageninduced arthritis (CIA) rats [11] Inflammatory bowel disease model: DSS-induced mice 50 mg/kg [12] RA 250 or 500 mg/twice a day [13,14] Oral lichen planus 80 mg/d [15] Resveratrol Polyphenolic Phytoalexin Autoimmune myocarditis model: Cardiay myosin immunized rats 50 mg/kg [16] RA model: BIICinduced rats 200 or 400 mg/kg [17] SLE model: pristine-induced mouse 25 or 50 mg/kg [18] RA 1 g/d [19] Quercetin Flavonoid RA model: Zymosan-induced mice [20] RA model: CIA mice 30 or 150 mg/kg [21,22] SLE model: chronic graft vs. ...
... RA model: CIA mice 50 µg/mL; 50 mg/kg/d [26] human monocyte-derived dendritic cells [27] Multiple sclerosis (MS) model: experimental autoimmune encephalomyelitis (EAE) rats 50, 100 or 200 mg/kg/d [28] RA 60-120 mg/d [26,29] Polyphenolic Phytoalexin Autoimmune myocarditis model: Cardiay myosin immunized rats 50 mg/kg [16] RA model: BIIC-induced rats 200 or 400 mg/kg [17] SLE model: pristine-induced mouse 25 or 50 mg/kg [18] RA 1 g/d [19] Quercetin Rheumatoid arthritis (RA) model: collageninduced arthritis (CIA) rats [11] Inflammatory bowel disease model: DSS-induced mice 50 mg/kg [12] RA 250 or 500 mg/twice a day [13,14] Oral lichen planus 80 mg/d [15] Resveratrol Polyphenolic Phytoalexin Autoimmune myocarditis model: Cardiay myosin immunized rats 50 mg/kg [16] RA model: BIICinduced rats 200 or 400 mg/kg [17] SLE model: pristine-induced mouse 25 or 50 mg/kg [18] RA 1 g/d [19] Quercetin Flavonoid RA model: Zymosan-induced mice [20] RA model: CIA mice 30 or 150 mg/kg [21,22] SLE model: chronic graft vs. ...
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Most of the immunosuppressive drugs used in the clinic to prevent organ rejection or to treat autoimmune disorders were originally isolated from fungi or bacteria. Therefore, in addition to plants, these are valuable sources for identification of new potent drugs. Many side effects of established drugs limit their usage and make the identification of new immunosuppressants necessary. In this review, we present a comprehensive overview of natural products with potent anti-inflammatory activities that have been tested successfully in different models of chronic inflammatory autoimmune diseases. Some of these candidates already have passed first clinical trials. The anti-inflammatory potency of these natural products was often comparable to those of established drugs, and they could be used at least in addition to standard therapy to reduce their dose to minimize unwanted side effects. A frequent mode of action is the inhibition of classical inflammatory signaling pathways, such as NF-κB, in combination with downregulation of oxidative stress. A drawback for the therapeutic use of those natural products is their moderate bioavailability, which can be optimized by chemical modifications and, in addition, further safety studies are necessary. Altogether, very interesting candidate compounds exist which have the potential to serve as starting points for the development of new immunosuppressive drugs.
... Due to its structure, curcumin is a free radical scavenger, reducing redox-related inflammatory signaling [15]. Moreover, various researches showcased its ability to diminish other signaling pathways, including those related to the activity of NF-κB, JAK-STAT, MAPK, or mTOR complex proteins [16][17][18]. Profitable attributes of curcumin have been shown to lay a heavy impact on the functionality of RA FLS by reducing their survivability and hence the number of overproliferating cells [19], decreasing expression of IL-1β, TNF-α, and COX-2 proteins and diminishing production of tissue destroying metalloproteinases (MMP-1, MMP-3, and MMP-13) [16,20,21]. Presented antiinflammatory properties, safety, and low cost of usage make curcumin a great candidate for potential therapies, which are already tested in trials conducted on patients with RA [17,19,22]. ...
... Profitable attributes of curcumin have been shown to lay a heavy impact on the functionality of RA FLS by reducing their survivability and hence the number of overproliferating cells [19], decreasing expression of IL-1β, TNF-α, and COX-2 proteins and diminishing production of tissue destroying metalloproteinases (MMP-1, MMP-3, and MMP-13) [16,20,21]. Presented antiinflammatory properties, safety, and low cost of usage make curcumin a great candidate for potential therapies, which are already tested in trials conducted on patients with RA [17,19,22]. Nonetheless, more experiments are still required to completely establish all of the curcumin's benefits in RA treatments. ...
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Rheumatoid arthritis (RA) is one of the most prevalent autoimmune diseases, affecting approximately 1% of the total global population. Curcumin, a natural polyphenol is a substance that could potentially mitigate the course of this disease. To evaluate curcumin’s anti-inflammatory impact on synoviocytes in the RA model, a set of experiments was conducted on SW982 cells, stimulated by IL-1β, IL-6, or TNF-α to emulate inflammation. During the research, the curcumin effect was evaluated by measuring cell survivability, expression of MMP1 gene, subcellular localization of P70S6K1 protein, and its phosphorylated form and amount of produced IL-6 and TNF-α. Results of conducted experiments presented a positive impact of curcumin on synoviocytes in the RA model, by reducing SW982 cells’ survivability, decreasing levels of MMP1 gene expression and TNF-α protein production, which altogether confirm beneficial effects of the curcumin therapy in a RA in vitro model.
... Due to CUR chemical characteristics, it is considered to be a potent anti-inflammatory phytochemical that can interact with different inflammatory pathways that generated wide range pre-clinical and clinical therapeutic potentials for CUR [9,10]. In the past decade, a growing interest was noticed in CUR-based therapies in prophylaxis and treatment for different diseases, including CVD (atherosclerosis, diabetic cardiomyopathy, arrhythmia, hypertrophic cardiomyopathy, and heart failure) [11][12][13][14][15][16][17][18][19], cancer (colon cancer, breast cancer, and multiple myeloma) [20][21][22][23][24][25][26][27], neurodegenerative diseases (Parkinson's, Alzheimer's disease, and multiple sclerosis) [8,[28][29][30], autoimmune diseases (osteoarthritis and rheumatoid arthritis) [31,32], psychological disorders [33][34][35][36][37], diabetes [38][39][40], pulmonary diseases [41][42][43], gastrointestinal disorders (gastric ulcers, indigestion, and dyspepsia) [44][45][46][47][48], ophthalmic disorders [49][50][51], and skin disorders [52][53][54]. ...
... This effect is attributable to inhibition of cardiomyocyte Due to CUR chemical characteristics, it is considered to be a potent anti-inflammatory phytochemical that can interact with different inflammatory pathways that generated wide range pre-clinical and clinical therapeutic potentials for CUR [9,10]. In the past decade, a growing interest was noticed in CUR-based therapies in prophylaxis and treatment for different diseases, including CVD (atherosclerosis, diabetic cardiomyopathy, arrhythmia, hypertrophic cardiomyopathy, and heart failure) [11][12][13][14][15][16][17][18][19], cancer (colon cancer, breast cancer, and multiple myeloma) [20][21][22][23][24][25][26][27], neurodegenerative diseases (Parkinson's, Alzheimer's disease, and multiple sclerosis) [8,[28][29][30], autoimmune diseases (osteoarthritis and rheumatoid arthritis) [31,32], psychological disorders [33][34][35][36][37], diabetes [38][39][40], pulmonary diseases [41][42][43], gastrointestinal disorders (gastric ulcers, indigestion, and dyspepsia) [44][45][46][47][48], ophthalmic disorders [49][50][51], and skin disorders [52][53][54]. ...
... Non-specific. Generally safe [49,50]. ...
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Vestibular disorders may generate complex signs and symptoms, which may alter pa-tients' balance and the quality of life. Dizziness and vertigo can strongly affect daily activities and relations. Despite the presence of conventional drugs, maneuvers, and surgery, another interesting therapeutic opportunity is offered by nutraceuticals. These molecules are often used in the treatment of dizziness and vertigo, but the rationale of their application is not always solidly demonstrated by the scientific evidence. Several substances have shown a variable level of efficacy/useful-ness in this field, but there is lack of important evidence for most of them. From a medico-legal point of view, specific information must be provided to the patient regarding the efficacy and possibilities that the use of these preparations can allow. Administering the right nutraceutical to the proper patient is a fundamental clinical skill. Integrating conventional drug treatment with nutraceutical administration seems to be easy, but it may be difficult considering the (in part unexplored) phar-macodynamics and pharmacokinetics of nutraceuticals. The aim of the scientific community should be to elevate nutraceuticals to the same law and technical dignity of conventional drugs.
... Results show that curcumin administration showed the significantly improvement in overall Disease Activity Score and American College of Rheumatology compare with diclofenac sodium. 74 Clinical trials of curcumin in the treatment of arthritis have produced promising results. However, curcumin is not yet available as a treatment for arthritis due to limited data. ...
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Ying Peng,1 Mingyue Ao,1 Baohua Dong,1 Yunxiu Jiang,1 Lingying Yu,1 Zhimin Chen,1 Changjiang Hu,1,2 Runchun Xu1 1State Key Laboratory of Southwestern Chinese Medicine Resources; Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 2Neo-Green Pharmaceutical Co., Ltd., Chengdu, People’s Republic of ChinaCorrespondence: Zhimin Chen; Changjiang Hu Email chenzhimin@cdutcm.edu.cn; 654460129@qq.comAbstract: Curcumin is a natural compound with great potential for disease treatment. A large number of studies have proved that curcumin has a variety of biological activities, among which anti-inflammatory effect is a significant feature of it. Inflammation is a complex and pervasive physiological and pathological process. The physiological and pathological mechanisms of inflammatory bowel disease, psoriasis, atherosclerosis, COVID-19 and other research focus diseases are not clear yet, and they are considered to be related to inflammation. The anti-inflammatory effect of curcumin can effectively improve the symptoms of these diseases and is expected to be a candidate drug for the treatment of related diseases. This paper mainly reviews the anti-inflammatory effect of curcumin, the inflammatory pathological mechanism of related diseases, the regulatory effect of curcumin on these, and the latest research results on the improvement of curcumin pharmacokinetics. It is beneficial to the further study of curcumin and provides new ideas and insights for the development of curcumin anti-inflammatory preparations.Keywords: anti-inflammatory, osteoarthritis, psoriasis, atherosclerotic, pharmacokinetics, prodrug
... It is a non-toxic and highly promising natural compound with a long history of use without any side effects. [10] A review article in 2012 showed that curcumin modulates multiple molecular targets and exerts multifaceted pharmacological activities, including anti-inflammation effects for the treatment and prevention of chronic inflammatory diseases. [11] Also, it is found that curcumin relieves neurogenic pain by down-regulating inflammatory mediator expression. ...
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Background: Migraine is a prevalent health condition associated with significant pain and disability. Neurogenic inflammation has a key role in migraine pathophysiology. Curcumin is a well-known herb compound with anti-inflammatory function. This study was aimed to evaluate the effects of curcumin supplementation on clinical features, as well as on serum levels of calcitonine gene-related peptide (CGRP) and interleukin-6 (IL-6). Methods: This randomized double-blind placebo-controlled clinical trial was carried out on 44 women with migraine, receiving either 500 mg curcumin twice a day or placebo supplements for 8 weeks. Serum CGRP and IL-6 concentration, and clinical symptoms including headache severity, duration and frequency were measured at the baseline and end of study. Results: After 8-week intervention, compared with placebo, curcumin supplementation led to significand reduction in CGRP (P < 0.001), IL-6 (P = 0.041), severity (P = 0.001), and duration of headache (P = 0.007). Headache frequency showed marginal improvement in curcumin group, compared to controls (P = 0.052). Within-analysis indicated significant decrease in CGRP and severity (P < 0.001), frequency (P = 0.014) and duration (P = 0.003) and no significant decrease in IL-6 (P = 0.454), compared to baseline in curcumin group. There were no significant changes in body mass index (BMI), weight, percent body fat (PBF), and percent body muscle (PBM) between the two groups. Conclusions: Curcumin supplementation improved the pro-inflammatory markers and clinical features of migraine headaches and that could be contributed to could be to its anti-inflammatory properties.
... Following CUR treatment, interesting achievements have been reported in rheumatoid arthritis (RA) [74]. RA is a chronic proinflammatory disease featured by uncontrolled synovial fibroblast growth where smoking and stress have been identified as leading causes [75,76]. ...
Article
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Due to its vast therapeutic potential, the plant-derived polyphenol curcumin is utilized in an ever-growing number of health-related applications. Here, we report the extraction methodologies, therapeutic properties, advantages and disadvantages linked to curcumin employment, and the new strategies addressed to improve its effectiveness by employing advanced nanocarriers. The emerging nanotechnology applications used to enhance CUR bioavailability and its targeted delivery in specific pathological conditions are collected and discussed. In particular, new aspects concerning the main strategic nanocarriers employed for treating inflammation and oxidative stress-related diseases are reported and discussed, with specific emphasis on those topically employed in conditions such as wounds, arthritis, or psoriasis and others used in pathologies such as bowel (colitis), neurodegenerative (Alzheimer’s or dementia), cardiovascular (atherosclerosis), and lung (asthma and chronic obstructive pulmonary disease) diseases. A brief overview of the relevant clinical trials is also included. We believe the review can provide the readers with an overview of the nanostrategies currently employed to improve CUR therapeutic applications in the highlighted pathological conditions.
... Thus, the working group has chosen to list potentially relevant supplements using the conditional to facilitate the discussions with patients about existing studies, without going as far as recommending them. Note that other studies, namely on turmeric, have been done but their quality was not sufficient to be cited in the recommendation [78,79]. ...
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This article presents the 1st set of dietary recommendations of the French Society for Rheumatology for patients suffering from chronic inflammatory rheumatic diseases (IRD) made by a working group consisting of 12 rheumatology experts, 3 physician nutrition specialists, 1 internal medicine specialist, 1 registered dietician and 3 representatives from patient associations. This group relied on a systematic literature review and on expert opinions, while taking into consideration not only the joint effects of diet in IRD but also the extra-articular ones. Eight general principles and nine recommendations were established. The general principles emphasize that nutritional advice is not a substitute for pharmacological treatment of IRD and that it is an integral part of the patients’ overall care, which could help the patient actively participate in their care. The recommendations propose supporting weight loss in subjects who are overweight or obese, a Mediterranean-type diet and supplementation in polyunsaturated fatty acids, mainly omega-3. Conversely, gluten-free diets (in the absence of celiac disease), vegetarian/vegan diets, fasting and elimination of dairy products should not be proposed. Supplementation with vitamins or trace elements is not indicated for controlling chronic IRD activity, while the use of probiotics or spices is not recommended given the limited or disparate data.
... The use and evaluation of the traditional folk plants E. cardamomum and C. longa in terms of their anti-inflammatory activities have been remarkable because of the positive results obtained in several studies where these plants have been used to reduce the symptoms of various chronic inflammatory diseases [28]. In the development of such research, numerous bioactive compounds present in its essential oils have been identified, which differ in proportions and presence depending on the region where the plant was collected, the time of collection, or the type of extraction [13]. ...
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The genus Zingiberaceae has been widely used for phytotherapeutic purposes in traditional medicine throughout the world for its anti-inflammatory activity. Experimental studies have established that inflammation caused by chronic infections represents a risk factor for different forms of cancer. The objective of this study was focused on determining the anti-inflammatory capacity and cytotoxic activity of aqueous extracts of Elettaria cardamomum (cardamom) and Curcuma Longa (turmeric). The extracts were obtained by maceration and, through GC-MS/MS, a total of 11 different chemical components were determined in the aqueous extract of cardamom and 7 in the extract of turmeric. The main compounds found in cardamom and turmeric were α-terpinyl acetate (54.46%) and β-turmerone (33.45%), respectively. RT-qPCR results showed significantly lower gene expression levels of innate inflammatory cytokines (IL-6 and TNF-α) compared to the control (LPS). Also, it was observed that the extracts do not possess cytotoxic activity against different cell lines, where E. cardamomum showed EC50 (µg/mL) of 473.84 (HeLa cells), 237.36 (J774A.1 cells), 257.51 (Vero E6 cells), and 431.16 (Balb/C peritoneal cells) and C. longa showed EC50 (µg/mL) of 351.17 (HeLa cells), 430.96 (J774A.1 cells), 396.24 (Vero E6 cells), and 362.86 (Balb/C peritoneal cells). The results of this research suggest that natural extracts of E. cardamomum and C. longa possess anti-inflammatory effects and no cytotoxic activity against HeLa, J774A.1, Vero E6, and Balb/C peritoneal cell lines, Finally, it was observed that the extracts also decreased nitric oxide (NO) production in peritoneal macrophages.
... Moreover, it is mostly used as a spice and a food-coloring agent in Southeastern Asian cuisine [2]. Curcumin, a natural compound isolated from C. longa, has multiple applications in treatment of various diseases such as cardiovascular diseases [3], liver disease [4,5], obesity [6,7], cancer [8], inflammatory diseases [9,10], and aging [11,12]. ...
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Sleep disturbances, as well as sleep-wake rhythm disorders, are characteristic symptoms of Alzheimer’s disease (AD) that may head the other clinical signs of this neurodegenerative disease. Age-related structural and physiological changes in the brain lead to changes in sleep patterns. Conditions such as AD affect the cerebral cortex, basal forebrain, locus coeruleus, and the hypothalamus, thus changing the sleep-wake cycle. Sleep disorders likewise adversely affect the course of the disease. Since the sleep quality is important for the proper functioning of the memory, impaired sleep is associated with problems in the related areas of the brain that play a key role in learning and memory functions. In addition to synthetic drugs, utilization of medicinal plants has become popular in the treatment of neurological diseases. Curcuminoids, which are in a diarylheptanoid structure, are the main components of turmeric. Amongst them, curcumin has multiple applications in treatment regimens of various diseases such as cardiovascular diseases, obesity, cancer, inflammatory diseases, and aging. Besides, curcumin has been reported to be effective in different types of neurodegenerative diseases. Scientific studies exclusively showed that curcumin leads significant improvements in the pathological process of AD. Yet, its low solubility hence low bioavailability is the main therapeutic limitation of curcumin. Although previous studies have focused different types of advanced nanoformulations of curcumin, new approaches are needed to solve the solubility problem. This review summarizes the available scientific data, as reported by the most recent studies describing the utilization of curcumin in the treatment of AD and sleep deprivation-related consequences.
... Also, turmeric has an anticarcinogenic effectinduction of apoptosis (Khar et al., 2001), pro/antimutagenic activity (Shukla et al., 2002), antioxidant effect (Masuda et al., 2001) and anti-inflammatory activity (Phan et al., 2001). Turmeric reduces aches and discomfort (Kuptniratsaikul et al., 2014), helps stiff joints (Chandran and Goel, 2012). Turmeric has anti-pathogenic bacterial activity (Mahady et al., 2002;Moghadamtousi et al., 2014), antifungal effect (Jayaprakasha et al., 2001) antiviral effect (Taher et al., 2003), antiprotozoan activity (Koide et al., 2002), antifibrotic effect (Punithavathi et al., 2000) and antivenom effect (Araujo and Leon, 2001;Moghadamtousi et al., 2014). ...
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The objective was to add certain herbs rich in active physiological ingredients for skimmed-milk yoghurt and cast ultrafiltration (UF)-Kariesh cheese to find out their suitability as fortifiers en route to innovate functional products. Yoghurt was made using cow's skimmed milk fortified with the milled herbal aqueous extract (10% w/w) at the level of nil (control), 1, 2, or 3% (w/w) of turmeric, sage or marjoram. Cheese was made using UF-skimmed milk concentrated, to the desired final cheese total solids (TS) % and fortified as mentioned before. Skim milk powder was used to avoid any dilution in the final TS %, whether of yoghurt milk or pre-cheese. Organ-oleptically, it was accepted the herbal extract providing that its level did not exceed 1.0% for yoghurt or 2% for cheese. The protein content exhibited no difference in yoghurt and reduction in cheese due to herbs because which the ash content decreased in yoghurt and increased in cheese, in those the fiber presented because of herbs. Turmeric encouraged the growth of bacterial starter culture and acid production versus marjoram or sage. The Streptococcus thermophilus count was always higher than that of Lactobacillus delbrueckii ssp. bulgaricus. But their counts in cheese were lower versus yoghurt. In conclusion, skimmed-milk yoghurt and cast UF-Kariesh cheese could meet the intended health purposes when fortified with 1% for the former or 2% for the latter using aqueous extract (10%) of sage, marjoram or rather turmeric, those of many impressive health benefits.
... De werkzaamheid van curcumine werd jaren geleden voor het eerst aangetoond rond 1980, toen een dubbelblinde cross-over studie van curcumine versus de krachtige ontstekingsremmer gebruikt bij renpaarden fenylbutazon bij beide geneesmiddelen een significante verbetering lieten zien in ochtendstijfheid, wandeltijd, gewrichtszwelling, met de volledige afwezigheid van negatieve effecten in de curcumine-groep [5], terwijl fenylbutazon 3 (drie) jaar later van de markt werd gehaald omdat het het immuunsysteem van sommige mensen had gedefunctionaliseerd, waardoor ze hun leven hadden verloren [6]. Een ander onderzoek toonde aan dat van 45 (vijfenveertig) patiënten bij wie diagnostisch de reumatoïde artritis werd gesteld, gerandomiseerd in 3 (drie) groepen (curcumine, het standaardgeneesmiddel of beide) dat onderaan de streep een vermindering van de ziekteactiviteit werd vastgesteld, evenals een vermindering van de gevoeligheid en zwelling en dus verbetering in alle 3 (drie) groepen, maar dat de (2) twee groepen welke curcumine consumptie bevatte de hoogste percentages significante verbetering vertoonden hetgeen beter was dan die in de medicijngroep hetgeen dus demonstreert dat curcumine niet alleen veilig en effectief was, maar ook verrassend effectiever in het verlichten van pijn in vergelijking met het beste medicijn naar keuze zonder enige duidelijke nadelige effecten, waarbij zelfs curcumine beschermend leek aangezien er meer negatieve effecten waren in de diclofenac-natrium geneesmiddelgroep dan de gecombineerde geneesmiddel-en curcuminegroep [7]. ...
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Website link: www.nutritionfactsnederlands.nl/videoscript/2022/1/17/kurkuma-alomvattend-artikel [Turmeric-SOURCES BELOW] The pungent, bitter, astringent smelling brightly yellow-orange golden (the alleppey turmeric also called the Indian turmeric exemplars have a deep yellow to orange-yellow color) or (exclusive or) brown (the Chinese turmeric exemplars have typically a brownish color) or (exclusive or) red (which red color is created by combining dried turmeric with calcium hydroxide powder and when red it is also called "kunkum" and "kumkuma") spice powder from the dried ginger-like vegetable but colored on the inside root stalks and the rhizomes of the perennial flowering herb plant living in tropical warm temperature areas and needing plenty of rainfalls to thrive commonly named turmeric which species name is curcuma longa linnaeus (alsoIndiase saffraan" and "Indian saffron" since Marco Polo wrote a that it is a vegetable that has all the properties of true saffron as well as the smell and the color but yet it is not really saffron) categorizable in the plant genus curcuma (also called kurkuma which name may be derived from the Sanskrit "kuṅkuma" which is referring to both turmeric and saffron) in the ginger family zingiberaceae (and thus a relatively close relative of ginger) possibly because it contains the non-steroidal polyphenolic (because of the multiple chemically defined aromatic phenol rings) and multiple hydroxyl group (which aromatic phenol rings and hydroxyl groups give it its antioxidant property) containing the polar readily in water soluble potentially powerful antioxidant curcuminoid diferuloylmethane biologically active compound molecule turmeric curcumin (also called "curcumine", "kurkumine" and "kurkumin") that is contained and thus can be found in turmeric as it makes up of approximately 5 [%] of its mass [105] (for which a convenient useful pragmatic sidenote would be that curcumin's blood serum level bioavailability by increased absorption in the colon can be synergistically potentially boosted thus increased up to 2'000 [%] in human animals when consuming it together with the black pepper piper nigrum that contains the compound peperine [1] which is responsible for about 5 [%] of its mass [106] and which is also responsible for the pungent flavor of pepper and also inhibits the livers metabolism mechanism to make substances water-soluble so they can be more easily excreted suppressing this mechanism leading to higher blood levels of bioavailability of curcumin as within an hour you can see a little bump in the level in the bloodstream of curcumin when the mechanism is unsuppressed because the liver is actively trying to get rid of it while compared to when also consuming peperine with the same amount of curcumin consumed the bioavailability shoots up to 2'000 [%] [1], which does not take much black pepper since a little pinch of 1/20 of a teaspoon is enough to considerably boost levels [107], which concomitant combination would work great in a curry recipe for example since the bioavailability of curcumin is normally very low and thus the nutritional value is poorer when not consumed with black pepper since just a tiny bit gets into our bloodstream after eating a nice curry unless we add some black pepper [1]; and another way to boost the absorption of curcumin is to consume it in the whole food turmeric root form (relatively fresh or dried as a powder) as compared to an extract because natural oils found in turmeric root and turmeric powder can enhance the bioavailability of curcumin 7 (seven) to 8 (eight) fold [107]; and when eaten together with a relatively large amount of fatty acid containing foods such as nuts, e.g. walnuts, almonds or pecans, also ensures increased bioavailability as curcumin can be directly absorbed into the bloodstream through the lymphatic system and thus thereby in part bypassing the liver [107]) which curcumin pigment also gives turmeric its brightly deep yellow to orange-yellow golden color which turmeric is possibly usable as
... De werkzaamheid van curcumine werd jaren geleden voor het eerst aangetoond rond 1980, toen een dubbelblinde cross-over studie van curcumine versus de krachtige ontstekingsremmer gebruikt bij renpaarden fenylbutazon bij beide geneesmiddelen een significante verbetering lieten zien in ochtendstijfheid, wandeltijd, gewrichtszwelling, met de volledige afwezigheid van negatieve effecten in de curcumine-groep [5], terwijl fenylbutazon 3 (drie) jaar later van de markt werd gehaald omdat het het immuunsysteem van sommige mensen had gedefunctionaliseerd, waardoor ze hun leven hadden verloren [6]. Een ander onderzoek toonde aan dat van 45 (vijfenveertig) patiënten bij wie diagnostisch de reumatoïde artritis werd gesteld, gerandomiseerd in 3 (drie) groepen (curcumine, het standaardgeneesmiddel of beide) dat onderaan de streep een vermindering van de ziekteactiviteit werd vastgesteld, evenals een vermindering van de gevoeligheid en zwelling en dus verbetering in alle 3 (drie) groepen, maar dat de (2) twee groepen welke curcumine consumptie bevatte de hoogste percentages significante verbetering vertoonden hetgeen beter was dan die in de medicijngroep hetgeen dus demonstreert dat curcumine niet alleen veilig en effectief was, maar ook verrassend effectiever in het verlichten van pijn in vergelijking met het beste medicijn naar keuze zonder enige duidelijke nadelige effecten, waarbij zelfs curcumine beschermend leek aangezien er meer negatieve effecten waren in de diclofenac-natrium geneesmiddelgroep dan de gecombineerde geneesmiddel-en curcuminegroep [7]. ...
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De prikkelende, bittere, neus-samentrekkend ruikende fel geeloranje gouden (de alleppey kurkuma ook wel de Indiase kurkuma exemplaren genoemd hebben een diepgele tot oranjegele kleur) of (exclusief of) bruin (de Chinese kurkuma exemplaren hebben een typisch bruinachtige kleur) of (exclusief of) rood (welke rode kleur ontstaat door gedroogde kurkuma te combineren met calciumhydroxide poeder en wanneer het rood is wordt het ook wel het "kunkum" en "kumkuma" genoemd) kruidenpoeder van de gedroogde gemberachtige groente maar aan de binnenkant gekleurde wortelstelen en de wortelstokken van de meerjarige bloeiende kruidenplant die leeft in gebieden met tropisch warme temperaturen en veel regen nodig heeft om te gedijen welke gewoonlijk kurkuma genoemd met de soortnaam curcuma longa linnaeus (ookmeritorious earth", "Indiase saffraan" en "Indian saffron" omdat Marco Polo schreef dat het een groente is die alle eigenschappen heeft die echte saffraan ook heeft, waaronder de geur en de kleur, maar toch niet gelijk is aan echte saffraan) categoriseerbaar in het plantengeslacht curcuma (ook kurkuma genoemd, waarvan de naam kan zijn afgeleid van het Sanskriet "kuṅkuma" dat verwijst naar zowel kurkuma als saffraan) in de gemberfamilie zingiberaceae (en dus een relatief naaste verwant van gember) mogelijk omdat het de niet-steroïde polyfenolische (vanwege de meerdere chemisch gedefinieerde aromatische fenolringen) en de meervoudige hydroxylgroep (welke chemisch gedefinieerde aromatische fenolringen en meerdere hydroxylgroepen het zijn antioxiderende eigenschap geven) bevat het polair gemakkelijk in water oplosbaar potentieel krachtige antioxidant curcuminoïde diferuloylmethaan biologisch actieve verbinding molecuul kurkuma curcumine (ook wel "curcumine", "kurkumine" en "kurkumin" genoemd) dat aanwezig is en dus kan worden gevonden in kurkuma, aangezien het ongeveer 5 [%] van zijn massa uitmaakt [105] (waarvoor een handige nuttige pragmatische kanttekening zou zijn dat de biologische beschikbaarheid van curcumine in het bloedserum door verhoogde absorptie in de dikke darm synergetisch potentieel kan worden versterkt en dus verhoogd tot 2'000 [%] bij menselijke dieren bij gepaarde consumptie samen met de zwarte peper piper nigrum die de verbinding peperine [1] bevat die verantwoordelijk is voor ongeveer 5 [%] van zijn massa [106] en tevens ook verantwoordelijk is voor de scherpe smaak van peper en het remt inhibiterend ook het metabolische vermogen van de lever om stoffen in water oplosbaar te maken zodat ze gemakkelijker kunnen worden uitgescheiden hetgeen leidt tot verhoging van het biologisch beschikbare niveau van curcumine in de bloedbaan omdat wanneer het mechanisme niet wordt onderdrukt de lever actief probeert om er vanaf te komen en je dus maar een relatief kleine piek in bloodbuis niveau van crucumine ziet terwijl vergeleken met wanneer gepaard ook peperine wordt geconsumeerd met dezelfde hoeveelheid curcumine de biologische beschikbaarheid omhoog schiet tot wel 2000 [%] [ 1], waarvoor niet veel zwarte peper nodig is, aangezien een klein snuifje van 1/20 van een theelepel genoeg is om het niveau aanzienlijk te verhogen [107], een combinatie die bijvoorbeeld uitstekend zou werken in een curryrecept, omdat de biologische beschikbaarheid van curcumine normaal gesproken erg laag is en daarom is de voedingswaarde lager als het niet wordt geconsumeerd met zwarte peper, aangezien er slechts een klein beetje in onze bloedbaan komt na het eten van een lekkere curry, tenzij we wat zwarte peper toevoegen [1]; en een andere manier om de opname van curcumine te stimuleren, is door het in de vorm van kurkumawortel te consumeren (relatief vers of gedroogd als poeder) in vergelijking met een extract, omdat natuurlijke oliën in kurkumawortel en kurkumapoeder de biologische beschikbaarheid van curcumine kunnen verbeteren met een verschil van (zeven) tot 8 (acht) keer hogere biologische beschikbaarheid [107]; en wanneer het samen gegeten
... Several clinical trials have already been conducted in humans in chronic-inflammation and joint-pain pathologies using different formulations of curcumin [23,52,53]. For example, Meriva has shown strong therapeutic potential in inflammatory knee-pain disease, by reducing patients' pain and inflammation in plasma [23]. ...
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Paclitaxel is widely used in the treatment of various types of solid malignancies. Paclitaxel-induced peripheral neuropathy (PIPN) is often characterized by burning pain, cold, and mechanical allodynia in patients. Currently, specific pharmacological treatments against PIPN are lacking. Curcumin, a polyphenol of Curcuma longa, shows antioxidant, anti-inflammatory, and neuroprotective effects and has recently shown efficacy in the mitigation of various peripheral neuropathies. Here, we tested, for the first time, the therapeutic effect of 1.5% dietary curcumin and Meriva (a lecithin formulation of curcumin) in preventing the development of PIPN in C57BL/6J mice. Curcumin or Meriva treatment was initiated one week before injection of paclitaxel and continued throughout the study (21 days). Mechanical and cold sensitivity as well as locomotion/motivation were tested by the von Frey, acetone, and wheel-running tests, respectively. Additionally, sensory-nerve-action-potential (SNAP) amplitude by caudal-nerve electrical stimulation, electronic microscopy of the sciatic nerve, and inflammatory-protein quantification in DRG and the spinal cord were measured. Interestingly, a higher concentration of curcumin was observed in the spinal cord with the Meriva diet than the curcumin diet. Our results showed that paclitaxel-induced mechanical hypersensitivity was partially prevented by the curcumin diet but completely prevented by Meriva. Both the urcumin diet and the Meriva diet completely prevented cold hypersensitivity, the reduction in SNAP amplitude and reduced mitochondrial pathology in sciatic nerves observed in paclitaxel-treated mice. Paclitaxel-induced inflammation in the spinal cord was also prevented by the Meriva diet. In addition, an increase in α7 nAChRs mRNA, known for its anti-inflammatory effects, was also observed in the spinal cord with the Meriva diet in paclitaxel-treated mice. The use of the α7 nAChR antagonist and α7 nAChR KO mice showed, for the first time in vivo, that the anti-inflammatory effects of curcumin in peripheral neuropathy were mediated by these receptors. The results presented in this study represent an important advance in the understanding of the mechanism of action of curcumin in vivo. Taken together, our results show the therapeutic potential of curcumin in preventing the development of PIPN and further confirms the role of α7 nAChRs in the anti-inflammatory effects of curcumin.
... It is a non-toxic and highly promising natural compound with a long history of use without any side effects. [10] A review article in 2012 showed that curcumin modulates multiple molecular targets and exerts multifaceted pharmacological activities, including anti-inflammation effects for the treatment and prevention of chronic inflammatory diseases. [11] Also, it is found that curcumin relieves neurogenic pain by down-regulating inflammatory mediator expression. ...
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ackground: Migraine is a prevalent health condition associated with significant pain and disability. Neurogenic inflammation has a key role in migraine pathophysiology. Curcumin is a well-known herb compound with anti-inflammatory function. This study was aimed to evaluate the effects of curcumin supplementation on clinical features, as well as on serum levels of calcitonine gene-related peptide (CGRP) and interleukin-6 (IL-6). Methods: This randomized double-blind placebo-controlled clinical trial was carried out on 44 women with migraine, receiving either 500 mg curcumin twice a day or placebo supplements for 8 weeks. Serum CGRP and IL-6 concentration, and clinical symptoms including headache severity, duration and frequency were measured at the baseline and end of study. Results: After 8-week intervention, compared with placebo, curcumin supplementation led to significand reduction in CGRP (P < 0.001), IL-6 (P = 0.041), severity (P = 0.001), and duration of headache (P = 0.007). Headache frequency showed marginal improvement in curcumin group, compared to controls (P = 0.052). Within-analysis indicated significant decrease in CGRP and severity (P < 0.001), frequency (P = 0.014) and duration (P = 0.003) and no significant decrease in IL-6 (P = 0.454), compared to baseline in curcumin group. There were no significant changes in body mass index (BMI), weight, percent body fat (PBF), and percent body muscle (PBM) between the two groups. Conclusions: Curcumin supplementation improved the pro-inflammatory markers and clinical features of migraine headaches and that could be contributed to could be to its anti-inflammatory properties.
... The clinical effectiveness of curcumin in treating inflammation was studied in patients diagnosed with osteoarthritis, and significant reductions in myeloperoxidase, collagen degradation activity, and C-reactive protein levels were observed; also, additional symptoms like pain and effusion were reduced [184] . In 45 patients with active rheumatoid arthritis, curcumin (500 mg) was used in combination with diclofenac sodium (50 mg) and there was a significant reduction in their disease activity score compared with the group provided only with diclofenac sodium [185] . In yet another clinical study, patients with acute rhinitis were administered 500 mg of curcumin orally. ...
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The unending morbidity and mortality that results from cancer, as well as adverse reactions due to chemotherapy and the enormous economic burden of treatment and hospitalization, advocates for the necessity of chemopreventive measures. Cancer chemoprevention refers to the use of agents capable of reversing, reducing, or slowing down the pathology of cancer at various stages. Fortunately, a few therapeutic drugs with relatively low toxicity (e.g., tamoxifen, finasteride), and a sparse number of vaccines (hepatitis B, HPV), are used to prevent specific cancers. In the general population, however, therapeutic options for cancer prevention are not common. Nonetheless, it is generally agreed that diet affects the genesis of cancer, and phytochemicals have the capacity of functioning as cancer chemoprevention agents. This is supported by epidemiological studies and clearly documented with animal models designed to mimic human carcinogenesis. Additionally, some public health strategies, such as recommendations for greater consumption of fruits and vegetables, reflect the merits of cancer chemoprevention. Here, we focus on some well-established natural product cancer chemopreventive agents, including resveratrol (grapes), epigallocatechin-3-gallate (green tea), sulforaphane (cruciferous vegetables), anthocyanins (grapes and berries), curcumin (turmeric), silibinin (milk thistle), and lycopene (tomatoes). As aptly demonstrated by genomic analysis and other methods, the mechanistic underpinning is variable and complex. In addition, responses may be mediated through indirect mechanisms, such as interaction with the microbiome. Furthermore, ancillary applications of chemopreventive agents are worthy of consideration, such as management of sequelae induced by chemotherapy. Recognizing the loss of millions of cancer patients every year, it is obvious that negating malignant metastatic conditions remains of paramount importance. In meeting this objective, cancer chemoprevention offers great promise.
... Animal studies have indicated that oral curcumin possess antinociceptive [21] and indicated the involvement of ATP-sensitive potassium channels [22]. Pilot human studies of curcumin have demonstrated promise for improving the symptoms of rheumatoid arthritis and inflammatory bowel disease [23,24]. Curcumin also demonstrated antiviral, anti-inflammatory, antibacterial, antifungal, antidiabetic, antifertility and cardiovascular protective and immunostimulant activity [11]. ...
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Curcuma longa (turmeric) has traditionally been used in Ayurvedic, Unani and herbal drugs to cure numerous ailments. Due to the high demand, the quantitative standardization of herbal products is challenging to maintain their quality. We aim to develop a rapid, sensitive and validated high-performance thin-layer chromatography (HPTLC) method for the simultaneous determination and quantification of curcumin I, curcumin II and curcumin III in C. longa and herbal formulation. The three standards were separated using centrifugal preparative thin-layer chromatography (CPTLC) silica gel and identified by different spectroscopic methods. The developed HPTLC method was validated by following ICH guidelines (linearity; limit of detection, LOD; limit of quantitation; accuracy; precision; and robustness). The calibration curves of both the compounds were linear (50–500 ng/spot), with a correlation coefficient (r2) of >999. The developed HPTLC method was effectively applied to the concurrent detection and quantification of curcumins I–III in fresh, dry rhizomes and the herbal formulation of C. longa extracts was obtained by hot and cold extraction methods.
... Regarding safety, adverse events were reported more frequently in the diclofenac treatment arm than in the curcumin treatment arm. However, it is also not clear how many patients were on concomitant steroids during the trial [21]. Moreover, the results suggest that curcumin as a monotherapy has the potential to reduce the number of swollen joints from 12 to <1 within 8 weeks. ...
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Plant-derived nutraceuticals are proposed as new key instruments to represent a profound “back to basics” shift in medical treatment. Data accumulated over the past ten years suggest that curcumin, the major active compound of the turmeric plant, has anti-inflammatory properties. It has yet to be determined whether the anti-inflammatory profile of curcumin is potent enough to justify the application of this substance as a nutritional supplement for patients with rheumatic diseases. To address this question, the most relevant in vitro studies that investigate the mechanism of action of curcumin were reviewed in this article. In addition, a total of 18 animal and human trials were evaluated. The pleiotropic, anti-inflammatory and immunomodulatory effects of curcumin were observed in animal studies. In addition, human trials demonstrated promising findings. In these studies, curcumin was able to reduce the expression of proinflammatory cytokines, lower the level of the C-reactive protein and improve clinical parameters. A limiting factor of the application of curcumin is the inconsistent bioavailability of the substance. Therefore, new formulations have been developed to improve the pharmacodynamic profile of curcumin. The future acceptance of the substance is dependent on new controlled clinical trials with a standardised formulation of curcumin administered as well as standard of care.
... More over curcumin treatment could not produce any other harmful effect. Consequently, this study concluded that curcumin alone had more safe and protective effects than diclofanic sodium in the treatment of rheumatoid arthritis (Chandran & Goel, 2012). ...
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Plant based traditional health care is one of the ancient remedies used to prevent and treat different health related disorders. Due to increasing cost of medicine in the modern era, people are now moving towards the utilization of ancient ethno medicinal plants based remedies to prevent and treat diseases as well as to maintain their health. Curcuma longa, commonly known as turmeric has been used since ancient times as ethno medicinal plant due to its pharmacological and therapeutic potential. The rhizome of this plant is commonly used to prevent the lifestyle related disorders. Its biologically active components can also be extracted and utilized directly to enhance the efficacy. Purpose of this review is to highlight the importance of turmeric as it contains various biologically active components that are beneficial in prevention and treatment of various health related disorders. Turmeric has been demonstrated to exhibit anti-cancer, immunostimulant, skin protection, ulcer treating, anti-inflammatory, anti-malarial, anti-bacterial, anti-fungal, anti-viral, anti-parasitic, anti-hyperglycemic, anti-oxidant, anti-hyperlipidemic, hepatoprotective, renal protection and hematological parameters maintenance properties. There is no evidence of adverse effects of turmeric in literature. Only the people who are allergic to it can have side effects otherwise it is almost stomach friendly due to which it can be used for treatment of various health related disorders.
Chapter
The liver controls the body's internal environment via various physiological and metabolic processes, either independently or together with other organs. Liver disease is defined as an injury to the hepatic cells and tissues, mainly caused by viral infections, toxic compounds, high doses of drugs, and excessive alcohol intake. There are an estimated two million hepatic disease–associated deaths recorded annually worldwide with a diverse etiology. Numerous medicinal plants and their phytochemicals have been reported to display hepatoprotective activity. Among those, bioflavonoids, low-molecular-weight phenolics possessing a basic C6–C3–C6 structure, have been reported to have the ability to treat hepatic diseases. In the current study, we aimed to summarize hepatic diseases and strategies to treat them and added a brief note on the bioflavonoids that have been tested against hepatic diseases.
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Rheumatoid arthritis (RA) is a debilitating disease associated with locomotion impairment, and conventional therapeutic drugs are not optimal for managing RA. There is an avalanche of medications used for the management of RA. Still, studies have shown that they are associated with severe side effects, including hepatotoxicity, retinopathy, and cardiotoxicity disorders of the central nervous system (CNS), skin, blood, and infections. Complementary and alternative medicine (CAM) is currently gaining attention as a novel panacea for managing debilitating diseases, such as RA. Nigerian folk herbal remedies are replete with a plethora of curative medicine, albeit unvalidated scientifically but with seemingly miraculous provenance. Studies of the identification of bioactive compounds present in these botanicals using advanced spectral analytical techniques have enhanced our understanding of the role of Nigerian herbal remedies in the treatment and management of RA. Interestingly, experimental studies abound that the bioactive compounds present in the extracts of plant botanicals protected animals from the development of RA in different experimental models and reduced the toxicity associated with conventional therapeutics. Validated mechanisms of RA amelioration in human and animal models include suppression of the expression of NF-κB, IL-1β, TNF-α, IL-6, IL-8, IL-17, IL-23, chemokines, TGF-β, RANKL, RANK, iNOS, arginase, COX-2, VEGFA, VEGFR, NFATC1, and TRAP in the synoviocytes. Decreased ROS, NO, MDA, carbonyl groups, and PGE2 in the synovial fluid increased the expression of PPARα/γ; antioxidant and anti-inflammatory molecules also improve RA etiology. In this mini-review, we discuss the global burden of RA, the novel role of plant-based botanicals as potential therapeutics against signaling pathways in RA. Also addressed is the possible repurposing/reprofiling of plant botanicals to increase their therapeutic index among RA patients that patronize traditional healers in Nigeria with a global projection
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Curcumin is a natural component extracted from the rhizomes of turmeric (Curcuma longa), a natural plat with known medicinal uses for more than 4000 years. Most turmeric therapeutic effects are attributed to curcumin, a yellow-coloured extract. Curcumin has received considerable attention due to its biological activities, such as its use in arthritis, liver and neurodegenerative diseases, obesity, and several types of cancers. Most of these curcumin therapeutic activities are related to its antioxidant and anti-inflammatory effects. However, the clinical application of curcumin is hampered by some limitations that prevent its extensive clinical application. Curcumin high hydrophobicity of curcumin and limited water solubility are among the most important limitations. This poor solubility will result in low bioavailability due to its poor absorption into plasma and the target tissues. Curcumin also has rapid metabolism, which will significantly lower its bioavailability and shorten its half-life. Moreover, curcumin is photosensitive with limited chemical stability during manufacturing and storage. These limitations have been overcome by applying nanotechnology using several types of nanoparticles (NPs). This includes using NPs such as liposomes, niosomes, gold nanoparticles, and many others to improve the curcumin solubility and bioavailability. This review focuses on the different types of NPs investigated and the outcomes generated by their use in the most recent studies in this field. To follow the latest advances in the field of site-specific drug delivery using nanomaterials, an electronic databases search was conducted using PubMed, Google scholar and Scopus using the following keywords: lipid-based nanoparticles, curcumin delivery, niosomes, and liposomes.
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This review is aimed to summarize the pain relieving effect of non-drug substances, mostly prescribed as integrators in treatment of pain including, especially in chronic postoperative pain (CPSP) and in chronic back pain after acute episodes. Their use reflects the fact that the current treatments for these syndromes continue to pose problems of unsatisfactory responses in a significant portion of patients and/or of an excess of side effects like those noted in the present opioid crisis. As integrators are frequently introduced into the market without adequate clinical testing this review is aimed to collect the present scientific evidence either preclinical or clinical for their effectiveness. In particular, we reviewed the data on the use of: B vitamins; vitamin C; vitamin D; Alpha Lipoic Acid (ALA); N-acetylcysteine (NAC); Acetyl L-Carnitine (ALC); Curcumin; Boswellia serrata; Magnesium; Coenzyme Q10 and Palmitoylethanolamide (PEA). The combination of preclinical findings and clinical observations strongly indicate that these compounds deserve a more careful attention, some of them having interesting clinical potentials also in preventing chronic pain after acute episode. In particular examining their putative mechanisms of action it emerges that combinations of few of them may exert an extraordinary spectrum of activities on a large variety of pain-associated pathways and may be eventually used in combination with more traditional pain killers in order to extend the duration of the effect and to lower the doses. Convincing examples of effective combinations against pain are vitamin B complex plus gabapentin for CPSP, including neuropathic pain; vitamin B complex plus diclofenac against low back pain and also in association with gabapentin, ALA, for burning mouth syndrome. These as well as other examples need, however, careful controlled independent clinical studies confirming their role in therapy.
Chapter
Curcumin is an herbal medicine that has been used for a very long time in Asian countries, including India. Curcumin is a key active ingredient that is extracted from turmeric. Turmeric is a rhizomatous plant of the ginger family, and modern scientific studies have demonstrated its extensive pharmacological activity, such as inflammation relief and anti-oxidant effects. The neuroprotective effect of turmeric has also been reported in several experimental studies on the animal brain and neuronal tissue. These functional properties of curcumin have great potential in the treatment of spinal cord injury (SCI). Curcumin is a valid and effective therapeutic agent that could alleviate the catastrophic secondary injury process of the spinal cord, including inflammation, edema, free radical injury, fibrosis, and glial scar formation. This potential is supported by the immune pathological results obtained from several animal experiments, and significantly better outcomes were achieved in the evaluation using the Basso, Beattie, and Bresnahan locomotor rating scale for neurological function recovery. However, the evidence-based effectiveness of curcumin for SCI remains in the experimental stage, and questions pertaining to its clinical application, such as dose-safety verification and bioavailability remain unanswered.
Article
Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease characterized by synovial inflammation and joint bone and cartilage destruction. Curcumin can improve joint inflammation in rats with arthritis and inhibit synovial revascularization and abnormal proliferation of fibroblasts. However, it is unclear whether curcumin affects the RA progression. The TNF-α-stimulated primary RA fibroblast-like synoviocytes (RA-FLS) and SV-40 transformed MH7A cells were used as the in vitro model of RA. A mouse model of collagen-induced arthritis (CIA) was used as the in vivo model. The effects of curcumin on cell proliferation, apoptosis, migration, invasion, and inflammatory response were assessed by colony formation, flow cytometry, wound scratch, Transwell assays, and western blotting analysis. Arthritis index scores and degree of paw swelling in mice were assessed to evaluate RA. Curcumin inhibited the TNF-α-induced proliferation, migration, invasion of MH7A and RA-FLS cells and promoted cell apoptosis. Administration with curcumin reversed the CIA-induced increase in arthritis scores, hind paw edema, and loss of appetite, while these effects were rescued by insulin-like growth factor 1, the upstream cytokine of PI3K/AKT. Moreover, curcumin suppressed the inflammatory response by reducing TNF-α, IL-6, and IL-17 secretion in CIA-stimulated mice. Curcumin has an excellent anti-RA effect in vivo and in vitro, which is exerted by inhibiting the expression of pro-inflammatory factors TNF-a, IL-6 and IL-17 and inhibiting the activation of PI3K/AKT signaling pathway. Thus, curcumin may be a promising candidate for anti-RA treatment.
Chapter
Rheumatoid arthritis (RA) is a chronic inflammatory and debilitating joint disorder that causes severe impairment and reduces the quality of life. The available synthetic medicines used as standard therapy for RA have numerous side effects that can compromise their therapeutic outcomes. Thus, the demand for alternative and complementary medicines is increasing. A search of English articles in PubMed, Scopus, Google Scholar, and Web of Science databases was carried out on probable mechanisms of action of herbs with the antirheumatic property. Herbal medicines stated in folk medicine face acceptance concerns by the medical community because of the lack of scientific documents regarding their physio-pharmacological mechanisms. This chapter aims to review the possible antirheumatic effects of various herbs, including Rosmarinus officinalis L., Curcuma longa, and Crocus sativus, their related mechanisms, and preclinical applications, in order to recall the therapeutic properties of herbal medicine. However, more clinical trials are required to confirm the safety and efficacy of these antirheumatic herbal medicines.
Article
The high demand for transplantable corneas is unlikely to subside anytime soon as there is a persistent shortage of cadaveric cornea. The goal of this study was to fabricate film scaffolds with desirable properties of a corneal endothelial cells (CECs) carrier. We used biocompatible materials (curcumin (CC) and silk fibroin (SF)) to construct transparent film scaffolds for CEC regeneration. The film scaffolds were subjected to surface analysis, transparency, stiffness, thermal characterization, and hydrophilicity evaluation. Biological activity of CECs on CC/SF film was analyzed by MTT assay, morphological analysis, mRNA expression, and histological study. Our results showed that the CC/SF film scaffolds had enhanced roughness and transparency compared to the pristine SF film scaffold. The hydrophilicity of the CC/SF film scaffolds showed a topographical environment that encouraged cellular interaction and tissue integration. All the films showed stable thermal characters and an improved capacity for cell growth when a proper amount of CC was incorporated into the SF film scaffolds. The results indicate that a robust scaffold is suitable for CEC transplantation.
Article
Phytochemicals are a diverse group of compounds found in various fruits, vegetables, nuts, and legumes. Many phytochemicals have been observed to possess health benefits. Some have been found to be chemoprotective or can act as chemotherapeutics by inducing autophagy, apoptosis, or otherwise regulating the cell cycle. Many also act as potent antioxidants. Flavonoids are a subclass of bioactive phytochemicals consisting of two phenolic benzene rings, joined together by a heterocyclic pyran or pyrone. It has been observed in multiple studies that there is a correlation between diets rich in flavonoids and a reduction in cancer levels, heart disease, neurodegenerative diseases, and other pathologies. As foods containing flavonoids are widely consumed, and their mechanisms of action are still only partially understood, this review was compiled to compare the effects and mechanisms of action of some of the most widely characterized and publicized flavonoids. The flavonoids silibinin, quercetin, isorhamnetin, luteolin, curcumin genkwanin, and acacetin, together with flavonoid extracts from papaw and Tephroseris kirilowii (Turcz) Holub, a member of the Daisy family, were found to be potent regulators of the cell cycle. The decision to overview these specific flavonoids was based on their therapeutic effects, and/or their potential effects. The sparsity of data comparing these flavonoids was also a key consideration. These flavonoids all modulated to some extent the pathways of autophagy and/or apoptosis and regulated the cell cycle, inflammation, and free radical levels. This explains why they are protective of healthy or moderately damaged cells, but toxic to neoplastic or pre‐cancerous cells.
Article
This systematic review was designed to determine the clinical efficacy and safety of curcumin supplementation for pediatric patients based on clinical trials in children. We systematically searched electronic databases including PubMed, EMBASE, Web of Science, and Scopus for all studies that investigated curcumin administration in the pediatric population without any time frame limitation. Finally, we identified 16 studies for this review. Clinical efficacy and safety of curcumin were assessed in children with inflammatory and immune disorders (including asthma, inflammatory bowel disease (IBD), and juvenile idiopathic arthritis (JIA)), metabolic disorders, autosomal dominant polycystic kidney disease (ADPKD), cystic fibrosis (CF), tetralogy of Fallot (TOF), and infectious diseases. Curcumin was administered in a wide range of doses (45 mg–4,000 mg daily) and durations (2–48 weeks). Overall, curcumin was well tolerated in all studies and improved the severity of inflammatory and immune disorders and metabolic diseases. However, more studies are needed to clarify the role of curcumin supplementation among children with ADPKD, CF, TOF, and infectious diseases. Because of substantial heterogeneity in methodological quality, design, outcomes, dose, duration of intake, formulations, and study populations across studies, no quantitative analysis was performed. Additional large-scale, randomized, placebo-controlled clinical trials are needed to confirm the results of the conducted studies.
Chapter
Increasing experimental and epidemiological evidence has shown the progression of degenerative diseases globally despite the advent of novel drug discoveries in the management of these diseases. Plants are rich in bioactive compounds and act additively or synergistically to confer good health benefits through disease prevention. Food bioactives, otherwise called bioactive compounds in food, are the image behind the curtain of food in that they hide behind food while promoting health and preventing diseases. Therefore, food bioactives are the additional constituents in food aside from the basic nutritional constituents. These food bioactives include alkaloids, polyphenols, polyunsaturated fatty acids, flavonoids, terpenoids, saponins, carotenoids, peptides, and omega-3. Consumption of food rich in bioactive compounds has been linked to reduced incidence and progression of these degenerative diseases through protection against oxidative damage, modulation/alteration of the activities of important enzymes, and certain metabolic processes. This chapter describes food bioactives as the food image behind disease prevention and health promotion.
Article
Curcuma longa and its constituents, mainly curcumin, showed various of pharmacological effects in previous studies. This review article provides updated and comprehensive experimental and clinical evidence regarding the effects of C. longa and curcumin on respiratory, allergic, and immunologic disorders. Using appropriate keywords, databases including PubMed, Science Direct, and Scopus were searched until the end of October 2021. C. longa extracts and its constituent, curcumin, showed the relaxant effect on tracheal smooth muscle, which indicates their bronchodilatory effect in obstructive pulmonary diseases. The preventive effects of extracts of C. longa and curcumin were shown in experimental animal models of different respiratory diseases through antioxidant, immunomodulatory, and anti-inflammatory mechanisms. C. longa and curcumin also showed preventive effects on some lung disorders in the clinical studies. It was shown that the effects of C. longa on pulmonary diseases were mainly due to its constituent, curcumin. Pharmacological effects of C. longa extracts and curcumin on respiratory, allergic, and immunologic disorders indicate the possible therapeutic effect of the plant and curcumin on these diseases.
Chapter
Background Curcumin is an antioxidant agent that improves glycemia in animal models of diabetes. Clinically curcumin use is limited due to poor solubility, weak absorption, and low bioavailability; therefore, this study to investigate the effects of curcumin’s analog, difluorinated curcumin (CDF), on fasting blood glucose (FBG), oral glucose tolerance test (OGTT), and insulin tolerance test (ITT), in streptozotocin (STZ)-induced diabetic rats was undertaken. Methods STZ-induced diabetes rats were randomly assigned to six groups (7 rats per group). They were treated daily by oral gavage with curcumin (200 and 100 mg/kg/day), CDF (200 and 100 mg/kg/day), and metformin (200 mg/kg/day) as a positive control group, for 4 weeks. Two diabetic control (DC) and normal control (NC) groups (non-diabetic rats) received normal saline and citrate buffer, respectively. FBG was measured at the beginning and end of the treatment (Day 0 and week 4) and OGTT and ITT were performed to determine glucose tolerance and insulin sensitivity. Results Cur100, CDF 100, and CDF200 significantly decreased FBG levels after 4 weeks oral administration by −34% (−150 mg/dL ± 70, p = 0.02), −36% (123 mg/dL ±67, p < 0.04), and − 40% (−189 mg/dL ± 91, p = 0.03), respectively. Glucose sensitivity by OGTT showed a significant improvement in glucose tolerance ability in all treated groups compared with DC group. ITT demonstrated that insulin response improved significantly in Cur100 and CDF 200 groups. Conclusion Overall, CDF improved glucose tolerance and insulin sensitivity, while reducing FBG compared to curcumin, suggesting that curcumin analogs may have therapeutic utility in diabetes.
Article
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Neuroinflammation is characterized by reactive microglia and astrocytes (collectively called gliosis) in the central nervous system and is considered as one of the main pathological hallmarks in different neurodegenerative diseases such as Alzheimer’s disease, age-related dementia, and multiple sclerosis. Upon activation, glia undergoes structural and morphological changes such as the microglial cells swell in size and astrocytes become bushy, which play both beneficial and detrimental roles. Hence, they are unable to perform the normal physiological role in brain immunity. Curcumin, a cytokine suppressive anti-inflammatory drug, has a high proven pre-clinical potency and efficacy to reverse chronic neuroinflammation by attenuating the activation and morphological changes that occur in the microglia and astrocytes. This review will highlight the recent findings on the tree structure changes of microglia and astrocytes in neuroinflammation and the effects of curcumin against the activation and morphology of glial cells.
Article
Organoid is a burgeoning model that have emerged in the past decade. Tumor organoids can simulate specific aspects of the 3D structure, cell type composition and function of real tumors to make up for the deficiencies of cell models and animal models. Curcumin has been found to be effective in suppressing various phases of colorectal cancer development. Nevertheless, there is no clear evidence that the results obtained on cultured cells or animal models can be translated in humans. Therefore, we constructed patient-derived organoids of colorectal cancer to show the curcumin responses of these organoids. Then, a MS-based non-targeted metabolomic strategy was to gain a system-level understanding of the mechanism of curcumin on colorectal cancer patient-derived organoids. Then non-targeted metabonomic analysis found that curcumin mainly regulated the phenylalanine, tyrosine and tryptophan biosynthesis, nicotinate and nicotinamide metabolism, purine metabolism in the organoids of colorectal cancer. Our research provided a reference for further revealing the role of curcumin in human-derived colorectal cancer-like solid tumors.
Article
Turmeric is an indispensable culinary spice in different cultures and a principal component in traditional remedies. Toxic metanil yellow (MY), acid orange 7 (AO) and lead chromate (LCM) are deliberately added to adulterate turmeric powder. This work compares the ability of multivariate chemometric models with those of artificial intelligent networks to enhance the selectivity of spectral data for the rapid assay of these three adulterants in turmeric powder. Using a custom experimental design, we provide a data-driven optimization for the sensitive parameters of the partial least squares model (PLS), artificial neural network (ANN) and genetic algorithm (GA). The optimized models are validated using sets of genuine turmeric samples from five different geographical regions spiked with standard adulterant concentrations. The optimized GA-PLS and GA-ANN models reduce the root mean square error of prediction by 18.4%, 31.1% and 55.3% and 25.0%, 69.9% and 88.4% for MY, AO and LCM, respectively.
Article
Density functional theory (DFT) calculations were performed to investigate the curcumin adsorption at the surfaces of two boron nitride (BN) nanostructures including nanosheet (BNNS) and nanotube (BNNT). The singular models were optimized to reach the stabilized structures and to evaluate electronic features. Next, performing optimization processes on interacting systems yielded formations of bimolecular complexes through occurrence of physical interactions. For curcumin, keto and enol tautomeric forms were investigated for participating in interactions with the BN nanostructures, in which the enol form was seen for participating in stronger interactions with both of BNNS and BNNT surfaces in comparison with the keto form. Based on such interactions, electronic molecular orbital features detected the effects of molecular communications to show benefit of employing BN nanostructures for drug delivery purposes. Moreover, BNNS was seen to work better than BNNT for such purpose of adsorption and detection of curcumin substance.
Article
Full-text available
Curcumin, a polyphenol found in turmeric, has attracted attention from both the medical and culinary worlds because it is the primary source of the spice's medicinal qualities. Oxidative and inflammatory diseases, metabolic syndrome, arthritis, anxiety, and hyperlipidemia can all be managed with this supplement. As a result, active persons may benefit from the supplement's ability to reduce inflammation and muscular soreness following exercise. For those who have not been diagnosed with a medical ailment, even a little dose of the complex can have health benefits. Its antioxidant and anti-inflammatory properties are responsible for most of these advantages. Curcumin's poor bioavailability, which appears to be mostly attributable to poor absorption, fast metabolism, and rapid elimination, does not contribute to the related health benefits. Bioavailability can be improved by a variety of factors. Curcumin (diferuloylmethane) is one of turmeric's most potent, non-toxic, and major bioactive ingredients. Curcumin has a weak bioavailability and low absorption rate. Curcumin nanoparticles can be used to treat cancer and wound infections, according to the findings of this study. Antibacterial, antiviral, and antiprotozoan properties of curcumin nanoparticles are excellent. As a result of this, curcumin-loaded nanoparticles can be used for drug administration in nano-gel, microemulsion, and nano-cream forms of the nanoparticle. An important component of turmeric known as curcumin is the curcuma longa linn rhizome. Since its discovery in the 16th century, curcumin has been used to treat a wide range of ailments. Curcumin's anti-oxidant and anti-inflammatory properties play a significant role in a wide range of maladies, including cancer, cardiovascular disease, Alzheimer's disease, inflammatory disorders, neurological diseases, and so on. Although natural curcumin has made amazing achievements in therapeutic applications, the clinical implications of native curcumin are hindered by restricted solubility, chemical-physical instability, poor bioavailability, rapid metabolism and poor phartacokinetics. There are several intriguing biological effects of curcumin that have been summarised here.
Article
Systemic autoimmune diseases like rheumatoid arthritis, multiple sclerosis, and systemic lupus erythematosus represent various autoimmune conditions identified by immune system dysregulation. The activation of immune cells, auto‐antigen outbreak, inflammation, and multi‐organ impairment is observed in these disorders. The immune system is an essential complex network of cells and chemical mediators which defends the organism's integrity against foreign microorganisms, and its precise operation and stability are compulsory to avoid a wide range of medical complications. Curcumin is a phenolic ingredient extracted from turmeric and belongs to the Zingiberaceae, or ginger family. Curcumin has multiple functions, such as inhibiting inflammation, oxidative stress, tumor cell proliferation, cell death, and infection. Nevertheless, the immunomodulatory influence of curcumin on immunological reactions/processes remains mostly unknown. In the present narrative review, we sought to provide current information concerning the preclinical and clinical uses of curcumin in systemic autoimmune diseases.
Article
Colorectal cancer (CRC) is one of the most frequent malignancies worldwide and remains one of the leading causes of cancer-related deaths in the United States. The high degree of morbidity and mortality associated with this disease is largely due to the inadequate efficacy of current treatments as well the development of chemoresistance. In recent years, several pharmaceutical agents screened from natural products have shown the promise to offer a safe, inexpensive, and synergistically multi-targeted treatment option in various cancer. Given the growing evidence of anti-carcinogenic properties of two natural compounds, melatonin (MLT) and andrographis (Andro), we aimed to evaluate their synergistic anti-cancer effects in CRC. We demonstrate that indeed these two compounds possessed a synergistic anti-cancer effect in terms of their ability to inhibit cell viability, suppression of colony-formation and induction of apoptosis (p<0.05). In line with our in-vitro findings, we were able to validate this combinatorial anti-cancer activity in xenograft animal models (p<0.001) as well as tumor-derived 3D organoids (p<0.01). RNA-sequencing analysis revealed candidate pathways and genes that mediated anti-tumor efficacy of MLT and Andro in CRC, among which autophagy pathway and related genes, including NR4A1, CTSL and Atg12, were found to be primarily responsible for the increased anti-cancer effect by the two natural products. In conclusion, our data reveal a potent and synergistic therapeutic effect of MLT and Andro in the treatment of CRC and provides a rationale for suppressing autophagy in cancer cells as a potential therapeutic strategy for CRC.
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В статье изложены современные представления о фенотипах остеоартрита (ОА), принципах немедикаментозного и медикаментозного лечения, предложенных в международных рекомендациях. Представлены основные результаты публикаций, рассматривающих возможности применения компонентов лекарственных растений и нутрицевтиков (босвеллия, куркума, экстракт черного перца, гиалуроновая кислота, коллаген) у пациентов с остеоартритом с учетом их эффективности и безопасности. The article presents current views on the phenotypes of osteoarthritis (OA), principles of non-pharmacological treatment and pharmacological therapy proposed in the international recommendations. We have summarized main results of publications considering the possibility of using medicinal plant components and nutraceuticals (Boswellia, turmeric, black pepper extract, hyaluronic acid, collagen) in patients with osteoarthritis with regard to their effectiveness and safety.
Book
The Chemistry inside Spices & Herbs: Research and Development brings comprehensive information about the chemistry of spices and herbs with a focus on recent research in this field. The book is an extensive 2-part collection of 20 chapters contributed by experts in phytochemistry with the aim to give the reader deep knowledge about phytochemical constituents in herbal plants and their benefits. The contents include reviews on the biochemistry and biotechnology of spices and herbs, herbal medicines, biologically active compounds and their role in therapeutics among other topics. Chapters which highlight natural drugs and their role in different diseases and special plants of clinical significance are also included. Part II continues from the previous part with chapters on the treatment of skin diseases and oral problems. This part focuses on clinically important herbs such as turmeric, fenugreek, ashwagandha (Indian winter cherry), basil, Terminalia chebula (black myrobalan). In terms of phytochemicals, this part presents chapters that cover resveratrol, piperine and circumin. Audience: This book is an ideal resource for scholars (in life sciences, phytomedicine and natural product chemistry) and general readers who want to understand the importance of herbs, spices and traditional medicine in pharmaceutical and clinical research.
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Rheumatoid arthritis [RA] is a painful disorder that causes inflammation in synovial membrane followed by damage to cartilage and bone. Several therapies are available for its management that include anti-inflammatory and disease- modifying antirheumatic drugs. Due to the severe side effects associated with them, phytotherapy may serve as a promising and beneficial approach for management of rheumatoid arthritis and the therapeutic potential can be attributed to their ability to target various inflammatory mediators including nitric oxide [NO], cytokines, chemokines, adhesion molecules, nuclear factor kappa-b [NF-kb], lipoxygenase [LOXs] and arachidonic acid [AA]. Further, nanomedicine could serve as a prominent formulation strategy to overcome the challenges associated with phytoconstituents like poor bioavailability, high first pass metabolism and lower stability. Present review focuses on providing an exhaustive account of various phytoconstituents that have significant potential in RA management, their drawbacks, reported novel drug formulations, regulatory aspects involved therein.
Article
Curcumin, a polyphenol found in turmeric, has attracted attention from both the medical and culinary worlds because it is the primary source of the spice's medicinal qualities. Oxidative and inflammatory diseases, metabolic syndrome, arthritis, anxiety, and hyperlipidemia can all be managed with this supplement. As a result, active persons may benefit from the supplement's ability to reduce inflammation and muscular soreness following exercise. For those who have not been diagnosed with a medical ailment, even a little dose of the complex can have health benefits. Its antioxidant and anti-inflammatory properties are responsible for most of these advantages. Curcumin's poor bioavailability, which appears to be mostly attributable to poor absorption, fast metabolism, and rapid elimination, does not contribute to the related health benefits. Bioavailability can be improved by a variety of factors. Curcumin (diferuloylmethane) is one of turmeric's most potent, non-toxic, and major bioactive ingredients. Curcumin has a weak bioavailability and low absorption rate. Curcumin nanoparticles can be used to treat cancer and wound infections, according to the findings of this study. Antibacterial, antiviral, and antiprotozoan properties of curcumin nanoparticles are excellent. As a result of this, curcumin-loaded nanoparticles can be used for drug administration in nano-gel, microemulsion, and nano-cream forms of the nanoparticle. An important component of turmeric known as curcumin is the curcuma longa linn rhizome. Since its discovery in the 16th century, curcumin has been used to treat a wide range of ailments. Curcumin's anti-oxidant and anti-inflammatory properties play a significant role in a wide range of maladies, including cancer, cardiovascular disease, Alzheimer's disease, inflammatory disorders, neurological diseases, and so on. Although natural curcumin has made amazing achievements in therapeutic applications, the clinical implications of native curcumin are hindered by restricted solubility, chemical-physical instability, poor bioavailability, rapid metabolism and poor pharmacokinetics. There are several intriguing biological effects of curcumin that have been summarised here.
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Full-text available
Patients with advanced cancer exhibit multifaceted defects in their immune capacity, which are likely to contribute to an increased susceptibility to infections and disease progression. We demonstrated earlier that curcumin inhibits tumor growth and prevents immune cell death in tumor-bearing hosts. Here we report that tumor-induced immunodepletion involves apoptosis of thymic CD4+/CD8+ single/double positive cells as well as loss of circulating CD4+/CD8+ T cells. Administration of curcumin to tumor-bearing animals resulted in restoration of progenitor, effecter, and circulating T cells. In fact, tumor burden decreased the expression level of the pro-proliferative protein Bcl-2 while increasing the pro-apoptotic protein Bax in T cells. Curcumin down-regulated the Bax level while augmenting Bcl-2 expression in these cells, thereby protecting the immunocytes from tumor-induced apoptosis. A search for the upstream mechanism revealed down-regulation of the common cytokine receptor gamma chain (gammac) expression in T cells by tumor-secreted prostaglandin E2. As a result, Jak-3 and Stat-5a phosphorylation and to a lesser extent Stat-5b phosphorylation were also decreased in T cells. These entire phenomena could be reverted back by curcumin, indicating that this phytochemical restored the cytokine-dependent Jak-3/Stat-5a signaling pathway in T cells of tumor bearers. Overexpressed Stat-5a/constitutively active Stat-5a1*6 but not Stat-5b could efficiently elevate Bcl-2 levels and protect T cells from tumor-induced death, whereas C-terminal truncated Stat-5a713 overexpression failed to do so, indicating the importance of Stat-5a signaling in T cell survival. Thus, these results raise the possibility of inclusion of curcumin in successful therapeutic regimens against cancer.
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In recent years, there has been a growing interest, supported by a large number of experimental and epidemiological studies, for the beneficial effects of some phenolic substances, contained in commonly used spices and herbs, in preventing various age-related pathologic conditions, ranging from cancer to neurodegenerative diseases. Although the exact mechanisms by which polyphenols promote these effects remain to be elucidated, several reports have shown their ability to stimulate a general xenobiotic response in the target cells, activating multiple defense genes. Data from our and other laboratories have previously demonstrated that curcumin, the yellow pigment of curry, strongly induces heme-oxygenase-1 (HO-1) expression and activity in different brain cells via the activation of heterodimers of NF-E2-related factors 2 (Nrf2)/antioxidant responsive element (ARE) pathway. Many studies clearly demonstrate that activation ofNrf2 target genes, and particularly HO-1, in astrocytes and neurons is strongly protective against inflammation, oxidative damage, and cell death. In the central nervous system, the HO system has been reported to be very active, and its modulation seems to play a crucial role in the pathogenesis of neurodegenerative disorders. Recent and unpublished data from our group revealed that low concentrations of epigallocatechin-3-gallate, the major green tea catechin, induces HO-1 by ARE/Nrf2 pathway in hippocampal neurons, and by this induction, it is able to protect neurons against different models of oxidative damages. Furthermore, we have demonstrated that other phenolics, such as caffeic acid phenethyl ester and ethyl ferulate, are also able to protect neurons via HO-1 induction. These studies identify a novel class of compounds that could be used for therapeutic purposes as preventive agents against cognitive decline.
Article
Full-text available
In recent years, there has been a growing interest, supported by a large number of experimental and epidemiological studies, for the beneficial effects of some phenolic substances, contained in commonly used spices and herbs, in preventing various age-related pathologic conditions, ranging from cancer to neurodegenerative diseases. Although the exact mechanisms by which polyphenols promote these effects remain to be elucidated, several reports have shown their ability to stimulate a general xenobiotic response in the target cells, activating multiple defense genes. Data from our and other laboratories have previously demonstrated that curcumin, the yellow pigment of curry, strongly induces heme-oxygenase-1 (HO-1) expression and activity in different brain cells via the activation of heterodimers of NF-E2-related factors 2 (Nrf2)/antioxidant responsive element (ARE) pathway. Many studies clearly demonstrate that activation ofNrf2 target genes, and particularly HO-1, in astrocytes and neurons is strongly protective against inflammation, oxidative damage, and cell death. In the central nervous system, the HO system has been reported to be very active, and its modulation seems to play a crucial role in the pathogenesis of neurodegenerative disorders. Recent and unpublished data from our group revealed that low concentrations of epigallocatechin-3-gallate, the major green tea catechin, induces HO-1 by ARE/Nrf2 pathway in hippocampal neurons, and by this induction, it is able to protect neurons against different models of oxidative damages. Furthermore, we have demonstrated that other phenolics, such as caffeic acid phenethyl ester and ethyl ferulate, are also able to protect neurons via HO-1 induction. These studies identify a novel class of compounds that could be used for therapeutic purposes as preventive agents against cognitive decline.
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Patients with arthritis frequently are at increased risk for future cardiovascular (CV) events. We investigated the performance of the cardiac biomarkers N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high sensitivity C-reactive protein (hsCRP) for predicting CV events in patients with arthritis taking chronic nonsteroidal antiinflammatory drugs (NSAID). We evaluated 2-year CV outcomes in a prospective, nested biomarker study among patients (N = 6273) with rheumatoid arthritis and osteoarthritis treated with NSAID in the MEDAL (Multinational Etoricoxib and Diclofenac Arthritis Long-term) trial. Patients were stratified by quartiles of baseline NT-proBNP and established cutpoints of NT-proBNP and hsCRP. NT-proBNP demonstrated a strong graded relationship with CV outcomes, including CV death (p for trend < 0.0001), myocardial infarction (MI) (p for trend = 0.02), heart failure (HF) (p for trend < 0.0001), and a composite of thrombotic events (CV death, MI, stroke) or HF (p for trend < 0.0001). Baseline levels of hsCRP were not associated with CV events (CV death/MI/stroke/HF; p for trend = 0.65). NT-proBNP remained strongly predictive of CV events after adjustment for age, sex, diabetes, hypertension, hyperlipidemia, smoking, type of arthritis, body mass index, creatinine clearance, history of CV disease, and hsCRP (CV death/MI/stroke/HF: Q4 vs Q1 hazard ratio 3.53, 95% CI 1.89-6.58). Patients with a NT-proBNP level below 100 pg/ml had a 0.94% rate of thrombotic events or heart failure at 2 years. NT-proBNP is a simple and robust noninvasive indicator of CV risk in patients with arthritis. Risk stratification based on NT-proBNP may facilitate identification of patients with arthritis who are at low CV risk during chronic NSAID treatment.
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In 2005, the Healthcare Effectiveness Data and Information Set (HEDIS) introduced a quality measure to assess the receipt of disease-modifying antirheumatic drugs (DMARDs) among patients with rheumatoid arthritis (RA). To identify sociodemographic, community, and health plan factors associated with DMARD receipt among Medicare managed care enrollees. We analyzed individual-level HEDIS data for 93,143 patients who were at least 65 years old with at least 2 diagnoses of RA within a measurement year (during 2005-2008). Logistic regression models with generalized estimating equations were used to determine factors associated with DMARD receipt and logistic regression was used to adjust health plan performance for case mix. Receipt or nonreceipt of DMARD. The mean age of patients was 74 years; 75% were women and 82% were white. Overall performance on the HEDIS measure for RA was 59% in 2005, increasing to 67% in 2008 (P for trend <.001). The largest difference in performance was based on age: patients aged 85 years and older had a 30 percentage point lower rate of DMARD receipt (95% confidence interval [CI], -29 to -32 points; P < .001), compared with patients 65 to 69 years of age, even after adjusting for other factors. Lower percentage point rates were also found for patients who were men (-3 points; 95% CI, -5 to -2 points; P < .001), of black race (-4 points; 95% CI, -6 to -2 points; P < .001), with low personal income (-6 points; 95% CI, -8 to -5 points; P < .001), with the lowest zip code-based socioeconomic status (-4 points; 95% CI, -6 to 2 points; P < .001), or enrolled in for-profit health plans (-4 points; 95% CI, -7 to 0 points; P < .001); and in the Middle Atlantic region (-7 points; 95% CI, -13 to -2 points; P < .001) and South Atlantic regions (-11 points; 95% CI, -20 to -3 points; P < .001) as compared with the Pacific region. Performance varied widely by health plan, ranging from 16% to 87%. Among Medicare managed care enrollees carrying a diagnosis of RA between 2005 and 2008, 63% received a DMARD. Receipt of DMARDs varied based on demographic factors, socioeconomic status, geographic location, and health plan.
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Curcumin, the bioactive component of turmeric, Curcuma longa has an exceptionally wide spectrum of activities including antioxidant, anti-inflammatory and anti-cancer properties, and is currently under different phases of clinical trials for various types of soft tissue cancers. However, although in vitro and animal studies have shown anticancer activities of curcumin for virtually all types of human cancers, its poor bioavailability in the human body has severely limited its application to these diseases. Methods to increase its oral bioavailability are a subject of intense current research. Reconstituting curcumin with the non-curcuminoid components of turmeric has been found to increase the bioavailability substantially. In the present clinical study to determine the bioavailability of curcuminoids, a patented formulation, BCM-95((R))CG was tested on human volunteer group. Normal curcumin was used in the control group. Curcumin content in blood was estimated at periodical intervals. After a washout period of two weeks the control group and drug group were crossed over BCM-95((R))CG and curcumin, respectively. It was also compared with a combination of curcumin-lecithin-piperine which was earlier shown to provide enhanced bioavailability. The results of the study indicate that the relative bioavailability of BCM-95((R))CG (Biocurcumax) was about 6.93-fold compared to normal curcumin and about 6.3-fold compared to curcumin-lecithin-piperine formula. BCM-95((R))CG thus, has potential for widespread application for various chronic diseases.
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The objective of this study was to determine the efficacy and safety of Curcuma domestica extracts in pain reduction and functional improvement in patients with knee osteoarthritis. The design and setting were a randomized controlled study at a university hospital in Bangkok, Thailand. One-hundred and seven (107) patients with primary knee osteoarthritis (OA) with pain score of > or =5 were randomized to receive ibuprofen 800 mg per day or C. domestica extracts 2 g per day for 6 weeks. The main outcomes were improvement in pain on level walking, pain on stairs, and functions of knee assessed by time spent during 100-m walk and going up and down a flight of stairs. The adverse events were also recorded. Fifty-two (52) and 55 patients were randomized to C. domestica extracts and ibuprofen groups, respectively. Baseline characteristics of the patients in both groups were not different. The mean scores of the aforementioned outcomes at weeks 0, 2, 4, and 6 were significantly improved when compared with the baseline values in both groups. There was no difference in those parameters between the patients receiving ibuprofen and C. domestica extracts, except pain on stairs (p = 0.016). No significant difference of adverse events between both groups was found (33.3% versus 44.2%, p = 0.36 in C. domestica extracts and ibuprofen groups, respectively). C. domestica extracts seem to be similarly efficacious and safe as ibuprofen for the treatment of knee OA.
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To determine the efficacy and safety of etanercept and etanercept plus sulfasalazine versus sulfasalazine in patients with rheumatoid arthritis (RA) despite sulfasalazine therapy. Patients were randomly assigned to etanercept (25 mg twice weekly; sulfasalazine was discontinued at baseline), etanercept plus sulfasalazine (unchanged regimen of 2-3 g/day) or sulfasalazine in a double-blind, randomised, 2-year study in adult patients with active RA despite sulfasalazine therapy. Efficacy was assessed using the American College of Rheumatology criteria, disease activity scores (DAS) and patient-reported outcomes (PRO). Demographic variables and baseline disease characteristics were comparable among treatment groups; mean DAS 5.1, 5.2 and 5.1 for etanercept (n = 103), etanercept plus sulfasalazine (n = 101) and sulfasalazine (n = 50), respectively. Withdrawal due to lack of efficacy was highest with sulfasalazine (26 (52%) vs 6 (6%) for either etanercept group, p<0.001). Patients receiving etanercept or etanercept plus sulfasalazine had a more rapid initial response, which was sustained at 2 years, than those receiving sulfasalazine: mean DAS 2.8, 2.5 versus 4.5, respectively (p<0.05); ACR 20 response was achieved by 67%, 77% versus 34% of patients, respectively (p<0.01) Overall, PRO followed a similar pattern; a clinically significant improvement in health assessment questionnaire was achieved by 76%, 78% versus 40% of patients, respectively (p<0.01). Commonly reported adverse events occurring in the etanercept groups were injection site reactions and pharyngitis/laryngitis (p<0.01). Etanercept and etanercept plus sulfasalazine are efficacious for the long-term management of patients with RA. The addition of etanercept or substitution with etanercept should be considered as treatment options for patients not adequately responding to sulfasalazine.
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Rheumatoid arthritis is a chronic inflammatory disease characterized by uncontrolled proliferation of synovial tissue and a wide array of multisystem comorbidities. Prevalence is estimated to be 0.8 percent worldwide, with women twice as likely to develop the disease as men. Untreated, 20 to 30 percent of persons with rheumatoid arthritis become permanently work-disabled within two to three years of diagnosis. Genetic and environmental factors play a role in pathogenesis. Although laboratory testing and imaging studies can help confirm the diagnosis and track disease progress, rheumatoid arthritis primarily is a clinical diagnosis and no single laboratory test is diagnostic. Complications of rheumatoid arthritis may begin to develop within months of presentation; therefore, early referral to or consultation with a rheumatologist for initiation of treatment with disease-modifying antirheumatic drugs is recommended. Several promising new disease-modifying drugs recently have become available, including leflunomide, tumor necrosis factor inhibitors, and anakinra. Nonsteroidal anti-inflammatory drugs, corticosteroids, and nonpharmacologic modalities also are useful. Patients who do not respond well to a single disease-modifying drug may be candidates for combination therapy. Rheumatoid arthritis is a lifelong disease, although patients can go into remission. Physicians must be aware of common comorbidities. Progression of rheumatoid arthritis is monitored according to American College of Rheumatology criteria based on changes in specific symptoms and laboratory findings. Predictors of poor outcomes in early stages of rheumatoid arthritis include low functional score early in the disease, lower socioeconomic status, early involvement of many joints, high erythrocyte sedimentation rate or C-reactive protein level at disease onset, positive rheumatoid factor, and early radiologic changes.
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c-Fos/AP-1 controls the expression of inflammatory cytokines and matrix-degrading matrix metalloproteinases (MMPs) important in arthritis via promoter AP-1 binding motif. Among inflammatory cytokines, IL-1β is the most important inducer of a variety of MMPs, and mainly responsible for cartilage breakdown and osteoclastogenesis. IL-1β and c-Fos/AP-1 influence each other’s gene expression and activity, resulting in an orchestrated cross-talk that is crucial to arthritic joint destruction, where TNFα can act synergistically with them. While how to stop the degradation of bone and cartilage, i.e., to control MMP, has long been the central issue in the research of rheumatoid arthritis (RA), selective inhibition of c-Fos/AP-1 does resolve arthritic joint destruction. Thus, the blockade of IL-1β and/or c-Fos/AP-1 can be promising as an effective therapy for rheumatoid joint destruction in addition to the currently available TNFα blocking agents that act mainly on arthritis.
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Epigenetic regulation, which includes changes in DNA methylation, histone modifications, and alteration in microRNA (miRNA) expression without any change in the DNA sequence, constitutes an important mechanism by which dietary components can selectively activate or inactivate gene expression. Curcumin (diferuloylmethane), a component of the golden spice Curcuma longa, commonly known as turmeric, has recently been determined to induce epigenetic changes. This review summarizes current knowledge about the effect of curcumin on the regulation of histone deacetylases, histone acetyltransferases, DNA methyltransferase I, and miRNAs. How these changes lead to modulation of gene expression is also discussed. We also discuss other nutraceuticals which exhibit similar properties. The development of curcumin for clinical use as a regulator of epigenetic changes, however, needs further investigation to determine novel and effective chemopreventive strategies, either alone or in combination with other anticancer agents, for improving cancer treatment.
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Rheumatoid arthritis (RA) is associated with progressive joint destruction, with functional status influenced by both disease activity and radiographic progression. The case for early aggressive treatment of RA is based on large amounts of good data in many countries. Studies with conventional disease-modifying anti-rheumatic drugs in early RA have shown improved outcomes compared with later treatment, especially if an aggressive approach with combinations of drugs is used. Early intervention with tumour necrosis factor (TNF) inhibitors has been shown to improve clinical outcomes, induce remission and prevent radiographic progression. It also improves patients' functional status, health-related quality of life, and reduces fatigue. Patients with RA have reduced productivity, an increased number of lost work days and retire early; enabling patients to work should be at the core of a therapy's cost-effectiveness. Introduction of anti-TNF therapy early in RA has been shown to decrease job loss and reduce the amount of working time missed. Although the drug costs of initial treatment with combination therapy including a TNF inhibitor are high, these may be compensated by the reduction in lost productivity, making such a strategy cost-effective overall. In addition, some patients who respond well to combination therapy may be able to stop the TNF inhibitor. It is important to assess the benefits of any intervention not just to healthcare costs but to society as a whole, and physicians should be advocates for optimal access to effective therapies for their patients.
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Claims that Traditional/Alternative medicine (TM/AM) remedies are effective are routinely ignored by Western Medicine. However, the results of a clinical trial that demonstrated the clinical efficacy of Tripterygium wilfordii Hook F. (TW), a TM used as an anti-inflammatory, were recently published in the Annals of Internal Medicine. Why this article was published in a peer reviewed Allopathic medical journal is an important question that begs examination and may lay the future promise of TM/AM therapeutic interventions.
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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.
Article
To measure the efficacy and safety of diclofenac sodium gel in patients with primary hand osteoarthritis (OA). In a randomized, double-blind, placebo-controlled trial, men and women aged > or = 40 years diagnosed with primary OA in the dominant hand were randomly assigned to self-apply topical 1% diclofenac sodium gel (Voltaren Gel) (n = 198) or vehicle (n = 187) to both hands 4 times daily for 8 weeks. Primary outcome measures included OA pain intensity (100-mm visual analog scale), total Australian/Canadian Osteoarthritis Hand Index (AUSCAN) score, and global rating of disease activity at 4 and 6 weeks. Secondary outcomes included onset of efficacy in Weeks 1 and 2, durability of efficacy at 8 weeks, measures of disease activity in the dominant hand, pain intensity in the non-dominant hand, AUSCAN subindices, end of study rating of efficacy, and Osteoarthritis Research Society International response criteria. Diclofenac sodium gel decreased pain intensity scores by 42%-45%, total AUSCAN scores by 35%-40%, and global rating of disease by 36%-40%. Significant differences favoring diclofenac sodium gel over vehicle were observed at Week 4 for pain intensity and AUSCAN, with a trend for global rating of disease activity. At Week 6, diclofenac sodium gel treatment significantly improved each primary outcome measure compared with vehicle. Secondary outcomes generally supported the primary outcomes. The most common treatment-related adverse event (AE) was application-site paresthesia. Most AE were mild. No cardiac events, gastrointestinal bleeding, or ulcers were reported. Topical diclofenac sodium gel was generally well tolerated and effective in primary hand OA. (NCT ID: NCT00171665).
Article
c-Fos/AP-1 controls the expression of inflammatory cytokines and matrix-degrading matrix metalloproteinases (MMPs) important in arthritis via promoter AP-1 binding motif. Among inflammatory cytokines, IL-1beta is the most important inducer of a variety of MMPs, and mainly responsible for cartilage breakdown and osteoclastogenesis. IL-1beta and c-Fos/AP-1 influence each other's gene expression and activity, resulting in an orchestrated cross-talk that is crucial to arthritic joint destruction, where TNFalpha can act synergistically with them. While how to stop the degradation of bone and cartilage, i.e., to control MMP, has long been the central issue in the research of rheumatoid arthritis (RA), selective inhibition of c-Fos/AP-1 does resolve arthritic joint destruction. Thus, the blockade of IL-1beta and/or c-Fos/AP-1 can be promising as an effective therapy for rheumatoid joint destruction in addition to the currently available TNFalpha blocking agents that act mainly on arthritis.
Article
Because of its long-term effectiveness in clinical practice, methotrexate (MTX) is currently the preferred disease-modifying antirheumatic drug (DMARD) for patients with active rheumatoid arthritis (RRA). However, many patients do not experience remission and continue to have signs and symptoms of active disease while receiving a maximally tolerated dose. The aims of this meta-analysis were to estimate the efficacy and tolerability of the various dosage schemes of infliximab versus MTX for the treatment of active RA, to eliminate size-related uncertainty of effects, and to identify subgroups of patients who benefit most from infliximab + MTX therapy. Using the MEDLINE online database (inception through November 2006) and the Cochrane Database of Systematic Reviews (Issue 4, 2006), we identified English-language articles on randomized controlled clinical trials. Studies investigating infliximab + MTX regimens versus a control group receiving MTX alone to assess efficacy in active RA, using the American College of Rheumatology (ACR) criteria for 20% improvement (ACR20), 50% improvement (ACR50), and 70% improvement (ACR70), were considered eligible for the meta-analysis. Pooled odds ratios (ORs) and 95% CIs were calculated to compare the relative risks and benefits of adding infliximab to MTX. From a total of 78 initially identified studies, 42 were considered potentially eligible for this review and 12 were considered eligible for the meta-analysis. Overall, 4899 patients were randomized to either infliximab + MTX (3919 patients) or MTX alone (980 patients). Mean patient age ranged from 44.6 to 56 years in the MTX-only arms and from 45.8 to 56 years in the infliximab + MTX arms. The proportion of female patients ranged from 66.6% to 100% in the MTX arms and from 68% to 100% in the infliximab arms. Infliximab 3 mg/kkg + MTX was more effective than MTX alone (OR = 3.52 [2.14-5.79] for reaching ACR20; 2.87 [2.228-3.61] for ACR50; and 2.42 [1.87-3.13] for ACR70). Infliximab 10 mg/kkg + MTX was also more effective than MTX alone (OR = 5.06 [3.88-6.59] for reaching ACR20; 5.72 [4.05-8.08] for ACR50; and 7.32 [2.28-23.50] for ACR70). Infliximab 10-mm/kg regimens appeared to be more effective than infliximab 3-mg/kg regimens (P = NS, P = 0.001, and P = NS for reaching ACR20, ACR50, and ACR70, respectively), without being associated with an increased risk for adverse events. Infliximab 10 mg/kg appeared to be more effective in trials of longer duration (> or = 54 weeks) compared with those of shorter duration (P = 0.03, P = 0.02, and P = 0.01 for reaching ACR20, ACR50, and ACR70, respectively) and in those that enrolled patients with severe disease activity (P = 0.05, P = 0.05, and P = NS for reaching ACR20, ACR50, and ACR70, respectively). Steroid coadministration (P < 0.001, P < 0.001, and P = NS for reaching ACR20, ACR50, and ACR70, respectively), previous DMARD exposure (P < 0.001, P < 0.001, and P = 0.04 for reaching ACR20, ACR50, and ACR70, respectively), and MTX naivete (P = NS, P < 0.001, and P =0.013 for reaching ACR20, ACR50, and ACR70, respectively) correlated with higher infliximab efficacy. Based on this meta-analysis, higher dose infliximab (10 mg/kg) in combination with MTX appeared to be more effective than the standard 3 mg/kg dose, particularly for patients with severe disease activity.The benefits of high-dose treatment appeared to accrue over time, and patients who received higher doses of infliximab did not experience a higher incidence of severe adverse events. The addition of oral low-dose steroids significantly enhanced infliximab efficacy.
Article
In this study, the effect of curcumin on the formalin-induced pain was investigated in rats. Interaction between curcumin and opioid system using morphine and naloxone was also examined. A biphasic pain response was induced after intraplantar injection of formalin (50 microL, 1%). Curcumin, morphin and naloxone had no effect on the early phase of pain. Late phase of pain was suppressed by curcumin at the doses of 100 and 200 mg kg(-1) body weigh. Morphine (1 mg kg(-1) BW) reduced, whereas naloxone (1 mg kg(-1) BW) did not affect the late phase of pain. Currcumin did not influence the morphine-induced antinociception, but reversed the effect of naloxone on pain. Present findings indicate that curcumin may produce antinociception by activation of both opioid and non opioid mechanisms of pain.
Article
The present study was planned to evaluate the role of curcumin in the formalin-induced orofacial pain in rats that mimics typical human orofacial pain. Adult Wistar rats of either sex received an injection of 50 microL of 5% v/v subcutaneous formalin injection into one vibrissal pad and consequent facial grooming behavior was monitored. Animals exhibited two distinct periods of nocifensive grooming: (a) an acute phase lasting 0-6 min; and (b) a tonic phase lasting 6-45 min. The analgesic response of curcumin was observed at doses of 25, 50, 100, 200, 400 and 600 mg/kg i.p., administered 15 min prior to formalin injection. Another group received subanalgesic dose of diclofenac (0.2 mg/kg) and curcumin 25 mg/kg. Curcumin and diclofenac were administered 15 and 5 min prior to formalin injection respectively. Curcumin produced a dose-dependent inhibition of facial grooming in both acute and tonic phases compared to vehicle and potentiated the subanalgesic dose of diclofenac. The study results for the first time demonstrated the per se antinocifensive effect of curcumin and also exhibited a synergistic interaction with the subanalgesic dose of an NSAID in the facial pain model. More studies are necessary to elucidate the mechanisms of curcumin in this model of pain.
Article
In the present study, the effect of chronic oral administration of curcumin in the presence or absence of morphine and noloxone was investigated on the visceral nociception induced by acetic acid in rats. Intraperitoneal injection of acetic acid (1 mL, 2%) produced contractions in the abdominal musculature (writhes). The latency time to the beginning of the first writhe was measured and the total number of writhes in the 1 h after acetic acid injection was counted. The latency time to the beginning of the first writhe was significantly (p < 0.05) increased and the number of writhes was significantly (p < 0.05) decreased by curcumin (20 and 40 mg kg(-1) body weight). The same results were obtained after subcutaneous injection of morphine (1 mg kg(-1) b.wt.). Naloxone at the dose of 1 mg kg(-1) body weight had no effect on pain intensity. Curcumin significantly (p < 0.05) enhanced the effect of morphine on the visceral pain responses, however did not reverse the effect of naloxone. Present data suggest that in the acetic acid-induced visceral nociception of rats, curcumin may produce an antinociceptive effect and the endogenous analgesic opioid system is involved in the curcumin-induced antinociception.
Article
Neutralization of tumor necrosis factor a (TNF-alpha) for three to six months reduces the symptoms and signs of rheumatoid arthritis. However, the capacity of this approach to effect a more sustained benefit and its effect on joint damage are not known. We treated 428 patients who had active rheumatoid arthritis despite methotrexate therapy with placebo or infliximab, a chimeric monoclonal antibody against TNF-alpha, in intravenous doses of 3 or 10 mg per kilogram of body weight every 4 or 8 weeks in combination with oral methotrexate for 54 weeks. We assessed clinical responses with use of the criteria of the American College of Rheumatology, the quality of life with a health-status questionnaire, and the effect on joint damage radiographically. The combination of infliximab and methotrexate was well tolerated and resulted in a sustained reduction in the symptoms and signs of rheumatoid arthritis that was significantly greater than the reduction associated with methotrexate therapy alone (clinical response, 51.8 percent vs. 17.0 percent; P<0.001). The quality of life was also significantly better with infliximab plus methotrexate than with methotrexate alone. Radiographic evidence of joint damage increased in the group given methotrexate, but not in the groups given infliximab and methotrexate (mean change in radiographic score, 7.0 vs. 0.6, P<0.001). Radiographic evidence of progression of joint damage was absent in infliximab-treated patients whether or not they had a clinical response. In patients with persistently active rheumatoid arthritis despite methotrexate therapy, repeated doses of infliximab in combination with methotrexate provided clinical benefit and halted the progression of joint damage.
Article
Curcumin, a major yellow pigment and active component of turmeric, has been shown to possess anti-inflammatory and anti-cancer activities. Cyclooxygenase (COX)-2 plays an important role in colon carcinogenesis. To investigate the effect of curcumin on COX-2 expression, we treated HT-29 human colon cancer cells with various concentrations of curcumin. Curcumin inhibited the cell growth of HT-29 cells in a concentration- and time-dependent manner. Curcumin markedly inhibited the mRNA and protein expression of COX-2, but not COX-1. These data suggest that a non-toxic concentration of curcumin has a significant effect on the in vitro growth of HT-29 cells, specifically inhibits COX-2 expression, and may have value as a safe chemopreventive agent for colon cancer.
Article
Rheumatoid arthritis (RA) is a progressive polyarthritis that is responsible for over nine million office visits annually. It is likely that most nurse practitioners will care for one or more patients with RA because approximately 1% of the adult population is affected by this disabling disorder. The guideline reviewed in this month's column describes the recommended care of patients who have been previously diagnosed with RA.
Article
To compare the efficacy and safety of adalimumab plus methotrexate (MTX) versus MTX monotherapy or adalimumab monotherapy in patients with early, aggressive rheumatoid arthritis (RA) who had not previously received MTX treatment. This was a 2-year, multicenter, double-blind, active comparator–controlled study of 799 RA patients with active disease of <3 years' duration who had never been treated with MTX. Treatments included adalimumab 40 mg subcutaneously every other week plus oral MTX, adalimumab 40 mg subcutaneously every other week, or weekly oral MTX. Co-primary end points at year 1 were American College of Rheumatology 50% improvement (ACR50) and mean change from baseline in the modified total Sharp score. Combination therapy was superior to both MTX and adalimumab monotherapy in all outcomes measured. At year 1, more patients receiving combination therapy exhibited an ACR50 response (62%) than did patients who received MTX or adalimumab monotherapy (46% and 41%, respectively; both P < 0.001). Similar superiority of combination therapy was seen in ACR20, ACR70, and ACR90 response rates at 1 and 2 years. There was significantly less radiographic progression (P ≤ 0.002) among patients in the combination treatment arm at both year 1 and year 2 (1.3 and 1.9 Sharp units, respectively) than in patients in the MTX arm (5.7 and 10.4 Sharp units) or the adalimumab arm (3.0 and 5.5 Sharp units). After 2 years of treatment, 49% of patients receiving combination therapy exhibited disease remission (28-joint Disease Activity Score <2.6), and 49% exhibited a major clinical response (ACR70 response for at least 6 continuous months), rates approximately twice those found among patients receiving either monotherapy. The adverse event profiles were comparable in all 3 groups. In this population of patients with early, aggressive RA, combination therapy with adalimumab plus MTX was significantly superior to either MTX alone or adalimumab alone in improving signs and symptoms of disease, inhibiting radiographic progression, and effecting clinical remission.
Article
While fruits and vegetables are recommended for prevention of cancer and other diseases, their active ingredients (at the molecular level) and their mechanisms of action less well understood. Extensive research during the last half century has identified various molecular targets that can potentially be used not only for the prevention of cancer but also for treatment. However, lack of success with targeted monotherapy resulting from bypass mechanisms has forced researchers to employ either combination therapy or agents that interfere with multiple cell-signaling pathways. In this review, we present evidence that numerous agents identified from fruits and vegetables can interfere with several cell-signaling pathways. The agents include curcumin (turmeric), resveratrol (red grapes, peanuts and berries), genistein (soybean), diallyl sulfide (allium), S-allyl cysteine (allium), allicin (garlic), lycopene (tomato), capsaicin (red chilli), diosgenin (fenugreek), 6-gingerol (ginger), ellagic acid (pomegranate), ursolic acid (apple, pears, prunes), silymarin (milk thistle), anethol (anise, camphor, and fennel), catechins (green tea), eugenol (cloves), indole-3-carbinol (cruciferous vegetables), limonene (citrus fruits), beta carotene (carrots), and dietary fiber. For instance, the cell-signaling pathways inhibited by curcumin alone include NF-kappaB, AP-1, STAT3, Akt, Bcl-2, Bcl-X(L), caspases, PARP, IKK, EGFR, HER2, JNK, MAPK, COX2, and 5-LOX. The active principle identified in fruit and vegetables and the molecular targets modulated may be the basis for how these dietary agents not only prevent but also treat cancer and other diseases. This work reaffirms what Hippocrates said 25 centuries ago, let food be thy medicine and medicine be thy food.
Article
To evaluate the efficacy, including radiographic changes, and safety of etanercept and methotrexate (MTX), used in combination and alone, in patients with rheumatoid arthritis (RA) in whom previous treatment with a disease-modifying antirheumatic drug other than MTX had failed. Patients with RA were treated with etanercept (25 mg subcutaneously twice weekly), oral MTX (up to 20 mg weekly), or combination therapy with etanercept plus MTX through a second year, in a double-blinded manner. Clinical response was assessed using American College of Rheumatology (ACR) criteria and the Disease Activity Score (DAS), in a modified intent-to-treat analysis with the last observation carried forward (LOCF) and in a population of completers. Radiographs of the hands, wrists, and forefeet were scored for erosions and joint space narrowing at annual intervals. A total of 503 of 686 patients continued into year 2 of the study. During the 2 years, significantly fewer patients receiving combination therapy withdrew from the study (29% of the combination therapy group, 39% of the etanercept group, and 48% of the MTX group). Both the LOCF and the completer analyses yielded similar results. The ACR 20% improvement (ACR20), ACR50, and ACR70 responses and the remission rates (based on a DAS of <1.6) were significantly higher with combination therapy than with either monotherapy (P<0.01). Similarly, improvement in disability (based on the Health Assessment Questionnaire) was greater with combination therapy (P<0.01). The combination therapy group showed significantly less radiographic progression than did either group receiving monotherapy (P<0.05); moreover, radiographic progression was significantly lower in the etanercept group compared with the MTX group (P<0.05). For the second consecutive year, overall disease progression in the combination therapy group was negative, with the 95% confidence interval less than zero. Adverse events were similar in the 3 treatment groups. Etanercept in combination with MTX reduced disease activity, slowed radiographic progression, and improved function more effectively than did either monotherapy over a 2-year period. No increase in toxicity was associated with combination treatment with etanercept plus MTX.
Article
Diabetic neuropathic pain, an important microvascular complication in diabetes mellitus is recognised as one of the most difficult types of pain to treat. A lack of the understanding of its aetiology, inadequate relief, development of tolerance and potential toxicity of classical antinociceptives warrant the investigation of the newer agents to relieve this pain. The aim of the present study was to explore the antinociceptive effect of curcumin and its effect on tumour necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) release in streptozotocin induced diabetic mice. Four weeks after a single intraperitoneal injection of streptozotocin (200 mg/kg), mice were tested in the tail immersion and hot-plate assays. Diabetic mice exhibited significant hyperalgesia along with increased plasma glucose and decreased body weights as compared with control mice. Chronic treatment with curcumin (15, 30 and 60 mg/kg body weight; p.o.) for 4 weeks starting from the 4th week of streptozotocin injection significantly attenuated thermal hyperalgesia and the hot-plate latencies. Curcumin also inhibited the TNF-alpha and NO release in a dose dependent manner. These results indicate an antinociceptive activity of curcumin possibly through its inhibitory action on NO and TNF-alpha release and point towards its potential to attenuate diabetic neuropathic pain.
Article
Diabetic neuropathic pain, an important microvascular complication in diabetes mellitus, is recognized as one of the most difficult types of pain to treat. The underlying mechanisms of painful symptoms may be closely associated with hyperglycaemia but a lack of the understanding of its proper aetiology, inadequate relief, development of tolerance and potential toxicity of classical antinociceptives warrant the investigation of newer agents to relieve this pain. The aim of the present study was to explore the antinociceptive effect of insulin and its combinations with resveratrol and curcumin in attenuating diabetic neuropathic pain. The study also aimed to examine the effect of these combinations on tumour necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) levels in streptozotocin (STZ) induced diabetic mice. Four weeks after a single intraperitoneal injection of streptozotocin (200 mg/kg), mice were tested in the tail immersion and hot-plate assays. Diabetic mice exhibited significant hyperalgesia along with increased plasma glucose and decreased body weights compared with control mice. Chronic treatment with insulin (10 IU/kg/day, s.c.) and its combinations with antioxidants (resveratrol 20 mg/kg or curcumin 60 mg/kg, p.o.) for 4 weeks starting from the 4th week of STZ injection significantly attenuated thermal hyperalgesia and the hot-plate latencies. There was a significant inhibition of TNF-alpha and NO levels when these drugs were given in combination compared with their effects per se. These results indicate an antinociceptive activity of resveratrol and curcumin and point towards the beneficial effect of these combinations with insulin in attenuating diabetic neuropathic pain, possibly through the participation of NO and TNF-alpha.
Article
Curcumin, an active ingredient of turmeric (Curcuma longa), inhibits proliferation and induces apoptosis in cancer cells, but the sequence of events leading to cell death is poorly defined. The objective of this study was to examine the molecular mechanisms by which multidomain pro-apoptotic Bcl-2 family members Bax and Bak regulate curcumin-induced apoptosis using mouse embryonic fibroblasts (MEFs) deficient in Bax, Bak or both genes. Curcumin treatment resulted an increase in the protein levels of both Bax and Bak, and mitochondrial translocation and activation of Bax in MEFs to trigger drop in mitochondrial membrane potential, cytosolic release of apoptogenic molecules [cytochrome c and second mitochondria-derived activator of caspases (Smac)/direct inhibitor of apoptosis protein-binding protein with low isoelectric point], activation of caspase-9 and caspase-3 and ultimately apoptosis. Furthermore, MEFs derived from Bax and Bak double-knockout (DKO) mice exhibited even greater protection against curcumin-induced release of cytochrome c and Smac, activation of caspase-3 and caspase-9 and induction of apoptosis compared with wild-type MEFs or single-knockout Bax(-/-) or Bak(-/-) MEFs. Interestingly, curcumin treatment also caused an increase in the protein level of apoptosis protease-activating factor-1 in wild-type MEFs. Smac N7 peptide enhanced curcumin-induced apoptosis, whereas Smac siRNA inhibited the effects of curcumin on apoptosis. Mature form of Smac sensitized Bax and Bak DKO MEFs to undergo apoptosis by acting downstream of mitochondria. The present study demonstrates the role of Bax and Bak as a critical regulator of curcumin-induced apoptosis and over-expression of Smac as interventional approaches to deal with Bax- and/or Bak-deficient chemoresistant cancers for curcumin-based therapy.
Article
Turmeric, derived from the plant Curcuma longa, is a gold-colored spice commonly used in the Indian subcontinent, not only for health care but also for the preservation of food and as a yellow dye for textiles. Curcumin, which gives the yellow color to turmeric, was first isolated almost two centuries ago, and its structure as diferuloylmethane was determined in 1910. Since the time of Ayurveda (1900 Bc) numerous therapeutic activities have been assigned to turmeric for a wide variety of diseases and conditions, including those of the skin, pulmonary, and gastrointestinal systems, aches, pains, wounds, sprains, and liver disorders. Extensive research within the last half century has proven that most of these activities, once associated with turmeric, are due to curcumin. Curcumin has been shown to exhibit antioxidant, anti-inflammatory, antiviral, antibacterial, antifungal, and anticancer activities and thus has a potential against various malignant diseases, diabetes, allergies, arthritis, Alzheimer's disease, and other chronic illnesses. These effects are mediated through the regulation of various transcription factors, growth factors, inflammatory cytokines, protein kinases, and other enzymes. Curcumin exhibits activities similar to recently discovered tumor necrosis factor blockers (e.g., HUMIRA, REMICADE, and ENBREL), a vascular endothelial cell growth factor blocker (e.g., AVASTIN), human epidermal growth factor receptor blockers (e.g., ERBITUX, ERLOTINIB, and GEFTINIB), and a HER2 blocker (e.g., HERCEPTIN). Considering the recent scientific bandwagon that multitargeted therapy is better than monotargeted therapy for most diseases, curcumin can be considered an ideal "Spice for Life".
Article
There is now some evidence that chronic fatigue syndrome is accompanied by an activation of the inflammatory response system and by increased oxidative and nitrosative stress. Nuclear factor kappa beta (NFkappabeta) is the major upstream, intracellular mechanism which regulates inflammatory and oxidative stress mediators. In order to examine the role of NFkappabeta in the pathophysiology of CFS, this study examines the production of NFkappabeta p50 in unstimulated, 10 ng/mL TNF-alpha (tumor necrosis factor alpha) and 50 ng/mL PMA (phorbolmyristate acetate) stimulated peripheral blood lymphocytes of 18 unmedicated patients with CFS and 18 age-sex matched controls. The unstimulated (F=19.4, df=1/34, p=0.0002), TNF-alpha-(F=14.0, df=1/34, p=0.0009) and PMA-(F=7.9, df=1/34, p=0.008) stimulated production of NFkappabeta were significantly higher in CFS patients than in controls. There were significant and positive correlations between the production of NFkappabeta and the severity of illness as measured with the FibroFatigue scale and with symptoms, such as aches and pain, muscular tension, fatigue, irritability, sadness, and the subjective feeling of infection. The results show that an intracellular inflammatory response in the white blood cells plays an important role in the pathophysiology of CFS and that previous findings on increased oxidative stress and inflammation in CFS may be attributed to an increased production of NFkappabeta. The results suggest that the symptoms of CFS, such as fatigue, muscular tension, depressive symptoms and the feeling of infection reflect a genuine inflammatory response in those patients. It is suggested that CFS patients should be treated with antioxidants, which inhibit the production of NFkappabeta, such as curcumin, N-Acetyl-Cysteine, quercitin, silimarin, lipoic acid and omega-3 fatty acids.
Article
Although turmeric (Curcuma longa; an Indian spice) has been described in Ayurveda, as a treatment for inflammatory diseases and is referred by different names in different cultures, the active principle called curcumin or diferuloylmethane, a yellow pigment present in turmeric (curry powder) has been shown to exhibit numerous activities. Extensive research over the last half century has revealed several important functions of curcumin. It binds to a variety of proteins and inhibits the activity of various kinases. By modulating the activation of various transcription factors, curcumin regulates the expression of inflammatory enzymes, cytokines, adhesion molecules, and cell survival proteins. Curcumin also downregulates cyclin D1, cyclin E and MDM2; and upregulates p21, p27, and p53. Various preclinical cell culture and animal studies suggest that curcumin has potential as an antiproliferative, anti-invasive, and antiangiogenic agent; as a mediator of chemoresistance and radioresistance; as a chemopreventive agent; and as a therapeutic agent in wound healing, diabetes, Alzheimer disease, Parkinson disease, cardiovascular disease, pulmonary disease, and arthritis. Pilot phase I clinical trials have shown curcumin to be safe even when consumed at a daily dose of 12g for 3 months. Other clinical trials suggest a potential therapeutic role for curcumin in diseases such as familial adenomatous polyposis, inflammatory bowel disease, ulcerative colitis, colon cancer, pancreatic cancer, hypercholesteremia, atherosclerosis, pancreatitis, psoriasis, chronic anterior uveitis and arthritis. Thus, curcumin, a spice once relegated to the kitchen shelf, has moved into the clinic and may prove to be "Curecumin".