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A Systematic Review of the Clinical Use of Curcumin for the Treatment of Osteoarthritis
Abstract
Osteoarthritis is characterized by degeneration of joint structure over time, resulting in limitation of joint mobility. There is growing evidence that curcumin has anti-inflammatory properties and could be a potential therapeutic option for chronic inflammatory diseases. Hence, curcumin could potentially have a positive impact on osteoarthritis symptoms. This systematic review aimed to estimate the effects of curcumin on osteoarthritis. We systematically searched PubMed, ISI, Scopus, and Google Scholar up to March 4, 2020 to identify randomized controlled trials that evaluated the effects of consumption of all types of curcumin compounds in the treatment of osteoarthritis, especially in patients with knee osteoarthritis. Seventeen trials were identified. The duration of the included studies varied from 4 weeks to 8 months. Across all trials, 13 studies involved screening using Western Ontario and McMaster Universities (WOMAC) scores and 11 studies used visual analog scales (VAS) for recording pain from baseline to post-intervention. There was a significant improvement in VAS and overall WOMAC scores with oral administration of various types of curcumin formulations with no severe adverse effects. In conclusion, different types of curcumin compounds may be beneficial as an alternative or complementary agent for the management of osteoarthritis. Moreover, certain curcumin compounds with higher bioavailability tended to show more positive effects.
... Curcumin has been extensively studied under experimental conditions as well as human clinical studies including treatment of osteoarthritis [23,[28][29][30][31], and bioavailability of curcuminoids plays an important role in the bioactivity such as exhibiting antioxidant and anti-inflammatory properties [32]. A recent study that used cell-based experimental models of osteoarthritis demonstrated that curcumin suppresses inflammation by blocking the NF-jB-Sox9 signaling pathway that plays a critical role in initiation of pathogenesis of osteoarthritis [29]. ...
... Curcumin has been extensively studied under experimental conditions as well as human clinical studies including treatment of osteoarthritis [23,[28][29][30][31], and bioavailability of curcuminoids plays an important role in the bioactivity such as exhibiting antioxidant and anti-inflammatory properties [32]. A recent study that used cell-based experimental models of osteoarthritis demonstrated that curcumin suppresses inflammation by blocking the NF-jB-Sox9 signaling pathway that plays a critical role in initiation of pathogenesis of osteoarthritis [29]. Curcumin enhances the antioxidant activities, inhibits oxidative stress, modulates immune functions, protects against cartilage damage, blocks inflammation pathways, and inhibits chondrocyte apoptosis [33]. ...
Background:
Despite its broad range of biological activities, use of curcumin is limited because of poor bioavailability. Here we report a novel curcumin formulation, Curcuwin Ultra+ (CU+), with superior bioavailability as compared to 95% turmeric extract (TUR 1800).
Methods:
A randomized, double-blind, three-treatment, crossover oral bioavailability study was conducted in 24 healthy volunteers under fasting conditions. Subjects received a single dose of CU+ 250 mg, 500 mg and 1900 mg of TUR1800 as per randomization schedule and blood samples were collected at 4 h and 0 h before dosing, and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24 h post dose. Total curcuminoids were measured as curcumin, demethoxycurcumin, bisdemethoxycurcumin, and tetrahydrocurcumin using a validated LC-MS/MS method.
Results:
CU+ achieved a significantly higher (p < 0.05) maximum plasma concentration (Cmax) and total systemic exposure (AUC0-6 and AUC0-12) for total curcuminoids as compared to TUR 1800. We observed 101 and 100 times higher Cmax respectively for 250 and 500 mg doses of CU+ as compared to 1900 mg of TUR1800. Similarly, AUC0-6 was 144 and 149 times higher whereas AUC0-12 was 99 and 113 times higher respectively for 250 and 500 mg doses of CU+ as compared to 1900 mg dose of TUR1800. Further, CU+ showed 40% faster absorption (p < 0.05). No safety issues were observed.
Conclusion:
CU+, which is designed for increased absorption and protection of curcuminoids from intestinal degradation, demonstrated superior bioavailability as compared to TUR1800 at considerably smaller doses. Additional clinical studies will help to demonstrate the impact of its increased bioavailability on efficacy.
Clinical trial registration:
CTRI/2020/10/028508 (Clinical Trials Registry-India).
... This means that no additional risk of liver, coagulation, and electrolyte damage exists in patients taking curcumin. Regarding the safety of curcumin as a treatment or complementary treatment in other diseases, reports have been published [24,25], and in this study, it was also confirmed that it is without complications in patients suffering from severe brain trauma. In this study, we used a dose of 500 mg of curcumin per day, while some studies used doses of 1200 mg per day and did not report any toxicity [23,24]. ...
Background and Aim: Traumatic brain injury (TBI) is one of the critical causes of death in trauma patients. In this study, the effect of nanocurcumin on the outcome of severe TBI was investigated for the first time in humans. Methods and Materials/Patients: This randomized, double-blind, and paralleled controlled study included 128 patients aged from 18 to 70 years with severe brain trauma. Patients were randomly assigned to control group (standard care treatment+placebo) and intervention group (standard care treatment+oral nanocurcumin). Changes in the level of consciousness, cerebral edema, kidney function, liver enzymes, sodium and potassium electrolytes, and brain function were followed up and compared until 6 months after discharge. Results: The Mean±SD in the intervention (14.44±31.86 years) and control patients (14.86±33.34 years) had no significant difference (P=0.543). Both groups were similar in terms of gender (P=0.669). The average level of consciousness in the intervention group increased by about 3 units (P=0.004) and more than 2 units (P=0.002) at discharge compared with the control group. By comparing the optimal performance of patients in the first (P=0.389) trimester and second (P=0.309) trimester after discharge, no significant difference was observed between the intervention and control groups. The amount of brain edema caused by severe brain trauma on the seventh day of treatment in the intervention group was lower than that in the control group (P=0.038). Conclusion: Administrating oral nanocurcumin supplement in patients with severe brain trauma along with their routine treatment is effective in improving brain edema and their level of consciousness without causing coagulation, and liver and kidney complications. These findings are not only statistically significant but also clinically vital.
... Curcumin is a polyphenol with anti-inflammatory properties extracted from turmeric that has shown promising preclinical results in treating FXTAS (85) but has not been studied clinically. Curcumin has a notable anti-inflammatory effect and pain relief for the treatment of general pain syndrome and osteoarthritis (86). However, more comprehensive long-term studies are needed, as many of the controlled trials are of low quality with industry funding. ...
Individuals with the fragile X premutation report symptoms of chronic pain from multiple systems, have increased incidence of comorbid conditions where pain is a prominent feature, and pathophysiology that supports disrupted pain regulation, inflammation, and energy imbalance. Less is known about how pain manifests for the subpopulation of carriers that develop the motor and cognitive changes of fragile X-associated tremor and ataxia syndrome (FXTAS), and how pain may differ between men and women. We gathered data collected from 104 males and females with FXTAS related to chronic pain, comorbid conditions related to pain, and medications used for pain control to further explore the types of pain experienced and to better characterize how individuals with the fragile X premutation experience pain sensation across genders. We found that women experience significantly more pain symptoms than men, particularly allodynia (20 vs. 2.0%, p = 0.008), peripheral neuropathy pain (43.9 vs. 25.4%, p = 0.0488), migraine (43.9 vs. 14.5%, p = 0.0008), fibromyalgia (26.8 vs. 0%, p = 0.0071) and back pain (48.5 vs. 23.4%, p = 0.008). We found onset of peripheral neuropathy predicts the onset of ataxia (β = 0.63 ± 0.25, p = 0.019) and tremor (β = 0.56 ± 0.17, p = 0.004) across gender. Women also report significantly more anxiety (82.9 vs. 39.7%, p < 0.001), which has implications for ideal pain treatment. These pain symptoms need to be recognized in the medical history and treated appropriately, with consideration for overlapping comorbidities.
... Furthermore, curcumin possess anti-inflammatory and antioxidant effects on different organs other than the nerves and muscles [28]. Therefore, improvement in motor function may be attributed to the effect of curcumin on joints [29] rather than to the pathology of DM itself. ...
Canine degenerative myelopathy (DM), recognized as a spontaneous model of amyotrophic lateral sclerosis, is known as a late-onset progressive degenerative disease of the spinal cord. Because of the progressive nature of DM, many dogs are elected to be euthanized, resulting in limited information on the end-stage clinical presentation. We investigated the long-term clinical course from diagnosis to natural death to further deepen our understanding of the entire clinical picture of this disease. Because curcumin was administered in some cases, the therapeutic effect of curcumin on DM was also examined. Forty dogs included in this study were client-owned Pembroke Welsh Corgis with a definitive diagnosis of DM by necropsy and histopathology. Dogs were excluded from this study if they died from another disease or were elected to be euthanized. Information on the long-term clinical symptoms of DM was investigated based on a questionnaire, which was collected from the dog owners. Urinary incontinence and respiratory disorder were observed in most dogs, as was respiratory impairment-correlated death. In contrast, signs consistent with brainstem dysfunction were noticed at the terminal stage in a small portion of dogs. Although further studies with more cases are needed, the results of this study suggest that administration of curcumin is effective in slowing the progression of DM.
In the face of the COVID-19 pandemic, many people around the world have increased their healthy behaviors to prevent transmission of the virus and potentially improve their immune systems. Therefore, the role of diet and food compounds such as spices with bioactive and antiviral properties may be important in these efforts. In this chapter, we review the efficacy of spices such as turmeric (curcumin), cinnamon, ginger, black pepper, saffron, capsaicin, and cumin by investigating the effects of these compounds of COVID-19 disease severity biomarkers.
Migraine, a neurovascular condition, is a chronic and lifelong disease that affects about 15% of the population worldwide. Although the exact pathophysiology and etiology of migraine are still unclear, oxidative stress, inflammation, and neuroendocrine imbalances are identified as the critical risk factors for migraine attacks. Curcumin is an active component and a polyphenolic diketone compound extracted from turmeric. Curcumin is a promising candidate for preventing and controlling migraine due to its anti‑inflammatory, antioxidative, anti-protein aggregate, and analgesic effects. In the present review, we have evaluated experimental and clinical studies investigating the impact of liposomal curcumin and nano-curcumin on the frequency and severity of migraine attacks in patients. Although the results are promising, more studies should be conducted in this area to show the exact efficacies of curcumin on clinical symptoms of migraine and investigate its potential mechanisms.
Curcumin is extracted from the rhizomes Curcuma longa L. It is known for its anti‐inflammatory and anti‐oxidant activities. Despite its safety and potential for use against various diseases, curcumin's utility is restricted due to its low oral bioavailability. Co‐administration of curcumin along with piperine could potentially improve the bioavailability of curcumin. The present review aimed to provide an overview of the efficacy and safety of curcumin‐piperine co‐supplementation in human health. The findings of this comprehensive review show the beneficial effects of curcumin‐piperine in improving glycemic indices, lipid profile and antioxidant status in diabetes, improving the inflammatory status caused by obesity and metabolic syndrome, reducing oxidative stress and depression in chronic stress and neurological disorders, also improving chronic respiratory diseases, asthma and COVID‐19. Further high‐quality clinical trial studies are needed to firmly establish the clinical efficacy of the curcumin‐piperine supplement.
Receptor-interacting protein 2 (RIP2) is a key mediator implicated in multiple cellular processes, and its dysregulation has been recently reported in colitis, asthma and other inflammatory diseases. However, the effects of RIP2 on osteoarthritis (OA) and the underlying mechanisms remain unclear. In this study, we found that RIP2 expression was upregulated in human articular cartilage tissues with OA and interleukin-1β (IL-1β)-treated chondrocytes. Knockdown of RIP2 inhibited IL-1β-induced extracellular matrix (ECM) and oxidative stress. Moreover, knockdown of TRAF3 reversed the effect of RIP2 silencing on cartilage degradation and oxidative stress in IL-1β-induced chondrocytes. In addition, p38 mitogen-activated protein kinase (MAPK) activator dehydrocorydalmine chloride (Dc) also reversed the effect of RIP2 silencing on IL-1β-induced chondrocytes. Taken together, our data reveal that RIP2 knockdown inhibits cartilage degradation and oxidative stress in IL-1β-treated chondrocytes by regulating TRAF3 expression and p38 MAPK pathway activation.
Curcumin (Cur) is an active derivative extracted from turmeric which exerts a wide range of interactions with biomolecules through complex signaling pathways. Cur has been extensively shown to possess potential antitumor properties. In addition, there is growing body of evidence suggesting that Cur may exert potential anti-estrogen and anti-androgen activity. In vitro and in vivo studies suggest that anticancer properties of Cur against tumors affecting the reproductive system in females and males may be underlied by the Cur-mediated inhibition of androgen and estrogen signaling pathways. In this review we examine various studies assessing the crosstalk between Cur and both androgen and estrogen hormonal activity. Also, we discuss the potential chemopreventive and antitumor role of Cur in the most prevalent cancers affecting the reproductive system in females and males.
Background
Osteoarthritis is the most common joint damage that leads to cartilage destruction, pain, and disability. The aim of this study is to investigate the effects of resistance exercises and Nano curcumin supplementation on synovial levels of collagenase-2 and NO in patients with knee osteoarthritis.
Methods
Forty women with primary knee osteoarthritis were divided into four groups including control, exercise, supplementation, and supplementation /exercises. The resistance exercise group performed exercises in 16 weeks (three sessions per week). The supplement group consumed one Nano curcumin capsule (1000 mg) per day for 16 weeks. Exercise and supplementation group also performed resistance exercises along with consuming Nano curcumin. Synovial fluid samplings were done in two stages of pre-test (24 h before training and supplementation) and post-test (48 h after the last session of treatment and supplementation). The obtained synovial fluid was used to measure the synovial level of collagenase -II and nitric oxide.
Results
Although, there were not any significant correlations between resistance exercise, nanocurcumum supplementation, and synovial levels of collagenase-2 and NO among women with knee osteoarthritis, we observed interesting reduced levels of both markers following the supplementation.
Conclusions
It can be concluded that the Nano curcumin supplementation can be an effective method to reduce the levels of these inflammatory factors in synovial fluids of cases with knee Osteoarthritis. Longer duration of the protocol may have more promoting results.
Trial registration
The project was registered at Iranian Registry of Clinical Trials (Trial registration number: IRCT20161208031300N1).
Neurodegenerative diseases (NDs) result from progressive deterioration of selectively susceptible neuron populations in different central nervous system (CNS) regions. NDs are classified in accordance with the primary clinical manifestations (e.g., parkinsonism, dementia, or motor neuron disease), the anatomic basis of neurodegeneration (e.g., frontotemporal degenerations, extrapyramidal disorders, or spinocerebellar degenerations), and fundamental molecular abnormalities (e.g., mutations, mitochondrial dysfunction, and its related molecular alterations). NDs include the Alzheimer disease and Parkinson disease, among others. There is a growing evidence that mitochondrial dysfunction and its related mutations in the form of oxidative/nitrosative stress and neurotoxic compounds play major roles in the pathogenesis of various NDs. Curcumin, a polyphenol and nontoxic compound, obtained from turmeric, has been shown to have a therapeutic beneficial effect in various disorders especially on the CNS cells. It has been shown that curcumin has considerable neuro‐ and mitochondria‐protective properties against broad‐spectrum neurotoxic compounds and diseases/injury‐associating NDs. In this article, we have reviewed the various effects of curcumin on mitochondrial dysfunction in NDs.
Objectives
Comparison of two doses of bio-optimized Curcuma longa extract (BCL) in the management of symptomatic knee osteoarthritis (OA).
Methods
A prospective, randomized, 3-month, double-blind, multicenter, three-group, placebo-controlled trial assessing Patient Global Assessment of Disease Activity (PGADA) and serum sColl2-1, a biomarker of cartilage degradation, as co-primary endpoints. Pain on visual analog scale (VAS), Knee injury and Osteoarthritis Outcome Score (KOOS), and paracetamol/non-steroidal anti-inflammatory drug (NSAID) consumption were used as secondary endpoints.
Results
One hundred fifty patients with knee OA were followed for 90 days. Low and high doses of BCL showed a greater decrease of PGADA than placebo. Analysis of sColl2-1 showed in the placebo and BCL low-dose groups, but not in the BCL high-dose group, a transient but non-significant increase of sColl2-1 between T0 and T1. Thereafter, in all groups, sColl2-1 decreased between T1 and T3 (all p < 0.01), but no difference between the groups was found. Pain reduction at day 90 in the low- and high-dose BCL groups (− 29.5 mm and − 36.5 mm) was higher than that in the placebo (− 8 mm; p = 0.018). The global KOOS significantly decreased overtime, but changes were comparable across treatment arms. The ratio of patients with adverse events (AE) related to the product was similar in the placebo and treatment groups, but the number of AE linked to the product was higher in the high-dose BCL group compared to the placebo (p = 0.012).
Conclusions
BCL appeared safe and well-tolerated with no evidence of severe adverse effects. Efficacy analysis suggested positive trends for measurements of PGADA and serum levels of an OA biomarker and showed a rapid and significant decrease of pain in knee OA (Trial registration: NCT02909621, 21 September 2016 - retrospectively registered).
Purpose: Osteoarthritis is the single most common cause of disability in older adults with an estimated 10% to 15% prevalence in individuals above 60 years. The contemporary medications include nonsteroidal anti-inflammatory drugs acetaminophen, cyclooxygenase-2 inhibitors, and surgical interventions. In view of safety issues regarding their longterm use, necessitating search for effective and safe alternatives, we evaluated Capsule Longvida® Optimized Curcumin prepared using solid lipid curcumin particles (SLCP) technology in patients with knee osteoarthritis. Patients and methods: Eligible patients fulfilling American College of Rheumatology Criteria were randomized to SLCP group (400 mg twice daily delivering 80 mg of curcumin per capsule) or Ibuprofen with placebo group (400 mg each once daily) for 90 days. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the Visual Analog Scale (VAS) were used for clinical assessment of knee pain and function. Degree of knee flexion and swelling were also noted. Blood biochemistry included hemogram, blood urea, creatinine, Random blood sugar and inflammatory markers viz. PGE2, TNF α, IL6, IL1β and LTB4 while urine examination included degenerative marker CTX II. The parametric data was analyzed using unpaired t test while non-parametric data was analyzed using Friedman's test or Mann Whitney t test as applicable. A level of p<0.05 was considered as statistically significant. Results: Out of 50 recruitments, 25 from the Ibuprofen group and 17 from the SLCP group completed the study with significant improvements in VAS and WOMAC scores indicating comparable efficacy of SLCP in alleviating pain with Ibuprofen. None of the markers displayed significant changes. Except one withdrawal in the study group due to rash and itching, the study drug was found safe. Conclusions: SLCP in a dose of 160 mg daily was found to be effective and safe in alleviating symptoms in patients suffering from knee osteoarthritis when administered for 90 days.
Background
The purpose of this study was to compare the efficacy and safety of curcumin with those of diclofenac in the treatment of knee osteoarthritis (OA).
Methods
In this randomized, open-label, parallel, active controlled clinical study, 139 patients with knee OA were randomly assigned to receive either a curcumin 500-mg (BCM-95®) capsule three times daily or a diclofenac 50-mg tablet two times daily for 28 days. Patients underwent assessment at baseline and days 7, 14, and 28. The main outcome measure was severity of pain using visual analogue scale score at days 14 and 28. Knee Injury and Osteoarthritis Outcome Score (KOOS) (at days 14 and 28), anti-flatulent effect (at day 7), anti-ulcer effect, weight-lowering effect, and patient’s and physician’s global assessment of therapy at day 28 were included as secondary outcome measures. Safety after treatment was evaluated by recording adverse events and laboratory investigation.
Results
At days 14 and 28, patients receiving curcumin showed similar improvement in severity of pain and KOOS scale when compared with diclofenac, and the difference was not statistically significant. At day 7, the patients who received curcumin experienced a significantly greater reduction in the number of episodes of flatulence compared with diclofenac (P <0.01). At day 28, a weight-lowering effect (P <0.01) and anti-ulcer effect (P <0.01) of curcumin were observed. None of the patients required H2 blockers in the curcumin group, and 19 patients required H2 blockers in the diclofenac group (0% versus 28%, respectively; P <0.01). Adverse effects were significantly less in the curcumin group (13% versus 38% in the diclofenac group; P <0.01). Patient’s and physician’s global assessment of therapy was similar in the two treatment groups.
Conclusion
Curcumin has similar efficacy to diclofenac but demonstrated better tolerance among patients with knee OA. Curcumin can be an alternative treatment option in the patients with knee OA who are intolerant to the side effects of non-steroidal anti-inflammatory drugs.
Trial registration
ISRCTN, ISRCTN10074826. Registered 21 November 2017 - Retrospectively registered.
Background:
Curene® is a bioavailable formulation of turmeric Curcucma longa extract comprising naturally derived curcuminoids formulated with proprietary Aquasome® technology. Curcuminoids were found to have anti-inflammatory properties by inhibiting Cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) enzyme and hence have potential application in the treatment of Osteoarthritis (OA). To evaluate the safety and efficacy of Curene® a randomized, double blind, placebo controlled, parallel-group study was conducted in subjects with knee OA. Significant improvements in clinical endpoints were observed during the trial along with excellent safety profile.
Methods:
Fifty (50) subjects aged between 40 and 75 years who were suffering from unilateral or bilateral OA of the knee for greater than 3 months according to American College of Rheumatology (ACR) criteria were enrolled. They were randomized into two treatment groups; one group received Curene® 500 mg once daily and the other group received placebo. Efficacy was evaluated using change from baseline in Visual Analogue Scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score. Biochemical and hematological parameters including urine analysis were performed to evaluate the safety of Curene® in OA patients.
Result:
Forty-six (46) subjects completed the study. The reduction from baseline in total WOMAC score (also subscale scores) and VAS score resulted in statistically significant difference when compared to placebo. It was also found to be safe and well tolerated as there was no incidence of treatment related AEs.
Conclusion:
Curene® results in statistically significant and clinically meaningful reduction in pain, stiffness, and improvement in physical functioning in subjects suffering from knee OA. Curene® also demonstrates excellent safety profile during the study.
Trial registration:
This trial is registered with Clinical Trial Registry, India, CTRI/2017/07/009044, registered on 14th July 2017, http://ctri.nic.in/Clinicaltrials/showallp.php?mid1=19264&EncHid=&userName=ocius%20life%20sciences.
Backround: Visual analogue scales (VAS) are psychometric measuring instruments designed to document the characteristics of disease-related symptom severity in individual patients and use this to achieve a rapid (statistically measurable and reproducible) classification of symptom severity and disease control. VAS can also be used in routine patient history taking and to monitor the course of a chronic disease such as allergic rhinitis (AR). More specifically, the VAS has been used to assess effectiveness of AR therapy in real life, both in intermittent and persistent disease. Methods: This position paper takes a detailed look at the historical development of VAS and its methodspecific principles. Particular focus is put on aspects of practical application in daily routine and on a critical discussion of the advantages and disadvantages of the individual methods. Results: VAS are well validated for the measurement of AR symptoms and correlate well with the ARIA (allergic rhinitis and its impact on asthma) severity classification and also correlated wellwith rTNSS and RQLQ. Moreover, several treatment studies on AR have used VAS as an evaluation parameter. Thanks to the use of new (real-life and real-time) communication technologies, such as smartphone apps, VAS can be used relatively simply and highly effectively to assess disease control. Discussion: The VAS lends itself very well to digitization and has now been incorporated into a smartphone app (called Allergy Diary) to assess AR control and direct treatment decisions as part of an AR clinical decision support system (CDSS). MASK Rhinitis has developed this app, which is currently available in 15 different languages.
Background
The aim of this clinical trial was to assess the efficacy and safety of curcuminoid complex extract from turmeric rhizome with turmeric volatile oil (CuraMed®) and its combination with boswellic acid extract from Indian frankincense root (Curamin®) vs placebo for the treatment of 40- to 70-year-old patients with osteoarthritis (OA). Methods
The effects of CuraMed® 500-mg capsules (333 mg curcuminoids) and Curamin® 500-mg capsules (350 mg curcuminoids and 150 mg boswellic acid) taken orally three times a day for 12 weeks in 201 patients was investigated in a three-arm, parallel-group, randomized, double-blinded, placebo-controlled trial. Primary outcome efficacy measures included OA physical function performance-based tests, the WOMAC recommended index of joint pain, morning stiffness, limitations of physical function, and the patients’ global assessment of disease severity. ResultsFavorable effects of both preparations compared to placebo were observed after only 3 months of continuous treatment. A significant effect of Curamin® compared to placebo was observed both in physical performance tests and the WOMAC joint pain index, while superior efficacy of CuraMed vs placebo was observed only in physical performance tests. The effect size compared to placebo was comparable for both treatment groups but was superior in the Curamin® group. The treatments were well tolerated. Conclusions
Twelve-week use of curcumin complex or its combination with boswellic acid reduces pain-related symptoms in patients with OA. Curcumin in combination with boswellic acid is more effective. Combining Curcuma longa and Boswellia serrata extracts in Curamin® increases the efficacy of OA treatment presumably due to synergistic effects of curcumin and boswellic acid. Trial registrationThis trial is registered at the database www.clinicaltrials.gov. https://clinicaltrials.gov/ct2/show/NCT02390349?term=EuroPharma&rank=1. Study registration number: NCT02390349.
The purpose of this study was to investigate the short-term of Theracurmin dose and exercise type on pain, walking ability, and muscle function in patients with knee osteoarthritis. Twenty-five patients with knee osteoarthritis randomly selected to Theracurmin intake (T) group and Theracurmin in combined with exercise (T+E) group. T group (n= 13) was taken orally a capsule of 700 mg, 3 times per day, (total 2,100 mg, 35 mg/kg-body weight). T+E group (n= 12) performed aerobic training of 30-min walking and weight training for increasing leg muscular strength. After treatment, the number of steps, muscle mass, range of motion of knee, and the muscle strength in flexion and extension significantly increased. The percent body fat, visual analogue scale, The Western Ontario and McMaster score, centers of pressure with closed eye, 10-m walking ability, stair ascending speed were significantly decreased after treatment. Although no difference observed between the T and T+E groups, the 4-week intake of Theracurmin with and without exercise appeared to be effective in reducing the pain and enhancing muscular and balancing function. Therefore, Theracurmin intake for early symptoms and additional exercise as symptoms alleviate might be an effective way of delaying and managing osteoarthritis, and additional studies investigating the effects of Theracurmin and exercise on osteoarthritis could be beneficial.
Turmeric, a spice that has long been recognized for its medicinal properties, has received interest from both the medical/scientific world and from culinary enthusiasts, as it is the major source of the polyphenol curcumin. It aids in the management of oxidative and inflammatory conditions, metabolic syndrome, arthritis, anxiety, and hyperlipidemia. It may also help in the management of exercise-induced inflammation and muscle soreness, thus enhancing recovery and performance in active people. In addition, a relatively low dose of the complex can provide health benefits for people that do not have diagnosed health conditions. Most of these benefits can be attributed to its antioxidant and anti-inflammatory effects. Ingesting curcumin by itself does not lead to the associated health benefits due to its poor bioavailability, which appears to be primarily due to poor absorption, rapid metabolism, and rapid elimination. There are several components that can increase bioavailability. For example, piperine is the major active component of black pepper and, when combined in a complex with curcumin, has been shown to increase bioavailability by 2000%. Curcumin combined with enhancing agents provides multiple health benefits. The purpose of this review is to provide a brief overview of the plethora of research regarding the health benefits of curcumin.
Cytokines are small secreted proteins released by different types of cells with specific effects on cellular signaling and communication via binding to their receptors on the cell surface. IL-10 is known to be a pleiotropic and potent anti-inflammatory and immunosuppressive cytokine that is produced by both innate and adaptive immunity cells including dendritic cells, macrophages, mast cells, natural killer cells, eosinophils, neutrophils, B cells, CD8⁺ T cells, and TH1, TH2, and TH17 and regulatory T cells. Both direct and indirect activation of the stress axis promotes IL-10 secretion. IL-10 deregulation plays a role in the development of a large number of inflammatory diseases such as neuropathic pain, Parkinson's disease, Alzheimer's disease, osteoarthritis, rheumatoid arthritis, psoriasis, systemic lupus erythematosus, type 1 diabetes, inflammatory bowel disease, and allergy. Curcumin is a natural anti-inflammatory compound able to induce the expression and production of IL-10 and enhancing its action on a large number of tissues. In vitro and in pre-clinical models curcumin is able to modulate the disease pathophysiology of conditions such as pain and neurodegenerative diseases, bowel inflammation, and allergy, but also of infections and cancer through its effect on IL-10 secretion. In humans, at least one part of the positive effects of curcumin on health could be related to its ability to enhance IL-10 –mediated effects.
Backround
Visual analogue scales (VAS) are psychometric measuring instruments designed to document the characteristics of disease-related symptom severity in individual patients and use this to achieve a rapid (statistically measurable and reproducible) classification of symptom severity and disease control. VAS can also be used in routine patient history taking and to monitor the course of a chronic disease such as allergic rhinitis (AR). More specifically, the VAS has been used to assess effectiveness of AR therapy in real life, both in intermittent and persistent disease.
Methods
This position paper takes a detailed look at the historical development of VAS and its method-specific principles. Particular focus is put on aspects of practical application in daily routine and on a critical discussion of the advantages and disadvantages of the individual methods.
Results
VAS are well validated for the measurement of AR symptoms and correlate well with the ARIA (allergic rhinitis and its impact on asthma) severity classification and also correlated well with rTNSS and RQLQ. Moreover, several treatment studies on AR have used VAS as an evaluation parameter. Thanks to the use of new (real-life and real-time) communication technologies, such as smartphone apps, Discussion: VAS can be used relatively simply and highly effectively to assess disease control. The VAS lends itself very well to digitization and has now been incorporated into a smartphone app (called Allergy Diary) to assess AR control and direct treatment decisions as part of an AR clinical decision support system (CDSS). MASK Rhinitis has developed this app, which is currently available in 15 different languages.
Background and purposeCurcuma longa L. (CL), an Indian herb, has been used to treat many disorders because of its wide spectrum of pharmacological activities. It has been shown to exhibit anti-oxidant and anti-inflammatory properties, and is being used as herbal remedy since ancient times. Osteoarthritis of knee (KOA) is a chronic painful disorder in which prolong use of non-steroidal anti-inflammatory drugs (NSAIDs) or steroids may result into many serious side effects; hence, there is a need to develop herbal drugs, having good analgesia without side effects. Therefore, we planned to evaluate the efficacy of CL in KOA. Methods
The study was designed as a randomized, double-blind, placebo-controlled trial in patients of KOA. After obtaining ethical clearance and written informed consent, a total of 160 patients of KOA were randomly enrolled into two groups to receive either CL extract or placebo along with the standard drug regimen. The patients were assessed on day 0, day 60, and day 120. On the days of their visit, the clinical prognosis was assessed by visual analog scale (VAS) and Western Ontario and McMaster Universities (WOMAC) Osteoarthritis index. On these days, the radiographs were also taken for Kellgren and Lawrence grading and blood samples were collected for assessing the changes in levels of IL-1β and biomarkers of oxidative stress, such as reactive oxygen species and malondialdehyde (MDA). ResultsOver all significant improvement was observed in the patients of CL extract group as compared to placebo group. Clinically, the VAS and WOMAC scores became better, and simultaneously, the levels of biomarkers, viz., IL-1β, ROS, and MDA, were also significantly (p < 0.05) improved. Conclusion
It may be concluded that on chronic administration, CL suppresses inflammation and brings clinical improvement in patients of KOA, which may be observed by decreased level of IL-1β and VAS/WOMAC scores, respectively. At the same time, CL decreases the oxidative stress also.
Osteoarthritis is a degenerative disease of the joint affecting aging populations worldwide. It has an underlying inflammatory cause, which contributes to the loss of chondrocytes, leading to diminished cartilage layer at the affected joints. Compounds with anti-inflammatory properties are potential treatment agents for osteoarthritis. Curcumin derived from Curcuma species is an anti-inflammatory compound as such. This review aims to summarize the antiosteoarthritic effects of curcumin derived from clinical and preclinical studies. Many clinical trials have been conducted to determine the effectiveness of curcumin in osteoarthritic patients. Extracts of Curcuma species, curcuminoids and enhanced curcumin, were used in these studies. Patients with osteoarthritis showed improvement in pain, physical function, and quality of life after taking curcumin. They also reported reduced concomitant usage of analgesics and side effects during treatment. In vitro studies demonstrated that curcumin could prevent the apoptosis of chondrocytes, suppress the release of proteoglycans and metal metalloproteases and expression of cyclooxygenase, prostaglandin E-2, and inflammatory cytokines in chondrocytes. These were achieved by blocking the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) system in the chondrocytes, by preventing the activation of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha, phosphorylation, and translocation of the p65 subunit of NF-κB complexes into the nucleus. In conclusion, curcumin is a potential candidate for the treatment of osteoarthritis. More well-planned randomized control trials and enhanced curcumin formulation are required to justify the use of curcumin in treating osteoarthritis.
Background: Silymarin has powerful antioxidant properties, but its effects on athletic performance are poorly understood. Objectives: The present study was undertaken to evaluate the effects of 4 weeks of endurance or strength exercise, with or without silymarin, on body composition, paraoxonase (PON), leptin and adiponectin levels in untrained men. Methods: A total of 45 untrained men were divided into 5 groups (n = 9): endurance training with placebo (ET + P), endurance training with 140 mg of silymarin/day (ET + S), strength training with placebo (ST + P), strength training with 140 mg of silymarin/day (ST + S) and placebo (C). Anthropometrical and VO2max measurements and ELISA assay for PON, leptin and adiponectin levels were performed at the beginning and after the 4-week of the study Results: There was a significant decrease in weight and body mass index in the ET + P and ET + S groups and increases in ST + P and ST + S (P < 0.05) groups. Body fat declined in all four trained groups (P < 0.001). Peak oxygen uptake (VO2max) improved in both ET + P and ET + S subjects. Paraoxonase (PON) was increased only in ET + S group (P < 0.05). Adiponectin was increased in all four groups (P < 0.05). Circulating leptin remained unchanged within all interventions. Conclusions: The present study has demonstrated that a combination of exercise and silymarin can improve body composition and adiponectin levels.
In spite of the unequivocal efficacy of statins in reducing primary and secondary cardiovascular (CV) events, the use of these drugs in a considerable number of patients is limited because of statin intolerance, mainly statin-associated muscle symptoms (SAMS). SAMS encompass a broad spectrum of clinical presentations, including mild muscular aching and other types of myalgias, myopathy with the significant elevation of creatine kinase, and the rare but life-threatening rhabdomyolysis. Among several pathophysiologic mechanisms of SAMS, mitochondrial dysfunction is thought to be one of the main one. Curcumin is the polyphenolic ingredient of Curcuma longa L., which has various pharmacological properties against a vast range of diseases. Curcumin has several mechanisms of actions relevant to the treatment of SAMS. These effects include the capacity to prevent and reduce delayed onset muscle soreness by blocking the nuclear factor (NF)-кB inflammatory pathway, attenuation of muscular atrophy, enhancement of muscle fiber regeneration following injury, analgesic and antioxidant effects. Curcumin can also increase the levels of cyclic adenosine monophosphate (cAMP), which leads to an increase in the number of mitochondrial DNA duplicates in skeletal muscle cells. Finally, owing to its essential lipid-modifying properties, curcumin might serve as an adjunct to statin therapy in patients with SAMS, allowing for effective lowering of low-density lipoprotein cholesterol and possibly for statin dose reduction. Owing to the paucity of effective treatments, and the safety of curcumin in clinical practice, proof-of-concept trials are recommended to assess the potential benefit of this phytochemical in the treatment of SAMS.
Background:
Curcumin has been shown to have chondroprotective potential in vitro. However, its effect on disease and symptom modification in osteoarthritis (OA) is largely unknown. This study aimed to determine whether curcumin could slow progression of OA and relieve OA-related pain in a mouse model of destabilization of the medial meniscus (DMM).
Methods:
Expression of selected cartilage degradative-associated genes was evaluated in human primary chondrocytes treated with curcumin and curcumin nanoparticles and assayed by real-time PCR. The mice subjected to DMM surgery were orally administered curcumin or topically administered curcumin nanoparticles for 8 weeks. Cartilage integrity was evaluated by Safranin O staining and Osteoarthritis Research Society International (OARSI) score, and by immunohistochemical staining of cleaved aggrecan and type II collagen, and levels of matrix metalloproteinase (MMP)-13 and ADAMTS5. Synovitis and subchondral bone thickness were scored based on histologic images. OA-associated pain and symptoms were evaluated by von Frey assay, and locomotor behavior including distance traveled and rearing.
Results:
Both curcumin and nanoparticles encapsulating curcumin suppressed mRNA expression of pro-inflammatory mediators IL-1β and TNF-α, MMPs 1, 3, and 13, and aggrecanase ADAMTS5, and upregulated the chondroprotective transcriptional regulator CITED2, in primary cultured chondrocytes in the absence or presence of IL-1β. Oral administration of curcumin significantly reduced OA disease progression, but showed no significant effect on OA pain relief. Curcumin was detected in the infrapatellar fat pad (IPFP) following topical administration of curcumin nanoparticles on the skin of the injured mouse knee. Compared to vehicle-treated controls, topical treatment led to: (1) reduced proteoglycan loss and cartilage erosion and lower OARSI scores, (2) reduced synovitis and subchondral plate thickness, (3) reduced immunochemical staining of type II collagen and aggrecan cleavage epitopes and numbers of chondrocytes positive for MMP-13 and ADAMTS5 in the articular cartilage, and (4) reduced expression of adipokines and pro-inflammatory mediators in the IPFP. In contrast to oral curcumin, topical application of curcumin nanoparticles relieved OA-related pain as indicated by reduced tactile hypersensitivity and improved locomotor behavior.
Conclusion:
This study provides the first evidence that curcumin significantly slows OA disease progression and exerts a palliative effect in an OA mouse model.
Curcumin is a bioactive polyphenol occurring in the rhizomes of Curcuma
longa. It is well-reputed for its chemopreventive and anticancer properties; however, recent evidence has revealed numerous biological and pharmacological effects of curcumin that are relevant to the treatment of non-cancer diseases. Mechanistically, curcumin exerts its pharmacological effects through anti-inflammatory and antioxidant mechanisms via interaction with different signaling molecules and transcription factors. In addition, epigenetic modulators such as microRNAs (miRs) have emerged as novel targets of curcumin. Curcumin was found to modulate the expression of several pathogenic miRs in brain, ocular, renal, and liver diseases. The present systematic review was conducted to identify miRs that are regulated by curcumin in non-cancer diseases.
The influence of emulsifier type on the ability of excipient emulsions to improve the solubility, stability, and bioaccessibility of powdered curcumin was examined. Oil-in-water emulsions prepared using three different emulsifiers (whey protein isolate, caseinate, or Tween 80) were mixed with curcumin powder and then incubated at either 30 ºC (to simulate applications of salad dressings) or 100 ºC (to simulate applications of cooking sauces). The transfer of curcumin into the excipient emulsions was appreciably higher for excipient emulsions held at 100 ºC than those held at 30 ºC, and was appreciably higher for surfactant-stabilized emulsions than protein-stabilized emulsions. For example, the amounts of curcumin transferred into emulsions held at 30 and 100 ºC were 66 and 280 µg/mL for Tween 80, but only 17 and 208 µg/mL for caseinate. The total curcumin concentration in the digesta and mixed micelle phases collected after excipient emulsions were exposed to a simulated gastrointestinal tract (mouth, stomach, and small intestine) depended on emulsifier type. The total amount of curcumin within the digesta was higher for protein-stabilized emulsions than surfactant-stabilized ones, which was attributed to the ability of the proteins to protect curcumin from chemical degradation. For example, the digesta contained 204 µg/mL curcumin for caseinate emulsions, but only 111 µg/mL for Tween 80 emulsions. This study shows the potential of designing excipient emulsions to increase the oral bioavailability of curcumin for food and pharmaceutical applications.
Curcumin (Cur) and bisdemethoxycurcumin (BDMC), extracted from Curcuma longa, are poorly water-soluble polyphenol compounds that have shown anti-inflammatory potential for the treatment of osteoarthritis. To increase cellular uptake of Cur and BDMC in bone tissue, soybean phosphatidylcholines were used for liposome formulation. In this study, curcuminoid (Cur and BDMC)-loaded liposomes were characterized in terms of particle size, encapsulation efficiency, liposome stability, and cellular uptake. The results show that there is about 70% entrapment efficiency of Cur and BDMC in liposomes and that particle sizes are stable after liposome formation. Both types of liposome can inhibit macrophage inflammation and osteoclast differential activities. In comparison with free drugs (Cur and BDMC), curcuminoid-loaded liposomes were less cytotoxic and expressed high cellular uptake of the drugs. Of note is that Cur-loaded liposomes can prevent liposome-dependent inhibition of osteoblast differentiation and mineralization, but BDMC-loaded liposomes could not. With interleukin (IL)-1β stimulation, curcuminoid-loaded liposomes can successfully downregulate the expression of inflammatory markers on osteoblasts, and show a high osteoprotegerin (OPG)/receptor activator of nuclear factor κB ligand (RANKL) ratio to prevent osteoclastogenesis. In the present study, we demonstrated that Cur and BDMC can be successfully encapsulated in liposomes and can reduce osteoclast activity and maintain osteoblast functions. Therefore, curcuminoid-loaded liposomes may slow osteoarthritis progression.
Nanotechnology is an advanced scientific technique in the 21stcentury. By analyzing the relationship between nanotechnology and biological medicine, nanotechnology and bioavailability and the advances and the existing problems of Bioavailability enhancement, the application of nanotechnological methods for the mechanism research on bioavailability enhancement of herbal drugs were discussed. It is indicated that nanotechnology is one of the fastest developmental, the most potential and the far-reaching high and new technologies in current world, and it greatly promotes the development of biological medicine and bioavailability enhancement of herbal drugs. With the application of nanotechnology of nanomization of herbal drugs, it will make the development of nanoherbal medicine possess high bioavaibility, which consequently will open the new era of herbal drug discovery. It's pointed out that breakthrough will be achieved from the research of the nanomization of herbal phytochemicals like-nanocurcumin, nanopiperine, nanoberberine etc.
Background
We previously developed a surface-controlled water-dispersible form of curcumin and named it Theracurmin® (Theracurmin; Theravalues, Tokyo, Japan). The area under the blood concentration–time curve of Theracurmin in humans was 27-fold higher than that of curcumin powder. We determined the clinical effects of orally administered Theracurmin in patients with knee osteoarthritis during 8 weeks of treatment.
Methods
Fifty patients with knee osteoarthritis of Kellgren–Lawrence grade II or III and who were aged more than 40 years were enrolled in this randomized, double-blind, placebo-controlled, prospective clinical study. Placebo or Theracurmin containing 180 mg/day of curcumin was administered orally every day for 8 weeks. To monitor adverse events, blood biochemistry analyses were performed before and after 8 weeks of each intervention. The patients’ knee symptoms were evaluated at 0, 2, 4, 6, and 8 weeks by the Japanese Knee Osteoarthritis Measure, the knee pain visual analog scale (VAS), the knee scoring system of the Japanese Orthopedic Association, and the need for nonsteroidal anti-inflammatory drugs.
Results
At 8 weeks after treatment initiation, knee pain VAS scores were significantly lower in the Theracurmin group than in the placebo group, except in the patients with initial VAS scores of 0.15 or less. Theracurmin lowered the celecoxib dependence significantly more than placebo. No major side effects were observed with Theracurmin treatment.
Conclusion
Theracurmin shows modest potential for the treatment of human knee osteoarthritis.
Background:
Osteoarthritis of the knee is the most common chronic joint disease that involves middle aged and elderly persons. There are different clinical instruments to quantify the health status of patients with knee osteoarthritis and one example is the WOMAC score that has been translated and adapted into different languages. The purpose of this study was cultural adaptation, validation and reliability testing of the Persian version of the WOMAC index in Iranians with knee osteoarthritis.
Methods:
We translated the original WOMAC questionnaire into Persian by the forward and backward technique, and then its psychometric study was done on 169 native Persian speaking patients with knee degenerative joint disease. Mean age of patients was 53.9 years. The SF-36 and KOOS were used to assess construct validity.
Results:
Reliability testing resulted in a Cronbach's alpha of 0.917, showing the internal consistency of the questionnaire to be a reliable tool. Inter-correlation matrix among different scales of the Persian WOMAC index yielded a highly significant correlation between all subscales including stiffness, pain, and physical function. In terms of validity, Pearson`s correlation coefficient was significant between three domains of the WOMAC with PF, RP, BP, GH, VT, and PCS dimensions of the SF-36 health survey (P<0.005) and KOOS (P<0.0001) .
Conclusions:
The Persian WOMAC index is a valid and reliable patient- reported clinical instrument for knee osteoarthritis.
To determine the efficacy and safety of Curcuma domestica extracts in pain reduction and functional improvement.
367 primary knee osteoarthritis patients with a pain score of 5 or higher were randomized to receive ibuprofen 1,200 mg/day or C. domestica extracts 1,500 mg/day for 4 weeks. The main outcomes were Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total, WOMAC pain, WOMAC stiffness, and WOMAC function scores. Adverse events (AEs) were also recorded.
185 and 182 patients were randomly assigned into C. domestica extracts and ibuprofen groups, respectively. The baseline characteristics were no different between groups. The mean of all WOMAC scores at weeks 0, 2, and 4 showed significant improvement when compared with the baseline in both groups. After using the noninferiority test, the mean difference (95% confidence interval) of WOMAC total, WOMAC pain, and WOMAC function scores at week 4 adjusted by values at week 0 of C. domestica extracts were noninferior to those for the ibuprofen group (P=0.010, P=0.018, and P=0.010, respectively), except for the WOMAC stiffness subscale, which showed a trend toward significance (P=0.060). The number of patients who developed AEs was no different between groups. However, the number of events of abdominal pain/discomfort was significantly higher in the ibuprofen group than that in the C. domestica extracts group (P=0.046). Most subjects (96%-97%) were satisfied with the treatment, and two-thirds rated themselves as improved in a global assessment.
C. domestica extracts are as effective as ibuprofen for the treatment of knee osteoarthritis. The side effect profile was similar but with fewer gastrointestinal AE reports in the C. domestica extracts group.
Nonsteroidal anti-inflammatory Drugs (NSAIDs) is one of the most commonly use medication for treatment of knee osteoarthritis which has the analgesic and anti-inflammation by inhibition of prostaglandin synthesis via COX-1 and COX-2 isoenzyme. The problem of prolong using NSAIDs has side effect on kidney, liver and GI system. Curcumin longa extract Curcumin) is the Asian herbal medicine that has the anti-inflammatory effect by down regulate activation of NF-kappaB and proinflammatory cytokines such as Tumor Necrotic Factor-alpha, Interleukin-1, Interleukin-8, and Nitric Oxide Syntase. Many research data had advocate for the combination therapy which can increase safety and efficacy with less side effect compare with monotherapy regimen especially when the medicine has the different mechanism of action. The present study is the double blind prospective randomized control trial to evaluate the efficacy of curcumin as an adjuvant therapy of diclofenac in primary knee osteoarthritis. 44 patients were randomized to take NSAIDs (diclofenac) 75 mg/d with placebo and the other 44 took NSAIDs (diclofenac) 75 mg/d with curcumin 1,000 mg/d for 3 months. The authors evaluated the Visual Analog Scale (VAS) for pain and Knee Injury and Osteoarthritis Outcome Score (KOOS) every month for 3 months. At the end of study 36 patients were completed for the first group and 37 for the study group. There was no difference in VAS [p-value = 0.923 (F = 0.009)]. The KOOS was analyzed in 5 categories symptom, pain, function in daily living, function in sport and recreation and knee related quality of life. The curcumin with diclofenac group had tendency to be better in Pain and Function in daily living, but there were no statistic different in all group [p-value = 0.412 (F = 0.683), p-value = 0.814 (F = 0.056), p-value = 0.446 (F = 0.589), p-value = 0.224 (F = 1.511) and p-value = 0.938 (F = 0.006)]. In conclusion, the adjuvant therapy ofcurcumin with diclofenac has the potential beneficial effect in comparison with diclofenac alone, but no statistical significance.
Background and Aims
With an aging society, a multitude of physical, mental, and emotional challenges are being faced both in the general population and by those with chronic disorders. An enhanced understanding of ‘quality of life’ could be considered a major criterion for improved clinical care. We performed a meta-analysis to examine the effect of oral curcumin on improving the health-related quality of life (HRQOL).
Methods
A systematic search was performed through PubMed, Clarivate Web of Science, Scopus, and Embase up to February 2020 using relevant keywords. Trials that met the inclusion criteria were included in this study. We applied the standardized mean difference (SMD) in a random-effects model to analyze the impact of combined trials. Additionally, we used the Cochrane Risk Bias Tool to evaluate any potential risks of bias.
Results
A total of 10 studies were considered eligible and included in the meta-analysis. We found an overall significant effect of oral curcumin supplementation on improved HRQOL (SMD: 2.46, 95% CI: 1.30, 3.63; I2=97.4). In the subgroup analysis, curcumin showed significantly favorable effects on HRQOL in trials with a short duration of curcumin intervention (<5 months) and those that used curcumin formulations with high bioavailability.
Conclusion
Oral curcumin has a strong positive impact on HRQOL. Our analysis supports the use of an improved-bioavailability formulation of curcumin to improve HRQOL. However, given the heterogeneity among the studies included in this review, additional evidence from well-designed, large, and long-term trials is still required.
Curcumin is the major bioactive polyphenolic ingredient of turmeric. Increasing evidence indicates that the health benefits of curcumin are mediated through its anti-inflammatory and antioxidant effects. Inflammasomes are essential components of inflammatory pathways that activate caspase-1 leading to pyroptosis and stimulate maturation and secretion of the proinflammatory cytokines, interleukin‐1β (IL-1β) and interleukin-18 (IL-18) through nuclear factor kappa-B (NF‐κB) signaling. The current review outlines the mechanisms of curcumin as an inflammasome modulator in inflammatory-related diseases. Regulation of NF‐κB signaling and interleukins secretion is the most prominent functional mechanism of curcumin in modulating inflammasomes. More importantly, curcumin can exert its anti-inflammatory role mainly through the down-regulation of NLRP3 inflammasomes. Given the fundamental role of inflammation in diseases, such as arthritis, cancer and cardiorenal disease, curcumin may have a pivotal therapeutic role through its ability to produce beneficial anti-inflammatory effects.
Objective
Osteoarthritis is a degenerative disease of the joints. Non-steroidal anti-inflammatory drugs (NSAIDs) are being used for the treatment of the osteoarthritis. However, their use is limited due to complications such as gastrointestinal bleeding. Therefore, it is necessary to find alternative treatments for osteoarthritis. Recently, nanomicelle curcumin has been developed to increase the oral bioavailability of curcumin. The aim of this study was to evaluate the effect of nanocurcumin on the alleviation of the symptoms of knee osteoarthritis patients.
Methods
In this randomized, double-blind controlled trial, the intervention group was administered 40 mg of nanocurcumin capsule every 12 hours over a period of six weeks, and the control group received the placebo (similar components of nanomicelle curcumin capsules yet without curcumin). In the final analysis, 36 patients in the nanocurcumin group and 35 patients in the placebo group were enrolled. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was filled for patients in their first visit and at the end of six weeks. Differences were statistically significant at P-value < 0.05.
Results
There were no significant differences between the two groups regarding gender, age, Kellgren score, and the duration of the disease before the intervention. A significant decrease was observed in the overall score, along with the scores of pain, stiffness and physical activity subscales of the WOMAC questionnaire in patients of the nanocurcumin group compared with the placebo group.
Conclusion
Nanocurcumin significantly improves the symptoms of osteoarthritis patients.
Curcumin is the major constituent of turmeric (Curcuma longa). Turmeric has been widely used as a spice in foods and for therapeutic applications such as anti-inflammatory, antihyperlipidemic, and antimicrobial activities. Turmeric and curcumin are nonmutagenic and nongenotoxic. Oral use of turmeric and curcumin did not have reproductive toxicity in animals at certain doses. Studies on human did not show toxic effects, and curcumin was safe at the dose of 6 g/day orally for 4–7 weeks. However, some adverse effects such as gastrointestinal upsets may occur. Moreover, oral bioavailable formulations of curcumin were safe for human at the dose of 500 mg two times in a day for 30 days, but there are still few trials and more studies are needed specially on nanoformulations and it should be discussed in a separate article. In addition, curcumin is known as a generally recognized as safe substance. This review discusses the safety and toxicity of turmeric and curcumin in medicine. Turmeric and curcumin are nontoxic for human especially in oral administration. Turmeric and curcumin are also safe in animals. They are nonmutagenic and are safe in pregnancy in animals but more studies in human are needed.
There is great interest in developing colloidal delivery systems to enhance the water-solubility and oral bioavailability of curcumin, which is a hydrophobic nutraceutical claimed to have several health benefits. In this study, a natural emulsifier was used to form sophorolipid-coated curcumin nanoparticles. The curcumin was loaded into sophorolipid micelles using a pH-driven mechanism based on the decrease in curcumin solubility at lower pH values. The sophorolipid-coated curcumin nanoparticles formed using this mechanism were relatively small (61 nm) and negatively charged (-41 mV). The nanoparticles also had a relatively high encapsulation efficiency (82%) and loading capacity (14%) for curcumin, which was present in an amorphous state. Both in vitro and in vivo studies showed that the curcumin nanoparticles had an appreciably higher bioavailability than free curcumin crystals (2.7-3.6-fold), which was mainly attributed to their higher bioaccessibility. These results may facilitate the development of natural colloidal systems that can enhance the oral bioavailability and bioactivity of curcumin in food, dietary supplement, and pharmaceutical products.
Non-alcoholic fatty liver disease (NAFLD) is a major cause of liver diseases, and is closely related to metabolic syndrome and its related conditions, diabetes mellitus and dyslipidemia. On the other hand, NAFLD as a multisystem disease increases the risk of several chronic diseases include type 2 diabetes mellitus, cardiovascular disease (CVD), and chronic kidney disease. The main objective was to review the efficacy of bioactive natural compounds assessed by clinical trials. Search literature using four databases (PubMed, EBSCO, Web of Science, and Ovid Medline) to review publications that focused on the impact of bioactive natural compounds in NAFLD treatment. Due to the lack of effective pharmacological treatments available for NAFLD, lifestyle modifications such as following a healthy diet, vigorous physical activity, and weight reduction remain the first line of treatment for NAFLD. However, due to the poor adherence to this type of treatment, especially for long-term weight loss diets some of which may have harmful effects on the liver, finding novel therapeutic agents for NAFLD treatment and/or preventing NAFLD progression has garnered significant interest. Although the therapeutic agents of NAFLD treatment have been reviewed previously, to date, no summary has been conducted of clinical trials examining the effects of herbal compounds on NAFLD-related biomarkers. This review highlights the beneficial role of herbal bioactives and medicinal plants in NAFLD treatment, particularly as complementary to a healthy lifestyle. All natural products described in this review seem to have some benefits to improve oxidative stress, cellular inflammation and insulin-resistance, which always remain as the "primum movens" of NAFLD pathogenesis.
The impact of molecular environment on the chemical stability of curcumin was determined. Equal amounts of curcumin were incorporated into different kinds of delivery system: aqueous dimethyl sulfoxide (DMSO) solutions; oil-in-water emulsions; or filled hydrogel beads. Two types of filled hydrogel beads were fabricated by injecting solutions containing curcumin-loaded lipid droplets and gelling polysaccharides (alginate or chitosan) into ionic gelling solutions (calcium or tripolyphosphate) using an extrusion device. The delivery systems were then incubated under acidic (pH 3) and neutral (pH 7) conditions at 55 °C for 14 days. The initial rate of curcumin degradation, determined by measuring the color change (b* value) over time, depended on storage pH and delivery system type. At pH 7, the curcumin degradation rate increased in the following order: chitosan beads < emulsion < aqueous solution < alginate beads, but at pH 3 it increased in a different order: emulsion < aqueous solutions < chitosan beads < alginate beads. Overall, our results showed that curcumin was more stable under acidic than neutral conditions. Interestingly, encapsulation of curcumin in alginate beads promoted its degradation at both acidic and neutral pH, but encapsulation in chitosan beads enhanced its stability at pH 7 by reduced it at pH 3. These effects may be related to the different charge status of the polysaccharides used to fabricate the hydrogel beads: alginate is anionic, whereas chitosan is cationic. Overall, our results provide valuable information for the design and development of emulsion-based delivery systems to encapsulate and protect curcumin for functional food applications.
Aim:
To critically appraise and evaluate the evidence for effectiveness of curcuminoids in the treatment of osteoarthritis (OA) in adults.
Methods:
We conducted electronic searches in Medline, Embase, AMED, Cinahl and the Cochrane library. We included randomized controlled trials (RCTs) that investigated the effectiveness of orally-administered curcuminoids in OA in adults, and assessed risk of bias using the Cochrane risk of bias criteria. We used a random-effect model for meta-analysis.
Results:
We included seven studies with a total of 797 participants with primarily knee OA. All studies were conducted in Asia. The overall risk of bias was moderate. Compared with placebo, curcuminoids significantly reduced knee pain (visual analogue scale): (standardized mean difference: -3.45; 95% CI: -5.52 to -1.38; I(2) = 95% P = 0.001), and improved quality of life (Lequesne pain-function index): (mean difference: -2.69; 95% CI: -3.48 to -1.90; I(2) = 0% P < 0.00001). There were significantly fewer effects on pain relief, knee stiffness and physical function with curcuminoids compared with ibuprofen. Significant improvements in Western Ontario and McMaster Universities Arthritis Index total scores, with significant reductions in the use of rescue medication were also observed with curcuminoids. No serious adverse events were reported.
Conclusions:
Curcuminoids may have some beneficial effects on knee pain and quality of life in patients with knee OA. However, they are less effective at relieving pain compared with ibuprofen. Curcuminoids appear safe on the short-term, and may reduce the need for rescue medication. Published RCTs vary in reporting quality, are characterized by small sample sizes, and have all been conducted in Asia. Further clinical trials are therefore warranted.
Curcumin is a dietary polyphenol from turmeric with numerous pharmacological activities. Novel animal and human studies indicate that curcumin can affect different immune cells, such as various T lymphocyte subsets, macrophages, dendritic cells, B lymphocytes and natural killer cells, which results in decreasing severity of various diseases with immunological etiology. The present review provides a comprehensive overview of the effects of curcumin on different immune cells and immune system-related diseases. This article is protected by copyright. All rights reserved.
Curcumin, the bioactive polyphenolic ingredient of turmeric, has been extensively studied for its effects on human papilloma virus (HPV) infection as well as primary and malignant squamous cervical cancers. HPV infections, especially those related to HPV 16 and 18 types, have been established as the leading cause of cervical cancer; however, there are also additional contributory factors involved in the etiopathogenesis of cervical cancers. Curcumin has emerged as having promising chemopreventive and anticancer effects against both HPV-related and nonrelated cervical cancers. In this review, we first discuss the biological relevance of curcumin and both its pharmacological effects and pharmaceutical considerations from a chemical point of view. Next, the signaling pathways that are modulated by curcumin and are relevant to the elimination of HPV infection and treatment of cervical cancer are discussed. We also present counter arguments regarding the effects of curcumin on signaling pathways and molecular markers dysregulated by benzo(a)pyrene (Bap), a carcinogen found in pathological cervical lesions of women who smoke frequently, and estradiol, as two important risk factors involved in persistent HPV-infection and cervical cancer. Finally, various strategies to enhance the pharmacological activity and pharmacokinetic characteristics of curcumin are discussed with examples of studies in experimental models of cervical cancer.
Curcumin, a hydrophobic polyphenol, is the principal constituent extracted from dried rhizomes of Curcuma longa L. (turmeric). Curcumin is known as a strong anti-oxidant and anti-inflammatory agent that has different pharmacological effects. In addition, several studies have demonstrated that curcumin is safe even at dosages as high as 8 g per day; however, instability at physiological pH, low solubility in water and rapid metabolism results in a low oral bioavailability of curcumin. The phytosomal formulation of curcumin (a complex of curcumin with phosphatidylcholine) has been shown to improve curcumin bioavailability. Existence of phospholipids in phytosomes leads to specific physicochemical properties such as amphiphilic nature that allows dispersion in both hydrophilic and lipophilic media. The efficacy and safety of curcumin phytosomes has been shown against several human diseases including cancer, osteoarthritis, diabetic microangiopathy and retinopathy, and inflammatory diseases. This review focuses on the pharmacokinetics as well as pharmacological and clinical effects of phytosomal curcumin.
Background:
Curcumin, a polyphenol from turmeric, is a dietary phytochemical with a diversity of health benefits including strong anti-tumor effects. Curcumin undergoes a rapid metabolism resulting in a low oral bioavailability. 3, 4-difluorobenzylidene curcumin or (CDF) is a novel fluorinated curcumin analogue which has been shown to be about 3 times more bioavailable than curcumin. This review aimed to summarize the findings of studies related to pharmacokinetic and pharmacological characteristics of CDF.
Methods:
A systematic literature search was prformed in Scopus and Medline to identify all published articles dealing with CDF.
Results:
Biodistribution assays have revealed that curcumin is mostly distributed to the heart and lung tissues while CDF is preferentially accumulated in pancreas where its tissue concentrations reach two folds higher than that of curcumin. Moreover, CDF has been reported to possess stronger cytotoxic effects compared with CMN in both monolayer and spheroid cultures of different tumor cell lines including chemo-resistant ones. CDF can promote tumor suppression through multiple mechanisms including inhibition of self-renewal capacity of cancer stem/stem-like cells, clonogenicity invasiveness and angiogenesis of tumor cells, while increasing the sensitivity of cells to chemotherapy. These effects are the results of the modulatory action of CDF on diverse targets, such as miRNAs (miR-21, miR-101, miR-210, miR34a and miR34c), PTEN, CD44, EGFR, EpCAM, EZH2, HIF-1α, and VEGF.
Conclusions:
This review presents an overview of the findings on metabolism and pharmacological activities of CDF, and also highlights potential opportunities to use this novel curcumin analogue in the treatment of cancer.
Ageing-associated changes that affect articular tissues promote the development of osteoarthritis (OA). Although ageing and OA are closely linked, they are independent processes. Several potential mechanisms by which ageing contributes to OA have been elucidated. This Review focuses on the contributions of the following factors: age-related inflammation (also referred to as 'inflammaging'); cellular senescence (including the senescence-associated secretory phenotype (SASP)); mitochondrial dysfunction and oxidative stress; dysfunction in energy metabolism due to reduced activity of 5'-AMP-activated protein kinase (AMPK), which is associated with reduced autophagy; and alterations in cell signalling due to age-related changes in the extracellular matrix. These various processes contribute to the development of OA by promoting a proinflammatory, catabolic state accompanied by increased susceptibility to cell death that together lead to increased joint tissue destruction and defective repair of damaged matrix. The majority of studies to date have focused on articular cartilage, and it will be important to determine whether similar mechanisms occur in other joint tissues. Improved understanding of ageing-related mechanisms that promote OA could lead to the discovery of new targets for therapies that aim to slow or stop the progression of this chronic and disabling condition.
Osteoarthritis is the most common joint disorder with increasing prevalence due to aging of the population. Its multi-factorial etiology includes oxidative stress and the overproduction of reactive oxygen species, which regulate intracellular signalling processes, chondrocytes senescence and apoptosis, extracellular matrix synthesis and degradation along with synovial inflammation and dysfunction of the subchondral bone. As disease-modifying drugs for osteoarthritis are rare, targeting the complex oxidative stress signalling pathways would offer a valuable perspective for exploration of potential therapeutic strategies in the treatment of this devastating disease.
ABSTRACT Oxidative stress is implicated in the pathogenesis of osteoarthritis. Curcuminoids are natural polyphenols with strong antioxidant capacity and may thus be helpful in the treatment of osteoarthritis. The present randomized double-blind placebo-controlled trial investigated the efficacy of curcuminoids in reducing systemic oxidative burden in patients suffering from knee osteoarthritis. Forty patients with mild-to-moderate primary knee osteoarthritis were given curcuminoid capsules (1500 mg/day in 3 divided doses; n = 19) or matched placebo capsules (n = 21) for a period of 6 weeks. Curcuminoids were co-administered with piperine (15 mg/day) in order to improve the bioavailability. Serum activities of superoxide dismutase (SOD) and concentrations of reduced glutathione (GSH) and malonedialdehyde (MDA) were determined spectrophotometrically at baseline and at the end of the treatment period in both groups. Serum activities of SOD as well as GSH and MDA concentrations were comparable between the study groups at baseline (p > 0.05). There was a significant elevation in serum SOD activities (mean change: 2.94 ± 3.73 vs. -0.38 ± 1.33; p < 0.001), a borderline significant elevation in GSH concentrations (mean change: 1.39 ± 2.78 vs. -0.02 ± 1.62; p = 0.064) and a significant reduction in MDA concentrations (mean change: -5.26 ± 4.46 vs. -2.49 ± 3.81; p = 0.044) in the curcuminoids compared with the placebo group. Changes in serum activities of SOD and concentrations of GSH and MDA during the course of trial were significantly correlated. Short-term supplementation with curcuminoids attenuates systemic oxidative stress in patients with osteoarthritis. These antioxidant effects may account for the reported therapeutic effects of curcuminoids in relieving osteoarthritis symptoms.
Objective: Osteoarthritis (OA) is a degenerative joint disease associated with inflammation. The present study aimed to determine changes in serum levels of inflammatory biomarkers in OA patients whose clinical symptoms were improved as a result of supplementation with curcuminoids.
Methods: This study was a randomized double-blind placebo-control parallel-group clinical trial in which 40 subjects with mild-to-moderate degree knee OA were randomly allocated to receive either pure curcuminoids (1 500 mg/day in 3 divided doses; n=19) or matched placebo (n=21) for 6 weeks. In order to enhance the bioavailability of curcuminoids, piperine (15 mg/day) was added to the treatment regimen. Serum levels of interleukins 4 (IL-4) and 6 (IL-6), tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β) and high-sensitivity C-reactive protein (hs-CRP), together with erythrocyte sedimentation rate (ESR) were determined at baseline as well as at the end of trial.
Results: Serum concentrations of IL-4 (p=0.001), IL-6 (p=0.006) and hs-CRP (p=0.004) were significantly reduced in the curcuminoid group whilst serum levels of TNF-α and TGF-β and mean ESR remained unaltered by the end of trial (p>0.05). In the placebo group, serum concentrations of IL-4 (p=0.001), IL-6 (p=0.003), TNF-α (p=0.003) and TGF-β (p=0.005) were significantly reduced but mean hs-CRP and ESR values remained statistically unchanged (p>0.05). Comparison of the magnitude of changes in the evaluated inflammatory biomarkers did not indicate any significant difference between the study groups (p>0.05).
Conclusion: Significant improvement in clinical symptoms of OA in curcuminoid-treated subjects cannot be attributed to the systemic anti-inflammatory effects of these phytochemicals.
Treatment of osteoarthritis (OA) is challenging owing to the inefficacy and long-term adverse events of currently available medications including non-steroidal anti-inflammatory drugs. Curcuminoids are polyphenolic phytochemicals with established anti-inflammatory properties and protective effects on chondrocytes. The aim of this study is to investigate the clinical efficacy of curcuminoids in patients suffering from knee OA. A pilot randomized double-blind placebo-control parallel-group clinical trial was conducted among patients with mild-to-moderate knee OA. Patients were assigned to curcuminoids (1500 mg/day in 3 divided doses; n = 19) or matched placebo (n = 21) for 6 weeks. Efficacy measures were changes in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), visual analogue scale (VAS) and Lequesne's pain functional index (LPFI) scores during the study. There was no significant difference in age, gender, body mass index, and VAS, WOMAC and LPFI scores between the study groups at baseline (p > 0.05). Treatment with curcuminoids was associated with significantly greater reductions in WOMAC (p = 0.001), VAS (p < 0.001) and LPFI (p = 0.013) scores compared with placebo. With respect to WOMAC subscales, there were significant improvements in the pain and physical function scores (p < 0.001) but not stiffness score (p > 0.05). There was no considerable adverse effect in both groups. To conclude, curcuminoids represent an effective and safe alternative treatment for OA. Copyright © 2014 John Wiley & Sons, Ltd.
To determine the relative incidence, prevalence, costs and impact on disability of 8 common conditions treated by rehabilitation professionals.
Structured review of the literature SETTING: United States PARTICIPANTS: N/A INTERVENTIONS: N/A MAIN OUTCOME MEASURES: disease associated incidence, prevalence, direct and indirect costs and impact on activity and work limitations.
Back pain and arthritis (osteoarthritis and rheumatoid arthritis) are the most common and costly conditions that we examined, affecting over 100 million individuals and costing over $200 billion per year. Traumatic brain injury, while less common than arthritis and back pain, carries enormous per capita direct and indirect costs, mostly due to the young age of those involved and the severe disability that it may cause. Finally, stroke, which is often listed as the most common cause of disability, is likely second to both arthritis and back pain in its impact on functional limitations.
Of the common rehabilitation diagnoses we studied, musculoskeletal conditions such and back pain and arthritis likely have the most impact on the health care system due to their high prevalence and impact on disability.
Osteoarthritis (OA) is the most widespread chronic degenerative joint disorder, characterized by progressive destruction of articular cartilage, subchondral bone alterations, formation of osteophytes and synovitis. MicroRNAs (miRNAs) are a class of endogenous and non-coding single-strand RNAs with a length of about 22 nucleotides, and many of them are evolutionarily conserved. miRNAs have been implicated in the process of development and pathogenesis of diseases, and tissue-specific miRNA functional studies in mice have revealed both pathogenic and protective functions. miRNA-140 (miR-140) was shown to be specifically expressed in cartilage tissues in developing zebrafish and mouse embryos during the development of both long and flat bones. Recently, miR-140 has been reported in many studies to play significant roles in OA pathogenesis. Although the previous results were not always consistent, the molecular mechanisms of the regulation and dual function of miR-140 in cartilage homeostasis and development have been established in previous studies. Further elucidation of the molecular basis of miR-140 will uncover synergistic inhibitory effects of miR-140 and other factors on OA pathogenesis, and provide a novel means of treating OA disease.