Curcumin Extract
CLINICAL STUDIES ON THE FOLLOWING INGREDIENTS:
Mitochondrial Dysfunction Associated with mtDNA in Metabolic Syndrome and Obesity
Abstract
Metabolic syndrome (MetS) is a precursor to the major health diseases associated with high mortality in industrialized countries: cardiovascular disease and diabetes. An important component of the pathogenesis of the metabolic syndrome is mitochondrial dysfunction, which is associated with tissue hypoxia, disruption of mitochondrial integrity, increased production of reactive oxygen species, and a decrease in ATP, leading to a chronic inflammatory state that affects tissues and organ systems. The mitochondrial AAA + protease Lon (Lonp1) has a broad spectrum of activities. In addition to its classical function (degradation of misfolded or damaged proteins), enzymatic activity (proteolysis, chaperone activity, mitochondrial DNA (mtDNA)binding) has been demonstrated. At the same time, the spectrum of Lonp1 activity extends to the regulation of cellular processes inside mitochondria, as well as outside mitochondria (nuclear localization). This mitochondrial protease with enzymatic activity may be a promising molecular target for the development of targeted therapy for MetS and its components. The aim of this review is to elucidate the role of mtDNA in the pathogenesis of metabolic syndrome and its components as a key component of mitochondrial dysfunction and to describe the promising and little-studied AAA + LonP1 protease as a potential target in metabolic disorders.
Source: Todosenko N, Khaziakhmatova O, Malashchenko V, Yurova K, Bograya M, Beletskaya M, Vulf M, Gazatova N, Litvinova L. “Mitochondrial Dysfunction Associated with mtDNA in Metabolic Syndrome and Obesity.” International Journal of Molecular Sciences. 2023; 24(15):12012.
Curcumin induces mitochondrial biogenesis by increasing cyclic AMP levels via phosphodiesterase 4A inhibition in skeletal muscle
Abstract
Background: Previous research has suggested that curcumin potentially induces mitochondrial biogenesis in skeletal muscle via increasing cyclic AMP (cAMP) levels. However, the regulatory mechanisms for this phenomenon remain unknown. The purpose of the present study was to clarify the mechanism by which curcumin activates cAMP-related signalling pathways that upregulate mitochondrial biogenesis and respiration in skeletal muscle.
Methods: The effect of curcumin treatment (i.p., 100 mg/kg-BW/d for 28 d) on mitochondrial biogenesis was determined in rats. The effects of curcumin and exercise (swimming for 2 h/d for 3 d) on the cAMP signalling pathway were determined in the absence and presence of phosphodiesterase (PDE) or protein kinase A (PKA) inhibitors. Mitochondrial respiration, citrate synthase (CS) activity, cAMP content and protein expression of cAMP/PKA signalling molecules were analysed.
Results: Curcumin administration increased cytochrome c oxidase subunit (COX-IV) protein expression, and CS and complex I activity, consistent with the induction of mitochondrial biogenesis by curcumin. Mitochondrial respiration was not altered by curcumin treatment. Curcumin and PDE inhibition tended to increase cAMP levels with or without exercise. In addition, exercise increased the phosphorylation of phosphodiesterase 4A (PDE4A), whereas curcumin treatment strongly inhibited PDE4A phosphorylation regardless of exercise. Furthermore, curcumin promoted AMP-activated protein kinase (AMPK) phosphorylation and PPAR gamma coactivator (PGC-1α) deacetylation. Inhibition of PKA abolished the phosphorylation of AMPK.
Conclusion: The present results suggest that curcumin increases cAMP levels via inhibition of PDE4A phosphorylation, which induces mitochondrial biogenesis through a cAMP/PKA/AMPK signalling pathway. Our data also suggest the possibility that curcumin utilises a regulatory mechanism for mitochondrial biogenesis that is distinct from the exercise-induced mechanism in skeletal muscle.
Source: Hamidie RDR, Shibaguchi T, Yamada T, Koma R, Ishizawa R, Saito Y, Hosoi T, Masuda K. “Curcumin induces mitochondrial biogenesis by increasing cyclic AMP levels via phosphodiesterase 4A inhibition in skeletal muscle.” Br J Nutr. (2021);126(11):1642-1650.
The effect of curcumin supplementation on weight loss and anthropometric indices: an umbrella review and updated meta-analyses of randomized controlled trials
Abstract
Background: Curcumin supplementation may promote weight loss and ameliorate obesity-related complications through its antioxidative and anti-inflammatory properties.
Objective: An umbrella review and updated meta-analysis of randomized controlled trials (RCTs) was conducted to evaluate the effect of curcumin supplementation on anthropometric indices.
Methods: Systematic reviews and meta-analyses (SRMAs) of RCTs were identified from electronic databases (Medline, Scopus, Cochrane, and Google Scholar) up to 31 March, 2022, without language restriction. SRMAs were included if they assessed curcumin supplementation on any of the following: BMI, body weight (BW), or waist circumference (WC). Subgroup analyses were performed, stratifying by patient types, severity of obesity, and curcumin formula. The study protocol was a priori registered.
Results: From an umbrella review, 14 SRMAs with 39 individual RCTs were included with a high degree of overlap. In addition, searching was updated from the last search of included SRMAs in April 2021 up to 31 March, 2022, and we found 11 additional RCTs, bringing the total up to 50 RCTs included in the updated meta-analyses. Of these, 21 RCTs were deemed of high risk of bias. Curcumin supplementation significantly reduced BMI, BW, and WC with mean differences (MDs) of -0.24 kg/m2 (95% CI: -0.32, -0.16 kg/m2), -0.59 kg (95% CI: -0.81, -0.36 kg), and -1.32 cm (95% CI: -1.95, -0.69 cm), respectively. The bioavailability-enhanced form reduced BMI, BWs, and WC more, with MDs of -0.26 kg/m2 (95% CI: -0.38, -0.13 kg/m2), -0.80 kg (95% CI: -1.38, -0.23 kg) and -1.41 cm (95% CI: -2.24, -0.58 cm), respectively. Significant effects were also seen in subgroups of patients, especially in adults with obesity and diabetes.
Conclusions: Curcumin supplementation significantly reduces anthropometric indices, and bioavailability-enhanced formulas are preferred. Augmenting curcumin supplement with lifestyle modification should be an option for weight reduction. This trial was registered at PROSPERO as CRD42022321112 (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022321112).
Source: Unhapipatpong C, Polruang N, Shantavasinkul PC, Julanon N, Numthavaj P, Thakkinstian A. “The effect of curcumin supplementation on weight loss and anthropometric indices: an umbrella review and updated meta-analyses of randomized controlled trials.” Am J Clin Nutr. 2023 May;117(5):1005-1016.
Bisphenol-A Mediated Inhibition of Hippocampal Neurogenesis Attenuated by Curcumin via Canonical Wnt Pathway
Abstract
Bisphenol A (BPA) is an environmental xenoestrogenic endocrine disruptor, utilized for production of consumer products, and exerts adverse effects on the developing nervous system. Recently, we found that BPA impairs the finely tuned dynamic processes of neurogenesis (generation of new neurons) in the hippocampus of the developing rat brain. Curcumin is a natural polyphenolic compound, which provides neuroprotection against various environmental neurotoxicants and in the cellular and animal models of neurodegenerative disorders. Here, we have assessed the neuroprotective efficacy of curcumin against BPA-mediated reduced neurogenesis and the underlying cellular and molecular mechanism(s). Both in vitro and in vivo studies showed that curcumin protects against BPA-induced hippocampal neurotoxicity. Curcumin protects against BPA-mediated reduced neural stem cells (NSC) proliferation and neuronal differentiation and enhanced neurodegeneration. Curcumin also enhances the expression/levels of neurogenic and the Wnt pathway genes/proteins, which were reduced due to BPA exposure in the hippocampus. Curcumin-mediated neuroprotection against BPA-induced neurotoxicity involved activation of the Wnt/β-catenin signaling pathway, which was confirmed by the use of Wnt specific activators (LiCl and GSK-3β siRNA) and inhibitor (Dkk-1). BPA-mediated increased β-catenin phosphorylation, decreased GSK-3β levels, and β-catenin nuclear translocation were significantly reversed by curcumin, leading to enhanced neurogenesis. Curcumin-induced protective effects on neurogenesis were blocked by Dkk-1 in NSC culture treated with BPA. Curcumin-mediated enhanced neurogenesis was correlated well with improved learning and memory in BPA-treated rats. Overall, our results conclude that curcumin provides neuroprotection against BPA-mediated impaired neurogenesis via activation of the Wnt/β-catenin signaling pathway.
Source: Tiwari SK, Agarwal S, Tripathi A, Chaturvedi RK. “Bisphenol-A Mediated Inhibition of Hippocampal Neurogenesis Attenuated by Curcumin via Canonical Wnt Pathway.” Mol Neurobiol. (2016);53(5):3010-3029.
A Review of the Role of Curcumin in Metal Induced Toxicity
Abstract
Metal toxicity poses a potential global threat to the environment and living beings. Their numerous agricultural, medical, industrial, domestic, and technological applications result in widespread distribution in the environment which raises concern on the potential effects of metals in terms of health hazards and environmental pollution. Chelation therapy has been the preferred medical treatment for metal poisoning. The chelating agent bounds metal ions to form complex cyclic structures known as ‘chelates’ to intensify their excretion from the body. The main disadvantage of synthetic chelators is that the chelation process removes vital nutrients along with toxic metals. Natural compounds are widely available, economical, and have minimal adverse effects compared to classical chelators. Herbal preparations can bind to the metal, reduce its absorption in the intestines, and facilitate excretion from the body. Curcumin, a bioactive substance in turmeric, is widely used as a dietary supplement. Most studies have shown that curcumin protects against metal-induced lipid peroxidation and mitigates adverse effects on the antioxidant system. This review article provides an analysis to show that curcumin imparts promising metal toxicity-ameliorative effects that are related to its intrinsic antioxidant activity.
Source: Smirnova E, Moniruzzaman M, Chin S, Sureshbabu A, Karthikeyan A, Do K, Min T. “A Review of the Role of Curcumin in Metal Induced Toxicity.” Antioxidants (Basel). (2023);12(2):243.
Protective effect of curcumin against heavy metals-induced liver damage
Abstract
Occupational or environmental exposures to heavy metals produce several adverse health effects. The common mechanism determining their toxicity and carcinogenicity is the generation of oxidative stress that leads to hepatic damage. In addition, oxidative stress induced by metal exposure leads to the activation of the nuclear factor (erythroid-derived 2)-like 2/Kelch-like ECH-associated protein 1/antioxidant response elements (Nrf2/Keap1/ARE) pathway. Since antioxidant and chelating agents are generally used for the treatment of heavy metals poisoning, this review is focused on the protective role of curcumin against liver injury induced by heavy metals. Curcumin has shown, in clinical and preclinical studies, numerous biological activities including therapeutic efficacy against various human diseases and anti-hepatotoxic effects against environmental or occupational toxins. Curcumin reduces the hepatotoxicity induced by arsenic, cadmium, chromium, copper, lead and mercury, prevents histological injury, lipid peroxidation and glutathione (GSH) depletion, maintains the liver antioxidant enzyme status and protects against mitochondrial dysfunction. The preventive effect of curcumin on the noxious effects induced by heavy metals has been attributed to its scavenging and chelating properties, and/or to the ability to induce the Nrf2/Keap1/ARE pathway. However, additional research is needed in order to propose curcumin as a potential protective agent against liver damage induced by heavy metals.
Source: García-Niño WR, Pedraza-Chaverrí J. “Protective effect of curcumin against heavy metals-induced liver damage.” Food Chem Toxicol. 2014 Jul;69:182-201.
Protective and Detoxifying Effects Conferred by Dietary Selenium and Curcumin against AFB1-Mediated Toxicity in Livestock: A Review
Abstract
Aflatoxin B1 (AFB1), among other aflatoxins of the aflatoxin family, is the most carcinogenic and hazardous mycotoxin to animals and human beings with very high potency leading to aflatoxicosis. Selenium is an essential trace mineral possessing powerful antioxidant functions. Selenium is widely reported as an effective antioxidant against aflatoxicosis. By preventing oxidative liver damage, suppressing pro-apoptotic proteins and improving immune status in AFB1 affected animals; selenium confers specific protection against AFB1 toxicity. Meticulous supplementation of animal feed by elemental selenium in the organic and inorganic forms has proven to be effective to ameliorate AFB1 toxicity. Curcumin is another dietary agent of importance in tackling aflatoxicosis. Curcumin is one of the major active ingredients in the tubers of a spice Curcuma longa L., a widely reported antioxidant, anticarcinogenic agent with reported protective potential against aflatoxin-mediated liver damage. Curcumin restricts the aflatoxigenic potential of Aspergillus flavus. Curcumin inhibits cytochrome P450 isoenzymes, particularly CYP2A6 isoform; thereby reducing the formation of AFB1-8, 9-epoxide and other toxic metabolites causing aflatoxicosis. In this review, we have briefly reviewed important aflatoxicosis symptoms among animals. With the main focus on curcumin and selenium, we have reviewed their underlying protective mechanisms in different animals along with their extraction and production methods for feed applications.
Source: Limaye A, Yu R-C, Chou C-C, Liu J-R, Cheng K-C. “Protective and Detoxifying Effects Conferred by Dietary Selenium and Curcumin against AFB1-Mediated Toxicity in Livestock: A Review.” Toxins. (2018); 10(1):25.
Curcumin restores mitochondrial functions and decreases lipid peroxidation in liver and kidneys of diabetic db/db mice
Abstract
Background: Nitrosative and oxidative stress play a key role in obesity and diabetes-related mitochondrial dysfunction. The objective was to investigate the effect of curcumin treatment on state 3 and 4 oxygen consumption, nitric oxide (NO) synthesis, ATPase activity and lipid oxidation in mitochondria isolated from liver and kidneys of diabetic db/db mice.
Results: Hyperglycaemia increased oxygen consumption and decreased NO synthesis in liver mitochondria isolated from diabetic mice relative to the control mice. In kidney mitochondria, hyperglycaemia increased state 3 oxygen consumption and thiobarbituric acid-reactive substances (TBARS) levels in diabetic mice relative to control mice. Interestingly, treating db/db mice with curcumin improved or restored these parameters to normal levels; also curcumin increased liver mitochondrial ATPase activity in db/db mice relative to untreated db/db mice.
Conclusions: These findings suggest that hyperglycaemia modifies oxygen consumption rate, NO synthesis and increases TBARS levels in mitochondria from the liver and kidneys of diabetic mice, whereas curcumin may have a protective role against these alterations.
Source: Soto-Urquieta MG, López-Briones S, Pérez-Vázquez V, Saavedra-Molina A, González-Hernández GA, Ramírez-Emiliano J. “Curcumin restores mitochondrial functions and decreases lipid peroxidation in liver and kidneys of diabetic db/db mice.” Biol Res. (2014);47(1):74.
Tetrahydrocurcumin epigenetically mitigates mitochondrial dysfunction in brain vasculature during ischemic stroke
Abstract
The objectives of this study are to identify the mechanism of mitochondrial dysfunction during cerebral ischemic/reperfusion (I/R) injury and the therapeutic potential of tetrahydrocurcumin (THC) to mitigate mitochondrial dysfunction in experimental stroke model. In our study, 8-10 weeks old male C57BL/6 wild-type mice were subjected to middle cerebral artery occlusion (MCAO) for 40 min, followed by reperfusion for 72 h. THC (25mg/kg-BW/day) was injected intraperitoneally once daily for 3 days after 4 h of ischemia. The experimental groups were: (i) sham, (ii) I/R and (iii) I/R + THC. We noticed that THC treatment in ischemic mice significantly improved the functional capacity and motor co-ordination along with reduced neuroscore, infarct volume, brain edema and microvascular leakage in brain parenchyma. The study revealed that level of total homocysteine (tHcy), homocysteine metabolizing enzymes, mitochondrial oxidative stress were significantly altered in I/R mice compared to sham. We also observed alteration in mitochondrial transition pore, ATP production and O2 consumption in the ischemic brain as compared to sham. Further, elevated matrix metalloproteinases-9 (MMP-9) activity and reduced tight junction protein expressions intensified the brain vascular impairment in I/R mice compared to sham. Interestingly, we found that levels of mitophagy markers, fusion and fission proteins were significantly altered. However THC treatment in I/R mice almost normalized the above functional and molecular changes. Mechanistic study demonstrated that DNA Methyltransferase 1 (DNMT1) expression was higher and was associated with reduced mitochondrial tissue inhibitor of metalloproteinases 2 (TIMP-2) expression through hyper-methylation of CpG island of TIMP-2 promoter in I/R mice compared to sham. However, administration of epigenetic inhibitor, 5-Azacytidine (5-Aza) abrogated I/R induced hyper-methylation of TIMP-2 promoter and maintaining the extracellular matrix (ECM) integrity. In conclusion, this study suggests that THC epigenetically ameliorates mitochondrial dysfunction in brain vasculature during Ischemic Stroke.
Source: Mondal NK, Behera J, Kelly KE, George AK, Tyagi PK, Tyagi N. “Tetrahydrocurcumin epigenetically mitigates mitochondrial dysfunction in brain vasculature during ischemic stroke.” Neurochem Int. (2019);122:120-138.
The enhanced bioavailability of free curcumin and bioactive-metabolite tetrahydrocurcumin from a dispersible, oleoresin-based turmeric formulation
Abstract
Background: Curcuminoids have been widely studied for human health and disease applications, yet bioavailability remains a hurdle to actualizing all the benefits ascribed to them. The lack of standardization in analysis method, confusion about what constitutes an ideal analyte, and conflicting thoughts around dosing strategies have made it difficult to draw parity between bioavailability and bioactivity and establish a baseline for formulation comparisons.
Methods: This randomized double-blinded, 2-way cross over, single oral dose, comparative bioavailability study differentially evaluates curcumin at the time of its absorption and along various biotransformation pathways, to include free curcumin, the readily usable form of curcumin; individual and composite totals of curcumin and its analogues as exogenously cleaved conjugates, for example, total curcumin, total demethoxycurcumin (DMC), total bisdemethoxycurcumin (BDMC), and total curcuminoids respectively; and the bioactive metabolite of curcumin, total tetrahydrocurcumin (THC). As a primary study objective, the relative bioavailability of CURCUGEN, a novel dispersible, 50% curcuminoids-concentrated turmeric extract was compared to the standard curcumin reference product, curcuminoids 95% standardized extract (C-95), using the maximum concentration (Cmax), and area under the curve (AUC0-t) of free curcumin, total curcumin, total DMC, total BDMC and the curcumin active metabolite, as total THC.
Results: The evaluation of free curcumin demonstrated that the Cmax and AUC0-t of the CURCUGEN was 16.1 times and 39 times higher than the Cmax and AUC0-t of C-95. Furthermore, total curcumin, total DMC, total BDMC, and total curcuminoids resulted in AUC0-t of the CURCUGEN at 49.5-, 43.5-, 46.8-, and 52.5-fold higher than C-95, respectively. The relative bioavailability of CURCUGEN for total THC was found to be 31 times higher when compared to C-95.
Conclusion: As the first human pharmacokinetics study to apply best-practice recommendations and pharmaceutically-aligned guidance in the comprehensive evaluation of a novel curcuminoids formulation, we have established the novelty of said formulation while better standardizing for the common variances and discrepancies between curcuminoids and their derivatives in the literature and commercial marketing, alike.
Source: Panda SK, Nirvanashetty S, Missamma M, Jackson-Michel S. “The enhanced bioavailability of free curcumin and bioactive-metabolite tetrahydrocurcumin from a dispersible, oleoresin-based turmeric formulation.” Medicine (Baltimore). (2021);100(27):e26601.
The effect of curcumin (turmeric) on Alzheimer's disease: An overview
Abstract
This paper discusses the effects of curcumin on patients with Alzheimer's disease (AD). Curcumin (Turmeric), an ancient Indian herb used in curry powder, has been extensively studied in modern medicine and Indian systems of medicine for the treatment of various medical conditions, including cystic fibrosis, haemorrhoids, gastric ulcer, colon cancer, breast cancer, atherosclerosis, liver diseases and arthritis. It has been used in various types of treatments for dementia and traumatic brain injury. Curcumin also has a potential role in the prevention and treatment of AD. Curcumin as an antioxidant, anti-inflammatory and lipophilic action improves the cognitive functions in patients with AD. A growing body of evidence indicates that oxidative stress, free radicals, beta amyloid, cerebral deregulation caused by bio-metal toxicity and abnormal inflammatory reactions contribute to the key event in Alzheimer's disease pathology. Due to various effects of curcumin, such as decreased Beta-amyloid plaques, delayed degradation of neurons, metal-chelation, anti-inflammatory, antioxidant and decreased microglia formation, the overall memory in patients with AD has improved. This paper reviews the various mechanisms of actions of curcumin in AD and pathology.
Source: Mishra S, Palanivelu K. “The effect of curcumin (turmeric) on Alzheimer's disease: An overview.” Ann Indian Acad Neurol. (2008);11(1):13-9.
The Impact of Curcumin on Immune Response: An Immunomodulatory Strategy to Treat Sepsis
Abstract
Primary and secondary immunodeficiencies cause an alteration in the immune response which can increase the rate of infectious diseases and worsened prognoses. They can also alter the immune response, thus, making the infection even worse. Curcumin is the most biologically active component of the turmeric root and appears to be an antimicrobial agent. Curcumin cooperates with various cells such as macrophages, dendritic cells, B, T, and natural killer cells to modify the body's defence capacity. Curcumin also inhibits inflammatory responses by suppressing different metabolic pathways, reduces the production of inflammatory cytokines, and increases the expression of anti-inflammatory cytokines. Curcumin may also affect oxidative stress and the non-coding genetic material. This review analyses the relationships between immunodeficiency and the onset of infectious diseases and discusses the effects of curcumin and its derivatives on the immune response. In addition, we analyse some of the preclinical and clinical studies that support its possible use in prophylaxis or in the treatment of infectious diseases. Lastly, we examine how nanotechnologies can enhance the clinical use of curcumin.
Source: Allegra A, Mirabile G, Ettari R, Pioggia G, Gangemi S. “The Impact of Curcumin on Immune Response: An Immunomodulatory Strategy to Treat Sepsis.” Int J Mol Sci. (2022);23(23):14710.
The Effects of Curcumin on Diabetes Mellitus: A Systematic Review
Abstract
Diabetes mellitus (DM) is an ensemble of metabolic conditions that have reached pandemic proportions worldwide. Pathology’s multifactorial nature makes patient management, including lifelong drug therapy and lifestyle modification, extremely challenging. Currently, there is growing evidence about the effectiveness of using herbal supplements in preventing and controlling DM. Curcumin is a bioactive component found Curcuma longa, which exhibits several physiological and pharmacological properties such as antioxidant, anti-inflammatory, anticancer, neuroprotective, and anti-diabetic activities. For these reasons, our objective is to systematically review the effects of Curcuma longa or curcumin on DM. Databases such as PUBMED and EMBASE were searched, and the final selection included sixteen studies that fulfilled the inclusion criteria. The results showed that curcumin’s anti-diabetic activity might be due to its capacity to suppress oxidative stress and inflammatory process. Also, it significantly reduces fasting blood glucose, glycated hemoglobin, and body mass index. Nanocurcumin is also associated with a significant reduction in triglycerides, VLDL-c, total cholesterol, LDL-c, HDL-c, serum C reactive protein, and plasma malonaldehyde. Therefore, it can be considered in the therapeutic approach of patients with DM.
Source: Marton LT, Pescinini-E-Salzedas LM, Camargo MEC, Barbalho SM, Haber JFDS, Sinatora RV, Detregiachi CRP, Girio RJS, Buchaim DV, Cincotto Dos Santos Bueno P. “The Effects of Curcumin on Diabetes Mellitus: A Systematic Review.” Front Endocrinol (Lausanne). (2021);12:669448.
Protective Effects of Curcumin in Cardiovascular Diseases—Impact on Oxidative Stress and Mitochondria
Abstract
Cardiovascular diseases (CVDs) contribute to a large part of worldwide mortality. Similarly, two of the major risk factors for these diseases, aging and obesity, are also global problems. Aging, the gradual decline of body functions, is non-modifiable. Obesity, a modifiable risk factor for CVDs, also predisposes to type 2 diabetes mellitus (T2DM). Moreover, it affects not only the vasculature and the heart but also specific fat depots, which themselves have a major impact on the development and progression of CVDs. Common denominators of aging, obesity, and T2DM include oxidative stress, mitochondrial dysfunction, metabolic abnormalities such as altered lipid profiles and glucose metabolism, and inflammation. Several plant substances such as curcumin, the major active compound in turmeric root, have been used for a long time in traditional medicine and for the treatment of CVDs. Newer mechanistic, animal, and human studies provide evidence that curcumin has pleiotropic effects and attenuates numerous parameters which contribute to an increased risk for CVDs in aging as well as in obesity. Thus, curcumin as a nutraceutical could hold promise in the prevention of CVDs, but more standardized clinical trials are required to fully unravel its potential.
Source: Cox FF, Misiou A, Vierkant A, Ale-Agha N, Grandoch M, Haendeler J, Altschmied J. “Protective Effects of Curcumin in Cardiovascular Diseases-Impact on Oxidative Stress and Mitochondria.” Cells. (2022);11(3):342.
The efficacy of high- and low-dose curcumin in knee osteoarthritis: A systematic review and meta-analysis
Abstract
Objectives: The aim of this study was to critically appraise and evaluate effects of low- and high-dose curcuminoids on pain and functional improvement in patients with knee osteoarthritis (OA) and to compare adverse events (AEs) between curcuminoids and non-steroid anti-inflammatory drugs (NSAIDs).
Methods: We systematically reviewed all randomized controlled trials (RCTs) on curcuminoids in knee osteoarthritis from the PubMed, Embase, Cochrane Library, AMED, Cinahl, ISI Web of Science, Chinese medical database, and Indian Scientific databases from inception to June 21, 2021.
Results: We included eleven studies with a total of 1258 participants with primary knee OA. The meta-analysis results showed that curcuminoids were significantly more effective than comparators regarding visual analogue scale (VAS) and Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain scores. However, no significant difference in pain relief or AEs between the high-dose (daily dose ≥1000 mg or total dose ≥42 gm) and low-dose (daily dose <1000 mg or total dose <42 gm) curcuminoid treatments was observed. When comparing curcumininoids versus NSAIDs, a significant difference in VAS pain was found. For AE analysis, three of our included studies used NSAIDs as comparators, with all reporting higher AE rates in the NSAID group, though significance was reached in only one study.
Conclusions: The results of our meta-analysis suggest that low- and high-dose curcuminoids have similar pain relief effects and AEs in knee OA. Curcuminoids are also associated with better pain relief than NSAIDs; therefore, using curcuminoids as an adjunctive treatment in knee OA is recommended.
Source: Hsiao AF, Lien YC, Tzeng IS, Liu CT, Chou SH, Horng YS. “The efficacy of high- and low-dose curcumin in knee osteoarthritis: A systematic review and meta-analysis.” Complement Ther Med. (2021);63:102775.
Curcumin and proton pump inhibitors for functional dyspepsia: a randomised, double blind controlled trial
Abstract
Objective: To compare the efficacy of curcumin versus omeprazole in improving patient reported outcomes in people with dyspepsia.
Design: Randomised, double blind controlled trial, with central randomisation.
Setting: Thai traditional medicine hospital, district hospital, and university hospitals in Thailand.
Participants: Participants with a diagnosis of functional dyspepsia.
Interventions: The interventions were curcumin alone (C), omeprazole alone (O), or curcumin plus omeprazole (C+O). Patients in the combination group received two capsules of 250 mg curcumin, four times daily, and one capsule of 20 mg omeprazole once daily for 28 days.
Main outcome measures: Functional dyspepsia symptoms on days 28 and 56 were assessed using the Severity of Dyspepsia Assessment (SODA) score. Secondary outcomes were the occurrence of adverse events and serious adverse events.
Results: 206 patients were enrolled in the study and randomly assigned to one of the three groups; 151 patients completed the study. Demographic data (age 49.7±11.9 years; women 73.4%), clinical characteristics and baseline dyspepsia scores were comparable between the three groups. Significant improvements were observed in SODA scores on day 28 in the pain (-4.83, -5.46 and -6.22), non-pain (-2.22, -2.32 and -2.31) and satisfaction (0.39, 0.79 and 0.60) categories for the C+O, C, and O groups, respectively. These improvements were enhanced on day 56 in the pain (-7.19, -8.07 and -8.85), non-pain (-4.09, -4.12 and -3.71) and satisfaction (0.78, 1.07, and 0.81) categories in the C+O, C, and O groups, respectively. No significant differences were observed among the three groups and no serious adverse events occurred.
Conclusion: Curcumin and omeprazole had comparable efficacy for functional dyspepsia with no obvious synergistic effect.
Source: Kongkam P, Khongkha W, Lopimpisuth C, Chumsri C, Kosarussawadee P, Phutrakool P, Khamsai S, Sawanyawisuth K, Sura T, Phisalprapa P, Buamahakul T, Siwamogsatham S, Angsusing J, Poonniam P, Wanaratna K, Teerachaisakul M, Pongpirul K. “Curcumin and proton pump inhibitors for functional dyspepsia: a randomised, double blind controlled trial.” BMJ Evid Based Med. 2023 Nov 22;28(6):399-406.
Therapeutic potential of curcumin in eye diseases
Abstract
Curcumin (diferuloylmethane) derived from the rhizome of Curcuma longa L. has been used for thousands of years in traditional Chinese medicine and Ayurvedic medicine in Asian countries to treat liver diseases, rheumatoid diseases, diabetes, atherosclerosis, infectious diseases and cancer. It exhibits a wide range of pharmacological properties, which include antioxidant, anti-inflammatory, antimutagenic, antimicrobial and anticancer activity. Herein the mechanisms of curcumin impact on oxidative stress, angiogenesis and inflammatory processes are described indicating that curcumin use may inhibit those pathological conditions and restore body homeostasis. Its effectiveness was also proved for major eye diseases. In this review, the influence of curcumin on eye diseases, such as glaucoma, cataract, age-related macular degeneration, diabetic retinopathy, corneal neovascularization, corneal wound healing, dry eye disease, conjunctivitis, pterygium, anterior uveitis are reported. The analysis of a number of clinical and preclinical investigations indicates that curcumin may be used as a therapeutic agent in the treatment of various eye disorders.
Source: Radomska-Leśniewska DM, Osiecka-Iwan A, Hyc A, Góźdź A, Dąbrowska AM, Skopiński P. “Therapeutic potential of curcumin in eye diseases.” Cent Eur J Immunol. (2019);44(2):181-189.
Curcumin in Depression: Potential Mechanisms of Action and Current Evidence—A Narrative Review
Abstract
Major depressive disorder (MDD) is one of the most prevalent and debilitating disorders. Current available treatments are somehow limited, so alternative therapeutic approaches targeting different biological pathways are being investigated to improve treatment outcomes. Curcumin is the main active component in the spice turmeric that has been used for centuries in Ayurvedic medicine to treat a variety of conditions, including anxiety and depressive disorders. In the past decades, curcumin has drawn researchers' attention and displays a broad range of properties that seem relevant to depression pathophysiology. In this review, we break down the potential mechanisms of action of curcumin with emphasis on the diverse systems that can be disrupted in MDD. Curcumin has displayed, in a number of studies, a potency in modulating neurotransmitter concentrations, inflammatory pathways, excitotoxicity, neuroplasticity, hypothalamic–pituitary–adrenal disturbances, insulin resistance, oxidative and nitrosative stress, and endocannabinoid system, all of which can be involved in MDD pathophysiology. To date, a handful of clinical trials have been published and suggest a benefit of curcumin in MDD. With evidence that is progressively growing, curcumin appears as a promising alternative option in the management of MDD.
Source: Ramaholimihaso T, Bouazzaoui F, Kaladjian A. “Curcumin in Depression: Potential Mechanisms of Action and Current Evidence-A Narrative Review.” Front Psychiatry. (2020);11:572533.
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