Fact-checked by Grok 2 weeks ago

Curcuminoid

Curcuminoids are a class of natural phenolic compounds characterized by a diarylheptanoid structure, primarily consisting of curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione, C₂₁H₂₀O₆), demethoxycurcumin, and bisdemethoxycurcumin.^[1]^[2] These compounds are biosynthesized in the rhizomes of plants in the Curcuma genus, particularly Curcuma longa (turmeric), where they constitute 3–5% of the dry weight and impart the characteristic yellow color used traditionally as a spice and dye.^[3]^[4] Chemically, curcuminoids feature a central seven-carbon chain with two aromatic rings bearing methoxy and hydroxy substituents, enabling their lipophilic nature and very low water solubility (approximately 0.6 μg/mL for curcumin at neutral pH).^[2]^[3]^[5] They exhibit keto-enol tautomerism, with the enol form predominating in organic solvents and contributing to their stability under acidic conditions but instability in alkaline environments or under light exposure.^[4]^[6] Extraction typically involves solvents like ethanol or acetone from turmeric rhizomes, yielding oleoresins rich in these bioactive molecules.^[3] Curcuminoids have garnered significant attention for their pharmacological properties, including potent antioxidant, anti-inflammatory, and anticancer activities, attributed to their ability to modulate pathways such as NF-κB inhibition and reactive oxygen species scavenging.^[7]^[2] Clinical studies suggest potential benefits in managing conditions like metabolic syndrome, arthritis, and neurodegenerative diseases, with recent umbrella reviews (as of 2025) supporting improvements in lipid profiles, blood pressure, inflammatory markers, and oxidative stress, though their therapeutic efficacy is limited by poor bioavailability, prompting research into enhanced formulations such as nanoparticles and phospholipid complexes.^[7]^[4]^[8] Ongoing investigations continue to explore their role in food preservation, nutraceuticals, and pharmaceutical applications due to their generally recognized as safe (GRAS) status by regulatory bodies.^[3]^[9]

Overview

Definition and composition

Curcuminoids are a class of natural polyphenols classified as diarylheptanoids, primarily found in the rhizomes of turmeric (Curcuma longa). These compounds are characterized by a linear heptanoid chain flanked by two aromatic rings, contributing to their bioactive properties. The term "curcuminoid" derives from curcumin, the principal member, which was first isolated in 1815 by scientists Henri-Auguste Vogel and Pierre-Joseph Pelletier from turmeric rhizomes as a yellow coloring matter.^[1]^[10] In turmeric extracts, curcuminoids typically comprise curcumin (also known as diferuloylmethane), demethoxycurcumin, and bisdemethoxycurcumin, with relative proportions of approximately 77%, 17%, and 3–6%, respectively. Curcumin, the most abundant, has the molecular formula C₂₁H₂₀O₆ and a molecular weight of 368.38 g/mol. These proportions can vary slightly depending on the source material.^[11]^[1] The total curcuminoid content in dried turmeric rhizomes ranges from 2.5% to 6% by weight, influenced by factors such as turmeric cultivars and post-harvest processing methods. For instance, selective breeding and optimized drying can enhance concentrations within this range. Curcuminoids are also present in related species, such as Curcuma mangga.^[12]

Natural occurrence

Curcuminoids are primarily found in the rhizomes of Curcuma longa, a perennial herbaceous plant belonging to the Zingiberaceae family and native to tropical South Asia.^[13] This species, commonly known as turmeric, thrives in humid, tropical environments with well-drained sandy or clay loam soils having a pH range of 4.5–7.5 and high organic content.^[14] Optimal growth occurs in regions with monsoon climates, where high rainfall supports its development in forested or cultivated areas.^[15] Turmeric is widely cultivated across tropical Asia, with India accounting for approximately 80% of global production, followed by significant contributions from China, Indonesia, and Myanmar.^[16] The plant also grows wild in the forests of South and Southeast Asia, particularly in high-rainfall zones, though commercial cultivation dominates supply.^[15] Factors such as soil nutrients, altitude, and environmental conditions influence curcuminoid levels, with nutrient-rich loamy soils and tropical monsoon regimes yielding higher concentrations.^[17] Harvesting time further affects content, with rhizomes aged 7–9 months typically exhibiting elevated curcuminoid levels compared to earlier stages.^[14] In addition to C. longa, curcuminoids occur in smaller amounts in other Curcuma species, including C. aromatica, C. xanthorrhiza, and traces in C. amada (mango ginger).^[18] These related plants, also native to South and Southeast Asia, contribute to regional biodiversity but are less commercially significant for curcuminoid extraction.^[19] Historically, turmeric has been utilized in traditional systems such as Ayurveda and Traditional Chinese Medicine for its medicinal properties, as well as a spice and natural dye, long before the scientific isolation of curcuminoids in 1815.^[13] In Ayurveda, it was prescribed for anti-inflammatory uses dating back over 4,000 years, while in Chinese medicine, it addressed digestive issues by the 7th century CE.^[20]

Chemical properties

Molecular structures

Curcuminoids are a class of natural polyphenols characterized by a shared core molecular backbone consisting of 1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione, which features a central β-diketone linker connecting two ferulic acid-derived moieties with conjugated double bonds.^[1] This unsymmetrical diarylheptanoid scaffold allows for variations primarily in the substitution patterns on the aromatic rings, influencing their chemical identity while maintaining the overall heptadienone framework. Curcumin, the principal curcuminoid, possesses two methoxy groups on each of the terminal phenyl rings at the 3-positions, yielding the molecular formula C_{21}H_{20}O_{6}. It exhibits enol-keto tautomerism due to the β-diketone moiety, with the enol form predominating in the solid state owing to intramolecular hydrogen bonding that stabilizes the conjugated system.^[4]^[1] Demethoxycurcumin differs by lacking one methoxy group, replaced by a hydrogen on one phenyl ring, resulting in the formula C_{20}H_{18}O_{5} and a structure of (1E,6E)-1-(4-hydroxy-3-methoxyphenyl)-7-(4-hydroxyphenyl)hepta-1,6-diene-3,5-dione. Bisdemethoxycurcumin features the absence of both methoxy groups, one from each ring, giving C_{19}H_{16}O_{4} and a symmetric bis(4-hydroxycinnamoyl)methane core.^[21]^[22] The heptadienone chain in these curcuminoids adopts a predominantly trans (E,E) configuration at the double bonds, contributing to the extended conjugation responsible for their characteristic properties; however, cis isomers can form under degradative conditions or specific synthetic routes.^[23]^[1] Semi-synthetic analogs, such as tetrahydrocurcumin, are derived by hydrogenating the double bonds in the heptadienone chain of curcumin, yielding 1,7-bis(4-hydroxy-3-methoxyphenyl)heptane-3,5-dione without altering the aromatic substitutions.^[24]^[25]

Physical and chemical characteristics

Curcuminoids, particularly curcumin as the primary representative, appear as a bright yellow-orange crystalline powder, imparting the characteristic color to turmeric due to strong absorption in the visible spectrum with a maximum wavelength around 425 nm as measured by UV-Vis spectrophotometry.^[23]^[26] Solubility of curcuminoids is notably poor in water, typically less than 0.01 mg/mL at neutral pH (around 7), but they exhibit high solubility in organic solvents such as ethanol, dimethyl sulfoxide (DMSO), and acetone.^[27]^[28] Solubility increases under alkaline conditions due to deprotonation of the phenolic groups, though this is accompanied by rapid degradation.^[23] Stability of curcuminoids is highly sensitive to environmental factors; they degrade rapidly in neutral and alkaline aqueous solutions, with a half-life of approximately 1-2 hours under light or heat exposure, while remaining more stable in acidic conditions (pH 1-6).^[29]^[28] Degradation products include vanillin and ferulic acid, accelerated by sunlight or basic pH.^[23] Chemically, curcuminoids feature a β-diketone moiety that facilitates metal chelation, particularly with transition metals like Fe³⁺ and Cu²⁺, forming stable coordination complexes.^[30] This structure also enables reactivity through nucleophilic addition at the α,β-unsaturated sites and antioxidant activity via hydrogen atom donation from the phenolic hydroxyl groups.^[23]^[31] The melting point of curcumin is approximately 183°C, reflecting its thermal stability in dry form, while the octanol-water partition coefficient (logP ≈ 3.3) underscores its lipophilic nature.^[4]^[28]

Production

Extraction from natural sources

Curcuminoids are primarily extracted from the rhizomes of Curcuma longa, commonly known as turmeric, which contains 2-5% curcuminoids by dry weight.^[3] Traditional extraction methods involve solvent-based techniques applied to dried and ground turmeric rhizomes. These typically employ organic solvents such as ethanol or acetone in processes like Soxhlet extraction or maceration, where the powdered rhizome is soaked or refluxed to dissolve the curcuminoids. Yields from these methods generally range from 2-5% curcuminoids relative to the dry rhizome weight, with ethanol achieving up to 72% extraction efficiency under optimized conditions of 1 hour at 35°C.^[3]^[32]^[32] Modern techniques enhance efficiency and sustainability over traditional solvent methods. Supercritical CO₂ extraction (SFE) uses carbon dioxide under high pressure and moderate temperature as an eco-friendly solvent, yielding up to 3.1% extract from turmeric with over 90% recovery of curcuminoids, avoiding residual solvents common in organic extractions.^[33]^[34] Ultrasound-assisted extraction (UAE) and microwave-assisted extraction (MAE) further improve speed and yield; UAE can achieve 72% curcumin recovery at 35°C with a 1:25 solid-to-solvent ratio, while MAE reaches 88.6% efficiency in 25 minutes at 80°C using ethanol.^[35]^[35]^[35] Following extraction, purification isolates curcuminoids from the crude oleoresin. Column chromatography on silica gel separates the mixture into individual components like curcumin, demethoxycurcumin, and bisdemethoxycurcumin, with yields of 68-81% for purified fractions. Alternatively, crystallization from solvents such as acetone/2-propanol achieves up to 99.4% purity in a single step via seeded cooling. Extracts are standardized to 95% total curcuminoids for use in supplements, ensuring consistent potency.^[36]^[37]^[37] India dominates this market, accounting for approximately 70% of global exports through advanced processing facilities.^[38]^[39] Quality control in extraction ensures purity and safety, with high-performance liquid chromatography (HPLC) serving as the standard for profiling curcuminoid content and verifying compliance with pharmacopeial monographs. Hexane, a non-polar solvent sometimes used in early methods, is increasingly avoided due to potential residual contamination risks in food-grade products.^[40]^[41]

Synthetic methods

The classical laboratory synthesis of curcumin, the primary curcuminoid, involves the acid-catalyzed condensation of two equivalents of vanillin with one equivalent of acetylacetone. This method, developed by Pavolini in 1937, utilizes boric anhydride as the condensing agent and typically achieves yields of around 10% after purification.^[42]^[43] Subsequent refinements, such as Pabon's 1964 procedure incorporating tri-sec-butyl borate and n-butylamine, elevated yields to approximately 80% while maintaining a one-pot reaction format suitable for laboratory-scale production.^[44] These approaches provide high-purity curcumin (>95%) for research standards, contrasting with natural extracts that contain mixtures of curcuminoids. Modern variants emphasize efficiency and sustainability. Microwave-assisted synthesis accelerates the condensation reaction for demethoxycurcumin and related analogs, reducing reaction times from hours to minutes under solvent-free conditions and improving yields to 85-90% in solid-phase setups.^[45] Greener routes include enzymatic modifications using lipases for esterification of curcuminoids, enabling the production of lipophilic derivatives with enhanced solubility while minimizing organic solvent use.^[46] Analog production expands the curcuminoid family for targeted applications. Tetrahydrocurcumin, a reduced form with greater stability, is obtained via catalytic hydrogenation of curcumin using palladium on carbon in ethanol, yielding up to 95% of the colorless product.^[47] Fluorinated derivatives, synthesized by substituting fluorine on the aromatic rings during the vanillin-acetylacetone condensation, exhibit improved metabolic stability due to resistance to enzymatic degradation.^[48] Synthetic methods support scalability for high-purity reference standards in pharmaceutical research, where costs can be up to half that of natural extraction processes (e.g., $60/kg versus $120/kg), though they enable precise structural modifications unavailable in plant-derived materials.^[49] Key post-2000 patents cover synthetic analogs, such as tetrahydrocurcuminoid mixtures for antioxidant applications by Sabinsa Corporation.^[50]

Bioavailability and formulations

Solubility and stability challenges

Curcuminoids, particularly curcumin, exhibit low aqueous solubility due to their hydrophobic nature, with a solubility of approximately 0.6 μg/mL in pure water and a logP value of 3.29, which severely limits their dissolution and absorption in the gastrointestinal (GI) tract.^[51] This poor solubility contributes to an oral bioavailability of less than 1% in humans, as the majority of ingested curcumin remains undissolved and unabsorbed.^[52] In addition to solubility barriers, curcumin undergoes rapid metabolism primarily through first-pass effects in the liver and intestines, where it is extensively conjugated via glucuronidation and sulfation to form inactive metabolites such as curcumin glucuronide and curcumin sulfate. This metabolic process, mediated by phase II enzymes, results in a short plasma half-life of approximately 1-2 hours for native curcumin in humans, with plasma concentrations often becoming undetectable shortly after administration.^[53] Curcumin also faces significant instability in the GI tract, where it degrades due to pH variations and enzymatic activity; while relatively stable at acidic pH (e.g., half-life of about 175 days at pH 5.97), it rapidly breaks down at neutral to alkaline pH levels encountered in the intestines, with a chemical half-life of 10-20 minutes at neutral pH and 37°C.^[51] Consequently, only 1-2% of orally administered curcumin reaches systemic circulation in its unchanged form, further compounded by bioreduction to metabolites like tetrahydrocurcumin.^[52] Pharmacokinetic studies in humans underscore these challenges, showing peak plasma concentrations (C_max) of approximately 0.01-0.1 μM following a 4 g oral dose, often as low as 11.1 nmol/L after 3.6 g, with poor distribution to tissues without formulation aids.^[52] Factors such as interactions with food matrices, which can alter dissolution rates, and individual variability in cytochrome P450 enzyme activity, influencing metabolism rates, exacerbate these bioavailability limitations.

Enhancement strategies

To address the poor aqueous solubility and rapid degradation of curcuminoids, which limit their oral bioavailability to less than 1% in native form, various formulation strategies have been employed to enhance absorption and systemic exposure.^[51] Liposomal encapsulation involves incorporating curcuminoids into phospholipid bilayers, protecting them from gastrointestinal degradation and facilitating cellular uptake via endocytosis, resulting in 5- to 10-fold improvements in bioavailability compared to unformulated curcumin.^[54] Solid dispersions with hydrophilic polymers like polyvinylpyrrolidone (PVP) convert curcuminoids into an amorphous state, dramatically increasing dissolution rates; for instance, the Curcuwin formulation achieved a 136-fold rise in area under the curve (AUC) for total curcuminoids.^[51] Cyclodextrin complexation, particularly with β-cyclodextrin, forms inclusion complexes where the hydrophobic cavity of the cyclodextrin encapsulates the aromatic rings of curcumin, enhancing water solubility by 20- to 50-fold and boosting plasma levels up to 39-fold relative to standard extracts.^[55] This host-guest interaction stabilizes curcuminoids against hydrolysis and improves their permeation across intestinal barriers.^[56] Nanoparticle systems, such as poly(lactic-co-glycolic acid) (PLGA) or chitosan-based nanoparticles, enable sustained release and targeted delivery; PLGA nanoparticles have demonstrated 5.6- to 55-fold higher bioavailability in rats through controlled erosion and mucoadhesion, while chitosan variants provide up to 2.6-fold enhancement via positive surface charge promoting intestinal adhesion.^[57]^[58] Micellar solubilization using surfactants like polysorbates further disperses curcuminoids into nanoscale micelles, improving solubility and absorption for prolonged circulation.^[51] Other innovations include phospholipid complexes, known as phytosomes, which bind curcumin to phospholipids like phosphatidylcholine for better membrane compatibility, yielding approximately 5.8-fold bioavailability gains.^[9] Co-administration with piperine, an alkaloid from black pepper, inhibits hepatic and intestinal glucuronidation enzymes, dramatically elevating curcumin bioavailability by up to 2000% as shown in human pharmacokinetic studies.^[59] Self-emulsifying drug delivery systems (SEDDS), which spontaneously form oil-in-water emulsions upon dilution in the gut, achieve up to 94-fold increases in curcumin AUC through enhanced lymphatic transport.^[51] Theracurmin, a colloidal nanoparticle dispersion approved under FDA GRAS status, utilizes submicron particles (around 0.19 μm) to yield 27- to 42-fold higher systemic exposure compared to curcumin powder, with faster absorption (T_max of 1.5-3 hours versus 8 hours).^[60]^[61] In 2025, emerging strategies include PEG-based gastroretentive self-emulsifying systems for prolonged gastric retention and absorption enhancement, as well as sustainably derived turmeric nanoparticles to improve gastrointestinal stability and bioavailability.^[62]^[63] These strategies collectively transform curcuminoids from poorly absorbable compounds into viable therapeutic agents.

Biological activities

Antioxidant and anti-inflammatory effects

Curcuminoids, particularly curcumin, exhibit potent antioxidant activity primarily through direct scavenging of reactive oxygen species (ROS) and reactive nitrogen species (RNS). This occurs via hydrogen atom donation from the phenolic hydroxyl groups, with the enol tautomer facilitating efficient hydrogen transfer to free radicals, stabilizing them and preventing further oxidative damage.^[64]^[65] Curcuminoids also enhance endogenous antioxidant defenses by upregulating the Nrf2 pathway, which activates the antioxidant response element (ARE) to increase expression of enzymes such as glutathione (GSH) and superoxide dismutase (SOD). This indirect mechanism helps maintain cellular redox balance and mitigates oxidative stress in various models.^[66]^[67]^[68] In addition to radical scavenging, curcuminoids chelate transition metals like iron (Fe) and copper (Cu), inhibiting Fenton reactions that generate hydroxyl radicals from hydrogen peroxide. This metal-binding property contributes to their protective effects against metal-induced oxidative damage. Curcumin demonstrates strong DPPH radical scavenging with an IC50 value of approximately 10 μM, underscoring its efficacy in free radical assays.^[69]^[70]^[71] In vitro studies confirm these antioxidant actions, showing that curcuminoids reduce lipid peroxidation in cell models, such as protecting erythrocytes from oxidative hemolysis and inhibiting linoleic acid oxidation. Structure-activity relationships reveal that curcumin possesses superior activity compared to demethoxycurcumin, with the methoxy groups enhancing radical stabilization and overall potency.^[72]^[73]^[74] The anti-inflammatory effects of curcuminoids stem from inhibition of NF-κB activation, a key transcription factor that drives pro-inflammatory gene expression. By suppressing NF-κB nuclear translocation, curcuminoids reduce production of cytokines such as TNF-α and IL-6 in stimulated cells. They also modulate the COX-2/PGE2 pathway, directly inhibiting COX-2 enzyme activity to limit prostaglandin E2 synthesis and associated inflammation.^[75]^[76] These effects are observed in a dose-dependent manner, with concentrations of 1-10 μM proving effective in in vitro antioxidant and anti-inflammatory assays, balancing efficacy without inducing pro-oxidant behavior at higher doses.^[77]^[78]

Anticancer and other pharmacological activities

Curcuminoids, particularly curcumin, exhibit significant anticancer properties through multiple mechanisms, including the induction of apoptosis in cancer cells. Curcumin activates the intrinsic mitochondrial pathway of apoptosis by upregulating caspase-3 and caspase-9, leading to proteolytic cleavage of downstream targets and programmed cell death in various tumor models, such as prostate and melanoma cells.^[79]^[80] Additionally, curcumin inhibits angiogenesis by suppressing vascular endothelial growth factor (VEGF) expression and signaling, thereby reducing endothelial cell proliferation, migration, and tube formation in models of intestinal microvascular and hepatocellular carcinoma angiogenesis.^[81]^[82] It also promotes cell cycle arrest at the G2/M phase, as evidenced by flow cytometry in head and neck squamous cell carcinoma and colorectal cancer cells, where curcumin modulates cyclin-dependent kinases and p53 phosphorylation to halt progression and sensitize cells to apoptosis.^[83]^[84] In antidiabetic applications, curcuminoids enhance insulin sensitivity and glucose homeostasis by activating AMP-activated protein kinase (AMPK), which inhibits hepatic gluconeogenesis and promotes glucose uptake in skeletal muscle and adipose tissue in high-fat diet-induced diabetic models.^[85]^[86] This activation contributes to reduced hemoglobin A1c (HbA1c) levels and improved glycemic control, as observed in clinical and preclinical studies where curcumin supplementation lowered fasting blood glucose and enhanced insulin signaling via IRS-1/PI3K pathways.^[87] Furthermore, curcumin inhibits α-glucosidase activity in vitro, delaying carbohydrate digestion and postprandial hyperglycemia, with inhibitory concentrations comparable to acarbose in assays using turmeric extracts and synthetic derivatives.^[88]^[89] Curcuminoids demonstrate neuroprotective effects, partly due to their ability to cross the blood-brain barrier (BBB) and accumulate in brain tissue, as confirmed by pharmacokinetic studies in rodent models.^[90] In Alzheimer's disease models, curcumin reduces amyloid-β (Aβ) aggregation and fibril formation by binding to Aβ peptides and inhibiting their self-assembly, thereby mitigating neurotoxicity and plaque burden in vitro and in transgenic mice.^[91]^[90] For antidepressant activity, curcumin upregulates brain-derived neurotrophic factor (BDNF) expression via the PI3K/Akt pathway, enhancing neurogenesis and synaptic plasticity in depression-like models induced by chronic stress.^[92]^[93] Antimicrobial properties of curcuminoids target both Gram-positive and Gram-negative bacteria, including Helicobacter pylori and Staphylococcus aureus. Against H. pylori, curcumin inhibits growth and urease activity, disrupting biofilms and enhancing eradication in gastric infection models, with minimum inhibitory concentrations as low as 25 μg/mL.^[94]^[95] For S. aureus, including methicillin-resistant strains (MRSA), curcumin exhibits bactericidal effects by damaging bacterial cell membranes, increasing permeability and leading to leakage of intracellular contents, as shown in time-kill assays.^[96]^[97] Other pharmacological activities include promotion of wound healing through enhanced collagen deposition and extracellular matrix remodeling. In cutaneous wound models, topical curcumin increases type I and III collagen synthesis by fibroblasts, accelerates granulation tissue formation, and reduces healing time by modulating matrix metalloproteinases (MMPs) and transforming growth factor-β (TGF-β).^[98]^[99] Additionally, curcuminoids display antiparasitic effects, particularly against Leishmania species, where they induce parasite death by disrupting mitochondrial function and reactive oxygen species generation in promastigote and amastigote forms, with nanoformulations enhancing efficacy in murine cutaneous leishmaniasis.^[100]^[101] Regarding structure-activity relationships, demethoxycurcumin, a major curcuminoid analog lacking one methoxy group, shows enhanced potency in neuroprotection compared to curcumin. In rotenone-induced Parkinson's models, demethoxycurcumin more effectively mitigates oxidative stress, restores mitochondrial membrane potential, and preserves dopaminergic neurons via stronger activation of Nrf2/ARE pathways.^[102]^[103]

Research and applications

Preclinical and mechanistic studies

Preclinical studies on curcuminoids have extensively utilized in vitro models to assess their effects on cellular processes, particularly in cancer cell lines. For instance, in the HT-29 human colon cancer cell line, curcumin exhibits antiproliferative activity with IC50 values ranging from 4.7 to 17 μM, depending on exposure duration and experimental conditions.^[104]^[105] Similar inhibitory effects have been observed across various cancer cell lines, where curcuminoids demonstrate IC50 values of 5-50 μM for proliferation inhibition, often through induction of apoptosis and cell cycle arrest.^[106]^[107] In animal models, curcuminoids have shown therapeutic potential in inflammatory and metabolic conditions. Rodent models of arthritis, such as collagen-induced arthritis in rats, reveal that oral administration of curcumin at doses of 30-50 mg/kg significantly reduces paw swelling by 40-60%, alongside decreases in inflammatory markers like TNF-α and IL-1β.^[108]^[109] In diabetes models, such as streptozotocin-induced diabetic rats, curcumin supplementation at 100-200 mg/kg lowers blood glucose levels by 20-30% and improves insulin sensitivity, attributed to enhanced antioxidant defenses and reduced oxidative stress.^[110]^[111] Mechanistic investigations have employed advanced omics approaches to elucidate curcuminoids' multi-target actions. Microarray analyses in cancer cell lines, including breast and lung models, indicate that curcumin modulates over 100 genes, upregulating apoptosis-related pathways like p53 and downregulating proliferation factors such as NF-κB.^[112]^[113] Proteomics studies further map these effects, revealing alterations in signaling cascades, including PI3K/Akt and MAPK pathways, which contribute to anti-inflammatory and anticancer outcomes in colorectal and pancreatic cancer models.^[114]^[115] Key preclinical findings prior to 2025 confirm curcuminoids' pleiotropic effects, targeting multiple pathways simultaneously for broad therapeutic potential. Recent 2025 updates integrate multi-omics data, showing how curcumin influences metabolomics and epigenomics in neurodegenerative models, enhancing understanding of its neuroprotective mechanisms through integrated pathway analyses.^[116]^[117] Despite these promising results, preclinical research highlights limitations related to bioavailability, necessitating high doses of 100-500 mg/kg in animal studies to achieve systemic effects, as native curcumin exhibits rapid metabolism and poor absorption.^[118]^[119]

Clinical trials and therapeutic potential

By 2025, over 100 randomized controlled trials (RCTs) have investigated curcuminoids, primarily focusing on their anti-inflammatory and antioxidant properties in various chronic conditions.^[120] Meta-analyses of these trials indicate consistent evidence of efficacy, particularly when using enhanced bioavailability formulations, though results vary due to differences in dosing, duration, and patient populations.^[121] In osteoarthritis, meta-analyses of RCTs demonstrate that curcuminoids at doses of 500-2000 mg/day reduce knee pain by approximately 20-30% compared to placebo, comparable to nonsteroidal anti-inflammatory drugs, with improvements in joint function and reduced inflammatory markers like C-reactive protein.^[122] For inflammatory bowel disease, particularly ulcerative colitis, adjunctive curcumin therapy achieves clinical remission in about 50% of cases in small-to-medium RCTs, with pooled odds ratios favoring remission (OR 2.9, 95% CI 1.5-5.5) and response rates up to 65% when combined with mesalamine.^[123] In metabolic syndrome, meta-analyses show curcumin supplementation lowers low-density lipoprotein cholesterol by 10-15%, alongside reductions in triglycerides and improvements in glycemic control, based on trials involving prediabetic and obese participants.^[86] Small RCTs from 2020-2022 on COVID-19 adjunct therapy report reduced symptom severity, shorter hospitalization duration, and lower mortality rates with curcumin doses of 500-1000 mg/day, though larger confirmatory studies are lacking.^[124] Enhanced formulations have improved trial outcomes by addressing curcumin's poor bioavailability. Theracurmin, a nanoparticle dispersion, achieves up to 27-fold higher plasma curcumin levels (AUC 0-6 h) compared to standard curcumin, enabling effective dosing in RCTs for inflammation and cancer.^[125] Longvida, a solid lipid particle formulation optimized for brain delivery, crosses the blood-brain barrier more efficiently, supporting its use in neurological trials.^[126] Curcuminoids show therapeutic potential as adjunctive agents in oncology and neurodegeneration. Phase II trials indicate benefits in cancer prevention, such as reduced aberrant crypt foci in colorectal neoplasia (40% reduction at 4 g/day) and modulation of inflammatory pathways in pancreatic and endometrial cancers, though progression-free survival data remain preliminary.^[127] For Alzheimer's disease, RCTs with bioavailable forms like Theracurmin report 28% improvements in memory scores and reduced amyloid/tau burden in mild cases after 18 months of 400 mg/day supplementation.^[128] Despite promising results, clinical trials exhibit heterogeneity in formulations, outcome measures, and trial quality, limiting generalizability; larger Phase III studies are needed to establish standardized dosing and long-term efficacy.^[129]

Safety and toxicology

Adverse effects and toxicity

Curcuminoids demonstrate low acute toxicity, with oral LD50 values exceeding 2000 mg/kg body weight in rats and often surpassing 5000 mg/kg in various rodent models, resulting in no observed lethality or significant clinical signs at therapeutic doses typically ranging from 500 to 2000 mg/day.^[130]^[131] Chronic exposure to high doses of curcuminoids, particularly above 4 g/day, can lead to gastrointestinal upset, including diarrhea, nausea, and abdominal discomfort, though these effects are generally mild and resolve upon dose reduction.^[132] Rare instances of hepatotoxicity have been reported with prolonged use of high-dose supplements, especially formulations with enhanced bioavailability, manifesting as elevated liver enzymes and, in severe cases, acute liver injury, but such events occur infrequently and are often linked to individual susceptibility or product contaminants. Reports of hepatotoxicity have been increasing in recent years, particularly with enhanced bioavailability formulations, as noted in 2025 clinical cases and surveillance updates.^[133]^[134]^[133] Genotoxicity studies indicate that curcuminoids are non-mutagenic, showing negative results in the Ames bacterial reverse mutation test across multiple strains.^[135] At low doses, they exhibit antimutagenic effects, potentially protecting against DNA damage induced by other agents.^[136] Special caution is recommended for vulnerable populations; pregnant individuals should avoid therapeutic doses of curcuminoids due to their potential uterine stimulant properties, which may increase the risk of contractions or bleeding.^[137] Similarly, those with gallbladder disorders or gallstones are advised to use caution, as curcuminoids have choleretic effects that stimulate bile production and gallbladder contraction, potentially exacerbating biliary issues.^[138]^[139] As of 2025, post-marketing surveillance data from clinical registries and adverse event reporting systems reveal a low incidence of adverse events associated with standardized curcuminoid extracts, generally below 1%, with most reports involving mild gastrointestinal symptoms rather than serious outcomes.^[140] These findings underscore the overall favorable safety profile when used within recommended limits, though ongoing monitoring emphasizes the importance of quality-controlled formulations to minimize risks from impurities.

Regulatory status and interactions

Curcumin, the primary bioactive compound in turmeric, holds Generally Recognized as Safe (GRAS) status from the U.S. Food and Drug Administration (FDA) when used as a spice or direct food additive, with multiple GRAS notices affirming its safety for incorporation into foods such as yogurts, nutrition bars, and medical foods at levels up to 60 mg per serving. In the European Union, high-purity curcumin extracts (up to 95% curcuminoids) are classified as novel foods under Regulation (EU) 2015/2283, requiring pre-market authorization due to insufficient historical consumption data in that form, though lower-purity turmeric preparations used traditionally are not subject to this category. In 2024, a proposal was submitted to the European Commission to restrict curcumin use in food supplements due to emerging safety concerns; as of 2025, it remains under review. In India, curcumin is recognized and approved within the Ayurvedic pharmacopoeia for topical use in wound healing formulations, leveraging its traditional role in promoting tissue repair and reducing inflammation. For dietary supplements, the United States Pharmacopeia (USP) provides a monograph standardizing curcuminoid content, typically specifying extracts with 70-80% total curcuminoids, while many commercial products are standardized to 95% curcuminoids to ensure potency and consistency. The World Health Organization (WHO), through the Joint FAO/WHO Expert Committee on Food Additives (JECFA), has established an acceptable daily intake (ADI) for curcumin of 0-3 mg/kg body weight, equating to approximately 210 mg for a 70 kg adult, based on multigenerational reproductive toxicity studies in rats; higher doses up to 8 g/day have been tolerated in short-term human studies but exceed the ADI and require medical supervision. Curcumin exhibits pharmacokinetic interactions primarily through inhibition of cytochrome P450 3A4 (CYP3A4), which can decrease the metabolism of substrates like warfarin, potentially elevating its anticoagulant effects and increasing bleeding risk, and statins such as simvastatin, raising plasma concentrations and the potential for myopathy. Conversely, curcumin has been shown to enhance the efficacy of certain chemotherapies, including doxorubicin, by modulating multidrug resistance mechanisms like ATP-binding cassette transporters and NF-κB signaling, thereby sensitizing resistant tumor cells in preclinical models. Key contraindications include concurrent use with anticoagulants like warfarin or aspirin, as curcumin's antiplatelet properties may amplify bleeding risks, and iron supplements, where curcumin's chelating effects reduce iron absorption and could exacerbate deficiency in susceptible individuals. Patients on these regimens should consult healthcare providers for monitoring or dose adjustments. As of 2025, the global curcumin supplement market is valued at approximately USD 113.8 million, driven by rising demand for natural anti-inflammatory agents, with the World Health Organization emphasizing stringent quality control measures, including verification of curcuminoid content and screening for contaminants like heavy metals, to mitigate risks in an expanding unregulated sector.

References

[1]
Curcumin | C21H20O6 | CID 969516 - PubChem - NIH
Curcumin is a beta-diketone that is methane in which two of the hydrogens are substituted by feruloyl groups. A natural dyestuff found in the root of ...
[2]
Biological activities of curcuminoids, other biomolecules from ...
Curcuminoids have extensive biological activity as an antioxidant, neuroprotective, antitumor, anti-inflammatory, anti-acidogenic, radioprotective and ...
[3]
Curcumin: Overview of Extraction Methods, Health Benefits, and ...
May 17, 2023 · Curcumin is the principal curcuminoid found in the rhizomes of turmeric. Due to its therapeutic action against cancer, depression, diabetes, ...
[4]
Turmeric and Its Major Compound Curcumin on Health - NIH
Thus, this review aims to offer an in-depth discussion of curcumin applications for food and biotechnological industries, and on health promotion and disease ...
[5]
Biomedical Applications and Bioavailability of Curcumin—An ...
According to the current IUPAC rules, the name of curcumin is 1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione [3,16].
[6]
Curcumin: A Review of Its' Effects on Human Health - PMC
Oct 22, 2017 · Research suggests that curcumin can help in the management of oxidative and inflammatory conditions, metabolic syndrome, arthritis, anxiety, and hyperlipidemia.Missing: structure | Show results with:structure
[7]
Advancements in curcuminoid formulations: An update on ... - NIH
Jul 18, 2025 · Here, we provide a current review of strategies aimed at improving the bioavailability of curcuminoids, a group of compounds with ...Missing: sources | Show results with:sources<|control11|><|separator|>
[8]
Discovery of Curcumin, a Component of the Golden Spice, and Its ...
However, it was not until 1910 that Milobedzka and Lampe identified the chemical structure of curcumin as diferuloylmethane, or 1,6-heptadiene-3,5-dione-1,7-bis ...
[9]
Curcumin - The Nutraceutical With Pleiotropic Effects? Which ... - NIH
Among the curcuminoids, curcumin accounts for approximately 77%, demethoxycurcumin accounts for 17% and bisdemethoxycurcumin accounts for 3–6% (Figure 1) (23, ...
[10]
Turmeric (Curcuma longa L.) extract in different solvents
Aug 5, 2025 · The total curcuminoid complex found in the rhizome of turmeric was approximately 2.5 to 6% (Pawar et al., 2018). Curcuminoids are poorly ...
[11]
Turmeric, the Golden Spice - Herbal Medicine - NCBI Bookshelf - NIH
Turmeric is a product of Curcuma longa, a rhizomatous herbaceous perennial plant belonging to the ginger family Zingiberaceae, which is native to tropical South ...
[12]
Turmeric - Agriculture - Vikaspedia
Depending upon the variety, the crop becomes ready for harvest in 7-9 months after planting during January-March. Early varieties mature in 7-8 months, medium ...
[13]
Curcuma longa (turmeric) | CABI Compendium
Distribution. The natural range of turmeric is in the high rainfall areas of Asia and South-east Asia, but as it is so popular it has been ...Missing: habitat | Show results with:habitat
[14]
Indian Turmeric Export: A Golden Opportunity for Global Markets
According to market reports, India accounts for nearly 80% of the global turmeric production, making it the largest supplier to countries across the world.
[15]
[PDF] Differential effect of soil and environment on metabolic expression of ...
The present result showed that soil nutrients, environmental factors and altitude play important role in rhizome yield, essential oil and curcumin contents in ...Missing: harvesting | Show results with:harvesting
[16]
A Comprehensive Review on the Therapeutic Potential of Curcuma ...
Curcumin is a flavonoid having a lipophilic affinity that is practically water-insoluble (Dave et al., 2017) yet quite stable at the stomach's acidic pH. C.
[17]
Curcuma - an overview | ScienceDirect Topics
Turmeric is native to Southeast Asia but is cultivated extensively worldwide now. Zedoary is native to northeast India and Indonesia, but widely cultivated in ...Missing: habitat | Show results with:habitat
[18]
Turmeric benefits: A look at the evidence - Harvard Health
Mar 22, 2024 · Turmeric has been used for thousands of years in Ayurvedic medicine and traditional Chinese medicine ... While turmeric spice typically ...<|control11|><|separator|>
[19]
Demethoxycurcumin | C20H18O5 | CID 5469424 - PubChem - NIH
Demethoxycurcumin is a beta-diketone that is curcumin in which one of the methoxy groups is replaced by hydrogen. It is found in Curcuma zedoaria and Etlingera ...
[20]
Bisdemethoxycurcumin | C19H16O4 | CID 5315472 - PubChem - NIH
Bisdemethoxycurcumin is a beta-diketone that is methane in which two of the hydrogens are substituted by 4-hydroxycinnamoyl groups.
[21]
The Chemistry of Curcumin: From Extraction to Therapeutic Agent
In solution it exists as cis-trans isomers where the trans-form in which the two phenolic-methoxy groups are on the opposite sides of the curcumin backbone ...Missing: stereochemistry | Show results with:stereochemistry
[22]
Tetrahydrocurcumin | C21H24O6 | CID 124072 - PubChem - NIH
Tetrahydrocurcumin is a beta-diketone that is curcumin in which both of the double bonds have been reduced to single bonds. It has a role as a metabolite.
[23]
Molecular Mechanisms of Curcumin and Its Semisynthetic ... - NIH
This review focuses on curcumin's therapeutic effectiveness in vitro and in vivo in prostate cancer models.
[24]
Stability of curcumin in different solvent and solution media
Curcumin has absorption maximum around 430 nm in different polar solvent and surfactant solutions (Fig. 1(a) main diagram). In w/o μe (microemulsion) and DMSO ...
[25]
Methods to Improve the Solubility of Curcumin from Turmeric - PMC
Jan 11, 2023 · Unfortunately, curcumin is characterized by poor water solubility (0.6 µg/mL [25]), which also means low bioavailability (its level in the serum ...
[26]
Curcumin and its Derivatives: Their Application in ... - PubMed Central
Curcumin, also known as diferuloylmethane (C21H20O6), is a low molecular mass (368.37 g/mol) polyphenol compound with a melting temperature of approximately 183 ...Missing: backbone | Show results with:backbone
[27]
Degradation of curcumin: From mechanism to biological implications
Sep 9, 2016 · Protein increases the half life of curcumin from a few minutes to 1-2 h. ... Stability of curcumin in buffer solutions and characterization of its ...
[28]
Metal–Curcumin Complexes in Therapeutics: An Approach to ...
Curcumin usually reacts with metals through the β-diketone moiety to generate metal–curcumin complexes. It is well established that curcumin strongly chelates ...
[29]
Metal chelating ability and antioxidant properties of Curcumin-metal ...
Metal chelation enhances the antioxidant properties of Curcumin. ... Curcumin can exist in two tautomeric forms: β-diketone (CurK) and β-keto ...
[30]
Curcumin Extraction, Isolation, Quantification and Its Application in ...
(74) found that ethanol as a solvent led to the maximum curcumin extraction yield as 72% in 1 h at 35°C, compared to the methanol, acetone, and ethyl acetate.
[31]
Supercritical Fluid Extraction with CO2 of Curcuma longa L. in ... - NIH
Sep 14, 2022 · The yield of water-free extract ranges between below 2.3% for extraction settings under 100 bar and 40 °C and above 3.1% for pressure settings ...
[32]
(PDF) Supercritical Fluid Extraction with CO2 of Curcuma longa L. in ...
Oct 13, 2025 · In comparison, supercritical fluid-based extraction recovered over 90 % of curcuminoids and produced the highest curcumin yield [39]. Organic- ...<|separator|>
[33]
Revolutionizing Curcumin Extraction: New Insights From Non ...
Jul 8, 2025 · UAE achieved a maximum yield of 72% under optimized conditions (temperature: 35°C; solid-to-solvent ratio: 1:25; particle size: 0.09 mm; ...Missing: CO2 | Show results with:CO2
[34]
Extraction and Purification of Curcuminoids from Crude Curcumin by ...
May 15, 2017 · In this work a method is developed for the extraction and purification of the three curcuminoids, curcumin (CUR), demethoxycurcumin (DMC), ...Missing: standardization | Show results with:standardization
[35]
Purification of Curcumin from Ternary Extract-Similar Mixtures of ...
There are two methods for separation of CUR from the mixture of CURDs described in the literature: by means of column or thin layer chromatography and by ...
[36]
Turmeric Oleoresin Market Size, Share & Growth 2025 to 2035
May 8, 2025 · The market is expected to be around USD 82.77 million in 2025 and is expected to rise up to USD 131.03 million by 2035 at a compound annual growth rate (CAGR) ...
[37]
India's Golden Revolution: Turmeric Export Growth - IBEF
Sep 4, 2025 · In 2023, worldwide turmeric trade reached US$ 587 million, with exports reaching US$ 320 million. Exporting value surged 13.56% during 2017–23.
[38]
https://www.ibef.org/blogs/india-s-golden-revolution-transforming-turmeric-into-a-global-powerhouse
[39]
Properties, Extraction Methods, and Delivery Systems for Curcumin ...
In order to extract turmeric oil, researchers have used steam distillation, hydro-distillation, and extraction using hexane. Hexane was combined with the oils ...
[40]
Turmeric : isolation and synthesis of important biological molecules
The main constituents of turmeric are curcuminoids. The major curcuminoids present in turmeric are curcumin (1), demethoxycurcumin (2) and bisdemethoxycurcumin ...
[41]
A synthesis of curcumin and related compounds - Pabon - 1964
Curcumin has been prepared in 80% yield from vanillin and acetylacetone/B2O3 in the presence of tri-sec. butyl borate and butylamine.
[42]
Solid-Phase Microwave Assisted Synthesis of Curcumin Analogs
Jul 1, 2012 · Turmeric contains three important analogs, curcumin, demethoxycurcumin (DMC) and bisdemethoxycurcumin ... Solid-Phase Microwave Assisted Synthesis ...
[43]
Enzyme-Catalyzed Glycosylation of Curcumin and Its Analogues by ...
Aug 29, 2019 · Overall, our study provides insights into the enzymatic synthesis of curcumin and its two analogues monoglucosides, expands the enzymatic ...
[44]
Visually Following the Hydrogenation of Curcumin to ...
Jun 20, 2013 · (8) Curcumin (1) can be easily hydrogenated to yield tetrahydrocurcumin (THC) (2) (Scheme 1), and 2 has also been reported to have potent ...Experimental Overview · Results · Assessment of Student Learning · References
[45]
Novel fluorinated curcuminoids and their pyrazole and isoxazole ...
... improve physicochemical properties such as lipophilicity and metabolic stability. ... Synthesis and thermal stability of rare earth compounds REF3, REF3·nH2O and ...
[46]
Curcumin Suppliers "Guaranteeing" Natural ... - Nutritional Outlook
Oct 14, 2016 · According to Rafi, synthetic curcumin may cost up to half as much as natural curcumin-for instance, $60/kg versus $120/kg.
[47]
US7355081B2 - Curcumin analogues and uses thereof
The present invention relates to compounds capable of acting as androgen receptor antagonists, pharmaceutical formulations containing the same, and methods ...Missing: post- | Show results with:post-
[48]
Improving Curcumin Bioavailability: Current Strategies and Future ...
Oct 17, 2021 · Poor absorption, fast metabolism, and rapid systemic clearance are the most important factors contributing to low curcumin levels in plasma and ...
[49]
Recent Developments in Delivery, Bioavailability, Absorption and ...
... curcumin dispersion in aqueous solution compared to the free form of curcumin. ... The PLGA and PLGA-PEG nanoparticles increased the curcumin mean half-life in ...
[50]
https://patents.google.com/patent/US7355081B2/en
[51]
Design of curcumin-loaded PLGA nanoparticles formulation with ...
Feb 1, 2010 · Curcumin-loaded PLGA nanoparticles showed enhanced cellular uptake, increased bioactivity in vitro, and superior bioavailability in vivo ...
[52]
Analysis of different innovative formulations of curcumin ... - PubMed
Conclusion: The data presented suggest that γ-cyclodextrin curcumin formulation (CW8) significantly improves the absorption of curcuminoids in healthy humans.
[53]
Effect of Cyclodextrin Complexation of Curcumin on its Solubility and ...
Solubility, phase solubility, and in vitro dissolution studies showed that curcumin has higher affinity for hydroxypropyl-β-CD (HPβCD) than other CDs. HPβCD ...
[54]
PLGA nanoparticles improve the oral bioavailability of curcumin in rats
Sep 14, 2011 · After oral administration of CUR-PLGA-NPs, the relative bioavailability was 5.6-fold and had a longer half-life compared with that of native ...
[55]
Preparation of curcumin-loaded chitosan/lecithin nanoparticles with ...
Moreover, the in vivo pharmacokinetic studies showed that the CCL NPs could lead to a ~ 2.64-fold increase in oral bioavailability compared with that of free ...
[56]
Influence of piperine on the pharmacokinetics of curcumin ... - PubMed
In this study, the effect of combining piperine, a known inhibitor of hepatic and intestinal glucuronidation, was evaluated on the bioavailability of curcumin ...
[57]
[PDF] GRAS Notice 000686, Curcumin from turmeric (Curcuma longa L.)
Jan 3, 2017 · This GRAS notice is for BCM-95 (curcumin) from turmeric, intended as a nutrient supplement in foods like yogurt, nutrition bars, smoothies and ...
[58]
Comparative pharmacokinetics of Theracurmin, a highly ... - NIH
Therefore, the aim of this study was to compare the bioavailability of curcumin administered as two different products of Theracurmin as well as curcumin powder ...
[59]
H-Atom Transfer Is A Preferred Antioxidant Mechanism of Curcumin
The importance of H-atom donation vs electron donation in free radical scavenging and antioxidant mechanisms of curcumin is discussed.
[60]
The role of electron-transfer and H-atom donation on the ... - PubMed
Dec 1, 2012 · Data confirmed that the antioxidant activity of curcumin's enol isomer (CurE) is not only higher than keto isomer (CurK) but also more than ...
[61]
Curcumin Protects Osteoblasts From Oxidative Stress-Induced ...
Jun 16, 2020 · Our findings demonstrated that Cur could protect osteoblasts against OS-induced dysfunction via GSK3β-Nrf2 signaling and provide a promising way for ...
[62]
Cadmium-induced toxicity is rescued by curcumin: A review - PubMed
Sep 10, 2017 · Overproduction of reactive oxygen species (ROS) as the main mechanism ... scavenging and chelating activities or Nrf2/Keap1/ARE pathway induction.
[63]
https://www.sciencedirect.com/science/article/pii/S0963996925014607
[64]
A Review of the Role of Curcumin in Metal Induced Toxicity - PMC
There are three main functional groups: an aromatic ring, β-diketone, and an alkene bridge. The β-diketone provides flexibility, and the aromatic rings provide ...
[65]
Improved Synthesis of Asymmetric Curcuminoids and ... - PubMed
Apr 14, 2022 · ... radical scavenging abilities comparable to that of curcumin (IC50 = 10.14 ± 1.04 μM). Furthermore, all the synthetic asymmetric curcuminoids ...Missing: IC50 | Show results with:IC50
[66]
Theoretical Exploration of Enhanced Antioxidant Activity in Copper ...
Feb 12, 2024 · Metal chelating ability and antioxidant properties of Curcumin-metal complexes - A DFT approach ... Both iron and copper are Fenton catalysts.
[67]
Comparative antioxidant activities of curcumin and its demethoxy ...
Stronger antioxidant activities toward lipid peroxidation and red blood cell hemolysis were also demonstrated in the hydrogenated derivatives. By the model of ...
[68]
Antioxidant activities of curcumin, demethoxycurcumin and ...
This is the first report on antioxidant activity of individual curcuminoids using the phosphomolybdenum method and linoleic acid peroxidation method.
[69]
Comparative Studies on the Antioxidant Profiles of Curcumin ... - MDPI
In the present study, our results demonstrated that curcumin and bisdemethoxycurcumin decreased hemolysis, inhibited lipid peroxidation, and restored the SOD ...
[70]
Anti-Inflammatory Effects of Curcumin in the Inflammatory Diseases
Nov 2, 2021 · Chemical structure of curcuminoids (include curcumin, demethoxycurcumin, bisdemethoxycurcumin). Inflammation is a complex physiological and ...
[71]
Curcumin blocks prostaglandin E2 biosynthesis through direct ...
Aug 14, 2009 · Curcumin modulates the expression or activation state of various transcription factors (e.g., NFκB), protein kinases (e.g., protein kinase C), ...
[72]
A State of the Art of Antioxidant Properties of Curcuminoids in ...
PC12 cells were treated simultaneously with ROT (0.1–1 μM) and curcumin (10 μM) for 24 h. PC12 treated curcumin increased cell viability and reduced oxidative ...Missing: transfer | Show results with:transfer
[73]
Curcumin: a potential anti-photoaging agent - Frontiers
According to Rainey (Rainey et al., 2015), extremely low doses (≤1 μM) of curcumin act as potent antioxidants. However, at moderate doses (5–10 μM), curcumin ...
[74]
Curcumin inhibits proliferation and induces apoptosis of human ...
Moreover, treatment with 0-30 µg/mL curcumin decreased the mitochondrial membrane potential and activated the caspase-3 and caspase-9 in a dose- and time- ...
[75]
Curcumin induces apoptosis through the mitochondria-mediated ...
Effects of curcumin on caspase-3 activities ... Caspase-3 is a key executioner of apoptosis, which is activated by an initiator caspase such as caspase-9.
[76]
Curcumin inhibits angiogenesis and improves defective ... - NIH
Curcumin significantly inhibited the tumor growth accelerated by VEGF in a dose-dependent manner and improved anemia and extramedullary hematopoiesis in livers ...Missing: G2/ | Show results with:G2/
[77]
Curcumin inhibits VEGF-mediated angiogenesis in human intestinal ...
Our findings suggest that curcumin exerts an inhibitory effect on microvascular endothelial growth, proliferation, migration and tube formation, and suppresses ...
[78]
Curcumin induces G2/M cell cycle arrest and apoptosis of head and ...
We observed that CUR significantly induced apoptosis and cell cycle arrest, inhibited angiogenesis in HNSCC. ... VEGF and tumor angiogenesis was investigated. And ...Missing: review | Show results with:review
[79]
Revisiting Curcumin in Cancer Therapy: Recent Insights into ... - MDPI
In colorectal cancer cells (CRCs), curcumin exhibits anticancer effects by activating intrinsic and extrinsic apoptosis through the modulation of molecular ...
[80]
Curcumin activates AMPK and suppresses gluconeogenic gene ...
Oct 16, 2009 · Several lines of evidence suggest that curcumin may play a beneficial role in animal models of diabetes, both by lowering blood glucose levels ...Missing: sensitivity review
[81]
Curcuminoids for Metabolic Syndrome: Meta-Analysis Evidences ...
Jun 9, 2022 · Curcumin has been reported to activate AMP-activated protein kinase (AMPK) to inhibit adipocyte differentiation. Stimulation of AMPK down- ...Table 2 · Curcumin Effect On Oxidative... · Metabolomics And...<|control11|><|separator|>
[82]
Ameliorative Effects of Curcumin on Type 2 Diabetes Mellitus - PMC
In a clinical trial, the findings detected that curcumin could improve insulin resistance, lower blood glucose levels, and reduce circulating glycogen synthase ...
[83]
α-amylase and α-glucosidase as the target enzymes - PMC - NIH
Nov 12, 2020 · Our initial assessment suggested this new class of curcumin derivatives as good antidiabetic compounds through inhibition of α-Amy and α-Gls ...
[84]
Curcumin as a mild natural α‐glucosidase inhibitor: a study on its ...
Oct 29, 2021 · Curcumin, natural dietary ingredient, is considered as mild effective inhibitors for α-glucosidase to prevent type 2 diabetes.<|control11|><|separator|>
[85]
Protective Effects of Indian Spice Curcumin Against Amyloid Beta in ...
Recent research on amyloid-β and curcumin has revealed that curcumin prevents amyloid-β aggregation and crosses the blood brain barrier (BBB), reach brain cells ...3. Curcumin And Alzheimer's... · 5. Curcumin And Amyloid Beta · 6. Curcumin And Its...
[86]
REVIEW: Curcumin and Alzheimer's Disease - PMC - PubMed Central
Recent reports have suggested therapeutic potential of curcumin in the pathophysiology of Alzheimer's disease (AD).In Vitro Studies With... · Anti‐aβ Aggregation... · In Vivo Studies With...
[87]
Anti-inflammatory effect of curcumin on neurological disorders
Oct 8, 2025 · Experimental evidence indicates that curcumin exerts neuroprotective effects by modulating the BDNF/PI3k/Akt signaling pathway, which plays a ...
[88]
SciELO Brasil - Curcumin in Alzheimer's Disease and Depression ...
A decrease in BDNF levels is associated with Alzheimer's disease and depression. • Curcumin supplementation improves BDNF levels in Alzheimer's and depression.
[89]
Antimicrobial activity of curcumin against Helicobacter pylori isolates ...
Feb 9, 2009 · Curcumin showed immense therapeutic potential against H. pylori infection as it was highly effective in eradication of H. pylori from infected mice.Missing: Staphylococcus membranes
[90]
Turmeric and curcumin as adjuncts in controlling Helicobacter pylori ...
Jun 3, 2024 · Curcumin inhibits H. pylori growth and urease activity, and may increase eradication success when added to triple regimens. It also has ...Missing: Staphylococcus membranes
[91]
Bactericidal Activity of Curcumin I Is Associated with Damaging ... - NIH
Mar 26, 2015 · Our study shows the strong antibacterial potential of curcumin I against all the tested bacteria from Gram-positive as well as Gram-negative groups.
[92]
Antibacterial Action of Curcumin against Staphylococcus aureus - NIH
Oct 24, 2016 · This review focuses on the antibacterial activities of curcumin against both methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA).
[93]
Curcumin improves wound healing by modulating collagen and ...
Curcumin increased cellular proliferation and collagen synthesis at the wound site, as evidenced by increase in DNA, total protein and type III collagen content ...
[94]
Curcumin accelerates cutaneous wound healing via multiple ... - NIH
The effects of curcumin treatment on wound healing evidently involve all phases, including inflammation, collagen deposition, development of granulation tissue, ...
[95]
Leishmanicidal effect of curcumin in vitro - PubMed
From a study to find anti-parasitic agents from natural resources, we found that curcumin showed the cytotoxicity against leishmania in vitro.
[96]
In vitro and in vivo anti-parasitic activity of curcumin nanoemulsion ...
Jun 18, 2024 · The present study aimed to assess the anti-leishmanial effects of curcumin nanoemulsion (CUR-NE) against Leishmania major (MRHO/IR/75/ER) in ...
[97]
Neuroprotective effect of Demethoxycurcumin, a natural ... - PubMed
Apr 18, 2017 · This study investigated the neuro-protective effects of the demethoxycurcumin (DMC), a derivative of curcumin against rotenone induced ...
[98]
Demethoxycurcumin, a Natural Derivative of Curcumin ... - PubMed
Feb 20, 2018 · Curcumin and their derivatives have been shown to be potent neuroprotective effectDemethoxycurcumin (DMC) amolerated the rotenone induced ...
[99]
Combination of Tolfenamic acid and curcumin induces colon cancer ...
Jan 19, 2016 · In HT29 cells, the IC50 values for TA and Cur were 55.3 μM and 12.9 μM at 24 h and 46.8 μM and 4.7 μM at 48 h, respectively. As seen in ...
[100]
Curcumin affects apoptosis of colorectal cancer cells through ATF6 ...
Jan 4, 2024 · The IC50 values of curcumin for SW620 and HT-29 cells were determined using Graphpad Prism8.0 software, yielding values of 17.42 μM and ...
[101]
Evaluation of in vitro anti-proliferative and immunomodulatory ... - NIH
Dose-response curves were obtained and demonstrated IC50 values of the curcuminoids ranged from 11.0 to 28.2 μg/ml in three cancer cell lines. On the ...
[102]
IC50 values of C212 and curcumin in cancer cell lines (48-h ...
A number of downstream targets including VEGF, Akt and STAT3 undergo suppression by curcumin in suppressing progression of hematological cancers. Curcumin ...<|control11|><|separator|>
[103]
Phytosomal curcumin alleviates collagen-induced arthritis...
Results: Phytosomal curcumin reduced the clinical severity and paw swelling in CIA-induced rats, which was accompanied by a reduction in the number of ...
[104]
Full article: Curcumin alleviates rheumatoid arthritis progression ...
Curcumin reduced arthritis index and foot swelling in CII-stimulated mice ... The anti-inflammatory effects of curcumin have been reported in previous studies ...
[105]
Potential Effect of Curcumin in Lowering Blood Glucose Level ... - NIH
Sep 4, 2024 · Our study indicates that curcumin has a beneficial effect in diabetic rats by reducing blood glucose levels and a protective effect on the pancreas.
[106]
Antidiabetic Properties of Curcumin II: Evidence from In Vivo Studies
Administration of C57BL/KsJ-db/db mice with curcumin (0.02% wt/wt) for 6 weeks resulted in significantly reduced serum glucose and HbA1c levels and an increased ...
[107]
Effects of curcumin on global gene expression profiles in the highly ...
In the present study, microarray gene expression analysis was applied to identify the curcumin-regulated genes in a highly invasive human breast carcinoma cell ...
[108]
Anti-invasive gene expression profile of curcumin in lung ... - PubMed
In this study, microarray analysis of gene expression profiles were used to characterize the anti-invasive mechanisms of curcumin in highly invasive lung ...Missing: studies | Show results with:studies
[109]
Phosphoproteomic Analysis Identifies Signaling Pathways ... - PubMed
Materials and methods: Phosphoproteomic analyses were performed using SW480 and SW620 human colon cancer cells to identify curcumin-affected signaling pathways.Missing: mapping | Show results with:mapping
[110]
SWATH-MS based quantitative proteomics analysis reveals that ...
Jul 25, 2018 · SWATH-MS based quantitative proteomics analysis reveals that curcumin alters the metabolic enzyme profile of CML cells by affecting the activity ...
[111]
The Neuroprotective Role of Curcumin: From Molecular Pathways to ...
Sep 6, 2025 · The Neuroprotective Role of Curcumin: From Molecular Pathways to Clinical Translation-A Narrative Review. Nutrients. 2025 Sep 6;17(17):2884 ...Missing: demethoxycurcumin | Show results with:demethoxycurcumin
[112]
Unraveling the Systems Biology of Curcumin: A Mini-review of its ...
Sep 10, 2025 · Curcumin demonstrates significant regulatory influence over multiple DM-associated signaling pathways, primarily by modulating inflammation, ...
[113]
Novel Curcumin Oral Delivery Systems - Anticancer Research
Available evidence indicates that only minute amounts of free curcumin reach the peripheral blood after high-dose oral administration in animals and humans.
[114]
Curcumin | Linus Pauling Institute | Oregon State University
Metabolism and Bioavailability. Clinical trials in humans indicate that the systemic bioavailability of orally administered curcumin is relatively low (3-5) and ...
[115]
Curcumin and multiple health outcomes: critical umbrella review of ...
Jun 5, 2025 · The findings suggest that curcumin has potentially positive effects on lipid profiles, blood pressure, inflammatory markers and oxidative stress.
[116]
Is Curcumin Intake Really Effective for Chronic Inflammatory ... - MDPI
The objective of this review was to clarify the effect of curcumin on chronic inflammatory metabolic disease by examining meta-analyses of randomized controlled ...
[117]
Efficacy and safety of curcumin therapy for knee osteoarthritis
Mar 1, 2024 · The SUCRA results suggest that curcumin is the most effective intervention to reduce the VAS pain scores of KOA patients (Fig. 5A). The results ...
[118]
Curcumin use in ulcerative colitis: is it ready for prime time? A ... - NIH
The pooled odds ratio for clinical remission with curcumin use was 2.9 (95%CI 1.5-5.5, I2=45, P=0.002), clinical response was 2.6 (95%CI 1.5-4.5, I2=74%, P= ...
[119]
Effectiveness of Curcumin on Outcomes of Hospitalized COVID-19 ...
Six studies were identified which showed that curcumin supplementation led to a significant decrease in common symptoms, duration of hospitalization and deaths.
[120]
A novel amorphous preparation improved curcumin bioavailability in ...
Theracurmin® achieved a 27-fold higher area under the plasma concentration-time curve (AUC) at 0–6 h in humans compared with native curcumin. The Cmax of ...
[121]
Curcumin Formulations for Better Bioavailability: What We Learned ...
Mar 13, 2023 · We extensively reviewed clinical trials on various generations of curcumin formulations and their safety and efficacy in the treatment of many diseases.
[122]
Natural Products for Cancer Prevention and Interception - NIH
Jan 20, 2024 · Those taking 4 g of curcumin daily had a 40% reduction in ACF, whereas a separate clinical trial evaluating individuals with familial ...
[123]
Curcumin improves memory and mood, new UCLA study says
Jan 22, 2018 · In memory tests, the people taking curcumin improved by 28 percent over the 18 months. Those taking curcumin also had mild improvements in mood, ...
[124]
Curcumin for the clinical treatment of inflammatory bowel diseases
Mar 23, 2025 · This meta-analysis of 13 placebo-controlled RCTs found that curcumin showed significant benefits in achieving remission and clinical response in ...Abstract · Introduction · Results · Discussion
[125]
Acute and chronic toxicity studies in mice and hamsters
Most previous articles have reported LD50 of curcumin to be approximately 2 g/kg bw (in GHS category 5 of OECD guidelines for oral toxicity studies) in rats and ...
[126]
Systematic and comprehensive investigation of the toxicity of ... - NIH
Nov 19, 2015 · ... lethal dose, 50% (LD50) of CEC for mice was >5,000 mg/kg bw. Acute toxicity in rats. No clinical signs of toxicity were observed in any of ...
[127]
cumin Supplement Side Effects & Diarrhea - ConsumerLab.com
Aug 8, 2017 · Yes, unfortunately diarrhea is one of the reported side-effects of curcumin supplements. The risk of diarrhea may increase with higher doses of curcumin.
[128]
Turmeric - LiverTox - NCBI Bookshelf - NIH
Jun 16, 2025 · One reason given for the safety and lack of hepatotoxicity of curcumin was that it is poorly absorbed by the oral route, and it was unclear ...
[129]
Acute liver injury following turmeric use in Tuscany: An analysis of ...
Jul 13, 2020 · In all cases, hepatotoxicity was associated with Curcuma longa formulations with high bioavailability and high dosage of curcumin/curcuminoids.Abstract · METHODS · RESULTS · DISCUSSION
[130]
An Evaluation of the Genotoxicity and Subchronic Oral Toxicity ... - NIH
A bacterial reverse mutation test was conducted to investigate the mutagenic potential of synthetic curcumin according to the procedures described by Ames et al ...
[131]
A dose dependent anti-genotoxic effect of turmeric - ScienceDirect
Curcumin is able to protect DNA against oxidative damage [6], and exhibits anti-mutagenic activity in the Ames Salmonella test [7]. It also shows an anti ...
[132]
Turmeric - Uses, Side Effects, and More - WebMD
It might cause a menstrual period or stimulate the uterus, putting the pregnancy at risk. Do not take medicinal amounts of turmeric if you are pregnant.
[133]
Turmeric: potential adverse effects - Welsh Medicines Advice Service
Oct 22, 2024 · Avoid turmeric and curcumin in individuals with bile duct obstruction, cholangitis (bile duct inflammation), liver disease, gallstones, or any biliary disease.Missing: choleretic | Show results with:choleretic
[134]
Effect of different curcumin dosages on human gall bladder - Rasyid
Nov 14, 2002 · A 20 mg amount of curcumin is capable of contracting the gall bladder by up to 29% within an observation time of 2 h.Missing: choleretic | Show results with:choleretic
[135]
Curcumin supplementation improves the clinical outcomes ... - Nature
Aug 4, 2025 · Mild adverse effects were reported, including nausea (13.9%), headache (11.1%), yellow stool (11.1%), and diarrhea (5.6%). It is concluded that ...