Part of how curcumin works as a chemopreventive agent is via activating its antioxidant and phase II detoxifying enzymes, as well as nuclear factor (erythroid-2 related) factor 2 (Nrf2)[1]. With IC50s of 25, 19, and 17.5 μM for 24, 48, and 72-hour MTT experiments, respectively, curcumin suppresses the proliferation of T47D cells. For 24, 48, and 72 hours of exposure, the IC50s of the curcumin and silibinin mixture against T47D cells are 17.5, 15, and 12 μM, respectively[2]. AGS and HT-29 cell lines exhibit apoptotic cell death in response to curcumin (2.5-80 μM); the IC50 values for these cell lines are 21.9±0.1 and 40.7±0.5 μM, respectively. In AGS and HT-29 cells, caspase activity are necessary for curcumin-induced apoptosis. Curcumin causes mitochondrial Ca2+ overloading and ER Ca2+ decline[3]. Curcumin dose-dependently promotes LNCaP and PC-3 cells to enter the G2/M cell cycle arrest. Curcumin decreases the protein levels of c-Jun and AR while increasing the protein level of the NF-kappaB inhibitor IkappaBalpha[5].

Compared to the rats exposed to CMS, curcumin (10 mg/kg, po) significantly avoids declines in the percentage of sucrose consumption. When stressed rats are treated with curcumin, their levels of TNF-α and IL-6 are significantly prevented from rising[4]. In chronic constriction injury (CCI) rats, curcumin reduces the binding of p300/CREB-binding protein (CBP) at the brain-derived neurotrophic factor (BDNF) promoter at 20 mg/kg (ip), as well as the binding of P300/CBP at 40 mg/kg and the binding of all four proteins of p300/CBP and H3K9ac/H4K5ac at 60 mg/kg[6].

Absorption, Distribution and Excretion
Curcumin has a low absorption rate in the gastrointestinal tract. In a rat study, a single oral dose of 2 g of curcumin resulted in plasma concentrations below 5 μg/mL, indicating low intestinal absorption. After oral administration of 1 g/kg body weight of curcumin to rats, approximately 75% of the dose was excreted in feces, with only trace amounts detected in urine. When rats received a single oral dose of 400 mg of curcumin, approximately 60% was absorbed, and 40% was excreted unchanged in feces within 5 days. Following intraperitoneal injection, 73% of the drug was excreted in feces, and 11% in bile. Radioactivity was detected in the liver and kidneys of rats after oral administration of radiolabeled curcumin. Currently, there are no pharmacokinetic data. Following oral and intraperitoneal injection of (3)H-curcumin, most of the radioactive material was excreted in feces. Curcumin administered intravenously and intraperitoneally was well excreted in the bile of cannulated rats.
After oral administration of 1 g/kg curcumin, approximately 75% is excreted in feces, with very low levels in urine. Measurements of plasma concentration and bile excretion indicate poor intestinal absorption of curcumin.
This study aimed to develop a thermosensitive nasal hydrogel of curcumin and improve its brain-targeting efficiency. The study evaluated the hydrogel's gelation temperature, gelation time, drug release characteristics, ciliary toxicity, and nasobrain transport in a rat model. The developed nasal hydrogel, composed of Pluronic F127 and Poloxamer 188, exhibited a shorter gelation time, a longer ciliary transport time, and maintained curcumin retention in the rat nasal cavity for an extended period at body temperature. Dialysis membrane assays showed that the hydrogel's drug release mechanism was diffusion-controlled release; while non-membrane assays showed dissolution-controlled release. Ciliary toxicity studies demonstrated that the hydrogel maintained the integrity of the nasal mucosa for 14 days after application. Following intranasal administration of curcumin hydrogel, the targeting efficiencies of the drug in the brain, cerebellum, hippocampus, and olfactory bulb were 1.82 times, 2.05 times, 2.07 times, and 1.51 times higher than those after intravenous administration of curcumin solution, respectively. This indicates that the hydrogel significantly improved the distribution of curcumin in rat brain tissue, particularly in the cerebellum and hippocampus. We have developed a thermosensitive curcumin nasal gel with good gelation, release properties, biocompatibility, and enhanced brain absorption efficiency. /Curcumin Intranasal Thermosensitive Hydrogel/
…However, the systemic bioavailability of curcumin is low, therefore improving its bioavailability is crucial for its clinical application. Many approaches, such as adjuvant drug delivery systems and structural modifications, have been shown to have potential effects.
For more data on the absorption, distribution, and excretion (complete) of curcumin (6 types in total), please visit the HSDB record page.

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Metabolism/Metabolites
Curcumin is initially rapidly metabolized in the intestine, forming curcumin glucuronide and curcumin sulfate via O-binding. Other metabolites include tetrahydrocurcumin, hexahydrocurcumin, and hexahydrocurcumol, which are formed through reduction reactions. Curcumin may also undergo intense secondary metabolism in the liver, with its major metabolites being glucuronides of tetrahydrocurcumin and hexahydrocurcumin, as well as other metabolites such as dihydroferruvic acid and trace amounts of ferulic acid. Hepatic metabolites are expected to be excreted via bile. Some curcumin metabolites, such as tetrahydrocurcumin, retain their anti-inflammatory and antioxidant properties.
Following intravenous and intraperitoneal injection of (3)H-curcumin, it is excreted in the bile of cannulated rats. The major metabolites are glucuronides of tetrahydrocurcumin and hexahydrocurcumin. The minor metabolites are dihydroferruvic acid and trace amounts of ferulic acid.
Known human metabolites of curcumin include curcumin 4-O-glucuronide and O-demethylcurcumin.

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Biological half-life
No pharmacokinetic data are currently available.

Interactions
Arsenic contamination in groundwater in West Bengal, India, has long been a health concern. DNA oxidative stress is considered a potential mechanism of arsenic carcinogenicity. Curcumin, a phytochemical derived from turmeric, is a potent antioxidant and antimutagenic agent. Utilizing curcumin to prevent DNA damage may be an effective strategy against arsenic toxicity. This field trial in Chakta district, West Bengal, evaluated the role of curcumin in combating arsenic genotoxicity. DNA damage in human lymphocytes was assessed using comet assays and fluorescence-activated DNA unwinding assays. Blood curcumin levels were analyzed using high-performance liquid chromatography (HPLC). Arsenic-induced oxidative stress and the antagonistic effect of curcumin were investigated by observing the generation of reactive oxygen species (ROS), lipid peroxidation, and protein carbonylation. Researchers also analyzed antioxidant enzymes such as catalase, superoxide dismutase, glutathione reductase, glutathione S-transferase, glutathione peroxidase, and non-enzymatic glutathione. Blood samples from endemic areas showed severe DNA damage, elevated levels of reactive oxygen species (ROS) and lipid peroxidation, and decreased antioxidant activity. Three months of curcumin intervention reduced DNA damage, inhibited ROS generation and lipid peroxidation, and enhanced antioxidant activity. Therefore, curcumin may have a protective effect against arsenic-induced DNA damage. This study aimed to determine whether curcumin could alleviate acute and chronic radiation-induced skin toxicity and to detect the expression of inflammatory cytokines (interleukin [IL]-1, IL-6, IL-18, IL-1Ra, tumor necrosis factor [TNF]-α, and lymphotoxin-β) or pro-fibrotic cytokines (transforming growth factor [TGF]-β) in the acute and chronic phases. Curcumin was administered to C3H/HeN mice via gavage or intraperitoneal injection at the following times: 5 days before radiation; 5 days after radiation; or 5 days before and 5 days after radiation. Skin damage was assessed in mice 15–21 days (acute phase) and 90 days (chronic phase) after a single 50 Gy radiation dose to the hind limb. Skin and muscle tissues were collected for cytokine mRNA assays. Administration of curcumin before and after radiation therapy significantly reduced acute and chronic skin toxicity in mice (p < 0.05). Furthermore, curcumin significantly reduced the mRNA expression levels of early-response cytokines (IL-1, IL-6, IL-18, TNF-α, and lymphotoxin-β) and the pro-fibrotic cytokine TGF-β in skin tissue 21 days post-radiation. Curcumin demonstrated a protective effect against radiation-induced skin damage in mice, characterized by downregulation of inflammatory and pro-fibrotic cytokines in irradiated skin and muscle, particularly in the early stages of radiation therapy. These results may provide a molecular basis for the application of curcumin in clinical radiation therapy. This study aimed to evaluate the protective effect of curcumin against selenium-induced hepatotoxicity and nephrotoxicity in Wistar rats. Light microscopy revealed mononuclear cell infiltration, vacuolation, necrosis, and significant degeneration in the livers of rats treated with selenium alone. Liver sections from the control group showed normal parenchymal cell morphology, with intact hepatocytes and sinusoids. In the kidneys of rats treated with selenium alone, vacuolar degeneration, cell proliferation accompanied by fibrosis, thickening of capillary walls, and atrophy of the glomerular capillary plexus were observed in the epithelial cells. Similar changes were observed in rats simultaneously treated with selenium and curcumin, as well as in rats treated with selenium first and then curcumin 24 hours later. Notably, rats treated with curcumin first and then selenium 24 hours later did not exhibit selenium-induced liver and kidney degeneration. This clearly demonstrates that curcumin has a protective effect against selenium toxicity. To understand the possible mechanism of action of curcumin, researchers used immunohistochemistry to analyze the expression of inducible nitric oxide synthase (iNOS). The results showed increased iNOS expression in liver and kidney tissues induced by selenium alone. This high level of iNOS was inhibited in rat liver and kidney tissues pretreated with curcumin for 24 hours before being treated with selenium. Based on histological results, it can be concluded that curcumin has a protective effect against selenium-induced hepatotoxicity and nephrotoxicity, which may be achieved through the regulation of iNOS expression by curcumin. A mononuclear (1:1) zinc complex of curcumin, Zn(II)-curcumin, was synthesized, and its anti-ulcer activity against pyloric ligation-induced gastric ulcers in rats was investigated. The structure of Zn(II)-curcumin was determined by elemental analysis, nuclear magnetic resonance (NMR), and thermogravimetric-differential thermal analysis (TG-DTA). It was found that the zinc atom is coordinated with an acetate group and a water molecule through the ketone-enol group of curcumin. Compared with the control group (P<0.001) and curcumin alone (24 mg/kg, P<0.05), Zn(II)-curcumin (12, 24, and 48 mg/kg) inhibited gastric injury in a dose-dependent manner and significantly reduced gastric volume, free acidity, total acidity, and pepsin activity. Reverse transcription polymerase chain reaction (RT-PCR) analysis showed that, compared with the control group, Zn(II)-curcumin significantly inhibited the induced expression of nuclear factor-κB (NF-κB), transforming growth factor-β1 (TGF-β1), and interleukin-8 (IL-8) (P<0.05). These results indicate that Zn(II)-curcumin prevented pyloric ligation-induced damage in rats by inhibiting NF-κB activation and subsequent pro-inflammatory cytokine production, suggesting a synergistic effect between curcumin and zinc…/Zn(II)-curcumin complex/
For more complete data on interactions of curcumin (12 in total), please visit the HSDB record page.

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Non-human toxicity values
Mice oral LD50 > 2000 mg/kg body weight / solid lipid curcumin granules /
Rat oral LD50 > 2000 mg/kg body weight / solid lipid curcumin granules /
Zebrafish embryo LD50 7.5 μM (24 hours); Zebrafish larva LD50 5 μM (24 hours)
Mice oral LD50 > 2000 mg/kg
Rat oral LD50 > 5000 mg/kg /curcumin oil /

[1]. Curcumin attenuates arsenic-induced hepatic injuries and oxidative stress in experimental mice through activation of Nrf2 pathway, promotion of arsenic methylation and urinary excretion. Food Chem Toxicol. 2013 Jul 18. pii: S0278-6915(13)004.

[2]. Curcumin and Silibinin Inhibit Telomerase Expression in T47D Human Breast Cancer Cells. Asian Pac J Cancer Prev. 2013;14(6):3449-53.

[3]. Cao A, et all. Curcumin induces apoptosis in human gastric carcinoma AGS cells and colon carcinoma HT-29 cells through mitochondrial dysfunction and endoplasmic reticulum stress. Apoptosis. 2013 Jul 24. [Epub ahead of print].

[4]. Antidepressant-like effects of curcumin in chronic mild stress of rats: Involvement of its anti-inflammatory action. Prog Neuropsychopharmacol Biol Psychiatry. 2013 Jul 20. pii: S0278-5846(13)00150-4.

[5]. Curcumin induces cell cycle arrest and apoptosis of prostate cancer cells by regulating the expression of IkappaBalpha, c-Jun and androgen receptor. Pharmazie. 2013 Jun;68(6):431-4.

[6]. Curcumin alleviates neuropathic pain by inhibiting p300/CBP histone acetyltransferase activity-regulated expression of BDNF and cox-2 in a rat model. PLoS One. 2014 Mar 6;9(3):e91303.

[7]. Curcumin, a novel p300/CREB-binding protein-specific inhibitor of acetyltransferase, represses the acetylation of histone/nonhistone proteins and histone acetyltransferase-dependent chromatin transcription. J Biol Chem. 2004 Dec 3;279(49):51163-71.

[8]. Curcumin induces stabilization of Nrf2 protein through Keap1 cysteine modification. Biochem Pharmacol. 2020 Mar;173:113820.

Therapeutic Uses
Curcumin (Cum) has been reported to possess potential chemopreventive and chemotherapeutic activities, influencing multiple processes and inducing cell cycle arrest, differentiation, and apoptosis, thus playing a role in various cancers. However, the low solubility of curcumin limits its further application in cancer treatment. Previously, we reported the preparation of curcumin-loaded nanoparticles (Cum-NPs) using amphiphilic methoxy polyethylene glycol-polycaprolactone (mPEG-PCL) block copolymers. This study demonstrates that Cum-NPs exhibit superior antitumor efficacy compared to free curcumin in lung cancer treatment. In vivo evaluation further confirmed that, in an established A549 transplant mouse model, Cum-NPs could delay tumor growth, thus demonstrating a superior anticancer effect compared to free curcumin. Furthermore, at therapeutic doses, Cum-NPs showed minimal toxicity to normal tissues, including bone marrow, liver, and kidneys. These results demonstrate that curcumin nanoparticles (Cum-NPs) can effectively inhibit the growth of human lung cancer with minimal toxicity to normal tissues, showing promise as a clinically effective treatment. Therefore, further research is warranted to evaluate the feasibility of its clinical application. / Curcumin-loaded nanoparticles /
Exploring Therapy
Amyloid (Aβ) accumulation in senile plaques is a hallmark lesion of Alzheimer's disease (AD). Molecular design targeting amyloid pathology in tissues is receiving increasing attention, both in diagnosis and treatment. Curcumin is a fluorescent molecule with high affinity for Aβ peptides, but its low solubility limits its clinical application. We designed curcumin-modified nanoliposomes with curcumin exposed on their surface. These nanoliposomes are monodisperse and stable. In vitro experiments showed that they are non-toxic, downregulate amyloid secretion, and partially inhibit Aβ-induced toxicity. They potently labeled Aβ deposits in postmortem brain tissue of Alzheimer's disease (AD) patients and APPxPS1 mice. Injection of curcumin-conjugated nanoliposomes into the hippocampus and neocortex of these mice revealed that the nanoliposomes could specifically stain Aβ deposits in vivo. Curcumin-conjugated nanoliposomes hold promise for the diagnosis and targeted drug delivery of Alzheimer's disease. In this preclinical study, researchers explored the application of curcumin-conjugated nanoliposomes as a potential diagnostic and targeted drug delivery system for Alzheimer's disease. Results showed that the nanoliposomes could strongly label Aβ deposits in human and mouse brain tissues and downregulate amyloid peptide secretion in vitro, preventing Aβ-induced toxicity. /Curcumin-conjugated nanoliposomes/
Exploring Therapeutics
The anti-inflammatory agent curcumin can selectively eliminate malignant cells rather than normal cells. This study investigated the effects of curcumin on Lewis lung cancer (LLC) cell lines and characterized the surviving cell subpopulations after curcumin treatment. Cell density was measured after 30 hours of treatment with curcumin concentrations ranging from 10 to 60 μM. Due to the high cell loss rate at a concentration of 60 μM, this concentration was chosen to screen surviving cells and establish a new cell line. The resulting cell line grew approximately 20% slower than the original LLC cell line and, according to ELISA results, had lower levels of two biomarkers, NF-κB and ALDH1A (used to identify more aggressive cancer cells). The authors also subcutaneously injected cells from both the original and surviving cell lines into syngeneic C57BL/6 mice and monitored tumor growth over three weeks, finding that the curcumin-treated surviving cell line remained tumorigenic. Since it has been reported that curcumin combined with light exposure can more effectively kill cancer cells, the authors investigated whether this approach could enhance the therapeutic effect of curcumin on LLC cells. When LLC cells were exposed to both curcumin and fluorescent light, cell death induced by 20 μM curcumin increased by approximately 50%, supporting the potential of curcumin combined with white light for treatment. This study is the first to characterize a curcumin-tolerant subset of lung cancer cells. Studies have shown that high concentrations of curcumin either screen for subpopulations of cells with lower invasiveness or induce the production of such cells. These findings further support curcumin as an adjunct therapy to traditional chemotherapy or radiotherapy for lung cancer and other cancers. 5-Fluorouracil (5-FU) is the first rationally designed antimetabolite that exerts its therapeutic effect by inhibiting thymidylate synthase (TS), an enzyme essential for DNA synthesis and repair. However, long-term exposure to 5-fluorouracil (5-FU) induces thymidylate synthase (TS) overexpression, leading to resistance in cancer cells. Multiple studies have confirmed that curcumin is an effective chemosensitizer that can counteract resistance induced by various chemotherapeutic drugs. This study is the first to demonstrate, at the mechanistic level, that curcumin can effectively enhance the sensitivity of breast cancer cells to 5-FU, thereby reducing its toxicity and resistance. Studies have found that 10 μM 5-FU and 10 μM curcumin can exert synergistic cytotoxic effects in different types of breast cancer cells by enhancing apoptosis, and this effect is independent of cell receptor status. The study also found that curcumin can enhance the sensitivity of breast cancer cells to 5-fluorouracil (5-FU) by downregulating nuclear factor-κB (NF-κB) in a TS-dependent manner. This finding was confirmed by silencing TS and inactivating NF-κB, both of which reduced the chemosensitizing effect of curcumin. Silencing TS inhibited 5-FU-induced NF-κB activation, while inactivating NF-κB did not affect 5-FU-induced TS upregulation, confirming that TS is upstream of NF-κB and regulates NF-κB activation in the 5-FU-induced signaling pathway. Although the Akt/PI3 kinase and mitogen-activated protein kinase pathways can be activated by 5-FU and downregulated by curcumin, they do not play a role in regulating this synergistic effect. Because curcumin is a pharmacologically safe and cost-effective compound, its combination with 5-fluorouracil (5-FU) may enhance the therapeutic index of 5-FU if in vivo studies and clinical trials confirm this. For more complete data on the therapeutic uses of curcumin (out of 23), please visit the HSDB record page. Pharmacodynamics: Intravenous injection of 25 mg/kg body weight of curcumin in rats increased bile flow by 80% to 120%. In an inflammatory rat model, curcumin inhibited edema formation. In nude mice injected subcutaneously with prostate cancer cells, curcumin significantly reduced cell proliferation and significantly increased apoptosis and microvessel density. Curcumin may exert its choleretic effect by increasing bile excretion of bile acids, cholesterol, and bilirubin, as well as increasing bile solubility. Curcumin inhibited arachidonic acid-induced platelet aggregation in vitro.

C21H20O6

368.38

368.125

458-37-7

Curcumin-d6;1246833-26-0

969516

Yellow to orange solid powder

1.3±0.1 g/cm3

593.2±50.0 °C at 760 mmHg

183 °C

209.7±23.6 °C

0.0±1.8 mmHg at 25°C

1.672

2.85

2

6

8

27

507

0

COC1=C(C=CC(=C1)/C=C/C(=O)CC(=O)/C=C/C2=CC(=C(C=C2)O)OC)O

VFLDPWHFBUODDF-FCXRPNKRSA-N

InChI=1S/C21H20O6/c1-26-20-11-14(5-9-18(20)24)3-7-16(22)13-17(23)8-4-15-6-10-19(25)21(12-15)27-2/h3-12,24-25H,13H2,1-2H3/b7-3+,8-4+

(1E,6E)-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione

Turmeric Yellow NSC32982Diferuloylmethane NSC-32982Curcumincurcumin I C.I. 75300 Natural Yellow 3

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~100 mg/mL (~271.46 mM)

Solubility in Formulation 1: ≥ 3 mg/mL (8.14 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 30.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: 3 mg/mL (8.14 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 30.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: 25 mg/mL (67.86 mM) in 1% (w/v) carboxymethylcellulose (CMC) (add these co-solvents sequentially from left to right, and one by one), Suspension solution; with ultrasonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)