from NIH PubChem
EXPL THER Curcumin (Cum) has been reported to have potential chemo-preventive and chemotherapeutic activity through influencing various processes, inducing cell cycle arrest, differentiation and apoptosis in a series of cancers. However, the poor solubility of Cum limits its further applications in the treatment of cancer. /The authors/ have previously reported Cum-loaded nanoparticles (Cum-NPs) prepared with amphilic methoxy poly(ethylene glycol)-polycaprolactone (mPEG-PCL) block copolymers. The current study demonstrated superior antitumor efficacy of Cum-NPs over free Cum in the treatment of lung cancer. In vivo evaluation further demonstrated superior anticancer effects of Cum-NPs by delaying tumor growth compared to free Cum in an established A549 transplanted mice model. Moreover, Cum-NPs showed little toxicity to normal tissues including bone marrow, liver and kidney at a therapeutic dose. These results suggest that Cum-NPs are effective to inhibit the growth of human lung cancer with little toxicity to normal tissues, and could provide a clinically useful therapeutic regimen. They thus merit more research to evaluate the feasibility of clinical application./ Curcumin-loaded nanoparticles/ Abstract:PubMed
Yin HT et al; Asian Pac J Cancer Prev 14 (1): 409-12 (2013)
EXPL THER Accumulation of amyloid peptide (Abeta) in senile plaques is a hallmark lesion of Alzheimer disease (AD). The design of molecules able to target the amyloid pathology in tissue is receiving increasing attention, both for diagnostic and for therapeutic purposes. Curcumin is a fluorescent molecule with high affinity for the Abeta peptide but its low solubility limits its clinical use. Curcumin-conjugated nanoliposomes, with curcumin exposed at the surface, were designed. They appeared to be monodisperse and stable. They were non-toxic in vitro, down-regulated the secretion of amyloid peptide and partially prevented Abeta -induced toxicity. They strongly labeled Abeta deposits in post-mortem brain tissue of AD patients and APPxPS1 mice. Injection in the hippocampus and in the neocortex of these mice showed that curcumin-conjugated nanoliposomes were able to specifically stain the Abeta deposits in vivo.Curcumin-conjugated nanoliposomes could find application in the diagnosis and targeted drug delivery in AD. In this preclinical study, curcumin-conjugated nanoliposomes were investigated as possible diagnostics and targeted drug delivery system in Alzheimer’s disease, demonstrating strong labeling of Abeta deposits both in human tissue and in mice, and in vitro downregulation of amyloid peptide secretion and prevention of Abeta -induced toxicity./ Curcumin-conjugated nanoliposomes/ Abstract: PubMed
Lazar AN et al; Nanomedicine 9 (5): 712-21 (2013)
EXPL THER The anti-inflammatory agent curcumin can selectively eliminate malignant rather than normal cells. The present study examined the effects ofcurcumin on the Lewis lung carcinoma (LLC) cell line and characterized a subpopulation surviving curcumin treatments. Cell density was measured aftercurcumin was applied at concentrations between 10 and 60 uM for 30 hours. Because of the high cell loss at 60 uM, this dose was chosen to select for surviving cells that were then used to establish a new cell line. The resulting line had approximately 20% slower growth than the original LLC cell line and based on ELISA contained less of two markers, NF-kB and ALDH1A, used to identify more aggressive cancer cells. /The authors/ also injected cells from the original and surviving lines subcutaneously into syngeneic C57BL/6 mice and monitored tumor development over three weeks and found that the curcuminsurviving-line remained tumorigenic. Because curcumin has been reported to kill cancer cells more effectively when administered with light, /the authors/ examined this as a possible way of enhancing the efficacy of curcumin against LLC cells. When LLC cells were exposed to curcumin and light from a fluorescent lamp source, cell loss caused by 20 uM curcumin was enhanced by about 50%, supporting a therapeutic use of curcumin in combination with white light. This study is the first to characterize a curcumin-surviving subpopulation among lung cancer cells. It shows that curcumin at a high concentration either selects for an intrinsically less aggressive cell subpopulation or generates these cells. The findings further support a role for curcumin as an adjunct to traditional chemical or radiation therapy of lung and other cancers.[Yan D et al; J Cancer 3: 32-41 (2012)] Full text: PMC3253430 Abstract: PubMed
EXPL THER 5-Fluorouracil (5-FU) is the first rationally designed antimetabolite, which achieves its therapeutic efficacy through inhibition of the enzymethymidylate synthase (TS), which is essential for the synthesis and repair of DNA. However, prolonged exposure to 5-FU induces TS overexpression, which leads to 5-FU resistance in cancer cells. Several studies have identified curcumin as a potent chemosensitizer against chemoresistance induced by various chemotherapeutic drugs. In this study, /investigators/ report for the first time, with mechanism-based evidences, that curcumin can effectively chemosensitize breast cancer cells to 5-FU, thereby reducing the toxicity and drug resistance. /The authors/ found that 10 uM 5-FU and 10 uM curcumin induces a synergistic cytotoxic effect in different breast cancer cells, independent of their receptor status, through the enhancement of apoptosis. Curcumin was found to sensitize the breast cancer cells to 5-FU through TS-dependent downregulation of nuclear factor-kB (NF-kB), and this observation was confirmed by silencing TS and inactivating NF-kB, both of which reduced the chemosensitizing efficacy of curcumin. Silencing of TS suppressed 5-FU-induced NF-kB activation, whereas inactivation of NF-kB did not affect 5-FU-induced TS upregulation, confirming that TS is upstream of NF-kB and regulates the activation of NF-kB in 5-FU-induced signaling pathway. Although Akt/PI3kinase and mitogen-activated protein kinase pathways are activated by 5-FU and downregulated by curcumin, they do not have any role in regulating the synergism. As curcumin is a pharmacologically safe and cost-effective compound, its use in combination with 5-FUmay improve the therapeutic index of 5-FU, if corroborated by in vivo studies and clinical trials.[Vinod BS et al; Cell Death Dis 4: e505 (2013)] Full text:PMC3734809 Abstract: PubMed
EXPL THER This study was carried out to evaluate the anti parasitic potential of silver, chitosan, and curcumin nanoparticles as anti-Giardia agents. Non-treated infected control rats were inoculated with Giardia lamblia cysts in a dose of 2×10+5 cysts/rat. Experimental group was infected then treated withcurcumin, curcumin nanoparticles, chitosan, chitosan nanoparticles, and silver nanoparticles as single or combined therapy. The number of Giardia cysts in stools and trophozoites in intestinal sections were detected. Toxicity of nanoparticles was evaluated by comparing hematological and histopathological parameters of the normal control group and treated non-infected control group. The amount of silver was also measured in the liver, kidney, small intestine, lung, and brain of rats treated with silver nanoparticles. The number of the parasites in stool and small intestinal sections decreased in treated infected rats compared with infected non-treated ones. The effect in the single therapy was better with nanoparticles, and the best effect was detected in nano-silver. The combined therapy gave better results than single. Combination between nanoparticles was better than the combination of nano-forms and native chitosan andcurcumin. The best effect was detected in combinations of nano-silver and nano-chitosan but with no full eradication. In conclusion, the highest effect and complete cure was gained by combining the three nano-forms. The parasite was successfully eradicated from stool and intestine. None of the treatments exhibited any toxicity. Accumulated silver in different organs was within the safe limits./ Curcumin nanoparticles/ Abstract: PubMed
Said DE et al; Parasitol Res 111 (2): 545-54 (2012)
EXPL THER Radiation pneumonitis (RP) is an important dose-limiting toxicity during thoracic radiotherapy. Previous investigations have shown that curcumin is used for the treatment of inflammatory conditions and cancer, suggesting that curcumin may prevent RP and sensitize cancer cells to irradiation. However, the clinical advancement of curcumin is limited by its poor water solubility and low bioavailability after oral administration. Here, a water-soluble liposomalcurcumin system was developed to investigate its prevention and sensitizing effects by an intravenous administration manner in mice models. The results showed that liposomal curcumin inhibited nuclear factor-kappaB pathway and downregulated inflammatory factors including tumor necrosis factor-alpha, interleukin (IL)-6, IL-8, and transforming growth factor-beta induced by thoracic irradiation. Furthermore, the combined treatment with liposomal curcumin and radiotherapy increased intratumoral apoptosis and microvessel responses to irradiation in vivo. The significantly enhanced inhibition of tumor growth also was observed in a murine lung carcinoma (LL/2) model. There were no obvious toxicities observed in mice. The current results indicate that liposomal curcumin can effectively mitigate RP, reduce the fibrosis of lung, and sensitize LL/2 cells to irradiation. This study also suggests that the systemic administration of liposomalcurcumin is safe and deserves to be investigated for further clinical application./Liposomal curcumin/[Shi HS et al; Int J Nanomedicine 7: 2601-11 (2012)] Full text: PMC3368513 Abstract: PubMed
EXPL THER The up regulation of gut mucosal cytokines such as tumor necrosis factor (TNF)-alpha and oxidative stress have been related to inflammatory bowel diseases (IBD) such as ulcerative colitis (UC) and Crohn’s disease (CD). This study investigated an immune-mediated model of colitis. TNF-alpha injected intraperitonally to mice induced a dose-dependent recruitment of neutrophils into abdominal mesentery. The leukocytes influx induced by TNF-alpha (10 ug/kg body weight) increased by 3 fold liver and colon damage scores. TNF-alpha-colitis was characterized by hemorrhagic edemas and crypt abscesses massively infiltrated by inflammatory cells, namely neutrophils. Moreover, TNF-alpha-toxicity resulted in liver steatosis and foci of necrosis infiltrated by Kupffer cells and neutrophils in parenchyma and around the centrilobular veins. The involvement of oxidative stress was evaluated using aminoguanidine (AG) as selective inhibitor of inducible NO synthase (iNOS) and curcumin (Cur), the polyphenolic antioxidant of turmeric (Curcuma longa L.). TNF-alpha-toxicity led to significant increase in myeloperoxidase (MPO, an index of neutrophils infiltration), nitrites (stable nitric oxide metabolites) and malondialdehyde (MDA, a marker of lipid peroxides) levels and cell apoptosis in liver and colon. AG and Cur treatments significantly attenuated the hallmarks of oxidative stress, neutrophils influx and ROS-related cellular and histological damages, in TNF-alpha-treated mice. Taken together, /these/ results provide insights into the role of phagocytes-derived oxidants in TNF-alpha-colitis in mice. Cur and AG, by inhibiting neutrophils priming and iNOsynthase could be effective against oxidative bowel damages induced in IBD by imbalanced gut immune response. Abstract: PubMed
Mouzaoui S et al; Int Immunopharmacol 12 (1): 302-11 (2012)
EXPL THER Photodynamic therapy is a technique that involves the activation of photosensitizers by light in the presence of tissue oxygen, resulting in the production of reactive radicals capable of inducing cell death. The present study assessed the overall susceptibility of pathogens of salivary flora to photodynamic therapy after sensitization with curcumin and exposure to blue light at 450 nm. A randomized trial was executed with 13 adult volunteers. Three different groups were analyzed: L-D- (no light, no drug; control group), L-D+ (treated only with the drug; curcumin group) and L+D+ (treated with drug and light; photodynamic therapy group). Non-stimulated saliva samples were collected for bacterial counts at baseline and after the experimental phase, and adverse events experienced were recorded. Serial dilutions were performed, and the resulting samples were cultured on blood agar plates in microaerophilic conditions. The number of colony-forming units was then determined. There was a considerable difference between the two experimental groups with regard to effectiveness of bacterial reduction. In the L-D+ group, the bacterial decline was considerably smaller (9%) than in the L+D+ group, with a 68% decrease in bacteria. A statistically significant reduction in the bacterial population was observed only in the photodynamic therapy group (p<0.05). Photodynamic therapy was found to be effective in the reduction of salivary microorganisms. No significant reduction was found for the group in which only curcumin was used, proving the absence of dark toxicity of the drug. This work shows that overall disinfection of the mouth can be done with a simple procedure involving photodynamic action. Abstract: PubMed
Araujo NC et al; Photomed Laser Surg 30 (2): 96-101 (2012)
EXPL THER Previous studies suggested that curcumin is a potential agent against glioblastomas (GBMs). However, the in vivo efficacy of curcumin in gliomas remains not established. In this work, /the authors/ examined the mechanisms underlying apoptosis, selectivity, efficacy and safety of curcumin from in vitro (U138MG, U87, U373 and C6 cell lines) and in vivo (C6 implants) models of GBM. In vitro, curcumin markedly inhibited proliferation and migration and induced cell death in liquid and soft agar models of GBM growth. Curcumin effects occurred irrespective of the p53 and PTEN mutational status of the cells. Interestingly, curcumin did not affect viability of primary astrocytes, suggesting that curcumin selectivity targeted transformed cells. In U138MG and C6 cells,curcumin decreased the constitutive activation of PI3K/Akt and NFkappaB survival pathways, down-regulated the antiapoptotic NFkappaB-regulated protein bcl-xl and induced mitochondrial dysfunction as a prelude to apoptosis. Cells developed an early G2/M cell cycle arrest followed by sub-G1 apoptosis and apoptotic bodies formation. Caspase-3 activation occurred in the p53-normal cell type C6, but not in the p53-mutant U138MG. Besides its apoptotic effect,curcumin also synergized with the chemotherapeutics cisplatin and doxorubicin to enhance GBM cells death. In C6-implanted rats, intraperitoneal curcumin(50 mg/kg/d) decreased brain tumors in 9/11 (81.8%) animals against 0/11 (0%) in the vehicle-treated group. Importantly, no evidence of tissue (transaminases,creatinine and alkaline phosphatase), metabolic (cholesterol and glucose), oxidative or hematological toxicity was observed. In summary, data presented here suggest curcumin as a potential agent for therapy of GBMs. Abstract: PubMed
Zanotto-Filho A et al; J Nutr Biochem 23 (6): 591-601 (2012)
EXPL THER Curcumin has been shown to have high cytotoxicity towards various cancer cell lines, but its water insolubility and instability make its bioavailability exceedingly low and, thus, it is generally inactive in in vivo anticancer tests. Here, we report an intracellular-labile amphiphilic surfactant-likecurcumin prodrug–curcumin conjugated with two short oligo(ethylene glycol) (Curc-OEG) chains via beta-thioester bonds that are labile in the presence of intracellular glutathione and esterase. Curc-OEG formed stable nanoparticles in aqueous conditions and served two roles–as an anticancer prodrug and a drug carrier. As an anticancer prodrug, the formed nanoparticles had a high and fixed curcumin-loading content of 25.3 wt%, and released active curcumin in the intracellular environment. Curc-OEG had high inhibition ability to several cancer cell lines due to apoptosis. Intravenously injected Curc-OEG significantly reduced the tumor weights and tumor numbers in the athymic mice xenografted with intraperitoneal SKOV-3 tumors and subcutaneous (mammary fat pad) MDA-MB-468 tumors. Preliminary systemic toxicity studies found that Curc-OEG did not cause acute and subchronic toxicities to mouse visceral organs at high doses. As drug carriers, Curc-OEG nanoparticles could carry other anticancer drugs, such as doxorubicin and camptothecin, and ship them into drug-resistant cells, greatly enhancing the cytotoxicity of the loaded drug. Thus, Curc-OEG is a promising prototype that merits further study for cancer therapy./ Molecular carrier system/ Abstract: PubMed
Tang H et al; Nanomedicine (Lond) 5 (6): 855-65 (2010)
EXPL THER This study aims at the formulation of curcumin with biodegradable thermoresponsive chitosan-g-poly (N-vinylcaprolactam) nanoparticles (TRC-NPs) for cancer drug delivery. The spherical curcumin-loaded nanoparticles of size 220 nm were characterized, and the biological properties were studied using flow cytometry and cytotoxicity by MTT assay. The in vitro drug release was higher at above LCST compared to that at below LCST. TRC-NPs in the concentration range of 100-1000 ug/mL were non-toxic to an array of cell lines. The cellular localization of the curcumin-loaded TRC-NPs was confirmed from green fluorescence inside the cells. The time-dependent curcumin uptake by the cells was quantified by UV spectrophotometer. Curcumin-loaded TRC-NPs showed specific toxicity to cancer cells at above their LCST. Flow cytometric analysis showed increased apoptosis on PC3 compared to L929 by curcumin-loaded TRC-NPs. These results indicate that novel curcumin-loaded TRC-NPs could be a promising candidate for cancer drug delivery. /Curcumin-loaded biocompatible thermoresponsive polymeric nanoparticles/ Abstract: PubMed
Rejinold NS et al; J Colloid Interface Sci 360 (1): 39-51 (2011)
EXPL THER Inflammatory bowel disease (IBD) is a major source of morbidity in children and adults. Its incidence is rising, particularly in young people. IBD carries a lifelong risk of cancer, which is proportional to disease duration. Drug and surgical treatments rarely offer cure and often carry a high side effect burden. Dietary therapy is highly effective in Crohn’s disease. For these reasons, there is much interest in developing novel dietary treatments in IBD.Curcumin, a component of the spice turmeric, and an anti-inflammatory and anti-cancer agent, shows preclinical and clinical potential in IBD. Its mechanisms of action are unknown. /This study’s/ aim was to assess the effect of curcumin on key disease mediators p38 mitogen-activated protein kinase (MAPK), IL-1beta, IL-10 and matrix metalloproteinase-3 (MMP-3) in the gut of children and adults with IBD. Colonic mucosal biopsies and colonic myofibroblasts (CMF) from children and adults with active IBD were cultured ex vivo with curcumin. p38 MAPK, NF-kappaB and MMP-3 were measured by immunoblotting. IL-1beta and IL-10 were measured by ELISA. /Investigators/ show reduced p38 MAPK activation in curcumin-treated mucosal biopsies, enhanced IL-10 and reduced IL-1beta. /They/ demonstrate dose-dependent suppression of MMP-3 in CMF with curcumin. /They/ conclude that curcumin, a naturally occurring food substance with no known human toxicity, holds promise as a novel therapy in IBD. Abstract: PubMed
Epstein J et al; Br J Nutr 103 (6): 824-32 (2010)
EXPL THER Curcumin (CCM), a yellow natural polyphenol extracted from turmeric (Curcuma longa), has potent anti-cancer properties as has been demonstrated in various human cancer cells. However, the widespread clinical application of this efficient agent in cancer and other diseases has been limited by its poor aqueous solubility and bioavailability. In this study, we prepared novel CCM-loaded human serum albumin (HSA) nanoparticles (CCM-HSA-NPs) for intravenous administration using albumin bound technology. Field emission scanning electron microscopy (FE-SEM) and dynamic light scattering (DLS) investigation confirmed a narrow size distribution in the 130-150nm range. Furthermore, CCM-HSA-NPs showed much greater water solubility (300-fold) than free CCM, and on storage, the biological activity of CCM-HSA-NPs was preserved with negligible activity loss. In vivo distributions and vascular endothelial cells transport studies demonstrated the superiority of CCM-HSA-NPs over CCM. Amounts of CCM in tumors after treatment with CCM-HSA-NPs were about 14 times higher at 1hr after injection than that achieved by CCM. Furthermore, vascular endothelial cell binding of CCM increased 5.5-fold, and transport of CCM across a vascular endothelial cell monolayer by Transwell testing was 7.7-fold greater for CCM-HSA-NPs than CCM. Finally, in vivo antitumor tests revealed that CCM-HSA-NPs (10 or 20mg/kg) had a greater therapeutic effect (50% or 66% tumor growth inhibition vs. PBS-treated controls) than CCM (18% inhibition vs. controls) in tumor xenograft HCT116 models without inducing toxicity. /Investigators/ attribute this potent antitumor activity of CCM-HSA-NPs to enhanced water solubility, increased accumulation in tumors, and an ability to traverse vascular endothelial cell. / curcumin-loaded human serum albumin (HSA) nanoparticles/ Abstract: PubMed
Kim TH et al; Int J Pharm 403 (1-2): 285-91 (2011)
EXPL THER In-stent restenosis is the major problem of percutaneous coronary interventions. Drug-eluting stent became a landmark in the treatment of coronary disease. Curcumin could be used for drug-eluting stent due to its antithrombogenity and antiproliferative properties. In this paper, 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assays were performed to decide the optimal concentration of curcumin for inhibiting the proliferation of vascular smooth muscle cells (VSMC). The result disclosed that more than 80% of VSMC were inhibited when the concentration of curcuminranged from 2.5 ug/mL to 10 ug/mL (P < 0.05, compared to ethanol). Three weight percent curcumin-loaded films (3wt%, 5wt%, 8wt%) were prepared using a biodegradable polymer (poly (lactic acid-co-glycol acid), PLGA) as the carrier of curcumin. The release of lactate dehydrogenase (LDH) was used to evaluate the immediate toxicity of the curcumin-loaded PLGA films, and the three concentration curcumin-loaded films were revealed to be of no acute toxicity to the smooth muscle cells. The results of Alamar Blue test indicated that the curcumin-loaded films had better antiproliferation effect than did the 316 stainless steel (SS). Therefore, these films may be used for stent coating to inhibit the in-stent restenosis induced by VSMC proliferation./ curcumin-loaded films/ Abstract:PubMed
Ren L et al; Sheng Wu Yi Xue Gong Cheng Xue Za Zhi 25 (4): 874-8 (2008)
EXPL THER The present work is aimed at evaluating the radioprotective effect of curcumin, a naturally occurring phenolic compound on gamma-radiation induced toxicity. The cellular changes were estimated by using lipid peroxidative indices like thiobarbituric acid reactive substances (TBARS), the antioxidantssuperoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and reduced glutathione (GSH). The DNA damage was analyzed by using cytokinesis blocked micronucleus assay and dicentric aberration (DC). The gamma-radiation at different doses (1, 2 and 4Gy) were found to significantly increase micronuclei (MN), DC frequencies and TBARS level whereas the levels of GSH and antioxidant enzymes were significantly decreased. The maximum damage to lymphocytes was observed at 4Gy irradiation. Curcumin pretreatment (1, 5 and 10 ug/mL) significantly decreased the frequency of MN and DC. The levels of TBARS decreased and activities of SOD, CAT and GPx significantly increased along with GSH levels. At 1Gy irradiation all the concentrations ofcurcumin (1, 5 and 10 ug/mL) significantly protected the lymphocytes from radiation damage. At 2Gy irradiation, 5 and 10 ug/mL of curcumin showed significant radioprotection. Since the highest damage was observed at 4Gy irradiation both 1 and 5 ug/mL of curcumin pretreatment were not sufficient to protect the lymphocytes from radiation damage but 10 ug/mL of curcumin significantly protected the cultured lymphocytes from radiation damage. Thus, pretreatment with curcumin gives protection to lymphocytes against gamma-radiation induced cellular damage. Abstract: PubMed
Srinivasan M et al; Mutat Res 611 (1-2): 96-103 (2006)
EXPL THER In recent years, considerable interest has been focused on curcumin a compound, isolated from turmeric. Curcumin is used as a coloring, flavoring agent and has been traditionally used in medicine and cuisine in India. The varied biological properties of curcumin and lack of toxicity even when administered at higher doses makes it attractive to explore its use in various disorders like tumors of skin, colon, duodenum, pancreas, breast and other skin diseases. This chapter reviews the data on the use of curcumin for the chemoprevention and treatment of various skin diseases like scleroderma, psoriasis and skin cancer. Curcumin protects skin by quenching free radicals and reducing inflammation through nuclear factor-KB inhibition. Curcumin treatment also reduced wound-healing time, improved collagen deposition and increased fibroblast and vascular density in wounds thereby enhancing both normal and impaired wound-healing. Curcumin has also been shown to have beneficial effect as a proangiogenic agent in wound-healing by inducing transforming growth factor-beta, which induces both angiogenesis and accumulation of extracellular matrix, which continues through the remodeling phase of wound repair. These studies suggest the beneficial effects of curcumin and the potential of this compound to be developed as a potent nontoxic agent for treating skin diseases.Abstract: PubMed
Thangapazham RL et al; Adv Exp Med Biol 595: 343-57 (2007)
EXPL THER Curcumin is a food chemical present in tumeric (Curcuma longa) that has pharmacological activity to suppress carcinogenesis and inhibits multiple signaling pathways such as nuclear factor kappaB (NF-kappaB), cyclooxygenase-2 (Cox-2) and interleukin-8 (IL-8). Oral curcumin has poor oral bioavailability limiting its clinical activity; however, a patent pending liposomal formulation of curcumin was developed to improve drug delivery and has demonstrated activity in multiple cancers. This study was designed to determine the minimum effective dose (MED) as well as the optimal dosing schedule of liposomalcurcumin in a xenograft mouse model of human pancreatic cancer. The MED determination and optimal schedule was evaluated in female athymic nude mice injected subcutaneously with MiaPaCa-2 cells. Dosing was initiated at an average tumor size of 5mm. For the MED, mice were treated with the following dose levels of liposomal curcumin: no treatment, liposome only, 1 mg/kg, 2 mg/kg, 5 mg/kg, 10 mg/kg, 20 mg/kg and 40 mg/kg given by tail vein injection three times weekly for 28 days. For the optimum dosing schedule, three additional schedules were evaluated and compared to the control of three times weekly; daily (five days per week), every four days, and weekly for 28 days. All mice were weighed and tumor measurements taken three times weekly to evaluate toxicity and efficacy. The 20 mg/kg dose had the greatest decrease in tumor growth at 52% decrease in tumor growth when compared to no treatment control mice. MED was determined to be 20 mg/kg and was used for the optimal dosing schedule determination. Daily dosing and three times per week dosing had greater inhibition of tumor growth with no discernable difference than once weekly or every 4 day dosing. No toxicity was observed at any dose or schedule. The MED for liposomal curcumin is 20 mg/kg given once daily three times per week to achieve optimal tumor growth inhibition. This was dose recommended for additional preclinical studies to define safety and tolerability of liposomal curcumin in rat and dog models. /Liposomal curcumin/ Abstract: PubMed
Mach CM et al; Anticancer Res 29 (6): 1895-9 (2009)
EXPL THER Ionizing radiation is known to induce oxidative stress through generation of reactive oxygen species (ROS) resulting in imbalance of the pro-oxidant and antioxidant in the cells, which is suggested to culminate in cell death. The present work was aimed to evaluate the radioprotective effect ofcurcumin, a yellow pigment of turmeric on gamma-radiation-induced toxicity in primary cultures of isolated rat hepatocytes. Hepatocytes were isolated from the liver of rats by collagenase perfusion. The cellular changes were estimated using lipid peroxidative indices like thiobarbituric acid reactive substances (TBARS), the antioxidants superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and reduced glutathione (GSH), ceruloplasmin, vitamins A, E and C and uric acid. The comet assay is a sensitive and rapid technique for quantifying and analyzing DNA damage in individual cells was exposed under gamma-radiation. The increase in the severity of DNA damage was observed with the increase dose (1, 2 and 4Gy) of gamma-radiation in cultured hepatocytes. TBARS were increased significantly, whereas the levels of GSH, vitamins C, E and A, ceruloplasmin, uric acid and antioxidant enzymes were significantly decreased in gamma-irradiated hepatocytes. The maximum damage to hepatocytes was observed at 4Gy irradiation. On pretreatment withcurcumin (1, 5 and 10ug/mL) showed a significant decrease in the levels of TBARS and DNA damage. The antioxidant enzymes were increased significantly along with the levels of GSH, vitamins A, E and C, uric acid and ceruloplamin. The maximum protection of hepatocytes was observed at 10ug/mL of curcuminpretreatment. Thus, pretreatment with curcumin helps in protecting the hepatocytes against gamma-radiation-induced cellular damage and can be developed as an effective radioprotector during radiotherapy in near future. Abstract: PubMed
Srinivasan M et al; Environ Toxicol Pharmacol 24 (2): 98-105 (2007)
EXPL THER Increasing evidence suggests that many neurons may die through apoptosis in Alzheimer’s disease (AD). Mitochondrial dysfunction has been implicated in this process of neuronal cell death. One promising approach for preventing AD is based upon anti-apoptosis to decrease death of nerve cells. In this study, /the authors/ observed the memory improving properties of curcumin in mice and investigated the neuroprotective effect of curcumin in vitro and in vivo. The mice were given AlCl(3) orally and injections of D-galactose intraperitoneally for 90 days to establish the AD animal model. From day 45, the curcumingroup was treated with curcumin for 45 days. Subsequently, the step-through test, neuropathological changes in the hippocampus and the expression of Bax and Bcl-2 were carried out to evaluate the effect of curcumin on the AD model mice. In cultured PC12 cells, AlCl(3) exposure induced apoptosis. The MTT assay was used to measure cell viabilities; flow cytometric analysis to survey the rate of cell apoptosis; DNA-binding fluorochrome Hoechst 33258 to observe nuclei changes in apoptotic cells and Western blot analysis of Bax, Bcl-2 to investigate the mechanisms by which curcumin protects cells from toxicity.Curcumin significantly improved the memory ability of AD mice in the step-through test, as indicated by the reduced number of step-through errors (P < 0.05) and prolonged step-through latency (P < 0.05). Curcumin also attenuated the neuropathological changes in the hippocampus and inhibited apoptosis accompanied by an increase in Bcl-2 level (P < 0.05), but the activity of Bax did not change (P > 0.05). AlCl(3) significantly reduced the viability of PC12 cells (P < 0.01). Curcumin increased cell viability in the presence of AlCl(3) (P < 0.01). The rate of apoptosis decreased significantly in the curcumin group (P < 0.05) when measured by flow cytometric analysis. Curcumin protected cells by increasing Bcl-2 level (P < 0.05), but the level of Bax did not change (P > 0.05). This study demonstrates that curcumin improves the memory ability of AD mice and inhibits apoptosis in cultured PC12 cells induced by AlCl(3). Its mechanism may involve enhancing the level of Bcl-2. Abstract: PubMed
Pan R et al; Chin Med J (Engl) 121 (9): 832-9 (2008)
EXPL THER Alzheimer’s disease (AD) involves amyloid beta (Abeta) accumulation, oxidative damage, and inflammation, and risk is reduced with increased antioxidant and anti-inflammatory consumption. The phenolic yellow curry pigment curcumin has potent anti-inflammatory and antioxidant activities and can suppress oxidative damage, inflammation, cognitive deficits, and amyloid accumulation. Since the molecular structure of curcumin suggested potential Abeta binding, we investigated whether its efficacy in AD models could be explained by effects on Abeta aggregation. Under aggregating conditions in vitro,curcumin inhibited aggregation (IC(50) = 0.8 uM) as well as disaggregated fibrillar Abeta40 (IC(50) = 1 uM), indicating favorable stoichiometry for inhibition.Curcumin was a better Abeta40 aggregation inhibitor than ibuprofen and naproxen, and prevented Abeta42 oligomer formation and toxicity between 0.1 and 1.0 uM. Under EM, curcumin decreased dose dependently Abeta fibril formation beginning with 0.125 uM. The effects of curcumin did not depend on Abeta sequence but on fibril-related conformation. AD and Tg2576 mice brain sections incubated with curcumin revealed preferential labeling of amyloid plaques. In vivo studies showed that curcumin injected peripherally into aged Tg mice crossed the blood-brain barrier and bound plaques. When fed to aged Tg2576 mice with advanced amyloid accumulation, curcumin labeled plaques and reduced amyloid levels and plaque burden. Hence, curcumin directly binds small beta-amyloid species to block aggregation and fibril formation in vitro and in vivo. These data suggest that low dose curcumin effectively disaggregates Abeta as well as prevents fibril and oligomer formation, supporting the rationale for curcumin use in clinical trials preventing or treating AD. Abstract: PubMed
Yang F et al; J Biol Chem 280 (7): 5892-901 (2005)
EXPL THER The true therapeutic benefit of the use of natural products, especially acceptable dietary components such as curcumin, which can spare the normal cells and boost host immunity, has opened new horizons in cancer prevention and treatment. In our model system we used Ehrlich’s ascites carcinoma cells grown in peritoneal carity of Swiss albino mice and curcumin was fed every alternative day. Here, /the authors/ report that curcumin administration to tumor-bearing mice decreased tumor cell number significantly in a dose-dependent manner. Furthermore, tumor-induced depletion of immune cell number of the host, as was evidenced from the decrease in bone marrow progenitor as well as thymic and splenic mononuclear cell numbers, was reintrated bycurcumin. In fact, curcumin inhibited tumor-induced apoptosis of both thymocytes and splenocytes thereby restoring immune cell numbers to normal level in treated Ehrlich’s ascites carcinoma-bearing mice. Moreover, curcumin was not toxic to the host; rather in tumor-bearing mice it inhibited hematopoietic toxicity, acted as a hepatoprotective agent and activated depressed anti-oxidant and detoxification systems. The ability of curcumin to regress tumor as well as to protect the host from tumor-induced immunosuppression and toxicity strongly supports the candidacy of curcumin as a potential agent for the dietary therapy of cancer. Abstract: PubMed
Pal S et al; Cancer Detect Prev 29 (5): 470-8 (2005)
EXPL THER Disseminated intravascular coagulation (DIC) is a lethal situation in severe infections, characterized by the systemic formation of microthrombi complicated with bleeding tendency and organ dysfunction. Current clinical trials are not promising. In this study, /researchers/ investigated the protective effect of curcumin in a lipopolysaccharide (LPS)-induced DIC model in rats. Experimental DIC was induced by sustained infusion of LPS (10 mg/kg body weight) for 4 hr through the tail vein. Curcumin (60 mg/kg body weight) was given intraperitoneally 3 hr before LPS infusion. Results showed that, in vivo,curcumin reduced the mortality rate of LPS-infused rats by decreasing the circulating TNF-alpha levels and the consumption of peripheral platelets and plasma fibrinogen. Furthermore, in vivo curcumin also has the effect of preventing the formation of fibrin deposition in the glomeruli of kidney. These results reveal the therapeutic potential of curcumin in infection-related coagulopathy of DIC. Abstract: PubMed
Chen HW et al; J Endotoxin Res 13 (1): 15-23 (2007)
EXPL THER The present investigation was an attempt to evaluate the possible ameliorative effect of curcumin on aflatoxin-induced lipid peroxidation in liver, kidney and testis of mice in vitro. Tissues were collected from healthy Swiss strain male albino mice Mus musculus weighing 30-35 g. The homogenates were treated with aflatoxin (2-10 mg/mL) with and without curcumin (25-200 mg/mL). The results revealed that addition of aflatoxin (2-10 mg/mL) to homogenates caused significant increase in lipid-peroxidation which was maximal at 6 mg/mL aflatoxin concentration. However, concurrent addition of aflatoxin (6 mg/mL) and curcumin (25-200 mg/mL) caused concentration-dependent amelioration in aflatoxin-induced lipid peroxidation. Abstract: PubMed
Mathuria N, Verma RJ; Acta Pol Pharm 64 (5): 413-6 (2007)
Iv & ip doses of (3)H-curcumin excreted in bile of cannulated rats. Major metab were glucuronides of tetrahydrocurcumin & hexahydrocurcumin. Minor metab was dihydroferulic acid together with traces of ferulic acid.
Mechanism of Action
Curcumin, a polyphenolic natural product, exhibits therapeutic activity against a number of diseases, attributed mainly to its chemical structure and unique physical, chemical, and biological properties. It is a diferuloyl methane molecule [1,7-bis (4-hydroxy-3- methoxyphenyl)-1,6-heptadiene-3,5-dione)] containing two ferulic acid residues joined by a methylene bridge. It has three important functionalities: an aromatic o-methoxy phenolic group, alpha, beta-unsaturated beta-diketo moiety and a seven carbon linker. Extensive research in the last two decades has provided evidence for the role of these different functional groups in its crucial biological activities. A few highlights of chemical structural features associated with the biological activity of curcumin are: The o-methoxyphenol group and methylenic hydrogen are responsible for the antioxidant activity of curcumin, and curcumin donates an electron/ hydrogen atom to reactive oxygen species. Curcumin interacts with a number of biomolecules through non-covalent and covalent binding. The hydrogen bonding and hydrophobicity of curcumin, arising from the aromatic and tautomeric structures along with the flexibility of the linker group are responsible for the non-covalent interactions. The alpha, beta-unsaturated beta-diketone moiety covalently interacts with protein thiols, through Michael reaction. The beta-diketo group forms chelates with transition metals, thereby reducing the metal induced toxicity and some of the metal complexes exhibit improved antioxidant activity as enzyme mimics. New analogues with improved activity are being developed with modifications on specific functional groups of curcumin… Abstract:PubMed
Priyadarsini KI; Curr Pharm Des 19 (11): 2093-100 (2013)
The present study demonstrates that curcumin acts as pro-oxidant and sensitizes human lung adenocarcinoma epithelial cells (A549) to apoptosis via intracellular redox status mediated pathway. Results indicated that curcumin induced cell toxicity (light microscopy and MTT assay) and apoptosis (AnnexinV-FITC/PI labeling and caspase-3 activity) in these cells. These events seem to be mediated through generation of reactive oxygen species (ROS) and superoxideradicals (SOR) and enhanced levels of lipid peroxidation. These changes were accompanied by increase in oxidized glutathione (GSSG), reduced glutathione (GSH) and gamma-glutamylcysteine synthetase (gamma-GCS) activity, but decrease in GSH/GSSG ratio. The induction of apoptosis and decrease inGSH/GSSG ratio was also accompanied by sustained phosphorylation and activation of p38 mitogen activated protein kinase (MAPK). On the other hand, addition of N-acetyl cysteine (NAC), an antioxidant, blocked the curcumin-induced ROS production and rescued malignant cells from curcumin-induced apoptosis through caspase-3 deactivation. However, L-buthionine sulfoximine (BSO), a GSH synthesis blocking agent, further enhanced curcumin-induced ROS production and apoptosis in A549 cells. Decreased GSH/GSSG ratio seems to be a crucial factor for the activation of MAPK signaling cascade bycurcumin. The study therefore, provides an insight into the molecular mechanism involved in sensitization of lung adenocarcinoma cells to apoptosis bycurcumin. Abstract: PubMed
Kaushik G et al; Indian J Exp Biol 50 (12): 853-61 (2012)
Curcumin has many pharmaceutical applications, many of which arise from its potent antioxidant properties. The present research examined the antioxidant activities of curcumin in polar solvents by a comparative study using ESR, reduction of ferric iron in aqueous medium and intracellular ROS/toxicity assays. ESR data indicated that the steric hindrance among adjacent big size groups within a galvinoxyl molecule limited the curcumin to scavenge galvinoxyl radicals effectively, while curcumin showed a powerful capacity for scavenging intracellular smaller oxidative molecules such as H2O2, HO-, ROO-. Cell viability and ROS assays demonstrated that curcumin was able to penetrate into the polar medium inside the cells and to protect them against the highly toxic and lethal effects of cumene hydroperoxide. Curcumin also showed good electron-transfer capability, with greater activity than trolox in aqueous solution. Curcumin can readily transfer electron or easily donate H-atom from two phenolic sites to scavenge free radicals. The excellent electron transfer capability of curcumin is because of its unique structure and different functional groups, including a beta-diketone and several pi electrons that have the capacity to conjugate between two phenyl rings. Therefore, since curcumin is inherently a lipophilic compound, because of its superb intracellular ROS scavenging activity, it can be used as an effective antioxidant for ROS protection within the polar cytoplasm.[Barzegar A, Moosavi-Movahedi AA; PLoS One 6 (10): e26012 (2011)] Full text:PMC3189944 Abstract: PubMed
Curcumin (diferuloylmethane), the yellow pigment in Indian saffron (Curcuma longa; also called turmeric, haldi, or haridara in the East and curry powder in the West), has been consumed by people for centuries as a dietary component and for a variety of proinflammatory ailments. Extensive research within the last decade in cell culture and in rodents has revealed that curcumin can sensitize tumors to different chemotherapeutic agents including doxorubicin, 5-FU,paclitaxel, vincristine, melphalan, butyrate, cisplatin, celecoxib, vinorelbine, gemcitabine, oxaliplatin, etoposide, sulfinosine, thalidomide, and bortezomib. Chemosensitization has been observed in cancers of the breast, colon, pancreas, gastric, liver, blood, lung, prostate, bladder, cervix, ovary, head and neck, and brain and in multiple myeloma, leukemia, and lymphoma. Similar studies have also revealed that this agent can sensitize a variety of tumors to gamma radiation including glioma, neuroblastoma, cervical carcinoma, epidermal carcinoma, prostate cancer, and colon cancer. How curcumin acts as a chemosensitizer and radiosensitizer has also been studied extensively. For example, it downregulates various growth regulatory pathways and specific genetic targets including genes for NF-kappaB, STAT3, COX2, Akt, antiapoptotic proteins, growth factor receptors, and multidrug-resistance proteins. Although it acts as a chemosensitizer and radiosensitizer for tumors in some cases, curcumin has also been shown to protect normal organs such as liver, kidney, oral mucosa, and heart from chemotherapy and radiotherapy-induced toxicity. The protective effects of curcumin appear to be mediated through its ability to induce the activation of NRF2 and induce the expression of antioxidant enzymes (e.g., hemeoxygenase-1, glutathione peroxidase, modulatory subunit of gamma-glutamyl-cysteine ligase, and NAD(P)H:quinone oxidoreductase 1, increase glutathione (a product of the modulatory subunit of gamma-glutamyl-cysteineligase), directly quench free radicals, and inhibit p300 HAT activity. Abstract: PubMed
Goel A, Aggarwal BB; Nutr Cancer 62 (7): 919-30 (2010)
Curcumin is a naturally occurring compound which is known to induce heme oxygenase 1 (HO-1), although the underlying mechanism has not been fully elucidated. This study investigates in detail the mechanism of HO-1 induction by curcumin in human hepatoma cells… Curcumin was found to induce HO-1 at doses of 10 to 25 uM. At both non-toxic and toxic doses, HO-1 induction was found to correlate with production of reactive oxygen species (ROS), suggesting a causative relationship. This was reinforced by the finding that pretreatment with the antioxidants N-acetylcysteine, vitamin E and catalase prevented HO-1 induction by curcumin. ROS production appeared to be mitochondrial in origin, and curcumin treatment resulted in depolarisation of the mitochondrial membrane potential. Nrf2 was induced by curcumin treatment, which was also partly ROS dependent. Using siRNA, Nrf2 was demonstrated to contribute to HO-1 induction. A panel of kinase inhibitors was used to examine the contribution of MAP kinases to the induction of HO-1 by curcumin. PKC and p38 MAPK activity are required for full induction of HO-1. Furthermore, curcumin also inhibited protein phosphatase activity. In conclusion, curcumin treatment results in ROS generation, activation of Nrf2 and MAP kinases and the inhibition of phosphatase activity in hepatocytes, and when curcumin is not administered in toxic doses, these multiple pathways converge to induce HO-1. Abstract: PubMed
McNally SJ et al; Int J Mol Med 19 (1): 165-72 (2007)
Curcumin is the active ingredient of turmeric that has been consumed as a dietary spice for ages. Turmeric is widely used in traditional Indian medicine to cure biliary disorders, anorexia, cough, diabetic wounds, hepatic disorders, rheumatism, and sinusitis. Extensive investigation over the last five decades has indicated that curcumin reduces blood cholesterol, prevents low-density lipoprotein oxidation, inhibits platelet aggregation, suppresses thrombosis and myocardial infarction, suppresses symptoms associated with type II diabetes, rheumatoid arthritis, multiple sclerosis, and Alzheimer’s disease, inhibits HIV replication, enhances wound healing, protects from liver injury, increases bile secretion, protects from cataract formation, and protects from pulmonary toxicity and fibrosis. Evidence indicates that the divergent effects of curcumin are dependent on its pleiotropic molecular effects. These include the regulation of signal transduction pathways and direct modulation of several enzymatic activities. Most of these signaling cascades lead to the activation of transcription factors.Curcumin has been found to modulate the activity of several key transcription factors and, in turn, the cellular expression profiles. Curcumin has been shown to elicit vital cellular responses such as cell cycle arrest, apoptosis, and differentiation by activating a cascade of molecular events. In this chapter, we briefly review the effects of curcumin on transcription factors NF-KB, AP-1, Egr-1, STATs, PPAR-gamma, beta-catenin, nrf2, EpRE, p53, CBP, and androgen receptor (AR) and AR-related cofactors giving major emphasis to the molecular mechanisms of its action. Abstract: PubMed
Shishodia S et al; Adv Exp Med Biol 595: 127-48 (2007)
What is it?
Turmeric is a plant. You probably know turmeric as the main spice in curry. It has a warm, bitter taste and is frequently used to flavor or color curry powders, mustards, butters, and cheeses. But the root of turmeric is also used widely to make medicine.
Turmeric is used for arthritis, heartburn (dyspepsia), stomach pain, diarrhea, intestinal gas, stomach bloating, loss of appetite, jaundice, liver problems and gallbladder disorders.
It is also used for headaches, bronchitis, colds, lung infections, fibromyalgia, leprosy, fever, menstrual problems, and cancer. Other uses include depression, Alzheimer’s disease, water retention, worms, and kidney problems.
Some people apply turmeric to the skin for pain, ringworm, bruising, leech bites, eye infections, inflammatory skin conditions, soreness inside of the mouth, and infected wounds.
In food and manufacturing, the essential oil of turmeric is used in perfumes, and its resin is used as a flavor and color component in foods.
Don’t confuse turmeric with Javanese turmeric root (Curcuma zedoaria).