Combined Treatment Of Curcumin Research Articles

Effect of combined treatment of curcumin and sodium bicarbonate on quality characteristics of refrigerated beef meatballs

In this study, we assessed the impact of curcumin (CC), sodium bicarbonate (SB), and their combination on the quality characteristics of refrigerated beef meatballs, aiming to ascertain the composite preservation effects of the combined use of CC and SB in meat products. Our findings revealed that, compared to the control group, CC, SB, and their combined treatment significantly reduced the levels of thiobarbituric acid reactive substances, total sulfhydryl losses, total survival counts, and total volatile basal nitrogen values of beef meatballs during storage (P < 0.05). Additionally, these treatments effectively delayed the colour and texture degradation of the meatballs and protected the structure of the meatball myofibrillar proteins. SB exhibited a significant reduction in cooking loss (P < 0.05) by enhancing the pH of beef meatballs and inducing the conversion of α-helix to β-sheet structure in myofibrillar proteins. Furthermore, beef meatballs treated with CC, SB, and their combination displayed dense microstructure and superior sensory quality through storage. The combined treatment of CC and SB yielded the most considerable improvement in the quality of refrigerated beef meatballs. Therefore, CC and SB can be used in combination in meat products to mitigate quality deterioration during storage.

Evaluation of Cross-Talk and Alleviate Potential of Cytotoxic Factors Induced by Deoxynivalenol in IPEC-J2 Cells Interference with Curcumin.

Deoxynivalenol (DON) is a mycotoxin produced by Fusarium graminearum, and curcumin (CUR) is a natural polyphenolic compound found in turmeric. However, the combined treatment of CUR and DON to explore the mitigating effect of CUR on DON and their combined mechanism of action is not clear. Therefore, in this study, we established four treatment groups (CON, CUR, DON and CUR + DON) to investigate their mechanism in the porcine intestinal epithelial cells (IPEC-J2). In addition, the cross-talk and alleviating potential of CUR interfering with DON-induced cytotoxic factors were evaluated by in vitro experiments; the results showed that CUR could effectively inhibit DON-exposed activated TNF-α/NF-κB pathway, attenuate DON-induced apoptosis, and alleviate DON-induced endoplasmic reticulum stress and oxidative stress through PERK/CHOP pathways, which were verified at both mRNA and protein levels. In conclusion, these promising findings may contribute to the future use of CUR as a novel feed additive to protect livestock from the harmful effects of DON.

Mesenchymal Stem Cells and Curcumin Effectively Mitigate Freund's Adjuvant- induced Arthritis via their Anti-inflammatory and Gene Expression of COX-1, IL-6 and IL-4.

Rheumatoid arthritis (RA) is a type of arthritis that damages joints and can affect the thymus and the spleen. RA is an autoimmune disorder in which the immune system targets the body's own tissues. The causes of RA are unknown, although a genetic link is thought to be involved. The objective of this research was to evaluate the effect of curcumin, mesenchymal stem cells (MSCs), and their combination on the disruption of serum cytokines, ankle joint, thymus and spleen histopathology, and affected genes in complete Freund's adjuvant (CFA)-induced arthritis in male and female Wistar rats. Experimental animals were organized into 16 groups (6 animals for each), eight groups including male rats and the other eight groups including females rats. The groups are normal control, CMC, curcumin, MSCs, CFA, CFA/curcumin, CFA/ MSCs and the arthritic group treated with MSCs and curcumin. One subcutaneous injection of 0.1 mL CFA was given to rats into the right hind leg footpad to induce RA. The arthritic rats were intravenously injected three times with bone marrow-derived MSCs (BM-MSCs) and/or treated orally with curcumin daily (100 mg per kg body weight per day) for 21 days. Curcumin and BM-MSCs work together to dramatically (P < 0.05) restore the high serum PGE2 and IL-17 levels and lower the IL-13 level in arthritic rats to normal levels. Deleterious effects on the spleen and thymus histological structure were counteracted. Gene expression of COX-1 and IL-6 was increased and IL-4 was decreased; these changes were improved by the combination treatment (P < 0.05). Based on these findings, additive therapeutic effects on RA occur from the combined treatment of curcumin and BM-MSCs compared with their individual use (P < 0.05). Thus, it can be said that both curcumin and BM-MSCs are effective at reducing inflammation while also having beneficial effects on the ankle joint, thymus and spleen.

Combining curcumin and aspirin ameliorates preeclampsia-like symptoms by inhibiting the placental TLR4/NF-κB signaling pathway in rats.

Preeclampsia (PE) is a common medical complication of pregnancy characterized by high blood pressure and proteinuria after the 20th gestational week. This study aimed to investigate the potency of the combination of curcumin and aspirin in the treatment of PE and explore the underlying mechanisms. The PE model was constructed in female rats by administering 0.5mg/mL N-nitro-L-arginine methyl ester from gestational days (GDs) 6 to 16. The pregnant female rats were divided into five groups according to the drug treatment. The curcumin or aspirin was given to the rats by tail vein injection (0.36 mg/kg) or gavage treatment (1.5mg/kg BW/day) from GD4 to GD18. Treatment with curcumin and aspirin combination significantly reduced the systolic blood pressure and proteinuria in the PE rats. Meanwhile, in comparison to the PE rats treated with single-dose curcumin or aspirin, the rats treated with combined curcumin and aspirin showed significantly decreased sFlt-1, increased placental growth factor, and alleviated oxidative stress in both blood and placental tissues, which are abnormal in no-treated PE rats. Furthermore, dramatically decreased inflammatory cytokines secretion and TLR4 and NF-κB p65 expression in placental tissues were also observed in the PE rats with combined treatment compared to those of no-treated, signal-dose curcumin or aspirin-treated PE rats. Our results suggested that the combined treatment of curcumin and aspirin significantly ameliorates the symptoms of PE in rats, which is most likely due to the inhibition of the placental TLR4/NF-κB p65 signaling pathway.

The Combination Treatment of Curcumin and Probucol Protects Chondrocytes from TNF-α Induced Inflammation by Enhancing Autophagy and Reducing Apoptosis via the PI3K-Akt-mTOR Pathway.

Osteoarthritis (OA) is a chronic joint disease characterized by cholesterol accumulation in chondrocytes, cartilage degeneration, as well as extracellular matrix (ECM) destruction, and joint dysfunction. Curcumin, a chemical that can reduce cholesterol levels in OA patients, also can inhibit the progression of OA. However, a high concentration of curcumin may also trigger apoptosis in normal chondrocytes. Besides curcumin, probucol that is found can also effectively decrease the cholesterol level in OA patients. Considering that high cholesterol is a risk factor of OA, it is speculated that the combination treatment of curcumin and probucol may be effective in the prevention of OA. To investigate the possible effects of such two chemicals on OA pathophysiology, chondrocyte apoptosis and autophagy behavior under inflammatory cytokine stress were studied, and specifically, the PI3K-Akt-mTOR signaling pathway was studied. Methods. Cell proliferation, colony formation, and EdU assay were performed to identify the cytotoxicity of curcumin and probucol on chondrocytes. Transwell assay was conducted to evaluate chondrocyte migration under TNF-α inflammation stress. Immunofluorescence, JC-1, flow cytometry, RT-PCR, and western blot were used to investigate the signal variations related to autophagy and apoptosis in chondrocytes and cartilage. A histological study was carried out on OA cartilage. Glycosaminoglycan (GAG) release was determined to evaluate the ECM degradation under stress. Results. Compared with a single intervention with curcumin or probucol, a combined treatment of these two chemicals is more effective in terms of protecting chondrocytes from stress injury induced by inflammatory cytokines. The promoted protection may be attributed to the inhibition of apoptosis and the blockage of the autophagy-related PI3K/Akt/mTOR pathway. Such results were also verified in vitro by immunofluorescence staining of OA chondrocytes and in vivo by immunohistochemistry staining of cartilage. Besides, in vivo studies also showed that when applied in combination, curcumin and probucol could block the PI3K-AKT-mTOR signaling pathway; promote COL-II expression; suppress P62, MMP-3, and MMP-13 expression; and inhibit TNF-α-stimulated cartilage degradation. Moreover, the combined medication could help reduce the release of ECM GAGs in OA cartilage and alleviate the severity of OA. Conclusion. A combined treatment of curcumin and probucol could be used to protect chondrocytes from inflammatory cytokine stress via inhibition of the autophagy-related PI3K/Akt/mTOR pathway both in vitro and in vivo, which might be of potential pharmaceutical value for OA prevention and therapy.

Refrigeration temperature enhanced synergistic interaction of curcumin and 460 nm light-emitting diode against Staphylococcus saprophyticus at neutral pH

Abstract Objectives As considered highly resistant to antibiotics like mecillinam, the rise of Staphylococcus saprophyticus (S. saprophyticus) contamination of fresh foods and food processing environments necessitates the development of a new antimicrobial approach for food safety control. This study aimed to investigate the synergistic effect of food-grade curcumin (CUR) and blue light-emitting diode (LED) on S. saprophyticus. Materials and Methods S. saprophyticus was subjected to the synergistic treatment at 4 and 25 °C. The influence of parameters, including CUR concentration, light dose, and pH incubation time on the inactivation of S. saprophyticus was characterized through plate counting method. Results: The combined treatment of CUR and blue light irradiation significantly (P &amp;lt; 0.05) reduced bacterial counts and the antimicrobial effect was in a CUR concentration and light dose-dependent manner. Moreover, refrigeration temperature (4 °C) significantly (P &amp;lt; 0.05) enhanced the antibacterial effect at neutral pH condition (6.2–7.2), resulting in approximately 6.0 log reductions. Under acidic condition (pH 2.2–5.2), there was no significant difference in bacterial population reduction between treatments at both temperatures. Conclusions These findings proposed that synergistic interaction of CUR and 460 nm LED under refrigerated temperature could enhance the inactivation of S. saprophyticus at neutral pH condition.

Evaluation of biophysical as well as biochemical potential of curcumin and resveratrol during prostate cancer

Purpose The present study evaluated biochemical as well as biophysical mechanisms behind the synergistic effects of curcumin and resveratrol during prostate carcinogenesis. Methods The rats were segregated into five groups that included normal control, 3,2′-dimethyl-4-aminobiphenyl (DMAB)treated, DMAB + curcumin treated, DMAB + resveratrol-treated and DMAB + curcumin + resveratrol-treated. Results The DMAB treatment resulted in a significant increase in the levels of lipid peroxidation (LPO) in DMAB treated rats. Also, significant changes were recorded in the enzyme activities of both drug metabolising enzyme and antioxidant enzymes after DMAB treatment. Further, radiorespirometric studies showed a significant increase in the 14C-glucose turnover as well as 14C-glucose uptake in the prostate slices of DMAB treated rats. Moreover, a significant rise in cell proliferation was confirmed indirectly by enhanced uptake of 3H-thymidine in the prostate slices of DMAB treated rats. Interestingly, combined treatment of curcumin and resveratrol to DMAB treated animals resulted in a significant decrease in lipid peroxidation, 14C glucose uptakes/turnover and 3H-thymidine uptake in the DMAB treated rats. Besides this, curcumin and resveratrol in combination significantly modulated biochemical indices including drug-metabolising enzymes; antioxidant enzymes in DMBA treated rats. Conclusion The study, therefore, concludes that the combination of curcumin and resveratrol holds strong modulatory potential against prostate carcinogenesis.

A combined treatment of curcumin, piperine, and taurine alters the circulating levels of IL-10 and miR-21 in hepatocellular carcinoma patients: a pilot study.

Investigating and evaluating possible alternative therapeutic strategies to control hepatocellular carcinoma (HCC) is a critical need because of its high prevalence and being one of the most lethal cancers. Curcumin and taurine showed potent anti-tumor activities in pre-clinical and clinical studies by targeting multiple pathways. Thus, this study was designed to assess the effect of a combined treatment consisted of curcumin, piperine, and taurine on circulating levels of interleukin-10 (IL-10), and microRNAs miR-141 and miR-21. Twenty eligible HCC patients administrated an oral dose of 4 g curcumin, 40 mg piperine, and 500 mg taurine daily for three successive treatment cycles, each was a 30-day. The level of IL-10 along with the expression levels of miR-141, and miR-21 were monitored in serum before starting the treatment and after each cycle. Patients were followed-up for a period of 24 months. The combined treatment was able to produce a significant decrease in the levels of serum IL-10, and miR-21 while it resulted in a non-significant up-regulation of serum miR-141 expression level. At the end of the follow-up period, the median overall survival (OS) rate was found to be 17.00 months with a worse OS in patients with high baseline levels of circulating IL-10 and miR-21 compared to those with low levels. In contrast, a low baseline level of circulating miR-141 was associated with poor prognosis. The combined treatment may be able to increase the OS rate by altering the circulating level of IL-10 and miR-21.

Traditional Chinese Medicine Curcumin Sensitizes Human Colon Cancer to Radiation by Altering the Expression of DNA Repair-related Genes.

The aim of the present study was to investigate the radio-sensitizing efficacy of curcumin, a traditional Chinese medicine (TCM) on colon cancer cells in vitro and in vivo. Human colon cancer HT-29 cells were treated with curcumin (2.5 μM), irradiation (10 Gy) and the combination of irradiation and curcumin. Cell proliferation was assessed using the MTT assay. Apoptotic cells were detected by Annexin V-PE/7-AAD analysis. PCR was performed to determine differential-expression profiling of 95 DNA-repair genes in irradiated cells and cells treated with both irradiation and curcumin. Differentially-expressed genes were confirmed by Western blotting. In vivo radio-sensitizing efficacy of curcumin was assessed in a xenograft mouse model of HT-29 colon cancer. Curcumin was administrated daily by intraperitoneal injection at 20 mg/kg/dose. Mice received irradiation (10 Gy) twice weekly. Apoptosis of the cancer cells following treatment was determined by TUNEL staining. Irradiation induced proliferation inhibition and apoptosis of HT-29 cells in vitro. Concurrent curcumin treatment sensitized the HT-29 tumor to irradiation (p<0.01). DNA repair-related genes CCNH and XRCC5 were upregulated and LIG4 and PNKP downregulated by the combination of curcumin and irradiation compared with irradiation alone (p<0.05). Combined treatment of curcumin and irradiation resulted in a significantly greater tumor-growth inhibition and apoptosis compared to irradiation treatment alone (p<0.01). Curcumin sensitizes human colon cancer in vitro and in vivo to radiation. Downregulation of LIG4 and PNKP and upregulation of XRCC5 and CCNH DNA-repair-related genes were involved in the radio-sensitizing efficacy of curcumin in colon cancer.

Comparative Insilico Docking Analysis of Curcumin and Resveratrol on Breast Cancer Proteins and their Synergistic Effect on MCF-7 Cell Line

Object: To compare the molecular activity of curcumin and resveratrol on selected breast cancer protein receptors and to investigate their combination for synergism against human breast cancer MCF-7 cell line. Method: Curcumin and resveratrol were subjected to insilico docking studies using glide to investigate the drug activity against HER2, human oestrogen receptor, ERBB2, epidermal growth factor tyrosine protein kinase C-SRC, and HSP90 proteins. MTT assay was used to assess cell viability of curcumin and resveratrol individually and in combination at 1:1,1:3 and 3:1 ratio respectively. Results: The insilico study revealed good glide score and glide energy for these drugs against breast cancer protein. Curcumin and resveratrol has more binding affinity for proteins with varying amino acid interaction sites. IC50 for curcumin and resveratrol was observed to be 21.29 and 38.30 μg/ml respectively. IC50 for the combined treatment with curcumin and resveratrol at the ratio of 1:1,1:3 and 3:1 were observed to be 28.06, 15.20 and 8.29 μg/ml respectively. Combined treatment of curcumin and resveratrol at equal ratio exhibited additive effects while at the ratio of 1:3 and 3:1 exhibited a strong synergistic effect on the cytotoxicity of MCF-7 cell line. Conclusion: Insilico docking analysis helped in identifying and organizing the structural similarity/diversity at the molecular level activity of curcumin and resveratrol. In vitro cell line study provides an insight into the potential application of curcumin and resveratrol codelivery for the chemoprevention and treatment of breast cancer. Key words: Combinatorial effect, Curcumin, Resveratrol, Human breast cancer MCF -7 cells, Insilico anticancer screening, Synergism.

Essential turmeric oils enhance anti-inflammatory efficacy of curcumin in dextran sulfate sodium-induced colitis

Turmeric has been used as a medicinal herb for thousands of years for treatment of various disorders. Although curcumin is the most studied active constituents of turmeric, accumulating evidence suggests that other components of turmeric have additional anti-inflammatory and anti-tumorigenic properties. Herein, we investigated anti-inflammatory efficacy and associated gene expression alterations of a specific, curcumin preparation containing essential turmeric oils (ETO-curcumin) in comparison to standard curcumin at three specific doses (0, 5, 25 or 50 mg/kg), in an animal model of dextran sodium sulfate (DSS)-induced colitis. The present study showed that both ETO and standard curcumin treatments provided protection against DSS-induced inflammation. However, ETO-curcumin improved disease activity index (DAI) dose-dependently, while the anti-inflammatory efficacy of standard curcumin remained constant, suggesting that ETO-curcumin may provide superior anti-inflammatory efficacy compared to standard curcumin. Gene expression analysis revealed that anti-inflammatory cytokines including IL-10 and IL-11 as well as FOXP3 were upregulated in the colon by ETO-curcumin. Collectively, these findings suggest that the combined treatment of curcumin and essential turmeric oils provides superior protection from DSS-induced colitis than curcumin alone, highlighting the anti-inflammatory potential of turmeric.

Combinatorial effect of curcumin with docetaxel modulates apoptotic and cell survival molecules in prostate cancer.

Docetaxel is the most commonly used chemotherapeutic agent to target androgen signaling in metastatic prostate cancer (PCa); however, prolonged treatment with docetaxel results in drug-resistant cancer cells. Combination therapies have the potential of increasing the effectiveness of drug treatment as well as decreasing the side effects. Curcumin is a nontoxic organic compound with multifaceted chemopreventive potential. In this study, we evaluated whether curcumin can reinforce the effect of docetaxel on PCa cells. The PCa cell lines DU145 and PC3 were treated with curcumin and docetaxel alone or in combination. After completion of the treatment cell proliferation and the expression of pro-survival and anti-apoptotic markers and the signaling molecules were analyzed. The combined treatment of curcumin and docetaxel inhibited the proliferation and induced apoptosis significantly higher than the curcumin and docetaxel-treated group alone. Interestingly, the combined treatment with curcumin and docetaxel modulates the expression of RTKs, PI3K, phospho-AKT, NF-kappa B, p53, and COX-2. These results suggest that curcumin can be a potential therapeutic contender in enhancing the efficacy of docetaxel in PCa treatment.

Curcumin and Extracellular Matrix Proteins Synergistically Act to Inhibit the Proliferation of Breast Cancer Cells

Aim: Natural substances have been gaining attention as they are accessible, cheap and associated with milder adverse effects as compared with conventional treatment. Curcumin is polyphenol derived from turmeric plant and is known to possess anti-inflammatory, antioxidant and antimetastatic effects. In the present work, the effect of curcumin individually and in combination with extracellular matrix proteins has been systematically studied on the breast cancer cell line, MCF-7. Materials &amp; methods: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed to screen the effect of various concentrations of curcumin on MCF-7 cells. Flow cytometry and caspase-3 assays were done to detect apoptosis. Nitric oxide and reactive oxygen species generation levels were also examined as both are known to play very important roles in cancer initiation and progression. Results: It was observed that at low concentrations curcumin exhibited significant antiproliferative activity which was supported with increased apoptosis and reduced levels of reactive oxygen species and nitric oxide. Moreover, the combined treatment of curcumin and proteins further boosted the antiproliferative effect of low concentrations of curcumin indicating that they act synergistically to inhibit the proliferation of breast cancer cells. Conclusion: This finding could be further investigated for development of novel anticancer therapies.

Sonodynamic action of curcumin on foodborne bacteria Bacillus cereus and Escherichia coli

Bacterial contamination is an important cause of foodborne diseases. The present study aimed to investigate sonodynamic action of curcumin on foodborne bacteria Bacillus cereus (B. cereus) and Escherichia coli (E. coli). The uptake of curcumin was measured for optimizing the concentration incubation time before ultrasound sonication, and colony forming units (CFU) were counted after ultrasound treatment. The chromosomal DNA fragmentation of bacteria was analyzed and the effect of hypoxic condition on the antibacterial efficacy of sonodynamic action of curcumin was also assessed in this study. The results showed that the maximum uptake of curcumin in B. cereus and E. coli occurred in 50min after curcumin incubation. Curcumin had sonodynamic bactericidal activity in a curcumin dose-dependent manner, and 5.6-log reduction in CFU of B. cereus was observed after curcumin treatment (2.0μM), however, only 2-log reduction in CFU of E. coli after 40μM curcumin treatment. No significant change in chromosomal DNA was found after the combined treatment of curcumin and ultrasound. The survival of B. cereus and E. coli after sonodynamic treatment in hypoxic group was significantly higher than that in normal oxygen group. These findings indicated that sonodynamic action of curcumin had significant inactivation effect on foodborne bacteria, and B. cereus was more sensitive to sonodynamic treatment of curcumin than E. coli. Sonodynamic antibacterial activity of curcumin might be dependent on the oxygen environment.

Sonodynamic inactivation of methicillin-resistant Staphylococcus aureus in planktonic condition by curcumin under ultrasound sonication

Methicillin-Resistant Staphylococcus aureus (MRSA) is an important cause of difficult-to-treat infections. The present study aims to investigate sonodynamic inactivation of MRSA in planktonic condition using curcumin under ultrasound sonication. Dark toxicity of curcumin to MRSA was investigated to choose the concentration range of curcumin used in the study. The uptake of curcumin in MRSA was observed before ultrasound sonication. After sonication colony forming units (CFUs) and bacterial viability were investigated using fluorescence assay. Additionally, chromosomal DNA fragmentation was also analyzed. Curcumin showed no dark toxicity to MRSA in the concentration range of⩽500μM. The maximum uptake of curcumin in MRSA occurred in 50min after curcumin incubation. Counting of CFUs showed that curcumin had significantly sonodynamic killing effect on MRSA in a curcumin dose-dependent manner, and 5-log reduction in CFU was observed after curcumin treatment (40μM) at room temperature in the dark for 50min followed by exposure to ultrasound with intensity of 1.56W/cm2 for 5min. The ratio of green-fluorescent intensity to red-fluorescent intensity was obviously decreased after curcumin treatment under ultrasound sonication. No significant change in chromosomal DNA was found in the cultured MRSA after the combined treatment of curcumin and ultrasound. These results demonstrated that sonodynamic action of curcumin had significant inactivation of MRSA in planktonic condition.

Study to Evaluate Molecular Mechanics behind Synergistic Chemo-Preventive Effects of Curcumin and Resveratrol during Lung Carcinogenesis

BackgroundThe combination approach is the future of the war against cancer and the present study evaluated molecular mechanics behind the synergistic effects of curcumin and resveratrol during lung carcinogenesis.MethodsThe mice were segregated into five groups which included normal control, Benzo[a]pyrene[BP] treated, BP+curcumin treated, BP+resveratrol treated and BP+curcumin+resveratrol treated.ResultsThe morphological analyses of tumor nodules confirmed lung carcinogenesis in mice after 22 weeks of single intra-peritoneal[i.p] injection of BP at a dose of 100 mg/Kg body weight. The BP treatment resulted in a significant increase in the protein expressions of p53 in the BP treated mice. Also, a significant increase in the protein expression of phosphorylated p53[ser15] confirmed p53 hyper-phosphorylation in BP treated mice. On the other hand, enzyme activities of caspase 3 and caspase 9 were noticed to be significantly decreased following BP treatment. Further, radiorespirometric studies showed a significant increase in the 14C-glucose turnover as well as 14C-gulcose uptake in the lung slices of BP treated mice. Moreover, a significant rise in the cell proliferation was confirmed indirectly by enhanced uptake of 3H-thymidine in the lung slices of BP treated mice. Interestingly, combined treatment of curcumin and resveratrol to BP treated animals resulted in a significant decrease in p53 hyper-phosphorylation, 14C glucose uptakes/turnover and 3H-thymidine uptake in the BP treated mice. However, the enzyme activities of caspase 3 and caspase 9 showed a significant increase upon treatment with curcumin and resveratrol.ConclusionThe study, therefore, concludes that molecular mechanics behind chemo-preventive synergism involved modulation of p53 hyper-phosphorylation, regulation of caspases and cellular metabolism enzymes.

Curcumin Lowers Erlotinib Resistance in Non-Small Cell Lung Carcinoma Cells With Mutated EGF Receptor

Non-small cell lung cancer (NSCLC) patients with activating mutations in the epidermal growth factor receptor (EGFR) are responsive to erlotinib, an EGFR-tyrosine kinase inhibitor (EGFR-TKI). However, patients with secondary somatic EGFR mutations are resistant to EGFR-TKI treatment. In this study, we investigated the effect of curcumin on the tumor growth of erlotinib-resistant NSCLC cells. Cell proliferation was determined by MTT assay. Apoptosis was examined using TUNEL staining. Protein expression of genes was determined by Western blot. Tumor growth was assessed in a xenograft mouse model. Results showed that erlotinib had a stronger effect on the induction of apoptosis in erlotinib-sensitive PC-9 cells but showed a weaker effect on erlotinib-resistant H1975 and H1650 cells than cisplatin and curcumin. Furthermore, curcumin significantly increased the cytotoxicity of erlotinib to erlotinib-resistant NSCLC cells, enhanced erlotinib-induced apoptosis, downregulated the expressions of EGFR, p-EGFR, and survivin, and inhibited the NF-κB activation in erlotinib-resistant NSCLC cells. The combination of curcumin and erlotinib exhibited the same effects on apoptosis as the combination of curcumin and cisplatin in erlotinib-resistant NSCLC cells. Moreover, the combined treatment of curcumin and erlotinib significantly inhibited tumor growth of erlotinib-resistant NSCLC cells in vivo. Our results indicate that curcumin is a potential adjuvant for NSCLC patients during erlotinib treatment.

Curcumin potentiates the anti-arthritic effect of prednisolone in Freund's complete adjuvant-induced arthritic rats

The present study was aimed at investigating the effect of curcumin in combination with prednisolone for the effective treatment of arthritis with reduced side effects when glucocorticoids therapy is indicated. Arthritis was induced in wistar rats by subplantar injection of Freund's complete adjuvant, and animals were observed for the symptoms of arthritis during the period of 21 days. Combined treatment of curcumin with various doses of prednisolone (1.25, 2.5 and 5 mg/kg) was evaluated in order to ascertain the efficacy and toxicity induced by steroid. Arthritic animals showed significant increase in tumour necrosis factor-α and IL-1β levels in paw tissue and IL-1β in serum. Combined therapy of curcumin with low doses of prednisolone showed pronounced beneficial effect on joint swelling, leucocyte count and biochemical parameters compared with prednisolone groups. Among the different doses used in the study, prednisolone at 1.25 mg/kg in combination with curcumin showed beneficial anti-arthritic activity and also reduced the steroid toxicity. This is evidenced by increase in body weight, low toxicity to immune organs, reduction in leucocyte count, increase in spleen anti-oxidant enzymes and potent inhibition of cytokines in combination group. Therefore, combined treatment of curcumin with low doses of prednisolone may find therapeutic use in arthritis.

Protective effects of combined therapy of gliclazide with curcumin in experimental diabetic neuropathy in rats

Diabetic neuropathy is the most common chronic complication of diabetes. The aim of the present study was to evaluate the protective effects of curcumin against neuropathy in gliclazide-treated diabetic rats. Diabetes was induced by an intraperitoneal injection of streptozotocin (45 mg/kg). Diabetic animals were given gliclazide (10 mg/kg, orally) alone or combined with curcumin (100 mg/kg, orally) or gabapentin (30 mg/kg, intraperitoneally as a positive control). Behavioral responses to thermal (hot plate and tail flick) and mechanical (tail pinch) pain, and some biochemical tests (serum glucose, C-peptide, peroxynitrite, lipid peroxides, and tumor necrosis factor-α) were assessed after 5 consecutive weeks of daily treatment. Combined treatment of curcumin with gliclazide significantly increased hot-plate and tail-flick latencies in comparison with that of the diabetic control group. The threshold of mechanical hyperalgesia was also significantly elevated. Serum glucose and C-peptide levels were significantly increased in the combined treatment compared with the diabetic control group, whereas serum levels of peroxynitrite, lipid peroxide, and tumor necrosis factor-α production were significantly decreased. The data suggest that the combination of curcumin with gliclazide may protect against the development of diabetic neuropathy, with favorable effects with respect to the gliclazide/gabapentin combination.

Curcumin potentiates antitumor activity of l-asparaginase via inhibition of the AKT signaling pathway in acute lymphoblastic leukemia

l-asparaginase (L-ASP) is a universal component of therapy for acute lymphoblastic leukemia (ALL). Curcumin is a naturally occurring yellow pigment that is derived from the rhizome of Curcuma longa. In this study, we evaluated the cytotoxicity of the combined treatment of L-ASP and curcumin in three ALL cell lines. Synergistic cytotoxicity was observed in all three cell lines following the combined treatment of curcumin and L-ASP. Our results revealed that curcumin significantly enhanced the antitumor effect of L-ASP in the three ALL cell lines compared to that for L-ASP alone ( p < 0.05). Curcumin and L-ASP co-treatments induced apoptosis, via activation and cleavage of caspase-8 and BID cleavage accompanied by release of cytochrome c and activation of caspase-9/3, compared to the group treated with only L-ASP and the control group. Furthermore, the combination of curcumin and L-ASP led to significant reductions in phosphorylated AKT and expression of AKT-regulated gene products (FoxO1, GSK3β, IKKα, NF-κB, XIAP) compared with the group treated with only L-ASP and the control group. Overall, our findings suggest that curcumin potentiates the antitumor effects of L-ASP in acute lymphoblastic leukemia by constitutively inhibiting AKT and AKT-regulated gene products.