63 публикувани проучвания за BCM-95 в резюме - 2ра част

37.    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-infammatory and anti-tumorigenic properties. Herein, we investigated anti-infammatory efcacy and associated gene expression alterations of a specifc, curcumin preparation containing essential turmeric oils (ETO-curcumin) in comparison to standard curcumin at three specifc 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 infammation. However, ETO-curcumin improved disease activity index (DAI) dose-dependently, while the anti-infammatory efcacy of standard curcumin remained constant, suggesting that ETO-curcumin may provide superior anti-infammatory efcacy compared to standard curcumin. Gene expression analysis revealed that anti-infammatory cytokines including IL-10 and IL-11 as well as FOXP3 were upregulated in the colon by ETO-curcumin. Collectively, these fndings suggest that the combined treatment of curcumin and essential turmeric oils provides superior protection from DSS-induced colitis than curcumin alone, highlighting the antiinfammatory potential of turmeric. [Toden S, Theiss AL, Wang X, Goel A. Essential turmeric oils enhance anti-inflammatory efficacy of curcumin in dextran sulfate sodium-induced colitis. Scientific reports. 2017 Apr 11;7(1):814.]

38.    Efficacy and safety of curcumin and its combination with boswellic acid in osteoarthritis: a comparative, randomized, double-blind, placebo-controlled study. The aim of this clinical trial was to assess the efficacy and safety of curcuminoid complex extract from turmeric rhizome with turmeric volatile oil (CuraMed®) and its combination with boswellic acid extract from Indian frankincense root (Curamin®) vs placebo for the treatment of 40- to 70-year-old patients with osteoarthritis (OA). The effects of CuraMed® 500-mg capsules (333 mg curcuminoids) and Curamin® 500-mg capsules (350 mg curcuminoids and 150 mg boswellic acid) taken orally three times a day for 12 weeks in 201 patients was investigated in a three-arm, parallel-group, randomized, double-blinded, placebo-controlled trial. Primary outcome efficacy measures included OA physical function performance-based tests, the WOMAC recommended index of joint pain, morning stiffness, limitations of physical function, and the patients’ global assessment of disease severity. Favorable effects of both preparations compared to placebo were observed after only 3 months of continuous treatment. A significant effect of Curamin® compared to placebo was observed both in physical
performance tests and the WOMAC joint pain index, while superior efficacy of CuraMed vs placebo was observed only in physical performance tests. The effect size compared to placebo was comparable for both treatment groups but was superior in the Curamin® group. The treatments were well tolerated. Twelve-week use of curcumin complex or its combination with boswellic acid reduces pain-related symptoms in patients with OA. Curcumin in combination with boswellic acid is more effective. Combining Curcuma longa and Boswellia serrata extracts in Curamin® increases the efficacy of OA treatment presumably due to synergistic effects of curcumin and boswellic acid. [Haroyan A, Mukuchyan V, Mkrtchyan N, Minasyan N, Gasparyan S, Sargsyan A, Narimanyan M, Hovhannisyan A. Efficacy and safety of curcumin and its combination with boswellic acid in osteoarthritis: a comparative, randomized, double-blind, placebo-controlled study. BMC complementary and alternative medicine. 2018 Dec;18(1):7.]

39.    Suppression of proliferation and invasive behavior of human metastatic breast cancer cells by dietary supplement BreastDefend. Integrative cancer therapies. The study was to evaluate the effect of the dietary supplement BreastDefend (BD) on the proliferation and invasive behavior of highly metastatic human breast cancer cells in vitro. Cell proliferation and cytotoxicity of BD was evaluated in MDA-MB-231 cells treated with BD (0-40 μg/mL) by MTT assay and trypan blue staining, respectively. Expression of cell cycle regulatory genes were determined by DNA-microarray analysis. Effect of BD on invasiveness was assessed by cellular adhesion, migration, and invasion assays. BD treatment of cells MDA-MB-231 resulted in the cytostatic inhibition of cell proliferation with IC50 22.2, 19.1, and 17.5 μg/mL for 24, 48, and 72 hours, respectively. The inhibition of proliferation was mediated by the upregulation expression of CCNG1, CHEK1, CDKN1C, GADD45A, and E2F2, whereas BD downregulated expression of CCNA1 and CDK6 genes. The induction of expression of GADD45A and inhibition of expression of cyclin A1 (gene CCNA1) by BD was also confirmed on the protein level. BD treatment suppressed the invasive behavior of MDA-MB-231 cells by the inhibition of cellular adhesion, migration, and invasion. This inhibition of invasiveness was mediated by the suppression of secretion of urokinase plasminogen activator (uPA), and by the downregulation of expression of CXCR4 in breast cancer cells treated with BD. Conclusion: BD inhibits proliferation and invasive behavior of the highly metastatic human breast cancer cells in vitro. BD may have a therapeutic potential for prevention or treatment of highly metastatic breast cancers. [Jiang J, Wojnowski R, Jedinak A, Sliva D. Suppression of proliferation and invasive behavior of human metastatic breast cancer cells by dietary supplement BreastDefend. Integrative cancer therapies. 2011 Jun;10(2):192-200.]

40.    Suppression of growth and invasive behavior of human prostate cancer cells by ProstaCaidTM: Mechanism of activity. Since the use of dietary supplements as alternative treatments or adjuvant therapies in cancer treatment is growing, a scientifc verifcation of their biological activity and the detailed mechanisms of their action are necessary for the acceptance of dietary supplements in conventional cancer treatments. In the present study we have evaluated the anti-cancer effects of dietary supplement ProstaCaid™ (PC) which contains mycelium from medicinal mushrooms (Ganoderma lucidum, Coriolus versicolor, Phellinus linteus), saw palmetto berry, pomegranate, pumpkin seed, green tea [40% epigallocatechin-3-gallate (EGCG)], Japanese knotweed (50% resveratrol), extracts of turmeric root (BCM-95®), grape skin, pygeum bark, sarsaparilla root, Scutellaria barbata, eleuthero root, Job's tears, astragalus root, skullcap, dandelion, coptis root, broccoli, and stinging nettle, with purifed vitamin C, vitamin D3, selenium, quercetin, citrus bioflavonoid complex, β sitosterolzinc, lycopene, α lipoic acid, boron, berberine and 3.3'-diinodolymethane (DIM). We show that PC treatment resulted in the inhibition of cell proliferation of the highly invasive human hormone refractory (independent) PC-3 prostate cancer cells in a dose- and timedependent manner with IC50 56.0, 45.6 and 39.0 µg/ml for 24, 48 and 72 h, respectively. DNA-microarray analysis demonstrated that PC inhibits proliferation through the modulation of expression of CCND1, CDK4, CDKN1A, E2F1, MAPK6 and PCNA genes. In addition, PC also suppresses metastatic behavior of PC-3 by the inhibition of cell adhesion, cell migration and cell invasion, which was associated with the down-regulation of expression of CAV1, IGF2, NR2F1, and PLAU genes and suppressed secretion of the urokinase plasminogen activator (uPA) from PC-3 cells. In conclusion, the dietary supplement PC is a promising natural complex with the potency to inhibit invasive human prostate cancer. [Jiang J, Eliaz I, Sliva D. Suppression of growth and invasive behavior of human prostate cancer cells by ProstaCaidTM: Mechanism of activity. International journal of oncology. 2011 Jun 1;38(6):1675-82.]

41.    ProstaCaid induces G2/M cell cycle arrest and apoptosis in human and mouse androgen-dependent and-independent prostate cancer cells..The anticancer effects of ProstaCaid, a novel integrative blend of vitamins, minerals, multiherb extracts, and derivatives, were tested in human and mouse androgen–dependent (AD) and –independent (AI) prostate cancer cell lines. ProstaCaid shows growth inhibitory effects on both human and mouse AD prostate cancer cells (LNCaP and CASP 2.1) and AI prostate cancer cells (PC3 and CASP 1.1) in a dose-/time-dependent manner. Consistently, long-term treatment with ProstaCaid also reduced colony formation capacities of prostate cancer cells. Flow cytometry assays revealed that ProstaCaid induces G2/M arrest and apoptosis in LNCaP and PC3 cells after 72 hours of treatment. Immunoblotting assay demonstrated that 25 mg/mL of ProstaCaid treatment resulted in (1) the reduction of cyclin D1, cyclin B1, and Cdc2 expression in a time-dependent way; (2) increase in p21WAF1/Cip1 as early as 12 hours after the treatments in PC3 cells and reduction to base line at the 72-hour time point; and (3) repression of Bcl-2, BclxL, and induction of Bim as well as the cleavages of caspase-3 and poly(ADP-ribose) polymerase (PARP) at 72 hours of treatment, suggesting caspase-3-dependent apoptosis. Moreover, ProstaCaid suppressed activation of AKT and MAPK signaling pathways in PC3 and LNCaP cells by reducing phosphorylation levels of AKT, its downstream target S6 ribosomal protein and GSK3b, and ERK1/2, respectively. In summary, these findings strongly suggest that ProstaCaid may be a potential chemopreventive and therapeutic agent for both AD and, more  importantly, AI prostate cancer. [Yan J, Katz AE. ProstaCaid induces G2/M cell cycle arrest and apoptosis in human and mouse androgen-dependent and-independent prostate cancer cells. Integrative cancer therapies. 2010 Jun;9(2):186-96.]

42.    Comparative bioavailability of curcumin, turmeric and Biocurcumax™ in traditional vehicles using non-everted rat intestinal sac model. The bioavailability of curcumin from turmeric, Biocurcumax and as plain curcumin was investigated using conventional vehicles by a non-everted rat intestinal model. Results of ex vivo intestinal permeability studies showed an enhancement in the permeability of curcumin with increase in lipophilicity of the vehicle used. Maximum permeability of curcumin was obtained from corn oil (13.4%) followed by clarified butter (9.82%), milk (4.24%) and aqueous suspension (1.66%) in 8 h. Another very interesting and important observation was that the permeation of curcumin was more from turmeric and Biocurcumax than from plain curcumin. These studies strongly suggest that curcumin may be consumed as turmeric/Biocurcumax in lipophilic vehicles instead of plain curcumin for maximum beneficial effects. [Maheshwari M. Comparative bioavailability of curcumin, turmeric and Biocurcumax™ in traditional vehicles using non-everted rat intestinal sac model. Journal of Functional Foods. 2010 Jan 1;2(1):60-5.]

43.    Clinical Evaluation Of A Herbal Formulation, Rhulief™, In The Management Of Knee Osteoarthritis. 28 subjects with diagnosed osteoarthritis of the knee were randomized to a 500 mg blend BCM-95 curcumin and Bospure® Boswellia twice a day or to the prescription drug celecoxib (one brand name is Celebrex®) 100 mg twice a day. Symptom scoring and clinical evaluation yielded superior results on pain relief and distance walked for the BCM- 95 and Bospure blend compared to celecoxib. BCM-95 and Bospure equaled celecoxib on joint flexibility. No serious adverse effects noted. [Antony B, Kizhakedath R, Benny M, Kuruvilla Bt. Clinical evaluation of a herbal formulation, Rhulief™, In the Management of Knee Osteoarthritis. Osteoarthritis and Cartilage 2011 Sep 1 (Vol. 19, Pp. S145-S146).

44.    Effect of Biocurcumax TM Curcumin (BCM-95) On Treatment of Moderate Chronic Periodontitis. Controlling inflammation is a major approach in periodontal
treatments, but scaling and root planing are not always effective enough. Curcumin is anti-inflammatory and can adjust inflammatory reactions and its efficacy and immunity is proven. The present research aimed at evaluating the potential of Curcumin BCM-95 in treatment of patients with chronic periodontitis. In a double blind clinical trial, the clinical parameters including, Gingival Sulcus Bleeding Index (GSBI), Loe and Silness Gingival Index (GI), Probing Pocket Depth (PPD), and Clinical Attachment Level (CAL) were recorded at the beginning of the study, at week 6, and month 4. In case group, patients with moderate chronic periodontitis who had no systemic disease with at least one periodontal pocket with 4-6mm depth in each quadrant and bleeding on probing were chosen. After scaling and root planing, the patients took 2 Curcumin oral capsules per day for 4 weeks. The patients in the control group were given placebos. The effect of time was found to be significant in PPD, GI, CAL, and GSBI. Moreover, significant differences were seen between PPD average measurements before medication, at first follow up, and second follow-up (P<0.05). But, in GI, GSBI, and CAL the group effect was not significant. In other words, the reduction was seen in these parameters in both groups but they were not significant. The effect of Biocurcumax TM Curcumin (BCM-95) was significant in treatment of moderate chronic periodontitis in PPD between the two groups which reduced this parameter. [Amoian B, Ehsani H, Moghadamnia A, Dabagh Satari F, Ehsani H. Effect of Biocurcumax TM Curcumin (BCM-95) On Treatment of Moderate Chronic Periodontitis. Journal of Mazandaran University of Medical Sciences. 2018 Mar 15;27(158):45-55.]


45.    Role of curcumin as an adjuvant in treatment of advanced head and neck squamous cell carcinoma. Chemoradiation forms the major line of treatment in advanced head and neck squamous cell carcinoma, but the benefit of chemotherapeutic agents is at the expense of various toxicities. Curcumin has demonstrated promising results in in-vivo and in-vitro studies as a radiosensitiser. The objective of the study was to determine the role of curcumin as an adjuvant in patients undergoing chemo radiation for advanced head and neck cancers. Study involved 21 patients who underwent chemo radiotherapy for advanced head and neck cancers. They were randomized into two groups. Group A received 500 mg of curcumin while, Group B received placebo along with chemoradiation. The response was assessed using RECIST criteria at three months post treatment using contrast enhanced computerized tomography scan. Overall 58.3% patients had partial response and 41.7% patients had stable disease in group A. In group B, 33.3% patients had a partial response and 66.6% patient had a stable disease. Patients receiving curcumin along with chemoradiation had a marginal decrease in tumour volume and 58.3% patients had partial response and 41.7% had stable disease. A statistical significance could not be achieved due to lack of stage-match controls. Further studies are required to validate the role of curcumin as an adjuvant in the treatment of head and neck squamous cell carcinomas. [Arun P, Sagayaraj A, Mohiyuddin SMA, Santhosh D. Role of curcumin as an adjuvant in treatment of advanced head and neck squamous cell carcinoma. Int J Otorhinolaryngol Head Neck Surg 2018;4:1388-93.]

46.    (a) Evaluation of hepatoprotective activity of combination of Phyllanthus niruri and Curcuma longa extracts in wistar rats. Hepatoprotective activity of combination of Phyllanthus niruri PN) and Curcuma longa(CL) extract was evaluated against carbon tetrachloride(CCl4) induced liver damage. Combination of PN+CL extract at a dose of 400mg/kg, orally was coadministered with CCl4 (0.5 mg/kg i.p) to rats for 7 days. On 8th day serum enzyme levels such as AST, ALT, ALP, TB were determined. Thiopentone induced sleeping time is estimated as an indirect index of functionality of liver. Liver tissue was used to estimate antioxidants such as MDA, GST levels and for histopathological assessment. There was a significant increase in serum enzyme levels and duration of thiopentone induced sleep time in CCl4 treated rats. Coadministration of PN+CL extract combination with CCl4 significantly prevented the rise in serum enzyme levels and normalize the duration of thiopentone induced sleep time. Combination of PN +CL produced significant reduction and increase in MDA & GST liver levels respectively. Histological section of liver in animals treated with CCl4 showed centrilobular area of necrosis with derangement in hepatic architecture. PN+CL administration prevented these deleterious changes, histological section of liver in rats treated with PN+CL showed normal hepatic parenchyma. Combination of PN+CL extract showed significant hepatoprotection against CCl4 induced liver damage. [Adiga S, Vinay BS, Kamath S, Gaonkar B, Panda A, Rao KM, Bairy KL. Evaluation of hepatoprotective activity of combination of Phyllanthus niruri and Curcuma longa extracts in wistar rats. Research Journal of Pharmaceutical, Biological and Chemical Sciences. 2012 Jul 1;3(3):1260-8.]

46.(b)  Hepatoprotective activity of combination of Phyllanthus niruri and Curcuma longa extracts against ethanol induced toxicity in wistar rats. Alcohol is an important substance with addictive potential. Alcohol is metabolised in the liver. Free radicals generated during the metabolism of alcohol is responsible for hepatic damage. Options available for treatment of alcohol induced liver disease was inadequate in modern medicine. Phyllanthus niruri and Curcuma longa have been shown to have hepatoprotective activity. Hence this study was undertaken to evaluate the effects of Phyllanthus niruri and Curcuma longa in combination to prevent alcohol induced hepatotoxicity. Evaluation was done by comapring the levels of liver enzymes, bilirubin, antioxidants, thiopentone induced sleeping time and liver hisotpathology in various groups of albino rats after administration of ethanol. Treatment with extracts of Phyllanthus niruri and Curcuma longa caused a significant reduction in liver enzymes, bilirubin levels and increase in antioxidants. The results of our study indicate that combination of Phyllanthus niruri and Curcuma longa possess significant hepatoprotective activity against alcohol induced liver damage. [Vinay BS, Adiga S, Kamath S, Rao KM, Avin S. Hepatoprotective activity of combination of Phyllanthus niruri and Curcuma longa extracts against ethanol induced toxicity in wistar rats. International Journal of Pharma and Bio Sciences. 2016;7(1):P12-8.]

47.    Curcumin Inhibits Polycomb Repressive Complex 2 through lncRNA-PVT1 and Enhances Gemcitabine Sensitivity in Chemoresistant Pancreatic Cancer. Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies, and a major cause of PDAC-associated mortality is acquisition of resistance to chemotherapy. Curcumin is a phenolic compound extracted from turmeric, and is known for its potent anti-inflammatory, anti-oxidative and anti-tumorigenic properties. Accumulating evidence suggests that curcumin can overcome de-novo chemoresistance and re-sensitize tumors to various chemotherapeutic drugs. Recently, polycomb repressive complex 2 (PRC2) was reported to be involved in drug resistant through interaction with several long non-coding RNAs (lncRNAs). Our data provide previously unrecognized evidence for curcumin-induced sensitization to gemcitabine, through co-modulation of PRC2 and PVT1 in PDAC. These data highlight the potential adjunctive therapeutic role for curcumin together with conventional chemotherapeutic drugs in patients with PDAC. [Yoshida K, Toden S, Weng W, Shigeyasu K, Han H, Becerra C, Boland CR, Goel A. Su2060 Curcumin Inhibits Polycomb Repressive Complex 2 through lncRNA-PVT1 and Enhances Gemcitabine Sensitivity in Chemoresistant Pancreatic Cancer. Gastroenterology. 2016 Apr 1;150(4):S624.]

48.    Impact of a 3-weeks randomized double-blind cross-over study curuminoid supplementation on endotoxemia, inflammatory markers, and lipid profiles in healthy overweight and obese adults. Postprandial endotoxaemia (increased bacterial lipopolysaccharide [LPS] level in the circulation) is associated to the increase of pro-inflammatory markers after intake of high-fat high-calorie meals . Endotoxaemia is a potential driver for chronic low-grade inflammation, linked to non-communicable chronic diseases. Curcumin (turmeric) has potential anti-inflammatory and hypolipidemic properties; and was shown to attenuate the effect of LPS-induced endotoxaemia in rats . The aim of this study was to investigate whether curcuminoid supplementation affected postprandial endotoxaemia, inflammatory markers, and lipid profiles in humans. Healthy volunteers (n = 16, 50 % men and 50 % women, aged 19–43 y, BMI 25–44 kg/m2 , fat mass 19–53 %) participated in a double-blinded, placebo-controlled, cross-over study (4 weeks wash-out period). Participants were randomized to 1 capsule per day, curcuminoids (380 mg) or placebo, for three weeks. Postprandial endotoxaemia was induced by single high-fat high-calorie meal intake (929 kcal, 65 g fat, 63 %E). Blood samples were collected before and after each leg of the study. Endotoxaemia markers (sCD14 & LBP) and inflammatory markers (CRP, TNF-α, IL-6, IL-1β, and IL-10) were measured with immunoassays; lipids were measured colorimetrically. Two participants dropped-out. There was no change in LBP for either trial leg. Subgroup analysis however indicated a 22 % decrease in LBP in volunteers with very high fat mass (n = 5) after leg A (p = 0•02). No differences were seen in CRP level after either leg, with large inter-individual variability (36•4–1028•3 ng/mL). sCD14 decreased after both legs (leg A, p = 0•015; leg B, p = 0•019). There were no effects on TNF-α, IL-6, and IL-1β. HDL level (before high-fat meal) was significantly higher after leg A (p = 0•01) with no different after the meal. No other effects were seen on total cholesterol, LDL, and triglycerides. HDL is the main lipoprotein removing LPS from the circulation, transporting LPS to the hepatocytes for clearance (4). Thus increased HDL level could be of benefit to reduce LPS and inhibit subsequent inflammatory responses. Assessing LPS level in plasma will give a better understanding of this effect. [Nuraiza M, Edwards CA, Combet E. Impact of a 3-weeks randomized double-blind cross-over study curuminoid supplementation on endotoxemia, inflammatory markers, and lipid profiles in healthy overweight and obese adults. Proceedings of the Nutrition Society. 2016;75(OCE3).]

49.    Curcumin inhibits cancer-associated fibroblast-driven prostate cancer invasion through MAOA/mTOR/HIF-1α signaling. Cancer-associated fbroblasts (CAFs) are key determinants in the malignant progression of cancer, supporting tumorigenesis and metastasis. CAFs also mediate epithelial to mesenchymal transition (EMT) in tumor cells and their achievement of stem cell traits. Curcumin has recently been found to possess anticancer activities via its effect on a variety of biological pathways involved in cancer progression. In this study, we found that CAFs could induce prostate cancer cell EMT and invasion through a monoamine oxidase A (MAOA)/mammalian target of rapamycin (mTOR)/hypoxia-inducible factor-1α (HIF-1α) signaling pathway, which exploits reactive oxygen species (ROS) to drive a migratory and aggressive phenotype of prostate carcinoma cells. Moreover, CAFs was able to increase CXC chemokine receptor 4 (CXCR4) and interleukin-6 (IL-6) receptor expression in prostate cancer cells. However, curcumin abrogated CAF-induced invasion and EMT, and inhibited ROS production and CXCR4 and IL-6 receptor expression in prostate cancer cells through inhibiting MAOA/mTOR/HIF-1α signaling, thereby supporting the therapeutic effect of curcumin in prostate cancer. [Du Y, Long Q, Zhang L, Shi Y, Liu X, Li X, Guan B, Tian Y, Wang X, Li L, He D. Curcumin inhibits cancer-associated fibroblast-driven prostate cancer invasion through MAOA/mTOR/HIF-1α signaling. International journal of oncology. 2015 Dec 1;47(6):2064-72.]

50.    ProstaCaid™ inhibits tumor growth in a xenograft model of human prostate cancer. We have recently demonstrated that the dietary supplement ProstaCaid™ (PC) inhibits growth and invasive behavior of PC-3 human prostate cancer cells in vitro. In the present study, we evaluated toxicity and whether PC suppresses growth of prostate cancer in a xenograft model of human prostate cancer cells implanted in mice. Here, we show that an oral administration of PC (100, 200 and 400 mg/kg) did not affect body weight or activity of liver enzymes (ALT, AST) and did not show any sign of toxicity in liver, spleen, kidney, lung and heart tissues in mice. In addition, PC treatment resulted in the inhibition of tumor volumes (1024.6±378.6 vs. 749.3±234.3, P<0.001) in a xenograft model of prostate cancer with human hormone refractory (independent) PC-3 prostate cancer cells. Moreover, qRT-PCR analysis demonstrated signifcant upregulation of expression of CDKN1A (p21) and inhibition of expression of IGF2, NR2F2 and PLAU (uPA) genes by an oral administration of PC in prostate cancer xenografts. Our study demonstrates that the concentrations of the dietary supplement ProstaCaid tested did not show signs of toxicity, and its oral application has signifcant anticancer activity in vivo and can be considered as an alternative treatment for prostate cancer patients. [Jiang J, Loganathan J, Eliaz I, Terry C, Sandusky GE, Sliva D. ProstaCaid™ inhibits tumor growth in a xenograft model of human prostate cancer. International journal of oncology. 2012 May 1;40(5):1339-44.]

51.    BreastDefend™ prevents breast-to-lung cancer metastases in an orthotopic animal model of triple-negative human breast cancer. It was recently demonstrated that a natural dietary supplement BreastDefend (BD), which contains extracts from medicinal mushrooms (Coriolus versicolor, Ganoderma lucidum, Phellinus linteus), medicinal herbs (Scutellaria barbata, Astragalus membranaceus, Curcuma longa), and purifed biologically active nutritional compounds (diindolylmethane and quercetin), inhibits proliferation and metastatic behavior of MDA-MB-231 invasive human breast cancer cells in vitro. In the present study, we evaluated whether BD suppresses growth and breast-to lung cancer metastasis in an orthotopic model of human breast cancer cells implanted in mice. Oral application of BD (100 mg/kg of body weight for 4 weeks) by intragastric gavage did not affect body weight or activity of liver enzymes and did not show any sign of toxicity in liver, spleen, kidney, lung and heart tissues in mice. Moreover, BD signifcantly decreased the change in tumor volume over time compared to the control group (p=0.002). BD treatment also markedly decreased the incidence of breast-to-lung cancer metastasis from 67% (control) to 20% (BD) (p<0.05) and the number of metastases from 2.8 (0.0, 48.0) in the control group to 0.0 (0.0, 14.2) in the BD treatment group (p<0.05). Finally, anti-metastatic activity of BD in vivo was further confrmed by the downregulation of expression of PLAU (urokinase plasminogen activator, uPA) and CXCR4 (C-X-C chemokine receptor-4) genes in breast tumors. In conclusion, BD may be considered as a biological therapeutic agent against invasive breast cancers. [Jiang J, Thyagarajan-Sahu A, Loganathan J, Eliaz I, Terry C, Sandusky GE, Sliva D. BreastDefend™ prevents breast-to-lung cancer metastases in an orthotopic animal model of triple-negative human breast cancer. Oncology reports. 2012 Oct 1;28(4):1139-45.]

52.    Curcumin supplementation mitigates NASH development and progression in female Wistar rats. Curcumin, a naturally occurring plant polyphenolic compound, may  have beneficial effects in nonalcoholic steatohepatitis (NASH) development. We examined whether curcumin supplementation could be used in both prevention and treatment of NASH with fibrosis. Female Wistar rats were provided ad libitum access to a “western diet” (WD) high in fat (43% kcal), sucrose (29% kcal), and cholesterol (2% w/v), as well as 15% fructose drinking water. Intraperitoneal CC14 injections (0.5 mL/kg) were also administered at weeks 1, 2, 4, and 6 to accelerate development of a NASH with fibrosis phenotype. Rats were randomized to four groups (n = 9–12/group) and fed ad libitum: (1) WD for 8-weeks (8WD), (2) WD enriched with curcumin for 8-weeks (8WD+C; 0.2% curcumin, BCM-95, DolCas Biotech) to assess prevention, (3) WD for 12-weeks (12WD), (4) WD for 8-weeks followed by 4-weeks WD+C (12WD+C) to assess treatment. Curcumin prevention (8WD vs. 8WD+C) attenuated (P < 0.05) histological liver inflammation, molecular markers of fibrosis (Col1a1 mRNA) and a serum marker of liver injury (AST). Curcumin treatment (12WD vs. 12WD+C) reduced (P < 0.05) hepatocellular inflammation, steatosis, NAFLD Activity Scores, and serum markers of liver injury (AST, ALP). Moreover, curcumin treatment also increased hepatic pACC/ACC, ApoB100, and SOD1 protein, and decreased hepatic FGF-21 levels; whereas, curcumin prevention increased hepatic glutathione levels. Both curcumin prevention and treatment reduced molecular markers of hepatic fibrosis (Col1a1 mRNA) and inflammation (TNF-a, SPP1 mRNA). Curcumin supplementation beneficially altered the NASH phenotype in female Wistar rats, particularly the reversal of hepatocellular inflammation. [Cunningham RP, Moore MP, Moore AN, Healy JC, Roberts MD, Rector RS, Martin JS. Curcumin supplementation mitigates NASH development and progression in female Wistar rats. Physiological reports. 2018 Jul;6(14):e13789.]

53.    Oral Bioavailability of BCM-95® in Dogs. This study looked specifically at bioavailability in dogs for veterinary purposes. Curcuminoids, the biologically active components of tumeric, have been shown to have high antioxidant, and anti-inflammatory activity. Both in vitro and in vivo studies on model systems in multiple species have demonstrated a wide range of effects that support the use of curcumin in a wide range of conditions. However, these applications are constrained by the relatively poor bioavailability of curcumin. A comparison was made in dogs of a standard commercial curcumin extract and a unique highly bioavailable enhanced formulation of BCM-95 curcumin (reported as the veterinary NMXCC-95 designation).  Two groups of 3 dogs, weighing 12–15 kg were dosed with 2 gram equivalents of curcumin either as curcumin powdered extract or NMXCC95TM following a 12 hour fast. After a one week washout dogs received the other formulation. Plasma curcumin levels were determined for 0–8 hr samples by HPLC method. The standard curcumin extract had a shorter Tmax compared to the
NXMCC95TM formulation (1.5 hrs vs 3.17 hrs), but the enhanced formulation reached a 3-fold higher Cmax (296.4 vs 98.6 ng/g) and a 7-fold higher AUC over 8 hrs (1381 vs 199 nghr/g). Furthermore the plasma levels with NMXCC95TM remained elevated at 8 hrs (107.162.7 ng/g) while levels from standard curcumin extract returned close to zero (6.38.2 ng/g). These data show that the enhanced formulation of curcumin NMXCC95TM has a substantially higher bioavailability in dogs than standard powdered curcumin extract and has the potential to serve as an effective control of conditions with an underlying inflammatory basis. [Antony B, Butchin RK, Griffin DW. Bioavailability of a novel, bioenhanced preparation in dogs. Poster Presentation. 2009 ACVIM Forum/Canadian VMA Convention: June 3-6, 2009; Montréal, Québec, Canada.]

54.    A combination of curcumin and oligomeric proanthocyanidins offer superior anti-tumorigenic properties in colorectal cancer. Combining anti-cancer agents in cancer therapies is becoming increasingly popular due to improved efcacy, reduced toxicity and decreased emergence of resistance. Here, the hypothesis was that dietary agents such as oligomeric proanthocyanidins (OPCs) and curcumin cooperatively modulate cancer-associated cellular mechanisms to inhibit carcinogenesis. By a series of in vitro assays in colorectal cancer cell lines, we showed that the anti-tumorigenic properties of the OPCs-curcumin combination were superior to the efects of individual compounds. By RNA-sequencing based geneexpression profling in six colorectal cancer cell lines, we identifed the cooperative modulation of key cancer-associated pathways such as DNA replication and cell cycle pathways. Moreover, several pathways, including protein export, glutathione metabolism and porphyrin metabolism were more efectively modulated by the combination of OPCs and curcumin. We validated genes belonging to these pathways, such as HSPA5, SEC61B, G6PD, HMOX1 and PDE3B to be cooperatively modulated by the OPCs-curcumin combination. We further confrmed that the OPCs-curcumin combination more potently suppresses colorectal carcinogenesis and modulated expression of genes identifed by RNA-sequencing in mice xenografts and in colorectal cancer patient-derived organoids. Overall, by delineating the cooperative mechanisms of action of OPCs and curcumin, we make a case for the clinical co-administration of curcumin and OPCs as a treatment therapy for patients with colorectal cancer. [Ravindranathan P, Pasham D, Balaji U, Cardenas J, Gu J, Toden S, Goel A. A combination of curcumin and oligomeric proanthocyanidins offer superior anti-tumorigenic properties in colorectal cancer. Scientific reports. 2018 Sep 14;8(1):13869.]

55.    Curcumin downregulates expression of opioid-related nociceptin receptor gene (OPRL1) in isolated neuroglia cells. Curcumin (CC) exerts polyvalent pharmacological actions and multi-target effects, including pain relief and anti-nociceptive activity. In combination with Boswellia serrata extract (BS), curcumin shows greater efficacy in knee osteoarthritis management, presumably due to synergistic interaction of the ingredients. The aim of the study was to elucidate the molecular mechanisms underlying the analgesic activity of curcumin and its synergistic interaction with BS. Gene expression profling by transcriptome-wide mRNA sequencing in human T98G neuroglia cells treated with CC (Curamed), BS, and the combination of CC and BS (CC-BS; Curamin), followed by interactive pathways analysis of the regulated genes was performed. Treatment with CC and with CC-BS selectively downregulated opioid-related nociceptin receptor 1gene (OPRL1) expression by 5.9-fold and 7.2-fold, respectively. No changes were detected in the other canonical opioid receptor genes: OPRK1, OPRD1, and OPRM1. Nociceptin reportedly increases the sensation of pain in supra-spinal pain transduction pathways. Thus, CC and CC-BS may downregulate OPRL1, consequently inhibiting production of the nociception receptor NOP, leading to pain relief. In neuroglia cells, CC and CC-BS inhibited signaling pathways related to opioids, neuropathic pain, neuroinflammation, osteoarthritis, and rheumatoid diseases. CC and CC-BS also downregulated ADAM metallopeptidase gene ADAMTS5 expression by 11.2-fold and 13.5-fold, respectively. ADAMTS5 encodes a peptidase that plays a crucial role in osteoarthritis development via inhibition of a corresponding signaling pathway. It is  reported for the first time that CC and CC-BS act as nociceptin receptor antagonists, selectively downregulating opioid-related nociceptin receptor 1 gene (OPRL1) expression, which is associated with pain relief. BS alone did not affect OPRL1 expression, but rather appears to potentiate the effects of CC via multiple mechanisms, including synergistic interactions of molecular networks. [Seo EJ, Efferth T, Panossian A. Curcumin downregulates expression of opioid-related nociceptin receptor gene (OPRL1) in isolated neuroglia cells. Phytomedicine. 2018 Nov 15;50:285-99.]

56.    The effects of curcumin supplementation on liver enzymes, lipid profile, glucose homeostasis, and hepatic steatosis and fibrosis in patients with non-alcoholic fatty liver disease. Nonalcoholic fatty liver disease (NAFLD) is a major global health problem. The most common cause of death in these patients is due to cardiovascular disorders. The aim of this study was to examine the effects of curcumin supplementation on cardiovascular risk factors in patients with NAFLD. In this randomized, placebo-controlled, clinical trial, fifty two patients with NAFLD were randomly assigned to receive life style recommendations plus either 1500 mg curcumin or placebo for 12 weeks. Anthropometric indices, blood lipid profile, insulin resistance, as well as hepatic steatosis and fibrosis scores were measured at the beginning and the end of the study, and compared between and within groups. Hepatic fibrosis, serum cholesterol, glucose and alanin aminotransferase (ALT) reduced significantly only in curcumin group (p < 0.05). Anthropometric indices, blood lipid profile, insulin resistance, and hepatic steatosis decreased significantly in both groups (p < 0.05), without any significant difference between two groups.The results showed that daily intake of 1500 mg curcumin plus weight loss is not superior to weight loss alone in amelioration of cardiovascular risk factors in patients with NAFLD. Further studies with different dosages of curcumin are needed to be able to conclude about the effects of this dietary supplement on cardiovascular risk factors and NAFLD characteristics. [Saadati S, Hatami B, Yari Z, Shahrbaf MA, Eghtesad S, Mansour A, Poustchi H, Hedayati M, Aghajanpoor-pasha M, Sadeghi A, Hekmatdoost A. The effects of curcumin supplementation on liver enzymes, lipid profile, glucose homeostasis, and hepatic steatosis and fibrosis in patients with non-alcoholic fatty liver disease. European journal of clinical nutrition. 2019 Mar;73(3):441.]

57.    Safety and efficacy of curcumin versus diclofenac in knee osteoarthritis: a randomized open-label parallel-arm study. The purpose of this study was to compare the efficacy and safety of curcumin with those of diclofenac in the treatment of knee osteoarthritis (OA). In this randomized, open-label, parallel, active controlled clinical study, 139 patients with knee OA were randomly assigned to receive either a curcumin 500-mg (BCM-95®) capsule three times daily or a diclofenac 50-mg tablet two times daily for 28 days. Patients underwent assessment at baseline and days 7, 14, and 28. The main outcome measure was severity of pain using visual analogue scale score at days 14 and 28. Knee Injury and Osteoarthritis Outcome Score (KOOS) (at days 14 and 28), anti-flatulent effect (at day 7), anti-ulcer effect, weight-lowering effect, and patient’s and physician’s global assessment of therapy at day 28 were included as secondary outcome measures. Safety after treatment was evaluated by recording adverse events and laboratory investigation. At days 14 and 28, patients receiving curcumin showed similar improvement in severity of pain and KOOS scale when compared with diclofenac, and the difference was not statistically significant. At day 7, the patients who received curcumin experienced a significantly greater reduction in the number of episodes of flatulence compared with diclofenac (P <0.01). At day 28, a weight-lowering effect (P <0.01) and anti-ulcer effect (P <0.01) of curcumin were observed. None of the patients required H2 blockers in the curcumin group, and 19 patients required H2 blockers in the diclofenac group (0% versus 28%, respectively; P <0.01). Adverse effects were significantly less in the curcumin group (13% versus 38% in the diclofenac group; P <0.01). Patient’s and physician’s global assessment of therapy was similar in the two treatment groups. Curcumin has similar efficacy to diclofenac but demonstrated better tolerance among patients with knee OA. Curcumin can be an alternative treatment option in the patients with knee OA who are intolerant to the side effects of non-steroidal anti-inflammatory drugs. [Shep D, Khanwelkar C, Gade P, Karad S. Safety and efficacy of curcumin versus diclofenac in knee osteoarthritis: a randomized open-label parallel-arm study. Trials. 2019;20(1):214.]

58.    The effects of curcumin supplementation on high‐sensitivity C‐reactive protein, serum adiponectin, and lipid profile in patients with type 2 diabetes. Diabetes mellitus is one of the most common and important metabolic diseases in human. Curcumin, which is a natural polyphenol found in turmeric, can be used in treatment of diabetes complications for its antidiabetic, anti‐inflammatory, and antioxidant properties. In this double‐blind randomized clinical trial, 44 patients with Type 2 diabetes randomly assigned to curcumin or placebo group. Patients consumed either 1,500‐mg curcumin or placebo daily for 10 weeks. Anthropometric measurements were measured at baseline and at the end of the study. Serum concentrations of triglyceride (TG), total cholesterol, high‐density lipoprotein cholesterol, low‐density lipoprotein cholesterol, high‐sensitivity C‐reactive protein, and adiponectin were determined after 12‐hr fasting at the beginning and end of study. The mean serum level of TG decreased in curcumin group compared with baseline (109 ± 36 vs. 124 ± 36; p < 0.05). At the end of study, the mean concentration of high‐sensitivity C‐reactive protein decreased in the curcumin group compared to the control (2.9 ± 2.9 vs. 3.4 ± 4.2; p < 0.05). The mean serum concentration of adiponectin increased (64 ± 3 vs. 63 ± 4; p < 0.05) in the treatment group compared with the placebo at the end of the study. The results of the current study indicate that curcumin consumption may reduce diabetes complications through decreasing TG level as well as indicators of inflammation. [Adibian M, Hodaei H, Nikpayam O, Sohrab G, Hekmatdoost A, Hedayati M. The effects of curcumin supplementation on high‐sensitivity C‐reactive protein, serum adiponectin, and lipid profile in patients with type 2 diabetes: A randomized, double‐blind, placebo‐controlled trial. Phytotherapy Research. 2019 Mar 12.]

59.    Evaluation of Antinociceptive Activity of Bcm95 and Bospure® in Rodents. The analgesic activity of BCM95, BosPure®and its formulations in different ratios in rodents is evaluated. The antinociceptive effect of test drugs were investigated in mice and rats using two models: writhing test and formalin test. Ten groups were studied, each group consisting of 6 animals, Group I to X received: 2% gum acacia, Aspirin /Morphine s.c (formalin test), BCM95, BosPure®, Crude boswellia extract, BCM95:BosPure® 1:1, BCM95:BosPure®3:1, BCM95:BosPure®1:3, BCM95 + BosPure® + Soy, BCM95 + BosPure® micronised orally respectively 45 min before the experiment. Solution of 0.6% acetic acid was injected i.p to the mice, placed individually in the glass beakers to record the number of writhes. In formalin test model wistar rats (150-200 g) were injected with 50 ul of a 5% (v/v) solution of formalin into the sub plantar region of the right hind paw and the number of flinches in initial phase and second phase was recorded. At all the doses the test drugs produced a significant inhibition of writhing (V = 6; P < 0.01) compared to control. In formalin test all the test groups showed significant reduction in number of flinches in the second phase when compared to control (V = 6; P < 0.01) similar to analgesics with peripheral action like NSAIDs. Conclusions: BCM95, BosPure® and its formulations in different ratios possess antinociceptive activity in both the models. BCM95: BosPure® in 1:1 ratio showed better analgesic activity than other test groups in both models. [Sahana D Acharya, RS Nishith, BS Nischal, UP Rathnakar, Sheetal Ullal, Ashok K Shenoy. Evaluation of Antinociceptive Activity of Bcm95 and Bospure® in Rodents. Indian Journal of Pharmacology, December 2013, Volume 45, Supplement S187.]

60.    The effect of curcumin supplementation on anthropometric indices, insulin resistance and oxidative stress in patients with type 2 diabetes. Diabetes mellitus is a common metabolic disorders in human and affect a lot of people around the world. Curcumin is a component of turmeric and in many studies therapeutic effects such as anti-hypertensive, antihyperlipidemia, anti-hyperglycemia for this substance are shown. The aim of this study was to investigate the effect of curcumin supplementation on anthropometric indices glycemic control and oxidative stress in overweight patients with type 2 diabetes. In this randomized, double-blind, placebo-controlled trial, 53 participants with type 2 diabetes were divided randomly into the experimental and control groups to receive either 1500 mg curcumin or placebo capsule three times in a day for 10 weeks. Supplementation with curcumin in type 2 diabetes compare to placebo causes a signifcant changes in mean weight (-0.64±0.22 vs. 0.19±0.37 p < 0.05), body mass index (BMI) (0.3±0.03 vs. 0.1±0 p < 0.05), waist circumference (WC) (-1.2±0.4 vs. -0.43±0.11 p < 0.05) and fasting blood sugar (FBS) (-7±2 vs. 3±0.2 p < 0.05) but did not show any diference for hemoglobin A1c (HbA1c), insulin, malondialdehyde (MDA), total antioxidant capacity (TAC), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) and pancreatic B cell function (HOMA-B) at end of study. This study indicated that daily administration of 1500 mg curcumin has positive efects in reducing fasting blood glucose and weight in patients with type 2 diabetes.  [Hodaei H, Adibian M, Nikpayam O, Hedayati M, Sohrab G. The effect of curcumin supplementation on anthropometric indices, insulin resistance and oxidative stress in patients with type 2 diabetes: a randomized, double-blind clinical trial. Diabetology & metabolic syndrome. 2019 Dec;11(1):41.]

61.    Effect of curcumin supplementation on serum expression of select cytokines and chemokines in a female rat model of nonalcoholic steatohepatitis. It is recently reported that curcumin supplementation in a metabolically (i.e., Western diet [WD]) and chemically (i.e., CCl4) induced female rat model of non-alcoholic steatohepatitis (NASH) was associated with lower liver pathology scores and molecular markers of inflammation. This occurred when curcumin was given during induction of disease (preventative arm; 8-week WD with or without curcumin [8WD + C vs. 8WD]) as well as when given after disease development (treatment arm; 12-week WD with or without curcumin during weeks 9–12 [12WD + C vs. 12WD]). Herein, the findings from that study was extended by determining the effects of curcumin supplementation on cytokine/chemokine expression in serum collected from these same rats. 24 cytokines/chemokines were assayed. IL-2 (+ 80%) and IL-13 (+ 83%) were greater with curcumin supplementation in the prevention arm. IL-2 (+ 192%), IL-13 (+ 87%), IL-17A (+ 81%) and fractalkine (+ 121%) were higher while RANTES was lower (− 22%) with curcumin supplementation in the treatment arm (p < 0.05 for all). RANTES concentrations also correlated significantly with hepatic pathology scores of inflammation (r = 0.417, p = 0.008). Select serum cytokines/chemokines were affected with curcumin supplementation in this female rat model of NASH. Moreover, curcumin’s effect(s) on RANTES and its association with liver disease pathogenesis and progression may warrant further investigation. [Pickich MB, Hargrove MW, Phillips CN, Healy JC, Moore AN, Roberts MD, Martin JS. Effect of curcumin supplementation on serum expression of select cytokines and chemokines in a female rat model of nonalcoholic steatohepatitis. BMC research notes. 2019 Dec;12(1):1-7]

62.    Comparing different non-invasive methods in assessment of the effects of curcumin on hepatic fibrosis in patients with non-alcoholic fatty liver disease. The aim of this study was to examine the effects of curcumin supplementation on hepatic fibrosis using different fibrosis assessment methods. Nonalcoholic fatty liver disease (NAFLD) may progress to hepatic fibrosis. Detection of hepatic fibrosis should be measured by liver biopsy, which is an invasive method. Thus, some non-invasive methods are suggested. Hepatic fibrosis was evaluated in forty six patients with NAFLD before and three months after supplementation with 1.5 gram curcumin or placebo. Methods of assessments included fibroscan, and calculating non-invasive marker panel including FIB-4 (Fibrosis4), NFS (NAFLD fibrosis score), APRI (AST (Aspartate amino transferase) Platelet Ratio Index), and BARD (body mass index, AST/ALT (Alanine aminotransferase ratio, diabetes). Fibrosis score was reduced significantly after curcumin supplementation using fibroscan (p<0.01), FIB-4 (p<0.05) and APRI (p<0.05) tests, while fibrosis score did not change significantly using BARD and NFS methods (p>0.05). Results revealed that fibroscan, FIB-4, and APRI are similar in assessment of hepatic fibrosis changes after curcumin supplementation. [Saadati S, Hekmatdoost A, Hatami B, Mansour A, Zahra Z, Hedayati M, Sadeghi A. Comparing different non-invasive methods in assessment of the effects of curcumin on hepatic fibrosis in patients with non-alcoholic fatty liver disease. Gastroenterology and hepatology from bed to bench. 2018;11(Suppl 1):S8.]

63.    Curcumin and inflammation in non-alcoholic fatty liver disease: a randomized, placebo controlled clinical trial. The aim of the present study was to evaluate the effects of curcumin supplementation on inflammatory indices, and hepatic features in patients with non-alcoholic fatty liver disease (NAFLD). Fifty patients with NAFLD were randomized to receive lifestyle modification advice plus either 1500 mg curcumin or the same amount of placebo for 12 weeks. Curcumin supplementation was associated with significant decrease in hepatic fibrosis (p < 0.001), and nuclear factor-kappa B activity (p < 0.05) as compared with the baseline. Hepatic steatosis and serum level of liver enzymes, and tumor necrosis-α (TNF-α) significantly reduced in both groups (p < 0.05). None of the changes were significantly different between two groups. Our results indicated that curcumin supplementation plus lifestyle modification is not superior to lifestyle modification alone in amelioration of inflammation. [Saadati S, Sadeghi A, Mansour A, Yari Z, Poustchi H, Hedayati M, Hatami B, Hekmatdoost A. Curcumin and inflammation in non-alcoholic fatty liver disease: a randomized, placebo controlled clinical trial. BMC gastroenterology. 2019 Dec;19(1):133.]