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Curcumin Therapy to Treat Vascular Dysfunction in Children and Young Adults with ADPKD: A Randomized Controlled Trial.
Nowak, KL, Farmer-Bailey, H, Wang, W, You, Z, Steele, C, Cadnapaphornchai, MA, Klawitter, J, Patel, N, George, D, Jovanovich, A, et al
Clinical journal of the American Society of Nephrology : CJASN. 2022;(2):240-250
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Abstract
BACKGROUND AND OBJECTIVES Clinical manifestations of autosomal dominant polycystic kidney disease (ADPKD), including evidence of vascular dysfunction, can begin in childhood. Curcumin is a polyphenol found in turmeric that reduces vascular dysfunction in rodent models and humans without ADPKD. It also slows kidney cystic progression in a murine model of ADPKD. We hypothesized that oral curcumin therapy would reduce vascular endothelial dysfunction and arterial stiffness in children/young adults with ADPKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS In a randomized, placebo-controlled, double-blind trial, 68 children/young adults 6-25 years of age with ADPKD and eGFR>80 ml/min per 1.73 m2 were randomized to either curcumin supplementation (25 mg/kg body weight per day) or placebo administered in powder form for 12 months. The coprimary outcomes were brachial artery flow-mediated dilation and aortic pulse-wave velocity. We also assessed change in circulating/urine biomarkers of oxidative stress/inflammation and kidney growth (height-adjusted total kidney volume) by magnetic resonance imaging. In a subgroup of participants ≥18 years, vascular oxidative stress was measured as the change in brachial artery flow-mediated dilation following an acute infusion of ascorbic acid. RESULTS Enrolled participants were 18±5 (mean ± SD) years, 54% were girls, baseline brachial artery flow-mediated dilation was 9.3±4.1% change, and baseline aortic pulse-wave velocity was 512±94 cm/s. Fifty-seven participants completed the trial. Neither coprimary end point changed with curcumin (estimated change [95% confidence interval] for brachial artery flow-mediated dilation [percentage change]: curcumin: 1.14; 95% confidence interval, -0.84 to 3.13; placebo: 0.33; 95% confidence interval, -1.34 to 2.00; estimated difference for change: 0.81; 95% confidence interval, -1.21 to 2.84; P=0.48; aortic pulse-wave velocity [centimeters per second]: curcumin: 0.6; 95% confidence interval, -25.7 to 26.9; placebo: 6.5; 95% confidence interval, -20.4 to 33.5; estimated difference for change: -5.9; 95% confidence interval, -35.8 to 24.0; P=0.67; intent to treat). There was no curcumin-specific reduction in vascular oxidative stress or changes in mechanistic biomarkers. Height-adjusted total kidney volume also did not change as compared with placebo. CONCLUSIONS Curcumin supplementation does not improve vascular function or slow kidney growth in children/young adults with ADPKD. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER Curcumin Therapy to Treat Vascular Dysfunction in Children and Young Adults with ADPKD, NCT02494141. PODCAST This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2022_02_07_CJN08950621.mp3.
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Curcumin from Turmeric Rhizome: A Potential Modulator of DNA Methylation Machinery in Breast Cancer Inhibition.
Fabianowska-Majewska, K, Kaufman-Szymczyk, A, Szymanska-Kolba, A, Jakubik, J, Majewski, G, Lubecka, K
Nutrients. 2021;(2)
Abstract
One of the most systematically studied bioactive nutraceuticals for its benefits in the management of various diseases is the turmeric-derived compounds: curcumin. Turmeric obtained from the rhizome of a perennial herb Curcuma longa L. is a condiment commonly used in our diet. Curcumin is well known for its potential role in inhibiting cancer by targeting epigenetic machinery, with DNA methylation at the forefront. The dynamic DNA methylation processes serve as an adaptive mechanism to a wide variety of environmental factors, including diet. Every healthy tissue has a precise DNA methylation pattern that changes during cancer development, forming a cancer-specific design. Hypermethylation of tumor suppressor genes, global DNA demethylation, and promoter hypomethylation of oncogenes and prometastatic genes are hallmarks of nearly all types of cancer, including breast cancer. Curcumin has been shown to modulate epigenetic events that are dysregulated in cancer cells and possess the potential to prevent cancer or enhance the effects of conventional anti-cancer therapy. Although mechanisms underlying curcumin-mediated changes in the epigenome remain to be fully elucidated, the mode of action targeting both hypermethylated and hypomethylated genes in cancer is promising for cancer chemoprevention. This review provides a comprehensive discussion of potential epigenetic mechanisms of curcumin in reversing altered patterns of DNA methylation in breast cancer that is the most commonly diagnosed cancer and the leading cause of cancer death among females worldwide. Insight into the other bioactive components of turmeric rhizome as potential epigenetic modifiers has been indicated as well.
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Targeting of the tumor microenvironment by curcumin.
Fu, X, He, Y, Li, M, Huang, Z, Najafi, M
BioFactors (Oxford, England). 2021;(6):914-932
Abstract
The tumor microenvironment (TME) is made up of several cells and molecules that affect the survival of cancer cells. Indeed, certain (immunosuppressive) cells which promote tumors can promote the growth of tumors by stimulating the proliferation of cancer cells and promoting angiogenesis. During tumor growth, antitumoral immunity includes natural killer cells and CD8+ T cells cannot overcome immunosuppressive responses and cancer cell proliferation. In order to achieve the appropriate therapeutic response, we must kill cancer cells and suppress the release of immunosuppressive molecules. The balance between anti-tumor immunity and immunosuppressive cells, such as regulatory T cells (Tregs), cancer-associated fibroblasts, tumor-associated macrophages, and myeloid-derived suppressor cells plays a key role in the suppression or promotion of cancer cells. Curcumin is a plant-derived agent that has shown interesting properties for cancer therapy. It has shown that not only directly inhibit the growth of cancer cells, but can also modulate the growth and activity of immunosuppressant and tumor-promoting cells. In this review, we explain how curcumin modulates interactions within TME in favor of tumor treatment. The potential modulating effects of curcumin on the responses of cancer cells to treatment modalities such as immunotherapy will also be discussed.
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Impact of phytochemicals and plant extracts on viability and proliferation of NK cell line NK-92 - a closer look at immunomodulatory properties of goji berries extract in human colon cancer cells.
Kwaśnik, P, Lemieszek, MK, Rzeski, W
Annals of agricultural and environmental medicine : AAEM. 2021;(2):291-299
Abstract
INTRODUCTION Due to the fact that lymphocytes NK (natural killer cells) are the first line of defence of the body against cancer, one of the goals of modern immunotherapy is the enhancement of their natural activities for the effective recognition, detection, and elimination of cancer cells. OBJECTIVE The aim of the study was to evaluate the influence of selected phytochemicals (curcumin and resveratrol) and plant extracts (chlorella and goji berries) on NK cells viability and proliferation, as well as cytotoxic activity against colon cancer - one of the most common cancer worldwide. MATERIAL AND METHODS The impact of phytochemicals, viability and proliferation of plant extracts on NK cells was examined in NK-92 cells using both LDH and MTT assays. The immunomodulatory properties of selected compounds were tested against human colon cancer cell line LS180 using the MTT test. RESULTS Extracts of chlorella and goji berries significantly increased NK cell proliferation, while curcumin and resveratrol did not affect this process. Curcumin, as well as extracts of chlorella and goji berries, did not impact NK viability, while resveratrol significantly increased it. LDH test revealed the cytotoxic effect of chlorella extract and curcumin in NK-92 cell cultures. On the contrary, goji berries extract significantly decreased LDH level, while resveratrol did not affect the integrity of NK cell membranes. Studies conducted in co-cultures NK cells, also directly eliminated colon cancer cells. CONCLUSIONS Performed studies revealed immunomodulatory properties of goji berries extract, which improved viability and proliferation of NK cells, and above all, significantly increased their ability to recognize and eliminate colon cancer cells.
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A Comparative Study to Evaluate Efficacy of Curcumin and Aloe Vera Gel along with Oral Physiotherapy in the Management of Oral Submucous Fibrosis: A Randomized Clinical Trial.
Nerkar Rajbhoj, A, Kulkarni, TM, Shete, A, Shete, M, Gore, R, Sapkal, R
Asian Pacific journal of cancer prevention : APJCP. 2021;(S1):107-112
Abstract
UNLABELLED Rationale (Hypothesis): The antioxidant,anti-inflammatory,immunomodulatory and anti-tumorigenic properties of natural plant's extracts like aloe Vera and curcumin may produce beneficial therapeutic effects on OSMF patients and may lead to their symptomatic relief. Also, increase in the tissue elasticity with the help of oral physiotherapy excercises , would help in reinforcing increment in mouth opening. AIM: The aim of the study is to compare the efficacy of Curcumin gel with Aloe Vera gel when both the gel are supplemented along with oral physiotherapy in the management of OSMF. MATERIALS AND METHODS A study of parallel group trial design, using simple randomization technique, was conducted on confirmed cases of OSMF. Patients were divided into two groups, one group(30 patients) was given curcumin gel(Curenext) and other group (30 patients) aloe Vera gel (Aloe Vera 100% relief) and each group was asked to do same oral physiotherapy excercises supplementally. Follow-up was done for 6 weeks and patients were assessed on the basis of improvement in mouth opening and burning sensation at 2, 4, and 6 weeks. RESULTS There was an improvement in both the parameters at subsequent visits, but the Aloe Vera gel showed better improvement than curcumin gel in burning sensation after 6 weeks of treatment which was highly statistically significant p < 0.01. CONCLUSION Curcumin gel and Aloe Vera gel are effective in improving OSMF symptoms, but aloe Vera gel is more efficacious in burning sensation improvement without any side effects. Hence, we can advocate these drugs as adjuvant treatment in addition to the recommended treatment.
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Effect of eight-week curcumin supplementation with endurance training on glycemic indexes in middle age women with type 2 diabetes in Iran, A preliminary study.
Zamani, SK, Rezagholizadeh, DM
Diabetes & metabolic syndrome. 2021;(3):963-967
Abstract
BACKGROUND AND AIMS The purpose of this study was to determine the effects of curcumin supplementation & endurance training on glycemic indexes in middle-aged women with type 2 diabetes. METHODS 40 middle-aged women with type 2 diabetes were randomly divided into four groups (control, curcumin, training & curcumin + training). Endurance training protocol included running on treadmill for eight weeks, three sessions per week and each session for 45-60 min, with a maximum intensity of 50-70% of MHR. The experimental groups received a supplementation of curcumin as a daily dose of 80 mg curcumin soft gel for 8 weeks while the control group was subjected to no supplementation or exercise during this period. One day before and one day after the eight-week experimental period, blood samples were taken from the subjects to measure the glycemic indexes, including fasting blood glucose, glycosylated hemoglobin, and serum insulin levels. T-test and two-way covariance analysis tests were used for analyzing the findings at a significant level of less than 0.05. RESULTS Eight weeks of curcumin supplementation and endurance training, whether done separately or simultaneously, significantly reduced fasting blood glucose, glycosylated hemoglobin and serum insulin levels (P < 0.05). The combination of curcumin supplementation and endurance training compared to the other two interventions caused a significant further decrease in these glycemic indexes (P < 0.05). CONCLUSION The findings of this study showed that eight weeks of curcumin supplementation and endurance training helped each other in improving the glycemic indexes of women with type 2 diabetes.
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Curcumin and Biochemical Parameters in Metabolic-Associated Fatty Liver Disease (MAFLD)-A Review.
Różański, G, Kujawski, S, Newton, JL, Zalewski, P, Słomko, J
Nutrients. 2021;(8)
Abstract
Metabolic-associated fatty liver disease (MAFLD), formerly non-alcoholic fatty liver disease (NAFLD), is characterized by excessive fat accumulation in hepatocytes. It is the most common chronic liver disease worldwide and is a significant public health problem. In the absence of pharmacological therapy, other treatments such as diet, physical activity, or supplementation are sought. Non-pharmacological therapies may include curcumin supplementation, which has been shown to have many health-promoting properties, including antioxidant, anti-inflammatory, and anti-cancer effects. For this reason, we reviewed available databases to analyze publications describing the effect of curcumin supplementation on biochemical parameters in MAFLD. Nine studies (eight RCTs and one CT) based solely on supplementation of patients with curcumin were included in this review. The results from the individual trials were varied and did not allow clear conclusions. Although they suggest that curcumin shows some potential in the treatment of MAFLD, further research is needed.
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Curcumin Alleviates Palmitic Acid-Induced LOX-1 Upregulation by Suppressing Endoplasmic Reticulum Stress in HUVECs.
Luo, R, Zhao, L, Li, S, Chen, P, Wang, L, Yu, H, Cai, K, Yu, Q, Tian, W
BioMed research international. 2021;:9983725
Abstract
Excessive free fatty acid- (FFA-) induced endothelial lipotoxicity is involved in the pathogenesis of atherosclerosis. Endoplasmic reticulum (ER) stress is mechanistically related to endothelial lipotoxicity. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is the major oxidatively modified low-density lipoprotein (OxLDL) receptor in endothelial cells and is highly abundant in atherosclerotic lesions. Curcumin reduces the LOX-1 expression; however, the mechanism underlying this effect remains unknown. In the current study, we explored whether curcumin ameliorates palmitic acid- (PA-) induced endothelial lipotoxicity and LOX-1 upregulation by reducing ER stress in human umbilical vein endothelial cells (HUVECs). We built endothelial lipotoxicity in vitro and found that LOX-1 was upregulated after PA stimulation, during which ER stress played an important role. Next, we observed that curcumin substantially alleviated PA-induced lipotoxicity by restoring cell viability, increasing angiogenesis, and decreasing lipid deposition. Furthermore, LOX-1 upregulation in HUVECs was blocked by curcumin, possibly via ER stress suppression. Overall, our findings demonstrated that curcumin alleviates endothelial lipotoxicity and LOX-1 upregulation, and ER stress inhibition may play a critical role in this effect.
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Nanocurcumin supplementation ameliorates Behcet's disease by modulating regulatory T cells: A randomized, double-blind, placebo-controlled trial.
Abbasian, S, Soltani-Zangbar, MS, Khabbazi, A, Farzaneh, R, Malek Mahdavi, A, Motavalli, R, Hajialilo, M, Yousefi, M
International immunopharmacology. 2021;(Pt B):108237
Abstract
Current research was designed to assess the effects of nanocurcumin supplementation on regulatory T (Treg) cells frequency and function in Behçet's disease (BD). In this randomized double-masked, placebo-controlled trial, 36 BD subjects were randomly put into two groups to take one 80 mg nanocurcumin capsule or placebo daily for 8 weeks. Before and after trial, disease activity, Treg cells frequency and expression of related immunologic parameters including forkhead box protein P3 (Foxp3) transcription factor messenger RNA (mRNA) and microRNAs (miRNAs) such as miRNA-25 and miRNA-106b as well as cytokines including transforming growth factor (TGF)-β and interleukin (IL)-10 were studied. Thirty-two patients (17 in the nanocurcumin and 15 in the placebo groups) completed the trial. Treg cells frequency increased significantly in the nanocurcumin group compared with baseline (P < 0.001) and placebo group (P < 0.001). Moreover, FoxP3, TGF-β, IL-10, miRNA-25, and miRNA-106b mRNA expression levels increased considerably in the nanocurcumin group compared to baseline (P < 0.001) and placebo group (P < 0.001, P < 0.001, P = 0.025, P = 0.011, and P < 0.001, respectively). Significant increases in serum TGF-β and IL-10 were seen in nanocurcumin group compared with baseline (P < 0.001) and placebo group (P = 0.001 and P < 0.001, respectively). Significant decrease in disease activity was found in nanocurcumin group compared with placebo group (P = 0.044). Our study provided a promising view for desirable effects of nanocurcumin supplementation in improving immunological parameters and disease activity in BD.
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Microparticles vs. Macroparticles as Curcumin Delivery Vehicles: Structural Studies and Cytotoxic Effect in Human Adenocarcinoma Cell Line (LoVo).
Wezgowiec, J, Tsirigotis-Maniecka, M, Saczko, J, Wieckiewicz, M, Wilk, KA
Molecules (Basel, Switzerland). 2021;(19)
Abstract
This study aimed to characterize the hydrogel micro- and macro-particles designed to deliver curcumin to human colon cancer cells (LoVo). Six series of vehicles based on sodium alginate (micro- and macro-particles, uncoated, coated with chitosan or gelatin) were synthesized. The uncoated microparticles were fabricated using an emulsion-based technique and the uncoated macroparticles with an extrusion technique, with both coupled with ionotropic gelation. The surface morphology of the particles was examined with scanning electron microscopy and the average size was measured. The encapsulation efficiency, moisture content, and swelling index were calculated. The release of curcumin from the particles was studied in an experiment simulating the conditions of the stomach, intestine, and colon. To evaluate the anticancer properties of such targeted drug delivery systems, the cytotoxicity of both curcumin-loaded and unloaded carriers to human colon cancer cells was assessed. The microparticles encapsulated much less of the payload than the macroparticles and released their content in a more prolonged manner. The unloaded carriers were not cytotoxic to LoVo cells, while the curcumin-loaded vehicles impaired their viability-more significantly after incubation with microparticles compared to macroparticles. Gelatin-coated or uncoated microparticles were the most promising carriers but their potential anticancer activity requires further thorough investigation.