Therapeutic potency of curcumin for allergic diseases: A focus on immunomodulatory actions.

In light of increasing research evidence on the molecular mechanisms of allergic diseases, the crucial roles of innate and acquired immunity in the disease's pathogenesis have been well highlighted. In this respect, much attention has been paid to the modulation of unregulated and unabated inflammatory responses aiming to suppress pathologic immune responses in treating allergic diseases. One of the most important natural compounds with a high potency of immune modulation is curcumin, an active polyphenol compound derived from turmeric, Curcuma longa L. Curcumin's immunomodulatory action mainly arises from its interactions with an extensive collection of immune cells such as mast cells, eosinophils, epithelial cells, basophils, neutrophils, and lymphocytes. Up to now, there has been no detailed investigation of curcumin's immunomodulatory actions in allergic diseases. So, the present review study aims to prepare an overview of the immunomodulatory effects of curcumin on the pathologic innate immune responses and dysregulated functions of T helper (TH) subtypes, including TH1, TH2, TH17, and regulator T cells (Tregs) by gathering evidence from several studies of In-vitro and In-vivo. As the second aim of the present review, we also discuss some novel strategies to overcome the limitation of curcumin in clinical use. Finally, this review also assesses the therapeutic potential of curcumin regarding its immunomodulatory actions in allergic diseases.

The Effect of Curcumin Phytosome on the Treatment of Patients with Non-alcoholic Fatty Liver Disease: A Double-Blind, Randomized, Placebo-Controlled Trial.

Non-alcoholic fatty liver disease (NAFLD) is a global health problem with increasing prevalence among overweight and obese patients. It is strongly associated with conditions of insulin resistance including type 2 diabetes mellitus (T2DM) and obesity. It has detrimental consequences ranged from simple steatosis to irreversible hepatic fibrosis and cirrhosis. Curcumin is a dietary polyphenol with potential effect in improving NAFLD. Therefore, the aim of this trial was to examine the effect of curcumin supplementation on various aspects of NAFLD. In this trial, a total number of 80 patients were randomised to receive either curcumin at 250 mg daily or placebo for 2 months. Lipid profiles, hepatic enzymes, anthropometric indices and hepatic fat mass were assessed at the baseline and the end of the trial, and compared within the groups. The grade of hepatic steatosis, and serum aspartate aminotransferase (AST) levels were significantly reduced in the curcumin group (p = 0.015 and p = 0.007, respectively) compared to the placebo. There was also a significant reduction in high density lipoprotein (HDL) levels and anthropometric indices in both groups with no significant differences between the two groups. Low dose phospholipid curcumin supplementation each day for 2 months showed significant reduction in hepatic steatosis and enzymes in patients with NAFLD compared to placebo. Further studies of longer duration and higher dosages are needed to assess its effect on other parameters of NAFLD including cardiovascular risk.

Curcumin and Piperine Combination for the Treatment of Patients with Non-alcoholic Fatty Liver Disease: A Double-Blind Randomized Placebo-Controlled Trial.

BACKGROUND: Experimental and clinical studies have revealed that curcumin may be an effective therapy for non-alcoholic fatty liver disease (NAFLD). Hence, the aim of this study was to assess the effect of curcumin plus piperine administration on NAFLD. METHODS: Adults 18-65 years-old diagnosed with NAFLD by liver sonography were randomly allocated to curcumin (500 mg/day) or placebo groups for 2 months. All participants received both dietary and exercise advice. Anthropometric and biochemical measurements as well as hepatic ultrasound were performed at baseline and final conditions. RESULTS: Seventy-nine participants were recruited and randomly allocated into the curcumin (n = 39) or placebo (n = 40) groups. There were no significant differences between placebo and curcumin groups for demographic and clinical characteristics and NAFLD grade at baseline. After the treatment period, the curcumin group exhibited lower alkaline phosphatase (-16.2 ± 22.8 versus -6.0 ± 22.5 mg/dL, p = 0.04) concentrations and severity of NAFLD compared with the placebo group (p = 0.04). CONCLUSION: Results of this clinical trial suggest that short-term treatment with curcumin plus piperine administration improves NAFLD severity.

The Effects of Curcumin Plus Piperine Supplementation in Patients with Acute Myocardial Infarction: A Randomized, Double-Blind, and Placebo-Controlled Trial.

BACKGROUND: Acute myocardial infarction (AMI) is a leading cause of death and disability worldwide. Previous investigations have demonstrated that curcumin has a cardioprotective effect and may improve myocardial injury. So this study was performed to assess whether supplementation with curcumin could diminish myocardial injury following AMI. METHODS: To conduct this randomized, double-blinded, and placebo-controlled clinical trial, seventy-two patients with acute myocardial infarction, aged 18-75 years, were enrolled and randomly divided into the active intervention and control groups. The active intervention group (n = 38) received curcumin capsules with piperine supplement (500 mg/day, 95% curcuminoids) for 8 weeks, whereas the control group (n = 34) received a placebo capsule. At the baseline and end of the study, ejection fraction was assessed, and blood samples were taken from all patients to measure the levels of cardiac troponin I(cTnI), lipid profile, FBG, HbA1C, liver enzymes, renal function parameters, and electrolytes. RESULTS: In this trial, curcumin supplementation significantly reduced the levels of HbA1C (-0.3 ± 2.2 vs. +1.1 ± 1.3, P = 0.002), LDL (-10.3 ± 20.7 vs. +0.2 ± 22.5, P = 0.039), ALT (-10.2 ± 28.5 vs. +7.3 ± 39.2, P = 0.029), and ALP (+6.4 ± 39.5 vs. +38.0 ± 69.0, P = 0.018) compared to the placebo group. Moreover, the serum concentration of HDL significantly improved in comparison with the placebo group (+4.5 ± 8.9 vs. -1.6 ± 7.7, P = 0.002). However, no substantial difference was perceived between the groups regarding the ejection fraction and serum levels of cTnI, FBG, renal function parameters, and electrolytes. CONCLUSION: Our results indicated that daily intake of 500 mg of curcumin capsules with piperine supplement for 8 weeks modified lipid profile, liver enzymes, and glycemic status, but did not have any effect on ejection fraction and serum concentration of cardiac troponin I, renal function parameters, and electrolytes in acute myocardial infarction patients.

A pilot study of the effect of curcumin on epigenetic changes and DNA damage among patients with non-alcoholic fatty liver disease: A randomized, double-blind, placebo-controlled, clinical trial.

BACKGROUND: The enhancement of oxidative stress in non-alcoholic fatty liver disease (NAFLD) patients may cause mutation in DNA by deamination of cytosine to 5-hydroxyuracil or uracil. This study aimed to discover the effects of curcumin on NAFLD progress, DNA damage caused by oxidative stress, and promoter methylation of mismatch repair enzymes. MATERIAL AND METHODS: in this study, 54 NAFLD patients were randomly devided into two groups, according to a double blind parallel design either phytosomal curcumin (250 mg/day) or placebo for 8 weeks. Fasting blood samples and anthropometric measures were taken twice, once at the baseline and once at the end of the study. Promoter methylation and 8-hydroxy-2' -deoxyguanosine (8-OHdG) concentration as DNA damage mediator were measured by restriction enzymes and enzyme-linked immunosorbent assay, respectively. RESULT: Analysis was performed on 44 patients. According to our between groups analysis, curcumin significantly reduced the methylation in MutL homolog 1 (MLH1) and MutS homolog 2 (MSH2) promoter regions. The within-group comparison revealed that anthropometric variables significantly decreased. However, the result of the between groups comparison indicated no significant changes in the anthropometric variables except for BMI. Liver enzymes and 8-OHdG did not significantly change at the end of the study, neither in curcumin group nor in placebo group. CONCLUSION: Curcumin might be able to reduce the risk of mismatch base pair in DNA among the NAFLD patients. However, it did not change the DNA damage mediator and liver enzymes. For confirming these results, more studies with longer duration, more numbers of examined genes, higher dose of curcumin, and larger sample size are required.

Effect of Phytosomal Curcumin on Circulating Levels of Adiponectin and Leptin in Patients with Non-Alcoholic Fatty Liver Disease: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is associated with insulin resistance and changes in serum adipocytokine levels. The aim of the current study was to evaluate the effect of phytosomal curcumin on serum adiponectin and leptin levels in patients with NAFLD. METHODS: In this randomized double-blind, placebo-controlled trial, 65 eligible patients were randomly allocated into curcumin and placebo recipient groups using a blocked randomized technique. Parameters of weight, height, body mass index (BMI), fasting blood sugar (FBS), lipid profile, aspartate aminotransferase (AST), alanine aminotransferase (ALT), adiponectin, leptin, and the leptin:adiponectin ratio were measured at baseline and eight weeks after intervention. RESULTS: High-density lipoprotein cholesterol (HDL-C) levels increased significantly in the curcumin group compared to the placebo group (p=0.01). Serum adiponectin levels increased significantly (p<0.001) and serum leptin levels decreased significantly (p<0.001) with a decrease in the leptin: adiponectin ratio in the curcumin group compared to the placebo group after 8 weeks of intervention. CONCLUSIONS: Non-alcoholic fatty liver disease was associated with changes in serum adipokines levels. Phytosomal curcumin effectively improved leptin and adiponectin levels. It is possible that curcumin efficacy will increase with long-term use of higher doses of this substance.

The effect of curcumin with piperine supplementation on pro-oxidant and antioxidant balance in patients with non-alcoholic fatty liver disease: a randomized, double-blind, placebo-controlled trial.

Background The main causes of the progression of non-alcoholic fatty liver disease (NAFLD) are enhanced levels of reactive oxygen species and lipid peroxidation products. Therefore, the usage of antioxidant agents for the prevention and remedy of this disorder was recommended. Curcumin is proposed to treat NAFLD due to its high antioxidative activity. The aim of this study was to examine the effect of curcumin with piperine supplementation on oxidative stress in subjects with NAFLD. Methods In this double-blind, placebo-controlled trial, 55 subjects were randomly divided into two groups (curcumin with piperine and placebo). The participants received administrations of curcumin (500 mg) in combination with piperine (5 mg) and placebo daily for 8 weeks. Oxidative stress was assessed by measuring serum pro-oxidant and antioxidant balance (PAB) assay before and after the intervention. Results The serum PAB values did not significantly change between the treatment group vs. age and gender-matched placebo group after 8 weeks of supplementation. Also, curcumin in combination with piperine did not show a significant decrease (p = 0.06) in PAB levels compared to baseline. Conclusions The present study demonstrated that a dose of curcumin, co-supplied with piperine might be less than a dose in which curcumin can significantly decrease PAB values in these patients.

A pilot study of the effect of phospholipid curcumin on serum metabolomic profile in patients with non-alcoholic fatty liver disease: a randomized, double-blind, placebo-controlled trial.

BACKGROUND/OBJECTIVES: Curcumin, a natural polyphenol compound in the spice turmeric, has been found to have potent anti-oxidative and anti-inflammatory activity. Curcumin may treat non-alcoholic fatty liver disease (NAFLD) through its beneficial effects on biomarkers of oxidative stress (OS) and inflammation, which are considered as two feature of this disease. However, the effects of curcumin on NAFLD have been remained poorly understood. This investigation evaluated the effects of administrating curcumin on metabolic status in NAFLD patients. SUBJECTS/METHODS: Fifty-eight NAFLD patients participated in a randomized, double-blind, placebo-controlled parallel design of study. The subjects were allocated randomly into two groups, which either received 250 mg phospholipid curcumin or placebo, one capsule per day for a period of 8 weeks. Fasting blood samples were taken from each subject at the start and end of the study period. Subsequently, metabolomics analysis was performed for serum samples using NMR. RESULTS: Compared with the placebo, supplementing phospholipid curcumin resulted in significant decreases in serum including 3- methyl-2-oxovaleric acid, 3-hydroxyisobutyrate, kynurenine, succinate, citrate, α-ketoglutarate, methylamine, trimethylamine, hippurate, indoxyl sulfate, chenodeoxycholic acid, taurocholic acid, and lithocholic acid. This profile of metabolic biomarkers could distinguish effectively NAFLD subjects who were treated with curcumin and placebo groups, achieving value of 0.99 for an area under receiver operating characteristic curve (AUC). CONCLUSIONS: Characterizing the serum metabolic profile of the patients with NAFLD at the end of the intervention using NMR-based metabolomics method indicated that the targets of curcumin treatment included some amino acids, TCA cycle, bile acids, and gut microbiota.

Anti-Inflammatory Effect of Crocus sativus on Serum Cytokine Levels in Subjects with Metabolic Syndrome: A Randomized, Double-Blind, Placebo- Controlled Trial.

BACKGROUND/AIMS: A growing body of evidence supports an important role of inflammatory cytokines in the development and progression of the Metabolic Syndrome (MetS), which explains, at least in part, its relationship with an increased cardiovascular-risk. Several studies have reported the therapeutic-impact of crocus-sativus in a preclinical/clinical setting. Here we have explored the effects of crocus-sativus, on the serum concentrations of twelve serum cytokines in subjects with MetS in a randomized control trial. METHODS: Forty four adult volunteers, who met the diagnostic-criteria of MetS, were enrolled and randomly divided into 2 groups, to receive 100 mg/day crocus-sativus for 12 weeks. 12 cytokines, including IL-1α, IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, TNF-α, MCP-1, IFN-γ, EGF, and VEGF were measured using sandwich chemi-luminescence assays before/after therapy. RESULTS: Individuals with MetS who received crocus-sativus had significantly (P<0.05) lower levels of total-cholesterol, low density-lipoprotein-cholesterol and triglyceride (TG), fasting-blood-sugar and hsCRP, however the serum concentration of high density-lipoprotein-cholesterol markedly enhanced after therapy (e.g., TG level reduced from 148.86±71.49 to 101.90±38.19 after therapy, P= 0.003). Moreover, we observed that treatment with Crocus-sativus affected the serumconcentrations of some pro-/anti-inflamatory cytokines. In particular, the level of VEGF was increased from 12.64 pg/mL (95% CI: 9.60-17.67) to 16.59 (95% CI: 11.33-35.98, P= 0.033. Similar results were detected for IL-6 and EGF. CONCLUSION: Our findings provide a novel insight into the therapeutic effects of this therapy in MetS patients via perturbation of serum cytokines and reducing the levels of triglyceride and LDL/TC, but further studies are required in larger populations.