Effects of curcuminoids on inflammatory and oxidative stress biomarkers and clinical outcomes in critically ill patients: A randomized double-blind placebo-controlled trial.

Experimental studies have suggested the beneficial effects of curcuminoids as natural polyphenols against traumatic brain injury (TBI). The aim of this study was to investigate the effects of supplementation with curcuminoids on inflammatory and oxidative stress biomarkers, clinical outcomes and nutritional status in critically ill patients with TBI. A total of 62 ICU-admitted adult patients with TBI were randomly allocated to receive either a daily dose of 500 mg curcuminoids or matched placebo via enteral nutrition for 7 consecutive days based on stratified block randomization by age and sex. Inflammatory and oxidative stress as well as clinical outcomes and nutritional status of the patients were measured at baseline and at the end of the study. There were no overall group effects regarding to all dependent variables. Compared with baseline, serum levels of IL-6, TNF-α, MCP-1 and CRP were significantly reduced in patients receiving curcuminoids (p < .05) without any significant changes in placebo group; however, changes in the activities of GPx and SOD in serum were not significant between two groups. Moreover, APACHEII and NUTRIC score were significantly improved following curcuminoids consumption in comparison with placebo (p < .05). The findings of this study suggest that short-term supplementation with curcuminoids may have beneficial effects on inflammation, clinical outcomes and nutritional status of critically ill patients with TBI.

Postprandial glycemia and insulin secretion following glutamine administration: A randomized controlled trial.

Objective: The objective of the present study is to investigate the effects of glutamine administration on postprandial glycemia, insulin, and C-peptide concentration in patients with type 2 diabetes. Methods: A randomized, double-blind, placebo-controlled trial was conducted on patients with type 2 diabetes so that 33 subjects were recruited in each group. The patients were randomly allocated to receive either 30 g/d glutamine or placebo (with instructions to take in half glass of ice-cold water 5 to 10 min before each main meal) for 6 weeks. Postprandial C-peptide, insulin, and glucose were measured at the baseline and at the end of the study at 30 and 90 min after consuming a meal comprising wheat-cake and reduced fat milk. Results: The repeated measures ANOVA revealed no significant difference between the groups for glucose and insulin after 6 weeks of intervention (p > 0.05). However, C-peptide was reduced in both intervention groups at all measurement points. Between-group differences remained significant by the end of the study (p = 0.02). Conclusions: Glutamine supplementation before each main meal does not represent an effective nutritional strategy to improve postprandial glycemic control or postprandial insulin secretion in type 2 diabetes patients.

Effects of supplementation with curcuminoids on serum adipokines in critically ill patients: a randomized double-blind placebo-controlled trial.

Previous studies have shown a beneficial effect of curcuminoids supplementation on serum concentrations of adipokines; however, there are no published studies that have examined this effect among critically ill patients. We aimed to assess the effects of supplementation with curcuminoids on serum concentrations of leptin and adiponectin in critically ill patients with traumatic brain injury (TBI). In this trial, 62 critically ill patients with TBI, aged 18-65 years, were randomly allocated to receive either 500 mg/day curcuminoids (co-administered with 5 mg/day piperine) or matched placebo for 7 days. Patients in both intervention groups received routine treatments for TBI as well as enteral nutrition. Serum concentrations of leptin and adiponectin were measured at baseline and at the end of trial. We found a significant reduction in serum levels of leptin in both curcuminoids (47.1%) and placebo (22.8%) groups; though the magnitude of reduction was greater in the former (p < .05). Supplementation with curcumioinds was not found to alter serum concentrations of adiponectin (p > .05). Supplementation with curcumioinds significantly reduced serum levels of leptin but had no significant effect on adiponectin levels in critically ill patients with TBI. Further clinical trials, particularly those with a long-term period, are needed to confirm our findings.

The Beneficial Effects of Alpha Lipoic Acid Supplementation on Lp-PLA2 Mass and Its Distribution between HDL and apoB-Containing Lipoproteins in Type 2 Diabetic Patients: A Randomized, Double-Blind, Placebo-Controlled Trial.

Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a new specific vascular inflammation biomarker that is carried by the lipoproteins in the blood and plays a prominent role in the pathogenesis of atherosclerosis. Increased Lp-PLA2 levels and impaired Lp-PLA2 distribution across high-density lipoprotein (HDL) and non-HDL lipoproteins have been reported in diabetic patients, which is associated with the increase in cardiovascular disease (CVD) risk. This study is aimed at investigating the effect of alpha lipoic acid (ALA), as an antioxidant with potential cardioprotective properties, on the Lp-PLA2 mass and its distribution in diabetic patients. In a double-blind, randomized, placebo-controlled clinical trial, seventy diabetic patients were randomly allocated to ALA (1200 mg ALA as two 600 mg capsules/day) and placebo (two maltodextrin capsules/day) groups. The serum levels of total Lp-PLA2 mass, HDL-Lp-PLA2, oxidized low-density lipoproteins (ox-LDL), apolipoprotein A1 (apo A1), lipid profiles, fasting blood sugar (FBS), and insulin were measured, and apolipoprotein B- (apoB-) associated Lp-PLA2 and homeostasis model of assessment index (HOMA-IR) were calculated at the baseline and after 8 weeks of intervention. ALA significantly decreased the ox-LDL, total Lp-PLA2 mass, apoB-associated Lp-PLA2, and percent of apoB-associated Lp-PLA2 and triglyceride and increased the percent of HDL-Lp-PLA2 compared with the placebo group but had no significant effect on HDL-Lp-PLA2 mass, apo A1, lipid profiles, and glycemic indices. There was a positive correlation between the reduction in the ox-LDL level and total Lp-PLA2 mass in the ALA group. In conclusion, ALA may decrease the CVD risk by reducing the ox-LDL and Lp-PLA2 mass and improving the Lp-PLA2 distribution among lipoproteins in type 2 diabetic patients.

Anti-leukemic activity of Satureja bachtiarica occurs by apoptosis in human cells.

Failure of apoptosis contributes to leukemia progression. We investigated extracts of a native Iranian plant, Satureja bachtiarica, for possible anti-leukemia activity by induction of apoptosis and changes to the cell cycle. Growth inhibition caused by aqueous, butanol, dichloromethane and hexane extracts of S. bachtiarica on K562 and Jurkat leukemia cells was assessed using a colorimetric assay. Extracts were analyzed for induction of apoptosis and cell cycle arrest using flow cytometry and measurement of caspase-3 activity. Dichloromethane and hexane extracts inhibited leukemia cell proliferation in a dose-dependent manner. The IC50 values of these extracts were 22-33 µg/ml. Flow cytometric determination of annexinV/propidium iodide positive cells verified a significantly increased percentage of apoptotic cells compared to negative controls. Both 50 µg/ml dichloromethane and hexane extracts induced apoptosis in 89-97% of K562 and 94-97% of Jurkat cells 48 h after treatment. The effects of extracts on the cell cycle included significantly increased numbers of K562 and Jurkat cells in the subG1 phase and decreased numbers of cells in the G1, S and G2/M phases. After 24 h, we found increased levels of caspase-3 activation in cells treated with 25 µg/ml dichloromethane and hexane extracts compared to untreated cells. Our findings indicate the anti-leukemic effects of dichloromethane and hexane extracts of S. bachtiarica due to induction of apoptosis and inhibition of cell cycle progression.

The Effect of Oligopin Supplementation on Hormonal and Metabolic Profiles in the Polycystic Ovary Syndrome: A Randomized Controlled Trial.

Background: A double blind clinical trial was performed to evaluate whether the polycystic ovary syndrome (PCOS)-specific serum markers and metabolic parameters would change in the women with PCOS during the three-month administration of oligopin. Methods: In this double-blind multicenter trial, we randomly assigned 80 PCOS women, based on a 1:1 ratio, to receive oligopin (n= 40) or maltodextrin as placebo (n = 40) for up to 3 months. As PCOS-specific outcomes, we investigated the changes in testosterone, sex hormone binding globulin (SHBG), free androgen index (FAI), dehydroepiandrosterone (DHEA), follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Secondary end points were metabolic (fasting glycaemia, hemoglobin A1c (HbA1c), lipids, insulin resistance (HOMA-IR)), anthropometrics parameters and blood pressure from the baseline to the end of treatment. We investigated serum transaminase, alkaline phosphatase (ALP), creatinine (Cr) and blood urea nitrogen (BUN) levels as hepatic and kidney outcomes, respectively. Results: The first participant was enrolled on April 18, 2018, and the last study visit took place on May 14, 2019. PCOS-specific serum parameters did not change during the three-month administration of oligopin (p > 0.05), except for a small increase in the FSH levels (p=0.03). Oligopin neither changed the metabolic profile nor the anthropometric parameters or blood pressure. ALP levels was significantly increased in placebo group, as compared with oligopin (p=0.01). Conclusion: Oligopin supplementation does not seem to be exerting a beneficial effect on both hormonal and metabolic parameters in the women with PCOS. Clinical Trial Registration: www.irct.ir, identifier IRCT20140406017139N3.

A placebo controlled randomized clinical trial of Crocus sativus L. (saffron) on depression and food craving among overweight women with mild to moderate depression.

WHAT IS KNOWN AND OBJECTIVE: Crocus sativus L., commonly known as saffron, has known anti-depressive properties. However, its effects on food craving and body weight in depressed patients are unknown. Hence, we aimed to evaluate the effects of saffron capsules on food craving, body weight and depression among overweight women with mild and moderate depression compared to the placebo. METHODS: Seventy-three women with BMI ≥ 25 comorbid with mild-to-moderate depression were recruited in this 12-week double-blind, placebo-controlled randomized clinical trial. Participants were randomly assigned into one of the two groups receiving daily either 30 mg of Crocus sativus capsules (15 mg twice/day) or placebo capsules (twice/day). We performed body composition assessments, and beck depression inventory-II at the baseline, and then 2, 4, 8 and 12 weeks later. One month after the participants stopped taking the capsules, weight differences were measured and compared between groups. RESULTS AND DISCUSSION: Fifty-two patients finished the study. The demographic and clinical variables at baseline were the same in two groups. Mean depression scores in the saffron group significantly decreased compared to placebo (mean ± SD: -8.4 score ± 5.9 vs -3.9 ± 5.5; t[50] = 2; P = .007; 95% CI: 1.3-7.7). There was not a significant effect of saffron on food craving using repeated-measures ANOVA, F(1, 29) = 0.38, P = .54. Patients in the saffron group showed fewer side effects. WHAT IS NEW AND CONCLUSION: Saffron capsules were not effective in reducing food craving, but as a safe over-the-counter supplement, it may help reduce the symptoms of depression in patients who experience mild or moderate depression and are overweight.

Therapeutic effects of supplementation with Curcuminoids in critically ill patients receiving enteral nutrition: a randomized controlled trial protocol.

BACKGROUND: Curcuminoids are dietary polyphenols that can improve health indices through different mechanisms such as anti-inflammatory, antioxidant and immunoregulatory properties. Due to the lack of evidences on the efficacy of curcuminoids in critically ill patients, this study was designed to investigate the effects of short-term curcuminoids supplementation on inflammatory, oxidative stress and adipokine indices as well as nutritional and clinical status in Traumatic Brain Injury (TBI) patients admitted in the Intensive Care Unit (ICU). METHODS: The present trial will be performed in the ICU of Sina and Shohadaye Tajrish hospitals of Tehran, Iran. Sixty-two critically ill patients with TBI will be enrolled based on the eligibility criteria. The patients will be randomly assigned into two groups. For 7 days, they will received either 500 mg curcuminoids in combination with 5 mg piperine or matched placebo. A general questionnaire, consent form as well as NUTRIC, SOFA and APACHEII scoring system and anthropometrics will be assessed at baseline. The inflammatory markers including TNF-α, IL-6, MCP-1 and CRP, oxidative stress indices (GPx and SOD) and adipokines (leptin and adiponetctin) will be measured at baseline and at the end of the study. In addition, dietary intake, concomitant drugs and laboratory tests will be recorded daily. DISCUSSION: To the best of our knowledge, this is the first clinical trial investigating the effect of curcuminoids supplementation in critically ill patient with TBI. The findings of the present study will provide evidence on the efficacy and safety of curcuminoids in these patients. TRIAL REGISTRATION NUMBER: (http://www.irct.ir, identifier: IRCT20180619040151N1), Registration date:18.09.2018.

Tumor Cell Death via Apoptosis and Improvement of Activated Lymphocyte Cytokine Secretion by Extracts from Euphorbia Hebecarpa and Euphorbia Petiolata.

Background: Immunomodulatory materials from natural herbs and the characterization of their immune enhancement effects may have tremendous potential as cancer treatment. The aim of the present study was to investigate the apoptosis-inducing activities of Euphorbia hebecarpa Boiss and Euphorbia petiolata Banks & Sol. plant extracts and their effects on cytokine secretion by lymphocytes. Materials and Methods: We assessed the apoptosis-inducing effect of the plants' hexane extracts on previously determined sensitive cell lines (HeLa for E. hebecarpa and K562 for E. petiolata) by flow cytometry and measurement of caspase 3 activation. The apoptosis-related gene expressions were examined by real-time PCR. The effects of the extracts on lymphocyte proliferation and cytokine secretion were examined. Results: Flow cytometry analysis showed that the inhibitory effect of the extracts on tumor cell growth was due to cell apoptosis. The plant extracts at the 100 µg/ml dose induced apoptosis in HeLa (98.5 ± 0.1%) and K562 (57.7 ± 1.9%) cells. The extracts increased caspase 3 activation (≈2-fold>control). Real-time PCR showed Fas and Bax gene upregulation and Bcl-2 downregulation, which resulted in an increased Bax/Bcl-2 expression ratio. The extracts increased lymphocyte proliferation and increased levels of IFN-γ production in the presence and absence of mitogen (p < 0.05). They significantly increased IL-4 and decreased IL-10 secretion by mitogen-stimulated lymphocytes. E. hebecarpa also increased IL-17 release. Conclusion: These results have shown that both extracts possess antitumor activity by inducing apoptosis, possibly through both intrinsic and extrinsic pathways. In addition, they induced secretion of different T helper subset related cytokines that are effective in the immune response against cancer.

Effects of French maritime pine bark extract (Oligopin®) supplementation on bone remodeling markers in postmenopausal osteopenic women: A randomized clinical trial.

French maritime pine bark extract (FMPBE; Oligopin®), a dietary supplement, is rich in procyanidin. The objective of this study was to determine the effects of FMPBE on bone remodeling in postmenopausal osteopenic women. This randomized, double-blinded, placebo-controlled clinical trial was conducted on 40 postmenopausal osteopenic women. Individuals were randomly assigned to either FMPBE (250 mg/day, n = 21) or placebo (250-mg starch/day, n = 19) for 12 weeks. Biochemical indices, including bone remodeling marker, were assessed before and after the intervention. After the 12-week intervention, that is, FMPBE supplementation, a significant increase in bone alkaline phosphatase (BAP), procollagen type 1 amino-terminal propeptide (P1NP) levels and a significant decrease in C-terminal telopeptide of type I collagen (CTx1) were observed. Compared with the control group, FMPBE supplementation resulted in a significant increase in P1NP (0.015), BAP levels (0.001), and BAP/CTx1 ratio (p = 0.001) and a significant decrease in CTx1 levels (0.006). FMPBE supplementation for 12 weeks in postmenopausal osteopenic women produced favorable effects on bone markers. Meanwhile, further research is needed to determine whether FMPBE supplements can be used as a preventive strategy for bone loss in postmenopausal osteopenic women.

Modulation of in vitro proliferation and cytokine secretion of human lymphocytes by Mentha longifolia extracts.

OBJECTIVE: Mentha longifolia L. Hudson has been used in folk medicine for various purposes especially for its anti-inflammatory effects. Lymphocytes play a central role in development of inflammation. In the present study, we investigated the immunomodulatory effects of different extracts of M. longifolia on human peripheral blood lymphocytes (PBLs), as main players in development of inflammation. MATERIALS AND METHODS: PBLs stimulated with phytohemagglutinin (PHA) were cultured in the presence of the plant extracts. The effects of the extracts on activation of cells were determined by BrdU assay. The viability of cells was examined by flow cytometry using propidium iodide staining. Also, IFN-γ (T helper 1, TH1) and IL-4 (TH2) secretion was measured by ELISA. RESULTS: Except for the water extract which had a weak inhibitory effect, treatment of cells with more than 1µg/ml of butanol, hexane, ethyl acetate and dichloromethane extracts resulted in strong inhibition of cells proliferation (IC50 4.6-9.9 µg/ml). Flow cytometry analysis showed that these extracts at ≤10µg/ml were non-cytotoxic. Dichloromethane and ethyl acetate extracts at 10 µg/ml decreased IFN-γ production in a dose-dependent manner from 919±91.1 pg/ml in PHA-only-treated cells to 568±22.6 pg/ml (in dichloromethane-treated cells) and 329±12.3 pg/ml (in ethyl acetate-treated cells) (p<0.001). At 10 µg/ml, the ethyl acetate extract increased IL-4 secretion compared to PHA-only-treated cells (p<0.05). The hexane extract decreased IFN-γ level but did not affectIL-4 production. CONCLUSION: Reduction of IFN-γ and augmentation of IL-4 secretion induced by the extracts suggested the potential of M. longifolia to inhibit TH1 inflammatory responses toward a TH2 dominant response.

Omega-3 supplementation effects on body weight and depression among dieter women with co-morbidity of depression and obesity compared with the placebo: A randomized clinical trial.

PURPOSE: We aimed to evaluate the effects of the omega-3 supplementation on body weight and depression among women with co-morbidity of depression and obesity seeking weight reduction compared with the placebo. METHODS: Sixty five patients with co-morbidity of depression and overweight/obesity (BMI ≥ 25) signed the informed consent form and enrolled into this 12-week double-blind, placebo-controlled randomized clinical Trial. Subsequently, participants randomly assigned into one of the two groups receiving daily 6 capsules of omega-3 (each capsule containing 180 mg EPA, and 120 mg DHA) or 6 capsules of placebo (two with each meal). We performed body composition assessments and Beck depression inventory at the baseline, and weeks 2, 4, 8, and 12 after the start of the study. One month after stopping the capsules at the follow-up visit, weight was measured to compare weight relapse between the two groups. RESULTS: Forty five patients finished the study. No significant differences were seen between groups regarding demographic and clinical variables at baseline. Using repeated measures ANOVA, omega-3 significantly reduced depression compared with the placebo (P = 0.05). Mean ± SD weight reduction in omega-3 group 3.07 ± 3.4 kg and in the placebo group was 1.16 ± 2.7 kg and the difference between groups was significant using independent sample t-test (p = 0.049). Patients in the omega-3 group did not show significantly more side effects compared to the placebo but they were not successful in preventing weight regain one month after the end of the study. CONCLUSION: Based on our findings omega-3 capsule as a safe over-the-counter supplement might be helpful in reducing the signs of depression and also body weight in patients with co-morbidity of depression and obesity.

The Effect of Eicosapentaenoic Acid on the Serum Levels and Enzymatic Activity of Paraoxonase 1 in the Patients With Type 2 Diabetes Mellitus.

Paraoxonase 1 is known as one of the most important ant oxidative enzymes associated with HDL-c, and because of its antioxidant and antiinflammatory activities. EPA has the antioxidant, anti inflammatory, antithrombogenic, and antiarteriosclerotic properties. Therefore, we investigated the effect of EPA supplementation on the serum levels and activity of PON1 in type 2 diabetic patients. This study was designed as a randomized, double-blind, and placebo-controlled clinical trial. Thirty-six patients with type 2 diabetes were given written; informed consent randomly was classified into 2 groups. They were supplemented with 2 g/day of the capsules of EPA or placebo for eight weeks. Blood sample was given for measurement of the serum levels of lipids, the activity of PON1, FBS and HbA1c. The patients supplemented with EPA showed a significant increase in the serum levels and activity of PON1 and the serum ratio of PON1/HDL-c. There were no significant differences between the two groups regarding any demographic, clinical or biochemical data, total energy intake, and macronutrient intake at the baseline during the intervention, except for a significant increase of protein intake and the levels of HbA1c in the placebo group, and a significant increase of HDL-c, as well as a slight reduction of total cholesterol, LDL-c, TG and FBS in the supplement group. EPA is atheroprotective via increase in the serum levels and activity of PON1, as well as change in the serum levels of lipids, FBS and HbA1c.

Nutrients as novel therapeutic approaches for metabolic disturbances in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders among women. This disease is characterized by infertility, menstrual dysfunction, and hyperandrogenism. Also, PCOS is often associated with hyperlipidemia and impaired glucose tolerance, conditions that are associated with cardiovascular disorder, type 2 diabetes, cancer and hypertension. Evidence supports that some nutrients may affect the hormonal and metabolic disturbances of PCOS. Here in this study, we aimed to review the available literature that assessed the nutrients such as inostol, isoflavonids, resveratrol, vitamin D, and PUFA (polyunsaturated fatty acids), known to influence the hormonal and metabolic disturbances of PCOS, along with the strategies and future directions of nutrient supplementations in such patients.

Effect of glutamine supplementation on cardiovascular risk factors in patients with type 2 diabetes.

OBJECTIVE: The aim of this study was to assess clinical relevance of long-term oral glutamine supplementation on lipid profile and inflammatory and metabolic factors in patients with diabetes. METHOD: Sixty-six patients with type 2 diabetes between the ages of 18 and 65 y were randomized to receive glutamine 30 g/d (10 g powder, three times a day) or placebo, in a double-blind, placebo-controlled trial during a 6-wk treatment period. Fifty-three patients completed the trial. Independent samples t test and analysis of covariance were used. RESULTS: After a 6-wk treatment period, a significant difference was observed between the two groups in body fat mass (P = 0.01) and percentage of body fat (P = 0.008). Moreover, a significant reduction in waist circumference (P < 0.001) and a tendency for an increase in fat-free mass (P = 0.03), with no change in body weight and body mass index (BMI) was found. Enhancement in body fat-free mass was mainly attributed to trunk (P = 0.03). There was a downward trend in systolic blood pressure (P = 0.005) but not diastolic. Fasting blood glucose (mmol/L) concentration significantly decreased after the 6-wk intervention (P = 0.04). Mean hemoglobin A1c was significantly different between the groups at week 6 (P = 0.04). No significant difference was detected for fasting insulin, homeostasis model assessment for insulin resistance and quantitative insulin sensitivity index between groups (P > 0.05). No significant difference was observed between groups in total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and triglyceride. No treatment effect on C-reactive protein was found (P = 0.44). CONCLUSION: We demonstrated that the 6-wk supplementation with 30 g/d glutamine markedly improved some cardiovascular risk factors, as well as body composition, in patients with type 2 diabetes. Future glutamine dose-response studies are warranted in these areas.

Augmentation of lymphocytes activation and T cell modulation by the extracts from some Euphorbia species.

CONTEXT: Euphorbia is an important Euphorbiaceae genus that is traditionally being used for various infections, inflammation, and cancer. OBJECTIVE: The present study investigated the possible in vitro immunomodulatory effect of three species of Euphorbia genus including Euphorbia microciadia Boiss, Euphorbia osyridea Boiss, and Euphorbia heteradenia Jaub. & Sp. on lymphocyte activation and cytokine secretion. MATERIALS AND METHODS: Human lymphocytes were cultured in the presence of various concentrations (0.1-200 µg/ml) of the butanol/hexane extracts of the plants in the presence or absence of phytohemmagglutinin (PHA). The activation of lymphocytes after 48 h was determined by a proliferation assay. The release of T cell cytokines was studied to determine the dominant T cell subsets involved in the immune response. RESULTS: All three plant extracts increased the proliferation of PHA-treated lymphocytes (maximum; 132% of control). Extract treatment of lymphocytes in the absence of PHA resulted in an increased proliferation of the cells indicating their lymphocyte mitogenic activity (maximum at 10 µg/ml E. microciadia extract; 494.5 ± 42.2% of control, p < 0.01). The extracts of E. microciadia and E. osyridea could increase IL-4 and IL-10 secretion but not IFN-γ production showing their capacity to deviate immune response toward a Th2 pattern. Euphorbia heteradenia did not change the release of IL-4 and IFN-γ cytokines but increased IL-10 production. The three extracts stimulated lymphocytes to produce IL-17 which showed their possible effects on Th17 cells activation. CONCLUSION: The studied extracts had the ability to modulate T cell responses suggesting their possible beneficial effects on immune host defense.

The hypoglycemic effect of Juglans regia leaves aqueous extract in diabetic patients: A first human trial.

BACKGROUND: Juglans regia L. (J. regia ) is one of the medicinal plants traditionally used for treatment of diabetes in Iranian medicine. The effect of this plant has already been investigated on animal models; however, this is the first study conducted on human subjects. The aim of this study is to investigate the hypoglycemic effect of J. regia leaves aqueous extract in type 2 diabetes patients. Fifty eight Iranian male and female patients with type 2 diabetes were enrolled. The patients were randomly allocated into two groups. One group (n = 30) received J. regia leaves extract while the other group (n = 28) received placebo. Fasting blood samples were collected at the beginning of the study and after two months for determination of HbA1c and blood glucose level as a main outcome and insulin, SGOT, SGPT, and ALP level as secondary outcome. RESULTS: Our analysis showed that serum fasting HbA1C and blood glucose levels were significantly decreased and the insulin level was increased in patients in the J. regia arm. CONCLUSIONS: The results indicate that J. regia aqueous extract favorably affects blood levels of glucose, insulin and HbA1C in type 2 diabetic patients.

Effects of Juglans regia L. leaf extract on hyperglycemia and lipid profiles in type two diabetic patients: a randomized double-blind, placebo-controlled clinical trial.

ETHNOPHARMACOLOGICAL RELEVANCE: The Juglans regia L. leaf has been traditionally used for treatment of diabetes mellitus in Iran. But yet, no controlled human study has determined its efficacy in diabetic patients. The present study was designed to investigate the effects of the Juglans regia leaf extract on hyperglycemia and lipid profiles in type II diabetic patients. MATERIALS AND METHOD: Total 61 patients, suffering from type II diabetes with fasting blood glucose (FBG) between 150 and 200mg/dL, glycated hemoglobin (HbA1c) between 7% and 9% and aged between 40 and 60 years were selected, and randomly divided in to two groups of Juglans regia and placebo. First group received 100mg Juglans regia leaf extract in capsules form two times a day for 3 months and other group received 100mg placebo capsule with the same dosage. The standard anti-diabetic therapy (metformin and glibenclamide, and nutritional regimen) was continued in both groups. At the baseline and after three months the FBG, insulin, HbA1c, cholesterol, triglyceride, HDL, LDL and liver and renal function tests were determined. In addition general satisfaction with the treatment was identified using health questionnaires. RESULTS: The results indicated that FBG, HbA1c, total cholesterol and triglyceride levels in Juglans regia treated patients significantly decreased compared with the baseline and with placebo group. Patients in Juglans regia group were significantly satisfied with Juglans regia treatment compared with the placebo group. No liver, kidney and other side effects were observed in the groups, except more GI events (specially a mild diarrhea) associated with extract treatment at the beginning of the study. CONCLUSION: In conclusion, treatment of type II diabetic patients with 100mg Juglans regia leaf extract two times a day for three months improves lipid profile and glycemic control without any tangible adverse effects.

Effects of EPA supplementation on plasma fatty acids composition in hypertriglyceridemic subjects with FABP2 and PPARα genotypes.

BACKGROUND: Fatty acid binding protein 2 (FABP2) and peroxisome proliferator-activated receptor α (PPARα) are involved in cellular uptake and metabolism of fatty acids. Polymorphism of FABP2 and PPARα may influence plasma levels of fatty acids in those who take supplemental eicosapentaenoic acid (EPA). The purpose of this study was to study the potential associations between the Ala54/Thr polymorphism in FABP2 protein and the Leu162/Val in exon 5 and G/C in intron 7 of PPARα with plasma fatty acids composition after EPA supplementation. METHODS: Twenty three FABP2 Ala54 and twenty three Thr54 carriers with hypertriglyceridemia were enrolled in this study. Participants took 2 g of pure EPA daily for 8 wks. Plasma fatty acids composition was determined and changes from the baseline were measured. RESULTS: Although EPA supplementation increased the level of plasma EPA and ω-3 fatty acids in both carriers of FABP2 and PPARα genes, these effects were more pronounced in Thr54 and Val162 carriers. EPA supplementation decreased the level of some n-6 fatty acids such as arachidonic acid. CONCLUSION: EPA consumption has more favorable effects on blood n-3 fatty acids and can change the level of plasma n-3 fatty acids, particularly EPA. Because the FABP2 Thr54 polymorphism appears to be prevalent in hypertriglyceridemic subjects, increasing EPA intake in these subjects could be an effective strategy for preventing cardiovascular diseases. Finally, diets and micronutrient recommendations should be individualized for high risk people.

Inhibition of nitric oxide production and proinflammatory cytokines by several medicinal plants.

BACKGROUND: A number of medicinal plants have been used to treat various immunological diseases. Nitric oxide (NO) has an important regulatory role in the various types of inflammatory processes. OBJECTIVE: To investigate the NO modulatory activity of the extracts of several medicinal plants native to Iran including Dracocephalum kotschyi, Linum persicum, Dionysia termeana, Salvia mirzayanii, Ferulago angulata and Euphorbia cheiradenia. METHODS: The methanolic extracts of the plants were prepared and examined for their effects on the NO production by lipopolysaccharide-stimulated mouse macrophages. The level of TNF-α and IL-1ß pro-inflammatory cytokines in the macrophage culture were detected using enzyme-linked immunosorbent assay. RESULTS: All the extracts at concentration of 50 µg/ml demonstrated a significant decrease in NO production (p<0.001) after a 24-hour treatment. This inhibitory effect was also seen after 48 hours. Among the extracts, L. persicum was the strongest extract in reducing the NO production at 1 µg/ml after both 24 and 48-hours (nearly 100% inhibition, p<0.001). S. mirzayanii extract with 66.2 ± 8% inhibition at 50 µg/ml, showed the mildest effects in 48 hour culture. In cytokine release determination, the extract of L. persicum significantly inhibited both TNF-α and IL-1ß cytokines production by stimulated macrophages (p<0.001). D. kotschyi, D. termeana and F. angulata decreased secretion of IL-1ß from the cells. CONCLUSION: These results indicate the presence of anti-inflammatory and macrophage inhibitory substances in these plants.