Acute cardiovascular effects of bitter orange extract (p‐synephrine) consumed alone and in combination with caffeine in human subjects: A placebo‐controlled,double‐blind study

The purpose was to examine cardiovascular responses to supplementation with p‐synephrine alone and in combination with caffeine during quiet sitting. Sixteen subjects were given (in double‐blind manner) either 103 mg of p‐synephrine (S), 233 mg of caffeine +104 mg of p‐synephrine (LC + S), 240 mg of caffeine (LC), 337 mg of caffeine +46 mg of p‐synephrine (HC + S), 325 mg of caffeine (HC), or a placebo. The subjects sat quietly for 3 hr while heart rate (HR) and blood pressure were measured. Only HC + S and HC significantly increased mean systolic blood pressure (SBP) during the second hour and tended to increase mean SBP during the third hour. Mean diastolic blood pressure in S was significantly lower than the other trials during the first and second hours, and mean arterial pressure was significantly lower in S compared to the LC, LC + S, HC, and HC + S trials. No differences were observed in HR. Consumption of p‐synephrine may acutely reduce diastolic blood pressure and mean arterial pressure and not affect SBP or HR during quiet sitting. The addition of p‐synephrine to caffeine did not augment SBP or HR indicating that consumption of up to 104 mg of p‐synephrine does not induce cardiovascular stress during quiet sitting.     

The effects of black seed supplementation on cardiovascular risk factors in patients with nonalcoholic fatty liver disease: A randomized,double‐blind,placebo‐controlled clinical trial

Nonalcoholic fatty liver disease (NAFLD) is highly related to cardiovascular disorders risk factors. This study aimed to evaluate the effects of black seed (Nigella sativa) supplementation on cardiovascular disorders risk factors in patients with NAFLD. This randomized, double‐blind, placebo‐controlled clinical trial was conducted on 50 patients with NAFLD. Participants were assigned to receive a lifestyle modification plus 2 g/day of either N. sativa or placebo for 12 weeks. Compared with the placebo, N. sativa supplementation led to significant reductions in serum glucose (?7.95 vs. ?1.22; p = .041), serum insulin (?3.87 vs. ?1.07; p = .027), homeostatic model of assessment for insulin resistance (?1.02 vs. ?0.28; p = .021), and a significant increase in quantitative insulin sensitivity check index (0.03 vs. 0.006; p = .002). All of these changes were remained significant after adjusting for known confounding variables; however, there was no significant difference in lipid profile changes between the two groups (p = .05). N. sativa supplementation significantly decreased hepatic steatosis percentage compared with the placebo after adjustment for confounding variables (p = .005). In conclusion, our results indicate that daily intake of 2‐g N. sativa plus lifestyle modification is superior to lifestyle modification alone in amelioration of insulin resistance and hepatic steatosis in patients with NAFLD.     

Metabolic benefits of curcumin supplementation in patients with metabolic syndrome: A systematic review and meta‐analysis of randomized controlled trials

The finding of studies on the effect of curcumin extract on metabolic factor in patients with metabolic syndrome has had arguable results. This systematic review with meta‐analysis of randomized controlled trials (RCT) aimed to analyze the effect of curcumin/turmeric on metabolic factors in patients with metabolic syndrome. The PICO strategy was used to establish the guiding question of this review. Several databases for RCT were searched until September 2018. Of the 144 articles initially identified, seven trials met the eligibility criteria. A random‐effects model with a mean weight difference (WMD) and a 95% confidence interval was performed for quantitative data synthesis. Pooled estimates of WMD were calculated between intervention and control groups using random‐effects model in the presence of high level of heterogeneity between the studies. The results showed significant improvement of fasting blood glucose (p = 0.01), triglycerides (p < 0.001), high‐density lipoprotein cholesterol (p = 0.003), and diastolic blood pressure (p = 0.007) levels. Curcumin was not associated with a significant change in waist circumference measurement (p = 0.6) and systolic blood pressure level (p = 0.269). Curcumin supplementation improves some components of metabolic syndrome.     

Efficacy of artichoke leaf extract in non‐alcoholic fatty liver disease: A pilot double‐blind randomized controlled trial

Non‐alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide and is potentially treatable, though there are few therapeutic agents available. Artichoke leaf extract (ALE) has shown potential as a hepatoprotective agent. This study sought to determine if ALE had therapeutic utility in patients with established NAFLD. In this randomized double‐blind placebo‐controlled parallel‐group trial, 100 subjects with ultrasound‐diagnosed NAFLD were randomized to either ALE 600 mg daily or placebo for a 2‐month period. NAFLD response was assessed by liver ultrasound and serological markers including the aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio and AST to platelet ratio index (APRI) score. Ninety patients completed the study (49 ALE and 41 placebo) with no side effects reported. ALE treatment compared with placebo: Doppler sonography showed increased hepatic vein flow (p < .001), reduced portal vein diameter (p < .001) and liver size (p < .001), reduction in serum ALT (p < .001) and AST (p < .001) levels, improvement in AST/ALT ratio and APRI scores (p < .01), and reduction in total bilirubin. ALE supplementation reduced total cholesterol, low‐density lipoprotein cholesterol, high‐density lipoprotein cholesterol, non‐high‐density lipoprotein cholesterol, and triglyceride concentrations (p = .01). This study has shown beneficial effects of ALE supplementation on both ultrasound liver parameters and liver serum parameters (ALT, AST, APRI ratio, and total bilirubin) in patients with NAFLD.     

A comparison between the effects of flaxseed oil and fish oil supplementation on cardiovascular health in type 2 diabetic patients with coronary heart disease: A randomized,double‐blinded,placebo‐controlled trial

This study compared the effects of flaxseed and fish oil supplementation on cardiovascular risk parameters in diabetic patients with coronary heart disease. Participants were randomly allocated into three intervention groups to receive either 1,000 mg of omega‐3 fatty acids from fish oil or 1,000 mg of omega‐3 fatty acids from flaxseed oil or placebo (n = 30 each group) twice a day for 12 weeks. A significant reduction in insulin levels (.04) was observed following flaxseed oil and fish oil supplementation compared with the placebo. In addition, a significant reduction in high‐sensitivity C‐reactive protein (.02) was seen after flaxseed oil supplementation compared with the placebo and a significant increase in total nitrite (.001) was seen after flaxseed oil and fish oil intake compared with placebo. Additionally, a significant increase in total antioxidant capacity (p < .001) after consuming flaxseed oil and fish oil compared with placebo and glutathione levels (.001) after consuming fish oil compared with flaxseed oil and placebo was observed. Overall, our study revealed the beneficial effects of flaxseed oil and fish oil supplementation on few metabolic profiles. This study suggests that the effect of flaxseed oil in reducing insulin and increasing total nitrite and total antioxidant capacity is similar to fish oil.     

Possible therapeutic effect of carvacrol on asthmatic patients: A randomized,double blind,placebo‐controlled,Phase II clinical trial

The relaxant effects of carvacrol, a phenolic monoterpene, on tracheal smooth muscle and its preventive effect on asthmatic animals were reported. The effect of carvacrol in asthmatic patients was examined in the placebo group (Group P, n = 11) receiving placebo and treatment group (Group C, n = 12), which received carvacrol capsule (1.2 mg/kg/day) for 2 months in a double‐blind manner. Pulmonary function tests, respiratory symptoms, hematological indices, and high‐sensitivity C‐reactive protein (hs‐CRP) were measured before, 1 and 2 months after starting treatment. At the end of treatment period, Pulmonary function tests values in Group C were significantly increased (p < .05 to p < .001). Most respiratory symptoms were also significantly reduced in Group C at the end of 2‐month treatment (p < .05 to p < .001). Total and differential white blood cell (p < .05 to p < .001), as well as serum levels of hs‐CRP in Group C were also significantly reduced after 2‐month treatment with carvacrol (p < .001). Mean corpuscular hemoglobin concentration and hematocrit were changed in Group C (p < .05 and p < .01, respectively). However, in Group P, there was no significant changes in the evaluated parameters. Pulmonary function tests were increased but respiratory symptoms, inflammatory cells, and hs‐CRP were reduced in asthmatic patients who received carvacrol that indicates its therapeutic effect on asthma.     

Effect of sour tea supplementation on liver enzymes,lipid profile,blood pressure,and antioxidant status in patients with non‐alcoholic fatty liver disease: A double‐blind randomized controlled clinical trial

The aim of this study was to evaluate the efficacy of sour tea supplementation in patients with nonalcoholic fatty liver disease (NAFLD). Seventy NAFLD patients were enrolled in this randomized, double‐blind, placebo‐controlled clinical trial. Participants received sour tea in the form of a 450 mg capsule or a placebo capsule daily for 8 weeks. Anthropometric indices, liver enzymes, lipid profile, blood pressure, and antioxidant status were evaluated at the baseline and at the end of the study. Sixty‐one participants completed the study. After 8 weeks, sour tea administration significantly decreased serum triglyceride (TG) (p = .03), alanine aminotransferase (ALT) (p = .01), and aspartate aminotransferase (AST) (p = .004) levels compared with the placebo. In addition, sour tea supplementation resulted in a significant reduction in systolic blood pressure (SBP) (p = .03) and diastolic blood pressure (DBP) (p = .04), and a significant increase in serum total antioxidant capacity (TAC) levels (p ? .001) compared with the placebo. However, no significant changes in anthropometric measures, total cholesterol (TC), low‐density lipoprotein cholesterol (LDL‐c), and high‐density lipoprotein cholesterol (HDL‐c) levels were observed after sour tea supplementation compared with the placebo (p > .05). Sour tea supplementation may be effective in improving serum TG, liver enzymes, and blood pressure in patients diagnosed with NAFLD. Further studies are needed to address the exact mechanism of action of these effects.     

Blood pressure lowering and anti‐inflammatory effects of hesperidin in type 2 diabetes; a randomized double‐blind controlled clinical trial

Elevated levels of reactive oxygen species under diabetic condition lead to vascular complications and inflammation. This study aimed to examine the effects of hesperidin supplement on blood pressure and inflammatory markers in type 2 diabetes. In this research, 64 patients were randomly allocated to receive 500 mg/day hesperidin or placebo capsules for 6 weeks. Data on systolic blood pressure (SBP), diastolic blood pressure, serum total antioxidant capacity (TAC), tumor necrosis factor alpha, interleukin 6 (IL‐6), and high‐sensitivity C‐reactive protein (hs‐CRP) were collected at the baseline and at the end of the study. In the hesperidin group, SBP (122.7 ± 8.5 vs. 119.0 ± 7.4; p = .005), mean arterial blood pressure (94.2 ± 5.5 vs. 91.8 ± 5.5; p = .009), IL‐6 (8.3 ± 2.1 vs. 7.4 ± 1.8; p = .001), and hs‐CRP (1.9 ± 1.2 vs. 1.1 ± 0.9; p < .000) decreased whereas TAC increased (0.74 ± 0.1 vs. 0.82 ± 0.1; p < .000) in comparison to the baseline values. There was a significant difference in mean percent change of SBP, diastolic blood pressure, mean arterial blood pressure, serum TAC, and inflammatory markers (tumor necrosis factor alpha, IL‐6, and hs‐CRP) between hesperidin and control groups following intervention in adjusted models (p < .05). These results suggest that hesperidin may have antihypertensive and anti‐inflammatory effects in type 2 diabetes.     

The effects of fenugreek seed extract supplementation in patients with Alzheimer's disease: A randomized,double-blind,placebo-controlled trial

The aim of the current randomized control trial (RCT) study was to investigate the effects of fenugreek seed extract on memory, depression, quality of life, blood pressure, and serum malondialdehyde (MDA) and total antioxidant capacity (TAC) levels in adult AD patients. This randomized clinical trial was conducted in geriatric homes in Iran. The study participants included 82 AD patients with mild-to-moderate memory deficit. Patients in the intervention group received 5 cc of fenugreek seed extract for 4 months and subjects in the control group received a placebo. Memory, depression, quality of life, and BP levels, as well as serum MDA and TAC, were assessed before and after the intervention. There was a significant increase in serum levels of TAC (p < 0.001) and a reduction in serum MDA status (p < 0.001) after 4 months of fenugreek seed extract supplementation. In addition, increasing levels of memory (p < 0.001) and quality of life (p < 0.001), as well as reduction of depression (p = 0.002), systolic BP (p < 0.001), and diastolic BP (p < 0.001) levels were detected in the intervention group compared with baseline. Fenugreek seed extract supplementation in AD patients shows promising positive effects on memory, quality of life, BP, and selective oxidative indices levels.     

Effects of ginseng supplementation on selected markers of inflammation: A systematic review and meta‐analysis

The present meta‐analysis was performed to evaluate the efficacy of ginseng administration on serum level of inflammatory biomarkers. We performed a systematic search of all available randomized controlled trials (RCTs) conducted up to June 2018 in the following electronic databases: PubMed, Scopus, Cochrane, and Google Scholar. RCTs that investigated the effect ginseng supplementation on high‐sensitivity C‐reactive protein (hs‐CRP), tumor necrosis factor‐α (TNF‐α), and interleukin‐6 (IL‐6) were included for final analysis. A total of seven RCTs were included in the meta‐analysis. Results indicated significant reduction in IL‐6 (mean difference [MD]: ?0.265 pg/ml, 95% CI [?0.396, ?0.135], p < .001) and TNF‐α (MD: ?2.471 pg/ml, 95% CI [?2.904, ?2.039], p < .001) and no significant change in hs‐CRP (MD: ?0.125 mg/L, 95% CI [?0.597, 0.347], p = .604). Although there was publication bias across studies, trim and fill analysis showed that results from unpublished studies could not change the results for CRP. However, removing one study in sensitivity analysis did reveal a significant reduction in CRP. We conclude that ginseng supplementation significantly lowered IL‐6 and TNF‐α but did not significantly lower CRP. However, these findings were not robust, because they showed sensitivity for CRP and IL‐6, and future long‐term well‐designed dose‐escalating trials are required.     

Effects of curcumin/turmeric supplementation on obesity indices and adipokines in adults: A grade-assessed systematic review and dose–response meta-analysis of randomized controlled trials

In the present study, we explored the effect of curcumin/turmeric supplementation on anthropometric indices of obesity, leptin, and adiponectin. We searched PubMed, Scopus, Web of Science, Cochrane Library, and Google Scholar up to August 2022. Randomized clinical trials (RCTs) investigating the impact of curcumin/turmeric on obesity indices and adipokines were included. We applied the Cochrane quality assessment tool to evaluate the risk of bias. The registration number is CRD42022350946. Sixty eligible RCTs, with a total sample size of 3691 individuals were included for quantitative analysis. We found that supplementation with curcumin/turmeric significantly reduced body weight (WMD: −0.82 kg, 95% CI: −1.30, −0.35; p = 0.001), body mass index (WMD: −0.30 kg/m², 95% CI: −0.53, −0.06, p = 0.013), waist circumference (WMD: −1.31 cm, 95% CI: −1.94, −0.69, p < 0.001), body fat percentage (WMD: −0.88%, 95% CI: −1.51, −0.25, p = 0.007), leptin (WMD = −4.46 ng/mL; 95% CI: −6.70, −2.21, p < 0.001), and increased adiponectin (WMD = 2.48 μg/mL; 95% CI: 1.34, 3.62, p < 0.001). Overall, our study shows that supplementation with curcumin/turmeric significantly improves anthropometric indices of obesity and adiposity-related adipokines (leptin and adiponectin). However, due to high between-studies heterogeneity, we should interpret the results with caution.     

A randomized,double-blind placebo-controlled add-on trial to assess the efficacy,safety, and anti-atherogenic effect of spirulina platensis in patients with inadequately controlled type 2 diabetes mellitus

The efficacy of spirulina platensis (S. platensis) as an add-on therapy to metformin and its effect on atherogenic keys in patients with uncontrolled Type 2 Diabetes Mellitus (T2DM) was evaluated. Sixty patients were randomly assigned to S. platensis (2 g/day) or placebo group for three months while continuing metformin as their usual treatment. The efficacy of S. platensis was determined using the pre- and post-intervention HbA1c levels (primary outcome) as well as tracking FBS and lipid profiles levels (TC, LDL-C, TG, and HDL-C) as secondary outcomes at the different treatment time points (0,30,60,90 days). During the three–month intervention period, supplementation with S. platensis resulted in a significant lowering of HbA1c (↓1.43, p < 0.001) and FBS (↓ 24.94 mg/dL, p < 001) levels. Mean TG in the intervention group was found to be significantly lower in the intervention group than in controls (p < 0.001). Total cholesterol (TC) and its fraction, LDL-C, exhibited a fall (↓41.36 mg/dL and ↓38.4 mg/dL, respectively; p < 0.001) coupled with a marginal increase in the level of HDL-C (↑3 mg/dL; p < 0.001). Add-on therapy with S. platensis was superior to metformin regarding long-term glucose regulation and controlling blood glucose levels of subjects with T2DM. Also, as a functional supplement, S. platensis has a beneficial effect on atherogenic keys (TG and HDL-C) with no adverse events.     

Effect of curcumin supplementation on disease severity in patients with liver cirrhosis: A randomized controlled trial

Recent reports indicated that curcumin had beneficial effects in animal models of liver injury and cirrhosis. Current study aimed to investigate the effects of curcumin supplementation in patients with liver cirrhosis. In this randomized double‐blind placebo‐controlled trial, 70 patients with liver cirrhosis aged 20–70 years were randomly divided into two groups to receive 1,000 mg/day curcumin (n = 35) or placebo (n = 35) for 3 months. Model for end‐stage liver disease (MELD) (i), MELD, MELD‐Na, and Child–Pugh scores were used to assess the severity of cirrhosis. Sixty patients (29 in the curcumin group and 31 in the placebo group) completed the study. MELD(i) (15.55 ± 3.78 to 12.41 ± 3.07), MELD (15.31 ± 3.07 to 12.03 ± 2.79), MELD‐Na (15.97 ± 4.02 to 13.55 ± 3.51), and Child–Pugh (7.17 ± 1.54 to 6.72 ± 1.31) scores decreased significantly in the curcumin group after 3‐month intervention (p < .001, p < .001, p = .001, and p = .051, respectively), whereas they increased significantly in the placebo group (p < .001, p < .001, p < .001, p = .001, respectively). Significant differences were only observed between the two groups in MELD(i), MELD, MELD‐Na, and Child–Pugh scores after 3‐month intervention (p < .001 for all of them). In this pilot study, beneficial effects of curcumin supplementation were observed in decreasing disease activity scores and severity of cirrhosis in patients with cirrhosis.     

Effect of Curcuma longa on vascular function in native Tamilians with type 2 diabetes mellitus: A randomized,double‐blind,parallel arm,placebo‐controlled trial

Diabetes mellitus is characterized by increased central arterial stiffness and endothelial dysfunction leading to increased risk of cardiovascular complications. The aim of this study is to evaluate the effect of Curcuma longa on arterial stiffness and endothelial dysfunction in patients with type 2 diabetes mellitus. This randomized controlled trial was conducted in 136 patients of type 2 diabetes. Among them, 114 completed at least one follow‐up visit and included for data analysis. Arterial stiffness parameters were measured at baseline and every month for 3 months and endothelial dysfunction markers at baseline and after 3 months of treatment with C. longa or placebo. These parameters were compared between the two groups. Both C. longa and placebo groups were comparable at baseline. After 3 months of treatment, C. longa produced significant reduction from baseline in carotid–femoral pulse wave velocity (p = .002), left brachial–ankle pulse wave velocity (p = .001), aortic augmentation pressure (p = .007), aortic augmentation index (p = .007), and aortic augmentation index at heart rate 75 (p = .018) as compared with the placebo group. Three months treatment with C. longa significantly decreases arterial stiffness as compared with placebo in type 2 diabetes mellitus patients.     

The Effects of Curcumin and Curcumin–Phospholipid Complex on the Serum Pro‐oxidant–Antioxidant Balance in Subjects with Metabolic Syndrome

Metabolic syndrome (MetS) is defined by a clustering of metabolic and anthropometric abnormalities and is associated by an increased risk of cardiovascular disease. We have investigated the effect of curcumin supplementation on the serum pro‐oxidant–antioxidant balance (PAB) in patients with MetS. This double‐blind, randomized, placebo‐controlled trial was conducted over 6 weeks. Subjects (n = 120) were randomly allocated to one of three groups (curcumin, phospholipidated curcumin, and placebo). The curcumin group received 1 g/day of simple curcumin, the phospholipidated curcumin group received 1 g/day of phospholipidated curcumin (containing 200 mg of pure curcumin), and the control group received 1 g/day of placebo. Serum PAB was measured before and after the intervention (at baseline and at 6 weeks). Data analyses were performed using spss software (version 16.0). Serum PAB increased significantly in the curcumin group (p < 0.001), but in the phospholipidated curcumin group, elevation of PAB level was not significant (p = 0.053). The results of our study did not suggest any improvement of PAB following supplementation with curcumin in MetS subjects. Copyright © 2017 John Wiley & Sons, Ltd.     

Hesperidin improves hepatic steatosis,hepatic enzymes,and metabolic and inflammatory parameters in patients with nonalcoholic fatty liver disease: A randomized,placebo‐controlled,double‐blind clinical trial

This study aimed to evaluate the effects of hesperidin on nonalcoholic fatty liver disease (NAFLD) characteristics. In this randomized, double‐blind, controlled clinical trial, 50 NAFLD patients were supplemented with either 1‐g hesperidin capsule or identical placebo capsule for 12 weeks. During the intervention, both groups were advised to follow healthy lifestyle habits including dietary and physical activity recommendations. At the end of the study, hesperidin supplementation, compared with placebo, was associated with a significant reduction in alanine aminotransferase (p = .005), γ‐glutamyltransferase (p = .004), total cholesterol (p = .016), triglyceride (p = .049), hepatic steatosis (p = .041), high‐sensitivity C‐reactive protein (p = .029), tumor necrosis factor‐α, and nuclear factor‐κB (NF‐κB). In conclusion, our results indicate that hesperidin supplementation accompanied with lifestyle modification is superior to lifestyle modification alone in management of NAFLD at least partially through inhibiting NF‐κB activation and improving lipid profile. Further studies with higher dose of hesperidin are required to find the optimal dose.     

The effects of curcumin‐containing supplements on biomarkers of inflammation and oxidative stress: A systematic review and meta‐analysis of randomized controlled trials

Besides other benefits, curcumin is getting more recognized for its antioxidant and anti‐inflammatory properties, highlighting the importance of curcumin application for chronic disease prevention. This systematic review and meta‐analysis of randomized controlled trials (RCTs) was conducted to assess the influence of curcumin‐containing supplements on biomarkers of inflammation and oxidative stress. MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials were searched till January 2018 for eligible studies. The selected studies were evaluated for their quality using the Cochrane risk of bias tool and relevant data were extracted from included studies. Data were pooled using the inverse variance method and expressed as standardized mean difference (SMD) with 95% confidence intervals (95% CI). Fifteen RCTs were included in the final analysis. The meta‐analysis indicated that curcumin supplementation significantly decreased interleukin 6 (IL‐6) (SMD ?2.08; 95% CI [?3.90, ?0.25]; p = 0.02), high‐sensitivity C‐reactive protein (hs‐CRP) (SMD ?0.65; 95% CI [?1.20, ?0.10], p = 0.02), and malondialdehyde (MDA) concentrations (SMD ?3.14; 95% CI [‐4.76, ?1.53], p < 0.001). Though, curcumin supplementation had no significant effect on tumor necrosis factor‐alpha (SMD ?1.62; 95% CI [?3.60, 0.36]; p = 0.10) and superoxide dismutase levels (SMD 0.34; 95% CI [?1.06, 1.74], p = 0.63). Overall, this meta‐analysis suggests that taking curcumin‐containing supplements may exert anti‐inflammatory and antioxidant properties through a significant reduction in IL‐6, hs‐CRP, and MDA levels.     

The impact of pycnogenol supplementation on plasma lipids in humans: A systematic review and meta‐analysis of clinical trials

The effects of pycnogenol on plasma lipids are controversial. A systematic review and meta‐analysis of clinical trials were conducted to obtain a conclusive result in humans. PubMed, Scopus, and Google Scholar were systematically searched until March 2018, to explore the clinical trials that examined the effect of pycnogenol supplementation on lipid parameters among adult human. Methodological quality of the eligible studies was evaluated using the Cochrane Collaboration's tool. To estimate the effect size, changes in blood lipids were implemented. Results were pooled using a random effects model. Potential sources of heterogeneity were explored by subgroup analysis. A systematic review and meta‐analysis of 14 clinical trials with 1,065 participants suggested a significant increase in plasma concentration of high density lipoprotein cholesterol (HDL‐C; 3.27 mg/dL; 95% CI [0.19, 6.36]; p = 0.038). In contrast, plasma levels of total cholesterol (TC; ?4.45 mg/dL, 95% CI [?11.24, 2.34]; p = 0.199), triacylglycerol (TAG; ?3.64 mg/dL; 95% CI [?17.89, 10.61]; p = 0.616), and low density lipoprotein cholesterol (LDL‐C; ?3.61 mg/dl; 95% CI [?8.76, 1.55]; p = 0.171) were not altered. Adjustment for confounding variables was poor in included studies. Also, these studies did not assess dietary lipid intake. The results indicate that pycnogenol supplementation improves levels of HDL‐C; however, the changes in TC, TAG, and LDL‐C were not clinically relevant. Since there are few phytochemicals that have a significant increasing effect on HDL‐C levels, pycnogenol may have important role in prevention of cardiovascular diseases.     

The effect of sumac supplementation on insulin resistance,inflammation, oxidative stress,and antioxidant capacity in adults with metabolic syndrome: A randomized crossover clinical trial

The impact of sumac supplementation was not previously examined in patients with metabolic syndrome (MetS). So, we investigated the influence of sumac supplementation on insulin resistance, inflammation, oxidative stress, and antioxidant markers in adults with MetS. The current study was a single-center, triple-blind, randomized, placebo-controlled crossover clinical trial that was conducted on 47 patients with MetS. Participants were randomly divided into two groups of intervention and control in the first phase. They received capsules containing 500 mg sumac or placebo (lactose) twice a day, after lunch and dinner, for 6 weeks. After a 2-week washout period, the subjects crossed over to the alternate arm. In both arms, fasting venous blood samples were obtained at baseline and at the sixth week of the intervention to determine glycemic status, high-sensitivity C-reactive protein (hs-CRP), malondialdehyde (MDA), total antioxidant capacity (TAC), and antioxidant enzymes activity. The mean (±SD) age, weight, and body mass index of participants were respectively 58.7 ± 5.83 years, 79.9 ± 14.35 kg, and 31.6 ± 4.6 kg/m²; 80.9% of subjects were females (n = 38). Based on per-protocol analyses, the serum fasting insulin concentration was unexpectedly decreased in the placebo group (change in sumac vs. control: 0.95 ± 3.9 vs. −1.17 ± 3.9 mU/L; p = 0.04). Sumac supplementation, compared to control, has marginally enhanced catalase activity (change in sumac vs. control: 2.91 ± 9.5 vs. −1.07 ± 9.1 nmol/min/ml; p = 0.06). This supplementation has also increased serum TAC and the activity of superoxide dismutase, but these changes were not significant. This intervention did not affect other insulin resistance, inflammatory, or oxidative stress markers. We found that 1 g/day sumac consumption for 6 weeks, as adjuvant therapy, could improve the antioxidant defense system in adults with MetS but did not affect insulin resistance, inflammation, or oxidative stress.     

Celastrol inhibits growth and metastasis of human gastric cancer cell MKN45 by down‐regulating microRNA‐21

Celastrol could inhibit cancer cell growth in vitro. However, effect(s) of celastrol on gastric cancer is not well studied. Therefore, we investigated the effects of celastrol on human gastric cancer cell line MKN45 and the underlying mechanisms. We found that celastrol inhibited cell proliferation, migration, and invasion and induced cell apoptosis and G2/M cell cycle arrest (p < .05, p < .01, or p < .001). Under celastrol treatment, overexpression of microRNA‐21 (miR‐21) increased cell viability, migration, and invasion and inhibited cell apoptosis compared with negative control (p < .05, p < .01, or p < .001). In addition, the phosphorylation of PTEN was significantly up‐regulated, whereas PI3K, AKT, p65, and IκBα phosphorylation was statistically decreased by celastrol (p < .05 or p < .01) and then further reversed by miR‐21 overexpression (p < .05 or p < .01). On the other side, miR‐21 silence showed contrary results (p < .05) as relative to miR‐21 overexpression. In conclusion, celastrol inhibits proliferation, migration, and invasion and inactivates PTEN/PI3K/AKT and nuclear factor κB signaling pathways in MKN45 cells by down‐regulating miR‐21.