The dynamic interplay between cardiac mitochondrial health and myocardial structural remodeling in metabolic heart disease, aging, and heart failure.

This review provides a holistic perspective on the bi-directional relationship between cardiac mitochondrial dysfunction and myocardial structural remodeling in the context of metabolic heart disease, natural cardiac aging, and heart failure. First, a review of the physiologic and molecular drivers of cardiac mitochondrial dysfunction across a range of increasingly prevalent conditions such as metabolic syndrome and cardiac aging is presented, followed by a general review of the mechanisms of mitochondrial quality control (QC) in the heart. Several important mechanisms by which cardiac mitochondrial dysfunction triggers or contributes to structural remodeling of the heart are discussed: accumulated metabolic byproducts, oxidative damage, impaired mitochondrial QC, and mitochondrial-mediated cell death identified as substantial mechanistic contributors to cardiac structural remodeling such as hypertrophy and myocardial fibrosis. Subsequently, the less studied but nevertheless important reverse relationship is explored: the mechanisms by which cardiac structural remodeling feeds back to further alter mitochondrial bioenergetic function. We then provide a condensed pathogenesis of several increasingly important clinical conditions in which these relationships are central: diabetic cardiomyopathy, age-associated declines in cardiac function, and the progression to heart failure, with or without preserved ejection fraction. Finally, we identify promising therapeutic opportunities targeting mitochondrial function in these conditions.

Curcumin: A dietary phytochemical for boosting exercise performance and recovery.

Curcumin, as the main natural compound in the turmeric plant (Curcuma longa), is a yellowish polyphenol that has been used traditionally in Asian countries as a medicinal herb for various types of disease and pathological conditions caused by inflammation and oxidative stress. In the present review, we conducted a comprehensive literature search for evidence that shows the effect of curcumin on factors influencing exercise performance, including muscle damage, muscle soreness, inflammation, and oxidative stress. During exercise, reactive oxygen species and inflammation are increased. Thus, if there is no balance between endogenous and exogenous antioxidants and increases in oxidative stress and inflammation, which is important for maintaining redox homeostasis in skeletal muscle, it can lead to muscle soreness and muscle damage and ultimately result in reduced exercise performance. Due to the anti-oxidant and anti-inflammatory properties of curcumin, it can increase exercise performance and decrease exercise-induced muscle soreness and muscle damage. It appears that curcumin supplementation can have positive effects on exercise performance and recovery, muscle damage and pain, inflammation, and oxidative stress. However, there is still a need to precisely evaluate factors to more accurately assess/quantify the beneficial therapeutic effects of curcumin with regard to enhancing exercise performance and recovery.

Efficacy of nigella sativa oil on endothelial function and atherogenic indices in patients with coronary artery diseases: A randomized, double-blind, placebo-control clinical trial.

A therapeutic compound with antioxidant and anti-inflammatory effects might be a practical approach in endothelial dysfunction caused by oxidation and inflammation associated with atherosclerosis. Therefore, we aim to examine the efficacy of Nigella sativa (NS) oil supplementation on endothelial function and atherogenic indices in coronary artery disease (CAD) patients. Sixty individuals aged between 35 to 65 years old were recruited and divided into two groups, receiving either 2 g/daily of NS oil or sunflower oil as the placebo for 8 weeks. Serum levels of adhesion molecules, oxidative markers, and atherogenic parameters were evaluated at the starting point and the end of supplementation. Serum levels of vascular cell adhesion protein 1 (sVCAM-1) [-264.44 95% C, (156.83, 372.04)], intercellular adhesion molecule 1 (sICAM-1) [-132.38 95% C, (40.64, 224.1)], and malondialdehyde (MDA) [-0.21 95% C, (0.03, 0.40)] declined significantly following NS supplementation, while total antioxidant capacity increased [0.03 95% C, (0.03, 0.16)]. NS oil supplementation demonstrated a potential beneficial effect on endothelial function by reducing ICAM-1, VCAM-1 levels and affecting oxidative markers. However, further studies are necessary to elucidate NS oil as a therapeutic agent and complementary therapy in patients with stable CAD.

Effect of Nigella sativa supplementation on kidney function, glycemic control, oxidative stress, inflammation, quality of life, and depression in diabetic hemodialysis patients: study protocol for a double-blind, randomized controlled trial.

BACKGROUND AND OBJECTIVES: The kidney is probably the most crucial target of microvascular damage in diabetes, which can ultimately eventuate end-stage renal disease (ESRD). Hemodialysis is the most usual way of renal replacement therapy in ESRD. Patients receiving hemodialysis are susceptible to many complications like hyperglycemia, inflammation, depression, anxiety, and poor quality of life. So, they are constrained to consume many drugs. Medicinal herbs are used in different cultures as a reliable source of natural remedies. This study aims to determine the efficacy of Nigella sativa (NS) oil supplementation on blood glucose, kidney function tests, inflammation, oxidative stress, quality of life, and depression in hemodialysis patients. METHODS AND ANALYSIS: This double-blind, randomized controlled trial will enroll 46 patients with diabetes mellitus who give hemodialysis thrice a week. Patients who have an inflammatory or infectious disease and who are receiving nonsteroidal anti-inflammatory drugs will be excluded. Patients will be randomized to the treatment and control group, which will be recommended using two soft gels of NS and paraffin oil, respectively. Laboratory tests will be assessed at baseline and end of the study, including fasting blood sugar, glycated albumin, insulin, creatinine, blood urea nitrogen, urea, uric acid, superoxide dismutase, malondialdehyde, total antioxidant capacity, high sensitive C reactive protein, and 24-h urine volume. Also, the kidney disease and quality of life and hospital anxiety and depression scale questionnaires will be evaluated. DISCUSSION: Previous studies have reported a positive effect of Nigella sativa supplementation in chronic kidney disease, but there is no evidence that this plant is safe in hemodialysis patients. The results of this study can be helpful in better control of blood sugar and kidney function and reduce complications in diabetic hemodialysis patients. TRIAL REGISTRATION: Iranian Registry of Clinical Trials . Registered on 31 May 2020.

Efficacy of Cuminum Cyminum supplementation on lipid profile and anthropometric parameters: A systematic review and meta-analysis of randomized controlled clinical trials.

We aimed to evaluate the effect of Cuminum Cyminum (CC) supplementation on lipid profile and selected anthropometric parameters. PubMed, Scopus, Web of Science, and Embase databases were systematically searched until May 2021. The random-effect model was used to study the effect sizes. The sources of heterogeneity were assessed using subgroup analysis and meta-regression. Publication bias was studied by funnel plots. The GRADE approach was used to assess the overall quality of the evidence.The data from our eight included studies have indicated that CC supplementation can lower body mass index (BMI) (WMD = -0.88 kg/m2 ; 95%CI: -1.58, -0.18; p = .023) and total cholesterol (TC) (WMD = -3.96 mg/dl; 95%CI: -6.51, -1.04; p=.008). Also, after adjusting for publication bias, CC was shown to be effective in improving waist circumference (WC), high-density lipoprotein (HDL-C), and triglycerides (TG) levels. Although, the current evidence has not shown that CC supplementation can affect low-density lipoprotein (LDL-C), our subgroup analysis has indicated that CC supplementation with supplementation length of more than 8 weeks is associated with beneficial effects on LDL-C.While CC might be a suitable choice in managing BMI and TC, further high-quality studies are needed to confirm its efficacy in the clinical setting.

The effects of Cuminum cyminum on glycemic parameters: A systematic review and meta-analysis of controlled clinical trials.

ETHNOPHARMACOLOGICAL RELEVANCE: Cuminum Cyminum (CC) is a traditional herbal medicine using as an antiseptic, anti-carcinogenic, anti-mutagenic, anti-cancer, anti-hypertensive, anti-inflammatory, and antioxidant. Recently hypoglycemic characteristics of CC have been indicated. AIM OF THE STUDY: We intended to conduct a meta-analysis on the effect of CC supplementation on glycemic parameters in patients with different chronic diseases. MATERIALS AND METHODS: PubMed, Embase, Web of Science, and Scopus were searched until May 2021. Random effect model was conducted to perform the meta-analysis. Source of heterogeneity was explored using the meta-regression and subgroup analyses. The Cochrane Collaboration's tool was used to assess the quality of studies. The GRADE approach was used to assess the quality of evidence. RESULTS: Findings of eight studies showed that CC supplementation reduced FBS (SMD = -1.4 mg/dl; 95 % CI: -2.29, -0.51; P = 0.002), HbA1c (SMD = -1.71 %; 95 % CI: -3.24, -0.18; P = 0.028), and HOMA-ß (SMD = 0.46; 95 % CI: -0.62, 1.55; P = 0.404) significantly. Also, CC increased QUICKI level (SMD = 0.89; 95 % CI: 0.37, 1.4; P = 0.001. However, no significant effect of CC was observed on insulin (SMD = -0.70 µIU/dl; 95 % CI: -1.84, 0.45; P = 0.234) and HOMA-IR (SMD = 0.46; 95 % CI: -0.62, 1.55; P = 0.404). CONCLUSION: CC had an improving effect on FBS, HbA1C, HOMA-B, and QUICKI. The effect of CC on amending HOMA-IR was significant after sensitivity analysis. However, the insulin level was not changed significantly.

A comprehensive insight into the potential effects of resveratrol supplementation on SIRT-1: A systematic review.

BACKGROUND AND AIMS: Silent information regulator 1 (Sirt1) involved in histone stability, transcriptional activity, and translocation. This systematic review aimed to summarize the effects of Resveratrol on Sirt1 expression. MATERIALS AND METHODS: Electronic databases including Scopus, Medline and web of knowledge were searched up to March 2020. RESULTS: Out of 801 studies identified in our search finally 12 articles included. Totally six studies evaluated the effects of resveratrol on SIRT1 gene expression, and six articles investigate protein expression. CONCLUSION: The results of the included studies showed that resveratrol supplementation had beneficial effects on protein and gene expression of SIRT1.

Effects of Nigella sativa oil supplementation on selected metabolic parameters and anthropometric indices in patients with coronary artery disease: A randomized, double-blind, placebo-controlled clinical trial.

Various metabolic parameters are risk factors related to the amplified risk of atherosclerotic cardiovascular disease. A wide variety of data exist on Nigella sativa (NS) and metabolic parameters. The current study is designed to examine NS supplementation on lipid profile, blood pressure, glycemic control, anthropometric indices, and insulin resistance in individuals with coronary artery disease (CAD). In a randomized, double-blind, placebo-controlled clinical trial, 60 patients with CAD received either 2 g of NS oil or sunflower oil as a placebo for 8 weeks. Biochemical and anthropometric measurements were assessed. NS significantly reduced weight (-1.82 Kg; 95% C, [2.72, 4.13]), body mass index (-0.67 kg/m2 ; 95% C, [0.33, 1.01]), waist circumference (-2.15 cm; 95% C, [1.06, 3.23]), hip circumference (-1.26 cm; 95% C, [0.61, 1.910]), waist-to-hip ratio (0.008; 95%C, [0.001, 0.01]), systolic (-9.52 mmHg; 95% C, [7.14, 11.9]), diastolic blood pressure (-8.26 mmHg; 95% C, [4.89, 11.62]), and fasting blood glucose (FBS) (-4.32 mg/dl; 95% C, [-0.51, 9.15]) as compared with the placebo group. The results indicate a potential beneficiary effect of NS on the metabolic parameters in CAD patients including improvements in anthropometric indices, blood pressure, and FBS.

Profiling inflammatory cytokines following zinc supplementation: a systematic review and meta-analysis of controlled trials.

Chronic inflammation has been considered as the main cause of chronic diseases. Zn has anti-inflammatory effects by decreasing the expression of inflammatory markers. The present systematic review and meta-analysis study aims to evaluate the impact of Zn supplementation on inflammation. PubMed (Medline), Scopus, Web of Science, and Embase databases were searched up to 10 December 2020. Controlled trials which have investigated the effects of Zn supplementation on serum/plasma levels of inflammatory cytokines in subjects aged >15 years were included. A pooled meta-analysis was performed using a random effect model. Sensitivity analysis was performed to determine the robustness of the observed effect sizes. A total of twelve studies was included in meta-analysis. Zn could decrease IL-6 levels (standardised mean difference (SMD) = -0·76 pg/ml; 95 % CI -1·28, -0·24; P = 0·004). There was no significant change in TNF-α (SMD = 0·42 pg/ml; 95 % CI -0·31, 1·16; P = 0·257) and IL-2 levels (SMD = 1·64 pg/ml; 95 % CI -1·31, 4·59; P = 0·277) following Zn supplementation. However, Zn could increase IL-2 significantly after the deletion of one arm in sensitivity analysis (SMD = 2·96 pg/ml; 95 % CI 2·03, 3·88; P < 0·05). Conclusively, Zn supplementation can decrease the IL-6 level. Zn increased IL-2 level after the sensitivity analysis. Zn supplementation has not ameliorative effects on TNF-α.

A comprehensive insight into potential roles of Nigella sativa on diseases by targeting AMP-activated protein kinase: a review.

OBJECTIVES: Nigella sativa (NS) is a known medicinal herb with numerous therapeutic effects such as antidiabetic, anti-proliferative, anti-inflammatory, and anti-cancer activities. It has been indicated that NS can regulate cellular metabolism by adjusting transduction signaling pathways. Adenosine monophosphate-activated protein kinase (AMPK) is one of the main physiological processes, such as energy hemostasis, cellular metabolism, and autophagy regulators. Herb-derived medicines have always been considered as one of the main AMPK activators, and surprisingly recent data has demonstrated that it can be a target for NS and its derivatives. EVIDENCE ACQUISITION: The literature search was conducted in PubMed, SCOPUS, Embase, ProQuest, and Google Scholar electronic resources. Published articles up to September 2020 were considered, and those of which investigated Nigella sativa effects on the AMPK pathway after meeting the inclusion criteria were included. RESULTS: The search was performed on several online databases such as PubMed, Scopus, Embase, ProQuest, and Google Scholar from inception until January 2020. Among the initial search, 245 studies were found. After removing duplicated data and meeting the inclusion criteria, only 14 studies were selected. They included the effects of NS and its bioactive compounds as anti-hyperglycemic (n = 5), on liver function (n = 4), cancers (n = 3), and on Neuroinflammation and Atherosclerosis (n = 2). Most of the included studies are animals or in-vitro investigations. CONCLUSION: In this review, we discuss the latest findings on the molecular mechanism of NS effecting the AMPK signaling pathway. We also focus on the therapeutic effects of NS, including the prevention and treatment of metabolic and pro-inflammatory disease by targeting the AMPK pathway.

A comprehensive insight into the effect of glutamine supplementation on metabolic variables in diabetes mellitus: a systematic review.

Diabetes mellitus is one of the most important threats to human health in the twenty-first century. The use of complementary and alternative medicine to prevent, control, and reduce the complications of diabetes mellitus is increasing at present. Glutamine amino acid is known as a functional food. The purpose of this systematic review is to determine the potential role of glutamine supplementation on metabolic variables in diabetes mellitus. For this review, PubMed, SCOPUS, Embase, ProQuest, and Google Scholar databases were searched from inception through April 2020. All clinical trial and animal studies assessing the effects of glutamine on diabetes mellitus were eligible for inclusion. 19 studies of 1482 articles met the inclusion criteria. Of the 19 studies, nine studies reported a significant increase in serum GLP-1 levels. Also, eight studies showed reducing in serum levels of fasting blood sugar, four studies reducing in postprandial blood sugar, and triglyceride after glutamine supplementation. Although glutamine resulted in a significant increase in insulin production in seven studies, the findings on Hb-A1c levels were inconclusive. In addition to, despite of the results was promising for the effects of glutamine on weight changes, oxidative stress, and inflammation, more precise clinical trials are needed to obtain more accurate results. In conclusion, glutamine supplementation could improve glycemic control and levels of incretins (such as GLP-1 and GIP) in diabetes mellitus. However, more studies are needed for future studies.

The effect of green coffee extract supplementation on lipid profile: A systematic review of clinical trial and in-vivo studies.

BACKGROUND AND AIMS: Dyslipidemia is an important and common risk factor for cardiovascular disease and increases the risk of mortality. Green coffee extract (GCE) contains bioactive polyphenols, especially Chlorogenic acid (CGA), that due to the antioxidant characteristic, have a desirable effect on metabolic factors. This review conducted to focus on the effect of GCE on lipid profiles. METHODS: PubMed, Scopus, and web of science were searched until November 2019. All clinical studies and in-vivo studies that provide sufficient information about outcomes include to this review. RESULTS: Out of 3270 studies obtained in our searching, only 32 articles were eligible for analysis. Five double-blind, randomized clinical trial studies, two Cross-over studies, one Quasi-experimental study, and twenty animal studies were included in this systematic review-all articles evaluated according to the checklist of aim and inclusion and exclusion criteria. Generally, the results of the included studies showed there is controversy about the effect of GCE and CGA on lipid profile improvement. CONCLUSIONS: Although, a higher dosage of GCE and administration of CGA with longer duration leads to better results. However, investigating the effectiveness and safety dosage as a lipid-lowering agent needs further studies with differential dosage and periods.

The effects of N-acetylcysteine on inflammatory and oxidative stress biomarkers: A systematic review and meta-analysis of controlled clinical trials.

Prolonged inflammation could be considered as the leading cause of chronic diseases such as cardiovascular disorders, type two diabetes, and obesity. N-acetylcysteine (NAC) is considered an antioxidant. The present meta-analysis aims to determine the efficacy of NAC in alleviating inflammation and oxidative stress. PubMed-Medline, SCOPUS, Web of Science and Embase databases and Google Scholar were searched up to Nov 2019. Random effect analysis was used to perform meta-analysis. Subgroup analyses were carried out to find heterogeneity sources. Meta-regression analysis was used to explore linear relationship between effect size and variables. Trim and fill analysis were performed in case of the presence of publication bias. Quality assessment was performed using Cochrane Collaboration's tool. A total of 28 studies were included in meta-analysis. NAC significantly decreased malondialdehyde (MDA) (SMD = -1.44 µmol/L; 95% CI: -2.05, -0.84; P < 0.001), IL-8 (WMD = -2.56 pg/ml; 95% CI: -3.89, -1.23; P < 0.001) and homocysteine (WMD = -1.45 pg/ml; 95% CI: -2.74, -0.17; P = 0.027) levels. There were no significant effects of NAC supplementation on CRP (SMD = -0.1 g/L; 95% CI: -0.52, 0.32; P = 0.647), TNF- α (WMD = -0.2 pg/ml; 95% CI: -0.65, 0.25; P = 0.378) and IL-6 (WMD = -0.41 pg/ml; 95% CI: -1.15, 0.32; P = 0.270) levels. However, NAC effects were significant in ameliorating TNF-α and IL-6 using sensitivity analysis. NAC significantly decreased MDA, IL-8, and homocysteine levels. The effects of NAC on amending TNF-α and IL-6 levels were significant after sensitivity analysis. No significant change was observed on CRP levels.