Effect of polyphenols against complications of COVID-19: current evidence and potential efficacy.

The COVID-19 pandemic that started in 2019 and resulted in significant morbidity and mortality continues to be a significant global health challenge, characterized by inflammation, oxidative stress, and immune system dysfunction.. Developing therapies for preventing or treating COVID-19 remains an important goal for pharmacology and drug development research. Polyphenols are effective against various viral infections and can be extracted and isolated from plants without losing their therapeutic potential. Researchers have developed methods for separating and isolating polyphenols from complex matrices. Polyphenols are effective in treating common viral infections, including COVID-19, and can also boost immunity. Polyphenolic-based antiviral medications can mitigate SARS-CoV-2 enzymes vital to virus replication and infection. Individual polyphenolic triterpenoids, flavonoids, anthraquinonoids, and tannins may also inhibit the SARS-CoV-2 protease. Polyphenol pharmacophore structures identified to date can explain their action and lead to the design of novel anti-COVID-19 compounds. Polyphenol-containing mixtures offer the advantages of a well-recognized safety profile with few known severe side effects. However, studies to date are limited, and further animal studies and randomized controlled trials are needed in future studies. The purpose of this study was to review and present the latest findings on the therapeutic impact of plant-derived polyphenols on COVID-19 infection and its complications. Exploring alternative approaches to traditional therapies could aid in developing novel drugs and remedies against coronavirus infection.

The favorable impacts of cardamom on related complications of diabetes: A comprehensive literature systematic review.

BACKGROUND AND AIM: Complementary and alternative medicine plays an increasing role in preventing, and regulatory, complications associated with diabetes. There are plenty of polyphenolic compounds found in Elettaria cardamomum (Cardamom) such as luteolin, limonene, pelargonidin, caffeic acid, kaempferol, gallic acid, and quercetin which can be used in many metabolic diseases. METHOD: The objective of this systematic review was to appraise evidence from clinical and in vivo studies on the effects of cardamom on inflammation, blood glucose, oxidative stress and dyslipidemia of diabetes mellitus. According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statements, the present study was carried out. Studies were conducted by searching databases such as EMBASE, Scopus, PubMed, Google Scholar, web of sciences, and Cochrane Library from the commencement until April 2022. RESULTS: All available human and animal studies examining the effects of cardamom on diabetes were published in the form of English articles. Finally, only 14 of the 241 articles met the criteria for analysis. Of the 14 articles, 8 were in vivo studies, and 6 were clinical trial studies. Most studies have indicated the beneficial effects of cardamom on insulin resistance, oxidative stress and inflammation. Cardamom also improved dyslipidemia, but had no substantial effect on weight loss. CONCLUSION: According to most studies, cardamom supplementation enhanced antioxidant enzyme production and activity in diabetes mellitus and decreased oxidative stress and inflammatory factors. Despite this, the exact mechanism of the disease needs to be identified through more clinical trials.

Effects of curcumin on blood pressure: A systematic review and dose-response meta-analysis.

AIMS: This systematic review and dose-response meta-analysis were conducted to summarize data from available clinical trials on the effects of curcumin supplementation on systolic BP (SBP) and diastolic BP (DBP). DATA SYNTHESIS: Using related keywords, multiple databases, including the Web of Sciences, Scopus, Embase, PubMed, Cochrane Library, and Google Scholar, were searched until November 2022. We chose the studies that examined the effects of curcumin on systolic blood pressure (SBP) and diastolic blood pressure (DBP). Seventeen eligible studies with a total sample size of 1377 participants were included in the meta-analysis. The findings of the meta-analysis did not indicate any significant effect of curcumin on SBP (WMD = -0.06 mmHg, 95% CI: -0.62, 0.50, p = 0.85; I2 = 44.2%) and DBP (WMD = -0.18 mmHg, 95% CI: -1.17, 0.82, p = 0.62; I2 = 77.2%). Moreover, in our dose-response analysis, we found that the dose and duration of curcumin supplementation were non-significantly associated with the reduction of SBP and DBP. However, subgroup analysis revealed a significant reduction only in DBP levels (WMD: -0.76 mmHg, 95% CI: -1.46,-0.05; P = 0.03) but not in SBP in studies with ≥12-week supplementation. Also, a significant reduction in SBP (WMD: -1.55 mmHg, 95% CI: -2.85, -0.25; P = 0.01) and DBP (WMD: -1.73 mmHg, 95% CI: 2.67, -0.79; P < 0.01) was noticed by curcumin supplementation in studies performed on women. CONCLUSIONS: The current study suggests that consuming curcumin may improve DBP when administered for long durations ≥12 weeks. However, more trials are required to confirm these findings.

A comprehensive insight into the molecular and cellular mechanisms of action of resveratrol on complications of sepsis a systematic review.

Sepsis and septic shock are still one of the most important medical challenges. Sepsis is an extreme and uncontrolled response of the innate immune system to invading pathogenesis. Resveratrol (3,5,4'-trihydroxytrans-stilbene), is a phenolic and non-flavonoid compound naturally produced by some plants and fruits. The object of the current study is to systematically review the impacts of resveratrol and its mechanisms of function in the management of sepsis and its related complications. The guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statements were applied to perform the study (PROSPERO: CRD42021289357). We searched Embase, Web of Science, Google Scholar, Science Direct, PubMed, ProQuest, and Scopus databases up to January 2023 by using the relevant keywords. Study criteria were met by 72 out of 1415 articles screened. The results of this systematic review depict that resveratrol can reduces the complications of sepsis by affecting inflammatory pathways, oxidative stress, and modulating immune responses. Future human randomized clinical trials are necessary due to the promising therapeutic effects of resveratrol on sepsis complications and the lack of clinical trials in this regard.

The effects of whey protein on blood pressure: A systematic review and dose-response meta-analysis of randomized controlled trials.

AIMS: This systematic review and dose-response meta-analysis was conducted to summarize data from available clinical trials on the effects of whey protein (WP) supplementation on blood pressure (BP) in adults. DATA SYNTHESIS: A comprehensive literature search was conducted in the electronic databases PubMed, Web of Science, ProQuest, Embase, and SCOPUS from inception to October 2022. Weighted mean differences (WMD) and 95% confidence intervals (CI) were calculated to assess pooled effect sizes. Heterogeneity between studies was assessed using the Cochran's Q test and I2. Subgroup analysis was performed to assess potential sources of heterogeneity. The dose-response relationship was assessed using fractional polynomial modeling. Of the 2,840 records, 18 studies with 1,177 subjects were included. Pooled analysis showed that whey protein supplementation resulted in a significant reduction in systolic blood pressure (WMD: -1.54 mmHg; 95% CI: -2.85 to -0.23, p = 0.021), with significant heterogeneity between studies (I2 = 64.2%, p < 0.001), but not for diastolic blood pressure (DBP) (WMD: -0.27 mmHg; 95% CI: -1.14, 0.59, p = 0.534) with high heterogeneity between studies (I2 = 64.8%, p < 0.001). However, WP supplementation significantly reduced DBP at a dose of ˃30 g/day, in RCTs that used WP isolate powder for their intervention, in sample sizes ≤100, in studies with an intervention duration of ≤10 weeks, and in those studies that were conducted in patients with hypertension and had participants with a BMI of 25-30 kg/m2. CONCLUSION: This meta-analysis demonstrated that WP intake significantly reduced SBP levels. Further large-scale studies are needed to specify the exact mechanism, and optimal dosage of WP supplementation to obtain a beneficial effect on BP.

Association between plant-based diets and metabolic syndrome in obese adults from Iran: a cross-sectional study.

BACKGROUND: Metabolic syndrome (MetS) is a common chronic disease with several complications. Given that, studies on the association of plant-based diet indices (PDIs) with risk of MetS among adults with obesity, are limited, we aimed to examine the association between PDIs (including overall PDI, healthy PDI (hPDI), unhealthy PDI (uPDI)) and MetS in Iranian adults with obesity. METHODS: In Tabriz, Iran, a total of 347 adults between the ages of 20 and 50 participated in this cross-sectional research study. We created an overall PDI, hPDI, and uPDI from validated semi-quantitative food-frequency questionnaire (FFQ) data. To investigate the association between hPDI, overall PDI, uPDI, and MetS and its components, a binary logistic regression analysis was performed. RESULTS: The average age was 40.78 ± 9.23 years, and the average body mass index was 32.62 ± 4.80 kg/m2. There was no significant association between overall PDI (OR: 0.87; 95% CI: 0.54-1.47), hPDI (OR: 0.82; 95% CI: 0.48-1.40), and uPDI (OR: 0.83; 95% CI: 0.87-2.46) with MetS, even after adjustment for confounders. Moreover, our findings showed that participants with the highest adherence to uPDI had a higher chance of hyperglycemia (OR: 2.50; 95% CI: 1.13-5.52). Also, this association was significant in the first (OR: 2.51; 95% CI: 1.04-6.04) and second (OR: 2.58; 95% CI: 1.05-6.33) models, after controlling for covariates. However, in both adjusted and crude models, we did not find a significant association between hPDI and PDI scores and MetS components such as high triglyceride, high waist circumference, low High-density lipoprotein cholesterol, raised blood pressure, and hyperglycemia. Moreover, those in the top tertile of uPDI had higher fasting blood sugar and insulin levels when compared with those in the first tertile, and subjects in the last tertile of hPDI compared with participants in the first tertile had lower weight, waist-to-hip ratio, and fat-free mass. CONCLUSION: We found a direct significant association between uPDI and odds of hyperglycemia in the whole population of study. Future large-scale, prospective studies on PDIs and the MetS are necessary to confirm these findings.

Effects of synbiotics supplementation on anthropometric and lipid profile parameters: Finding from an umbrella meta-analysis.

Introduction: Several systematic reviews and meta-analyses have been carried out to assess the impact of synbiotics on lipid profiles and anthropometric parameters. In this regard, an umbrella meta-analysis was performed to provide a more accurate view of the overall impacts of synbiotic supplementation on lipid profile and anthropometric parameters. Methods: Databases such as PubMed, Scopus, Embase, Web of Science, and Google Scholar were searched for this study from inception to January 2022. A random-effects model was applied to evaluate the effects of synbiotic supplementation on lipid profile and anthropometric parameters. The methodological quality of eligible articles was evaluated using the AMSTAR2 questionnaire. The GRADE approach was used to evaluate the overall certainty of the evidence in the meta-analyses. Results: Meta-analyses of 17 studies revealed significant decreases in body mass index (BMI) (ES: -0.13 kg/m2; 95% CI: -0.19, -0.06, p < 0.001, I2 = 0.0%, p = 0.870), BW (ES: -1.30 kg; 95% CI: -2.19, -0.41, p = 0.004, I2 = 88.9%, p < 0.001), waist circumference (WC) (ES: -1.80 cm; 95% CI: -3.26, -0.34, p = 0.016, I2 = 94.1%, p < 0.001), low-density lipoprotein cholesterol (LDL-C) (ES: -2.81 mg/dl; 95% CI: -3.90, -1.72, p < 0.001, I2 = 95.1%, p < 0.001), total cholesterol (TC) (ES = -2.24 mg/dl; 95% CI: -3.18, -1.30, p < 0.001, I2 = 94.5%, p < 0.001), and triglyceride (TG) (ES: -0.43 mg/dl; 95% CI: -0.79, -0.07, p = 0.019, I2 = 78.0%, p < 0.001) but not high-density lipoprotein cholesterol (HDL-C) (ES: 0.23 mg/dl; 95% CI: -0.11, 0.56, p = 0.193, I2 = 45.2%, p = 0.051) following synbiotic supplementation. Discussion: The present umbrella meta-analysis suggests synbiotic supplementation can slightly improve lipid profile and anthropometric indices and might be a therapeutic option for obesity and its related disorders. Systematic review registration: www.crd.york.ac.uk/prospero, identifier CRD42022304376.

Effects of luteolin on sepsis: A comprehensive systematic review.

BACKGROUND: Sepsis and septic shock are the main causes of mortality and complications in intensive care units all over the world. Luteolin is thought to have a significant role as a free radical scavenger, an anti-inflammatory agent, and an immune system modulator. The object of this review is to conduct a systematic review of the effects of luteolin and its mechanisms of action in the treatment of sepsis and its complications. METHOD: The investigation was carried out in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines (PROSPERO: CRD42022321023). We searched Embase, Web of Science, Google Scholar, Science Direct, PubMed, ProQuest, and Scopus databases up to  January 2023 by using the relevant keywords. RESULTS: Out of 1,395 records screened, 33 articles met the study criteria. In the collected papers, the main reported findings are that luteolin can affect inflammation-initiating pathways such as toll-like receptors and high mobility group box-1 and reduces the expression of genes that produce inflammatory cytokines, such as the Nod receptor protein-3, and nuclear factor kappa-light chain-enhancer of activated B cells. Luteolin also reduces the overactivity of macrophages, neutrophil extracellular traps and lymphocytes by regulating the immune response. CONCLUSION: Most studies revealed luteolin's positive benefits on sepsis through several pathways. Luteolin showed the capacity to reduce inflammation and oxidative stress, control immunological response, and prevent organ damage (in vivo studies) during sepsis. Large-scale in vivo experiments are necessary to elucidate its potential impacts on sepsis.

The association between healthy lifestyle score and risk of metabolic syndrome in Iranian adults: a cross-sectional study.

BACKGROUND: Lifestyle risk factors, such as obesity, physical inactivity, smoking, and having an unhealthy diet are significantly associated to the risk of developing metabolic diseases such as type 2 diabetes, insulin resistance, and metabolic syndrome (MetS). Consequently, it is important to examine multiple lifestyle risk factors instead of single ones. Moreover, the combined effects of these factors on risk of MetS are not fully investigated. This study investigated the relationship between HLS and MetS and its components among apparently healthy adults living in Tabriz-Iran. METHODS: This cross-sectional study includes 347 apparently healthy adults aged 20-50. To assess healthy lifestyle, four habits were used to examine HLS: physical activity (PA), smoking, healthy eating index-2015 (HEI-2015), and body mass index (BMI). Smoking status, PA, and dietary intakes (147-item) of study participants were evaluated using valid questionnaires. The lifestyle score ranged from zero (non-healthy) to four (most healthy) points. Binary logistic regression with adjusted models was used to examine the association of HLS and MetS, and its components. P < 0.05 was considered statistically significant. RESULTS: In the current study, the average age and BMI of study participants were 40.78 ± 9.23 years old and 29.23 ± 5.97 kg/m2, respectively. Participants in the highest quartile of HLS had significantly lower waist circumference (WC), BMI, weight, and had less fasting blood sugar (FBS), and triglyceride (TG) compared to the lowest quartile of HLS. Individuals in the second quartile of HLS had 24% greater odds for having MetS compared with those in the first quartile (adjusted OR: 1.24; 95% CI: 1.05-2.66). A significant reduction in hyperglycemia (adjusted OR: 0.85, 95% CI: 0.55-0.96) and high TG (adjusted OR: 0.83; 95% CI: 0.55-0.93) risk was also observed in the highest category of HLS compared to the lowest category. Moreover, after taking potential confounders into account, low score of HLS was associated with increased odds of MetS in women (adjusted OR: 1.32; 95% CI: 1.03-2.91). CONCLUSION: The results showed that the lowest adherence to HLS was associated with higher odds MetS in women, after adjusting for all covariates. Moreover, adherence to a healthy lifestyle was related to lower odds of hyperglycemia and high TG in Iranian adults. To confirm these results, prospective studies are required.

Omega-3 polyunsaturated fatty acids in the treatment of non-alcoholic fatty liver disease: An umbrella systematic review and meta-analysis.

There has been conflicting evidence from meta-analyses on the effect of polyunsaturated fatty acids (PUFA) on non-alcoholic fatty liver disease (NAFLD). Therefore, in this umbrella meta-analysis, we are evaluating whether omega-3 PUFA supplementation has any benefit in treating NAFLD. Electronic databases such as PubMed, Web of Science, Scopus, Embase and Google Scholar were assessed to October 2022. This meta-analysis included all meta-analyses that examined the effect of PUFAs on liver fat and liver function tests [aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT)]. Meta-analysis was conducted using a random effects model. Subgroup analyses and sensitivity analyses were also performed. In total, eight articles involving 6,561 participants met the eligibility criteria. Advantageous impacts PUFA supplementation were observed on ALT (ESWMD  = -6.72 IU/L; 95% CI: -8.61, -4.84; p < 0.001, and ESSMD  = -0.52 IU/L; 95% CI: -0.84, -0.20, p < 0.001), AST (ESWMD  = -3.73 IU/L, 95% CI: -5.93, -1.53, p < 0.001, and ESSMD  = -0.65 IU/L; 95% CI: -1.08, -0.22, p = 0.003), GGT levels (ESWMD  = -4.20 IU/L, 95% CI: -6.85, -1.55, p = 0.002), and liver fat (ESWMD  = -5.16; 95% CI: -8.49, -1.82, p < 0.001). Intervention with omega-3 PUFAs improves ALT, AST, GGT, and liver fat in patients with NAFLD. Thus, omega-3 PUFAs could be considered as a therapeutic option in the treatment of NAFLD.

Effects of Chromium Supplementation on Lipid Profile: an Umbrella of Systematic Review and Meta-analysis.

Dyslipidemia is one of the most well-established modifiable risk factors for cardiovascular disease (CVD) development. Several meta-analyses have revealed the improving effects of chromium on dyslipidemia, while some studies have reported controversial results. This study aimed to summarize meta-analyses of randomized controlled trials (RCTs) that examined the effects of chromium supplementation on lipid profiles in adults. The literature search was conducted using Embase, Scopus, Web of Science, Cochrane Central Library, and PubMed databases with appropriate keywords from the beginning to May 2022. Based on the pooled analysis results, a random-effects model was used to determine the effects of chromium on blood lipid levels. Heterogeneity, publication bias, and sensitivity analysis were also evaluated using standard methods. A total of eight meta-analyses were included in this study. The pooled analysis of eight meta-analyses did not find any significant effect of chromium supplementation on triglycerides (TG) (ES = - 0.20 mg/dl; 95% CI: - 0.50, 0.10, p = 0.185), total cholesterol (TC) (ES = - 0.14 mg/dl, 95% CI: - 0.43, 0.16; p = 0.369), low-density lipoprotein cholesterol (LDL-c) (ES = - 0.08 mg/dl; 95% CI: - 0.19, 0.03; p = 0.142), and high-density lipoprotein cholesterol (HDL-C) levels (ES: 0.05 mg/dl, 95% CI: - 0.05, 0.14, p = 0.312). However, subgroup analysis by the intervention dose suggested that chromium supplementation in doses higher than 500 µg/day could significantly decrease TG. The available evidence proposes no beneficial effects of chromium intervention on blood lipids. As a result, it cannot be used as a single therapy to treat adults with lipid abnormalities.

Evaluating the effects of curcumin nanomicelles on clinical outcome and cellular immune responses in critically ill sepsis patients: A randomized, double-blind, and placebo-controlled trial.

Introduction: In sepsis, the immune system is overreacting to infection, leading to organ dysfunction and death. The purpose of this study was to investigate the impacts of curcumin nanomicelles on clinical outcomes and cellular immune responses in critically ill sepsis patients. Method: For 10 days, 40 patients in the intensive care units (ICU) were randomized between the nano curcumin (NC) and placebo groups in a randomized study. We evaluated serum levels of biochemical factors, inflammatory biomarkers, the mRNA expression levels of FOXP3, NLRP-3, IFN-γ, and NF-κp genes in the PBMCs, and clinical outcomes before the beginning of the supplementation and on days 5 and 10. Results: NLR family pyrin domain containing 3 (NLRP3), interferon gamma (IFN-γ), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) mRNA expression levels significantly P = 0.014, P = 0.014, and P = 0.019, respectively) decreased, but forkhead box P3 (FOXP3) mRNA expression levels increased significantly (P = 0.008) in the NC group compared to the placebo group after 10 days. NC supplementation decreased serum levels of IL-22, IL-17, and high mobility group box 1 (HMGB1) (P < 0.05). Nevertheless, biochemical factors and nutritional status did not differ significantly (P > 0.05). NC supplementation resulted in decreased sequential organ failure assessment and multiple organ dysfunction syndromes scores, while it did not have significant impacts on length of stay in the ICU, systolic blood pressure, diastolic blood pressure, a saturation of oxygen (%), and respiratory rate (breaths/min) PaO2/FiO2 (p > 0.05). Conclusion: For critically ill patients with sepsis, NC supplementation may be an effective therapeutic strategy. More randomized clinical trials involving longer follow-up periods and different doses are needed to achieve the best results.

Hemodynamic stability during menstrual cycle in women undergoing elective surgery.

Objective: Hemodynamic changes occur in almost one-third of patients undergoing spinal anesthesia, which are likely to effect vital organ. The aim of this study is to determine the hemodynamic effect of spinal anesthesia during different phases of menstrual cycle. Methods: This is a descriptive cross-sectional study, two hundred and seventy-three patients who underwent spinal anesthesia for elective surgery were enrolled in this study. Of all the patients, 141 patients were in the luteal phase and 132 patients were in the follicular phase of their menstrual cycle. Analytical epidemiological study was conducted using questionnaires. Blood pressure and heart rate of patients before, immediately after, and 1 h after spinal anesthesia were recorded, and the data were analyzed using SPSS software. Results: In the follicular phase before anesthesia, systolic blood pressure (SBP) was 127.5 ± 3.9, diastolic blood pressure (DBP) was 80.3 ± 6.2 mmHg and heart rate (HR) was 82.0 ± 8.5bpm, while, immediately after the induction of anesthesia following recordings were measured; 109.7 ± 9.13, 71.8 ± 2.8 mmHg and 70.0 ± 8.10bpm, respectively. In the luteal phase, it was 126.9 ± 3.12, 81.6 ± 9.3 mmHg and 80.2 ± 4.4bpm, and 122.0 ± 9.12, 78.6 ± 8.5 mmHg and 75.9 ± 6.5bpm respectively before and immediately after anesthesia, these changes in the menstrual phase was significant (P < 0.001). In the follicular phase an hour after spinal anesthesia, the mean SBP was 100.3 ± 3.9, DBP was 71.2 ± 7.5, MAP was 87.0 ± 4.7 mmHg and HR 67.5 ± 5.7bpm and following was seen in luteal phase; 115.4 ± 1.8, 75.9 ± 2.3, 97.3 ± 3.5 mm Hg and 74.0 ± 7.4bpm, respectively. These values were significantly lower in the follicular phase (P < 0.001). Conclusion: Spinal anesthesia in the luteal phase as compared to the follicular phase of the menstrual cycle shows less variation in hemodynamic parameters.

Potential roles of genistein in polycystic ovary syndrome: A comprehensive systematic review.

Polycystic ovary syndrome (PCOS) is one of the most prevalent polygenic endocrine disorders in reproductive-age women. Genistein is a soy-isolated phytoestrogen and isoflavone with antioxidant, anti-inflammatory, estrogenic, and antineoplastic activity. This systematic review aimed to investigate the therapeutic effects and mechanisms of actions of genistein in PCOS. The present study was conducted according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. We searched PubMed, Scopus, Embase, and Google Scholar databases up to February 2022 using relative keywords. Studies published in English evaluated genistein's effects on PCOS, and its related symptoms were considered. Out of 298 records screened, only 13 articles met the inclusion criteria: Nine animal and 4 human studies. The results of the current study indicated that genistein supplementation may effectively improve PCOS-related symptoms by decreasing insulin resistance and anthropometric indices, improving ovarian morphology and regulating reproductive hormones, and reducing oxidative stress and inflammation by influencing biological pathways. According to the current literature, genistein may diminish the dues of PCOS. Therefore, this study shows that genistein can be considered an effective agent. in reducing the complications of PCOS. However, further studies are recommended for a broad conclusion on the exact mechanism of genistein in PCOS patients.

The favorable impacts of silibinin polyphenols as adjunctive therapy in reducing the complications of COVID-19: A review of research evidence and underlying mechanisms.

The proceeding pandemic of coronavirus disease 2019 is the latest global challenge. Like most other infectious diseases, inflammation, oxidative stress, and immune system dysfunctions play a pivotal role in the pathogenesis of COVID-19. Furthermore, the quest of finding a potential pharmaceutical therapy for preventing and treating COVID-19 is still ongoing. Silymarin, a mixture of flavonolignans extracted from the milk thistle, has exhibited numerous therapeutic benefits. We reviewed the beneficial effects of silymarin on oxidative stress, inflammation, and the immune system, as primary factors involved in the pathogenesis of COVID-19. We searched PubMed/Medline, Web of Science, Scopus, and Science Direct databases up to April 2022 using the relevant keywords. In summary, the current review indicates that silymarin might exert therapeutic effects against COVID-19 by improving the antioxidant system, attenuating inflammatory response and respiratory distress, and enhancing immune system function. Silymarin can also bind to target proteins of SARS-CoV-2, including main protease, spike glycoprotein, and RNA-dependent RNA-polymerase, leading to the inhibition of viral replication. Although multiple lines of evidence suggest the possible promising impacts of silymarin in COVID-19, further clinical trials are encouraged.

The therapeutic effects and mechanisms of action of resveratrol on polycystic ovary syndrome: A comprehensive systematic review of clinical, animal and in vitro studies.

Polycystic ovary syndrome (PCOS) is one of the most important and common polygenic endocrine disorders among women of reproductive age. Resveratrol, a natural phenol, is involved in various biological activities, including antioxidant, antiseptic, anti-inflammatory, anti-ageing and anti-cancer effects. This systematic review aimed to investigate the therapeutic effects and mechanisms of actions of resveratrol in PCOS. The present study was conducted according to the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis statements. We searched PubMed, Science Direct, Google Scholar, Scopus, ISI Web of Science, ProQuest and Embase databases up to August 2021 by using the relative keywords. Original studies published in the English language that assessed the effects of resveratrol on PCOS and its associated complications were considered. Out of 417 records screened, only 24 articles met the inclusion criteria: 10 in vitro, 10 animal and 4 human studies. The results obtained in the present study showed that resveratrol supplementation might be effective in improving PCOS-related symptoms by reducing insulin resistance, alleviating dyslipidaemia, improving ovarian morphology and anthropometric indices, regulating the reproductive hormones and reducing inflammation and oxidative stress by affecting biological pathways. According to the available evidence, resveratrol may reduce the complications of PCOS. However, further studies are recommended for a comprehensive conclusion on the exact mechanism of resveratrol in PCOS patients.

A comprehensive insight into effects of resveratrol on molecular mechanism in rheumatoid arthritis: A literature systematic review.

AIM: Rheumatoid arthritis (RA) is an inflammatory autoimmune disease, which is characterized by massive pain and destruction of synovial joints, leads to bone erosion, damage to cartilage, and disability. Several studies suggested that resveratrol supplementation may be effective in the prevention and management of RA. Therefore, a systematic review was conducted to summarize published studies that assess the effect of resveratrol supplementation on the complications of RA. METHODS: A comprehensive search to identify in vitro, animal, and human studies investigating the impact of resveratrol on the complications of RA was performed up to February 2022. Two independent reviewers evaluated studies based on inclusion/exclusion criteria and performed data extraction. RESULTS: All studies examining the effects of resveratrol supplementation on the complications of RA were included. From a total of 571 retrieved articles, 32 studies were eligible for the current systematic review. The evidence reviewed here indicates that resveratrol supplementation may exert beneficial effects on the complications of RA by attenuating inflammation and oxidative stress, modulating the immune response, and down-regulating the messenger RNA expression of genes related to inflammatory pathways. CONCLUSION: Due to the promising therapeutic effects of resveratrol on RA complications and limited number of human studies in this subject, further clinical trials are suggested.

Nano-curcumin supplementation in critically ill patients with sepsis: a randomized clinical trial investigating the inflammatory biomarkers, oxidative stress indices, endothelial function, clinical outcomes and nutritional status.

Sepsis is a severe reaction and excessive immune response to infection, which can lead to organ dysfunction, and death. This study aimed to investigate the protective effect of nano-curcumin (NC) on inflammatory biomarkers, endothelial function, oxidative stress indices, biochemical factors, nutritional status, and clinical outcomes in patients with sepsis. In the present double-blind placebo-controlled randomized clinical trial, 40 ICU-admitted patients were randomly allocated into either NC or placebo group for 10 days. Both nano-curcumin (160 mg) and placebo were administered via a nasogastric tube twice a day. The mRNA expression of nuclear-related factor 2 (Nrf-2), BCL2 associated X (BAX), B-cell lymphoma 2 (BCL-2), and toll-like receptor 4 (TLR-4) genes in the peripheral blood mononuclear cells (PBMCs), and the serum levels of primary, secondary, tertiary, and exploratory outcomes were assessed before the baseline and on days 5 and 10. There were significant improvements in the primary outcomes, including inflammatory markers (IL-6, IL-18, IL-1ß, IL-10, TLR-4, BCL-2 and BAX), markers of endothelial function (ICAM-1 and VCAM-1), and oxidative stress indices (malondialdehyde (MDA), nuclear-related factor 2 (Nrf-2), catalase, superoxide dismutase (SOD), and TAC) (p < 0.005) in the NC group compared to the placebo group after 10 days, while no significant increase was observed in the glutathione peroxidase (GPx) level between the two groups. However, no significant decrease was observed in the levels of secondary outcomes, including biochemical factors (creatinine, fasting blood sugar (FBS), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), total bilirubin, triglycerides (TG) and total cholesterol (TC)) (P > 0.05). Our results showed that in the tertiary outcome (nutritional status), there was no significant increase (P > 0.05) except for TLC (P = 0.003). NC supplementation also resulted in a significant decrease in the exploratory outcomes including the SOFA score and the duration of mechanical ventilation (P < 0.05). Supplementation with NC may be a promising treatment strategy for critically ill patients with sepsis. However, further experiments are suggested to investigate the effects of nano-curcumin on biochemical pathways involved in sepsis.

The potential role of saffron (Crocus Sativus L.) and its components in oxidative stress in diabetes mellitus: A systematic review.

BACKGROUND AND AIMS: Diabetes mellitus is one of the most important life-threatening metabolic diseases of the 21st century. The use of complementary and alternative medicine in diabetic patients seems to be increasing. Saffron, a valuable herbal medicine, has several pharmacological properties such as anti-oxidant effect, which can play important role in ameliorating the complications of diabetes. The aim of this study was to systematically review the therapeutic effects of saffron and its bioactive components on oxidative stress in diabetes mellitus. METHODS: In this systematic review, databases such as PubMed, SCOPUS, Embase, ProQuest, and Web of Sciences were searched from the beginning to December 2021. All eligible in vitro, animal, and human studies that examined the effect of saffron on oxidative stress indices in diabetes were prepared in the form of a full article in English. RESULTS: In the end, only 31of the 389 articles met the criteria for analysis. Of the 31 articles, 4 were in-vitro studies, 25 were animal studies, and 2 were clinical trials studies. Saffron supplementation may activate insulin receptor substrate 1 (IRS1) and peroxisome proliferator-activated receptor gamma (PPAR-γ), which can improve hyperglycemia and insulin transduction signal in adipose tissue, and regulate glucose metabolism, leading to an increased nuclear factor erythroid 2-related factor 2 (Nrf2), HO-1 expression, amelioration of mitochondrial function, and an increased levels of antioxidant enzymes. CONCLUSION: Most studies have shown that saffron supplementation significantly enhanced the production and activity of antioxidant enzymes and decreased oxidative stress indices in diabetes mellitus. However, human pharmacokinetic and more accurate clinical trial studies are needed to determine dose ranges and the exact mechanisms of action of saffron and its active components in diabetes.

Does nano-curcumin supplementation improve hematological indices in critically ill patients with sepsis? A randomized controlled clinical trial.

Sepsis is the final common pathway to death for severe infectious diseases worldwide. The present trial aimed to investigate the effects of nano-curcumin supplementation on hematological indices in critically ill patients with sepsis. Fourteen ICU-admitted patients were randomly allocated into either nano-curcumin or placebo group for 10 days. The blood indices, serum levels of inflammatory biomarker and presepsin as well as nutrition status, and clinical outcomes were assessed before the intervention and on days 5 and 10. White blood cells, neutrophils, platelets, erythrocyte sedimentation rate (ESR), and the levels of interleukin-8 significantly decreased in the nano-curcumin group compared to the placebo after 10 days of intervention (p = .024, p = .045, p = .017, p = .041, and p = .004, respectively). There was also a marginal meaningful decrease in serum presepsin levels in the intervention group compared to the placebo at the end of the study (p = .054). However, total lymphocyte count showed a significant increase in the nano-curcumin group compared to the placebo at the end-point (p = .04). No significant differences were found in the level of lymphocyte and the ratios of neutrophil/lymphocyte and platelet/lymphocyte between the study groups. Moreover, no significant between-group differences were observed for other study outcomes, post-intervention. Collectively, nano-curcumin may be a useful adjuvant therapy in critically ill patients with sepsis. However, further trials are suggested to examine the effects of nano-curcumin in the management of sepsis and its complications. PRACTICAL APPLICATIONS: Curcumin (1,7-bis[4-hydroxy-3-methoxyphenyl]-1,6-heptadiene-3,5- dione) or diferuloylmethane is widely used in medicine due to its several biological properties. Recent evidence has shown that curcumin possesses multiple pharmacological activities including immune-modulatory, antioxidant, anti-inflammatory, anti-cancer, and anti-microbial effects. In this study, it was observed that nano-curcumin at a dose of 160 mg for 10 days, without side effects, reduced some inflammatory factors and regulated the immune responses in sepsis patients. For the first time, this trial was conducted to determine the effect of nano-curcumin on hematological indices and the serum levels of presepsin and IL-8.