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.

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.

Therapeutic Effects and Mechanisms of Action of Garlic (Allium sativum) on Nonalcoholic Fatty Liver Disease: A Comprehensive Systematic Literature Review.

Nonalcoholic fatty liver disease (NAFLD) is globally the leading cause of hepatic dysfunction. Garlic has many physiological benefits, including anti-inflammatory, antioxidant, anticancer, lipid-lowering, and antidiabetes effects. The present study aimed to systematically review the effects of garlic (Allium sativum) and its mechanisms of function in managing NAFLD and its associated complications. The guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statements were applied to perform the study (CRD42021289348). The Scopus, Embase, Web of Science, Cochrane PubMed, and Google Scholar databases were searched until February 2022. According to the inclusion criteria, finally, 12 studies were entered into the study. The evidence provided in the study revealed that garlic could regulate the development of NAFLD via several mechanisms of action, such as lowering body weight, modulating lipid and glucose metabolism, and reducing inflammation and oxidative stress (OS). Overall, the beneficial effects of garlic in the treatment of NAFLD make it a potential therapeutic and efficient agent in managing NAFLD and its related risk factors. There is an insufficient number of clinical trials addressing the effects of garlic in humans; therefore, conducting more human research in the future is recommended.

A comprehensive systematic review of the therapeutic effects and mechanisms of action of quercetin in sepsis.

BACKGROUND: Sepsis is a life-threatening condition caused by a dysregulated host response to infection. Several studies have indicated that flavonoids exhibit a wide variety of biological actions including free radical scavenging and antioxidant activities. Quercetin, one of the most extensively distributed flavonoids in the vegetables and fruits, presents various biological activities including modulation of oxidative stress, anti-infectious, anti-inflammatory, and neuroprotective activities. METHODS: The present systematic review was conducted according to the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statements. We searched Web of Sciences, Google Scholar, PubMed, Scopus, and Embase databases up to February 2021 by using the relevant keywords. RESULTS: Out of 672 records screened, 35 articles met the study criteria. The evidence reviewed here indicates that quercetin supplementation may exert beneficial effects on sepsis by attenuating inflammation and oxidative stress, downregulating the mRNA expression of toll-like receptors (TLRs), modulating the immune response, and alleviating sepsis-related organ dysfunctions. CONCLUSION: Due to the promising therapeutic effects of quercetin on sepsis complications and the lack of clinical trials in this regard, future human randomized clinical trials are warranted.

A Comprehensive insight into the effect of chromium supplementation on oxidative stress indices in diabetes mellitus: A systematic review.

Diabetes mellitus is a metabolic disorder defined as an increase in blood glucose levels (hyperglycaemia) and insufficient production or action of insulin produced by the pancreas. Chronic hyperglycaemia leads to increased reactive oxygen species (ROS) production and oxidative stress, which consequently results in insulin resistance, beta cell degeneration, dyslipidaemia, and glucose intolerance in diabetic patients. Chromium has an essential role in the metabolism of proteins, lipids, and carbohydrates through increasing insulin efficiency. This systematic review aimed to evaluate chromium supplementation's potential roles in oxidative stress indices in diabetes mellitus. A systematic search was performed in PubMed, Scopus, Google Scholar, Cochrane, and Science Direct databases until November 2020. All clinical trials and animal studies that assessed chromium's effect on oxidative stress indices in diabetes mellitus and were published in English-language journals were included. Finally, only 33 out of 633 articles met the required criteria for further analysis. Among 33 papers, 25 studies were performed on animals, and eight investigations were conducted on humans. Twenty-eight studies of chromium supplementation lead to reducing oxidative stress indices. Also, 23 studies showed that chromium supplementation markedly increased antioxidant enzymes' activity and improved levels of antioxidant indices. In conclusion, chromium supplementation decreased oxidative stress in diabetes mellitus. However, further clinical trials are suggested in a bid to determine the exact mechanisms.

Chromium picolinate balances the metabolic and clinical markers in nonalcoholic fatty liver disease: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) is a complicated disease and is considered as a severe global health problem affecting 30% of adults worldwide. The present study aimed to evaluate changes in oxidative stress, adipokines, liver enzyme, and body composition following treatment with chromium picolinate (CrPic) among patients with NAFLD. PARTICIPANTS AND METHODS: The current randomized, double-blind, placebo-controlled study was conducted on 46 NAFLD patients with the age range of 20-65 years. Patients were randomly classified into two groups, receiving either 400 µg CrPic tablets in two divided doses of 200 µg (23 patients) or placebo (23 patients) daily for 12 weeks. The participants' body composition and biochemical parameters were evaluated at the baseline and after 12 weeks. RESULTS: Serum levels of liver enzymes reduced significantly only in the CrPic group (P < 0.05 for all), but not between the groups after the intervention. Besides, there were significant differences between the study groups regarding body weight and body fat mass, total antioxidant capacity, superoxide dismutase, malondialdehyde, leptin, and adiponectin post-intervention (P = 0.017, P = 0.032, P = 0.003, P = 0.023, P = 0.012, P = 0.003, and P = 0.042, respectively). However, glutathione peroxidase and resistin levels did not differ significantly between groups (P = 0.127 and P = 0.688, respectively). DISCUSSION AND CONCLUSION: This study showed that consuming 400 µg/day of CrPic for 12 weeks in patients with NAFLD causes a significant change in leptin, adiponectin, oxidative stress (expect glutathione peroxidase), and body weight, compared to baseline. Nevertheless, it does not affect liver enzymes. Therefore, the CrPic supplementation may improve adipokines, some anthropometric indices, and oxidative stress in patients with NAFLD.