Major depression is a devastating disease affecting an increasing number of people from a young age worldwide, a situation that is expected to be worsened by the COVID-19 pandemic. New approaches for the treatment of this disease are urgently needed since available treatments are not effective for all patients, take a long time to produce an effect, and are not well-tolerated in many cases; moreover, they are not safe for all patients. There is solid evidence showing that the antioxidant capacity is lower and the oxidative damage is higher in the brains of depressed patients as compared with healthy controls. Mitochondrial disfunction is associated with depression and other neuropsychiatric disorders, and this dysfunction can be an important source of oxidative damage. Additionally, neuroinflammation that is commonly present in the brain of depressive patients highly contributes to the generation of reactive oxygen species (ROS). There is evidence showing that pro-inflammatory diets can increase depression risk; on the contrary, an anti-inflammatory diet such as the Mediterranean diet can decrease it. Therefore, it is interesting to evaluate the possible role of plant-derived antioxidants in depression treatment and prevention as well as other biomolecules with high antioxidant and anti-inflammatory potential such as the molecules paracrinely secreted by mesenchymal stem cells. In this review, we evaluated the preclinical and clinical evidence showing the potential effects of different antioxidant and anti-inflammatory biomolecules as antidepressants, with a focus on difficult-to-treat depression and conventional treatment-resistant depression.

/pdf/antioxidant-biomolecules-and-their-potential-for-the-3rv5cy1j.pdf

Antioxidant Biomolecules and Their Potential for the Treatment of Difficult-to-Treat Depression and Conventional Treatment-Resistant Depression

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.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.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.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. 

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

Major depressive disorder (MDD) is a life‐threatening disease that presents several characteristics. The pathogenesis of depression still remains poorly understood. Moreover, the mechanistic interactions of natural components in treating depression to target autophagy and neuroinflammation are yet to be evaluated. This study overviewed the effects of plant‐derived natural components in regulating critical pathways, particularly neuroinflammation and autophagy, associated with depression. A list of natural components, including luteolin, apigenin, hyperforin, resveratrol, salvianolic acid b, isoliquiritin, nobiletin, andrographolide, and oridonin, have been investigated. All peer‐reviewed journal articles were searched by Scopus, MEDLINE, PubMed, Web of Science, and Google Scholar using the appropriated keywords, including depression, neuroinflammation, autophagy, plant, natural components, etc. The neuroinflammation and autophagy dysfunction are critically associated with the pathophysiology of depression. Natural components with higher efficiency and lower complications can be used for targeting neuroinflammation and autophagy. These components with different doses showed the beneficial antidepressant properties in rodents. These can modulate autophagy markers, mainly AMPK, LC3II/LC3I ratio, Beclin‐1. Moreover, they can regulate the NLRP3 inflammasome, resulting in the suppression of proinflammatory cytokines (e.g., IL‐1β and IL‐18). Future in vitro and in vivo studies are required to develop novel therapeutic approaches based on plant‐derived active components to treat MDD.

Targeting autophagy and neuroinflammation pathways with plant‐derived natural compounds as potential antidepressant agents

Rheumatic diseases (RDs) are often complicated by chronic symptoms and frequent side-effects associated with their treatment. Saffron, a spice derived from the Crocus sativus L. flower, is a popular complementary and alternative medicine among patients with RDs. The present systematic review aimed to summarize the available evidence regarding the efficacy of supplementation with saffron on disease outcomes and comorbidities in patients with RD diagnoses. PubMed, CENTRAL, clinicaltrials.gov and the grey literature were searched until October 2021, and relevant randomized controlled trials (RCTs) were screened for eligibility using Rayyan. Risk of bias was assessed using the Cochrane’s Risk of Bias-2.0 (RoB) tool. A synthesis without meta-analysis (SWiM) was performed by vote counting and an effect direction plot was created. Out of 125 reports, seven fulfilled the eligibility criteria belonging to five RCTs and were included in the SWiM. The RCTs involved patients with rheumatoid arthritis, osteoarthritis and fibromyalgia, and evaluated outcomes related to pain, disease activity, depression, immune response, inflammation, oxidative stress, health, fatigue and functional ability. The majority of trials demonstrated some concerns regarding overall bias. Moreover, the majority of trialists failed to adhere to the formula elaborations suggested by the CONSORT statement for RCTs incorporating herbal medicine interventions. Standardization of herbal medicine confirms its identity, purity and quality; however, the majority of trials failed to adhere to these guidelines. Due to the great heterogeneity and the lack of important information regarding the standardization and content of herbal interventions, it appears that the evidence is not enough to secure a direction of effect for any of the examined outcomes.

Effect of Crocus sativus (Saffron) Intake on Top of Standard Treatment, on Disease Outcomes and Comorbidities in Patients with Rheumatic Diseases: Synthesis without Meta-Analysis (SWiM) and Level of Adherence to the CONSORT Statement for Randomized Controlled Trials Delivering Herbal Medicine Interventions

Depressive disorders can affect up to 350 million people worldwide, and in developed countries, the percentage of patients with depressive disorders may be as high as 10%. During depression, activation of pro-inflammatory pathways, mitochondrial dysfunction, increased markers of oxidative stress, and a reduction in the antioxidant effectiveness of the body are observed. It is estimated that approximately 30% of depressed patients do not respond to traditional pharmacological treatments. However, more and more attention is being paid to the influence of active ingredients in food on the course and risk of neurological disorders, including depression. The possibility of using foods containing polyphenols as an element of diet therapy in depression was analyzed in the review. The possibility of whether the consumption of products such as polyphenols could alleviate the course of depression or prevent the progression of it was also considered. Results from preclinical studies demonstrate the potential of phenolic compounds have the potential to reduce depressive behaviors by regulating factors related to oxidative stress, neuroinflammation, and modulation of the intestinal microbiota.

/pdf/anti-inflammatory-antioxidant-and-neuroprotective-effects-of-1lyf4jyf.pdf

Anti-Inflammatory, Antioxidant, and Neuroprotective Effects of Polyphenols—Polyphenols as an Element of Diet Therapy in Depressive Disorders

Oxidative stress (OS), the absence of equilibrium between prooxidants and antioxidants in the body, has been shown to play a pivotal role in the initiation and progression of many diseases. Saffron has been noted for its antioxidant capacity and can be used to improve OS parameters in unhealthy patients. Our aim was to evaluate the efficacy of saffron supplementation on OS parameters in unhealthy patients in randomized controlled trials (RCTs). We searched Medline, EMBASE, Cochrane CENTRAL, Scopus, and Web of Science without language restrictions for RCTs up until April 2021. Studies were included if they compared any form of saffron supplementation to placebo or no supplementation on OS parameters in unhealthy patients. Using a random-effects model with calculated standardized mean difference (SMD) and 95% confidence intervals (CI), we quantitatively synthesized the data. Heterogeneity was assessed using Cochrane's I 2 values. Ten randomized controlled trials were eligible for this review. Seven were included in the meta-analysis and indicated an association between saffron intake and a statistically significant decrease in malondialdehyde (MDA) levels (SMD: -0.40; 95% CI: -0.63, -0.17; I 2 = 32.6%) and a significant increase in total antioxidant capacity (TAC, SMD: 0.24; 95% CI: 0.05, 0.42; I 2 = 00.0%). Saffron intake was shown to significantly impact MDA and TAC, indicating its beneficial properties in improving OS in unhealthy patients. However, additional RCTs are required to evaluate the effect on other OS parameters.

Ava sadat Hosseini

Papers

Effect of saffron supplementation on oxidative stress parameters: A systematic review and meta-analysis of randomized placebo-controlled trials.

The effect of chromium intake on oxidative stress parameters: A systematic review and meta-analysis.