The effect of dietary interventions on inflammatory biomarkers among people with multiple sclerosis: A protocol for systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Multiple sclerosis (MS) is a chronic neuroinflammatory disease of the central nervous system, characterized by demyelination and neurodegeneration, which has a profound impact on the quality of life. Dysregulated inflammatory processes are a major driver of MS progression, with many areas of research being dedicated to modulating inflammation in people with MS. Several dietary patterns have been associated with improvements in inflammatory biomarkers; although, the findings have been inconsistent. Thus, this study aims to evaluate the effects of dietary interventions on inflammatory markers in adults with MS. METHODS: Electronic databases, including PubMed/MEDLINE, Web of Science, Scopus, and Cochrane/Central, will be searched. Screening, selection, and extraction of data, along with quality assessment of included studies, will be done by two separate reviewers, and any potential conflicts will be settled through discussion. Two reviewers will independently assess the risk of bias in included studies using the Cochrane Risk of Bias Tool. If plausible, the results will be synthesized and pooled for meta-analysis. The overall quality of evidence of each study will be evaluated using the NutriGRADE tool, which is a modification to the Grading Recommendations Assessment, Development, and Evaluation (GRADE) developed specifically for nutrition research. DISCUSSION: Studies have demonstrated conflicting results regarding the effects of dietary interventions on serum levels of inflammatory biomarkers among people with MS. Thus, it is expected that the planned systematic review and meta-analysis will yield robust evidence on the effects of diet on inflammatory profile in the setting of MS.

Prevention of recognition memory loss and moderation of mitochondrial dynamic tendency toward fusion by flavone derivatives in Aß-injected rats: a comparison between two flavonoids with different polarity.

Growing evidence sheds light on the use of flavonoids as the promising alternatives for the treatment of chronic conditions, including cancer and neurodegenerative disorders. Accordingly, in the present study, we aimed at evaluating the effects of oral intake of two structurally different flavonoids 5-hydroxy-6,7,4'-trimethoxyflavone (flavone 1) and 5,7,4'-trihydroxyflavone (flavone 2) on recognition memory, hippocampal protein level of immediate early gene cFos and mitochondrial dynamic markers in Amyloid ß (Aß)-injected rats. Recognition aspect of memory and level of proteins were measured using novel object recognition test and Western blot, respectively. Our data indicated that even though flavone 1 was more effective than flavone 2 to prevent memory impairment, feeding with both flavones alleviated memory in Aß-injected rats. Furthermore, in flavones-administered rats, mitochondrial dynamic balancing returned to the control level by the decline in Dynamin-related protein-1 protein level, a known marker for mitochondrial fission, and elevation in protein level of mitochondrial fusion factors Mitofusins 1 and 2. In parallel with behavior results, flavone 1 was more effectual on mitochondrial dynamic moderating. The more neuroprotective effects of flavone 1 could be attributed to its methylated structure leading to crossing of the blood-brain barrier with ease and metabolic stability and bioactivity.

Beneficial Effect of Flavone Derivatives on Aß-Induced Memory Deficit Is Mediated by Peroxisome Proliferator-Activated Receptor γ Coactivator 1α: A Comparative Study.

In the present study, the neuroprotective effect of 5-hydroxy-6,7,4'-trimethoxyflavone (flavone 1), a natural flavone, was investigated in comparison with another flavone, 5,7,4'-trihydroxyflavone (flavone 2) on the hippocampus of amyloid beta (Aß)-injected rats. Rats were treated with the 2 flavones (1 mg/kg/d) for 1 week before Aß injection. Seven days after Aß administration, memory function of rats was assessed in a passive avoidance test (PAT). Changes in the levels of mitochondrial transcription factor A (TFAM), peroxisome proliferator-activated receptor γ coactivator 1 α (PGC-1α), phospho-adenosine monophosphate (AMP)-activated protein kinase (pAMPK), AMPK, phospho-cAMP-responsive element-binding protein (CREB), CREB, and nuclear respiratory factor 1 (NRF-1) proteins were determined by Western blot analysis. Our results showed an improvement in memory in rats pretreated with flavonoids. At the molecular level, phosphorylation of CREB, known as the master modulator of memory processes, increased. On the other hand, the level of mitochondrial biogenesis factors, PGC-1α and its downstream molecules NRF-1 and TFAM significantly increased by dietary administration of 2 flavones. In addition, flavone 1 and flavone 2 prevented mitochondrial swelling and mitochondrial membrane potential reduction. Our results provided evidence that flavone 1 is more effective than flavone 2 presumably due to its O-methylated groups. In conclusion, it seems that in addition to classical antioxidant effect, flavones exert part of their protective effects through mitochondrial biogenesis.