A role for flavonoids in the prevention and/or treatment of cognitive dysfunction, learning, and memory deficits: a review of preclinical and clinical studies.

OBJECTIVE: Natural food substances, due to high rates of antioxidants, antiviral and anti-inflammatory properties, have been proposed to have the potential for the prevention or treatment of cognitive deficits, learning and memory deficits and neuro inflammation. In particular, medicinal plants with rich amounts of beneficial components such as flavonoids are one of the most promising therapeutic candidates for the cognitive deficit and memory loss. Herein, we aimed to review the impact of medicinal plants with focus on flavonoids on cognitive dysfunction, learning and memory loss by considering their signaling pathways. METHODS: We extracted 93 preclinical and clinical studies related to the effects of flavonoids on learning and memory and cognition from published papers between 2000 and 2021 in the MEDLINE/PubMed, Cochrane Library, SCOPUS, and Airiti Library databases. RESULTS: In the preclinical studies, at least there seem to be two main neurological and biological processes in which flavonoids contribute to the improvement and/or prevention of learning, memory deficit and cognitive dysfunction: (1) Regulation of neurotransmission system and (2) Enhancement of neurogenesis, synaptic plasticity and neuronal survival. CONCLUSION: Although useful effects of flavonoids on learning and memory in preclinical investigations have been approved, more clinical trials are required to find out whether flavonoids and/or other ingredients of plants have the potent to prevent or treat neurodegenerative disorders.

Effects of vitamin D supplementation on depression and some selected pro-inflammatory biomarkers: a double-blind randomized clinical trial.

BACKGROUND: Both augmented inflammatory reaction and low vitamin D status are associated with depression but the magnitude of their relationships is unclear. This study was, therefore, conducted to evaluate the effects of vitamin D supplementation on serum 25(OH)D concentration, depression severity and some pro-inflammatory biomarkers in patients with mild to moderate depression. METHODS: An 8-week double-blind randomized clinical trial (RCT) was performed on 56 (18-60 yrs) patients with mild to moderate depression, randomly assigned to intervention (50,000 IU cholecalciferol 2wks-1) and control (placebo) groups. Serum 25(OH)D, intact parathyroid hormone (iPTH), interlukin (IL)-1ß, IL-6, high-sensitivity C-reactive protein (hs-CRP) and depression severity (Beck Depression Inventory-II) (BDI-II)) were initially and finally assessed. RESULTS: At the end point, statistically significant changes were observed only in intervention group as compared with controls including increased 25(OH)D concentration (+ 40.83 ± 28.57 vs. + 5.14 ± 23.44 nmol L-1, P < 0.001) and decreased depression severity (-11.75 ± 6.40 vs. -3.61 ± 10.40, P = 0.003). No significant within- or between group differences were observed in serum IL-1ß, IL-6 and hs-CRP concentrations. CONCLUSION: Increased circulating 25(OH)D concentrations following 8-week vitamin D supplementation (50,000 IU 2wks-1) resulted in a significant decrease in BDI-II scores in patients with mild to moderate depression. However, this effect was independent of the serum concentrations of the studied inflammatory biomarkers. TRIAL REGISTRATION: The clinical trial registration code was obtained from the Iranian Registry of Clinical Trials (date of registration: 17/09/2018, registration number: IRCT20170926036425N1) and ClinicalTrials.gov (date of registration: 04/12/2018, registration number: NCT03766074).

Effect of Eicosapentaenoic Acid Supplementation on Paraoxonase 2 Gene Expression in Patients with Type 2 Diabetes Mellitus: a Randomized Double-blind Clinical Trial

Type 2 diabetes mellitus (T2DM) is recognized as one of the most prevalent metabolic diseases, and it is mostly associated with oxidative stress, atherosclerosis and dyslipidemia. Paraoxonase 2 (PON2) due to its antioxidant properties may play a role in the atherosclerosis development. Although long-chain omega-3 polyunsaturated fatty acids, such as eicosapentaenoic acid (EPA) have been shown to reduce the risk of cardiovascular disease, the exact mechanism of action is still unknown. Our goal in this study was to determine the effect of EPA administration on gene expression of PON2 in patients with T2DM. Present study was a randomized, controlled double-blind trial. Thirty-six patients with T2DM were randomly allocated to receive 2 g/day EPA (n = 18) or placebo (n = 18) for 8 weeks. There were no significant differences between 2 groups concerning demographic or biochemical variables, and dietary intakes as well (p > 0.05). However, patients received EPA showed a significant increase in the gene expression of PON2 compared with placebo group (p = 0.027). In addition, high-density lipoprotein cholesterol increased and fasting blood sugar decreased significantly after EPA supplementation compared with control group. Taken together, supplementation with 2 g/day EPA could be atheroprotective via the upregulation of PON2 in patients with T2DM. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03258840

The Effect of Pycnogenol Supplementation on Plasma C-Reactive Protein Concentration: a Systematic Review and Meta-Analysis

Pycnogenol is a standardized extract from the bark of the French maritime pine. The aim of the present systematic review and meta-analysis was to clarify the effect of Pycnogenol supplementation on C-reactive protein (CRP) concentration. To identify eligible studies in order to find clinical trials which examined the effect of Pycnogenol supplementation on the level of CRP in adult participants, PubMed, Scopus, and Google Scholar were systematically searched until December 2017. Mean of CRP was collected to estimate the effect size of the supplementation. Potential sources of heterogeneity were explored by subgroup analysis. Five trials including 324 participants were included in this meta-analysis. Pooled effect size showed significant effect of Pycnogenol supplementation on CRP (−1.22 mg/dL, 95% confidence interval, −2.43, −0.003; I2 = 99%, pheterogeneity 150 mg/d category (I2 = 0.0%, p = 0.42). There was significant difference between-subgroup heterogeneity (p < 0.001). Furthermore, no evidence of publication bias for CRP (p = 0.27, Begg's test and p = 0.62, Egger's test) was seen. Present systematic review and meta-analysis suggested Pycnogenol consumption can decrease the level of CRP and have anti-inflammatory effect. So, Pycnogenol as an anti-inflammatory agent might be a priority in interventions. Further studies with large-scale and better design are needed to confirm this result.

Erythrocyte Membrane Unsaturated (Mono and Poly) Fatty Acids Profile in Newly Diagnosed Basal Cell Carcinoma Patients

Studies have reported different changes in the fatty acid composition of red blood cell (RBC) total lipids in patients with various types of cancer. It has been indicated that n-3/n-6 ratio plays a key role in the general consequence of skin photocarcinogenesis. However, to our knowledge there was no study examining the unsaturated fatty acid profile in basal cell carcinoma (BCC) patients. So, we explore the fatty acid composition of RBCs in newly diagnosed BCC patients in a hospital-based case-control study. This study has been conducted on new case BCC patients in Razi Hospital, Tehran, Iran. Fatty acid concentration in erythrocyte membranes defined as relative values after extraction, purification and preparation, by gas chromatography.Analysis revealed that heptadecenoic acid (p = 0.010) and oleic acid (p < 0.001) was significantly higher in BCC patients in comparison with control group. Among polyunsaturated fatty acids (PUFAs), linoleic acid (LA), and arachidonic acid (AA) were significantly higher in BCC patients (p < 0.001). It has been indicated that n-3 was significantly lower (p = 0.040) and n-6 was significantly higher (p = 0.002) in BCC patients. In addition, total PUFA (p < 0.001) and n-6 PUFAs/n-3 PUFAs (p = 0.002) were significantly higher in BCC patients compared to the control group. Here we indicated that new case BCC patient had significantly higher n-6 PUFA and lower n-3 along with other differences in unsaturated fatty acid in comparison with healthy subjects. Our study provides evidence that lipids are important in BCC development.

A Comparative Study of Nurses as Case Manager and Telephone Follow-up on Clinical Outcomes of Patients with Severe Mental Illness.

BACKGROUND: Providing community-based mental health services is crucial and is an agreed plan between the Iranian Mental Health Office and the Regional Committee for the Eastern Mediterranean (affiliated with WHO). The aim of this study was to determine the effectiveness of home-visit clinical case-management services on the hospitalization rate and other clinical outcomes in patients with severe mental illness. METHODS: A total of 182 patients were randomly allocated into three groups, namely, home-visit (n=60), telephone follow-up (n=61) and as-usual care (n=61) groups. Trained nurses as clinical case-managers provided home-visit services and the telephone follow-up tasks. Hospitalization rate as a measure of recurrence, as well as burden, knowledge, general health condition of caregivers with positive/negative symptoms, satisfaction, quality of life, and social skills of the consumers were assessed as the main and secondary outcomes, respectively. RESULTS: Most clinical variables were improved in both intervention groups compared with the control group. During the one year follow-up, the rate of rehospitalization for the telephone follow-up and as-usual groups were respectively 1.5 and 2.5 times higher than the home-visit group. CONCLUSION: Trained clinical case-managers are capable of providing continuous care services to patients with severe mental illness. The telephone follow-up services could also have beneficiary outcome for the consumers, their caregivers, and the health system network.