Can Berberine Serve as a New Therapy for Parkinson's Disease?

Parkinson's disease (PD) is a neurodegenerative disorder characterized by dopaminergic neurodegeneration and deposition of alpha-synuclein. Mechanisms associated with PD etiology include oxidative stress, apoptosis, autophagy, and abnormalities in neurotransmission, to name a few. Drugs used to treat PD have shown significant limitations in their efficacy. Therefore, recent focus has been placed on the potential of active plant ingredients as alternative, complementary, and efficient treatments. Berberine is an isoquinoline alkaloid that has shown promise as a pharmacological treatment in PD, given its ability to modulate several molecular pathway associated with the disease. Here, we review contemporary knowledge supporting the need to further characterize berberine as a potential treatment for PD.

Effects of flaxseed oil supplementation on biomarkers of inflammation and oxidative stress in patients with metabolic syndrome and related disorders: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: This systematic review and meta-analysis of randomized controlled trials (RCTs) was performed to analyze the effects of flaxseed oil supplementation on biomarkers of inflammation and oxidative stress in patients with metabolic syndrome (MetS) and related disorders. METHODS: Databases including PubMed, Scopus, EMBASE, Web of Science, and Cochrane Central library were searched until January 31th, 2019. RESULTS: 14 effect sizes from 12 studies were identified eligible to be included in current meta-analysis. Flaxseed supplementation resulted in a significant reduction in interleukin 6 (IL-6) (WMD: -0.22; 95% CI: -0.43, -0.01) and malondialdehyde (MDA) (WMD: -0.17; 95% CI: -0.31, -0.03) and a significant increase in total antioxidant capacity (TAC) levels (WMD: 137.25; 95% CI: 68.04, 206.47). Flaxseed oil supplementation did not affect other biomarkers of inflammation and oxidative stress. CONCLUSIONS: Overall, this meta-analysis demonstrated flaxseed oil supplementation decreased IL-6 and MDA levels, and increased TAC, but did not affect other biomarkers of inflammation and oxidative stress among patients with MetS and related disorders. This suggests that flaxseed oil supplementation may have played an indirect role in improved clinical symptoms in diseases with metabolic disorders.

A systematic review and meta-analysis: The effects of probiotic supplementation on metabolic profile in patients with neurological disorders.

BACKGROUND AND OBJECTIVE: The objective of meta-analysis of randomized controlled trials (RCTs) was to evaluate the effects of probiotic supplementation on metabolic status in patients with neurological disorders. METHODS: The following databases were search up to April 2019: Pubmed, Scopus, Google scholar, Web of Science, and Cochrane Central Register of Controlled Trials. The quality of the relevant extracted data was assessed according to the Cochrane risk of bias tool. Data were pooled by the use of the inverse variance method and expressed as mean difference with 95 % Confidence Intervals (95 % CI). RESULTS: Nine studies were included in this meta-analysis. The findings suggested that probiotic supplementation resulted in a significant reduction in C-reactive protein (CRP) [Weighted Mean Difference (WMD): -1.06; 95 % CI: -1.80, -0.32] and malondialdehyde (MDA) levels (WMD: -0.32; 95 % CI: -0.46, -0.18). Supplementation with probiotics also significantly reduced insulin (WMD: -3.02; 95 % CI: -3.88, -2.15) and homeostatic model assessment for insulin resistance (HOMA-IR) (WMD: -0.71; 95 % CI: -0.89, -0.52). Probiotics significantly reduced triglycerides (WMD: -18.38; 95 % CI: -25.50, -11.26) and VLDL-cholesterol (WMD: -3.16; 95 % CI: -4.53, -1.79), while they increased HDL-cholesterol levels (WMD: 1.52; 95 % CI: 0.29, 2.75). CONCLUSION: This meta-analysis demonstrated that taking probiotic by patients with neurological disorders had beneficial effects on CRP, MDA, insulin, HOMA-IR, triglycerides, VLDL-cholesterol and HDL-cholesterol levels, but did not affect other metabolic parameters.

The effects of quercetin supplementation on lipid profiles and inflammatory markers among patients with metabolic syndrome and related disorders: A systematic review and meta-analysis of randomized controlled trials.

Aims: This systematic review and meta-analysis of randomized controlled trials (RCTs) was performed to determine the effect of quercetin administration on lipid profiles and inflammatory markers among patients with metabolic syndrome (MetS) and related disorders.Methods: We searched systematically online databases including Cochrane Library, EMBASE, MEDLINE, and Web of Science to identify the relevant RCTs until November 2018. Q-test and I2 statistics were applied to assess heterogeneity among included studies. Data were combined using fixed- or random-effects model and presented as standardized mean difference (SMD) with 95% confidence interval (CI).Results: Out of 591 citations, 16 RCTs were included in the meta-analysis. The pooled findings showed that quercetin consumption significantly decreased total-cholesterol (SMD = -0.98; 95% CI, -1.48, -0.49; p < 0.001; I2: 94.0), LDL-cholesterol (SMD = -0.88; 95% CI, -1.35, -0.41; p < 0.001; I2: 92.7) and C-reactive protein (CRP) levels (-0.64; 95% CI, -1.03, -0.25; p = 0.001; I2: 90.2). While, quercetin supplementation did not significantly affect triglycerides (TG) (SMD = -0.32; 95% CI, -0.68, 0.04; p = 0.08; I2: 84.8), HDL-cholesterol (SMD = 0.20; 95% CI, -0.20, 0.24; p = 0.84; I2: 70.6), interleukin 6 (IL-6) (SMD = -0.69; 95% CI, -1.69, 0.31; p = 0.17; I2: 94.5) and tumor necrosis factor-alpha (TNF-α) levels (SMD = -0.06; 95% CI, -0.25, 0.14; p = 0.58; I2: 35.6)Conclusions: In summary, the current meta-analysis demonstrated that quercetin supplementation significantly reduced total-cholesterol, LDL-cholesterol, and CRP levels, yet did not affect triglycerides, HDL-cholesterol, IL-6 and TNF-α among patients with MetS and related disorders.

Melatonin and Parkinson Disease: Current Status and Future Perspectives for Molecular Mechanisms.

Parkinson disease (PD) is a chronic and neurodegenerative disease with motor and nonmotor symptoms. Multiple pathways are involved in the pathophysiology of PD, including apoptosis, autophagy, oxidative stress, inflammation, α-synuclein aggregation, and changes in the neurotransmitters. Preclinical and clinical studies have shown that melatonin supplementation is an appropriate therapy for PD. Administration of melatonin leads to inhibition of some pathways related to apoptosis, autophagy, oxidative stress, inflammation, α-synuclein aggregation, and dopamine loss in PD. In addition, melatonin improves some nonmotor symptom in patients with PD. Limited studies, however, have evaluated the role of melatonin on molecular mechanisms and clinical symptoms in PD. This review summarizes what is known regarding the impact of melatonin on PD in preclinical and clinical studies.

The effects of resveratrol intake on weight loss: a systematic review and meta-analysis of randomized controlled trials.

This systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to summarize the effect of resveratrol intake on weight loss. We searched the following databases until July 2018: MEDLINE, EMBASE, Web of Science and Cochrane Central Register of Controlled Trials. Data were pooled using the inverse variance method and expressed as standardized mean difference (SMD) with 95% confidence intervals (95% CI). Out of 831 reports, 36 RCTs were eligible for including to our meta-analysis. The pooled results, using random-effects model showed that resveratrol supplementation significantly decreased body weight (SMD = -0.17; 95% CI, -0.33, -0.01; P = 0.03; I2: 62.6), body mass index (BMI) (SMD = -0.20; 95% CI, -0.35, -0.05; P = 0.01; I2: 60.6), fat mass (SMD = -0.32; 95% CI, -0.62, -0.03; P = 0.03; I2: 77.9) and waist circumference (WC) (SMD = -0.42; 95% CI, -0.68, -0.16; P = 0.001; I2: 75.2), and significantly increased lean mass (SMD = 1.21; 95% CI, 0.75, 1.67; P < 0.001; I2: 87.6). We found no significant effect of resveratrol administration on leptin (SMD = -0.20; 95% CI, -0.68, 0.27; P = 0.40; I2: 85.3) and adiponectin levels (SMD = 0.08; 95% CI, -0.39, 0.55; P = 0.74; I2: 91.0). Resveratrol supplementation significantly decreased body weight in obese patients (SMD -0.43; 95% CI, -0.60, -0.26) compared with other diseases (SMD 0.02; 95% CI, -0.29, 0.33), and type 2 diabetes mellitus (SMD -0.17; 95% CI, -0.37, 0.02). Overall, the current meta-analysis demonstrated that resveratrol intake significantly reduced weight, BMI, WC and fat mass, and significantly increased lean mass, but did not affect leptin and adiponectin levels.

The Effects of Resveratrol Supplementation on Endothelial Function and Blood Pressures Among Patients with Metabolic Syndrome and Related Disorders: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: There are current trials investigating the effect of resveratrol supplementation on endothelial function and blood pressures among patients with metabolic syndrome (MetS); however, the findings are controversial. AIM: This systematic review and meta-analysis of randomized controlled trials (RCTs) were carried out to summarize the effects of resveratrol supplementation on endothelial activation and blood pressures among patients with MetS and related disorders. METHODS: We searched systematically online databases including: PubMed-Medline, Embase, ISI Web of Science and Cochrane Central Register of Controlled Trials until October, 2018. Two independent authors extracted data and assessed the quality of included articles. Data were pooled using the fixed- or random-effects model and considered as standardized mean difference (SMD) with 95% confidence intervals (95% CI). RESULTS: Out of 831 electronic citations, 28 RCTs (with 33 findings reported) were included in the meta-analyses. The findings showed that resveratrol intervention significantly increased flow-mediated dilatation (FMD) levels (SMD 1.77; 95% CI 0.25, 3.29; P = 0.02; I2: 96.5). However, resveratrol supplements did not affect systolic blood pressure (SBP) (SMD - 0.27; 95% CI - 0.57, 0.03; P = 0.07; I2: 88.9) and diastolic blood pressure (DBP) (SMD - 0.21; 95% CI - 0.52, 0.11; P = 0.19; I2: 89.8). CONCLUSIONS: Resveratrol supplementation significantly increased FMD among patients with MetS and related disorders, but did not affect SBP and DBP. Additional prospective studies are needed to investigate the effect of resveratrol supplementation on endothelial function and blood pressures, using higher-dose of resveratrol with longer durations.

The Effects of Quercetin Supplementation on Blood Pressures and Endothelial Function Among Patients with Metabolic Syndrome and Related Disorders: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: This systematic review and meta-analysis of randomized controlled trials (RCTs) were performed to determine the effect of quercetin administration on blood pressures and endothelial function among patients with metabolic syndrome (MetS) and related disorders. METHODS: We searched systematically online databases including Cochrane Library, EMBASE, MEDLINE, and Web of Science to identify the relevant RCTs until December 2018. Q-test and I2 statistics were applied to assess heterogeneity among the included studies. Data were pooled using a random-effects model and weighted mean difference (WMD) was considered as the overall effect size. RESULTS: Out of 284 citations, 8 RCTs were included in the meta-analysis. We found a significant reduction in systolic blood pressure (SBP) (WMD: -1.69; 95% CI: -3.22, -0.17) following the intake of quercetin supplements. However, quercetin supplementation did not significantly affect diastolic blood pressure (DBP) (WMD: -3.14; 95% CI: -8.24, 1.95), vascular cell adhesion molecule 1 (VCAM-1) (WMD: -24.49; 95% CI: -53.74, 4.77) and intercellular adhesion molecule 1 (ICAM-1) (WMD: -5.78; 95% CI: -12.93, 1.38). CONCLUSION: In summary, the current meta-analysis demonstrated that quercetin supplementation significantly reduced SBP, yet did not affect DBP, VCAM-1 and ICAM-1 among patients with MetS and related disorders.

The effects of omega-3 fatty acids and vitamin E co-supplementation on gene expression related to inflammation, insulin and lipid in patients with Parkinson's disease: A randomized, double-blind, placebo-controlled trial.

OBJECTIVE: This study was conducted to evaluate the effects of omega-3 fatty acids and vitamin E co-supplementation on gene expression related to inflammation, insulin and lipid in subjects with Parkinson's disease (PD). PATIENTS AND METHODS: This randomized, double-blind, placebo-controlled clinical trial was performed in 40 subjects with PD. Participants were randomly allocated into two groups to take either 1000 mg/day of omega-3 fatty acids from flaxseed oil plus 400 IU/day of vitamin E supplements or placebo (n = 20 each group) for 12 weeks. Gene expression related to inflammation, insulin and lipid were quantified in peripheral blood mononuclear cells (PBMC) of PD patients with RT-PCR method. RESULTS: After the 12-week intervention, compared with the placebo, omega-3 fatty acids and vitamin E co-supplementation downregulated gene expression of tumor necrosis factor alpha (TNF-α) (P = 0.002) in PBMC of subjects with PD. In addition, omega-3 fatty acids and vitamin E co-supplementation upregulated peroxisome proliferator-activated receptor gamma (PPAR-γ) (P = 0.03), and downregulated oxidized low-density lipoprotein receptor (LDLR) (P = 0.002) in PBMC of subjects with PD compared with the placebo. We did not observe any significant effect of omega-3 fatty acids and vitamin E co-supplementation on gene expression of interleukin-1 (IL-1) and IL-8 in PBMC of patients with PD. CONCLUSIONS: Overall, omega-3 fatty acids and vitamin E co-supplementation for 12 weeks in PD patients significantly improved gene expression of TNF-α, PPAR-γ and LDLR, but did not affect IL-1 and IL-8.

The effects of resveratrol supplementation on biomarkers of inflammation and oxidative stress among patients with metabolic syndrome and related disorders: a systematic review and meta-analysis of randomized controlled trials.

There are several current trials investigating the effect of resveratrol supplementation on biomarkers of inflammation and oxidative stress among patients with metabolic syndrome (MetS); however, their findings are controversial. This systematic review and meta-analysis of randomized controlled trials (RCTs) were conducted to summarize the existing evidence and collectively determine the effects of resveratrol supplementation on biomarkers of inflammation and oxidative stress among patients with MetS and related disorders. Two authors independently searched electronic databases, including MEDLINE, EMBASE, Cochrane Library, and Web of Science databases, until May 2018 in order to find relevant RCTs. The quality of the selected RCTs was evaluated using the Cochrane Collaboration risk of bias tool. Cochran's Q test and I-square (I2) statistic were used to determine whether heterogeneity exists across included trials. Standardized mean difference (SMD) and 95% CI between two intervention groups were used to determine pooled effect sizes. Out of 317 potential citations selected based on keywords, 24 RCTs met the inclusion criteria and were eligible for the current meta-analysis. The pooled results obtained by using the random-effects model showed that resveratrol supplementation significantly decreased C-reactive protein (CRP) (SMD = -0.55; 95% CI, -0.84, -0.26; P < 0.001; I2: 84.0) and tumor necrosis factor-α (TNF-α) (SMD = -0.68; 95% CI, -1.08, -0.28; P = 0.001; I2: 81.3) concentrations among patients with MetS and related disorders. Interleukin 6 (IL-6) (SMD = 0.05; 95% CI, -0.31, 0.41; P = 0.79; I2: 85.0) and superoxide dismutase (SOD) (SMD = 0.21; 95% CI, -3.16, 3.59; P = 0.90; I2: 97.7) concentrations did not significantly change following resveratrol supplementation. Resveratrol supplementation showed a promising lowering effect on some of the inflammatory markers among patients with MetS and related disorders. Additional prospective studies regarding the effect of resveratrol supplementation on biomarkers of inflammation and oxidative stress by using higher doses of resveratrol and longer duration of supplementation are necessary.

The effects of omega-3 fatty acids and vitamin E co-supplementation on clinical and metabolic status in patients with Parkinson's disease: A randomized, double-blind, placebo-controlled trial.

The current research was performed to evaluate the effects of omega-3 fatty acids and vitamin E co-supplementation on clinical signs and metabolic status in people with Parkinson's disease (PD). This randomized double-blind placebo-controlled clinical trial was conducted in 60 patients with PD. Participants were randomly assigned into two groups to receive either 1000 mg omega-3 fatty acids from flaxseed oil plus 400 IU vitamin E supplements (n = 30) or placebo (n = 30) for 12 weeks. Unified Parkinson's disease rating stage (UPDRS) were recorded at baseline and the after 3-month intervention. After 12 weeks' intervention, compared with the placebo, omega-3 fatty acids and vitamin E co-supplementation led to a significant improve in UPDRS (-3.3 ± 10.0 vs. +4.4 ± 14.9, P = 0.02). Furthermore, co-supplementation decreased high-sensitivity C-reactive protein (hs-CRP) (-0.3 ± 0.6 vs. +0.3 ± 0.3 µg/mL, P < 0.001), and increased total antioxidant capacity (TAC) (+65.2 ± 68.7 vs. +16 ± 52.4 µmol/L, P = 0.003) and glutathione (GSH) concentrations (+41.4 ± 80.6 vs. -19.6 ± 55.9 µmol/L, P = 0.001) compared with the placebo. Additionally, co-supplementation meaningfully decreased insulin (-2.1 ± 4.9 vs. +1.4 ± 6.2 µIU/mL, P = 0.01), homeostasis model of assessment-estimated insulin resistance (-0.7 ± 1.8 vs.+0.3 ± 1.6, P = 0.02) and Beta cell function (-5.9 ± 13.9 vs. +5.7 ± 25.5, P = 0.03), and increased quantitative insulin sensitivity check index (+0.009 ± 0.02 vs. -0.006 ± 0.03, P = 0.03) compared with the placebo. Overall, our study demonstrated that omega-3 fatty acids and vitamin E co-supplementation in people with PD had favorable effects on UPDRS, hs-CRP, TAC, GSH and markers of insulin metabolism.