greenmedinfo--2020-05-13--This study suggests that 25-hydroxyvitamin D treatment may relieve the offspring's MetS.

Metabolic syndrome is a disorder of energy use and storage , which is characterized by central obesity , dyslipidemia , and raised blood pressure and blood sugar levels .
Maternal 25-hydroxyvitamin D deﬁciency is known to cause metabolic changes , chronic disease , and increased adiposity in adulthood .
However , the underlying mechanism of induced metabolic syndrome ( MetS ) in the offspring in vitamin D deficient pregnant mothers remains unclear .
We identified that maternal 25-hydroxyvitamin D deficiency enhances oxidative stress , which leads to the development of MetS in the mother and her offspring .
Further , @ @ @ @ @ @ @ analyses revealed that maternal 25-hydroxyvitamin D deficiency inhibited the activation of the Nrf2/carbonyl reductase 1 ( CBR1 ) pathwayin maternal placenta , liver , and pancreas , as well as the offspring 's liver and pancreas .
Further analyses uncovered that application of 25-hydroxyvitamin D activated the Nrf2/CBR1 pathway , relieving the oxidative stress in BRL cells , suggesting that 25-hydroxyvitamin D regulates oxidative stress in offspring and induces the activation of the Nrf2/CBR1 pathway .
Taken together , our study finds that maternal 25-hydroxyvitamin D deficiency is likely to result in offspring @ @ @ @ @ @ @ .
Depression of the Nrf2/CBR1 pathway in both mothers and their offspring is one of the causes of oxidative stress leading to MetS .
This study suggests that 25-hydroxyvitamin D treatment may relieve the offspring 's MetS .

Metabolic syndrome is a disorder of energy use and storage, which is characterized by central obesity, dyslipidemia, and raised blood pressure and blood sugar levels. Maternal 25-hydroxyvitamin D deﬁciency is known to cause metabolic changes, chronic disease, and increased adiposity in adulthood. However, the underlying mechanism of induced metabolic syndrome (MetS) in the offspring in vitamin D deficient pregnant mothers remains unclear. We identified that maternal 25-hydroxyvitamin D deficiency enhances oxidative stress, which leads to the development of MetS in the mother and her offspring. Further, immunohistochemical, Western blotting, and qRT-PCR analyses revealed that maternal 25-hydroxyvitamin D deficiency inhibited the activation of the Nrf2/carbonyl reductase 1 (CBR1) pathwayin maternal placenta, liver, and pancreas, as well as the offspring's liver and pancreas. Further analyses uncovered that application of 25-hydroxyvitamin D activated the Nrf2/CBR1 pathway, relieving the oxidative stress in BRL cells, suggesting that 25-hydroxyvitamin D regulates oxidative stress in offspring and induces the activation of the Nrf2/CBR1 pathway. Taken together, our study finds that maternal 25-hydroxyvitamin D deficiency is likely to result in offspring's MetS probablyabnormal nutrition transformation across placenta. Depression of the Nrf2/CBR1 pathway in both mothers and their offspring is one of the causes of oxidative stress leading to MetS. This study suggests that 25-hydroxyvitamin D treatment may relieve the offspring's MetS.


greenmedinfo--2020-05-13--Effects of vitamin D supplementation on depression and some involved neurotransmitters.

BACKGROUND : Low vitamin D levels are associated with a dysregulated hypothalamic-pituitary-adrenal ( HPA ) axis and depression but a causal relationship has not been established .
This study aimed to evaluate the effects of vitamin D supplementation on depression severity , serum 25 ( OH ) D , and some neurotransmitters in patients with mild to moderate depression .
METHODS : An 8-week double-blind randomized clinical trial was conducted on 56 subjects with mild to moderate depression , aged 43.0 ± 1.15yrs .
The patients were randomly allocated into two groups : intervention ( 50,000 IU cholecalciferol/2wks ) and @ @ @ @ @ @ @ ( serum 25 ( OH ) D , iPTH , oxytocin and platelet serotonin ) , and depression severity ( Beck Depression Inventory-II ( BDI-II ) ) were initially and finally assessed .
RESULTS : Following intervention , significant changes were observed in the intervention group compared to the controls : 25 ( OH ) D concentrations increased ( +40.83±28.57 vs. +5.14±23.44 nmol/L , P < 0.001 ) and BDI scores decreased ( -11.75±6.40 vs. -3.61±10.40 , P = 0.003 ) .
Oxytocin concentrations were significantly reduced in controls ( -6.49±13.69 ng/mL , @ @ @ @ @ @ @ -group differences were insignificant .
Within- and between-group differences of platelet serotonin concentrations were not significant ; however , the increment in controls was higher ( +0.86±10.82 vs. +0.26±9.38 ng/mL , P = 0.83 ) .
LIMITATIONS : Study duration may not reflect the long-term effects of vitamin D on depression .
It seems necessary to assess tryptophan-hydroxylasetypes1 & 2 in relation to vitamin D in serotonin pathways .
CONCLUSIONS : Eight-week supplementation with 50,000 IU/2wks vitamin D , elevated 25 ( OH ) D concentration of subjects with mild to moderate depression @ @ @ @ @ @ @ However , there was no evidence that the anti-depressive effect of vitamin D supplementation is mediated by the measured neurotransmitters .

BACKGROUND: Low vitamin D levels are associated with a dysregulated hypothalamic-pituitary-adrenal (HPA) axis and depression but a causal relationship has not been established. This study aimed to evaluate the effects of vitamin D supplementation on depression severity, serum 25(OH)D, and some neurotransmitters in patients with mild to moderate depression.
METHODS: An 8-week double-blind randomized clinical trial was conducted on 56 subjects with mild to moderate depression, aged 43.0 ± 1.15yrs. The patients were randomly allocated into two groups: intervention (50,000 IU cholecalciferol/2wks) and control (placebo). Biochemical parameters (serum 25(OH)D, iPTH, oxytocin and platelet serotonin), and depression severity (Beck Depression Inventory-II (BDI-II)) were initially and finally assessed.
RESULTS: Following intervention, significant changes were observed in the intervention group compared to the controls: 25(OH)D concentrations increased (+40.83±28.57 vs. +5.14±23.44 nmol/L, P<0.001) and BDI scores decreased (-11.75±6.40 vs. -3.61±10.40, P = 0.003). Oxytocin concentrations were significantly reduced in controls (-6.49±13.69 ng/mL, P = 0.01), but between -group differences were insignificant. Within- and between-group differences of platelet serotonin concentrations were not significant; however, the increment in controls was higher (+0.86±10.82 vs. +0.26±9.38 ng/mL, P = 0.83).
LIMITATIONS: Study duration may not reflect the long-term effects of vitamin D on depression. It seems necessary to assess tryptophan-hydroxylasetypes1&2 in relation to vitamin D in serotonin pathways.
CONCLUSIONS: Eight-week supplementation with 50,000 IU/2wks vitamin D, elevated 25(OH)D concentration of subjects with mild to moderate depression and significantly improved their depression severity. However, there was no evidence that the anti-depressive effect of vitamin D supplementation is mediated by the measured neurotransmitters.


greenmedinfo--2020-05-13--Role of vitamin D in preventing and treating selected extraskeletal diseases.

Evidence is accumulating that vitamin D may have beneficial effects on respiratory tract , autoimmune , neuro-degenerative , and mental diseases .
The present umbrella review of systematic reviews ( SRs ) of cohort studies and randomised controlled trials ( RCTs ) , plus single Mendelian randomisation studies aims to update current knowledge on the potential role of vitamin D in preventing and treating these extraskeletal diseases .
Altogether , 73 SRs were identified .
Observational data on primary prevention suggest an inverse association between vitamin D status and the risk of acute respiratory tract infections ( ARI ) , @ @ @ @ @ @ @ , whereas studies regarding asthma , multiple sclerosis ( MS ) , and type 1 diabetes mellitus ( T1DM ) are scarce .
SRs of RCTs support observational data only for the risk of ARI .
No respective RCTs are available for the prevention of chronic obstructive pulmonary disease ( COPD ) , MS , and T1DM .
SRs of RCTs indicate beneficial therapeutic effects in vitamin D-deficient patients with asthma and COPD , while effects on major depression and T1DM need to be further elucidated .
Mendelian randomisation studies do not consistently @ @ @ @ @ @ @ several limitations of the included SRs and existing RCTs do not permit definitive conclusions regarding vitamin D and the selected diseases , further high-quality RCTs are warranted .

Evidence is accumulating that vitamin D may have beneficial effects on respiratory tract, autoimmune, neuro-degenerative, and mental diseases. The present umbrella review of systematic reviews (SRs) of cohort studies and randomised controlled trials (RCTs), plus single Mendelian randomisation studies aims to update current knowledge on the potential role of vitamin D in preventing and treating these extraskeletal diseases. Altogether, 73 SRs were identified. Observational data on primary prevention suggest an inverse association between vitamin D status and the risk of acute respiratory tract infections (ARI), dementia and cognitive decline, and depression, whereas studies regarding asthma, multiple sclerosis (MS), and type 1 diabetes mellitus (T1DM) are scarce. SRs of RCTs support observational data only for the risk of ARI. No respective RCTs are available for the prevention of chronic obstructive pulmonary disease (COPD), MS, and T1DM. SRs of RCTs indicate beneficial therapeutic effects in vitamin D-deficient patients with asthma and COPD, while effects on major depression and T1DM need to be further elucidated. Mendelian randomisation studies do not consistently support the results of SRs. Since several limitations of the included SRs and existing RCTs do not permit definitive conclusions regarding vitamin D and the selected diseases, further high-quality RCTs are warranted.


greenmedinfo--2020-05-13--Vitamin D supplementation has significant therapeutic benefits in the management of fibromyalgia syn

Vitamin D supplementation has significant therapeutic benefits in the management of fibromyalgia syndrome.

Numerous studies have been conducted to evaluate the frequency of hypovitaminosis D in patients with fibromyalgia syndrome ( FMS ) and its association with FMS symptoms .
This study aimed at assessing the effect of hypovitaminosis D on the symptoms and quality of life of patients with fibromyalgia.A total of 74 FMS patients with hypovitaminosis D were randomly assigned into group A ( Trazodone 25 mg at bedtime + vitamin D 50 000 IU weekly ) and group B ( Trazodone 25 mg at bedtime + placebo ) .
Serum vitamin D level , Widespread Pain Index ( WPI ) @ @ @ @ @ @ @ , Pittsburgh Sleep Quality Index ( PSQI ) , and Short Form Health Survey ( SF-36 ) were used at the beginning of the treatment and 4 and 8 weeks post treatment.Significant improvements were observed in WPI , FIQ , and PSQI scores in both groups .
Moreover , combination of vitamin D and Trazodone resulted in significant improvement of SF-36 scores compared to Trazodone therapy .
Improvement in pain-related indices including the WPI and the physical component score ( PCS ) fraction of SF-36 was more noticeable in vitamin D/Trazodone combination therapy.This @ @ @ @ @ @ @ significant therapeutic benefits in the management of FMS , especially in pain reduction of patients with fibromyalgia .
According to our results , a combination of vitamin D supplements and a conventional antidepressant , when given to vitamin D-deficient fibromyalgia patients , could significantly improve both physical and psychological symptoms .

Numerous studies have been conducted to evaluate the frequency of hypovitaminosis D in patients with fibromyalgia syndrome (FMS) and its association with FMS symptoms. This study aimed at assessing the effect of hypovitaminosis D on the symptoms and quality of life of patients with fibromyalgia.A total of 74 FMS patients with hypovitaminosis D were randomly assigned into group A (Trazodone 25 mg at bedtime + vitamin D 50 000 IU weekly) and group B (Trazodone 25 mg at bedtime + placebo). Serum vitamin D level, Widespread Pain Index (WPI), Fibromyalgia Impact Questionnaire (FIQ), Pittsburgh Sleep Quality Index (PSQI), and Short Form Health Survey (SF-36) were used at the beginning of the treatment and 4 and 8 weeks post treatment.Significant improvements were observed in WPI, FIQ, and PSQI scores in both groups. Moreover, combination of vitamin D and Trazodone resulted in significant improvement of SF-36 scores compared to Trazodone therapy. Improvement in pain-related indices including the WPI and the physical component score (PCS) fraction of SF-36 was more noticeable in vitamin D/Trazodone combination therapy.This study suggests that vitamin D supplementation has significant therapeutic benefits in the management of FMS, especially in pain reduction of patients with fibromyalgia. According to our results, a combination of vitamin D supplements and a conventional antidepressant, when given to vitamin D-deficient fibromyalgia patients, could significantly improve both physical and psychological symptoms.


greenmedinfo--2020-05-13--Low levels of serum vitamin D3 are associated with fibromyalgia syndrome in pre-menopausal women.

Objectives : This study aims to investigate the prevalence of fibromyalgia syndrome ( FMS ) among patients with low and adequate vitamin D levels in premenopausal women .
Patients and methods : Between October 2012 and April 2013 , a total of 80 premenopausal patients ( mean age 38.1±7.1 years ; range , 18 to 50 years ) with non-specific musculoskeletal symptoms were included in the study .
The determination of 25-hydroxyvitamin D3 ( 25 ( OH ) D3 ) deficiency was based on a reference value of 25 ng/mL .
Patients with deficient serum 25 ( OH ) D3 @ @ @ @ @ @ @ ) comprised the patient group , while those with adequate serum 25 ( OH ) D3 levels ( ≥25 ng/mL , n=40 ) comprised the control group .
Data including demographic characteristics , laboratory parameters ( i.e.
, calcium , phosphorus , alkaline phosphatase [ ALP ] , and parathyroid hormone [ PTH ] ) , and clinical findings ( i.e.
, proximal muscle weakness [ PMW ] and periarticular sensitivity [ PAS ] ) were recorded and compared between the groups .
Pain severity was evaluated using the visual analog scale ( @ @ @ @ @ @ @ using the Beck Depression Inventory ( BDI ) , and quality of life ( QoL ) was evaluated using the Short Form 36 ( SF-36 ) .
The diagnosis of FMS was made based onthe 2010 criteria of the American College of Rheumatology .
Results : Although there were no statistically significant differences in the demographic characteristics between the groups , ALP and PTH levels were higher in the patient group ( p < 0.05 ) .
The VAS , frequency of FMS , PMW , and PAS were also significantly higher in @ @ @ @ @ @ @ ) .
Depression and the mental and physical component scores of the SF-36 did not significantly differ between the two groups ( p < 0.05 ) .
Conclusion : Our study results suggest that patients with low 25 ( OH ) D3 levels may more frequently experience FMS and pain than healthy individuals .

Objectives: This study aims to investigate the prevalence of fibromyalgia syndrome (FMS) among patients with low and adequate vitamin D levels in premenopausal women.
Patients and methods: Between October 2012 and April 2013, a total of 80 premenopausal patients (mean age 38.1±7.1 years; range, 18 to 50 years) with non-specific musculoskeletal symptoms were included in the study. The determination of 25-hydroxyvitamin D3 (25(OH)D3) deficiency was based on a reference value of 25 ng/mL. Patients with deficient serum 25(OH)D3 levels (<25 ng/mL, n=40) comprised the patient group, while those with adequate serum 25(OH)D3 levels (≥25 ng/mL, n=40) comprised the control group. Data including demographic characteristics, laboratory parameters (i.e., calcium, phosphorus, alkaline phosphatase [ALP], and parathyroid hormone [PTH]), and clinical findings (i.e., proximal muscle weakness [PMW] and periarticular sensitivity [PAS]) were recorded and compared between the groups. Pain severity was evaluated using the visual analog scale (VAS), psychological status was evaluated using the Beck Depression Inventory (BDI), and quality of life (QoL) was evaluated using the Short Form 36 (SF-36). The diagnosis of FMS was made based onthe 2010 criteria of the American College of Rheumatology.
Results: Although there were no statistically significant differences in the demographic characteristics between the groups, ALP and PTH levels were higher in the patient group (p<0.05). The VAS, frequency of FMS, PMW, and PAS were also significantly higher in the patient group (p<0.05). Depression and the mental and physical component scores of the SF-36 did not significantly differ between the two groups (p<0.05).
Conclusion: Our study results suggest that patients with low 25(OH)D3 levels may more frequently experience FMS and pain than healthy individuals.


greenmedinfo--2020-05-13--Vitamin D supplementation can reduce negative emotions.

BACKGROUND : The several meta-analyses of the effect of vitamin D on depression have produced inconsistent results and studies dealing with anxiety were not incorporated .
There has been no comprehensive analysis of how results are affected by the nature of the sample or the dosage and duration of supplementation .
The study is aimed to investigate whether vitamin D supplementation reduces negative emotions and to analyze the possible influence of sample and regimen .
METHOD : We conducted a systematic review and meta-analysis of randomized controlled trials comparing the effect of vitamin D and placebo on negative emotion .
@ @ @ @ @ @ @ before February 2019 .
RESULTS : The analysis covered 25 trials with a total of 7,534 participants and revealed an effect of vitamin D on negative emotion ( Hedges ' g = -0.4990 , 95 % CI [ -0.8453 , -0.1528 ] , p = .0047 , I = 97.7 % ) .
Subgroup analysis showed that vitamin D had an effect on patients with major depressive disorder and on subjects with serum 25 ( OH ) D levels ≤50 nmol/L .
The pooled data from trials of vitamin D supplementation lasting ≥8 @ @ @ @ @ @ @ vitaminD had an effect .
CONCLUSIONS : Our results support the hypothesis that vitamin D supplementation can reduce negative emotions .
Patients with major depressive disorder and individuals with vitamin D deficiency are most likely to benefit from supplementation .
But to interpret the results with high heterogeneity should still be cautious .

BACKGROUND: The several meta-analyses of the effect of vitamin D on depression have produced inconsistent results and studies dealing with anxiety were not incorporated. There has been no comprehensive analysis of how results are affected by the nature of the sample or the dosage and duration of supplementation. The study is aimed to investigate whether vitamin D supplementation reduces negative emotions and to analyze the possible influence of sample and regimen.
METHOD: We conducted a systematic review and meta-analysis of randomized controlled trials comparing the effect of vitamin D and placebo on negative emotion. Databases were searched for relevant articles published before February 2019.
RESULTS: The analysis covered 25 trials with a total of 7,534 participants and revealed an effect of vitamin D on negative emotion (Hedges' g = -0.4990, 95% CI [-0.8453, -0.1528], p = .0047, I = 97.7%). Subgroup analysis showed that vitamin D had an effect on patients with major depressive disorder and on subjects with serum 25(OH)D levels ≤50 nmol/L. The pooled data from trials of vitamin D supplementation lasting ≥8 weeks and dosage ≤4,000 IU/day indicated that vitaminD had an effect.
CONCLUSIONS: Our results support the hypothesis that vitamin D supplementation can reduce negative emotions. Patients with major depressive disorder and individuals with vitamin D deficiency are most likely to benefit from supplementation. But to interpret the results with high heterogeneity should still be cautious.


greenmedinfo--2020-05-13--Vitamin D deficiency may be one of the causes of suicidal behaviour in adolescents.

BACKGROUND : Psychiatric disorders are the most common cause of suicide attempts .
Some studies have shown there is a relationship between low vitamin D levels and psychiatric disorders .
In this study , we examined the relationship between suicidal behavior and vitamin D levels in adolescents .
METHOD : This study included 215 patients who presented to the pediatric emergency department due to a suicide attempt ( patient group ) and 200 healthy individuals ( control group ) .
Demographic and clinical features of both groups were recorded , and serum vitamin D , calcium , and phosphorus levels @ @ @ @ @ @ @ in terms of these factors .
All data were analyzed using the SPSS 20.0 ( SPSS Inc. , Illinois , USA ) software program .
RESULTS : The mean vitamin D level was 19.4± 10 ng/mL in the control group and 12.3 ± 6 ng/mL in the patient group ( t = 8.8 and P = .01 ) .
The mean serum total calcium level was 9.9 ± 0.3 mg/dL in the control group and 9.4 ± 0.5 mg/dL in the patient group ( P CONCLUSIONS : Vitamin D deficiency , which is @ @ @ @ @ @ @ of the causes of suicidal behavior in adolescents .
Therefore , we believe that physicians who treat adolescents should consider vitamin D levels in routine examinations .

BACKGROUND: Psychiatric disorders are the most common cause of suicide attempts. Some studies have shown there is a relationship between low vitamin D levels and psychiatric disorders. In this study, we examined the relationship between suicidal behavior and vitamin D levels in adolescents.
METHOD: This study included 215 patients who presented to the pediatric emergency department due to a suicide attempt (patient group) and 200 healthy individuals (control group). Demographic and clinical features of both groups were recorded, and serum vitamin D, calcium, and phosphorus levels were measured. The groups were compared in terms of these factors. All data were analyzed using the SPSS 20.0 (SPSS Inc., Illinois, USA) software program.
RESULTS: The mean vitamin D level was 19.4± 10 ng/mL in the control group and 12.3 ± 6 ng/mL in the patient group (t = 8.8 and P = .01). The mean serum total calcium level was 9.9 ± 0.3 mg/dL in the control group and 9.4 ± 0.5 mg/dL in the patient group (P<.01).
CONCLUSIONS: Vitamin D deficiency, which is a treatable condition, may be one of the causes of suicidal behavior in adolescents. Therefore, we believe that physicians who treat adolescents should consider vitamin D levels in routine examinations.


greenmedinfo--2020-05-13--The association between low vitamin D levels and suicide attempts in adolescents.


greenmedinfo--2020-05-13--This study determines the positive efficacy of vitamin D supplementation for chronic liver disease.

BACKGROUND : Hepatic fibrosis ( HF ) is the common pathological basis of chronic liver disease ( CLD ) .
Many data indicate that serum vitamin D ( VD ) levels in patients with liver fibrosis are significantly lower than those without liver fibrosis , and lower level of serum 1,25 ( OH ) 2D3 is also an independent risk factor for patients with liver fibrosis combined with other diseases .
VD has the functions of anti-fibrosis , regulating cell proliferation and differentiation , anti-inflammatory , and immune regulation , Therefore , serum 1,25 ( OH ) 2D3 level may @ @ @ @ @ @ @ liver fibrosis .
But there is absent convincing evidence-based medicine to confirm the efficacy of VD supplementation for CLD .
Thus , we aimed to conduct this meta-analysis to summarize the efficacy of VD supplementation on the progression of fibrosis in patients with CLD .
METHODS : The study only selects clinical randomized controlled trials of VD supplementation for CLD .
We will search each database from the built-in until September 2020 .
The English literature mainly searches Cochrane Library , Pubmed , EMBASE , and Web of Science .
While the Chinese @ @ @ @ @ @ @ VIP , and Wangfang database .
Meanwhile , we will retrieve clinical trial registries and gray literature .
Two researchers worked independently on literature selection , data extraction and quality assessment .
The dichotomous data is represented by relative risk ( RR ) , and the continuous is expressed by mean difference ( MD ) or standard mean difference ( SMD ) , eventually the data is synthesized using a fixed effect model ( FEM ) or a random effect model ( REM ) depending on the heterogeneity .
The serum VD level @ @ @ @ @ @ @ hepatic fibrosis were evaluated as the main outcomes .
While several secondary outcomes were also evaluated in this study .
The statistical analysis of this Meta-analysis was conducted by RevMan software version 5.3 .
RESULTS : This meta-analysis will further determine the beneficial efficacy of VD supplementation on the progression of fibrosis in patients with CLD .
CONCLUSION : This study determines the positive efficacy of VD supplementation for CLD .
ETHICS AND DISSEMINATION : This review is based solely on a secondary study of published literatures and does not require ethics committee @ @ @ @ @ @ @ in conference papers , magazines or peer-reviewed journals .

BACKGROUND: Hepatic fibrosis (HF) is the common pathological basis of chronic liver disease (CLD). Many data indicate that serum vitamin D (VD) levels in patients with liver fibrosis are significantly lower than those without liver fibrosis, and lower level of serum 1,25(OH)2D3 is also an independent risk factor for patients with liver fibrosis combined with other diseases. VD has the functions of anti-fibrosis, regulating cell proliferation and differentiation, anti-inflammatory, and immune regulation, Therefore, serum 1,25(OH)2D3 level may be negatively correlated with the progression of liver fibrosis. But there is absent convincing evidence-based medicine to confirm the efficacy of VD supplementation for CLD. Thus, we aimed to conduct this meta-analysis to summarize the efficacy of VD supplementation on the progression of fibrosis in patients with CLD.
METHODS: The study only selects clinical randomized controlled trials of VD supplementation for CLD. We will search each database from the built-in until September 2020. The English literature mainly searches Cochrane Library, Pubmed, EMBASE, and Web of Science. While the Chinese literature comes from CNKI, CBM, VIP, and Wangfang database. Meanwhile, we will retrieve clinical trial registries and gray literature. Two researchers worked independently on literature selection, data extraction and quality assessment. The dichotomous data is represented by relative risk (RR), and the continuous is expressed by mean difference (MD) or standard mean difference (SMD), eventually the data is synthesized using a fixed effect model (FEM) or a random effect model (REM) depending on the heterogeneity. The serum VD level, hepatic function and serological indexes of hepatic fibrosis were evaluated as the main outcomes. While several secondary outcomes were also evaluated in this study. The statistical analysis of this Meta-analysis was conducted by RevMan software version 5.3.
RESULTS: This meta-analysis will further determine the beneficial efficacy of VD supplementation on the progression of fibrosis in patients with CLD.
CONCLUSION: This study determines the positive efficacy of VD supplementation for CLD.
ETHICS AND DISSEMINATION: This review is based solely on a secondary study of published literatures and does not require ethics committee approval. Its conclusion will be disseminated in conference papers, magazines or peer-reviewed journals.
REGISTRATION NUMBER: INPLASY202040054.


greenmedinfo--2020-05-13--Vitamin D therapy in adults with inflammatory bowel disease.

BACKGROUND : Vitamin D deficiency has been implicated in the pathogenesis of inflammatory bowel disease .
Emerging literature suggests that optimization of vitamin D levels may be associated with improvements in disease activity and quality of life .
We conducted a meta-analysis exploring the effect of vitamin D on serum 25-hydroxyvitamin D ( s-25 [ OH ] D ) levels , clinical improvement , and biomarkers .
METHODS : MEDLINE , EMBASE , the Cochrane Library , and sources for grey literature were searched from inception until September 2019 .
The primary outcome was s-25 ( OH ) D mean @ @ @ @ @ @ @ 2 test and the I2 statistic .
Review Manager software v. 5.3 was used .
RESULTS : Twelve randomized controlled trials ( n = 611 ) and 4 observational studies ( n = 359 ) were included in the meta-analysis .
On average , in the randomized controlled trials , vitamin D supplementation increased s-25 ( OH ) D levels by 15.50 ng/mL ( 95 % confidence interval [ CI ] , 11.08-19.92 , P≤ 0.00001 , I2 = 90 % ) and in observational studies they increased by 18.39 ng/mL ( 95 @ @ @ @ @ @ @ 0.0001 , I2 = 82 % ) .
Subgroup analyses between vitamin D and placebo groups revealed that vitamin D increased s-25 ( OH ) D by 14.85 ng/mL ( 95 % CI , 9.96-19.73 , P ≤ 0.00001 , I2 = 90 % ) and when highdoses of vitamin D were compared with low doses , high doses increased s-25 ( OH ) D by 18.27 ng/mL ( 95 % CI , 5.44-31.10 , P = 0.005 , I2 = 90 % ) .
The Harvey Bradshaw Index improved by -1.47 points @ @ @ @ @ @ @ -0.47 , P = 0.004 , I2 = 0 % ) and the high-sensitivity C-reactive protein decreased by -1.58 mg/L ( 95 % CI , -2.95 to -0.21 , P = 0.02 , I2 = 0 % ) .
CONCLUSIONS : Vitamin D supplementation in patients with IBD and vitamin D deficiency is effective at correcting vitamin D levels and is associated with improvement in clinical and biochemical disease activity scores .

BACKGROUND: Vitamin D deficiency has been implicated in the pathogenesis of inflammatory bowel disease. Emerging literature suggests that optimization of vitamin D levels may be associated with improvements in disease activity and quality of life. We conducted a meta-analysis exploring the effect of vitamin D on serum 25-hydroxyvitamin D (s-25[OH]D) levels, clinical improvement, and biomarkers.
METHODS: MEDLINE, EMBASE, the Cochrane Library, and sources for grey literature were searched from inception until September 2019. The primary outcome was s-25(OH)D mean differences. Heterogeneity was assessed using theχ 2 test and the I2 statistic. Review Manager software v. 5.3 was used.
RESULTS: Twelve randomized controlled trials (n = 611) and 4 observational studies (n = 359) were included in the meta-analysis. On average, in the randomized controlled trials, vitamin D supplementation increased s-25(OH)D levels by 15.50 ng/mL (95% confidence interval [CI], 11.08-19.92, P≤ 0.00001, I2 = 90%) and in observational studies they increased by 18.39 ng/mL (95% CI, 8.91-27.88, P = 0.0001, I2 = 82%). Subgroup analyses between vitamin D and placebo groups revealed that vitamin D increased s-25(OH)D by 14.85 ng/mL (95% CI, 9.96-19.73, P ≤ 0.00001, I2 = 90%) and when highdoses of vitamin D were compared with low doses, high doses increased s-25(OH)D by 18.27 ng/mL (95% CI, 5.44-31.10, P = 0.005, I2 = 90%). The Harvey Bradshaw Index improved by -1.47 points (95% CI, -2.47 to -0.47, P = 0.004, I2 = 0%) and the high-sensitivity C-reactive protein decreased by -1.58 mg/L (95% CI, -2.95 to -0.21, P = 0.02, I2 = 0%).
CONCLUSIONS: Vitamin D supplementation in patients with IBD and vitamin D deficiency is effective at correcting vitamin D levels and is associated with improvement in clinical and biochemical disease activity scores.


greenmedinfo--2020-05-13--Vitamin D deficiency was associated with a smaller brain tissue volume and hippocampus volume.

BACKGROUND & AIM : Vitamin D deficiency has been linked to an increased risk of dementia .
To strengthen this evidence and establish whether vitamin D can indeed play a role in early prevention of neurodegeneration , knowledge on underlying pathways is crucial .
Therefore , we aimed to investigate the association of vitamin D status with brain tissue volumes , hippocampus volume , white matter integrity , and markers of cerebral small vessel disease ( CSVD ) in a dementia-free population .
METHODS : In this cross-sectional analysis , 2,716 participants free of dementia from the population-based Rotterdam Study @ @ @ @ @ @ @ concentration assessment and brain magnetic resonance imaging ( MRI ) scanning between 2006 and 2009 .
Outcomes of interest included brain tissue volume ( total , white matter , grey matter and hippocampus volume ) , white matter integrity ( fractional anisotropy ( FA ) and mean diffusivity ( MD ) ) , and markers of CSVD ( white matter hyper intensity ( WMH ) volume , presence of lacunes and microbleeds ) .
Associations between vitamin D status , both in categories and continuous , and these brain measurements were assessed using @ @ @ @ @ @ @ adjusting for lifestyle and other disease risk factors .
CONCLUSIONS : In this dementia-free population , vitamin D deficiency was associated with a smaller brain tissue volume and hippocampus volume .
More research , in particular with a longitudinal design , is needed to further elucidate the role of vitamin D in neurodegeneration .

BACKGROUND & AIM: Vitamin D deficiency has been linked to an increased risk of dementia. To strengthen this evidence and establish whether vitamin D can indeed play a role in early prevention of neurodegeneration, knowledge on underlying pathways is crucial. Therefore, we aimed to investigate the association of vitamin D status with brain tissue volumes, hippocampus volume, white matter integrity, and markers of cerebral small vessel disease (CSVD) in a dementia-free population.
METHODS: In this cross-sectional analysis, 2,716 participants free of dementia from the population-based Rotterdam Study underwent serum 25(OH)D concentration assessment and brain magnetic resonance imaging (MRI) scanning between 2006 and 2009. Outcomes of interest included brain tissue volume (total, white matter, grey matter and hippocampus volume), white matter integrity (fractional anisotropy (FA) and mean diffusivity (MD)), and markers of CSVD (white matter hyper intensity (WMH) volume, presence of lacunes and microbleeds). Associations between vitamin D status, both in categories and continuous, and these brain measurements were assessed using multivariable linear and logistic regression models, adjusting for lifestyle and other disease risk factors.
RESULTS: We observed that vitamin D deficiency (25(OH)D < 30 nmol/L) was independently associated with smaller brain tissue volume, smaller white matter volume and smaller hippocampus volume as compared to a sufficient vitamin D status (≥50 nmol/L). Vitamin D per 10 nmol/L increment and an insufficient (30-50 nmol/L) as compared to sufficient vitamin D status were not associated with the brain measures of interest. Moreover, vitamin D status was not associated with grey matter volume, white matter integrity or CSVD markers.
CONCLUSIONS: In this dementia-free population, vitamin D deficiency was associated with a smaller brain tissue volume and hippocampus volume. More research, in particular with a longitudinal design, is needed to further elucidate the role of vitamin D in neurodegeneration.


greenmedinfo--2020-05-13--Findings suggest that high magnesium intake alone may improve cognitive function in older adults.

PURPOSE : Reduced cognitive function associated with aging has gained increasing attention as the US population ages .
Magnesium plays a critical role in vitamin D biosynthesis and metabolism ; and deficiencies in magnesium and vitamin D show associations with poor cognition .
However , no study has examined their interaction .
This study aimed to evaluate the associations of magnesium intake and serum 25-hydroxyvitamin D ( 25 ( OH ) D ) concentrations , indicating vitamin D status , with cognition , and interaction between these nutrients in older adults .
METHODS : Based on the National Health and @ @ @ @ @ @ @ the study included 2466 participants aged ≥ 60 years who completed the Digit Symbol Substitution Test ( DSST ) and had data available on serum 25 ( OH ) D and magnesium intake .
Cognitive impairment was defined as a DSST score lower than the lowest quartile .
Serum 25 ( OH ) D concentrations were measured by HPLC-tandem mass spectrometry .
RESULTS : Higher total magnesium intake was independently associated with higher DSST scores ( highest quartile vs lowest : β = 4.34 , 95 % CI 1.14-7.54 ) .
The association @ @ @ @ @ @ @ score was primarily observed among women , non-Hispanic whites , physically active participants and those with sufficient vitamin D status , although the interactions were not significant .
The odds of cognitive impairment was reduced with increasing intake of total magnesium ( p trend CONCLUSIONS : Findings suggest that high magnesium intake alone may improve cognitive function in older adults , and the association may be stronger among subjects with sufficient vitamin D status .
Further studies are needed to confirm these findings .

PURPOSE: Reduced cognitive function associated with aging has gained increasing attention as the US population ages. Magnesium plays a critical role in vitamin D biosynthesis and metabolism; and deficiencies in magnesium and vitamin D show associations with poor cognition. However, no study has examined their interaction. This study aimed to evaluate the associations of magnesium intake and serum 25-hydroxyvitamin D (25(OH)D) concentrations, indicating vitamin D status, with cognition, and interaction between these nutrients in older adults.
METHODS: Based on the National Health and Nutrition Survey (NHANES) 2011-2014, the study included 2466 participants aged ≥ 60 years who completed the Digit Symbol Substitution Test (DSST) and had data available on serum 25(OH)D and magnesium intake. Cognitive impairment was defined as a DSST score lower than the lowest quartile. Serum 25(OH)D concentrations were measured by HPLC-tandem mass spectrometry.
RESULTS: Higher total magnesium intake was independently associated with higher DSST scores (highest quartile vs lowest:β = 4.34, 95% CI 1.14-7.54). The association of total magnesium intake with high DSST score was primarily observed among women, non-Hispanic whites, physically active participants and those with sufficient vitamin D status, although the interactions were not significant. The odds of cognitive impairment was reduced with increasing intake of total magnesium (p trend < 0.01) and higher level of serum 25(OH)D (p trend = 0.05).
CONCLUSIONS: Findings suggest that high magnesium intake alone may improve cognitive function in older adults, and the association may be stronger among subjects with sufficient vitamin D status. Further studies are needed to confirm these findings.


greenmedinfo--2020-05-13--Deficient vitamin D levels were significantly associated with the risk of suicidal ideation.

OBJECTIVES : Vitamin D deficiency has been reported to be associated with various neuropsychiatric disorders .
However , there are few studies addressing deficient vitamin D levels and suicidal ideation .
METHODS : Serum vitamin D of 157,211 Korean adult participants were measured using electrochemiluminescence immunoassay .
A self-reported questionnaire was used to assess whether participants experienced suicidal ideation .
Logistic regression model was used to estimate the odds ratio ( OR ) of suicidal ideation according to vitamin D levels .
The regression was adjusted for a range of covariates .
RESULTS : Compared with sufficient vitamin D levels @ @ @ @ @ @ @ D levels ( < 10 ng/mL ) were significantly associated with the risk of suicidal ideation ( OR = 1.138 , 95 % Cl = 1.027-1.262 ) .
However , the OR of suicidal ideation was not significantly different between the vitamin D insufficient group ( 10-19.99 ng/mL ) and sufficient group ( ≥20 ng/mL ) ( OR = 0.988 , 95 % Cl = 0.932-1.047 ) .
CONCLUSION : Deficient vitamin D levels were significantly associated with the risk of suicidal ideation .
However , the risk of suicidal ideation was not @ @ @ @ @ @ @ group and sufficient group .

OBJECTIVES: Vitamin D deficiency has been reported to be associated with various neuropsychiatric disorders. However, there are few studies addressing deficient vitamin D levels and suicidal ideation.
METHODS: Serum vitamin D of 157,211 Korean adult participants were measured using electrochemiluminescence immunoassay. A self-reported questionnaire was used to assess whether participants experienced suicidal ideation. Logistic regression model was used to estimate the odds ratio (OR) of suicidal ideation according to vitamin D levels. The regression was adjusted for a range of covariates.
RESULTS: Compared with sufficient vitamin D levels (≥20 ng/mL), deficient vitamin D levels (<10 ng/mL) were significantly associated with the risk of suicidal ideation (OR = 1.138, 95% Cl = 1.027-1.262). However, the OR of suicidal ideation was not significantly different between the vitamin D insufficient group (10-19.99 ng/mL) and sufficient group (≥20 ng/mL) (OR = 0.988, 95% Cl = 0.932-1.047).
CONCLUSION: Deficient vitamin D levels were significantly associated with the risk of suicidal ideation. However, the risk of suicidal ideation was not significantly different between the vitamin D insufficient group and sufficient group.


greenmedinfo--2020-05-13--Association of 25-hydroxy vitamin D with asthma and its severity in children.

Background : Universally , asthma has high prevalence rates and this has led numerous studies done into its causes .
Despite extensive study on asthma the association between 25-Hydroxy Vitamin D ( 25 ( OH ) vit .
D ) and asthma remains uncertain .
In this study , the associations of 25 ( OH ) vit .
D levels with asthma and with the severity of asthma were evaluated .
Methods : This was a case-control study performed in 2015 in the city of Isfahan .
In this study 520 children were studied .
Children with asthma were classified @ @ @ @ @ @ @ for reasons other than respiratory problems and asthma were considered as controls .
Serum 25 ( OH ) vit .
D levels were then examined and compared between the two groups .
Differences among groups were stated to be statistically significant when-values Results : There were 260 asthmatic children and 260 controls in the present study .
The mean 25 ( OH ) vit .
D levels in the case group was 25.5 ± 16.62 and 16.76 ± 31.40 the control group and this difference was statistically significant ( P Conclusions : As @ @ @ @ @ @ @ the lower level of 25 ( OH ) vit .
D correlated with the higher severity of asthma manifestations .
Therefore , it is recommended that 25 ( OH ) vit .
D levels get routinely checked especially in severe asthma cases and if the deficiency presents , appropriate therapeutic measures be used to reduce the asthma severity .

Background: Universally, asthma has high prevalence rates and this has led numerous studies done into its causes. Despite extensive study on asthma the association between 25-Hydroxy Vitamin D (25(OH) vit. D) and asthma remains uncertain. In this study, the associations of 25(OH) vit. D levels with asthma and with the severity of asthma were evaluated.
Methods: This was a case-control study performed in 2015 in the city of Isfahan. In this study 520 children were studied. Children with asthma were classified as cases and children who were referred for reasons other than respiratory problems and asthma were considered as controls. Serum 25 (OH) vit. D levels were then examined and compared between the two groups. Differences among groups were stated to be statistically significant when-values < 0.05.
Results: There were 260 asthmatic children and 260 controls in the present study. The mean 25 (OH) vit. D levels in the case group was 25.5 ± 16.62 and 16.76 ± 31.40 the control group and this difference was statistically significant (P < 0.05). 25(OH) vit. D levels were found to be 28.05 ± 16.98 in non-severe asthma and 21.41 ± 15.20 in severe asthma. Consequently 25(OH) vit. D level had inverse relationship with asthma severity (P = 0.002).
Conclusions: As the results of this study showed, the lower level of 25(OH) vit. D correlated with the higher severity of asthma manifestations. Therefore, it is recommended that 25(OH) vit. D levels get routinely checked especially in severe asthma cases and if the deficiency presents, appropriate therapeutic measures be used to reduce the asthma severity.


greenmedinfo--2020-05-13--Combining vitamin D plus high-fiber intake would help reduce the prevalence of diabetes.

Vitamin D and fiber intake are nutritional factors that could affect the development of type 2 diabetes ( T2D ) , potentially by reducing insulin resistance .
Therefore , we hypothesized that the influence of vitamin D on T2D might depend on fiber intake .
This study investigated the association between vitamin D status and T2D according to fiber intake .
The present study analyzed data from 9,656 American adults ( ≥20 years old ) who participated in the National Health and Nutrition Examination Survey ( NHANES ) 2007-2010 .
The serum concentration of 25-hydroxyvitamin D [ 25 ( OH @ @ @ @ @ @ @ biomarker for vitamin D status .
The T2D classification was based on two criteria : T2Dwas identified using only self-reported questionnaire data and T2Dwas identified based on both survey and laboratory data .
The deficient vitamin D status ( < 50 nmol/L ) was used as the reference group .
After controlling for sociodemographic , behavioral , and dietary factors , the odds ratios ( ORs ) were 0.72 ( 95 % confidence interval [ CI ] : 0.58 , 0.90 ) for T2Dand 0.60 ( 0.50 , 0.80 ) for T2Din the @ @ @ @ @ @ @ ) .
Furthermore , the total vitamin D concentration exhibited dose-dependent associations with lower OR values for T2D ( for trend = .005 ) and T2D ( for trend

Vitamin D and fiber intake are nutritional factors that could affect the development of type 2 diabetes (T2D), potentially by reducing insulin resistance. Therefore, we hypothesized that the influence of vitamin D on T2D might depend on fiber intake. This study investigated the association between vitamin D status and T2D according to fiber intake. The present study analyzed data from 9,656 American adults (≥20 years old) who participated in the National Health and Nutrition Examination Survey (NHANES) 2007-2010. The serum concentration of 25-hydroxyvitamin D [25(OH)D] was used as a biomarker for vitamin D status. The T2D classification was based on two criteria: T2Dwas identified using only self-reported questionnaire data and T2Dwas identified based on both survey and laboratory data. The deficient vitamin D status (<50 nmol/L) was used as the reference group. After controlling for sociodemographic, behavioral, and dietary factors, the odds ratios (ORs) were 0.72 (95% confidence interval [CI]: 0.58, 0.90) for T2Dand 0.60 (0.50, 0.80) for T2Din the sufficient vitamin D status (≥75 nmol/L). Furthermore, the total vitamin D concentration exhibited dose-dependent associations with lower OR values for T2D(for trend = .005) and T2D(for trend<.001). Among participants with high-fiber intake, the OR values for T2Dwere 0.60 (95% CI: 0.42, 0.90) at suboptimal vitamin D status and 0.49 (95% CI: 0.31, 0.77) at sufficient vitamin D status. Moreover, the significant dose-dependent association persisted in the high-fiber-intake subgroup (for trend = .004). Therefore, combining vitamin D plus high-fiber intake would help reduce the prevalence of diabetes, although the interaction analysis results were not statistically significant.


greenmedinfo--2020-05-13--Vitamin D supplementation rescues aberrant NF-κB pathway activation and partially ameliorates Rett s

Vitamin D supplementation rescues aberrant NF-κB pathway activation and partially ameliorates Rett syndrome phenotypes in Mecp2 mutant mice.

Rett syndrome ( RTT ) is a severe , progressive X-linked neurodevelopmental disorder caused by mutations in the transcriptional regulatorWe previously identified aberrant NF-κB pathway up-regulation in brains of-null mice and demonstrated that genetically attenuating NF-κB rescues some characteristic neuronal RTT phenotypes .
These results raised the intriguing question of whether NF-κB pathway inhibitors might provide a therapeutic avenue in RTT .
Here , we investigate whether the known NF-κB pathway inhibitor vitamin D ameliorates neuronal phenotypes in-mutant mice .
Vitamin D deficiency is prevalent among RTT patients , and we find that-null mice similarly have significantly reduced 25 ( @ @ @ @ @ @ @ wildtype littermates .
We identify that vitamin D rescues aberrant NF-κB pathway activation and reduced neurite outgrowth ofknockdown cortical neuronsFurther , dietary supplementation with vitamin D in early symptomatic malehemizygous null and femaleheterozygous mice ameliorates reduced neocortical dendritic morphology and soma size phenotypes , and modestly improves reduced lifespan of-nulls .
These results elucidate fundamental neurobiology of RTT and provide foundation that NF-κB pathway inhibition might be a therapeutic target for RTT.There is currently no effective treatment for Rett syndrome ( RTT ) ; however , selectively re-expressingin adult mice has shown that @ @ @ @ @ @ @ suggesting that restoration of homeostasis of downstream targets of MeCP2 could also reverse or alleviate RTT symptoms .
One such potential target is the NF-κB pathway , which is aberrantly up-regulated in the brain of-mutant mice .
Genetically reducing NF-κB signaling in these mice improves neuronal phenotypes .
Here , we identify that the known NF-κB inhibitor vitamin D reduces the aberrant NF-κB signaling inknockdown neurons , and partially ameliorates neuronal size and complexity phenotypes in both male and female-mutant mice .
Thus , this simple , cost-effective dietary supplement could contribute toward @ @ @ @ @ @ @

Rett syndrome (RTT) is a severe, progressive X-linked neurodevelopmental disorder caused by mutations in the transcriptional regulatorWe previously identified aberrant NF-κB pathway up-regulation in brains of-null mice and demonstrated that genetically attenuating NF-κB rescues some characteristic neuronal RTT phenotypes. These results raised the intriguing question of whether NF-κB pathway inhibitors might provide a therapeutic avenue in RTT. Here, we investigate whether the known NF-κB pathway inhibitor vitamin D ameliorates neuronal phenotypes in-mutant mice. Vitamin D deficiency is prevalent among RTT patients, and we find that-null mice similarly have significantly reduced 25(OH)D serum levels compared to wildtype littermates. We identify that vitamin D rescues aberrant NF-κB pathway activation and reduced neurite outgrowth ofknockdown cortical neuronsFurther, dietary supplementation with vitamin D in early symptomatic malehemizygous null and femaleheterozygous mice ameliorates reduced neocortical dendritic morphology and soma size phenotypes, and modestly improves reduced lifespan of-nulls. These results elucidate fundamental neurobiology of RTT and provide foundation that NF-κB pathway inhibition might be a therapeutic target for RTT.There is currently no effective treatment for Rett syndrome (RTT); however, selectively re-expressingin adult mice has shown that RTT symptoms can be partially reversed, suggesting that restoration of homeostasis of downstream targets of MeCP2 could also reverse or alleviate RTT symptoms. One such potential target is the NF-κB pathway, which is aberrantly up-regulated in the brain of-mutant mice. Genetically reducing NF-κB signaling in these mice improves neuronal phenotypes. Here, we identify that the known NF-κB inhibitor vitamin D reduces the aberrant NF-κB signaling inknockdown neurons, and partially ameliorates neuronal size and complexity phenotypes in both male and female-mutant mice. Thus, this simple, cost-effective dietary supplement could contribute toward a partial therapeutic avenue in RTT.


greenmedinfo--2020-05-13--Assessment of cognitive impairment and its correlation with vitamin D levels patients on maintenance

Assessment of cognitive impairment and its correlation with vitamin D levels patients on maintenance hemodialysis.

Cognitive impairment ( CI ) is common in patients with chronic kidney disease , and its prevalence increases in patients @ @ @ @ @ .
Different factors were identified to be the cause of cognitive dysfunction , of which @ @ @ @ @ known to have pleiotropic effects , has been implicated for the neurocognitive decline of functions @ @ @ @ @ of cognitive dysfunction in patients on HD in our center and also studied the deficiency @ @ @ @ @ .

Cognitive impairment (CI) is common in patients with chronic kidney disease, and its prevalence increases in patients on hemodialysis (HD). Different factors were identified to be the cause of cognitive dysfunction, of which Vitamin D, which is known to have pleiotropic effects, has been implicated for the neurocognitive decline of functions. We assessed the prevalence of cognitive dysfunction in patients on HD in our center and also studied the deficiency of Vitamin D on CI.


greenmedinfo--2020-05-14--Rosmarinic acid alleviates ethanol-induced lipid accumulation by repressing fatty acid biosynthesis.

Recent studies have demonstrated that rosmarinic acid is a valuable natural product for treatment of alcoholic liver disease .
However , the mechanisms whereby rosmarinic acid improves alcoholic liver disease remain unclear .
Here we performed experiments using a non-transformed mouse hepatocyte cell line ( AML12 ) .
Oil-red O staining demonstrated that rosmarinic acid reduced ethanol-induced lipid accumulation .
It was shown that rosmarinic acid prevented ethanol-induced elevation of the malondialdehyde level .
We also found that rosmarinic acid inhibited ethanol-induced mRNA expression of tumor necrosis factor-α and interleukin 6 .
Metabolomics analysis revealed that rosmarinic acid ameliorated ethanol-induced @ @ @ @ @ @ @ In addition , palmitic acid was a candidate biomarker in cells exposed to ethanol or ethanol plus rosmarinic acid .
Rosmarinic acid prevented the ethanol-induced increase in sorbitol that is a component of the polyol pathway .
Moreover , we confirmed that rosmarinic acid attenuated ethanol-induced mRNA expression of fatty acid synthase , probably by modulating the AMPK/SREBP-1c pathway .
Furthermore , rosmarinic acid prevented the ethanol-induced decrease ineight metabolites that are involved in mitochondrial metabolism , including glycine and succinic acid which are the components of carnitine synthesis .
These results provide @ @ @ @ @ @ @ of rosmarinic acid in alleviating ethanol-induced injury .

Recent studies have demonstrated that rosmarinic acid is a valuable natural product for treatment of alcoholic liver disease. However, the mechanisms whereby rosmarinic acid improves alcoholic liver disease remain unclear. Here we performed experiments using a non-transformed mouse hepatocyte cell line (AML12). Oil-red O staining demonstrated that rosmarinic acid reduced ethanol-induced lipid accumulation. It was shown that rosmarinic acid prevented ethanol-induced elevation of the malondialdehyde level. We also found that rosmarinic acid inhibited ethanol-induced mRNA expression of tumor necrosis factor-α and interleukin 6. Metabolomics analysis revealed that rosmarinic acid ameliorated ethanol-induced fatty acid biosynthesis in the cytoplasm. In addition, palmitic acid was a candidate biomarker in cells exposed to ethanol or ethanol plus rosmarinic acid. Rosmarinic acid prevented the ethanol-induced increase in sorbitol that is a component of the polyol pathway. Moreover, we confirmed that rosmarinic acid attenuated ethanol-induced mRNA expression of fatty acid synthase, probably by modulating the AMPK/SREBP-1c pathway. Furthermore, rosmarinic acid prevented the ethanol-induced decrease ineight metabolites that are involved in mitochondrial metabolism, including glycine and succinic acid which are the components of carnitine synthesis. These results provide a crucial insight into the molecular mechanism of rosmarinic acid in alleviating ethanol-induced injury.


greenmedinfo--2020-05-14--A review of the anti-inflammatory effects of rosmarinic acid on inflammatory diseases.

Inflammatory diseases are caused by abnormal immune responses and are characterized by an imbalance of inflammatory mediators and cells .
@ @ @ @ @ anti-inflammatory activity of natural products has attracted wide attention .
Rosmarinic acid ( RosA ) @ @ @ @ @ that is an ester of caffeic acid and 3 , 4-dihydroxyphenyl lactic acid .
It @ @ @ @ @ , like those of the Boraginaceae and Lamiaceae families .
RosA has a wide range @ @ @ @ @ anti-oxidative , anti-apoptotic , anti-tumorigenic , and anti-inflammatory effects .
The anti-inflammatory effects of RosA @ @ @ @ @ various inflammatory diseases like arthritis , colitis , and atopic dermatitis .
This article mainly @ @ @ @ @ RosA on inflammatory diseases and depicts a small amount of clinical research data .
The @ @ @ @ @ to discuss the anti-inflammatory effects of RosA in inflammatory diseases and its underlying mechanism .

Inflammatory diseases are caused by abnormal immune responses and are characterized by an imbalance of inflammatory mediators and cells. In recent years, the anti-inflammatory activity of natural products has attracted wide attention. Rosmarinic acid (RosA) is a water-soluble phenolic compound that is an ester of caffeic acid and 3, 4-dihydroxyphenyl lactic acid. It is discovered in many plants, like those of the Boraginaceae and Lamiaceae families. RosA has a wide range of pharmacological effects, including anti-oxidative, anti-apoptotic, anti-tumorigenic, and anti-inflammatory effects. The anti-inflammatory effects of RosA have been revealed throughandstudies of various inflammatory diseases like arthritis, colitis, and atopic dermatitis. This article mainly describes the preclinical research of RosA on inflammatory diseases and depicts a small amount of clinical research data. The purpose of this review is to discuss the anti-inflammatory effects of RosA in inflammatory diseases and its underlying mechanism.


greenmedinfo--2020-05-14--Nephroprotective effect of green tea, rosmarinic acid and rosemary on N-diethylnitrosamine initiated

Nephroprotective effect of green tea, rosmarinic acid and rosemary on N-diethylnitrosamine initiated and ferric nitrilotriacetate promoted acute renal toxicity.

The present study was designed to investigate the chemoprotective effect of green tea extract ( GTE ) , rosmarinic acid ( RA ) and rosemary extract ( RE ) against diethylnitrosamine ( DEN ) initiated and ferric nitrilotriacetate ( Fe-NTA ) promoted nephrotoxicity in rats .
Forty male rats were categorized into five : Group I included healthy rats , group II received DEN+Fe-NTA , group III received 200 mg/kg b.wt .
of RE+DEN+Fe-NTA , group IV received 1 g/kg b.wt .
of GTE+DEN+Fe-NTA and group V received 50 mg/kg b.wt .
of RA+DEN+Fe-NTA .
RE , GTE , RA @ @ @ @ @ @ @ single intraperitoneal administration of DEN ( 160 mg/kg ) till the end of the experiment .
Eighteen days after DEN , a single intraperitoneal dose of Fe-NTA ( 5 mg Fe/kg ) was administrated to rats to promote nephrotoxicity .
The biochemical parameters were analyzed in serum at time intervals while the malondialdehyde ( MDA ) and tumor necrosis factor-alpha ( TNF-α ) were assessed in both serum and renal tissues .
Kidney from each group was histopathologically examined at time intervals .
The administration of Fe-NTA after DEN dose to albino rats @ @ @ @ @ @ @ by a highly significant elevation of serum urea , creatinine , uric acid ( =0.000 ) , serum and renal MDA and TNF-α ( =0.000 ) with vacuolation of epithelial lining renal tubules .
The administration of RE , GTE and RA prior to DEN+Fe-NTA treatment significantly ameliorated the observed increased levels of the above mentioned parameters .
GTE , RA & RE exerted a protective effect against renal toxicity with GTE showing a more pronounced effect on renal function parameters while RA showed the best antioxidant impact .

The present study was designed to investigate the chemoprotective effect of green tea extract (GTE), rosmarinic acid (RA) and rosemary extract (RE) against diethylnitrosamine (DEN) initiated and ferric nitrilotriacetate (Fe-NTA) promoted nephrotoxicity in rats. Forty male rats were categorized into five: Group I included healthy rats, group II received DEN+Fe-NTA, group III received 200 mg/kg b.wt. of RE+DEN+Fe-NTA, group IV received 1 g/kg b.wt. of GTE+DEN+Fe-NTA and group V received 50 mg/kg b.wt. of RA+DEN+Fe-NTA. RE, GTE, RA were given orally for 14 days before single intraperitoneal administration of DEN (160 mg/kg) till the end of the experiment. Eighteen days after DEN, a single intraperitoneal dose of Fe-NTA (5 mg Fe/kg) was administrated to rats to promote nephrotoxicity. The biochemical parameters were analyzed in serum at time intervals while the malondialdehyde (MDA) and tumor necrosis factor-alpha (TNF-α) were assessed in both serum and renal tissues. Kidney from each group was histopathologically examined at time intervals. The administration of Fe-NTA after DEN dose to albino rats resulted in acute nephrotoxicity which was characterized by a highly significant elevation of serum urea, creatinine, uric acid (=0.000), serum and renal MDA and TNF-α (=0.000) with vacuolation of epithelial lining renal tubules. The administration of RE, GTE and RA prior to DEN+Fe-NTA treatment significantly ameliorated the observed increased levels of the above mentioned parameters. GTE, RA&RE exerted a protective effect against renal toxicity with GTE showing a more pronounced effect on renal function parameters while RA showed the best antioxidant impact.


greenmedinfo--2020-05-14--Rosmarinic acid exerts a neuroprotective effect on spinal cord injury.

Spinal cord injury ( SCI ) is a severe central nervous system injury for which few efficacious drugs are available .
Rosmarinic acid ( RA ) , a water-soluble polyphenolic phytochemical , has antioxidant , anti-inflammatory , and anti-apoptotic properties .
However , the effect of RA on SCI is unclear .
We investigated the therapeutic effect and underlying mechanism of RA on SCI .
Using a rat model of SCI , we showed that RA improved locomotor recovery after SCI and significantly mitigated neurological deficit , increased neuronal preservation , and reduced apoptosis .
Also , RA inhibited activation @ @ @ @ @ @ @ , IL-6 , and IL-1β and MDA .
Moreover , proteomics analyses identified the Nrf2 and NF-κB pathways as targets of RA .
Pretreatment with RA increased levels of Nrf2 and HO-1 and reduced those of TLR4 and MyD88 as well as phosphorylation of IκB and subsequent nuclear translocation of NF-κB-p65 .
Using HO- and LPS-induced PC12 cells , we found that RA ameliorated the HO-induced decrease in viability and increase in apoptosis and oxidative injury by activating the Nrf2/HO-1 pathway .
Also , LPS-induced cytotoxicity and increased apoptosis and inflammatory injury in @ @ @ @ @ @ @ inhibiting the TLR4/NF-κB pathway .
The Nrf2 inhibitor ML385 weakened the effect of RA on oxidant stress , inflammation and apoptosis in SCI rats , and significantly increased the nuclear translocation of NF-κB .
Therefore , the neuroprotective effect on SCI of RA may be due to its antioxidant and anti-inflammatory properties , which are mediated by modulation of the Nrf2/HO-1 and TLR4/NF-κB pathways .
Moreover , RA activated Nrf2/HO-1 , which amplified its inhibition of the NF-κB pathway .

Spinal cord injury (SCI) is a severe central nervous system injury for which few efficacious drugs are available. Rosmarinic acid (RA), a water-soluble polyphenolic phytochemical, has antioxidant, anti-inflammatory, and anti-apoptotic properties. However, the effect of RA on SCI is unclear. We investigated the therapeutic effect and underlying mechanism of RA on SCI. Using a rat model of SCI, we showed that RA improved locomotor recovery after SCI and significantly mitigated neurological deficit, increased neuronal preservation, and reduced apoptosis. Also, RA inhibited activation of microglia and the release of TNF-α, IL-6, and IL-1β and MDA. Moreover, proteomics analyses identified the Nrf2 and NF-κB pathways as targets of RA. Pretreatment with RA increased levels of Nrf2 and HO-1 and reduced those of TLR4 and MyD88 as well as phosphorylation of IκB and subsequent nuclear translocation of NF-κB-p65. Using HO- and LPS-induced PC12 cells, we found that RA ameliorated the HO-induced decrease in viability and increase in apoptosis and oxidative injury by activating the Nrf2/HO-1 pathway. Also, LPS-induced cytotoxicity and increased apoptosis and inflammatory injury in PC-12 cells were mitigated by RA by inhibiting the TLR4/NF-κB pathway. The Nrf2 inhibitor ML385 weakened the effect of RA on oxidant stress, inflammation and apoptosis in SCI rats, and significantly increased the nuclear translocation of NF-κB. Therefore, the neuroprotective effect on SCI of RA may be due to its antioxidant and anti-inflammatory properties, which are mediated by modulation of the Nrf2/HO-1 and TLR4/NF-κB pathways. Moreover, RA activated Nrf2/HO-1, which amplified its inhibition of the NF-κB pathway.


greenmedinfo--2020-05-14--Vitamin D Deficiency in Pregnancy Linked to Higher ADHD Risk in Children

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Before beginning any type of @ @ @ @ @ treatment regimen , it is advisable to seek the advice of a licensed healthcare professional @

This website is for information purposes only. By providing the information contained herein we are not diagnosing, treating, curing, mitigating, or preventing any type of disease or medical condition. Before beginning any type of natural, integrative or conventional treatment regimen, it is advisable to seek the advice of a licensed healthcare professional.
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greenmedinfo--2020-05-14--Carvacrol suppresses learning and memory dysfunction and hippocampal damages caused by chronic cereb

Carvacrol suppresses learning and memory dysfunction and hippocampal damages caused by chronic cerebral hypoperfusion.

Chronic cerebral hypoperfusion ( CCH ) is a common phenomenon in many neurological diseases such as vascular dementia and Alzheimer 's disease .
Several drugs have been investigated to prevent and treat the CCH .
The carvacrol ( CAR ) has been shown to have beneficial effects on various neurodegenerative and neuropsychiatric disorders .
Accordingly , the present study was designed to evaluate the effect of CAR on neuronal damages in hippocampus in a well-defined model for CCH .
Forty-eight male Wistar rats were equally divided into four groups of sham ( A ) , CCH ( B ) , @ @ @ @ @ @ @ ( C and D ) .
The animals were subjected to permanent bilateral occlusion of the carotid arteries ( 2-vessel occlusion , 2VO ) to induce CCH model .
Cognitive function was evaluated by Morris water maze test .
Morphological changes of hippocampus were assessed using Nissl staining .
Free radical scavenging activity was measured by 1,1-diphenyl-2-picrylhydrazyl ( DPPH ) assay .
Moreover , catalase ( CAT ) and superoxide dismutase ( SOD ) activities and lipid peroxidation levels were measured using biochemical analysis .
CAR significantly improved the spatial learning and memory @ @ @ @ @ @ @ test .
CAR also significantly attenuated neuronal necrosis as well as malondialdehyde ( MDA ) and elevated the levels of SOD and CAT activity in the hippocampus .
The results indicate that CAR produces significant neuroprotective effects on neuronal damages induced by CCH .
Protective effect of CAR may be mediated by antioxidative effect of this drug .

Chronic cerebral hypoperfusion (CCH) is a common phenomenon in many neurological diseases such as vascular dementia and Alzheimer's disease. Several drugs have been investigated to prevent and treat the CCH. The carvacrol (CAR) has been shown to have beneficial effects on various neurodegenerative and neuropsychiatric disorders. Accordingly, the present study was designed to evaluate the effect of CAR on neuronal damages in hippocampus in a well-defined model for CCH. Forty-eight male Wistar rats were equally divided into four groups of sham (A), CCH (B), CCH+ CAR 25, and 50 mg/kg/daily (C and D). The animals were subjected to permanent bilateral occlusion of the carotid arteries (2-vessel occlusion, 2VO) to induce CCH model. Cognitive function was evaluated by Morris water maze test. Morphological changes of hippocampus were assessed using Nissl staining. Free radical scavenging activity was measured by 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. Moreover, catalase (CAT) and superoxide dismutase (SOD) activities and lipid peroxidation levels were measured using biochemical analysis. CAR significantly improved the spatial learning and memory deficits assessed using the Morris water maze test. CAR also significantly attenuated neuronal necrosis as well as malondialdehyde (MDA) and elevated the levels of SOD and CAT activity in the hippocampus. The results indicate that CAR produces significant neuroprotective effects on neuronal damages induced by CCH. Protective effect of CAR may be mediated by antioxidative effect of this drug.


greenmedinfo--2020-05-14--Co-administration of curcumin or carvacrol and doxorubicin for 24 days could improve the heart funct

Co-administration of curcumin or carvacrol and doxorubicin for 24 days could improve the heart function and structural changes.

Doxorubicin ( DOX ) is a cardiotoxic drug .
To reduce the harmful effects of DOX , two plant-derived components @ @ @ @ @ ) and carvacrol ( CAR ) , were considered .
This study aimed to assess @ @ @ @ @ and CAR on DOX-induced cardiotoxicity using physiological and stereological evaluations .
Male rats were randomly @ @ @ @ @ Group 's I-VI received phosphate-buffered saline ( PBS ) , CUR ( 100 mg kg @ @ @ @ @ 50 mg kg day ) , DOX ( 4 mg kg week ) , DOX-CUR @ @ @ @ @ .
On day 24 , plasma troponin I and ECG were analyzed and the left @ @ @ @ @ The results showed a fivefold increase in troponin I in the DOX-treated animals compared to @ @ @ @ @ , heart rate and QRS amplitude , respectively , reduced by 18 % and 31 @ @ @ @ @ QRS duration , respectively , increased by 41 % and 24 % in the DOX @ @ @ @ @ PBS rats (

Doxorubicin (DOX) is a cardiotoxic drug. To reduce the harmful effects of DOX, two plant-derived components, including curcumin (CUR) and carvacrol (CAR), were considered. This study aimed to assess the protective effects of CUR and CAR on DOX-induced cardiotoxicity using physiological and stereological evaluations. Male rats were randomly allocated to six groups. Group's I-VI received phosphate-buffered saline (PBS), CUR (100 mg kg day), CAR (50 mg kg day), DOX (4 mg kg week), DOX-CUR, and DOX-CAR, respectively. On day 24, plasma troponin I and ECG were analyzed and the left ventricle underwent stereological assessment. The results showed a fivefold increase in troponin I in the DOX-treated animals compared to the PBS ones. Additionally, heart rate and QRS amplitude, respectively, reduced by 18% and 31% and QT interval and QRS duration, respectively, increased by 41% and 24% in the DOX group in comparison with the PBS rats ( < .05). The total volume of the myocardium and vessels and the number of cardiomyocyte nuclei also, respectively, decreased by 30%, 45%, and 43% in the DOX group compared to the PBS animals (atrophy of the ventricular tissues, < .01). Besides, the mean volumes of the connective tissue and cardiomyocytes, respectively, increased by 46% and 52% in the DOX group ( < .01). In the DOX-CUR and DOX-CAR groups, the changes were prevented extensively in comparison with the DOX group ( < .01). Co-administration of CUR or CAR and doxorubicin for 24 days could improve the heart function and structural changes.


greenmedinfo--2020-05-14--Enhancement in site-specific delivery of carvacrol against methicillin resistant Staphylococcus aure

Enhancement in site-specific delivery of carvacrol against methicillin resistant Staphylococcus aureus induced skin infections.

Methicillin resistant ( MRSA ) induced skin infections have become a challenging problem due to the escalating antibiotic resistance .
Carvacrol ( CAR ) has been reported to be effective against MRSA .
However , due to its characteristics , CAR exhibits low skin retention .
In this study , CAR was formulated into site-specific nanoparticle ( NPs ) delivery system using poly ( ε-caprolactone ) ( PCL ) , following incorporation into a hydrogel matrix to facilitate dermal delivery .
The release study exhibited significantly higher release of CAR from PCL NPs in the presence of bacterial lipase , @ @ @ @ @ @ @ Moreover , encapsulation of CARin PCL NPs resulted in a two-fold increase in its anti-MRSA activity .
Dermatokinetic studies revealed that the NPs loaded hydrogel was able to enhance skin retention of CAR after 24 h ( 83.29 ± 3.15 % ) , compared to free CAR-loaded hydrogel ( 0.85 ± 0.14 % ) .
Importantly , this novel approach exhibitedeffective antimicrobial activity in an ex-vivo skin infection model .
Hence , these findings have proven the concept that the loading of CAR into a responsive NPs system can lead to sustained antimicrobial @ @ @ @ @ @ @ may provide a novel effective approach for treatment of MRSA induced skin infections .
However , further studies must be conducted to investigate in-vivo efficacy of the developed system in an appropriate infection model .

Methicillin resistant(MRSA) induced skin infections have become a challenging problem due to the escalating antibiotic resistance. Carvacrol (CAR) has been reported to be effective against MRSA. However, due to its characteristics, CAR exhibits low skin retention. In this study, CAR was formulated into site-specific nanoparticle (NPs) delivery system using poly(ε-caprolactone) (PCL), following incorporation into a hydrogel matrix to facilitate dermal delivery. The release study exhibited significantly higher release of CAR from PCL NPs in the presence of bacterial lipase, highlighting its potential for differential delivery. Moreover, encapsulation of CARin PCL NPs resulted in a two-fold increase in its anti-MRSA activity. Dermatokinetic studies revealed that the NPs loaded hydrogel was able to enhance skin retention of CAR after 24 h (83.29 ± 3.15%), compared to free CAR-loaded hydrogel (0.85 ± 0.14%). Importantly, this novel approach exhibitedeffective antimicrobial activity in an ex-vivo skin infection model. Hence, these findings have proven the concept that the loading of CAR into a responsive NPs system can lead to sustained antimicrobial effect at the desired site, and may provide a novel effective approach for treatment of MRSA induced skin infections. However, further studies must be conducted to investigate in-vivo efficacy of the developed system in an appropriate infection model.


greenmedinfo--2020-05-14--The results indicated that carvacrol protected from learning and memory impairment and the brain tis

The results indicated that carvacrol protected from learning and memory impairment and the brain tissue inflammation and oxidative stress.

Inflammation can cause memory impairment .
In the present study , the effect of carvacrol on brain tissue inflammation and oxidative stress as well as learning and memory in lipopolysaccharide ( LPS ) -challenged rats was evaluated .
The animals were grouped and treated : ( 1 ) control which received vehicle instead of LPS and carvacrol , ( 2 ) LPS ( 1 mg/kg ; i.p .
120 min before behavioral tests ) , and ( 3-5 ) in these groups , 25 , 50 , or 100 mg/kg of carvacrol ( i.p . )
was administered 30 min @ @ @ @ @ @ @ water maze test , compared to LPS group , administration of all three doses of carvacrol shortened the elapsed time and the traveleddistance to find the platform , while it prolonged the traveled time in the target area .
In a passive avoidance test , administration of all 25 , 50 , and 100 mg/kg carvacrol significantly increased the latency at the 3 h , 24 h , 48 h , and 72 h after the shock compared to the LPS group .
Interleukin ( IL ) -6 , malondialdehyde ( MDA ) @ @ @ @ @ @ @ metabolites were increased in the brain by LPS injection , while thiol , superoxide dismutase ( SOD ) , and catalase ( CAT ) were decreased .
Pretreatment with carvacrol reduced IL-6 , NO metabolites , and MDA , while it improved thiol content , CAT , and SOD.The results indicated that carvacrol protected from learning and memory impairment and the brain tissue inflammation and oxidative stress in LPS-challenged rats .

Inflammation can cause memory impairment. In the present study, the effect of carvacrol on brain tissue inflammation and oxidative stress as well as learning and memory in lipopolysaccharide (LPS)-challenged rats was evaluated. The animals were grouped and treated: (1) control which received vehicle instead of LPS and carvacrol, (2) LPS (1 mg/kg; i.p. 120 min before behavioral tests), and (3-5) in these groups, 25, 50, or 100 mg/kg of carvacrol (i.p.) was administered 30 min prior to LPS. In a Morris water maze test, compared to LPS group, administration of all three doses of carvacrol shortened the elapsed time and the traveleddistance to find the platform, while it prolonged the traveled time in the target area. In a passive avoidance test, administration of all 25, 50, and 100 mg/kg carvacrol significantly increased the latency at the 3 h, 24 h, 48 h, and 72 h after the shock compared to the LPS group. Interleukin(IL)-6, malondialdehyde (MDA), and NO (nitric oxide) metabolites were increased in the brain by LPS injection, while thiol, superoxide dismutase (SOD), and catalase (CAT) were decreased. Pretreatment with carvacrol reduced IL-6, NO metabolites, and MDA, while it improved thiol content, CAT, and SOD.The results indicated that carvacrol protected from learning and memory impairment and the brain tissue inflammation and oxidative stress in LPS-challenged rats.


greenmedinfo--2020-05-14--Carvacrol has significant potential as an inhibitor of memory degeneration in neurodegenerative dise

Carvacrol has significant potential as an inhibitor of memory degeneration in neurodegenerative diseases.

Neuroinflammation is an important process underlying a wide variety of neurodegenerative diseases .
Carvacrol ( CAR ) is a phenolic monoterpene commonly used as a food additive due to its antibacterial properties , but it has also been shown to exhibit strong antioxidative , anti-inflammatory , and neuroprotective effects .
Here , we sought to investigate the effects of CAR on inflammation in the hippocampus and prefrontal cortex , as well as the molecular mechanisms underlying these effects .
In our study , lipopolysaccharide was injected into the lateral ventricle of rats to induce memory impairment and neuroinflammation .
Daily @ @ @ @ @ @ @ , and 100 mg/kg ) for 21 days improved recognition , discrimination , and memory impairments relative to untreated controls .
CAR administration significantly attenuated expression of several inflammatory factors in the brain , including interleukin-1β , tumor necrosis factor-α , and cyclooxygenase-2 .
In addition , CAR significantly increased expression of brain-derived neurotrophic factor ( BDNF ) mRNA , and decreased expression of Toll-like receptor 4 ( TLR4 ) mRNA .
Taken together , these results show that CAR can improve memory impairment caused byneuroinflammation .
This cognitive enhancement is due to @ @ @ @ @ @ @ its regulation of BDNF and TLR4 .
Thus , CAR has significant potential as an inhibitor of memory degeneration in neurodegenerative diseases .

Neuroinflammation is an important process underlying a wide variety of neurodegenerative diseases. Carvacrol (CAR) is a phenolic monoterpene commonly used as a food additive due to its antibacterial properties, but it has also been shown to exhibit strong antioxidative, anti-inflammatory, and neuroprotective effects. Here, we sought to investigate the effects of CAR on inflammation in the hippocampus and prefrontal cortex, as well as the molecular mechanisms underlying these effects. In our study, lipopolysaccharide was injected into the lateral ventricle of rats to induce memory impairment and neuroinflammation. Daily administration of CAR (25, 50, and 100 mg/kg) for 21 days improved recognition, discrimination, and memory impairments relative to untreated controls. CAR administration significantly attenuated expression of several inflammatory factors in the brain, including interleukin-1β, tumor necrosis factor-α, and cyclooxygenase-2. In addition, CAR significantly increased expression of brain-derived neurotrophic factor (BDNF) mRNA, and decreased expression of Toll-like receptor 4 (TLR4) mRNA. Taken together, these results show that CAR can improve memory impairment caused byneuroinflammation. This cognitive enhancement is due to the anti-inflammatory effects of CAR medicated by its regulation of BDNF and TLR4. Thus, CAR has significant potential as an inhibitor of memory degeneration in neurodegenerative diseases.


greenmedinfo--2020-05-14--Carvacrol protects against diabetes-induced hypercontractility in the aorta through activation of th

Carvacrol protects against diabetes-induced hypercontractility in the aorta through activation of the PI3K/Akt pathway.

Vascular complications induced by diabetes constitute the principal cause of morbidity and mortality in diabetic patients .
It has been reported that carvacrol ( CAR ) possesses a wide range of biological activities .
The effects of CAR on diabetes-induced vasculopathy remain unknown .
In this study , diabetic mice were created by the intraperitoneal injection of streptozotocin ( STZ ) in male C57BL/6 J mice to investigate whether CAR provided a protective effect against diabetes-induced vasculopathy and to investigate the underlying mechanisms .
We found that CAR decreased blood glucose levels in diabetic mice .
Moreover , CAR ameliorated @ @ @ @ @ @ @ by an increased thickness in the intima-media width and an increased number of vascular smooth muscle cells ( VSMCs ) layers .
Further studies revealed that CAR inhibited hypercontractility in the aortas of diabetic mice and VSMCs in response to hyperglycemia , as evidenced by the relaxation of phenylephrine ( PE ) -induced vasoconstriction , the decreased expression of smooth muscle ( SM ) -α-actin , and the increased expression of Ki67 and proliferating cell nuclear antigen ( PCNA ) .
Furthermore , the PI3K/Akt signaling pathway was inhibited in the aortas of @ @ @ @ @ @ @ hyperglycemia , while CAR treatment activated the PI3K/Akt signaling pathway .
In conclusion , our results strongly suggest that CAR plays a protective role in diabetes-induced aortic hypercontractility , possibly by activating the PI3K/Akt signaling pathway .
CAR is a potential drug for the treatment of diabetic vasculopathy .

Vascular complications induced by diabetes constitute the principal cause of morbidity and mortality in diabetic patients. It has been reported that carvacrol (CAR) possesses a wide range of biological activities. The effects of CAR on diabetes-induced vasculopathy remain unknown. In this study, diabetic mice were created by the intraperitoneal injection of streptozotocin (STZ) in male C57BL/6 J mice to investigate whether CAR provided a protective effect against diabetes-induced vasculopathy and to investigate the underlying mechanisms. We found that CAR decreased blood glucose levels in diabetic mice. Moreover, CAR ameliorated diabetes-induced aortic morphological alterations, as evidenced by an increased thickness in the intima-media width and an increased number of vascular smooth muscle cells (VSMCs) layers. Further studies revealed that CAR inhibited hypercontractility in the aortas of diabetic mice and VSMCs in response to hyperglycemia, as evidenced by the relaxation of phenylephrine(PE)-induced vasoconstriction, the decreased expression of smooth muscle (SM)-α-actin, and the increased expression of Ki67 and proliferating cell nuclear antigen (PCNA). Furthermore, the PI3K/Akt signaling pathway was inhibited in the aortas of diabetic mice and VSMCs in response to hyperglycemia, while CAR treatment activated the PI3K/Akt signaling pathway. In conclusion,our results strongly suggest that CAR plays a protective role in diabetes-induced aortic hypercontractility, possibly by activating the PI3K/Akt signaling pathway. CAR is a potential drug for the treatment of diabetic vasculopathy.


greenmedinfo--2020-05-14--Antiproliferative and anti-invasion effects of carvacrol on PC3 human prostate cancer cells.

Background : One of the most effective parameters in the progression of the prostate cancer is interleukin ( IL ) -6 through affecting pSTAT3 , pERK1/2 , and pAKT cell signaling proteins .
Carvacrol is an herbal antioxidant with antitumor effects .
The purpose of this study was to investigate the effects of carvacrol ongene expression , pSTAT3 , pAKT , pERK1/2 cellular signaling proteins , and invasion in human prostate cancer PC3 cells .
Methods : PC3 cell viability was evaluated by MTT assay with different concentrations of carvacrol ( 0-800μM ) .gene expression and cellular concentration of pSTAT3 @ @ @ @ @ @ @ using the real-time reverse transcription quantitative polymerase chain reaction ( RT-qPCR ) and western blotting technic , respectively .
PC3 cell invasion was determined by invasion assay test .
Results : Carvacrol ICfor PC3 prostate cancer cells was 360μM .
Carvacrol led to a significant reduction ( < 0.05 ) forgene expression in a dose-dependent manner compared to control .
IL-6 protein reduced 41.5 % and 52.7 % when compared with control cells at 360 and 420μM of carvacrol , respectively .
Carvacrol led to a decline in pSTAT3 , pAKT , and @ @ @ @ @ @ @ .
PC3 potential invasion was significantly reduced after treatment with carvacrol in a dose-dependent manner .
Conclusions : Decreased IL-6 protein level by carvacrol resulted in diminishing of pSTAT3 , pERK1/2 , and pAKT signaling proteins , which leads to the reduction of the cell survival , proliferation , and invasion in PC3 cells .

Background: One of the most effective parameters in the progression of the prostate cancer is interleukin (IL)-6 through affecting pSTAT3, pERK1/2, and pAKT cell signaling proteins. Carvacrol is an herbal antioxidant with antitumor effects. The purpose of this study was to investigate the effects of carvacrol ongene expression, pSTAT3, pAKT, pERK1/2 cellular signaling proteins, and invasion in human prostate cancer PC3 cells.
Methods: PC3 cell viability was evaluated by MTT assay with different concentrations of carvacrol (0-800μM).gene expression and cellular concentration of pSTAT3, pERK1/2, and pAKT were investigated using the real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blotting technic, respectively. PC3 cell invasion was determined by invasion assay test.
Results: Carvacrol ICfor PC3 prostate cancer cells was 360μM. Carvacrol led to a significant reduction (<0.05) forgene expression in a dose-dependent manner compared to control. IL-6 protein reduced 41.5% and 52.7% when compared with control cells at 360 and 420μM of carvacrol, respectively. Carvacrol led to a decline in pSTAT3, pAKT, and pERK1/2 above 360 μM compared to control. PC3 potential invasion was significantly reduced after treatment with carvacrol in a dose-dependent manner.
Conclusions: Decreased IL-6 protein level by carvacrol resulted in diminishing of pSTAT3, pERK1/2, and pAKT signaling proteins, which leads to the reduction of the cell survival, proliferation, and invasion in PC3 cells.


greenmedinfo--2020-05-14--Anti-inflammatory and antioxidant activity of carvacrol in the respiratory system.

Carvacrol is a monoterpene present in the essential oil of a number of plants and has been widely used in traditional medicine because it is considered to have a range of therapeutic effects including in relation to respiratory disease .
To conduct a systematic review and meta-analysis to assess the anti-inflammatory and antioxidant activities of carvacrol when used in the treatment of respiratory disorders .
A comprehensive literature search using Scopus , MEDLINE-PubMed , Cochrane and Web of Science was undertaken .
Papers related to the anti-inflammatory or antioxidant properties of carvacrol in the treatment of an injury in the @ @ @ @ @ @ @ published in the period up to and including August 2019 .
A total of 152 studies were initially identified , with only 17 meeting the inclusion criteria .
Five of the studies were performed in humans , and 12 were performed in rodents .
Among the 17 studies included in the systematic review , we performed the meta-analysis with nine of the studies with animals .
Carvacrol had a positive effect on the reduction of interleukin ( IL ) -1β , IL-4 , IL-8 and malondialdehyde ( MDA ) ; however , the @ @ @ @ @ @ @ on IL-6 and tumor necrosis factor alpha ( TNF-α ) , probably due to the methodological quality of the studies and their heterogeneity .
Current evidence supports the antioxidant and anti-inflammatoryeffects of carvacrol , but its relationship with the reduction of some inflammatory mediators in animals with lung injury needs further elucidation .

Carvacrol is a monoterpene present in the essential oil of a number of plants and has been widely used in traditional medicine because it is considered to have a range of therapeutic effects including in relation to respiratory disease. To conduct a systematic review and meta-analysis to assess the anti-inflammatory and antioxidant activities of carvacrol when used in the treatment of respiratory disorders. A comprehensive literature search using Scopus, MEDLINE-PubMed, Cochrane and Web of Science was undertaken. Papers related to the anti-inflammatory or antioxidant properties of carvacrol in the treatment of an injury in the respiratory system in in vivo studies and published in the period up to and including August 2019. A total of 152 studies were initially identified, with only 17 meeting the inclusion criteria. Five of the studies were performed in humans, and 12 were performed in rodents. Among the 17 studies included in the systematic review, we performed the meta-analysis with nine of the studies with animals. Carvacrol had a positive effect on the reduction of interleukin (IL)-1β, IL-4, IL-8 and malondialdehyde (MDA); however, the analysis indicated that carvacrol had no effect on IL-6 and tumor necrosis factor alpha (TNF-α), probably due to the methodological quality of the studies and their heterogeneity. Current evidence supports the antioxidant and anti-inflammatoryeffects of carvacrol, but its relationship with the reduction of some inflammatory mediators in animals with lung injury needs further elucidation.


greenmedinfo--2020-05-14--Carvacrol loaded nanostructured lipid carriers as a promising parenteral formulation for leishmanias

Carvacrol loaded nanostructured lipid carriers as a promising parenteral formulation for leishmaniasis treatment.

Leishmaniasis are a group of neglected infectious diseases caused by protozoa of the genus Leishmania with distinct presentations .
The available leishmaniasis treatment options are either expensive and/or ; cause adverse effects and some are ineffective for resistant Leishmania strains .
Therefore , molecules derived from natural products as the monoterpene carvacrol , have attracted interest as promising anti-leishmania agents .
However , the therapeutic use of carvacrol is limited due to its low aqueous solubility , rapid oxidation and volatilization .
Thus , the development of nanostructured lipid carriers ( NLCs ) was proposed in the present study as @ @ @ @ @ @ @ limitations and enable the use of carvacrol in leishmaniasis therapy .
Carvacrol NLCs were obtained using a warm microemulsion method , and evaluated regarding the influence of lipid matrix and components concentration on the NLCs formation .
NLCs were characterized by DSC and XRD as well .
In addition , to the in vitro carvacrol release from NLCs , the in vitro cytotoxicity and leishmanicidal activity assays , and the in vivo pharmacokinetics evaluation of free and encapsulated carvacrol were performed .
NLCs containing carvacrol were obtained successfully using a warm microemulsion dilution @ @ @ @ @ @ @ lowest particle size ( 98.42± 0.80 nm ) , narrowest size distribution ( suitable for intravenous administration ) , and the highest encapsulation efficiency was produced by using beeswax as solid lipid ( HLB=9 ) and 5 % of lipids and surfactant .
The in vitro release of carvacrol from NLCs was fitted to the Korsmeyer and Peppas , and Weibull models , demonstrating that the release mechanism is probably the Fickian diffusion type .
Moreover , carvacrol encapsulation in NLCs provided a lower cytotoxicity in comparison to free carvacrol ( p < @ @ @ @ @ @ @ leishmanicidal efficacy in the amastigote form .
Finally , the in vivo pharmacokinetics of carvacrol after IV bolus administration suggests that this phenolic monoterpene undergoes enterohepatic circulation and therefore presented a long half-life ( t ) and low clearance ( Cl ) .
In addition , C , mean residence time ( MRT ) and Vof encapsulated carvacrol were higher than free carvacrol ( p < 0.05 ) , favoring a higher distribution of carvacrol in the target tissues .
Thus , it is possible to conclude that the developed NLCs are a @ @ @ @ @ @ @

Leishmaniasis are a group of neglected infectious diseases caused by protozoa of the genus Leishmania with distinct presentations. The available leishmaniasis treatment options are either expensive and/or; cause adverse effects and some are ineffective for resistant Leishmania strains. Therefore, molecules derived from natural products as the monoterpene carvacrol, have attracted interest as promising anti-leishmania agents. However, the therapeutic use of carvacrol is limited due to its low aqueous solubility, rapid oxidation and volatilization. Thus, the development of nanostructured lipid carriers (NLCs) was proposed in the present study as a promising nanotechnology strategy to overcome these limitations and enable the use of carvacrol in leishmaniasis therapy. Carvacrol NLCs were obtained using a warm microemulsion method, and evaluated regarding the influence of lipid matrix and components concentration on the NLCs formation. NLCs were characterized by DSC and XRD as well. In addition, to the in vitro carvacrol release from NLCs, the in vitro cytotoxicity and leishmanicidal activity assays, and the in vivo pharmacokinetics evaluation of free and encapsulated carvacrol were performed. NLCs containing carvacrol were obtained successfully using a warm microemulsion dilution method. The NLCs formulation with the lowest particle size (98.42± 0.80 nm), narrowest size distribution (suitable for intravenous administration), and the highest encapsulation efficiency was produced by using beeswax as solid lipid (HLB=9) and 5% of lipids and surfactant. The in vitro release of carvacrol from NLCs was fitted to the Korsmeyer and Peppas, and Weibull models, demonstrating that the release mechanism is probably the Fickian diffusion type. Moreover, carvacrol encapsulation in NLCs provided a lower cytotoxicity in comparison to free carvacrol (p<0.05), increasing its in vitro leishmanicidal efficacy in the amastigote form. Finally, the in vivo pharmacokinetics of carvacrol after IV bolus administration suggests that this phenolic monoterpene undergoes enterohepatic circulation and therefore presented a long half-life (t) and low clearance (Cl). In addition, C, mean residence time (MRT) and Vof encapsulated carvacrol were higher than free carvacrol (p<0.05), favoring a higher distribution of carvacrol in the target tissues. Thus, it is possible to conclude that the developed NLCs are a promising delivery system for leishmaniasis treatment.


greenmedinfo--2020-05-14--Carvacrol prodrugs with antimicrobial activity loaded on clay nanocomposites.

BACKGROUND : Carvacrol , an essential oil with antimicrobial activity against a wide range of pathogens , and its water @ @ @ @ @ ) were intercalated into montmorillonite ( VHS ) interlayers to improve their stability in physiological @ @ @ @ @ in the intestine .
METHODS : Intercalation of prodrugs by cation exchange with montmorillonite interlayer @ @ @ @ @ powder diffraction and confirmed by Fourier transform infrared spectroscopy and thermal analysis .
RESULTS : @ @ @ @ @ that montmorillonite successfully controlled the release of the adsorbed prodrugs and promoted their bioactivation only @ @ @ @ @ carvacrol could develop its maximum antimicrobial activity .
The amount of WSCP1 , WSCP2 , @ @ @ @ @ were 38 % , 54 % , and 45 % at acid pH in 120 @ @ @ @ @ , 78 % , and 44 % at pH 6.8 in 240 min , respectively @ @ @ @ @ hybrids successfully controlled conversion of the prodrugs to carvacrol , avoiding premature degradation of the @ @

BACKGROUND: Carvacrol, an essential oil with antimicrobial activity against a wide range of pathogens, and its water soluble carvacrol prodrugs (WSCP1-3) were intercalated into montmorillonite (VHS) interlayers to improve their stability in physiological media and promote their absorption in the intestine.
METHODS: Intercalation of prodrugs by cation exchange with montmorillonite interlayer counterions was verified by X-ray powder diffraction and confirmed by Fourier transform infrared spectroscopy and thermal analysis.
RESULTS: In vitro release studies demonstrated that montmorillonite successfully controlled the release of the adsorbed prodrugs and promoted their bioactivation only in the intestinal tract where carvacrol could develop its maximum antimicrobial activity. The amount of WSCP1, WSCP2, and WSCP3 released from VHS were 38%, 54%, and 45% at acid pH in 120 min, and 65%, 78%, and 44% at pH 6.8 in 240 min, respectively.
CONCLUSIONS: The resultant hybrids successfully controlled conversion of the prodrugs to carvacrol, avoiding premature degradation of the drug.