greenmedinfo--2020-05-15--Impact of evening primrose oil consumption on psychological symptoms of postmenopausal women.

OBJECTIVE : The purpose of this study was to determine the efficacy and safety of evening primrose oil on women @ @ @ @ @ .
METHODS : A double-blinded randomized placebo-controlled trial carried out from September 2018 to February @ @ @ @ @ Iran .
Eligible women randomly received either 1,000 mg of evening primrose oil capsules daily @ @ @ @ @ weeks .
The Main outcome measures were psychological symptoms based on the psychological subscale of @ @ @ @ @ Independent samples t test was used for intergroup comparisons and paired samples t test for @ @ @ @ @ ≤ 0.05 was considered statistically significant .
RESULTS : The 8-week treatment was completed by @ @ @ @ @ baseline psychological score did not differ among the two groups .
After intervention , the @ @ @ @ @ differed significantly among groups ( P CONCLUSIONS : This study could provide evidence regarding the @ @ @ @ @ oil for the psychological symptoms of postmenopausal women .
Longer trials are necessary to make @ @ @ @ @ use of evening primrose oil and its safety in clinical practice .

OBJECTIVE: The purpose of this study was to determine the efficacy and safety of evening primrose oil on women's psychological symptoms during menopause.
METHODS: A double-blinded randomized placebo-controlled trial carried out from September 2018 to February 2019 in Bandar Abbas, Iran. Eligible women randomly received either 1,000 mg of evening primrose oil capsules daily or matching placebo for 8 weeks. The Main outcome measures were psychological symptoms based on the psychological subscale of the Menopause Rating Scale. Independent samples t test was used for intergroup comparisons and paired samples t test for pre- andpost-treatment comparisons. P ≤ 0.05 was considered statistically significant.
RESULTS: The 8-week treatment was completed by 189 women. The mean baseline psychological score did not differ among the two groups. After intervention, the psychological score, however, differed significantly among groups (P < 0.01). To distinguish the effect of evening primrose oil, we compared the reduction in the psychological score in each group. Regarding mean differences of the psychological score in both groups, there was a prominent alleviation in the intervention group mean difference: -3.44 (95% confidence interval of difference: -4.01 to -1.20) (P < 0.01). In addition, only one patient reported gastric upset in the intervention group.
CONCLUSIONS: This study could provide evidence regarding the potential benefits of evening primrose oil for the psychological symptoms of postmenopausal women. Longer trials are necessary to make more reliable decisions about the use of evening primrose oil and its safety in clinical practice.


greenmedinfo--2020-05-15--Evening primrose oil ameliorates hyperleptinemia and reproductive hormone disturbances in obesity.

Obesity is a public health burden disturbing all body functions and reproductive hormones .
As obesity increases among females , there will be a rising challenge to physicians in care from fertility problems .
Evening primrose oil ( EPR oil ) contains essential fatty acids including omega-6 linoleic acid with strong anti-inflammatory activity .
Since EPR oil has utility in alleviating dysmenorrhea , this study aimed to ascertain its modulatory effect on systemic inflammation , reproductive hormones and estrus cycle irregularity in female obese rats .
Thirty-two female rats were distributed to 4 groups : ( i ) normal , @ @ @ @ @ @ @ , and ( iii and iv ) dietary obese female rats treated with EPR oil ( 5 or 10 g/kg ) .
Rats were examined for estrus regularity by taking vaginal smears daily during the last 2 weeks of the experiment .
Serum level of insulin , leptin , adiponectin , and inflammatory cytokines was measured .
In addition , serum lipid profile , and liver enzyme activities were estimated .
Adipose tissues were taken for histopathologic examination as well as determination of gene expression for leptin , leptin receptors , adiponectin , @ @ @ @ @ @ @ weight gain ( 90.69± 8.9 ) , irregular prolonged estrus cycles ( 83.33 % ) , increased serum levels of insulin , leptin , prolactin and testosterone and decreased gonadotropin levels .
EPR oil exhibited a curative effect on obesity-related irregularity in estrus cycle and ovarian pathology .
The underlying molecular mechanismmay be related to reduction of systemic inflammation , alleviating insulin resistance and modulation of adipokine expression .
EPR oil may be considered as a promising therapeutic intervention against obesity-related female hormonal disturbances and estrus irregularity .

Obesity is a public health burden disturbing all body functions and reproductive hormones. As obesity increases among females, there will be a rising challenge to physicians in care from fertility problems. Evening primrose oil (EPR oil) contains essential fatty acids including omega-6 linoleic acid with strong anti-inflammatory activity. Since EPR oil has utility in alleviating dysmenorrhea, this study aimed to ascertain its modulatory effect on systemic inflammation, reproductive hormones and estrus cycle irregularity in female obese rats. Thirty-two female rats were distributed to 4 groups: (i) normal, (ii) dietary obese-control female rats, and (iii and iv) dietary obese female rats treated with EPR oil (5 or 10 g/kg). Rats were examined for estrus regularity by taking vaginal smears daily during the last 2 weeks of the experiment. Serum level of insulin, leptin, adiponectin, and inflammatory cytokines was measured. In addition, serum lipid profile, and liver enzyme activities were estimated. Adipose tissues were taken for histopathologic examination as well as determination of gene expression for leptin, leptin receptors, adiponectin, and visfatin. Obese rats exhibited significant weight gain (90.69± 8.9), irregular prolonged estrus cycles (83.33%), increased serum levels of insulin, leptin, prolactin and testosterone and decreased gonadotropin levels. EPR oil exhibited a curative effect on obesity-related irregularity in estrus cycle and ovarian pathology. The underlying molecular mechanismmay be related to reduction of systemic inflammation, alleviating insulin resistance and modulation of adipokine expression. EPR oil may be considered as a promising therapeutic intervention against obesity-related female hormonal disturbances and estrus irregularity.


greenmedinfo--2020-05-15--Antibacterial and antioxidant activity of extracts from rose fruits.

The aim of the present study was to determine the antioxidant and antimicrobial properties in freeze-dried extracts of rose fruits ( ) obtained using various extraction techniques and to determine the effect of a selected extract on bacterial survival in model fluids imitating protein food .
Ethanolic extracts from rose fruits showed higher antioxidant activity compared to other tested extracts .
The rose fruits aqueous extract showed the highest inhibitory activity against most of the 10 bacterial strains tested .
From the group of Gram-positive bacteria , thestrain proved to be the most sensitive to the action of the rose @ @ @ @ @ @ @ andwere the most sensitive .
The reduction in the number of bacterial cells in matrices imitating protein food depended on the concentration of the aqueous extract used .
However , at none of the concentrations used was a complete inhibition of bacterial growth observed .
We have confirmed that the traditional extraction and freeze-drying of rose fruits is still suitable for the food industry due to obtaining extracts with good antibacterial and antioxidant properties and the use of bio-solvents , such as water or ethanol , which are easily available in high purity @ @ @ @

The aim of the present study was to determine the antioxidant and antimicrobial properties in freeze-dried extracts of rose fruits () obtained using various extraction techniques and to determine the effect of a selected extract on bacterial survival in model fluids imitating protein food. Ethanolic extracts from rose fruits showed higher antioxidant activity compared to other tested extracts. The rose fruits aqueous extract showed the highest inhibitory activity against most of the 10 bacterial strains tested. From the group of Gram-positive bacteria, thestrain proved to be the most sensitive to the action of the rose extract. From the Gram-negative bacteria:andwere the most sensitive. The reduction in the number of bacterial cells in matrices imitating protein food depended on the concentration of the aqueous extract used. However, at none of the concentrations used was a complete inhibition of bacterial growth observed. We have confirmed that the traditional extraction and freeze-drying of rose fruits is still suitable for the food industry due to obtaining extracts with good antibacterial and antioxidant properties and the use of bio-solvents, such as water or ethanol, which are easily available in high purity and completely biodegradable.


greenmedinfo--2020-05-15--The results showed that Rosa roxburghii Tratt fruit is rich in phenolic acids, and that it exerted l

Background : Rosa roxburghii Tratt fruit is extensively used as a medicinal and edible resource in China due to its @ @ @ @ @ research , we aimed to characterize its phenolic acid composition and investigate the potential hypolipidemic @ @ @ @ @ a rat model of hyperlipidemia .
Methods : We evaluated the effects of hydroalcoholic extract @ @ @ @ @ ( HRT ) on serum lipids , body weight , activities of lipoprotein metabolism and @ @ @ @ @ expression of lipid metabolism in hyperlipidemic rats .
Results : HRT significantly reduced body weight @ @ @ @ @ liver lipid levels in the hyperlipidemic rats .
In addition , HRT treatment improved the @ @ @ @ @ lipoprotein lipase , and hepatic lipase , downregulated the mRNA and protein expressions of sterol @ @ @ @ @ acetyl CoA carboxylase , and upregulated the mRNA and protein expressions of peroxisome proliferator-activated receptorα @ @ @ @ @ hepatic tissue .
Conclusions : The results showed that Rosa roxburghii Tratt fruit is rich @ @ @ @ @ that it exerted lipid lowering effects in the hyperlipidemic rats .

Background: Rosa roxburghii Tratt fruit is extensively used as a medicinal and edible resource in China due to its unique bioactivities. In this research, we aimed to characterize its phenolic acid composition and investigate the potential hypolipidemic effect of this plant in a rat model of hyperlipidemia.
Methods: We evaluated the effects of hydroalcoholic extract of Rosa roxburghii Tratt fruit (HRT) on serum lipids, body weight, activities of lipoprotein metabolism and antioxidant enzymes, and gene expression of lipid metabolism in hyperlipidemic rats.
Results: HRT significantly reduced body weight gain and decreased serum and liver lipid levels in the hyperlipidemic rats. In addition, HRT treatment improved the activities of antioxidant enzymes, lipoprotein lipase, and hepatic lipase, downregulated the mRNA and protein expressions of sterol regulatory element-binding protein 1c and acetyl CoA carboxylase, and upregulated the mRNA and protein expressions of peroxisome proliferator-activated receptorα and low-density lipoprotein receptor in hepatic tissue.
Conclusions: The results showed that Rosa roxburghii Tratt fruit is rich in phenolic acids, and that it exerted lipid lowering effects in the hyperlipidemic rats.


greenmedinfo--2020-05-15--Mangiferin ameliorates hyperuricemic nephropathy which is associated with downregulation of AQP2 and

Mangiferin ameliorates hyperuricemic nephropathy which is associated with downregulation of AQP2 and increased urinary uric acid excretion.

Hyperuricemia is characterized by abnormally high level of circulating uric acid in the blood and is associated with increased risk of kidney injury .
The pathophysiological mechanisms leading to hyperuricemic nephropathy ( HN ) involve oxidative stress , endothelial dysfunction , inflammation , and fibrosis .
Mangiferin is a bioactive C-glucoside xanthone , which has been exerting anti-inflammatory , anti-fibrotic , and antioxidative effects in many diseases .
This study aimed to evaluate the effect of mangiferin treatment in HN .
In a mouse model of HN , we observed lower circulating urate levels and ameliorated renal dysfunction with mangiferin @ @ @ @ @ @ @ renal inflammation and fibrosis .
We next investigated the mechanism of urate lowering effect of mangiferin .
Metabolic cage experiment showed that mangiferin-administrated mice excreted significantly more urinary uric acid due to elevated urine output , but no marked change in urine uric acid concentration .
Expressions of water channels and urate transporters were further assessed by western blot .
Renal AQP2 expression was decreased , yet urate transporters URAT1 , GLUT9 , and OAT1 expressions were not affected by mangiferin in HN mice .
Moreover , mangiferin treatment also normalized xanthine oxidase @ @ @ @ @ @ @ which would decrease uric acid synthesis and improve oxidative stress , respectively .
Therefore , our results reveal a novel mechanism whereby mangiferin can reduce serum uric acid levels by promoting AQP2-related urinary uric acid excretion .
This study suggested that mangiferin could be a multi-target therapeutic candidate to prevent HNmechanisms that involve increased excretion and decreased production of uric acid and modulation of inflammatory , fibrotic , and oxidative pathways .

Hyperuricemia is characterized by abnormally high level of circulating uric acid in the blood and is associated with increased risk of kidney injury. The pathophysiological mechanisms leading to hyperuricemic nephropathy (HN) involve oxidative stress, endothelial dysfunction, inflammation, and fibrosis. Mangiferin is a bioactive C-glucoside xanthone, which has been exerting anti-inflammatory, anti-fibrotic, and antioxidative effects in many diseases. This study aimed to evaluate the effect of mangiferin treatment in HN. In a mouse model of HN, we observed lower circulating urate levels and ameliorated renal dysfunction with mangiferin treatment, which was associated with reduced renal inflammation and fibrosis. We next investigated the mechanism of urate lowering effect of mangiferin. Metabolic cage experiment showed that mangiferin-administrated mice excreted significantly more urinary uric acid due to elevated urine output, but no marked change in urine uric acid concentration. Expressions of water channels and urate transporters were further assessed by western blot. Renal AQP2 expression was decreased, yet urate transporters URAT1, GLUT9, and OAT1 expressions were not affected by mangiferin in HN mice. Moreover, mangiferin treatment also normalized xanthine oxidase and SOD activity in HN mice, which would decrease uric acid synthesis and improve oxidative stress, respectively. Therefore, our results reveal a novel mechanism whereby mangiferin can reduce serum uric acid levels by promoting AQP2-related urinary uric acid excretion. This study suggested that mangiferin could be a multi-target therapeutic candidate to prevent HNmechanisms that involve increased excretion and decreased production of uric acid and modulation of inflammatory, fibrotic, and oxidative pathways.


greenmedinfo--2020-05-15--Mangiferin exert cardioprotective and anti-apoptotic effects in heart failure.

Mangiferin is a well-known xanthone extracted from mango leaves ( Mangifera indica Linn ) .
Mangiferin is widely distributed in the bark , peel , leaf , seed , stalk , and kernel of mango and higher plants .
The pharmacological properties of mangiferin , including its antioxidant , anticancer , antiaging , antiviral , hepatoprotective , analgesic , and immunomodulatory activities , have been described in several studies .
We investigated the effect of mangiferin on isoproterenol-induced apoptosis .
Experimental heart failure was induced in rats by intraperitoneal administration of isoproterenol ( 5 mg/kg ) for 7 consecutive days @ @ @ @ @ @ @ : group I ( sham rats ) , group II ( isoproterenol alone control ) , group III ( isoproterenol + 25 mg/kg mangiferin ) , group IV ( isoproterenol + 50 mg/kg mangiferin ) , and group V ( isoproterenol + 0.0225 mg/kg digitalis as a positive control ) .
Hemodynamic parameters and body weight , heart weight and liver weight , apoptosis induction , and caspase-3 , Bax , and Bcl-2 protein levels were measured , and a histopathological analysis of cardiomyocytes was performed .
In addition , apoptosis and protein @ @ @ @ @ @ @ Bax , and Bcl-2 were measured in cardiac H9c2 cells .
Mangiferin supplementation significantly increased heart rate and improved the maximum rate of decrease in left ventricular ( LV ) pressure , the maximum rate of increase in LV pressure , and LV systolic pressure .
Mangiferin reduced inflammatory cell infiltration and the number of broken myocardial fibers , and decreased apoptosis in cardiomyocytes by reducing proteins levels of caspase-3 and Bax and increasing those of Bcl-2 .
Our findings suggest that mangiferin has a cardioprotective effect against isoproterenol-induced apoptosis in cardiomyocytes .

Mangiferin is a well-known xanthone extracted from mango leaves (Mangifera indica Linn). Mangiferin is widely distributed in the bark, peel, leaf, seed, stalk, and kernel of mango and higher plants. The pharmacological properties of mangiferin, including its antioxidant, anticancer, antiaging, antiviral, hepatoprotective, analgesic, and immunomodulatory activities, have been described in several studies. We investigated the effect of mangiferin on isoproterenol-induced apoptosis. Experimental heart failure was induced in rats by intraperitoneal administration of isoproterenol (5 mg/kg) for 7 consecutive days. Rats were divided into five groups: group I (sham rats), group II (isoproterenol alone control), group III (isoproterenol + 25 mg/kg mangiferin), group IV (isoproterenol + 50 mg/kg mangiferin), and group V (isoproterenol + 0.0225 mg/kg digitalis as a positive control). Hemodynamic parameters and body weight, heart weight and liver weight, apoptosis induction, and caspase-3, Bax, and Bcl-2 protein levels were measured, and a histopathological analysis of cardiomyocytes was performed. In addition, apoptosis and protein expression of caspase-3, cleaved caspase-3, Bax, and Bcl-2 were measured in cardiac H9c2 cells. Mangiferin supplementation significantly increased heart rate and improved the maximum rate of decrease in left ventricular (LV) pressure, the maximum rate of increase in LV pressure, and LV systolic pressure. Mangiferin reduced inflammatory cell infiltration and the number of broken myocardial fibers, and decreased apoptosis in cardiomyocytes by reducing proteins levels of caspase-3 and Bax and increasing those of Bcl-2. Our findings suggest that mangiferin has a cardioprotective effect against isoproterenol-induced apoptosis in cardiomyocytes.


greenmedinfo--2020-05-15--Mangiferin attenuates LPS/D-GalN-induced acute liver injury by promoting HO-1 in kupffer cells.

Acute liver injury and its terminal phase , hepatic failure , trigger a series of complications , including hepatic encephalopathy , systematic inflammatory response syndrome , and multiorgan failure , with relatively high morbidity and mortality .
Liver transplantation is the ultimate intervention , but the shortage of donor organs has limited clinical success .
Mangiferin ( MF ) , a xanthone glucoside , has been reported to have excellent anti-inflammatory efficacy .
Here , a lipopolysaccharide ( LPS ) /D-galactosamine ( D-GalN ) -induced acute liver injury mouse model was established to investigate the protective role of MF and @ @ @ @ @ @ @ with MF improved survival , decreased serum aminotransferase activities , and inhibited hepatic TNF-α production in LPS/D-GalN-challenged mice .
Through Kupffer cell ( KC ) deletion by GdCland KC adoptive transfer , KCs were confirmed to be involved in these beneficial effects of MF .
MF reduced LPS-mediated TNF-α production via the suppression of the TLR4/NF-κB signaling pathway .
MF promoted HO-1 expression , but the knockdown of HO-1 prevented TNF-α inhibition , suggesting that the damage-resistance effects of HO-1 occurred via the suppression of TNF-α synthesis .
When HO-1-silenced KCs were transferred @ @ @ @ @ @ @ the protective effect of MF against LPS/D-GalN-induced acute liver injury was reduced , illustrating the role of KC-derived HO-1 in the anti-injury effects of MF .
Collectively , MF attenuated acute liver injury induced by LPS/D-GalN via the inhibition of TNF-α production by promoting KCs to upregulate HO-1 expression .

Acute liver injury and its terminal phase, hepatic failure, trigger a series of complications, including hepatic encephalopathy, systematic inflammatory response syndrome, and multiorgan failure, with relatively high morbidity and mortality. Liver transplantation is the ultimate intervention, but the shortage of donor organs has limited clinical success. Mangiferin (MF), a xanthone glucoside, has been reported to have excellent anti-inflammatory efficacy. Here, a lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced acute liver injury mouse model was established to investigate the protective role of MF and the underlying mechanisms of action. Pretreatment with MF improved survival, decreased serum aminotransferase activities, and inhibited hepatic TNF-α production in LPS/D-GalN-challenged mice. Through Kupffer cell (KC) deletion by GdCland KC adoptive transfer, KCs were confirmed to be involved in these beneficial effects of MF. MF reduced LPS-mediated TNF-α production via the suppression of the TLR4/NF-κB signaling pathway. MF promoted HO-1 expression, but the knockdown of HO-1 prevented TNF-α inhibition, suggesting that the damage-resistance effects of HO-1 occurred via the suppression of TNF-α synthesis. When HO-1-silenced KCs were transferred to the liver with KC deletion, the protective effect of MF against LPS/D-GalN-induced acute liver injury was reduced, illustrating the role of KC-derived HO-1 in the anti-injury effects of MF. Collectively, MF attenuated acute liver injury induced by LPS/D-GalN via the inhibition of TNF-α production by promoting KCs to upregulate HO-1 expression.


greenmedinfo--2020-05-15--Mangiferin relieves lipopolysaccharide-induced injury by up-regulating miR-181a via targeting PTEN i

Mangiferin relieves lipopolysaccharide-induced injury by up-regulating miR-181a via targeting PTEN in ATDC5 cells.

Background : Mangiferin ( MF ) was reported to possess anti-inflammatory activity .
This investigation tried to probe into the underlying mechanism of MF in osteoarthritis .
Methods : ATDC5 cells were pretreated with series concentrations of MF ( 0.1 , 1 , 5 , 10 , 15 , 20μM ) for 2 h and then were exposed to lipopolysaccharide ( LPS ) ( 5 μg/ml ) for 12 h to construct the inflammatory injury model .
The cell viability , productions of pro-inflammatory cytokines and enzymes were respectively measured by employing CCK-8 assay , western blot , ELISA , @ @ @ @ @ @ @ .
miR-181a expression was altered by employing cell transfection .
Dichloro-dihydro-fluorescein diacetate ( DCFH-DA ) method was employed for detection of reactive oxygen species ( ROS ) generation .
Dual luciferase activity assay was conducted for analyzing the relationship betweenmiR-181a and PTEN .
The underlying mechanism was determined by employing western blot .
Results : High doses of MF treatment ( 15 and 20μM ) noticeably induced inflammatory injury exhibiting as increased the productions of pro-inflammatory cytokines , enzymes and ROS , activated NF-κB pathway and deactivated PTEN/PI3K/AKT pathway in ATDC5 cells .
@ @ @ @ @ @ @ inflammatory injury through deactivation of NF-κB pathway and activation of PTEN/PI3K/AKT pathway .
PTEN was a target of miR-181a .
Inhibition of miR-181a remarkably reversed MF-triggered impacts on ATDC5 cells .
Conclusion : MF attenuated LPS-induced inflammatory damage through miR-181a/PTEN axis and thereby inhibiting NF-κB pathway and activating PI3K/AKT pathway .

Background: Mangiferin (MF) was reported to possess anti-inflammatory activity. This investigation tried to probe into the underlying mechanism of MF in osteoarthritis.
Methods: ATDC5 cells were pretreated with series concentrations of MF (0.1, 1, 5, 10, 15, 20μM) for 2 h and then were exposed to lipopolysaccharide (LPS) (5 μg/ml) for 12 h to construct the inflammatory injury model. The cell viability, productions of pro-inflammatory cytokines and enzymes were respectively measured by employing CCK-8 assay, western blot, ELISA, and quantitative reverse-transcription (qRT)-PCR. miR-181a expression was altered by employing cell transfection. Dichloro-dihydro-fluorescein diacetate (DCFH-DA) method was employed for detection of reactive oxygen species (ROS) generation. Dual luciferase activity assay was conducted for analyzing the relationship betweenmiR-181a and PTEN. The underlying mechanism was determined by employing western blot.
Results: High doses of MF treatment (15 and 20μM) noticeably induced inflammatory injury exhibiting as increased the productions of pro-inflammatory cytokines, enzymes and ROS, activated NF-κB pathway and deactivated PTEN/PI3K/AKT pathway in ATDC5 cells. Besides, MF treatment notably remitted LPS-induced inflammatory injury through deactivation of NF-κB pathway and activation of PTEN/PI3K/AKT pathway. PTEN was a target of miR-181a. Inhibition of miR-181a remarkably reversed MF-triggered impacts on ATDC5 cells.
Conclusion: MF attenuated LPS-induced inflammatory damage through miR-181a/PTEN axis and thereby inhibiting NF-κB pathway and activating PI3K/AKT pathway.


greenmedinfo--2020-05-15--Mangiferin activates Nrf2 to attenuate cardiac fibrosis via redistributing glutaminolysis-derived gl

Mangiferin activates Nrf2 to attenuate cardiac fibrosis via redistributing glutaminolysis-derived glutamate.

Cardiac injury is followed by fibrosis , characterized by myofibroblast activation .
Excessive deposition of extracellular matrix ( ECM ) impairs the plasticity of myocardium and results in myocardial systolic and diastolic dysfunction .
Mangiferin is a xanthonoid derivative rich in plants mangoes and iris unguicularis , exhibiting the ability to ameliorate metabolic disorders .
This study aims to investigate whether mangiferin attenuates cardiac fibrosis via redox regulation .
The transverse aortic constriction ( TAC ) in mice induced cardiac fibrosis with impaired heart function .
Oral administration of mangiferin ( 50 mg/kg , 4 weeks ) inhibited myofibroblast activation @ @ @ @ @ @ @ impaired left ventricular contractive function was also improved by mangiferin .
TGF-β1 stimulation increased glutaminolysis to fuel intracellular glutamate pool for the increased demands of nutrients to support cardiac myofibroblast activation .
Mangiferin degraded Keap1 to promote Nrf2 protein accumulation by improving its stability , leading to Nrf2 activation .
Nrf2 transcriptionally promotes the synthesis of antioxidant proteins .
By activating Nrf2 , mangiferin promoted the synthesis of glutathione ( GSH ) in cardiac fibroblasts , likely due to the consumption of glutaminolysis-derived glutamate as a source .
Meanwhile , mangiferin promoted the @ @ @ @ @ @ @ extracellular cystine to support GSH generation .
As a result of redistribution , the reduced glutamate availability failed to support myofibroblast activation .
In support of this , the addition of extracellular glutamate or α-ketoglutarate diminished the inhibitory effects of mangiferin on cardiac myofibroblast proliferation and activation .
Moreover , cardiac knockdown of Nrf2 attenuated the cardioprotective effects of mangiferin in mice subjected to TAC .
In conclusion , we demonstrated that activated myofibroblasts were sensitive to glutamate availability .
Mangiferin activatedNrf2 and redistributed intracellular glutamate for the synthesis of GSH , consequently @ @ @ @ @ @ @ glutamate availability .
These results address that pharmacological activation of Nrf2 could restrain cardiac fibrosis via metabolic regulation .

Cardiac injury is followed by fibrosis, characterized by myofibroblast activation. Excessive deposition of extracellular matrix (ECM) impairs the plasticity of myocardium and results in myocardial systolic and diastolic dysfunction. Mangiferin is a xanthonoid derivative rich in plants mangoes and iris unguicularis, exhibiting the ability to ameliorate metabolic disorders. This study aims to investigate whether mangiferin attenuates cardiac fibrosis via redox regulation. The transverse aortic constriction (TAC) in mice induced cardiac fibrosis with impaired heart function. Oral administration of mangiferin (50 mg/kg, 4 weeks) inhibited myofibroblast activation with reduced formation of ECM. The impaired left ventricular contractive function was also improved by mangiferin. TGF-β1 stimulation increased glutaminolysis to fuel intracellular glutamate pool for the increased demands of nutrients to support cardiac myofibroblast activation. Mangiferin degraded Keap1 to promote Nrf2 protein accumulation by improving its stability, leading to Nrf2 activation. Nrf2 transcriptionally promotes the synthesis of antioxidant proteins. By activating Nrf2, mangiferin promoted the synthesis of glutathione (GSH) in cardiac fibroblasts, likely due to the consumption of glutaminolysis-derived glutamate as a source. Meanwhile, mangiferin promoted the exchange of intracellular glutamatefor the import of extracellular cystine to support GSH generation. As a result of redistribution, the reduced glutamate availability failed to support myofibroblast activation. In support of this, the addition of extracellular glutamate or α-ketoglutarate diminished the inhibitory effects of mangiferin on cardiac myofibroblast proliferation and activation. Moreover, cardiac knockdown of Nrf2 attenuated the cardioprotective effects of mangiferin in mice subjected to TAC. In conclusion, we demonstrated that activated myofibroblasts were sensitive to glutamate availability. Mangiferin activatedNrf2 and redistributed intracellular glutamate for the synthesis of GSH, consequently impairing cardiac myofibroblast activation due to decreased glutamate availability. These results address that pharmacological activation of Nrf2 could restrain cardiac fibrosis via metabolic regulation.


greenmedinfo--2020-05-15--Tomatidine may be a promising drug for osteoporosis.

BACKGROUND As a common metabolic disorder , osteoporosis is characterized by decreasing bone mass density and increased possibility of fragility fracture .
The incidence of senile osteoporosis increases year by year .
There is no gold standard of treatment for osteoporosis .
Tomatidine is the aglycone derivative of tomatine , having the ability to treat various diseases , including osteoporosis .
However , the mechanism by which tomatidine improves osteoporosis has not been fully elucidated .
Tomatidine is a potential and promising drug for osteoporosis .
MATERIAL AND METHODS In this study , the KEGG pathways that tomatidine-targeted genes enriched @ @ @ @ @ @ @ The KEGG pathways involved in osteoporosis that were also associated with tomatidine-targeted genes were selected .
After analysis of these pathways , essential genes that may be involved in this biological process were identified and validated experimentally .
RESULTS We found 110 osteoporosis related KEGG pathways and 76 tomatidine-targeted genes-related KEGG pathways were obtained .
39 shared KEGG pathways were identified .
The top 5 pathways were : pathway of chronic myeloid leukemia , pathway of B cell receptor signaling , pathway in cancer , bladder cancer pathway , and progesterone-mediated oocyte maturation @ @ @ @ @ @ @ , RAF1 were involved in all the 5 pathways .
The p53 signaling pathway and the MAPK signaling pathway were involved in the 5 KEGG pathways .
In vitro experiments showed that downregulating p53 expression could be potentially protective for osteoporosis .
CONCLUSIONS Tomatidine can improve osteoporosis , and one of the mechanisms of its action is achieved by modulating p53 .
Tomatidine may be a promising drug for osteoporosis .

BACKGROUND As a common metabolic disorder, osteoporosis is characterized by decreasing bone mass density and increased possibility of fragility fracture. The incidence of senile osteoporosis increases year by year. There is no gold standard of treatment for osteoporosis. Tomatidine is the aglycone derivative of tomatine, having the ability to treat various diseases, including osteoporosis. However, the mechanism by which tomatidine improves osteoporosis has not been fully elucidated. Tomatidine is a potential and promising drug for osteoporosis. MATERIAL AND METHODS In this study, the KEGG pathways that tomatidine-targeted genes enriched in were obtained using bioinformatics methods. The KEGG pathways involved in osteoporosis that were also associated with tomatidine-targeted genes were selected. After analysis of these pathways, essential genes that may be involved in this biological process were identified and validated experimentally. RESULTS We found 110 osteoporosis related KEGG pathways and 76 tomatidine-targeted genes-related KEGG pathways were obtained. 39 shared KEGG pathways were identified. The top 5 pathways were: pathway of chronic myeloid leukemia, pathway of B cell receptor signaling, pathway in cancer, bladder cancer pathway, and progesterone-mediated oocyte maturation pathway. MAPK1, MAP2K1, MAPK3, RAF1 were involved in all the 5 pathways. The p53 signaling pathway and the MAPK signaling pathway were involved in the 5 KEGG pathways. In vitro experiments showed that downregulating p53 expression could be potentially protective for osteoporosis. CONCLUSIONS Tomatidine can improve osteoporosis, and one of the mechanisms of its action is achieved by modulating p53. Tomatidine may be a promising drug for osteoporosis.


greenmedinfo--2020-05-15--Chemopreventive activity of Tualang honey against oral squamous cell carcinoma-in vivo.

OBJECTIVE : The aim of this study was to evaluate the chemopreventive activity of Malaysian jungle Tualang honey ( TH ) after oral carcinogenesis induced with 4-nitroquinoline 1-oxide ( 4 NQO ) .
STUDY DESIGN : A total of 28 male Sprague-Dawley ( SD ) rats were distributed into 4 groups as follows : group 1 ( nontreated group ) ; group 2 ( control ) , which received 4 NQO during 8 weeks in drinking water only ; and groups 3 and 4 , which received 4 NQO for 8 weeks in drinking water and treated with TH 1000 @ @ @ @ @ @ @ for 10 weeks .
All rats from all experiments were sacrificed after 22 weeks , and the incidence of oral neoplasms and histopathologic changes were microscopically evaluated .
Moreover , immunohistochemical expression was analyzed in tongue specimens by using image analysis software .
The expression of particular genes associated with oral cancer were assessed by using RTProfiler PCR Array ( Qiagen , Germantown , MD ) .
RESULTS : TH significantly reduced the incidence of oral squamous cell carcinoma ( OSCC ) and suppressed cancer cell proliferation via diminishing the expression of CCND1 @ @ @ @ @ @ @ , TH preserved cellular adhesion ( epithelial polarity ) through overexpression ofβ-catenin and e-cadherin and inhibited the OSCC aggressiveness by downregulating TWIST1 and RAC1 .
CONCLUSIONS : Our data suggest that TH exerts chemopreventive activity in an animal model in which oral cancer was induced by using 4 NQO .

OBJECTIVE: The aim of this study was to evaluate the chemopreventive activity of Malaysian jungle Tualang honey (TH) after oral carcinogenesis induced with 4-nitroquinoline 1-oxide (4 NQO).
STUDY DESIGN: A total of 28 male Sprague-Dawley (SD) rats were distributed into 4 groups as follows: group 1 (nontreated group); group 2 (control), which received 4 NQO during 8 weeks in drinking water only; and groups 3 and 4, which received 4 NQO for 8 weeks in drinking water and treated with TH 1000 mg/kg and 2000 mg/kg by oral gavage for 10 weeks. All rats from all experiments were sacrificed after 22 weeks, and the incidence of oral neoplasms and histopathologic changes were microscopically evaluated. Moreover, immunohistochemical expression was analyzed in tongue specimens by using image analysis software. The expression of particular genes associated with oral cancer were assessed by using RTProfiler PCR Array (Qiagen, Germantown, MD).
RESULTS: TH significantly reduced the incidence of oral squamous cell carcinoma (OSCC) and suppressed cancer cell proliferation via diminishing the expression of CCND1, EGFR, and COX-2. Furthermore, TH preserved cellular adhesion (epithelial polarity) through overexpression ofβ-catenin and e-cadherin and inhibited the OSCC aggressiveness by downregulating TWIST1 and RAC1.
CONCLUSIONS: Our data suggest that TH exerts chemopreventive activity in an animal model in which oral cancer was induced by using 4 NQO.


greenmedinfo--2020-05-15--Propolis extract has bioactivity on the wall and cell membrane of Candida albicans.

ETHNOPHARMACOLOGICAL RELEVANCE : The use of natural products such as propolis extract ( PE ) is a promising alternative when topically administered to replace conventional antifungals , mostly due to its therapeutic applications , ease of access and low toxicity .
However , despite being the subject of several mycology studies , they focus primarily on exploiting their antimicrobial activity , lacking information on the mechanisms of action of PE on Candida spp.
, characterizing its antifungal potential .
AIM OF THE STUDY : To elucidate the bioactivity of PE on the cellular structure of Candida albicans .
MATERIALS AND @ @ @ @ @ @ @ albicans clinical isolates plus a reference strain of C. albicans ATCC 90028 were used in this study .
The PE was characterized and its effect on C. albicans was determined by susceptibility and growth kinetics assays ; interference on C. albicans germination and filamentation ; evaluation of the integrity of the C. albicans cell wall and membrane , as well as its mutagenic potential .
RESULTS : The PE presented strong inhibitory activity , which showed its greatest antifungal activity at 12 h with dose and time dependent fungistatic characteristics , effectively inhibiting @ @ @ @ @ @ @ In addition , PE caused membrane and cell wall damage with intracellular content extravasation .
Moreover , PE was not mutagenic .
CONCLUSIONS : The bioactivity of PE is mainly related to the loss of integrity membrane as well as the integrity of the cell wall and consequent increase in permeability , without mutagenic effects .

ETHNOPHARMACOLOGICAL RELEVANCE: The use of natural products such as propolis extract (PE) is a promising alternative when topically administered to replace conventional antifungals, mostly due to its therapeutic applications, ease of access and low toxicity. However, despite being the subject of several mycology studies, they focus primarily on exploiting their antimicrobial activity, lacking information on the mechanisms of action of PE on Candida spp., characterizing its antifungal potential.
AIM OF THE STUDY: To elucidate the bioactivity of PE on the cellular structure of Candida albicans.
MATERIALS AND METHODS: A total of seven C. albicans clinical isolates plus a reference strain of C. albicans ATCC 90028 were used in this study. The PE was characterized and its effect on C. albicans was determined by susceptibility and growth kinetics assays; interference on C. albicans germination and filamentation; evaluation of the integrity of the C. albicans cell wall and membrane, as well as its mutagenic potential.
RESULTS: The PE presented strong inhibitory activity, which showed its greatest antifungal activity at 12 h with dose and time dependent fungistatic characteristics, effectively inhibiting and interfering on C. albicans filamentation. In addition, PE caused membrane and cell wall damage with intracellular content extravasation. Moreover, PE was not mutagenic.
CONCLUSIONS: The bioactivity of PE is mainly related to the loss of integrity membrane as well as the integrity of the cell wall and consequent increase in permeability, without mutagenic effects.


greenmedinfo--2020-05-15--Protective effect and mechanism of action of rosmarinic acid on radiation-induced parotid gland inju

Protective effect and mechanism of action of rosmarinic acid on radiation-induced parotid gland injury.

The parotid glands are damaged by oxidative stress and a series of pathophysiological changes after irradiation .
Rosmarinic acid ( RA ) is a natural antioxidant that provides a radioprotective effect against harmful damage from ionizing radiation .
The present study aims to explore the protective effects of RA on radiation-induced parotid gland injury and its underlying mechanism .
Sprague-Dawley rats were irradiated with 15 Gy X-ray and treated with different concentrations of RA ( 30 , 60 , and 120 mg/kg ) or amifostine ( AMI , 250 mg/kg ) .
Saliva secretion function , oxidative stress , apoptosis @ @ @ @ @ @ @ were determined by the measurement of the salivary flow rate , enzyme-linked immunosorbent assay , transferase-mediated DUTP Nick end labeling , Western blot , quantitative real time polymerase chain reaction , and hematoxylin and eosin staining .
Here , we show that RA treatment significantly attenuated reactive oxygen species by a direct hindrance effect and the indirect activation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha/nicotinamide adenine dinucleotide phosphate oxidase 4 signaling .
Rosmarinic acid not only reduced apoptosis by inhibiting p53/jun N-terminal kinase activation but also reduced parotid gland tissue fibrosis by downregulating @ @ @ @ @ @ @ , RA has the obvious advantages of late efficacy and convenient usage .
Moreover , 60 mg/kg is the minimum effective dose of RA .
Therefore , RA can potentially be applied as a therapeutic radioprotective agent to treat radiation-induced parotid gland injury in the future .

The parotid glands are damaged by oxidative stress and a series of pathophysiological changes after irradiation. Rosmarinic acid (RA) is a natural antioxidant that provides a radioprotective effect against harmful damage from ionizing radiation. The present study aims to explore the protective effects of RA on radiation-induced parotid gland injury and its underlying mechanism. Sprague-Dawley rats were irradiated with 15 Gy X-ray and treated with different concentrations of RA (30, 60, and 120 mg/kg) or amifostine (AMI, 250 mg/kg). Saliva secretion function, oxidative stress, apoptosis, the inflammatory response, and fibrosis were determined by the measurement of the salivary flow rate, enzyme-linked immunosorbent assay, transferase-mediated DUTP Nick end labeling, Western blot, quantitative real time polymerase chain reaction, and hematoxylin and eosin staining. Here, we show that RA treatment significantly attenuated reactive oxygen species by a direct hindrance effect and the indirect activation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha/nicotinamide adenine dinucleotide phosphate oxidase 4 signaling. Rosmarinic acid not only reduced apoptosis by inhibiting p53/jun N-terminal kinase activation but also reduced parotid gland tissue fibrosis by downregulating inflammatory factor levels. Compared to AMI, RA has the obvious advantages of late efficacy and convenient usage. Moreover, 60 mg/kg is the minimum effective dose of RA. Therefore, RA can potentially be applied as a therapeutic radioprotective agent to treat radiation-induced parotid gland injury in the future.


greenmedinfo--2020-05-16--Your iPhone May Emit Over Two Times the Legal RF Radiation Limits

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By providing the information contained herein we are not diagnosing , treating @ @ @ @ @ or preventing any type of disease or medical condition .
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--2020-05-16--10 Cognitive Benefits of Astaxanthin and Lutein


greenmedinfo--2020-05-16--The results reported here are very promising and indicate that CBD-enriched cannabis extract may ame

The results reported here are very promising and indicate that CBD-enriched cannabis extract may ameliorate multiple autism spectrum disorders symptoms.

Autism Spectrum Disorders comprise conditions that may affect cognitive development , motor skills , social interaction , communication , and behavior .
This set of functional deficits often results in lack of independence for the diagnosed individuals , and severe distress for patients , families , and caregivers .
There is a mounting body of evidence indicating the effectiveness of pure cannabidiol ( CBD ) and CBD-enrichedextract ( CE ) for the treatment of autistic symptoms in refractory epilepsy patients .
There is also increasing data support for the hypothesis that non-epileptic autism shares underlying etiological mechanisms with epilepsy .
@ @ @ @ @ @ @ a cohort of 18 autistic patients undergoing treatment with compassionate use of standardized CBD-enriched CE ( with a CBD to THC ratio of 75/1 ) .
Among the 15 patients who adhered to the treatment ( 10 non-epileptic and five epileptic ) only one patient showed lack of improvement in autistic symptoms .
Due to adverse effects , three patients discontinued CE use before 1 month .
After 6-9 months of treatment , most patients , including epileptic and non-epileptic , showed some level of improvement in more than one of the eight @ @ @ @ @ @ @ ; Behavioral Disorders ; Motor Deficits ; Autonomy Deficits ; Communication and Social Interaction Deficits ; Cognitive Deficits ; Sleep Disorders and Seizures , with very infrequent and mild adverse effects .
The strongest improvements were reported for Seizures , Attention Deficit/Hyperactivity Disorder , Sleep Disorders , and Communication and Social Interaction Deficits .
This was especially true for the 10 non-epileptic patients , nine of which presented improvement equal to or above 30 % in at least one of the eight categories , six presented improvement of 30 % or more in @ @ @ @ @ @ @ improvement equal to or above 30 % in at least four symptom categories .
Ten out of the 15 patients were using other medicines , and nine of these were able to keep the improvements even after reducing or withdrawing other medications .
The results reported here are very promising and indicate that CBD-enriched CE may ameliorate multiple ASD symptoms even in non-epileptic patients , with substantial increase in life quality for both ASD patients and caretakers .

Autism Spectrum Disorders comprise conditions that may affect cognitive development, motor skills, social interaction, communication, and behavior. This set of functional deficits often results in lack of independence for the diagnosed individuals, and severe distress for patients, families, and caregivers. There is a mounting body of evidence indicating the effectiveness of pure cannabidiol (CBD) and CBD-enrichedextract (CE) for the treatment of autistic symptoms in refractory epilepsy patients. There is also increasing data support for the hypothesis that non-epileptic autism shares underlying etiological mechanisms with epilepsy. Here we report an observational study with a cohort of 18 autistic patients undergoing treatment with compassionate use of standardized CBD-enriched CE (with a CBD to THC ratio of 75/1). Among the 15 patients who adhered to the treatment (10 non-epileptic and five epileptic) only one patient showed lack of improvement in autistic symptoms. Due to adverse effects, three patients discontinued CE use before 1 month. After 6-9 months of treatment, most patients, including epileptic and non-epileptic, showed some level of improvement in more than one of the eight symptom categories evaluated: Attention Deficit/Hyperactivity Disorder; Behavioral Disorders; Motor Deficits; Autonomy Deficits; Communication and Social Interaction Deficits; Cognitive Deficits; Sleep Disorders and Seizures, with very infrequent and mild adverse effects. The strongest improvements were reported for Seizures, Attention Deficit/Hyperactivity Disorder, Sleep Disorders, and Communication and Social Interaction Deficits. This was especially true for the 10 non-epileptic patients, nine of which presented improvement equal to or above 30% in at least one of the eight categories, six presented improvement of 30% or more in at least two categories and four presented improvement equal to or above 30% in at least four symptom categories. Ten out of the 15 patients were using other medicines, and nine of these were able to keep the improvements even after reducing or withdrawing other medications. The results reported here are very promising and indicate that CBD-enriched CE may ameliorate multiple ASD symptoms even in non-epileptic patients, with substantial increase in life quality for both ASD patients and caretakers.


greenmedinfo--2020-05-16--Blaylock: Face Masks Pose Serious Risks to the Healthy


greenmedinfo--2020-05-16--CBD loaded microparticles as a potential formulation to improve paclitaxel and doxorubicin-based che

CBD loaded microparticles as a potential formulation to improve paclitaxel and doxorubicin-based chemotherapy in breast cancer.

Cannabidiol ( CBD ) has emerged as a potential agent for breast cancer management .
In this work , the @ @ @ @ @ solution ( CBD ) and encapsulated in polymeric microparticles when combined with paclitaxel ( PTX @ @ @ @ @ ) in breast cancer treatment has been evaluated for the first time using MCF-7 and @ @ @ @ @ previously administered at suboptimal concentrations ( cell death

Cannabidiol (CBD) has emerged as a potential agent for breast cancer management. In this work, the potential use of cannabidiol in solution (CBD) and encapsulated in polymeric microparticles when combined with paclitaxel (PTX) and doxorubicin (DOX) in breast cancer treatment has been evaluated for the first time using MCF-7 and MDA-MB-231 cells. CBD, previously administered at suboptimal concentrations (cell death < 10%), enhanced the PTX and DOX effect in both breast cancer cells. The co-administration of CBDand PTX or DOX showed a synergistic effect. PLGA-502 was selected as the most suitable polymer to develop CBD-loaded microparticles. The developed formulation (CBD-Mps) was effective as monotherapy, showing extended antiproliferative activity for at least 10 days, and when combined with PTX or DOX. In fact, the use of CBD-Mps allows the combination of both, pre and co-administration strategies, with a single administration, also showing a significant increase in PTX and DOX antiproliferative activity. Finally, the anticancer effect of both CBDand CBD-Mps as monotherapy or in combination with PTX was also confirmed in ovo, usingMDA-MB-231-derived tumours. This data evidences the promising inclusion of CBD in conventional breast cancer chemotherapy and the use of CBD-Mps for the extended release of this cannabinoid, optimising the effect of the chemotherapeutic agents.


greenmedinfo--2020-05-16--Dr. Blaylock: Face Masks Pose Serious Risks to the Healthy

Dr. Russell Blaylock warns that not only do face masks fail to protect the healthy from getting sick , but they also create serious health risks to the wearer .
The bottom line is that if you are not sick , you should not wear a face mask .
As businesses reopen , many are requiring shoppers and employees to wear a face mask .
Costco , for instance , will not allow shoppers into the store without wearing a face mask .
Many employers are requiring all employees to wear a face mask while at work .
In some @ @ @ @ @ @ @ face mask if they are outside of their own home .
⁃ TN Editor With the advent of the so-called COVID-19 pandemic , we have seen a number of medical practices that have little or no scientific support as regards reducing the spread of this infection .
One of these measures is the wearing of facial masks , either a surgical-type mask , bandana or N95 respirator mask .
When this pandemic began and we knew little about the virus itself or its epidemiologic behavior , it was assumed that it would behave @ @ @ @ @ @ @ , like other respiratory viruses .
Little has presented itself after intense study of this virus and its behavior to change this perception .
This is somewhat of an unusual virus in that for the vast majority of people infected by the virus , one experiences either no illness ( asymptomatic ) or very little sickness .
Only a very small number of people are at risk of a potentially serious outcome from the infection -- mainly those with underlying serious medical conditions in conjunction with advanced age and frailty , those with @ @ @ @ @ @ @ near the end of their lives .
There is growing evidence that the treatment protocol issued to treating doctors by the Center for Disease Control and Prevention ( CDC ) , mainly intubation and use of a ventilator ( respirator ) , may have contributed significantly to the high death rate in these select individuals .
As for the scientific support for the use of face mask , a recent careful examination of the literature , in which 17 of the best studies were analyzed , concluded that , `` None of the @ @ @ @ @ @ @ use and protection against influenza infection .
`` 1 Keep in mind , no studies have been done to demonstrate that either a cloth mask or the N95 mask has any effect on transmission of the COVID-19 virus .
Any recommendations , therefore , have to be based on studies of influenza virus transmission .
And , as you have seen , there is no conclusive evidence of their efficiency in controlling flu virus transmission .
It is also instructive to know that until recently , the CDC did not recommend wearing a @ @ @ @ @ @ @ , unless a person was known to be infected , that is , until recently .
Non-infected people need not wear a mask .
When a person has TB we have them wear a mask , not the entire community of non-infected .
The recommendations by the CDC and the WHO are not based on any studies of this virus and have never been used to contain any other virus pandemic or epidemic in history .
Now that we have established that there is no scientific evidence necessitating the wearing of a face @ @ @ @ @ @ @ to wearing a face mask , especially for long periods ?
Several studies have indeed found significant problems with wearing such a mask .
This can vary from headaches , to increased airway resistance , carbon dioxide accumulation , to hypoxia , all the way to serious life-threatening complications .
There is a difference between the N95 respirator mask and the surgical mask ( cloth or paper mask ) in terms of side effects .
The N95 mask , which filters out 95 % of particles with a median diameter > 0.3 µm2 @ @ @ @ @ @ @ breathing ) to a greater degree than a soft mask , and is more often associated with headaches .
In one such study , researchers surveyed 212 healthcare workers ( 47 males and 165 females ) asking about presence of headaches with N95 mask use , duration of the headaches , type of headaches and if the person had preexisting headaches.2 They found that about a third of the workers developed headaches with use of the mask , most had preexisting headaches that were worsened by the mask wearing , and 60 % @ @ @ @ @ @ @ to the cause of the headaches , while straps and pressure from the mask could be causative , the bulk of the evidence points toward hypoxia and/or hypercapnia as the cause .
That is , a reduction in blood oxygenation ( hypoxia ) or an elevation in blood C02 ( hypercapnia ) .
It is known that the N95 mask , if worn for hours , can reduce blood oxygenation as much as 20 % , which can lead to a loss of consciousness , as happened to the hapless fellow driving around @ @ @ @ @ @ @ mask , causing him to pass out , and to crash his car and sustain injuries .
I am sure that we have several cases of elderly individuals or any person with poor lung function passing out , hitting their head .
This , of course , can lead to death .
A more recent study involving 159 healthcare workers aged 21 to 35 years of age found that 81 % developed headaches from wearing a face mask.3 Some had pre-existing headaches that were precipitated by the masks .
All felt like the @ @ @ @ @ @ @ , no one is telling the frail elderly and those with lung diseases , such as COPD , emphysema or pulmonary fibrosis , of these dangers when wearing a facial mask of any kind -- which can cause a severe worsening of lung function .
This also includes lung cancer patients and people having had lung surgery , especially with partial resection or even the removal of a whole lung .
While most agree that the N95 mask can cause significant hypoxia and hypercapnia , another study of surgical masks found significant reductions @ @ @ @ @ @ @ this study , researchers examined the blood oxygen levels in 53 surgeons using an oximeter .
They measured blood oxygenation before surgery as well as at the end of surgeries.4 The researchers found that the mask reduced the blood oxygen levels ( pa02 ) significantly .
The longer the duration of wearing the mask , the greater the fall in blood oxygen levels .
The importance of these findings is that a drop in oxygen levels ( hypoxia ) is associated with an impairment in immunity .
Studies have shown that hypoxia can @ @ @ @ @ @ @ used to fight viral infections called the CD4+ T-lymphocyte .
This occurs because the hypoxia increases the level of a compound called hypoxia inducible factor-1 ( HIF-1 ) , which inhibits T-lymphocytes and stimulates a powerful immune inhibitor cell called the Tregs .
.
This sets the stage for contracting any infection , including COVID-19 and making the consequences of that infection much graver .
In essence , your mask may very well put you at an increased risk of infections and if so , having a much worse outcome.5,6,7 People with cancer @ @ @ @ @ @ @ , will be at a further risk from prolonged hypoxia as the cancer grows best in a microenvironment that is low in oxygen .
Low oxygen also promotes inflammation which can promote the growth , invasion and spread of cancers.8,9 Repeated episodes of hypoxia has been proposed as a significant factor in atherosclerosis and hence increases all cardiovascular ( heart attacks ) and cerebrovascular ( strokes ) diseases.10 There is another danger to wearing these masks on a daily basis , especially if worn for several hours .
When a person is infected @ @ @ @ @ @ @ expel some of the virus with each breath .
If they are wearing a mask , especially an N95 mask or other tightly fitting mask , they will be constantly rebreathing the viruses , raising the concentration of the virus in the lungs and the nasal passages .
We know that people who have the worst reactions to the coronavirus have the highest concentrations of the virus early on .
And this leads to the deadly cytokine storm in a selected number .
It gets even more frightening .
Newer evidence suggests that @ @ @ @ @ @ @ the brain.11,12 In most instances it enters the brain by way of the olfactory nerves ( smell nerves ) , which connect directly with the area of the brain dealing with recent memory and memory consolidation .
By wearing a mask , the exhaled viruses will not be able to escape and will concentrate in the nasal passages , enter the olfactory nerves and travel into the brain.13 It is evident from this review that there is insufficient evidence that wearing a mask of any kind can have a significant impact in preventing @ @ @ @ @ @ @ fact that this virus is a relatively benign infection for the vast majority of the population and that most of the at-risk group also survive , from an infectious disease and epidemiological standpoint , by letting the virus spread through the healthier population we will reach a herd immunity level rather quickly that will end this pandemic quickly and prevent a return next winter .
During this time , we need to protect the at-risk population by avoiding close contact , boosting their immunity with compounds that boost cellular immunity and in general @ @ @ @ @ @ @ not attack and insult those who have chosen not to wear a mask , as these studies suggest that is the wise choice to make .
[ For additional research questioning the value of face masks read : FACE IT : The Evidence Proving the Effectiveness of Community Mask Wearing Does n't Exist ; The WHO Agrees .
For information that challenges the dominant narrative about COVID-19 use the resource : www.QuestioningCovid.com ] 1. bin-Reza F et al .
The use of mask and respirators to prevent transmission of influenza : A systematic @ @ @ @ @ @ @ Viruses 2012 ; 6 ( 4 ) :257-67 .
2 .
Zhu JH et al .
Effects of long-duration wearing of N95 respirator and surgical facemask : a pilot study .
J Lung Pulm Resp Res 2014:4:97-100 .
3 .
Ong JJY et al .
Headaches associated with personal protective equipment- A cross-sectional study among frontline healthcare workers during COVID-19 .
Headache 2020 ; 60 ( 5 ) :864-877 .
4 .
Bader A et al .
Preliminary report on surgical mask induced deoxygenation during major surgery .
Neurocirugia 2008 ; 19:12-126 .
@ @ @ @ @ @ @ Hypoxia enhances immunosuppression by inhibiting CD4+ effector T cell function and promoting Treg activity .
Cell Physiol Biochem 2017 ; 41:1271-84 .
7 .
Sceneay J et al .
Hypoxia-driven immunosuppression contributes to the pre-metastatic niche .
Oncoimmunology 2013 ; 2:1 e22355 .
11 .
Baig AM et al .
Evidence of the COVID-19 virus targeting the CNS : Tissue distribution , host-virus interaction , and proposed neurotropic mechanisms .
ACS Chem Neurosci 2020 ; 11:7:995-998 .
12 .
Wu Y et al .
Nervous system involvement after infection with COVID-19 and other @ @ @ @ @ @ @ , In press .
13 .
Perlman S et al .
Spread of a neurotropic murine coronavirus into the CNS via the trigeminal and olfactory nerves .
Virology 1989 ; 170:556-560 .

Originally published on www.technocracy.news
Dr. Russell Blaylock warns that not only do face masks fail to protect the healthy from getting sick, but they also create serious health risks to the wearer. The bottom line is that if you are not sick, you should not wear a face mask. As businesses reopen, many are requiring shoppers and employees to wear a face mask. Costco, for instance, will not allow shoppers into the store without wearing a face mask. Many employers are requiring all employees to wear a face mask while at work. In some jurisdictions, all citizens must wear a face mask if they are outside of their own home. ⁃ TN Editor
With the advent of the so-called COVID-19 pandemic, we have seen a number of medical practices that have little or no scientific support as regards reducing the spread of this infection. One of these measures is the wearing of facial masks, either a surgical-type mask, bandana or N95 respirator mask. When this pandemic began and we knew little about the virus itself or its epidemiologic behavior, it was assumed that it would behave, in terms of spread among communities, like other respiratory viruses. Little has presented itself after intense study of this virus and its behavior to change this perception.
This is somewhat of an unusual virus in that for the vast majority of people infected by the virus, one experiences either no illness (asymptomatic) or very little sickness. Only a very small number of people are at risk of a potentially serious outcome from the infection--mainly those with underlying serious medical conditions in conjunction with advanced age and frailty, those with immune compromising conditions and nursing home patients near the end of their lives. There is growing evidence that the treatment protocol issued to treating doctors by the Center for Disease Control and Prevention (CDC), mainly intubation and use of a ventilator (respirator), may have contributed significantly to the high death rate in these select individuals.
By wearing a mask, the exhaled viruses will not be able to escape and will concentrate in the nasal passages, enter the olfactory nerves and travel into the brain. Russell Blaylock, MD
As for the scientific support for the use of face mask, a recent careful examination of the literature, in which 17 of the best studies were analyzed, concluded that, "None of the studies established a conclusive relationship between mask/respirator use and protection against influenza infection."1 Keep in mind, no studies have been done to demonstrate that either a cloth mask or the N95 mask has any effect on transmission of the COVID-19 virus. Any recommendations, therefore, have to be based on studies of influenza virus transmission. And, as you have seen, there is no conclusive evidence of their efficiency in controlling flu virus transmission.
It is also instructive to know that until recently, the CDC did not recommend wearing a face mask or covering of any kind, unless a person was known to be infected, that is, until recently. Non-infected people need not wear a mask. When a person has TB we have them wear a mask, not the entire community of non-infected. The recommendations by the CDC and the WHO are not based on any studies of this virus and have never been used to contain any other virus pandemic or epidemic in history.
Now that we have established that there is no scientific evidence necessitating the wearing of a face mask for prevention, are there dangers to wearing a face mask, especially for long periods? Several studies have indeed found significant problems with wearing such a mask. This can vary from headaches, to increased airway resistance, carbon dioxide accumulation, to hypoxia, all the way to serious life-threatening complications.
There is a difference between the N95 respirator mask and the surgical mask (cloth or paper mask) in terms of side effects. The N95 mask, which filters out 95% of particles with a median diameter >0.3 µm2 , because it impairs respiratory exchange (breathing) to a greater degree than a soft mask, and is more often associated with headaches. In one such study, researchers surveyed 212 healthcare workers (47 males and 165 females) asking about presence of headaches with N95 mask use, duration of the headaches, type of headaches and if the person had preexisting headaches.2
They found that about a third of the workers developed headaches with use of the mask, most had preexisting headaches that were worsened by the mask wearing, and 60% required pain medications for relief. As to the cause of the headaches, while straps and pressure from the mask could be causative, the bulk of the evidence points toward hypoxia and/or hypercapnia as the cause. That is, a reduction in blood oxygenation (hypoxia) or an elevation in blood C02 (hypercapnia). It is known that the N95 mask, if worn for hours, can reduce blood oxygenation as much as 20%, which can lead to a loss of consciousness, as happened to the hapless fellow driving around alone in his car wearing an N95 mask, causing him to pass out, and to crash his car and sustain injuries. I am sure that we have several cases of elderly individuals or any person with poor lung function passing out, hitting their head. This, of course, can lead to death.
A more recent study involving 159 healthcare workers aged 21 to 35 years of age found that 81% developed headaches from wearing a face mask.3 Some had pre-existing headaches that were precipitated by the masks. All felt like the headaches affected their work performance.
Unfortunately, no one is telling the frail elderly and those with lung diseases, such as COPD, emphysema or pulmonary fibrosis, of these dangers when wearing a facial mask of any kind--which can cause a severe worsening of lung function. This also includes lung cancer patients and people having had lung surgery, especially with partial resection or even the removal of a whole lung.
While most agree that the N95 mask can cause significant hypoxia and hypercapnia, another study of surgical masks found significant reductions in blood oxygen as well. In this study, researchers examined the blood oxygen levels in 53 surgeons using an oximeter. They measured blood oxygenation before surgery as well as at the end of surgeries.4 The researchers found that the mask reduced the blood oxygen levels (pa02) significantly. The longer the duration of wearing the mask, the greater the fall in blood oxygen levels.
The importance of these findings is that a drop in oxygen levels (hypoxia) is associated with an impairment in immunity. Studies have shown that hypoxia can inhibit the type of main immune cells used to fight viral infections called the CD4+ T-lymphocyte. This occurs because the hypoxia increases the level of a compound called hypoxia inducible factor-1 (HIF-1), which inhibits T-lymphocytes and stimulates a powerful immune inhibitor cell called the Tregs. . This sets the stage for contracting any infection, including COVID-19 and making the consequences of that infection much graver. In essence, your mask may very well put you at an increased risk of infections and if so, having a much worse outcome.5,6,7
People with cancer, especially if the cancer has spread, will be at a further risk from prolonged hypoxia as the cancer grows best in a microenvironment that is low in oxygen. Low oxygen also promotes inflammation which can promote the growth, invasion and spread of cancers.8,9 Repeated episodes of hypoxia has been proposed as a significant factor in atherosclerosis and hence increases all cardiovascular (heart attacks) and cerebrovascular (strokes) diseases.10
There is another danger to wearing these masks on a daily basis, especially if worn for several hours. When a person is infected with a respiratory virus, they will expel some of the virus with each breath. If they are wearing a mask, especially an N95 mask or other tightly fitting mask, they will be constantly rebreathing the viruses, raising the concentration of the virus in the lungs and the nasal passages. We know that people who have the worst reactions to the coronavirus have the highest concentrations of the virus early on. And this leads to the deadly cytokine storm in a selected number.
It gets even more frightening. Newer evidence suggests that in some cases the virus can enter the brain.11,12 In most instances it enters the brain by way of the olfactory nerves (smell nerves), which connect directly with the area of the brain dealing with recent memory and memory consolidation. By wearing a mask, the exhaled viruses will not be able to escape and will concentrate in the nasal passages, enter the olfactory nerves and travel into the brain.13
It is evident from this review that there is insufficient evidence that wearing a mask of any kind can have a significant impact in preventing the spread of this virus. The fact that this virus is a relatively benign infection for the vast majority of the population and that most of the at-risk group also survive, from an infectious disease and epidemiological standpoint, by letting the virus spread through the healthier population we will reach a herd immunity level rather quickly that will end this pandemic quickly and prevent a return next winter. During this time, we need to protect the at-risk population by avoiding close contact, boosting their immunity with compounds that boost cellular immunity and in general, care for them.
One should not attack and insult those who have chosen not to wear a mask, as these studies suggest that is the wise choice to make.
[For additional research questioning the value of face masks read: FACE IT: The Evidence Proving the Effectiveness of Community Mask Wearing Doesn't Exist; The WHO Agrees. For information that challenges the dominant narrative about COVID-19 use the resource: www.QuestioningCovid.com]
The decision to wear a mask is highly personal and should not be universally mandated; measures that are meant to protect the community are ineffective if they hurt individuals in that community. Please email and tweet your state and local officials now and urge them to do their part to make sure that mask-wearing is voluntary, not mandatory.
TAKE ACTION NOW
References
1. bin-Reza F et al. The use of mask and respirators to prevent transmission of influenza: A systematic review of the scientific evidence. Resp Viruses 2012;6(4):257-67.
2. Zhu JH et al. Effects of long-duration wearing of N95 respirator and surgical facemask: a pilot study. J Lung Pulm Resp Res 2014:4:97-100.
3. Ong JJY et al. Headaches associated with personal protective equipment- A cross-sectional study among frontline healthcare workers during COVID-19. Headache 2020;60(5):864-877.
4. Bader A et al. Preliminary report on surgical mask induced deoxygenation during major surgery. Neurocirugia 2008;19:12-126.
5. Shehade H et al. Cutting edge: Hypoxia-Inducible Factor-1 negatively regulates Th1 function. J Immunol 2015;195:1372-1376.
6. Westendorf AM et al. Hypoxia enhances immunosuppression by inhibiting CD4+ effector T cell function and promoting Treg activity. Cell Physiol Biochem 2017;41:1271-84.
7. Sceneay J et al. Hypoxia-driven immunosuppression contributes to the pre-metastatic niche. Oncoimmunology 2013;2:1 e22355.
8. Blaylock RL. Immunoexcitatory mechanisms in glioma proliferation, invasion and occasional metastasis. Surg Neurol Inter 2013;4:15.
9. Aggarwal BB. Nucler factor-kappaB: The enemy within. Cancer Cell 2004;6:203-208.
10. Savransky V et al. Chronic intermittent hypoxia induces atherosclerosis. Am J Resp Crit Care Med 2007;175:1290-1297.
11. Baig AM et al. Evidence of the COVID-19 virus targeting the CNS: Tissue distribution, host-virus interaction, and proposed neurotropic mechanisms. ACS Chem Neurosci 2020;11:7:995-998.
12. Wu Y et al. Nervous system involvement after infection with COVID-19 and other coronaviruses. Brain Behavior, and Immunity, In press.
13. Perlman S et al. Spread of a neurotropic murine coronavirus into the CNS via the trigeminal and olfactory nerves. Virology 1989;170:556-560.


greenmedinfo--2020-05-16--Cannabidiol attenuates behavioral changes in a rodent model of schizophrenia through 5-HT1A, but not

Cannabidiol attenuates behavioral changes in a rodent model of schizophrenia through 5-HT1A, but not CB1 and CB2 receptors.

Preclinical and clinical data indicate that cannabidiol ( CBD ) , a non-psychotomimetic compound from the Cannabis sativa plant , can induce antipsychotic-like effects .
In an animal model of schizophrenia based on the antagonism of NMDA receptors , the behavioral and molecular changes induced by repeated treatment with the NMDA receptor antagonist MK-801 were prevented when CBD was co-administered with MK-801 .
It is unknown , however , if CBD would reverse these changes once they have been established .
Thus , in the present study we used male C57BL/6J mice , 6 weeks old , to evaluate whether @ @ @ @ @ @ @ starting after the end of the repeated treatment with MK-801 for 14 days , would reverse MK-801-induced deficits in the social interaction ( SI ) and novel object recognition ( NOR ) tests , which have been used to investigate the negative and cognitive symptoms of schizophrenia , respectively .
We also assessed whether CBD effects would be blocked by pretreatment with AM251 , a CB1 receptor antagonist , AM630 , a CB2 receptor antagonist , or WAY100635 , a 5-HT1A receptor antagonist .
CBD and the second-generation antipsychotic clozapine , used as @ @ @ @ @ @ @ in the SI and NOR tests induced by repeated administered MK-801 .
CBD effects were blocked by WAY100635 , but not by AM251 or AM630 .
These data suggest that CBD induces antipsychotic-like effects by activating 5-HT1A receptors and indicate that this compound could be an interesting alternative for the treatment of negative and cognitive symptoms of schizophrenia .

Preclinical and clinical data indicate that cannabidiol (CBD), a non-psychotomimetic compound from the Cannabis sativa plant, can induce antipsychotic-like effects. In an animal model of schizophrenia based on the antagonism of NMDA receptors, the behavioral and molecular changes induced by repeated treatment with the NMDA receptor antagonist MK-801 were prevented when CBD was co-administered with MK-801. It is unknown, however, if CBD would reverse these changes once they have been established. Thus, in the present study we used male C57BL/6J mice, 6 weeks old, to evaluate whether daily CBD injection for seven days, starting after the end of the repeated treatment with MK-801 for 14 days, would reverse MK-801-induced deficits in the social interaction (SI) and novel object recognition (NOR) tests, which have been used to investigate the negative and cognitive symptoms of schizophrenia, respectively. We also assessed whether CBD effects would be blocked by pretreatment with AM251, a CB1 receptor antagonist, AM630, a CB2 receptor antagonist, or WAY100635, a 5-HT1A receptor antagonist. CBD and the second-generation antipsychotic clozapine, used as a positive control, attenuated the impairments in the SI and NOR tests induced by repeated administered MK-801. CBD effects were blocked by WAY100635, but not by AM251 or AM630. These data suggest that CBD induces antipsychotic-like effects by activating 5-HT1A receptors and indicate that this compound could be an interesting alternative for the treatment of negative and cognitive symptoms of schizophrenia.


greenmedinfo--2020-05-16--CBD reverts the mesenchymal invasive phenotype of breast cancer cells induced by the inflammatory cy

CBD reverts the mesenchymal invasive phenotype of breast cancer cells induced by the inflammatory cytokine IL-1β.

Cannabidiol ( CBD ) has been used to treat a variety of cancers and inflammatory conditions with controversial results .
In previous work , we have shown that breast cancer MCF-7 cells , selected by their response to inflammatory IL-1β cytokine , acquire a malignant phenotype ( 6D cells ) through an epithelial-mesenchymal transition ( EMT ) .
We evaluated CBD as a potential inhibitor of this transition and inducer of reversion to a non-invasive phenotype .
It decreased 6D cell viability , downregulating expression of receptor CB1 .
TheCBD blocked migration and progression of the IL-1β-induced signaling pathway IL-1β/IL-1RI/β-catenin @ @ @ @ @ @ @ reestablished the epithelial organization lost by dispersion of the cells and re-localized E-cadherin and β-catenin at the adherens junctions .
It also prevented β-catenin nuclear translocation and decreased over-expression of genes for ∆Np63α , BIRC3 , and ID1 proteins , induced by IL-1β for acquisition of malignant features .
Cannabidiol inhibited the protein kinase B ( AKT ) activation , a crucial effector in the IL-1β/IL-1RI/β-catenin pathway , indicating that at this point there is crosstalk between IL-1β and CBD signaling which results in phenotype reversion .
Our 6D cell system allowed step-by-step @ @ @ @ @ @ @ understanding of mechanisms by which CBD blocks and reverts the effects of inflammatory IL-1β in the EMT .

Cannabidiol (CBD) has been used to treat a variety of cancers and inflammatory conditions with controversial results. In previous work, we have shown that breast cancer MCF-7 cells, selected by their response to inflammatory IL-1β cytokine, acquire a malignant phenotype (6D cells) through an epithelial-mesenchymal transition (EMT). We evaluated CBD as a potential inhibitor of this transition and inducer of reversion to a non-invasive phenotype. It decreased 6D cell viability, downregulating expression of receptor CB1. TheCBD blocked migration and progression of the IL-1β-induced signaling pathway IL-1β/IL-1RI/β-catenin, the driver of EMT. Cannabidiol reestablished the epithelial organization lost by dispersion of the cells and re-localized E-cadherin and β-catenin at the adherens junctions. It also prevented β-catenin nuclear translocation and decreased over-expression of genes for ∆Np63α, BIRC3, and ID1 proteins, induced by IL-1β for acquisition of malignant features. Cannabidiol inhibited the protein kinase B (AKT) activation, a crucial effector in the IL-1β/IL-1RI/β-catenin pathway, indicating that at this point there is crosstalk between IL-1β and CBD signaling which results in phenotype reversion. Our 6D cell system allowed step-by-step analysis of the phenotype transition and better understanding of mechanisms by which CBD blocks and reverts the effects of inflammatory IL-1β in the EMT.


greenmedinfo--2020-05-16--Cannabidiol: A brief review of its therapeutic and pharmacologic efficacy in the management of joint

Cannabidiol: A brief review of its therapeutic and pharmacologic efficacy in the management of joint disease.

Cannabis use in the management of musculoskeletal diseases has gained advocacy since several states have legalized its recreational use .
Cannabidiol ( CBD ) , a commercially available , non-neurotropic marijuana constituent , has shown promise in arthritic animal models by attenuating pro-inflammatory immune responses .
Additional research has demonstrated the benefit of CBD in decreasing the endogenous pain response in mice subjected to acute arthritic conditions , and further studies have highlighted improved fracture healing following CBD use in murine mid-femoral fractures .
However , there is a lack of high-quality , novel research investigating the use of CBD @ @ @ @ @ @ @ accounts and retrospective reviews , perhaps due to legal ramifications limiting the enrollment of patients .
The purpose of this review article is to highlight the extent of current research on CBD and its biochemical and pharmacologic efficacy in the treatment of joint disease , as well as the evidence for use of CBD and cannabis in patients undergoing joint arthroplasty .
Based on available literature relying on retrospective data and case reports , it is challenging to propose a recommendation for CBD usein perioperative pain management .
Additionally , a number of @ @ @ @ @ @ @ different methods of administration , and it is important to remember that these products are non-pharmaceuticals .
However , given the increased social relevance of CBD and cannabis-based medicines , future , prospective controlled studies evaluating their efficacy are needed .

Cannabis use in the management of musculoskeletal diseases has gained advocacy since several states have legalized its recreational use. Cannabidiol (CBD), a commercially available, non-neurotropic marijuana constituent, has shown promise in arthritic animal models by attenuating pro-inflammatory immune responses. Additional research has demonstrated the benefit of CBD in decreasing the endogenous pain response in mice subjected to acute arthritic conditions, and further studies have highlighted improved fracture healing following CBD use in murine mid-femoral fractures. However, there is a lack of high-quality, novel research investigating the use of CBD in human musculoskeletal diseases aside from anecdotal accounts and retrospective reviews, perhaps due to legal ramifications limiting the enrollment of patients. The purpose of this review article is to highlight the extent of current research on CBD and its biochemical and pharmacologic efficacy in the treatment of joint disease, as well as the evidence for use of CBD and cannabis in patients undergoing joint arthroplasty. Based on available literature relying on retrospective data and case reports, it is challenging to propose a recommendation for CBD usein perioperative pain management. Additionally, a number of CBD products currently available as supplements with different methods of administration, and it is important to remember that these products are non-pharmaceuticals. However, given the increased social relevance of CBD and cannabis-based medicines, future, prospective controlled studies evaluating their efficacy are needed.


greenmedinfo--2020-05-16--Cannabidiol and other non-psychoactive cannabinoids for prevention and treatment of gastrointestinal

Cannabidiol and other non-psychoactive cannabinoids for prevention and treatment of gastrointestinal disorders.

is an aromatic annual flowering plant with several botanical varieties , used for different purposes , like the production of fibers , the production of oil from the seeds , and especially for recreational or medical purposes .
Phytocannabinoids ( terpenophenolic compounds derived from the plant ) , include the well-known psychoactive cannabinoidΔ-tetrahydrocannabinol , and many non-psychoactive cannabinoids , like cannabidiol .
The endocannabinoid system ( ECS ) comprises of endocannabinoid ligands , enzymes for synthesis and degradation of such ligands , and receptors .
This system is widely distributed in the gastrointestinal tract , where phytocannabinoids exert potent effects @ @ @ @ @ @ @ inflammatory ) conditions .
Herein , we will first look at the hemp plant as a possible source of new functional food ingredients and nutraceuticals that might be eventually useful to treat or even prevent gastrointestinal conditions .
Subsequently , we will briefly describe the ECS and the general pharmacology of phytocannabinoids .
Finally , we will revise the available data showing that non-psychoactive phytocannabinoids , particularly cannabidiol , may be useful to treat different disorders and diseases of the gastrointestinal tract .
With the increasing interest in the development of functional foods @ @ @ @ @ @ @ phytocannabinoids are hoped to find a place as nutraceuticals and food ingredients also for a healthy gastrointestinal tract function .

is an aromatic annual flowering plant with several botanical varieties, used for different purposes, like the production of fibers, the production of oil from the seeds, and especially for recreational or medical purposes. Phytocannabinoids (terpenophenolic compounds derived from the plant), include the well-known psychoactive cannabinoidΔ-tetrahydrocannabinol, and many non-psychoactive cannabinoids, like cannabidiol. The endocannabinoid system (ECS) comprises of endocannabinoid ligands, enzymes for synthesis and degradation of such ligands, and receptors. This system is widely distributed in the gastrointestinal tract, where phytocannabinoids exert potent effects, particularly under pathological (i.e., inflammatory) conditions. Herein, we will first look at the hemp plant as a possible source of new functional food ingredients and nutraceuticals that might be eventually useful to treat or even prevent gastrointestinal conditions. Subsequently, we will briefly describe the ECS and the general pharmacology of phytocannabinoids. Finally, we will revise the available data showing that non-psychoactive phytocannabinoids, particularly cannabidiol, may be useful to treat different disorders and diseases of the gastrointestinal tract. With the increasing interest in the development of functional foods for a healthy life, the non-psychoactive phytocannabinoids are hoped to find a place as nutraceuticals and food ingredients also for a healthy gastrointestinal tract function.


greenmedinfo--2020-05-16--Two-weeks treatment with cannabidiol improves biophysical and behavioral deficits associated with ex

Two-weeks treatment with cannabidiol improves biophysical and behavioral deficits associated with experimental type-1 diabetes.

The prevalence rates of depression and anxiety are at least two times higher in diabetic patients , increasing morbidity and mortality .
Cannabidiol ( CBD ) has been identified as a therapeutic agent viable to treat diverse psychiatric disorders .
Thus , this study aimed to investigate the effect of CBD treatment ( once a day for 14 days starting two weeks after diabetes induction ; at doses of 0 , 3 , 10 or 30 mg/kg , i.p . )
on depression- and anxiety-like behaviors associated with experimental diabetes induced by streptozotocin ( 60 mg/kg ; i.p . )
@ @ @ @ @ @ @ , blood glucose , and weight gain were evaluated in all experimental groups , including a positive control group treated with imipramine .
The rats were tested in the modified forced swimming test ( mFST ) and elevated plus maze ( EPM ) test .
Besides , the levels of serotonin ( 5-HT ) , noradrenaline ( NA ) and dopamine ( DA ) in two emotion-related brain regions , the prefrontal cortex ( PFC ) and hippocampus ( HIP ) were evaluated using high-pressure liquid chromatography .
Our results showed that CBD @ @ @ @ @ @ @ of 30 mg/kg ) reduced the exaggerated depressive- and anxiogenic-like behaviors of diabetic ( DBT ) rats , which may be associated with altered 5-HT , NA and/or DA levels observed in the PFC and HIP .
Treatment with CBD ( higher dose ) also induced a significant increase in weight gain and the insulin levels ( and consequently reduced glycemia ) in DBT rats .
The long-term CBD effects gave rise to novel therapeutic strategies to limit the physiological and neurobehavioral deficits in DBT rats .
This approachprovided evidence that CBD can @ @ @ @ @ @ @ diabetic patients .

The prevalence rates of depression and anxiety are at least two times higher in diabetic patients, increasing morbidity and mortality. Cannabidiol (CBD) has been identified as a therapeutic agent viable to treat diverse psychiatric disorders. Thus, this study aimed to investigate the effect of CBD treatment (once a day for 14 days starting two weeks after diabetes induction; at doses of 0, 3, 10 or 30 mg/kg, i.p.) on depression- and anxiety-like behaviors associated with experimental diabetes induced by streptozotocin (60 mg/kg; i.p.) in rats. Levels of plasma insulin, blood glucose, and weight gain were evaluated in all experimental groups, including a positive control group treated with imipramine. The rats were tested in the modified forced swimming test (mFST) and elevated plus maze (EPM) test. Besides, the levels of serotonin (5-HT), noradrenaline (NA) and dopamine (DA) in two emotion-related brain regions, the prefrontal cortex (PFC) and hippocampus (HIP) were evaluated using high-pressure liquid chromatography. Our results showed that CBD treatment (only at the higher dose of 30 mg/kg) reduced the exaggerated depressive- and anxiogenic-like behaviors of diabetic (DBT) rats, which may be associated with altered 5-HT, NA and/or DA levels observed in the PFC and HIP. Treatment with CBD (higher dose) also induced a significant increase in weight gain and the insulin levels (and consequently reduced glycemia) in DBT rats. The long-term CBD effects gave rise to novel therapeutic strategies to limit the physiological and neurobehavioral deficits in DBT rats. This approachprovided evidence that CBD can be useful for treating psychiatry comorbidities in diabetic patients.


greenmedinfo--2020-05-16--CBD inhibitory effects on the NLRP3 inflammasome may contribute to the overall anti-inflammatory eff

Cannabidiol ( CBD ) , a phytocannabinoid , has been reported to have anti-inflammatory effects associated with NLRP3 inflammasome activation , but its mechanism of anti-inflammasome action remains unclear .
Herein , we report CBD 's effect on NLRP3 inflammasome activation and its modulation of P2X7 , an inflammasome activation-related receptor , in human THP-1 monocytes .
CBD ( 0.1 , 1 , and 10μM ) exerted anti-inflammasome activity in LPS-nigericin-stimulated THP-1 monocytes by reducing media IL-1β concentration ( by 63.9 % , 64.1 % , and 83.1 % , respectively ) , which was similar to the known NLRP3 @ @ @ @ @ @ @ % vs 20.8 % and 17.4 % , respectively ; at 10 μM ) .CBD ( 10 μM ) decreased nigericin-alone- and nigericin-lipopolysaccharide-induced potassium efflux by 13.7 % and 13.0 % , respectively , in THP-1 monocytes , strongly suggesting P2X7 receptor modulation .
Computational docking data supported the potential for CBD binding to the P2X7 receptor via interaction with GLU 172 and VAL 173 residues .
Overall , the observed CBD suppressive effect on NLRP3 inflammasome activation in THP-1 monocytes was associated with decreased potassium efflux , as well as in silico @ @ @ @ @ @ @ inhibitory effects on the NLRP3 inflammasome may contribute to the overall anti-inflammatory effects reported for this phytocannabinoid .

Cannabidiol (CBD), a phytocannabinoid, has been reported to have anti-inflammatory effects associated with NLRP3 inflammasome activation, but its mechanism of anti-inflammasome action remains unclear. Herein, we report CBD's effect on NLRP3 inflammasome activation and its modulation of P2X7, an inflammasome activation-related receptor, in human THP-1 monocytes. CBD (0.1, 1, and 10μM) exerted anti-inflammasome activity in LPS-nigericin-stimulated THP-1 monocytes by reducing media IL-1β concentration (by 63.9%, 64.1%, and 83.1%, respectively), which was similar to the known NLRP3 inflammasome inhibitors oridonin and MCC950 (16.9% vs 20.8% and 17.4%, respectively; at 10 μM).CBD (10 μM) decreased nigericin-alone- and nigericin-lipopolysaccharide-induced potassium efflux by 13.7% and 13.0%, respectively, in THP-1 monocytes, strongly suggesting P2X7 receptor modulation. Computational docking data supported the potential for CBD binding to the P2X7 receptor via interaction with GLU 172 and VAL 173 residues. Overall, the observed CBD suppressive effect on NLRP3 inflammasome activation in THP-1 monocytes was associated with decreased potassium efflux, as well as in silico prediction of P2X7 receptor binding. CBD inhibitory effects on the NLRP3 inflammasome may contribute to the overall anti-inflammatory effects reported for this phytocannabinoid.


greenmedinfo--2020-05-16--CBD seems to exert an anti-inflammatory and antioxidant activity favoring a faster resolution of ora

CBD seems to exert an anti-inflammatory and antioxidant activity favoring a faster resolution of oral mucositis.

PURPOSE : The aim of this study was to evaluate the clinical , histological , hematological and oxidative stress effects of cannabidiol ( CBD ) in mice with induced oral mucositis .
METHODS : We used 90 mice of the CF-1 strain in which oral mucositis was induced using a protocol with 5-fluorouracil ( 5-FU ) chemotherapy .
The animals were divided randomly into 10 study groups .
Three groups were treated with different doses of CBD ( 3 , 10 and 30 mg/kg ) , while 2 were control groups ( positive control : 5-FU+mechanical trauma + placebo ; @ @ @ @ @ @ @ placebo ) , and 2 experimental times were studied ( 4 and 7 days ) .
All treatments were by intraperitoneal administration .
RESULTS : In the clinical evaluation , the groups treated with CBD showed less severity of oral lesions compared with the positive control at both experimental times .
The intensity of the inflammatory response was also lower in the groups treated with this drug , but there was no statistically significant difference when compared with the positive control .
With regard to erythrocyte , leukocyte and platelet counts and antioxidant @ @ @ @ @ @ @ CBD showed better results , but only some of these variables showed statistically significant differences .
CONCLUSIONS : CBD seems to exert an anti-inflammatory and antioxidant activity favoring a faster resolution of oral mucositis in this animal model .

PURPOSE: The aim of this study was to evaluate the clinical, histological, hematological and oxidative stress effects of cannabidiol (CBD) in mice with induced oral mucositis.
METHODS: We used 90 mice of the CF-1 strain in which oral mucositis was induced using a protocol with 5-fluorouracil (5-FU) chemotherapy. The animals were divided randomly into 10 study groups. Three groups were treated with different doses of CBD (3, 10 and 30 mg/kg), while 2 were control groups (positive control: 5-FU+mechanical trauma + placebo; and negative control: mechanical trauma + placebo), and 2 experimental times were studied (4 and 7 days). All treatments were by intraperitoneal administration.
RESULTS: In the clinical evaluation, the groups treated with CBD showed less severity of oral lesions compared with the positive control at both experimental times. The intensity of the inflammatory response was also lower in the groups treated with this drug, but there was no statistically significant difference when compared with the positive control. With regard to erythrocyte, leukocyte and platelet counts and antioxidant enzyme activity, the groups treated with CBD showed better results, but only some of these variables showed statistically significant differences.
CONCLUSIONS: CBD seems to exert an anti-inflammatory and antioxidant activity favoring a faster resolution of oral mucositis in this animal model.