greenmedinfo--2020-08-11--Pisum sativum defensin 1 eradicates mouse metastatic lung nodules from B16F10 melanoma cells.

d1 is a pea plant defensin which can be actively expressed inand shows broad antifungal activity .
This activity is dependent on fungal membrane glucosylceramide ( GlcCer ) , which is also important for its internalization , nuclear localization , and endoreduplication .
Certain cancer cells present a lipid metabolism imbalance resulting in the overexpression of GlcCer in their membrane .
In this work , in vitroassays using B16F10 cells showed that labeled fluorescein isothiocyanate FITC-d1 internalized into live cultured cells and targeted the nucleus , which underwent fragmentation , exhibiting approximately 60 % of cells in the sub-G0/G1 stage @ @ @ @ @ @ @ , and the participation of cyclin-F was suggested .
In a murine lung metastatic melanoma model , intravenous injection ofd1 together with B16F10 cells drastically reduced the number of nodules at concentrations above 0.5 mg/kg .
Additionally , the administration of 1 mg/kgd1 decreased the number of lung inflammatory cells to near zero without weight loss , unlike animals that received melanoma cells only .
It is worth noting that 1 mg/kgd1 alone did not provoke inflammation in lung tissue or weight or vital signal losses over 21 days , inferring no whole @ @ @ @ @ @ @ could be a promising prototype for human lung anti-metastatic melanoma therapy .

d1 is a pea plant defensin which can be actively expressed inand shows broad antifungal activity. This activity is dependent on fungal membrane glucosylceramide (GlcCer), which is also important for its internalization, nuclear localization, and endoreduplication. Certain cancer cells present a lipid metabolism imbalance resulting in the overexpression of GlcCer in their membrane. In this work, in vitroassays using B16F10 cells showed that labeled fluorescein isothiocyanate FITC-d1 internalized into live cultured cells and targeted the nucleus, which underwent fragmentation, exhibiting approximately 60% of cells in the sub-G0/G1 stage. This phenomenon was dependent on GlcCer, and the participation of cyclin-F was suggested. In a murine lung metastatic melanoma model, intravenous injection ofd1 together with B16F10 cells drastically reduced the number of nodules at concentrations above 0.5 mg/kg. Additionally, the administration of 1 mg/kgd1 decreased the number of lung inflammatory cells to near zero without weight loss, unlike animals that received melanoma cells only. It is worth noting that 1 mg/kgd1 alone did not provoke inflammation in lung tissue or weight or vital signal losses over 21 days, inferring no whole animal cytotoxicity. These results suggest thatd1 could be a promising prototype for human lung anti-metastatic melanoma therapy.


greenmedinfo--2020-08-13--The effects of chrysin on lipopolysaccharide-induced sepsis.

Chrysin ( CR ) is a flavone found in propolis and many plants .
Lipopolysaccharide ( LPS ) is a component of the cell wall of gram-negative bacteria that causes sepsis .
The purpose of this study was to investigate the effects of CR on LPS-induced sepsis in rats .
LPS intraperitoneal and a single dose and CR were given orally for 10 days .
Rats were sacrificed , blood samples were taken , liver , lung , and kidney tissues were dissected , homogenized , and histopathological analysis was carried out .
When CR groups compared to sepsis group @ @ @ @ @ @ @ of aspartate transaminase ( AST ) and alanine aminotransferase ( ALT ) , interleukin-1 beta ( IL-1β ) , interleukin-10 ( IL-10 ) , tumor necrosis factor-α ( TNF-α ) , interleukin-6 ( IL-6 ) , and levels of malondialdehyde ( MDA ) in tissues .
CR also increased the levels of superoxide dismutase ( SOD ) , catalase ( CAT ) , and glutathione peroxidase ( GSH-Px ) in tissues.Histopathological findings were consistent with biochemical findings .
Conclusion , CR could reduce the oxidative stress markers and cytokines in sepsis .
PRACTICAL @ @ @ @ @ @ @ the antioxidant and anti-inflammatory effects of chrysin , known as a flavolonoid , which are found in many plants and foods such as honey and propolis .
In this study , experimental sepsis model was created using LPS .
According to the results of the study , CR can attribute to the ameliorating of oxidative damage in tissues ( lung , liver , and kidney ) and it can suppress the sepsis-associated acutetissue injury via reduction of inflammation in rats .
Even , CR can be used as a pharmacological agent in inflammatory @ @ @ @ @ @ @ many cases causing oxidation .

Chrysin (CR) is a flavone found in propolis and many plants. Lipopolysaccharide (LPS) is a component of the cell wall of gram-negative bacteria that causes sepsis. The purpose of this study was to investigate the effects of CR on LPS-induced sepsis in rats. LPS intraperitoneal and a single dose and CR were given orally for 10 days. Rats were sacrificed, blood samples were taken, liver, lung, and kidney tissues were dissected, homogenized, and histopathological analysis was carried out. When CR groups compared to sepsis group, CR significantly decreased the serum levels of aspartate transaminase (AST) and alanine aminotransferase (ALT), interleukin-1 beta (IL-1β), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and levels of malondialdehyde (MDA) in tissues. CR also increased the levels of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in tissues.Histopathological findings were consistent with biochemical findings. Conclusion, CR could reduce the oxidative stress markers and cytokines in sepsis. PRACTICAL APPLICATIONS: Our approach is to determine the antioxidant and anti-inflammatory effects of chrysin, known as a flavolonoid, which are found in many plants and foods such as honey and propolis. In this study, experimental sepsis model was created using LPS. According to the results of the study, CR can attribute to the ameliorating of oxidative damage in tissues (lung, liver, and kidney) and it can suppress the sepsis-associated acutetissue injury via reduction of inflammation in rats. Even, CR can be used as a pharmacological agent in inflammatory diseases caused by other sources and in many cases causing oxidation.


greenmedinfo--2020-08-12--Natural anti-inflammatory compounds as treatment candidates in Alzheimer’s disease.

Alzheimer 's disease ( AD ) is a chronic neurodegenerative brain disorder characterized by memory impairment , dementia , oxidative @ @ @ @ @ Currently , only a few drugs are available in the market with various adverse effects @ @ @ @ @ drugs with protective action against the disease , research is turning to the identification of @ @ @ @ @ .
Natural compounds with anti-inflammatory activity could be good candidates for developing effective therapeutic strategies @ @ @ @ @ Resveratrol , Quercetin , Huperzine-A , Rosmarinic acid , genistein , obovatol , and Oxyresvertarol @ @ @ @ @ treatment of AD .
Several alkaloids such as galantamine , oridonin , glaucocalyxin B , @ @ @ @ @ have been shown anti-inflammatory effects in AD models in vitro as well as in-vivo .
@ @ @ @ @ from plants represent interesting candidates for the treatment of AD .
This review highlights the @ @ @ @ @ natural products along with their synthetic derivatives to counteract AD in the CNS .

Alzheimer's disease (AD) is a chronic neurodegenerative brain disorder characterized by memory impairment, dementia, oxidative stress in elderly people. Currently, only a few drugs are available in the market with various adverse effects. So to develop new drugs with protective action against the disease, research is turning to the identification of plant products as a remedy. Natural compounds with anti-inflammatory activity could be good candidates for developing effective therapeutic strategies. Phytochemicals including Curcumin, Resveratrol, Quercetin, Huperzine-A, Rosmarinic acid, genistein, obovatol, and Oxyresvertarol were reported molecules for the treatment of AD. Several alkaloids such as galantamine, oridonin, glaucocalyxin B, tetrandrine, berberine, anatabine have been shown anti-inflammatory effects in AD models in vitro as well as in-vivo. In conclusion, natural products from plants represent interesting candidates for the treatment of AD. This review highlights the potential of specific compounds from natural products along with their synthetic derivatives to counteract AD in the CNS.


greenmedinfo--2020-08-12--Rosmarinic acid-induced apoptosis and cell cycle arrest in triple-negative breast cancer cells.

Rosmarinic acid ( RA ) is a polyphenolic compound with various pharmacological properties , including , anti-inflammatory , immunomodulatory , and neuroprotective , as well as having antioxidant and anticancer activities .
This study evaluated the effects and mechanisms of RA in two racially different triple-negative breast cancer ( TNBC ) cell lines .
Results obtained show that RA significantly caused cytotoxic and antiproliferative effects in both cell lines in a dose- and time-dependent manner .
Remarkably , RA induced cell cycle arrest-related apoptosis and altered the expression of many apoptosis-involved genes differently .
In MDA-MB-231 cells , RA arrested @ @ @ @ @ @ @ contrast , the data suggest that RA causes S-phase arrest in MDA-MB-468 cells , leading to a 2-fold increase in the apoptotic effect compared to MDA-MB-231 cells .
Further , in MDA-MB-231 cells , RA significantly upregulated the mRNA expression of three genes : harakiri ( HRK ) , tumor necrosis factor receptor superfamily 25 ( TNFRSF25 ) , and BCL-2 interacting protein 3 ( BNIP3 ) .
In contrast , in the MDA-MB-468 cell line , the compound induced a significant transcription activation in three genes , including TNF , growth arrest @ @ @ @ @ @ @ ) , and BNIP3 .
Furthermore , RA repressed the expression of TNF receptor superfamily 11B ( TNFRSF11B ) inMDA-MB-231 cells in comparison to the ligand TNF superfamily member 10 ( TNFSF10 ) and baculoviral IAP repeat-containing 5 ( BIRC5 ) in MDA-MB-468 cells .
In conclusion , the data suggest that the polyphenol RA may have a potential role in TNBC therapies , particularly in MDA-MB-468 cells .

Rosmarinic acid (RA) is a polyphenolic compound with various pharmacological properties, including, anti-inflammatory, immunomodulatory, and neuroprotective, as well as having antioxidant and anticancer activities. This study evaluated the effects and mechanisms of RA in two racially different triple-negative breast cancer (TNBC) cell lines. Results obtained show that RA significantly caused cytotoxic and antiproliferative effects in both cell lines in a dose- and time-dependent manner. Remarkably, RA induced cell cycle arrest-related apoptosis and altered the expression of many apoptosis-involved genes differently. In MDA-MB-231 cells, RA arrested the cells in the G/Gphase. In contrast, the data suggest that RA causes S-phase arrest in MDA-MB-468 cells, leading to a 2-fold increase in the apoptotic effect compared to MDA-MB-231 cells. Further, in MDA-MB-231 cells, RA significantly upregulated the mRNA expression of three genes: harakiri (HRK), tumor necrosis factor receptor superfamily 25 (TNFRSF25), and BCL-2 interacting protein 3 (BNIP3). In contrast, in the MDA-MB-468 cell line, the compound induced a significant transcription activation in three genes, including TNF, growth arrest and DNA damage-inducible 45 alpha (GADD45A), and BNIP3. Furthermore, RA repressed the expression of TNF receptor superfamily 11B (TNFRSF11B) inMDA-MB-231 cells in comparison to the ligand TNF superfamily member 10 (TNFSF10) and baculoviral IAP repeat-containing 5 (BIRC5) in MDA-MB-468 cells. In conclusion, the data suggest that the polyphenol RA may have a potential role in TNBC therapies, particularly in MDA-MB-468 cells.


greenmedinfo--2020-08-12--Mangiferin: The Health-Boosting Antioxidant in Mangos

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greenmedinfo--2020-08-12--Protective effects of rosmarinic acid on doxorubicin-induced testicular damage.

BACKGROUND : We investigated the protective effects of rosmarinic acid ( RA ) on testicular damage induced by doxorubicin ( DXR ) in rats .
METHODS : In total , 21 rats were divided into 3 groups : the control group that received no treatment , the DXR group that received intraperitoneal ( i.p . )
DXR on day 7 and the DXR + RA group that received intragastric RA for 10 days with i.p .
DXR on day 7 .
The rats were sacrificed on day 11 for histological and biochemical analyses .
To assess oxidative damage , glutathione @ @ @ @ @ @ @ MDA ) levels were measured .
RESULTS : The median modified Johnsen score of the DXR + RA group was higher than that of the DXR group ( p = 0.002 ) .
The rats with the narrowest seminiferous tubules were in the DXR group ( 0.17± 0.03 ) , and the difference between the DXR + RA and DXR groups was statistically significant ( p = 0.002 ) .
The number of apoptotic cells in the DXR group was significantly higher than that in the control group , and there were significantly @ @ @ @ @ @ @ RA group than in the DXRgroup ( p = 0.002 ) .
The MDA level was lowest in the control group and highest in the DXR group , and the level observed in the DXR + RA group significantly lower than that in the DXR group ( p = 0.002 ) .
The GPx level was highest in the control group , with the level observed in the DXR + RA group significantly higher than that in the DXR group ( p = 0.002 ) .
The testosterone level was lowest in the @ @ @ @ @ @ @ group , and that observed in the DXR + RA group was significantly higher than that in the DXR group ( p = 0.018 ) .
CONCLUSIONS : RA can correct DXR-induced testicular damage through its antioxidant properties .
However , the mechanism underlying the effects of RA requires further investigation , and long-term and comparative human studies are also needed .

BACKGROUND: We investigated the protective effects of rosmarinic acid (RA) on testicular damage induced by doxorubicin (DXR) in rats.
METHODS: In total, 21 rats were divided into 3 groups: the control group that received no treatment, the DXR group that received intraperitoneal (i.p.) DXR on day 7 and the DXR + RA group that received intragastric RA for 10 days with i.p. DXR on day 7. The rats were sacrificed on day 11 for histological and biochemical analyses. To assess oxidative damage, glutathione peroxidase (GPx) and malondialdehyde (MDA) levels were measured.
RESULTS: The median modified Johnsen score of the DXR + RA group was higher than that of the DXR group (p = 0.002). The rats with the narrowest seminiferous tubules were in the DXR group (0.17± 0.03), and the difference between the DXR + RA and DXR groups was statistically significant (p = 0.002). The number of apoptotic cells in the DXR group was significantly higher than that in the control group, and there were significantly fewer apoptotic cells in the DXR + RA group than in the DXRgroup (p = 0.002). The MDA level was lowest in the control group and highest in the DXR group, and the level observed in the DXR + RA group significantly lower than that in the DXR group (p = 0.002). The GPx level was highest in the control group, with the level observed in the DXR + RA group significantly higher than that in the DXR group (p = 0.002). The testosterone level was lowest in the DXR group and highest in the control group, and that observed in the DXR + RA group was significantly higher than that in the DXR group (p = 0.018).
CONCLUSIONS: RA can correct DXR-induced testicular damage through its antioxidant properties. However, the mechanism underlying the effects of RA requires further investigation, and long-term and comparative human studies are also needed.


greenmedinfo--2020-08-12--Protective role of chrysin on doxorubicin-induced oxidative stress and DNA damage in rat testes.

This study investigated the role of chrysin ( CR ) in DNA damage likely to occur in the testicle and oxidative stress caused by doxorubicin ( DXR ) .
Twenty-eight rats were divided into four groups as control , DXR , DXR + CR and CR groups .
Sperm parameters , oxidative status , testicular biopsy score , DNA damage and plasma testosterone levels were analysed .
Noticeable reductions in sperm count , motility and testosterone were detected in the DXR group compared to controls .
In addition , significant increases in malondialdehyde ( MDA ) , catalase ( CAT @ @ @ @ @ @ @ , and in abnormal sperm rates were detected .
Severe degenerative changes occurred in the tubules of DXR rat testes ; the inter-tubular areas were oedematous .
Immunofluorescence staining was conducted with 8-OhDG ( 8 oxo-2'-deoxyguanosine ) to evaluate DNA damage , and severe positivity was found in tubular gaps in the DXR rat testes .
When the DXR + CR group was compared with the DXR group , the abnormal sperm rate was found to have decreased significantly .
Positivity in the tubular space and degenerative changes in the seminiferous tubules were @ @ @ @ @ @ @ of CR with DXR to reduce the possible adverse effects of DXR , a medicine preferred in cancer therapy .

This study investigated the role of chrysin (CR) in DNA damage likely to occur in the testicle and oxidative stress caused by doxorubicin (DXR). Twenty-eight rats were divided into four groups as control, DXR, DXR + CR and CR groups. Sperm parameters, oxidative status, testicular biopsy score, DNA damage and plasma testosterone levels were analysed. Noticeable reductions in sperm count, motility and testosterone were detected in the DXR group compared to controls. In addition, significant increases in malondialdehyde (MDA), catalase (CAT) and glutathione (GSH) levels, and in abnormal sperm rates were detected. Severe degenerative changes occurred in the tubules of DXR rat testes; the inter-tubular areas were oedematous. Immunofluorescence staining was conducted with 8-OhDG (8 oxo-2'-deoxyguanosine) to evaluate DNA damage, and severe positivity was found in tubular gaps in the DXR rat testes. When the DXR + CR group was compared with the DXR group, the abnormal sperm rate was found to have decreased significantly. Positivity in the tubular space and degenerative changes in the seminiferous tubules were also diminished. We recommend the administration of CR with DXR to reduce the possible adverse effects of DXR, a medicine preferred in cancer therapy.


greenmedinfo--2020-08-12--Chrysin has a beneficial impact on oxidative and inflammation damage in the liver of aged male rats.

AIMS : The purpose of this research was to investigate the effect of chrysin on one of the natural antioxidants on aging progression in the animal model .
BACKGROUND : Oxidative stress and inflammation increase in hepatic tissue during aging , leading to liver dysfunction .
OBJECTIVE : The current research was conducted to show the effect of chrysin on the activities of antioxidant enzyme ( catalase , glutathione peroxidase , and superoxide dismutase ) , serum nitric oxide ( NO ) , and lipid peroxidation as well as inflammatory cytokines ( TNF-α , IL-6 , and IL-1β ) of @ @ @ @ @ @ @ rats of different ages , 2 , 10 , and 20 months randomly divided into six groups as follows ( n=8 , per each group ) : young control rats ( C2 ) , young CH-treated rats ( CH2 ) , middle-aged control rats ( C10 ) , middle-aged CH-treated group ( CH10 ) , aged control group ( C20 ) , and aged CH-treated group ( CH20 ) .
Chrysin ( 20 mg/kg ) was administrated intraperitoneally once a day for 30 days .
RESULT : Present findings indicated that chrysin treatment @ @ @ @ @ @ @ peroxidation , TNF-α , and IL-1β as well as serum levels of NO .
CONCLUSION : The findings suggest that chrysin could be effective against the progression of age-induced damage by modulation oxidant-antioxidant system and inflammatory response .

AIMS: The purpose of this research was to investigate the effect of chrysin on one of the natural antioxidants on aging progression in the animal model.
BACKGROUND: Oxidative stress and inflammation increase in hepatic tissue during aging, leading to liver dysfunction.
OBJECTIVE: The current research was conducted to show the effect of chrysin on the activities of antioxidant enzyme (catalase, glutathione peroxidase, and superoxide dismutase), serum nitric oxide (NO), and lipid peroxidation as well as inflammatory cytokines (TNF-α, IL-6, and IL-1β) of aging rats.
METHOD: Male Wistar rats of different ages, 2, 10, and 20 months randomly divided into six groups as follows (n=8, per each group): young control rats (C2), young CH-treated rats (CH2), middle-aged control rats (C10), middle-aged CH-treated group (CH10), aged control group (C20), and aged CH-treated group (CH20). Chrysin (20 mg/kg) was administrated intraperitoneally once a day for 30 days.
RESULT: Present findings indicated that chrysin treatment ameliorated the increased liver levels of lipid peroxidation, TNF-α, and IL-1β as well as serum levels of NO.
CONCLUSION: The findings suggest that chrysin could be effective against the progression of age-induced damage by modulation oxidant-antioxidant system and inflammatory response.


greenmedinfo--2020-08-12--Chrysin rescues rat myocardium from ischemia-reperfusion injury via PPAR-γ/Nrf2 activation.

Pharmacological strategies aimed at co-activating peroxisome proliferator-activated receptor-gamma ( PPAR-γ ) /nuclear factor erythroid 2-related factor 2 ( Nrf2 ) pathway have shown promising results in alleviating myocardial injury .
The aim of the study was to evaluate the role of chrysin , a PPAR-γ agonist , in ischemia-reperfusion ( IR ) -induced myocardial infarction ( MI ) in rats and to explore the molecular mechanism driving this activity .
To evaluate this hypothesis , chrysin ( 60 mg/kg , orally ) , PPAR-γ antagonist ( GW9662 , 1 mg/kg , intraperitoneally ) , or both were administered to rats @ @ @ @ @ @ @ day , one-stage ligation of left anterior descending coronary artery for 45 min followedby 60 min of reperfusion was performed .
Chrysin significantly decreased infarct size and improved cardiac functions following IR-induced MI .
This improvement was corroborated by augmented PPAR-γ/Nrf2 expression as confirmed by immunohistochemistry and western blotting analysis .
Chrysin exhibitedstrong anti-oxidant property as demonstrated by increased GSH and CAT levels and decreased 8-OHdG and TBARS levels .
Our findings also imply that chrysin significantly inhibited inflammatory response as validated by decreased NF-κB , IKK-β , CRP , TNF-α and MPO @ @ @ @ @ @ @ positivity , a marker of apoptotic response and normalized cardiac injury markers .
The histopathological and ultrastructural analysis further supported the functional and biochemical outcomes , showing preserved myocardial architecture .
Intriguingly , co-administration with GW9662 significantly diminished the cardioprotective effect of chrysin as demonstrated by depressed myocardial function , decreased PPAR-γ/Nrf2 expression and increased oxidative stress .
In conclusion , the present study demonstrates that co-activation of PPAR-γ/Nrf2 by chrysin may be crucial for its cardioprotective effect .

Pharmacological strategies aimed at co-activating peroxisome proliferator-activated receptor-gamma (PPAR-γ)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway have shown promising results in alleviating myocardial injury. The aim of the study was to evaluate the role of chrysin, a PPAR-γ agonist, in ischemia-reperfusion (IR)-induced myocardial infarction (MI) in rats and to explore the molecular mechanism driving this activity. To evaluate this hypothesis, chrysin (60 mg/kg, orally), PPAR-γ antagonist (GW9662, 1 mg/kg, intraperitoneally), or both were administered to rats for 28 days. On the 29th day, one-stage ligation of left anterior descending coronary artery for 45 min followedby 60 min of reperfusion was performed. Chrysin significantly decreased infarct size and improved cardiac functions following IR-induced MI. This improvement was corroborated by augmented PPAR-γ/Nrf2 expression as confirmed by immunohistochemistry and western blotting analysis. Chrysin exhibitedstrong anti-oxidant property as demonstrated by increased GSH and CAT levels and decreased 8-OHdG and TBARS levels. Our findings also imply that chrysin significantly inhibited inflammatory response as validated by decreased NF-κB, IKK-β, CRP, TNF-α and MPO levels. In addition, chrysin decreasedTUNEL/DAPI positivity, a marker of apoptotic response and normalized cardiac injury markers. The histopathological and ultrastructural analysis further supported the functional and biochemical outcomes, showing preserved myocardial architecture. Intriguingly, co-administration with GW9662 significantly diminished the cardioprotective effect of chrysin as demonstrated by depressed myocardial function, decreased PPAR-γ/Nrf2 expression and increased oxidative stress. In conclusion, the present study demonstrates that co-activation of PPAR-γ/Nrf2 by chrysin may be crucial for its cardioprotective effect.


greenmedinfo--2020-08-12--Five Seeds to Improve Your Health

Five Seeds to Improve Your Health


greenmedinfo--2020-08-12--Chrysin inhibits high glucose-induced migration on chorioretinal endothelial cells.

BACKGROUND : Diabetes mellitus ( DM ) is a chronic inflammatory disease , which causes multiple complications .
Diabetic retinopathy ( DR ) is among these complications and is a dominant cause of vision loss for diabetic patients .
Numerous studies have shown that chrysin , a flavonoid , has many biological activities such as anti-oxidation and anti-inflammation .
However , it is rarely used in ocular diseases .
In this study , we examined the inhibitory effects of flavonoid on high glucose induced migration of chorioretinal endothelial cells ( RF/6A cells ) and its mechanism .
MATERIALS AND METHODS @ @ @ @ @ @ @ with chrysin was examined with a 3- ( 4,5-dimethyl-2-thiazolyl ) -2,5-diphenyl-2H-tetrazolium bromide ( MTT ) assay .
The migration of RF/6A cells was assessed by the transwell migration and scratch wound assays .
The expression of AKT , ERK , vascular endothelial growth factor ( VEGF ) , HIF-1α and MMP-2 were determined by western blotting .
To observe the mRNA expression of VEGF receptor ( VEGFR ) , qRT-PCR , was utilized .
RESULTS : The results showed that chrysin can dose-dependently inhibit the RF/6A cell migration in vitro transwell and the @ @ @ @ @ @ @ high glucose .
After pretreatment of RF/6A cells with different concentrations of chrysin , they did not produce any cytotoxicity in MTT assay .
Moreover , chrysin down-regulated both phosphorylated AKT and ERK , as well as attenuated the expression levels of MMP-2 .
It also decreased the expression of the VEGF transcription factor and VEGF .
Furthermore , it was shown that chrysin could suppress the protein and mRNA expression levels of VEGFR .
CONCLUSION : The results indicate that chrysin could down-regulate the phosphorylation of AKT , ERK and MMP-2 and @ @ @ @ @ @ @ in a high glucose environment .
It further inhibits the high glucose-induced migration of RE/6A cells .
Therefore , chrysin may have the potential for visual protection .

BACKGROUND: Diabetes mellitus (DM) is a chronic inflammatory disease, which causes multiple complications. Diabetic retinopathy (DR) is among these complications and is a dominant cause of vision loss for diabetic patients. Numerous studies have shown that chrysin, a flavonoid, has many biological activities such as anti-oxidation and anti-inflammation. However, it is rarely used in ocular diseases. In this study, we examined the inhibitory effects of flavonoid on high glucose induced migration of chorioretinal endothelial cells (RF/6A cells) and its mechanism.
MATERIALS AND METHODS: The viability of RF/6A cells treated with chrysin was examined with a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The migration of RF/6A cells was assessed by the transwell migration and scratch wound assays. The expression of AKT, ERK, vascular endothelial growth factor (VEGF), HIF-1α and MMP-2 were determined by western blotting. To observe the mRNA expression of VEGF receptor (VEGFR), qRT-PCR, was utilized.
RESULTS: The results showed that chrysin can dose-dependently inhibit the RF/6A cell migration in vitro transwell and the scratch wound assays which are induced by high glucose. After pretreatment of RF/6A cells with different concentrations of chrysin, they did not produce any cytotoxicity in MTT assay. Moreover, chrysin down-regulated both phosphorylated AKT and ERK, as well as attenuated the expression levels of MMP-2. It also decreased the expression of the VEGF transcription factor and VEGF. Furthermore, it was shown that chrysin could suppress the protein and mRNA expression levels of VEGFR.
CONCLUSION: The results indicate that chrysin could down-regulate the phosphorylation of AKT, ERK and MMP-2 and reduce the effects of VEGF and VEGFR in a high glucose environment. It further inhibits the high glucose-induced migration of RE/6A cells. Therefore, chrysin may have the potential for visual protection.


greenmedinfo--2020-08-12--Bioavailability and in vivo antioxidant activity of a standardized polyphenol mixture extracted from

Bioavailability and in vivo antioxidant activity of a standardized polyphenol mixture extracted from brown propolis.

Propolis is a complex mixture of natural sticky and resinous components produced by honeybees from living plant exudates .
Globally , research has been dedicated to studying the biological properties and chemical composition of propolis from various geographical and climatic regions .
However , the chemical data and biological properties of Mexican brown propolis are scant .
The antioxidant activity of the ethanolic extract of propolis ( EEP ) sample collected in México and the isolated compounds is described .
Cytotoxic activity was evaluated in a central nervous system and cervical cancer cell lines .
Cytotoxicity of EEP was evaluated @ @ @ @ @ @ @ cancer ( HeLa , SiHa , and CasKi ) measured by the 3- ( 3,5-dimethylthiazol-2-yl ) 2,5-diphenyltetrazolium ( MTT ) assay .
The antibacterial activity was tested using the minimum inhibitory concentration ( MIC ) assay .
Twelve known compounds were isolated and identified by nuclear magnetic resonance spectroscopy ( NMR ) .
Additionally , forty volatile compounds were identified by means of headspace-solid phase microextraction with gas chromatography and mass spectrometry time of flight analysis ( HS-SPME/GC-MS-TOF ) .
The main volatile compounds detected include nonanal ( 18.82 % ) , α-pinene @ @ @ @ @ @ @ ( 10.13 % ) , and α-pinene ( 8.04 % ) .
EEP showed an anti-proliferative effect on glioma cells better than temozolomide , also decreased proliferation and viability in cervical cancer cells , but its effectiveness was lower compared to cisplatin .

Propolis is a complex mixture of natural sticky and resinous components produced by honeybees from living plant exudates. Globally, research has been dedicated to studying the biological properties and chemical composition of propolis from various geographical and climatic regions. However, the chemical data and biological properties of Mexican brown propolis are scant. The antioxidant activity of the ethanolic extract of propolis (EEP) sample collected in México and the isolated compounds is described. Cytotoxic activity was evaluated in a central nervous system and cervical cancer cell lines. Cytotoxicity of EEP was evaluated in a C6 cell line and cervical cancer (HeLa, SiHa, and CasKi) measured by the 3-(3,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium (MTT) assay. The antibacterial activity was tested using the minimum inhibitory concentration (MIC) assay. Twelve known compounds were isolated and identified by nuclear magnetic resonance spectroscopy (NMR). Additionally, forty volatile compounds were identified by means of headspace-solid phase microextraction with gas chromatography and mass spectrometry time of flight analysis (HS-SPME/GC-MS-TOF). The main volatile compounds detected include nonanal (18.82%), α-pinene (12.45%), neryl alcohol (10.13%), and α-pinene (8.04%). EEP showed an anti-proliferative effect on glioma cells better than temozolomide, also decreased proliferation and viability in cervical cancer cells, but its effectiveness was lower compared to cisplatin.


greenmedinfo--2020-08-12--pinocembrin ameliorates diabetic nephropathy when there is no kidney damage.

Propolis is a resinous beehive product that has been used worldwide in traditional medicine to prevent and treat colds , wounds , rheumatism , heart disease and diabetes .
Diabetic nephropathy is the final stage of renal complications caused by diabetes and for its treatment there are few alternatives .
The present study aimed to determine the chemical composition of three propolis samples collected in Chihuahua , Durango and Zacatecas and to evaluate the effect of pinocembrin in a model of diabetic nephropathy in vivo .
Previous research demonstrated that propolis of Chihuahua possesses hypoglycemic and antioxidant activities .
Two @ @ @ @ @ @ @ before renal damage ) and corrective ( once renal damage is established ) .
In the preventive scheme , pinocembrin treatment avoids death of the rats , improves lipid profile , glomerular filtration rate , urinary protein , avoid increases in urinary biomarkers , oxidative stress and glomerular basement membrane thickness .
Whereas , in the corrective scheme , pinocembrin only improves lipid profile without showing improvement in any other parameters , even pinocembrin exacerbated the damage .
In conclusion , pinocembrin ameliorates diabetic nephropathy when there is no kidney damage but when @ @ @ @ @ @ @ kidney damage .

Propolis is a resinous beehive product that has been used worldwide in traditional medicine to prevent and treat colds, wounds, rheumatism, heart disease and diabetes. Diabetic nephropathy is the final stage of renal complications caused by diabetes and for its treatment there are few alternatives. The present study aimed to determine the chemical composition of three propolis samples collected in Chihuahua, Durango and Zacatecas and to evaluate the effect of pinocembrin in a model of diabetic nephropathy in vivo. Previous research demonstrated that propolis of Chihuahua possesses hypoglycemic and antioxidant activities. Two different schemes were assessed, preventive (before renal damage) and corrective (once renal damage is established). In the preventive scheme, pinocembrin treatment avoids death of the rats, improves lipid profile, glomerular filtration rate, urinary protein, avoid increases in urinary biomarkers, oxidative stress and glomerular basement membrane thickness. Whereas, in the corrective scheme, pinocembrin only improves lipid profile without showing improvement in any other parameters, even pinocembrin exacerbated the damage. In conclusion, pinocembrin ameliorates diabetic nephropathy when there is no kidney damage but when it is already present, pinocembrin accelerates kidney damage.


greenmedinfo--2020-08-12--These findings suggested anti-steatohepatitis potential of naringin in diabetics.

AIMS : Recent findings have instituted the role of hyperglycemia-related AGE/RAGE and NF-κB in instigating reactive oxygen species ( ROS ) mediated mitochondrial dysfunction and apoptosis of hepatocyte , which leads to steatohepatitis .
Naringin , a flavanone glycoside found to possess myriads of pharmacological benefits along with its antioxidant and anti-inflammatory properties .
Consequently , we aimed to decipher the effect of naringin on RAGE/NF-κB mediated mitochondrial apoptosis in type 2 diabetes mellitus ( T2DM ) -induced steatohepatitis .
MAIN METHODS : Hepatic HepG2 cells were cultured in palmitic acid medium with and without naringin .
Lipid content was @ @ @ @ @ @ @ Red staining .
Cellular apoptosis was determined by Annexin V-FITC/PI staining .
An experimental T2DM-induced steatohepatitis was developed in Sprague Dawley rats by high-fat diet ( HFD ) for 12 weeks .
The naringin was administrated orally at a dose of 100 mg/kg , daily for eight weeks .
Glucose and insulin tolerance test was performed .
Liver sections were stained by hematoxylin-eosin and picrosirius red .
The mRNA and protein expression of RAGE and NF-κB were determined by qPCR , Immunofluorescence , and Immunoblotting .
Mitochondrial membrane potential ( MMP ) , @ @ @ @ @ @ @ FACS .
KEY FINDINGS : Palmitic acid encountered HepG2 cells and HFD fed rats exhibited hyperlipidemia , insulin resistance , abnormal aminotransferases , steatosis , and fibrosis .
Besides , the level of AGEs , RAGE , NF-κB , and oxidative stress were exacerbated .
Moreover , MMP , cellular and mitochondrial ROS were altered in diabetic rats .
Nevertheless , the naringin treatment ameliorated the steatohepatitis by improving the levels of aforementioned parameters .
SIGNIFICANCE : Collectively , these findings suggested anti-steatohepatitis potential of naringin in diabetics .

AIMS: Recent findings have instituted the role of hyperglycemia-related AGE/RAGE and NF-κB in instigating reactive oxygen species (ROS) mediated mitochondrial dysfunction and apoptosis of hepatocyte, which leads to steatohepatitis. Naringin, a flavanone glycoside found to possess myriads of pharmacological benefits along with its antioxidant and anti-inflammatory properties. Consequently, we aimed to decipher the effect of naringin on RAGE/NF-κB mediated mitochondrial apoptosis in type 2 diabetes mellitus (T2DM)-induced steatohepatitis.
MAIN METHODS: Hepatic HepG2 cells were cultured in palmitic acid medium with and without naringin. Lipid content was examined by Oil Red O and Nile Red staining. Cellular apoptosis was determined by Annexin V-FITC/PI staining. An experimental T2DM-induced steatohepatitis was developed in Sprague Dawley rats by high-fat diet (HFD) for 12 weeks. The naringin was administrated orally at a dose of 100 mg/kg, daily for eight weeks. Glucose and insulin tolerance test was performed. Liver sections were stained by hematoxylin-eosin and picrosirius red. The mRNA and protein expression of RAGE and NF-κB were determined by qPCR, Immunofluorescence, and Immunoblotting. Mitochondrial membrane potential (MMP), cellular and mitochondrial ROS were measured by FACS.
KEY FINDINGS: Palmitic acid encountered HepG2 cells and HFD fed rats exhibited hyperlipidemia, insulin resistance, abnormal aminotransferases, steatosis, and fibrosis. Besides, the level of AGEs, RAGE, NF-κB, and oxidative stress were exacerbated. Moreover, MMP, cellular and mitochondrial ROS were altered in diabetic rats. Nevertheless, the naringin treatment ameliorated the steatohepatitis by improving the levels of aforementioned parameters.
SIGNIFICANCE: Collectively, these findings suggested anti-steatohepatitis potential of naringin in diabetics.


greenmedinfo--2020-08-12--Differential modulation of the phospholipidome of proinflammatory human macrophages by flavonoids.

The immunomodulatory activity of flavonoids is increasingly appreciated .
Macrophage phospholipids ( PLs ) play crucial roles in cell-mediated inflammatory responses .
However , little is known on how these PLs are affected upon flavonoid treatment .
In this work , we have used mass-spectrometry-based lipidomics to characterize the changes in the phospholipidome of proinflammatory human-macrophage-like cells ( THP-1-derived and LPS+IFN-γ-stimulated ) incubated with non-cytotoxic concentrations of three flavonoids : quercetin , naringin and naringenin .
One hundred forty-seven PL species belonging to various classes were identified , and their relative abundances were determined .
Each flavonoid displayed its own @ @ @ @ @ @ @ produced the strongest impact , acting both on constitutive PLs ( phosphatidylcholines , phosphatidylethanolamines and sphingomyelins ) and on minor signaling lipids , such as phosphatidylinositol ( PI ) and phosphatidylserine ( PS ) species .
Conversely , naringin hardly affected structural PLs , producing changes in signaling molecules that were opposite to those seen in quercetin-treated macrophages .
In turn , albeit sharing some effects with quercetin , naringenin did not change PI and PS levels and interfered with a set of phosphatidylcholines distinct from those modulated by quercetin .
These results @ @ @ @ @ @ @ specific remodeling of macrophage phospholipidome , paving the way to future studies on the role of cellular phospholipids in flavonoid-mediated immunomodulatory effects .

The immunomodulatory activity of flavonoids is increasingly appreciated. Macrophage phospholipids (PLs) play crucial roles in cell-mediated inflammatory responses. However, little is known on how these PLs are affected upon flavonoid treatment. In this work, we have used mass-spectrometry-based lipidomics to characterize the changes in the phospholipidome of proinflammatory human-macrophage-like cells (THP-1-derived and LPS+IFN-γ-stimulated) incubated with non-cytotoxic concentrations of three flavonoids: quercetin, naringin and naringenin. One hundred forty-seven PL species belonging to various classes were identified, and their relative abundances were determined. Each flavonoid displayed its own unique signature of induced effects. Quercetin produced the strongest impact, acting both on constitutive PLs (phosphatidylcholines, phosphatidylethanolamines and sphingomyelins) and on minor signaling lipids, such as phosphatidylinositol (PI) and phosphatidylserine (PS) species. Conversely, naringin hardly affected structural PLs, producing changes in signaling molecules that were opposite to those seen in quercetin-treated macrophages. In turn, albeit sharing some effects with quercetin, naringenin did not change PI and PS levels and interfered with a set of phosphatidylcholines distinct from those modulated by quercetin. These results demonstrate that flavonoids bioactivity involves profound and specific remodeling of macrophage phospholipidome, paving the way to future studies on the role of cellular phospholipids in flavonoid-mediated immunomodulatory effects.


greenmedinfo--2020-08-12--Glioma progression is suppressed by Naringenin and APO2L combination therapy.

Naringenin ( NG ) is a natural antioxidant flavonoid which is isolated from citrus fruits , and has been reported to inhibit colon cancer proliferation .
However , the effects of NG treatment on glioma remain to be elucidated .
The present study aimed to explore the effects of NG on glioma in vitro and in vivo .
Also , the interactions between NG and APO2 ligand ( APO2L ; also known as tumor necrosis factor-related apoptosis-inducing ligand ) were investigated in glioma .
A synergistic effect of NG and APO2L combination on apoptotic induction was observed , though glioma @ @ @ @ @ @ @ After NG treatment , glioma cells resumed the sensitivity to APO2L and cell apoptosis was induced via the activation of caspases , elevation of decoy receptors 4 and 5 ( DR4 and DR5 ) and induction of p53 .
Coadministration of NG and APO2L decreased levels of anti-apoptotic B cell lymphoma 2 ( Bcl-2 ) family members Bcl-2 and Bcl-extra large ( Bcl-xL ) , while increased levels of proapoptotic factors Bcl-2-associated agonist of cell death ( Bad ) and Bcl-2 antagonist/killer 1 ( Bak ) .
Furthermore , an in vivo mouse @ @ @ @ @ @ @ cotreatment markedly suppressed glioma growth by activating apoptosis in tumor tissues when compared with NG or APO2L monotherapy .
The present study provides a novel therapeutic strategy for glioma by potentiating APO2L-induced apoptosis via the combination with NG in glioma tumor cells .

Naringenin (NG) is a natural antioxidant flavonoid which is isolated from citrus fruits, and has been reported to inhibit colon cancer proliferation. However, the effects of NG treatment on glioma remain to be elucidated. The present study aimed to explore the effects of NG on glioma in vitro and in vivo. Also, the interactions between NG and APO2 ligand (APO2L; also known as tumor necrosis factor-related apoptosis-inducing ligand) were investigated in glioma. A synergistic effect of NG and APO2L combination on apoptotic induction was observed, though glioma cells were insensitive to APO2L alone. After NG treatment, glioma cells resumed the sensitivity to APO2L and cell apoptosis was induced via the activation of caspases, elevation of decoy receptors 4 and 5 (DR4 and DR5) and induction of p53. Coadministration of NG and APO2L decreased levels of anti-apoptotic B cell lymphoma 2 (Bcl-2) family members Bcl-2 and Bcl-extra large (Bcl-xL), while increased levels of proapoptotic factors Bcl-2-associated agonist of cell death (Bad) and Bcl-2 antagonist/killer 1 (Bak). Furthermore, an in vivo mouse xenograft model demonstrated that NG and APO2L cotreatment markedly suppressed glioma growth by activating apoptosis in tumor tissues when compared with NG or APO2L monotherapy. The present study provides a novel therapeutic strategy for glioma by potentiating APO2L-induced apoptosis via the combination with NG in glioma tumor cells.


greenmedinfo--2020-08-12--Naringenin downregulates inflammation-mediated nitric oxide overproduction and potentiates endogenou

Naringenin downregulates inflammation-mediated nitric oxide overproduction and potentiates endogenous antioxidant status during hyperglycemia.

Nitric oxide is a key regulating factor for physiological functions , when elevated during inflammatory conditions , NO , can @ @ @ @ @ Naringenin , a bioflavonoid has shown to possess anti-inflammatory action .
However , its role @ @ @ @ @ been elucidated till date .
This study was designed to investigate antioxidant potential of naringenin @ @ @ @ @ and antioxidant status with an improved glycemic profile in diabetic rats .
From total rats @ @ @ @ @ saline , while remaining received single intraperitoneal injection of alloxan and were then equally divided @ @ @ @ @ , and 4 , which latter received no-treatment , metformin ( 50 mg kg day @ @ @ @ @ mg kg day ) , respectively , for 1 month .
Results showed that naringenin @ @ @ @ @ ( p

Nitric oxide is a key regulating factor for physiological functions, when elevated during inflammatory conditions, NO, can lower endogenous antioxidants level. Naringenin, a bioflavonoid has shown to possess anti-inflammatory action. However, its role in NO-mediated responses has not been elucidated till date. This study was designed to investigate antioxidant potential of naringenin against inflammation-mediated nitric oxide overproduction and antioxidant status with an improved glycemic profile in diabetic rats. From total rats, Group 1 received normal saline, while remaining received single intraperitoneal injection of alloxan and were then equally divided into group 2, 3, and 4, which latter received no-treatment, metformin (50 mg kg day) and naringenin (50 mg kg day), respectively, for 1 month. Results showed that naringenin significantly downregulated levels of glucose (p < .05), lipid profile, inflammatory biomarkers, and nitric oxide (p < .01) in alloxan-induced diabetic rats. It also improved SOD level as compared to that of metformin treatment. This work delivers that naringenin exerts antioxidant effect by downregulating inflammation-mediated nitric oxide overproduction. PRACTICAL APPLICATIONS: Naringenin is a well-recognized member of bioflavonoids and is commonly present in citrus fruits like oranges, grapes, and berries. The foremost property of naringenin is its antioxidant potential, which aids in decreasing the burden of oxidative stress by declining the generation of free radicals. The overproduction of these oxygenor nitrogen reactive species are considered as underlying cause of undesired biological activities likeor nitrite-mediated inflammation and altered metabolic parameters. Hence, this study was designed to investigate the antioxidant potential of naringenin as natural flavone to downregulate the inflammation-mediated nitric oxide overproduction and improve glycemic profile. The therapeutic perspective of naringenin from current study against nitric oxide overproduction and to eradicate inflammation via controlling of levels of pro-inflammatory mediators suggests that naringenin holds the forthcoming vision as a supportive constituent alone or in combination with some other conventional medicinal agents against conditions like metabolic disorders.


greenmedinfo--2020-08-12--Naringenin as a potential immunomodulator in therapeutics.

Naringenin , a citrus flavonoid that possesses various biological activities , has emerged as a potential therapeutic agent for the management of a variety of diseases .
Studies using cell culture system have shown that naringenin can inhibit inflammatory response in diverse cell types .
Moreover , research using various animal models has further demonstrated therapeutic potentials of naringenin in the treatment of several inflammation-related disorders , such as sepsis , fulminant hepatitis , fibrosis and cancer .
The mechanism of action of naringenin is not completely understood but recent mechanistic studies revealed that naringenin suppresses inflammatory cytokine production through @ @ @ @ @ @ @ , naringenin not only inhibits cytokine mRNA expression but also promotes lysosome-dependent cytokine protein degradation .
This unique property of naringenin stands in sharp contrast with some widely-studied natural products such as apigenin and curcumin , which regulate cytokine production essentially at the transcriptional level .
Therefore , naringenin may provide modality for the development of novel anti-inflammatory agent .
This review article summarizes our recent studies in understanding how naringenin acts in cells and animal models .
Particularly , we will discuss the anti-inflammatory activities of naringenin in various disease context and @ @ @ @ @ @ @ , in the treatment of inflammatory related disease .

Naringenin, a citrus flavonoid that possesses various biological activities, has emerged as a potential therapeutic agent for the management of a variety of diseases. Studies using cell culture system have shown that naringenin can inhibit inflammatory response in diverse cell types. Moreover, research using various animal models has further demonstrated therapeutic potentials of naringenin in the treatment of several inflammation-related disorders, such as sepsis, fulminant hepatitis, fibrosis and cancer. The mechanism of action of naringenin is not completely understood but recent mechanistic studies revealed that naringenin suppresses inflammatory cytokine production through both transcriptional and post-transcriptional mechanisms. Surprisingly, naringenin not only inhibits cytokine mRNA expression but also promotes lysosome-dependent cytokine protein degradation. This unique property of naringenin stands in sharp contrast with some widely-studied natural products such as apigenin and curcumin, which regulate cytokine production essentially at the transcriptional level. Therefore, naringenin may provide modality for the development of novel anti-inflammatory agent. This review article summarizes our recent studies in understanding how naringenin acts in cells and animal models. Particularly, we will discuss the anti-inflammatory activities of naringenin in various disease context and its potential use, as an immunomodulator, in the treatment of inflammatory related disease.


greenmedinfo--2020-08-12--Structure-based drug designing for potential antiviral activity of selected natural products from Ay

Structure-based drug designing for potential antiviral activity of selected natural products from Ayurveda against SARS-CoV-2 spike glycoprotein and its cellular receptor.

The recent outbreak of COVID-19 caused by SARS-CoV-2 brought a great global public health and economic concern .
SARS-CoV-2 is an enveloped RNA virus , from the genusAlthough few molecules have been tested and shown some efficacy against SARS-CoV-2 in humans but a safe and cost-effective attachment inhibitors are still required for the treatment of COVID-19 .
Natural products are gaining attention because of the large therapeutic window and potent antiviral , immunomodulatory , anti-inflammatory , and antioxidant properties .
Therefore , this study was planned to screen natural products from Ayurveda that have the potential to modulate host immune @ @ @ @ @ @ @ entry in host cells by interfering its interaction with cellular receptor and may be used to develop an effective and broad-spectrum strategy for the management of COVID-19 as well as other coronavirus infections incoming future .
To decipher the antiviral activity of the selected natural products , molecular docking was performed .
Further , the drug-likeness , pharmacokinetics and toxicity parameters of the selected natural products were determined .
Docking results suggest that curcumin and nimbin exhibits highest interaction with spike glycoprotein ( MolDock score - 141.36 and - 148.621 kcal/mole ) and @ @ @ @ @ @ @ and - 140.108 kcal/mole ) as compared with other selected natural products/drugs and controls .
Also , the pharmacokinetics data illustrated that all selected natural products have better pharmacological properties ( low molecular weight ; no violation of Lipinski rule of five , good absorption profiles , oral bioavailability , good blood-brain barrier penetration , and low toxicity risk ) .
Our study exhibited that curcumin , nimbin , withaferin A , piperine , mangiferin , thebaine , berberine , and andrographolide have significant binding affinity towards spike glycoprotein of SARS-CoV-2 and ACE2 @ @ @ @ @ @ @ therapeutic and/or prophylactic agent for restricting viral attachment to the host cells .
However , few other natural products like resveratrol , quercetin , luteolin , naringenin , zingiberene , and gallic acid has the significant binding affinity towards ACE2 receptor only and therefore may be used for ACE2-mediated attachment inhibition of SARS-CoV-2 .

The recent outbreak of COVID-19 caused by SARS-CoV-2 brought a great global public health and economic concern. SARS-CoV-2 is an enveloped RNA virus, from the genusAlthough few molecules have been tested and shown some efficacy against SARS-CoV-2 in humans but a safe and cost-effective attachment inhibitors are still required for the treatment of COVID-19. Natural products are gaining attention because of the large therapeutic window and potent antiviral, immunomodulatory, anti-inflammatory, and antioxidant properties. Therefore, this study was planned to screen natural products from Ayurveda that have the potential to modulate host immune system as well as block the virus entry in host cells by interfering its interaction with cellular receptor and may be used to develop an effective and broad-spectrum strategy for the management of COVID-19 as well as other coronavirus infections incoming future. To decipher the antiviral activity of the selected natural products, molecular docking was performed. Further, the drug-likeness, pharmacokinetics and toxicity parameters of the selected natural products were determined. Docking results suggest that curcumin and nimbin exhibits highest interaction with spike glycoprotein (MolDock score - 141.36 and - 148.621 kcal/mole) and ACE2 receptor (MolDock score - 142.647 and - 140.108 kcal/mole) as compared with other selected natural products/drugs and controls. Also, the pharmacokinetics data illustrated that all selected natural products have better pharmacological properties (low molecular weight; no violation of Lipinski rule of five, good absorption profiles, oral bioavailability, good blood-brain barrier penetration, and low toxicity risk). Our study exhibited that curcumin, nimbin, withaferin A, piperine, mangiferin, thebaine, berberine, and andrographolide have significant binding affinity towards spike glycoprotein of SARS-CoV-2 and ACE2 receptor and may be useful as a therapeutic and/or prophylactic agent for restricting viral attachment to the host cells. However, few other natural products like resveratrol, quercetin, luteolin, naringenin, zingiberene, and gallic acid has the significant binding affinity towards ACE2 receptor only and therefore may be used for ACE2-mediated attachment inhibition of SARS-CoV-2.


greenmedinfo--2020-08-12--COVID-19 and heme oxygenase: novel insight into the disease and potential therapies.

The COVID-19 pandemic needs therapies that are presently available and safe .
We propose that subjects with metabolic syndrome , old age , and male gender have the greatest morbidity and mortality and have low stress proteins , in particular , low intracellular heme oxygenase ( HO-1 ) , making them particularly vulnerable to the disease .
Additionally , COVID-19 's heme reduction may contribute to even lower HO-1 .
Low-grade inflammation associated with these risk factors contributes to triggering a cytokine storm that spreads to multi-organ failure and near death .
The high mortality of those treated with ventilator @ @ @ @ @ @ @ inflammation .
The cytoprotective and anti-inflammatory properties of HO-1 can limit the infection 's damage .
A paradox of COVID-19 hospital admissions data suggests that fewer cigarette-smokers are admitted compared with non-smokers in the general population .
This unexpected observation may result from smoke induction of HO-1 .
Therapies with anti-viral properties that raise HO-1 include certain anesthetics ( sevoflurane or isoflurane ) , hemin , estrogen , statins , curcumin , resveratrol , and melatonin .
Controlled trials of these HO-1 inducers should be done in order to prevent or treat COVID-19 @ @

The COVID-19 pandemic needs therapies that are presently available and safe. We propose that subjects with metabolic syndrome, old age, and male gender have the greatest morbidity and mortality and have low stress proteins, in particular, low intracellular heme oxygenase (HO-1), making them particularly vulnerable to the disease. Additionally, COVID-19's heme reduction may contribute to even lower HO-1. Low-grade inflammation associated with these risk factors contributes to triggering a cytokine storm that spreads to multi-organ failure and near death. The high mortality of those treated with ventilator assistance may partially be explained by ventilator-induced inflammation. The cytoprotective and anti-inflammatory properties of HO-1 can limit the infection's damage. A paradox of COVID-19 hospital admissions data suggests that fewer cigarette-smokers are admitted compared with non-smokers in the general population. This unexpected observation may result from smoke induction of HO-1. Therapies with anti-viral properties that raise HO-1 include certain anesthetics (sevoflurane or isoflurane), hemin, estrogen, statins, curcumin, resveratrol, and melatonin. Controlled trials of these HO-1 inducers should be done in order to prevent or treat COVID-19 disease.


greenmedinfo--2020-08-12--These results suggested that high vitamin D concentration was associated with lower odds ratio of ga

These results suggested that high vitamin D concentration was associated with lower odds ratio of gastric cancer in Korean adults.

Sufficient vitamin D levels are associated with reducedinfections , which can cause gastric carcinogenesis .
We examined associations between vitamin D concentrations and gastric cancer ( GC ) prevalence in a Korean population .
We analyzed data of 33,119 adults using serum 25-hydroxyvitamin D ( 25 ( OH ) D ) concentrations as a biomarker of vitamin D status .
Participants were classified with GC if previously diagnosed as such by a physician .
After controlling for age , sex and body mass index ( model A ) , odds ratio ( OR ) for GC was 0.81 ( 95 @ @ @ @ @ @ @ 0.70 , 0.95 ) , with a 5-ng/mL increment in total 25 ( OH ) D concentrations .
In fully adjusted models ( model B ) , the OR for GC was 0.84 ( 95 % CI : 0.72 , 0.98 ) , with a 5-ng/mL increment in total vitamin D. Following the classification of vitamin D concentrations into three categories or for GC in model A was 0.52 ( 95 % CI : 0.30 , 0.92 ) comparing between higher ( ≥20 ng/mL ) and lower ( < 12 ng/mL ) total @ @ @ @ @ @ @ In model B OR for GC was 0.57 ( 95 % CI : 0.32 , 1.00 ) comparing between higher and lower total 25 ( OH ) D concentrations .
Our results suggested that high vitamin D concentration was associated with lower ORs of GC in Korean adults .

Sufficient vitamin D levels are associated with reducedinfections, which can cause gastric carcinogenesis. We examined associations between vitamin D concentrations and gastric cancer (GC) prevalence in a Korean population. We analyzed data of 33,119 adults using serum 25-hydroxyvitamin D (25(OH)D) concentrations as a biomarker of vitamin D status. Participants were classified with GC if previously diagnosed as such by a physician. After controlling for age, sex and body mass index (model A), odds ratio (OR) for GC was 0.81 (95% confidence interval [CI]: 0.70, 0.95), with a 5-ng/mL increment in total 25(OH)D concentrations. In fully adjusted models (model B), the OR for GC was 0.84 (95% CI: 0.72, 0.98), with a 5-ng/mL increment in total vitamin D. Following the classification of vitamin D concentrations into three categories or for GC in model A was 0.52 (95% CI: 0.30, 0.92) comparing between higher (≥20 ng/mL) and lower (<12 ng/mL) total 25(OH)D concentrations. In model B OR for GC was 0.57 (95% CI: 0.32, 1.00) comparing between higher and lower total 25(OH)D concentrations. Our results suggested that high vitamin D concentration was associated with lower ORs of GC in Korean adults.


greenmedinfo--2020-08-12--Impact of a ketogenic diet on metabolic parameters in patients with obesity or overweight and with o

Impact of a ketogenic diet on metabolic parameters in patients with obesity or overweight and with or without type 2 diabetes.

The aim of this meta-analysis was to explore the efficacy of a ketogenic diet in metabolic control in patients with overweight or obesity and with or without type 2 diabetes .
Embase , PubMed , and Cochrane Library were searched for randomized controlled trials that enrolled patients with overweight or obesity on a ketogenic diet for metabolic control .
Fourteen studies were included in meta-analysis .
The effects of ketogenic diets on glycemic control were greater for diabetic patients relative to those of low-fat diets , indicated by lower glycated hemoglobin ( SMD , -0.62 ; < 0.001 ) and @ @ @ @ @ @ @ -0.29 ; = 0.02 ) , while comparable effects were observed for nondiabetic patients .
Ketogenic diets led to substantial weight reduction ( SMD , -0.46 ; = 0.04 ) irrespective of patients ' diabetes status at baseline and improved lipid profiles in terms of lower triglyceride ( SMD , -0.45 ; = 0.01 ) and greater high-density lipoprotein ( SMD , 0.31 ; = 0.005 ) for diabetic patients .
Other risk markers showed no substantial between-group difference post intervention .
Our study findings confirmed that ketogenic diets were more effective in @ @ @ @ @ @ @ weight , and lipid controls in patients with overweight or obesity , especially those with preexisting diabetes , as compared to low-fat diets .
This effect may contribute to improvements in metabolic dysfunction-related morbidity and mortality in these patient populations .

The aim of this meta-analysis was to explore the efficacy of a ketogenic diet in metabolic control in patients with overweight or obesity and with or without type 2 diabetes. Embase, PubMed, and Cochrane Library were searched for randomized controlled trials that enrolled patients with overweight or obesity on a ketogenic diet for metabolic control. Fourteen studies were included in meta-analysis. The effects of ketogenic diets on glycemic control were greater for diabetic patients relative to those of low-fat diets, indicated by lower glycated hemoglobin (SMD, -0.62;<0.001) and homeostatic model assessment index (SMD, -0.29;= 0.02), while comparable effects were observed for nondiabetic patients. Ketogenic diets led to substantial weight reduction (SMD, -0.46;= 0.04) irrespective of patients' diabetes status at baseline and improved lipid profiles in terms of lower triglyceride (SMD, -0.45;= 0.01) and greater high-density lipoprotein (SMD, 0.31;= 0.005) for diabetic patients. Other risk markers showed no substantial between-group difference post intervention. Our study findings confirmed that ketogenic diets were more effective in improving metabolic parameters associated with glycemic, weight, and lipid controls in patients with overweight or obesity, especially those with preexisting diabetes, as compared to low-fat diets. This effect may contribute to improvements in metabolic dysfunction-related morbidity and mortality in these patient populations.


greenmedinfo--2020-08-12--Cuban brown propolis interferes in the crosstalk between colorectal cancer cells and M2 macrophages.

Tumor-associated macrophages ( TAMs ) , primarily the M2 phenotype , are involved in the progression and metastasis of colorectal cancer ( CRC ) .
Cuban brown propolis ( Cp ) and its main component Nemorosone ( Nem ) displays an antiproliferative effect on different cancer cells , including CRC cell lines .
However , whether Cp and Nem could exploit its effect on CRC cells by targeting their relationship with TAMs remains to be elucidated .
In this study , we differentiated the human monocytic THP-1 cells to M2 macrophages and confirmed this transition by immunofluorescence ( IF ) @ @ @ @ @ @ @ MTT assay was performed to determine the effect of Cp and Nem on the viability of CRC HT-29 cells co-cultured with M2 macrophages .
Furthermore , the migration and invasion abilities of HT-29 cells were determined by Transwell assays and the expression levels of epithelial-mesenchymal transition ( EMT ) markers were analyzed by IF staining .
We demonstrated that Cp and Nem reduced the viability of M2 macrophages and , accordingly , the activity of the MMP-9 metalloprotein .
Moreover , we demonstrated that M2 macrophages produce soluble factors that positively regulate HT-29 @ @ @ @ @ @ @ These M2-mediated effects were counteracted by Cp and Nem treatments , which also played a role in regulating the expression of the EMT markers E-cadherin and vimentin .
Taken together , our results indicate that Nem contained in Cp interferes in the crosstalk between CRC cells and TAMs , by targeting M2 macrophages .

Tumor-associated macrophages (TAMs), primarily the M2 phenotype, are involved in the progression and metastasis of colorectal cancer (CRC). Cuban brown propolis (Cp) and its main component Nemorosone (Nem) displays an antiproliferative effect on different cancer cells, including CRC cell lines. However, whether Cp and Nem could exploit its effect on CRC cells by targeting their relationship with TAMs remains to be elucidated. In this study, we differentiated the human monocytic THP-1 cells to M2 macrophages and confirmed this transition by immunofluorescence (IF) staining, qRT-PCR and zymography. An MTT assay was performed to determine the effect of Cp and Nem on the viability of CRC HT-29 cells co-cultured with M2 macrophages. Furthermore, the migration and invasion abilities of HT-29 cells were determined by Transwell assays and the expression levels of epithelial-mesenchymal transition (EMT) markers were analyzed by IF staining. We demonstrated that Cp and Nem reduced the viability of M2 macrophages and, accordingly, the activity of the MMP-9 metalloprotein. Moreover, we demonstrated that M2 macrophages produce soluble factors that positively regulate HT-29 cell growth, migration and invasion. These M2-mediated effects were counteracted by Cp and Nem treatments, which also played a role in regulating the expression of the EMT markers E-cadherin and vimentin. Taken together, our results indicate that Nem contained in Cp interferes in the crosstalk between CRC cells and TAMs, by targeting M2 macrophages.


greenmedinfo--2020-08-12--Six months of vitamin D supplementation led to a decrease in some inflammatory markers in patients w

BACKGROUND : A low serum 25-hydroxyvitamin D ( 25 ( OH ) D ) concentration has been associated with a higher risk of type 2 diabetes mellitus ( T2DM ) , especially in older people .
Our aim in this randomized controlled trial was to evaluate the effect of vitamin D treatment on inflammatory markers in non-obese Lebanese patients with T2DM , living in Beirut , Lebanon .
METHODS : Non-Obese patients with T2DM ( = 88 ) , deficient/insufficient in vitamin D , were randomly assigned into one of two groups-a treatment group receiving 30,000 IU cholecalciferol/week for a @ @ @ @ @ @ @ placebo group .
Serum concentrations of TNF-α , high-sensitivity C-reactive protein ( hs-CRP ) , and Interleukin-6 ( IL-6 ) were the primary outcomes .
A homeostatic model of insulin resistance ( HOMA-IR ) was assessed , in addition to serum concentrations of fasting blood glucose ( FBG ) , HbA1C , ( 25 ( OH ) D ) , and PTH .
RESULTS : The vitamin D group showed higher blood levels of ( 25 ( OH ) D ) ( < 0.0001 ) , and a significant reduction in hs-CRP and @ @ @ @ @ @ @ to placebo .
The decrease perceived in IL-6 concentrations was not significant ( = 0.1 ) .
No significant changes were seen in FBG ( = 0.9 ) and HbA1c levels ( = 0.85 ) .
CONCLUSION : Six months of vitamin D supplementation led to a decrease in some inflammatory markers in patients with T2DM .
Additional studies with a larger sample and a longer period are advised in this regard .
This trial was registered at ClinicalTrial.gov ; Identifier number : NCT03782805 .

BACKGROUND: A low serum 25-hydroxyvitamin D (25(OH) D) concentration has been associated with a higher risk of type 2 diabetes mellitus (T2DM), especially in older people. Our aim in this randomized controlled trial was to evaluate the effect of vitamin D treatment on inflammatory markers in non-obese Lebanese patients with T2DM, living in Beirut, Lebanon.
METHODS: Non-Obese patients with T2DM (= 88), deficient/insufficient in vitamin D, were randomly assigned into one of two groups-a treatment group receiving 30,000 IU cholecalciferol/week for a period of six months, and a placebo group. Serum concentrations of TNF-α, high-sensitivity C-reactive protein (hs-CRP), and Interleukin-6 (IL-6) were the primary outcomes. A homeostatic model of insulin resistance (HOMA-IR) was assessed, in addition to serum concentrations of fasting blood glucose (FBG), HbA1C, (25(OH) D), and PTH.
RESULTS: The vitamin D group showed higher blood levels of (25(OH) D) (<0.0001), and a significant reduction in hs-CRP and TNF-α concentrations (<0.0001) compared to placebo. The decrease perceived in IL-6 concentrations was not significant (= 0.1). No significant changes were seen in FBG (= 0.9) and HbA1c levels (= 0.85).
CONCLUSION: Six months of vitamin D supplementation led to a decrease in some inflammatory markers in patients with T2DM. Additional studies with a larger sample and a longer period are advised in this regard. This trial was registered at ClinicalTrial.gov; Identifier number: NCT03782805.


greenmedinfo--2020-08-12--Magnesium sulfate-rich natural mineral waters in the treatment of functional constipation.

Functional constipation ( FC ) is a chronic constipation for which no physiological , anatomical or iatrogenic origin can be @ @ @ @ @ a high impact on a patient 's quality of life and healthcare costs .
Since @ @ @ @ @ low physical activity and a diet low in fiber and/or water , first-line recommendations focus @ @ @ @ @ sufficient fiber and water intake .
In case of inefficacy of these measures , numerous @ @ @ @ @ either over the counter or on prescription .
Magnesium sulfate has a long history in @ @ @ @ @ and magnesium sulfate-rich mineral waters have been used for centuries for their laxative properties .
@ @ @ @ @ and sulfate has since been widely demonstrated .
Nevertheless , it appears that no clinical @ @ @ @ @ efficacy in FC had been conducted before the 21st century .
In this paper , @ @ @ @ @ reporting the efficacy of magnesium sulfate-rich natural mineral waters .
In view of their reported @ @ @ @ @ sulfate-rich natural mineral waters may represent a natural treatment for FC .

Functional constipation (FC) is a chronic constipation for which no physiological, anatomical or iatrogenic origin can be evidenced. This condition has a high impact on a patient's quality of life and healthcare costs. Since FC is frequently associated with low physical activity and a diet low in fiber and/or water, first-line recommendations focus on sufficient activity, and sufficient fiber and water intake. In case of inefficacy of these measures, numerous drug treatments are available, either over the counter or on prescription. Magnesium sulfate has a long history in the treatment of FC, and magnesium sulfate-rich mineral waters have been used for centuries for their laxative properties. The laxative effect of magnesium and sulfate has since been widely demonstrated. Nevertheless, it appears that no clinical studies aiming at demonstrating their efficacy in FC had been conducted before the 21st century. In this paper, we reviewed the clinical data reporting the efficacy of magnesium sulfate-rich natural mineral waters. In view of their reported efficacy and safety, magnesium sulfate-rich natural mineral waters may represent a natural treatment for FC.


greenmedinfo--2020-08-12--The impact of dietary supplementation of whole foods and polyphenols on atherosclerosis.

The purpose of this review is to highlight current research on the benefits of supplementation with foods with a diverse polyphenol composition , including fruits , vegetables , nuts , grains , oils , spices , and teas in blunting atherosclerosis .
We searched PubMed for publications utilizing whole food or polyphenols prepared from whole foods in Apolipoprotein E ( ApoE ) or Low-Density Lipoprotein Receptor ( LDLR ) knockout mice , and identified 73 studies in which plaque was measured .
The majority of the studies reported a reduction in plaque .
Nine interventions showed no effect , while @ @ @ @ @ @ @ and safrole-2 ' , 3'-oxide ( SFO ) increased plaque .
The mechanisms by which atherosclerosis was reduced include improved lipid profile , antioxidant status , and cholesterol clearance , and reduced inflammation .
Importantly , not all dietary interventions that reduce plaque showed an improvement in lipid profile .
Additionally , we found that , out of 73 studies , only 9 used female mice and only 6 compared both sexes .
Only one study compared the two models ( LDLR vs. ApoE ) , showing that the treatment worked in one @ @ @ @ @ @ @ supplementations work in both male and female animals , suggesting that increasing the variety of foods with different polyphenol compositions may be more effective in mitigating atherosclerosis .

The purpose of this review is to highlight current research on the benefits of supplementation with foods with a diverse polyphenol composition, including fruits, vegetables, nuts, grains, oils, spices, and teas in blunting atherosclerosis. We searched PubMed for publications utilizing whole food or polyphenols prepared from whole foods in Apolipoprotein E (ApoE) or Low-Density Lipoprotein Receptor (LDLR) knockout mice, and identified 73 studies in which plaque was measured. The majority of the studies reported a reduction in plaque. Nine interventions showed no effect, while three usingmushroom, HYJA-ri-4 rice variety, and safrole-2', 3'-oxide (SFO) increased plaque. The mechanisms by which atherosclerosis was reduced include improved lipid profile, antioxidant status, and cholesterol clearance, and reduced inflammation. Importantly, not all dietary interventions that reduce plaque showed an improvement in lipid profile. Additionally, we found that, out of 73 studies, only 9 used female mice and only 6 compared both sexes. Only one study compared the two models (LDLR vs. ApoE), showing that the treatment worked in one but not the other. Not all supplementations work in both male and female animals, suggesting that increasing the variety of foods with different polyphenol compositions may be more effective in mitigating atherosclerosis.


greenmedinfo--2020-08-12--Dietary selenium intakes and musculoskeletal function in very old adults.

: Selenium is a trace element essential for health .
Severe selenium deficiencies are associated with poor musculoskeletal ( MSK ) function .
However , the effects of moderate deficiency on MSK function , especially in older adults , is unclear .
: To determine the associations between selenium intake and MSK function in very old adults .
: Selenium intake at baseline and , hand-grip strength ( HGS ) and timed-up-and-go ( TUG ) at four phases over 5 years , were available in 791 participants in the Newcastle 85+ Study , a community-based , longitudinal cohort of≥85 year @ @ @ @ @ @ @ selenium intake and HGS and TUG in cross-sectional analyses at baseline using multivariate analyses and , prospectively using linear mixed models to explore HGS and TUG changes over 5 years in association with baseline selenium intake .
: At baseline , 53 % of participants had selenium intakes that were classified as low .
These individuals had 2.80 kg lower HGS and were 2.30 s slower performing the TUG , cross-sectionally .
In multivariate , baseline analyses , selenium intake had no significant impact on HGS or TUG .
Selenium intake had no @ @ @ @ @ @ @ .
: Low selenium intake is common among very old adults and , in cross-sectional analyses , is associated with poorer MSK function .

: Selenium is a trace element essential for health. Severe selenium deficiencies are associated with poor musculoskeletal (MSK) function. However, the effects of moderate deficiency on MSK function, especially in older adults, is unclear.: To determine the associations between selenium intake and MSK function in very old adults.: Selenium intake at baseline and, hand-grip strength (HGS) and timed-up-and-go (TUG) at four phases over 5 years, were available in 791 participants in the Newcastle 85+ Study, a community-based, longitudinal cohort of≥85 year old individuals. We investigated relationships between selenium intake and HGS and TUG in cross-sectional analyses at baseline using multivariate analyses and, prospectively using linear mixed models to explore HGS and TUG changes over 5 years in association with baseline selenium intake.: At baseline, 53% of participants had selenium intakes that were classified as low. These individuals had 2.80 kg lower HGS and were 2.30 s slower performing the TUG, cross-sectionally. In multivariate, baseline analyses, selenium intake had no significant impact on HGS or TUG. Selenium intake had no significant effect on MSK function, prospectively.: Low selenium intake is common among very old adults and, in cross-sectional analyses, is associated with poorer MSK function.


greenmedinfo--2020-08-13--Perinatal exposure to glyphosate or a glyphosate-based formulation disrupts hormonal and uterine mil

Perinatal exposure to glyphosate or a glyphosate-based formulation disrupts hormonal and uterine milieu during the receptive state in rats.

We investigated the effects of perinatal exposure to a glyphosate-based herbicide ( GBH ) or glyphosate alone ( Gly ) on female fertility and the hormonal and uterine milieu during the preimplantation period .
F0 pregnant rats orally received a GBH or Gly in a dose of 2 mg of glyphosate/kg/day from gestational day ( GD ) 9 until weaning .
F1 females were evaluated to determine the reproductive performance on GD19 ; and the sex steroid serum levels , the expression of estrogen receptor alpha ( ERα ) , progesterone receptor ( PR ) and implantation-related genes on GD5 @ @ @ @ @ @ @ Gly induced preimplantation losses in F1 rats .
GBH and Gly groups exhibited higher 17β-estradiol serum levels , without changes in progesterone .
Both compounds increased the uterine ERα protein expression , with no differences at transcript level ; and only Gly decreased PR mRNA expression .
Also , GBH and Gly downregulated Hoxa10 and Lif genes , with no difference in Muc1 and Areg expression .
To conclude , perinatal exposure to a GBH or Gly disrupted critical hormonal and uterine molecular targets during the receptive state , possibly associated with the @ @ @ @ @ @ @ were found in GBH- and Gly-exposed rats , suggesting that the active principle might be the main responsible for the deleterious effects .

We investigated the effects of perinatal exposure to a glyphosate-based herbicide (GBH) or glyphosate alone (Gly) on female fertility and the hormonal and uterine milieu during the preimplantation period. F0 pregnant rats orally received a GBH or Gly in a dose of 2 mg of glyphosate/kg/day from gestational day (GD) 9 until weaning. F1 females were evaluated to determine the reproductive performance on GD19; and the sex steroid serum levels, the expression of estrogen receptor alpha (ERα), progesterone receptor (PR) and implantation-related genes on GD5 (preimplantation period). GBH and Gly induced preimplantation losses in F1 rats. GBH and Gly groups exhibited higher 17β-estradiol serum levels, without changes in progesterone. Both compounds increased the uterine ERα protein expression, with no differences at transcript level; and only Gly decreased PR mRNA expression. Also, GBH and Gly downregulated Hoxa10 and Lif genes, with no difference in Muc1 and Areg expression. To conclude, perinatal exposure to a GBH or Gly disrupted critical hormonal and uterine molecular targets during the receptive state, possibly associated with the implantation failures. Overall, similar results were found in GBH- and Gly-exposed rats, suggesting that the active principle might be the main responsible for the deleterious effects.


greenmedinfo--2020-08-13--What Are the Benefits of Hyperbaric Oxygen Therapy?

This website is for information purposes only .
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.
© Copyright 2008-2023 GreenMedInfo.com, Journal Articles copyright of original owners, MeSH copyright NLM.


greenmedinfo--2020-08-13--Oral and topical exposure to glyphosate in herbicide formulation impact the gut microbiota and survi

Oral and topical exposure to glyphosate in herbicide formulation impact the gut microbiota and survival rates of honey bees.

Honey bees are important agricultural pollinators that rely on a specific gut microbiota for regulation of immune system and defense against pathogens .
Environmental stressors that affect the bee gut microbial community , such as antibiotics and glyphosate , can indirectly compromise bee health .
Most of the experiments demonstrating these effects have been done under laboratory conditions with pure chemicals .
Here , we investigated the oral and topical effects of variable concentrations of glyphosate in herbicide formulation on the honey bee gut microbiota and health under laboratory and field conditions .
In all of these conditions , the @ @ @ @ @ @ @ water , affected the abundance of beneficial bacteria in the bee gut in a dose-dependent way .
Mark-recapture experiments also demonstrated that bees exposed to the formulation were more likely to disappear from the colony , once reintroduced after exposure .
Although no visible effects were observed for hives exposed to the formulation in field experiments , challenge trials with the pathogenperformed under laboratory conditions , revealed that bees from hives exposed to the formulation exhibited increased mortality compared to bees from control hives .
In the field experiments , glyphosate was detected @ @ @ @ @ @ @ showing that worker bees transfer xenobiotics to the hive , thereby extending exposure and increasing the chances of exposure to recently emerged bees .
These findings show that different routes of exposure to glyphosate-based herbicide can affect honey bees and their gut microbiota.The honey bee gut microbial community plays a vital role in immune response and defense against opportunistic pathogens .
Environmental stressors , such as the herbicide glyphosate , may affect the gut microbiota , with negative consequences for bee health .
Glyphosate is usually sprayed in the field mixed with adjuvants @ @ @ @ @ @ @ adjuvants may also enhance undesired effects in non-targeted organisms .
This seems to be the case for glyphosate-based herbicide on honey bees .
As we show in this study , oral exposure to either pure glyphosate or glyphosate in commercial herbicide formulation perturbs the gut microbiota of honey bees , and topical exposure to the formulation also has a direct effect on honey bee health , increasing mortality in a dose-dependent way and leaving surviving bees with a perturbed microbiota .
Understanding the effects of herbicide formulations on honey bees may help to @ @ @ @ @ @

Honey bees are important agricultural pollinators that rely on a specific gut microbiota for regulation of immune system and defense against pathogens. Environmental stressors that affect the bee gut microbial community, such as antibiotics and glyphosate, can indirectly compromise bee health. Most of the experiments demonstrating these effects have been done under laboratory conditions with pure chemicals. Here, we investigated the oral and topical effects of variable concentrations of glyphosate in herbicide formulation on the honey bee gut microbiota and health under laboratory and field conditions. In all of these conditions, the formulation, dissolved in sucrose syrup or water, affected the abundance of beneficial bacteria in the bee gut in a dose-dependent way. Mark-recapture experiments also demonstrated that bees exposed to the formulation were more likely to disappear from the colony, once reintroduced after exposure. Although no visible effects were observed for hives exposed to the formulation in field experiments, challenge trials with the pathogenperformed under laboratory conditions, revealed that bees from hives exposed to the formulation exhibited increased mortality compared to bees from control hives. In the field experiments, glyphosate was detected in honey collected from exposed hives, showing that worker bees transfer xenobiotics to the hive, thereby extending exposure and increasing the chances of exposure to recently emerged bees. These findings show that different routes of exposure to glyphosate-based herbicide can affect honey bees and their gut microbiota.The honey bee gut microbial community plays a vital role in immune response and defense against opportunistic pathogens. Environmental stressors, such as the herbicide glyphosate, may affect the gut microbiota, with negative consequences for bee health. Glyphosate is usually sprayed in the field mixed with adjuvants, which enhance herbicidal activity. These adjuvants may also enhance undesired effects in non-targeted organisms. This seems to be the case for glyphosate-based herbicide on honey bees. As we show in this study, oral exposure to either pure glyphosate or glyphosate in commercial herbicide formulation perturbs the gut microbiota of honey bees, and topical exposure to the formulation also has a direct effect on honey bee health, increasing mortality in a dose-dependent way and leaving surviving bees with a perturbed microbiota. Understanding the effects of herbicide formulations on honey bees may help to protect these important agricultural pollinators.


greenmedinfo--2020-08-13--Are glyphosate and glyphosate-based herbicides endocrine disruptors that alter female fertility?

Numerous evidences have alerted on the toxic effects of the exposure to glyphosate on living organisms .
Glyphosate is the herbicide most used in crops such as maize and soybean worldwide , which implies that several non-target species are at a high risk of exposure .
Although the Environmental Protection Agency ( EPA-USA ) has reaffirmed that glyphosate is safe for users , there are controversial studies that question this statement .
Some of the reported effects are due to exposure to high doses ; however , recent evidences have shown that exposure to low doses could also alter the @ @ @ @ @ @ @ with consequences on fertility .
Different animal models of exposure to glyphosate or glyphosate-based herbicides ( GBHs ) have shown that the effects on the female reproductive tract may be related to the potential and/or mechanisms of actions of an endocrine-disrupting compound .
Studies have also demonstrated that the exposure to GBHs alters the development and differentiation of ovarian follicles and uterus , affecting fertility when animals are exposed before puberty .
In addition , exposure to GBHs during gestation could alter the development of the offspring ( F1 and F2 ) .
@ @ @ @ @ @ @ endocrine-disrupting effect of GBHs is the modulation of estrogen receptors and molecules involved in the estrogenic pathways .
This review summarizes the endocrine-disrupting effects of exposure to glyphosate and GBHs at low or '' environmentally relevant '' doses in the female reproductive tissues .
Data suggesting that , at low doses , GBHs may have adverse effects on the female reproductive tract fertility are discussed .

Numerous evidences have alerted on the toxic effects of the exposure to glyphosate on living organisms. Glyphosate is the herbicide most used in crops such as maize and soybean worldwide, which implies that several non-target species are at a high risk of exposure. Although the Environmental Protection Agency (EPA-USA) has reaffirmed that glyphosate is safe for users, there are controversial studies that question this statement. Some of the reported effects are due to exposure to high doses; however, recent evidences have shown that exposure to low doses could also alter the development of the female reproductive tract, with consequences on fertility. Different animal models of exposure to glyphosate or glyphosate-based herbicides (GBHs) have shown that the effects on the female reproductive tract may be related to the potential and/or mechanisms of actions of an endocrine-disrupting compound. Studies have also demonstrated that the exposure to GBHs alters the development and differentiation of ovarian follicles and uterus, affecting fertility when animals are exposed before puberty. In addition, exposure to GBHs during gestation could alter the development of the offspring (F1 and F2). The main mechanism described associated with the endocrine-disrupting effect of GBHs is the modulation of estrogen receptors and molecules involved in the estrogenic pathways. This review summarizes the endocrine-disrupting effects of exposure to glyphosate and GBHs at low or"environmentally relevant"doses in the female reproductive tissues. Data suggesting that, at low doses, GBHs may have adverse effects on the female reproductive tract fertility are discussed.


greenmedinfo--2020-08-13--Glyphosate and its formulation roundup impair pig oocyte maturation.

Glyphosate , formulated as glyphosate-based herbicides ( GBHs ) including the best-known formulation Roundup , is the world 's most widely used herbicide .
During the last years , the growing and widespread use of GBHs has raised a great concern about the impact of environmental contamination on animal and human health including potential effect on reproductive systems .
Using an in vitro model of pig oocyte maturation , we examined the biological impact of both glyphosate and Roundup on female gamete evaluating nuclear maturation , cytoplasmic maturation and developmental competence of oocytes , steroidogenic activity of cumulus cells as @ @ @ @ @ @ @ GSH ) and ROS of oocytes .
Our results indicate that although exposure to glyphosate and Roundup during in vitro maturation does not affect nuclear maturation and embryo cleavage , it does impair oocyte developmental competence in terms of blastocyst rate and cellularity .
Moreover , Roundup at the same glyphosate-equivalent concentrations was shown to be more toxic than pure glyphosate , altering steroidogenesis and increasing oocyte ROS levels , thus confirming that Roundup adjuvants enhance glyphosate toxic effects and/or are biologically active in their side-effect and therefore should be considered and tested @ @ @ @

Glyphosate, formulated as glyphosate-based herbicides (GBHs) including the best-known formulation Roundup, is the world's most widely used herbicide. During the last years, the growing and widespread use of GBHs has raised a great concern about the impact of environmental contamination on animal and human health including potential effect on reproductive systems. Using an in vitro model of pig oocyte maturation, we examined the biological impact of both glyphosate and Roundup on female gamete evaluating nuclear maturation, cytoplasmic maturation and developmental competence of oocytes, steroidogenic activity of cumulus cells as well as intracellular levels of glutathione (GSH) and ROS of oocytes. Our results indicate that although exposure to glyphosate and Roundup during in vitro maturation does not affect nuclear maturation and embryo cleavage, it does impair oocyte developmental competence in terms of blastocyst rate and cellularity. Moreover, Roundup at the same glyphosate-equivalent concentrations was shown to be more toxic than pure glyphosate, altering steroidogenesis and increasing oocyte ROS levels, thus confirming that Roundup adjuvants enhance glyphosate toxic effects and/or are biologically active in their side-effect and therefore should be considered and tested as active ingredients.


greenmedinfo--2020-08-13--The glyphosate formulation Roundup® LB plus influences the global metabolome of pig gut microbiota i

The glyphosate formulation Roundup® LB plus influences the global metabolome of pig gut microbiota in vitro.

Glyphosate is the world 's most widely used herbicide , and its potential side effects on the intestinal microbiota of various animals , from honeybees to livestock and humans , are currently under discussion .
Pigs are among the most abundant livestock animals worldwide and an impact of glyphosate on their intestinal microbiota function can have serious consequences on their health , not to mention the economic effects .
Recent studies that addressed microbiota-disrupting effects focused on microbial taxonomy but lacked functional information .
Therefore , we chose an experimental design with a short incubation time in which effects on @ @ @ @ @ @ @ but functional effects can be detected .
We cultivated intestinal microbiota derived from pig colon in chemostats and investigated the acute effect of 228 mg/d glyphosate acid equivalents from Roundup® LB plus , a frequently applied glyphosate formulation .
The applied glyphosate concentration resembles a worst-case scenario for an 8-9 week-old pig and relates to the maximum residue levels of glyphosate on animal fodder .
The effects were determinedon the functional level by metaproteomics , targeted and untargeted meta-metabolomics , while variations in community structure were analyzed by 16S rRNA gene profiling and @ @ @ @ @ @ @ flow cytometry .
Roundup® LB plus did not affect the community taxonomy or the enzymatic repertoire of the cultivated microbiota in general or on the expression of the glyphosate target enzyme 5-enolpyruvylshikimate-3-phosphate synthase in detail .
On the functional level , targeted metabolite analysis of short chain fatty acids ( SCFAs ) , free amino acids and bile acids did not reveal significant changes , whereas untargeted meta-metabolomics did identify some effects on the functional level .
This multi-omics approach provides evidence for subtle metabolic effects of Roundup® LB plus under the conditions @ @

Glyphosate is the world's most widely used herbicide, and its potential side effects on the intestinal microbiota of various animals, from honeybees to livestock and humans, are currently under discussion. Pigs are among the most abundant livestock animals worldwide and an impact of glyphosate on their intestinal microbiota function can have serious consequences on their health, not to mention the economic effects. Recent studies that addressed microbiota-disrupting effects focused on microbial taxonomy but lacked functional information. Therefore, we chose an experimental design with a short incubation time in which effects on the community structure are not expected, but functional effects can be detected. We cultivated intestinal microbiota derived from pig colon in chemostats and investigated the acute effect of 228 mg/d glyphosate acid equivalents from Roundup® LB plus, a frequently applied glyphosate formulation. The applied glyphosate concentration resembles a worst-case scenario for an 8-9 week-old pig and relates to the maximum residue levels of glyphosate on animal fodder. The effects were determinedon the functional level by metaproteomics, targeted and untargeted meta-metabolomics, while variations in community structure were analyzed by 16S rRNA gene profiling and on the single cell level by microbiota flow cytometry. Roundup® LB plus did not affect the community taxonomy or the enzymatic repertoire of the cultivated microbiota in general or on the expression of the glyphosate target enzyme 5-enolpyruvylshikimate-3-phosphate synthase in detail. On the functional level, targeted metabolite analysis of short chain fatty acids (SCFAs), free amino acids and bile acids did not reveal significant changes, whereas untargeted meta-metabolomics did identify some effects on the functional level. This multi-omics approach provides evidence for subtle metabolic effects of Roundup® LB plus under the conditions applied.