greenmedinfo--2020-09-27--Ethanolic extract of Malacca leaves has the potential to protect against liver damage in mice infect

Ethanolic extract of Malacca leaves has the potential to protect against liver damage in mice infected with P. berghei.

Background and Aim : Although existing research confirms the antiparasitic effect of the Malacca plant against , its effect on the liver , one of the target organs ofhas not been investigated .
Therefore , this study was conducted to explore the potential of the ethanolic extract of Malacca ( ) leaves in preventing liver damage in mice ( ) caused byinfection .
Materials and Methods : This study was conducted using the livers of 18 mice fixed in 10 % neutral-buffered formalin .
A completely randomized design with a unidirectional pattern comprising six treatments was used in this study @ @ @ @ @ @ @ replications .
Treatment 0 was the negative control group infected with , treatment 1 was the positive control group infected withfollowed by chloroquine administration at a dose of 5 mg/kg BW , and treatments 2 , 3 , 4 , and 5 were groups infected withand administered Malacca leaf ethanolic extracts at doses of 100 , 300 , 600 , and 1200 mg/kg BW , respectively .
The extracts were administered orally using a gastric tube for 4 consecutive days .
Mice were sacrificed on the 7day and livers were collected for histopathological @ @ @ @ @ @ @ the livers of mice infected withdemonstrated the presence of hemosiderin , hydropic degeneration , fat degeneration , necrosis , and megalocytosis .
However , all these histopathological changes were reduced in the livers of-infected mice treated with various doses of Malacca leaf ethanolic extract .
The differences between the treatments were found be statistically significant ( p < 0.05 ) .
Conclusion : Ethanolic extract of Malacca leaves has the potential to protect against liver damage in mice infected with .
The dose of 600 mg/kg BW was found to be the most @ @ @ @ @ @ @ , 300 , and 1200 mg/kg BW .

Background and Aim: Although existing research confirms the antiparasitic effect of the Malacca plant against, its effect on the liver, one of the target organs ofhas not been investigated. Therefore, this study was conducted to explore the potential of the ethanolic extract of Malacca () leaves in preventing liver damage in mice () caused byinfection.
Materials and Methods: This study was conducted using the livers of 18 mice fixed in 10% neutral-buffered formalin. A completely randomized design with a unidirectional pattern comprising six treatments was used in this study, with each treatment consisting of three replications. Treatment 0 was the negative control group infected with, treatment 1 was the positive control group infected withfollowed by chloroquine administration at a dose of 5 mg/kg BW, and treatments 2, 3, 4, and 5 were groups infected withand administered Malacca leaf ethanolic extracts at doses of 100, 300, 600, and 1200 mg/kg BW, respectively. The extracts were administered orally using a gastric tube for 4 consecutive days. Mice were sacrificed on the 7day and livers were collected for histopathological examination.
Results: Histopathological examination of the livers of mice infected withdemonstrated the presence of hemosiderin, hydropic degeneration, fat degeneration, necrosis, and megalocytosis. However, all these histopathological changes were reduced in the livers of-infected mice treated with various doses of Malacca leaf ethanolic extract. The differences between the treatments were found be statistically significant (p<0.05).
Conclusion: Ethanolic extract of Malacca leaves has the potential to protect against liver damage in mice infected with. The dose of 600 mg/kg BW was found to be the most effective compared with the doses of 100, 300, and 1200 mg/kg BW.


greenmedinfo--2020-09-27--The key findings indicated the synergistic effects of DOX and T. pratense against TNBC xenografts.

Therapeutic strategies against triple-negative breast cancer ( TNBC ) are associated with drug-induced toxicities .
The tropical edible red clover ( L. ) is rich in polyphenolic compounds which confer the plant potential anticancer properties .
The aim of this study was to investigate the effects ofand doxorubicin ( DOX ) on the apoptosis and proliferation of 4T1 tumor cells in an allograft model of tumor-bearing BALB/c mice .
Fifty-six female 4T1-tumor bearing- BALB/c mice were randomly divided into 7 groups ( = 8/group ) to receive different doses and combinations of DOX andextract for 35 days .
On the @ @ @ @ @ @ @ ) , IL-12 and IFN-γ cytokines , and glutathione peroxidase ( GPx ) activity were measured .
Tumor 's ferric reducing antioxidant power ( FRAP ) and the expressions of apoptosis-related genes ( p53 , Bax , Bcl-2 , and caspase-3 ) were also evaluated .
Immunohistochemical staining for Ki-67 and p53 were performed .
Our results showed that the co-treatment of DOX and ( 100-400 mg/kg ) inhibited the proliferation of 4T1 tumor cells in dose- and time-dependent manners .
The co-treatment of DOX and ( especially at the dose of 400 @ @ @ @ @ @ @ E2 ( as a stimulant for breast tumor growth ) and increased the serum levels of IL-12 and IFN-γ along with significant increments in serum GPx and tumor FRAP activities .
The co-administration of DOX andalso decreased the expression of Ki-67 proliferation marker and increased the number p53 positive ( i.e.
, apoptotic ) cells within tumors .
This was accompanied with the upregulation of pro-apoptotic and down-regulation of antiapoptotic genes .
The key findings indicated the synergistic effects of DOX andagainst TNBC xenografts .

Therapeutic strategies against triple-negative breast cancer (TNBC) are associated with drug-induced toxicities. The tropical edible red clover (L.) is rich in polyphenolic compounds which confer the plant potential anticancer properties. The aim of this study was to investigate the effects ofand doxorubicin (DOX) on the apoptosis and proliferation of 4T1 tumor cells in an allograft model of tumor-bearing BALB/c mice. Fifty-six female 4T1-tumor bearing- BALB/c mice were randomly divided into 7 groups ( = 8/group) to receive different doses and combinations of DOX andextract for 35 days. On the 36th day, serum estradiol (E2), IL-12 and IFN-γ cytokines, and glutathione peroxidase (GPx) activity were measured. Tumor's ferric reducing antioxidant power (FRAP) and the expressions of apoptosis-related genes (p53, Bax, Bcl-2, and caspase-3) were also evaluated. Immunohistochemical staining for Ki-67 and p53 were performed. Our results showed that the co-treatment of DOX and(100-400 mg/kg) inhibited the proliferation of 4T1 tumor cells in dose- and time-dependent manners. The co-treatment of DOX and(especially at the dose of 400 mg/kg) decreased the serum level of E2 (as a stimulant for breast tumor growth) and increased the serum levels of IL-12 and IFN-γ along with significant increments in serum GPx and tumor FRAP activities. The co-administration of DOX andalso decreased the expression of Ki-67 proliferation marker and increased the number p53 positive (i.e., apoptotic) cells within tumors. This was accompanied with the upregulation of pro-apoptotic and down-regulation of antiapoptotic genes. The key findings indicated the synergistic effects of DOX andagainst TNBC xenografts.


greenmedinfo--2020-09-27--Flavonoids-mediated SIRT1 signaling activation in hepatic disorders.

The prevalence of various hepatic diseases increases dramatically worldwide and regarded as a serious health problem .
Sirtuins are one of the main strategic controllers of different cellular processes , including cell cycle , mitochondrial biogenesis , insulin secretion , redox balance , inflammation , and apoptosis .
SIRT1 is the most prominent and broadly studied member of sirtuins that implicated in health status and longevity .
Therefore , targeting the SIRT1 signaling pathways may be a reasonable therapeutic approach to treat different diseases , including hepatic disorders .
Flavonoids are polyphenolic compounds widely present in different plants and possess @ @ @ @ @ @ @ this review , we focused on the flavonoids , ( - ) -epicatechin , ampelopsin , baicalin , delphinidin , fisetin , epigallocatechin-3-gallate , luteolin , pinocembrin , quercetin , silibinin , trans-chalcone and xanthohumol , to verify whether their potential promising hepatoprotective effects are related to activation of SIRT1 .
Additionally , molecular modeling simulations were applied to explore the potential binding mode of these flavonoids to SIRT1 .
The complied information and molecular docking simulations suggested that SIRT1 signaling is involved in the beneficial pharmacologic activities of flavonoids in different hepatic @ @

The prevalence of various hepatic diseases increases dramatically worldwide and regarded as a serious health problem. Sirtuins are one of the main strategic controllers of different cellular processes, including cell cycle, mitochondrial biogenesis, insulin secretion, redox balance, inflammation, and apoptosis. SIRT1 is the most prominent and broadly studied member of sirtuins that implicated in health status and longevity. Therefore, targeting the SIRT1 signaling pathways may be a reasonable therapeutic approach to treat different diseases, including hepatic disorders. Flavonoids are polyphenolic compounds widely present in different plants and possess beneficial effects against diverse diseases. In this review, we focused on the flavonoids, (-)-epicatechin, ampelopsin, baicalin, delphinidin, fisetin, epigallocatechin-3-gallate, luteolin, pinocembrin, quercetin, silibinin, trans-chalcone and xanthohumol, to verify whether their potential promising hepatoprotective effects are related to activation of SIRT1. Additionally, molecular modeling simulations were applied to explore the potential binding mode of these flavonoids to SIRT1. The complied information and molecular docking simulations suggested that SIRT1 signaling is involved in the beneficial pharmacologic activities of flavonoids in different hepatic diseases.


greenmedinfo--2020-09-28--A combination of olive leaf and fruit extracts may be used efficiently and safely in reducing hypert

A combination of olive leaf and fruit extracts may be used efficiently and safely in reducing hypertension and MetS markers.

BACKGROUND : The role of herbal products in the prevention of cardiovascular disease requires supporting evidence .
This open pilot study assessed the effect of 2-month supplementation of a combination of olive leaf and fruit extracts ( Tensiofytol , Tilman SA , Baillonville , Belgium ) in the clinical management of hypertension and metabolic syndrome ( MetS ) .
METHODS : A total of 663 ( pre ) -hypertensive patients were enrolled by general practitioners and supplemented for two months with Tensiofytol , two capsules per day ( 100 mg/d of oleuropein and 20 mg/d of hydroxytyrosol ) .
Systolic @ @ @ @ @ @ @ were measured before and after treatment .
Markers of MetS , high-density lipoprotein cholesterol ( HDL-C ) , triglycerides ( TG ) , fasting blood glucose ( FG ) and waist circumference ( WC ) , were also examined .
RESULTS : Significant reductions ( < 0.0001 ) in SBP/DBP ( 13± 10/7.1 ± 6.6 mmHg ) were observed and similarly in pre-diabetic and diabetic patients .
Improvements in SBP/DPB were independent of age and gender but greater for elevated baseline SBP/DBP .
Tensiofytolsupplementation also significantly improved markers of MetS , with a @ @ @ @ @ @ @ , WC ( 1.4 % ) and FG ( 4.8 % ) and an increase of HDL-C ( 5.3 % ) .
Minor side effects were reported in 3.2 % patients .
CONCLUSIONS : This real-life , observational , non-controlled , non-randomized pilot study shows that supplementation of a combination of olive leaf and fruit extracts may be used efficiently and safely in reducing hypertension and MetS markers .

BACKGROUND: The role of herbal products in the prevention of cardiovascular disease requires supporting evidence. This open pilot study assessed the effect of 2-month supplementation of a combination of olive leaf and fruit extracts (Tensiofytol, Tilman SA, Baillonville, Belgium) in the clinical management of hypertension and metabolic syndrome (MetS).
METHODS: A total of 663 (pre)-hypertensive patients were enrolled by general practitioners and supplemented for two months with Tensiofytol, two capsules per day (100 mg/d of oleuropein and 20 mg/d of hydroxytyrosol). Systolic and diastolic blood pressures (SBP/DBP) were measured before and after treatment. Markers of MetS, high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), fasting blood glucose (FG) and waist circumference (WC), were also examined.
RESULTS: Significant reductions (<0.0001) in SBP/DBP (13± 10/7.1 ± 6.6 mmHg) were observed and similarly in pre-diabetic and diabetic patients. Improvements in SBP/DPB were independent of age and gender but greater for elevated baseline SBP/DBP. Tensiofytolsupplementation also significantly improved markers of MetS, with a decrease of TG (11%), WC (1.4%) and FG (4.8%) and an increase of HDL-C (5.3%). Minor side effects were reported in 3.2% patients.
CONCLUSIONS: This real-life, observational, non-controlled, non-randomized pilot study shows that supplementation of a combination of olive leaf and fruit extracts may be used efficiently and safely in reducing hypertension and MetS markers.


greenmedinfo--2020-09-28--Antidiabetic effect of olive leaf extract on streptozotocin-induced diabetes mellitus.

BACKGROUND : recently , a relationship between diabetic complications and oxidative stress has been emphasized .
There have been some studies showing the effect of olive leaf on hyperglycemia and diabetic complications due to its antioxidant properties .
In many studies the effect of olive leaf on plasma total antioxidant level has been measured by different methods .
Our study represents the first time it has been measured by a new method of total thiol disulfide homeostasis .
AIM : chronic exposure to hyperglycemia and hyperlipidemia contributes to the pathogenesis of diabetic complications through oxidative stress mediators .
Thiol is @ @ @ @ @ @ @ in humans , and thiol disulfide homeostasis is a new oxidative stress marker .
We aimed to investigate the effect of olive leaf extract ( OLE ) obtained from fresh leaves of Olea europaea , var oleaster on diabetic complications through their hypoglycemic and antioxidant effect in diabetic rats .
METHODS : twenty-eight Wistar albino rats aged 12-13 weeks were used in the study .
The rats were divided into a control group ( C ) , a diabetic control group ( DC ) , a diabetic group treated with 200 mg/kg OLE @ @ @ @ @ @ @ group treated with 400 mg/kg OLE ( D+400 ) , having 7 rats in each group .
The treatment groups received OLE by the gavage method for 21 days .
At the end of the study , all rats were sacrificed by cervical dislocation .
Blood samples collected from the heart were centrifuged and glucose , total cholesterol , triglyceride , urea , uric acid , creatinine , alanine aminotransferase ( ALT ) , aspartate aminotransferase ( AST ) , lipid hydroperoxide ( LOOH ) level , and thiol-disulfide homeostasis were determined .
@ @ @ @ @ @ @ was performed on complete blood .
In addition , a tail flick test and hot plate modeling were performed to indicate pain perception loss .
RESULTS : it was observed that OLE had no effect on serum glucose and HbA1c levels .
On the contrary , OLE reduced the levels of total cholesterol ( p < 0.01 ) , urea ( p < 0.01 ) and hot plate latency ( p < 0.01 ) in a significant manner .
Also , OLE showed a tendency to reduce LOOH levels and to increase thiol @ @ @ @ @ @ @ > 0.05 ) .
CONCLUSION : OLE supplementation for 21 days , at the amounts used , can not protect against hyperglycemia but may be protective against hypercholesterolemia and tissue damage as caused by diabetes mellitus in rats .

BACKGROUND: recently, a relationship between diabetic complications and oxidative stress has been emphasized. There have been some studies showing the effect of olive leaf on hyperglycemia and diabetic complications due to its antioxidant properties. In many studies the effect of olive leaf on plasma total antioxidant level has been measured by different methods. Our study represents the first time it has been measured by a new method of total thiol disulfide homeostasis.
AIM: chronic exposure to hyperglycemia and hyperlipidemia contributes to the pathogenesis of diabetic complications through oxidative stress mediators. Thiol is one of the most important antioxidant barriers in humans, and thiol disulfide homeostasis is a new oxidative stress marker. We aimed to investigate the effect of olive leaf extract (OLE) obtained from fresh leaves of Olea europaea, var oleaster on diabetic complications through their hypoglycemic and antioxidant effect in diabetic rats.
METHODS: twenty-eight Wistar albino rats aged 12-13 weeks were used in the study. The rats were divided into a control group (C), a diabetic control group (DC), a diabetic group treated with 200 mg/kg OLE (D+200), and a diabetic group treated with 400 mg/kg OLE (D+400), having 7 rats in each group. The treatment groups received OLE by the gavage method for 21 days. At the end of the study, all rats were sacrificed by cervical dislocation. Blood samples collected from the heart were centrifuged and glucose, total cholesterol, triglyceride, urea, uric acid, creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST), lipid hydroperoxide (LOOH) level, and thiol-disulfide homeostasis were determined. The hemoglobin A1c (HbA1c) analysis was performed on complete blood. In addition, a tail flick test and hot plate modeling were performed to indicate pain perception loss.
RESULTS: it was observed that OLE had no effect on serum glucose and HbA1c levels. On the contrary, OLE reduced the levels of total cholesterol (p<0.01), urea (p<0.01) and hot plate latency (p<0.01) in a significant manner. Also, OLE showed a tendency to reduce LOOH levels and to increase thiol levels in a dose-dependent manner (p>0.05).
CONCLUSION: OLE supplementation for 21 days, at the amounts used, cannot protect against hyperglycemia but may be protective against hypercholesterolemia and tissue damage as caused by diabetes mellitus in rats.


greenmedinfo--2020-09-28--This study suggests the ability of olive leaf extract to reduce the biofilm formation and virulence

This study suggests the ability of olive leaf extract to reduce the biofilm formation and virulence factor production of P. aeruginosa.

Biofilm acts as a complex barrier against antibiotics .
In this study , we investigated the inhibitory activities of ( olive ) leaves ( green tea ) , , , , , and Propolis extracts on the biofilm formation , pyocyanin production , and twitching motility ofisolates .
Moreover , we investigated the effect of olive leaf extract on the transcription of some biofilm related genes .
A total of 204 isolates ofwere collected from different Egyptian hospitals .
A susceptibility test , carried out using the disc diffusion method , revealed that 49 % of the isolates were multidrug-resistant @ @ @ @ @ @ @ isolates were biofilm-forming , of which 26 % were strong biofilm producers .
At subinhibitory concentrations , green tea and olive leaf extracts had the highest biofilm inhibitory effects with 84.8 % and 82.2 % , respectively .
The expression levels of , , , andtreated with these extracts were significantly reduced ( < 0.05 ) by around 97-99 % compared to untreated isolates .
This study suggests the ability of olive leaf extract to reduce the biofilm formation and virulence factor production ofthrough the down regulation of quorum sensing ( QS ) @ @ @ @ @ @ @ our dependence on antibiotics and to handle biofilm-related infections of opportunistic pathogens more efficiently .

Biofilm acts as a complex barrier against antibiotics. In this study, we investigated the inhibitory activities of(olive) leaves(green tea),,,,, and Propolis extracts on the biofilm formation, pyocyanin production, and twitching motility ofisolates. Moreover, we investigated the effect of olive leaf extract on the transcription of some biofilm related genes. A total of 204 isolates ofwere collected from different Egyptian hospitals. A susceptibility test, carried out using the disc diffusion method, revealed that 49% of the isolates were multidrug-resistant. More than 90% of the isolates were biofilm-forming, of which 26% were strong biofilm producers. At subinhibitory concentrations, green tea and olive leaf extracts had the highest biofilm inhibitory effects with 84.8% and 82.2%, respectively. The expression levels of,,, andtreated with these extracts were significantly reduced (<0.05) by around 97-99% compared to untreated isolates. This study suggests the ability of olive leaf extract to reduce the biofilm formation and virulence factor production ofthrough the down regulation of quorum sensing (QS) genes. This may help in reducing our dependence on antibiotics and to handle biofilm-related infections of opportunistic pathogens more efficiently.


greenmedinfo--2020-09-28--These results demonstrate that fisetin is a promising agent for protecting against sepsis-induced in

These results demonstrate that fisetin is a promising agent for protecting against sepsis-induced inflammatory response and organ injury.

Sepsis-induced multiple organ dysfunction and inflammatory response are life-threatening symptoms without effective treatment .
Fisetin , a dietary flavonoid extracted from berries and family Fabaceae , has displayed neuroprotective and anti-oxidant activities .
In this study we investigated whether fisetin exerted a protective effect against sepsis-induced multiple organ dysfunction in mouse cecum ligation and puncture ( CLP ) model .
The mice were injected with fisetin ( 10 mg/kg , ip ) 0.5 h prior to CLP , and sacrificed 18 h after CLP .
We found that fisetin administration significantly alleviated CLP-induced lung , liver and kidney injury , @ @ @ @ @ @ @ interleukin ( IL ) -6 , tumor necrosis factor ( TNF ) -α and IL-1β in bronchoalveolar lavage fluid ( BALF ) .
In lipopolysaccharide ( LPS ) -treated mouse bone marrow-derived macrophages ( BMDMs ) , application of fisetin ( 3-10 μM ) dose-dependently inhibited the expression levels of IL-6 , TNF-α , IL-1β , and inducible nitric oxide synthase ( iNOS ) .
Furthermore , fisetin dose-dependently inhibited the phosphorylation of p38 MAPK , MK2 , and transforming growth factor-β-activated kinase ( TAK ) 1 via attenuating the interaction between TAK1 @ @ @ @ @ @ @ .
These results demonstrate that fisetin is a promising agent for protecting against sepsis-induced inflammatory response and organ injury via inhibiting macrophage activation .

Sepsis-induced multiple organ dysfunction and inflammatory response are life-threatening symptoms without effective treatment. Fisetin, a dietary flavonoid extracted from berries and family Fabaceae, has displayed neuroprotective and anti-oxidant activities. In this study we investigated whether fisetin exerted a protective effect against sepsis-induced multiple organ dysfunction in mouse cecum ligation and puncture (CLP) model. The mice were injected with fisetin (10 mg/kg, ip) 0.5 h prior to CLP, and sacrificed 18 h after CLP. We found that fisetin administration significantly alleviated CLP-induced lung, liver and kidney injury, as well as the expression levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α and IL-1β in bronchoalveolar lavage fluid (BALF). In lipopolysaccharide (LPS)-treated mouse bone marrow-derived macrophages (BMDMs), application of fisetin (3-10 μM) dose-dependently inhibited the expression levels of IL-6, TNF-α, IL-1β, and inducible nitric oxide synthase (iNOS). Furthermore, fisetin dose-dependently inhibited the phosphorylation of p38 MAPK, MK2, and transforming growth factor-β-activated kinase (TAK) 1 via attenuating the interaction between TAK1 and TAK-binding proteins (TAB) 1. These results demonstrate that fisetin is a promising agent for protecting against sepsis-induced inflammatory response and organ injury via inhibiting macrophage activation.


greenmedinfo--2020-09-28--Targeting SARS-CoV-2 spike protein of COVID-19 with naturally occurring phytochemicals.

Spike glycoprotein , a class I fusion protein harboring the surface of SARS-CoV-2 ( SARS-CoV-2S ) , plays a seminal role in the viral infection starting from recognition of the host cell surface receptor , attachment to the fusion of the viral envelope with the host cells .
Spike glycoprotein engages host Angiotensin-converting enzyme 2 ( ACE2 ) receptors for entry into host cells , where the receptor recognition and attachment of spike glycoprotein to the ACE2 receptors is a prerequisite step and key determinant of the host cell and tissue tropism .
Binding of spike glycoprotein to the ACE2 @ @ @ @ @ @ @ , including transition from a metastable pre-fusion to a post-fusion form , thereby allowing membrane fusion and internalization of the virus .
From ancient times people have relied on naturally occurring substances like phytochemicals to fight against diseases and infection .
Among these phytochemicals , flavonoids and non-flavonoids have been the active sources of different anti-microbial agents .
We performed molecular docking studies using 10 potential naturally occurring compounds ( flavonoids/non-flavonoids ) against the SARS-CoV-2 spike protein and compared their affinity with an FDA approved repurposed drug hydroxychloroquine ( HCQ ) .
Further @ @ @ @ @ @ @ simulation and energy landscape studies with fisetin , quercetin , and kamferol revealed that these molecules bind with the hACE2-S complex with low binding free energy .
The study provided an indication that these molecules might have the potential to perturb the binding of hACE2-S complex .
In addition , ADME analysis also suggested that these molecules consist of drug-likeness property , which may be further explored as anti-SARS-CoV-2 agents .
Communicated by Ramaswamy H. Sarma .

Spike glycoprotein, a class I fusion protein harboring the surface of SARS-CoV-2 (SARS-CoV-2S), plays a seminal role in the viral infection starting from recognition of the host cell surface receptor, attachment to the fusion of the viral envelope with the host cells. Spike glycoprotein engages host Angiotensin-converting enzyme 2 (ACE2) receptors for entry into host cells, where the receptor recognition and attachment of spike glycoprotein to the ACE2 receptors is a prerequisite step and key determinant of the host cell and tissue tropism. Binding of spike glycoprotein to the ACE2 receptor triggers a cascade of structural transitions, including transition from a metastable pre-fusion to a post-fusion form, thereby allowing membrane fusion and internalization of the virus. From ancient times people have relied on naturally occurring substances like phytochemicals to fight against diseases and infection. Among these phytochemicals, flavonoids and non-flavonoids have been the active sources of different anti-microbial agents. We performed molecular docking studies using 10 potential naturally occurring compounds (flavonoids/non-flavonoids) against the SARS-CoV-2 spike protein and compared their affinity with an FDA approved repurposed drug hydroxychloroquine (HCQ). Further, our molecular dynamics (MD) simulation and energy landscape studies with fisetin, quercetin, and kamferol revealed that these molecules bind with the hACE2-S complex with low binding free energy. The study provided an indication that these molecules might have the potential to perturb the binding of hACE2-S complex. In addition, ADME analysis also suggested that these molecules consist of drug-likeness property, which may be further explored as anti-SARS-CoV-2 agents. Communicated by Ramaswamy H. Sarma.


greenmedinfo--2020-09-28--Enhanced oral bioavailability and neuroprotective effect of fisetin through its SNEDDS against roten

Enhanced oral bioavailability and neuroprotective effect of fisetin through its SNEDDS against rotenone-induced Parkinson's disease.

Fisetin ( FS ) was reported to have various pharmacological activities .
But due to its lower aqueous solubility and @ @ @ @ @ not in much use .
As solubility and bioavailability plays and important role in the @ @ @ @ @ research work we tried to improve the oral bioavailability of fisetin .
In this research @ @ @ @ @ drug delivery system ( SNEDDS ) of fisetin .
Developed SNEDDS were subjected for pharmacokinetic @ @ @ @ @ Parkinson 's disease ( PD ) model in rats .
Higher Cmax and area under @ @ @ @ @ indicated that SNEDDS improved the oral bioavailability of FS and also increased the mean residence @ @ @ @ @ .
Results of behavior parameters ( locomotor , muscle co-ordination and catalepsy ) , biochemical @ @ @ @ @ , GSH , SOD and CAT ) and ELISA ( soluble alfa synuclein , BDNF @ @ @ @ @ confirmed the significantly improved ( p

Fisetin (FS) was reported to have various pharmacological activities. But due to its lower aqueous solubility and oral bioavailability, it is not in much use. As solubility and bioavailability plays and important role in the pharmacological activity, in this research work we tried to improve the oral bioavailability of fisetin. In this research work, we developed self-nanoemulsifying drug delivery system (SNEDDS) of fisetin. Developed SNEDDS were subjected for pharmacokinetic and pharmacodynamics studies against rotenone-induced Parkinson's disease (PD) model in rats. Higher Cmax and area under the curve during pharmacokinetic study indicated that SNEDDS improved the oral bioavailability of FS and also increased the mean residence time of drug in plasma. Results of behavior parameters (locomotor, muscle co-ordination and catalepsy), biochemical estimation (TBARS, nitrite, GSH, SOD and CAT) and ELISA (soluble alfa synuclein, BDNF, TNF-α and IL-6) confirmed the significantly improved (p < 0.05) neuroprotection in rats treated with FS loaded SNEDDS as compared to rats treated with naïve FS. This study suggests that SNEDDS improved the oral bioavailability of FS which further helped in improving its neuroprotective activity in rat model of PD. It further suggests the potential use of FS-SNEDDS in effective management of PD condition.


greenmedinfo--2020-09-28--Fisetin inhibits vascular endothelial growth factor-induced angiogenesis in retinoblastoma cells.

Fisetin is a small phytochemical molecule with antitumor activity .
Angiogenesis is a basic process that occurs during tumor growth and metastasis .
The vascular endothelial growth factor ( VEGF ) /VEGF receptor ( VEGFR ) pathway is a key regulator of angiogenesis .
The aim of the present study was to evaluate whether fisetin affects angiogenesis through the VEGFR pathway .
In the present study , Y79 cells were treated with 100 ng/ml VEGF in the presence of fisetin at concentrations of 0 , 25 , 50 and 100µM .
A Cell Counting Kit-8 assay was used to detect @ @ @ @ @ @ @ were used to assess cell migration and invasion , respectively .
Reverse transcription-quantitative polymerase chain reaction analysis was applied to measure the expression level of VEGFR mRNA and western blot analysis was used to measure the protein expression of VEGFR .
An immunofluorescence assay was used to detect the expression of VEGFR .
Angiogenesiswas assessed by a tube formation assay .
The results demonstrated that fisetin significantly inhibited the proliferation of Y79 cells in a time- and dose-dependent manner .
Fisetin also inhibited the migration and invasion of Y79 cells in a dose-dependent @ @ @ @ @ @ @ expression of VEGFR in Y79 cells in a dose-dependent manner and tumor angiogenesis .
Thus , fisetin was found to inhibit angiogenesis via inhibition of the VEGF/VEGFR signaling pathway , and could be used as a candidate drug to inhibit angiogenesis in retinoblastoma .

Fisetin is a small phytochemical molecule with antitumor activity. Angiogenesis is a basic process that occurs during tumor growth and metastasis. The vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) pathway is a key regulator of angiogenesis. The aim of the present study was to evaluate whether fisetin affects angiogenesis through the VEGFR pathway. In the present study, Y79 cells were treated with 100 ng/ml VEGF in the presence of fisetin at concentrations of 0, 25, 50 and 100µM. A Cell Counting Kit-8 assay was used to detect proliferation and the Transwell and Matrigel assays were used to assess cell migration and invasion, respectively. Reverse transcription-quantitative polymerase chain reaction analysis was applied to measure the expression level of VEGFR mRNA and western blot analysis was used to measure the protein expression of VEGFR. An immunofluorescence assay was used to detect the expression of VEGFR. Angiogenesiswas assessed by a tube formation assay. The results demonstrated that fisetin significantly inhibited the proliferation of Y79 cells in a time- and dose-dependent manner. Fisetin also inhibited the migration and invasion of Y79 cells in a dose-dependent manner. Furthermore, fisetin inhibited the expression of VEGFR in Y79 cells in a dose-dependent manner and tumor angiogenesis. Thus, fisetin was found to inhibit angiogenesis via inhibition of the VEGF/VEGFR signaling pathway, and could be used as a candidate drug to inhibit angiogenesis in retinoblastoma.


greenmedinfo--2020-09-28--Fisetin alleviates hepatic and adipocyte fibrosis and insulin resistance.

The present study aimed to investigate the protective role of the flavonoid fisetin ( FI ) on inflammation-mediated metabolic diseases , especially tissue fibrosis and insulin resistance ( IR ) in high-fat diet ( HFD ) -induced obese mice .
C57BL/6J mice were fed with normal-fat diet , HFD ( 40 kcal % fat ) , or HFD +0.02 % ( w/w ) FI for 16 weeks .
Dietary FI supplementation improved hepatic steatosis by restricting lipogenesis , while promoting lipolysis in the liver .
FI also prevented adiposity via an increase in the expression of genes involved in FA @ @ @ @ @ @ @ of genes involved in lipogenesis in white adipose tissue .
In addition , FI increased brown adipose tissue ( BAT ) and skeletal muscle weights , thermogenic gene mRNA expression in BAT , and tricarboxylic acid cycle-related gene expression in skeletal muscle , which may be linked to the prevention of nonalcoholic fatty liver disease as well as adiposity .
Moreover , FI supplementation decreased excessive reactive oxygen species production by increasing paraoxonase activity , adipokine dysregulation , proinflammatory cytokine production , and extracellular matrix amassment in the liver .
FI supplementation ameliorated @ @ @ @ @ @ @ pancreatic islet dysfunction , and it declined hepatic gluconeogenesis and proinflammatory responses .
Taken together , the present findings indicate that FI can protect against HFD-induced inflammation-mediated disorders , including fibrosis and IR .

The present study aimed to investigate the protective role of the flavonoid fisetin (FI) on inflammation-mediated metabolic diseases, especially tissue fibrosis and insulin resistance (IR) in high-fat diet (HFD)-induced obese mice. C57BL/6J mice were fed with normal-fat diet, HFD (40 kcal% fat), or HFD +0.02% (w/w) FI for 16 weeks. Dietary FI supplementation improved hepatic steatosis by restricting lipogenesis, while promoting lipolysis in the liver. FI also prevented adiposity via an increase in the expression of genes involved in FA oxidation and a decrease in the expression of genes involved in lipogenesis in white adipose tissue. In addition, FI increased brown adipose tissue (BAT) and skeletal muscle weights, thermogenic gene mRNA expression in BAT, and tricarboxylic acid cycle-related gene expression in skeletal muscle, which may be linked to the prevention of nonalcoholic fatty liver disease as well as adiposity. Moreover, FI supplementation decreased excessive reactive oxygen species production by increasing paraoxonase activity, adipokine dysregulation, proinflammatory cytokine production, and extracellular matrix amassment in the liver. FI supplementation ameliorated IR, in part, by normalizing pancreatic islet dysfunction, and it declined hepatic gluconeogenesis and proinflammatory responses. Taken together, the present findings indicate that FI can protect against HFD-induced inflammation-mediated disorders, including fibrosis and IR.


greenmedinfo--2020-09-28--This study has revealed a prime mechanism involved in the cardioprotective effects of fisetin.

The methodology exploring the cardioprotective potential of the flavonoid Fisetin through its ability to modulate PPAR-γ was unraveled in the present study .
Computational modelling through molecular docking based binding study of interactions between Fiestin and PPAR-γ revealed the potential role of Fisetin as an agonist of PPAR-γ .
A murine model of cardiac ischemia-reperfusion injury was used to explore this further .
Male Wistar Rats were randomly assigned to five groups .
Fisetin ( 20 mg/kg ; p. o ) was administered for 28 days .
Ischemia was induced for 45 min on the 29th day followed by 60 @ @ @ @ @ @ @ the expression of PPAR-γ in heart tissue significantly Cardioprotection was assessed by measurement of hemodynamic parameters , infarct size , ELISA for oxidative stress , immunohistochemistry and TUNEL assay for apoptosis , and western blot analysis for MAPK proteins and inflammation .
PPAR-γ activation by fisetin led to significantly reduced infarct size , suppression of oxidative stress , reduction of cardiac injury markers , alleviation of inflammation , and inhibition of apoptosis The MAPK-based molecular mechanism showed a rise in a key prosurvival kinase , ERK1/ERK2 and suppression of JNK and p38 proteins @ @ @ @ @ @ @ were reversed on the administration of a specific antagonist of PPAR-γ .
In conclusion , through our experiments , we have proved that fisetin protects the heart against ischemia-reperfusion injury and the evident cardioprotection is PPAR-γ dependant .
In conclusion , our study has revealed a prime mechanism involved in the cardioprotective effects of fisetin .
Hence , Fisetin may be evaluated in further clinical studies as a cardioprotective agent in patients undergoing reperfusion interventions .

The methodology exploring the cardioprotective potential of the flavonoid Fisetin through its ability to modulate PPAR-γ was unraveled in the present study. Computational modelling through molecular docking based binding study of interactions between Fiestin and PPAR-γ revealed the potential role of Fisetin as an agonist of PPAR-γ. A murine model of cardiac ischemia-reperfusion injury was used to explore this further. Male Wistar Rats were randomly assigned to five groups. Fisetin (20 mg/kg; p. o) was administered for 28 days. Ischemia was induced for 45 min on the 29th day followed by 60 min of reperfusion. Fisetin pretreatment upregulated the expression of PPAR-γ in heart tissue significantly Cardioprotection was assessed by measurement of hemodynamic parameters, infarct size, ELISA for oxidative stress, immunohistochemistry and TUNEL assay for apoptosis, and western blot analysis for MAPK proteins and inflammation. PPAR-γ activation by fisetin led to significantly reduced infarct size, suppression of oxidative stress, reduction of cardiac injury markers, alleviation of inflammation, and inhibition of apoptosis The MAPK-based molecular mechanism showed a rise in a key prosurvival kinase, ERK1/ERK2 and suppression of JNK and p38 proteins. The aforementioned beneficial findings of fisetin were reversed on the administration of a specific antagonist of PPAR-γ. In conclusion, through our experiments, we have proved that fisetin protects the heart against ischemia-reperfusion injury and the evident cardioprotection is PPAR-γ dependant. In conclusion, our study has revealed a prime mechanism involved in the cardioprotective effects of fisetin. Hence, Fisetin may be evaluated in further clinical studies as a cardioprotective agent in patients undergoing reperfusion interventions.


greenmedinfo--2020-09-28--Effects of emulsion formulations of oleuropein isolated from ethanol extract of olive leaf in diabet

Effects of emulsion formulations of oleuropein isolated from ethanol extract of olive leaf in diabetic rats.

This study was designed to investigate the effects of emulsion formulations of oleuropein isolated from ethanol extract of olive leaf in streptozotocin-diabetic rats .
The rats were treated with the administration of the emulsion containing oleuropein at a low ( 150 mg/kg b.wt . )
and high ( 225 mg/kg b.wt . )
dose for 30 days .
At the end of the study , blood samples were drawn from the heart of the rats to determine blood glucose , alanine transaminase , and aspartate transaminase levels .
In addition , their liver tissues were dissected to determine the levels @ @ @ @ @ @ @ and superoxide dismutase activity .
According to the results for both dose treatments , a statistically significant increase in superoxide dismutase activities and glutathione levels of the treated diabetic rats was observed when compared with those of the diabetic control rats .
On the other hand , a statistically significant decrease in the levels of thiobarbituric acid-reactive substances , aspartate transaminase and alanine transaminase of the treated diabetic rats was determined .
It should be highlighted that the administrations at the high dose were more effective compared to that of the low dose @ @ @ @ @ @ @ the blood glucose levels of the diabetic rats exposed to the high dose was observed .

This study was designed to investigate the effects of emulsion formulations of oleuropein isolated from ethanol extract of olive leaf in streptozotocin-diabetic rats. The rats were treated with the administration of the emulsion containing oleuropein at a low (150 mg/kg b.wt.) and high (225 mg/kg b.wt.) dose for 30 days. At the end of the study, blood samples were drawn from the heart of the rats to determine blood glucose, alanine transaminase, and aspartate transaminase levels. In addition, their liver tissues were dissected to determine the levels of glutathione and thiobarbituric acid-reactive substances, and superoxide dismutase activity. According to the results for both dose treatments, a statistically significant increase in superoxide dismutase activities and glutathione levels of the treated diabetic rats was observed when compared with those of the diabetic control rats. On the other hand, a statistically significant decrease in the levels of thiobarbituric acid-reactive substances, aspartate transaminase and alanine transaminase of the treated diabetic rats was determined. It should be highlighted that the administrations at the high dose were more effective compared to that of the low dose. Furthermore, a substantial decrease in the blood glucose levels of the diabetic rats exposed to the high dose was observed.


greenmedinfo--2020-09-28--The effect of oleuropein on apoptotic pathway regulators in breast cancer cells.

In spite of advancements in breast cancer therapy , this disease is still one of the significant causes of women fatalities globally .
Dysregulation of miRNA plays a pivotal role in the initiation and progression of cancer .
Therefore , the administration of herbal compounds with anticancer effects through controlling microRNA expression can be considered as a promising therapy for cancer .
Oleuropein is the most prevalent phenolic compound in olive .
Given its domestic consumption , low cost , and nontoxicity for human beings , oleuropein can be used in combination with the standard chemotherapy drugs .
To this @ @ @ @ @ @ @ oleuropein on two breast cancer cell lines ( MCF7 and MDA-MB-231 ) .
Our findings revealed that oleuropein significantly decreased cell viability in a dose- and time-dependent manner , while it increased the apoptosis in MCF7 and MDA-MB-231 cells .
In the presence of oleuropein , the expression levels of miR-125b , miR-16 , miR-34a , p53 , p21 , and TNFRS10B increased , while that of bcl-2 , mcl1 , miR-221 , miR-29a and miR-21 decreased .
The findings pointed out that oeluropein may induce apoptosis via not only increasing the expression @ @ @ @ @ @ @ , but also decreasing the expression of anti-apoptotic genes and oncomiR .
Consequently , oleuropein can be regarded as a suitable herbal medication for cancer therapy .

In spite of advancements in breast cancer therapy, this disease is still one of the significant causes of women fatalities globally. Dysregulation of miRNA plays a pivotal role in the initiation and progression of cancer. Therefore, the administration of herbal compounds with anticancer effects through controlling microRNA expression can be considered as a promising therapy for cancer. Oleuropein is the most prevalent phenolic compound in olive. Given its domestic consumption, low cost, and nontoxicity for human beings, oleuropein can be used in combination with the standard chemotherapy drugs. To this end, we examined the effect of oleuropein on two breast cancer cell lines (MCF7 and MDA-MB-231). Our findings revealed that oleuropein significantly decreased cell viability in a dose- and time-dependent manner, while it increased the apoptosis in MCF7 and MDA-MB-231 cells. In the presence of oleuropein, the expression levels of miR-125b, miR-16, miR-34a, p53, p21, and TNFRS10B increased, while that of bcl-2, mcl1, miR-221, miR-29a and miR-21 decreased. The findings pointed out that oeluropein may induce apoptosis via not only increasing the expression of pro-apoptotic genes and tumor suppressor miRNAs, but also decreasing the expression of anti-apoptotic genes and oncomiR. Consequently, oleuropein can be regarded as a suitable herbal medication for cancer therapy.


greenmedinfo--2020-09-28--Oleuropein improved post cerebral stroke cognitive function by promoting histone acetylation and pho

Oleuropein improved post cerebral stroke cognitive function by promoting histone acetylation and phosphorylation of cAMP response element-binding protein.

Background : Post-stroke cognitive impairment ( PSCI ) is commonest clinical disorder in which peripheral cholinergic activity is important .
Oleuropein ( OLP ) is polyphenol is present in olive oil .
Here we evaluated the effect of OLP in cognitive dysfunction rats in post cerebral stroke model .
Methods : The post cerebral stroke cognitive dysfunction PSD rat model was created by occlusion of transient middle cerebral artery .
The rats were divided into 6 groups named , Sham + Vehicle , Sham + OLP ( 50 mg/kg ) , PSD rats + Vehicle , PSD rats + OLP @ @ @ @ @ @ @ ) .
The spatial learning was assessed by Morris water maze ( MWM ) .
The expression of choline acetyltransferase ( ChAT ) , acetylcholine ( ACH ) , extent of histone acetylation and phosphorylation of cAMP response element-binding protein ( CREB ) were evaluated by Western blot assay and immunofluorescence staining .
Results : Treatment of OLP at various doses showed higher number of spontaneous and rewarded alterations and lesser percentage bias compared to vehicle treated PSD rats .
OLP resulted in decreased levels of ChAT and ACH , whereas the degree @ @ @ @ @ @ @ improved in dose dependent pattern .
Conclusion : treatment of OLP improved PSCI via increasing the phosphorylation of CREB and histone acetylation , thus attenuating cholinergic activity .

Background: Post-stroke cognitive impairment (PSCI) is commonest clinical disorder in which peripheral cholinergic activity is important. Oleuropein (OLP) is polyphenol is present in olive oil. Here we evaluated the effect of OLP in cognitive dysfunction rats in post cerebral stroke model.
Methods: The post cerebral stroke cognitive dysfunction PSD rat model was created by occlusion of transient middle cerebral artery. The rats were divided into 6 groups named, Sham + Vehicle, Sham + OLP (50 mg/kg), PSD rats + Vehicle, PSD rats + OLP (20, 50 or 100 mg/kg). The spatial learning was assessed by Morris water maze (MWM). The expression of choline acetyltransferase (ChAT), acetylcholine (ACH), extent of histone acetylation and phosphorylation of cAMP response element-binding protein (CREB) were evaluated by Western blot assay and immunofluorescence staining.
Results: Treatment of OLP at various doses showed higher number of spontaneous and rewarded alterations and lesser percentage bias compared to vehicle treated PSD rats. OLP resulted in decreased levels of ChAT and ACH, whereas the degree of histone acetylation and phosphorylation of CREB improved in dose dependent pattern.
Conclusion: treatment of OLP improved PSCI via increasing the phosphorylation of CREB and histone acetylation, thus attenuating cholinergic activity.


greenmedinfo--2020-09-28--Sayer Ji: Biopolitics, the Corona World Order, and the Human Connection Movement [LIVESTREAM]

In this livestream , Sayer Ji dives deep into the meta issues we are facing today , both as individuals @ @ @ @ @ Covid-19 as an event horizon for humanity , and the ontological fork in the road @ @ @ @ @ asked to make a decision about which direction we will take .
 Make sure @ @ @ @ @ group which unlike almost all other social media platforms , is censorship free , and @ @ @ @ @ of our real time updates : https : //t.me/sayeregengmi Sign up to get the free @ @ @ @ @

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greenmedinfo--2020-09-28--The results revealed that oleuropein is able to significantly reduce cytotoxicity, apoptosis, genoto

Oleuropein is one of the most abundant and important phenolic compounds in fruits and olive leaves .
In this research @ @ @ @ @ oleuropein was investigated versus 2 Gy of gamma radiation on human peripheral blood mononuclear cells @ @ @ @ @ study was to evaluate the effects of oleuropein radiation protection and to find an effective @ @ @ @ @ with oleuropein at the concentration of 100 μM ( optimum concentration ) , incubated for @ @ @ @ @ exposed to 2Gy gamma rays .
The anti-radiation effect of oleuropein was assessed by MTT @ @ @ @ @ comet assay , and micronucleus ( MN ) assay.It was found that pre-treatment with oleuropein @ @ @ @ @ 75 , 100 , 200 , 400 , and 800 nM -1 , 5 , @ @ @ @ @ , 25 , 30 , 40 , 50 , 75 , 100 , 125 , @ @ @ @ @ µM ) significantly increased the percentage of cell viability compared to the irradiated group ( @

Oleuropein is one of the most abundant and important phenolic compounds in fruits and olive leaves . In this research, the radioprotective effect of oleuropein was investigated versus 2 Gy of gamma radiation on human peripheral blood mononuclear cells. The aim of this study was to evaluate the effects of oleuropein radiation protection and to find an effective radioprotector.Human mononuclear cells were treated with oleuropein at the concentration of 100 μM (optimum concentration), incubated for 24 hours, and then exposed to 2Gy gamma rays. The anti-radiation effect of oleuropein was assessed by MTT assay, flow cytometry, comet assay, and micronucleus (MN) assay.It was found that pre-treatment with oleuropein (25, 50, 75, 100, 200, 400, and 800 nM -1, 5, 10, 15, 20, 25, 30, 40, 50, 75, 100, 125, 150, 175, 200 µM) significantly increased the percentage of cell viability compared to the irradiated group (p < 0.001) . Moreover, oleuropein treatment with the above concentrations defined without γ-ray did not show any cytotoxicity effect in human mononuclear cells . The LDdose was calculated as 2.9 Gy, whereas by 200, 150, 50, and 100 µM oleuropein prior to radiation (1, 2,and 4 Gy) , radiation LDincreased to 3.36, 3.54, 3.81, and greater than 4 Gy, in that order. A very noticeable dose-modifying factor (DMF) of 1.16, 1.23, 1.31, and 1.72 was observed for 200, 150, 50, and 100µM, in order . Therefore, 100 µM of oleuropein was selected as the desirable dose for radio-protection trial, and 2 Gy gamma rays were used for further research. Human mononuclear cells treatment with oleuropein (100 µM) prior to 2Gy gamma rays significantly decreased apoptosis, genomic damage, and MN occurrence in human mononuclear caused by γ-radiation (p < 0.001) . Further more, treatment with oleuropein (100 µM) without radiation did not lead to apoptosis, genotoxicity, or clastogenic effects caused by oleuropein in human mononuclear cells.The results revealed that oleuropein is able to significantly reduce cytotoxicity, apoptosis, genotoxic, and clastogenic effects of gamma rays.


greenmedinfo--2020-09-28--Oleuropein might be considered as a potential antimetastatic agent for prostate cancer.

In this study , we investigated whether olive leaf and oleuropein have the potential to stop cell motility , which a metastatic cell behavior by blocking voltage-gated sodium channels ( VGSCs ) .
For this purpose , it was first prepared the aqueous extract of olive leaves ( AOLE ) .
Then it was assayed the effect on the motility of MAT-LyLu , a highly metastatic Dunning rat prostate adenocarcinoma cells of this extract .
The phenolic content of AOLE was analyzed using LC-MS/MS instrument .
It was observed that oleuropein was the most finding compound in AOLE .
Therefore @ @ @ @ @ @ @ inhibitory effect of AOLE on the MAT-LyLu cell movement was tested .
Nontoxic oleuropein concentrations and those that did not affect proliferation on MAT-LyLu cells were determined .
Subsequently , it was examined the effects of oleuropein on the lateral and vertical movement of MAT-LyLu cells .
To elucidate the mechanism of oleuropein affecting cell motility , whether it suppressed mRNA expression of , which encodes the VGSC was analyzed .
Accordingly , oleuropein suppressed the movement of MAT-LyLu cells by reducingmRNA expression .
In conclusion , we report the first time that @ @ @ @ @ @ @ antimetastatic agent for prostate cancer due to its blocking effect on VGSC-mediated cell motility .

In this study, we investigated whether olive leaf and oleuropein have the potential to stop cell motility, which a metastatic cell behavior by blocking voltage-gated sodium channels (VGSCs). For this purpose, it was first prepared the aqueous extract of olive leaves (AOLE). Then it was assayed the effect on the motility of MAT-LyLu, a highly metastatic Dunning rat prostate adenocarcinoma cells of this extract. The phenolic content of AOLE was analyzed using LC-MS/MS instrument. It was observed that oleuropein was the most finding compound in AOLE. Therefore, whether oleuropein was responsible for the inhibitory effect of AOLE on the MAT-LyLu cell movement was tested. Nontoxic oleuropein concentrations and those that did not affect proliferation on MAT-LyLu cells were determined. Subsequently, it was examined the effects of oleuropein on the lateral and vertical movement of MAT-LyLu cells. To elucidate the mechanism of oleuropein affecting cell motility, whether it suppressed mRNA expression of, which encodes the VGSC was analyzed. Accordingly, oleuropein suppressed the movement of MAT-LyLu cells by reducingmRNA expression. In conclusion, we report the first time that oleuropein might be considered as a potential antimetastatic agent for prostate cancer due to its blocking effect on VGSC-mediated cell motility.


greenmedinfo--2020-09-29--High dietary oleic acid in olive oil-supplemented diet enhanced omega-3 fatty acid in blood plasma.

This study was conducted to investigate the effect of dietary oleic acid in olive oil-supplemented diets on the blood lipid profile and fatty acid composition in blood plasma and adipose tissue of rats .
A total of 60 Sprague Dawley rats with mean body weight of 249 g ± 3.04 g were equally divided into three diet groups : control ( CON ) contained 10 % coconut oil , olive50 contained 5 % coconut oil and 5 % olive oil , and olive100 contained 10 % olive oil .
Oleic acid ( OA ) level was highest in olive100 followed @ @ @ @ @ @ @ final body weight ( BW ) of the rats was significantly affected by the intake of OA , in which rats fed olive100 had the lowest final BW , which signified that OA could be associated with weight loss .
Olive oil intake significantly increased levels of the high-density lipoprotein cholesterol ( HDL-C ) and exhibited a potential attenuation effect on the glutamic-oxaloacetic transaminase and the glutamic-pyruvic transaminase , and a potential role in the reduction of triglycerides in the bloodstream of the animals .
In terms of fatty acid composition , significantly @ @ @ @ @ @ @ plasma and adipose tissues of rats fed olive100 .
Omega-3 polyunsaturated fatty acids ( PUFAs ) , such as linolenic ( C18:3-3 ) , eicosapentaenoic ( C20:5-3 ) , and docosahexaenoic ( C22:6-3 ) , and-6 PUFA arachidonic ( C20:4-6 ) were also significantly increased in the blood plasma of rats fed olive100 .
These findings suggest that the intake of dietary high OA may enhance the omega-3 fatty acid levels in the blood plasma of rats and may have a positive effect in reducing risks to cardiovascular disease , as evidenced by @ @ @ @ @ @ @ and decreased TG levels in the blood plasma of experimental animals .

This study was conducted to investigate the effect of dietary oleic acid in olive oil-supplemented diets on the blood lipid profile and fatty acid composition in blood plasma and adipose tissue of rats. A total of 60 Sprague Dawley rats with mean body weight of 249 g ± 3.04 g were equally divided into three diet groups: control (CON) contained 10% coconut oil, olive50 contained 5% coconut oil and 5% olive oil, and olive100 contained 10% olive oil. Oleic acid (OA) level was highest in olive100 followed by the olive50 and control. The final body weight (BW) of the rats was significantly affected by the intake of OA, in which rats fed olive100 had the lowest final BW, which signified that OA could be associated with weight loss. Olive oil intake significantly increased levels of the high-density lipoprotein cholesterol (HDL-C) and exhibited a potential attenuation effect on the glutamic-oxaloacetic transaminase and the glutamic-pyruvic transaminase, and a potential role in the reduction of triglycerides in the bloodstream of the animals. In terms of fatty acid composition, significantly high OA was observed in the blood plasma and adipose tissues of rats fed olive100. Omega-3 polyunsaturated fatty acids (PUFAs), such as linolenic (C18:3-3), eicosapentaenoic (C20:5-3), and docosahexaenoic (C22:6-3), and-6 PUFA arachidonic (C20:4-6) were also significantly increased in the blood plasma of rats fed olive100. These findings suggest that the intake of dietary high OA may enhance the omega-3 fatty acid levels in the blood plasma of rats and may have a positive effect in reducing risks to cardiovascular disease, as evidenced by weight loss, increased HDL-C levels, and decreased TG levels in the blood plasma of experimental animals.


greenmedinfo--2020-09-29--The use of coconut oil as a treatment strategy for xerostomia post-HNC radiation is feasible, inexpe

Background : Xerostomia is a common complication following radiation therapy for head and neck cancer ( HNC ) , for which there is no single , universally accepted therapy .
Coconut oil has been anecdotally suggested to provide relief for this complication .
This study sought to examine the feasibility and effectiveness of coconut oil as a therapy for radiation-induced xerostomia .
Methods : A feasibility study was performed among 30 patients with xerostomia subsequent to radiation for HNC .
Coconut oil samples were provided along with a protocol for use over a 2-week period and the option to continue @ @ @ @ @ @ @ were also instructed to keep diaries to document their patterns of use .
The Xerostomia-related Quality of Life Scale ( XeQOLS ) was administered at baseline and 3-month follow-up .
Descriptive methods were used to summarize patterns of coconut oil use and paired-tests were used to assess changes in XeQOLS scores over time .
Results : The mean total duration of coconut oil use during the study period was 16 days ( 1-71 ) .
The average number of uses per day was 3 ( 1-5 ) , with an average amount per @ @ @ @ @ @ @ .
Twelve patients ( 41.4 % ) continued coconut oil use beyond the advised period .
There was no statistically significant difference in XeQOLS scores pre- and post-treatment .
There were no adverse events during the study period .
Conclusions : The use of coconut oil as a treatment strategy for xerostomia post-HNC radiation is feasible , inexpensive , and safe .
This study demonstrates that there may be a group of HNC patients that benefit from its use .

Background: Xerostomia is a common complication following radiation therapy for head and neck cancer (HNC), for which there is no single, universally accepted therapy. Coconut oil has been anecdotally suggested to provide relief for this complication. This study sought to examine the feasibility and effectiveness of coconut oil as a therapy for radiation-induced xerostomia.
Methods: A feasibility study was performed among 30 patients with xerostomia subsequent to radiation for HNC. Coconut oil samples were provided along with a protocol for use over a 2-week period and the option to continue if they found it beneficial. Patients were also instructed to keep diaries to document their patterns of use. The Xerostomia-related Quality of Life Scale (XeQOLS) was administered at baseline and 3-month follow-up. Descriptive methods were used to summarize patterns of coconut oil use and paired-tests were used to assess changes in XeQOLS scores over time.
Results: The mean total duration of coconut oil use during the study period was 16 days (1-71). The average number of uses per day was 3 (1-5), with an average amount per use of 5 mL (1.2-8.5). Twelve patients (41.4%) continued coconut oil use beyond the advised period. There was no statistically significant difference in XeQOLS scores pre- and post-treatment. There were no adverse events during the study period.
Conclusions: The use of coconut oil as a treatment strategy for xerostomia post-HNC radiation is feasible, inexpensive, and safe. This study demonstrates that there may be a group of HNC patients that benefit from its use.


greenmedinfo--2020-09-29--The role of coconut oil in treating patients affected by plaque-induced gingivitis.

OBJECTIVES : The aim of the study was to evaluate the coconut oil pulling efficacy as adjuvant in reducing plaque formation and in treating plaque-induced gingivitis .
MATERIALS AND METHODS : A sample of 20 patients was divided into two groups : a study and a control group .
In the study group , coconut oil , in form of mouthwash , was administered to a sample of patients affected by gingivitis , aged between 18 and 35 .
The protocol established a daily application of the product for 30 days , where clinical parameters for plaque formation and gingivitis-plaque @ @ @ @ @ @ @ ( BI ) -will be evaluated during the recalls on a specific periodontal chart .
The control group did not associate a coadjuvant to the normal daily oral health procedures and the same clinical parameters were evaluated at t0 and after 30 days ( t1 ) .
The data were statistically analyzed using Student's-test , establishing the significance level as < 0.05 .
RESULTS : PI and BI decreased in both groups , with a more relevant and significant drop in the study group , from a mean value of PI of 58.0 @ @ @ @ @ @ @ BI of 33.5 to 5.0 .
In the control group , the values decreased , respectively , from 53.9 to 29.1 for PI , and from 33.5 to 16.2 .
Furthermore , no significant side effect was reported during coconut oil pulling therapy .
CONCLUSIONS : The collected data showed significant and promising improvements in reducing plaque formation and gingivitis .
However , further researches have to be performed to have more consistent and statistically significant data on larger samples and to fully understand the mechanisms of action and effectiveness .

OBJECTIVES: The aim of the study was to evaluate the coconut oil pulling efficacy as adjuvant in reducing plaque formation and in treating plaque-induced gingivitis.
MATERIALS AND METHODS: A sample of 20 patients was divided into two groups: a study and a control group. In the study group, coconut oil, in form of mouthwash, was administered to a sample of patients affected by gingivitis, aged between 18 and 35. The protocol established a daily application of the product for 30 days, where clinical parameters for plaque formation and gingivitis-plaque index (PI), bleeding index (BI)-will be evaluated during the recalls on a specific periodontal chart. The control group did not associate a coadjuvant to the normal daily oral health procedures and the same clinical parameters were evaluated at t0 and after 30 days (t1). The data were statistically analyzed using Student's-test, establishing the significance level as<0.05.
RESULTS: PI and BI decreased in both groups, with a more relevant and significant drop in the study group, from a mean value of PI of 58.0 to 19.3 and a mean value of BI of 33.5 to 5.0. In the control group, the values decreased, respectively, from 53.9 to 29.1 for PI, and from 33.5 to 16.2. Furthermore,no significant side effect was reported during coconut oil pulling therapy.
CONCLUSIONS: The collected data showed significant and promising improvements in reducing plaque formation and gingivitis. However, further researches have to be performed to have more consistent and statistically significant data on larger samples and to fully understand the mechanisms of action and effectiveness.


greenmedinfo--2020-09-29--T. officinale flower water syrup possesses beneficial properties by regulating prostanoids and antio

T. officinale flower water syrup possesses beneficial properties by regulating prostanoids and antioxidant status.

ETHNOPHARMACOLOGICAL RELEVANCE : Taraxacum officinale ( L. ) , commonly called dandelion has been used for centuries as a natural medicine to treat inflammatory diseases including some metabolic alterations associated with obesity .
AIM OF THE STUDY : Based on animal experiments this study aims to explore the potential mechanisms of action of T. officinale flower water syrup ( TOFS ) together with a normal-fat diet in the intervention of obesity .
MATERIALS AND METHODS : Obese male albino-Wistar rats ( n = 8 ) at 25 weeks of age were fed with a normal-fat diet with or without added @ @ @ @ @ @ @ 4 weeks .
The reactivity of thoracic aorta and antioxidant capacity were studied .
RESULTS : TOFS delivered daily 926.8 μg of L-chicoric acid , 20.19 μg of luteolin and 3.379 g of sucrose .
TOFS showed beneficial effects by regulating blood lipids ( HDL , x1.11-fold increase ) , thereby lowering the risk factors for atherosclerosis ( TC/HDL , x0.90-fold ) .
The antioxidant status was improved via an increase in plasmasuperoxide radical scavenging ( SOD , x1.6-fold ) and a decrease in lipid peroxidation ( MDA , x0.81-fold ) .
Moreover @ @ @ @ @ @ @ ( x0.53-fold ) , Zn ( x0.72-fold ) and the Cu/Zn molar ratio ( x0.60-fold ) .
A marker for liver damage/disease was beneficially decreased ( ALP , x0.87-fold ) .
TOFSmodulated in a significant way COX-depended relaxation to ACh ( p = 0.05 ) but not to CORM-2 ( p = 0.1651 ) in isolated thoracic arteries , by decreased participation of vasoconstrictor prostanoids .
The vascular contraction to prostaglandin Fwas also decreased ( x0.62-fold ) .
We observed no change in the feed intake , body weight , organ-to-body weight ratio @ @ @ @ @ @ @ , AST , ALT , TBARS/carbonyls ( in heart , liver , kidneys , spleen ) and carbonyls ( in blood plasma , thoracic arteries ) ; as well as F-isoprostanes in urine .
Vascular response to the vasodilators ACh , SNP , A23187 , CORM-2 , pinacidil , NS-1619 and to the vasoconstrictors NA , U-46619 , ET-1 as well as hyperpolarizing mechanism ( s ) were not modified .

ETHNOPHARMACOLOGICAL RELEVANCE: Taraxacum officinale (L.), commonly called dandelion has been used for centuries as a natural medicine to treat inflammatory diseases including some metabolic alterations associated with obesity.
AIM OF THE STUDY: Based on animal experiments this study aims to explore the potential mechanisms of action of T. officinale flower water syrup (TOFS) together with a normal-fat diet in the intervention of obesity.
MATERIALS AND METHODS: Obese male albino-Wistar rats (n = 8) at 25 weeks of age were fed with a normal-fat diet with or without added 27.82% TOFS (w/w) for 4 weeks. The reactivity of thoracic aorta and antioxidant capacity were studied.
RESULTS: TOFS delivered daily 926.8 μg of L-chicoric acid, 20.19 μg of luteolin and 3.379 g of sucrose. TOFS showed beneficial effects by regulating blood lipids (HDL, x1.11-fold increase), thereby lowering the risk factors for atherosclerosis (TC/HDL, x0.90-fold). The antioxidant status was improved via an increase in plasmasuperoxide radical scavenging (SOD, x1.6-fold) and a decrease in lipid peroxidation (MDA, x0.81-fold). Moreover, the following were decreased: Cu (x0.53-fold), Zn (x0.72-fold) and the Cu/Zn molar ratio (x0.60-fold). A marker for liver damage/disease was beneficially decreased (ALP, x0.87-fold). TOFSmodulated in a significant way COX-depended relaxation to ACh (p = 0.05) but not to CORM-2 (p = 0.1651) in isolated thoracic arteries, by decreased participation of vasoconstrictor prostanoids. The vascular contraction to prostaglandin Fwas also decreased (x0.62-fold). We observed no change in the feed intake, body weight, organ-to-body weight ratio, blood glucose, CAT, FRAP, AST, ALT, TBARS/carbonyls (in heart, liver, kidneys, spleen) and carbonyls (in blood plasma, thoracic arteries); as well as F-isoprostanes in urine. Vascular response to the vasodilators ACh, SNP, A23187, CORM-2, pinacidil, NS-1619 and to the vasoconstrictors NA, U-46619, ET-1 as well as hyperpolarizing mechanism(s) were not modified.
CONCLUSIONS: TOFS possesses beneficial properties by regulating prostanoids and antioxidant status.


greenmedinfo--2020-09-29--Comparison of ameliorative effects of Taraxacum syriacum and N-acetylcysteine against acetaminophen-

Comparison of ameliorative effects of Taraxacum syriacum and N-acetylcysteine against acetaminophen-induced oxidative stress in the liver and kidney.

Taraxacum syriacum ( TS ) with natural antioxidant and pharmacological activities may be considered for treatment of oxidative stress induced by acetaminophen ( APAP ) .
The aim of the present study was to evaluate the ameliorative effects of the ethanol extract of TS root against hepatorenal toxicity induced by APAP in comparison to N-acetylcysteine ( NAC ) as a standard drug .
Thirty male Wistar rat were randomly divided into five groups .
Control group ; APAP ( 1g/kg ) group ; APAP-NAC ( 160 mg/kg ) group and APAP-TS100 and APAP-TS200 groups : APAP plus 100 and 200 @ @ @ @ @ @ @ After 7 days treatment , serum and liver and kidney tissues were prepared and evaluated .
TS extract ameliorated the increased lipid peroxidation level and decreased antioxidant enzymes activities and glutathione level in liver and kidney of APAP-treated rats .
Moreover , treatment with the TS extract caused significant reduction in the histopathological damages and high levels of serum biochemical markers of hepatic and renal functions after APAP treatment .
This study suggests that theextract of TS roots has dose-dependent ameliorative effect against APAP-induced oxidative damage in liver and kidney due to its @ @ @ @ @ @ @ The overall efficacy of the extract at 200 mg/kg dose is comparable with NAC .

Taraxacum syriacum (TS) with natural antioxidant and pharmacological activities may be considered for treatment of oxidative stress induced by acetaminophen (APAP). The aim of the present study was to evaluate the ameliorative effects of the ethanol extract of TS root against hepatorenal toxicity induced by APAP in comparison to N-acetylcysteine (NAC) as a standard drug. Thirty male Wistar rat were randomly divided into five groups. Control group; APAP (1g/kg) group; APAP-NAC (160 mg/kg) group and APAP-TS100 and APAP-TS200 groups: APAP plus 100 and 200 mg/kg of TS extract, respectively. After 7 days treatment, serum and liver and kidney tissues were prepared and evaluated. TS extract ameliorated the increased lipid peroxidation level and decreased antioxidant enzymes activities and glutathione level in liver and kidney of APAP-treated rats. Moreover, treatment with the TS extract caused significant reduction in the histopathological damages and high levels of serum biochemical markers of hepatic and renal functions after APAP treatment. This study suggests that theextract of TS roots has dose-dependent ameliorative effect against APAP-induced oxidative damage in liver and kidney due to its free radical scavenging and antioxidant properties. The overall efficacy of the extract at 200 mg/kg dose is comparable with NAC.


greenmedinfo--2020-09-29--Regulation of glycolysis and the Warburg effect in wound healing.

One of the most significant adverse postburn responses is abnormal scar formation , such as keloids .
Despite its prolificacy , the underlying pathophysiology of keloid development is unknown .
We recently demonstrated that NLRP3 inflammasome , the master regulator of inflammatory and metabolic responses ( e.g.
, aerobic glycolysis ) , is essential for physiological wound healing .
Therefore , burn patients who develop keloids may exhibit altered immunometabolic responses at the site of injury , which interferes with normal healing and portends keloid development .
Here , we confirmed keloid NLRP3 activation ( cleaved caspase-1 [ P < @ @ @ @ @ @ @ 0.05 ] , IL-18 [ P < 0.01 ] ) and upregulation in Glut1 ( P < 0.001 ) and glycolytic enzymes .
Burn skin similarly displayed enhanced glycolysis and Glut1 expression ( P < 0.01 ) .
However , Glut1 was significantly higher in keloid compared with nonkeloid burn patients ( > 2 SD above mean ) .
Targeting aberrant glucose metabolism with shikonin , a pyruvate kinase M2 inhibitor , dampened NLRP3-mediated inflammation ( cleaved caspase-1 [ P < 0.05 ] , IL-1β [ P < 0.01 ] ) and improved @ @ @ @ @ @ @ burn skin exhibited evidence of Warburg-like metabolism , similar to keloids .
Targeting this altered metabolism could change the trajectory toward normal scarring , indicating the clinical possibility of shikonin for abnormal scar prevention .

One of the most significant adverse postburn responses is abnormal scar formation, such as keloids. Despite its prolificacy, the underlying pathophysiology of keloid development is unknown. We recently demonstrated that NLRP3 inflammasome, the master regulator of inflammatory and metabolic responses (e.g., aerobic glycolysis), is essential for physiological wound healing. Therefore, burn patients who develop keloids may exhibit altered immunometabolic responses at the site of injury, which interferes with normal healing and portends keloid development. Here, we confirmed keloid NLRP3 activation (cleaved caspase-1 [P<0.05], IL-1β [P<0.05], IL-18 [P<0.01]) and upregulation in Glut1 (P<0.001) and glycolytic enzymes. Burn skin similarly displayed enhanced glycolysis and Glut1 expression (P<0.01). However, Glut1 was significantly higher in keloid compared with nonkeloid burn patients (>2 SD above mean). Targeting aberrant glucose metabolism with shikonin, a pyruvate kinase M2 inhibitor, dampened NLRP3-mediated inflammation (cleaved caspase-1 [P<0.05], IL-1β [P<0.01]) and improved healing in vivo. In summary, burn skin exhibited evidence of Warburg-like metabolism, similar to keloids. Targeting this altered metabolism could change the trajectory toward normal scarring, indicating the clinical possibility of shikonin for abnormal scar prevention.


greenmedinfo--2020-09-29--Shikonin may be a novel therapeutic agent for patients with cholangiocarcinoma.

BACKGROUND/AIM : Pyruvate kinase M2 ( PKM2 ) is an enzyme that is predominantly overexpressed in various types of cancer @ @ @ @ @ in liver fluke-associated cholangiocarcinoma ( CCA ) remains unclear .
This study aimed to investigate @ @ @ @ @ , a PKM2 inhibitor , in CCA cells .
MATERIALS AND METHODS : Immunohistochemistry and @ @ @ @ @ PKM2 expression in CCA tissues and cells .
Antiproliferative effects of shikonin were evaluated using @ @ @ @ @ bromide , colony-formation and trypan blue exclusion assays .
The anti-metastatic activity of shikonin was @ @ @ @ @ assay .
Mechanisms by which shikonin inhibited CCA progression were determined .
RESULTS : PKM2 @ @ @ @ @ to normal bile duct epithelial cells .
Shikonin significantly inhibited growth , and migration of @ @ @ @ @ death .
A mechanistic study revealed that antitumor effects of shikonin in CCA cells depended @ @ @ @ @ oxygen species .
CONCLUSION : Shikonin may be a novel therapeutic agent for patients with @ @

BACKGROUND/AIM: Pyruvate kinase M2 (PKM2) is an enzyme that is predominantly overexpressed in various types of cancer. The role of PKM2 in liver fluke-associated cholangiocarcinoma (CCA) remains unclear. This study aimed to investigate the antitumor activity of shikonin, a PKM2 inhibitor, in CCA cells.
MATERIALS AND METHODS: Immunohistochemistry and immunoblotting were used to determine PKM2 expression in CCA tissues and cells. Antiproliferative effects of shikonin were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, colony-formation and trypan blue exclusion assays. The anti-metastatic activity of shikonin was determined using the Boyden chamber assay. Mechanisms by which shikonin inhibited CCA progression were determined.
RESULTS: PKM2 was overexpressed in CCA compared to normal bile duct epithelial cells. Shikonin significantly inhibited growth, and migration of CCA cells while inducing their death. A mechanistic study revealed that antitumor effects of shikonin in CCA cells depended on increased production of reactive oxygen species.
CONCLUSION: Shikonin may be a novel therapeutic agent for patients with CCA.


greenmedinfo--2020-09-29--Shikonin ameliorates experimental autoimmune encephalomyelitis.

OBJECTIVES : Multiple sclerosis is a common autoimmune inflammatory disease of the central nervous system .
There are several underlying mechanisms for the pathogenesis of the disease , including inflammation , oligodendrocyte apoptosis and oxidative stress .
METHODS : The mechanism of action of shikonin was investigated in the C57BL/6 experimental autoimmune encephalomyelitis ( EAE ) model of multiple sclerosis .
KEY FINDINGS : The results revealed that EAE induction significantly increased the extent of demyelination in the corpus callosum tissues of the animals , while treatment of the mice with shikonin significantly decreased the extent of demyelination .
Real-time @ @ @ @ @ @ @ samples from the EAE mice revealed significant enhancement in the expression levels of tumour necrosis factor-α ( TNF-α ) , interferon-γ ( IFN-γ ) and Bax genes as well as a reduction in the expression levels of transforming growth factor-ß ( TGF-β ) and Bcl2 .
But , shikonin treatment significantly reduced the expression levels of TNF-α , IFN-γ and Bax .
On the other hand , the expression levels of TGF-β andBcl2 as well as the activity of glutathione peroxidase-1 ( GPX-1 ) enzyme were significantly increased following the shikonin treatment .
@ @ @ @ @ @ @ and antioxidative effects of shikonin , which may have an important healing effect on the severity of EAE .

OBJECTIVES: Multiple sclerosis is a common autoimmune inflammatory disease of the central nervous system. There are several underlying mechanisms for the pathogenesis of the disease, including inflammation, oligodendrocyte apoptosis and oxidative stress.
METHODS: The mechanism of action of shikonin was investigated in the C57BL/6 experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis.
KEY FINDINGS: The results revealed that EAE induction significantly increased the extent of demyelination in the corpus callosum tissues of the animals, while treatment of the mice with shikonin significantly decreased the extent of demyelination. Real-time polymerase chain reaction-based analysis of the brain samples from the EAE mice revealed significant enhancement in the expression levels of tumour necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and Bax genes as well as a reduction in the expression levels of transforming growth factor-ß (TGF-β) and Bcl2. But, shikonin treatment significantly reduced the expression levels of TNF-α, IFN-γ and Bax. On the other hand, the expression levels of TGF-β andBcl2 as well as the activity of glutathione peroxidase-1 (GPX-1) enzyme were significantly increased following the shikonin treatment.
CONCLUSIONS: This study emphasized the immune-modulatory and antioxidative effects of shikonin, which may have an important healing effect on the severity of EAE.


greenmedinfo--2020-09-29--Shikonin overcomes drug resistance and induces necroptosis by regulating the miR-92a-1-5p/MLKL axis

Shikonin overcomes drug resistance and induces necroptosis by regulating the miR-92a-1-5p/MLKL axis in chronic myeloid leukemia.

Development of resistance to tyrosine kinase inhibitors ( TKIs ) targeting the BCR/ABL fusion protein represents a major challenge in the treatment of chronic myeloid leukemia ( CML ) .
Since apoptosis resistance is the fundamental mechanism impeding TKIs ' therapeutic effects , alternative approaches that induce nonapoptotic cell death are being pursued to treat TKI-resistant CML .
Induction of necroptosis , a distinct , caspase-independent form of programmed cell death , may be a valuable strategy in this respect .
The present study shows that shikonin , an herbal compound used in traditional Chinese medicine , overcomes TKI resistance @ @ @ @ @ @ @ via activation of RIPK1/RIPK3/MLKL signaling .
This effect occurs both in vitro and in vivo and involves downregulation of miR-92a-1-5p , a poor-prognosis marker frequently overexpressed in leukemia patients .
Based on gene expression experiments , we conclude that miR-92a-1-5p promotes CML progression by inhibiting MLKL expression .
Accordingly , we show that antagomiR-mediated in vivo inhibition of miR-92a-1-5p reduces the growth of CML tumors in mice through necroptosis induction .
Our research suggests that therapies that relieve MLKL suppression by targeting miR-92a-1-5p may represent a useful strategy to treat TKI-refractory CML .

Development of resistance to tyrosine kinase inhibitors (TKIs) targeting the BCR/ABL fusion protein represents a major challenge in the treatment of chronic myeloid leukemia (CML). Since apoptosis resistance is the fundamental mechanism impeding TKIs' therapeutic effects, alternative approaches that induce nonapoptotic cell death are being pursued to treat TKI-resistant CML. Induction of necroptosis, a distinct, caspase-independent form of programmed cell death, may be a valuable strategy in this respect. The present study shows that shikonin, an herbal compound used in traditional Chinese medicine, overcomes TKI resistance in BCR/ABL-positive CML cells by inducing necroptosis via activation of RIPK1/RIPK3/MLKL signaling. This effect occurs both in vitro and in vivo and involves downregulation of miR-92a-1-5p, a poor-prognosis marker frequently overexpressed in leukemia patients. Based on gene expression experiments, we conclude that miR-92a-1-5p promotes CML progression by inhibiting MLKL expression. Accordingly, we show that antagomiR-mediated in vivo inhibition of miR-92a-1-5p reduces the growth of CML tumors in mice through necroptosis induction. Our research suggests that therapies that relieve MLKL suppression by targeting miR-92a-1-5p may represent a useful strategy to treat TKI-refractory CML.


greenmedinfo--2020-09-29--The present results may facilitate the clinical application of shikonin as an anti-inflammatory agen

The present results may facilitate the clinical application of shikonin as an anti-inflammatory agent in treating COPD.

Shikonin has been reported to exhibit a wide variety of medical functions .
However , the strong non-selective cytotoxicity of @ @ @ @ @ application .
The aim of the present study was to investigate the effects of shikonin @ @ @ @ @ pro-inflammation functions of monocytes and macrophages .
The present results suggested that the non-cytotoxic doses @ @ @ @ @ ( LPS ) -induced reactive oxygen species production , NF-κB activation and TNF-α expression in @ @ @ @ @ AMP-activated protein kinase ( AMPK ) signaling pathway .
In addition , the non-cytotoxic doses @ @ @ @ @ expression via AMPK signaling activation in primary murine bone marrow-derived macrophages , and also in @ @ @ @ @ obstructive pulmonary disease ( COPD ) .
The presentresults indicated that the low-toxic dose of @ @ @ @ @ and TNF-α expression in mice .
Collectively , the present results may provide clinical and @ @ @ @ @ and other TNF-α-related inflammatory disorders .

Shikonin has been reported to exhibit a wide variety of medical functions. However, the strong non-selective cytotoxicity of shikonin can restrict its clinical application. The aim of the present study was to investigate the effects of shikonin at non-cytotoxic doses on the pro-inflammation functions of monocytes and macrophages. The present results suggested that the non-cytotoxic doses of shikonin effectively inhibited lipopolysaccharide (LPS)-induced reactive oxygen species production, NF-κB activation and TNF-α expression in RAW 264.7 mouse macrophages via AMP-activated protein kinase (AMPK) signaling pathway. In addition, the non-cytotoxic doses of shikonin downregulated LPS-induced TNF-α expression via AMPK signaling activation in primary murine bone marrow-derived macrophages,and also in monocytes culturedfrom patients with chronic obstructive pulmonary disease (COPD). The presentresults indicated that the low-toxic dose of shikonin suppressed LPS-induced endotoxin shock and TNF-α expression in mice. Collectively, the present results may provide clinical and translational relevance for treating COPD and other TNF-α-related inflammatory disorders.


greenmedinfo--2020-09-29--Protective role of wogonin against cadmium induced testicular toxicity.

The present study was conducted to identify possible health - promoting effects of wogonin ( Wog ) on testicular dysfunction in rats caused by cadmium .
Pre-treatment of cadmium chloride ( Cd : 5 mg/kg b.wt . )
administered rats with wogonin ( 10 mg/kg b.wt ) resulted in significant improvement in Cd-induced decrease in body and organ ( testes and epididymides ) weights .
Wogonin treatment significantly improved Cd-induced reduction in sperm quality and quantity , steroidogenic gene ( SFI , StAR , CYP11A1 , 3β-HSD , CYP17A1 and 17β-HSD ) and protein ( SF1 , StAR and CYP17A1 @ @ @ @ @ @ @ Wogonin treatment provided significant protection to Cd-induced aggression in testicular oxidative ( elevated levels of MDA ) and anti-oxidative ( diminished activities of SOD , CAT andGPx ) status .
Wog significantly up-regulated mRNA levels of Nrf2 , NQO1 and HO-1 and down-regulation of Keap1 in cadmium treated testes .
Wogonin administration significantly suppressed Cd-stimulated increase in inflammatory reactions ( increase in NF-κB p65 DNA , p-IKKβ , TNF-α levels and decrease inIL-10 levels ) .
Wogonin prevented apoptotic damage by enhanced protein distribution of caspase-9 , caspase-3 , and Bax due to @ @ @ @ @ @ @ significant protection to histo-morphometric changes resulted after Cd administration .
Taken together , the findings of this study provided clear evidence of the therapeutic potential of Cd-induced testicular toxicity at least partly due to its antioxidant , anti-inflammatory and anti-apoptotic properties .

The present study was conducted to identify possible health - promoting effects of wogonin (Wog) on testicular dysfunction in rats caused by cadmium. Pre-treatment of cadmium chloride (Cd: 5 mg/kg b.wt.) administered rats with wogonin (10 mg/kg b.wt) resulted in significant improvement in Cd-induced decrease in body and organ (testes and epididymides) weights. Wogonin treatment significantly improved Cd-induced reduction in sperm quality and quantity, steroidogenic gene (SFI, StAR, CYP11A1, 3β-HSD, CYP17A1 and 17β-HSD) and protein (SF1, StAR and CYP17A1) expressions and serum testosterone levels. Wogonin treatment provided significant protection to Cd-induced aggression in testicular oxidative (elevated levels of MDA) and anti-oxidative (diminished activities of SOD, CAT andGPx) status. Wog significantly up-regulated mRNA levels of Nrf2, NQO1 and HO-1 and down-regulation of Keap1 in cadmium treated testes. Wogonin administration significantly suppressed Cd-stimulated increase in inflammatory reactions (increase in NF-κB p65 DNA, p-IKKβ, TNF-α levels and decrease inIL-10 levels). Wogonin prevented apoptotic damage by enhanced protein distribution of caspase-9, caspase-3, and Bax due to Cd exposure. Furthermore, Wogonin presented significant protection to histo-morphometric changes resulted after Cd administration. Taken together, the findings of this study provided clear evidence of the therapeutic potential of Cd-induced testicular toxicity at least partly due to its antioxidant, anti-inflammatory and anti-apoptotic properties.


greenmedinfo--2020-09-29--Wogonin induces apoptosis and reverses sunitinib resistance of renal cell carcinoma cells.

Wogonin , an active component derived from Scutellaria baicalensis , has shown anti-tumor activities in several malignancies .
However , the roles of wogonin in RCC cells remain elusive .
Here , we explored the effects of wogonin on RCC cells and the underlying mechanisms .
We found that wogonin showed significant cytotoxic effects against RCC cell lines 786-O and OS-RC-2 , with much lower cytotoxic effects on human normal embryonic kidney cell line HEK-293 cells .
Wogonin treatment dramatically inhibited the proliferation , migration , and invasion of RCC cells .
We further showed that by inhibiting CDK4-RB pathway @ @ @ @ @ @ @ DNA replication , induced DNA damage and apoptosis in RCC cells .
Moreover , we found that the levels of p-RB , CDK4 , and Cyclin D1 were up-regulated in sunitinib resistant 786-O , OS-RC-2 , and TK-10 cells , and inhibition of CDK4 by palbociclib or wogonin effectively reversed the sunitinib resistance , indicating that the hyperactivation of CDK4-RB pathway may at least partially contribute to the resistance of RCC to sunitinib .
Together , our findings demonstrate that wogonin could induce apoptosis and reverse sunitinib resistance of RCC cellsinhibiting CDK4-RB pathway @ @ @ @ @ @ @ in the future management of RCC patients .

Wogonin, an active component derived from Scutellaria baicalensis, has shown anti-tumor activities in several malignancies. However, the roles of wogonin in RCC cells remain elusive. Here, we explored the effects of wogonin on RCC cells and the underlying mechanisms. We found that wogonin showed significant cytotoxic effects against RCC cell lines 786-O and OS-RC-2, with much lower cytotoxic effects on human normal embryonic kidney cell line HEK-293 cells. Wogonin treatment dramatically inhibited the proliferation, migration, and invasion of RCC cells. We further showed that by inhibiting CDK4-RB pathway, wogonin transcriptionally down-regulated CDC6, disturbed DNA replication, induced DNA damage and apoptosis in RCC cells. Moreover, we found that the levels of p-RB, CDK4, and Cyclin D1 were up-regulated in sunitinib resistant 786-O, OS-RC-2, and TK-10 cells, and inhibition of CDK4 by palbociclib or wogonin effectively reversed the sunitinib resistance, indicating that the hyperactivation of CDK4-RB pathway may at least partially contribute to the resistance of RCC to sunitinib. Together, our findings demonstrate that wogonin could induce apoptosis and reverse sunitinib resistance of RCC cellsinhibiting CDK4-RB pathway, thus suggesting a potential therapeutic implication in the future management of RCC patients.


greenmedinfo--2020-09-29--Wogonin facilitates hematoma clearance and neurobehavioral recovery by targeting PPAR-γ.

Intracerebral hemorrhage ( ICH ) is a cerebrovascular disease with high mortality and morbidity for which effective treatments are currently lacking .
Wogonin is a major flavonoid compound isolated from Scutellaria radix .
Accumulating evidence suggests that wogonin plays a crucial role in anti-inflammatory and anti-oxidative stress .
Treatment of microglia with nuclear receptor agonists augments the expression of phagocytosis-related genes .
However , the neuroprotective effects of wogonin in ICH remain obscure .
In this study , we elucidated an innovative mechanism by which wogonin acts to enhance phagocytosis in a murine model of ICH .
Wogonin promoted hematoma @ @ @ @ @ @ @ by upregulating the expression of Axl , MerTK , CD36 , and LAMP2 in perihematomal microglia and BV2 cells .
Treatment of a murine model of ICH with wogonin stimulated microglial phagocytosis in vitro .
Further , we demonstrated that wogonin dramatically attenuated inflammatory and oxidative stress responses in a murine model of ICH by reducing the expression of pro-inflammatory cytokines and pro-oxidant enzymes such as TNF-α , IL-1β , and inducible nitric oxide synthase ( iNOS ) after ICH .
The effects of wogonin were abolished by administration of the PPAR-γ inhibitor @ @ @ @ @ @ @ suggest that wogonin facilitates hematoma clearance and neurobehavioral recovery by targeting PPAR-γ .

Intracerebral hemorrhage (ICH) is a cerebrovascular disease with high mortality and morbidity for which effective treatments are currently lacking. Wogonin is a major flavonoid compound isolated from Scutellaria radix. Accumulating evidence suggests that wogonin plays a crucial role in anti-inflammatory and anti-oxidative stress. Treatment of microglia with nuclear receptor agonists augments the expression of phagocytosis-related genes. However, the neuroprotective effects of wogonin in ICH remain obscure. In this study, we elucidated an innovative mechanism by which wogonin acts to enhance phagocytosis in a murine model of ICH. Wogonin promoted hematoma clearance and improved neurological recovery after ICH by upregulating the expression of Axl, MerTK, CD36, and LAMP2 in perihematomal microglia and BV2 cells. Treatment of a murine model of ICH with wogonin stimulated microglial phagocytosis in vitro. Further, we demonstrated that wogonin dramatically attenuated inflammatory and oxidative stress responses in a murine model of ICH by reducing the expression of pro-inflammatory cytokines and pro-oxidant enzymes such as TNF-α, IL-1β, and inducible nitric oxide synthase (iNOS) after ICH. The effects of wogonin were abolished by administration of the PPAR-γ inhibitor GW9662. In conclusion, our data suggest that wogonin facilitates hematoma clearance and neurobehavioral recovery by targeting PPAR-γ.


greenmedinfo--2020-09-29--CDC Comes Clean: New Fatality Rate is a Shocker!

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By providing the information contained herein we are not diagnosing , treating @ @ @ @ @ or preventing any type of disease or medical condition .
Before beginning any type of @ @ @ @ @ treatment regimen , it is advisable to seek the advice of a licensed healthcare professional @


greenmedinfo--2020-09-29--The Invention of an Epidemic

The Invention of an Epidemic


greenmedinfo--2020-09-29--Medicine as a Religion

Medicine as a Religion


greenmedinfo--2020-09-29--Blockchain Education, a Ticket to Digital Serfdom