greenmedinfo--2020-04-28--Ginsenoside Rg3 ameliorates acute exacerbation of COPD by suppressing neutrophil migration

Acute Exacerbation of Chronic Obstructive Pulmonary Disease ( AECOPD ) is an irreversible inflammatory airways disease responsible for global health burden , involved with a complex condition of immunological change .
Exacerbation-mediated neutrophilia is an important factor in the pathogenesis of cigarette smoke-induced AECOPD .
Ginsenoside Rg3 , a red-ginseng-derived compound , has multiple pharmacological properties such as anti-inflammatory and antitumor activities .
Here , we investigated a protective role of Rg3 against AECOPD , focusing on neutrophilia .
14-week-cigarette smoke ( CS ) exposure and non-typeable Haemophilus inflenzae ( NTHi ) infection were used to establish the AECOPD murine @ @ @ @ @ @ @ , 40 mg/kg ) was administered intragastrically from the 12th week of CS exposure before infection , and this led to improved lung function and lung morphology , and reduced neutrophilic inflammation , indicating a suppressive effect on neutrophil infiltration by Rg3 .
Further investigations on the mechanismof Rg3 on neutrophils were carried out using bronchial epithelial cell ( BEAS-2B ) and neutrophil co-culture and transepithelial migration model .
Pre-treatment of neutrophils with Rg3 reduced neutrophil migration , which seemed to be the result of inhibition of phosphatidylinositol ( PtdIns ) 3-kinases ( @ @ @ @ @ @ @ , Rg3 could inhibit exacerbation-induced neutrophilia in COPD by negatively regulating PI3K activities in neutrophils .
This study provides a potential natural drug against AECOPD neutrophil inflammation .

Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD) is an irreversible inflammatory airways disease responsible for global health burden, involved with a complex condition of immunological change. Exacerbation-mediated neutrophilia is an important factor in the pathogenesis of cigarette smoke-induced AECOPD. Ginsenoside Rg3, a red-ginseng-derived compound, has multiple pharmacological properties such as anti-inflammatory and antitumor activities. Here, we investigated a protective role of Rg3 against AECOPD, focusing on neutrophilia. 14-week-cigarette smoke (CS) exposure and non-typeable Haemophilus inflenzae (NTHi) infection were used to establish the AECOPD murine model. Rg3 (10, 20, 40 mg/kg) was administered intragastrically from the 12th week of CS exposure before infection, and this led to improved lung function and lung morphology, and reduced neutrophilic inflammation, indicating a suppressive effect on neutrophil infiltration by Rg3. Further investigations on the mechanismof Rg3 on neutrophils were carried out using bronchial epithelial cell (BEAS-2B) and neutrophil co-culture and transepithelial migration model. Pre-treatment of neutrophils with Rg3 reduced neutrophil migration, which seemed to be the result of inhibition of phosphatidylinositol (PtdIns) 3-kinases(PI3K) activation within neutrophils. Thus, Rg3 could inhibit exacerbation-induced neutrophilia in COPD by negatively regulating PI3K activities in neutrophils. This study provides a potential natural drug against AECOPD neutrophil inflammation.


greenmedinfo--2020-04-28--Available findings demonstrated the preclinical evidence that Ginsenoside-Rb1 has a potential neurop

Available findings demonstrated the preclinical evidence that Ginsenoside-Rb1 has a potential neuroprotective effects.

Background : Ischemic stroke is the most common type of stroke , while pharmacological therapy options are limited .
Ginsenosides are the major bioactive compounds in Ginseng and have been found to have various pharmacological effects in the nervous system .
In the present study , we sought to evaluate the effects of Ginsenoside-Rb1 ( G-Rb1 ) , an important ingredient of ginsenosides , and the probable neuroprotective mechanisms in experimental ischemic strokes .
Methods : Studies of G-Rb1 on ischemic stroke animal models were identified from 7 databases .
No clinical trials were included in the analysis .
The @ @ @ @ @ @ @ , infarct volume , evans blue content and/or brain water content ( BWC ) .
The second outcome measures were the possible neuroprotective mechanisms .
All the data were analyzed by Rev Man 5.3 .
Result : Pooled preclinical data showed that compared with the controls , G-Rb1 could improve neurological function ( Zea Longa ( n = 367 , P < 0.01 ) ; mNSS ( n = 70 , P < 0.01 ) ; Water maze test ( n = 48 , P < 0.01 ) ; Bederson ( n = @ @ @ @ @ @ @ , infarct area ( TTC ( n = 211 , P < 0.01 ) ; HE ( n = 26 , P < 0.01 ) ) , as well as blood-brain barrier function ( BWC ( n = 64 , P < 0.01 ) ; Evans blue content ( n=26 , P < 0.05 ) ) .
It also can increase BDNF ( n = 26 , P < 0.01 ) , Gap-43 ( n = 16 , P < 0.01 ) , SOD ( n = 30 , P < 0.01 ) @ @ @ @ @ @ @ P < 0.01 ) , Nissl-positive cells ( n = 12 , P < 0.01 ) , Nestin-positive cells ( n = 10 , P < 0.05 ) , and reduce Caspase-3 ( n = 36 , P < 0.01 ) , IL-1 ( n = 32 , P < 0.01 ) , TNF-α ( n = 72 , P < 0.01 ) , MDA ( n = 18 , P < 0.01 ) , NO ( n = 44 , P < 0.01 ) , NOX ( n = 32 , P @ @ @ @ @ @ @ = 6 , P < 0.05 ) , NF-κB ( P < 0.05 ) and TUNEL-positive cells ( n = 52 , P < 0.01 ) .
Conclusion : Available findings demonstrated the preclinical evidence that G-Rb1 has a potential neuroprotective effect , largely through attenuating brain water content , promoting the bioactivities of neurogenesis , anti-apoptosis , anti-oxidative , anti-inflammatory , energy supplement and cerebral circulation .

Background: Ischemic stroke is the most common type of stroke, while pharmacological therapy options are limited. Ginsenosides are the major bioactive compounds in Ginseng and have been found to have various pharmacological effects in the nervous system. In the present study, we sought to evaluate the effects of Ginsenoside-Rb1 (G-Rb1), an important ingredient of ginsenosides, and the probable neuroprotective mechanisms in experimental ischemic strokes.
Methods: Studies of G-Rb1 on ischemic stroke animal models were identified from 7 databases. No clinical trials were included in the analysis. The primary outcome measures were neurological function scores, infarct volume, evans blue content and/or brain water content (BWC). The second outcome measures were the possible neuroprotective mechanisms. All the data were analyzed by Rev Man 5.3.
Result: Pooled preclinical data showed that compared with the controls, G-Rb1 could improve neurological function (Zea Longa (n = 367, P<0.01); mNSS (n = 70, P<0.01); Water maze test (n = 48, P<0.01); Bederson (n = 16, P<0.01)), infarct area (TTC (n = 211, P<0.01); HE (n = 26, P<0.01)), as well as blood-brain barrier function (BWC (n = 64, P<0.01); Evans blue content (n=26, P<0.05)). It also can increase BDNF (n = 26, P<0.01), Gap-43 (n = 16, P<0.01), SOD (n = 30, P<0.01), GSH (n = 16, P<0.01), Nissl-positive cells (n = 12, P<0.01), Nestin-positive cells (n = 10, P<0.05), and reduce Caspase-3 (n = 36, P<0.01), IL-1 (n = 32, P<0.01), TNF-α (n = 72, P<0.01), MDA (n = 18, P<0.01), NO (n = 44, P<0.01), NOX (n = 32, P<0.05), ROS (n = 6, P<0.05), NF-κB (P<0.05) and TUNEL-positive cells (n = 52, P<0.01).
Conclusion: Available findings demonstrated the preclinical evidence that G-Rb1 has a potential neuroprotective effect, largely through attenuating brain water content, promoting the bioactivities of neurogenesis, anti-apoptosis, anti-oxidative, anti-inflammatory, energy supplement and cerebral circulation.


greenmedinfo--2020-04-28--Effects of red and fermented ginseng and ginsenosides on allergic disorders.

Both white ginseng ( WG , dried root ofsp . )
and red ginseng ( RG , steamed and dried @ @ @ @ @ reported to exhibit a variety of pharmacological effects such as anticancer , antidiabetic , and @ @ @ @ @ contain hydrophilic sugar-conjugated ginsenosides and polysaccharides as the bioactive constituents .
When taken orally , @ @ @ @ @ into hydrophobic ginsenosides compound K , Rh1 , and Rh2 that are absorbable into the @ @ @ @ @ the pharmacological effects more strongly than hydrophilic parental constituents .
To enforce these metabolites , @ @ @ @ @ developed .
Moreover , natural products including ginseng are frequently used for the treatment of @ @ @ @ @ this review introduces the current knowledge related to the effectiveness of ginseng on allergic disorders @ @ @ @ @ , atopic dermatitis , and pruritus .
We discuss how ginseng , its constituents , @ @ @ @ @ immune responses .
We also describe how ginseng controls allergic disorders .

Both white ginseng (WG, dried root ofsp.) and red ginseng (RG, steamed and dried root ofsp.) are reported to exhibit a variety of pharmacological effects such as anticancer, antidiabetic, and neuroprotective activities. These ginsengs contain hydrophilic sugar-conjugated ginsenosides and polysaccharides as the bioactive constituents. When taken orally, their hydrophilic constituents are metabolized into hydrophobic ginsenosides compound K, Rh1, and Rh2 that are absorbable into the blood. These metabolites exhibit the pharmacological effects more strongly than hydrophilic parental constituents. To enforce these metabolites, fermented WG and RG are developed. Moreover, natural products including ginseng are frequently used for the treatment of allergic disorders. Therefore, this review introduces the current knowledge related to the effectiveness of ginseng on allergic disorders including asthma, allergic rhinitis, atopic dermatitis, and pruritus. We discuss how ginseng, its constituents, and its metabolites regulate allergy-related immune responses. We also describe how ginseng controls allergic disorders.


greenmedinfo--2020-04-28--Biofilm inhibiting activity of betacyanins from red pitahaya.

AIMS : To investigate the biofilm inhibitory activity of betacyanins from red pitahaya ( Hylocereus polyrhizus ) and red spinach ( Amaranthus dubius ) against Staphylococcus aureus and Pseudomonas aeruginosa biofilms .
METHODS AND RESULTS : The pulp of red pitahaya and the leaves of red spinach were extracted using methanol followed by subfractionation to obtain betacyanin fraction .
The anti-biofilm activity was examined using broth microdilution assay on polystyrene surfaces and expressed as minimum biofilm inhibitory concentration ( MBIC ) .
The betacyanin fraction from red spinach showed better anti-biofilm activity ( MBIC : 0·313-1·25 mg ml ) against @ @ @ @ @ @ @ betacyanin fraction from red pitahaya showed better anti-biofilm activity ( MBIC : 0·313-0·625 mg ml ) against four P. aeruginosa strains .
Both betacyanin fraction significantly reduced hydrophobicity of Staph .
aureus and P. aeruginosa strains .
Numbers of Staph .
aureus and P. aeruginosa attached to polystyrene were also reduced without affecting their cell viability .
CONCLUSION : Betacyanins can act as anti-biofilm agents against the initial step of biofilm formation , particularly on a hydrophobic surface like polystyrene .
SIGNIFICANCE AND IMPACT OF THE STUDY : This study is the first @ @ @ @ @ @ @ a biofilm inhibitory agent .
Betacyanin could potentially be used to reduce the risk of biofilm-associated infections .

AIMS: To investigate the biofilm inhibitory activity of betacyanins from red pitahaya (Hylocereus polyrhizus) and red spinach (Amaranthus dubius) against Staphylococcus aureus and Pseudomonas aeruginosa biofilms.
METHODS AND RESULTS: The pulp of red pitahaya and the leaves of red spinach were extracted using methanol followed by subfractionation to obtain betacyanin fraction. The anti-biofilm activity was examined using broth microdilution assay on polystyrene surfaces and expressed as minimum biofilm inhibitory concentration (MBIC). The betacyanin fraction from red spinach showed better anti-biofilm activity (MBIC: 0·313-1·25 mg ml) against five Staph. aureus strains while the betacyanin fraction from red pitahaya showed better anti-biofilm activity (MBIC: 0·313-0·625 mg ml) against four P. aeruginosa strains. Both betacyanin fraction significantly reduced hydrophobicity of Staph. aureus and P. aeruginosa strains. Numbers of Staph. aureus and P. aeruginosa attached to polystyrene were also reduced without affecting their cell viability.
CONCLUSION: Betacyanins can act as anti-biofilm agents against the initial step of biofilm formation, particularly on a hydrophobic surface like polystyrene.
SIGNIFICANCE AND IMPACT OF THE STUDY: This study is the first to investigate the use of betacyanin as a biofilm inhibitory agent. Betacyanin could potentially be used to reduce the risk of biofilm-associated infections.


greenmedinfo--2020-04-28--Red dragon fruit extract has potential in lowering lactic acid level and CK activity in male rats re

BACKGROUND : Heavy physical exercise causes relative hypoxia .
In hypoxic condition , the cell 's energy comes from anaerobic metabolism that produces lactic acid .
An increment of oxygen need leads to ischemia-reperfusion , triggers free radical formation and damages muscles .
Creatine kinase ( CK ) is a marker of muscle tissue damage .
Red dragon fruit ( RDF ) has potential as antioxidant to reduce free radical formation .
AIM : This study aims to determine RDF extract potential to reduce the lactic acid level and CK activity after heavy physical exercise .
METHODS : A total @ @ @ @ @ @ @ ) were randomly divided into 4 groups : group NORDF , treated heavy physical exercise and distilled water ; group RDF100 , treated heavy physical exercise and at 100 mg/kg BW RDF extract ; group RDF200 , treated heavy physical exercise and at 200 mg/kg BW RDF extract and group RDF300 , treated heavy physical exercise and at 300 mg/kg BW RDF extract .
The rats swam for 20 minutes , 3 times a week for 3 weeks .
RESULTS : RDF300 group showed lower lactic acid level and CK activity as compared @ @ @ @ @ @ @ 0.00 ) and RDF100 ( p = 0.00 ) groups , but RDF300 are not significantly different for lactic acid ( p = 0.45 ) and for CK ( p = 0.68 ) .
CONCLUSION : Red dragon fruit extract has potential in lowering lactic acid level and CK activity in male rats receiving heavy physical exercise .

BACKGROUND: Heavy physical exercise causes relative hypoxia. In hypoxic condition, the cell's energy comes from anaerobic metabolism that produces lactic acid. An increment of oxygen need leads to ischemia-reperfusion, triggers free radical formation and damages muscles. Creatine kinase (CK) is a marker of muscle tissue damage. Red dragon fruit (RDF) has potential as antioxidant to reduce free radical formation.
AIM: This study aims to determine RDF extract potential to reduce the lactic acid level and CK activity after heavy physical exercise.
METHODS: A total of 32 male rats (Rattus Norvegicus) were randomly divided into 4 groups: group NORDF, treated heavy physical exercise and distilled water; group RDF100, treated heavy physical exercise and at 100 mg/kg BW RDF extract; group RDF200, treated heavy physical exercise and at 200 mg/kg BW RDF extract and group RDF300, treated heavy physical exercise and at 300 mg/kg BW RDF extract. The rats swam for 20 minutes, 3 times a week for 3 weeks.
RESULTS: RDF300 group showed lower lactic acid level and CK activity as compared to that of NORDF (p = 0.00) and RDF100 (p = 0.00) groups, but RDF300 are not significantly different for lactic acid (p = 0.45) and for CK (p = 0.68).
CONCLUSION: Red dragon fruit extract has potential in lowering lactic acid level and CK activity in male rats receiving heavy physical exercise.


greenmedinfo--2020-04-28--Pitaya peel has the potential as a treatment for anxiety disorders.

Pitaya is a Cactacea with potential for economic exploitation , due to its high commercial value and its functional components - such betalains , oligosaccharides and phenolic compounds .
Although the biological activities of pitaya have been studied using in vivo and in vitro models ( anti-inflammatory and antiproliferative activities , as example ) , its anxiolytic-like effect is still unexplored .
Therefore , the aim of this work was to perform a characterization of pulp and peel of pitaya ( Hylocereus polyrhizus ( F.A.C .
Weber ) Britton & Rose ) using UPLC-QTOF-MS , and to assess its toxicity @ @ @ @ @ @ @ Danio rerio ) .
The results showed 16 and 15 compounds ( in pulp and peel , respectively ) , including maltotriose , quercetin-3-O-hexoside , and betalains , putatively identified by UPLC-QTOF-MS .
Thus , pitaya pulp and peel showed no toxicity in both models tested ( Vero cell lines and zebrafish model , LC ˃ 1 mg/mL ) ; and a significant anxiolytic activity , since the treated fish reduced the permanence in the clear zone ( Light & Dark Test ) compared to that in the control , exhibiting anxiolytic-simile effect @ @ @ @ @ @ @ were reduced by pre-treatment with the flumazenil suggesting that the pulp and peel of pitaya are anxiolytics agents mediated via the GABAergic system .
These findings suggested that H. polyrizhus has the potential of developing an alternative plant-derived anxiolytic therapy .
In addition , pitaya peel ( which is a waste in the food industry ) should be regarded as a valuable product , which has the potential as an economic value-added ingredient for anxiety disorders .

Pitaya is a Cactacea with potential for economic exploitation, due to its high commercial value and its functional components - such betalains, oligosaccharides and phenolic compounds. Although the biological activities of pitaya have been studied using in vivo and in vitro models (anti-inflammatory and antiproliferative activities, as example), its anxiolytic-like effect is still unexplored. Therefore, the aim of this work was to perform a characterization of pulp and peel of pitaya (Hylocereus polyrhizus (F.A.C. Weber) Britton&Rose) using UPLC-QTOF-MS, and to assess its toxicity and anxiolytic-like effect in adult zebrafish (Danio rerio). The results showed 16 and 15 compounds (in pulp and peel, respectively), including maltotriose, quercetin-3-O-hexoside, and betalains, putatively identified by UPLC-QTOF-MS. Thus, pitaya pulp and peel showed no toxicity in both models tested (Vero cell lines and zebrafish model, LC ˃ 1 mg/mL); and a significant anxiolytic activity, since the treated fish reduced the permanence in the clear zone (Light&Dark Test) compared to that in the control, exhibiting anxiolytic-simile effect of diazepam. However, these effects were reduced by pre-treatment with the flumazenil suggesting that the pulp and peel of pitaya are anxiolytics agents mediated via the GABAergic system. These findings suggested that H. polyrizhus has the potential of developing an alternative plant-derived anxiolytic therapy. In addition, pitaya peel (which is a waste in the food industry) should be regarded as a valuable product, which has the potential as an economic value-added ingredient for anxiety disorders.


greenmedinfo--2020-04-28--Terpenoid-lupeol of red dragon fruit and its immunomodulatory activity.

Red dragon fruit ( Hylocereus polyrhizus , ( F.A.C .
Weber ) Britton and Rose ) has been reported to have various biological activities such as antimicrobial , anti-hypercholesterolemia , anti-diabetes mellitus , cardiovascular risk reduction , health supplement , and melanoma cell inhibitory .
The red thick peel of this fruit is just practically a waste that is possibly utilized to maintain health , therefore this research aimed to isolate and identify active compounds of H. Polyrhizus peels which can improve the immune system of body .
In order to simplify methanol extract was partition and fractionation .
The @ @ @ @ @ @ @ separated and purified using preparative thin layer chromatography .
The identification of the compounds structure was conducted through spectroscopic techniques , including UV , FT-IR , CNMR and 1HNMR spectroscopy .
The data of spectra revealed that the isolate is lupeol .
The statistical analysis of macrophage activity showed that the isolate with concentrations of 100 , 50 , 25 , 12.5 and 6.25μg/mL could activate the macrophages higher than control negative .
Terpenoid generated from the isolation of Hylocereus polyrhizus was identified as lupeol ( 1-isopropenyl-3a,5a,5b,8,8,11a-hexamethyl-eicosahydrocyclopenya [ α ] chrysen-9ol .
In @ @ @ @ @ @ @ had an immunomodulatory activity by increases macrophage phagocytosis of latex beads .

Red dragon fruit (Hylocereus polyrhizus, (F.A.C. Weber) Britton and Rose) has been reported to have various biological activities such as antimicrobial, anti-hypercholesterolemia, anti-diabetes mellitus, cardiovascular risk reduction, health supplement, and melanoma cell inhibitory. The red thick peel of this fruit is just practically a waste that is possibly utilized to maintain health, therefore this research aimed to isolate and identify active compounds of H. Polyrhizus peels which can improve the immune system of body. In order to simplify methanol extract was partition and fractionation. The active compounds of petroleum ether fraction were separated and purified using preparative thin layer chromatography. The identification of the compounds structure was conducted through spectroscopic techniques, including UV, FT-IR,CNMR and 1HNMR spectroscopy. The data of spectra revealed that the isolate is lupeol. The statistical analysis of macrophage activity showed that the isolate with concentrations of 100, 50, 25, 12.5 and 6.25μg/mL could activate the macrophages higher than control negative. Terpenoid generated from the isolation of Hylocereus polyrhizus was identified as lupeol (1-isopropenyl-3a,5a,5b,8,8,11a-hexamethyl-eicosahydrocyclopenya [α] chrysen-9ol. In vitro test shows that the isolated compound had an immunomodulatory activity by increases macrophage phagocytosis of latex beads.


greenmedinfo--2020-04-28--Autumn royal and egnatia grape extracts differently modulate cell proliferation in human colorectal

Autumn royal and egnatia grape extracts differently modulate cell proliferation in human colorectal cancer cells.

OBJECTIVE : Polyphenols extracted by table grape have been demonstrated to decrease cell proliferation in vitro and to exert anti-atherosclerotic and antithrombotic activities , regulating cell functions .
Grape polyphenolic profile is affected by climate as well as grape cultivar .
This study was aimed to characterize the berry skin polyphenolic composition , antioxidant activity and antiproliferative properties of two black grape cultivars , Autumn Royal and Egnatia .
METHODS : The phenolic composition of grape skin extracts ( GSEs ) was determined by HPLC analyses .
The antioxidant activity was determined using DPPH , ABTS and ORAC tests .
@ @ @ @ @ @ @ cancer cell lines were used to test the effects of GSEs in vitro .
Cell proliferation and cell cycle were assessed with the MTT method and a Muse cell analyzer , respectively .
qPCR and Western Blotting analysis were used to evaluate gene and protein expression , respectively .
RESULTS : The total polyphenolic content and the total antioxidant capacity were significantly higher in Autumn Royal than in Egnatia .
However , table grape Egnatia showed greater ability to affect cell proliferation and apoptosis , as well as to exert a growth arrest @ @ @ @ @ @ @ , particularly in Caco2 cell line .
CONCLUSION : These data suggest that the new grape variety Egnatia is an interesting source of phenolic compounds that could be of interest in the food and pharmaceutical industries .

OBJECTIVE: Polyphenols extracted by table grape have been demonstrated to decrease cell proliferation in vitro and to exert anti-atherosclerotic and antithrombotic activities, regulating cell functions. Grape polyphenolic profile is affected by climate as well as grape cultivar. This study was aimed to characterize the berry skin polyphenolic composition, antioxidant activity and antiproliferative properties of two black grape cultivars, Autumn Royal and Egnatia.
METHODS: The phenolic composition of grape skin extracts (GSEs) was determined by HPLC analyses. The antioxidant activity was determined using DPPH, ABTS and ORAC tests. Caco2, HT29 and SW480 human colon cancer cell lines were used to test the effects of GSEs in vitro. Cell proliferation and cell cycle were assessed with the MTT method and a Muse cell analyzer, respectively. qPCR and Western Blotting analysis were used to evaluate gene and protein expression, respectively.
RESULTS: The total polyphenolic content and the total antioxidant capacity were significantly higher in Autumn Royal than in Egnatia. However, table grape Egnatia showed greater ability to affect cell proliferation and apoptosis, as well as to exert a growth arrest in S phase of the cell cycle, particularly in Caco2 cell line.
CONCLUSION: These data suggest that the new grape variety Egnatia is an interesting source of phenolic compounds that could be of interest in the food and pharmaceutical industries.


greenmedinfo--2020-04-28--Allium hookeri root extract regulates asthmatic changes through immunological modulation of Th1/Th2‑

Allium hookeri root extract regulates asthmatic changes through immunological modulation of Th1/Th2‑related factors in an ovalbumin‑induced asthma.

In 2013 , WHO estimated that approximately 235 million people suffered from asthma worldwide .
Asthma is a hyper responsive disorder , which is related to an imbalance between the T‑helper type 1 and 2 cells ( henceforth , Th1 and Th2 , respectively ) .
Allium hookeri is a plant that is widely used for culinary purposes and also in traditionalAsian medicine .
The present study was conducted to elucidate the anti‑asthmatic effects and mechanism of action of A. hookeri root extracts ( AHRE ) in an ovalbumin ( OVA ) ‑induced asthma mouse model .
The mice were @ @ @ @ @ @ @ the control , the OVA‑treated group , the dexamethasone‑treated group , the 30 mg/kg AHRE‑treated group , and the 300 mg/kg AHRE‑treated group .
The total WBC count and the differential cell count in the bronchoalveolar fluid , the level of serum IgE , the histopathological changes in the lung , and changes in the cell surface molecules , the asthma‑related cytokine levels , and Th cell transcription factors were evaluated .
AHRE significantly ameliorated asthmatic changes , such as the total WBC count , eosinophil count , and the level of IgE @ @ @ @ @ @ @ hypersecretion , epithelial hyperplasia , and eosinophil infiltration inthe lungs .
AHRE significantly inhibited the expression of CD68+ cells and MHC class II+ molecules , Th1 cell transcription factor ( T‑bet ) activation , Th2 cell transcription factor ( GATA‑3 ) activation , and TNF‑α in the lung tissue .
Furthermore , it suppressed cell surface molecules , such as CD4+and CD8+ ; Th1‑related cytokines , such as IFN‑γ and IL‑12p40 ; Th2‑related cytokines , such as IL‑4 and IL‑5 ; and Th17‑related cytokines , such as IL‑6 and TNF‑α , in a @ @ @ @ @ @ @ be considered a promising anti‑asthmatic drug .

In 2013, WHO estimated that approximately 235 million people suffered from asthma worldwide. Asthma is a hyper responsive disorder, which is related to an imbalance between the T‑helper type 1 and 2 cells (henceforth, Th1 and Th2, respectively). Allium hookeri is a plant that is widely used for culinary purposes and also in traditionalAsian medicine. The present study was conducted to elucidate the anti‑asthmatic effects and mechanism of action of A. hookeri root extracts (AHRE) in an ovalbumin (OVA)‑induced asthma mouse model. The mice were divided into five groups, namely, the control, the OVA‑treated group, the dexamethasone‑treated group, the 30 mg/kg AHRE‑treated group, and the 300 mg/kg AHRE‑treated group. The total WBC count and the differential cell count in the bronchoalveolar fluid, the level of serum IgE, the histopathological changes in the lung, and changes in the cell surface molecules, the asthma‑related cytokine levels, and Th cell transcription factors were evaluated. AHRE significantly ameliorated asthmatic changes, such as the total WBC count, eosinophil count, and the level of IgE; in addition, it reduced mucus hypersecretion, epithelial hyperplasia, and eosinophil infiltration inthe lungs. AHRE significantly inhibited the expression of CD68+ cells and MHC class II+ molecules, Th1 cell transcription factor (T‑bet) activation, Th2 cell transcription factor (GATA‑3) activation, and TNF‑α in the lung tissue. Furthermore, it suppressed cell surface molecules, such as CD4+and CD8+; Th1‑related cytokines, such as IFN‑γ and IL‑12p40; Th2‑related cytokines, such as IL‑4 and IL‑5; and Th17‑related cytokines, such as IL‑6 and TNF‑α, in a dose‑dependent manner. Thus, AHRE may be considered a promising anti‑asthmatic drug.


greenmedinfo--2020-04-28--Allium hookeri root extract inhibits adipogenesis by promoting lipolysis in high fat diet-induced ob

Allium hookeri root extract inhibits adipogenesis by promoting lipolysis in high fat diet-induced obese mice.

( AH ) is widely consumed as a herbal medicine .
It possesses biological activity against metabolic diseases .
The objective of this study was to investigate effects of AH root water extract ( AHR ) on adipogenesis in 3T3-L1 cells and in high-fat diet ( HFD ) -induced obese mice .
AHR inhibited lipid accumulation during adipocyte differentiation by downregulation of gene expression , such as hormone sensitive lipase ( HSL ) , lipoprotein lipase ( LPL ) and an adipogenic gene , CCAAT/enhancer binding protein-α in 3T3-L1 preadipocytes .
Oral administration of AHR significantly suppressed body weight gain @ @ @ @ @ @ @ levels , and adipocyte cell size in HFD-induced obese mice .
Moreover , AHR significantly decreased hepatic mRNA expression levels of cholesterol synthesis genes , such as 3-hydroxy-3-methylglutaryl CoA reductase , sterol regulatory element-binding transcription factor ( SREBP ) -2 , and low-density lipoprotein receptor , as well as fatty acid synthesis genes , such as SREBP-1c and fatty acid synthase .
Serum triglyceride levels were also lowered by AHR , likely as a resultof the upregulating gene involved in fatty acid β-oxidation , carnitine palmitoyltransferase 1a , in the liver .
AHR @ @ @ @ @ @ @ receptor-γ , which might have promoted HSL and LPL-medicated lipolysis , thereby reducing white adipose tissue weight .
In conclusion , AHR treatment can improve metabolic alterations induced by HFD in mice by modifying expression levels of genes involved in adipogenesis , lipogenesis , and lipolysis in the white adipose tissue and liver .

(AH) is widely consumed as a herbal medicine. It possesses biological activity against metabolic diseases. The objective of this study was to investigate effects of AH root water extract (AHR) on adipogenesis in 3T3-L1 cells and in high-fat diet (HFD)-induced obese mice. AHR inhibited lipid accumulation during adipocyte differentiation by downregulation of gene expression, such as hormone sensitive lipase (HSL), lipoprotein lipase (LPL) and an adipogenic gene, CCAAT/enhancer binding protein-α in 3T3-L1 preadipocytes. Oral administration of AHR significantly suppressed body weight gain, adipose tissue weight, serum leptin levels, and adipocyte cell size in HFD-induced obese mice. Moreover, AHR significantly decreased hepatic mRNA expression levels of cholesterol synthesis genes, such as 3-hydroxy-3-methylglutaryl CoA reductase, sterol regulatory element-binding transcription factor (SREBP)-2, and low-density lipoprotein receptor, as well as fatty acid synthesis genes, such as SREBP-1c and fatty acid synthase. Serum triglyceride levels were also lowered by AHR, likely as a resultof the upregulating gene involved in fatty acid β-oxidation, carnitine palmitoyltransferase 1a, in the liver. AHR treatment activated gene expression of peroxisome proliferator-activated receptor-γ, which might have promoted HSL and LPL-medicated lipolysis, thereby reducing white adipose tissue weight. In conclusion, AHR treatment can improve metabolic alterations induced by HFD in mice by modifying expression levels of genes involved in adipogenesis, lipogenesis, and lipolysis in the white adipose tissue and liver.


greenmedinfo--2020-04-29--These findings indicate that combination therapy of ω-3 fatty acids and nano-curcumin can be conside

These findings indicate that combination therapy of ω-3 fatty acids and nano-curcumin can be considered as a promising new approach in migraine prevention.

BACKGROUND : Migraine is a common neuroinflammatory disorder characterized by recurrent attacks of pain .
Human and experimental models of migraine studies have demonstrated the role played by COX-2/ iNOS in migraine 's neuroinflammatory pathogenesis .
COX-2 and iNOS are closely linked and both contribute to inflammation and neurogenic pain in the central nervous system .
Omega- 3 fatty acids and curcumin , an active polyphenol of turmeric , have anti-inflammatory and neuroprotective effects through several mechanisms , including the suppression of COX-2 and iNOS gene expression , as well as their serum levels .
The aim of the present @ @ @ @ @ @ @ ofω-3 fatty acids , nano-curcumin , and a combination of the two , on neuroinflammation and clinical symptoms in migraine patients .
METHODS : This study reports the results of a clinical trial over a 2-month period , involving 74 episodic migraine patients who receivedω-3 fatty acids , nano-curcumin , a combination of them , or a placebo .
At the start and end of the study , the expression of COX-2/iNOS ( in peripheral mononuclear blood cells isolated from patients ) and COX-2/iNOS serum levels were measured , using real-time PCR and @ @ @ @ @ @ @ and duration of pain attacks were also recorded .
RESULTS : The results of the present trial showed thatω-3 fatty acids and nano-curcumin can reinforce each other 's effects in the downregulation of COX-2/iNOS mRNA , as well as reduce their serum levels .
In addition , the combination of ω-3 and nano-curcumin significantly reduced the frequency , severity and duration of headaches ( P < 0.05 ) .
CONCLUSION : These findings indicate that combination therapy ofω-3 fatty acids and nano-curcumin can be considered as a promising new approach in migraine prevention @

BACKGROUND: Migraine is a common neuroinflammatory disorder characterized by recurrent attacks of pain. Human and experimental models of migraine studies have demonstrated the role played by COX-2/ iNOS in migraine's neuroinflammatory pathogenesis. COX-2 and iNOS are closely linked and both contribute to inflammation and neurogenic pain in the central nervous system. Omega- 3 fatty acids and curcumin, an active polyphenol of turmeric, have anti-inflammatory and neuroprotective effects through several mechanisms, including the suppression of COX-2 and iNOS gene expression, as well as their serum levels. The aim of the present study is to evaluate the nutrigenomic effects ofω-3 fatty acids, nano-curcumin, and a combination of the two, on neuroinflammation and clinical symptoms in migraine patients.
METHODS: This study reports the results of a clinical trial over a 2-month period, involving 74 episodic migraine patients who receivedω-3 fatty acids, nano-curcumin, a combination of them, or a placebo. At the start and end of the study, the expression of COX-2/iNOS (in peripheral mononuclear blood cells isolated from patients) and COX-2/iNOS serum levels were measured, using real-time PCR and ELISA respectively. The frequency, severity and duration of pain attacks were also recorded.
RESULTS: The results of the present trial showed thatω-3 fatty acids and nano-curcumin can reinforce each other's effects in the downregulation of COX-2/iNOS mRNA, as well as reduce their serum levels. In addition, the combination of ω-3 and nano-curcumin significantly reduced the frequency, severity and duration of headaches (P<0.05).
CONCLUSION: These findings indicate that combination therapy ofω-3 fatty acids and nano-curcumin can be considered as a promising new approach in migraine prevention.


greenmedinfo--2020-04-29--Effects of curcumin on microglial cells.

Microglia are innate immune system cells which reside in the central nervous system ( CNS ) .
Resting microglia regulate the homeostasis of the CNS via phagocytic activity to clear pathogens and cell debris .
Sometimes , however , to protect neurons and fight invading pathogens , resting microglia transform to an activated-form , producing inflammatory mediators , such as cytokines , chemokines , iNOS/NO and cyclooxygenase-2 ( COX-2 ) .
Excessive inflammation , however , leads to damaged neurons and neurodegenerative diseases ( NDs ) , such as Parkinson 's disease ( PD ) , Alzheimer 's disease ( @ @ @ @ @ @ @ HD ) , multiple sclerosis ( MS ) and amyotrophic lateral sclerosis ( ALS ) .
Curcumin is a phytochemical isolated from Curcuma longa .
It is widely used in Asia and has many therapeutic properties , including antioxidant , anti-viral , anti-bacterial , anti-mutagenic , anti-amyloidogenic and anti-inflammatory , especially with respect to neuroinflammation and neurological disorders ( NDs ) .
Curcumin is a pleiotropic molecule that inhibits microglia transformation , inflammatory mediators and subsequent NDs .
In this mini-review , we discuss the effects of curcumin on microglia and explore the @ @ @

Microglia are innate immune system cells which reside in the central nervous system (CNS). Resting microglia regulate the homeostasis of the CNS via phagocytic activity to clear pathogens and cell debris. Sometimes, however, to protect neurons and fight invading pathogens, resting microglia transform to an activated-form, producing inflammatory mediators, such as cytokines, chemokines, iNOS/NO and cyclooxygenase-2 (COX-2). Excessive inflammation, however, leads to damaged neurons and neurodegenerative diseases (NDs), such as Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's disease (HD), multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). Curcumin is a phytochemical isolated from Curcuma longa. It is widely used in Asia and has many therapeutic properties, including antioxidant, anti-viral, anti-bacterial, anti-mutagenic, anti-amyloidogenic and anti-inflammatory, especially with respect to neuroinflammation and neurological disorders (NDs). Curcumin is a pleiotropic molecule that inhibits microglia transformation, inflammatory mediators and subsequent NDs. In this mini-review, we discuss the effects of curcumin on microglia and explore the underlying mechanisms.


greenmedinfo--2020-04-29--Curcumin attenuates oxidative stress in RAW264.7 cells by increasing the activity of antioxidant enz

Curcumin attenuates oxidative stress in RAW264.7 cells by increasing the activity of antioxidant enzymes and activating the Nrf2-Keap1 pathway.

Large-scale breeding environments often lead to oxidative stress .
Macrophages play an important role in the immune system and are vulnerable to reactive oxygen species ( ROS ) , which result in macrophage death .
Curcumin is the main active component of turmeric and exerts antioxidant effects .
Here , we measured the activity of some antioxidant enzymes and chose the Nrf2-Keap1 signaling pathway to study the protective effects of curcumin on macrophages under oxidative stress in vitro .
We used RAW264.7 cells as a research model , and oxidative damage was induced by hydrogen peroxide ( H2O2 ) .
@ @ @ @ @ @ @ assay .
Flow cytometry was used to measure cellular ROS and apoptosis .
The effect of curcumin on Nrf2-Keap1 signaling pathway-related genes was analyzed by qRT-PCR .
Furthermore , the translocation of Nrf2 protein was also investigated by Western blot analysis of total and nuclear proteins .
All curcumin-treated groups exhibited increased activity of catalase ( CAT ) , superoxide dismutase ( SOD ) and glutathione peroxidase ( GSH-PX ) .
Low- and middle-dose curcumin decreased malondialdehyde ( MDA ) and ROS levels , but high-dose curcumin increased MDA and ROS production .
@ @ @ @ @ @ @ from apoptosis , while apoptosis in the middle- and high-dose curcumin-treated groups were stagnant in the early stage .
Furthermore , middle-dose curcumin upregulated Nrf2 expression after H2O2 treatment for 4 h. Low- and middle-dose curcumin could activate Nrf2 and promote it to migrate into nuclei .
The translocation of Nrf2 to the nucleus to upregulate the expression of haemoxygenase-1 ( HO-1 ) was promoted in the low- and middle-dose curcumin-treated groups .
The middle-dose curcumin-treated group also exhibited enhanced expression of glutamate-cysteine ligase , a modifier subunit ( GLCM ) , but @ @ @ @ @ @ @ catalytic subunit ( GCLC ) .
Curcumin resisted oxidants by increasing the activity of antioxidant enzymes and activating the Nrf2-Keap1 pathway , which could potentially promote cell survival .

Large-scale breeding environments often lead to oxidative stress. Macrophages play an important role in the immune system and are vulnerable to reactive oxygen species (ROS), which result in macrophage death. Curcumin is the main active component of turmeric and exerts antioxidant effects. Here, we measured the activity of some antioxidant enzymes and chose the Nrf2-Keap1 signaling pathway to study the protective effects of curcumin on macrophages under oxidative stress in vitro. We used RAW264.7 cells as a research model, and oxidative damage was induced by hydrogen peroxide (H2O2). Cell viability was measured by an MTT assay. Flow cytometry was used to measure cellular ROS and apoptosis. The effect of curcumin on Nrf2-Keap1 signaling pathway-related genes was analyzed by qRT-PCR. Furthermore, the translocation of Nrf2 protein was also investigated by Western blot analysis of total and nuclear proteins. All curcumin-treated groups exhibited increased activity of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX). Low- and middle-dose curcumin decreased malondialdehyde (MDA) and ROS levels, but high-dose curcumin increased MDA and ROS production. We found that low-dose curcumin protected cells from apoptosis, while apoptosis in the middle- and high-dose curcumin-treated groups were stagnant in the early stage. Furthermore, middle-dose curcumin upregulated Nrf2 expression after H2O2 treatment for 4 h. Low- and middle-dose curcumin could activate Nrf2 and promote it to migrate into nuclei. The translocation of Nrf2 to the nucleus to upregulate the expression of haemoxygenase-1 (HO-1) was promoted in the low- and middle-dose curcumin-treated groups. The middle-dose curcumin-treated group also exhibited enhanced expression of glutamate-cysteine ligase, a modifier subunit (GLCM), but inhibited transcription of glutamate-cysteine ligase, a catalytic subunit (GCLC). Curcumin resisted oxidants by increasing the activity of antioxidant enzymes and activating the Nrf2-Keap1 pathway, which could potentially promote cell survival.


greenmedinfo--2020-04-29--Targeting regulatory T cells by curcumin: A potential for cancer immunotherapy.

Immune system has critical roles in fighting against several diseases like cancer .
Cancer cells evolve several ways to escape from the immune system to remain alive and trigger new phases of cancer progression .
Regulatory T cells are one of the key components in tumor immune tolerance and contribute to the evasion of cancer cells from the immune system .
Targeting regulatory T cells could provide new horizons in designing and development of effective therapeutic platforms for the treatment of various malignancies .
Curcumin is the bioactive pigment of turmeric and a well-known phytochemical with a wide range of @ @ @ @ @ @ @ evidence has demonstrated that curcumin affects manifold molecular pathways that are implicated in tumorigenesis and cancer metastasis .
In this regard , some studies have indicated that this phytochemical could target regulatory T cells and convert them into T helper 1 cells , which possess anti-tumor effects .
On the contrary , curcumin is able to increase the number of regulatory T cells in other conditions such as inflammatory bowel disease .
Herein , we describe the anti-cancer roles of curcumin via targeting regulatory T cells .
Moreover , we summarize the effects @ @ @ @ @ @ @ in other diseases .

Immune system has critical roles in fighting against several diseases like cancer. Cancer cells evolve several ways to escape from the immune system to remain alive and trigger new phases of cancer progression. Regulatory T cells are one of the key components in tumor immune tolerance and contribute to the evasion of cancer cells from the immune system. Targeting regulatory T cells could provide new horizons in designing and development of effective therapeutic platforms for the treatment of various malignancies. Curcumin is the bioactive pigment of turmeric and a well-known phytochemical with a wide range of pharmacological activities. A growing body of evidence has demonstrated that curcumin affects manifold molecular pathways that are implicated in tumorigenesis and cancer metastasis. In this regard, some studies have indicated that this phytochemical could target regulatory T cells and convert them into T helper 1 cells, which possess anti-tumor effects. On the contrary, curcumin is able to increase the number of regulatory T cells in other conditions such as inflammatory bowel disease. Herein, we describe the anti-cancer roles of curcumin via targeting regulatory T cells. Moreover, we summarize the effects of curcumin on regulatory T cell population in other diseases.


greenmedinfo--2020-04-29--The effect of oral consumption of propolis alone and in combination with silver nanoparticles on wou

The effect of oral consumption of propolis alone and in combination with silver nanoparticles on wound healing.

: Research to identify and develop compounds that facilitate wound healing is important , especially for hard-to-heal chronic wounds .
PURPOSE : This study was conducted to investigate the effects of orally administered propolis ( a resinous substance found in beehives ) , alone and in combination with silver nanoparticles ( SNPs ) , on the wound healing process in male rats .
METHODS : Forty ( 40 ) male Wistar rats were randomly divided into 4 groups of 10 each : 1 control group received no treatment , and 3 study groups received a daily dose of 1 ) @ @ @ @ @ @ @ ) propolis + 30 ppm SNPs , or 3 ) propolis + 60 ppm SNPs .
Healing rate was determined by wound surface area reduction on days 4 , 6 , 8 , and 10 post-surgery .
On day 12 after wound creation , histological changes of wound healing , including number of new vessels , inflammatory cells ( neutrophils , eosinophils , and mast cells ) and fibroblasts were counted based on morphology using a 400x objective lens , and collagen deposition density was determined using hematoxylin and eosin and trichrome staining @ @ @ @ @ @ @ based on a 0 to 4 scale from lowest to highest amount of improving tissue status and were analyzed using one-way analysis of variance , Tukey test , Kruskal-Wallis test , t test , and Mann-Whitney U test to examine differences among the groups .
Significance was set at P RESULTS : The rate of wound healing was significantly different between the control and the treated groups on days 4 , 6 , 8 , and 10 ( percent change was not assessed on day 12 ) post-surgery , especially in the propolis @ @ @ @ @ @ @ the control group .
This difference was more significant on days 6 ( wound healing percentage [ WHP ] : 75 % and 45 % ) and 8 ( WHP : 88 % and 65 % ) post-surgery ( P CONCLUSION : Oral propolis alone and in combination with 30 ppm SNPs appears to provide anti-inflammatory effects and increase fibroblast proliferation and collagen deposition in experimental wounds , which may explain the observed differences in healing .
Propolis + 60 ppm SNPs appears to have a cytotoxic effect .
Research confirming these results @ @ @ @ @ @ @ and humans is needed .

: Research to identify and develop compounds that facilitate wound healing is important, especially for hard-to-heal chronic wounds.
PURPOSE: This study was conducted to investigate the effects of orally administered propolis (a resinous substance found in beehives), alone and in combination with silver nanoparticles (SNPs), on the wound healing process in male rats.
METHODS: Forty (40) male Wistar rats were randomly divided into 4 groups of 10 each: 1 control group received no treatment, and 3 study groups received a daily dose of 1) propolis (100 mg/kg), 2) propolis + 30 ppm SNPs, or 3) propolis + 60 ppm SNPs. Healing rate was determined by wound surface area reduction on days 4, 6, 8, and 10 post-surgery. On day 12 after wound creation, histological changes of wound healing, including number of new vessels, inflammatory cells (neutrophils, eosinophils, and mast cells) and fibroblasts were counted based on morphology using a 400x objective lens, and collagen deposition density was determined using hematoxylin and eosin and trichrome staining, respectively. The histological scores were based on a 0 to 4 scale from lowest to highest amount of improving tissue status and were analyzed using one-way analysis of variance, Tukey test, Kruskal-Wallis test, t test, and Mann-Whitney U test to examine differences among the groups. Significance was set at P<.05.
RESULTS: The rate of wound healing was significantly different between the control and the treated groups on days 4, 6, 8, and 10 (percent change was not assessed on day 12) post-surgery, especially in the propolis + 30 ppm SNPs group compared to the control group. This difference was more significant on days 6 (wound healing percentage [WHP]: 75% and 45%) and 8 (WHP: 88% and 65% ) post-surgery (P<.001). Mean neutrophil count on day 12 was highest in the control (34.8± 2.97) and lowest in the propolis + 30 ppm SNPs group (16.55 ± 2.12). The number of eosinophils on day 12 was considerably higher in the control group (1.05 ± 4) compared to those in the propolis group (3 ± 0.70), propolis + 30 ppm SNPs group (60/0 ± 1/1), and propolis + 60 ppm SNPs group (0.5± 0.52) (P<.001). Mean propolis + 30 ppm SNPs scores for epithelialization and granulation tissue formation were 3 and 4, respectively; in the propolis + 60 ppm SNPs, scores were 2 and 3, respectively; in the propolis alone group scores were 2 and 3, respectively (statistical significance not computed for semiquantitative values). The highest fibroblast count was in the propolis + 30 ppm SNPs group (114.44± 3.90) compared to control group (73.2 ± 2.8); P<.001). The difference in collagen fiber density scores was also significant: 1.2± 0.42 in the control and 3.66 ± 0.50 in the propolis + 30 ppm SNPs group; (P<.001). The mean of collagen fiber density in the propolis + 60 ppm SNPs group was 2.63± 0.51.
CONCLUSION: Oral propolis alone and in combination with 30 ppm SNPs appears to provide anti-inflammatory effects and increase fibroblast proliferation and collagen deposition in experimental wounds, which may explain the observed differences in healing. Propolis + 60 ppm SNPs appears to have a cytotoxic effect. Research confirming these results and that examines toxicity levels in animals and humans is needed.


greenmedinfo--2020-04-29--Biogenic silver nanoparticles: in vitro and in vivo antitumor activity in bladder cancer.

ladder cancer is the fifth most common disease in the United States , and the treatment and alternatives for patients have not changed in the last decades .
Silver nanoparticles ( AgNP ) have been used in the treatment of various cancer , mainly because of the antineoplastic activity ; however , their use and the molecular mechanisms towards bladder cancer still unexplored .
Therefore , this work aims to evaluate in vitro and in vivo the antitumoral mechanisms of biogenic silver nanoparticles synthesized from Fusarium sp .
First , AgNP showed cytotoxicity in a dose- and time-response relationship , @ @ @ @ @ @ @ cell death via apoptosis , also inhibiting cell migration and proliferation .
Next , it was evaluated the antitumoral activity of AgNP against non-muscle invasive bladder cancer ( NMIBC ) .
Bladder cancer was chemically induced with N-methyl-N-nitrosourea ( MNU ) on C57BL/6Junib female mice and treated by intravesical route with AgNP concentrations of 0.5 , 0.2 , and 0.05 mg/mL .
Finally , treatment with AgNP ( 0.05 mg/mL ) led to 57.13 % of tumor regression , with 14.28 % of the animals showing normal urothelium and 42.85 % showing flat @ @ @ @ @ @ @ lesion .
Overall , these findings demonstrated that AgNP might be a cost-effective alternative and promising candidate for the treatment of bladder cancer .

ladder cancer is the fifth most common disease in the United States, and the treatment and alternatives for patients have not changed in the last decades. Silver nanoparticles (AgNP) have been used in the treatment of various cancer, mainly because of the antineoplastic activity; however, their use and the molecular mechanisms towards bladder cancer still unexplored. Therefore, this work aims to evaluate in vitro and in vivo the antitumoral mechanisms of biogenic silver nanoparticles synthesized from Fusarium sp. First, AgNP showed cytotoxicity in a dose- and time-response relationship, and detailed analysis demonstrated the induction of cell death via apoptosis, also inhibiting cell migration and proliferation. Next, it was evaluated the antitumoral activity of AgNP against non-muscle invasive bladder cancer (NMIBC). Bladder cancer was chemically induced with N-methyl-N-nitrosourea (MNU) on C57BL/6Junib female mice and treated by intravesical route with AgNP concentrations of 0.5, 0.2, and 0.05 mg/mL. Finally, treatment with AgNP (0.05 mg/mL) led to 57.13% of tumor regression, with 14.28% of the animals showing normal urothelium and 42.85% showing flat hyperplasia, considered to be a benign lesion. Overall, these findings demonstrated that AgNP might be a cost-effective alternative and promising candidate for the treatment of bladder cancer.


greenmedinfo--2020-04-29--The review concludes the results of recent studies on Ashwagandha suggesting its extensive potential

The review concludes the results of recent studies on Ashwagandha suggesting its extensive potential as neuroprotective in various brain disorders.

ETHNOPHARMACOLOGICAL RELEVANCE : Withania somnifera ( Family : Solanaceae ) , commonly known as Ashwagandha or Indian ginseng is distributed widely in India , Nepal , China and Yemen .
The roots of plant consist of active phytoconstituents mainly withanolides , alkaloids and sitoindosides and are conventionally used for the treatment of multiple brain disorders .
AIM OF THE REVIEW : This review aims to critically assess and summarize the current state and implication of Ashwagandha in brain disorders .
We have mainly focussed on the reported neuroactive phytoconstituents , available marketed products , pharmacological studies , mechanism of action @ @ @ @ @ @ @ effects of Ashwagandha in brain disorders .
MATERIALS AND METHODS : All the information and data was collected on Ashwagandha using keywords '' Ashwagandha '' along with '' Phytoconstituents '' , '' Ayurvedic , Unani and Homeopathy marketed formulation '' , '' Brain disorders '' , '' Mechanism '' and '' Patents '' .
Following sources were searched for data collection : electronic scientific databases such as Science Direct , Google Scholar , Elsevier , PubMed , Wiley On-line Library , Taylor and Francis , Springer ; books such as AYUSH Pharmacopoeia ; @ @ @ @ @ @ @ Identified neuroprotective phytoconstituents of Ashwagandha are sitoindosides VII-X , withaferin A , withanosides IV , withanols , withanolide A , withanolide B , anaferine , beta-sitosterol , withanolide D with key pharmacological effects in brain disorders mainly anxiety , Alzheimer 's , Parkinson 's , Schizophrenia , Huntington 's disease , dyslexia , depression , autism , addiction , amyotrophic lateral sclerosis , attention deficit hyperactivity disorder and bipolar disorders .
The literature survey does not highlight any toxic effects of Ashwagandha .
Further , multiple available marketed products and patents recognized its @ @ @ @ @ @ @ however , very few data is available on mechanistic pathway and clinical studies of Ashwagandha for various brain disorders is scarce and not promising .
CONCLUSION : The review concludes the results of recent studies on Ashwagandha suggesting its extensive potential as neuroprotective in various brain disorders as supported by preclinical studies , clinical trials and published patents .
However vague understanding of the mechanistic pathways involved in imparting the neuroprotective effect of Ashwagandha warrants further study to promote it as a promising drug candidate .

ETHNOPHARMACOLOGICAL RELEVANCE: Withania somnifera (Family: Solanaceae), commonly known as Ashwagandha or Indian ginseng is distributed widely in India, Nepal, China and Yemen. The roots of plant consist of active phytoconstituents mainly withanolides, alkaloids and sitoindosides and are conventionally used for the treatment of multiple brain disorders.
AIM OF THE REVIEW: This review aims to critically assess and summarize the current state and implication of Ashwagandha in brain disorders. We have mainly focussed on the reported neuroactive phytoconstituents, available marketed products, pharmacological studies, mechanism of action and recent patents published related to neuroprotective effects of Ashwagandha in brain disorders.
MATERIALS AND METHODS: All the information and data was collected on Ashwagandha using keywords"Ashwagandha"along with"Phytoconstituents","Ayurvedic, Unani and Homeopathy marketed formulation","Brain disorders","Mechanism"and"Patents". Following sources were searched for data collection: electronic scientific databases such as Science Direct, Google Scholar, Elsevier, PubMed, Wiley On-line Library, Taylor and Francis, Springer; books such as AYUSH Pharmacopoeia; authentic textbooks and formularies.
RESULTS: Identified neuroprotective phytoconstituents of Ashwagandha are sitoindosides VII-X, withaferin A, withanosides IV, withanols, withanolide A, withanolide B, anaferine, beta-sitosterol, withanolide D with key pharmacological effects in brain disorders mainly anxiety, Alzheimer's, Parkinson's, Schizophrenia, Huntington's disease, dyslexia, depression, autism, addiction, amyotrophic lateral sclerosis, attention deficit hyperactivity disorder and bipolar disorders. The literature survey does not highlight any toxic effects of Ashwagandha. Further, multiple available marketed products and patents recognized its beneficial role in various brain disorders; however, very few data is available on mechanistic pathway and clinical studies of Ashwagandha for various brain disorders is scarce and not promising.
CONCLUSION: The review concludes the results of recent studies on Ashwagandha suggesting its extensive potential as neuroprotective in various brain disorders as supported by preclinical studies, clinical trials and published patents. However vague understanding of the mechanistic pathways involved in imparting the neuroprotective effect of Ashwagandha warrants further study to promote it as a promising drug candidate.


greenmedinfo--2020-04-29--The β-sitosterol-mediated cardioprotective effects may involve the modulation of PPARγ/NF-κB signall

The β-sitosterol-mediated cardioprotective effects may involve the modulation of PPARγ/NF-κB signalling during myocardial I/R injury.

Myocardial ischemia/reperfusion ( I/R ) injury is a clinically severe complication , which can cause high rates of disability and mortality particularly in patients with myocardial infarction , yet the molecular mechanisms underlying this process remain unclear .
This study aimed to explore the protective effects of-sitosterol against myocardial I/R injury and to elucidate the underlying molecular mechanisms .
Our results showed that hypoxia/reoxygenation ( H/R ) treatment suppressed cell viability , induced cell apoptosis and reactive oxygen species production , increased caspase-3 and -9 activities , upregulated caspase-3 and -9 protein expressions , downregulated the Bcl-2 protein expression , @ @ @ @ @ @ @ attenuated H/R-induced cardiomyocyte injury .
Moreover , -sitosterol treatment counteracted the inhibitory effects of H/R treatment on the peroxisome proliferator-activated receptor gamma ( PPARγ ) expression and enhanced effects of H/R treatment on the NF-κB expression in cardiomyocytes .
Furthermore , inhibition of PPARγ impaired the protective actions of-sitosterol against H/R-induced cardiomyocyte injury .
In the I/R rats , -sitosterol treatment reduced the myocardial infarcted size and apoptosis , which was attenuated by the inhibition of PPARγ .
In conclusion , our results demonstrate that-sitosterol protected againstH/R-induced cardiomyocyte injury andmyocardial I/R injury .
@ @ @ @ @ @ @ of PPAR/NF-B signalling during myocardial I/R injury .
Further studies are required to further explore the clinical application of-sitosterol in the myocardial I/R injury .

Myocardial ischemia/reperfusion (I/R) injury is a clinically severe complication, which can cause high rates of disability and mortality particularly in patients with myocardial infarction, yet the molecular mechanisms underlying this process remain unclear. This study aimed to explore the protective effects of-sitosterol against myocardial I/R injury and to elucidate the underlying molecular mechanisms. Our results showed that hypoxia/reoxygenation (H/R) treatment suppressed cell viability, induced cell apoptosis and reactive oxygen species production, increased caspase-3 and -9 activities, upregulated caspase-3 and -9 protein expressions, downregulated the Bcl-2 protein expression, and reduced the mitochondrial membrane potential.-Sitosterol treatment attenuated H/R-induced cardiomyocyte injury. Moreover,-sitosterol treatment counteracted the inhibitory effects of H/R treatment on the peroxisome proliferator-activated receptor gamma (PPARγ) expression and enhanced effects of H/R treatment on the NF-κB expression in cardiomyocytes. Furthermore, inhibition of PPARγ impaired the protective actions of-sitosterol against H/R-induced cardiomyocyte injury. In the I/R rats,-sitosterol treatment reduced the myocardial infarcted size and apoptosis, which was attenuated by the inhibition of PPARγ. In conclusion, our results demonstrate that-sitosterol protected againstH/R-induced cardiomyocyte injury andmyocardial I/R injury. The-sitosterol-mediated cardioprotective effects may involve the modulation of PPAR/NF-B signalling during myocardial I/R injury. Further studies are required to further explore the clinical application of-sitosterol in the myocardial I/R injury.


greenmedinfo--2020-04-29--β-sitosterol assisted silver nanoparticles activates Nrf2 and triggers mitochondrial apoptosis via o

β-sitosterol assisted silver nanoparticles activates Nrf2 and triggers mitochondrial apoptosis via oxidative stress in human hepatocellular cancer cell line.

Cancer nanomedicine is an emerging field of cancer therapeutics .
Incidence of hepatocellular carcinoma is increasing worldwide and currently , it is the second leading cause of cancer-related deaths .
This study investigates the cytotoxic potential ofβ-sitosterol assisted silver nanoparticles ( BSS-SNPs ) in HepG2 cells .
The silver nanoparticles were synthesized using β-sitosterol as a reducing and stabilizing agent .
The characterization of BSS-SNPs was done by UV-visible spectrophotometry and transmission electron microscope ( TEM ) analysis .
HepG2 cells were treated with different concentrations of BSS-SNPs for 24 h and cytotoxicity was evaluated by MTT assay .
Intracellular @ @ @ @ @ @ @ diacetate staining .
The nuclear factor erythroid 2-related factor 2 ( Nrf-2 ) protein expression was investigated by immunofluorescence staining .
Morphology-related to apoptotic changes were analyzed by annexin V staining .
Intrinsic apoptosis pathway related molecular markers were investigated by western blotting and PCR analysis .
Spectrophotometry analysis confirmed a strong absorption peak at 420 nm , which showed the successful synthesis of BSS-SNPs .
The TEM analysis indicated the spherical , rod and hexagonal shaped BSS-SNPs with the size ranges from 5 to 55 nm .
BSS-SNPs significantly inhibited the proliferation @ @ @ @ @ @ @ HepG2 cells .
BSS-SNPs treatment caused apoptosis-related morphological changes and upregulated the pro-apoptotic markers such as bax , p53 , cytochrome c , caspases-9 , -3 and downregulated bcl-2 expressions .
Our findings suggest that BSS-SNPs might serve as potential drug candidates for hepatocellular carcinoma .

Cancer nanomedicine is an emerging field of cancer therapeutics. Incidence of hepatocellular carcinoma is increasing worldwide and currently, it is the second leading cause of cancer-related deaths. This study investigates the cytotoxic potential ofβ-sitosterol assisted silver nanoparticles (BSS-SNPs) in HepG2 cells. The silver nanoparticles were synthesized using β-sitosterol as a reducing and stabilizing agent. The characterization of BSS-SNPs was done by UV-visible spectrophotometry and transmission electron microscope (TEM) analysis. HepG2 cells were treated with different concentrations of BSS-SNPs for 24 h and cytotoxicity was evaluated by MTT assay. Intracellular ROS was investigated by 2',7' -dichlorofluorescin diacetate staining. The nuclear factor erythroid 2-related factor 2 (Nrf-2) protein expression was investigated by immunofluorescence staining. Morphology-related to apoptotic changes were analyzed by annexin V staining. Intrinsic apoptosis pathway related molecular markers were investigated by western blotting and PCR analysis. Spectrophotometry analysis confirmed a strong absorption peak at 420 nm, which showed the successful synthesis of BSS-SNPs. The TEM analysis indicated the spherical, rod and hexagonal shaped BSS-SNPs with the size ranges from 5 to 55 nm. BSS-SNPs significantly inhibited the proliferation and induced ROS and Nrf-2 expression in HepG2 cells. BSS-SNPs treatment caused apoptosis-related morphological changes and upregulated the pro-apoptotic markers such as bax, p53, cytochrome c, caspases-9, -3 and downregulated bcl-2 expressions. Our findings suggest that BSS-SNPs might serve as potential drug candidates for hepatocellular carcinoma.


greenmedinfo--2020-04-29--Antimicrobial activity of silver-treated bacteria against other multi-drug resistant pathogens in th

Antimicrobial activity of silver-treated bacteria against other multi-drug resistant pathogens in their environment.

Silver is a potent antimicrobial agent against a variety of microorganisms and once the element has entered the bacterial cell , it accumulates as silver nanoparticles with large surface area causing cell death .
At the same time , the bacterial cell becomes a reservoir for silver .
This study aims to test the microcidal effect of silver-killedO104 : H4 and its supernatant against fresh viable cells of the same bacterium and some other species , includingO157 : H7 , Multidrug Resistant ( MDR ) and Methicillin Resistant ( MRSA ) .
Silver-killed bacteria were examined by Transmission Electron Microscopy @ @ @ @ @ @ @ assay was used to test the antimicrobial efficacy and durability of both pellet suspension and supernatant of silver-killedO104 : H4 against other bacteria .
Both silver-killed bacteria and supernatant showed prolonged antimicrobial activity against the tested strains that extended to 40 days .
The presence of adsorbed silver nanoparticles on the bacterial cell and inside the cells was verified by TEM .
Silver-killed bacteria serve as an efficient sustained release reservoir for exporting the lethal silver cations .
This promotes its use as a powerful disinfectant for polluted water and as an effective @ @ @ @ @ @ @ and burn dressings to overcome the problem of wound contamination .

Silver is a potent antimicrobial agent against a variety of microorganisms and once the element has entered the bacterial cell, it accumulates as silver nanoparticles with large surface area causing cell death. At the same time, the bacterial cell becomes a reservoir for silver. This study aims to test the microcidal effect of silver-killedO104: H4 and its supernatant against fresh viable cells of the same bacterium and some other species, includingO157: H7, Multidrug Resistant (MDR)and Methicillin Resistant(MRSA). Silver-killed bacteria were examined by Transmission Electron Microscopy (TEM). Agar well diffusion assay was used to test the antimicrobial efficacy and durability of both pellet suspension and supernatant of silver-killedO104:H4 against other bacteria. Both silver-killed bacteria and supernatant showed prolonged antimicrobial activity against the tested strains that extended to 40 days. The presence of adsorbed silver nanoparticles on the bacterial cell and inside the cells was verified by TEM. Silver-killed bacteria serve as an efficient sustained release reservoir for exporting the lethal silver cations. This promotes its use as a powerful disinfectant for polluted water and as an effective antibacterial which can be included in wound and burn dressings to overcome the problem of wound contamination.


greenmedinfo--2020-04-29--Efficacy of a Peruvian botanical remedy (Sabell A4+) for treating liver disease and protecting gastr

Efficacy of a Peruvian botanical remedy (Sabell A4+) for treating liver disease and protecting gastric mucosal integrity.

The purpose of this study was to determine the efficacy of a Peruvian botanical formulation for treating disorders of hepatic function and gastric mucosal integrity .
The formulation A4+ ( Sabell Corporation ) contains extracts ofrhizome , flower , andleaf .
Individually these plants have been used as traditional remedies for liver disease .
We report the efficacy of A4+ and its components using a variety of in vitro and in vivo disease models .
The methods used included tests for antioxidant , anti-inflammatory , and antiviral activity as well as mouse models of liver disease , including Concanavalin A-induced @ @ @ @ @ @ @ model for evaluating sickness behaviour associated with liver disease .
Rat models were used to evaluate the gastric mucosal protective property of A4+ following indomethacin challenge and to evaluate its anti-inflammatory action in an '' air pouch '' model .
In all tests , A4+ proved to be more effective than placebo .
A4+ was antioxidant and anti-inflammatory and diminished Hepatitis C virus replication in vitro .
In animal models , A4+ was shown to protect the liver from immune-mediated hepatitis , improve behavioural function in animals with late stage liver disease , @ @ @ @ @ @ @ ulceration following NSAID exposure .
We conclude that A4+ ameliorated many aspects of liver injury , inhibited hepatitis C virus replication , and protected the gastric mucosa from NSAIDs .
These varied beneficial properties appear to result from positive interactions between the three constituent herbs .

The purpose of this study was to determine the efficacy of a Peruvian botanical formulation for treating disorders of hepatic function and gastric mucosal integrity. The formulation A4+ (Sabell Corporation) contains extracts ofrhizome,flower, andleaf. Individually these plants have been used as traditional remedies for liver disease. We report the efficacy of A4+ and its components using a variety of in vitro and in vivo disease models. The methods used included tests for antioxidant, anti-inflammatory, and antiviral activity as well as mouse models of liver disease, including Concanavalin A-induced immune-mediated hepatitis and a bile duct ligation model for evaluating sickness behaviour associated with liver disease. Rat models were used to evaluate the gastric mucosal protective property of A4+ following indomethacin challenge and to evaluate its anti-inflammatory action in an"air pouch"model. In all tests, A4+ proved to be more effective than placebo. A4+ was antioxidant and anti-inflammatory and diminished Hepatitis C virus replication in vitro. In animal models, A4+ was shown to protect the liver from immune-mediated hepatitis, improve behavioural function in animals with late stage liver disease, and protect the rat gastric mucosa from ulceration following NSAID exposure. We conclude that A4+ ameliorated many aspects of liver injury, inhibited hepatitis C virus replication, and protected the gastric mucosa from NSAIDs. These varied beneficial properties appear to result from positive interactions between the three constituent herbs.


greenmedinfo--2020-04-29--Curcumin as an ajuvant treatment of depression: mechanisms of action and application prospects.

Curcumin , a natural compound found in the rhizomes of turmeric , has a pronounced anti-inflammatory activity .
Rodent models @ @ @ @ @ activity is similar to the effect of antidepressants ( AD ) .
Experimental data indicate @ @ @ @ @ related to the effect of curcumin on the monoamine cycle , oxidative and nitrosative stress @ @ @ @ @ and immune systems .
A number of meta-analyzes indicate the effectiveness of the combined use @ @ @ @ @ the treatment of depression .
The mechanism of action of curcumin , as well as @ @ @ @ @ use are considered .

Curcumin, a natural compound found in the rhizomes of turmeric, has a pronounced anti-inflammatory activity. Rodent models of depression show that this activity is similar to the effect of antidepressants (AD). Experimental data indicate that this activity may be related to the effect of curcumin on the monoamine cycle, oxidative and nitrosative stress, neurogenesis, hypothalamic-pituitary-adrenal, and immune systems. A number of meta-analyzes indicate the effectiveness of the combined use of curcumin with antidepressants in the treatment of depression. The mechanism of action of curcumin, as well as the prospects for its further use are considered.


greenmedinfo--2020-04-29--Anti-H1N1 viral activity of three main active ingredients from zedoary oil.

Influenza virus is one of the most widespread infectious diseases in the world .
It poses a serious public health @ @ @ @ @ the emergence of drug-resistant virus strains , antiviral drugs are urgently needed to control virus @ @ @ @ @ In this study , three main active substances-curcumol , curdione and germacrone-were isolated from the @ @ @ @ @ They inhibited the replication of influenza A ( H1N1 ) virus in a dose-dependent manner @ @ @ @ @ compounds , the expression of viral protein and RNA synthesis were inhibited .
In vivo @ @ @ @ @ H1N1-induced lung damage and the load of virus in serum as well as whole blood @ @ @ @ @ analysis , after treatment with germacrone , the expression of antiviral protein and the amount @ @ @ @ @ reduced , further proving that germacrone can inhibit viral replication .
Our experiments have shown @ @ @ @ @ germacrone can inhibit the replication of H1N1 virus ; in particular , germacrone shows potential @ @ @ @ @ vivo as a therapeutic drug .

Influenza virus is one of the most widespread infectious diseases in the world. It poses a serious public health threat to humans. With the emergence of drug-resistant virus strains, antiviral drugs are urgently needed to control virus transmission and disease progression. In this study, three main active substances-curcumol, curdione and germacrone-were isolated from the traditional Chinese medicine zedoary. They inhibited the replication of influenza A (H1N1) virus in a dose-dependent manner. After treatment with these compounds, the expression of viral protein and RNA synthesis were inhibited. In vivo, these compounds also reduced H1N1-induced lung damage and the load of virus in serum as well as whole blood cells. In a proteomic analysis, after treatment with germacrone, the expression of antiviral protein and the amount of intracellular virus were significantly reduced, further proving that germacrone can inhibit viral replication. Our experiments have shown that curcumol, curdione and germacrone can inhibit the replication of H1N1 virus; in particular, germacrone shows potential both in vitro and in vivo as a therapeutic drug.


greenmedinfo--2020-04-29--Curcumol attenuates liver sinusoidal endothelial cell angiogenesis via regulating Glis-PROX1-HIF-1α

Curcumol attenuates liver sinusoidal endothelial cell angiogenesis via regulating Glis-PROX1-HIF-1α in liver fibrosis.

OBJECTIVE : Hepatic sinusoidal angiogenesis owing to dysfunctional liver sinusoidal endothelial cells ( LSECs ) accompanied by an abnormal angioarchitecture is a symbol related to liver fibrogenesis , which indicates a potential target for therapeutic interventions .
However , there are few researches connecting angiogenesis with liver fibrosis , and the deeper mechanism remains to be explored .
MATERIALS AND METHODS : Cell angiogenesis and angiogenic protein were examined in primary LSECs of rats , and multifarious cellular and molecular assays revealed the efficiency of curcumol intervention in fibrotic mice .
RESULTS : We found that curcumol inhibited angiogenic properties @ @ @ @ @ @ @ ( HIF-1α ) .
The transcription activation of HIF-1α was regulated by hedgehog signalling on the one hand , and the protein stabilization of HIF-1α was under the control of Prospero-related homeobox 1 ( PROX1 ) on the other .
A deubiquitinase called USP19 could be recruited by PROX1 and involved in ubiquitin-dependent degradation of HIF-1α .
Furthermore , our researches revealed that hedgehog signalling participated in the activation of PROX1 transcription probably in vitro .
Besides , curcumol was found to ameliorate liver fibrosis and sinusoid angiogenesis via hedgehog pathway in carbon @ @ @ @ @ @ @ mice .
The protein expression of key regulatory factors , PROX1 and HIF-1α , was consistent with the Smo , the marker protein of Hh signalling pathway .
CONCLUSIONS : In this article , we evidenced that curcumol controlling LSEC-mediated angiogenesis could be a promising therapeutic approach for liver fibrosis .

OBJECTIVE: Hepatic sinusoidal angiogenesis owing to dysfunctional liver sinusoidal endothelial cells (LSECs) accompanied by an abnormal angioarchitecture is a symbol related to liver fibrogenesis, which indicates a potential target for therapeutic interventions. However, there are few researches connecting angiogenesis with liver fibrosis, and the deeper mechanism remains to be explored.
MATERIALS AND METHODS: Cell angiogenesis and angiogenic protein were examined in primary LSECs of rats, and multifarious cellular and molecular assays revealed the efficiency of curcumol intervention in fibrotic mice.
RESULTS: We found that curcumol inhibited angiogenic properties through regulating their upstream mediator hypoxia-inducible factor-1α (HIF-1α). The transcription activation of HIF-1α was regulated by hedgehog signalling on the one hand, and the protein stabilization of HIF-1α was under the control of Prospero-related homeobox 1 (PROX1) on the other. A deubiquitinase called USP19 could be recruited by PROX1 and involved in ubiquitin-dependent degradation of HIF-1α. Furthermore, our researches revealed that hedgehog signalling participated in the activation of PROX1 transcription probably in vitro. Besides, curcumol was found to ameliorate liver fibrosis and sinusoid angiogenesis via hedgehog pathway in carbon tetrachloride (CCl) induced liver fibrotic mice. The protein expression of key regulatory factors, PROX1 and HIF-1α, was consistent with the Smo, the marker protein of Hh signalling pathway.
CONCLUSIONS: In this article, we evidenced that curcumol controlling LSEC-mediated angiogenesis could be a promising therapeutic approach for liver fibrosis.


greenmedinfo--2020-04-29--Curcumol inhibits the proliferation and metastasis of melanoma.

Melanoma is the most aggressive and treatment-resistant form of skin cancer .
Curcumol is a Chinese medicinal herb traditionally used as a cancer remedy .
However , the molecular mechanisms underlying the anticancer activity of curcumol in melanoma remains largely unknown .
In the present study , we observed that Curcumol decreased mouse melanoma B16 cell proliferation and migration .
The xenograft tumor assay showed that curcumol reduced melanoma volume and lung metastasis .
Curcumol upregulated the expression of E-cadherin and downregulated the expression of N-cadherin , MMP2 and MMP9 in mouse melanoma B16 cell .
Western blot analysis revealed @ @ @ @ @ @ @ to the nucleus and decreased p-ERK .
Furthermore , curcumol attenuated c-MET , P13K and p-AKT protein expression and upregulated miR-152-3p gene expression .
The dual-luciferase reporter assay indicated that c-MET was a target gene of miR-152-3p .
Reduced expression of miR-152-3p partially attenuated the effect of curcumol on mouse melanoma B16 cell proliferation and migration .
The decrease in c-MET , P13K and p-AKT protein expression following curcumol treatment in mouse melanoma B16 cells was notably attenuated by the miR-152-3p inhibitor .
Taken together , our findings suggested that curcumol attenuated melanoma @ @ @ @ @ @ @ promoted miR-152-3p expression to inactivate the c-MET/PI3K/AKT signaling pathway .

Melanoma is the most aggressive and treatment-resistant form of skin cancer. Curcumol is a Chinese medicinal herb traditionally used as a cancer remedy. However, the molecular mechanisms underlying the anticancer activity of curcumol in melanoma remains largely unknown. In the present study, we observed that Curcumol decreased mouse melanoma B16 cell proliferation and migration. The xenograft tumor assay showed that curcumol reduced melanoma volume and lung metastasis. Curcumol upregulated the expression of E-cadherin and downregulated the expression of N-cadherin, MMP2 and MMP9 in mouse melanoma B16 cell. Western blot analysis revealed that curcumol reduced the translocation of p65 to the nucleus and decreased p-ERK. Furthermore, curcumol attenuated c-MET, P13K and p-AKT protein expression and upregulated miR-152-3p gene expression. The dual-luciferase reporter assay indicated that c-MET was a target gene of miR-152-3p. Reduced expression of miR-152-3p partially attenuated the effect of curcumol on mouse melanoma B16 cell proliferation and migration. The decrease in c-MET, P13K and p-AKT protein expression following curcumol treatment in mouse melanoma B16 cells was notably attenuated by the miR-152-3p inhibitor. Taken together, our findings suggested that curcumol attenuated melanoma progression and concomitantly suppressed ERK/NF-κB signaling and promoted miR-152-3p expression to inactivate the c-MET/PI3K/AKT signaling pathway.


greenmedinfo--2020-04-29--Curcumol might represent a promising lead compound for the development of new targeted anti-cancer t

Curcumol might represent a promising lead compound for the development of new targeted anti-cancer therapeutics.

ETHNOPHARMACOLOGICAL RELEVANCE : Curcuma wenyujin is a Chinese traditional herbal medicine that is commonly used as an anti-oxidant , anti-proliferative , and anti-tumorigenic agent .
Curcumol is a representative index component for the quality control of the essential oil of Curcuma wenyujin , which is currently used as an anti-cancer drug , and is included in the State Pharmacopoeia Commission of the People 's Republic of China ( 2005 ) .
However , the mechanisms of action and molecular functions of curcumol are not yet fully elucidated .
AIM OF THE STUDY : This study aimed to identify new effects @ @ @ @ @ @ @ immunotherapy .
MATERIALS AND METHODS : The underlying mechanism of the inhibition of programmed cell death-ligand 1 ( PD-L1 ) activation by curcumol was investigated in vitro via homology modeling , molecular docking experiments , luciferase reporter assays , MTT assays , RT-PCR , western blotting , and immunofluorescence assays .
Changes in cellular proliferation , angiogenesis , and the tumor-killing activity of T-cells were analyzed via EdU labeling , colony formation , flow cytometry , wound-healing , Matrigel Transwell invasion , tube formation , and T-cell killing .
The anti-tumor activity of @ @ @ @ @ @ @ murine xenograft model using Hep3B cells .
RESULTS : Curcumol reduced the expression of phosphorylated signal transducer and activator of transcription 3 ( p-STAT3 ) via JAK1 , JAK2 , and Src pathways and inhibited hypoxia-inducible factor-1α ( HIF-1α ) protein synthesis via mTOR/p70S6K/eIF4E and MAPK pathways .
Furthermore , we revealed crosstalk between STAT3 and HIF-1α pathways , which collaboratively regulated PD-L1 activation , and that curcumol played a role in this regulation .
Curcumol inhibited cell proliferation , S-phase progression , tube formation , invasion , and metastasis by inhibiting PD-L1 @ @ @ @ @ @ @ activity of cytotoxic T-cells and their capacity for tumor cell killing by inhibiting PD-L1 .
In vivo experiments confirmed that curcumol inhibited tumor growth in a xenograft model .
CONCLUSIONS : These results illustrated that curcumol inhibits the expression of PD-L1 through crosstalk between HIF-1α and p-STAT3 ( T705 ) signaling pathways in hepatic cancer .
Thus , curcumol might represent a promising lead compound for the development of new targeted anti-cancer therapeutics .

ETHNOPHARMACOLOGICAL RELEVANCE: Curcuma wenyujin is a Chinese traditional herbal medicine that is commonly used as an anti-oxidant, anti-proliferative, and anti-tumorigenic agent. Curcumol is a representative index component for the quality control of the essential oil of Curcuma wenyujin, which is currently used as an anti-cancer drug, and is included in the State Pharmacopoeia Commission of the People's Republic of China (2005). However, the mechanisms of action and molecular functions of curcumol are not yet fully elucidated.
AIM OF THE STUDY: This study aimed to identify new effects of curcumol from the perspective of cancer immunotherapy.
MATERIALS AND METHODS: The underlying mechanism of the inhibition of programmed cell death-ligand 1 (PD-L1) activation by curcumol was investigated in vitro via homology modeling, molecular docking experiments, luciferase reporter assays, MTT assays, RT-PCR, western blotting, and immunofluorescence assays. Changes in cellular proliferation, angiogenesis, and the tumor-killing activity of T-cells were analyzed via EdU labeling, colony formation, flow cytometry, wound-healing, Matrigel Transwell invasion, tube formation, and T-cell killing. The anti-tumor activity of curcumol was assessed in vivo in a murine xenograft model using Hep3B cells.
RESULTS: Curcumol reduced the expression of phosphorylated signal transducer and activator of transcription 3 (p-STAT3) via JAK1, JAK2, and Src pathways and inhibited hypoxia-inducible factor-1α (HIF-1α) protein synthesis via mTOR/p70S6K/eIF4E and MAPK pathways. Furthermore, we revealed crosstalk between STAT3 and HIF-1α pathways, which collaboratively regulated PD-L1 activation, and that curcumol played a role in this regulation. Curcumol inhibited cell proliferation, S-phase progression, tube formation, invasion, and metastasis by inhibiting PD-L1. In addition, curcumol restored the activity of cytotoxic T-cells and their capacity for tumor cell killing by inhibiting PD-L1. In vivo experiments confirmed that curcumol inhibited tumor growth in a xenograft model.
CONCLUSIONS: These results illustrated that curcumol inhibits the expression of PD-L1 through crosstalk between HIF-1α and p-STAT3 (T705) signaling pathways in hepatic cancer. Thus, curcumol might represent a promising lead compound for the development of new targeted anti-cancer therapeutics.


greenmedinfo--2020-04-29--Gender differences in plasma vitamin C concentrations and cognitive function.

Background : A number of investigations have highlighted the importance of vitamin C in maintaining brain health .
Biologically , vitamin C has exhibited roles in neuromodulation , neurodevelopment , vascular support , and neuroprotection .
Vitamin C 's contribution to cognitive function in both cognitively intact and impaired cohorts has previously been assessed , with little focus on gender variability .
Objective : The present study explored the interaction between gender and plasma vitamin C on cognitive performance , and the effect of different amounts of plasma vitamin C ( adequate/inadequate ) on various cognitive tasks by gender .
@ @ @ @ @ @ @ in healthy adults ( = 80 , female = 52 , male = 28 , 24-96 y ) with a range of blood plasma vitamin C concentrations .
Cognitive assessments included the Swinburne University Computerized Cognitive Assessment Battery ( SUCCAB ) and 2 pen-and-paper tests , the Symbol Digits Modalities Test ( SDMT ) and the Hopkins Verbal Learning Test-Revised ( HVLT-R ) .
Food-frequency questionnaires were used to elucidate dietary consumption .
Results : After adjusting for a number of potential covariates such as age , number of prescribed medications and dose @ @ @ @ @ @ @ a significant interaction ( Conclusions : Further larger-scale investigations are required to establish a cause-and-effect relation and to elucidate whether differences in cognitive function between genders may be attributed to plasma vitamin C status.This trial was registered at https : //www.anzctr.org.au/Trial/Registration/TrialReview.aspx ?
id=369440 & isReview=true as ACTRN12615001140549 .

Background: A number of investigations have highlighted the importance of vitamin C in maintaining brain health. Biologically, vitamin C has exhibited roles in neuromodulation, neurodevelopment, vascular support, and neuroprotection. Vitamin C's contribution to cognitive function in both cognitively intact and impaired cohorts has previously been assessed, with little focus on gender variability.
Objective: The present study explored the interaction between gender and plasma vitamin C on cognitive performance, and the effect of different amounts of plasma vitamin C (adequate/inadequate) on various cognitive tasks by gender.
Methods: This retrospective analysis was conducted in healthy adults ( = 80, female = 52, male = 28, 24-96 y) with a range of blood plasma vitamin C concentrations. Cognitive assessments included the Swinburne University Computerized Cognitive Assessment Battery (SUCCAB) and 2 pen-and-paper tests, the Symbol Digits Modalities Test (SDMT) and the Hopkins Verbal Learning Test-Revised (HVLT-R). Food-frequency questionnaires were used to elucidate dietary consumption.
Results: After adjusting for a number of potential covariates such as age, number of prescribed medications and dose of vitamin C supplementation, results indicated a significant interaction ( < 0.001) between plasma vitamin C and gender on cognitive function, on both the computerized and pen-and-paper assessments. A novel finding was that the performance of males with inadequate plasma vitamin C was poorer on tasks involving components of memory (short/delayed), inhibition, and visual perception, whereas females presenting with inadequate vitamin C were more compromised on tasks involving psychomotor performance/motor speed. Additionally, females with adequate vitamin C concentrations exhibited higher performance than males on tasks involving recall, recognition, attention, and focus.
Conclusions: Further larger-scale investigations are required to establish a cause-and-effect relation and to elucidate whether differences in cognitive function between genders may be attributed to plasma vitamin C status.This trial was registered at https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=369440&isReview=true as ACTRN12615001140549.


greenmedinfo--2020-04-29--Bisdemethoxycurcumin enhances the sensitivity of non-small cell lung cancer cells to icotinib.

Non-small cell lung cancer ( NSCLC ) with epidermal growth factor receptor ( EGFR ) wild-type is intrinsic resistance to EGFR-tyrosine kinase inhibitors ( TKIs ) .
In this study , we assessed whether the combination of bisdemethoxycurcumin ( BDMC ) and icotinib could surmount primary EGFR-TKI resistance in NSCLC cells and investigated its molecular mechanism .
Results showed that the combination of BDMC and icotinib produced potently synergistic growth inhibitory effect on primary EGFR-TKI-resistant NSCLC cell lines H460 ( EGFR wild-type and K-ras mutation ) and H1781 ( EGFR wild-type and Her2 mutation ) .
Compared with BDMC or @ @ @ @ @ @ @ induced more significant apoptosis and autophagy via suppressing EGFR activity and interaction of Sp1 and HDCA1/HDCA2 , which was accompanied by accumulation of reactive oxygen species ( ROS ) , induction of DNA damage , and inhibition of cell migration and invasion .
ROS inhibitor ( NAC ) and autophagy inhibitors ( CQ or 3-MA ) partially reversed BDMC plus icotinib-induced growth inhibitory effect on the NSCLC cells .
Meanwhile , co-treatment with NAC attenuated the two drug combination-induced autophagy , apoptosis , DNA damage and decrease of cell migration and invasion ability @ @ @ @ @ @ @ abate the combination treatment-induced apoptosis and DNA damage , suggesting that there is crosstalk between different signaling pathways in the effect produced by the combination treatment .
Our data indicate that BMDC has the potential to improve the treatment of primary EGFR-TKI resistant NISCLC that can not be controlled with single-target agent , such as icotinib .

Non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) wild-type is intrinsic resistance to EGFR-tyrosine kinase inhibitors (TKIs). In this study, we assessed whether the combination of bisdemethoxycurcumin (BDMC) and icotinib could surmount primary EGFR-TKI resistance in NSCLC cells and investigated its molecular mechanism. Results showed that the combination of BDMC and icotinib produced potently synergistic growth inhibitory effect on primary EGFR-TKI-resistant NSCLC cell lines H460 (EGFR wild-type and K-ras mutation) and H1781 (EGFR wild-type and Her2 mutation). Compared with BDMC or icotinib alone, the two drug combination induced more significant apoptosis and autophagy via suppressing EGFR activity and interaction of Sp1 and HDCA1/HDCA2, which was accompanied by accumulation of reactive oxygen species (ROS), induction of DNA damage, and inhibition of cell migration and invasion. ROS inhibitor (NAC) and autophagy inhibitors (CQ or 3-MA) partially reversed BDMC plus icotinib-induced growth inhibitory effect on the NSCLC cells. Meanwhile, co-treatment with NAC attenuated the two drug combination-induced autophagy, apoptosis, DNA damage and decrease of cell migration and invasion ability. Also, 3-MA or CQ can abate the combination treatment-induced apoptosis and DNA damage, suggesting that there is crosstalk between different signaling pathways in the effect produced by the combination treatment. Our data indicate that BMDC has the potential to improve the treatment of primary EGFR-TKI resistant NISCLC that cannot be controlled with single-target agent, such as icotinib.


greenmedinfo--2020-04-29--Antifungal activity of zedoary turmeric oil against Phytophthora capsici through damaging cell membr

Antifungal activity of zedoary turmeric oil against Phytophthora capsici through damaging cell membrane.

Phytophthora capsici is a plant oomycete pathogen , which causes many devastating diseases on a broad range of hosts .
@ @ @ @ @ ) is a kind of natural plant essential oil that has been widely used in @ @ @ @ @ the antifungal activity of ZTO against phytopathogens remains unknown .
In this study , we @ @ @ @ @ capsici growth and development in vitro and in detached cucumber and Nicotiana benthamiana leaves .
@ @ @ @ @ in severe damage to the cell membrane of P. capsici , leading to the leakage @ @ @ @ @ also induced a significant increase in relative conductivity , malondialdehyde concentration and glycerol content .
@ @ @ @ @ volatile organic compounds from ZTO , and uncovered Curcumol , β-elemene , curdione and curcumenol @ @ @ @ @ mycelial growth of P. capsici .
Overall , our results not only shed new light @ @ @ @ @ ZTO , but also imply a promising alternative for the control of phytophthora blight caused @ @ @ @

Phytophthora capsici is a plant oomycete pathogen, which causes many devastating diseases on a broad range of hosts. Zedoary turmeric oil (ZTO) is a kind of natural plant essential oil that has been widely used in pharmaceutical applications. However, the antifungal activity of ZTO against phytopathogens remains unknown. In this study, we found ZTO could inhibit P. capsici growth and development in vitro and in detached cucumber and Nicotiana benthamiana leaves. Besides, ZTO treatment resulted in severe damage to the cell membrane of P. capsici, leading to the leakage of intracellular contents. ZTO also induced a significant increase in relative conductivity, malondialdehyde concentration and glycerol content. Furthermore, we identified 50 volatile organic compounds from ZTO, and uncovered Curcumol,β-elemene, curdione and curcumenol with strong inhibitory activities against mycelial growth of P. capsici. Overall, our results not only shed new light on the antifungal mechanism of ZTO, but also imply a promising alternative for the control of phytophthora blight caused by P. capsici.