greenmedinfo--2020-05-29--These results demonstrate potential preventive effects of grape-seed proanthocyanidin extract on hum

These results demonstrate potential preventive effects of grape-seed proanthocyanidin extract on human colon dysfunction.

PURPOSE : Anti-inflammatory and barrier-protective properties have been attributed to proanthocyanidins in the context of intestinal dysfunction , however little information is available about the impact of these phytochemicals on intestinal barrier integrity and immune response in the human .
Here we assessed the putative protective properties of a grape-seed proanthocyanidin extract ( GSPE ) against dextran sodium sulfate ( DSS ) -induced acute dysfunction of the human colon in an Ussing chamber system .
METHODS : Human proximal and distal colon tissues from colectomized patients were submitted ex vivo for a 30-min preventive GSPE treatment ( 50 or 200 @ @ @ @ @ @ @ with DSS ( 12 % w v ) .
Transepithelial electrical resistance ( TEER ) , permeation of a fluorescently-labeled dextran ( FD4 ) and proinflammatory cytokine release [ tumor necrosis factor ( TNF ) -α and interleukin ( IL ) -1β ] of colonic tissues were determined .
RESULTS : DSS reduced TEER ( 45-52 % ) in both the proximal and distal colon ; however , significant increments in FD4 permeation ( fourfold ) and TNF-α release ( 61 % ) were observed only in the proximal colon .
The preventive @ @ @ @ @ @ @ 20-32 % ) , FD4 permeation ( 66-73 % ) and TNF-α release ( 22-33 % ) of the proximal colon dose-dependently .
The distal colon was not responsive to the preventive treatment but showed areduction in IL-1β release below basal levels with the highest GSPE concentration .
CONCLUSIONS : Our results demonstrate potential preventive effects of GSPE on human colon dysfunction .
Further studies are required to test whether administering GSPE could be a complementary therapeutic approach in colonic dysfunction associated with metabolic disorders and inflammatory bowel disease .

PURPOSE: Anti-inflammatory and barrier-protective properties have been attributed to proanthocyanidins in the context of intestinal dysfunction, however little information is available about the impact of these phytochemicals on intestinal barrier integrity and immune response in the human. Here we assessed the putative protective properties of a grape-seed proanthocyanidin extract (GSPE) against dextran sodium sulfate (DSS)-induced acute dysfunction of the human colon in an Ussing chamber system.
METHODS: Human proximal and distal colon tissues from colectomized patients were submitted ex vivo for a 30-min preventive GSPE treatment (50 or 200 µg mL) followed by 1-h incubation with DSS (12% w v). Transepithelial electrical resistance (TEER), permeation of a fluorescently-labeled dextran (FD4) and proinflammatory cytokine release [tumor necrosis factor (TNF)-α and interleukin (IL)-1β] of colonic tissues were determined.
RESULTS: DSS reduced TEER (45-52%) in both the proximal and distal colon; however, significant increments in FD4 permeation (fourfold) and TNF-α release (61%) were observed only in the proximal colon. The preventive GSPE treatment decreased DSS-induced TEER loss (20-32%), FD4 permeation (66-73%) and TNF-α release (22-33%) of the proximal colon dose-dependently. The distal colon was not responsive to the preventive treatment but showed areduction in IL-1β release below basal levels with the highest GSPE concentration.
CONCLUSIONS: Our results demonstrate potential preventive effects of GSPE on human colon dysfunction. Further studies are required to test whether administering GSPE could be a complementary therapeutic approach in colonic dysfunction associated with metabolic disorders and inflammatory bowel disease.


greenmedinfo--2020-05-29--Heat sensitization of hepatitis A virus and tulane virus using grape seed extract, gingerol and curc

Heat sensitization of hepatitis A virus and tulane virus using grape seed extract, gingerol and curcumin.

Human noroviruses ( HNoV ) and hepatitis A virus ( HAV ) are predominantly linked to foodborne outbreaks worldwide .
As cell-culture systems to propagate HNoV in laboratories are not easily available , Tulane virus ( TV ) is used as a cultivable HNoV surrogate to determine inactivation .
Heat-sensitization of HAV and TV by '' generally recognized as safe '' ( GRAS ) substances can potentially reduce their time-temperature inactivation parameters during processing to ensure food safety .
Curcumin , gingerol ( from ginger ) , and grape seed extract ( GSE ) reportedly have anti-inflammatory , immune-modulating and @ @ @ @ @ @ @ study was to determine and compare the D-values and z-values of HAV and TV at 52-68 °C with or without curcumin ( 0.015 mg/ml ) , gingerol ( 0.1 mg/ml ) , or GSE ( 1 mg/ml ) in 2-ml glass vials .
HAV at ~7 log PFU/ml and TV at ~6 log PFU/ml were diluted in phosphate buffered saline ( PBS ) and added to two sets of six 2-mL sterile glass vials .
One set served as the control and the second set had the three extracts individually added for thermal @ @ @ @ @ @ @ 0-10 min .
The D-values for TV in PBS ranged from 4.55 ± 0.28 to 1.08 ± 0.16 min , and for HAV in PBS ranged from to 9.21 ± 0.24 to 0.67 ± 0.19 min at 52-68 °C .
Decreased D-values ( 52-58 °C ) for TV with curcumin ranging from 4.32 ± 0.25 to 0.62 ± 0.17 min , gingerol from 4.09 ± 0.18 to 0.72 ± 0.09 min and GSE from 3.82 ± 0.18 to 0.80 ± 0.07 min , with similar trends for HAV were observed .
The linear @ @ @ @ @ @

Human noroviruses (HNoV) and hepatitis A virus (HAV) are predominantly linked to foodborne outbreaks worldwide. As cell-culture systems to propagate HNoV in laboratories are not easily available, Tulane virus (TV) is used as a cultivable HNoV surrogate to determine inactivation. Heat-sensitization of HAV and TV by"generally recognized as safe'' (GRAS) substances can potentially reduce their time-temperature inactivation parameters during processing to ensure food safety. Curcumin, gingerol (from ginger), and grape seed extract (GSE) reportedly have anti-inflammatory, immune-modulating and antiviral properties. The objective of this study was to determine and compare the D-values and z-values of HAV and TV at 52-68 °C with or without curcumin (0.015 mg/ml), gingerol (0.1 mg/ml), or GSE (1 mg/ml) in 2-ml glass vials. HAV at ~7 log PFU/ml and TV at ~6 log PFU/ml were diluted in phosphate buffered saline (PBS) and added to two sets of six 2-mL sterile glass vials. One set served as the control and the second set had the three extracts individually added for thermal treatments in a circulating water bath for 0-10 min. The D-values for TV in PBS ranged from 4.55 ± 0.28 to 1.08 ± 0.16 min, and for HAV in PBS ranged from to 9.21 ± 0.24 to 0.67 ± 0.19 min at 52-68 °C. Decreased D-values (52-58 °C) for TV with curcumin ranging from 4.32 ± 0.25 to 0.62 ± 0.17 min, gingerol from 4.09 ± 0.18 to 0.72 ± 0.09 min and GSE from 3.82 ± 0.18 to 0.80 ± 0.07 min, with similar trends for HAV were observed. The linear model showed significant differences (p < 0.05) between the D-values of HAV and TV with and without plant extracts for most tested temperatures. This suggests that GRAS substances can potentially lower temperature and time regimens needed to inactivate HAV and TV.


greenmedinfo--2020-05-29--Vasorelaxant effects induced by red wine and pomace extracts of Magliocco dolce.

Several epidemiological studies demonstrate that moderate ( red ) wine consumption may afford protection against cardiovascular diseases .
Protection is ascribed to the biological activity of wine components , many of which , however , are discarded during winemaking .
In vitro rat thoracic aorta rings contracted with phenylephrine or KCl were used to assess the vasorelaxant activity of extracts from wine pomaces ( seeds and skins ) of the Calabrian autochthonous grape variety Magliocco dolce ( Arvino ) .
NMR spectroscopy was used to ascertain their chemical composition .
Data demonstrate that seed and skin , but not must @ @ @ @ @ @ @ preparations in an endothelium-dependent manner , similarly to the red wine extract , due to the presence of comparable amounts of bioactive constituents .
In rings pre-contracted with 20-30 mM KCl , only seed extracts showed a moderate relaxation .
The most efficacious vasodilating extract ( wine ) showed a good antioxidant profile in both [ ( 2,2-diphenyl-1-picrylhydrazyl ) acid ] radical ( DPPH ) and [ 2,2'-azino-bis ( 3-ethylbenzothiazoline-6-sulphonic acid ) ] radical ( ABTS ) assays .
In conclusion , winemaking from Magliocco dolce grape can provide potentially health-promoting by-products useful @ @ @ @ @

Several epidemiological studies demonstrate that moderate (red) wine consumption may afford protection against cardiovascular diseases. Protection is ascribed to the biological activity of wine components, many of which, however, are discarded during winemaking. In vitro rat thoracic aorta rings contracted with phenylephrine or KCl were used to assess the vasorelaxant activity of extracts from wine pomaces (seeds and skins) of the Calabrian autochthonous grape variety Magliocco dolce (Arvino). NMR spectroscopy was used to ascertain their chemical composition. Data demonstrate that seed and skin, but not must, extracts are capable of relaxing vascular preparations in an endothelium-dependent manner, similarly to the red wine extract, due to the presence of comparable amounts of bioactive constituents. In rings pre-contracted with 20-30 mM KCl, only seed extracts showed a moderate relaxation. The most efficacious vasodilating extract (wine) showed a good antioxidant profile in both [(2,2-diphenyl-1-picrylhydrazyl)acid] radical (DPPH) and [2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid)] radical (ABTS) assays. In conclusion, winemaking from Magliocco dolce grape can provide potentially health-promoting by-products useful in cardiovascular disease management.


greenmedinfo--2020-05-29--Ginkgo biloba and its constituent 6-hydroxykynurenic-acid as well as its proanthocyanidins exert neu

Ginkgo biloba and its constituent 6-hydroxykynurenic-acid as well as its proanthocyanidins exert neurorestorative effects against cerebral ischemia.

Neuroprotective effects against cerebral ischemia/reperfusion ( I/R ) injury byleaves are commonly attributed to the antioxidant activity of its proanthocyanidins .
Furthermore , preliminary experiments identified 6-hydroxykynurenic acid ( 6-HKA ) as a major contributor to this effect of extract ofleaves ( EGb ) prepared according to the Chinese Pharmacopoeia ( ChP ) .
In order to elucidate the specific contribution of both proanthocyanidins and 6-HKA to the overall neurorestorative effects of this extract according to ChP , EGb ChP was separated into pure 6-HKA and a newly developed Ginkgo proanthocyanidin extract ( GPE ) , enriched in proanthocyanidins but @ @ @ @ @ @ @ were divided into the groups : sham : 8 ; model ( placebo ) : 25 ; GPE 80 mg/kg : 13 ; GPE 40 mg/kg : 13 ; GPE 20 mg/kg : 16 ; grape seed extract ( negative control ) 40 mg/kg : 18 ; nimodipine ( positive control ) 2 mg/kg : 8 .
All non-sham animals were subjected to cerebral I/R injury by occluding the middle cerebral artery with a nylon suture that was removed after 2 hof ischemia to establish reperfusion .
For comparison , a parallel series @ @ @ @ @ @ @ In theseexperiments , neurological dysfunctions were reduced by both GPE and 6-HKA , and both average infarct size and concentrations of malondialdehyde ( MDA ) and super oxide dismutase ( SOD ) were significantly ameliorated as compared to the model group .
This data , therefore , demonstrates that the neuroprotective effects of EGb can not be explained by a purely chemical antioxidative effect alone as has been previously proposed , especially with regards to the proanthocyanidins .
A pharmacological neurorestorative effect of EGb on neurons and brain tissue itself seems to be @ @ @ @ @ @ @ presented observations .
This effect is most likely explained by the synergistic action of both its numerous phenolic constituents ( GPE ) and 6-hydroxykynurenic acid ( 6-HKA ) , which could be identified as one major contributor to the observed activity .

Neuroprotective effects against cerebral ischemia/reperfusion (I/R) injury byleaves are commonly attributed to the antioxidant activity of its proanthocyanidins. Furthermore, preliminary experiments identified 6-hydroxykynurenic acid (6-HKA) as a major contributor to this effect of extract ofleaves (EGb) prepared according to the Chinese Pharmacopoeia (ChP). In order to elucidate the specific contribution of both proanthocyanidins and 6-HKA to the overall neurorestorative effects of this extract according to ChP, EGb ChP was separated into pure 6-HKA and a newly developed Ginkgo proanthocyanidin extract (GPE), enriched in proanthocyanidins but not containing 6-HKA. Male Sprague-Dawley rats were divided into the groups: sham: 8; model (placebo): 25; GPE 80 mg/kg: 13; GPE 40 mg/kg: 13; GPE 20 mg/kg: 16; grape seed extract (negative control) 40 mg/kg: 18; nimodipine (positive control) 2 mg/kg: 8. All non-sham animals were subjected to cerebral I/R injury by occluding the middle cerebral artery with a nylon suture that was removed after 2 hof ischemia to establish reperfusion. For comparison, a parallel series of experiments were performed with 6-HKA. In theseexperiments, neurological dysfunctions were reduced by both GPE and 6-HKA, and both average infarct size and concentrations of malondialdehyde (MDA) and super oxide dismutase (SOD) were significantly ameliorated as compared to the model group. This data, therefore, demonstrates that the neuroprotective effects of EGb cannot be explained by a purely chemical antioxidative effect alone as has been previously proposed, especially with regards to the proanthocyanidins. A pharmacological neurorestorative effect of EGb on neurons and brain tissue itself seems to be a much more straightforward explanation for the presented observations. This effect is most likely explained by the synergistic action of both its numerous phenolic constituents (GPE) and 6-hydroxykynurenic acid (6-HKA), which could be identified as one major contributor to the observed activity.


greenmedinfo--2020-05-29--Mantonico and pecorello grape seed extracts: chemical characterization and evaluation of in vitro wo

Mantonico and pecorello grape seed extracts: chemical characterization and evaluation of in vitro wound-healing and anti-inflammatory activities.

The winemaking process produces a huge number of pomaces that generally are used for energy purposes .
Further valuable applications @ @ @ @ @ still under investigation .
The seeds of the white berries of Mantonico and Pecorellowere extracted @ @ @ @ @ using-hexane and chloroform as solvents .
Extracts were characterized by NMR and GC-MS analyses .
@ @ @ @ @ and anti-inflammatory agents in HaCaT and RAW 264.7 cell lines , respectively.-hexane Mantonico extract resulted @ @ @ @ @ healing sample , while-hexane Pecorello , containing a good number of carotenoids , resulted in @ @ @ @ @ These preliminary findings underlined the benefit of grape seed extracts valorization due to their health-promoting @ @

The winemaking process produces a huge number of pomaces that generally are used for energy purposes. Further valuable applications such as health-promoting properties are still under investigation. The seeds of the white berries of Mantonico and Pecorellowere extracted in a Soxhlet apparatus, using-hexane and chloroform as solvents. Extracts were characterized by NMR and GC-MS analyses. They were assayedas wound healing and anti-inflammatory agents in HaCaT and RAW 264.7 cell lines, respectively.-hexane Mantonico extract resulted in the most interesting wound healing sample, while-hexane Pecorello, containing a good number of carotenoids, resulted in a good anti-inflammatory candidate. These preliminary findings underlined the benefit of grape seed extracts valorization due to their health-promoting properties.


greenmedinfo--2020-05-29--Masks Don't Work - A Review of Science Relevant to COVID-19 Social Policy

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greenmedinfo--2020-05-29--Grape seed proanthocyanidin extract ameliorates hepatic lipid accumulation and inflammation.

Hepatic lipid metabolism disorder due to excessive fat accumulation in fish is a significant problem in aquaculture .
Studies have shown that grape seed procyanidin extract ( GSPE ) can regulate fish lipid metabolism and improve fish immunity .
However , the mechanism is unclear .
In this study , we used grass carp that stores excess fat in the liver as a model .
In vitro , GSPE treatment of hepatocytes for 3 h significantly decreased TG content , accompanied with decreased expression of SREBP-1c , FAS , and ACC and increased expression of PPARα , ATGL , and @ @ @ @ @ @ @ significantly decreased expression of pro-inflammatory cytokines ( TNFα , IL-6 , IL-1β , and NF-κB ) and increased the expression of anti-inflammatory cytokines ( IL-10 and TGF-β1 ) .
In vivo , the administration of GSPE significantly reduced high-fat diet-induced increase of serum CHOL , TG , and HDL , but increased LDL content .
GSPE treatment for 3 h increased expression of ATGL and LPL , and significantly decreased the expression of HFD-fed-induced SREBP-1c , ACC , FAS , PPARγ , PPARα , and H-FABP .
GSPE treatment for 3 h also @ @ @ @ @ @ @ ( TNFα , IL-6 , and IL-1β ) and increased the expression of the anti-inflammatory cytokine IL-10 .
The expression levels of the lipogenic miRNAs , miR-33 , and miR-122 , were suppressed both in vivo and in vitro by GSPE .
In summary , GSPE had hypolipidemic and potential anti-inflammatory effects in the liver , potentially mediated by miR-33 and miR-122 .

Hepatic lipid metabolism disorder due to excessive fat accumulation in fish is a significant problem in aquaculture. Studies have shown that grape seed procyanidin extract (GSPE) can regulate fish lipid metabolism and improve fish immunity. However, the mechanism is unclear. In this study, we used grass carp that stores excess fat in the liver as a model. In vitro, GSPE treatment of hepatocytes for 3 h significantly decreased TG content, accompanied with decreased expression of SREBP-1c, FAS, and ACC and increased expression of PPARα, ATGL, and LPL. GSPE treatment for 1 h significantly decreased expression of pro-inflammatory cytokines (TNFα, IL-6, IL-1β, and NF-κB) and increased the expression of anti-inflammatory cytokines (IL-10 and TGF-β1). In vivo, the administration of GSPE significantly reduced high-fat diet-induced increase of serum CHOL, TG, and HDL, but increased LDL content. GSPE treatment for 3 h increased expression of ATGL and LPL, and significantly decreased the expression of HFD-fed-induced SREBP-1c, ACC, FAS, PPARγ, PPARα, and H-FABP. GSPE treatment for 3 h also significantly decreased the expression of pro-inflammatory cytokines (TNFα, IL-6, and IL-1β) and increased the expression of the anti-inflammatory cytokine IL-10. The expression levels of the lipogenic miRNAs, miR-33, and miR-122, were suppressed both in vivo and in vitro by GSPE. In summary, GSPE had hypolipidemic and potential anti-inflammatory effects in the liver, potentially mediated by miR-33 and miR-122.


greenmedinfo--2020-05-29--Pomegranate, rosemary and antibiotic combinations may be an effective therapeutic agent for antibiot

Pomegranate, rosemary and antibiotic combinations may be an effective therapeutic agent for antibiotic resistance and biofilm formation of P. aeruginosa.

The combination of plant extract and antibiotic represents a template for developing of antibiofilm drugs .
This study investigated the synergistic effects of pomegranate/rosemary/antibiotic combinations against antibiotic resistance and biofilm formation of Pseudomonas aeruginosa .
The results showed that 17 ( 85 % ) of total P. aeruginosa isolates were biofilm producers ; however , 5 ( 25 % ) isolates were demonstrated as a strong biofilm producer .
The highest MIC level ( 1024 μg/ml ) of tested antibiotics against strong biofilm producer isolates was observed with piperacillin , however the MIC ranges of ceftazidime , gentamycin , imipenem @ @ @ @ @ @ @ reached to ( 256-1024 μg/ml ) , ( 32-1024 μg/ml ) , ( 8-1024 μg/ml ) , and ( 8-512 μg/ml ) , respectively .
PS-1 was the representative isolate for strong biofilm formation and high antibiotic resistance .
16S rRNA gene analysis suggested that PS-1 ( accession No .
MN619678 ) was identified as a strain of P. aeruginosa POA1 .
Pomegranate and rosemary extracts were the most effective extracts in biofilm inhibition , which significantly inhibited 91.93 and 90.83 % of PS-1 biofilm , respectively .
Notably , the synergism between @ @ @ @ @ @ @ reduced the MICs of used antibiotics at the level lower than the susceptibility breakpoints .
Pomegranate/rosemary/antibiotic combinations achieved the highest biofilm eradication , which ranging from 90.0 to 99.6 % , followed by the eradication ranges of pomegranate/rosemary combination , rosemary , and pomegranate extracts , which reached to ( 76.5-85.4 % ) , ( 53.1-73.7 % ) , and ( 41.2-71.5 % ) , respectively .
The findings suggest that pomegranate/rosemary/antibiotic combinations may be an effective therapeutic agent for antibiotic resistance and biofilm formation of P. aeruginosa .

The combination of plant extract and antibiotic represents a template for developing of antibiofilm drugs. This study investigated the synergistic effects of pomegranate/rosemary/antibiotic combinations against antibiotic resistance and biofilm formation of Pseudomonas aeruginosa. The results showed that 17 (85%) of total P. aeruginosa isolates were biofilm producers; however, 5 (25%) isolates were demonstrated as a strong biofilm producer. The highest MIC level (1024 μg/ml) of tested antibiotics against strong biofilm producer isolates was observed with piperacillin, however the MIC ranges of ceftazidime, gentamycin, imipenem, and levofloxacin against these isolates were reached to (256-1024 μg/ml), (32-1024 μg/ml), (8-1024 μg/ml), and (8-512 μg/ml),respectively. PS-1 was the representative isolate for strong biofilm formation and high antibiotic resistance. 16S rRNA gene analysis suggested that PS-1 (accession No. MN619678) was identified as a strain of P. aeruginosa POA1. Pomegranate and rosemary extracts were the most effective extracts in biofilm inhibition, which significantly inhibited 91.93 and 90.83% of PS-1 biofilm, respectively. Notably, the synergism between both plant extracts and antibiotics has significantly reduced the MICs of used antibiotics at the level lower than the susceptibility breakpoints. Pomegranate/rosemary/antibiotic combinations achieved the highest biofilm eradication, which ranging from 90.0 to 99.6%, followed by the eradication ranges of pomegranate/rosemary combination, rosemary, and pomegranate extracts, which reached to (76.5-85.4%), (53.1-73.7%), and (41.2-71.5%), respectively. The findings suggest that pomegranate/rosemary/antibiotic combinations may be an effective therapeutic agent for antibiotic resistance and biofilm formation of P. aeruginosa.


greenmedinfo--2020-05-29--Ellagic acid and human cancers: a systems pharmacology and docking study.

Research on anticancer properties of natural compounds , as effective materials that are available while causing minimal side effects , is growing .
Ellagic acid ( EA ) is a well-known polyphenolic compound , which has been found in both free and complex modes in several medicinal plants such as pomegranate , walnut , and berries .
Although many articles have reported anticancer properties for this compound , its mechanism of action has not been fully elucidated .
In this study , we used several online and offline bioinformatics tools and databases to identify the mechanism of action of EA @ @ @ @ @ @ @ bladder , blood , breast , cervical , colorectal , liver , pancreas , and prostate cancers .
In this context , after identifying and extracting EA-affected human genes/proteins that have been reported in various references , we built the related gene networks and determined functional hub genes .
In addition , docking was performed to recognize target proteins that react directly with EA and are in fact most affected by this compound .
Our findings revealed that EA exerts its anticancer effects by influencing specific hub genes in various types of cancers @ @ @ @ @ @ @ are affected by this natural compound .
Generally , it turned out that EA probably exerts most of its anticancer activities , through induction of apoptosis , as well as P53 and WNT signaling pathways , and also by affecting the expression of several hub genes such as CDKN1A , CDK4 , CDK2 , CDK6 , TP53 , JUN , CCNA2 , MAPK14 , CDK1 , and CCNB1 and especially interactions with some related proteins including P53 , CDK6 , and MAPK14 .

Research on anticancer properties of natural compounds, as effective materials that are available while causing minimal side effects, is growing. Ellagic acid (EA) is a well-known polyphenolic compound, which has been found in both free and complex modes in several medicinal plants such as pomegranate, walnut, and berries. Although many articles have reported anticancer properties for this compound, its mechanism of action has not been fully elucidated. In this study, we used several online and offline bioinformatics tools and databases to identify the mechanism of action of EA on various types of human malignancies including bladder, blood, breast, cervical, colorectal, liver, pancreas, and prostate cancers. In this context, after identifying and extracting EA-affected human genes/proteins that have been reported in various references, we built the related gene networks and determined functional hub genes. In addition, docking was performed to recognize target proteins that react directly with EA and are in fact most affected by this compound. Our findings revealed that EA exerts its anticancer effects by influencing specific hub genes in various types of cancers. Moreover, different cellular signaling pathways are affected by this natural compound. Generally, it turned out that EA probably exerts most of its anticancer activities, through induction of apoptosis, as well as P53 and WNT signaling pathways, and also by affecting the expression of several hub genes such as CDKN1A, CDK4, CDK2, CDK6, TP53, JUN, CCNA2, MAPK14, CDK1, and CCNB1 and especially interactions with some related proteins including P53, CDK6, and MAPK14.


greenmedinfo--2020-05-29--A herbal mixture from propolis, pomegranate, and grape pomace endowed with anti-inflammatory activit

A herbal mixture from propolis, pomegranate, and grape pomace endowed with anti-inflammatory activity in an in vivo rheumatoid arthritis model.

Rheumatoid arthritis ( RA ) is a chronic inflammatory autoimmune disease characterized by the production of inflammatory factors .
In order to overcome the side effects of currently used anti-inflammatory drugs , several attempts have been made to identify natural products capable of relieving RA symptoms .
In this work , a herbal preparation consisting of propolis , pomegranate peel , and Aglianico grape pomace ( PPP ) extracts ( 4:1:1 ) was designed and evaluated for its effect on a murine collagen-induced arthritis ( CIA ) model .
Firstly , the chemical contents of four different Italian propolis collected @ @ @ @ @ @ @ were here reported for the first time .
LC-MS analyses showed the presence of 38 constituents , identified in all propolis extracts , belonging to flavonoids and phenolic acids classes .
The Pietradefusi extract was the richest one and thus was selected to design the PPP preparation for the in vivo assay .
Our results highlight the impact of PPP on RA onset and progression .
By using in vivo CIA models , the treatment with PPP resulted in a delayed onset of the disease and alleviated the severity of the clinical symptoms @ @ @ @ @ @ @ PPP treatment was associated with a reduction in serum levels of IL-17 , IL-1b , and IL-17-triggering cytokines .

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by the production of inflammatory factors. In order to overcome the side effects of currently used anti-inflammatory drugs, several attempts have been made to identify natural products capable of relieving RA symptoms. In this work, a herbal preparation consisting of propolis, pomegranate peel, and Aglianico grape pomace (PPP) extracts (4:1:1) was designed and evaluated for its effect on a murine collagen-induced arthritis (CIA) model. Firstly, the chemical contents of four different Italian propolis collected in the Campania region (Italy) were here reported for the first time. LC-MS analyses showed the presence of 38 constituents, identified in all propolis extracts, belonging to flavonoids and phenolic acids classes. The Pietradefusi extract was the richest one and thus was selected to design the PPP preparation for the in vivo assay. Our results highlight the impact of PPP on RA onset and progression. By using in vivo CIA models, the treatment with PPP resulted in a delayed onset of the disease and alleviated the severity of the clinical symptoms. Furthermore, we demonstrated that early PPP treatment was associated with a reduction in serum levels of IL-17, IL-1b, and IL-17-triggering cytokines.


greenmedinfo--2020-05-29--From 9/11 to COVID-19: The United State[s] of Emergency


greenmedinfo--2020-05-29--Phenolic-rich pomegranate peel extract is evidenced as a safe herbal derived material promising for

The pomegranate phenolics are reported to have cutaneous benefits and to be effective in treating skin disorders , including hyperpigmentation .
In this context , a preparation method was developed by which to obtain phenolic-rich pomegranate peel extract .
Sinapic acid was presented as the major pomegranate peel phenolics , followed by gallic and ellagic acids , and 4 additional phenolics .
The extract exhibited strong antioxidant activity with antyrosinase inhibitory effect .
The skin hyperpigmentation treating potency was confirmed by the suppression of cellular melanogenesis through tyrosinase and TRP-2 inhibitions as examined in the B16F10 melanoma cells .
Cellular @ @ @ @ @ @ @ toward human dermal fibroblasts were evidenced , as well as an inhibitory effect against MMP-2 .
The extract was developed into the stable serum and mask .
The products were proved to be non-irritated in 30 Thai volunteers participating in a single application closed patch test .
A split-face , randomized , double-blind , placebo-controlled test of the skin lightening effect was evaluated in the 30 volunteers over 28 consecutive daily treatments and monitored by the Mexameter MX 18 .
The active serum and mask were better in facial skin lightening efficacy than @ @ @ @

The pomegranate phenolics are reported to have cutaneous benefits and to be effective in treating skin disorders, including hyperpigmentation. In this context, a preparation method was developed by which to obtain phenolic-rich pomegranate peel extract. Sinapic acid was presented as the major pomegranate peel phenolics, followed by gallic and ellagic acids, and 4 additional phenolics. The extract exhibited strong antioxidant activity with antyrosinase inhibitory effect. The skin hyperpigmentation treating potency was confirmed by the suppression of cellular melanogenesis through tyrosinase and TRP-2 inhibitions as examined in the B16F10 melanoma cells. Cellular antioxidant and proliferative activities of the extract toward human dermal fibroblasts were evidenced, as well as an inhibitory effect against MMP-2. The extract was developed into the stable serum and mask. The products were proved to be non-irritated in 30 Thai volunteers participating in a single application closed patch test. A split-face, randomized, double-blind, placebo-controlled test of the skin lightening effect was evaluated in the 30 volunteers over 28 consecutive daily treatments and monitored by the Mexameter MX 18. The active serum and mask were better in facial skin lightening efficacy than the placebo (p < 0.005). That was in accordance with the sensory evaluation scored by the volunteers. Phenolic-rich pomegranate peel extract is evidenced as a safe herbal derived material promising for skin hyperpigmentation treatment. Supportive information regarding chemical and biological profiles is presentedwith the confirmed safety and cutaneous benefits in volunteers.


greenmedinfo--2020-05-29--Berberine might attenuate the liver inflammatory response in the livers of rats with high-fat diet-i

Berberine might attenuate the liver inflammatory response in the livers of rats with high-fat diet-induced NAFLD.

BACKGROUND : Nonalcoholic fatty liver disease ( NAFLD ) has become the most common liver disease worldwide .
Recent studies have shown that the Angptl2 pathway mediated hepatic inflammatory response plays an important role in the progression of nonalcoholic fatty liver disease .
Our study investigated the possible molecular mechanisms of berberine ( BBR ) in the treatment of the liver inflammatory response in the livers of rats with high-fat diet-induced NAFLD via the Angptl2 pathway .
RESULTS : At the end of 12 weeks , compared with the control group rats , the high-fat- diet group rats showed obvious @ @ @ @ @ @ @ of pro-infalmmatory cytokines ( CCL2 , TNF-α ) were increased , the infiltration of inflammatory cells ( CCR2 ) was elevated , and the hepatic mRNA and protein levels of Angptl2 , NF-κB and Foxo1 were increased to different degrees .
Nevertheless , following treatment with BBR , liver tissue pathology , biochemical data , and Angptl2 pathway-related genes expression were significantly ameliorated .
CONCLUSIONS : Our findings demonstrate that BBR might attenuate the liver inflammatory response in the livers of rats with high-fat diet-induced NAFLD through the regulation of the Angptl2 pathway @

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has become the most common liver disease worldwide. Recent studies have shown that the Angptl2 pathway mediated hepatic inflammatory response plays an important role in the progression of nonalcoholic fatty liver disease. Our study investigated the possible molecular mechanisms of berberine (BBR) in the treatment of the liver inflammatory response in the livers of rats with high-fat diet-induced NAFLD via the Angptl2 pathway.
RESULTS: At the end of 12 weeks, compared with the control group rats, the high-fat- diet group rats showed obvious pathological and biochemical changes. The levels of pro-infalmmatory cytokines (CCL2, TNF-α) were increased, the infiltration of inflammatory cells (CCR2) was elevated, and the hepatic mRNA and protein levels of Angptl2, NF-κB and Foxo1 were increased to different degrees. Nevertheless, following treatment with BBR, liver tissue pathology, biochemical data, and Angptl2 pathway-related genes expression were significantly ameliorated.
CONCLUSIONS: Our findings demonstrate that BBR might attenuate the liver inflammatory response in the livers of rats with high-fat diet-induced NAFLD through the regulation of the Angptl2 pathway.


greenmedinfo--2020-05-29--Fingolimod in combination with berberine at reduced doses represents a novel therapy for ulcerative

Fingolimod in combination with berberine at reduced doses represents a novel therapy for ulcerative colitis.

The natural alkaloid berberine is being studied as a drug candidate for the treatment of ulcerative colitis ( UC ) .
Fingolimod is an immunomodulator approved for the treatment of multiple sclerosis .
Whether fingolimod use can be extended to UC and how it interacts with berberine remain unclear .
In the present study , the anti-inflammatory efficacies of berberine , fingolimod , and a combination of half-doses of them was examined in mice with dextran sulfate sodium-induced colitis .
In mice with subchronic colitis , 14-day oral administration of fingolimod had greater efficacy than berberine in ameliorating the disease @ @ @ @ @ @ @ , in mice with chronic colitis , 30-day oral administration of berberine was more effective than fingolimod except on splenic swelling .
Notably , the combination of half-doses of each drug was equally effective as the superior single drugs for two models and resulted in reduced splenic swelling in the chronic colitis model .
The inhibition of cytokine expression and STAT3 activation , as well as binding to the sphingosine 1-phosphate receptor by both drugs , contributed to the combination efficacy .
Our findings suggest that fingolimod in combination with berberine at reduced @ @ @ @ @ @ @ that attains satisfactory efficacy with reduced potentials for adverse effects .

The natural alkaloid berberine is being studied as a drug candidate for the treatment of ulcerative colitis (UC). Fingolimod is an immunomodulator approved for the treatment of multiple sclerosis. Whether fingolimod use can be extended to UC and how it interacts with berberine remain unclear. In the present study, the anti-inflammatory efficacies of berberine, fingolimod, and a combination of half-doses of them was examined in mice with dextran sulfate sodium-induced colitis. In mice with subchronic colitis, 14-day oral administration of fingolimod had greater efficacy than berberine in ameliorating the disease clinical severity and colon shortening. However, in mice with chronic colitis, 30-day oral administration of berberine was more effective than fingolimod except on splenic swelling. Notably, the combination of half-doses of each drug was equally effective as the superior single drugs for two models and resulted in reduced splenic swelling in the chronic colitis model. The inhibition of cytokine expression and STAT3 activation, as well as binding to the sphingosine 1-phosphate receptor by both drugs, contributed to the combination efficacy. Our findings suggest that fingolimod in combination with berberine at reduced doses represents a novel therapy for UC that attains satisfactory efficacy with reduced potentials for adverse effects.


greenmedinfo--2020-05-29--The antibacterial effect of silver nanoparticles on Staphylococcus epidermidis strains with differen

The antibacterial effect of silver nanoparticles on Staphylococcus epidermidis strains with different biofilm-forming ability.

Among many infectious diseases , infections caused by pathogens ofspecies exert a substantial influence upon human health , mainly due @ @ @ @ @ human skin and mucous membranes .
For that reason , an intensive search for new @ @ @ @ @ currently be observed worldwide .
In recent years , there has been growing interest in @ @ @ @ @ potential antibacterial effect .
The antibacterial activity of silver containing substances has been well recognized @ @ @ @ @ on the effect of silver nanoparticles on bacterial biofilm are scarce .
The aim of @ @ @ @ @ the influence of silver nanoparticles ( AgNPs ) with particle sizes in the range between @ @ @ @ @ and a concentration range from 1 to 10µg/mL , uponstrains with different biofilm-forming abilities ( @ @ @ @ @ revealed the highest level of antimicrobial activity for AgNPs in relation tostrains with BFA , @ @ @ @ @ the observed effect was proportional to the increasing particles ' size , and strains not @ @ @ @ @ to silver nanoparticles with the smallest examined size , which was 10 nm .

Among many infectious diseases, infections caused by pathogens ofspecies exert a substantial influence upon human health, mainly due to their continuous presence on human skin and mucous membranes. For that reason, an intensive search for new, effective anistaphyloccocal agents can currently be observed worldwide. In recent years, there has been growing interest in nanoparticles, as compounds with potential antibacterial effect. The antibacterial activity of silver containing substances has been well recognized, but thoughtful studies focused on the effect of silver nanoparticles on bacterial biofilm are scarce. The aim of this study was to assess the influence of silver nanoparticles (AgNPs) with particle sizes in the range between 10 and 100 nm, and a concentration range from 1 to 10µg/mL, uponstrains with different biofilm-forming abilities (BFAs). The studies revealed the highest level of antimicrobial activity for AgNPs in relation tostrains with BFA, and what is more, the observed effect was proportional to the increasing particles' size, and strains not forming biofilm were more susceptible to silver nanoparticles with the smallest examined size, which was 10 nm.


greenmedinfo--2020-05-29--AMPK and its activator berberine in the treatment of neurodegenerative diseases.

Neurodegenerative disorders are heterogeneous diseases associated with either acute or progressive neurodegeneration , causing the loss of neurons and axons @ @ @ @ @ ( CNS ) , showing high morbidity and mortality , and there are few effective @ @ @ @ @ the energy sensor adenosine 5'-monophosphate ( AMP ) -activated protein kinase ( AMPK ) and @ @ @ @ @ the common underlying pathological events of neurodegeneration including oxidative stress , neuroinflammation , mitochondrial disorder @ @ @ @ @ , autophagy disorder and neurovascular units disruption .
The above actions of berberine may mainly @ @ @ @ @ its downstream targets such as mammalian target of rapamycin ( mTOR ) , sirtuin1 ( @ @ @ @ @ erythroid-2 related factor-2 ( Nrf2 ) , nuclear factor-κB ( NF-κB ) , phosphoinositide 3-kinase @ @ @ @ @ PI3K/Akt ) , nicotinamide adenine dinucleotide ( NAD+ ) , and p38 mitogen-activated protein kinase @ @ @ @ @ It is hoped that this review will provide a powerful basis for further scientific exploration @ @ @ @ @ therapeutic potential against neurodegeneration .

Neurodegenerative disorders are heterogeneous diseases associated with either acute or progressive neurodegeneration, causing the loss of neurons and axons in the central nervous system (CNS), showing high morbidity and mortality, and there are few effective therapies. Here we summarized the energy sensor adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) and its agonist berberine can combat the common underlying pathological events of neurodegeneration including oxidative stress, neuroinflammation, mitochondrial disorder, glutamate excitotoxicity, apoptosis, autophagy disorder and neurovascular units disruption. The above actions of berberine may mainly depend on activating AMPK and its downstream targets such as mammalian target of rapamycin (mTOR), sirtuin1 (SIRT1) , nuclear factor erythroid-2 related factor-2 (Nrf2), nuclear factor-κB (NF-κB), phosphoinositide 3-kinase / protein kinase B (PI3K/Akt), nicotinamide adenine dinucleotide (NAD+ ), and p38 mitogen-activated protein kinase (p38 MAPK). It is hoped that this review will provide a powerful basis for further scientific exploration and development of berberine's therapeutic potential against neurodegeneration.


greenmedinfo--2020-05-29--Punicalagin played an important role in the attenuation of LPS-induced inflammatory responses in RAW

Punicalagin played an important role in the attenuation of LPS-induced inflammatory responses in RAW264.7 macrophages.

Punicalagin , a hydrolysable tannin of pomegranate juice , exhibits multiple biological effects , including inhibiting production of pro-inflammatory cytokines in macrophages .
Autophagy , an intracellular self-digestion process , has been recently shown to regulate inflammatory responses .
In this study , we investigated the anti-inflammatory potential of punicalagin in lipopolysaccharide ( LPS ) induced RAW264.7 macrophages and uncovered the underlying mechanisms .
Punicalagin significantly attenuated , in a concentration-dependent manner , LPS-induced release of NO and decreased pro-inflammatory cytokines TNF-α and IL-6 release at the highest concentration .
We found that punicalagin inhibited NF-κB and MAPK activation in @ @ @ @ @ @ @ revealed that punicalagin pre-treatment enhanced LC3II , p62 expression , and decreased Beclin1 expression in LPS-induced macrophages .
MDC assays were used to determine the autophagic process and the results worked in concert with Western blot analysis .
In addition , our observations indicated that LPS-induced releases of NO , TNF-α , and IL-6 were attenuated by treatment with autophagy inhibitor chloroquine , suggesting that autophagy inhibition participated in anti-inflammatory effect .
We also found that punicalagin downregulated FoxO3a expression , resulting in autophagy inhibition .
Overall these results suggested that punicalagin played @ @ @ @ @ @ @ LPS-induced inflammatory responses in RAW264.7 macrophages and that the mechanisms involved downregulation of the FoxO3a/autophagy signaling pathway .

Punicalagin, a hydrolysable tannin of pomegranate juice, exhibits multiple biological effects, including inhibiting production of pro-inflammatory cytokines in macrophages. Autophagy, an intracellular self-digestion process, has been recently shown to regulate inflammatory responses. In this study, we investigated the anti-inflammatory potential of punicalagin in lipopolysaccharide (LPS) induced RAW264.7 macrophages and uncovered the underlying mechanisms. Punicalagin significantly attenuated, in a concentration-dependent manner, LPS-induced release of NO and decreased pro-inflammatory cytokines TNF-α and IL-6 release at the highest concentration. We found that punicalagin inhibited NF-κB and MAPK activation in LPS-induced RAW264.7 macrophages. Western blot analysis revealed that punicalagin pre-treatment enhanced LC3II, p62 expression, and decreased Beclin1 expression in LPS-induced macrophages. MDC assays were used to determine the autophagic process and the results worked in concert with Western blot analysis. In addition, our observations indicated that LPS-induced releases of NO, TNF-α, and IL-6 were attenuated by treatment with autophagy inhibitor chloroquine, suggesting that autophagy inhibition participated in anti-inflammatory effect. We also found that punicalagin downregulated FoxO3a expression, resulting in autophagy inhibition. Overall these results suggested that punicalagin played an important role in the attenuation of LPS-induced inflammatory responses in RAW264.7 macrophages and that the mechanisms involved downregulation of the FoxO3a/autophagy signaling pathway.


greenmedinfo--2020-05-29--Advances on natural polyphenols as anticancer agents for skin cancer.

Polyphenols are one of most important phytochemicals distributing in herb plants , vegetables and fruits , which known as important anticancer agents .
Given the high incidence and mortality of skin cancer , this study aimed to uncover the chemopreventive effects of polyphenols against skin cancer metastasis .
Electronic databases including Scopus , PubMed , and Cochrane library were used to compile the literature from 2000 to August 2019 .
Only in vivo mechanistic studies with English full-texts were chosen for this review .
Polyphenols were included in this study if they were administered in purified form ; while total @ @ @ @ @ @ @ the 8254 primarily selected papers , only a final number of 34 studies were included .
The chemopreventive effects of polyphenols as anthocyanins , ellagitanins , EGCG , oleuropeindihydroxy phenyl , punicalagin , quercetin , resveratrol and theaflavin , were mainly examined in treatment of melanoma as the highly metastatic form of this cutaneous cancer .
Those properties are mediated by modulation of angiogenesis , apoptosis , inflammation , metastasis , proliferation , pathways such as EGFR/MAPK , mTOR/PI3K/Akt , JAK/STAT , FAK/RTK2 , PGE-2/VEGF , PGE-1/ERK/HIIF-1α , and modulation of related signals @ @ @ @ @ @ @ Bax , Bcl2 , Bclx , Bim , Puma , Noxa , ILs and MMPs .
Chemopreventive effects of polyphenols are mediated by several signaling pathways against skin carcinogenesis and metastasis , implying the importance of polyphenols to open up new horizons in development of anti-skin cancer therapeutic strategies .

Polyphenols are one of most important phytochemicals distributing in herb plants, vegetables and fruits, which known as important anticancer agents. Given the high incidence and mortality of skin cancer, this study aimed to uncover the chemopreventive effects of polyphenols against skin cancer metastasis. Electronic databases including Scopus, PubMed, and Cochrane library were used to compile the literature from 2000 to August 2019. Only in vivo mechanistic studies with English full-texts were chosen for this review. Polyphenols were included in this study if they were administered in purified form; while total extract and fractions were excluded. Among the 8254 primarily selected papers, only a final number of 34 studies were included. The chemopreventive effects of polyphenols as anthocyanins, ellagitanins, EGCG, oleuropeindihydroxy phenyl, punicalagin, quercetin, resveratrol and theaflavin, were mainly examined in treatment of melanoma as the highly metastatic form of this cutaneous cancer. Those properties are mediated by modulation of angiogenesis, apoptosis, inflammation, metastasis, proliferation, pathways such as EGFR/MAPK, mTOR/PI3K/Akt, JAK/STAT, FAK/RTK2, PGE-2/VEGF, PGE-1/ERK/HIIF-1α, and modulation of related signals including NF-κB, P21, Bim, Bax, Bcl2, Bclx, Bim, Puma, Noxa, ILs and MMPs. Chemopreventive effects of polyphenols are mediated by several signaling pathways against skin carcinogenesis and metastasis, implying the importance of polyphenols to open up new horizons in development of anti-skin cancer therapeutic strategies.


greenmedinfo--2020-05-29--Pomegranate as a aource of bioactive constituents: a review on their characterization, properties an

Pomegranate as a aource of bioactive constituents: a review on their characterization, properties and applications.

Increasing awareness about the use of compounds obtained from natural sources exerting health-beneficial properties , including antimicrobial and antioxidant effects , led to increased number of research papers focusing on the study of functional properties of target compounds to be used as functional foods or in preventive medicine .
Pomegranate has shown positive health properties due to the presence of bioactive constituents such as polyphenols , tannins , and anthocyanins .
Punicalagin is the major antioxidant , abundantly found in pomegranate 's peel .
Research has shown that pomegranate polyphenols not only have a strong antioxidant capacity but they also @ @ @ @ @ @ @ , and , andfactor , and inhibits fungi such as , and .
Compounds of natural origin inhibit the growth of various pathogens by extending the shelf life of foodstuffs and assuring their safety .
Therefore , the need to find compounds to be used in combination with antibiotics or as new antimicrobial sources , such as plant extracts .
On the basis of the above discussion , this review focuses on the health benefits of pomegranate , by summarizing the current body of research focusing on pomegranate bioactive constituents and their therapeutic @ @ @ @ @ @

Increasing awareness about the use of compounds obtained from natural sources exerting health-beneficial properties, including antimicrobial and antioxidant effects, led to increased number of research papers focusing on the study of functional properties of target compounds to be used as functional foods or in preventive medicine. Pomegranate has shown positive health properties due to the presence of bioactive constituents such as polyphenols, tannins, and anthocyanins. Punicalagin is the major antioxidant, abundantly found in pomegranate's peel. Research has shown that pomegranate polyphenols not only have a strong antioxidant capacity but they also inhibit the growth of pathogenic bacteria like,and,andfactor, and inhibits fungi such as, and. Compounds of natural origin inhibit the growth of various pathogens by extending the shelf life of foodstuffs and assuring their safety. Therefore, the need to find compounds to be used in combination with antibiotics or as new antimicrobial sources, such as plant extracts. On the basis of the above discussion, this review focuses on the health benefits of pomegranate, by summarizing the current body of research focusing on pomegranate bioactive constituents and their therapeutic potential against some pathogenic microbes.


greenmedinfo--2020-05-29--Punicalagin inhibits the viability, migration, invasion, and EMT by regulating GOLPH3 in breast canc

Punicalagin inhibits the viability, migration, invasion, and EMT by regulating GOLPH3 in breast cancer cells.

Breast cancer ( BC ) is one of the most common malignancies worldwide .
Punicalagin ( PN ) , which is a type of polyphenol , has been reported to act as a tumor suppressor .
This study aimed to investigate the effects of PN on cellular process in BC and its molecular mechanism .
The effects of various doses of PN on cell viability , migration , and invasion capacities of MCF-7 and MDA-MB-231 cells were detected by CCK-8 , wound-healing , and Transwell assays .
Golgi phosphoprotein 3 ( GOLPH3 ) was then transfected into the cells with @ @ @ @ @ @ @ expression level was examined by quantitative real-time polymerase chain reaction ( qRT-PCR ) and Western blot , and expressions of epithelial-mesenchymal transition ( EMT ) -related protein matrix metalloproteinase-2 ( MMP-2 ) , matrix metalloproteinase-9 ( MMP-9 ) , E-Cadherin , and N-Cadherin were measured by Western blot .
High dose of PN treatment ( 50 μM or higher ) significantly inhibited viability , migration , and invasion of MCF-7 and MDA-MB-231 cells , while overexpressed GOLPH3 promoted cell viability , migration , and invasion , and partially reversed the effects of PN @ @ @ @ @ @ @ inhibited the expressions of GOLPH3 , MMP-2 , MMP-9 , and N-Cadherin , and promoted E-Cadherin expression , while overexpression of GOLPH3 partly reversed above effects attributing to PN .
Thus , PN suppresses cell viability and metastasisregulating GOLPH3 in BC , which provides a possible therapeutic direction to the treatment of BC .

Breast cancer (BC) is one of the most common malignancies worldwide. Punicalagin (PN), which is a type of polyphenol, has been reported to act as a tumor suppressor. This study aimed to investigate the effects of PN on cellular process in BC and its molecular mechanism. The effects of various doses of PN on cell viability, migration, and invasion capacities of MCF-7 and MDA-MB-231 cells were detected by CCK-8, wound-healing, and Transwell assays. Golgi phosphoprotein 3 (GOLPH3) was then transfected into the cells with or without PN treatment, and GPLPH3 expression level was examined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot, and expressions of epithelial-mesenchymal transition (EMT)-related protein matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), E-Cadherin, and N-Cadherin were measured by Western blot. High dose of PN treatment (50 μM or higher) significantly inhibited viability, migration, and invasion of MCF-7 and MDA-MB-231 cells, while overexpressed GOLPH3 promoted cell viability, migration, and invasion, and partially reversed the effects of PN treatment on the BC cells. PN inhibited the expressions of GOLPH3, MMP-2,MMP-9, and N-Cadherin, and promoted E-Cadherin expression, while overexpression of GOLPH3 partly reversed above effects attributing to PN. Thus, PN suppresses cell viability and metastasisregulating GOLPH3 in BC, which provides a possible therapeutic direction to the treatment of BC.


greenmedinfo--2020-05-29--Punicalagin promotes the apoptosis in human cervical cancer.

Increasing attention of plant derived therapeutic agents against cancer , investigating the anti-proliferative efficiency of plant derived chemicals have achieved increasing momentum for the design of anticancer drug .
Punicalagin , dietary phytochemical altered the various cell signal transduction pathways associated with cell apoptosis and proliferation .
This investigation was intended to examine the efficiency of punicalagin lying on cell viability so as to examine the molecular based punicalagin mechanism stimulated apoptosis via exploring the expression of Bcl-2 family proteins , and caspases also the cell cycle regulatory proteins p53 and NF-κB signaling in human cervical cancer cells .
We @ @ @ @ @ @ @ mitochondrial membrane depolarization , reactive oxygen species ( ROS ) generation , TUNEL assay , AO/EtBr analysis in cervical cancer cells .
Our findings demonstrated that punicalagin repressed the viability of cervical cancer cells in a dosereliant mode via stimulating mitochondrial mediated apoptosis .
Moreover , our this study demonstrated that punicalagin blocked cervical cancer cell proliferation and stimulated cell apoptosis by suppressing NF-kappa B activity .
Hence our study suggested that punicalagin exhibits opposing actions on NF-kappa B signaling networks to block cancer cell progression acts as a classical candidate for anticancer @ @ @

Increasing attention of plant derived therapeutic agents against cancer, investigating the anti-proliferative efficiency of plant derived chemicals have achieved increasing momentum for the design of anticancer drug. Punicalagin, dietary phytochemical altered the various cell signal transduction pathways associated with cell apoptosis and proliferation. This investigation was intended to examine the efficiency of punicalagin lying on cell viability so as to examine the molecular based punicalagin mechanism stimulated apoptosis via exploring the expression of Bcl-2 family proteins, and caspases also the cell cycle regulatory proteins p53 and NF-κB signaling in human cervical cancer cells. We also analyzed the morphological characteristic changes through mitochondrial membrane depolarization, reactive oxygen species (ROS) generation, TUNEL assay, AO/EtBr analysis in cervical cancer cells. Our findings demonstrated that punicalagin repressed the viability of cervical cancer cells in a dosereliant mode via stimulating mitochondrial mediated apoptosis. Moreover, our this study demonstrated that punicalagin blocked cervical cancer cell proliferation and stimulated cell apoptosis by suppressing NF-kappa B activity. Hence our study suggested that punicalagin exhibits opposing actions on NF-kappa B signaling networks to block cancer cell progression acts as a classical candidate for anticancer drug designing.


greenmedinfo--2020-05-29--Intravenous Vitamin C as a Potential Antiviral Treatment


greenmedinfo--2020-05-30--Judy Mikovits, the Plandemic Video, and the Casualty of Truth: The Questionable Science on Both Side

Judy Mikovits, the Plandemic Video, and the Casualty of Truth: The Questionable Science on Both Sides of This Issue


greenmedinfo--2020-05-30--Sulforaphane suppresses carcinogenesis of colorectal cancer.

The long pre‑cancerous state of colorectal cancer ( CRC ) provides an opportunity to prevent the occurrence and development of CRC .
The detoxification of CRC food‑borne carcinogenic heterocyclic amines is highly dependent on UDP glucuronosyltransferase 1A ( UGT1A ) ‑mediated glucuronidation .
Sulforaphane ( SFN ) , a phytochemical , possesses antioxidant , anti‑inflammatory and anticarcinogenic effects on the prevention of CRC .
Previous studies revealed that SFN upregulates the expression of UGT1A .
The aim of the present study was to investigate the regulatory mechanism of SFN‑induced UGT1A upregulation and provide novel understanding on the basic research and @ @ @ @ @ @ @ study , the viability and proliferation of CRC cells ( HT‑29 and SW480 ) treated with SFN were assessed by MTT , colony formation and EdU assays .
Flow cytometry was used to detect the cell cycle arrest andapoptosis of cells treated with different concentrations of SFN .
The motility of cells was determined by wound healing and Transwell assays .
Nuclear factor , erythroid 2 like 2 ( Nrf2 ) short hairpin RNA ( shRNA ) and negative control shRNA lentiviruses were used for cell transfection .
Reverse transcription‑quantitative polymerase chain reaction @ @ @ @ @ @ @ the role of Nrf2 in SFN‑induced UGT1A .
HT‑29 and SW480 cells were divided into a control , an SFN and a PD98059 [ an extracellular signal‑regulated kinase ( ERK ) inhibitor ] + SFN group .
Western blottingdetected the protein levels of Nrf2 and UGT1A .
Intracellular levels of reactive oxygen species ( ROS ) were detected using a reactive oxygen assay kit .
The results revealed that SFN inhibits cell proliferation and colony formation , promotes apoptosis , and reduces the migratory ability of CRC cells .
The phosphorylation of ERK @ @ @ @ @ @ @ Furthermore , a significant increase in the levels of UGT1A was observed , which coincided with SFN‑induced upregulation of Nrf2 levels in nuclear fractions .
Pretreatment with PD58059 reversed the SFN‑induced subcellular translocation of Nrf2 and the expression of UGT1A .
In addition , SFN‑induced high levels of ROS in CRC cells may be associated with the ERK signaling pathway .
Collectively , these results indicated that SFN inhibited the proliferation of CRC cells and upregulated the expression of UGT1A in CRC cells via theERK/Nrf2 signaling pathway .

The long pre‑cancerous state of colorectal cancer (CRC) provides an opportunity to prevent the occurrence and development of CRC. The detoxification of CRC food‑borne carcinogenic heterocyclic amines is highly dependent on UDP glucuronosyltransferase 1A (UGT1A)‑mediated glucuronidation. Sulforaphane (SFN), a phytochemical, possesses antioxidant, anti‑inflammatory and anticarcinogenic effects on the prevention of CRC. Previous studies revealed that SFN upregulates the expression of UGT1A. The aim of the present study was to investigate the regulatory mechanism of SFN‑induced UGT1A upregulation and provide novel understanding on the basic research and chemoprevention of CRC. In the present study, the viability and proliferation of CRC cells (HT‑29 and SW480) treated with SFN were assessed by MTT, colony formation and EdU assays. Flow cytometry was used to detect the cell cycle arrest andapoptosis of cells treated with different concentrations of SFN. The motility of cells was determined by wound healing and Transwell assays. Nuclear factor, erythroid 2 like 2 (Nrf2) short hairpin RNA (shRNA) and negative control shRNA lentiviruses were used for cell transfection. Reverse transcription‑quantitative polymerase chain reaction and western blotting were employed to verify the role of Nrf2 in SFN‑induced UGT1A. HT‑29 and SW480 cells were divided into a control, an SFN and a PD98059 [an extracellular signal‑regulated kinase (ERK) inhibitor] + SFN group. Western blottingdetected the protein levels of Nrf2 and UGT1A. Intracellular levels of reactive oxygen species (ROS) were detected using a reactive oxygen assay kit. The results revealed that SFN inhibits cell proliferation and colony formation, promotes apoptosis, and reduces the migratory ability of CRC cells. The phosphorylation of ERK induced by SFN promoted Nrf2 accumulation. Furthermore, a significant increase in the levels of UGT1A was observed, which coincided with SFN‑induced upregulation of Nrf2 levels in nuclear fractions. Pretreatment with PD58059 reversed the SFN‑induced subcellular translocation of Nrf2 and the expression of UGT1A. In addition, SFN‑induced high levels of ROS in CRC cells may be associated with the ERK signaling pathway. Collectively, these results indicated that SFN inhibited the proliferation of CRC cells and upregulated the expression of UGT1A in CRC cells via theERK/Nrf2 signaling pathway.


greenmedinfo--2020-05-30--Sulforaphane as an adjunctive treatment for irritability in children with autism spectrum disorder.

AIM : Irritability related to autism spectrum disorder ( ASD ) complicates the management of ASD patients at home and in clinical settings .
In this randomized , double-blind , placebo-controlled clinical trial , we aimed to investigate the beneficial effects of adjuvant treatment with risperidone and sulforaphane in alleviating the irritability of children with ASD .
METHODS : Sixty drug-free patients aged 4-12 years were randomly assigned to one of two groups receiving risperidone plus sulforaphane or placebo .
Risperidone was started with a daily dose of 0.25 mg in patients weighing < 20 kg and 0.5 mg in @ @ @ @ @ @ @ to reach a maximum of 1 mg ( < 20 kg ) , 2.5 mg ( 20-45 kg ) , and 3.5 mg ( > 45 kg ) .
Sulforaphane was administered at a daily dose of 50 μmol ( ≤45 kg ) or 100 μmol ( > 45 kg ) .
The participants were assessed with the Aberrant Behavior Checklist - Community Edition at baseline and at Weeks 5 and 10 .
RESULTS : Compared to the placebo group , ASD patients in the sulforaphane group showed greater improvements in Irritability score @ @ @ @ @ @ @ 0.001 ) and Hyperactivity/Noncompliance score ( secondary outcome measure ; P = 0.015 ) , and significant Time × Treatment effect for Irritability ( P = 0.007 ) and Hyperactivity/Noncompliance ( P = 0.008 ) .
However , no difference was seen in improvements in the other secondary measures : Lethargy/Social Interaction score , Stereotypic Behavior score , Inappropriate Speech score , and frequency of adverse events .
CONCLUSION : Our results support the safety and efficacy of sulforaphane as an adjuvant to risperidone for improvement of irritability and hyperactivity symptoms in children @ @ @

AIM: Irritability related to autism spectrum disorder (ASD) complicates the management of ASD patients at home and in clinical settings. In this randomized, double-blind, placebo-controlled clinical trial, we aimed to investigate the beneficial effects of adjuvant treatment with risperidone and sulforaphane in alleviating the irritability of children with ASD.
METHODS: Sixty drug-free patients aged 4-12 years were randomly assigned to one of two groups receiving risperidone plus sulforaphane or placebo. Risperidone was started with a daily dose of 0.25 mg in patients weighing<20 kg and 0.5 mg in those weighing ≥20 kg and increased stepwise to reach a maximum of 1 mg (<20 kg), 2.5 mg (20-45 kg), and 3.5 mg (>45 kg). Sulforaphane was administered at a daily dose of 50 μmol (≤45 kg) or 100 μmol (>45 kg). The participants were assessed with the Aberrant Behavior Checklist - Community Edition at baseline and at Weeks 5 and 10.
RESULTS: Compared to the placebo group, ASD patients in the sulforaphane group showed greater improvements in Irritability score (primary outcome measure; P = 0.001) and Hyperactivity/Noncompliance score (secondary outcome measure; P = 0.015), and significant Time × Treatment effect for Irritability (P = 0.007) and Hyperactivity/Noncompliance (P = 0.008). However, no difference was seen in improvements in the other secondary measures: Lethargy/Social Interaction score, Stereotypic Behavior score, Inappropriate Speech score, and frequency of adverse events.
CONCLUSION: Our results support the safety and efficacy of sulforaphane as an adjuvant to risperidone for improvement of irritability and hyperactivity symptoms in children with ASD.


greenmedinfo--2020-05-30--Sulforaphane ameliorates serum starvation-induced muscle atrophy.

Oxidative stress , an imbalance of redox homeostasis , contributes to the pathogenesis and progress of muscle atrophy .
However , it is debated whether oxidative stress is a cause or consequence of muscle atrophy .
In this study , we investigated the relationship between menadione-induced oxidative stress and serum starvation-induced muscle atrophy in C2C12 myotubes .
We found that atrophic phenotypes including myotube diameter decrease , protein ubiquitination , and the expression of atrogenes like Forkhead box O , atrogin-1 and MuRF1 were detected under oxidative stress as well as during serum starvation .
Oxidative stress during serum starvation @ @ @ @ @ @ @ Both intracellular reactive oxygen species ( ROS ) and protein oxidation were increased in atrophic myotubes .
These results indicate that menadione-induced oxidative stress triggers muscle atrophy and vice versa .
Nuclear factor erythroid 2-related factor 2 ( Nrf2 ) is a key regulator of cellular response to oxidative stress and it is considered to have a cytoprotective role in the mitigation of muscle atrophy .
Transcription of heme oxygenase-1 ( HO-1 ) and NAD ( P ) H quinone dehydrogenase-1 ( NQO-1 ) , target genes of Nrf2 , was decreased during @ @ @ @ @ @ @ decreased nuclear translocation of Nrf2 .
Pre-treatment of sulforaphane ( SFN ) , a known Nrf2 inducer , before serum starvation showed a protective effect via Nrf2/HO-1 upregulation .
SFN can liberate Nrf2 from Keap1 , enabling the nuclear translocation of Nrf2 .
Consequently , the expression of HO-1 increased and intracellular ROS was significantly reduced by SFN pre-treatment .
These results demonstrate that oxidative stress mediates the pathophysiology of muscle atrophy , which can be improved via upregulation of the Nrf2-mediated antioxidant response .
This article is protected by copyright .
All @ @ @

Oxidative stress, an imbalance of redox homeostasis, contributes to the pathogenesis and progress of muscle atrophy. However, it is debated whether oxidative stress is a cause or consequence of muscle atrophy. In this study, we investigated the relationship between menadione-induced oxidative stress and serum starvation-induced muscle atrophy in C2C12 myotubes. We found that atrophic phenotypes including myotube diameter decrease, protein ubiquitination, and the expression of atrogenes like Forkhead box O, atrogin-1 and MuRF1 were detected under oxidative stress as well as during serum starvation. Oxidative stress during serum starvation was assessed to confirm the correlation. Both intracellular reactive oxygen species (ROS) and protein oxidation were increased in atrophic myotubes. These results indicate that menadione-induced oxidative stress triggers muscle atrophy and vice versa. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key regulator of cellular response to oxidative stress and it is considered to have a cytoprotective role in the mitigation of muscle atrophy. Transcription of heme oxygenase-1 (HO-1) and NAD(P)H quinone dehydrogenase-1 (NQO-1), target genes of Nrf2, was decreased during serum starvation, which is related to decreased nuclear translocation of Nrf2. Pre-treatment of sulforaphane (SFN), a known Nrf2 inducer, before serum starvation showed a protective effect via Nrf2/HO-1 upregulation. SFN can liberate Nrf2 from Keap1, enabling the nuclear translocation of Nrf2. Consequently, the expression of HO-1 increased and intracellular ROS was significantly reduced by SFN pre-treatment. These results demonstrate that oxidative stress mediates the pathophysiology of muscle atrophy, which can be improved via upregulation of the Nrf2-mediated antioxidant response. This article is protected by copyright. All rights reserved.


greenmedinfo--2020-05-30--Sulforaphane potentiates anticancer effects of doxorubicin and cisplatin and mitigates their toxic e

Sulforaphane potentiates anticancer effects of doxorubicin and cisplatin and mitigates their toxic effects.

The success of cancer therapy is often compromised by the narrow therapeutic index of many anticancer drugs and the occurrence @ @ @ @ @ association of anticancer therapies with natural compounds is an emerging strategy to improve the pharmaco-toxicological @ @ @ @ @ Sulforaphane , a phytochemical found in cruciferous vegetables , targets multiple pathways involved in cancer @ @ @ @ @ different cancers such as breast , brain , blood , colon , lung , prostate @ @ @ @ @ As examples to make the potentialities of the association chemotherapy raise , here we highlight @ @ @ @ @ available for two associations , each composed by a paradigmatic anticancer drug ( cisplatin or @ @ @ @ @

The success of cancer therapy is often compromised by the narrow therapeutic index of many anticancer drugs and the occurrence of drug resistance. The association of anticancer therapies with natural compounds is an emerging strategy to improve the pharmaco-toxicological profile of cancer chemotherapy. Sulforaphane, a phytochemical found in cruciferous vegetables, targets multiple pathways involved in cancer development, as recorded in different cancers such as breast, brain, blood, colon, lung, prostate, and so forth. As examples to make the potentialities of the association chemotherapy raise, here we highlight and critically analyze the information available for two associations, each composed by a paradigmatic anticancer drug (cisplatin or doxorubicin) and sulforaphane.


greenmedinfo--2020-05-30--Sulforaphane could enhance cisplatin sensitivity of ovarian carcinoma cells.

OBJECTIVES : Cisplatin is commonly applied as anticancer agent for various cancers , including ovarian cancer .
Unfortunately , the drug resistance frequently occurred which obstructing the effect of cisplatin on tumors .
The goal of our research was to investigate the reversal actions and the potential mechanisms of sulforaphane ( SFN ) on cisplatin resistance in ovarian carcinoma .
METHODS : The A2780 and IGROV1 cells and their cisplatin resistance cells A2780/CP70 and IGROV1-R10 were used in this study .
Cell viability was detected by CCK-8 .
The DNA repair was measured by comet assay .
The cisplatin transporter @ @ @ @ @ @ @ The concentration of intracellular cisplatin was detected by HPLC .
The luciferase activity assay was applied to determine the target site of miR-30a-3p on the 3'UTR of ERCC1 and ATP7A .
A2780/CP70 and IGROV1-R10 xenograft mouse model were established to confirm the antineoplastic action of SFN combined with cisplatin .
RESULTS : SFN reversed the resistance of A2780/CP70 and IGROV1-R10 ovarian carcinoma cells to cisplatin through inducing DNA damage and accumulation of intracellular cisplatin .
SFN treatment notably increased miR-30a-3p expression , which was decreased in cisplatin-resistant cells .
Moreover , overexpressed miR-30a-3p @ @ @ @ @ @ @ cells to cisplatin treatment , and inhibiting miR-30a-3p activity abated the reversal actions of SFN on cisplatin resistance .
The luciferase assay findings showed that miR-30a-3p binds to ERCC1 and ATP7A which are the key regulators for DNA repair and cisplatin transportation .
CONCLUSIONS : Our findings indicated that SFN could enhance cisplatin sensitivity of ovarian carcinoma cells through up-regulating miR-30a-3p to induce DNA damage and accumulation of intracellular cisplatin .

OBJECTIVES: Cisplatin is commonly applied as anticancer agent for various cancers, including ovarian cancer. Unfortunately, the drug resistance frequently occurred which obstructing the effect of cisplatin on tumors. The goal of our research was to investigate the reversal actions and the potential mechanisms of sulforaphane (SFN) on cisplatin resistance in ovarian carcinoma.
METHODS: The A2780 and IGROV1 cells and their cisplatin resistance cells A2780/CP70 and IGROV1-R10 were used in this study. Cell viability was detected by CCK-8. The DNA repair was measured by comet assay. The cisplatin transporter proteins were measured with western blotting. The concentration of intracellular cisplatin was detected by HPLC. The luciferase activity assay was applied to determine the target site of miR-30a-3p on the 3'UTR of ERCC1 and ATP7A. A2780/CP70 and IGROV1-R10 xenograft mouse model were established to confirm the antineoplastic action of SFN combined with cisplatin.
RESULTS: SFN reversed the resistance of A2780/CP70 and IGROV1-R10 ovarian carcinoma cells to cisplatin through inducing DNA damage and accumulation of intracellular cisplatin. SFN treatment notably increased miR-30a-3p expression, which was decreased in cisplatin-resistant cells. Moreover, overexpressed miR-30a-3p enhanced the sensitivity of A2780/CP70 and IGROV1-R10 cells to cisplatin treatment, and inhibiting miR-30a-3p activity abated the reversal actions of SFN on cisplatin resistance. The luciferase assay findings showed that miR-30a-3p binds to ERCC1 and ATP7A which are the key regulators for DNA repair and cisplatin transportation.
CONCLUSIONS: Our findings indicated that SFN could enhance cisplatin sensitivity of ovarian carcinoma cells through up-regulating miR-30a-3p to induce DNA damage and accumulation of intracellular cisplatin.


greenmedinfo--2020-05-30--Sulforaphane protects against skeletal muscle dysfunction in spontaneous type 2 diabetic Db/Db mice.

AIMS : Skeletal muscle diseases have become to be the most common complication in patients with type 2 diabetic mellitus ( T2DM ) .
However , the effective therapies against skeletal muscle diseases are not yet available .
Sulforaphane ( SFN ) is an organic isothiocyanate found in cruciferous plants .
Our aim was to explore whether SFN could attenuate the skeletal muscle diseases in spontaneous type 2 diabetic db/db mice .
MATERIALS AND METHODS : The db/m and littermate db/db mice were treated with SFN or dimethyl sulfoxide .
The grip strength of mice was measured by a grasping @ @ @ @ @ @ @ was used to perform the skeletal muscle .
The western blot was used to detect the nuclear factor E2-related factor 2/heme oxygenase 1 ( Nrf2/HO-1 ) signal pathway related proteins , and inflammatory and apoptotic associated proteins .
The mRNA levels of anti-inflammatory and anti-oxidative relative genes were detected by RT-QPCR .
KEY FINDINGS : We found that SFN could significantly increase the grip strength of the db/db mice .
The lean mass and gastrocnemius mass were increased in the db/db mice after administration with SFN .
Additionally , the db/db mice restored @ @ @ @ @ @ @ treatment .
Mechanistically , SFN could activate the Nrf2/HO-1 signal pathway , and downregulate the expression of inflammatory and apoptotic associated proteins .
Furthermore , SFN could also regulate the mRNA levels of anti-inflammatory and anti-oxidative related genes .
SIGNIFICANCE : Our results demonstrated that SFN can protect against skeletal muscle diseases in db/db type 2 diabetic mice and provide a potential drug to prevent skeletal muscle dysfunction in T2DM patients .

AIMS: Skeletal muscle diseases have become to be the most common complication in patients with type 2 diabetic mellitus (T2DM). However, the effective therapies against skeletal muscle diseases are not yet available. Sulforaphane (SFN) is an organic isothiocyanate found in cruciferous plants. Our aim was to explore whether SFN could attenuate the skeletal muscle diseases in spontaneous type 2 diabetic db/db mice.
MATERIALS AND METHODS: The db/m and littermate db/db mice were treated with SFN or dimethyl sulfoxide. The grip strength of mice was measured by a grasping forcing machine. The electron transmission microscopy was used to perform the skeletal muscle. The western blot was used to detect the nuclear factor E2-related factor 2/heme oxygenase 1 (Nrf2/HO-1) signal pathway related proteins, and inflammatory and apoptotic associated proteins. The mRNA levels of anti-inflammatory and anti-oxidative relative genes were detected by RT-QPCR.
KEY FINDINGS: We found that SFN could significantly increase the grip strength of the db/db mice. The lean mass and gastrocnemius mass were increased in the db/db mice after administration with SFN. Additionally, the db/db mice restored the skeletal muscle fiber organization after SFN treatment. Mechanistically, SFN could activate the Nrf2/HO-1 signal pathway, and downregulate the expression of inflammatory and apoptotic associated proteins. Furthermore, SFN could also regulate the mRNA levels of anti-inflammatory and anti-oxidative related genes.
SIGNIFICANCE: Our results demonstrated that SFN can protect against skeletal muscle diseases in db/db type 2 diabetic mice and provide a potential drug to prevent skeletal muscle dysfunction in T2DM patients.


greenmedinfo--2020-05-30--Sulforaphene enhances radiosensitivity of hepatocellular carcinoma through suppression of the NF-κB

Sulforaphene enhances radiosensitivity of hepatocellular carcinoma through suppression of the NF-κB pathway.

Sulforaphene ( SFE ) , a naturally occurring isothiocyanate found in cruciferous vegetables , has attracted increasing attention for its @ @ @ @ @ , including hepatocellular carcinoma ( HCC ) .
However , the precise role of SFE @ @ @ @ @ is still unclear .
Here , cell proliferation and apoptosis were detected by MTT and @ @ @ @ @ .
The activity of NF-κB was further evaluated by ELISA .
We also observed the @ @ @ @ @ on tumor growth .
The results showed that SFE inhibited cell proliferation and induced apoptosis @ @ @ @ @ increased NF-kB activity , while PDTC , a NF-kB inhibitor , enhanced radiation-induced cell death @ @ @ @ @ and the downstream gene expressions of the NF-kB pathway in HCC cells .
Moreover , @ @ @ @ @ of radiation on tumor growth both in vitro and in vivo .
This study indicated @ @ @ @ @ of HCC by blocking the NF-kB pathway .

Sulforaphene (SFE), a naturally occurring isothiocyanate found in cruciferous vegetables, has attracted increasing attention for its anti-cancer effect in many cancers, including hepatocellular carcinoma (HCC). However, the precise role of SFE in the radiosensitivity of HCC is still unclear. Here, cell proliferation and apoptosis were detected by MTT and flow cytometry assay, respectively. The activity of NF-κB was further evaluated by ELISA. We also observed the effect of SFE and/or radiation on tumor growth. The results showed that SFE inhibited cell proliferation and induced apoptosis in HCC cells. Radiation increased NF-kB activity, while PDTC, a NF-kB inhibitor, enhanced radiation-induced cell death. SFE inhibited NF-kB activity and the downstream gene expressions of the NF-kB pathway in HCC cells. Moreover, SFE enhanced the inhibitory effect of radiation on tumor growth both in vitro and in vivo. This study indicated that SFE sensitized the radiosensitivity of HCC by blocking the NF-kB pathway.


greenmedinfo--2020-05-30--Sulforaphene suppresses growth of colon cancer-derived tumors.

SCOPE : Cruciferous vegetables harbor a number of isothiocyanates that have been recognized for their cancer-related properties .
Out of @ @ @ @ @ naturally occurring derivative of sulforaphane ) has received little attention in studies of colon cancer @ @ @ @ @ remains to be elucidated .
METHODS AND RESULTS : We observed that sulforaphene inhibited growth @ @ @ @ @ lines HCT116 , HT-29 , KM12 , SNU-1040 , and DLD-1 , while exhibiting negligible @ @ @ @ @ Sulforaphene induced G2/M phase cell cycle arrest and apoptosis of colon cancer cells analyzed by @ @ @ @ @ phosphorylation of CDK1 and CDC25B at inhibitory sites , and upregulation of the p38 and @ @ @ @ @ further determined that sulforaphene is a potent inhibitor of microtubule polymerization while generating reactive oxygen @ @ @ @ @ glutathione .
These observations further extended into inhibitory effects against colon tumor growth in a @ @ @ @ @ : These findings demonstrate that sulforaphene may contribute to the anti-tumor effects of cruciferous vegetables @ @ @ @ @ isothiocyanates .

SCOPE: Cruciferous vegetables harbor a number of isothiocyanates that have been recognized for their cancer-related properties. Out of these, sulforaphene (a naturally occurring derivative of sulforaphane) has received little attention in studies of colon cancer and its mechanism of action remains to be elucidated.
METHODS AND RESULTS: We observed that sulforaphene inhibited growth of human colon cancer cell lines HCT116, HT-29, KM12, SNU-1040, and DLD-1, while exhibiting negligible toxicity toward nonmalignant cells. Sulforaphene induced G2/M phase cell cycle arrest and apoptosis of colon cancer cells analyzed by flow cytometry, concomitant with phosphorylation of CDK1 and CDC25B at inhibitory sites, and upregulation of the p38 and JNK pathways. It was further determined that sulforaphene is a potent inhibitor of microtubule polymerization while generating reactive oxygen species via the depletion of glutathione. These observations further extended into inhibitory effects against colon tumor growth in a mouse xenograft model.
CONCLUSION: These findings demonstrate that sulforaphene may contribute to the anti-tumor effects of cruciferous vegetables that contain sulforaphene and other isothiocyanates.


greenmedinfo--2020-05-30--Sulforaphene enhances the efficacy of photodynamic therapy in anaplastic thyroid cancer.

Sulforaphene ( SFE ) , a natural isothiocyanate from cruciferous vegetables has shown a potential anticancer effect against cervical and lung cancer .
Palliative treatments like photodynamic therapy ( PDT ) are being implemented for a long time however , the results are still not promising in case of aggressive cancers like anaplastic thyroid cancer .
The objective of this work is to establish an alternative method with the combination of photofrin-PDT and sulforaphene , a natural isothiocyanate from cruciferous vegetables , against human anaplastic thyroid cancer to enhance the efficacy of PDT .
In this study , cell viability @ @ @ @ @ @ @ was analyzed by MTT assay , Cell cycle arrest , MMP depolarization and ROS generation , analyzed by flow cytometry .
Western blot analysis of various proliferative proteins was performed to assess the activity of combination treatment against FRO cells .
From the results , sulforaphene alone showed no cytotoxicity against normal cells , however , combination of sulforaphene and photofrin mediated PDT showed a noticeable decrease in cell proliferation against FRO cells .
Combination treatment synergistically caused cell cycle arrest via ROS generation and MMP depolarization .
The expressions of Ras , @ @ @ @ @ @ @ modulated due to combination treatment .
PDT and SFE can induce apoptosis in anaplastic thyroid cancer cells individually but while treated in combination , it enhanced the apoptotic and anti-proliferative effect , much higher than the individual doses .
In summary , our work designates sulforaphene as a unique natural enhancer of efficacy with PDT against anaplastic thyroid cancer .

Sulforaphene (SFE), a natural isothiocyanate from cruciferous vegetables has shown a potential anticancer effect against cervical and lung cancer. Palliative treatments like photodynamic therapy (PDT) are being implemented for a long time however, the results are still not promising in case of aggressive cancers like anaplastic thyroid cancer. The objective of this work is to establish an alternative method with the combination of photofrin-PDT and sulforaphene, a natural isothiocyanate from cruciferous vegetables, against human anaplastic thyroid cancer to enhance the efficacy of PDT. In this study, cell viability of FRO cells due to combination treatment was analyzed by MTT assay, Cell cycle arrest, MMP depolarization and ROS generation, analyzed by flow cytometry. Western blot analysis of various proliferative proteins was performed to assess the activity of combination treatment against FRO cells. From the results, sulforaphene alone showed no cytotoxicity against normal cells, however, combination of sulforaphene and photofrin mediated PDT showed a noticeable decrease in cell proliferation against FRO cells. Combination treatment synergistically caused cell cycle arrest via ROS generation and MMP depolarization. The expressions of Ras, MEK, ERK, B-Raf proteins significantly modulated due to combination treatment. PDT and SFE can induce apoptosis in anaplastic thyroid cancer cells individually but while treated in combination, it enhanced the apoptotic and anti-proliferative effect, much higher than the individual doses. In summary, our work designates sulforaphene as a unique natural enhancer of efficacy with PDT against anaplastic thyroid cancer.


greenmedinfo--2020-05-30--Sulforaphene induces apoptosis and inhibits the invasion of esophageal cancer.

Background : As a novel type of isothiocyanate derived from radish seeds from cruciferous vegetables , sulforaphene ( SFE , 4-methylsufinyl-3-butenyl isothiocyanate ) has various important biological effects , such as anti-oxidative and anti-bacterial effects .
Recently , sulforaphene has attracted increasing attention for its anti-tumor effects and its ability to suppress the development of multiple tumors through different regulatory mechanisms .
However , it has not yet been widely investigated for the treatment of esophageal cancer .
Methods : We observed an increased apoptosis in esophageal cancer cells on sulforaphene treatment through flow cytometry ( FCM ) analysis and @ @ @ @ @ @ @ Through mass spectrometry ( MS ) analysis , we further detected global changes in the proteomes and phosphoproteomes of esophageal cancer cells on sulforaphene treatment .
The molecular mechanism of sulforaphene was verified by western blot , the effect and mechanism of SFE on esophageal cancer was further verified by patient-derived xenograft mouse model .
Results : We identified multiple cellular processes that were changed after sulforaphene treatment by proteomics .
We found that sulforaphene could repress the phosphorylation of CREB through MSK2 , leading to suppression of Bcl-2 and further promoted cell @ @ @ @ @ @ @ sulforaphene induces tumor cell apoptosis in mice .
Interestingly , we also observed the obvious inhibition of cell migration and invasion caused by sulforaphene treatment by inhibiting the expression of cadherin , indicating the complex effects of sulforaphene on the development of esophageal cancer .
Conclusions : Our data demonstrated that sulforaphene induced cell apoptosis and inhibits the invasion of esophageal cancer through a mechanism involving the inhibition of the MSK2-CREB-Bcl2 and cadherin pathway .
Sulforaphene could therefore serve as a promising anti-tumor drug for the treatment of esophageal cancer .

Background: As a novel type of isothiocyanate derived from radish seeds from cruciferous vegetables, sulforaphene (SFE, 4-methylsufinyl-3-butenyl isothiocyanate) has various important biological effects, such as anti-oxidative and anti-bacterial effects. Recently, sulforaphene has attracted increasing attention for its anti-tumor effects and its ability to suppress the development of multiple tumors through different regulatory mechanisms. However, it has not yet been widely investigated for the treatment of esophageal cancer.
Methods: We observed an increased apoptosis in esophageal cancer cells on sulforaphene treatment through flow cytometry (FCM) analysis and transmission electron microscopy (TEM). Through mass spectrometry (MS) analysis, we further detected global changes in the proteomes and phosphoproteomes of esophageal cancer cells on sulforaphene treatment. The molecular mechanism of sulforaphene was verified by western blot,the effect and mechanism of SFE on esophageal cancer was further verified by patient-derived xenograft mouse model.
Results: We identified multiple cellular processes that were changed after sulforaphene treatment by proteomics. We found that sulforaphene could repress the phosphorylation of CREB through MSK2, leading to suppression of Bcl-2 and further promoted cell apoptosis. Additionally, we confirmed that sulforaphene induces tumor cell apoptosis in mice. Interestingly, we also observed the obvious inhibition of cell migration and invasion caused by sulforaphene treatment by inhibiting the expression of cadherin, indicating the complex effects of sulforaphene on the development of esophageal cancer.
Conclusions: Our data demonstrated that sulforaphene induced cell apoptosis and inhibits the invasion of esophageal cancer through a mechanism involving the inhibition of the MSK2-CREB-Bcl2 and cadherin pathway. Sulforaphene could therefore serve as a promising anti-tumor drug for the treatment of esophageal cancer.


greenmedinfo--2020-05-30--Sulforaphene inhibition of adipogenesis via hedgehog signaling in 3T3-L1 adipocytes.

Obesity is a risk factor for numerous metabolic disorders .
In this study , we investigated the effects of the @ @ @ @ @ and sulforaphene ( SE ) on adipogenesis in 3T3-L1 adipocytes .
SE , a compound @ @ @ @ @ , inhibited adipogenesis by suppressing the adipogenic transcription factors peroxisome proliferator-activated receptorγ ( PPARγ , @ @ @ @ @ P < 0.05 ) and CCAAT/enhancer-binding proteinα ( C/EBPα , 36.1 ± 3.1 % , @ @ @ @ @ thereby reducing fat accumulation in 3T3-L1 adipocytes ( 45.6± 2.7 % , P < 0.05 @ @ @ @ @ effective .
SE exerted these activities through the activation of the Hedgehog ( Hh ) @ @ @ @ @ ( ( 2.1± 0.2 ) -fold , P < 0.05 ) and Gli1 ( ( @ @ @ @ @ P < 0.05 ) expression , which was suppressed by adipogenic signals .
These effects @ @ @ @ @ treatment with the Hh inhibitor vismodegib .
Thus , SE inhibits adipocyte differentiation via Hh @ @ @ @ @ effective natural agent for preventing adipocyte hyperplasia and obesity .

Obesity is a risk factor for numerous metabolic disorders. In this study, we investigated the effects of the isothiocyanates sulforaphane (SA) and sulforaphene (SE) on adipogenesis in 3T3-L1 adipocytes. SE, a compound that is abundant in radish, inhibited adipogenesis by suppressing the adipogenic transcription factors peroxisome proliferator-activated receptorγ (PPARγ, 69.2 ± 2.4%, P<0.05) and CCAAT/enhancer-binding proteinα (C/EBPα, 36.1 ± 3.1%, P<0.05), thereby reducing fat accumulation in 3T3-L1 adipocytes (45.6± 2.7%, P<0.05); SA was less effective. SE exerted these activities through the activation of the Hedgehog (Hh) signaling pathway by restoring Smo ((2.1± 0.2)-fold, P<0.05) and Gli1 ((2.8± 0.1)-fold, P<0.05) expression, which was suppressed by adipogenic signals. These effects of SE were abrogated by treatment with the Hh inhibitor vismodegib. Thus, SE inhibits adipocyte differentiation via Hh signaling and may be an effective natural agent for preventing adipocyte hyperplasia and obesity.


greenmedinfo--2020-05-30--The attenuation of traumatic brain injury via inhibition of oxidative stress and apoptosis by Tanshi

The attenuation of traumatic brain injury via inhibition of oxidative stress and apoptosis by Tanshinone IIA.

Traumatic brain injury ( TBI ) is a major source of mortality and long-term disability worldwide .
The mechanisms associated with TBI development are poorly understood , and little progress has been made in the treatment of TBI .
Tanshinone IIA is an effective agent to treat a variety of disorders ; however , the mechanisms of Tanshinone IIA on TBI remain unclear .
The aim of the present study was to investigate the therapeutic potential of Tanshinone IIA on TBI and its underlying molecular mechanisms .
Changes in microvascular permeability were examined to determine the extent of TBI with @ @ @ @ @ @ @ assessed by measuring the wet weight to dry weight ratio .
The expression levels of CD11 , interleukin- ( IL- ) 1 , and tumor necrosis factor- ( TNF- ) mRNA were determined by reverse transcription-quantitative PCR .
Aquaporin-4 ( AQP4 ) , glial fibrillary acidic protein ( GFAP ) , and p47phox protein expression levels were detected by western blotting .
Superoxide dismutase ( SOD ) , catalase and glutathione peroxidase ( GSH-PX ) activities , and malondialdehyde ( MDA ) content were determined using commercial kits .
Cell apoptosis was detected @ @ @ @ @ @ @ Tanshinone IIA ( 10 mg/kg/day , intraperitoneal administration ) significantly reduced brain water content and vascular permeability at 12 , 24 , 48 , and 72 h after TBI .
Tanshinone IIA downregulated the mRNA expression levels of various factors induced by TBI , including CD11 , IL-1 , and TNF- .
Notably , CD11 mRNA downregulation suggested that Tanshinone IIA inhibited microglia activation .
Further results showed that Tanshinone IIA treatment significantly downregulated AQP4 and GFAP expression .
TBI-induced oxidative stress and apoptosis were markedly reversed by Tanshinone IIA , with an @ @ @ @ @ @ @ a decrease in the MDA content .
Moreover , Tanshinone IIA decreased TBI-induced NADPH oxidase activation via the inhibition of p47phox .
Tanshinone IIA attenuated TBI , and its mechanism of action may involve the inhibition of oxidative stress and apoptosis .

Traumatic brain injury (TBI) is a major source of mortality and long-term disability worldwide. The mechanisms associated with TBI development are poorly understood, and little progress has been made in the treatment of TBI. Tanshinone IIA is an effective agent to treat a variety of disorders; however, the mechanisms of Tanshinone IIA on TBI remain unclear. The aim of the present study was to investigate the therapeutic potential of Tanshinone IIA on TBI and its underlying molecular mechanisms. Changes in microvascular permeability were examined to determine the extent of TBI with Evans blue dye. Brain edema was assessed by measuring the wet weight to dry weight ratio. The expression levels of CD11, interleukin- (IL-) 1, and tumor necrosis factor- (TNF-)mRNA were determined by reverse transcription-quantitative PCR. Aquaporin-4 (AQP4), glial fibrillary acidic protein (GFAP), and p47phox protein expression levels were detected by western blotting. Superoxide dismutase (SOD), catalase and glutathione peroxidase (GSH-PX) activities, and malondialdehyde (MDA) content were determined using commercial kits. Cell apoptosis was detected by western blotting and TUNEL staining. Tanshinone IIA (10 mg/kg/day, intraperitoneal administration) significantly reduced brain water content and vascular permeability at 12, 24, 48, and 72 h after TBI. Tanshinone IIA downregulated the mRNA expression levels of various factors induced by TBI, including CD11, IL-1, and TNF-. Notably, CD11 mRNA downregulation suggested that Tanshinone IIA inhibited microglia activation. Further results showed that Tanshinone IIA treatment significantly downregulated AQP4 and GFAP expression. TBI-induced oxidative stress and apoptosis were markedly reversed by Tanshinone IIA, with an increase in SOD and GSH-PX activities and a decrease in the MDA content. Moreover, Tanshinone IIA decreased TBI-induced NADPH oxidase activation via the inhibition of p47phox. Tanshinone IIA attenuated TBI, and its mechanism of action may involve the inhibition of oxidative stress and apoptosis.