greenmedinfo--2020-05-10--Immunomodulatory potential of nanocurcumin-based formulation.

Vitamins , minerals , and nanocurcumin play a substantial role in various nutraceutical/pharmaceutical formulations that are widely used in therapeutics , cosmetics , and dietary supplements .
The current study aimed to investigate the comparative in vitro immunomodulatory effect of a novel nanocurcumin-based formulation with curcumin in LPS-induced cytokine expression , NK cells ' activity , and phagocytosis .
The proinflammatory cytokines ( TNF-α , IL-1β , and MIP-1α ) and NK cells ' activity were measured in cell supernatants using ELISA assay ; however , phagocytosis activity was performed using colorimetric analysis .
The chemical characterization of novel nanocurcumin-based @ @ @ @ @ @ @ and mass spectra analysis ( m/z 369.04 ) confirmed the presence of the curcumin in highest peak concentration .
MTT assay in three tested cell-lines showed that the formulation was found non-toxic at all the tested concentrations .
The expression of TNF-α , IL-1β , and MIP-1α in splenocytes wassignificantly ( p ≤ 0.001 ) inhibited .
Besides , the NK cells ' activity and phagocytosis ( macrophage ) were increased significantly ( p ≤ 0.001 ) .
Overall , the promising results of this study indicated the significant immunomodulatory effect of nanocurcumin-based @ @ @ @ @ @ @ could be used against various inflammatory disorders such as allergy , asthma , autoimmune diseases , coeliac disease , inflammatory bowel disease , etc .

Vitamins, minerals, and nanocurcumin play a substantial role in various nutraceutical/pharmaceutical formulations that are widely used in therapeutics, cosmetics, and dietary supplements. The current study aimed to investigate the comparative in vitro immunomodulatory effect of a novel nanocurcumin-based formulation with curcumin in LPS-induced cytokine expression, NK cells' activity, and phagocytosis. The proinflammatory cytokines (TNF-α, IL-1β, and MIP-1α) and NK cells' activity were measured in cell supernatants using ELISA assay; however, phagocytosis activity was performed using colorimetric analysis. The chemical characterization of novel nanocurcumin-based formulation using LC-MS (R19.02 min) and mass spectra analysis (m/z 369.04) confirmed the presence of the curcumin in highest peak concentration. MTT assay in three tested cell-lines showed that the formulation was found non-toxic at all the tested concentrations. The expression of TNF-α, IL-1β, and MIP-1α in splenocytes wassignificantly (p ≤ 0.001) inhibited. Besides, the NK cells' activity and phagocytosis (macrophage) were increased significantly (p ≤ 0.001). Overall, the promising results of this study indicated the significant immunomodulatory effect of nanocurcumin-based formulation compared to the curcumin, which could be used against various inflammatory disorders such as allergy, asthma, autoimmune diseases, coeliac disease, inflammatory bowel disease, etc.


greenmedinfo--2020-05-10--Immunomodulatory activities of curcumin-stabilized silver nanoparticles.

We synthesized and characterized curcumin-stabilized silver nanoparticles ( Cur-AgNP ) and found them to be 45 nm by dynamic light scattering with a maximum absorbance at 406 nm .
We evaluated Cur-AgNP for immunomodulatory activities and their potential as an antiretroviral agent .
The antiretroviral effects of Cur-AgNP were determined in ACH-2 cells latently infected with human immunodeficiency virus ( HIV ) -1 .
ACH-2 cells , 200,000/ml , were treated with Cur-AgNP for 24-48 h. Expression of HIV-1 LTR and p24 , the pro-inflammatory cytokines , IL-1β , TNF-α , and NF-κB was quantitated .
Treatment of ACH-2 cells @ @ @ @ @ @ @ no toxic effects but significantly inhibited the expression of HIV-1 LTR ( -73 % , P < 0.01 ) and p24 ( -57 % , P < 0.05 ) , IL-1βα ( -61 % , P < 0.01 ) , TNF-αα ( -54 % , P < 0.05 ) , IL-6 ( -68 % , P < 0.01 ) , and NF-κB ( -79 % , P < 0.0001 ) as compared to untreated controls .
Thus , Cur-AgNP have therapeutic potential as direct antiretroviral agents , as well as having immunomodulatory activities @ @ @ @ @ @ @ by infection with HIV-1 .
Experimental controls , such as curcumin alone , and conventional silver nanoparticles capped with citric acid , produced no similar biological effects .
We conclude that treatment of HIV-1 infected cells with Cur-AgNP significantly reduced replication of HIV by inhibition of NF-κB nuclear translocation and the downstream expression of the pro-inflammatory cytokines IL-1β , TNF-α , and IL-6 .
Subsequent in vivo studies with Cur-AgNP using a humanized mouse model of HIV infection are underway .

We synthesized and characterized curcumin-stabilized silver nanoparticles (Cur-AgNP) and found them to be 45 nm by dynamic light scattering with a maximum absorbance at 406 nm. We evaluated Cur-AgNP for immunomodulatory activities and their potential as an antiretroviral agent. The antiretroviral effects of Cur-AgNP were determined in ACH-2 cells latently infected with human immunodeficiency virus (HIV)-1. ACH-2 cells, 200,000/ml, were treated with Cur-AgNP for 24-48 h. Expression of HIV-1 LTR and p24, the pro-inflammatory cytokines, IL-1β, TNF-α, and NF-κB was quantitated. Treatment of ACH-2 cells latently infected with HIV-1 with Cur-AgNP produced no toxic effects but significantly inhibited the expression of HIV-1 LTR (-73%, P<0.01) and p24 (-57%, P<0.05), IL-1βα (-61%, P<0.01), TNF-αα (-54%, P<0.05), IL-6 (-68%, P<0.01), and NF-κB (-79%, P<0.0001) as compared to untreated controls. Thus, Cur-AgNP have therapeutic potential as direct antiretroviral agents, as well as having immunomodulatory activities inhibiting the expression of pro-inflammatory mediators induced by infection with HIV-1. Experimental controls, such as curcumin alone, and conventional silver nanoparticles capped with citric acid, produced no similar biological effects. We conclude that treatment of HIV-1 infected cells with Cur-AgNP significantly reduced replication of HIV by inhibition of NF-κB nuclear translocation and the downstream expression of the pro-inflammatory cytokines IL-1β, TNF-α, and IL-6. Subsequent in vivo studies with Cur-AgNP using a humanized mouse model of HIV infection are underway.


greenmedinfo--2020-05-10--Comic Relief: What It's Like to Believe Everything the Media Tells You About COVID

In this brilliant comedic transformation of a truly harrowing and tragic situation , JP Sears creates a little light and levity out of the media-fueled COVID lockdown .
We hope that the tincture of sarcasm helps to heal parts of your mind and soul in this trying time !
Amazingly , many of the facts referenced in JP Sears ' skit are directly from the new science and evidence showing the original infection and case fatality rates for COVID-19 were wildly wrong .
To learn more , you can view our highly referenced reporting on Coronavirus : https : //www.greenmedinfo.com/disease/coronavirus-disease @ @ @ @ @ @ @ are going and you want your freedom to go outside , then go , like what 's science really ?
Sit back in your lazy boy and get ready to learn the realest truths..YOU WANT TO BELIEVE !
Slay your boredom and join me for an all new LIVE episode this Friday .
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https : //www.awakenwithjp.com/live What would it be like if you stopped thinking for yourself and believed everything the media tells you ?
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Visit our Re-post guidelines This article is copyrighted by GreenMedInfo LLC, 2020
In this brilliant comedic transformation of a truly harrowing and tragic situation, JP Sears creates a little light and levity out of the media-fueled COVID lockdown. We hope that the tincture of sarcasm helps to heal parts of your mind and soul in this trying time!
Amazingly, many of the facts referenced in JP Sears' skit are directly from the new science and evidence showing the original infection and case fatality rates for COVID-19 were wildly wrong. To learn more, you can view our highly referenced reporting on Coronavirus: www.GreenMedInfo.com/disease/coronavirus-disease
Video description and related links:
If you don't like how things are going and you want your freedom to go outside, then go, like what's science really? Sit back in your lazy boy and get ready to learn the realest truths..YOU WANT TO BELIEVE! Slay your boredom and join me for an all new LIVE episode this Friday. Reserve your spot here now! https://www.awakenwithjp.com/live
What would it be like if you stopped thinking for yourself and believed everything the media tells you? Here's what it might look like to be completely brainwashed by the news. *For Comedy Show schedule and tickets: https://awakenwithjp.com/events/ -
My NEW Awakened Shirts are available!
Claim yours here: https://awakenwithjp.com/shop
Click Here to join my PATREON - https://awakenwithjp.com/patron ---- Want to be the first to see my new videos with 24 hour early access? Just click this to receive the alerts! - https://m.me/awakenwithjp?ref=w6836464
Listen and Subscribe to my NEW Podcast here: https://podcasts.apple.com/ca/podcast... It's also available everywhere else you get podcasts. Just search and subscribe to "Awaken With JP Sears Show"
Order my new book at: https://HowToBeUltraSpiritual.com/
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greenmedinfo--2020-05-10--Curcumin has a good regulatory effect on BMSCs and this promising CS-C biomaterial creates a pro-reg

BACKGROUND : Adult full-thickness cutaneous wound repair suffers from an imbalanced immune response , leading to nonfunctional reconstructed tissue and fibrosis .
Although various treatments have been reported , the immune-mediated tissue regeneration driven by biomaterial offers an attractive regenerative strategy for damaged tissue repair .
METHODS : In this research , we investigated a specific bone marrow-derived mesenchymal stem cell ( BMSC ) sheet that was induced by the Traditional Chinese Medicine curcumin ( CS-C ) and its immunomodulatory effects on wound repair .
Comparisons were made with the BMSC sheet induced without curcumin ( CS-N ) and control @ @ @ @ @ @ @ vitro cultured BMSC sheets ( CS-C ) showed that curcumin promoted the proliferation of BMSCs and modified the features of produced extracellular matrix ( ECM ) secreted by BMSCs , especially the contents of ECM structural proteins such as fibronectin ( FN ) and collagen I and III , as well as the ratio of collagen III/I .
Two-photon fluorescence ( TPF ) and second-harmonic generation ( SHG ) imaging of mouse implantation revealed superior engraftment of BMSCs , maintained for 35 days in the CS-C group .
Most importantly , CS-C created @ @ @ @ @ @ @ stromal cell-derived factor 1 ( SDF1 ) was abundantly produced by CS-C , thus facilitating a mass migration of leukocytes from which significantly increased expression of signature T1 cells ( interferon gamma ) and M1 macrophages ( tumor necrosis factor alpha ) genes were confirmed at 7 days post-operation .
The number of T1 cells and associated pro-inflammatory M1 macrophages subsequently decreased sharply after 14 days post-operation , suggesting a rapid type I immune regression .
Furthermore , the CS-C group showed an increased trend towards M2 macrophage polarization in the early phase @ @ @ @ @ @ @ and collagen deposition that was closer to that of normal skin .
CONCLUSIONS : Curcumin has a good regulatory effect on BMSCs and this promising CS-C biomaterial creates a pro-regenerative immune microenvironment for cutaneous wound healing .

BACKGROUND: Adult full-thickness cutaneous wound repair suffers from an imbalanced immune response, leading to nonfunctional reconstructed tissue and fibrosis. Although various treatments have been reported, the immune-mediated tissue regeneration driven by biomaterial offers an attractive regenerative strategy for damaged tissue repair.
METHODS: In this research, we investigated a specific bone marrow-derived mesenchymal stem cell (BMSC) sheet that was induced by the Traditional Chinese Medicine curcumin (CS-C) and its immunomodulatory effects on wound repair. Comparisons were made with the BMSC sheet induced without curcumin (CS-N) and control (saline).
RESULTS: In vitro cultured BMSC sheets (CS-C) showed that curcumin promoted the proliferation of BMSCs and modified the features of produced extracellular matrix (ECM) secreted by BMSCs, especially the contents of ECM structural proteins such as fibronectin (FN) and collagen I and III, as well as the ratio of collagen III/I. Two-photon fluorescence (TPF) and second-harmonic generation (SHG) imaging of mouse implantation revealed superior engraftment of BMSCs, maintained for 35 days in the CS-C group. Most importantly, CS-C created a favorable immune microenvironment. The chemokine stromal cell-derived factor 1 (SDF1) was abundantly produced by CS-C, thus facilitating a mass migration of leukocytes from which significantly increased expression of signature T1 cells (interferon gamma) and M1 macrophages (tumor necrosis factor alpha) genes were confirmed at 7 days post-operation. The number of T1 cells and associated pro-inflammatory M1 macrophages subsequently decreased sharply after 14 days post-operation, suggesting a rapid type I immune regression. Furthermore, the CS-C group showed an increased trend towards M2 macrophage polarization in the early phase. CS-C led to an epidermal thickness and collagen deposition that was closer to that of normal skin.
CONCLUSIONS: Curcumin has a good regulatory effect on BMSCs and this promising CS-C biomaterial creates a pro-regenerative immune microenvironment for cutaneous wound healing.


greenmedinfo--2020-05-10--Curcumin and biodegradable membrane promote nerve regeneration and functional recovery after sciatic

Curcumin and biodegradable membrane promote nerve regeneration and functional recovery after sciatic nerve transection.

BACKGROUND : Curcumin has immunomodulatory anti-inflammatory , antioxidant , and neuroprotective properties .
The goal of this study was to determine the effects of curcumin and biodegradable membrane on nerve healing in rat sciatic nerve transected injuries .
METHODS : Rats were divided into groups : ( 1 ) control group ( Ctrl ) , ( 2 ) curcumin group ( Cur ) , ( 3 ) membrane group ( Mem ) , and ( 4 ) membrane and curcumin group ( Mem + Cur ) .
Functional recovery was evaluated at 2 , 4 , 6 , and 8 @ @ @ @ @ @ @ of the eighth week after surgery , histological assessments were done .
RESULTS : At the end of 8th week after surgery , functional assessments ( sciatic nerve index , withdrawal reflex latency , and electromyography ) in the Mem + Cur group improved compared with other groups ( P < 0.05 ) .
Histological results ( number of nerve fibers , diameter of nerve fibers , and myelin thickness ) improved in the Mem + Cur group compared with the control , Cur , and Mem groups ( P < 0.05 ) @ @ @ @ @ @ @ the positive effects of Mem + Cur on nerve regeneration of transected sciatic nerve in rat model .

BACKGROUND: Curcumin has immunomodulatory anti-inflammatory, antioxidant, and neuroprotective properties. The goal of this study was to determine the effects of curcumin and biodegradable membrane on nerve healing in rat sciatic nerve transected injuries.
METHODS: Rats were divided into groups: (1) control group (Ctrl), (2) curcumin group (Cur), (3) membrane group (Mem), and (4) membrane and curcumin group (Mem + Cur). Functional recovery was evaluated at 2, 4, 6, and 8 weeks after surgery. At the end of the eighth week after surgery, histological assessments were done.
RESULTS: At the end of 8th week after surgery, functional assessments (sciatic nerve index, withdrawal reflex latency, and electromyography) in the Mem + Cur group improved compared with other groups (P<0.05). Histological results (number of nerve fibers, diameter of nerve fibers, and myelin thickness) improved in the Mem + Cur group compared with the control, Cur, and Mem groups (P<0.05).
CONCLUSION: The present study showed the positive effects of Mem + Cur on nerve regeneration of transected sciatic nerve in rat model.


greenmedinfo--2020-05-11--Berberine exerted anticancer effects on human gastric cancer both in vitro and in vivo.

Aim : To further investigate the mechanism behind the antitumor properties of berberine regarding lipid metabolism .
Methods : Cell viability , proliferation , and apoptosis assays were performed to determine the antigrowth effects of berberine in vitro .
Ectopic xenograft models in Balb/c nude mice were established to determine the antitumor effects of berberine in vivo .
Results : Berberine inhibited cell viability and proliferation of MGC803 human gastric cancer cell lines in a time- and dose-dependent manner .
Berberine induced apoptosis of MGC803 and increased the apoptotic rate with higher doses .
Berberine induced the accumulation of fatty @ @ @ @ @ @ @ expression of FABPs and PPAR .
The FABP inhibitor BMS309403 recapitulated the effects of berberine on MGC803 cells .
In the xenograft model , berberine significantly decreased the tumor volume and tumor weight and induced apoptosis in tumor tissues .
Berberine significantly elevated the fatty acid content and inhibited the expression of FABPs and PPARin the MGC803 xenograft models .
Conclusion : Berberine exerted anticancer effects on human gastric cancer both in vitro and in vivo by inducing apoptosis , which was due to the reduced protein expression of FABPs and the accumulation @ @ @ @

Aim: To further investigate the mechanism behind the antitumor properties of berberine regarding lipid metabolism.
Methods: Cell viability, proliferation, and apoptosis assays were performed to determine the antigrowth effects of berberine in vitro. Ectopic xenograft models in Balb/c nude mice were established to determine the antitumor effects of berberine in vivo.
Results: Berberine inhibited cell viability and proliferation of MGC803 human gastric cancer cell lines in a time- and dose-dependent manner. Berberine induced apoptosis of MGC803 and increased the apoptotic rate with higher doses. Berberine induced the accumulation of fatty acid of MGC803 and suppressed the protein expression of FABPs and PPAR. The FABP inhibitor BMS309403 recapitulated the effects of berberine on MGC803 cells. In the xenograft model, berberine significantly decreased the tumor volume and tumor weight and induced apoptosis in tumor tissues. Berberine significantly elevated the fatty acid content and inhibited the expression of FABPs and PPARin the MGC803 xenograft models.
Conclusion: Berberine exerted anticancer effects on human gastric cancer both in vitro and in vivo by inducing apoptosis, which was due to the reduced protein expression of FABPs and the accumulation of fatty acid.


greenmedinfo--2020-05-11--The effect of Berberine on weight loss in order to prevent obesity: A systematic review.

This study provides a critical overview of experimental studies in vitro , in humans , and in animals that evaluated the efficacy of Berberine and its effect on management of obesity and the related metabolic consequences .
As a result of this review , we summarized the effects of Berberine in different models and the related mechanism of actions .
In preclinical models , Berberine demonstrates that it affects gut microbiota by reducing diversity of microbes starting at a dosage of 100 mg/kg/day .
Moreover , in animal models , Berberine explicates an action on glucose through the inhibition ofα-glycosidase @ @ @ @ @ @ @ Berberine is also known to be effective against differentiation of adipocytes through a decrease in LXRs , PPARs , and SREBPs expression at 150 mg/kg/day .
Other mechanism ascribed to Berberine are related to its inhibition of hepatic gluconeogenesis through the Phospheoenolpyruvate carboxykinase ( PEPCK ) , Glucose-6-phosphate ( G6Pase ) and AMP-activated protein kinase ( AMPK ) .
Furthermore , Berberine ( associated to Red Yeast Rice ) is effective in decreasing lipid levels in rats , which consequently lowers the change of weight gain at dosage of 40 mg/kg to 380mg/kg/day @ @ @ @ @ @ @ confirmed in human studies where Berberine can modulate the diversity of gut microbes at the dose of 500 mg/day .
In addition , Berberine is found to have a beneficial impact on gene regulation for the absorption of cholesterol at a daily dose of 300 mg in humans , an amelioration on glucose accumulation at 1.0 g daily dose was also observed .
For all these reasons , this review gives an important good account of the impact of Berberine in obesity treatment and prevention .

This study provides a critical overview of experimental studies in vitro, in humans, and in animals that evaluated the efficacy of Berberine and its effect on management of obesity and the related metabolic consequences. As a result of this review, we summarized the effects of Berberine in different models and the related mechanism of actions. In preclinical models, Berberine demonstrates that it affects gut microbiota by reducing diversity of microbes starting at a dosage of 100 mg/kg/day. Moreover, in animal models, Berberine explicates an action on glucose through the inhibition ofα-glycosidase at a dose of 200 mh/kg/day. Berberine is also known to be effective against differentiation of adipocytes through a decrease in LXRs, PPARs, and SREBPs expression at 150 mg/kg/day. Other mechanism ascribed to Berberine are related to its inhibition of hepatic gluconeogenesis through the Phospheoenolpyruvate carboxykinase (PEPCK), Glucose-6-phosphate (G6Pase) and AMP-activated protein kinase (AMPK). Furthermore, Berberine (associated to Red Yeast Rice) is effective in decreasing lipid levels in rats, which consequently lowers the change of weight gain at dosage of 40 mg/kg to 380mg/kg/day. All the above preclinical data are confirmed in human studies where Berberine can modulate the diversity of gut microbes at the dose of 500 mg/day. In addition, Berberine is found to have a beneficial impact on gene regulation for the absorption of cholesterol at a daily dose of 300 mg in humans, an amelioration on glucose accumulation at 1.0 g daily dose was also observed. For all these reasons, this review gives an important good account of the impact of Berberine in obesity treatment and prevention.


greenmedinfo--2020-05-11--Berberine inhibits free fatty acid and LPS-induced inflammation via modulating ER stress response in

Berberine inhibits free fatty acid and LPS-induced inflammation via modulating ER stress response in macrophages and hepatocytes.

Inflammation plays an essential role in the pathogenesis of non-alcoholic fatty liver disease ( NAFLD ) .
Berberine ( BBR ) , an isoquinoline alkaloid isolated from Chinese medicinal herbs , has been widely used to treat various diseases , including liver diseases for hundreds of years .
The previous studies have shown that BBR inhibits high fat-diet-induced steatosis and inflammation in rodent models of NAFLD .
However , the underlying molecular mechanisms remain unclear .
This study is aimed to identify the potential mechanisms by which BBR inhibits free fatty acid ( FFA ) and LPS-induced inflammatory response in @ @ @ @ @ @ @ macrophages and primary mouse hepatocytes were treated with palmitic acid ( PA ) or LPS or both with or without BBR ( 0-10μM ) for different periods ( 0-24 h ) .
The mRNA and protein levels of proinflammatory cytokines ( TNF-α , IL-6 , IL-1β , MCP-1 ) and ER stress genes ( CHOP , ATF4 , XBP-1 ) were detected by real-time RT-PCR , Western blot and ELISA , respectively .
The results indicated that BBR significantly inhibited PA and LPS-induced activation of ER stress and expression of proinflammatory cytokines in @ @ @ @ @ @ @ ERK1/2 was inhibited by BBR in a dose-dependent manner .
In summary , BBR inhibits PA/LPS-induced inflammatory responses through modulating ER stress-mediated ERK1/2 activation in macrophages and hepatocytes .

Inflammation plays an essential role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Berberine (BBR), an isoquinoline alkaloid isolated from Chinese medicinal herbs, has been widely used to treat various diseases, including liver diseases for hundreds of years. The previous studies have shown that BBR inhibits high fat-diet-induced steatosis and inflammation in rodent models of NAFLD. However, the underlying molecular mechanisms remain unclear. This study is aimed to identify the potential mechanisms by which BBR inhibits free fatty acid (FFA) and LPS-induced inflammatory response in mouse macrophages and hepatocytes. Mouse RAW264.7 macrophages and primary mouse hepatocytes were treated with palmitic acid (PA) or LPS or both with or without BBR (0-10μM) for different periods (0-24 h). The mRNA and protein levels of proinflammatory cytokines (TNF-α, IL-6, IL-1β, MCP-1) and ER stress genes (CHOP, ATF4, XBP-1) were detected by real-time RT-PCR, Western blot and ELISA, respectively. The results indicated that BBR significantly inhibited PA and LPS-induced activation of ER stress and expression of proinflammatory cytokines in macrophages and hepatocytes. PA/LPS-mediated activation of ERK1/2 was inhibited by BBR in a dose-dependent manner. In summary, BBR inhibits PA/LPS-induced inflammatory responses through modulating ER stress-mediated ERK1/2 activation in macrophages and hepatocytes.


greenmedinfo--2020-05-11--Berberine and its structural analogs have differing effects on functional profiles of individual gut

Berberine and its structural analogs have differing effects on functional profiles of individual gut microbiomes.

The understanding of the effects of compounds on the gut microbiome is limited .
In particular , it is unclear whether structurally similar compounds would have similar or distinct effects on the gut microbiome .
Here , we selected berberine ( BBR ) , an isoquinoline quaternary alkaloid , and 16 structural analogs and evaluated their effects on seven individual gut microbiomes cultured .
The responses of the individual microbiomes were evaluated by metaproteomic profiles and by assessing butyrate production .
We show that both interindividual differences and compound treatments significantly contributed to the variance of metaproteomic profiles .
BBR @ @ @ @ @ @ @ proteins involved in microbial defense and stress responses and enrichment of proteins from Verrucomicrobia , Proteobacteria , and Bacteroidetes phyla .
It also led to a decrease in proteins from the Firmicutes phylum and its Clostridiales order which correlated to decrease proteins involved in the butyrate production pathway and butyrate concentration .
Three of the compounds , sanguinarine , chelerythrine , and ethoxysanguinarine , activated bacterial protective mechanisms , enriched Proteobacteria , increased opacity proteins , and markedly reduced butyrate production .
Dihydroberberine had a similar function to BBR in enriching thegenus .
@ @ @ @ @ @ @ adverse impacts on the functionality of the gut microbiome , including a better maintenance of the butyrate level .
Our study shows thatmicrobiome assay can assess differential regulating effects of compounds with subtle differences and reveals that compound analogs can have distinct effects on the microbiome .

The understanding of the effects of compounds on the gut microbiome is limited. In particular, it is unclear whether structurally similar compounds would have similar or distinct effects on the gut microbiome. Here, we selected berberine (BBR), an isoquinoline quaternary alkaloid, and 16 structural analogs and evaluated their effects on seven individual gut microbiomes cultured. The responses of the individual microbiomes were evaluated by metaproteomic profiles and by assessing butyrate production. We show that both interindividual differences and compound treatments significantly contributed to the variance of metaproteomic profiles. BBR and eight analogs led to changes in proteins involved in microbial defense and stress responses and enrichment of proteins from Verrucomicrobia, Proteobacteria, and Bacteroidetes phyla. It also led to a decrease in proteins from the Firmicutes phylum and its Clostridiales order which correlated to decrease proteins involved in the butyrate production pathway and butyrate concentration. Three of the compounds, sanguinarine, chelerythrine, and ethoxysanguinarine, activated bacterial protective mechanisms, enriched Proteobacteria, increased opacity proteins, and markedly reduced butyrate production. Dihydroberberine had a similar function to BBR in enriching thegenus. In addition, it showed less overall adverse impacts on the functionality of the gut microbiome, including a better maintenance of the butyrate level. Our study shows thatmicrobiome assay can assess differential regulating effects of compounds with subtle differences and reveals that compound analogs can have distinct effects on the microbiome.


greenmedinfo--2020-05-11--The results of the current study support the use of berberine supplementation for the improvement of

BACKGROUND : and purpose : Clinical studies investigating the effects of berberine supplementation on anthropometric indices in humans have generated inconsistent results .
Thus , the objective of this systematic review and meta-analysis was to clarify the effects of berberine supplementation on obesity indices in human subjects .
METHODS : Several online medical databases were systematically searched up to February 2019 .
All clinical trials exploring the effects of berberine supplementation on indices of obesity were included .
The combined weighted mean difference ( WMD ) of eligible studies was assessed using a random-effects model .
We evaluated publication bias @ @ @ @ @ @ @ RESULTS : Overall , 10 studies were included .
The combined outcomes suggested a significant influence of berberine administration on body mass index ( BMI ) ( WMD : -0.29 kg/m , 95 % CI : -0.51 to -0.08 , p = 0.006 ) and waist circumference ( WC ) ( WMD : -2.75 cm , 95 % CI : -4.88 to -0.62 , p = 0.01 ) .
However , berberine supplementation yielded no significant decline in body weight ( BW ) ( WMD : -0.11 kg , 95 % CI : @ @ @ @ @ @ @ ) .
Following the dose-response evaluation , berberine intake was foundto significantly reduce BMI ( r = -0.02 ) and WC ( r = -0.72 ) based on treatment duration .
CONCLUSION : The results of the current study support the use of berberine supplementation for the improvement of obesity indices .

BACKGROUND: and purpose: Clinical studies investigating the effects of berberine supplementation on anthropometric indices in humans have generated inconsistent results. Thus, the objective of this systematic review and meta-analysis was to clarify the effects of berberine supplementation on obesity indices in human subjects.
METHODS: Several online medical databases were systematically searched up to February 2019. All clinical trials exploring the effects of berberine supplementation on indices of obesity were included. The combined weighted mean difference (WMD) of eligible studies was assessed using a random-effects model. We evaluated publication bias by using the Egger's test.
RESULTS: Overall, 10 studies were included. The combined outcomes suggested a significant influence of berberine administration on body mass index (BMI) (WMD: -0.29 kg/m, 95% CI: -0.51 to -0.08, p = 0.006) and waist circumference (WC) (WMD: -2.75 cm, 95% CI: -4.88 to -0.62, p = 0.01). However, berberine supplementation yielded no significant decline in body weight (BW) (WMD: -0.11 kg, 95% CI: -0.99 to 0.76, p = 0.79). Following the dose-response evaluation, berberine intake was foundto significantly reduce BMI (r = -0.02) and WC (r = -0.72) based on treatment duration.
CONCLUSION: The results of the current study support the use of berberine supplementation for the improvement of obesity indices.


greenmedinfo--2020-05-11--Red beetroot extract abrogates chlorpyrifos-induced cortical damage.

Organophosphorus insecticides including chlorpyrifos ( CPF ) are mainly used for agriculture , household , and military purposes ; their application is associated with various adverse reactions in animals and humans .
This study was conducted to evaluate the potential neuroprotective effect of red beetroot methanolic extract ( RBR ) against CPF-induced cortical damage .
Twenty-eight adult male Wistar albino rats were divided into 4 groups ( = 7 in each group ) : the control group was administered physiological saline ( 0.9 % NaCl ) , the CPF group was administered CPF ( 10 mg/kg ) , the RBR @ @ @ @ @ @ @ ) , and the RBR+CPF group was treated with RBR ( 300 mg/kg ) 1 hr before CPF ( 10 mg/kg ) supplementation .
All groups were treated for 28 days .
Rats exposed to CPF exhibited a significant decrease in cortical acetylcholinesterase activity and brain-derived neurotrophic factor and a decrease in glial fibrillary acidic protein .
CPF intoxication increased lipid peroxidation , inducible nitric oxide synthase expression , and nitric oxide production .
This was accompanied by a decrease in glutathione content and in the activities of glutathione peroxidase , glutathione reductase @ @ @ @ @ @ @ the cortical tissue .
Additionally , CPF enhanced inflammatory response , indicated by increased levels and expression of interleukin-1and tumor necrosis factor- .
CPF triggered neuronal apoptosis by upregulating Bax and caspase-3 and downregulating Bcl-2 .
However , RBR reversed the induced neuronal alterations following CPF intoxication .
Our findings suggest that RBR can minimize and prevent CPF neurotoxicity through its antioxidant , anti-inflammatory , and antiapoptotic activities .

Organophosphorus insecticides including chlorpyrifos (CPF) are mainly used for agriculture, household, and military purposes; their application is associated with various adverse reactions in animals and humans. This study was conducted to evaluate the potential neuroprotective effect of red beetroot methanolic extract (RBR) against CPF-induced cortical damage. Twenty-eight adult male Wistar albino rats were divided into 4 groups (= 7 in each group): the control group was administered physiological saline (0.9% NaCl), the CPF group was administered CPF (10 mg/kg), the RBR group was administered RBR (300 mg/kg), and the RBR+CPF group was treated with RBR (300 mg/kg) 1 hr before CPF (10 mg/kg) supplementation. All groups were treated for 28 days. Rats exposed to CPF exhibited a significant decrease in cortical acetylcholinesterase activity and brain-derived neurotrophic factor and a decrease in glial fibrillary acidic protein. CPF intoxication increased lipid peroxidation, inducible nitric oxide synthase expression, and nitric oxide production. This was accompanied by a decrease in glutathione content and in the activities of glutathione peroxidase, glutathione reductase, superoxide dismutase, and catalase in the cortical tissue. Additionally, CPF enhanced inflammatory response, indicated by increased levels and expression of interleukin-1and tumor necrosis factor-. CPF triggered neuronal apoptosis by upregulating Bax and caspase-3 and downregulating Bcl-2. However, RBR reversed the induced neuronal alterations following CPF intoxication. Our findings suggest that RBR can minimize and prevent CPF neurotoxicity through its antioxidant, anti-inflammatory, and antiapoptotic activities.


greenmedinfo--2020-05-11--Beetroot juice lowers blood pressure and improves endothelial function in pregnant eNOS-/- mice

KEY POINTS : Maternal hypertension is associated with increased rates of pregnancy pathologies , including fetal growth restriction , due at least in part to reductions in nitric oxide ( NO ) bioavailability and associated vascular dysfunction .
Dietary nitrate supplementation , from beetroot juice ( BRJ ) , has been shown to increase NO bioavailability and improve cardiovascular function in both preclinical and clinical studies .
This study is the first to investigate effects of dietary nitrate supplementation in a pregnant animal model .
Importantly , effects of nitrate-containing BRJ were compared with both 'placebo ' ( nitrate-depleted ) @ @ @ @ @ @ @ for potential nitrate-independent effects .
Our data show novel , nitrate-independent effects of BRJ to lower blood pressure and improve vascular function in endothelial nitric oxide synthase knockout ( eNOS ) mice .
These findings suggest potential beneficial effects of BRJ supplementation in pregnancy , and emphasise the importance of accounting for nitrate-independent effects of BRJ in study design and interpretation .
ABSTRACT : Maternal hypertension associates with adverse pregnancy outcomes , including fetal growth restriction ( FGR ) , due in part to reductions in nitric oxide ( NO ) bioavailability .
@ @ @ @ @ @ @ would increase NO bioavailability to reduce systolic blood pressure ( SBP ) , improve vascular function and increase fetal growth in pregnant endothelial NO synthase knockout ( eNOS ) mice , which exhibit hypertension , endothelial dysfunction and FGR .
Pregnant wildtype ( WT ) and eNOSmice were supplemented with nitrate-containing beetroot juice ( BRJ+ ) from gestational day ( GD ) 12.5 .
Control mice received an equivalent dose of nitrate-depleted BRJ ( BRJ- ) or normal drinking water .
At GD17.5 , maternal SBP was measured ; at GD18.5 , maternal @ @ @ @ @ @ @ ) blood flow and endothelial function were assessed , and pregnancy outcomes determined .
Plasma nitrate concentrations were increased in both WT and eNOSmice supplemented with BRJ+ ( P < 0.001 ) , whereas nitrite concentrations were increased only in eNOSmice ( P < 0.001 ) .
BRJ- did not alter nitrate/nitrite concentrations .
SBP was lowered and UtA endothelial function enhanced in eNOSmice supplemented with either BRJ+ or BRJ- , indicating nitrate-independent effects of BRJ .
Improvements in endothelial function in eNOSmice were abrogated in the presence of 25 mM KCl , @ @ @ @ @ @ @ animals .
At GD18.5 , eNOSfetuses were significantly smaller than WT animals ( P < 0.001 ) , however BRJ supplementation did not affect fetal weight .
BRJ may be a beneficial intervention in pregnancies associated with hypertension , endothelial dysfunction and reduced NO bioavailability .
Our data showing biological effects of non-nitrate components of BRJ have implications for both interpretation of previous findings and in the design of future clinical trials .
This article is protected by copyright .
All rights reserved .

KEY POINTS: Maternal hypertension is associated with increased rates of pregnancy pathologies, including fetal growth restriction, due at least in part to reductions in nitric oxide (NO) bioavailability and associated vascular dysfunction. Dietary nitrate supplementation, from beetroot juice (BRJ), has been shown to increase NO bioavailability and improve cardiovascular function in both preclinical and clinical studies. This study is the first to investigate effects of dietary nitrate supplementation in a pregnant animal model. Importantly, effects of nitrate-containing BRJ were compared with both 'placebo' (nitrate-depleted) BRJ as well as water to control for potential nitrate-independent effects. Our data show novel, nitrate-independent effects of BRJ to lower blood pressure and improve vascular function in endothelial nitric oxide synthase knockout (eNOS) mice. These findings suggest potential beneficial effects of BRJ supplementation in pregnancy, and emphasise the importance of accounting for nitrate-independent effects of BRJ in study design and interpretation.
ABSTRACT: Maternal hypertension associates with adverse pregnancy outcomes, including fetal growth restriction (FGR), due in part to reductions in nitric oxide (NO) bioavailability. We hypothesized that maternal dietary nitrate administration would increase NO bioavailability to reduce systolic blood pressure (SBP), improve vascular function and increase fetal growth in pregnant endothelial NO synthase knockout (eNOS) mice, which exhibit hypertension, endothelial dysfunction and FGR. Pregnant wildtype (WT) and eNOSmice were supplemented with nitrate-containing beetroot juice (BRJ+) from gestational day (GD) 12.5. Control mice received an equivalent dose of nitrate-depleted BRJ (BRJ-) or normal drinking water. At GD17.5, maternal SBP was measured; at GD18.5, maternal nitrate/nitrite concentrations, uterine artery (UtA) blood flow and endothelial function were assessed, and pregnancy outcomes determined. Plasma nitrate concentrations were increased in both WT and eNOSmice supplemented with BRJ+ (P<0.001), whereas nitrite concentrations were increased only in eNOSmice (P<0.001). BRJ- did not alter nitrate/nitrite concentrations. SBP was lowered and UtA endothelial function enhanced in eNOSmice supplemented with either BRJ+ or BRJ-, indicating nitrate-independent effects of BRJ. Improvements in endothelial function in eNOSmice were abrogated in the presence of 25 mM KCl, implicating enhanced EDH signalling in BRJ treated animals. At GD18.5, eNOSfetuses were significantly smaller than WT animals (P<0.001), however BRJ supplementation did not affect fetal weight. BRJ may be a beneficial intervention in pregnancies associated with hypertension, endothelial dysfunction and reduced NO bioavailability. Our data showing biological effects of non-nitrate components of BRJ have implications for both interpretation of previous findings and in the design of future clinical trials. This article is protected by copyright. All rights reserved.


greenmedinfo--2020-05-11--Anti-inflammatory, antioxidant, and immunomodulatory effects of curcumin in ovalbumin-sensitized rat

Anti-inflammatory, antioxidant, and immunomodulatory effects of curcumin in ovalbumin-sensitized rat.

BACKGROUND : Anti-inflammatory and antioxidant properties of curcumin have been shown .
In this study , anti-inflammatory , antioxidant , and immunomodulatory effects of curcumin in sensitized rat were evaluated .
METHODS : Six groups of rats including control ( C ) , ovalbumin-sensitized ( as a rat model of asthma , S ) , S groups treated with curcumin ( Cu 0.15 , 0.30 , and 0.60 mg/mL ) , and 1.25μg/mL dexamethasone ( S + D ) were studied .
Curcumin and dexamethasone were given in animals ' drinking water during sensitization period .
Total and differential WBC @ @ @ @ @ @ @ , IL-4 , IgE , oxidant , and antioxidant biomarker levels in bronchoalveolar lavage fluid ( BALF ) were examined .
RESULTS : Total WBC , neutrophil and eosinophil counts , levels of PLA2 , TP , IgE , IL-4 , NO , NO , and MDA in BALF were increased but lymphocyte percentage , SOD , CAT , thiol , and IFN-γ levels and IFN-γ/IL-4 ratio decreased in S animals compared to controls ( P CONCLUSION : Anti-inflammatory , antioxidant , and immunomodulatory effects of curcumin with more specific immunomodulatory effect on @ @ @ @ @ @ @ rats was shown.© 2017 BioFactors , 43 ( 4 ) :567-576 , 2017 .

BACKGROUND: Anti-inflammatory and antioxidant properties of curcumin have been shown. In this study, anti-inflammatory, antioxidant, and immunomodulatory effects of curcumin in sensitized rat were evaluated.
METHODS: Six groups of rats including control (C), ovalbumin-sensitized (as a rat model of asthma, S), S groups treated with curcumin (Cu 0.15, 0.30, and 0.60 mg/mL), and 1.25μg/mL dexamethasone (S + D) were studied. Curcumin and dexamethasone were given in animals' drinking water during sensitization period. Total and differential WBC count, PLA2, TP, IFN-γ, IL-4, IgE, oxidant, and antioxidant biomarker levels in bronchoalveolar lavage fluid (BALF) were examined.
RESULTS: Total WBC, neutrophil and eosinophil counts, levels of PLA2, TP, IgE, IL-4, NO, NO, and MDA in BALF were increased but lymphocyte percentage, SOD, CAT, thiol, and IFN-γ levels and IFN-γ/IL-4 ratio decreased in S animals compared to controls (P < 0.001 for all cases). Treatment with all concentrations of curcumin significantly improved total WBC, PLA2, TP, IgE, IL-4, IFN-γ, IFN-γ/IL-4 ratio, SOD, thiol, NO, and NOcompared to S group (P < 0.01 to P < 0.001). Two higher concentrations of curcumin significantly decreased neutrophil and eosinophil counts and MDA level but increased IFN-γ, CAT and lymphocyte values compared to S group (P < 0.001 for all cases). Dexamethasone treatment also significantly improved most of the measured parameters (P < 0.05 to P < 0.001) but it did not change IL-4 and IFN-γ levels and IFN-γ/IL-4 ratio.
CONCLUSION: Anti-inflammatory, antioxidant, and immunomodulatory effects of curcumin with more specific immunomodulatory effect on Th1/Th2 balance compared to dexamethasone in sensitized rats was shown.© 2017 BioFactors, 43(4):567-576, 2017.


greenmedinfo--2020-05-11--Betulinic acid shows anticancer activity against equine melanoma cells and permeates isolated equine

Betulinic acid shows anticancer activity against equine melanoma cells and permeates isolated equine skin in vitro.

BACKGROUND : Equine malignant melanoma ( EMM ) is a frequently occurring dermoepidermal tumor in grey horses .
Currently available @ @ @ @ @ inefficient .
Betulinic acid ( BA ) , a naturally occurring triterpenoid , is a @ @ @ @ @ .
To evaluate the potential of BA as a topical therapy for EMM , its @ @ @ @ @ melanoma cells and dermal fibroblasts and its percutaneous permeation through isolated equine skin were assessed @ @ @ @ @ BA showed antiproliferative and cytotoxic effects on both primary equine melanoma cells and fibroblasts in @ @ @ @ @ .
The lowest half-maximal inhibitory concentrations were obtained 96 h after the beginning of drug @ @ @ @ @ 23.6 μmol/L for melanoma cells eRGO1 and MelDuWi , respectively , in cytotoxicity assay ) @ @ @ @ @ compound were reached in the required skin layers in vitro .
CONCLUSION : BA is @ @ @ @ @ EMM treatment .
Further clinical studies in horses are necessary to assess safety and antitumoral @ @ @ @

BACKGROUND: Equine malignant melanoma (EMM) is a frequently occurring dermoepidermal tumor in grey horses. Currently available therapies are either challenging or inefficient. Betulinic acid (BA), a naturally occurring triterpenoid, is a promising compound for cancer treatment. To evaluate the potential of BA as a topical therapy for EMM, its anticancer effects on primary equine melanoma cells and dermal fibroblasts and its percutaneous permeation through isolated equine skin were assessed in vitro.
RESULTS: BA showed antiproliferative and cytotoxic effects on both primary equine melanoma cells and fibroblasts in a time- and dose-dependent manner. The lowest half-maximal inhibitory concentrations were obtained 96 h after the beginning of drug exposure (12.7 μmol/L and 23.6 μmol/L for melanoma cells eRGO1 and MelDuWi, respectively, in cytotoxicity assay). High concentrations of the compound were reached in the required skin layers in vitro.
CONCLUSION: BA is a promising substance for topical EMM treatment. Further clinical studies in horses are necessary to assess safety and antitumoral effects in vivo.


greenmedinfo--2020-05-11--The antitumor activity of betulinic acid-loaded nanoliposomes against colorectal cancer.

The purpose of this study is to develop betulinic acid loaded nanoliposomes to improve the chemotherapy effect of colorectal cancer @ @ @ @ @ anti-tumor effects of betulinic acid loaded nanoliposomeswere characterized and evaluated , and their effects on @ @ @ @ @ key anti-cancer targets were analyzed .
Moreover , their anticancer efficacy was assessed .
Compared @ @ @ @ @ the cellular uptake and anti-tumor activity of betulinic acid-loaded nanoliposomes were significantly enhanced ; these @ @ @ @ @ and glucose uptake of colorectal cancer cells .
Mechanistically , the anti-colorectal cancer effect of @ @ @ @ @ by their triggering of cellular apoptosis and regulating the potential glycolytic and glutaminolytic targets and @ @ @ @ @ was inhibited and colorectal cancer cells apoptosis , the anticancer effect of betulinic acid loaded @ @ @ @ @ in all , betulinic acid loaded nanoliposomes are expected to be an effective drug delivery @ @ @ @ @ .

The purpose of this study is to develop betulinic acid loaded nanoliposomes to improve the chemotherapy effect of colorectal cancer. The cellular uptake and anti-tumor effects of betulinic acid loaded nanoliposomeswere characterized and evaluated, and their effects on glycolysis, glutamine decomposition and key anti-cancer targets were analyzed. Moreover, their anticancer efficacy was assessed. Compared with free betulinic acid, the cellular uptake and anti-tumor activity of betulinic acid-loaded nanoliposomes were significantly enhanced; these nanoliposomes significantly suppressed the proliferation and glucose uptake of colorectal cancer cells. Mechanistically, the anti-colorectal cancer effect of betulinic acid-loaded nanoliposomes was confirmed by their triggering of cellular apoptosis and regulating the potential glycolytic and glutaminolytic targets and pathways. After tumor proliferation was inhibited and colorectal cancer cells apoptosis, the anticancer effect of betulinic acid loaded nanoliposomeswas significantly enhanced. All in all, betulinic acid loaded nanoliposomes are expected to be an effective drug delivery system for colorectal cancer treatment.


greenmedinfo--2020-05-11--Betulinic acid triggers apoptosis and inhibits migration and invasion of gastric cancer cells by imp

Betulinic acid triggers apoptosis and inhibits migration and invasion of gastric cancer cells by impairing EMT progress.

Gastric cancer ( GC ) is one of the most prevalent types of malignancies .
Betulinic acid ( BA ) is a natural pentacyclic triterpene with a lupine structure .
However , to the best of our knowledge , there is no research study on the anti-tumour and anti-metastasis effect of BA on GC .
In this study , we assessed the anti-cancer effect of BA on human GC cells in vitro and in vivo .
We first investigated the cytotoxicity and anti-proliferation effect of BA on GC cells of SNU-16 and NCI-N87 .
The results indicated that BA had @ @ @ @ @ @ @ cells in a dose- and time-dependent manner .
To further study the cytotoxic action of BA on GC cells , we assessed the apoptotic induction effect of BA on SNU-16 cells and found that BA distinctly induced apoptosis in SNU-16 cells .
In addition , BA inhibited the migratory and invasive abilities of SNU-16 cells .
Western-blot analysis revealed that BA suppressed the migration and invasion of GC cells by impairing epithelial-mesenchymal transition progression .
Furthermore , in vivo experiments showed that BA could delay tumour growth and inhibit pulmonary metastasis , which @ @ @ @ @ @ @ vitro studies .
Overall , we evaluated the anti-cancer effect of BA on human GC cells in vivo and in vitro , and the present study provides new evidence on the use of BA as a potential anti-cancer drug for GC treatment .
SIGNIFICANCE OF THE STUDY : BA significantly suppressed proliferation and triggered apoptosis in GC cells .
Additionally , BA remarkably inhibited migration and invasion of GC cells by impairing the epithelial-mesenchymal transition signalling pathway .
It is worth noting that BA drastically retarded tumour growth in the xenograft mouse model @ @ @ @ @ @ @ BA can be considered a candidate drug for GC therapy .

Gastric cancer (GC) is one of the most prevalent types of malignancies. Betulinic acid (BA) is a natural pentacyclic triterpene with a lupine structure. However, to the best of our knowledge, there is no research study on the anti-tumour and anti-metastasis effect of BA on GC. In this study, we assessed the anti-cancer effect of BA on human GC cells in vitro and in vivo. We first investigated the cytotoxicity and anti-proliferation effect of BA on GC cells of SNU-16 and NCI-N87. The results indicated that BA had significant cytotoxic and inhibitory effects on GC cells in a dose- and time-dependent manner. To further study the cytotoxic action of BA on GC cells, we assessed the apoptotic induction effect of BA on SNU-16 cells and found that BA distinctly induced apoptosis in SNU-16 cells. In addition, BA inhibited the migratory and invasive abilities of SNU-16 cells. Western-blot analysis revealed that BA suppressed the migration and invasion of GC cells by impairing epithelial-mesenchymal transition progression. Furthermore, in vivo experiments showed that BA could delay tumour growth and inhibit pulmonary metastasis, which is consistent with the results of in vitro studies. Overall, we evaluated the anti-cancer effect of BA on human GC cells in vivo and in vitro, and the present study provides new evidence on the use of BA as a potential anti-cancer drug for GC treatment. SIGNIFICANCE OF THE STUDY: BA significantly suppressed proliferation and triggered apoptosis in GC cells. Additionally, BA remarkably inhibited migration and invasion of GC cells by impairing the epithelial-mesenchymal transition signalling pathway. It is worth noting that BA drastically retarded tumour growth in the xenograft mouse model of GC. Our results indicated that BA can be considered a candidate drug for GC therapy.


greenmedinfo--2020-05-11--Betulinic acid-mediated tuning of PERK/CHOP signalling by Sp1 inhibition as a novel therapeutic stra

Betulinic acid-mediated tuning of PERK/CHOP signalling by Sp1 inhibition as a novel therapeutic strategy for glioblastoma.

Patients with glioblastoma are at high risk of local recurrences after initial treatment with standard therapy , and recurrent tumor cells appear to be resistant to first-line drug temozolomide .
Thus , finding an effective second-line agent for treating primary and recurrent glioblastomas is critical .
Betulinic acid ( BA ) , a natural product of plant origin , can cross the blood-brain barrier .
Here , we investigated the antitumor effects of BA on typical glioblastoma cell lines and primary glioblastoma cells from patients , as well as corresponding temozolomide-resistant cells .
Our findings verified that BA significantly reduced @ @ @ @ @ @ @ , gene-expression array analysis showed that the unfolded-protein response was significantly affected by BA .
Moreover , BA treatment increased activation of the protein kinase RNA-like endoplasmic reticulum kinase ( PERK ) /C/EBP homologous protein ( CHOP ) apoptotic pathway , and reduced specificity protein 1 ( Sp1 ) expression .
However , Sp1 overexpression reversed the observed cell-growth inhibition and PERK/CHOP signaling activation induced by BA .
Because temozolomide-resistant cells exhibited significantly increased Sp1 expression , we concluded that Sp1-mediated PERK/CHOP signaling inhibition protects glioblastoma against cancer therapies ; hence , BA @ @ @ @ @ @ @ as an effective therapeutic strategy to overcome such chemoresistance and tumor relapse .

Patients with glioblastoma are at high risk of local recurrences after initial treatment with standard therapy, and recurrent tumor cells appear to be resistant to first-line drug temozolomide. Thus, finding an effective second-line agent for treating primary and recurrent glioblastomas is critical. Betulinic acid (BA), a natural product of plant origin, can cross the blood-brain barrier. Here, we investigated the antitumor effects of BA on typical glioblastoma cell lines and primary glioblastoma cells from patients, as well as corresponding temozolomide-resistant cells. Our findings verified that BA significantly reduced growth in all examined cells. Furthermore, gene-expression array analysis showed that the unfolded-protein response was significantly affected by BA. Moreover, BA treatment increased activation of the protein kinase RNA-like endoplasmic reticulum kinase (PERK)/C/EBP homologous protein (CHOP) apoptotic pathway, and reduced specificity protein 1 (Sp1) expression. However, Sp1 overexpression reversed the observed cell-growth inhibition and PERK/CHOP signaling activation induced by BA. Because temozolomide-resistant cells exhibited significantly increased Sp1 expression, we concluded that Sp1-mediated PERK/CHOP signaling inhibition protects glioblastoma against cancer therapies; hence, BA treatment targeting this pathway can be considered as an effective therapeutic strategy to overcome such chemoresistance and tumor relapse.


greenmedinfo--2020-05-11--Lonicera caerulea L. polyphenols alleviate oxidative stress-induced intestinal environment imbalance

Lonicera caerulea L. polyphenols alleviate oxidative stress-induced intestinal environment imbalance and lipopolysaccharide-induced liver injury.

SCOPE : This study investigates the modulatory effects of Lonicera caerulea L. polyphenols ( LCPs ) on the intestinal environment and lipopolysaccharide ( LPS ) -induced liver injury via the nuclear factor erythroid-2-related factor 2/heme oxygenase-1 ( HO-1 ) /NQO1 and mitogen-activated protein kinase ( MAPK ) pathways in a rat model of oxidative stress damage ( OSD ) .
METHODS AND RESULTS : To examine the prebiotic properties of LCP , a model of high-fat-diet-induced OSD is established using Sprague Dawley rats .
In the colon , treatment with LCP for 8 weeks ameliorates enhanced intestinal permeability ( glucagon-like @ @ @ @ @ @ @ whereas claudin-2 protein decreases ) , intestinal inflammation ( levels of pro-inflammatory cytokines , such as tumor necrosis factor-α , interleukin-6 , cyclooxygenase-2 , and nuclear factor kappa-B p65 ( NF-κB p65 ) , decrease ) , and intestinal OSD ( through regulation of the Nrf2/HO-1/NQO1 pathway ) .
Moreover , LCP alleviates LPS-induced liver injury by suppressing the nuclear translocation of NF-κB p65 and activation of the MAPK signaling pathway .
Additionally , Bacilli , Lactobacillales , Lactobacillaceae , Lactobacillus , Akkermansia , Actinobacteria , Proteobacteria , Rothia , and Blautia are @ @ @ @ @ @ @ taxa related to intestinal OSD and LPS-induced liver injury in rats .
CONCLUSION : LCP treatment potentially modulates the intestinal environment and alleviates liver injury by suppressing oxidative-stress-related pathways and altering the composition of the intestinal microbiota .

SCOPE: This study investigates the modulatory effects of Lonicera caerulea L. polyphenols (LCPs) on the intestinal environment and lipopolysaccharide (LPS)-induced liver injury via the nuclear factor erythroid-2-related factor 2/heme oxygenase-1 (HO-1)/NQO1 and mitogen-activated protein kinase (MAPK) pathways in a rat model of oxidative stress damage (OSD).
METHODS AND RESULTS: To examine the prebiotic properties of LCP, a model of high-fat-diet-induced OSD is established using Sprague Dawley rats. In the colon, treatment with LCP for 8 weeks ameliorates enhanced intestinal permeability (glucagon-like peptide-2 content and occludin protein increase, whereas claudin-2 protein decreases), intestinal inflammation (levels of pro-inflammatory cytokines, such as tumor necrosis factor-α, interleukin-6, cyclooxygenase-2, and nuclear factor kappa-B p65 (NF-κB p65), decrease), and intestinal OSD (through regulation of the Nrf2/HO-1/NQO1 pathway). Moreover, LCP alleviates LPS-induced liver injury by suppressing the nuclear translocation of NF-κB p65 and activation of the MAPK signaling pathway. Additionally, Bacilli, Lactobacillales, Lactobacillaceae, Lactobacillus, Akkermansia, Actinobacteria, Proteobacteria, Rothia, and Blautia are found to be the key intestinal microbial taxa related to intestinal OSD and LPS-induced liver injury in rats.
CONCLUSION: LCP treatment potentially modulates the intestinal environment and alleviates liver injury by suppressing oxidative-stress-related pathways and altering the composition of the intestinal microbiota.


greenmedinfo--2020-05-11--The Exponential Lie of COVID Fatality Rates - A Mathematician Debunks Narrative with WHO's Own Data

In his jaw-dropping exposé , British mathematician Andrew Mather reveals how the the global COVID-19 lockdown was perpetuated through statistical misrepresentation and outright falsification , demonstrating this through the WHO 's own data .
`` The media may claim they were `` deceived '' by scientists .
The politicians may claim they were `` deceived '' by scientists .
I do not accept that excuse .
A : this is not difficult B : for a matter of such important it should have been critical that they knew the science was sound .
The triviality of the lie counts against @ @ @ @ @ @ @ excuse .
For a Professor Emeritus to claim `` he did n't understand exponential '' would be absurd .
He implicitly recognises that by going to great lengths to NOT state for himself any of the false memes he was tasked with spreading .
He cites others in every instance .
Nevertheless Gary Hanington put his name to an article designed to promote one simple message and one big lie : Covid-19 growth is exponential .
He compounded the deception by specifically including only those charts ( curves , countries ) which suggested @ @ @ @ @ @ @ countries , two of which would have utterly destroyed the `` exponential '' message , two of which would have diminished the perceived threat in the message , he illustrated that the intent was not an `` innocuous '' discussion of maths , but the promulgation of a false message , designed to incite fear and render people more amenable to actions designed to deprive them of liberty and do massive damage to their livelihoods and the economy .
A deliberate attempt to deceive with a view to coercing others makes him liable @ @ @ @ @ @ @ He is not alone by any means , nor is he significant , but we have to start somewhere .
No doubt the rich and powerful will escape , and likely the authorities will ignore this .
Nevertheless I encourage all Americans to consider this and see if some of those lawyers of yours would like to do something useful for a change .
It could happen .
You might even find an honest official .
That would be truly astonishing .
PDF : https : //peerlessreads.s3.us-east-2.am ... Hanington Article PDF : https @ @ @ @

In his jaw-dropping exposé, British mathematician Andrew Mather reveals how the the global COVID-19 lockdown was perpetuated through statistical misrepresentation and outright falsification, demonstrating this through the WHO's own data.
Video commentary from Mather's youtube channel Peerless Reads:
"The media may claim they were "deceived" by scientists. The politicians may claim they were "deceived" by scientists. I do not accept that excuse. A: this is not difficult B: for a matter of such important it should have been critical that they knew the science was sound. The triviality of the lie counts against them. Scientists however have no such excuse. For a Professor Emeritus to claim "he didn't understand exponential" would be absurd. He implicitly recognises that by going to great lengths to NOT state for himself any of the false memes he was tasked with spreading. He cites others in every instance. Nevertheless Gary Hanington put his name to an article designed to promote one simple message and one big lie: Covid-19 growth is exponential. He compounded the deception by specifically including only those charts (curves, countries) which suggested exponential growth. By omitting four key countries, two of which would have utterly destroyed the "exponential" message, two of which would have diminished the perceived threat in the message, he illustrated that the intent was not an "innocuous" discussion of maths, but the promulgation of a false message, designed to incite fear and render people more amenable to actions designed to deprive them of liberty and do massive damage to their livelihoods and the economy. A deliberate attempt to deceive with a view to coercing others makes him liable for the consequences of that deception. He is not alone by any means, nor is he significant, but we have to start somewhere. No doubt the rich and powerful will escape, and likely the authorities will ignore this. Nevertheless I encourage all Americans to consider this and see if some of those lawyers of yours would like to do something useful for a change. It could happen. You might even find an honest official. That would be truly astonishing. PDF: https://peerlessreads.s3.us-east-2.am... Hanington Article PDF: https://peerlessreads.s3.us-east-2.am..."


greenmedinfo--2020-05-12--A combination of Korean red ginseng extract and Glycyrrhiza glabra L. extract enhances their individ

A combination of Korean red ginseng extract and Glycyrrhiza glabra L. extract enhances their individual anti-obesity properties.

Anti-obesity activities of Korean red ginseng saponin fraction ( RGS ) and/orL .
extract ( GG ) were investigated in 3T3-L1 adipocytes and high-fat diet-induced C57BL/6J obese mice .
RGS and GG extracts were mixed at a mass ratio of 3:1 ( SG31 ) , 1:1 ( SG11 ) , or 1:3 ( SG13 ) .
SG31 showed the highest anti-obesity activity among the three different mass ratios of RGS and GG extracts .
SG31 showed higher inhibition efficiency on triglyceride ( TG ) accumulation than either single extract in 3T3-L1 adipocytes and without any cytotoxicity .
It also decreases @ @ @ @ @ @ @ such as C/EBPand SREBP-1c ( sterol regulatory element-binding protein 1c ) .
In the obese induced mouse model , SG31 significantly reduced white adipose tissue weight and body weight , attenuated dyslipidemia , and decreased serum TG levels .
In some indices , the activity of SG31 was even higher compared withwater extract , a positive control .
The possible mechanism by which SG31 causes the above results was by activating the AMP-activated protein kinase ( AMPK ) pathway and stimulating the secretion of adiponectin in adipose tissue to regulate energy metabolism balance @ @ @ @ @ @ @ of fatty acids .
Therefore , SG31 may have efficacy as an anti-obesity functional food or raw material if the results can be confirmed in human studies .

Anti-obesity activities of Korean red ginseng saponin fraction (RGS) and/orL. extract (GG) were investigated in 3T3-L1 adipocytes and high-fat diet-induced C57BL/6J obese mice. RGS and GG extracts were mixed at a mass ratio of 3:1 (SG31), 1:1 (SG11), or 1:3 (SG13). SG31 showed the highest anti-obesity activity among the three different mass ratios of RGS and GG extracts. SG31 showed higher inhibition efficiency on triglyceride (TG) accumulation than either single extract in 3T3-L1 adipocytes and without any cytotoxicity. It also decreases the expression of adipogenic and lipogenic genes such as C/EBPand SREBP-1c (sterol regulatory element-binding protein 1c). In the obese induced mouse model, SG31 significantly reduced white adipose tissue weight and body weight, attenuated dyslipidemia, and decreased serum TG levels. In some indices, the activity of SG31 was even higher compared withwater extract, a positive control. The possible mechanism by which SG31 causes the above results was by activating the AMP-activated protein kinase (AMPK) pathway and stimulating the secretion of adiponectin in adipose tissue to regulate energy metabolism balance, inhibit TG formation, and promote-oxidation of fatty acids. Therefore, SG31 may have efficacy as an anti-obesity functional food or raw material if the results can be confirmed in human studies.


greenmedinfo--2020-05-12--Licorice lollipops showed a promising effect in reducing caries by decreasing Streptococcus mutans c

PURPOSE : To assess the efficacy of licorice lollipops in reducing dental caries in children .
MATERIALS AND METHODS : A literature search was confined to the English language using MeSH terms congruent with PICO format in 'PubMed ' , 'Cochrane Library ' and 'Ovid ' , covering the period from April 1967 to December 2017 .
Searches in Google Scholar , grey literature and hand search of cross-references were performed to find additional data .
Suitable studies were selected based on the predefined inclusion and exclusion criteria .
Quality analysis and risk of bias of the selected studies were @ @ @ @ @ @ @ for risk of bias .
RESULTS : Overall 519 articles were retrieved , 516 ( electronic databases ) and 3 ( Google scholar ) .
516 publications were excluded due to non-availability of abstracts , or because they were unrelated studies , narrative reviews , and systematic reviews as well as letters to editors .
Only three studies were included for final analysis .
Quality analysis of these three studies showed that only one was of high quality , whereas the other two were rated as low .
CONCLUSION : Licorice lollipops showed @ @ @ @ @ @ @ decreasing Streptococcus mutans counts in the saliva .
Further research using randomised controlled clinical trial ( RCT ) designs with large sample size are recommended .

PURPOSE: To assess the efficacy of licorice lollipops in reducing dental caries in children.
MATERIALS AND METHODS: A literature search was confined to the English language using MeSH terms congruent with PICO format in 'PubMed', 'Cochrane Library' and 'Ovid', covering the period from April 1967 to December 2017. Searches in Google Scholar, grey literature and hand search of cross-references were performed to find additional data. Suitable studies were selected based on the predefined inclusion and exclusion criteria. Quality analysis and risk of bias of the selected studies were performed using the Cochrane Collaboration's tool for risk of bias.
RESULTS: Overall 519 articles were retrieved, 516 (electronic databases) and 3 (Google scholar). 516 publications were excluded due to non-availability of abstracts, or because they were unrelated studies, narrative reviews, and systematic reviews as well as letters to editors. Only three studies were included for final analysis. Quality analysis of these three studies showed that only one was of high quality, whereas the other two were rated as low.
CONCLUSION: Licorice lollipops showed a promising effect in reducing caries by decreasing Streptococcus mutans counts in the saliva. Further research using randomised controlled clinical trial (RCT) designs with large sample size are recommended.


greenmedinfo--2020-05-12--Gut Microbiome May Impact the Effectiveness of Flu Vaccine

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By providing the information contained herein we are not diagnosing , treating @ @ @ @ @ or preventing any type of disease or medical condition .
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This website is for information purposes only. By providing the information contained herein we are not diagnosing, treating, curing, mitigating, or preventing any type of disease or medical condition. Before beginning any type of natural, integrative or conventional treatment regimen, it is advisable to seek the advice of a licensed healthcare professional.
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greenmedinfo--2020-05-12--The antibacterial effect produced by ethanolic licorice root extract on S. mutans was comparable to

The antibacterial effect produced by ethanolic licorice root extract on S. mutans was comparable to chlorhexidine mouthwash.

AIM : The present study was done to determine the activity of licorice root extract on ( ) in comparison to chlorhexidine and fluoride mouthwash .
MATERIALS AND METHODS : In the current study , the different concentrations of aqueous and ethanolic licorice root extract were subjected to microbiological assay and zone of inhibition was determined againstby agar ditch method .
Minimum inhibitory concentration ( MIC ) of aqueous and ethanolic solution was obtained by using broth dilution method and agar dilution method .
Chlorhexidine and fluoride mouthwash were kept as a positive control in the present study .
One-way @ @ @ @ @ @ @ 5 % level of significance to analyze data .
RESULTS : Mean zone of inhibition of chlorhexidine mouthwash , fluoride mouthwash , aqueous and ethanolic licorice root extracts againstat 24 hours were 23 mm , 14.2 mm , 15.8 mm and 22.4 mm , respectively .
Minimum inhibitory concentration of aqueous and ethanolic licorice root extract onwas 20 mg/mL and 12.5 mg/mL , respectively by both broth dilution method and agar dilution method .
CONCLUSION : The antibacterial effect produced by ethanolic licorice root extract onwas comparable to chlorhexidine mouthwash while significantly higher @ @ @ @ @ @ @ mouthwash .
CLINICAL SIGNIFICANCE : The interest in the plants with antibacterial and anti-inflammatory activity has increased now days to treat various dental diseases as consequences of current problems associated with the conventional agents .
Licorice root is easily available , economically feasible and culturally acceptable and may possess minimal side effects as compared to conventional means of chemicotherapeutic agents used for reduction ofin oral cavity and hence can be recommended for prevention of dental caries .

AIM: The present study was done to determine the activity of licorice root extract on() in comparison to chlorhexidine and fluoride mouthwash.
MATERIALS AND METHODS: In the current study, the different concentrations of aqueous and ethanolic licorice root extract were subjected to microbiological assay and zone of inhibition was determined againstby agar ditch method. Minimum inhibitory concentration (MIC) of aqueous and ethanolic solution was obtained by using broth dilution method and agar dilution method. Chlorhexidine and fluoride mouthwash were kept as a positive control in the present study. One-way ANOVA along with Tukeytest were used at 5% level of significance to analyze data.
RESULTS: Mean zone of inhibition of chlorhexidine mouthwash, fluoride mouthwash, aqueous and ethanolic licorice root extracts againstat 24 hours were 23 mm, 14.2 mm, 15.8 mm and 22.4 mm, respectively. Minimum inhibitory concentration of aqueous and ethanolic licorice root extract onwas 20 mg/mL and 12.5 mg/mL, respectively by both broth dilution method and agar dilution method.
CONCLUSION: The antibacterial effect produced by ethanolic licorice root extract onwas comparable to chlorhexidine mouthwash while significantly higher in comparison with aqueous form and fluoride mouthwash.
CLINICAL SIGNIFICANCE: The interest in the plants with antibacterial and anti-inflammatory activity has increased now days to treat various dental diseases as consequences of current problems associated with the conventional agents. Licorice root is easily available, economically feasible and culturally acceptable and may possess minimal side effects as compared to conventional means of chemicotherapeutic agents used for reduction ofin oral cavity and hence can be recommended for prevention of dental caries.


greenmedinfo--2020-05-12--Effect of hot water extract of a glycyrrhizin-deficient strain of Glycyrrhiza uralensis on contact h

Effect of hot water extract of a glycyrrhizin-deficient strain of Glycyrrhiza uralensis on contact hypersensitivity.

To evaluate the medicinal properties of a glycyrrhizin ( GL ) -deficient strain of Glycyrrhiza uralensis , we investigated the @ @ @ @ @ water extract obtained from its roots on contact hypersensitivity in mice , and compared it @ @ @ @ @ water extract of a commercial crude drug , Glycyrrhiza Radix .
The hot water root @ @ @ @ @ contained glucoglycyrrhizin ( GGL ) and rhaoglucoglycyrrhizin ( RGL ) instead of GL , and @ @ @ @ @ contact hypersensitivity in a fashion similar to that of the crude drug extract .
We @ @ @ @ @ glycyrrhetinic acid ( GA ) , a major metabolite of GL , in mice serum @ @ @ @ @ hot water root extract of a GL-deficient strain .
We demonstrated that GGL underwent hydrolysis @ @ @ @ @ to form GA .
These results suggest that a GL-deficient strain of G. uralensis is @ @ @ @ @ the glycosides of GA work in a fashion similar to that of GL when orally @ @

To evaluate the medicinal properties of a glycyrrhizin (GL)-deficient strain of Glycyrrhiza uralensis, we investigated the anti-allergic effect of the hot water extract obtained from its roots on contact hypersensitivity in mice, and compared it with that of the hot water extract of a commercial crude drug, Glycyrrhiza Radix. The hot water root extract of the GL-deficient strain contained glucoglycyrrhizin (GGL) and rhaoglucoglycyrrhizin (RGL) instead of GL, and it showed anti-allergic activity against contact hypersensitivity in a fashion similar to that of the crude drug extract. We further confirmed the presence of glycyrrhetinic acid (GA), a major metabolite of GL, in mice serum after oral administration of the hot water root extract of a GL-deficient strain. We demonstrated that GGL underwent hydrolysis by intestinal microflora of mice to form GA. These results suggest that a GL-deficient strain of G. uralensis is a useful medicinal resource since the glycosides of GA work in a fashion similar to that of GL when orally administered.


greenmedinfo--2020-05-12--Paeoniflorin exerts neuroprotective effects in a transgenic mouse model of Alzheimer's disease via a

Paeoniflorin exerts neuroprotective effects in a transgenic mouse model of Alzheimer's disease via activation of adenosine A1 receptor.

Alzheimer 's disease ( AD ) is the most common cause of dementia , characterised by advanced cognitive and memory deterioration with no effective treatments available .
Previous in vitro and in vivo studies suggest that paeoniflorin ( PF ) , a major bioactive constituent of Radix Paeoniae , might possess anti-dementia properties ; however , the underlying mechanism remains unclear .
The aim of the current study was to determine the therapeutic effects of PF in a transgenic mouse model of AD and to identify its mechanism .
Transgenic mice with five familial AD mutations ( 5XFAD ) were @ @ @ @ @ @ @ that 28 days of PF ( 5 mg/kg , ip ) treatment significantly decreased the escape latency and path length in the Morris water maze test and increased the alternation rate in the T-maze test , compared to the vehicle treatment group .
In addition , PF treatment significantly alleviated amyloid β plaque burden , inhibited astrocyte activation , and decreased IL-1β and TNF-α expression in the brain of 5XFAD mice .
However , the anti-cognitive deficits , anti-amyloidogenic , and anti-inflammatory effects of PF were abolished by 1,3-dipropyl-8-cyclopentylxanthine ( DPCPX , 0.3 @ @ @ @ @ @ @ AR ) antagonist .
In conclusion , our results suggest that PF might act as a potential therapeutic agent for AD via activation of adenosine AR .

Alzheimer's disease (AD) is the most common cause of dementia, characterised by advanced cognitive and memory deterioration with no effective treatments available. Previous in vitro and in vivo studies suggest that paeoniflorin (PF), a major bioactive constituent of Radix Paeoniae, might possess anti-dementia properties; however, the underlying mechanism remains unclear. The aim of the current study was to determine the therapeutic effects of PF in a transgenic mouse model of AD and to identify its mechanism. Transgenic mice with five familial AD mutations (5XFAD) were used in this study. We showed that 28 days of PF (5 mg/kg, ip) treatment significantly decreased the escape latency and path length in the Morris water maze test and increased the alternation rate in the T-maze test, compared to the vehicle treatment group. In addition, PF treatment significantly alleviated amyloid β plaque burden, inhibited astrocyte activation, and decreased IL-1β and TNF-α expression in the brain of 5XFAD mice. However, the anti-cognitive deficits, anti-amyloidogenic, and anti-inflammatory effects of PF were abolished by 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 0.3 mg/kg), an adenosine Areceptor (AR) antagonist. In conclusion, our results suggest that PF might act as a potential therapeutic agent for AD via activation of adenosine AR.


greenmedinfo--2020-05-12--Antifungal effect of tea extracts on Candida albicans.

Determining whether tea extracts are effective in removing Candida albicans ( C. albicans ) from dentures is of interest .
@ @ @ @ @ the antifungal effect of tea extracts on C. albicans .
One green tea ( Anji @ @ @ @ @ and 2 oolong teas ( Tie Guan Yin , TGY ; Da Hong Pao , @ @ @ @ @ were tested .
C. albicans suspensions were inoculated on the plates and the numbers of @ @ @ @ @ in the culture medium were used to screen for the optimum tea extracts .
Polymethyl @ @ @ @ @ that contained C. albicans biofilms were then treated with the tea extracts and the numbers @ @ @ @ @ The antifungal activities of the tea extracts were not significantly correlated with their catechin concentrations @ @ @ @ @ mg/mL and DHP at 2.5 mg/mL significantly inhibited C. albicans in the culture medium , @ @ @ @ @ inhibitory effects against C. albicans biofilms on the PMMA surfaces .

Determining whether tea extracts are effective in removing Candida albicans (C. albicans) from dentures is of interest. This study aimed to investigate the antifungal effect of tea extracts on C. albicans. One green tea (Anji white tea, AGW) and 2 oolong teas (Tie Guan Yin, TGY; Da Hong Pao, DHP) of different concentrations were tested. C. albicans suspensions were inoculated on the plates and the numbers of colony-forming units (CFU) in the culture medium were used to screen for the optimum tea extracts. Polymethyl methacrylate (PMMA) specimens that contained C. albicans biofilms were then treated with the tea extracts and the numbers of CFU were counted. The antifungal activities of the tea extracts were not significantly correlated with their catechin concentrations. Although AGW at 10.0 mg/mL and DHP at 2.5 mg/mL significantly inhibited C. albicans in the culture medium, the extracts failed to exert inhibitory effects against C. albicans biofilms on the PMMA surfaces.


greenmedinfo--2020-05-12--Jiaogulan tea potentiates the antidiabetic effect of white tea.

The use of plant-based beverages to interfere with the onset of diabetes may be a promising approach towards type 2 diabetes mellitus ( T2DM ) .
The present study investigated the antidiabetic effects of the oral consumption of white tea and G. pentaphyllum ( Jiaogulan ) , especially their combination on HFD/STZ-induced T2DM in C57BL/6 mice .
White tea and Jiaogulan administration could mitigate glycolipid metabolic disorders in the diabetic mice by different degrees .
White tea administration markedly reduced the blood glucose and ameliorated the glucose intolerance compared to the T2DM mice .
Moreover , white tea consumption could @ @ @ @ @ @ @ damage , related to the Nrf-2 signaling pathway .
Jiaogulan prominently attenuated liver lipid accumulation by downregulation of SREBP levels .
However , interestingly , when white tea was used in combination with Jiaogulan , these effects were enhanced to a certain extent .
In particular , the combination significantly suppressed the hepatic G6Pase expressions by activating the AMPK pathway , thus inhibiting gluconeogenesis and improving insulin resistance .
On the other hand , the combined formula could regulate the PPAR expressions and ameliorate the hepaticinflammation , further activating the IRS/PI3K/AKT pathway and @ @ @ @ @ @ @ it was speculated that the antidiabetic effect of this combination may be associated with the AMPK/PI3K pathways .
Our findings might provide insight into the combined use of white tea withJiaogulan tea as a potential functional beverage or food for preventing T2DM .

The use of plant-based beverages to interfere with the onset of diabetes may be a promising approach towards type 2 diabetes mellitus (T2DM). The present study investigated the antidiabetic effects of the oral consumption of white tea and G. pentaphyllum (Jiaogulan), especially their combination on HFD/STZ-induced T2DM in C57BL/6 mice. White tea and Jiaogulan administration could mitigate glycolipid metabolic disorders in the diabetic mice by different degrees. White tea administration markedly reduced the blood glucose and ameliorated the glucose intolerance compared to the T2DM mice. Moreover, white tea consumption could protect the isletβ-cells against oxidative and inflammatory damage, related to the Nrf-2 signaling pathway. Jiaogulan prominently attenuated liver lipid accumulation by downregulation of SREBP levels. However, interestingly, when white tea was used in combination with Jiaogulan, these effects were enhanced to a certain extent. In particular, the combination significantly suppressed the hepatic G6Pase expressions by activating the AMPK pathway, thus inhibiting gluconeogenesis and improving insulin resistance. On the other hand, the combined formula could regulate the PPAR expressions and ameliorate the hepaticinflammation, further activating the IRS/PI3K/AKT pathway and exerting the antidiabetic potential. Therefore, it was speculated that the antidiabetic effect of this combination may be associated with the AMPK/PI3K pathways. Our findings might provide insight into the combined use of white tea withJiaogulan tea as a potential functional beverage or food for preventing T2DM.


greenmedinfo--2020-05-12--White tea plays important roles in ameliorating abnormal lipid metabolism in vitro.

Emerging in vivo and vitro data suggest that white tea extract ( WTE ) is capable of favourably modulating metabolic syndrome , especially by ameliorating abnormal lipid metabolism .
Microarray-based gene expression profiling was performed in HepG2 cells to analyze the effects of WTE from a systematic perspective .
Gene Ontology and pathway analysis revealed that WTE significantly affected pathways related to lipid metabolism .
WTE significantly downregulated apolipoprotein B ( APOB ) and microsomal triglyceride transfer protein ( MTTP ) expression and thereby reduced the production of very-low-density lipoprotein .
In the meanwhile , WTE stimulated low-density lipoprotein-cholesterol ( @ @ @ @ @ @ @ receptor ( LDLR ) , as a consequence of the activation of sterol regulatory element-binding protein 2 ( SREBP2 ) and peroxisome proliferator-activated receptorδ ( PPARδ ) .
Furthermore , WTE significantly downregulated triglycerides synthetic genes and reduced intracellular triglycerides accumulation .
Besides , we demonstrated that the tea catechins epigallocatechin-3-gallate ( EGCG ) and epicatechin-3-gallate ( ECG ) are abundant in WTE and contribute to the regulation of cholesterol metabolism related genes , including LDLR , MTTP and APOB .
Our findings suggest white tea plays important roles in ameliorating abnormal lipid @ @ @ @

Emerging in vivo and vitro data suggest that white tea extract (WTE) is capable of favourably modulating metabolic syndrome, especially by ameliorating abnormal lipid metabolism. Microarray-based gene expression profiling was performed in HepG2 cells to analyze the effects of WTE from a systematic perspective. Gene Ontology and pathway analysis revealed that WTE significantly affected pathways related to lipid metabolism. WTE significantly downregulated apolipoprotein B (APOB) and microsomal triglyceride transfer protein (MTTP) expression and thereby reduced the production of very-low-density lipoprotein. In the meanwhile, WTE stimulated low-density lipoprotein-cholesterol (LDL-c) uptake through targeting low-density lipoprotein receptor (LDLR), as a consequence of the activation of sterol regulatory element-binding protein 2 (SREBP2) and peroxisome proliferator-activated receptorδ (PPARδ). Furthermore, WTE significantly downregulated triglycerides synthetic genes and reduced intracellular triglycerides accumulation. Besides, we demonstrated that the tea catechins epigallocatechin-3-gallate (EGCG) and epicatechin-3-gallate (ECG) are abundant in WTE and contribute to the regulation of cholesterol metabolism related genes, including LDLR, MTTP and APOB. Our findings suggest white tea plays important roles in ameliorating abnormal lipid metabolism in vitro.


greenmedinfo--2020-05-12--The synergistic Antitumor effect of 5-fluorouracil combined with allicin against lung and colorectal

The synergistic Antitumor effect of 5-fluorouracil combined with allicin against lung and colorectal carcinoma cells.

5-fluorouracil ( 5-FU ) is an anticancer drug used to inhibit the proliferation of many different tumor cells .
Since severe events are associated with this compound , its combination with different anticancer drugs or adjuvants would allow the use of a significantly lower dose of 5-FU .
In this study , we highlighted that the combination of allicin with 5-FU inhibited the cell migration and proliferation of colorectal and lung cancer cells .
5-FU inhibited cell growth with a similar inhibitory concentration for both normal and tumor cells ( ~200µM ) , while allicin showed different inhibitory concentrations .
@ @ @ @ @ @ @ lung cancer cells were the most sensitive to allicin .
Compared to 5-FU and allicin single-agent treatments , the co-treatment showed a reduced viability rate , with < 0.05 .
The morphological changes were visible on all three cell lines , indicating that the treatment inhibited the proliferation of both normal and tumor cells .
We highlighted different cell death mechanisms-apoptosis for lung cancer and a non-apoptotic cell death for colorectal cancer .
The synergistic antitumor effect of 5-FU combined with allicin was visible against lung and colorectal carcinoma cells .
Better results @ @ @ @ @ @ @ 5-FU was combined with allicin than the single-agent treatment at IC50 .

5-fluorouracil (5-FU) is an anticancer drug used to inhibit the proliferation of many different tumor cells. Since severe events are associated with this compound, its combination with different anticancer drugs or adjuvants would allow the use of a significantly lower dose of 5-FU. In this study, we highlighted that the combination of allicin with 5-FU inhibited the cell migration and proliferation of colorectal and lung cancer cells. 5-FU inhibited cell growth with a similar inhibitory concentration for both normal and tumor cells (~200µM), while allicin showed different inhibitory concentrations. With an IC50 of 8.625 µM, lung cancer cells were the most sensitive to allicin. Compared to 5-FU and allicin single-agent treatments, the co-treatment showed a reduced viability rate, with<0.05. The morphological changes were visible on all three cell lines, indicating that the treatment inhibited the proliferation of both normal and tumor cells. We highlighted different cell death mechanisms-apoptosis for lung cancer and a non-apoptotic cell death for colorectal cancer. The synergistic antitumor effect of 5-FU combined with allicin was visible against lung and colorectal carcinoma cells. Better results were obtained when a lower concentration of 5-FU was combined with allicin than the single-agent treatment at IC50.


greenmedinfo--2020-05-12--Arctigenin suppresses cell proliferation via autophagy inhibition in hepatocellular carcinoma cells.

Autophagy is a catabolic process that degrades dysfunctional proteins and organelles and plays critical roles in cancer development .
Our preliminary screening identified that extracts of the fruits of Arctium lappa and the fruits of Forsythia suspensa notably suppressed the proliferation of hepatocellular carcinoma HepG2 cells and downregulated the autophagy .
In this study , we explored the effect of arctigenin ( ARG ) , a bioactive lignan in both extracts , on cell proliferation and autophagy-related proteins in HepG2 cells .
ARG inhibited the proliferation of HepG2 cells .
Analysis of autophagy-related proteins demonstrated that ARG might block the @ @ @ @ @ @ @ p62 ) accumulation .
The stage of inhibition in autophagy by ARG differed from those by the autophagy inhibitors 3-methyladenine ( 3-MA ) or chloroquine ( CQ ) .
ARG could also inhibit starvation-induced autophagy .
Further analysis of apoptosis-related proteins indicated that ARG did not affect caspase-3 activation and PARP cleavage , suggesting that the antiproliferative effect of ARG can occur independently of apoptosis .
In summary , our study showed that ARG suppresses cell proliferation and inhibits autophagy , and might lead to the development of agents for autophagy research and @ @ @

Autophagy is a catabolic process that degrades dysfunctional proteins and organelles and plays critical roles in cancer development. Our preliminary screening identified that extracts of the fruits of Arctium lappa and the fruits of Forsythia suspensa notably suppressed the proliferation of hepatocellular carcinoma HepG2 cells and downregulated the autophagy. In this study, we explored the effect of arctigenin (ARG), a bioactive lignan in both extracts, on cell proliferation and autophagy-related proteins in HepG2 cells. ARG inhibited the proliferation of HepG2 cells. Analysis of autophagy-related proteins demonstrated that ARG might block the autophagy that leads to sequestosome 1/p62 (p62) accumulation. The stage of inhibition in autophagy by ARG differed from those by the autophagy inhibitors 3-methyladenine (3-MA) or chloroquine (CQ). ARG could also inhibit starvation-induced autophagy. Further analysis of apoptosis-related proteins indicated that ARG did not affect caspase-3 activation and PARP cleavage, suggesting that the antiproliferative effect of ARG can occur independently of apoptosis. In summary, our study showed that ARG suppresses cell proliferation and inhibits autophagy, and might lead to the development of agents for autophagy research and cancer chemoprevention.


greenmedinfo--2020-05-12--Arctigenin enhances the cytotoxic effect of doxorubicin in MDA-MB-231 breast cancer cells.

Several reports have described the anti-cancer activity of arctigenin , a lignan extracted fromL .
Here , we investigated the effect of arctigenin ( ATG ) on doxorubicin ( DOX ) -induced cell death using MDA-MB-231 human breast cancer cells .
The results showed that DOX-induced cell death was enhanced by ATG/DOX co-treatment in a concentration-dependent manner and that this was associated with increased DOX uptake and the suppression of multidrug resistance-associated protein 1 ( MRP1 ) gene expression in MDA-MB-231 cells .
ATG enhanced DOX-induced DNA damage and decreased the phosphorylation of signal transducer and activator of transcription 3 @ @ @ @ @ @ @ RAD51 and survivin .
Cell death caused by ATG/DOX co-treatment was mediated by the nuclear translocation of apoptosis inducing factor ( AIF ) , reductions in cellular and mitochondrial Bcl-2 and Bcl-xL , and increases in mitochondrial BAX levels .
However , caspase-3 and -7 did not participate in DOX/ATG-induced cell death .
We also found that DOX/ATG-induced cell death was linked with activation of the p38 signaling pathway and suppressions of the phosphorylations and expressions of Akt and c-Jun N-terminal kinase .
Taken together , these results show that ATG enhances the @ @ @ @ @ @ @ breast cancer cells by inducing prolonged p21 expression and p38-mediated AIF-dependent cell death .
In conclusion , our findings suggest that ATG might alleviate the side effects and improve the therapeutic efficacy of DOX .

Several reports have described the anti-cancer activity of arctigenin, a lignan extracted fromL. Here, we investigated the effect of arctigenin (ATG) on doxorubicin (DOX)-induced cell death using MDA-MB-231 human breast cancer cells. The results showed that DOX-induced cell death was enhanced by ATG/DOX co-treatment in a concentration-dependent manner and that this was associated with increased DOX uptake and the suppression of multidrug resistance-associated protein 1 (MRP1) gene expression in MDA-MB-231 cells. ATG enhanced DOX-induced DNA damage and decreased the phosphorylation of signal transducer and activator of transcription 3 (STAT3) and the expressions of RAD51 and survivin. Cell death caused by ATG/DOX co-treatment was mediated by the nuclear translocation of apoptosis inducing factor (AIF), reductions in cellular and mitochondrial Bcl-2 and Bcl-xL, and increases in mitochondrial BAX levels. However, caspase-3 and -7 did not participate in DOX/ATG-induced cell death. We also found that DOX/ATG-induced cell death was linked with activation of the p38 signaling pathway and suppressions of the phosphorylations and expressions of Akt and c-Jun N-terminal kinase. Taken together, these results show that ATG enhances the cytotoxic activity of DOX in MDA-MB-231 human breast cancer cells by inducing prolonged p21 expression and p38-mediated AIF-dependent cell death. In conclusion, our findings suggest that ATG might alleviate the side effects and improve the therapeutic efficacy of DOX.