greenmedinfo--2020-08-21--Low serum vitamin B12 levels are independently associated with abnormal lipid profiles in healthy yo

Low serum vitamin B12 levels are independently associated with abnormal lipid profiles in healthy young Saudi women.

An abnormal lipid profile is an independent risk factor for cardiovascular diseases .
The relationship between vitamin B12 deficiency and lipid profile is inconclusive , with most studies conducted in unhealthy populations .
In this study , we aimed to assess the relationship between serum vitamin B12 levels and lipid profiles in a cross-sectional study that included 341 apparently healthy Saudi women , aged 19-30 years , from different colleges at King Saud University , Saudi Arabia .
Sociodemographic , anthropometric , biochemical , and lifestyle data were collected , including diet and physical activity .
Serum vitamin B12 deficiency @ @ @ @ @ @ @ < 148 pmol/L .
The prevalence of vitamin B12 deficiency was approximately 0.6 % .
Using multivariable linear regression models , serum vitamin B12 levels were found to be inversely associated with total cholesterol ( B = -0.26 ; < 0.001 ) , low-density lipoprotein cholesterol levels ( B = -0.30 ; < 0.001 ) , and triglyceride ( B = -0.16 ; < 0.01 ) after adjusting for potential confounders , while obesity indices of body mass index , central obesity , and fat percentage showed no association .
Therefore , we @ @ @ @ @ @ @ are independently associated with abnormal lipid profiles in healthy young Saudi women .
Further interventional studies are needed to determine whether improving serum vitamin B12 levels in a healthy population can improve lipid profiles .

An abnormal lipid profile is an independent risk factor for cardiovascular diseases. The relationship between vitamin B12 deficiency and lipid profile is inconclusive, with most studies conducted in unhealthy populations. In this study, we aimed to assess the relationship between serum vitamin B12 levels and lipid profiles in a cross-sectional study that included 341 apparently healthy Saudi women, aged 19-30 years, from different colleges at King Saud University, Saudi Arabia. Sociodemographic, anthropometric, biochemical, and lifestyle data were collected, including diet and physical activity. Serum vitamin B12 deficiency was defined as serum B12 level of<148 pmol/L. The prevalence of vitamin B12 deficiency was approximately 0.6%. Using multivariable linear regression models, serum vitamin B12 levels were found to be inversely associated with total cholesterol (B = -0.26;<0.001), low-density lipoprotein cholesterol levels (B = -0.30;<0.001), and triglyceride (B = -0.16;<0.01) after adjusting for potential confounders, while obesity indices of body mass index, central obesity, and fat percentage showed no association. Therefore, we conclude that low serum vitamin B12 levels are independently associated with abnormal lipid profiles in healthy young Saudi women. Further interventional studies are needed to determine whether improving serum vitamin B12 levels in a healthy population can improve lipid profiles.


greenmedinfo--2020-08-21--Vitamin B12 may inhibit RNA-dependent-RNA polymerase activity of nsp12 from the SARS-CoV-2 virus.

SARS-CoV-2 is the causative agent for the ongoing COVID19 pandemic , and this virus belongs to the Coronaviridae family .
Like other members of this family , the virus possesses a positive-sense single-stranded RNA genome .
The genome encodes for the nsp12 protein , which houses the RNA-dependent-RNA polymerase ( RdRP ) activity responsible for the replication of the viral genome .
A homology model of nsp12 was prepared using the structure of the SARS nsp12 ( 6NUR ) as a model .
The model was used to carry out in silico screening to identify molecules among natural products , @ @ @ @ @ @ @ can potentially inhibit the activity of nsp12 .
This exercise showed that vitamin B12 ( methylcobalamin ) may bind to the active site of the nsp12 protein .
A model of the nsp12 in complex with substrate RNA and incoming NTP showed that vitamin B12 binding site overlaps with that of the incoming nucleotide .
A comparison of the calculated energies of binding for RNA plus NTP and methylcobalamin suggested that the vitamin may bind to the active site of nsp12 with significant affinity .
It is , therefore , possible that methylcobalamin @ @ @ @ @ @ @ NTP and thus inhibit the RdRP activity of nsp12 .
Overall , our computational studies suggest that methylcobalamin form of vitamin B12 may serve as an effective inhibitor of the nsp12 protein .

SARS-CoV-2 is the causative agent for the ongoing COVID19 pandemic, and this virus belongs to the Coronaviridae family. Like other members of this family, the virus possesses a positive-sense single-stranded RNA genome. The genome encodes for the nsp12 protein, which houses the RNA-dependent-RNA polymerase (RdRP) activity responsible for the replication of the viral genome. A homology model of nsp12 was prepared using the structure of the SARS nsp12 (6NUR) as a model. The model was used to carry out in silico screening to identify molecules among natural products, or Food and Drug Administration-approved drugs that can potentially inhibit the activity of nsp12. This exercise showed that vitamin B12 (methylcobalamin) may bind to the active site of the nsp12 protein. A model of the nsp12 in complex with substrate RNA and incoming NTP showed that vitamin B12 binding site overlaps with that of the incoming nucleotide. A comparison of the calculated energies of binding for RNA plus NTP and methylcobalamin suggested that the vitamin may bind to the active site of nsp12 with significant affinity. It is, therefore, possible that methylcobalamin binding may prevent association with RNA and NTP and thus inhibit the RdRP activity of nsp12. Overall, our computational studies suggest that methylcobalamin form of vitamin B12 may serve as an effective inhibitor of the nsp12 protein.


greenmedinfo--2020-08-21--Effects of high intensity dynamic resistance exercise and whey protein supplements on osteosarcopeni

Effects of high intensity dynamic resistance exercise and whey protein supplements on osteosarcopenia.

The present study aimed to evaluate the effect of high intensity dynamic resistance exercise ( HIT-DRT ) and whey protein supplementation ( WPS ) on bone mineral density ( BMD ) and sarcopenia parameters in osteosarcopenic men .
Men≥ 72 years with osteosarcopenia ( = 43 ) were randomly assigned to a HIT-RT ( HIT-RT : = 21 ) or a non-training control group ( = 22 ) .
Supervised HIT-RT twice/week was applied for 18 months , while the control group maintained their habitual lifestyle .
Supplying WPS , total protein intake amounted to 1.5-1.6 ( HIT-RT ) and @ @ @ @ @ @ @ Both groups were supplied with calcium and vitamin D. Primary study outcomes were BMD and the sarcopenia Z-score .
After adjusting for multiplicity , we observed significant positive effects for sarcopenia Z-score ( standardized mean difference ( SMD ) : 1.40 ) , BMD at lumbar spine ( SMD : 0.72 ) and total hip ( SMD : 0.72 ) .
In detail , effect sizes for skeletal muscle mass changes were very pronounced ( 1.97 , < 0.001 ) , while effects for functional sarcopenia parameters were moderate ( 0.87 , = @ @ @ @ @ @ @ ( 0.39 , = 0.209 ; gait velocity ) .
Apart from one man who reported short periods of temporary worsening of existing joint pain , no HIT-RT/WPS-related adverse effects or injuries were reported .
We consider HIT-RT supported by whey protein supplementation as a feasible , attractive , safe and highly effective option to fight osteosarcopenia in older men .

The present study aimed to evaluate the effect of high intensity dynamic resistance exercise (HIT-DRT) and whey protein supplementation (WPS) on bone mineral density (BMD) and sarcopenia parameters in osteosarcopenic men. Men≥ 72 years with osteosarcopenia (= 43) were randomly assigned to a HIT-RT (HIT-RT:= 21) or a non-training control group (= 22). Supervised HIT-RT twice/week was applied for 18 months, while the control group maintained their habitual lifestyle. Supplying WPS, total protein intake amounted to 1.5-1.6 (HIT-RT) and 1.2 g/kg/body mass/d (control). Both groups were supplied with calcium and vitamin D. Primary study outcomes were BMD and the sarcopenia Z-score. After adjusting for multiplicity, we observed significant positive effects for sarcopenia Z-score (standardized mean difference (SMD): 1.40), BMD at lumbar spine (SMD: 0.72) and total hip (SMD: 0.72). In detail, effect sizes for skeletal muscle mass changes were very pronounced (1.97,<0.001), while effects for functional sarcopenia parameters were moderate (0.87,= 0.008; handgrip strength) or low (0.39,= 0.209; gait velocity). Apart from one man who reported short periods of temporary worsening of existing joint pain, no HIT-RT/WPS-related adverse effects or injuries were reported. We consider HIT-RT supported by whey protein supplementation as a feasible, attractive, safe and highly effective option to fight osteosarcopenia in older men.


greenmedinfo--2020-08-21--High intake of whey and pea protein for 5 days after intensive eccentric exercise mitigated the effl

High intake of whey and pea protein for 5 days after intensive eccentric exercise mitigated the efflux of muscle damage biomarkers.

This randomized trial compared pea protein , whey protein , and water-only supplementation on muscle damage , inflammation , delayed onset of muscle soreness ( DOMS ) , and physical fitness test performance during a 5-day period after a 90-min eccentric exercise bout in non-athletic non-obese males ( = 92 , ages 18-55 years ) .
The two protein sources ( 0.9 g protein/kg divided into three doses/day ) were administered under double blind procedures .
The eccentric exercise protocol induced significant muscle damage and soreness , and reduced bench press and 30-s Wingate performance .
Whey protein supplementation significantly @ @ @ @ @ @ @ muscle damage compared to water-only , with large effect sizes for creatine kinase and myoglobin during the fourth and fifth days of recovery ( Cohen 's d > 0.80 ) ; pea protein versus water supplementation had an intermediate non-significant effect ( Cohen 's d < 0.50 ) ; and no significant differences between whey and pea protein were found .
Whey and pea protein compared to water supplementation had no significant effects on post-exercise DOMS and the fitness tests .
In conclusion , high intake of whey protein for 5 days after @ @ @ @ @ @ @ muscle damage biomarkers , with the intake of pea protein having an intermediate effect .

This randomized trial compared pea protein, whey protein, and water-only supplementation on muscle damage, inflammation, delayed onset of muscle soreness (DOMS), and physical fitness test performance during a 5-day period after a 90-min eccentric exercise bout in non-athletic non-obese males (= 92, ages 18-55 years). The two protein sources (0.9 g protein/kg divided into three doses/day) were administered under double blind procedures. The eccentric exercise protocol induced significant muscle damage and soreness, and reduced bench press and 30-s Wingate performance. Whey protein supplementation significantly attenuated post-exercise blood levels for biomarkers of muscle damage compared to water-only, with large effect sizes for creatine kinase and myoglobin during the fourth and fifth days of recovery (Cohen's d>0.80); pea protein versus water supplementation had an intermediate non-significant effect (Cohen's d<0.50); and no significant differences between whey and pea protein were found. Whey and pea protein compared to water supplementation had no significant effects on post-exercise DOMS and the fitness tests. In conclusion, high intake of whey protein for 5 days after intensive eccentric exercise mitigated the efflux of muscle damage biomarkers, with the intake of pea protein having an intermediate effect.


greenmedinfo--2020-08-21--Characterization of whey-based fermented beverages supplemented with hydrolyzed collagen: Antioxidan

Characterization of whey-based fermented beverages supplemented with hydrolyzed collagen: Antioxidant activity and bioavailability.

In this study , the preparation of a milk whey-based beverage with the addition of different concentrations of hydrolyzed collagen @ @ @ @ @ % , 0.75 % , and 1 % ) was carried out .
The control @ @ @ @ @ of 0 % .
Physicochemical properties , viscosity , antioxidant activity , and microbiological parameters @ @ @ @ @ % collagen treatment showed the highest protein content ( 9.75± 0.20 g/L ) , as @ @ @ @ @ ATBS ( 48.30 % ) and DPPH ( 30.06 % ) .
There were no @ @ @ @ @ ) in the fat and lactose parameters .
However , the pH in the control @ @ @ @ @ beverages treated with hydrolyzed collagen .
Fourier transform-infrared spectroscopy showed spectra characteristic of lactose and @ @ @ @ @ increased significantly as the concentration of hydrolyzed collagen increased .
The addition of hydrolyzed collagen @ @ @ @ @ value , and the antioxidant activity of the beverage .
Hydrolyzed collagen acted as an @ @ @ @ @ was no presence of microorganism pathogens observed in thetreated beverages .

In this study, the preparation of a milk whey-based beverage with the addition of different concentrations of hydrolyzed collagen (0.3%, 0.5%, 0.75%, and 1%) was carried out. The control was considered at a concentration of 0%. Physicochemical properties, viscosity, antioxidant activity, and microbiological parameters were evaluated. The 1% collagen treatment showed the highest protein content (9.75± 0.20 g/L), as well as radical inhibition for ATBS (48.30%) and DPPH (30.06%). There were no significant differences (≥ 0.05) in the fat and lactose parameters. However, the pH in the control treatment was lower compared to beverages treated with hydrolyzed collagen. Fourier transform-infrared spectroscopy showed spectra characteristic of lactose and collagen amides. The viscosity increased significantly as the concentration of hydrolyzed collagen increased. The addition of hydrolyzed collagen increased the bioavailability, nutritional value, and the antioxidant activity of the beverage. Hydrolyzed collagen acted as an antimicrobial agent, as there was no presence of microorganism pathogens observed in thetreated beverages.


greenmedinfo--2020-08-21--Traditional fermented foods with anti-aging effect: A concentric review

Fermentation has been applied since antiquity as a way to preserve foodstuff or as a necessary step in the production of a variety of products .
The research was initially focused on accurate description of production procedure and identification of parameters that may affect the composition and dynamics of the developing micro-communities , since the major aim was standardization and commercial exploitation of the products .
Soon it was realized that consumption of these products was associated with an array of health benefits , such as anti-hypertensive , anti-inflammatory , anti-diabetic , anti-carcinogenic and anti-allergenic activities .
These were credited @ @ @ @ @ @ @ products as well as their metabolic activities and the bio-transformations that took place during the fermentation process .
Aging has been defined as a gradual decline in the physiological function and concomitantly homeostasis , which is experienced by all living beings over time , leading inevitably to age-associated injuries , diseases , and finally death .
Research has focused on effective strategies to delay this process and thus increase both lifespan and well-being .
Fermented food products seem to be a promising alternative due to the immunomodulatory effect of microorganisms and elevated amounts @ @ @ @ @ @ @ series of anti-aging related benefits have been reported , some of which have been attributed to specific compounds such as genistein and daidzein in soybeans , while others are yet to be discovered .
The present article aims to collect and critically discuss all available literature regarding the anti-aging properties of fermented food products .

Fermentation has been applied since antiquity as a way to preserve foodstuff or as a necessary step in the production of a variety of products. The research was initially focused on accurate description of production procedure and identification of parameters that may affect the composition and dynamics of the developing micro-communities, since the major aim was standardization and commercial exploitation of the products. Soon it was realized that consumption of these products was associated with an array of health benefits, such as anti-hypertensive, anti-inflammatory, anti-diabetic, anti-carcinogenic and anti-allergenic activities. These were credited to the microorganisms present in the fermented products as well as their metabolic activities and the bio-transformations that took place during the fermentation process. Aging has been defined as a gradual decline in the physiological function and concomitantly homeostasis, which is experienced by all living beings over time, leading inevitably to age-associated injuries, diseases, and finally death. Research has focused on effective strategies to delay this process and thus increase both lifespan and well-being. Fermented food products seem to be a promising alternative due to the immunomodulatory effect of microorganisms and elevated amounts of bioactive compounds. Indeed, a series of anti-aging related benefits have been reported, some of which have been attributed to specific compounds such as genistein and daidzein in soybeans, while others are yet to be discovered. The present article aims to collect and critically discuss all available literature regarding the anti-aging properties of fermented food products.


greenmedinfo--2020-08-21--Myc is involved in genistein protecting against LPS-induced myocarditis.

BACKGROUND : Genistein is widely used as a pharmacological compound as well as a food additive .
However , the pharmaceutical effects of Genistein on myocarditis and its potential mechanisms have not been studied in detail .
METHODS : H9c2 cells were continuously stimulated by lipopolysaccharide ( LPS ) for 12 h to simulate the in vitro model of myocarditis injury .
DrugBank , String , and GEO dataset were used to investigate specific genes that interacting with Genistein .
KEGG and GO enrichment analysis were employed to explore Myc-related signaling pathways .
Biological behaviors of H9c2 cells were observed @ @ @ @ @ @ @ , MTT and flow cytometry .
Expression levels of cytokines including TNF-α and ILs were evaluated by enzyme-linked immunosorbent assay .
Western blot was applied to detect the expression of Myc and MAPK pathway related proteins .
RESULTS : Genistein alleviated the damage of H9c2 cells subjected to LPS from the perspective of elevating cells growth ability , and inhibiting cells apoptosis and inflammatory response .
Through bioinformatics analysis , we identified Myc as the potential target of Genistein in myocarditis , and MAPK as the signaling pathway .
Significantly , Myc was @ @ @ @ @ @ @ importantly , by performing biological experiments , we discovered that Genistein relieved H9c2 cells apoptosis and inflammatory reaction which caused by LPS stimulation through inhibiting Myc expression .
Additionally , the marked augmentation of p-P38 MAPK and p-JNK expression in LPS-induced cardiomyocyte model were blocked by Genistein and si-Myc .
CONCLUSIONS : Our research revealed that Myc mediated the protective effects of Genistein on H9c2 cells damage caused by LPS partly through modulation of MAPK/JNK signaling pathway .

BACKGROUND: Genistein is widely used as a pharmacological compound as well as a food additive. However, the pharmaceutical effects of Genistein on myocarditis and its potential mechanisms have not been studied in detail.
METHODS: H9c2 cells were continuously stimulated by lipopolysaccharide (LPS) for 12 h to simulate the in vitro model of myocarditis injury. DrugBank, String, and GEO dataset were used to investigate specific genes that interacting with Genistein. KEGG and GO enrichment analysis were employed to explore Myc-related signaling pathways. Biological behaviors of H9c2 cells were observed with the support of cell counting kit-8, MTT and flow cytometry. Expression levels of cytokines including TNF-α and ILs were evaluated by enzyme-linked immunosorbent assay. Western blot was applied to detect the expression of Myc and MAPK pathway related proteins.
RESULTS: Genistein alleviated the damage of H9c2 cells subjected to LPS from the perspective of elevating cells growth ability, and inhibiting cells apoptosis and inflammatory response. Through bioinformatics analysis, we identified Myc as the potential target of Genistein in myocarditis, and MAPK as the signaling pathway. Significantly, Myc was highly up-regulated in myocarditis samples. More importantly, by performing biological experiments, we discovered that Genistein relieved H9c2 cells apoptosis and inflammatory reaction which caused by LPS stimulation through inhibiting Myc expression. Additionally, the marked augmentation of p-P38 MAPK and p-JNK expression in LPS-induced cardiomyocyte model were blocked by Genistein and si-Myc.
CONCLUSIONS: Our research revealed that Myc mediated the protective effects of Genistein on H9c2 cells damage caused by LPS partly through modulation of MAPK/JNK signaling pathway.


greenmedinfo--2020-08-21--Genistein inhibits the proliferation, migration and invasion of the squamous cell carcinoma cells.

PURPOSE : The main purpose of the current research work was to investigate the anticancer activity of Genistein - a plant derived isoflavone - in squamous cell carcinoma SK-MEL-28 ( SCC ) cells along with studying its effects on cellular apoptosis , DNA damage , cell migration and invasion and MEK/ERK/JNK signalling pathway .
METHODS : Cell proliferation was examined by CCK-8 ( Cell Counting Kit-8 ) assay while the effects on apoptosis were evaluated by DAPI staining and Comet assay using fluorescence microscopy .
Transwell assay was used for checking the effects on cell migration and invasion while western @ @ @ @ @ @ @ effects on the expression of MEK/ERK/JNK proteins .
RESULTS : The results showed that Genistein led to dose-dependent cytotoxic effects in these cells showing an IC50 value of 14.5μM .
It also led to dose-dependent apoptosis and induced DNA damage as shown by fluorescence microscopy .
Genistein also inhibited cell migration and invasion dose-dependently , along with inhibiting matrix metalloproteinase ( MMP ) -9 expression .
Genistein also led to inhibition of the expression of p-JNK with no apparent effects on the total JNK expression .
It also showed significant and dose-dependent inhibition @ @ @ @ @ @ @ proteins .
CONCLUSIONS : Genistein has a significant anticancer activity in SK-MEL-28 human SCC cells , inducing apoptosis , DNA damage , cell migration and invasion and inhibiting MEK/ERK and JNK signalling pathway .

PURPOSE: The main purpose of the current research work was to investigate the anticancer activity of Genistein - a plant derived isoflavone - in squamous cell carcinoma SK-MEL-28 (SCC) cells along with studying its effects on cellular apoptosis, DNA damage, cell migration and invasion and MEK/ERK/JNK signalling pathway.
METHODS: Cell proliferation was examined by CCK-8 (Cell Counting Kit-8) assay while the effects on apoptosis were evaluated by DAPI staining and Comet assay using fluorescence microscopy. Transwell assay was used for checking the effects on cell migration and invasion while western blot method was used to evaluate the effects on the expression of MEK/ERK/JNK proteins.
RESULTS: The results showed that Genistein led to dose-dependent cytotoxic effects in these cells showing an IC50 value of 14.5μM. It also led to dose-dependent apoptosis and induced DNA damage as shown by fluorescence microscopy. Genistein also inhibited cell migration and invasion dose-dependently, along with inhibiting matrix metalloproteinase (MMP)-9 expression. Genistein also led to inhibition of the expression of p-JNK with no apparent effects on the total JNK expression. It also showed significant and dose-dependent inhibition of the expression of p-MEK and p-ERK proteins.
CONCLUSIONS: Genistein has a significant anticancer activity in SK-MEL-28 human SCC cells, inducing apoptosis, DNA damage, cell migration and invasion and inhibiting MEK/ERK and JNK signalling pathway.


greenmedinfo--2020-08-21--Amelioration of PM 2.5-induced lung toxicity in rats by nutritional supplementation with biochanin A

Amelioration of PM 2.5-induced lung toxicity in rats by nutritional supplementation with biochanin A.

Epidemiological studies have shown that particulate matter with an aerodynamic diameter less than 2.5 μm ( PM ) is closely associated with human health issues , especially pulmonary diseases such as chronic obstructive pulmonary disease ( COPD ) , asthma and lung cancer .
In this study , particles were characterized by scanning electron microscopy ( SEM ) , microbeam energy-dispersive X-ray spectroscopy ( EDS ) , inductively coupled plasma mass spectrometry ( ICP-MS ) and high-performance liquid chromatography ( HPLC ) .
A rat model of PMexposure was established by nonsurgical intratracheal instillation , and the effects of biochanin @ @ @ @ @ @ @ .
BCA showed a protective effect ; it reduced PM-induced apoptosis and the production of proinflammatory factors , such as tumor necrosis factor-α ( TNF-α ) , interleukin-2 ( IL-2 ) , interleukin-6 ( IL-6 ) , and the chemokine interleukin-8 ( IL-8 ) , as measured using ELISA .
These effects were accompanied by increases in the levels of antioxidant enzymes and decreases in the levels of malondialdehyde ( MDA ) , lactate dehydrogenase ( LDH ) and alkaline phosphatase ( AKP ) .
Furthermore , isobaric tag for relative and absolute @ @ @ @ @ @ @ and bioinformatics tools were used to identify putative biomarkers , including XRCC1 , MP2K5 , IGJ , and F1LQ12 , and the results were verified by Western blot analysis .
In conclusion , our findings have scientific significance for the application of flavonoids in preventive and therapeutic strategies for PM-associated pulmonary diseases and for the promotion of human health .

Epidemiological studies have shown that particulate matter with an aerodynamic diameter less than 2.5 μm (PM) is closely associated with human health issues, especially pulmonary diseases such as chronic obstructive pulmonary disease (COPD), asthma and lung cancer. In this study, particles were characterized by scanning electron microscopy (SEM), microbeam energy-dispersive X-ray spectroscopy (EDS), inductively coupled plasma mass spectrometry (ICP-MS) and high-performance liquid chromatography (HPLC). A rat model of PMexposure was established by nonsurgical intratracheal instillation, and the effects of biochanin A (BCA) treatment were examined. BCA showed a protective effect; it reduced PM-induced apoptosis and the production of proinflammatory factors, such as tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2), interleukin-6 (IL-6), and the chemokine interleukin-8 (IL-8), as measured using ELISA. These effects were accompanied by increases in the levels of antioxidant enzymes and decreases in the levels of malondialdehyde (MDA), lactate dehydrogenase (LDH) and alkaline phosphatase (AKP). Furthermore, isobaric tag for relative and absolute quantitation (iTRAQ)-based analytical techniques and bioinformatics tools were used to identify putative biomarkers, including XRCC1, MP2K5, IGJ, and F1LQ12, and the results were verified by Western blot analysis. In conclusion, our findings have scientific significance for the application of flavonoids in preventive and therapeutic strategies for PM-associated pulmonary diseases and for the promotion of human health.


greenmedinfo--2020-08-21--The combination of Biochanin A and SB590885 potentiates the inhibition of tumour progression in hepa

The combination of Biochanin A and SB590885 potentiates the inhibition of tumour progression in hepatocellular carcinoma.

Background : Hepatocellular carcinoma ( HCC ) is the most aggressive and frequently diagnosed malignancy of the liver .
Despite aggressive therapy , life expectancy of many patients in these cases is extended by only a few months .
Hepatocellular carcinoma ( HCC ) has a particularly poor prognosis and would greatly benefit from more effective therapies .
Methods : The CCK-8 assay and colony formation assays were used to test the cell proliferation and viability .
The effects of combination Biochanin A and SB590885 on apoptosis and cell cycle arrest of HCC cells were analysed by flow cytometry .
@ @ @ @ @ @ @ signalling as well as apoptosis and cell cycle-related proteins in HCC cells were tested by western blotting .
The HCC cell xenograft model was established to test the tumor proliferation .
Serum and plasma were tested for liver and kidney safety markers ( ALP , ALT , AST , total bilirubin , creatinine , urea nitrogen ) by using SpectraMax i3X .
Results : The combination of natural product Biochanin A with the BRAF inhibitor SB590885 synergistically suppressed proliferation , and promoted cell cycle arrest and apoptosis in vitro .
Furthermore , we @ @ @ @ @ @ @ and SB590885 led to increased impairment of proliferation and HCC tumour inhibition through disrupting of the ERK MAPK and the PI3K/AKT pathways in vitro .
The volumes tumors and the weights of tumours were significantly reduced by the combination treatment compared to the control or single treatments in vivo .
In addition , we found that there was no significant hepatorenal toxicity with the drug combination , as indicated by the hepatorenal toxicity test .
Conclusion : The results identify an effective combination therapy for the most aggressive form of HCC and provide @ @ @ @ @ @ @ with advanced HCC .

Background: Hepatocellular carcinoma (HCC) is the most aggressive and frequently diagnosed malignancy of the liver. Despite aggressive therapy, life expectancy of many patients in these cases is extended by only a few months. Hepatocellular carcinoma (HCC) has a particularly poor prognosis and would greatly benefit from more effective therapies.
Methods: The CCK-8 assay and colony formation assays were used to test the cell proliferation and viability. The effects of combination Biochanin A and SB590885 on apoptosis and cell cycle arrest of HCC cells were analysed by flow cytometry. The expression of ERK MAPK and PI3K/AKT/mTOR signalling as well as apoptosis and cell cycle-related proteins in HCC cells were tested by western blotting. The HCC cell xenograft model was established to test the tumor proliferation. Serum and plasma were tested for liver and kidney safety markers (ALP, ALT, AST, total bilirubin, creatinine, urea nitrogen) by using SpectraMax i3X.
Results: The combination of natural product Biochanin A with the BRAF inhibitor SB590885 synergistically suppressed proliferation, and promoted cell cycle arrest and apoptosis in vitro. Furthermore, we demonstrated that the combination of Biochanin A and SB590885 led to increased impairment of proliferation and HCC tumour inhibition through disrupting of the ERK MAPK and the PI3K/AKT pathways in vitro. The volumes tumors and the weights of tumours were significantly reduced by the combination treatment compared to the control or single treatments in vivo. In addition, we found that there was no significant hepatorenal toxicity with the drug combination, as indicated by the hepatorenal toxicity test.
Conclusion: The results identify an effective combination therapy for the most aggressive form of HCC and provide the possibility of therapeutic improvement for patients with advanced HCC.


greenmedinfo--2020-08-21--Biochanin-A ameliorates pulmonary fibrosis.

BACKGROUND : Idiopathic Pulmonary Fibrosis ( IPF ) is a progressive inflammatory disorder driven by a fibrotic cascade of events such as epithelial to mesenchymal transition , extracellular matrix production and collagen formation in the lungs in a sequential manner .
IPF incidences were raising rapidly across the world .
FDA approved pirfenidone and nintedanib ( tyrosine kinase inhibitors ) are being used as a first-line treatment drugs for IPF , however , neither the quality of life nor survival rates have been improved because of patient noncompliance due to multiple side effects .
Thus , the development of novel @ @ @ @ @ @ @ fibrotic events is urgently needed to improve the survival of the patients suffering from devastating disease .
PURPOSE : The aim of this study was to investigate and validate the anti-fibrotic properties of Biochanin-A ( isoflavone ) against TGF-β mediated fibrosis in in vitro , ex vivo , in vivo models and to determine the molecular mechanisms that mediate these anti-fibrotic effects .
METHODS : The therapeutic activity of BCA was determined in in vitro/ex vivo models .
Cells were pre-treated with BCA and incubated in presence or absence of recombinant-TGF-β to stimulate @ @ @ @ @ @ @ fibrosis was developed by intratracheal administration of bleomycin in rats .
BCA treatment was given for 14 days from post bleomycin instillation and then various investigations ( collagen content , fibrosis gene/protein expression and histopathological changes ) were performed to assess the anti-fibrotic activity of BCA .
RESULTS : In vitro/ex vivo ( Primary normal , IPF cell line and primary IPF cells/ Precision cut mouse lung slices ) experiments revealed that , BCA treatment significantly ( p < 0.001 ) reduced the expression of TGF-β modulated fibrotic genes/protein expressions ( including their @ @ @ @ @ @ @ cascade of fibrotic events .
BCA treatment significantly ( p < 0.01 ) reduced the bleomycin-induced inflammatory cell-infiltration , inflammatory markers expression , collagen deposition and expression of fibrotic markers in lung tissues equivalent or better than pirfenidone treatment .
In addition , BCA treatment significantly ( p < 0.001 ) attenuated the TGF-β1/BLM-mediated increase of TGF-β/Smad2/3 phosphorylation and resulted in the reduction of pathological abnormalities in lung tissues determined by histopathology observations .
CONCLUSION : Collectively , BCA treatment demonstrated the remarkable therapeutic effects on TGF-β/BLM mediated pulmonary fibrosis using IPF cells @ @ @ @ @ @ @ may offer a novel treatment approach to halt and may be even rescue the devastating lung scarring of IPF .

BACKGROUND: Idiopathic Pulmonary Fibrosis (IPF) is a progressive inflammatory disorder driven by a fibrotic cascade of events such as epithelial to mesenchymal transition, extracellular matrix production and collagen formation in the lungs in a sequential manner. IPF incidences were raising rapidly across the world. FDA approved pirfenidone and nintedanib (tyrosine kinase inhibitors) are being used as a first-line treatment drugs for IPF, however, neither the quality of life nor survival rates have been improved because of patient noncompliance due to multiple side effects. Thus, the development of novel therapeutic approaches targeting TGF-β mediated cascade of fibrotic events is urgently needed to improve the survival of the patients suffering from devastating disease.
PURPOSE: The aim of this study was to investigate and validate the anti-fibrotic properties of Biochanin-A (isoflavone) against TGF-β mediated fibrosis in in vitro, ex vivo, in vivo models and to determine the molecular mechanisms that mediate these anti-fibrotic effects.
METHODS: The therapeutic activity of BCA was determined in in vitro/ex vivo models. Cells were pre-treated with BCA and incubated in presence or absence of recombinant-TGF-β to stimulate the fibrotic cascade of events. Pulmonary fibrosis was developed by intratracheal administration of bleomycin in rats. BCA treatment was given for 14 days from post bleomycin instillation and then various investigations (collagen content, fibrosis gene/protein expression and histopathological changes) were performed to assess the anti-fibrotic activity of BCA.
RESULTS: In vitro/ex vivo (Primary normal, IPF cell line and primary IPF cells/ Precision cut mouse lung slices) experiments revealed that, BCA treatment significantly (p <0.001) reduced the expression of TGF-β modulated fibrotic genes/protein expressions (including their functions) which are involved in the cascade of fibrotic events. BCA treatment significantly (p<0.01) reduced the bleomycin-induced inflammatory cell-infiltration, inflammatory markers expression, collagen deposition and expression of fibrotic markers in lung tissues equivalent or better than pirfenidone treatment. In addition, BCA treatment significantly (p<0.001) attenuated the TGF-β1/BLM-mediated increase of TGF-β/Smad2/3 phosphorylation and resulted in the reduction of pathological abnormalities in lung tissues determined by histopathology observations.
CONCLUSION: Collectively, BCA treatment demonstrated the remarkable therapeutic effects on TGF-β/BLM mediated pulmonary fibrosis using IPF cells and rodent models. This current study may offer a novel treatment approach to halt and may be even rescue the devastating lung scarring of IPF.


greenmedinfo--2020-08-21--Genistein suppresses the proliferative activity in Src-activated human gallbladder carcinoma cells.

Activated Src have been strongly implicated in the development , progression , and metastasis of many human cancers .
Although soy isoflavones exhibit potential anticancer activity , effects of isoflavones on oncogenic activity of Src remains unknown .
Using v-src-transfected human adenocarcinoma cells ( HAG/src3-1 ) , we investigated the functional role of Src in anti-proliferative activity of isoflavones including genistein , daidzein , glycitein and equol .
The growth of HAG/neo3-5 vehicle control cells was inhibited potently by genistein and equol , but modestly by daidzein and glycitein .
In contrast , Src activation conferred resistance to either daidzein @ @ @ @ @ @ @ the cells more sensitive to genistein , compared to HAG/neo3-5 cells .
Genistein significantly arrested HAG/src3-1 cells at G2/M , while neither daidzein , glycitein nor equol arrested the cells at any cell cycle phases .
Apoptosis was not induced by either isoflavones .
Genistein increased the expression levels of p53 and p21 with decreased phosphorylated p21 , but did not affect the levels of major cyclin-CDK complexes .
Taken together , genistein would be considered as the only isoflavone component that may potentially suppress Src-driven proliferative activity by arresting at G2/M induction @ @ @ @ @ @ @ providing the mechanistic rationale for the potential use of genistein for the prevention of human cancers with activated Src .

Activated Src have been strongly implicated in the development, progression, and metastasis of many human cancers. Although soy isoflavones exhibit potential anticancer activity, effects of isoflavones on oncogenic activity of Src remains unknown. Using v-src-transfected human adenocarcinoma cells (HAG/src3-1), we investigated the functional role of Src in anti-proliferative activity of isoflavones including genistein, daidzein, glycitein and equol. The growth of HAG/neo3-5 vehicle control cells was inhibited potently by genistein and equol, but modestly by daidzein and glycitein. In contrast, Src activation conferred resistance to either daidzein, glycitein or equol, but rendered the cells more sensitive to genistein, compared to HAG/neo3-5 cells. Genistein significantly arrested HAG/src3-1 cells at G2/M, while neither daidzein, glycitein nor equol arrested the cells at any cell cycle phases. Apoptosis was not induced by either isoflavones. Genistein increased the expression levels of p53 and p21 with decreased phosphorylated p21, but did not affect the levels of major cyclin-CDK complexes. Taken together, genistein would be considered as the only isoflavone component that may potentially suppress Src-driven proliferative activity by arresting at G2/M induction through increasing the p21 levels, thus providing the mechanistic rationale for the potential use of genistein for the prevention of human cancers with activated Src.


greenmedinfo--2020-08-21--Daidzein exhibits neuroprotective effects against neurotoxins induced toxicity in human neuroblastom

Daidzein exhibits neuroprotective effects against neurotoxins induced toxicity in human neuroblastoma SH-SY5Y cells.

Emerging data support that plant food based isoflavones have ameliorating effects on a variety of neurodegenerative diseases including Parkinson 's disease ( PD ) .
Our previous investigation revealed that dietary isoflavones including genistein ( GEN ) , daidzein ( DAI ) , and equol ( EQL ; a gut microbial metabolite of DAI ) showed promising blood-brain barrier permeability and anti-neuroinflammatory activity in murine microglial BV2 cells .
However , the neuroprotective effects of EQL against neurotoxins induced toxicity in PD related models remains unclear .
Herein , EQL , along with GEN and DAI , were evaluated for @ @ @ @ @ @ @ model with LPS-BV2-conditioned media and human neuroblastoma SH-SY5Y cells .
In addition , their neuroprotective effects against PD related neurotoxins including 6-hydroxydopamine ( 6-OHDA ) and 1-methyl-4-phenylpyridinium ( MPP ) induced cytotoxicity were evaluated in SH-SY5Y cells .
Furthermore , EQL was evaluated for its neuroprotective effects against MPPinduced neurotoxicity using in vivo PD model including Caenorhabditis elegans lifespan assay .
DAI ( 10 μM ) and EQL ( 10 and 20 μM ) showed cytoprotective effects by decreasing LPS-BV2-conditioned media induced cytotoxicity in SH-SY5Y cells by 29.2 , 32.4 and 27.2 % @ @ @ @ @ @ @ 20 μM ) also showed neuroprotective effects by decreasing 6-OHDA and MPPinduced cytotoxicity in SH-SY5Y cells by 30.6-34.5 and 17.9-18.9 % , respectively .
Additionally , data from the in vivo assay supported EQL 's neuroprotective effect as it increases survival of C. elegans exposed to MPPfrom 72 to 108 h. Our findings support a growing body of evidence of the neuroprotective effects of dietary isoflavones and further studies are warranted to elucidate their mechanisms of action .

Emerging data support that plant food based isoflavones have ameliorating effects on a variety of neurodegenerative diseases including Parkinson's disease (PD). Our previous investigation revealed that dietary isoflavones including genistein (GEN), daidzein (DAI), and equol (EQL; a gut microbial metabolite of DAI) showed promising blood-brain barrier permeability and anti-neuroinflammatory activity in murine microglial BV2 cells. However, the neuroprotective effects of EQL against neurotoxins induced toxicity in PD related models remains unclear. Herein, EQL, along with GEN and DAI, were evaluated for their cytoprotective effect in a non-contact co-culture model with LPS-BV2-conditioned media and human neuroblastoma SH-SY5Y cells. In addition, their neuroprotective effects against PD related neurotoxins including 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenylpyridinium (MPP) induced cytotoxicity were evaluated in SH-SY5Y cells. Furthermore, EQL was evaluated for its neuroprotective effects against MPPinduced neurotoxicity using in vivo PD model including Caenorhabditis elegans lifespan assay. DAI (10 μM) and EQL (10 and 20 μM) showed cytoprotective effects by decreasing LPS-BV2-conditioned media induced cytotoxicity in SH-SY5Y cells by 29.2, 32.4 and 27.2%, respectively. EQL (10 and 20 μM) also showed neuroprotective effects by decreasing 6-OHDA and MPPinduced cytotoxicity in SH-SY5Y cells by 30.6-34.5 and 17.9-18.9%, respectively. Additionally, data from the in vivo assay supported EQL's neuroprotective effect as it increases survival of C. elegans exposed to MPPfrom 72 to 108 h. Our findings support a growing body of evidence of the neuroprotective effects of dietary isoflavones and further studies are warranted to elucidate their mechanisms of action.


greenmedinfo--2020-08-21--Low dose of genistein alleviates phthalate-induced fetal testis disorder.

Mono- ( 2-ethylhexyl ) phthalate ( MEHP ) and genistein have been classified as endocrine-disrupting chemicals ( EDCs ) which interfere with the differentiation and development of the male reproductive system .
However , how these two EDCs would affect fetal rat testis development at a low dose was rarely studied .
In this study , we established the organ culture system and applied it to evaluate testicular effects following multiple EDC exposure at a low dose .
15.5 days postcoitum fetal rat testes were dissected , cultured , and exposed to vehicle ( control ) , GEN ( 1 @ @ @ @ @ @ @ 1 mol/L , M ) , or GEN ( 1 mol/L ) +MEHP ( 1 mol/L , G+M ) .
Testicular cell markers , testosterone concentration , redox state , testicular histology , and testicular ultrastructure were evaluated .
Our results showed that a low dose of MEHP suppressed the development of Sertoli cells , Leydig cells , and gonocytes by triggering oxidative injuries , which was consistent with the ultrastructural findings .
However , coadministration of genistein at a low dose could partially attenuate MEHP-induced fetal testis damage through antioxidative action .
@ @ @ @ @ @ @ may have a promising future on its protecting role for attenuating other EDC-induced reproductive disorders during early life .
Based on the results , it can be speculated that dietary intake of isoflavones may make the fetal testis less susceptible to phthalate-induced injury .

Mono-(2-ethylhexyl) phthalate (MEHP) and genistein have been classified as endocrine-disrupting chemicals (EDCs) which interfere with the differentiation and development of the male reproductive system. However, how these two EDCs would affect fetal rat testis development at a low dose was rarely studied. In this study, we established the organ culture system and applied it to evaluate testicular effects following multiple EDC exposure at a low dose. 15.5 days postcoitum fetal rat testes were dissected, cultured, and exposed to vehicle (control), GEN (1 mol/L, G), MEHP (1 mol/L, M), or GEN (1 mol/L)+MEHP (1 mol/L, G+M). Testicular cell markers, testosterone concentration, redox state, testicular histology, and testicular ultrastructure were evaluated. Our results showed that a low dose of MEHP suppressed the development of Sertoli cells, Leydig cells, and gonocytes by triggering oxidative injuries, which was consistent with the ultrastructural findings. However, coadministration of genistein at a low dose could partially attenuate MEHP-induced fetal testis damage through antioxidative action. Cotreatment of genistein at a low dose may have a promising future on its protecting role for attenuating other EDC-induced reproductive disorders during early life. Based on the results, it can be speculated that dietary intake of isoflavones may make the fetal testis less susceptible to phthalate-induced injury.


greenmedinfo--2020-08-21--These results provide novel insights into the antiobesity and antiglycation roles of dietary geniste

These results provide novel insights into the antiobesity and antiglycation roles of dietary genistein in obese subjects.

Our previous study has found that dietary genistein could ameliorate high-fat diet ( HFD ) -induced obesity and especially lower @ @ @ @ @ advanced glycation end product ( AGE ) accumulation in healthy mice exposed to genistein and @ @ @ @ @ is still unclear whether dietary genistein intervention has a similar beneficial effect in obese mice @ @ @ @ @ the mice were induced with obesity after being fed a HFD for nine weeks before @ @ @ @ @ of genistein , 0.1 % ( G 0.1 ) and 0.2 % ( G 0.2 @ @ @ @ @ for additional 19 weeks .
After 19 week treatment , genistein supplementation reduced body and @ @ @ @ @ liver MGO levels , and kidney AGE levels in mice .
Mechanistically , genistein upregulated @ @ @ @ @ and II and aldose reductase to detoxify MGO , and genistein and its microbial metabolites @ @ @ @ @ demethylangolensin , were able to trap endogenous MGOformation of MGO conjugates .
Taken together , @ @ @ @ @ into the antiobesity and antiglycation roles of dietary genistein in obese subjects .

Our previous study has found that dietary genistein could ameliorate high-fat diet (HFD)-induced obesity and especially lower methylglyoxal (MGO) and advanced glycation end product (AGE) accumulation in healthy mice exposed to genistein and HFD. However, it is still unclear whether dietary genistein intervention has a similar beneficial effect in obese mice. In this study, the mice were induced with obesity after being fed a HFD for nine weeks before being administered with two doses of genistein, 0.1% (G 0.1) and 0.2% (G 0.2), in the HFD for additional 19 weeks. After 19 week treatment, genistein supplementation reduced body and liver weights, plasma and liver MGO levels, and kidney AGE levels in mice. Mechanistically, genistein upregulated the expressions of glyoxalase I and II and aldose reductase to detoxify MGO, and genistein and its microbial metabolites, dihydrogenistein and 6'-hydroxy--demethylangolensin, were able to trap endogenous MGOformation of MGO conjugates. Taken together, our results provide novel insights into the antiobesity and antiglycation roles of dietary genistein in obese subjects.


greenmedinfo--2020-08-21--Genistein and galantamine combinations decrease β-amyloid peptide (1-42)-induced genotoxicity and ce

Genistein and galantamine combinations decrease β-amyloid peptide (1-42)-induced genotoxicity and cell death in SH-SY5Y cell line.

Alzheimer 's disease ( AD ) is the primary dementia-causing disease worldwide , involving a multifactorial combination of environmental , genetic , and epigenetic factors , with essential participation of age and sex .
Biochemically , AD is characterized by the presence of abnormal deposition of beta amyloid peptide ( Aβ ) , which in the brain is strongly correlated with oxidative stress , inflammation , DNA damage , and cholinergic impairment .
The multiple mechanisms involved in its etiology create significant difficulty in producing an effective treatment .
Neuroprotective properties of genistein and galantamine have been widely demonstrated through @ @ @ @ @ @ @ unknown a possible synergistic neuroprotective effect against Aβ .
In order to understand how genistein and galantamine combinations regulate the mechanisms of neuroprotection , we conducted a set of bioassays in vitro to evaluate cell viability , clonogenic survival , cell death , and anti-genotoxicity .
Through molecular docking and therapeutic viability assays , we analyzed the inhibitory activity exerted by genistein on three major protein targets ( AChE , BChE , and NMDA ) involved in AD .
The results showed that genistein and galantamine afforded significant protection at higher concentrations ; @ @ @ @ @ @ @ both compounds provided marked neuroprotection when they were combined .
In silico approaches showed that genistein has higher scores than the positive controls and low toxicity levels ; nevertheless , the therapeutic viability indicated that unlike galantamine , genistein can not undergo the action by P glycoprotein ( PGP ) and probably may be unable to cross the blood-brain barrier .
In conclusion , our results show that genistein and galantamine exert neuroprotective by decreasing genotoxicity and cell death .
In silico analysis , suggest that genistein modulates positively the expression of AChE @ @ @ @ @ @ @ this context , a combination of two or more drugs could inspire an attractive therapeutic strategy .

Alzheimer's disease (AD) is the primary dementia-causing disease worldwide, involving a multifactorial combination of environmental, genetic, and epigenetic factors, with essential participation of age and sex. Biochemically, AD is characterized by the presence of abnormal deposition of beta amyloid peptide (Aβ), which in the brain is strongly correlated with oxidative stress, inflammation, DNA damage, and cholinergic impairment. The multiple mechanisms involved in its etiology create significant difficulty in producing an effective treatment. Neuroprotective properties of genistein and galantamine have been widely demonstrated through different mechanisms; however, it is unknown a possible synergistic neuroprotective effect against Aβ. In order to understand how genistein and galantamine combinations regulate the mechanisms of neuroprotection, we conducted a set of bioassays in vitro to evaluate cell viability, clonogenic survival, cell death, and anti-genotoxicity. Through molecular docking and therapeutic viability assays, we analyzed the inhibitory activity exerted by genistein on three major protein targets (AChE, BChE, and NMDA) involved in AD. The results showed that genistein and galantamine afforded significant protection at higher concentrations; however, combinations of sub-effective concentrations of both compounds provided marked neuroprotection when they were combined. In silico approaches showed that genistein has higher scores than the positive controls and low toxicity levels; nevertheless, the therapeutic viability indicated that unlike galantamine, genistein cannot undergo the action by P glycoprotein (PGP) and probably may be unable to cross the blood-brain barrier. In conclusion, our results show that genistein and galantamine exert neuroprotective by decreasing genotoxicity and cell death. In silico analysis, suggest that genistein modulates positively the expression of AChE, BChE, and NMDA. In this context, a combination of two or more drugs could inspire an attractive therapeutic strategy.


greenmedinfo--2020-08-21--Dietary genistein supplementation protects against lipopolysaccharide-induced intestinal injury thro

Dietary genistein supplementation protects against lipopolysaccharide-induced intestinal injury through altering transcriptomic profile.

Genistein is abundant in the corn-soybean meal feed .
Little information is available about the effect of dietary genistein on the intestinal transcriptome of chicks , especially when suffering from intestinal injury .
In this study , 180 one-day-old male ROSS 308 broiler chickens were randomly allocated to 3 groups , with 4 replicates ( cages ) of 15 birds each .
The treatments were as follows : chicks received a basal diet ( CON ) , a basal diet and underwent lipopolysaccharide-challenge ( LPS ) , or a basal diet supplemented with 40 mg/kg genistein and underwent LPS-challenge ( @ @ @ @ @ @ @ injury and inflammatory reactions in the chicks .
Transcriptomic analysis identified 7,131 differently expressed genes ( 3,281 upregulated and 3,851 downregulated ) in the GEN group compared with the LPS group ( P adjusted value 1.5 ) , which revealed that dietary genistein exposure altered the gene expression profile and signaling pathways in the ileum of LPS-treated chicks .
Furthermore , dietary genistein improved intestinal morphology , mucosal immune function , tight junction , antioxidant activity , apoptotic process , and growth performance , which were adversely damaged by LPS injection .
Therefore @ @ @ @ @ @ @ chicks can alter RNA expression profile and ameliorate intestinal injury in LPS-challenged chicks , thereby improving the growth performance of chicks with intestinal injury .

Genistein is abundant in the corn-soybean meal feed. Little information is available about the effect of dietary genistein on the intestinal transcriptome of chicks, especially when suffering from intestinal injury. In this study, 180 one-day-old male ROSS 308 broiler chickens were randomly allocated to 3 groups, with 4 replicates (cages) of 15 birds each. The treatments were as follows: chicks received a basal diet (CON), a basal diet and underwent lipopolysaccharide-challenge (LPS), or a basal diet supplemented with 40 mg/kg genistein and underwent LPS-challenge (GEN). LPS injection induced intestinal injury and inflammatory reactions in the chicks. Transcriptomic analysis identified 7,131 differently expressed genes (3,281 upregulated and 3,851 downregulated) in the GEN group compared with the LPS group (P adjusted value < 0.05, |fold change|>1.5), which revealed that dietary genistein exposure altered the gene expression profile and signaling pathways in the ileum of LPS-treated chicks. Furthermore, dietary genistein improved intestinal morphology, mucosal immune function, tight junction, antioxidant activity, apoptotic process, and growth performance, which were adversely damaged by LPS injection. Therefore, adding genistein into the diet of chicks can alter RNA expression profile and ameliorate intestinal injury in LPS-challenged chicks, thereby improving the growth performance of chicks with intestinal injury.


greenmedinfo--2020-08-21--Genistein attenuates acute cerebral ischemic damage.

Postmenopausal women have a higher incidence of stroke compared to the age-matched males , and the estrogen was thought to be the main cause of such difference .
However , estrogen replacement therapy for the prevention of postmenopausal stroke shows controversial results and is widely disputed because of its serious side effects after chronic administration .
Genistein ( Gen ) , a natural phytestrogen with fewer side effects , has a protective effect against cerebral ischemia damage .
However , whether Gen could effectively prevent postmenopausal stroke has not been elucidated .
In the current study , reproductively senescent mice @ @ @ @ @ @ @ ) for 2 weeks before having transient cerebral ischemia insults .
Neurological scores , infarct volumes , and cell apoptosis were evaluated 24 h after reperfusion .
The levels of inflammatory factors and nod-like receptor protein 3 ( NLRP3 ) inflammasome-related proteins were also examined .
The results showed that Gen treatment reduced infarct volumes , improved neurological scores , attenuated apoptosis , and decreased inflammatory factor release .
The expression of NLRP3 inflammasome-related proteins in microglia was downregulated by Gen .
However , the overexpression of NLRP3 in microglia abrogated the Gen-induced @ @ @ @ @ @ @ the neuroprotective effect of Gen. Taken together , the results suggest that Gen treatment could attenuate the acute injury induced by cerebral ischemia in reproductively senescent micethe inhibition of the NLRP3 inflammasome in microglia , indicating that Gen could be a candidate drug for the treatment of stroke in postmenopausal women .

Postmenopausal women have a higher incidence of stroke compared to the age-matched males, and the estrogen was thought to be the main cause of such difference. However, estrogen replacement therapy for the prevention of postmenopausal stroke shows controversial results and is widely disputed because of its serious side effects after chronic administration. Genistein (Gen), a natural phytestrogen with fewer side effects, has a protective effect against cerebral ischemia damage. However, whether Gen could effectively prevent postmenopausal stroke has not been elucidated. In the current study, reproductively senescent mice were treated with Gen (10 mg/kg) for 2 weeks before having transient cerebral ischemia insults. Neurological scores, infarct volumes, and cell apoptosis were evaluated 24 h after reperfusion. The levels of inflammatory factors and nod-like receptor protein 3 (NLRP3) inflammasome-related proteins were also examined. The results showed that Gen treatment reduced infarct volumes, improved neurological scores, attenuated apoptosis, and decreased inflammatory factor release. The expression of NLRP3 inflammasome-related proteins in microglia was downregulated by Gen. However, the overexpression of NLRP3 in microglia abrogated the Gen-induced inhibition of inflammatory factor release and reversed the neuroprotective effect of Gen. Taken together, the results suggest that Gen treatment could attenuate the acute injury induced by cerebral ischemia in reproductively senescent micethe inhibition of the NLRP3 inflammasome in microglia, indicating that Gen could be a candidate drug for the treatment of stroke in postmenopausal women.


greenmedinfo--2020-08-21--Genistein attenuates cognitive deficits and neuroapoptosis in hippocampus induced by ketamine exposu

Genistein attenuates cognitive deficits and neuroapoptosis in hippocampus induced by ketamine exposure.

Ketamine is a frequently used anesthetic in pediatric patients that can cause cognitive impairment .
Genistein , a bioactive component of soy products , has been shown to suppress neuronal death through regulating the expression of apoptosis related genes .
In this study , we hypothesized that genistein could alleviate ketamine-induced cognitive impairment by ameliorating hippocampal neuronal loss and tested this hypothesis in rats .
Neonatal rats were treated with ketamine and genistein .
Hippocampal tissue was harvested for histological and biochemical analysis to determine neuronal apoptosis and proteins involved in the apoptotic pathways .
Behavioral assays including contextual fear @ @ @ @ @ @ @ were performed to assess cognitive functions , including learning and memory .
We found that in fear conditioning test , genistein restored freezing time in ketamine treated rats in a dose dependent manner .
Similarly , genistein attenuated impaired learning and memory in Morris water maze test in rats treated with ketamine .
Additionally , ketamine-induced neuronal apoptosis in rat hippocampus was attenuated by genistein treatment .
Finally , we found that genistein partially restored proteins associated with apoptosis , including Bax , Bcl-2 , cleaved caspase 3 , and phosphorylated GSK-3ß and @ @ @ @ @ @ @ and cognitive disruption induced by ketamine in rats .

Ketamine is a frequently used anesthetic in pediatric patients that can cause cognitive impairment. Genistein, a bioactive component of soy products, has been shown to suppress neuronal death through regulating the expression of apoptosis related genes. In this study, we hypothesized that genistein could alleviate ketamine-induced cognitive impairment by ameliorating hippocampal neuronal loss and tested this hypothesis in rats. Neonatal rats were treated with ketamine and genistein. Hippocampal tissue was harvested for histological and biochemical analysis to determine neuronal apoptosis and proteins involved in the apoptotic pathways. Behavioral assays including contextual fear conditioning test and Morris water maze test were performed to assess cognitive functions, including learning and memory. We found that in fear conditioning test, genistein restored freezing time in ketamine treated rats in a dose dependent manner. Similarly, genistein attenuated impaired learning and memory in Morris water maze test in rats treated with ketamine. Additionally, ketamine-induced neuronal apoptosis in rat hippocampus was attenuated by genistein treatment. Finally, we found that genistein partially restored proteins associated with apoptosis, including Bax, Bcl-2, cleaved caspase 3, and phosphorylated GSK-3ß and Akt. Genistein suppresses hippocampal neuronal loss and cognitive disruption induced by ketamine in rats.


greenmedinfo--2020-08-21--Advanced glycation end products in diabetes, cancer and phytochemical therapy.

The irreversible glycation and oxidation of proteins and lipids produces advanced glycation end products ( AGEs ) .
These modified @ @ @ @ @ the receptor for AGE ( RAGE ) , thereby activating its downstream signaling pathways , @ @ @ @ @ NF ) -κB and phosphoinositide 3-kinase ( PI3K ) /Akt , ultimately leading to diabetes @ @ @ @ @ review , we focus on the interaction of AGE-RAGE and their associated pathways .
We @ @ @ @ @ phytochemicals , such as genistein and curcumin , that trap dicarbonyl compounds including methylglyoxal ( @ @ @ @ @ arise from multiple pathways to block AGE formation and prevent its interaction with RAGE .

The irreversible glycation and oxidation of proteins and lipids produces advanced glycation end products (AGEs). These modified AGEs are triggered to bind the receptor for AGE (RAGE), thereby activating its downstream signaling pathways, such as nuclear factor (NF)-κB and phosphoinositide 3-kinase (PI3K)/Akt, ultimately leading to diabetes and cancers. In this review, we focus on the interaction of AGE-RAGE and their associated pathways. We also consider the activity of phytochemicals, such as genistein and curcumin, that trap dicarbonyl compounds including methylglyoxal (MG) and glyoxalase that arise from multiple pathways to block AGE formation and prevent its interaction with RAGE.


greenmedinfo--2020-08-21--Genistein inhibits lung cancer cell stem-like characteristics by modulating MnSOD and FoxM1 expressi

Genistein inhibits lung cancer cell stem-like characteristics by modulating MnSOD and FoxM1 expression.

Manganese superoxide dismutase ( MnSOD ) promotes invasive and migratory activities by upregulating Forkhead box protein M1 ( FoxM1 ) expression .
The present study investigated whether modulation of MnSOD and FoxM1 expression was responsible for the antitumor effects of genistein on cancer stem-like cells ( CSLCs ) derived from non-small cell lung cancer cells ( NSCLCs ) .
Spheroids prepared from H460 or A549 cells were defined as lung cancer stem-like cells ( LCSLCs ) and were treated with genistein .
The Cell Counting Kit-8 assay was performed to assess human lung fibroblast IMR-90 cell proliferation , as well @ @ @ @ @ @ @ following treatment with genistein .
MnSOD , FoxM1 , cluster of differentiation ( CD ) 133 , CD44 , BMI1 proto-oncogene , polycomb ring finger ( Bmi1 ) and Nanog homeobox ( Nanog ) protein expression levels were examined via western blotting .
The sphere formation assay was conducted to evaluate LCSLC self-renewal potential , and LSCLC migratory and invasive activities were analyzed using the wound healing and Transwell invasion assays , respectively .
Knockdown and overexpression of MnSOD and FOXM1 via short hairpin-RNA or cDNA transfection were performed .
The results indicated @ @ @ @ @ @ @ suppressed H460 and A549 cell viability compared with IMR-90 cells .
Sub-cytotoxic concentrations of genistein ( 20 and 40 µM ) inhibited sphere formation activity and decreased the protein expression levels of CD133 , CD44 , Bmi1 and Nanog in LCSLCs compared with the control group .
Genistein alsosuppressed the migratory and invasive activities of LCSLCs compared with the control group .
MnSOD and FoxM1 overexpression antagonized the effects of genistein ( 40 µM ) , whereas MnSOD and FoxM1 knockdown enhanced the inhibitory effects of genistein ( 20 µM ) on CSLC @ @ @ @ @ @ @ results suggested that genistein suppressed lung cancer cell CSLC characteristics by modulating MnSOD and FoxM1 expression levels .

Manganese superoxide dismutase (MnSOD) promotes invasive and migratory activities by upregulating Forkhead box protein M1 (FoxM1) expression. The present study investigated whether modulation of MnSOD and FoxM1 expression was responsible for the antitumor effects of genistein on cancer stem-like cells (CSLCs) derived from non-small cell lung cancer cells (NSCLCs). Spheroids prepared from H460 or A549 cells were defined as lung cancer stem-like cells (LCSLCs) and were treated with genistein. The Cell Counting Kit-8 assay was performed to assess human lung fibroblast IMR-90 cell proliferation, as well as NSCLC H460 and A549 cell proliferation following treatment with genistein. MnSOD, FoxM1, cluster of differentiation (CD)133, CD44, BMI1 proto-oncogene, polycomb ring finger (Bmi1) and Nanog homeobox (Nanog) protein expression levels were examined via western blotting. The sphere formation assay was conducted to evaluate LCSLC self-renewal potential, and LSCLC migratory and invasive activities were analyzed using the wound healing and Transwell invasion assays, respectively. Knockdown and overexpression of MnSOD and FOXM1 via short hairpin-RNA or cDNA transfection were performed. The results indicated that genistein (80 and 100µM) suppressed H460 and A549 cell viability compared with IMR-90 cells. Sub-cytotoxic concentrations of genistein (20 and 40 µM) inhibited sphere formation activity and decreased the protein expression levels of CD133, CD44, Bmi1 and Nanog in LCSLCs compared with the control group. Genistein alsosuppressed the migratory and invasive activities of LCSLCs compared with the control group. MnSOD and FoxM1 overexpression antagonized the effects of genistein (40 µM), whereas MnSOD and FoxM1 knockdown enhanced the inhibitory effects of genistein (20 µM) on CSLC characteristics of LCSLCs. Overall, the results suggested that genistein suppressed lung cancer cell CSLC characteristics by modulating MnSOD and FoxM1 expression levels.


greenmedinfo--2020-08-21--Genistein combined polysaccharide can inhibit intracrine androgen synthesis in prostate cancer cells

Genistein combined polysaccharide can inhibit intracrine androgen synthesis in prostate cancer cells.

Our group and others have previously shown that genistein combined polysaccharide ( GCP ) , an aglycone isoflavone-rich extract with high bioavailability and low toxicity , can inhibit prostate cancer ( CaP ) cell growth and survival as well as androgen receptor ( AR ) activity .
We now elucidate the mechanism by which this may occur using LNCaP and PC-346C CaP cell lines ; GCP can inhibit intracrine androgen synthesis in CaP cells .
UPLC-MS/MS and qPCR analyses demonstrated that GCP can mediate a ~3-fold decrease in testosterone levels ( < 0.001 ) and cause decreased expression of intracrine @ @ @ @ @ @ @ of 3βHSD ( < 0.001 ) , 17βHSD ( < 0.001 ) , CYP17A ( < 0.01 ) , SRB1 ( < 0.0001 ) , and StAR ( < 0.01 ) ) , respectively .
Reverse-phase HPLC fractionation and bioassay identified three active GCP fractions .
Subsequent NMR and LC-MS analysis of the fraction with the highest level of activity , fraction 40 , identified genistein as the primary active component of GCP responsible for its anti-proliferative , pro-apoptotic , and anti-AR activity .
GCP , fraction 40 , and genistein all mediated @ @ @ @ @ @ @ biological activities relative to vehicle control ( < 0.001 ) .
Genistein caused similar decreases in the expression of 17βHSD and CYP17A ( 2.5-fold ( < 0.001 ) and 1.5-fold decrease ( < 0.01 ) , respectively ) compared to GCP , however it did not cause altered expression of the other intracrine androgen synthesis pathway enzymes ; 3βHSD , SRB1 , and StAR .
Our combined data indicate that GCP and/or genistein may have clinical utility and that further pre-clinical studies are warranted .

Our group and others have previously shown that genistein combined polysaccharide (GCP), an aglycone isoflavone-rich extract with high bioavailability and low toxicity, can inhibit prostate cancer (CaP) cell growth and survival as well as androgen receptor (AR) activity. We now elucidate the mechanism by which this may occur using LNCaP and PC-346C CaP cell lines; GCP can inhibit intracrine androgen synthesis in CaP cells. UPLC-MS/MS and qPCR analyses demonstrated that GCP can mediate a ~3-fold decrease in testosterone levels (<0.001) and cause decreased expression of intracrine androgen synthesis pathway enzymes (~2.5-fold decrease of 3βHSD (<0.001), 17βHSD (<0.001), CYP17A (<0.01), SRB1 (<0.0001), and StAR (<0.01)), respectively. Reverse-phase HPLC fractionation and bioassay identified three active GCP fractions. Subsequent NMR and LC-MS analysis of the fraction with the highest level of activity, fraction 40, identified genistein as the primary active component of GCP responsible for its anti-proliferative, pro-apoptotic, and anti-AR activity. GCP, fraction 40, and genistein all mediated at least a ~2-fold change in these biological activities relative to vehicle control (<0.001). Genistein caused similar decreases in the expression of 17βHSD and CYP17A (2.5-fold (<0.001) and 1.5-fold decrease (<0.01), respectively) compared to GCP, however it did not cause altered expression of the other intracrine androgen synthesis pathway enzymes; 3βHSD, SRB1, and StAR. Our combined data indicate that GCP and/or genistein may have clinical utility and that further pre-clinical studies are warranted.


greenmedinfo--2020-08-21--Study of the radiosensitizing and radioprotective efficacy of bromelain.

This study hypothesizes that , bromelain ( BL ) acts as radiosensitizer of tumor cells and that it protects normal cells from radiation effects .
In vitro and in vivo studies have been carried out to prove that assumption .
In vitro MTT cell proliferation assay has shown that the irradiated Ehrlich ascites carcinoma ( EAC ) cell line could be sensitized by BL pretreatment .
In vivo : animals were randomly divided into 5 groups , Group 1 : control ( PBS i.p for 10 days ) , Group 2 : Ehrlich solid tumor ( EST ) bearing mice @ @ @ @ @ @ @ ( fractionated dose , 1 Gy × 5 ) , Group 4 : EST + BL ( 6 mg/kg , i.p ) , daily for 10 days , Group 5 : EST + BL for 10 days followed by γ-irradiation ( 1 Gy × 5 ) .
The size and weight of tumors in gamma-irradiated EST bearing mice treated with BL decreased significantly with a significant amelioration in the histopathological examination .
Besides , BL mitigated the effect of γ-irradiation on the liver relative gene expression of poly ADP ribose polymerase-1 ( PARP1 @ @ @ @ @ @ @ ( NF-κB ) , and peroxisome proliferator-activated receptor α ( PPAR-α ) , and it restored liver function via amelioration of paraoxonase1 ( PON1 ) activity , reactive oxygen species ( ROS ) content , lipid peroxidation ( LPO ) and serum aspartate transaminase ( AST ) , alanine transaminase ( ALT ) , and albumin ( ALB ) .
It is concluded that BL can be considered as a radio-sensitizer and radio-protector , suggesting a possible role in reducing radiation exposure dose during radiotherapy .

This study hypothesizes that, bromelain (BL) acts as radiosensitizer of tumor cells and that it protects normal cells from radiation effects. In vitro and in vivo studies have been carried out to prove that assumption. In vitro MTT cell proliferation assay has shown that the irradiated Ehrlich ascites carcinoma (EAC) cell line could be sensitized by BL pretreatment. In vivo: animals were randomly divided into 5 groups, Group 1: control (PBS i.p for 10 days), Group 2: Ehrlich solid tumor (EST) bearing mice, Group 3: EST + γ-radiation (fractionated dose, 1 Gy × 5), Group 4: EST + BL (6 mg/kg, i.p), daily for 10 days, Group 5: EST + BL for 10 days followed by γ-irradiation (1 Gy × 5). The size and weight of tumors in gamma-irradiated EST bearing mice treated with BL decreased significantly with a significant amelioration in the histopathological examination. Besides, BL mitigated the effect of γ-irradiation on the liver relative gene expression of poly ADP ribose polymerase-1 (PARP1), nuclear factor kappaactivated B cells (NF-κB), and peroxisome proliferator-activated receptor α (PPAR-α), and it restored liver function via amelioration of paraoxonase1 (PON1) activity, reactive oxygen species (ROS) content, lipid peroxidation (LPO) and serum aspartate transaminase (AST), alanine transaminase (ALT), and albumin (ALB). It is concluded that BL can be considered as a radio-sensitizer and radio-protector, suggesting a possible role in reducing radiation exposure dose during radiotherapy.


greenmedinfo--2020-08-21--These results confirmed the traditionally claimed benefits of corn silk on diabetes mellitus.

BACKGROUND : Corn silk is the elongated stigma of the female flower of Zea mays and traditionally used to treat diabetes mellitus ( DM ) .
OBJECTIVE : To investigate the beneficial effects of corn silk extract ( CSE ) on HFD/STZ-induced diabetic C56BL/6J mice .
METHOD : Establishment of a T2DM model through feeding HFD combined with STZ .
T2DM were randomly divided into 5 groups : diabetic control mice treated with vehicle ( model group , n=10 ) , metformin-treated group ( metformin : 150 mg/kg.d , n=10 ) , three CS-treated groups ( CS : 300 , @ @ @ @ @ @ @ .
After four weeks of CS treatment , the body weight , FBG , IR , TC , TG , LDL-C , MDA and SOD levels of mice were measured .
In addition , the liver tissue was histomorphologically analyzed by HE stain followed a light microscopy observation .
RESULTS : 4-week CSE treatment significantly reduced FBG and enhanced the glucose tolerance ; improved IR indicated by decreased HOMA-IR and elevated ISI ; alleviated hyperlipidemia indicated by decreased TC , TG , LDL-C , and increased HDL-C ; reduced oxidative stress by decreased @ @ @ @ @ @ @ hepatic lipid accumulation and prevented liver tissue morphological change in T2DM .
In addition , CSE treatments effectively prevent the weight gain loss of diabetic mice .
CONCLUSION : These results confirmed the traditionally claimed benefits of corn silk on DM , which suggested that the corn silk possessed the anti-diabetic potential and could be further developed as a cheap and plant-derived agent for the treatment of type 2 diabetes mellitus .

BACKGROUND: Corn silk is the elongated stigma of the female flower of Zea mays and traditionally used to treat diabetes mellitus (DM).
OBJECTIVE: To investigate the beneficial effects of corn silk extract (CSE) on HFD/STZ-induced diabetic C56BL/6J mice.
METHOD: Establishment of a T2DM model through feeding HFD combined with STZ. T2DM were randomly divided into 5 groups: diabetic control mice treated with vehicle (model group, n=10), metformin-treated group (metformin: 150 mg/kg.d, n=10), three CS-treated groups (CS: 300, 600 and 1200 mg/kg.d, n=10). After four weeks of CS treatment, the body weight, FBG, IR, TC, TG, LDL-C, MDA and SOD levels of mice were measured. In addition, the liver tissue was histomorphologically analyzed by HE stain followed a light microscopy observation.
RESULTS: 4-week CSE treatment significantly reduced FBG and enhanced the glucose tolerance; improved IR indicated by decreased HOMA-IR and elevated ISI; alleviated hyperlipidemia indicated by decreased TC, TG, LDL-C, and increased HDL-C; reduced oxidative stress by decreased MDA and elevated SOD activity; decreased hepatic lipid accumulation and prevented liver tissue morphological change in T2DM. In addition, CSE treatments effectively prevent the weight gain loss of diabetic mice.
CONCLUSION: These results confirmed the traditionally claimed benefits of corn silk on DM, which suggested that the corn silk possessed the anti-diabetic potential and could be further developed as a cheap and plant-derived agent for the treatment of type 2 diabetes mellitus.


greenmedinfo--2020-08-21--Corn silk crude polysaccharide exerts anti-pancreatic cancer activity by blocking the EGFR/PI3K/AKT/

Corn silk crude polysaccharide exerts anti-pancreatic cancer activity by blocking the EGFR/PI3K/AKT/CREB signaling pathway.

Pancreatic cancer is a highly lethal and malignant solid tumor .
Treatments for pancreatic cancer are seriously limited because it @ @ @ @ @ .
Hence , it is urgent to explore novel approaches for anti-pancreatic cancer therapy .
@ @ @ @ @ show that S1 , a crude polysaccharide from corn silk , may significantly inhibit pancreatic @ @ @ @ @ and in vivo .
Further studies reveal that S1 can induce pancreatic cancer cell apoptosis @ @ @ @ @ in S phase and impede pancreatic cancer cell migration and invasion .
Moreover , S1 @ @ @ @ @ pathway to exert its anti-pancreatic cancer activity .
However , S1 has almost no toxicity @ @ @ @ @ vivo .
These results provide evidence that S1 is a new functional food component that @ @ @ @ @ pancreatic cancer .

Pancreatic cancer is a highly lethal and malignant solid tumor. Treatments for pancreatic cancer are seriously limited because it is highly drug-resistant and immunosuppressive. Hence, it is urgent to explore novel approaches for anti-pancreatic cancer therapy. In this study, we show that S1, a crude polysaccharide from corn silk, may significantly inhibit pancreatic cancer cell proliferation in vitro and in vivo. Further studies reveal that S1 can induce pancreatic cancer cell apoptosis, arrest the cell cycle in S phase and impede pancreatic cancer cell migration and invasion. Moreover, S1 may block the EGFR/PI3K/AKT/CREB signaling pathway to exert its anti-pancreatic cancer activity. However, S1 has almost no toxicity either in vitro or in vivo. These results provide evidence that S1 is a new functional food component that can be developed to fight pancreatic cancer.


greenmedinfo--2020-08-21--Iminosugar idoBR1 isolated from cucumber Cucumis sativus reduces inflammatory activity.

Cucumbers have been anecdotally claimed to have anti-inflammatory activity for a long time , but the active principle was not @ @ @ @ @ 2,3,4,5 ) -3,4,5-trihydroxypiperidine-2-carboxylic acid , is an iminosugar amino acid isolated from fruits of certain @ @ @ @ @ .
It has no chromophore and analytically behaves like an amino acid making detection and @ @ @ @ @ anti-inflammatory activity reducing lipopolysaccharide ( LPS ) -induced tumor necrosis factor alpha ( TNF-α ) @ @ @ @ @ .
It showed selective inhibition of humanα-l-iduronidase and sialidases from both bacteria ( ) and @ @ @ @ @ and cucumber extract reduced the binding of hyaluronic acid ( HA ) to CD44 in @ @ @ @ @ function as an anti-inflammatory agent by inhibiting induced sialidase involved in the production of functionally @ @ @ @ @ Similar to the related iminosugars , idoBR1 is excreted unchanged in urine following consumption .
@ @ @ @ @ should be further evaluated .

Cucumbers have been anecdotally claimed to have anti-inflammatory activity for a long time, but the active principle was not identified. idoBR1, (2,3,4,5)-3,4,5-trihydroxypiperidine-2-carboxylic acid, is an iminosugar amino acid isolated from fruits of certain cucumbers,(Cucurbitaceae). It has no chromophore and analytically behaves like an amino acid making detection and identification difficult. It has anti-inflammatory activity reducing lipopolysaccharide (LPS)-induced tumor necrosis factor alpha (TNF-α) in THP-1 cells andhuman blood. It showed selective inhibition of humanα-l-iduronidase and sialidases from both bacteria () and human THP-1 cells. idoBR1 and cucumber extract reduced the binding of hyaluronic acid (HA) to CD44 in LPS-stimulated THP-1 cells and may function as an anti-inflammatory agent by inhibiting induced sialidase involved in the production of functionally active HA adhesive CD44. Similar to the related iminosugars, idoBR1 is excreted unchanged in urine following consumption. Its importance in the diet should be further evaluated.


greenmedinfo--2020-08-21--Novel perspective on Alzheimer's disease treatment: Rosmarinic acid molecular interplay with copper(

Novel perspective on Alzheimer's disease treatment: Rosmarinic acid molecular interplay with copper(II) and amyloid β.

Alzheimer 's disease is a severe disorder that affects millions of people worldwide .
It is a very debilitating disease @ @ @ @ @ moment .
The necessity of finding an effective treatment is very demanding , and the @ @ @ @ @ in a lot of effort to address this issue .
The major hallmark of Alzheimer @ @ @ @ @ of toxic aggregated species in the brain , impaired metal homeostasis , and high levels @ @ @ @ @ acid is a well-known potent antioxidant molecule , the efficacy of which has been proved @ @ @ @ @ vivo .
In this study , we investigated the possible role played by rosmarinic acid @ @ @ @ @ copper ( II ) -induced neurotoxicity .
Several spectroscopic techniques and biological assays were applied @ @ @ @ @ and to evaluate the cytotoxicity and the mutagenicity of rosmarinic acid and its Cu ( @ @ @ @ @ data indicate that rosmarinic acid is able to interfere with the interaction between amyloidβ and @ @ @ @ @ forming an original ternary association .

Alzheimer's disease is a severe disorder that affects millions of people worldwide. It is a very debilitating disease with no cure at the moment. The necessity of finding an effective treatment is very demanding, and the entire scientific community is putting in a lot of effort to address this issue. The major hallmark of Alzheimer's disease is the presence of toxic aggregated species in the brain, impaired metal homeostasis, and high levels of oxidative stress. Rosmarinic acid is a well-known potent antioxidant molecule, the efficacy of which has been proved both in vitro and in vivo. In this study, we investigated the possible role played by rosmarinic acid as a mediator of the copper(II)-induced neurotoxicity. Several spectroscopic techniques and biological assays were applied to characterize the metal complexes and to evaluate the cytotoxicity and the mutagenicity of rosmarinic acid and its Cu(II) complex. Our data indicate that rosmarinic acid is able to interfere with the interaction between amyloidβ and Cu(II) by forming an original ternary association.


greenmedinfo--2020-08-21--Protective roles and mechanisms of rosmarinic acid in cyclophosphamide-induced premature ovarian fai

Protective roles and mechanisms of rosmarinic acid in cyclophosphamide-induced premature ovarian failure.

The aim of this study was to investigate the protective effect of rosmarinic acid ( RA ) in a premature @ @ @ @ @ mouse model and the potential mechanisms .
The POF model was induced by a single @ @ @ @ @ cyclophosphamide ( CP ) .
Additionally , 40 mg/kg RA was administered for 7 days @ @ @ @ @ concentration of sex hormones was determined by fluorescence immunohistochemistry .
Histological analysis was performed after @ @ @ @ @ with hematoxylin and eosin .
The expression of the NLRP3 inflammasome was examined by western @ @ @ @ @ reaction .
The expression of apoptosis markers of cytochrome c and caspase-3 was also detected @ @ @ @ @ immunohistochemistry .
The results showed that RA not only decreased the ovarian index in POF @ @ @ @ @ abnormal secretion of reproductive hormones associated with POF .
Treatment with RA suppressed the ovarian @ @ @ @ @ and regulated the ovarian expression of apoptosis-related proteins .
The results suggested that RA exhibited @ @ @ @ @ POF potentially by suppressing apoptosis and the NLRP3 inflammasome .

The aim of this study was to investigate the protective effect of rosmarinic acid (RA) in a premature ovarian failure (POF) mouse model and the potential mechanisms. The POF model was induced by a single intraperitoneal injection of 120 mg/kg cyclophosphamide (CP). Additionally, 40 mg/kg RA was administered for 7 days before CP injection. The concentration of sex hormones was determined by fluorescence immunohistochemistry. Histological analysis was performed after ovarian tissue sections were stained with hematoxylin and eosin. The expression of the NLRP3 inflammasome was examined by western blot analysis and polymerase chain reaction. The expression of apoptosis markers of cytochrome c and caspase-3 was also detected by western blot analysis and immunohistochemistry. The results showed that RA not only decreased the ovarian index in POF mice but also improved the abnormal secretion of reproductive hormones associated with POF. Treatment with RA suppressed the ovarian expression of the NLRP3 inflammasome and regulated the ovarian expression of apoptosis-related proteins. The results suggested that RA exhibited a protective effect against CP-induced POF potentially by suppressing apoptosis and the NLRP3 inflammasome.


greenmedinfo--2020-08-21--A. hookeri aqueous extract can be effective in reducing HbA1c.

BACKGROUND : Allium hookeri is widely consumed as a vegetable and herbal medicine in Asia .
A. hookeri has been @ @ @ @ @ osteoblastic , anti-oxidant , and anti-diabetic effects in animal studies .
We investigated the anti-diabetic @ @ @ @ @ extract ( AHE ) in the Korean subjects .
RESULTS : Eight weeks after AHE @ @ @ @ @ significantly decreased in the AHE group compared with the placebo group .
No clinically significant @ @ @ @ @ were observed .
CONCLUSION : The findings suggest that AHE can be effective in reducing @ @ @ @ @ an adjunctive tool for improving glycemic control .
TRIAL REGISTRATION : The study protocol was @ @ @ @ @ NCT03330366 , October 30 , 2017 ) .

BACKGROUND: Allium hookeri is widely consumed as a vegetable and herbal medicine in Asia. A. hookeri has been reported anti-inflammatory, anti-obesity, osteoblastic, anti-oxidant, and anti-diabetic effects in animal studies. We investigated the anti-diabetic effects of A. hookeri aqueous extract (AHE) in the Korean subjects.
METHODS: Prediabetic subjects (100 ≤ fasting plasma glucose (FPG) < 126 mg/dL) who met the inclusion criteria were recruited for this study. The enrolled subjects (n = 30) were randomly divided into either an AHE (n = 15, 486 mg/day) or placebo (n = 15) group. Outcomes were measurements of FPG, glycemic response to an oral glucose tolerance test (OGTT), insulin, C-peptide, hemoglobin A1c (HbA1c), total cholesterol, triglyceride, HDL-cholesterol, and LDL-cholesterol. The t-test was used to assess differences between the groups. A p-value< 0.05 was considered statistically significant.
RESULTS: Eight weeks after AHE supplementation, HbA1c level was significantly decreased in the AHE group compared with the placebo group. No clinically significant changes in any safety parameter were observed.
CONCLUSION: The findings suggest that AHE can be effective in reducing HbA1c, indicating it as an adjunctive tool for improving glycemic control.
TRIAL REGISTRATION: The study protocol was retrospectively registered at www.clinicaltrials.gov ( NCT03330366 , October 30, 2017).


greenmedinfo--2020-08-21--Regulatory effect of Lactobacillus brevis Bmb6 on gut barrier functions in experimental colitis.

The integrity of gut barrier functions is closely associated with the pathogenesis of colitis .
It is speculated thatBmb6 alleviates colitis by improving the tight junction ( TJ ) of the inflamed intestinal epithelial layer .
In the present study , the regulatory effects ofBmb6 on the TJ barrier to ameliorate colitis-symptoms were investigated .
Preliminary screening showed thatBmb6 exhibited strong acid and bile acid tolerance , along with antioxidants andβ-galactosidase activities .
In a 14-day dextran sulfate sodium ( DSS ) -induced colitis mouse model , treatment withBmb6 significantly decreased in the disease activity index score .
In addition @ @ @ @ @ @ @ protected the structural integrity of the intestinal epithelial layer and mucin-secreting goblet cells from DSS-induced damage , with only slight infiltration of immune cells .
Interestingly , western blotting analyses showed that the expression of the TJ protein , zona occluden-1 , was restored in Bmb6-treated mice , but not in DSS-induced mice .
Consistently , the gene expression of inflammatory cytokines ( tumor necrosis factor-α and interferon-γ ) was also suppressed in the Bmb6-treated mice .
Hence , our findings suggest that suppression of inflammatory conditions enhanced expression of TJ protein , @ @ @ @ @ @ @ to a colitis-ameliorating effect inBmb6 .

The integrity of gut barrier functions is closely associated with the pathogenesis of colitis. It is speculated thatBmb6 alleviates colitis by improving the tight junction (TJ) of the inflamed intestinal epithelial layer. In the present study, the regulatory effects ofBmb6 on the TJ barrier to ameliorate colitis-symptoms were investigated. Preliminary screening showed thatBmb6 exhibited strong acid and bile acid tolerance, along with antioxidants andβ-galactosidase activities. In a 14-day dextran sulfate sodium (DSS)-induced colitis mouse model, treatment withBmb6 significantly decreased in the disease activity index score. In addition, histological analyses showed that treatment withBmb6 protected the structural integrity of the intestinal epithelial layer and mucin-secreting goblet cells from DSS-induced damage, with only slight infiltration of immune cells. Interestingly, western blotting analyses showed that the expression of the TJ protein, zona occluden-1, was restored in Bmb6-treated mice, but not in DSS-induced mice. Consistently, the gene expression of inflammatory cytokines (tumor necrosis factor-α and interferon-γ) was also suppressed in the Bmb6-treated mice. Hence, our findings suggest that suppression of inflammatory conditions enhanced expression of TJ protein, ZO-1, or vice versa, contributing to a colitis-ameliorating effect inBmb6.


greenmedinfo--2020-08-21--L. sakei (CJLS03) might help people with obesity reduce body fat mass without serious side effects.

BACKGROUND : The increased prevalence of obesity has led to increases in the prevalence of chronic diseases worldwide .
There is interest whether probiotics have an effect on obesity , but the effectiveness and safety of only a few probiotics for the treatment of obesity have been reported .
The purpose of this study was to investigate whether ingestion of Lactobacillus sakei ( CJLS03 ) derived from kimchi causes weight loss in people with obesity .
METHODS : This randomized , double-blind , placebo-controlled , clinical trial involved 114 adults with a body mass index ( BMI ) ≥25 kg/m2 @ @ @ @ @ @ @ or placebo group .
The groups received two allocations of either 5×109 colony-forming units of CJLS03/allocation or the equivalent vehicle for 12 weeks .
Demographic and biochemical parameters , and body composition including fat and muscle mass weremeasured at baseline and after 12 weeks .
Changes in body fat , weight , and waist circumference were compared between the two treatment groups .
Adverse events were monitored during study period .
RESULTS : Body fat mass decreased by 0.2 kg in the CJLS03 group and increased by 0.6 kg in the placebo group @ @ @ @ @ @ @ .
After the 12 weeks , waist circumference was 0.8 cm smaller in the CJLS03 group than in the placebo group ( P=0.013 ) .
BMI and body weight did not change after the 12 weeks .
Adverse events were mild and did not differ between the two groups .
CONCLUSION : These data suggest that L. sakei ( CJLS03 ) might help people with obesity reduce body fat mass without serious side effects ( ClinicalTrials.gov : NCT03248414 ) .

BACKGROUND: The increased prevalence of obesity has led to increases in the prevalence of chronic diseases worldwide. There is interest whether probiotics have an effect on obesity, but the effectiveness and safety of only a few probiotics for the treatment of obesity have been reported. The purpose of this study was to investigate whether ingestion of Lactobacillus sakei (CJLS03) derived from kimchi causes weight loss in people with obesity.
METHODS: This randomized, double-blind, placebo-controlled, clinical trial involved 114 adults with a body mass index (BMI)≥25 kg/m2 who were assigned randomly to a CJLS03 or placebo group. The groups received two allocations of either 5×109 colony-forming units of CJLS03/allocation or the equivalent vehicle for 12 weeks. Demographic and biochemical parameters, and body composition including fat and muscle mass weremeasured at baseline and after 12 weeks. Changes in body fat, weight, and waist circumference were compared between the two treatment groups. Adverse events were monitored during study period.
RESULTS: Body fat mass decreased by 0.2 kg in the CJLS03 group and increased by 0.6 kg in the placebo group (0.8 kg difference, P=0.018). After the 12 weeks, waist circumference was 0.8 cm smaller in the CJLS03 group than in the placebo group (P=0.013). BMI and body weight did not change after the 12 weeks. Adverse events were mild and did not differ between the two groups.
CONCLUSION: These data suggest that L. sakei (CJLS03) might help people with obesity reduce body fat mass without serious side effects (ClinicalTrials.gov: NCT03248414).


greenmedinfo--2020-08-21--Lactobacillus paraplantarum THG-G10 as a potential anti-acne agent with anti-bacterial and anti-infl

Lactobacillus paraplantarum THG-G10 as a potential anti-acne agent with anti-bacterial and anti-inflammatory activities.

Cutibacterium acnes ( formerly Propionibacterium acnes ) is the main bacterium targeted for the prevention and medical treatment of acne vulgaris .
Lactic acid bacteria ( LAB ) are a group of microorganisms classified by their ability to produce lactic acid through fermentation .
Although the activities of LAB have been studied , their potential anti-acne effects are not well known .
Here , Lactobacillus paraplantarum THG-G10 , which has anti-bacterial activity against C. acnes , was isolated from traditional Kimchi in Republic of Korea .
The anti-acne effects of dried cell-free supernatant of L. paraplantarum THG-G10 ( DC-G10 ) @ @ @ @ @ @ @ anti-inflammatory activities .
Anti-microbial activity was examined by a broth dilution assay : 25 mg/ml of DC-G10 inhibited the growth of C. acnes KCTC 5012 and KACC 1194 ; salicylic acid and benzoyl peroxide for acne treatment inhibited the growth of C. acnes KCTC 5012 and KACC 11946 at concentrations of 1.25 and 7.5 mg/ml , respectively ; and tea tree oil inhibited the growth ofC .
acnes KCTC 5012 but not the growth of C. acnes KACC 11946 at 50 mg/ml .
Anti-inflammatory activity was evaluated by a nitric oxide ( NO @ @ @ @ @ @ @ acid reduced LPS-induced NO production in RAW 264.7 cells in a dose-dependent manner .
In addition , the toxicities of erythromycin , salicylic acid , benzoyl peroxide , tea tree oil , and DC-G10 were examined in HaCaT cells and normal human dermal fibroblasts ( NHDFs ) .
In these cells , the cytotoxic effects of DC-G10 were weaker than the effects of erythromycin , benzoyl peroxide , and ascorbic acid .
Furthermore , scanning electron microscopy revealed that DC-G10 induces deleterious morphological changes in the bacterial cell membrane .
These results demonstrate @ @ @ @ @ @ @ safe treatment for acne vulgaris .

Cutibacterium acnes (formerly Propionibacterium acnes) is the main bacterium targeted for the prevention and medical treatment of acne vulgaris. Lactic acid bacteria (LAB) are a group of microorganisms classified by their ability to produce lactic acid through fermentation. Although the activities of LAB have been studied, their potential anti-acne effects are not well known. Here, Lactobacillus paraplantarum THG-G10, which has anti-bacterial activity against C. acnes, was isolated from traditional Kimchi in Republic of Korea. The anti-acne effects of dried cell-free supernatant of L. paraplantarum THG-G10 (DC-G10) were evaluated by determining its anti-microbial and anti-inflammatory activities. Anti-microbial activity was examined by a broth dilution assay: 25 mg/ml of DC-G10 inhibited the growth of C. acnes KCTC 5012 and KACC 1194; salicylic acid and benzoyl peroxide for acne treatment inhibited the growth of C. acnes KCTC 5012 and KACC 11946 at concentrations of 1.25 and 7.5 mg/ml, respectively; and tea tree oil inhibited the growth ofC. acnes KCTC 5012 but not the growth of C. acnes KACC 11946 at 50 mg/ml. Anti-inflammatory activity was evaluated by a nitric oxide (NO) assay: only DC-G10 and ascorbic acid reduced LPS-induced NO production in RAW 264.7 cells in a dose-dependent manner. In addition, the toxicities of erythromycin, salicylic acid, benzoyl peroxide, tea tree oil, and DC-G10 were examined in HaCaT cells and normal human dermal fibroblasts (NHDFs). In these cells, the cytotoxic effects of DC-G10 were weaker than the effects of erythromycin, benzoyl peroxide, and ascorbic acid. Furthermore, scanning electron microscopy revealed that DC-G10 induces deleterious morphological changes in the bacterial cell membrane. These results demonstrate that DC-G10 may be an effective and safe treatment for acne vulgaris.