greenmedinfo--2020-05-21--Puerarin alleviates lipopolysaccharide-induced myocardial fibrosis.

Myocardial fibrosis ( MFs ) is a crucial pathological process that results in cardiac failure in the development of multiple cardiovascular diseases .
Puerarin could reportedly be used to treat a variety of cardiovascular diseases .
However , the exact mechanism of puerarin on MFs was not clear enough .
The separated primary cardiac fibroblasts ( CFs ) were induced by lipopolysaccharide ( LPS ) and treated with puerarin .
The levels of TNF-α , IL-6 , HMGB1 , PARP-1 , α-SMA , collagen-1 , collagen-3 , NF-κB pathways were examined by ELISA , immunofluorescence , RT-qPCR , western blot @ @ @ @ @ @ @ MFs rats ' model was established using transverse aortic constriction ( TAC ) , and the degree of fibrosis was certified by masson staining .
We successfully separated primary CFs , and certified that LPS induction could upregulate the levels of PARP-1 , HMGB1 , inflammatory cytokines and fibrosis-related proteins ( α-SMA , collagen-1 and collagen-3 ) .
In addition , we proved that puerarin could weaken MFs , and PARP-1 andHMGB1 expressions , which were induced by LPS in primary CFs .
In terms of mechanism , HMGB1 expression could be promoted @ @ @ @ @ @ @ the therapeutic effect of puerarin on LPS-induced MFs .
Besides , PARP-1-HMGB1-NF-κB pathway was related to the protective effect of puerarin onMFs .
In vivo , we also verified the protective efficacy of puerarin on MFs induced by TAC , and puerarin also regulated HMGB1-mediated TLR4-NF-κB signaling pathway .
We demonstrated that puerarin could ameliorate MFs by downregulating PARP-1 to inhibit HMGB1-mediated TLR4-NF-κB signaling pathway inLPS-induced primary CFs and TAC-induced MFs rats ' model .

Myocardial fibrosis (MFs) is a crucial pathological process that results in cardiac failure in the development of multiple cardiovascular diseases. Puerarin could reportedly be used to treat a variety of cardiovascular diseases. However, the exact mechanism of puerarin on MFs was not clear enough. The separated primary cardiac fibroblasts (CFs) were induced by lipopolysaccharide (LPS) and treated with puerarin. The levels of TNF-α, IL-6, HMGB1, PARP-1, α-SMA, collagen-1, collagen-3, NF-κB pathways were examined by ELISA, immunofluorescence, RT-qPCR, western blot and immunohistochemistry assays. In addition, MFs rats' model was established using transverse aortic constriction (TAC), and the degree of fibrosis was certified by masson staining. We successfully separated primary CFs, and certified that LPS induction could upregulate the levels of PARP-1, HMGB1, inflammatory cytokines and fibrosis-related proteins (α-SMA, collagen-1 and collagen-3). In addition, we proved that puerarin could weaken MFs, and PARP-1 andHMGB1 expressions, which were induced by LPS in primary CFs. In terms of mechanism, HMGB1 expression could be promoted by PARP-1, and PARP-1 could attenuate the therapeutic effect of puerarin on LPS-induced MFs. Besides, PARP-1-HMGB1-NF-κB pathway was related to the protective effect of puerarin onMFs. In vivo, we also verified the protective efficacy of puerarin on MFs induced by TAC, and puerarin also regulated HMGB1-mediated TLR4-NF-κB signaling pathway. We demonstrated that puerarin could ameliorate MFs by downregulating PARP-1 to inhibit HMGB1-mediated TLR4-NF-κB signaling pathway inLPS-induced primary CFs and TAC-induced MFs rats' model.


greenmedinfo--2020-05-21--Puerarin may represent a chemopreventive and chemotherapeutic agent for liver cancer treatment.

Hepatocellular carcinoma ( HCC ) is one of the most common primary malignant tumors of the liver worldwide .
Liver resection and transplantation are currently the only effective treatments ; however , recurrence and metastasis rates are still high .
Previous studies have shown that the epithelial-mesenchymal transition ( EMT ) is a key step in HCC invasion and metastasis .
Inhibition of EMT has become a new therapeutic strategy for tumors .
Recently , puerarin , a well-characterized component of traditional Chinese medicine , has been isolated from Pueraria radix and exerts positive effects on many diseases , particularly @ @ @ @ @ @ @ , EdU immunofluorescence , colony formation , wound healing , and migration assays were used to detect the effects of puerarin on HCC cells .
We further analyzed the relationship between puerarin and miR-21/PTEN/EMT markers in HCC cell lines .
Our results showed that HCC cell proliferation , migration , invasion , tumor formation , and metastasis were reduced by puerarin in vitro and in vivo .
Additionally , puerarin inhibited the EMT process of HCC by affecting the expression of Slug and Snail .
Moreover , oncogenic miR-21 was inhibited by puerarin @ @ @ @ @ @ @ tumor suppressor gene PTEN .
Increasing miR-21 expression or decreasing PTEN expression reversed the inhibition effects of puerarin in HCC .
These data confirmed that puerarin affects HCC through the miR-21/PTEN/EMT regulatory axis .
Overall , puerarin may represent a chemopreventive and/or chemotherapeutic agent for HCC treatment .

Hepatocellular carcinoma (HCC) is one of the most common primary malignant tumors of the liver worldwide. Liver resection and transplantation are currently the only effective treatments; however, recurrence and metastasis rates are still high. Previous studies have shown that the epithelial-mesenchymal transition (EMT) is a key step in HCC invasion and metastasis. Inhibition of EMT has become a new therapeutic strategy for tumors. Recently, puerarin, a well-characterized component of traditional Chinese medicine, has been isolated from Pueraria radix and exerts positive effects on many diseases, particularly cancers. In this study, CCK-8, EdU immunofluorescence, colony formation, wound healing, and migration assays were used to detect the effects of puerarin on HCC cells. We further analyzed the relationship between puerarin and miR-21/PTEN/EMT markers in HCC cell lines. Our results showed that HCC cell proliferation, migration, invasion, tumor formation, and metastasis were reduced by puerarin in vitro and in vivo. Additionally, puerarin inhibited the EMT process of HCC by affecting the expression of Slug and Snail. Moreover, oncogenic miR-21 was inhibited by puerarin, coupled with an increase in the tumor suppressor gene PTEN. Increasing miR-21 expression or decreasing PTEN expression reversed the inhibition effects of puerarin in HCC. These data confirmed that puerarin affects HCC through the miR-21/PTEN/EMT regulatory axis. Overall, puerarin may represent a chemopreventive and/or chemotherapeutic agent for HCC treatment.


greenmedinfo--2020-05-21--Dietary puerarin supplementation alleviates oxidative stress in the small intestines.

This study was conducted to demonstrate that dietary puerarin supplementation alleviates oxidative stress in the small intestine of diquat-challenged piglets @ @ @ @ @ puerarin administration markedly alleviated diquat-induced intestinal injury , which was indicated by the improvement of @ @ @ @ @ and barrier function .
One of the potential mechanisms responsible for this was the decrease @ @ @ @ @ evidenced by the increase in activities of superoxide dismutase ( SOD ) , glutathione peroxidase @ @ @ @ @ total antioxidant capacity ( T-AOC ) in the small intestine .
Puerarin increased the protein @ @ @ @ @ 2 ( Nrf2 ) and its downstream enzymes , including heme oxygenase 1 ( HO-1 @ @ @ @ @ and its modifier subunit ( GCLc and GCLm ) in the jejunal mucosa of diquat-induced @ @ @ @ @ intestinal morphology , cell proliferation , and barrier function , and increased Nrf2 and its @ @ @ @ @ indicate that the dietary supplementation of puerarin attenuates the oxidative stress involving Nrf2 signaling pathways @ @ @ @

This study was conducted to demonstrate that dietary puerarin supplementation alleviates oxidative stress in the small intestine of diquat-challenged piglets. The results showed that puerarin administration markedly alleviated diquat-induced intestinal injury, which was indicated by the improvement of intestinal morphology, cell proliferation and barrier function. One of the potential mechanisms responsible for this was the decrease in oxidative stress, as evidenced by the increase in activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and total antioxidant capacity (T-AOC) in the small intestine. Puerarin increased the protein expression levels of NF-E2-related factor 2 (Nrf2) and its downstream enzymes, including heme oxygenase 1 (HO-1), glutamate-cysteine ligase catalytic and its modifier subunit (GCLc and GCLm) in the jejunal mucosa of diquat-induced piglets. Puerarin administration improved intestinal morphology, cell proliferation, and barrier function, and increased Nrf2 and its downstream enzymes. These findings indicate that the dietary supplementation of puerarin attenuates the oxidative stress involving Nrf2 signaling pathways in diquat-challenged piglets.


greenmedinfo--2020-05-21--These finding highlights the potential value of puerarin developing as an anti-diabetic agent.

BACKGROUND : Diabetes is characterized byβ-cell loss and dysfunction .
A strategy for diabetes treatment is to promote new β-cell formation .
Puerarin is an isoflavone from the root of Pueraria lobata ( Willd . )
Ohwi .
Our previous study demonstrated puerarin could ameliorate hyperglycemia in diabetic mice .
However , related mechanisms and potential roles of puerarin in β-cell neogenesis have not been elucidated .
PURPOSE : The present study aims to investigate whether anti-diabetic effect of puerarin is dependent on promotingβ-cell neogenesis via GLP-1R signaling activation .
METHODS : A high-fat diet ( HFD ) induced diabetic @ @ @ @ @ @ @ of puerarin in vivo , exendin-4 ( GLP-1R agonist ) and metformin were used as positive controls .
Moreover , related mechanisms and GLP-1R downstream signal transduction were explored in isolated cultured mouse pancreatic ductal cells .
RESULTS : Puerarin improved glucose homeostasis in HFD diabetic mice significantly .
Markers of newβ-cell formation ( insulin , PDX1 and Ngn3 ) were observed in pancreatic ducts of HFD mice treated by puerarin .
Of note , efficacy of puerarin in vivo was suppressed by GLP-1R antagonist exendin9-39 , but enhanced by exendin-4 respectively .
@ @ @ @ @ @ @ puerarin induced expressions of insulin and PDX1 , upregulated GLP-1R expression and activated β-catenin and STAT3 subsequently .
Expressions of insulin and PDX1 in ductal cells could be blocked by exendin9-39 , or β-catenin inhibitor ICG001 , or JAK2 inhibitor AG490 .
CONCLUSION : These data clarified puerarin ameliorated hyperglycemia of HFD mice via a novel mechanism involved promotingβ-cell neogenesis .
Our finding highlights the potential value of puerarin developing as an anti-diabetic agent .

BACKGROUND: Diabetes is characterized byβ-cell loss and dysfunction. A strategy for diabetes treatment is to promote new β-cell formation. Puerarin is an isoflavone from the root of Pueraria lobata (Willd.) Ohwi. Our previous study demonstrated puerarin could ameliorate hyperglycemia in diabetic mice. However, related mechanisms and potential roles of puerarin in β-cell neogenesis have not been elucidated.
PURPOSE: The present study aims to investigate whether anti-diabetic effect of puerarin is dependent on promotingβ-cell neogenesis via GLP-1R signaling activation.
METHODS: A high-fat diet (HFD) induced diabetic mouse model was applied to investigate effects of puerarin in vivo, exendin-4 (GLP-1R agonist) and metformin were used as positive controls. Moreover, related mechanisms and GLP-1R downstream signal transduction were explored in isolated cultured mouse pancreatic ductal cells.
RESULTS: Puerarin improved glucose homeostasis in HFD diabetic mice significantly. Markers of newβ-cell formation (insulin, PDX1 and Ngn3) were observed in pancreatic ducts of HFD mice treated by puerarin. Of note, efficacy of puerarin in vivo was suppressed by GLP-1R antagonist exendin9-39, but enhanced by exendin-4 respectively. In cultured mouse pancreatic ductal cells, puerarin induced expressions of insulin and PDX1, upregulated GLP-1R expression and activated β-catenin and STAT3 subsequently. Expressions of insulin and PDX1 in ductal cells could be blocked by exendin9-39, or β-catenin inhibitor ICG001, or JAK2 inhibitor AG490.
CONCLUSION: These data clarified puerarin ameliorated hyperglycemia of HFD mice via a novel mechanism involved promotingβ-cell neogenesis. Our finding highlights the potential value of puerarin developing as an anti-diabetic agent.


greenmedinfo--2020-05-21--Effects of puerarin on the pharmacokinetics of astragaloside IV in rats and its potential mechanism

Puerarin and astragaloside IV ( AS-IV ) are sometimes used together for the treatment of disease in Chinese clinics , however , the drug-drug interaction between puerarin and AS-IV is still unknown.This study investigates the effects of puerarin on the pharmacokinetics of astragaloside IV in rats and clarifies its main mechanism.The pharmacokinetic profiles of oral administration of astragaloside IV ( 20 mg/kg ) in Sprague-Dawley rats , with or without pre-treatment of puerarin ( 100 mg/kg/day for 7 days ) were investigated .
The effects of puerarin on the transport and metabolic stability of AS-IV were also investigated using Caco-2 @ @ @ @ @ @ @ results showed that puerarin could significantly increase the peak plasma concentration ( from 48.58 ± 7.26 to 72.71 ± 0.62 ng/mL ) , and decrease the oral clearance ( from 47.5 ± 8.91 to 27.15 ± 9.27 L/h/kg ) of AS-IV .
The Caco-2 cell transwell experiments indicated that puerarin could decrease the efflux ratio of astragaloside IV from 1.89 to 1.26 , and the intrinsic clearancerate of astragaloside IV was decreased by the pre-treatment with puerarin ( 34.8 ± 2.9 .
41.5 ± 3.8 μL/min/mg protein ) .These results indicated that puerarin @ @ @ @ @ @ @ astragaloside IV , via increasing the absorption of astragaloside IV or inhibiting the metabolism of astragaloside IV in rats .

Puerarin and astragaloside IV (AS-IV) are sometimes used together for the treatment of disease in Chinese clinics, however, the drug-drug interaction between puerarin and AS-IV is still unknown.This study investigates the effects of puerarin on the pharmacokinetics of astragaloside IV in rats and clarifies its main mechanism.The pharmacokinetic profiles of oral administration of astragaloside IV (20 mg/kg) in Sprague-Dawley rats, with or without pre-treatment of puerarin (100 mg/kg/day for 7 days) were investigated. The effects of puerarin on the transport and metabolic stability of AS-IV were also investigated using Caco-2 cell transwell model and rat liver microsomes.The results showed that puerarin could significantly increase the peak plasma concentration (from 48.58 ± 7.26 to 72.71 ± 0.62 ng/mL), and decrease the oral clearance (from 47.5 ± 8.91 to 27.15 ± 9.27 L/h/kg) of AS-IV. The Caco-2 cell transwell experiments indicated that puerarin could decrease the efflux ratio of astragaloside IV from 1.89 to 1.26, and the intrinsic clearancerate of astragaloside IV was decreased by the pre-treatment with puerarin (34.8 ± 2.9. 41.5 ± 3.8 μL/min/mg protein).These results indicated that puerarin could significantly change the pharmacokinetic profiles of astragaloside IV, via increasing the absorption of astragaloside IV or inhibiting the metabolism of astragaloside IV in rats.


greenmedinfo--2020-05-21--Astragaloside IV protects guman cardiomyocytes from hypoxia/reoxygenation injury by regulating miR-1

Astragaloside IV protects guman cardiomyocytes from hypoxia/reoxygenation injury by regulating miR-101a

Astragaloside IV ( AS/IV ) is one of the extracted components from the traditional Chinese medicine Astragalus which has been demonstrated to have potential capacity for anti-inflammation activity and for treating cardiovascular disease .
Our purpose was to determine the function and underlying molecular mechanism of AS/IV in hypoxia/reoxygenation ( H/R ) injured in cardiomyocytes .
Differentially expressed genes ( DEGs ) were screened using bioinformatic analysis , and the molecular targeting relationship was verified by the dual-luciferase report system .
H/R injured cardiomyocytes were employed to explore the effect of AS/IV .
QRT-PCR and Western blot analysis were applied @ @ @ @ @ @ @ proteins , respectively .
Additionally , superoxide dismutase ( SOD ) , lactic dehydrogenase ( LDH ) and MDA ( malondialdehyde ) levels were detected to determine the oxidative damage .
Cell viability was assessed by CCK-8 , and flow cytometry was used to evaluate cell apoptosis ratio .
TGFBR1 and TLR2 were selected as DEGs .
Additionally , AS/IV could enhance cell proliferation and upregulated miR-101a expression , which suppressed TGFBR1 and TLR2 expression in H/R injured cardiomyocytes .
Moreover , the results of Western blot exhibited that the downstream genes ( @ @ @ @ @ @ @ signaling pathway were suppressed , which meant AS/IV could inhibit this pathway in H/R injured cardiomyocytes .
Overall , this study demonstrated AS/IV could attenuate H/R injury in human cardiomyocytes via the miR-101a/TGFBR1/TLR2/MAPK signaling pathway axis , which means that it could serve as a possible alternate for H/R treatment .

Astragaloside IV (AS/IV) is one of the extracted components from the traditional Chinese medicine Astragalus which has been demonstrated to have potential capacity for anti-inflammation activity and for treating cardiovascular disease. Our purpose was to determine the function and underlying molecular mechanism of AS/IV in hypoxia/reoxygenation (H/R) injured in cardiomyocytes. Differentially expressed genes (DEGs) were screened using bioinformatic analysis, and the molecular targeting relationship was verified by the dual-luciferase report system. H/R injured cardiomyocytes were employed to explore the effect of AS/IV. QRT-PCR and Western blot analysis were applied to detect the expression of mRNA and proteins, respectively. Additionally, superoxide dismutase (SOD), lactic dehydrogenase (LDH) and MDA (malondialdehyde) levels were detected to determine the oxidative damage. Cell viability was assessed by CCK-8, and flow cytometry was used to evaluate cell apoptosis ratio. TGFBR1 and TLR2 were selected as DEGs. Additionally, AS/IV could enhance cell proliferation and upregulated miR-101a expression, which suppressed TGFBR1 and TLR2 expression in H/R injured cardiomyocytes. Moreover, the results of Western blot exhibited that the downstream genes (p-ERK and p-p38) in the MAPK signaling pathway were suppressed, which meant AS/IV could inhibit this pathway in H/R injured cardiomyocytes. Overall, this study demonstrated AS/IV could attenuate H/R injury in human cardiomyocytes via the miR-101a/TGFBR1/TLR2/MAPK signaling pathway axis, which means that it could serve as a possible alternate for H/R treatment.


greenmedinfo--2020-05-21--Astragaloside IV ameliorates radiation-induced senescence via antioxidative mechanism.

OBJECTIVES : Ageing is a universal and gradual process of organ deterioration .
Radiation induces oxidative stress in cells , which leads to genetic damage and affects cell growth , differentiation and senescence .
Astragaloside ( AS ) -IV has antioxidative , anti-apoptotic and anti-inflammatory properties .
METHODS : To study the protective mechanism of AS-IV on radiation-induced brain cell senescence , we constructed a radiation-induced brain cell ageing model , using biochemical indicators , senescence-associated galactosidase ( SA-β-gal ) senescence staining , flow cytometry and Western blotting to analyse the AS-IV resistance mechanism to radiation-induced brain cell senescence .
@ @ @ @ @ @ @ ( SOD ) activity and expressions of cyclin-dependent kinase ( CDK2 ) , CDK4 , cyclin E and transcription factor E2F1 proteins , and increased expressions of p21 , p16 , cyclin D and retinoblastoma ( RB ) proteins , malondialdehyde ( MDA ) activity , SA-β-gal-positive cells and cells stagnating in G1 phase .
After treatment with AS-IV , the level of oxidative stress in cells significantly decreased and expression of proteins related to the cell cycle and ageing significantly changed .
In addition , SA-β-gal-positive cells and cells arrested in G1 @ @ @ @ @ @ @ These data suggest that AS-IV can antagonize radiation-induced brain cells senescence ; and its mechanism may be related to p53-p21 and p16-RB signalling pathways of ageing regulation .

OBJECTIVES: Ageing is a universal and gradual process of organ deterioration. Radiation induces oxidative stress in cells, which leads to genetic damage and affects cell growth, differentiation and senescence. Astragaloside (AS)-IV has antioxidative, anti-apoptotic and anti-inflammatory properties.
METHODS: To study the protective mechanism of AS-IV on radiation-induced brain cell senescence, we constructed a radiation-induced brain cell ageing model, using biochemical indicators, senescence-associated galactosidase (SA-β-gal) senescence staining, flow cytometry and Western blotting to analyse the AS-IV resistance mechanism to radiation-induced brain cell senescence.
KEY FINDINGS: Radiation reduced superoxide dismutase (SOD) activity and expressions of cyclin-dependent kinase (CDK2), CDK4, cyclin E and transcription factor E2F1 proteins, and increased expressions of p21, p16, cyclin D and retinoblastoma (RB) proteins, malondialdehyde (MDA) activity, SA-β-gal-positive cells and cells stagnating in G1 phase. After treatment with AS-IV, the level of oxidative stress in cells significantly decreased and expression of proteins related to the cell cycle and ageing significantly changed. In addition, SA-β-gal-positive cells and cells arrested in G1 phase were significantly reduced.
CONCLUSIONS: These data suggest that AS-IV can antagonize radiation-induced brain cells senescence; and its mechanism may be related to p53-p21 and p16-RB signalling pathways of ageing regulation.


greenmedinfo--2020-05-21--Effect of astragaloside IV on cognitive dysfunction in rats with cerebrally infarcted.

Cerebral infarction is an acute cerebrovascular disease caused by abnormal blood circulation in the brain .
In the present study , we investigate the effect of astragaloside IV on cognitive dysfunction in cerebrally infarcted rats via transforming growth factor-β ( TGF-β ) / Smad signaling pathway .
For this purpose , 45 rats were divided into three groups including astragaloside , model , and control .
30 of 45 healthy adult male SD rats were randomly selected to establish an acute cerebral infarction model .
15 modeled rats were enrolled as a model and astragaloside group , and another 15 @ @ @ @ @ @ @ The rats in the astragaloside group were fed with astragaloside IV according to 1.08 g/kg body weight , and those in the blank group and model group were given matching normal saline .
The levels of TGF-β , Smad1 , Smad3 and Smad7 of TGF-β/Smad signaling transduction pathway at T0 ( week 0 ) , T1 ( week 3 ) and T2 ( week 6 ) were determined by enzyme-linked immunosorbent assay ( ELISA ) .
The modified neurological severity score ( mNSS ) was used to evaluate the improvement of cognitive dysfunction @ @ @ @ @ @ @ with cerebral infarctionin the astragaloside group was lower than that in the control group and model group ( P < 0.05 ) .
While the levels of TGF-β , Smad1 , Smad3 and Smad7 in the astragaloside group were higher than those in the control group and model group ( P < 0.05 ) .
Astragaloside IV plays an important role in improving cognitive dysfunction in rats with cerebral infarction while affecting the levels of TGF-β , Smad1 , Smad3 and Smad7 and activating TGF-β / Smad signaling pathway .

Cerebral infarction is an acute cerebrovascular disease caused by abnormal blood circulation in the brain. In the present study, we investigate the effect of astragaloside IV on cognitive dysfunction in cerebrally infarcted rats via transforming growth factor-β (TGF-β) / Smad signaling pathway. For this purpose, 45 rats were divided into three groups including astragaloside, model, and control. 30 of 45 healthy adult male SD rats were randomly selected to establish an acute cerebral infarction model. 15 modeled rats were enrolled as a model and astragaloside group, and another 15 rats as a blank control group. The rats in the astragaloside group were fed with astragaloside IV according to 1.08 g/kg body weight, and those in the blank group and model group were given matching normal saline. The levels of TGF-β, Smad1, Smad3 and Smad7 of TGF-β/Smad signaling transduction pathway at T0 (week 0), T1 (week 3) and T2 (week 6) were determined by enzyme-linked immunosorbent assay (ELISA). The modified neurological severity score (mNSS) was used to evaluate the improvement of cognitive dysfunction in rats. The mNSS of rats with cerebral infarctionin the astragaloside group was lower than that in the control group and model group (P< 0.05). While the levels of TGF-β, Smad1, Smad3 and Smad7 in the astragaloside group were higher than those in the control group and model group (P< 0.05). Astragaloside IV plays an important role in improving cognitive dysfunction in rats with cerebral infarction while affecting the levels of TGF-β, Smad1, Smad3 and Smad7 and activating TGF-β / Smad signaling pathway.


greenmedinfo--2020-05-21--Astragaloside IV suppresses development of hepatocellular carcinoma.

Hepatocellular carcinoma ( HCC ) , a common malignant tumor , has been regarded as a leading cause of cancer-related deaths globally .
Astragaloside IV ( AS-IV ) was reported to participate in the regulation of multiple tumors .
However , the role of AS-IV in HCC was still unclear in HCC .
Bioinformatics analysis and function or mechanism experiments including RT-qPCR , MTT assay , flow cytometry , Western blot , luciferase reporter assay and xenografts assays were applied to investigate the function of AS-IV , miR-150-5p and CTNNB1 .
We discovered that AS-IV treatment was supposed to significantly @ @ @ @ @ @ @ AS-IV accelerated cell apoptosis by inducing miR-150-5p in vitro and in vivo .
Furthermore , AS-IV increased cell apoptosis rate through reducingβ-catenin level in vitro and in vivo .
In detail , AS-IV triggered a decline of Bax and a rise of Bcl-2 in HCC cells and xenograft tissues .
In mechanism , we validated the combination between miR-150-5p and CTNNB1 .
Moreover , miR-150-5p could negatively regulate CTNNB1 level by binding to its3'UTR .
Finally , rescue assay demonstrated that CTNNB1 overexpression partially rescued the inhibitive effect on tumor growth and promotive @ @ @ @ @ @ @ amplification .
The up-regulation of miR-150-5p induced by AS-IV suppressed the progression of HCC by repressing β-catenin , providing a new molecular target for the utilization of AS-IV In the treatment of HCC .

Hepatocellular carcinoma (HCC), a common malignant tumor, has been regarded as a leading cause of cancer-related deaths globally. Astragaloside IV (AS-IV) was reported to participate in the regulation of multiple tumors. However, the role of AS-IV in HCC was still unclear in HCC. Bioinformatics analysis and function or mechanism experiments including RT-qPCR, MTT assay, flow cytometry, Western blot, luciferase reporter assay and xenografts assays were applied to investigate the function of AS-IV, miR-150-5p and CTNNB1. We discovered that AS-IV treatment was supposed to significantly increase miR-150-5p level. In addition, AS-IV accelerated cell apoptosis by inducing miR-150-5p in vitro and in vivo. Furthermore, AS-IV increased cell apoptosis rate through reducingβ-catenin level in vitro and in vivo. In detail, AS-IV triggered a decline of Bax and a rise of Bcl-2 in HCC cells and xenograft tissues. In mechanism, we validated the combination between miR-150-5p and CTNNB1. Moreover, miR-150-5p could negatively regulate CTNNB1 level by binding to its3'UTR. Finally, rescue assay demonstrated that CTNNB1 overexpression partially rescued the inhibitive effect on tumor growth and promotive influence on cell apoptosis caused by miR-150-5p amplification. The up-regulation of miR-150-5p induced by AS-IV suppressed the progression of HCC by repressing β-catenin, providing a new molecular target for the utilization of AS-IV In the treatment of HCC.


greenmedinfo--2020-05-21--Astragaloside IV promotes cerebral protection following angiogenesis and ischemic brain injury.

BACKGROUND : Astragaloside IV ( AS-IV ) is one of the main active ingredients of Astragalusmembranaceus .
Studies have shown that AS-IV stimulates angiogenesis , including cell proliferation , migration , and neovascularization .
However , the relevant mechanism remains unclear .
OBJECTIVE : This study aims to investigate whether AS-IV activates the HIF/VEGF/Notch signaling pathway through miRNA-210 to promote angiogenesisafter ischemic stroke .
METHODS : The present study established a rat model of middle cerebral artery occlusion ( MCAO ) and cultured human umbilical vein endothelial cells ( HUVECs ) under hypoxic conditions in vitro to investigate the role @ @ @ @ @ @ @ its underlying mechanism .
Through in vivo studies , the area of cerebral infarction was determined by 2,3,5-triPhenyltetrazolium chloride ( TTC ) staining .
Immunofluorescence staining and RT-qPCR were used to detect the expression changes of miRNA-210 and ephrinA3 in the ischemic cortex after ischemia .
Through in vitro studies , cell proliferation was measured by 3- ( 4,5-dimethylthiazol-2-yl ) -2,5-diphenyltetrazolium bromide ( MTT ) assay .
Subsequently , angiogenesis experiments were performed to observe the angiogenic ability .
RESULTS : Results revealed that AS-IV significantly reduced infarct size , promoted cell proliferation @ @ @ @ @ @ @ expression of the target gene ephrinA3 by increasing the expression of miRNA-210 and inducing activation of the HIF-VEGF-Notch signaling pathway .
CONCLUSIONS : AS-IV promotes cerebral protection following angiogenesis and ischemic brain injury .
The specific mechanism was activating the HIF/VEGF/Notch signaling pathway via miRNA-210 .

BACKGROUND: Astragaloside IV (AS-IV) is one of the main active ingredients of Astragalusmembranaceus. Studies have shown that AS-IV stimulates angiogenesis, including cell proliferation, migration, and neovascularization. However, the relevant mechanism remains unclear.
OBJECTIVE: This study aims to investigate whether AS-IV activates the HIF/VEGF/Notch signaling pathway through miRNA-210 to promote angiogenesisafter ischemic stroke.
METHODS: The present study established a rat model of middle cerebral artery occlusion (MCAO) and cultured human umbilical vein endothelial cells (HUVECs) under hypoxic conditions in vitro to investigate the role of AS-IV in promoting angiogenesis and reveal its underlying mechanism. Through in vivo studies, the area of cerebral infarction was determined by 2,3,5-triPhenyltetrazolium chloride (TTC) staining. Immunofluorescence staining and RT-qPCR were used to detect the expression changes of miRNA-210 and ephrinA3 in the ischemic cortex after ischemia. Through in vitro studies, cell proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Subsequently, angiogenesis experiments were performed to observe the angiogenic ability.
RESULTS: Results revealed that AS-IV significantly reduced infarct size, promoted cell proliferation and ductal formation, and inhibited the expression of the target gene ephrinA3 by increasing the expression of miRNA-210 and inducing activation of the HIF-VEGF-Notch signaling pathway.
CONCLUSIONS: AS-IV promotes cerebral protection following angiogenesis and ischemic brain injury. The specific mechanism was activating the HIF/VEGF/Notch signaling pathway via miRNA-210.


greenmedinfo--2020-05-21--The regulated profile of noncoding RNAs associated with inflammation by tanshinone IIA on atheroscle

The regulated profile of noncoding RNAs associated with inflammation by tanshinone IIA on atherosclerosis.

Atherosclerosis ( AS ) is the principal cause of heart attack , sudden cardiac death , stroke , and necrosis of the extremities , in which significant changes in gene expression associated with inflammation are found .
However , the molecular mechanisms of AS are not clearly elucidated .
In this study , ApoEmice were fed with a high fat diet for 12 weeks to induce atherosclerosis and half of the mice were treated with tanshinone IIA ( TAN ) .
Then sequencing analysis was performed to investigate the expression patterns of ncRNAs in AS plaques obtained from mice treated @ @ @ @ @ @ @ A total of 22 long noncoding RNAs ( lncRNAs ) , 74microRNAs ( miRNAs ) , 13 circular RNAs ( circRNAs ) , and 1359 mRNAs in AS plaque were more significantly regulated from TAN mice , compared with model mice .
Bioinformatics tools and databases were employed to investigate the potential ncRNA functions and their interaction .
Our data showed that the most significantly pathways regulated by TAN were associated with inflammation , and involved in the signaling pathways of Ras , Rap1 , MAPK , cAMP , T cell receptor , @ @ @ @ @ @ @ the competitive endogenous RNA ( ceRNA ) network had been constructed and the core nodes included circ-Tns3/let-7d-5p/Ctsl , circ-Wdr91/miR-378a-5p/Msr1 , and circ-Cd84/ miR-30c/ Tlr2 .
The DERNAs were validated by quantitative RT-PCR and dual luminescence reporter assay in RAW264.7 cells in vitro .
This study identified ceRNAs network regulated by TAN and elucidated the ncRNAs profile and signal pathways to attenuate AS comprehensively .
This research would contribute to further research on the pathogenesis of AS , and facilitate the development of novel therapeutics targeting ncRNAs .

Atherosclerosis (AS) is the principal cause of heart attack, sudden cardiac death, stroke, and necrosis of the extremities, in which significant changes in gene expression associated with inflammation are found. However, the molecular mechanisms of AS are not clearly elucidated. In this study, ApoEmice were fed with a high fat diet for 12 weeks to induce atherosclerosis and half of the mice were treated with tanshinone IIA (TAN). Then sequencing analysis was performed to investigate the expression patterns of ncRNAs in AS plaques obtained from mice treated with TAN and AS Model mice. A total of 22 long noncoding RNAs (lncRNAs), 74microRNAs (miRNAs), 13 circular RNAs (circRNAs), and 1359 mRNAs in AS plaque were more significantly regulated from TAN mice, compared with model mice. Bioinformatics tools and databases were employed to investigate the potential ncRNA functions and their interaction. Our data showed that the most significantly pathways regulated by TAN were associated with inflammation, and involved in the signaling pathways of Ras, Rap1, MAPK, cAMP, T cell receptor, and so on. In addition, the competitive endogenous RNA (ceRNA) network had been constructed and the core nodes included circ-Tns3/let-7d-5p/Ctsl, circ-Wdr91/miR-378a-5p/Msr1, and circ-Cd84/ miR-30c/ Tlr2. The DERNAs were validated by quantitative RT-PCR and dual luminescence reporter assay in RAW264.7 cells in vitro. This study identified ceRNAs network regulated by TAN and elucidated the ncRNAs profile and signal pathways to attenuate AS comprehensively. This research would contribute to further research on the pathogenesis of AS, and facilitate the development of novel therapeutics targeting ncRNAs.


greenmedinfo--2020-05-21--Improved tendon healing by a combination of tanshinone IIA and miR-29b inhibitor treatment.

: Despite significant advances in the materials and methods development used in surgical repair and postoperative rehabilitation , the adhesion formation remains the most common clinical problem in tendon injuries .
Therefore , the development of novel therapies is necessary for targeting at preventing tendon adhesion formation and improving tendon strength .
: We used rat fibroblasts for in vitro experiments to determine the optimal concentration of TSA in rats , and then set up negative control group , TSA intervention group , mir-29b interference adenovirus intervention group and TSA and mir-29b interference adenovirus co-intervention group .
By comparing cell @ @ @ @ @ @ @ , we verified the effect and mechanism of drugs on fibroblast function .
At the same time , the Sprague-Dawley rat Achilles tendon modelwas established in this study , which was divided into sham operation group and operation group .
Afterwards in the operation group , mir-29b inhibitor and placebo were injected every 3 days respectively .
Then the injection inhibitor group was divided into 5 groups which mean TSA was injected into the marked area at 0 , 6 , 24 and 72 hours after operation for 1 week , finally all @ @ @ @ @ @ @ weeks after operation .
Through the observation of general properties , histological observation of Achilles tendon injury , biomechanical test and cell and protein expression in rats ' tendon cell , the effect of drugs on tendon adhesion formation was analyzed .
: We demonstrated that the combination of miR-29b inhibitor and tanshinone IIA ( TSA ) could prevent tendon adhesion and also enhance tendon strength .
Mechanically , the miR-29b inhibitor could activate the TGF-β/Smad3 pathway to trigger endogenous pathways and induce a high proliferation of fibroblast .
Subsequently , we also @ @ @ @ @ @ @ miR-29b treatment gave less cell cytotoxicity in our rat model with better outcome of less tendon adhesion and enhanced strength .
: We conclude that the use of miR-29b inhibitor at the end of the tendon break could initiate endogenous repair mechanism and subsequently use of TSA should be able to inhibit the exogenous repair mechanism .
Therefore , the combination of both treatments could prevent tendon adhesion and ensure tendon strength .
Our findings suggested that this approach would be a feasible approach for tendon repair .

: Despite significant advances in the materials and methods development used in surgical repair and postoperative rehabilitation, the adhesion formation remains the most common clinical problem in tendon injuries. Therefore, the development of novel therapies is necessary for targeting at preventing tendon adhesion formation and improving tendon strength.: We used rat fibroblasts for in vitro experiments to determine the optimal concentration of TSA in rats, and then set up negative control group, TSA intervention group, mir-29b interference adenovirus intervention group and TSA and mir-29b interference adenovirus co-intervention group. By comparing cell proliferation and protein expression in different group, we verified the effect and mechanism of drugs on fibroblast function. At the same time, the Sprague-Dawley rat Achilles tendon modelwas established in this study, which was divided into sham operation group and operation group. Afterwards in the operation group, mir-29b inhibitor and placebo were injected every 3 days respectively. Then the injection inhibitor group was divided into 5 groups which mean TSA was injected into the marked area at 0, 6, 24 and 72 hours after operation for 1 week, finally all of the rats were died at 3 weeks after operation. Through the observation of general properties, histological observation of Achilles tendon injury, biomechanical test and cell and protein expression in rats' tendon cell, the effect of drugs on tendon adhesion formation was analyzed.: We demonstrated that the combination of miR-29b inhibitor and tanshinone IIA(TSA) could prevent tendon adhesion and also enhance tendon strength. Mechanically, the miR-29b inhibitor could activate the TGF-β/Smad3 pathway to trigger endogenous pathways and induce a high proliferation of fibroblast. Subsequently, we also found adding TSA after 6 hours of miR-29b treatment gave less cell cytotoxicity in our rat model with better outcome of less tendon adhesion and enhanced strength.: We conclude that the use of miR-29b inhibitor at the end of the tendon break could initiate endogenous repair mechanism and subsequently use of TSA should be able to inhibit the exogenous repair mechanism. Therefore, the combination of both treatments could prevent tendon adhesion and ensure tendon strength. Our findings suggested that this approach would be a feasible approach for tendon repair.


greenmedinfo--2020-05-21--How Governments are Hunting the Infected

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greenmedinfo--2020-05-21--Tanshinone IIA inhibits oral squamous cell carcinoma via reducing Akt-c-Myc signaling-mediated aerob

Tanshinone IIA inhibits oral squamous cell carcinoma via reducing Akt-c-Myc signaling-mediated aerobic glycolysis

Aerobic glycolysis is one of the hallmarks of human cancer cells .
Overexpression of hexokinase 2 ( HK2 ) plays @ @ @ @ @ maintaining of unlimited tumor cell growth .
In the present study , we found that @ @ @ @ @ ( OSCC ) cells exhibited an aerobic glycolysis phenotype .
Moreover , HK2 is highly @ @ @ @ @ and cell lines .
Depletion of HK2 inhibited OSCC cell growth in vitro and in @ @ @ @ @ product screening , we identified Tanshinone IIA ( Tan IIA ) as a potential anti-tumor @ @ @ @ @ HK2-mediated glycolysis .
Tan IIA decreased glucose consumption , lactate production , and promoted intrinsic @ @ @ @ @ The mechanism study revealed that Tan IIA inhibited the Akt-c-Myc signaling and promoted E3 ligase @ @ @ @ @ , which eventually reduced HK2 expression at the transcriptional level .
In summary , these @ @ @ @ @ aerobic glycolysis is a promising anti-tumor strategy for OSCC treatment .

Aerobic glycolysis is one of the hallmarks of human cancer cells. Overexpression of hexokinase 2 (HK2) plays a crucial role in the maintaining of unlimited tumor cell growth. In the present study, we found that the oral squamous cell carcinoma (OSCC) cells exhibited an aerobic glycolysis phenotype. Moreover, HK2 is highly expressed in OSCC patient derived-tissues and cell lines. Depletion of HK2 inhibited OSCC cell growth in vitro and in vivo. With a natural product screening, we identified Tanshinone IIA (Tan IIA) as a potential anti-tumor compound for OSCC through suppressing HK2-mediated glycolysis. Tan IIA decreased glucose consumption, lactate production, and promoted intrinsic apoptosis in OSCC cells. The mechanism study revealed that Tan IIA inhibited the Akt-c-Myc signaling and promoted E3 ligase FBW7-mediated c-Myc ubiquitination and degradation, which eventually reduced HK2 expression at the transcriptional level. In summary, these results indicate that targeting HK2-mediated aerobic glycolysis is a promising anti-tumor strategy for OSCC treatment.


greenmedinfo--2020-05-21--Honokiol reduces fungal load and inflammatory cytokines in aspergillus fumigatus keratitis.

Purpose : We characterized the effects of Honokiol ( HNK ) on Aspergillus fumigatus-caused keratomycosis and the underlying mechanisms .
HNK is known to have anti-inflammatory and antifungal properties , but the influence on fungal keratitis ( FK ) remains unknown .
Methods : In ex vivo , minimum inhibitory concentration and Cell Count Kit-8 assay were carried out spectrophotometrically to provide preferred concentration applied in vivo .
Time kill assay pointed that HNK was fungicidal and fungistatic chronologically .
Adherence assay , crystal violet staining , and membrane permeability assay tested HNK effects on different fungal stages .
In @ @ @ @ @ @ @ degree of keratitis outcome .
Myeloperoxidase ( MPO ) assay , flow cytometry ( FCM ) , and immunohistofluorescence staining ( IFS ) were done to evaluate neutrophil infiltration .
Plate count detected HNK fungicidal potentiality .
RT-PCR , Western blot , and enzyme-linked immunosorbent assay ( ELISA ) verified the anti-inflammatory activity of HNK collaboratively .
Results : In vitro , MIC90 HNK was 8µg/mL ( no cytotoxicity ) , and Minimal Fungicidal Concentration ( MFC ) was 12 µg/mL for A. fumigatus .
HNK played the fungistatic and fungicidal roles at @ @ @ @ @ @ @ inhibiting adherence at the beginning , diminishing biofilms formation , and increasing membrane permeability all the time .
In vivo , HNK improved C57BL/6 mice outcome by reducing disease severity ( clinical scores ) , neutrophil infiltration ( MPO , FCM , and IFS ) , and fungal loading ( plate count ) .
RT-PCR , Western blot , and ELISA revealed that HNK downregulated mRNA and protein expression levels of Toll-like receptor-2 ( TLR-2 ) , high mobility group box 1 ( HMGB1 ) , IL-1β , and TNF-α .
Conclusions : @ @ @ @ @ @ @ anti-inflammatory roles on keratomycosis by reducing survival of fungi , infiltration of leucocytes , and expression of HMGB1 , TLR-2 , and proinflammatory cytokines , providing a potential treatment for FK .

Purpose: We characterized the effects of Honokiol (HNK) on Aspergillus fumigatus-caused keratomycosis and the underlying mechanisms. HNK is known to have anti-inflammatory and antifungal properties, but the influence on fungal keratitis (FK) remains unknown.
Methods: In ex vivo, minimum inhibitory concentration and Cell Count Kit-8 assay were carried out spectrophotometrically to provide preferred concentration applied in vivo. Time kill assay pointed that HNK was fungicidal and fungistatic chronologically. Adherence assay, crystal violet staining, and membrane permeability assay tested HNK effects on different fungal stages. In vivo, clinical scores reflected the improvement degree of keratitis outcome. Myeloperoxidase (MPO) assay, flow cytometry (FCM), and immunohistofluorescence staining (IFS) were done to evaluate neutrophil infiltration. Plate count detected HNK fungicidal potentiality. RT-PCR, Western blot, and enzyme-linked immunosorbent assay (ELISA) verified the anti-inflammatory activity of HNK collaboratively.
Results: In vitro, MIC90 HNK was 8µg/mL (no cytotoxicity), and Minimal Fungicidal Concentration (MFC) was 12 µg/mL for A. fumigatus. HNK played the fungistatic and fungicidal roles at 6 and 24 hours, respectively, inhibiting adherence at the beginning, diminishing biofilms formation, and increasing membrane permeability all the time. In vivo, HNK improved C57BL/6 mice outcome by reducing disease severity (clinical scores), neutrophil infiltration (MPO, FCM, and IFS), and fungal loading (plate count). RT-PCR, Western blot, and ELISA revealed that HNK downregulated mRNA and protein expression levels of Toll-like receptor-2 (TLR-2), high mobility group box 1 (HMGB1), IL-1β, and TNF-α.
Conclusions: Our study suggested HNK played antifungal and anti-inflammatory roles on keratomycosis by reducing survival of fungi, infiltration of leucocytes, and expression of HMGB1, TLR-2, and proinflammatory cytokines, providing a potential treatment for FK.


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greenmedinfo--2020-05-21--Honokiol inhibits carotid artery atherosclerotic plaque formation by suppressing inflammation and ox

Honokiol inhibits carotid artery atherosclerotic plaque formation by suppressing inflammation and oxidative stress.

Honokiol is a natural active compound extracted from Chinese herbal medicine , .
In this study , the role of honokiol in the development of carotid artery atherosclerotic lesions was evaluated in an ApoE-/- mouse model fed with a normal diet ( ND ) or a Western-type diet ( WD ) for ten weeks .
After first two weeks , a perivascular collar was surgically placed on the right common carotid arteries of the mice .
Then , WD-fed mice were intraperitoneally injected with honokiol ( 10 or 20 mg/kg ) or administrated with 10 mg/kg atorvastatin calcium by gavage @ @ @ @ @ @ @ After that , the right common carotid arteries were excised for further experiments .
The result showed that honokiol substantially inhibited the development of atherosclerotic lesions .
Furthermore , honokiol downregulated the expression of pro-inflammatory markers , like tumor necrosis factor-α , interleukin ( IL ) -6 , and IL-1β .
Additionally , honokiol treatment decreased reactive oxygen species level and enhanced superoxide dismutase activity .
Nitric oxide level , inducible nitric oxide synthase ( iNOS ) expression , and aberrant activation of nuclear factor-κB pathway were also significantly inhibited by honokiol treatment @ @ @ @ @ @ @ honokiol protects against atherosclerotic plaque formation in carotid artery , and may be an effective drug candidate for the treatment of carotid artery atherosclerotic stenosis .

Honokiol is a natural active compound extracted from Chinese herbal medicine,. In this study, the role of honokiol in the development of carotid artery atherosclerotic lesions was evaluated in an ApoE-/- mouse model fed with a normal diet (ND) or a Western-type diet (WD) for ten weeks. After first two weeks, a perivascular collar was surgically placed on the right common carotid arteries of the mice. Then, WD-fed mice were intraperitoneally injected with honokiol (10 or 20 mg/kg) or administrated with 10 mg/kg atorvastatin calcium by gavage once a day for eight weeks. After that, the right common carotid arteries were excised for further experiments. The result showed that honokiol substantially inhibited the development of atherosclerotic lesions. Furthermore, honokiol downregulated the expression of pro-inflammatory markers, like tumor necrosis factor-α, interleukin (IL)-6, and IL-1β. Additionally, honokiol treatment decreased reactive oxygen species level and enhanced superoxide dismutase activity. Nitric oxide level, inducible nitric oxide synthase (iNOS) expression, and aberrant activation of nuclear factor-κB pathway were also significantly inhibited by honokiol treatment. Together, these findings suggest that honokiol protects against atherosclerotic plaque formation in carotid artery, and may be an effective drug candidate for the treatment of carotid artery atherosclerotic stenosis.


greenmedinfo--2020-05-21--Magnolia extract is effective for the chemoprevention of oral cancer through its ability to inhibit

Magnolia extract is effective for the chemoprevention of oral cancer through its ability to inhibit mitochondrial respiration at complex I

BACKGROUND : Magnolia extract ( ME ) is known to inhibit cancer growth and metastasis in several cell types in vitro and in animal models .
However , there is no detailed study on the preventive efficacy of ME for oral cancer , and the key components in ME and their exact mechanisms of action are not clear .
The overall goal of this study is to characterize ME preclinically as a potent oral cancer chemopreventive agent and to determine the key components and their molecular mechanism ( s ) that underlie its chemopreventive efficacy .
METHODS : The antitumor @ @ @ @ @ @ @ investigated in a 4-nitroquinoline-1-oxide ( 4NQO ) -induced mouse model and in two oral cancer orthotopic models .
The effects of ME on mitochondrial electron transport chain activity and ROS production in mouse oral tumors was also investigated .
RESULTS : ME did not cause detectable side effects indicating that it is a promising and safe chemopreventive agent for oral cancer .
Three major key active compounds in ME ( honokiol , magnolol and 4-O-methylhonokiol ) contribute to its chemopreventive effects .
ME inhibits mitochondrial respiration at complex I of the electron transport @ @ @ @ @ @ @ , and inhibits STAT3 phosphorylation , resulting in inhibition of the growth and proliferation of oral cancer cells .
CONCLUSION : Our data using highly relevant preclinical oral cancer models , which share histopathological features seen in human oral carcinogenesis , suggest a novel signaling and regulatory role for mitochondria-generated superoxide and hydrogen peroxide in suppressing oral cancer cell proliferation , progression , and metastasis .
Video abstract .

BACKGROUND: Magnolia extract (ME) is known to inhibit cancer growth and metastasis in several cell types in vitro and in animal models. However, there is no detailed study on the preventive efficacy of ME for oral cancer, and the key components in ME and their exact mechanisms of action are not clear. The overall goal of this study is to characterize ME preclinically as a potent oral cancer chemopreventive agent and to determine the key components and their molecular mechanism(s) that underlie its chemopreventive efficacy.
METHODS: The antitumor efficacy of ME in oral cancer was investigated in a 4-nitroquinoline-1-oxide (4NQO)-induced mouse model and in two oral cancer orthotopic models. The effects of ME on mitochondrial electron transport chain activity and ROS production in mouse oral tumors was also investigated.
RESULTS: ME did not cause detectable side effects indicating that it is a promising and safe chemopreventive agent for oral cancer. Three major key active compounds in ME (honokiol, magnolol and 4-O-methylhonokiol) contribute to its chemopreventive effects. ME inhibits mitochondrial respiration at complex I of the electron transport chain, oxidizes peroxiredoxins, activates AMPK, and inhibits STAT3 phosphorylation, resulting in inhibition of the growth and proliferation of oral cancer cells.
CONCLUSION: Our data using highly relevant preclinical oral cancer models, which share histopathological features seen in human oral carcinogenesis, suggest a novel signaling and regulatory role for mitochondria-generated superoxide and hydrogen peroxide in suppressing oral cancer cell proliferation, progression, and metastasis. Video abstract.


greenmedinfo--2020-05-21--Magnolol-inhibited progression of colorectal cancer.

Magnolol is one of the hydroxylated biphenyl compounds from the root and stem bark of , which shown to possess anti-colorectal cancer ( CRC ) effects .
However , the regulatory mechanism of magnolol on apoptosis and NF-κB signaling in human CRC has not been elucidated .
Thus , we investigated the inhibitory mechanism of magnolol on human and mouse CRC ( HT-29 and CT-26 ) in vitro and in vivo .
Results from reporter gene assay indicated that both magnolol and rottlerin ( PKCδ inhibitor ) reduced the endogenous NF-κB activity .
In addition , indolactam V ( PKCδ @ @ @ @ @ @ @ suppressed with both magnolol and rottlerin treatment .
Results from Western blotting also indicated that phosphorylation of PKCδ and NF-κB -related proteins involved in tumor progression were effectivelydecreased by magnolol treatment .
The invasion capacity of CRC cells was also attenuated by both magnolol and rottlerin .
Furthermore , magnolol triggered Fas/Fas-L mediated extrinsic apoptosis and mitochondria mediated intrinsic apoptosis were validated by flow cytometry .
Most importantly , tumor growth in both HT-29 and CT-26 bearing mice were suppressed by magnolol , but no pathologic change was detected in mice kidney , @ @ @ @ @ @ @ by immunohistochemistry ( IHC ) staining from tumor tissue , PKCδ/NF-κB signaling and downstream proteins expression were decreased , while apoptotic proteins expression was increased in the magnolol treated group .
According to these results , we suggest that the induction of apoptosis through extrinsic/intrinsic pathways and the blockage of PKCδ/NF-κB signaling are associated with the magnolol-inhibited progression of CRC .

Magnolol is one of the hydroxylated biphenyl compounds from the root and stem bark of, which shown to possess anti-colorectal cancer (CRC) effects. However, the regulatory mechanism of magnolol on apoptosis and NF-κB signaling in human CRC has not been elucidated. Thus, we investigated the inhibitory mechanism of magnolol on human and mouse CRC (HT-29 and CT-26) in vitro and in vivo. Results from reporter gene assay indicated that both magnolol and rottlerin (PKCδ inhibitor) reduced the endogenous NF-κB activity. In addition, indolactam V (PKCδ activator)-induced NF-κB signaling was significantly suppressed with both magnolol and rottlerin treatment. Results from Western blotting also indicated that phosphorylation of PKCδ and NF-κB -related proteins involved in tumor progression were effectivelydecreased by magnolol treatment. The invasion capacity of CRC cells was also attenuated by both magnolol and rottlerin. Furthermore, magnolol triggered Fas/Fas-L mediated extrinsic apoptosis and mitochondria mediated intrinsic apoptosis were validated by flow cytometry. Most importantly, tumor growth in both HT-29 and CT-26 bearing mice were suppressed by magnolol, but no pathologic change was detected in mice kidney, spleen, and liver. As confirmed by immunohistochemistry (IHC) staining from tumor tissue, PKCδ/NF-κB signaling and downstream proteins expression were decreased, while apoptotic proteins expression was increased in the magnolol treated group. According to these results, we suggest that the induction of apoptosis through extrinsic/intrinsic pathways and the blockage of PKCδ/NF-κB signaling are associated with the magnolol-inhibited progression of CRC.


greenmedinfo--2020-05-21--This study intends to provide reference for clinical use of traditional Chinese medicine to resist n

Since the outbreak of 2019-nCoV , the epidemic has developed rapidly and the situation is grim .
LANCET figured out that the 2019-nCoV is closely related to '' cytokine storm '' .
`` Cytokine storm '' is an excessive immune response of the body to external stimuli such as viruses and bacteria .
As the virus attacking the body , it stimulates the secretion of a large number of inflammatory factors : interleukin ( IL ) , interferon ( IFN ) , C-X-C motif chemokine ( CXCL ) and so on , which lead to cytokine cascade reaction .
With @ @ @ @ @ @ @ increase abnormally in tissues and organs , interfering with the immune system , causing excessive immune response of the body , resulting in diffuse damage of lung cells , pulmonary fibrosis , and multiple organ damage , even death .
Arachidonic acid ( AA ) metabolic pathway is principally used to synthesize inflammatory cytokines , such as monocyte chemotactic protein 1 ( MCP-1 ) , tumor necrosis factor ( TNF ) , IL , IFN , etc.
, which is closely related to the occurrence , development and regression of inflammation .
Therefore @ @ @ @ @ @ @ is benefit for inhibiting the release of inflammatory factors in the body and alleviating the '' cytokine storm '' .
Based on the pharmacophore models of the targets on AA metabolic pathway , the traditional Chinese medicine database 2009 ( TCMD 2009 ) was screened .
The potential herbs were ranked by the number of hit molecules , which were scored by pharmacophore fit value .
In the end , we obtained the potential active prescriptions on '' cytokine storm '' according to the potential herbs in the '' National novel coronavirus pneumonia @ @ @ @ @ @ @ sixth ) '' .
The results showed that the hit components with the inhibitory effect on AA were magnolignanⅠ , lonicerin and physcion-8-O-β-D-glucopy-ranoside , which mostly extracted from Magnoliae Officinalis Cortex , Zingiberis Rhizoma Recens , Lonicerae Japonicae Flos , Rhei Radix et Rhizoma , Salviae Miltiorrhizae Radix et Rhizoma , Scutellariae Radix , Gardeniae Fructus , Ginseng Radix et Rhizoma , ArctiiFructus , Dryopteridis Crassirhizomatis Rhizoma , Paeoniaeradix Rubra , Dioscoreae Rhizoma .
Finally the anti-2019-nCoV prescriptions were analyzed to obtain the potential active prescriptions on AA metabolic pathway , Huoxiang Zhengqi @ @ @ @ @ @ @ Qingwen Capsules , QingfeiPaidu Decoction , Xuebijing Injection , Reduning Injection and Tanreqing Injection were found that may prevent 2019-nCoV via regulate cytokines .
This study intends to provide reference for clinical use of traditional Chinese medicine to resist new coronavirus .

Since the outbreak of 2019-nCoV, the epidemic has developed rapidly and the situation is grim. LANCET figured out that the 2019-nCoV is closely related to"cytokine storm"."Cytokine storm" is an excessive immune response of the body to external stimuli such as viruses and bacteria. As the virus attacking the body, it stimulates the secretion of a large number of inflammatory factors: interleukin(IL), interferon(IFN), C-X-C motif chemokine(CXCL) and so on, which lead to cytokine cascade reaction. With the exudation of inflammatory factors, cytokines increase abnormally in tissues and organs, interfering with the immune system, causing excessive immune response of the body, resulting in diffuse damage of lung cells, pulmonary fibrosis, and multiple organ damage, even death. Arachidonic acid(AA) metabolic pathway is principally used to synthesize inflammatory cytokines, such as monocyte chemotactic protein 1(MCP-1), tumor necrosis factor(TNF), IL, IFN, etc., which is closely related to the occurrence, development and regression of inflammation. Therefore, the inhibition of AA metabolism pathway is benefit for inhibiting the release of inflammatory factors in the body and alleviating the"cytokine storm". Based on the pharmacophore models of the targets on AA metabolic pathway, the traditional Chinese medicine database 2009(TCMD 2009) was screened. The potential herbs were ranked by the number of hit molecules, which were scored by pharmacophore fit value. In the end, we obtained the potential active prescriptions on"cytokine storm" according to the potential herbs in the"National novel coronavirus pneumonia diagnosis and treatment plan(trial version sixth)". The results showed that the hit components with the inhibitory effect on AA were magnolignanⅠ, lonicerin and physcion-8-O-β-D-glucopy-ranoside, which mostly extracted from Magnoliae Officinalis Cortex, Zingiberis Rhizoma Recens, Lonicerae Japonicae Flos, Rhei Radix et Rhizoma, Salviae Miltiorrhizae Radix et Rhizoma, Scutellariae Radix, Gardeniae Fructus, Ginseng Radix et Rhizoma, ArctiiFructus, Dryopteridis Crassirhizomatis Rhizoma, Paeoniaeradix Rubra, Dioscoreae Rhizoma. Finally the anti-2019-nCoV prescriptions were analyzed to obtain the potential active prescriptions on AA metabolic pathway, Huoxiang Zhengqi Capsules, Jinhua Qinggan Granules, Lianhua Qingwen Capsules, QingfeiPaidu Decoction, Xuebijing Injection, Reduning Injection and Tanreqing Injection were found that may prevent 2019-nCoV via regulate cytokines. This study intends to provide reference for clinical use of traditional Chinese medicine to resist new coronavirus.


greenmedinfo--2020-05-21--Astaxanthin treatment induces maturation and functional change of myeloid-derived suppressor cells i

Astaxanthin treatment induces maturation and functional change of myeloid-derived suppressor cells in tumor-bearing mice.

Myeloid-derived suppressor cells ( MDSCs ) are immature myeloid cells which accumulate in stress conditions such as infection and tumor .
Astaxanthin ( ATX ) is a well-known antioxidant agent and has a little toxicity .
It has been reported that ATX treatment induces antitumor effects via regulation of cell signaling pathways , including nuclear factor erythroid-derived 2-related factor 2 ( Nrf2 ) signaling .
In the present study , we hypothesized that treatment with ATX might induce maturation of MDSCs and modulate their immunosuppressive activity .
Both in vivo and in vitro treatment with ATX resulted in up-regulation of @ @ @ @ @ @ @ class II , and CD11c on both polymorphonuclear ( PMN ) -MDSCs and mononuclear ( Mo ) -MDSCs .
Expression levels of functional mediators involved in immune suppression were significantly reduced , whereas mRNA levels of Nrf2 target genes were increased in ATX-treated MDSCs .
In addition , ATX was found to have antioxidant activity reducing reactive oxygen species level in MDSCs .
Finally , ATX-treated MDSCs were immunogenic enough to induce cytotoxic T lymphocyte response and contributed to the inhibition of tumor growth .
This demonstrates the role of ATX as a @ @ @ @ @ @ @ induction of differentiation and functional conversion of MDSCs .

Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells which accumulate in stress conditions such as infection and tumor. Astaxanthin (ATX) is a well-known antioxidant agent and has a little toxicity. It has been reported that ATX treatment induces antitumor effects via regulation of cell signaling pathways, including nuclear factor erythroid-derived 2-related factor 2 (Nrf2) signaling. In the present study, we hypothesized that treatment with ATX might induce maturation of MDSCs and modulate their immunosuppressive activity. Both in vivo and in vitro treatment with ATX resulted in up-regulation of surface markers such as CD80, MHC class II, and CD11c on both polymorphonuclear (PMN)-MDSCs and mononuclear (Mo)-MDSCs. Expression levels of functional mediators involved in immune suppression were significantly reduced, whereas mRNA levels of Nrf2 target genes were increased in ATX-treated MDSCs. In addition, ATX was found to have antioxidant activity reducing reactive oxygen species level in MDSCs. Finally, ATX-treated MDSCs were immunogenic enough to induce cytotoxic T lymphocyte response and contributed to the inhibition of tumor growth. This demonstrates the role of ATX as a regulator of the immunosuppressive tumor environment through induction of differentiation and functional conversion of MDSCs.


greenmedinfo--2020-05-21--Clinical applications of astaxanthin in the treatment of ocular diseases.

Astaxanthin is a naturally occurring red carotenoid pigment belonging to the family of xanthophylls , and is typically found in @ @ @ @ @ microalgae and seafood such as salmonids , shrimps and lobsters .
Due to its unique @ @ @ @ @ some important biologic properties , mostly represented by strong antioxidant , anti-inflammatory and antiapoptotic activities @ @ @ @ @ evidence suggests that astaxanthin is efficacious in the prevention and treatment of several ocular diseases @ @ @ @ @ to the posterior pole of the eye .
Therefore , the present review aimed at @ @ @ @ @ current clinical applications of astaxanthin in the management of ocular diseases .
The efficacy of @ @ @ @ @ of retinal diseases , ocular surface disorders , uveitis , cataract and asthenopia is reported @ @ @ @ @ studies , which highlight its ability of modulating several metabolic pathways , subsequently restoring the @ @ @ @ @ maximize its multitarget therapeutic effects , further long-term clinical trials are warranted in order to @ @ @ @ @ of administration and exact composition of the final product .

Astaxanthin is a naturally occurring red carotenoid pigment belonging to the family of xanthophylls, and is typically found in marine environments, especially in microalgae and seafood such as salmonids, shrimps and lobsters. Due to its unique molecular structure, astaxanthin features some important biologic properties, mostly represented by strong antioxidant, anti-inflammatory and antiapoptotic activities. A growing body of evidence suggests that astaxanthin is efficacious in the prevention and treatment of several ocular diseases, ranging from the anterior to the posterior pole of the eye. Therefore, the present review aimed at providing a comprehensive evaluation of current clinical applications of astaxanthin in the management of ocular diseases. The efficacy of this carotenoid in the setting of retinal diseases, ocular surface disorders, uveitis, cataract and asthenopia is reported in numerous animal and human studies, which highlight its ability of modulating several metabolic pathways, subsequently restoring the cellular homeostatic balance. To maximize its multitarget therapeutic effects, further long-term clinical trials are warranted in order to define appropriate dosage, route of administration and exact composition of the final product.


greenmedinfo--2020-05-21--Astaxanthin from haematococcus pluvialis ameliorates the chemotherapeutic drug doxorubicin induced l

Astaxanthin from haematococcus pluvialis ameliorates the chemotherapeutic drug doxorubicin induced liver injury.

The aim of this study is to probe a new function of astaxanthin ( AST ) from Haematococcus pluvialis on chemotherapeutic drug induced liver injury in mice .
Doxorubicin-induced liver injury was treated with different doses of AST , and the body weight , food intake , urinalysis , liver function , and oxidative stress indexes were examined .
The hepatocyte apoptosis level , pathological sections of liver tissue and the expression of antioxidant related genes were also determined .
This study found that DOX could induce serious liver injury through cytotoxicity .
AST treatment could decrease the level of @ @ @ @ @ @ @ , ALP and TBil ) , reduce the concentration of MDA and ROS , and increase the activities of SOD , CAT and GPX in the liver .
AST could also repair the damaged hepatocyte in mice with liver injury and reduce the degree of the cellular apoptosis .
In addition , AST could interfere with the expression of some related genes in the Keap1/Nrf2 signaling pathway by downregulating the expression of Keap1 and activating the transcription factor Nrf2 via enhancing the level of ERK , which upregulates downstream peroxiredoxins .
The present @ @ @ @ @ @ @ function of AST , indicating that AST could be used in the therapy of chemotherapy induced side effects .

The aim of this study is to probe a new function of astaxanthin (AST) from Haematococcus pluvialis on chemotherapeutic drug induced liver injury in mice. Doxorubicin-induced liver injury was treated with different doses of AST, and the body weight, food intake, urinalysis, liver function, and oxidative stress indexes were examined. The hepatocyte apoptosis level, pathological sections of liver tissue and the expression of antioxidant related genes were also determined. This study found that DOX could induce serious liver injury through cytotoxicity. AST treatment could decrease the level of liver function indexes (ALT, GOT, ALP and TBil), reduce the concentration of MDA and ROS, and increase the activities of SOD, CAT and GPX in the liver. AST could also repair the damaged hepatocyte in mice with liver injury and reduce the degree of the cellular apoptosis. In addition, AST could interfere with the expression of some related genes in the Keap1/Nrf2 signaling pathway by downregulating the expression of Keap1 and activating the transcription factor Nrf2 via enhancing the level of ERK, which upregulates downstream peroxiredoxins. The present research found and illustrated a new food function of AST, indicating that AST could be used in the therapy of chemotherapy induced side effects.


greenmedinfo--2020-05-21--Astaxanthin attenuates neuroinflammation in status epilepticus.

Background : As a life-threatening neurological emergency , status epilepticus ( SE ) is often refractory to available treatment .
Current studies have shown a causal role of neuroinflammation in patients with lower seizure thresholds and driving seizures .
The ATP-gated purinergic P2X7 receptor ( P2X7R ) is mainly expressed on the microglia , which function as gatekeepers of inflammation .
Although emerging evidence has demonstrated significant anti-inflammatory effects of astaxanthin ( AST ) in SE , the associated mechanism remains unclear .
Therefore , this study aimed to clarify the effects of AST on P2X7R-related inflammation in SE .
@ @ @ @ @ @ @ using lithium-pilocarpine , and AST was administered 1 h after SE induction .
Rat microglia were treated with lipopolysaccharide ( LPS ) , AST , ATP , 2,3-O-4-benzoyl-4-benzoyl-ATP ( BzATP ) and oxidized ATP ( oxATP ) .
The Morris water maze , immunohistochemistry , and Nissl staining were performed in rats .
Expressions of P2X7R and inflammatory cytokines ( such as cycloxygenase-2 ( Cox-2 ) , interleukin-1β ( IL-1β ) , and tumor necrosis factor-α ( TNF-α ) ) were detected using real-time polymerase chain reaction ( RT-PCR ) and Western blot @ @ @ @ @ @ @ microglia .
ATP concentration in the microglia was evaluated using ELISA .
Results : The AST alleviated hippocampal injury and improved cognitive dysfunction induced by SE .
AST also effectively inhibited inflammation and downregulated P2X7R expression in both rat brain and microglia .
The results also showed that AST reduced the extracellular ATP levels and that P2X7R expression could be increased by extracellular ATP .
In addition , BzATP upregulates the expression of P2X7R and inflammatory factors in microglia .
Conversely , it downregulates the expression of P2X7R and inflammatory factors .
Conclusion @ @ @ @ @ @ @ ATP-P2X7R mediated inflammation in SE .

Background: As a life-threatening neurological emergency, status epilepticus (SE) is often refractory to available treatment. Current studies have shown a causal role of neuroinflammation in patients with lower seizure thresholds and driving seizures. The ATP-gated purinergic P2X7 receptor (P2X7R) is mainly expressed on the microglia, which function as gatekeepers of inflammation. Although emerging evidence has demonstrated significant anti-inflammatory effects of astaxanthin (AST) in SE, the associated mechanism remains unclear. Therefore, this study aimed to clarify the effects of AST on P2X7R-related inflammation in SE.
Methods: SE was induced in rats using lithium-pilocarpine, and AST was administered 1 h after SE induction. Rat microglia were treated with lipopolysaccharide (LPS), AST, ATP, 2,3-O-4-benzoyl-4-benzoyl-ATP (BzATP) and oxidized ATP (oxATP). The Morris water maze, immunohistochemistry, and Nissl staining were performed in rats. Expressions of P2X7R and inflammatory cytokines (such as cycloxygenase-2 (Cox-2), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α)) were detected using real-time polymerase chain reaction (RT-PCR) and Western blot (WB) both in rats and microglia. ATP concentration in the microglia was evaluated using ELISA.
Results: The AST alleviated hippocampal injury and improved cognitive dysfunction induced by SE. AST also effectively inhibited inflammation and downregulated P2X7R expression in both rat brain and microglia. The results also showed that AST reduced the extracellular ATP levels and that P2X7R expression could be increased by extracellular ATP. In addition, BzATP upregulates the expression of P2X7R and inflammatory factors in microglia. Conversely, it downregulates the expression of P2X7R and inflammatory factors.
Conclusion: Our study suggests that AST attenuated ATP-P2X7R mediated inflammation in SE.


greenmedinfo--2020-05-21--The protective effect of haskap extracts could be related to their polyphenol content and high antio

Diets rich in polyphenols are known to reduce cancer among high-risk populations .
Haskap ( Lonicera caerulea L. ) berry has abundant phenolic acids and flavonoids , especially anthocyanins .
Tobacco-specific nitrosamine , 4- ( methylnitrosamino ) -1- ( 3-pyridyl ) -1-butanone ( NNK ) present in cigarette smoke is a major lung carcinogenic factor .
We analyzed the efficacy of anthocyanin-rich haskap berry extracts in preventing DNA damage induced by 4- [ ( acetoxymethyl ) nitrosamino ] -1- ( 3-pyridyl ) -1-butanone ( NNKOAc ) , a precursor of NKK , in human lung epithelial BEAS-2B cells in vitro @ @ @ @ @ @ @ haskap berries was extracted separately in ethanol and water and profiled .
Sub-lethal concentrations of NNKOAc were used to induce DNA damage in BEAS-2B cells , and cell viability assay was performed to confirm that the tested concentrations of haskap extracts were not cytotoxic to BEAS-2B cells .
Cells were pre-treated with the haskap extracts prior to NNKOAc exposure .
Dose-dependent DNA damage was observed with carcinogenic NNKOAc , but did not occur in the presence of the haskap extracts .
Pre-treatment of the cells with the haskap extracts significantly reduced NNKOAc-induced DNA @ @ @ @ @ @ @ reactive oxygen species and upregulated the ATM-dependent DNA damage repair cascade compared to non-treated BEAS-2B cells .
The protective effect of haskap extracts could be related to their polyphenol content and high antioxidant capacity .

Diets rich in polyphenols are known to reduce cancer among high-risk populations. Haskap (Lonicera caerulea L.) berry has abundant phenolic acids and flavonoids, especially anthocyanins. Tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) present in cigarette smoke is a major lung carcinogenic factor. We analyzed the efficacy of anthocyanin-rich haskap berry extracts in preventing DNA damage induced by 4-[(acetoxymethyl) nitrosamino]-1-(3-pyridyl)-1-butanone (NNKOAc), a precursor of NKK, in human lung epithelial BEAS-2B cells in vitro. A cocktail of monomeric polyphenols from haskap berries was extracted separately in ethanol and water and profiled. Sub-lethal concentrations of NNKOAc were used to induce DNA damage in BEAS-2B cells, and cell viability assay was performed to confirm that the tested concentrations of haskap extracts were not cytotoxic to BEAS-2B cells. Cells were pre-treated with the haskap extracts prior to NNKOAc exposure. Dose-dependent DNA damage was observed with carcinogenic NNKOAc, but did not occur in the presence of the haskap extracts. Pre-treatment of the cells with the haskap extracts significantly reduced NNKOAc-induced DNA damage, DNA fragmentation, and intracellular reactive oxygen species and upregulated the ATM-dependent DNA damage repair cascade compared to non-treated BEAS-2B cells. The protective effect of haskap extracts could be related to their polyphenol content and high antioxidant capacity.


greenmedinfo--2020-05-21--In-vitro growth inhibition of bacterial pathogens by probiotics and a synbiotic: product composition

In-vitro growth inhibition of bacterial pathogens by probiotics and a synbiotic: product composition matters.

A variety of activities potentially contribute to the beneficial effects of probiotic bacteria observed in humans .
Among these is @ @ @ @ @ growth of pathogenic bacteria in the gut .
The present study characterizes head-to-head the in-vitro @ @ @ @ @ relevant infectious bacterial strains by different types of probiotics and a synbiotic .
In-vitro growth @ @ @ @ @ products were a yeast mono strain probiotic containing , bacterial mono strain probiotics containing eitheror @ @ @ @ @ containing three , and a multi strain synbiotic containing nine different probiotic bacterial strains and @ @ @ @ @ ) .
Inhibition of pathogens was moderate byand , medium byand themixture and strong by @ @ @ @ @ Head-to-head in-vitro pathogen growth inhibition experiments can be used to differentiate products from different categories @ @ @ @ @ support the selection process of products for further clinical evaluation .

A variety of activities potentially contribute to the beneficial effects of probiotic bacteria observed in humans. Among these is a direct inhibition of the growth of pathogenic bacteria in the gut. The present study characterizes head-to-head the in-vitro pathogen growth inhibition of clinically relevant infectious bacterial strains by different types of probiotics and a synbiotic. In-vitro growth inhibition ofandwere determined. Investigated products were a yeast mono strain probiotic containing, bacterial mono strain probiotics containing eitheror, a multi strain probiotic containing three, and a multi strain synbiotic containing nine different probiotic bacterial strains and the prebiotic fructooligosaccharides (FOS). Inhibition of pathogens was moderate byand, medium byand themixture and strong by the multi strain synbiotic. Head-to-head in-vitro pathogen growth inhibition experiments can be used to differentiate products from different categories containing probiotic microorganisms and can support the selection process of products for further clinical evaluation.


greenmedinfo--2020-05-22--Dehydroascorbic acid, the oxidized form of vitamin C, improves renal histology and function in old m

Dehydroascorbic acid, the oxidized form of vitamin C, improves renal histology and function in old mice.

Oxidative stress and inflammation are crucial factors that increase with age .
In the progression of multiple age-related diseases , antioxidants and bioactive compounds have been recognized as useful antiaging agents .
Oxidized or reduced vitamin C exerts different actions on tissues and has different metabolism and uptake .
In this study , we analyzed the antiaging effect of vitamin C , both oxidized and reduced forms , in renal aging using laser microdissection , quantitative reverse-transcription polymerase chain reaction , and immunohistochemical analyses .
In the kidneys of old SAM mice ( 10 months of age ) , a @ @ @ @ @ @ @ , especially in the oxidized form ( dehydroascorbic acid [ DHA ] ) improves renal histology and function .
Serum creatinine levels and microalbuminuria also decrease after treatment with a decline in azotemia .
In addition , sodium-vitamin C cotransporter isoform 1 levels , which were increased during aging , are normalized .
In contrast , the pattern of glucose transporter 1 expression is not affected by aging or vitamin C treatment .
We conclude that oxidized and reduced vitamin C are potent antiaging therapies and that DHA reverses the kidney damage observed @ @ @ @ @ @ @ greater degree .

Oxidative stress and inflammation are crucial factors that increase with age. In the progression of multiple age-related diseases, antioxidants and bioactive compounds have been recognized as useful antiaging agents. Oxidized or reduced vitamin C exerts different actions on tissues and has different metabolism and uptake. In this study, we analyzed the antiaging effect of vitamin C, both oxidized and reduced forms, in renal aging using laser microdissection, quantitative reverse-transcription polymerase chain reaction, and immunohistochemical analyses. In the kidneys of old SAM mice (10 months of age), a model of accelerated senescence, vitamin C, especially in the oxidized form (dehydroascorbic acid [DHA]) improves renal histology and function. Serum creatinine levels and microalbuminuria also decrease after treatment with a decline in azotemia. In addition, sodium-vitamin C cotransporter isoform 1 levels, which were increased during aging, are normalized. In contrast, the pattern of glucose transporter 1 expression is not affected by aging or vitamin C treatment. We conclude that oxidized and reduced vitamin C are potent antiaging therapies and that DHA reverses the kidney damage observed in senescence-accelerated prone mouse 8 to a greater degree.


greenmedinfo--2020-05-22--COVID-19: The inflammation link and the role of nutrition in potential mitigation.

The novel coronavirus disease ( COVID-19 ) pandemic caused by severe acute respiratory syndrome coronavirus 2 ( SARS-CoV-2 ) has engulfed the world , affecting more than 180 countries .
As a result , there has been considerable economic distress globally and a significant loss of life .
Sadly , the vulnerable and immunocompromised in our societies seem to be more susceptible to severe COVID-19 complications .
Global public health bodies and governments have ignited strategies and issued advisories on various handwashing and hygiene guidelines , social distancing strategies , and , in the most extreme cases , some countries @ @ @ @ @ @ @ or lockdown protocols to prevent COVID-19 spread .
Notably , there are several significant risk factors for severe COVID-19 infection .
These include the presence of poor nutritional status and pre-existing noncommunicable diseases ( NCDs ) such as diabetes mellitus , chronic lung diseases , cardiovascular diseases ( CVD ) , obesity , and various other diseases that render the patient immunocompromised .
These diseases are characterized by systemic inflammation , which may be a common feature of these NCDs , affecting patient outcomes against COVID-19 .
In this review , we discuss @ @ @ @ @ @ @ currently under investigation intended to dampen the cytokine storm of severe COVID-19 infections .
Furthermore , nutritional status and the role of diet and lifestyle is considered , as it is known to affect patient outcomes in other severe infections and may play a role in COVID-19 infection .
This review speculates the importance of nutrition as a mitigation strategy to support immune function amid the COVID-19 pandemic , identifying food groups and key nutrients of importance that may affect the outcomes of respiratory infections .

The novel coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has engulfed the world, affecting more than 180 countries. As a result, there has been considerable economic distress globally and a significant loss of life. Sadly, the vulnerable and immunocompromised in our societies seem to be more susceptible to severe COVID-19 complications. Global public health bodies and governments have ignited strategies and issued advisories on various handwashing and hygiene guidelines, social distancing strategies, and, in the most extreme cases, some countries have adopted"stay in place"or lockdown protocols to prevent COVID-19 spread. Notably, there are several significant risk factors for severe COVID-19 infection. These include the presence of poor nutritional status and pre-existing noncommunicable diseases (NCDs) such as diabetes mellitus, chronic lung diseases, cardiovascular diseases (CVD), obesity, and various other diseases that render the patient immunocompromised. These diseases are characterized by systemic inflammation, which may be a common feature of these NCDs, affecting patient outcomes against COVID-19. In this review, we discuss some of the anti-inflammatory therapies that are currently under investigation intended to dampen the cytokine storm of severe COVID-19 infections. Furthermore, nutritional status and the role of diet and lifestyle is considered, as it is known to affect patient outcomes in other severe infections and may play a role in COVID-19 infection. This review speculates the importance of nutrition as a mitigation strategy to support immune function amid the COVID-19 pandemic, identifying food groups and key nutrients of importance that may affect the outcomes of respiratory infections.


greenmedinfo--2020-05-22--The preventive effect of lactoferrin-containing yogurt on gastroenteritis.

To evaluate the effects of bovine lactoferrin ( LF ) -containing yogurt on gastroenteritis in nursery school children during the winter season , we conducted a randomized prospective study .
A total of 1296 children were randomized into a group in which LF was provided in yogurt ( LF group , = 661 ) and a non-LF consumption group ( control group , = 635 ) .
The LF group was given LF-containing yogurt ( 100 mg/day ) on all 5 weekdays for approximately 15 weeks , and the control group consumed fruit jelly instead of the yogurt .
The @ @ @ @ @ @ @ LF group and 584 as the control group were analyzed .
The total number of children who were absent from school due to vomiting was significantly lower in the LF group compared to the control , accounting for≥3 days in any week : 10/234 ( 4.3 % ) vs. 49/584 ( 8.4 % ) , respectively ; = 0.04 .
Regarding the relationship between absences due to vomiting and the consumption of the LF-containing yogurt , the adjusted odds ratio for absence due to vomiting was 2.48 ( 95 % CI : 1.19-5.14 @ @ @ @ @ @ @ LF-containing yogurt≤2 days/week compared to the LF children who consumed the yogurt ≥ 3 days/week .
The consumption of LF-containing yogurt ( 100 mg/day ) for ≥3 days/week might help alleviate the symptom of vomiting in nursery school children during the winter .

To evaluate the effects of bovine lactoferrin (LF)-containing yogurt on gastroenteritis in nursery school children during the winter season, we conducted a randomized prospective study. A total of 1296 children were randomized into a group in which LF was provided in yogurt (LF group,= 661) and a non-LF consumption group (control group,= 635). The LF group was given LF-containing yogurt (100 mg/day) on all 5 weekdays for approximately 15 weeks, and the control group consumed fruit jelly instead of the yogurt. The final totals of 578 children as the LF group and 584 as the control group were analyzed. The total number of children who were absent from school due to vomiting was significantly lower in the LF group compared to the control, accounting for≥3 days in any week: 10/234 (4.3%) vs. 49/584 (8.4%), respectively;= 0.04. Regarding the relationship between absences due to vomiting and the consumption of the LF-containing yogurt, the adjusted odds ratio for absence due to vomiting was 2.48 (95% CI: 1.19-5.14) in the LF children who consumed LF-containing yogurt≤2 days/week compared to the LF children who consumed the yogurt ≥ 3 days/week. The consumption of LF-containing yogurt (100 mg/day) for ≥3 days/week might help alleviate the symptom of vomiting in nursery school children during the winter.


greenmedinfo--2020-05-22--After the Lockdown: A Global Coronavirus Vaccination Program


greenmedinfo--2020-05-22--Lactoferrin might be an effective therapeutic remedy for simultaneously reducing the inflammatory re

Lactoferrin might be an effective therapeutic remedy for simultaneously reducing the inflammatory response and inducing bone regeneration.

Guided bone regeneration refers to the process in which bone defects could be regenerated by facilitated healing through the use of membranes , potentially with the delivery of osteoinductive molecules , however , the regeneration often failed due to inflammation during bone formation .
In this study , we developed a membrane immobilized with lactoferrin to modulate both bone regeneration and inflammatory responses .
Lactoferrin was immobilized on electrospun nanofibers ( LF50 ) by exploiting an adhesive polydopamine coating method .
When human adipose-derived stem cells ( hADSCs ) were seeded onto the nanofibers , the LF50 significantly increased the @ @ @ @ @ @ @ gene expression of osteopontin was 6.9 ± 2.3 times greater in the cells on LF50 than the cells on unmodified nanofibers without lactoferrin .
In addition , the gene expression of tumor necrosis factor-alpha ( ) of the macrophage cell line ( RAW264.7 ) cultured on the LF50 was 0.3 ± 0.1 times reduced , indicating the lactoferrin was able to reduce inflammatory response .
With implantation of nanofibers onmouse calvarial defects , the LF50 resulted in 60.9 % ± 4.5 % of new bone formation , which was six times greater than @ @ @ @ @ @ @ , when the fibers were implanted onto themouse subcutaneous model challenged with lipopolysaccharide and interferon-γ , the area of inflammatory tissue was significantly reduced in the LF50 implanted group as 0.6 ± 0.1 mmas compared with the control group ( 1.1 ± 0.1 mm ) .
Taken together , the lactoferrin immobilization onto the nanofiber by polydopamine chemistry may be an effective delivery method for improving bone regeneration while regulating the inflammation .
Impact statementcritical-sized bone reconstruction remains challenging due to the severe inflammation , which would be an unavoidable problem during surgical @ @ @ @ @ @ @ aims to develop a guided nanofibrous membrane immobilized with lactoferrin , which has dual functions with osteoinduction and anti-inflammation .
The lactoferrin-immobilized fibers demonstrated significantly enhancedosteogenic differentiation of adipose-derived stem cells as well as decreased polarization of macrophage to M1 with relatively reduced amount than that reported from previous reports .
We also found that the membrane improvedbone regeneration and decreased inflammatory tissue formation .
Taken together , this system would be a new platform for successful bone regeneration .

Guided bone regeneration refers to the process in which bone defects could be regenerated by facilitated healing through the use of membranes, potentially with the delivery of osteoinductive molecules, however, the regeneration often failed due to inflammation during bone formation. In this study, we developed a membrane immobilized with lactoferrin to modulate both bone regeneration and inflammatory responses. Lactoferrin was immobilized on electrospun nanofibers (LF50) by exploiting an adhesive polydopamine coating method. When human adipose-derived stem cells (hADSCs) were seeded onto the nanofibers, the LF50 significantly increased the osteogenic differentiation. For example, the gene expression of osteopontin was 6.9 ± 2.3 times greater in the cells on LF50 than the cells on unmodified nanofibers without lactoferrin. In addition, the gene expression of tumor necrosis factor-alpha () of the macrophage cell line (RAW264.7) cultured on the LF50 was 0.3 ± 0.1 times reduced, indicating the lactoferrin was able to reduce inflammatory response. With implantation of nanofibers onmouse calvarial defects, the LF50 resulted in 60.9% ± 4.5% of new bone formation, which was six times greater than the results of other groups. Furthermore, when the fibers were implanted onto themouse subcutaneous model challenged with lipopolysaccharide and interferon-γ, the area of inflammatory tissue was significantly reduced in the LF50 implanted group as 0.6 ± 0.1 mmas compared with the control group (1.1 ± 0.1 mm). Taken together, the lactoferrin immobilization onto the nanofiber by polydopamine chemistry may be an effective delivery method for improving bone regeneration while regulating the inflammation. Impact statementcritical-sized bone reconstruction remains challenging due to the severe inflammation, which would be an unavoidable problem during surgical process. Therefore, the present study aims to develop a guided nanofibrous membrane immobilized with lactoferrin, which has dual functions with osteoinduction and anti-inflammation. The lactoferrin-immobilized fibers demonstrated significantly enhancedosteogenic differentiation of adipose-derived stem cells as well as decreased polarization of macrophage to M1 with relatively reduced amount than that reported from previous reports. We also found that the membrane improvedbone regeneration and decreased inflammatory tissue formation. Taken together, this system would be a new platform for successful bone regeneration.


greenmedinfo--2020-05-22--Recent studies have demonstrated that lactoferrin might have a beneficial effect in the prevention a

Recent studies have demonstrated that lactoferrin might have a beneficial effect in the prevention and treatment of obesity-related metabolic abnormalities.

Lactoferrin is a multipotent protein that belongs to the transferrin family .
It was first isolated from cow 's milk @ @ @ @ @ 1960s , it was also found in breast milk .
In the human body , @ @ @ @ @ in other body fluids , e.g.
, saliva , tears , and vaginal discharge .
@ @ @ @ @ receptors present on the membrane surface of many cells , such as neutrophils , hepatocytes @ @ @ @ @ .
Lactoferrin can bind iron .
Because of this property , it also has antibacterial @ @ @ @ @ activity .
Its antiinflammatory and anticancer activity has also been confirmed .
Recent studies have @ @ @ @ @ a beneficial effect in the prevention and treatment of obesity-related metabolic abnormalities , such as @ @ @ @ @ , and dyslipidaemia .
It is also worth to notice the potential relationship between polymorphisms @ @ @ @ @ for lactoferrin receptors and metabolic abnormalities in obese subjects .

Lactoferrin is a multipotent protein that belongs to the transferrin family. It was first isolated from cow's milk in 1939. In the 1960s, it was also found in breast milk. In the human body, lactoferrin can also be found in other body fluids, e.g., saliva, tears, and vaginal discharge. Its biological activity depends on receptors present on the membrane surface of many cells, such as neutrophils, hepatocytes, and intestinal epithelial cells. Lactoferrin can bind iron. Because of this property, it also has antibacterial, antiviral, and antifungal activity. Its antiinflammatory and anticancer activity has also been confirmed. Recent studies have demonstrated that lactoferrin might have a beneficial effect in the prevention and treatment of obesity-related metabolic abnormalities, such as type 2 diabetes, hypertension, and dyslipidaemia. It is also worth to notice the potential relationship between polymorphisms in lactoferrin gene, genes for lactoferrin receptors and metabolic abnormalities in obese subjects.