greenmedinfo--2020-03-23--Interaction of apigenin-7-O-glucoside with pyrimethamine against toxoplasma gondii growth.

Apigenin-7-O-glucoside , a flavonoid glucoside known to inhibit cancer cell growth , fungi growth , both intra and extracellular reactive oxygen species generation , causing cell arrest and damage to the plasma membrane , was tested alone or in combination with a dihydrofolate inhibitor ( pyrimethamine ) against ( ) growth .
The anti-activity was carried out using a high throughput antiparasitic drug screening cell-based assay known as 2- ( 2-methoxy-4-nitrophenyl ) -3- ( 4-nitrophenyl ) -5- ( 2,4-disulfophenyl ) -2H tetrazolium , monosodium salt ( WST-8 ) and fluorescence plate reader .
The 50 % effective concentration inhibition and @ @ @ @ @ @ @ and combination treatments againstwere 0.80 ( 0.38-1.29 ) µg/mL , 1.05 ( 0.275-2.029 ) µg/mL , and 0.40 ( 0-1.06 ) µg/mL for apigenin-7-O-glucoside , pyrimethamine , and apigenin-7-O-glucoside plus pyrimethamine , respectively .
Interestingly , the apigenin-7-O-glucoside plus pyrimethamine combination showed an additive inhibition effect againstgrowth in vitro using the fractional inhibitory concentration index method .
It was discovered that the apigenin-7-O-glucoside combination with pyrimethamine had a high selectivity index 62.5 , which implies 62-fold inhibition activity against the parasite versus human foreskin fibroblast cell cytotoxicity .
This new combination hit is @ @ @ @ @ @ @ future effective , safe , and less costly anti-drug development , if its in vivo activity shows similar findings .

Apigenin-7-O-glucoside, a flavonoid glucoside known to inhibit cancer cell growth, fungi growth, both intra and extracellular reactive oxygen species generation, causing cell arrest and damage to the plasma membrane, was tested alone or in combination with a dihydrofolate inhibitor (pyrimethamine) against() growth. The anti-activity was carried out using a high throughput antiparasitic drug screening cell-based assay known as 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H tetrazolium, monosodium salt (WST-8) and fluorescence plate reader. The 50% effective concentration inhibition and 95% confidence interval values for individual and combination treatments againstwere 0.80 (0.38-1.29)µg/mL, 1.05 (0.275-2.029) µg/mL, and 0.40 (0-1.06) µg/mL for apigenin-7-O-glucoside, pyrimethamine, and apigenin-7-O-glucoside plus pyrimethamine, respectively. Interestingly, the apigenin-7-O-glucoside plus pyrimethamine combination showed an additive inhibition effect againstgrowth in vitro using the fractional inhibitory concentration index method. It was discovered that the apigenin-7-O-glucoside combination with pyrimethamine had a high selectivity index 62.5, which implies 62-fold inhibition activity against the parasite versus human foreskin fibroblast cell cytotoxicity. This new combination hit is novel and will have the potential for future effective, safe, and less costly anti-drug development, if its in vivo activity shows similar findings.


greenmedinfo--2020-03-23--Effect of apigenin on whole transcriptome profile of TNFα-activated MDA-MB-468 triple negative breas

Effect of apigenin on whole transcriptome profile of TNFα-activated MDA-MB-468 triple negative breast cancer cells.

The lack of hormone receptors in triple negative breast cancer ( TNBC ) is associated with the inefficacy of anti-estrogen chemotherapies , leaving fewer options for patient treatment and higher mortality rates .
Additionally , as with numerous types of inflammatory breast cancer , infiltration of tumor associated macrophages and other leukocyte sub-populations within the tumor inevitably lead to aggressive , chemo-resistant , metastatic and invasive types of cancer which escape immune surveillance .
These processes are orchestrated by the release of potent cytokines , including TNFα , IL-6 and CCL2 from the stroma , tumor and immune cells within @ @ @ @ @ @ @ evaluated apigenin modulating effects on the pro-inflammatory activating action of TNFα in TNBC MDA-MB-468 cells , derived from an African American woman .
Initially , cell viability was determined to establish an optimal sub-lethal dose of TNFα and apigenin in MDA-MB-468 cells .
Subsequently , various treatments effects were evaluated using whole transcriptomic analysis of mRNA and long intergenic non-coding RNA with Affymetrix HuGene-2.1-st human microarrays .
Gene level differential expression analysis was conducted on 48,226 genes where TNFα caused significant upregulation of 53 transcripts and downregulation of 11 transcripts .
The largest @ @ @ @ @ @ @ +61.86 fold change ( FC ) ; false discovery rate ( FDR ) , P < 0.0001 ] ; which was down regulated by apigenin ( to +10.71 FC vs. Control ; FDR P-value < 0.001 ) , equivalent to an 83 % reduction .
Several TNFα deferentially upregulated transcripts were reduced by apigenin , including CXCL10 , C3 , PGLYRP4 , IL22RA2 , KMO , IL7R , ROS1 , CFB , IKBKe , SLITRK6 ( a checkpoint target ) and MMP13 .
Confirmation of CCL2 experimentally induced transcript alterations was corroborated at @ @ @ @ @ @ @ The high level of CCL2 transcript in the cell line was comparable to that in our previous studies in MDA-MB-231 cells .
The differential effects of TNFα were corroborated by ELISA , where the data revealed a > 10-fold higher releasing rate of CCL2 in MDA-MB-468 cells compared with in MDA-MB-231 cells , both of which were attenuated by apigenin .
The data obtained in the present study demonstrated a high level of CCL2 in MDA-MB-468 cells and a possible therapeutic role for apigenin in downregulating TNFα-mediated processes in these TNBC cells .

The lack of hormone receptors in triple negative breast cancer (TNBC) is associated with the inefficacy of anti-estrogen chemotherapies, leaving fewer options for patient treatment and higher mortality rates. Additionally, as with numerous types of inflammatory breast cancer, infiltration of tumor associated macrophages and other leukocyte sub-populations within the tumor inevitably lead to aggressive, chemo-resistant, metastatic and invasive types of cancer which escape immune surveillance. These processes are orchestrated by the release of potent cytokines, including TNFα, IL-6 and CCL2 from the stroma, tumor and immune cells within the tumor microenvironment. The present study evaluated apigenin modulating effects on the pro-inflammatory activating action of TNFα in TNBC MDA-MB-468 cells, derived from an African American woman. Initially, cell viability was determined to establish an optimal sub-lethal dose of TNFα and apigenin in MDA-MB-468 cells. Subsequently, various treatments effects were evaluated using whole transcriptomic analysis of mRNA and long intergenic non-coding RNA with Affymetrix HuGene-2.1-st human microarrays. Gene level differential expression analysis was conducted on 48,226 genes where TNFα caused significant upregulation of 53 transcripts and downregulation of 11 transcripts. The largest upward differential shift was for CCL2 [+61.86 fold change (FC); false discovery rate (FDR), P<0.0001]; which was down regulated by apigenin (to +10.71 FC vs. Control; FDR P-value<0.001), equivalent to an 83% reduction. Several TNFα deferentially upregulated transcripts were reduced by apigenin, including CXCL10, C3, PGLYRP4, IL22RA2, KMO, IL7R, ROS1, CFB, IKBKe, SLITRK6 (a checkpoint target) and MMP13. Confirmation of CCL2 experimentally induced transcript alterations was corroborated at the protein level by ELISA assays. The high level of CCL2 transcript in the cell line was comparable to that in our previous studies in MDA-MB-231 cells. The differential effects of TNFα were corroborated by ELISA, where the data revealed a>10-fold higher releasing rate of CCL2 in MDA-MB-468 cells compared with in MDA-MB-231 cells, both of which were attenuated by apigenin. The data obtained in the present study demonstrated a high level of CCL2 in MDA-MB-468 cells and a possible therapeutic role for apigenin in downregulating TNFα-mediated processes in these TNBC cells.


greenmedinfo--2020-03-23--Milk thistle has been found to exhibit antioxidant, lipid-lowering, antihypertensive, antidiabetic,

Milk thistle has been found to exhibit antioxidant, lipid-lowering, antihypertensive, antidiabetic, antiatherosclerotic, anti-obesity, and hepatoprotective effects.

Metabolic syndrome describes a complex metabolic risk factors including obesity , hypertension , dyslipidemia , and diabetes .
This syndrome @ @ @ @ @ such as weight gain , high blood pressure , high blood glucose , and disturbance @ @ @ @ @ syndrome has become as an important and increasing global health problem , so finding potentially @ @ @ @ @ effects is favorable for health problems .
Herbal therapy plays an important role for treatment @ @ @ @ @ marianum is a plant that is used for centuries as a herbal treatment in liver @ @ @ @ @ Silymarin is the main component of S. marianum and derived from fruits and seeds of @ @ @ @ @ ) .
S. marianum has been found to exhibit antioxidant , lipid-lowering , antihypertensive , @ @ @ @ @ , and hepatoprotective effects .
Therefore , the aim of this review is to summarize @ @ @ @ @ regarding the effect of S. marianum in metabolic syndrome and to identify the underlying mechanisms @ @ @

Metabolic syndrome describes a complex metabolic risk factors including obesity, hypertension, dyslipidemia, and diabetes. This syndrome is diagnosed by medical conditions such as weight gain, high blood pressure, high blood glucose, and disturbance in lipid profile. Metabolic syndrome has become as an important and increasing global health problem, so finding potentially novel solutions with less adverse effects is favorable for health problems. Herbal therapy plays an important role for treatment of different diseases. Silybum marianum is a plant that is used for centuries as a herbal treatment in liver and biliary tract diseases. Silymarin is the main component of S. marianum and derived from fruits and seeds of S. marianum (milk thistle). S. marianum has been found to exhibit antioxidant, lipid-lowering, antihypertensive, antidiabetic, antiatherosclerotic, anti-obesity, and hepatoprotective effects. Therefore, the aim of this review is to summarize different animal and human studies regarding the effect of S. marianum in metabolic syndrome and to identify the underlying mechanisms of action.


greenmedinfo--2020-03-23--The results showed that both apigenin and celery extracts caused kidney stone to decay.

Objective : Kidney stones ( nephrolithiasis ) is one of the kidney diseases in the form of stones that contain crystal and organic matrix components .
It is one of the most common diseases of the urinary tract .
Calcium stone is the most important type of stone ( 80 % ) found in the case of kidney stones .
Celery ( L. ) is a plant rich in flavonoids , which can break down calcium crystals .
Apigenin is considered to be one of the main flavonoids because of its presence and abundance in celery .
This research aimed @ @ @ @ @ @ @ with that of celery extract .
Materials and Methods : Wistar albino rats were given ethylene glycol 0.75 % ( vol/vol ) and ammonium chloride 2 % ( wt/vol ) orally for 7 days in all groups to induce hyperoxaluria and Rats treated by Apigenin at doses 1.2 , 2.4 , and 4.8 mg/kg of rat body weight and celery extract at doses of 200 , 400 , and 600 mg/kg of rat body weight as anticalculi .
Measurements of calcium levels in the kidneys and urine of rats was obtained using atomic @ @ @ @ @ @ @ analyzed with the IBM SPSS by ANOVA Method version 21.0 probability value < 0.05 was considered significant .
Result : The results showed that both apigenin and celery extracts caused kidney stone to decay .
From the data Apigenin and celery showed that calcium level in urine there were significant differences ( value < 0.05 ) in treated group from negative control group but calcium level in kidney there were not significant differences ( value > 0.05 ) .
Conclusion : Celery extract has better ability to break down kidney stones than apigenin @

Objective: Kidney stones (nephrolithiasis) is one of the kidney diseases in the form of stones that contain crystal and organic matrix components. It is one of the most common diseases of the urinary tract. Calcium stone is the most important type of stone (80%) found in the case of kidney stones. Celery (L.) is a plant rich in flavonoids, which can break down calcium crystals. Apigenin is considered to be one of the main flavonoids because of its presence and abundance in celery. This research aimed to compare the anticalculi effect of apigenin with that of celery extract.
Materials and Methods: Wistar albino rats were given ethylene glycol 0.75% (vol/vol) and ammonium chloride 2% (wt/vol) orally for 7 days in all groups to induce hyperoxaluria and Rats treated by Apigenin at doses 1.2, 2.4, and 4.8 mg/kg of rat body weight and celery extract at doses of 200, 400, and 600 mg/kg of rat body weight as anticalculi. Measurements of calcium levels in the kidneys and urine of rats was obtained using atomic absorption spectroscopy. Data obtained were statistically analyzed with the IBM SPSS by ANOVA Method version 21.0 probability value<0.05 was considered significant.
Result: The results showed that both apigenin and celery extracts caused kidney stone to decay. From the data Apigenin and celery showed that calcium level in urine there were significant differences (value<0.05) in treated group from negative control group but calcium level in kidney there were not significant differences (value>0.05).
Conclusion: Celery extract has better ability to break down kidney stones than apigenin.


greenmedinfo--2020-03-23--Althaea officinalis and Solanum nigrum exhibit gastroprotective and antioxidant potential in rats.

Recently , an alternative disease treatment approach is the research of medicaments from traditional medicine .
Plants with anti-oxidant capabilities are used as herbal treatments for ulcer diseases .
Medicinal/herbal extracts containing phytoconstituents have significant anti-ulcer activities in in vivo experiments on animal models , compared to reference drugs .
The current study aims to inspect gastro-protective as well as in vitro and in vivo anti-oxidant potential ofandextracts on pyloric-ligation/indomethacin-induced gastric-ulceration in rats .
Rats were divided into six groups : normal control , gastric ulcer control , two standard pretreatment groups receiving omeprazole and misoprostol , and two test @ @ @ @ @ @ @ orally for 14 days .
On the 15th day , animals , excluding the normal control group , were exposed to pyloric-ligation followed by indomethacin injection .
After four hours , the rat 's stomachs were removed and gastric juice and blood samples were collected .
Pyloric-ligation/indomethacin administration caused considerable elevation in ulcer number , ulcer index , acid and pepsin productivity , aggressive factors , and gastric mucosal lipid-peroxide contents .
Moreover , reduction in titratable acidity , gastric mucosal nitric-oxide , anti-oxidant contents , and protective factors accompanied gastric-ulceration .
Additionally @ @ @ @ @ @ @ reduction in cystathionine-β-synthase and heme-oxygenase-1 expression was witnessed .
Omeprazole , misoprostol , andpretreatments fixed blood and tissue biomarkers , thereby protecting them from pyloric-ligation/indomethacin-induced gastric-ulceration in rats , which is hopeful for clinical examinations .

Recently, an alternative disease treatment approach is the research of medicaments from traditional medicine. Plants with anti-oxidant capabilities are used as herbal treatments for ulcer diseases. Medicinal/herbal extracts containing phytoconstituents have significant anti-ulcer activities in in vivo experiments on animal models, compared to reference drugs. The current study aims to inspect gastro-protective as well as in vitro and in vivo anti-oxidant potential ofandextracts on pyloric-ligation/indomethacin-induced gastric-ulceration in rats. Rats were divided into six groups: normal control, gastric ulcer control, two standard pretreatment groups receiving omeprazole and misoprostol, and two test pretreatment groups receivingand. Pretreatments were administrated orally for 14 days. On the 15th day, animals, excluding the normal control group, were exposed to pyloric-ligation followed by indomethacin injection. After four hours, the rat's stomachs were removed and gastric juice and blood samples were collected. Pyloric-ligation/indomethacin administration caused considerable elevation in ulcer number, ulcer index, acid and pepsin productivity, aggressive factors, and gastric mucosal lipid-peroxide contents. Moreover, reduction in titratable acidity, gastric mucosal nitric-oxide, anti-oxidant contents, and protective factors accompanied gastric-ulceration. Additionally, elevation in pro-inflammatory cytokines content and reduction in cystathionine-β-synthase and heme-oxygenase-1 expression was witnessed. Omeprazole, misoprostol,andpretreatments fixed blood and tissue biomarkers, thereby protecting them from pyloric-ligation/indomethacin-induced gastric-ulceration in rats, which is hopeful for clinical examinations.


greenmedinfo--2020-03-23--Biochanin A has anti-inflammatory, estrogen-like, and glucose and lipid metabolism modulatory activi

Biochanin A has anti-inflammatory, estrogen-like, and glucose and lipid metabolism modulatory activity, as well as cancer preventive and neuroprotective effects.

Biochanin A ( BCA ) is an isoflavone mainly found in red clover with poor solubility and oral absorption that @ @ @ @ @ effects , including anti-inflammatory , estrogen-like , and glucose and lipid metabolism modulatory activity , @ @ @ @ @ , neuroprotective , and drug interaction effects .
BCA is already commercially available and is @ @ @ @ @ many types of supplements used to alleviate postmenopausal symptoms in women .
The activity of @ @ @ @ @ evaluated in humans .
However , the results of manyandstudies investigating the potential health benefits @ @ @ @ @ and the complex mechanisms by which BCA modulates transcription , apoptosis , metabolism , and @ @ @ @ @ .
Many efforts have been exerted to improve the poor bioavailability of BCA , and @ @ @ @ @ reported .
This review focuses on the major effects of BCA and its possible molecular @ @ @ @ @ and limitations in health maintenance and treatment .

Biochanin A (BCA) is an isoflavone mainly found in red clover with poor solubility and oral absorption that is known to have various effects, including anti-inflammatory, estrogen-like, and glucose and lipid metabolism modulatory activity, as well as cancer preventive, neuroprotective, and drug interaction effects. BCA is already commercially available and is among the main ingredients in many types of supplements used to alleviate postmenopausal symptoms in women. The activity of BCA has not been adequately evaluated in humans. However, the results of manyandstudies investigating the potential health benefits of BCA are available, and the complex mechanisms by which BCA modulates transcription, apoptosis, metabolism, and immune responses have been revealed. Many efforts have been exerted to improve the poor bioavailability of BCA, and very promising results have been reported. This review focuses on the major effects of BCA and its possible molecular targets, potential uses, and limitations in health maintenance and treatment.


greenmedinfo--2020-03-23--Schisanhenol may be a potential anti-liver fibrosis drug.

Liver fibrosis is a pathological manifestation induced by chronic liver injury and may cause cirrhosis and liver cancer with the chronic progression of fibrosis .
During the onset and progression of liver fibrosis , the activation of hepatic stellate cells ( HSCs ) is the core mechanism for the secretion of many extracellular matrices to induce fibrosis .
Lignans are reportedly the main effective components of Schisandra chinensis with good anti-fibrosis effects .
In this study , we compared the inhibiting effects of the seven lignan components from S. chinensis on HSC activation .
We found that the seven lignans @ @ @ @ @ @ @ LX-2 ) in various degrees .
Among all lignans , schisanhenol showed the best effect in inhibiting the activation of LX-2 with a dose-effect relationship .
Sal also inhibited the phosphorylations of Smad1 , Smad2 , Smad3 , extracellular regulated protein kinase ( ERK ) , c-Jun N-terminal kinase ( JNK ) , p38 , and nuclear transcription factor-κB ( NF-κB ) , as well as downregulated Smad4 .
All these findings suggested that schisanhenol may ameliorate liver fibrosis by inhibiting the transforming growth factor β ( TGF-β ) /Smad and mitogen-activated protein @ @ @ @ @ @ @ Remarkably , schisanhenol may be a potential anti-liver fibrosis drug and warrants further research .

Liver fibrosis is a pathological manifestation induced by chronic liver injury and may cause cirrhosis and liver cancer with the chronic progression of fibrosis. During the onset and progression of liver fibrosis, the activation of hepatic stellate cells (HSCs) is the core mechanism for the secretion of many extracellular matrices to induce fibrosis. Lignans are reportedly the main effective components of Schisandra chinensis with good anti-fibrosis effects. In this study, we compared the inhibiting effects of the seven lignan components from S. chinensis on HSC activation. We found that the seven lignans inhibited the activation of human HSCs (LX-2) in various degrees. Among all lignans, schisanhenol showed the best effect in inhibiting the activation of LX-2 with a dose-effect relationship. Sal also inhibited the phosphorylations of Smad1, Smad2, Smad3, extracellular regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK), p38, and nuclear transcription factor-κB (NF-κB), as well as downregulated Smad4. All these findings suggested that schisanhenol may ameliorate liver fibrosis by inhibiting the transforming growth factor β (TGF-β)/Smad and mitogen-activated protein kinase (MAPK) signaling pathways. Remarkably, schisanhenol may be a potential anti-liver fibrosis drug and warrants further research.


greenmedinfo--2020-03-23--Apigenin could be an attractive therapeutic potential for the treatment of renal fibrosis.

AIMS : The purpose of this study was to investigate the influences of apigenin on proliferation , differentiation and function of renal fibroblast after TGF-β1 stimulation and to uncover the underlying mechanisms .
BACKGROUND : Renal fibrosis is a common pathway leading to the progression of chronic kidney disease .
Activated fibroblasts contribute remarkably to the development of renal fibrosis .
Although apigenin has been demonstrated to play a protective role from fibrotic diseases , its pharmacological effect on renal fibroblast activation remains largely unknown .
OBJECTIVE : Here , we examined the functional role of apigenin in the activation @ @ @ @ @ @ @ factor ( TGF ) -β1 and its potential mechanisms .
METHOD : Cultured renal fibroblasts ( NRK-49F ) were exposed to apigenin ( 1 , 5 , 10 and 20µM ) followed by the stimulation of TGF-β1 ( 2 ng/mL ) for 24 h. The markers of fibroblast activation were determined .
In order to confirm the anti-fibrosis effect of apigenin , the expression of fibrosis-associated genes in renal fibroblasts was assessed .
RESULT : As a consequence , apigenin alleviated fibroblast proliferation and fibroblast-myofibroblast differentiation induced by TGF-β1 .
Notably , apigenin @ @ @ @ @ @ @ renal fibroblasts .
Moreover , apigenin treatment significantly increased phosphorylation of AMP-activated protein kinase ( AMPK ) .
Apigenin treatment also obviously reduced TGF-β1 induced phosphorylation of ERK1/2 but not Smad2/3 , p38 and JNK MAPK in renal fibroblasts .
CONCLUSION : In a summary , these results indicate that apigenin inhibits renal fibroblast proliferation , differentiation and function by AMPK activation and reduced of ERK1/2 phosphorylation , suggesting it could be an attractive therapeutic potential for the treatment of renal fibrosis .

AIMS: The purpose of this study was to investigate the influences of apigenin on proliferation, differentiation and function of renal fibroblast after TGF-β1 stimulation and to uncover the underlying mechanisms.
BACKGROUND: Renal fibrosis is a common pathway leading to the progression of chronic kidney disease. Activated fibroblasts contribute remarkably to the development of renal fibrosis. Although apigenin has been demonstrated to play a protective role from fibrotic diseases, its pharmacological effect on renal fibroblast activation remains largely unknown.
OBJECTIVE: Here, we examined the functional role of apigenin in the activation of renal fibroblasts response to transforming growth factor (TGF)-β1 and its potential mechanisms.
METHOD: Cultured renal fibroblasts (NRK-49F) were exposed to apigenin (1, 5, 10 and 20µM) followed by the stimulation of TGF-β1 (2 ng/mL) for 24 h. The markers of fibroblast activation were determined. In order to confirm the anti-fibrosis effect of apigenin, the expression of fibrosis-associated genes in renal fibroblasts was assessed.
RESULT: As a consequence, apigenin alleviated fibroblast proliferation and fibroblast-myofibroblast differentiation induced by TGF-β1. Notably, apigenin significantly inhibited the fibrosis-associated genes expression in renal fibroblasts. Moreover, apigenin treatment significantly increased phosphorylation of AMP-activated protein kinase (AMPK). Apigenin treatment also obviously reduced TGF-β1 induced phosphorylation of ERK1/2 but not Smad2/3, p38 and JNK MAPK in renal fibroblasts.
CONCLUSION: In a summary, these results indicate that apigenin inhibits renal fibroblast proliferation, differentiation and function by AMPK activation and reduced of ERK1/2 phosphorylation, suggesting it could be an attractive therapeutic potential for the treatment of renal fibrosis.


greenmedinfo--2020-03-23--Biochanin A enhances endothelium relaxation in the aortae of hypertensive and normotensive rats.

BACKGROUND : The plant-derived estrogen biochanin A is known to cause vasodilation , but its mechanism of action in hypertension remains unclear .
This study was undertaken to investigate the effects and mechanisms of biochanin A on the thoracic aorta in two-kidney , one clip ( 2K1C ) renovascular hypertensive rats .
METHODS : Hypertension was induced by clipping the left renal artery , and control age-matched rats were sham treated .
Thoracic aortae were mounted in tissue baths to measure isometric tension .
RESULTS : Biochanin A caused concentration-dependent relaxation in aortic rings from 2K1C hypertensive and sham-treated rats @ @ @ @ @ @ @ than in sham rats .
Biochanin A-induced relaxation was significantly attenuated by removing the endothelium in aortic rings from 2K1C rats , but not in sham rats .
N ( ω ) -Nitro-l-arginine methyl ester , a nitric oxide synthase inhibitor , or indomethacin , a cyclooxygenase inhibitor , did not affect the biochanin A-induced relaxation in aortic rings from 2K1C and sham rats .
By contrast , treatment with glibenclamide , a selective inhibitor of adenosine triphosphate-sensitive K ( + ) channels , or tetraethylammonium , an inhibitor of Ca ( 2+ @ @ @ @ @ @ @ , significantly reduced biochanin A-induced relaxation in aortic rings from both groups .
However , 4-aminopyridine , a selective inhibitor of voltage-dependent K ( + ) channels , inhibited the relaxation induced bybiochanin A in 2K1C rats , whereas no significant differences were observed in sham rats .
CONCLUSION : These results suggest that the enhanced relaxation caused by biochanin A in aortic rings from hypertensive rats is endothelium dependent .
Vascular smooth muscle K ( + ) channels may be involved in biochanin A-induced relaxation in aortae from hypertensive and normotensive rats @ @ @ @ @ @ @ of voltage-dependent K ( + ) channels contributes , at least in part , to the relaxant effect of biochanin A in renovascular hypertension .

BACKGROUND: The plant-derived estrogen biochanin A is known to cause vasodilation, but its mechanism of action in hypertension remains unclear. This study was undertaken to investigate the effects and mechanisms of biochanin A on the thoracic aorta in two-kidney, one clip (2K1C) renovascular hypertensive rats.
METHODS: Hypertension was induced by clipping the left renal artery, and control age-matched rats were sham treated. Thoracic aortae were mounted in tissue baths to measure isometric tension.
RESULTS: Biochanin A caused concentration-dependent relaxation in aortic rings from 2K1C hypertensive and sham-treated rats, which was greater in 2K1C rats than in sham rats. Biochanin A-induced relaxation was significantly attenuated by removing the endothelium in aortic rings from 2K1C rats, but not in sham rats. N (ω)-Nitro-l-arginine methyl ester, a nitric oxide synthase inhibitor, or indomethacin, a cyclooxygenase inhibitor, did not affect the biochanin A-induced relaxation in aortic rings from 2K1C and sham rats. By contrast, treatment with glibenclamide, a selective inhibitor of adenosine triphosphate-sensitive K(+) channels, or tetraethylammonium, an inhibitor of Ca(2+)-activated K(+) channels, significantly reduced biochanin A-induced relaxation in aortic rings from both groups. However, 4-aminopyridine, a selective inhibitor of voltage-dependent K(+) channels, inhibited the relaxation induced bybiochanin A in 2K1C rats, whereas no significant differences were observed in sham rats.
CONCLUSION: These results suggest that the enhanced relaxation caused by biochanin A in aortic rings from hypertensive rats is endothelium dependent. Vascular smooth muscle K(+) channels may be involved in biochanin A-induced relaxation in aortae from hypertensive and normotensive rats. In addition, an endothelium-derived activation of voltage-dependent K(+) channels contributes, at least in part, to the relaxant effect of biochanin A in renovascular hypertension.


greenmedinfo--2020-03-23--Biochanin A ameliorates histological changes of renal and cutaneous tissue related to ovariectomy an

Biochanin A ameliorates histological changes of renal and cutaneous tissue related to ovariectomy and/or anastrozole treatment.

AIMS : This study was designed to assess the beneficial role of biochanin A ( BCA ) in the protection of the cutaneous and renal tissues of ovariectomized rats , even in those treated with anastrozole ( ANA ) .
MATERIALS AND METHODS : For this purpose , 60 adult female Wistar rats were allocated into 6 equal groups .
Rats in group I ( sham ) underwent a sham operation and received distilled water orally .
In groups II and III , OVX rats received either distilled water orally or DMSO intraperitoneally , respectively .
In groups IV and @ @ @ @ @ @ @ orally with 0.5 mg ANA/kg.b.wt .
or administered 5 mg of BCA/kg.b.wt .
intraperitoneally , respectively .
In group VI ( OVX-ANA-BCA ) , OVX rats were co-treated with BCA and ANA .
All treatments were given daily for 20 weeks .
KEY FINDINGS : The IP administration of BCA significantly decreased serum levels of urea , creatinine , uric acid and MDA and significantly increased serum CAT , GSH and TAC and cutaneous IL-4 and GATA3 concentrations in the fifth and sixth groups compared to OVX-DMSO and OVX-ANA groups , respectively .
@ @ @ @ @ @ @ TNF-α and iNOS expression as well as up-regulation of cutaneous TGF-β expression .
Furthermore , BCA ameliorated to variable degrees histological changes of renal and cutaneous tissue related to ovariectomy and/or ANA treatment .
SIGNIFICANCE : These data suggest that BCA might be a useful alternative estrogen therapy for the management of renal and cutaneous changes observed in postmenopausal women , even in those treated with ANA .

AIMS: This study was designed to assess the beneficial role of biochanin A (BCA) in the protection of the cutaneous and renal tissues of ovariectomized rats, even in those treated with anastrozole (ANA).
MATERIALS AND METHODS: For this purpose, 60 adult female Wistar rats were allocated into 6 equal groups. Rats in group I (sham) underwent a sham operation and received distilled water orally. In groups II and III, OVX rats received either distilled water orally or DMSO intraperitoneally, respectively. In groups IV and V, OVX rats were either treated orally with 0.5 mg ANA/kg.b.wt. or administered 5 mg of BCA/kg.b.wt. intraperitoneally, respectively. In group VI (OVX-ANA-BCA), OVX rats were co-treated with BCA and ANA. All treatments were given daily for 20 weeks.
KEY FINDINGS: The IP administration of BCA significantly decreased serum levels of urea, creatinine, uric acid and MDA and significantly increased serum CAT, GSH and TAC and cutaneous IL-4 and GATA3 concentrations in the fifth and sixth groups compared to OVX-DMSO and OVX-ANA groups, respectively. Additionally, it induced down-regulation of renal TNF-α and iNOS expression as well as up-regulation of cutaneous TGF-β expression. Furthermore, BCA ameliorated to variable degrees histological changes of renal and cutaneous tissue related to ovariectomy and/or ANA treatment.
SIGNIFICANCE: These data suggest that BCA might be a useful alternative estrogen therapy for the management of renal and cutaneous changes observed in postmenopausal women, even in those treated with ANA.


greenmedinfo--2020-03-23--Asian medicinal plants have multilevel effects on melanogenesis and are of great clinical value for

Asian medicinal plants have multilevel effects on melanogenesis and are of great clinical value for the treatment of skin pigmentary disorders.

ETHNOPHARMACOLOGICAL RELEVANCE : Chloasma , senile plaques , vitiligo and other pigmentary disorders seriously affect patients ' appearance and life quality .
Medicinal plant is the product of long-term medical practice worldwide , with the advantages of outstanding curative properties and less side effects .
Recently , research were made to explore the value of medicinal plants in the treatment of pigmentary disorders , and remarkable results were achieved .
AIM OF THE REVIEW : This review outlines the current understanding of the role and potential mechanisms of medicinal plants ( including active ingredients , extracts and prescriptions ) in @ @ @ @ @ @ @ , provides the preclinical evidence for the clinical benefits .
This study hopes to provide comprehensive information and reliable basis for exploring new therapeutic strategies of plant drugs in the treatment of skin pigmented diseases .
METHODS : The literature information was obtained from the scientific databases ( up to Oct , 2017 ) , mainly from the PubMed , Web of Science and CNKI databases , and was to identify the experimental studies on the regulating melanogenesis role of the active agents from herbal medicine and the involved mechanisms .
The search @ @ @ @ @ @ @ pigmentary '' or '' pigmentation '' , '' melanogenesis '' , and '' traditional Chinese medicine '' or '' Chinese herbal medicine '' , '' herb '' , '' medicinal plant '' .
RESULTS : We summarized the function of medicinal plants involved in melanogenesis , especially Chinese medicine .
It was reported that the active ingredients , extracts , or prescriptions of medicinal plants can regulate the expression of genes related to melanogenesis by affecting the signaling pathways such as MAPK and PKA , thereby regulating pigment synthesis .
Some of them @ @ @ @ @ @ @ , geniposide ; Cornus officinalis Siebold & Zucc.
, Eclipta prostrata ( L. ) L. ; the Bairesi complex prescription , etc. )
.
While others have the opposite effect ( such as biochanin A , Gomisin N ; Panax ginseng C.A .
Meyer , Nardostachys chinensis Bat .
; Sanbaitang , etc. )
.
CONCLUSION : Asian medicinal plants , especially their active ingredients , have multilevel effects on melanogenesis by regulating melanogenesis-related genes or signaling pathways .
They are of great clinical value for the treatment of skin pigmentary disorders .
@ @ @ @ @ @ @ , and functional mechanism of the medicinal plants require further determination before studying their clinical efficacy .

ETHNOPHARMACOLOGICAL RELEVANCE: Chloasma, senile plaques, vitiligo and other pigmentary disorders seriously affect patients' appearance and life quality. Medicinal plant is the product of long-term medical practice worldwide, with the advantages of outstanding curative properties and less side effects. Recently, research were made to explore the value of medicinal plants in the treatment of pigmentary disorders, and remarkable results were achieved.
AIM OF THE REVIEW: This review outlines the current understanding of the role and potential mechanisms of medicinal plants (including active ingredients, extracts and prescriptions) in pigmentary disorders, especially Chinese medicinal plants, provides the preclinical evidence for the clinical benefits. This study hopes to provide comprehensive information and reliable basis for exploring new therapeutic strategies of plant drugs in the treatment of skin pigmented diseases.
METHODS: The literature information was obtained from the scientific databases (up to Oct, 2017), mainly from the PubMed, Web of Science and CNKI databases, and was to identify the experimental studies on the regulating melanogenesis role of the active agents from herbal medicine and the involved mechanisms. The search keywords for such work included:"pigmentary"or"pigmentation","melanogenesis", and"traditional Chinese medicine"or"Chinese herbal medicine","herb","medicinal plant".
RESULTS: We summarized the function of medicinal plants involved in melanogenesis, especially Chinese medicine. It was reported that the active ingredients, extracts, or prescriptions of medicinal plants can regulate the expression of genes related to melanogenesis by affecting the signaling pathways such as MAPK and PKA, thereby regulating pigment synthesis. Some of them can promote melanogenesis (such as isoliquiritigenin, geniposide; Cornus officinalis Siebold&Zucc., Eclipta prostrata (L.) L.; the Bairesi complex prescription, etc.). While others have the opposite effect (such as biochanin A, Gomisin N; Panax ginseng C.A. Meyer, Nardostachys chinensis Bat.; Sanbaitang, etc.).
CONCLUSION: Asian medicinal plants, especially their active ingredients, have multilevel effects on melanogenesis by regulating melanogenesis-related genes or signaling pathways. They are of great clinical value for the treatment of skin pigmentary disorders. However, the experimental effect, safety, and functional mechanism of the medicinal plants require further determination before studying their clinical efficacy.


greenmedinfo--2020-03-23--Quercetin inhibits IgE-mediated allergic conjunctivitis.

BACKGROUND : Allergic conjunctivitis ( AC ) resulting from conjunctival reactive inflammation is a common ocular surface disease .
Quercetin is known for its anti-allergic properties but its effects on conjunctivitis are less well understood .
PURPOSE : In this study , we evaluated the anti-allergic effects of quercetin in animal models of conjunctivitis , and explored its molecular mechanism ( s ) of action in cultured human mast cells ( MCs ) .
KEY RESULTS : Quercetin inhibited the ovalbumin ( OVA ) induced expression of IgE , HA , IL-4 , TNF-α and substance-P in the peripheral blood @ @ @ @ @ @ @ attenuated OVA induced MC degranulation , eosinophil number , substance P concentrations , and mRNA IL-4/TNF-α expression in the conjunctival tissue of AC models .
In vitro analysis showed that quercetin reduced DNP-HSA/IgE induced calcium ( Ca2+ ) influx , and suppressed degranulation and chemokine release in LAD2 cells ( human primary mast cell ) .
Quercetin also inhibited DNP-HSA/IgE induced Lyn/PLCγ/IP3R-Ca2+ activation , Lyn/ERK1/2 signaling , and Lyn/NF-κB activation in LAD2 cells , all of which promote inflammation .
When added alone , quercetin had no effect on PLCγ1 phosphorylation or expression @ @ @ @ @ @ @ .
Quercetin ( 200 μM ) and Lyn inhibitors ( Bafetinib , 10 μM ) inhibit the activity of Lyn kinase , and quercetin can reduce the activation of Lyn kinase by Lyn agonist ( Tolimidone , 10 μM ) .
These data can be preliminarily determined that quercetin can inhibit allergic conjunctivitis as a Lyn kinase inhibitor .
CONCLUSIONS AND IMPLICATIONS : This study illustrated the use of quercetin for the treatment of allergic conjunctivitis , which might act through its ability to inhibit Lyn/PLCγ/IP3R-Ca , Lyn/ERK1/2 , and Lyn/NF-κB signaling .
@ @ @ @ @ @ @ major mechanism by which quercetin dampens the inflammatory response in AC disease models .

BACKGROUND: Allergic conjunctivitis (AC) resulting from conjunctival reactive inflammation is a common ocular surface disease. Quercetin is known for its anti-allergic properties but its effects on conjunctivitis are less well understood.
PURPOSE: In this study, we evaluated the anti-allergic effects of quercetin in animal models of conjunctivitis, and explored its molecular mechanism(s) of action in cultured human mast cells (MCs).
KEY RESULTS: Quercetin inhibited the ovalbumin (OVA) induced expression of IgE, HA, IL-4, TNF-α and substance-P in the peripheral blood of AC mouse models. Quercetin also attenuated OVA induced MC degranulation, eosinophil number, substance P concentrations, and mRNA IL-4/TNF-α expression in the conjunctival tissue of AC models. In vitro analysis showed that quercetin reduced DNP-HSA/IgE induced calcium (Ca2+) influx, and suppressed degranulation and chemokine release in LAD2 cells (human primary mast cell). Quercetin also inhibited DNP-HSA/IgE induced Lyn/PLCγ/IP3R-Ca2+ activation, Lyn/ERK1/2 signaling, and Lyn/NF-κB activation in LAD2 cells, all of which promote inflammation. When added alone, quercetin had no effect on PLCγ1 phosphorylation or expression, but potently inhibited Lyn and phosphorylation-Lyn. Quercetin (200 μM) and Lyn inhibitors (Bafetinib, 10 μM) inhibit the activity of Lyn kinase, and quercetin can reduce the activation of Lyn kinase by Lyn agonist (Tolimidone, 10 μM). These data can be preliminarily determined that quercetin can inhibit allergic conjunctivitis as a Lyn kinase inhibitor.
CONCLUSIONS AND IMPLICATIONS: This study illustrated the use of quercetin for the treatment of allergic conjunctivitis, which might act through its ability to inhibit Lyn/PLCγ/IP3R-Ca, Lyn/ERK1/2, and Lyn/NF-κB signaling. The inhibition of Lyn likely represents a major mechanism by which quercetin dampens the inflammatory response in AC disease models.


greenmedinfo--2020-03-23--Red clover has a beneficial role in improving insulin sensitivity.

Flowering tops of Trifolium pratense L. ( Fabaceae ) are known for its traditional medicinal values .
In present study @ @ @ @ @ investigate effect of standardized aqueous extract of flowering tops of Trifolium pratense L. on insulin @ @ @ @ @ type 2 diabetic rats .
Type 2 diabetes was induced by feeding high fat diet @ @ @ @ @ streptozotocin .
Diabetic animals were treated with standardized aqueous extract at three different doses .
@ @ @ @ @ , lipid profile , glycohemoglobin , insulin sensitivity , HOMA-IR and liver glycogen content were @ @ @ @ @ and expression of SIRT1 in pancreatic tissue were measured in histopathological and immunohistological studies .
@ @ @ @ @ in hyperglycemia and improved insulin sensitivity .
Extract treatment also showed reduction in formation of @ @ @ @ @ glycogen level .
Histopathological study revealed protecting effect of extract in pancreatic tissue against hyperglycemia @ @ @ @ @ expression of SIRT1 in rat pancreatic tissue .
Results indicate that the aqueous extract of @ @ @ @ @ in improving insulin sensitivity and SIRT1 expression .

Flowering tops of Trifolium pratense L. (Fabaceae) are known for its traditional medicinal values. In present study, our aim was to investigate effect of standardized aqueous extract of flowering tops of Trifolium pratense L. on insulin resistance and SIRT1 expression in type 2 diabetic rats. Type 2 diabetes was induced by feeding high fat diet and administering low dose of streptozotocin. Diabetic animals were treated with standardized aqueous extract at three different doses. Parameters such as blood glucose, lipid profile, glycohemoglobin, insulin sensitivity, HOMA-IR and liver glycogen content were measured. Changes in morphology and expression of SIRT1 in pancreatic tissue were measured in histopathological and immunohistological studies. Aqueous extract treatment showed reduction in hyperglycemia and improved insulin sensitivity. Extract treatment also showed reduction in formation of glycated hemoglobin and improved liver glycogen level. Histopathological study revealed protecting effect of extract in pancreatic tissue against hyperglycemia induced damage. Treatment increased expression of SIRT1 in rat pancreatic tissue. Results indicate that the aqueous extract of Trifolium pratense had beneficial role in improving insulin sensitivity and SIRT1 expression.


greenmedinfo--2020-03-23--These findings suggest that red clover isoflavones are effective in reducing skin aging induced by e

Estrogens have a profound influence on skin .
The relative hypoestrogenism that accompanies menopause exacerbates the deleterious effects of both intrinsic and environmental aging .
Estrogens improve skin in many ways .
Among these , they increase collagen content , skin thickness and improve skin moisture .
There is evidence that diets with high levels of phytoestrogenic isoflavones are associated with a low incidence of menopausal symptoms and osteoporosis .
Plant extracts such as red clover , which contain high levels of isoflavones , have been used to reduce menopausal symptoms and have been shown to reduce bone loss in @ @ @ @ @ @ @ investigate the effects of red clover isoflavones on skin aging , the histology of the skin , skin thickness and the amount of total collagen determined by a colorimetric method , were studied in ovariectomized rats after treatment for 14 weeks with a red clover extract standardized to contain 11 % isoflavones determined by HPLC .
In ovariectomized rats the thickness and keratinization of the epidermis were reduced ; glands were less in number and vascularity was poor ; the distribution and morphology of the collagen bundles and elastic fibers were altered .
@ @ @ @ @ @ @ treated with red clover isoflavones ( 20 and 40 mg of total isoflavones daily for 14 weeks ) appeared well organized with a normal epidermis with uniform thickness and regular keratinization ; vascularity , collagen and elastic fibers were well developed .
The amount of collagen significantly increased in the treated group in comparison with the control group .
These findings suggest that red clover isoflavones are effective in reducing skin aging induced by estrogen deprivation .

Estrogens have a profound influence on skin. The relative hypoestrogenism that accompanies menopause exacerbates the deleterious effects of both intrinsic and environmental aging. Estrogens improve skin in many ways. Among these, they increase collagen content, skin thickness and improve skin moisture. There is evidence that diets with high levels of phytoestrogenic isoflavones are associated with a low incidence of menopausal symptoms and osteoporosis. Plant extracts such as red clover, which contain high levels of isoflavones, have been used to reduce menopausal symptoms and have been shown to reduce bone loss in healthy women. In this study to investigate the effects of red clover isoflavones on skin aging, the histology of the skin, skin thickness and the amount of total collagen determined by a colorimetric method, were studied in ovariectomized rats after treatment for 14 weeks with a red clover extract standardized to contain 11% isoflavones determined by HPLC. In ovariectomized rats the thickness and keratinization of the epidermis were reduced; glands were less in number and vascularity was poor; the distribution and morphology of the collagen bundles and elastic fibers were altered. Whereas the skin of the ovariectomized rats treated with red clover isoflavones (20 and 40 mg of total isoflavones daily for 14 weeks) appeared well organized with a normal epidermis with uniform thickness and regular keratinization; vascularity, collagen and elastic fibers were well developed. The amount of collagen significantly increased in the treated group in comparison with the control group. These findings suggest that red clover isoflavones are effective in reducing skin aging induced by estrogen deprivation.


greenmedinfo--2020-03-23--Red clover protect against inflammation and immune suppression induced by topical UV radiation.

Isoflavones derived from many edible plants have been reported to possess significant antioxidant , estrogenic and tyrosine kinase inhibitory activity .
Genistein has been found previously to provide protection from oxidative damage induced by UV radiation both in vitro and following dietary administration .
We have therefore examined the potential of a number of isoflavones from red clover ( Trifolium pratense ) and some metabolically related compounds to offer protection from UV irradiation in hairless mice by topical application after UV exposure .
We show that whereas the primary isoflavones , daidzein , biochanin A and formononetin , were inactive @ @ @ @ @ @ @ the metabolites equol , isoequol and the related derivative dehydroequol had powerful potential to reduce the inflammatory edema reaction and the suppression of contact hypersensitivity induced by moderate doses of solar-simulated UV radiation .
For equol the protection was concentration dependent and 5 microM equol markedly reduced the UV-induced inflammation but abrogated the UV-induced immunosuppression .
Equol protected similarly from immunosuppression induced by the putative epidermal mediator , cis-urocanic acid ( UCA ) , indicating a potential mechanism of action involving inactivation of this UV-photoproduct .
Since immunosuppression induced by both UV radiation @ @ @ @ @ @ @ oxidant-dependent response our observations support the actions of these topically applied isoflavones and their metabolites as antioxidants .
They also indicate that lotions containing equol , unlike topical UV sunscreens , more readily protect the immune system from photosuppression than from the inflammation of the sunburn reaction , even when applied after exposure , and thus such compounds may have a future role as sun-protective cosmetic ingredients .

Isoflavones derived from many edible plants have been reported to possess significant antioxidant, estrogenic and tyrosine kinase inhibitory activity. Genistein has been found previously to provide protection from oxidative damage induced by UV radiation both in vitro and following dietary administration. We have therefore examined the potential of a number of isoflavones from red clover (Trifolium pratense) and some metabolically related compounds to offer protection from UV irradiation in hairless mice by topical application after UV exposure. We show that whereas the primary isoflavones, daidzein, biochanin A and formononetin, were inactive, 20 microM lotions of genistein and the metabolites equol, isoequol and the related derivative dehydroequol had powerful potential to reduce the inflammatory edema reaction and the suppression of contact hypersensitivity induced by moderate doses of solar-simulated UV radiation. For equol the protection was concentration dependent and 5 microM equol markedly reduced the UV-induced inflammation but abrogated the UV-induced immunosuppression. Equol protected similarly from immunosuppression induced by the putative epidermal mediator, cis-urocanic acid (UCA), indicating a potential mechanism of action involving inactivation of this UV-photoproduct. Since immunosuppression induced by both UV radiation and by cis-UCA appears to be an oxidant-dependent response our observations support the actions of these topically applied isoflavones and their metabolites as antioxidants. They also indicate that lotions containing equol, unlike topical UV sunscreens, more readily protect the immune system from photosuppression than from the inflammation of the sunburn reaction, even when applied after exposure, and thus such compounds may have a future role as sun-protective cosmetic ingredients.


greenmedinfo--2020-03-23--Biochanin A from red clover inhibits melanogenesis and may be helpful for hyperpigmentation disorder

Biochanin A from red clover inhibits melanogenesis and may be helpful for hyperpigmentation disorders.

Our previous study showed that a methanol extract from Trifolium pratense exerted potent inhibitory activity on melanogenesis in mouse B16 @ @ @ @ @ present study , the active compound in this Chinese herb extract was isolated and identified @ @ @ @ @ spectrum , ( 1 ) H-NMR , and ( 13 ) C-NMR analysis .
The @ @ @ @ @ on melanogenesis were investigated in vitro in cultured melanoma cells and in vivo in zebrafish @ @ @ @ @ dose-dependently inhibited both melanogenesis and cellular tyrosinase activity in B16 cells and in zebrafish embryos @ @ @ @ @ containing 2 % biochanin A twice daily to the skin of mice also increased the @ @ @ @ @ week of treatment , and the increase continued for another 2 weeks .
Biochanin A @ @ @ @ @ candidate for use as a skin-whitening agent in the treatment of skin hyperpigmentation disorders .

Our previous study showed that a methanol extract from Trifolium pratense exerted potent inhibitory activity on melanogenesis in mouse B16 melanoma cells. In the present study, the active compound in this Chinese herb extract was isolated and identified as biochanin A by mass spectrum, (1)H-NMR, and (13)C-NMR analysis. The inhibitory effects of biochanin A on melanogenesis were investigated in vitro in cultured melanoma cells and in vivo in zebrafish and mice. Biochanin A dose-dependently inhibited both melanogenesis and cellular tyrosinase activity in B16 cells and in zebrafish embryos. Application of a cream containing 2% biochanin A twice daily to the skin of mice also increased the skin-whitening index value after 1 week of treatment, and the increase continued for another 2 weeks. Biochanin A was confirmed as a good candidate for use as a skin-whitening agent in the treatment of skin hyperpigmentation disorders.


greenmedinfo--2020-03-23--Irilone from red clover potentiates progesterone signaling.

The use of botanical dietary supplements is becoming increasingly popular for the alleviation of hormonal-based conditions such as hot flashes , premenstrual syndrome , and fertility .
Estrogen and progesterone receptors ( ER and PR ) play an essential role in these processes .
However , despite the fact that many therapies used to alleviate gynecological conditions act through PR-mediated mechanisms , few studies have investigated or identified any herbal natural product components that act on this receptor .
In the current study , we used a progesterone response element ( PRE ) -luciferase ( Luc ) reporter assay to @ @ @ @ @ @ @ red clover ( Trifolium pratense ) extract .
We found that the component irilone ( 1 ) potentiated the effect of progesterone in both endometrial and ovarian cancer cell lines .
In these cancers , progesterone action is generally associated with positive outcomes ; thus the potentiating effect of 1 may provide entirely new strategies for enhancing progesterone signaling as a means of mitigating conditions such as fibroids and endometriosis .
Formononetin ( 3 ) and biochanin A ( 4 ) exhibited mixed agonist activity , while prunetin ( 2 ) acted only @ @ @ @ @ @ @ results suggest that the effects of red clover extract repeatedly observed in cultured cells and the inverse correlation between risk of various cancers and flavonoid intake may be due , in part , to altered progesterone signaling .

The use of botanical dietary supplements is becoming increasingly popular for the alleviation of hormonal-based conditions such as hot flashes, premenstrual syndrome, and fertility. Estrogen and progesterone receptors (ER and PR) play an essential role in these processes. However, despite the fact that many therapies used to alleviate gynecological conditions act through PR-mediated mechanisms, few studies have investigated or identified any herbal natural product components that act on this receptor. In the current study, we used a progesterone response element (PRE)-luciferase (Luc) reporter assay to identify four phytoprogestins present in a standardized red clover ( Trifolium pratense) extract. We found that the component irilone (1) potentiated the effect of progesterone in both endometrial and ovarian cancer cell lines. In these cancers, progesterone action is generally associated with positive outcomes; thus the potentiating effect of 1 may provide entirely new strategies for enhancing progesterone signaling as a means of mitigating conditions such as fibroids and endometriosis. Formononetin (3) and biochanin A (4) exhibited mixed agonist activity, while prunetin (2) acted only as an antagonist. Collectively, these results suggest that the effects of red clover extract repeatedly observed in cultured cells and the inverse correlation between risk of various cancers and flavonoid intake may be due, in part, to altered progesterone signaling.


greenmedinfo--2020-03-23--Biochanin A reduces the abundance of proteolytic bacteria and production of ammonia.

Biochanin A is a naturally occurring flavonoid compound that is found in plant species such as red clover ( ) and alfalfa ( ) .
Flavonoids have been reported to regulate ruminal fermentation , and the objective of this study was to evaluate the effects of biochanin A on ruminal microbial composition and nitrogen metabolism .
The experiment was performed by in vitro batch culturing of a control ( without biochanin A ) and a biochanin A treatment .
Following a 24-h incubation , gas production and the amounts of ammonia-nitrogen ( NH-N ) , volatile fatty acid ( VFA @ @ @ @ @ @ @ .
Microbial population using 16S rRNA gene sequence .
We found that the addition of biochanin A significantly increased microbial gas production ; but had no effect on VFA production .
Biochanin A supplementation also resulted in reduced microbial urease activity with half the maximal inhibitory concentration of 320 nM and also inhibited the degradation rates of total amino acids , valine , lysine , methionine and leucine by 18 % , 56 % , 37 % , 13 % , and 12 % , respectively .
This inhibition of urease activity and @ @ @ @ @ @ @ reduction in the NH-N concentration .
High-throughput sequencing of the 16S rRNA sequence to monitor microbial composition showed that biochanin A significantly reduced the abundance of the proteolytic bacteriaand ureolytic bacteria , but increased the abundance of the lactic acid metabolizing bacteriaand .
In conclusion , biochanin A reduced the production of ammonia by inhibiting proteolytic bacteria and their decomposition of urea and amino acids .

Biochanin A is a naturally occurring flavonoid compound that is found in plant species such as red clover () and alfalfa (). Flavonoids have been reported to regulate ruminal fermentation, and the objective of this study was to evaluate the effects of biochanin A on ruminal microbial composition and nitrogen metabolism. The experiment was performed by in vitro batch culturing of a control (without biochanin A) and a biochanin A treatment. Following a 24-h incubation, gas production and the amounts of ammonia-nitrogen (NH-N), volatile fatty acid (VFA), and amino acids were measured. Microbial population using 16S rRNA gene sequence. We found that the addition of biochanin A significantly increased microbial gas production; but had no effect on VFA production. Biochanin A supplementation also resulted in reduced microbial urease activity with half the maximal inhibitory concentration of 320 nM and also inhibited the degradation rates of total amino acids, valine, lysine, methionine and leucine by 18%, 56%, 37%, 13%, and 12%, respectively. This inhibition of urease activity and amino acid decomposition resulted in a significant reduction in the NH-N concentration. High-throughput sequencing of the 16S rRNA sequence to monitor microbial composition showed that biochanin A significantly reduced the abundance of the proteolytic bacteriaand ureolytic bacteria, but increased the abundance of the lactic acid metabolizing bacteriaand. In conclusion, biochanin A reduced the production of ammonia by inhibiting proteolytic bacteria and their decomposition of urea and amino acids.


greenmedinfo--2020-03-23--Alcohol is an immunosuppressive agent.

Alcohol is an immunosuppressive agent.

Acute and chronic alcohol use leads to an impaired immune response and dysregulated inflammatory state that contributes to a markedly @ @ @ @ @ Via shared mechanisms of immune-mediated injury , alcohol can alter the clinical course of viral @ @ @ @ @ , hepatitis C , and human immunodeficiency virus .
These effects are most evident in @ @ @ @ @ cirrhosis .
This article provides an overview of alcohol 's effect on the immune system @ @ @ @ @ and outcomes of specific infectious diseases .

Acute and chronic alcohol use leads to an impaired immune response and dysregulated inflammatory state that contributes to a markedly increased risk of infection. Via shared mechanisms of immune-mediated injury, alcohol can alter the clinical course of viral infections such as hepatitis B, hepatitis C, and human immunodeficiency virus. These effects are most evident in patients with alcoholic hepatitis and cirrhosis. This article provides an overview of alcohol's effect on the immune system and contribution to the risks and outcomes of specific infectious diseases.


greenmedinfo--2020-03-23--REPLAY: Making Sense of Coronavirus + Resilience Strategies - Sayer Ji's Livestream, March 22nd, 202

REPLAY: Making Sense of Coronavirus + Resilience Strategies - Sayer Ji's Livestream, March 22nd, 2020

“ Making Sense of Coronavirus + Resiliency Strategies + Q and A ” Sayer Ji , founder of Greenmedinfo.com was live-streamed Sunday , March 22nd , at 7 pm EDT .
This livestream was inspired by the fact that publishing articles on various topics related to health , in this day and age , can be triggering and polarizing -- especially when it comes to Coronavirus .
As the founder of GreenMedInfo and the Regenerate Porject , I realize that nothing can replace an in-person opportunity to assure you that while we publish information that often adds perspective to , @ @ @ @ @ @ @ narratives portrayed by the mainstream media and official health authorities , the intention is always to provide you with factual , evidence-based information that serves you .
I believe you want to know and can handle the truth ( everyone will come to their own version of what that means ) , which , I believe , requires that we include , present , and respect a multitude of perspectives .
The reality is that it is very difficult to communicate what 's going on through the medium of text and articles alone @ @ @ @ @ @ @ `` a text without a context is a pretext '' ?
To me , that 's the inherent danger of what we do at GreenMedInfo as a publishing platform : that anything we put out there can become a projection screen for misunderstanding and fear , which may have the net effect of decreasing your sense of safety and security in these trying times .
Also , given that in today 's climate , simply holding a divergent medical perspective , belief , or opinion , can be characterized as a form of @ @ @ @ @ @ @ crime , it is important that we continue to allow for and engage in meaningful debate and freedom of speech , especially when the consequences of these medical ideas have resulted in the lockdown of over 1 billion people , at the time of this writing , for fear of contagion .
This is why I decided to do a livestream on 3/22/20 at 7 PM EDT .
I know that by showing up fully , I can communicate with far more nuance and equanimity , and hopefully share some of what I @ @ @ @ @ @ @ the past few months of analyzing and trying to make sense of what 's going on .
I also share what I have been doing personally to maintain resilience within myself , my family , and community .
You can bookmark this page or keep a tab open here : https : //www.regenerateproject .
com/livestream

Visit our Re-post guidelines This article is copyrighted by GreenMedInfo LLC, 2020
“Making Sense of Coronavirus + Resiliency Strategies + Q and A” Sayer Ji, founder of Greenmedinfo.com was live-streamed Sunday, March 22nd, at 7 pm EDT.
The event was created in order to dispel confusion, fear, and anger, related to the Coronavirus panic, and to clarify questions on articles published on the topic on GreenMedInfo.com, and provide resiliency strategies. The stream was hosted on Regenerateproject.com and you can still add your comments and questions there: https://www.regenerateproject.com/livestream
This livestream was inspired by the fact that publishing articles on various topics related to health, in this day and age, can be triggering and polarizing -- especially when it comes to Coronavirus.
As the founder of GreenMedInfo and the Regenerate Porject, I realize that nothing can replace an in-person opportunity to assure you that while we publish information that often adds perspective to, and sometimes even challenges, the dominant narratives portrayed by the mainstream media and official health authorities, the intention is always to provide you with factual, evidence-based information that serves you. I believe you want to know and can handle the truth (everyone will come to their own version of what that means), which, I believe, requires that we include, present, and respect a multitude of perspectives.
The reality is that it is very difficult to communicate what's going on through the medium of text and articles alone. Have you heard the phrase: "a text without a context is a pretext"? To me, that's the inherent danger of what we do at GreenMedInfo as a publishing platform: that anything we put out there can become a projection screen for misunderstanding and fear, which may have the net effect of decreasing your sense of safety and security in these trying times.
Also, given that in today's climate, simply holding a divergent medical perspective, belief, or opinion, can be characterized as a form of political speech, or worse, a crime, it is important that we continue to allow for and engage in meaningful debate and freedom of speech, especially when the consequences of these medical ideas have resulted in the lockdown of over 1 billion people, at the time of this writing, for fear of contagion.
This is why I decided to do a livestream on 3/22/20 at 7 PM EDT. I know that by showing up fully, I can communicate with far more nuance and equanimity, and hopefully share some of what I have been thinking and working through over the past few months of analyzing and trying to make sense of what's going on. I also share what I have been doing personally to maintain resilience within myself, my family, and community. You can bookmark this page or keep a tab open here: https://www.regenerateproject. com/livestream
Warm regards,
Sayer Ji.


greenmedinfo--2020-03-23--Research suggests silymarin has hepatoprotective, antiinflammatory, and regenerative properties.

Gastroenterology nurses and associates will find it helpful to be informed about milk thistle ( silybum marianum ) , a @ @ @ @ @ herb used by patients with liver disease .
Silymarin is a derivative from the milk @ @ @ @ @ effects that has been safely used for centuries to treat liver ailments .
Since the @ @ @ @ @ a reemergence of the marketing and use of silymarin .
Research results of some small @ @ @ @ @ , antiinflammatory , and regenerative properties producing a beneficial effect for some types of hepatitis @ @ @ @ @ however , whether silymarin might interfere with the effect of interferon or ribavirin .
A @ @ @ @ @ a larger population is needed .
It is certainly encouraging that a large collaborative study @ @ @ @ @ thistle therapy in hepatitis C. This study is funded by NCCAM , the National Institute @ @ @ @ @ ( NIAID ) , and the National Institute of Diabetes and Digestive and Kidney Diseases @ @ @ @ @ updates are available online at www.nccam.nih.gov and through the NCCAM Clearinghouse at 1-888-644-6226 .

Gastroenterology nurses and associates will find it helpful to be informed about milk thistle (silybum marianum), a popular, safe and promising herb used by patients with liver disease. Silymarin is a derivative from the milk thistle plant with few side effects that has been safely used for centuries to treat liver ailments. Since the 1970s, there has been a reemergence of the marketing and use of silymarin. Research results of some small studies suggest silymarin has hepatoprotective, antiinflammatory, and regenerative properties producing a beneficial effect for some types of hepatitis. It is unclear, however, whether silymarin might interfere with the effect of interferon or ribavirin. A well-designed, placebo-controlled study of a larger population is needed. It is certainly encouraging that a large collaborative study is currently underway for milk thistle therapy in hepatitis C. This study is funded by NCCAM, the National Institute of Allergy and Infectious Diseases (NIAID), and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Research updates are available online at www.nccam.nih.gov and through the NCCAM Clearinghouse at 1-888-644-6226.


greenmedinfo--2020-03-23--Antiliver fibrosis screening of active ingredients from Apium graveolens seeds.

Although several studies have been performed onL .
( celery ) seeds , their antiliver fibrosis effects remain to be unexplored .
Firstly , we detected the effects of celery seeds extracted with different concentrations of aqueous ethanol on the proliferation of HSC-LX2 cells .
Then , we detected the effects of fractions of the optimal effect extract on the proliferation and apoptosis of HSC-LX2 cells .
Finally , the compounds of petroleum ether ( PP ) , ethyl acetate ( PE ) , n-butyl alcohol ( PB ) , and water fractions ( PW ) of the optimal effect @ @ @ @ @ @ @ , to confirm the potentially antifibrotic compounds combined with pharmacodynamic experiment of monomer compounds .
The results revealed that 60 % ethanol extract of celery seeds ( 60-extract ) exhibited remarkable inhibition effect on the proliferation of HSC-LX2 cells compared with 95 % ethanol and aqueous extract .
Besides , it validated that the inhibition rates of PP , PE , PB , and PW on the proliferation of HSC-LX2 cells were 75.14 % , 73.52 % , 54.09 % , and 43.36 % , and their percentage of apoptotic cells were 37.5 @ @ @ @ @ @ @ , and 0.1 % at high doses , respectively .
Additionally , it was manifested that apigenin , aesculetin , and butylphthalide have major contribution to the overall compounds of celery seeds , and the inhibition effects on the cell proliferation clearly elevated with increase in their contents .
In essence , apigenin , aesculetin , and butylphthalide may hopefully become the natural products of antiliver fibrosis , which laid a foundation for the subsequent development of celery seeds as antiliver fibrosis drugs .

Although several studies have been performed onL.(celery) seeds, their antiliver fibrosis effects remain to be unexplored. Firstly, we detected the effects of celery seeds extracted with different concentrations of aqueous ethanol on the proliferation of HSC-LX2 cells. Then, we detected the effects of fractions of the optimal effect extract on the proliferation and apoptosis of HSC-LX2 cells. Finally, the compounds of petroleum ether (PP), ethyl acetate (PE), n-butyl alcohol (PB), and water fractions (PW) of the optimal effect extract were determined by GC-TOF-MS and UHPLC-MS/MS, to confirm the potentially antifibrotic compounds combined with pharmacodynamic experiment of monomer compounds. The results revealed that 60% ethanol extract of celery seeds (60-extract) exhibited remarkable inhibition effect on the proliferation of HSC-LX2 cells compared with 95% ethanol and aqueous extract. Besides, it validated that the inhibition rates of PP, PE, PB, and PW on the proliferation of HSC-LX2 cells were 75.14%, 73.52%, 54.09%, and 43.36%, and their percentage of apoptotic cells were 37.5%, 4.3%, 0.7%, and 0.1% at high doses, respectively. Additionally, it was manifested that apigenin, aesculetin, and butylphthalide have major contribution to the overall compounds of celery seeds, and the inhibition effects on the cell proliferation clearly elevated with increase in their contents. In essence, apigenin, aesculetin, and butylphthalide may hopefully become the natural products of antiliver fibrosis, which laid a foundation for the subsequent development of celery seeds as antiliver fibrosis drugs.


greenmedinfo--2020-03-24--A Fiasco in the Making? As the Coronavirus Pandemic Takes Hold, We Are Making Decisions Without Reli

A Fiasco in the Making? As the Coronavirus Pandemic Takes Hold, We Are Making Decisions Without Reliable Data

This website is for information purposes only .
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greenmedinfo--2020-03-25--The effect of BPA exposure on insulin resistance and type 2 diabetes - The impact of muscle contract

The effect of BPA exposure on insulin resistance and type 2 diabetes - The impact of muscle contraction.

Type 2 diabetes ( T2D ) is considered one of the leading causes of death worldwide .
In addition to physical inactivity and obesity , established risk factors for T2D , chemical contaminants consumed in industrialized food such as BPA might also be a contributor to the development of T2D .
Epidemiological studies have shown that BPA concentrations are higher in human specimens of T2D when compared to healthy subjects , while experimental studies suggested that bisphenol A ( BPA ) impairs the pathway by which insulin stimulates glucose uptake .
In skeletal muscle and adipocytes , insulin resistance is @ @ @ @ @ @ @ pathway to stimulate the translocation of glucose transporter , GLUT4 , to the cell membrane .
Recent results demonstrated that BPA impairs several components of insulin-induced glucose uptake pathway and affect the expression of GLUT4 .
Regular physical exercise delays or inhibits the development of T2D due to the physiologic processes taking place during muscle contraction , and the fact that skeletal muscle is the site for almost 80 % of the glucose transported under insulin stimulation .
In fact , the mechanism by which contraction induces glucose uptake in skeletal muscle is @ @ @ @ @ @ @ therefore , the effect of BPA on this mechanism is unknown .
We hypothesize that during the development of insulin resistance , BPA contributes to the impairment of the molecular pathway by which insulin induces glucose uptake while contraction-induced glucose uptake is not impaired .
At the late stages of T2D , BPA may affect GLUT4 expression that will decrease the ability of muscle contraction to induce glucose uptake .

Type 2 diabetes (T2D) is considered one of the leading causes of death worldwide. In addition to physical inactivity and obesity, established risk factors for T2D, chemical contaminants consumed in industrialized food such as BPA might also be a contributor to the development of T2D. Epidemiological studies have shown that BPA concentrations are higher in human specimens of T2D when compared to healthy subjects, while experimental studies suggested that bisphenol A (BPA) impairs the pathway by which insulin stimulates glucose uptake. In skeletal muscle and adipocytes, insulin resistance is developed by the impairment of the insulin pathway to stimulate the translocation of glucose transporter, GLUT4, to the cell membrane. Recent results demonstrated that BPA impairs several components of insulin-induced glucose uptake pathway and affect the expression of GLUT4. Regular physical exercise delays or inhibits the development of T2D due to the physiologic processes taking place during muscle contraction, and the fact that skeletal muscle is the site for almost 80% of the glucose transported under insulin stimulation. In fact, the mechanism by which contraction induces glucose uptake in skeletal muscle is partially independent of the insulin pathway, therefore, the effect of BPA on this mechanism is unknown. We hypothesize that during the development of insulin resistance, BPA contributes to the impairment of the molecular pathway by which insulin induces glucose uptake while contraction-induced glucose uptake is not impaired. At the late stages of T2D, BPA may affect GLUT4 expression that will decrease the ability of muscle contraction to induce glucose uptake.


greenmedinfo--2020-03-25--Bisphenol A-induced metabolic disorders: From exposure to mechanism of action.

Bisphenol A ( BPA ) is considered as ubiquitous xenooestrogen and an endocrine disrupting chemical which has deleterious effects on endocrine functions .
Human populations are continuously exposed to BPA as it is abundant in daily life .
It has been found to be associated with wide range of metabolic disorders notably type 2 diabetes mellitus ( DM ) .
Numerous epidemiological studies have been conducted to find its role in development of DM .
Experimental studies have found that BPA exposure is associated with pathogenesis of DM and also considered as a risk factor for gestational diabetes .
Being @ @ @ @ @ @ @ accumulated in adipose tissues where it alters the production of adipokines that play important roles in insulin resistance .
BPA induces apoptosis by caspase activation after mitochondrial damage and it impairs insulin signaling pathways by altering associated ion channel activity especially potassium channels .
Perinatal exposure of BPA makes offspring more susceptible to develop DM in early years .
Epigenetic modifications are the key mechanisms for BPA-induced metabolic re-programming , where BPA alters the expression of DNA methyltransferases involved in methylation of various genes .
In this way , DNA methyltransferase controls the @ @ @ @ @ @ @ for insulin secretion and signaling .
Furthermore , BPA induces histone modifications and alters miRNA expression .
In this article , we have briefly described the sources of BPA exposure to human being and summarized the evidence from epidemiological studies linking DM with BPA exposure .
Additionally , we have also highlighted the potential molecular pathways for BPA-induced DM .

Bisphenol A (BPA) is considered as ubiquitous xenooestrogen and an endocrine disrupting chemical which has deleterious effects on endocrine functions. Human populations are continuously exposed to BPA as it is abundant in daily life. It has been found to be associated with wide range of metabolic disorders notably type 2 diabetes mellitus (DM). Numerous epidemiological studies have been conducted to find its role in development of DM. Experimental studies have found that BPA exposure is associated with pathogenesis of DM and also considered as a risk factor for gestational diabetes. Being a lipophilic compound, BPA is preferably accumulated in adipose tissues where it alters the production of adipokines that play important roles in insulin resistance. BPA induces apoptosis by caspase activation after mitochondrial damage and it impairs insulin signaling pathways by altering associated ion channel activity especially potassium channels. Perinatal exposure of BPA makes offspring more susceptible to develop DM in early years. Epigenetic modifications are the key mechanisms for BPA-induced metabolic re-programming, where BPA alters the expression of DNA methyltransferases involved in methylation of various genes. In this way, DNA methyltransferase controls the expression of numerous genes including genes important for insulin secretion and signaling. Furthermore, BPA induces histone modifications and alters miRNA expression. In this article, we have briefly described the sources of BPA exposure to human being and summarized the evidence from epidemiological studies linking DM with BPA exposure. Additionally, we have also highlighted the potential molecular pathways for BPA-induced DM.


greenmedinfo--2020-03-25--Anti-inflammation associated protective mechanism of berberine and its derivatives on attenuating pe

Anti-inflammation associated protective mechanism of berberine and its derivatives on attenuating pentylenetetrazole-induced seizures.

Epileptic seizures are characterized by synchronized discharges of neurons , leading to the activation of inflammatory responses that in turn contributes to seizure progression .
Berberine ( BBR ) , a bioactive constituent extracted from berberis , has been known to relieve seizures in rodent models .
In this study , we synthesized two derivatives of berberine ( BBR-D1 and BBR-D2 ) to compare their seizure reducing effect with BBR in pentylenetetrazole ( PTZ ) -induced seizures in zebrafish .
We found a structure-activity relationship between hydrophilic/hydrophobic composition of the derivatives and their anticonvulsant activity .
We also investigated the @ @ @ @ @ @ @ during seizures .
BBR and its derivatives increased the seizure onset latency and suppressed the seizure-like behavior after PTZ treatment .
Zebrafish larvae pretreated with BBR and its derivatives showed recovery on c-fos expression and neuronal discharges during seizures .
The inflammatory responses occurred during the progression of seizures , including the recruitment of macrophages and neutrophils as well as an up-regulation of tumor necrosis factor alpha ( TNFα ) , interleukin 1 beta ( il1β ) , and interleukin 6 ( il6 ) .
This effect was significantly suppressed by the pretreatment @ @ @ @ @ @ @ results suggest that BBR and its derivatives attenuate PTZ-induced seizures and modulate anti-inflammatory effect to potentially protect zebrafish from the occurrence of further seizures .
From the tested compounds , BBR-D1 ( the hydrophilic berberrubine ) showed the strongest seizure reducing effect .
Graphical Abstract Two derivatives of berberine ( BBR-D1 and BBR-D2 ) were synthesized to compare their seizure reducing effect with BBR in pentylenetetrazole ( PTZ ) -induced seizures in zebrafish .
BBR and its derivatives increased the seizure onset latency and suppressed the seizure-like behavior after PTZ treatment .
Zebrafish @ @ @ @ @ @ @ showed recovery on c-fos expression and neuronal discharges during seizures.The inflammatory responses occurred during the progression of seizures , including the recruitment of macrophages and neutrophils as well as an up-regulation of tumor necrosis factor alpha ( TNFα ) , interleukin 1 beta ( il1β ) , and interleukin 6 ( il6 ) .
This effect was significantly suppressed by the pretreatment of BBR and its derivatives .

Epileptic seizures are characterized by synchronized discharges of neurons, leading to the activation of inflammatory responses that in turn contributes to seizure progression. Berberine (BBR), a bioactive constituent extracted from berberis, has been known to relieve seizures in rodent models. In this study, we synthesized two derivatives of berberine (BBR-D1 and BBR-D2) to compare their seizure reducing effect with BBR in pentylenetetrazole (PTZ)-induced seizures in zebrafish. We found a structure-activity relationship between hydrophilic/hydrophobic composition of the derivatives and their anticonvulsant activity. We also investigated the underlying mechanism related to their anti-inflammatory effect during seizures. BBR and its derivatives increased the seizure onset latency and suppressed the seizure-like behavior after PTZ treatment. Zebrafish larvae pretreated with BBR and its derivatives showed recovery on c-fos expression and neuronal discharges during seizures. The inflammatory responses occurred during the progression of seizures, including the recruitment of macrophages and neutrophils as well as an up-regulation of tumor necrosis factor alpha (TNFα), interleukin 1 beta (il1β), and interleukin 6 (il6). This effect was significantly suppressed by the pretreatment of BBR and its derivatives. Our results suggest that BBR and its derivatives attenuate PTZ-induced seizures and modulate anti-inflammatory effect to potentially protect zebrafish from the occurrence of further seizures. From the tested compounds, BBR-D1 (the hydrophilic berberrubine) showed the strongest seizure reducing effect. Graphical Abstract Two derivatives of berberine (BBR-D1 and BBR-D2) were synthesized to compare their seizure reducing effect with BBR in pentylenetetrazole (PTZ)-induced seizures in zebrafish. BBR and its derivatives increased the seizure onset latency and suppressed the seizure-like behavior after PTZ treatment. Zebrafish larvae pretreated with BBR and its derivatives showed recovery on c-fos expression and neuronal discharges during seizures.The inflammatory responses occurred during the progression of seizures, including the recruitment of macrophages and neutrophils as well as an up-regulation of tumor necrosis factor alpha (TNFα), interleukin 1 beta (il1β), and interleukin 6 (il6). This effect was significantly suppressed by the pretreatment of BBR and its derivatives.


greenmedinfo--2020-03-25--Autologous erythrocytes delivery of berberine hydrochloride with long-acting effect for hypolipidemi

Autologous erythrocytes delivery of berberine hydrochloride with long-acting effect for hypolipidemia treatment.

Discovery of novel pharmacological effects of berberine hydrochloride ( BH ) has made its clinical application valuable .
However , further development and applications of BH are hampered by its short half-life and the side effects associated with its intravenous ( iv ) injection .
To improve the hypolipidemia efficacy and reduce side effects , we encapsulated BH into biocompatible red blood cells ( RBCs ) to explore its sustained-release effect by hypotonic pre-swelling method .
Fromevaluation , BH loaded RBCs ( BH-RBCs ) presented similar morphology and osmotic fragility to native RBCs ( NRBCs ) .
After the loading @ @ @ @ @ @ @ % of Na/K-ATPase activity of NRBCs and phosphatidylserine externalization value of BH-RBCs was about 26.1 ± 2.9 % .
The survival test showed that the loaded cells could circulate in plasma for over 9 d. Forevaluation , a series of tests including pharmacokinetics study and hypolipidemic effect were carried out to examine the long-acting effect of BH-RBCs .
The results showed that the release of BH in the loaded cells could last for about 5 d and the hypolipidemic effect can still be observed on 5 d after injection .
BH-loaded autologous erythrocytes @ @ @ @ @ @ @ delivery system with long hypolipidemic effect .

Discovery of novel pharmacological effects of berberine hydrochloride (BH) has made its clinical application valuable. However, further development and applications of BH are hampered by its short half-life and the side effects associated with its intravenous (iv) injection. To improve the hypolipidemia efficacy and reduce side effects, we encapsulated BH into biocompatible red blood cells (RBCs) to explore its sustained-release effect by hypotonic pre-swelling method. Fromevaluation, BH loaded RBCs (BH-RBCs) presented similar morphology and osmotic fragility to native RBCs (NRBCs). After the loading process, the BH-RBCs maintained around 69% of Na/K-ATPase activity of NRBCs and phosphatidylserine externalization value of BH-RBCs was about 26.1 ± 2.9%. The survival test showed that the loaded cells could circulate in plasma for over 9 d. Forevaluation, a series of tests including pharmacokinetics study and hypolipidemic effect were carried out to examine the long-acting effect of BH-RBCs. The results showed that the release of BH in the loaded cells could last for about 5 d and the hypolipidemic effect can still be observed on 5 d after injection. BH-loaded autologous erythrocytes seem to be a promising sustained releasing delivery system with long hypolipidemic effect.


greenmedinfo--2020-03-25--Berberine combined with cyclosporine A alleviates acute graft-versus-host disease in murine models.

Graft-versus-host disease ( GVHD ) causes significant mortality after allogeneic hematopoietic stem cell transplantation ( allo-HSCT ) .
Berberine ( BBR ) is primarily used to alleviate inflammation caused by autoimmune disorders .
Herein the effect of BBR and cyclosporine A ( CsA ) on GVHD prevention in murine models is explored .
Acute GVHD was induced by total body irradiation and tail vein injection with the mixture of bone marrow cells and spleen lymphocytes .
Then models were treated with BBR ( 10 mg/kg ) , CsA ( 5 mg/kg ) or the combination of BBR and CsA ( @ @ @ @ @ @ @ a day for 10 days .
The survival rate , weight loss and GVHD index were monitored .
Then the histological changes , alanine aminotransferase ( ALT ) and aspartate aminotransferase ( AST ) activities , apoptosis and thelevels of inflammatory cytokines , oxidative stress and nuclear factor-κB ( NF-κB ) signaling in liver and intestine were analyzed .
Moreover , the levels of inflammatory cytokines and oxidative stress , and the count of T helper 1 ( Th1 ) cells and Th17 cells in peripheral blood were determined .
The results showed @ @ @ @ @ @ @ GVHD index scores , attenuated liver and intestinal injury , and inhibited ALT and AST activities , inflammation , oxidative stress and NF-κB activation in liver and intestine .
Additionally , BBR inhibited inflammation and reduced Th1 cell countsbut had no effect on Th17 cell counts .
Interestingly , the concomitant therapy of BBR and CsA was more potent than either BBR or CsA and effectively elevated the survival rate of GVHD models .
This present study provides a new therapeutic strategy for alleviation of acute GVHD .

Graft-versus-host disease (GVHD) causes significant mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Berberine (BBR) is primarily used to alleviate inflammation caused by autoimmune disorders. Herein the effect of BBR and cyclosporine A (CsA) on GVHD prevention in murine models is explored. Acute GVHD was induced by total body irradiation and tail vein injection with the mixture of bone marrow cells and spleen lymphocytes. Then models were treated with BBR (10 mg/kg), CsA (5 mg/kg) or the combination of BBR and CsA (10 mg/kg and 5 mg/kg) once a day for 10 days. The survival rate, weight loss and GVHD index were monitored. Then the histological changes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, apoptosis and thelevels of inflammatory cytokines, oxidative stress and nuclear factor-κB (NF-κB) signaling in liver and intestine were analyzed. Moreover, the levels of inflammatory cytokines and oxidative stress, and the count of T helper 1 (Th1) cells and Th17 cells in peripheral blood were determined. The results showed that BBR reduced GVHD-induced weight loss and GVHD index scores, attenuated liver and intestinal injury, and inhibited ALT and AST activities, inflammation, oxidative stress and NF-κB activation in liver and intestine. Additionally, BBR inhibited inflammation and reduced Th1 cell countsbut had no effect on Th17 cell counts. Interestingly, the concomitant therapy of BBR and CsA was more potent than either BBR or CsA and effectively elevated the survival rate of GVHD models. This present study provides a new therapeutic strategy for alleviation of acute GVHD.


greenmedinfo--2020-03-25--Berberine supplementation in psychiatric patients could be a preventive approach to reduce the metab

Berberine supplementation in psychiatric patients could be a preventive approach to reduce the metabolic adverse effects of antipsychotics.

Transient receptor potential vanilloid type 1 ( TRPV1 ) channels are emerging therapeutic targets for metabolic disorders .
Berberine , which is a modulator of TRPV1 , has proven antiobesity and antidiabetic potentials .
The present study was aimed to investigate the protective effects of berberine in olanzapine-induced alterations in hypothalamic appetite control , inflammation and metabolic aberrations in mice targeting TRPV1 channels .
Female BALB/c mice ( 18-23 g ) were treated with olanzapine ( 6 mg/kg , p.o . )
for six weeks to induce metabolic alterations , while berberine ( 100 and 200 mg/kg , p.o .
@ @ @ @ @ @ @ p.o ) were used as test and standard interventions respectively .
Weekly assessment of feed-water intake , body temperature and body weight was done , while locomotion was measured at the end of week 1 and 6 .
Serum glucose and lipid profile were assessed by biochemical methods , while other serum biomarkers were assessed by ELISA .
qPCR was used to quantify the mRNA expression in the hypothalamus .
Olanzapine treatment significantly increased the feed intake , weight gain , adiposity index , while reduced body temperature and locomotor activity which were @ @ @ @ @ @ @ reduced serum ghrelin and leptin levels as well decrease in hypothalamic mRNA expression of orexigenic neuropeptides , inflammatory markers and ghrelin receptor in olanzapine-treated mice .
Olanzapine treatment increased expression of TRPV1/TRPV3 in the hypothalamus which was significantly decreased by berberine treatment .
Our results suggest that berberine , by TRPV1/TRPV3 modulation , attenuated the olanzapine-induced metabolic alterations in mice .
Hence berberine supplementation in psychiatric patients could be a preventive approach to reduce the metabolic adverse effects of antipsychotics .

Transient receptor potential vanilloid type 1 (TRPV1) channels are emerging therapeutic targets for metabolic disorders. Berberine, which is a modulator of TRPV1, has proven antiobesity and antidiabetic potentials. The present study was aimed to investigate the protective effects of berberine in olanzapine-induced alterations in hypothalamic appetite control, inflammation and metabolic aberrations in mice targeting TRPV1 channels. Female BALB/c mice (18-23 g) were treated with olanzapine (6 mg/kg, p.o.) for six weeks to induce metabolic alterations, while berberine (100 and 200 mg/kg, p.o.) and metformin (100 mg/kg, p.o) were used as test and standard interventions respectively. Weekly assessment of feed-water intake, body temperature and body weight was done, while locomotion was measured at the end of week 1 and 6. Serum glucose and lipid profile were assessed by biochemical methods, while other serum biomarkers were assessed by ELISA. qPCR was used to quantify the mRNA expression in the hypothalamus. Olanzapine treatment significantly increased the feed intake, weight gain, adiposity index, while reduced body temperature and locomotor activity which were reversed by berberine treatment. Berberine treatment reduced serum ghrelin and leptin levels as well decrease in hypothalamic mRNA expression of orexigenic neuropeptides, inflammatory markers and ghrelin receptor in olanzapine-treated mice. Olanzapine treatment increased expression of TRPV1/TRPV3 in the hypothalamus which was significantly decreased by berberine treatment. Our results suggest that berberine, by TRPV1/TRPV3 modulation, attenuated the olanzapine-induced metabolic alterations in mice. Hence berberine supplementation in psychiatric patients could be a preventive approach to reduce the metabolic adverse effects of antipsychotics.


greenmedinfo--2020-03-25--Berberine is a potential candidate for the treatment of NASH.

Berberine ( BBR ) , an isoquinoline alkaloid originating from herbal plants , has been deemed beneficial for non-alcoholic fatty liver disease .
Increasing evidence has demonstrated that Nod-like receptor family pyrin domain containing 3 ( NLRP3 ) inflammasome activation and the subsequent pyroptosis contribute to the progression of non-alcoholic steatohepatitis ( NASH ) .
However , whether BBR impacts NLRP3 inflammasome activation and pyroptosis in NASH and the potential mechanism remains unclear .
In the current study , we found that BBR significantly decreased lipid accumulation , ameliorated reactive oxygen species ( ROS ) and lipid peroxides , Tumor @ @ @ @ @ @ @ , and phosphorylation of Nuclear factor kappa B ( NF-κB ) p65 bothandIn particular , BBR significantly inhibited NLRP3 expression , caspase-1 activity , and the pyroptosis executor , GSDMD-N , expression .
In addition , BBR displayed similar inhibitory effects on NLRP3 inflammasome and pyroptosis with a decrease in ROS levels and TXNIP expression as N-acetyl-cysteine , a ROS scavenger , did .
Whereas , the inhibitory effect of BBR on ROS , TXNIP expression , NLRP3 inflammasome activation and pyroptosis could be reversed by HOin AML12 cells .
This study demonstrates @ @ @ @ @ @ @ inflammasome activation and pyroptosis may be mediated by ROS/TXNIP axisfor the first time .
Our findings suggest BBR is a potential candidate for the treatment of NASH .

Berberine (BBR), an isoquinoline alkaloid originating from herbal plants, has been deemed beneficial for non-alcoholic fatty liver disease. Increasing evidence has demonstrated that Nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation and the subsequent pyroptosis contribute to the progression of non-alcoholic steatohepatitis (NASH). However, whether BBR impacts NLRP3 inflammasome activation and pyroptosis in NASH and the potential mechanism remains unclear. In the current study, we found that BBR significantly decreased lipid accumulation, ameliorated reactive oxygen species (ROS) and lipid peroxides, Tumor necrosis factor alpha (TNF-α) expression, and phosphorylation of Nuclear factor kappa B (NF-κB) p65 bothandIn particular, BBR significantly inhibited NLRP3 expression, caspase-1 activity, and the pyroptosis executor, GSDMD-N, expression. In addition, BBR displayed similar inhibitory effects on NLRP3 inflammasome and pyroptosis with a decrease in ROS levels and TXNIP expression as N-acetyl-cysteine, a ROS scavenger, did. Whereas, the inhibitory effect of BBR on ROS, TXNIP expression, NLRP3 inflammasome activation and pyroptosis could be reversed by HOin AML12 cells. This study demonstrates that BBR's inhibitory effect on NLRP3 inflammasome activation and pyroptosis may be mediated by ROS/TXNIP axisfor the first time. Our findings suggest BBR is a potential candidate for the treatment of NASH.