greenmedinfo--2020-10-15--Apple vinegar lowers the constipation problems faced by patients with schizophrenia treated with clo

Apple vinegar lowers the constipation problems faced by patients with schizophrenia treated with clozapine.

PURPOSE : Clozapine is one of the drugs that cause the highest level of weight gain .
Additionally , obese patients are at higher risk of developing various physical co-morbidities , such as type 2 diabetes and cardiovascular diseases .
Forty-nine percent of patients on clozapine suffer from constipation .
Apple vinegar ( AV ) had been assigned health benefits , such as weight loss , laxative properties , blood glucose lowering effects , and reducing the risk of heart disease .
Our hypothesis was that AV would lower the mean glycated haemoglobin level and reduce the level of constipation @ @ @ @ @ @ @ study with a 12-week follow-up .
All patients receiving clozapine treatment for schizophrenia at one outpatient clinic were eligible for inclusion .
Intervention : Ten millilitres of AV diluted in 200 ml drinking water with breakfast and dinner .
RESULTS : Forty patients were suitable for inclusion and nine completed the intervention .
Women had much higher-than-recommended body mass index .
Scores for constipation were high .
The reduction in constipation was of clinical interest ( 2.6 ( = 0.017 ) ) .
However , there were no statistically significant differences in glycated @ @ @ @ @ @ @ or triglyceride levels .
Patients with problems of constipation prior to the intervention experienced much better bowel habits and relief of their constipation .
CONCLUSION : AV lower the constipation problems faced by patients with schizophrenia treated with clozapine .
Further research , repeating this pilot study with a meaningfully larger sample size and randomized with placebo , is needed .

PURPOSE: Clozapine is one of the drugs that cause the highest level of weight gain. Additionally, obese patients are at higher risk of developing various physical co-morbidities, such as type 2 diabetes and cardiovascular diseases. Forty-nine percent of patients on clozapine suffer from constipation. Apple vinegar (AV) had been assigned health benefits, such as weight loss, laxative properties, blood glucose lowering effects, and reducing the risk of heart disease. Our hypothesis was that AV would lower the mean glycated haemoglobin level and reduce the level of constipation.
MATERIAL AND METHODS: Pilot intervention study with a 12-week follow-up. All patients receiving clozapine treatment for schizophrenia at one outpatient clinic were eligible for inclusion. Intervention: Ten millilitres of AV diluted in 200 ml drinking water with breakfast and dinner.
RESULTS: Forty patients were suitable for inclusion and nine completed the intervention. Women had much higher-than-recommended body mass index. Scores for constipation were high. The reduction in constipation was of clinical interest (2.6 ( = 0.017)). However, there were no statistically significant differences in glycated haemoglobin, cholesterol, HDL, LDL or triglyceride levels. Patients with problems of constipation prior to the intervention experienced much better bowel habits and relief of their constipation.
CONCLUSION: AV lower the constipation problems faced by patients with schizophrenia treated with clozapine. Further research, repeating this pilot study with a meaningfully larger sample size and randomized with placebo, is needed.


greenmedinfo--2020-10-15--Phloretin ameliorates acetic acid induced colitis.

BACKGROUND : Adverse effects associated with current therapy for Ulcerative colitis ( UC ) over prolonged treatment periods and the high relapse rate limit their use .
Incorporating fruits as regular diet has beneficial role in the management of UC .
Phloretin , a dihydrochalcone of apple reported for its anti-oxidant and anti-inflammatory effects .
Our study aims to evaluate the effectiveness of phloretin on experimentally induced ulcerative colitis in rats .
METHODS : In vitro study was performed using Raw 264.7 cells stimulated with LPS ( 1µg/mL ) and in in-vivo study , colitis was induced by intra rectal @ @ @ @ @ @ @ Phloretin ( 50 mg/kg ) was given orally for 3 days to Wistar rats after induction for post-treatment group and 1 day before induction to pre-treatment group Macroscopical , biochemical and histopathological evaluations were performed to assess the effectiveness .
RESULTS : A concentration dependent inhibition of MPO and iNOS activity was obtained in LPS stimulated neutrophil cells .
Phloretin exerted ameliorative effect in both pre and post treatment groups by restoring plasma ALP and LDH level and reduce inflammatory markers like myeloperoxidase , nitric oxide and eosinophil peroxidase level as well as @ @ @ @ @ @ @ acid induced ulcerative colitis in rats .
Antioxidative potency was confirmed by restoring tissue GSH level .
Phloretin prevents mucosal damage and it was confirmed by histopathological analysis .
CONCLUSION : Collectively , these findings provide an evidence that phloretin might be useful as a natural therapeutic agent in the management of UC as well as may pose a promising outcome for the future clinical usage .

BACKGROUND: Adverse effects associated with current therapy for Ulcerative colitis (UC) over prolonged treatment periods and the high relapse rate limit their use. Incorporating fruits as regular diet has beneficial role in the management of UC. Phloretin, a dihydrochalcone of apple reported for its anti-oxidant and anti-inflammatory effects. Our study aims to evaluate the effectiveness of phloretin on experimentally induced ulcerative colitis in rats.
METHODS: In vitro study was performed using Raw 264.7 cells stimulated with LPS (1µg/mL) and in in-vivo study, colitis was induced by intra rectal administration of 4% Acetic acid. Phloretin (50 mg/kg) was given orally for 3 days to Wistar rats after induction for post-treatment group and 1 day before induction to pre-treatment group Macroscopical, biochemical and histopathological evaluations were performed to assess the effectiveness.
RESULTS: A concentration dependent inhibition of MPO and iNOS activity was obtained in LPS stimulated neutrophil cells. Phloretin exerted ameliorative effect in both pre and post treatment groups by restoring plasma ALP and LDH level and reduce inflammatory markers like myeloperoxidase, nitric oxide and eosinophil peroxidase level as well as down regulates colon iCAM-1 gene in acetic acid induced ulcerative colitis in rats. Antioxidative potency was confirmed by restoring tissue GSH level. Phloretin prevents mucosal damage and it was confirmed by histopathological analysis.
CONCLUSION: Collectively, these findings provide an evidence that phloretin might be useful as a natural therapeutic agent in the management of UC as well as may pose a promising outcome for the future clinical usage.


greenmedinfo--2020-10-15--These findings suggest that phloretin improves hepatic steatosis.

Background : Phloretin is isolated from apple trees and could increase lipolysis in 3T3-L1 adipocytes .
Previous studies have found that phloretin could prevent obesity in mice .
In this study , we investigated whether phloretin ameliorates non-alcoholic fatty liver disease ( NAFLD ) in high-fat diet ( HFD ) -induced obese mice , and evaluated the regulation of lipid metabolism in hepatocytes .
Methods : HepG2 cells were treated with 0.5 mM oleic acid to induce lipid accumulation , and then treated with phloretin to evaluate the molecular mechanism of lipogenesis .
In another experiment , male C57BL/6 mice @ @ @ @ @ @ @ 60 % fat , w/w ) for 16 weeks .
After the fourth week , mice were treated with or without phloretin by intraperitoneal injection for 12 weeks .
Results : Phloretin significantly reduced excessive lipid accumulation and decreased sterol regulatory element-binding protein 1c , blocking the expression of fatty acid synthase in oleic acid-induced HepG2 cells .
Phloretin increased Sirt1 , and phosphorylation of AMP activated protein kinase to suppress acetyl-CoA carboxylase expression , reducing fatty acid synthesis in hepatocytes .
Phloretin also reduced body weight and fat weight compared to untreated @ @ @ @ @ @ @ weight and liver lipid accumulation and improved hepatocyte steatosis in obese mice .
In liver tissue from obese mice , phloretin suppressed transcription factors of lipogenesis and fatty acid synthase , and increased lipolysis and fatty acidβ-oxidation .
Furthermore , phloretin regulated serum leptin , adiponectin , triglyceride , low-density lipoprotein , and free fatty acid levels in obese mice .
Conclusions : These findings suggest that phloretin improves hepatic steatosis by regulating lipogenesis and the Sirt-1/AMPK pathway in the liver .

Background: Phloretin is isolated from apple trees and could increase lipolysis in 3T3-L1 adipocytes. Previous studies have found that phloretin could prevent obesity in mice. In this study, we investigated whether phloretin ameliorates non-alcoholic fatty liver disease (NAFLD) in high-fat diet (HFD)-induced obese mice, and evaluated the regulation of lipid metabolism in hepatocytes.
Methods: HepG2 cells were treated with 0.5 mM oleic acid to induce lipid accumulation, and then treated with phloretin to evaluate the molecular mechanism of lipogenesis. In another experiment, male C57BL/6 mice were fed normal diet or HFD (60% fat, w/w) for 16 weeks. After the fourth week, mice were treated with or without phloretin by intraperitoneal injection for 12 weeks.
Results: Phloretin significantly reduced excessive lipid accumulation and decreased sterol regulatory element-binding protein 1c, blocking the expression of fatty acid synthase in oleic acid-induced HepG2 cells. Phloretin increased Sirt1, and phosphorylation of AMP activated protein kinase to suppress acetyl-CoA carboxylase expression, reducing fatty acid synthesis in hepatocytes. Phloretin also reduced body weight and fat weight compared to untreated HFD-fed mice. Phloretin also reduced liver weight and liver lipid accumulation and improved hepatocyte steatosis in obese mice. In liver tissue from obese mice, phloretin suppressed transcription factors of lipogenesis and fatty acid synthase, and increased lipolysis and fatty acidβ-oxidation. Furthermore, phloretin regulated serum leptin, adiponectin, triglyceride, low-density lipoprotein, and free fatty acid levels in obese mice.
Conclusions: These findings suggest that phloretin improves hepatic steatosis by regulating lipogenesis and the Sirt-1/AMPK pathway in the liver.


greenmedinfo--2020-10-15--Phloretin treatment in prostate cancer cells induces cell growth inhibition and apoptosis.

Phloretin is a flavonoid existed in various plants and has been reported to possess anticarcinogenic activity .
However , the @ @ @ @ @ prostate cancer ( PCa ) remains unclear .
Here , ourandexperimental data demonstrate that phloretin @ @ @ @ @ activation of EGFR and then inhibits its downstream PI3K/AKT and MEK/ERK1/2 pathways in PCa cells @ @ @ @ @ pathways further decreases expression of Sp1 by inhibitinggene transcription , induces degradation of Sp1 protein @ @ @ @ @ nucleolin-enhanced translation of Sp1 mRNA by inhibiting nucleolin phosphorylation , and directly inactivates transcription activity @ @ @ @ @ Sp1 subsequently decreases the expression of Sp3/4 , VEGF , and Survivin and then upregulates @ @ @ @ @ cycle-related proteins in PCa cells .
Finally , phloretin treatment in PCa cells induces cell @ @ @ @ @ suggesting that phloretin may be an effective therapy compound in the treatment of prostate cancer @

Phloretin is a flavonoid existed in various plants and has been reported to possess anticarcinogenic activity. However, the anticancer mechanism of phloretin in prostate cancer (PCa) remains unclear. Here, ourandexperimental data demonstrate that phloretin inhibits the phosphorylation and the activation of EGFR and then inhibits its downstream PI3K/AKT and MEK/ERK1/2 pathways in PCa cells. Inhibition of these two pathways further decreases expression of Sp1 by inhibitinggene transcription, induces degradation of Sp1 protein by inhibiting GSK3phosphorylation, suppresses nucleolin-enhanced translation of Sp1 mRNA by inhibiting nucleolin phosphorylation, and directly inactivates transcription activity of Sp1. Inhibition of Sp1 subsequently decreases the expression of Sp3/4, VEGF, and Survivin and then upregulates apoptosis-related proteins and downregulates cell cycle-related proteins in PCa cells. Finally, phloretin treatment in PCa cells induces cell growth inhibition and apoptosis, suggesting that phloretin may be an effective therapy compound in the treatment of prostate cancer.


greenmedinfo--2020-10-15--Phloretin modulates human Th17/Treg cell differentiation in vitro via AMPK signalling.

Objective : We conducted studies to explore the effect of phloretin on glucose uptake , proliferation , and differentiation of human peripheral blood CD4T cells and investigated the mechanism of phloretin on inducing Th17/Treg development .
Methods : Naïve CD4T cells were purified from peripheral blood of healthy volunteers , stimulated with anti-CD3/CD28 antibodies , and polarized in vitro to generate Th17 or Treg cells .
Glucose uptake , proliferation , cell cycle , protein expression ( phospho-Stat3 , phospho-Stat5 ) , and Th17 and Treg cell numbers were analyzed by flow cytometry .
AMP-activated protein kinase ( AMPK ) @ @ @ @ @ @ @ could inhibit the glucose uptake and proliferation of activated CD4T cells .
The proliferation inhibition was due to the G0/G1 phase arrest .
Phloretin decreased Th17 cell generation and phospho-Stat3 expression as well as increased Treg cell generation and phospho-Stat5 expression in the process of inducing Th17/Treg differentiation .
The phosphorylation level of AMPK was significantly enhanced , while the phosphorylation level of mTOR was significantly decreased in activated CD4T cells under phloretin treatment .
The AMPK signaling inhibitor compound C ( Com C ) could neutralize the effect of phloretin , while @ @ @ @ @ @ @ could impact the Th17/Treg balance similar to phloretin during Th17/Treg induction .
Conclusion : Our results suggest that phloretin can mediate the Th17/Treg balance by regulating metabolism via the AMPK signal pathway .

Objective: We conducted studies to explore the effect of phloretin on glucose uptake, proliferation, and differentiation of human peripheral blood CD4T cells and investigated the mechanism of phloretin on inducing Th17/Treg development.
Methods: Naïve CD4T cells were purified from peripheral blood of healthy volunteers, stimulated with anti-CD3/CD28 antibodies, and polarized in vitro to generate Th17 or Treg cells. Glucose uptake, proliferation, cell cycle, protein expression (phospho-Stat3, phospho-Stat5), and Th17 and Treg cell numbers were analyzed by flow cytometry. AMP-activated protein kinase (AMPK) signaling was analyzed by western blot.. Phloretin could inhibit the glucose uptake and proliferation of activated CD4T cells. The proliferation inhibition was due to the G0/G1 phase arrest. Phloretin decreased Th17 cell generation and phospho-Stat3 expression as well as increased Treg cell generation and phospho-Stat5 expression in the process of inducing Th17/Treg differentiation. The phosphorylation level of AMPK was significantly enhanced, while the phosphorylation level of mTOR was significantly decreased in activated CD4T cells under phloretin treatment. The AMPK signaling inhibitor compound C (Com C) could neutralize the effect of phloretin, while the agonist 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) could impact the Th17/Treg balance similar to phloretin during Th17/Treg induction.
Conclusion: Our results suggest that phloretin can mediate the Th17/Treg balance by regulating metabolism via the AMPK signal pathway.


greenmedinfo--2020-10-15--In vitro anti-inflammatory potential of phloretin microemulsion as a new formulation for prospective

In vitro anti-inflammatory potential of phloretin microemulsion as a new formulation for prospective treatment of vaginitis.

Phloretin is a promising polyphenolic compound known for its anti-inflammatory properties , but its poor solubility and low bioavailability hinder @ @ @ @ @ current date , its potential in the treatment of vaginitis has not been explored , @ @ @ @ @ reported its formulation as nanoparticles to overcome its pharmaceutical challenges .
Therefore , in the @ @ @ @ @ formulated in microemulsion of 11 nm size , and itsanti-inflammatory properties were explored using histamine @ @ @ @ @ , protease inhibition assay , and membrane stabilization potential .
The anti-inflammatory properties of phloretin @ @ @ @ @ drug phloretin , and the reference standard non-steroidal anti-inflammatory drugs ( NSAIDs ) .
Results @ @ @ @ @ phloretin microemulsion significantly inhibited the release of the inflammatory mediators histamine and IL-6 , inhibited @ @ @ @ @ membrane stabilization potential .
Phloretin microemulsion exhibited comparable anti-inflammatory properties to the NSAIDs diclofenac and @ @ @ @ @ , it can be delineated as a promising therapeutic tool in topical treatment of vaginal @ @

Phloretin is a promising polyphenolic compound known for its anti-inflammatory properties, but its poor solubility and low bioavailability hinder its clinical applicability. Till current date, its potential in the treatment of vaginitis has not been explored, and only very few papers reported its formulation as nanoparticles to overcome its pharmaceutical challenges. Therefore, in the current study, phloretin was formulated in microemulsion of 11 nm size, and itsanti-inflammatory properties were explored using histamine and IL-6 release inhibition assays, protease inhibition assay, and membrane stabilization potential. The anti-inflammatory properties of phloretin microemulsion were compared to the drug phloretin, and the reference standard non-steroidal anti-inflammatory drugs (NSAIDs). Results proved that both phloretin and phloretin microemulsion significantly inhibited the release of the inflammatory mediators histamine and IL-6, inhibited protease action, and exhibited membrane stabilization potential. Phloretin microemulsion exhibited comparable anti-inflammatory properties to the NSAIDs diclofenac and indomethacin, and, hence, it can be delineated as a promising therapeutic tool in topical treatment of vaginal inflammation.


greenmedinfo--2020-10-15--Pharmaconutrition revisited for critically ill patients with coronavirus disease 2019 (COVID-19): Do

Pharmaconutrition revisited for critically ill patients with coronavirus disease 2019 (COVID-19): Does selenium have a place?

Coronavirus disease 2019 ( COVID-19 ) is a global pandemic causing one of the biggest challenges for critical care medicine .
Mortality from COVID-19 is much greater in elderly men , many of whom succumb to acute respiratory distress syndrome ( ARDS ) triggered by the viral infection .
Because there is no specific antiviral treatment against COVID-19 , new strategies are urgently needed .
Selenium is an essential trace element with antioxidant and immunomodulatory effects .
Poor nutritional status increases the pathogenicity of viruses and low selenium in particular can be a determinant of viral virulence .
In the @ @ @ @ @ @ @ demonstrated some reduction in overall mortality , including how reduced incidence of ventilator-associated pneumonia and infectious complications such as ARDS in the critically ill. Consequently , we postulate that intravenous selenium therapy , could be part of the therapeutic fight against COVID-19 in intensive care unit patients with ARDS and that outcomes could be affected by age , sex , and body weight .
Our working hypothesis addresses the question : Could high-dose selenite pharmaconutrition , as an early pharmacologic intervention , be effective at reducing the incidence and the progression from type @ @ @ @ @ @ @ severe ARDS , multiorgan failure , and new infectious complications in patients with COVID-19 patients ?

Coronavirus disease 2019 (COVID-19) is a global pandemic causing one of the biggest challenges for critical care medicine. Mortality from COVID-19 is much greater in elderly men, many of whom succumb to acute respiratory distress syndrome (ARDS) triggered by the viral infection. Because there is no specific antiviral treatment against COVID-19, new strategies are urgently needed. Selenium is an essential trace element with antioxidant and immunomodulatory effects. Poor nutritional status increases the pathogenicity of viruses and low selenium in particular can be a determinant of viral virulence. In the past decade, selenium pharmaconutrition studies have demonstrated some reduction in overall mortality, including how reduced incidence of ventilator-associated pneumonia and infectious complications such as ARDS in the critically ill. Consequently, we postulate that intravenous selenium therapy, could be part of the therapeutic fight against COVID-19 in intensive care unit patients with ARDS and that outcomes could be affected by age, sex, and body weight. Our working hypothesis addresses the question: Could high-dose selenite pharmaconutrition, as an early pharmacologic intervention, be effective at reducing the incidence and the progression from type 1 respiratory failure (non-ARDS) to severe ARDS, multiorgan failure, and new infectious complications in patients with COVID-19 patients?


greenmedinfo--2020-10-15--Selenium prevents interferon-gamma induced activation of TRPM2 channel and inhibits inflammation, mi

Selenium prevents interferon-gamma induced activation of TRPM2 channel and inhibits inflammation, mitochondrial oxidative stress, and apoptosis in microglia.

Microglia as the primary immune cells of brain act protective effects against injuries and infections in the central nervous system .
Inflammation via excessive Cainflux and oxygen radical species ( ROS ) generation is a known factor in many neurodegenerative disorders .
Importantly , the Capermeable TRPM2 channel is activated by oxidative stress .
Thus , TRPM2 could provide the excessive Cainflux in the microglia .
Although TRPM2 expression level is high in inflammatory cells , the interplay between mouse microglia and TRPM2 channel during inflammation is not fully identified .
Thus , it is important to understand the mechanisms @ @ @ @ @ @ @ neuronal regeneration and repair .
The data presented here indicate that TRPM2 channels were activated in microglia cells by interferon-gamma ( IFNγ ) .
The IFNγ treatment further increased apoptosis ( early and late ) and cytokine productions ( TNF-α , IL-1β , and IL-6 ) which were due to increased lipid peroxidation and ROS generations as well as increased activationsof caspase -3 ( Casp-3 ) and - 9 ( Casp-9 ) .
However , selenium treatment diminished activations of TRPM2 , cytokine , Casp-3 , and Casp-9 , and levels of lipid @ @ @ @ @ @ @ microglia that were treated with IFNγ .
Moreover , addition of either PARP1 inhibitors ( PJ34 or DPQ ) or TRPM2 blockers ( 2-APB or ACA ) potentiated the modulator effects of selenium .
These results clearly suggest that IFNγ leads to TRPM2 activation in microglia cells ; whereas , selenium prevents IFNγ-mediated TRPM2 activation and cytokine generation .
Together the interplay between IFNγreleased from microglia cells is importance in brain inflammation and may affect oxidative cytotoxicity in the microglia .
Graphical abstract Summary of pathways involved in IFNγ-induced TRPM2 activation and microglia @ @ @ @ @ @ @ ROS ) : Modulator role of selenium ( Se ) .
The IFNγ causes the microglia activation .
Nudix box domain of TRPM2 is sensitive to ROS .
The ROS induces DNA damage and ADPR-ribose ( ADPR ) production in the nucleus via PARP1 enzyme activation .
ADPR and ROS-induced TRPM2 activation stimulates excessive Cainflux .
ROS are produced in the mitochondria through the increase of free cytosolic Ca ( via TRPM2 activation ) by the IFNγ treatment , although they are diminished by the TRPM2 channel blocker ( ACA and 2-APB ) @ @ @ @ @ @ @ mechanism in the cell death and inflammatory effects of IFNγ is mediated by stimulation of ROS-mediated caspase ( caspase -3 and - 9 ) activations and cytokine production ( TNF-α , IL-1β , and IL-6 ) via TRPM2 activation , respectively .
The apoptotic , inflammatory , and oxidant actions of IFNγ are modulated through TRPM2 inhibition by the Se treatment .

Microglia as the primary immune cells of brain act protective effects against injuries and infections in the central nervous system. Inflammation via excessive Cainflux and oxygen radical species (ROS) generation is a known factor in many neurodegenerative disorders. Importantly, the Capermeable TRPM2 channel is activated by oxidative stress. Thus, TRPM2 could provide the excessive Cainflux in the microglia. Although TRPM2 expression level is high in inflammatory cells, the interplay between mouse microglia and TRPM2 channel during inflammation is not fully identified. Thus, it is important to understand the mechanisms and factors involved in order to enhance neuronal regeneration and repair. The data presented here indicate that TRPM2 channels were activated in microglia cells by interferon-gamma (IFNγ). The IFNγ treatment further increased apoptosis (early and late) and cytokine productions (TNF-α, IL-1β, and IL-6) which were due to increased lipid peroxidation and ROS generations as well as increased activationsof caspase -3 (Casp-3) and - 9 (Casp-9). However, selenium treatment diminished activations of TRPM2, cytokine, Casp-3, and Casp-9, and levels of lipid peroxidation and mitochondrial ROS production in the microglia that were treated with IFNγ. Moreover, addition of either PARP1 inhibitors (PJ34 or DPQ) or TRPM2 blockers (2-APB or ACA) potentiated the modulator effects of selenium. These results clearly suggest that IFNγ leads to TRPM2 activation in microglia cells; whereas, selenium prevents IFNγ-mediated TRPM2 activation and cytokine generation. Together the interplay between IFNγreleased from microglia cells is importance in brain inflammation and may affect oxidative cytotoxicity in the microglia. Graphical abstract Summary of pathways involved in IFNγ-induced TRPM2 activation and microglia death through excessive reactive oxygen species (ROS): Modulator role of selenium(Se). The IFNγ causes the microglia activation. Nudix box domain of TRPM2 is sensitive to ROS. The ROS induces DNA damage and ADPR-ribose (ADPR) production in the nucleus via PARP1 enzyme activation. ADPR and ROS-induced TRPM2 activation stimulates excessive Cainflux. ROS are produced in the mitochondria through the increase of free cytosolic Ca(via TRPM2 activation) by the IFNγ treatment, although they are diminished by the TRPM2 channel blocker (ACA and 2-APB) and PARP1 inhibitor treatments. The main mechanism in the cell death and inflammatory effects of IFNγ is mediated by stimulation of ROS-mediated caspase (caspase -3 and - 9) activations and cytokine production (TNF-α, IL-1β, and IL-6) via TRPM2 activation, respectively. The apoptotic, inflammatory, and oxidant actions of IFNγ are modulated through TRPM2 inhibition by the Se treatment.


greenmedinfo--2020-10-15--Progression of heart failure is attenuated by antioxidant therapy with N-acetylcysteine in myocardia

Progression of heart failure is attenuated by antioxidant therapy with N-acetylcysteine in myocardial infarcted female rats.

This study investigated the therapeutic potential of N-acetylcysteine ( NAC ) in the treatment of heart failure in female rats .
Myocardial infarcted ( MI ) rats were given NAC ( 250 mg/kg/day p.o . )
during 28 days after surgery ( MI + NAC ) or vehicle ( MI + Placebo ) , and sham-operated rats received the same treatments ( Sham + NAC and Sham + Placebo ) .
Electrocardiographic and echocardiographic analyses were performed in the last week of treatment .
Cardiac mRNA levels of types I and II superoxide dismutase ( SOD ) , catalase , @ @ @ @ @ @ @ GPX ) , nerve growth factor ( NGF ) , β1-adrenergic receptor ( β1ADR ) , and type 2 muscarinic receptor ( M2R ) were assessed .
Cardiac levels NADPH oxidase ( NOX ) activitytotal content of reduced thiols , and SOD , GPX , and catalase activity were assessed .
Compared to MI + Placebo group , MI + NAC group exhibited decreased NOX activity , increased content of reduced thiols , increased GPX activity , and normalized GPX III mRNA levels ( p < 0.05 ) .
Heart and lung weights @ @ @ @ @ @ @ volume and left atrium/aorta ratio were decreased , while LV posterior wall thickness and ejection fraction were increased in MI + NAC group versus MI + Placebo rats ( p < 0.05 ) .
Power density of low frequency band was decreased , while power density of high frequency and the root mean square of the successive differences were increased in MI + NAC rats versus MI + Placebo ( p < 0.05 ) .
These findings indicate that NAC promotes therapeutic effects in the progression of MI-induced heart failure in female rats @

This study investigated the therapeutic potential of N-acetylcysteine (NAC) in the treatment of heart failure in female rats. Myocardial infarcted (MI) rats were given NAC (250 mg/kg/day p.o.) during 28 days after surgery (MI + NAC) or vehicle (MI + Placebo), and sham-operated rats received the same treatments (Sham + NAC and Sham + Placebo). Electrocardiographic and echocardiographic analyses were performed in the last week of treatment. Cardiac mRNA levels of types I and II superoxide dismutase (SOD), catalase, types I and III glutathione peroxidase (GPX), nerve growth factor (NGF),β1-adrenergic receptor (β1ADR), and type 2 muscarinic receptor (M2R) were assessed. Cardiac levels NADPH oxidase (NOX) activitytotal content of reduced thiols, and SOD, GPX, and catalase activity were assessed. Compared to MI + Placebo group, MI + NAC group exhibited decreased NOX activity, increased content of reduced thiols, increased GPX activity, and normalized GPX III mRNA levels (p<0.05). Heart and lung weights, left ventricular (LV) end-diastolic volume and left atrium/aorta ratio were decreased, while LV posterior wall thickness and ejection fraction were increased in MI + NAC group versus MI + Placebo rats (p<0.05). Power density of low frequency band was decreased, while power density of high frequency and the root mean square of the successive differences were increased in MI + NAC rats versus MI + Placebo (p<0.05). These findings indicate that NAC promotes therapeutic effects in the progression of MI-induced heart failure in female rats.


greenmedinfo--2020-10-15--N-acetylcysteine was shown to protect zebrafish against the development of clofazimine-induced cardi

N-acetylcysteine was shown to protect zebrafish against the development of clofazimine-induced cardiac dysfunction.

BACKGROUND : Clofazimine ( CFZ ) , a riminophenazine , is now commonly used in the treatment of multidrug-resistant tuberculosis .
However , its use may be potentially associated with cardiac dysfunction in some individuals .
In this study , the zebrafish heart , by merit of its developmental and genetic characteristics being in homology with that of human , was chosen as an animal model for evaluation of such dysfunction .
METHODS : Morphological and physiological parameters were used to assess cardiac dysfunction .
Transcriptome analysis was performed , followed by validation with real-time quantitative PCR , for delineation @ @ @ @ @ @ @ Exposure of 2 dpf zebrafish to 4 mg/L CFZ for 2 days , adversely affected cardiac functions including significant decreases in HR , SV , CO , and FS , with observable pathophysiological developments of pericardial effusion and blood accumulation in the heart , in comparison with the control group .
In addition , genes which respond to xenobiotic stimulus , related to oxygen transport , glutathione metabolism and extracellular matrix -receptor interactions , were significantly enriched among the differentially up-regulated genes .
Antioxidant response element motif was enriched in the 5000 base @ @ @ @ @ @ @ genes .
Co-administration of N-acetylcysteine was shown to protect zebrafish against the development of CFZ-induced cardiac dysfunction .
CONCLUSIONS : This study suggests an important role of oxidative stress as a major pathogenetic mechanism of riminophenazine-induced cardiac dysfunction .

BACKGROUND: Clofazimine (CFZ), a riminophenazine, is now commonly used in the treatment of multidrug-resistant tuberculosis. However, its use may be potentially associated with cardiac dysfunction in some individuals. In this study, the zebrafish heart, by merit of its developmental and genetic characteristics being in homology with that of human, was chosen as an animal model for evaluation of such dysfunction.
METHODS: Morphological and physiological parameters were used to assess cardiac dysfunction. Transcriptome analysis was performed, followed by validation with real-time quantitative PCR, for delineation of the relevant genomics.
RESULTS: Exposure of 2 dpf zebrafish to 4 mg/L CFZ for 2 days, adversely affected cardiac functions including significant decreases in HR, SV, CO, and FS, with observable pathophysiological developments of pericardial effusion and blood accumulation in the heart, in comparison with the control group. In addition, genes which respond to xenobiotic stimulus, related to oxygen transport, glutathione metabolism and extracellular matrix -receptor interactions, were significantly enriched among the differentially up-regulated genes. Antioxidant response element motif was enriched in the 5000 base pair upstream regions of the differentially expressed genes. Co-administration of N-acetylcysteine was shown to protect zebrafish against the development of CFZ-induced cardiac dysfunction.
CONCLUSIONS: This study suggests an important role of oxidative stress as a major pathogenetic mechanism of riminophenazine-induced cardiac dysfunction.


greenmedinfo--2020-10-15--NAC restores T-cell numbers in tumors and increases the ability of M30 and aOX40 to slow tumor growt

BACKGROUND & AIMS : Non-alcoholic steatohepatitis causes loss of hepatic CD4T cells and promotes tumor growth .
The liver is the most common site of distant metastases from a variety of malignancies , many of which respond to immunotherapy .
We investigated the effects of steatohepatitis on the efficacy of immunotherapeutic agents against liver tumors in mice .
METHODS : Steatohepatitis was induced by feeding C57BL/6NCrl or BALB/c AnNCr mice a methionine and choline-deficient diet ( MCD ) or a choline-deficient L-amino acid-defined diet ( CDAA ) .
Mice were given intrahepatic or subcutaneous injections of B16 melanoma and CT26 @ @ @ @ @ @ @ intravenous injections of mRNA vaccine ( M30 ) or intraperitoneal injections of an antibody against OX40 ( aOX40 ) on days 3 , 7 , and 10 after injection of the tumor cells .
We measured tumor growth and analyzed immune cells in tumor tissues by flow cytometry .
Mice were given N-acetylcysteine ( NAC ) to prevent loss of CD4T cells from liver .
RESULTS : Administration of M30 and aOX40 inhibited growth of tumors from intrahepatic injections of B16 or CT26 cells in mice on regular diet .
However , M30 @ @ @ @ @ @ @ liver tumors from B16 or CT26 cells in mice with diet-induced steatohepatitis ( MCD or CDAA ) .
Steatohepatitis did not affect the ability of M30 to slow growth of subcutaneous B16 tumors .
In mice with steatohepatitis given NAC , which prevents loss of CD4T cells , M30 and aOX40 were able slow growth of hepatic tumors .
Flow cytometry analysis of liver tumors revealed reduced CD4T cells and effector memory cells in mice with vs without steatohepatitis CONCLUSIONS : Steatohepatitis reduces the abilities of immunotherapeutic agents such as M30 and aOX40 @ @ @ @ @ @ @ tumor infiltration by CD4T cells and effector memory cells .
NAC restores T-cell numbers in tumors and increases the ability of M30 and aOX40 to slow tumor growth in mice .

BACKGROUND & AIMS: Non-alcoholic steatohepatitis causes loss of hepatic CD4T cells and promotes tumor growth. The liver is the most common site of distant metastases from a variety of malignancies, many of which respond to immunotherapy. We investigated the effects of steatohepatitis on the efficacy of immunotherapeutic agents against liver tumors in mice.
METHODS: Steatohepatitis was induced by feeding C57BL/6NCrl or BALB/c AnNCr mice a methionine and choline-deficient diet (MCD) or a choline-deficient L-amino acid-defined diet (CDAA). Mice were given intrahepatic or subcutaneous injections of B16 melanoma and CT26 colon cancer cells, followed by given intravenous injections of mRNA vaccine (M30) or intraperitoneal injections of an antibody against OX40 (aOX40) on days 3, 7, and 10 after injection of the tumor cells. We measured tumor growth and analyzed immune cells in tumor tissues by flow cytometry. Mice were given N-acetylcysteine (NAC) to prevent loss of CD4T cells from liver.
RESULTS: Administration of M30 and aOX40 inhibited growth of tumors from intrahepatic injections of B16 or CT26 cells in mice on regular diet. However, M30 and/or aOX40 did not slow growth of liver tumors from B16 or CT26 cells in mice with diet-induced steatohepatitis (MCD or CDAA). Steatohepatitis did not affect the ability of M30 to slow growth of subcutaneous B16 tumors. In mice with steatohepatitis given NAC, which prevents loss of CD4T cells, M30 and aOX40 were able slow growth of hepatic tumors. Flow cytometry analysis of liver tumors revealed reduced CD4T cells and effector memory cells in mice with vs without steatohepatitis CONCLUSIONS: Steatohepatitis reduces the abilities of immunotherapeutic agents such as M30 and aOX40 to inhibit tumor liver growth by reducing tumor infiltration by CD4T cells and effector memory cells. NAC restores T-cell numbers in tumors and increases the ability of M30 and aOX40 to slow tumor growth in mice.


greenmedinfo--2020-10-15--6-shogaol suppresses induced human 786-O renal cell carcinoma osteoclastogenic activity and metastat

6-shogaol suppresses induced human 786-O renal cell carcinoma osteoclastogenic activity and metastatic potential.

2-Amino-1-methyl-6-phenylimidazo [ 4,5-b ] pyridine ( PhIP ) which can be detected in processed meats and red meats , is a potential carcinogen for renal cell carcinoma ( RCC ) .
Approximately 30 % of patients with metastatic RCC have bone metastases , and the prognosis of RCC with bone metastases is poor .
Thus , the aim of the present study was to investigate whether PhIP induced bone metastases and to develop novel therapeutic agents .
Our data revealed that PhIP pre-treatment increased the production of parathyroid hormone-related protein ( PTHrP ) in human 786-O renal cell carcinoma cells @ @ @ @ @ @ @ osteoblasts with PhIP-stimulated condition medium of 786-O increased the expression of the macrophage colony-stimulating factor ( M-CSF ) and receptor activator of nuclear factor kappa-B ligand ( RANKL ) , and decreased the expression of osteoprotegerin ( OPG ) .
In addition , PhIP-mediated PTHrP up-regulated as well as increased IL-8 secretion in 786-O cells , and then contributed to 786-O-mediated bone resorption .
Furthermore , 6-shogaol , which is an active ingredient in ginger , showed suppressive effects on PhIP-mediated bone resorption .
In summary , this is the first study to @ @ @ @ @ @ @ effect of human renal cell carcinoma 786-O on osteoclastogenesis activity directly by PTHrP .
In addition , 6-shogaol treatment reverses PhIP-mediated bone resorption .
It suggests that 6-shogaol treatment results in bone resorption activity in the RCC model in vitro .

2-Amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) which can be detected in processed meats and red meats, is a potential carcinogen for renal cell carcinoma (RCC). Approximately 30% of patients with metastatic RCC have bone metastases, and the prognosis of RCC with bone metastases is poor. Thus, the aim of the present study was to investigate whether PhIP induced bone metastases and to develop novel therapeutic agents. Our data revealed that PhIP pre-treatment increased the production of parathyroid hormone-related protein (PTHrP) in human 786-O renal cell carcinoma cells. Subsequently, the cultures of human osteoblasts with PhIP-stimulated condition medium of 786-O increased the expression of the macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kappa-B ligand (RANKL), and decreased the expression of osteoprotegerin (OPG). In addition, PhIP-mediated PTHrP up-regulated as well as increased IL-8 secretion in 786-O cells, and then contributed to 786-O-mediated bone resorption. Furthermore, 6-shogaol, which is an active ingredient in ginger, showed suppressive effects on PhIP-mediated bone resorption. In summary, this is the first study to demonstrate that PhIP pre-treatment increases the stimulatory effect of human renal cell carcinoma 786-O on osteoclastogenesis activity directly by PTHrP. In addition, 6-shogaol treatment reverses PhIP-mediated bone resorption. It suggests that 6-shogaol treatment results in bone resorption activity in the RCC model in vitro.


greenmedinfo--2020-10-16--Ganoderic acid D induces synergistic autophagic cell death except for apoptosis in esophageal squamo

Ganoderic acid D induces synergistic autophagic cell death except for apoptosis in esophageal squamous cell carcinoma cells.

ETHNOPHAMACOLOGICAL RELEVANCE : Ganoderma lucidum has been used as a medicinal mushroom for more than 2000 years in China .
Ganoderic acid D ( GAD ) as a representative active triterpenoid from Ganoderma lucidum is known to possess anticancer activity .
However , the mechanism involved in its anticancer cell process is still largely elusive .
AIM OF THE STUDY : Our study aimed to investigate the anticancer effects of GAD on the esophageal squamous cell carcinoma ( ESCC ) cells and the underlying mechanisms at the cell level .
MATERIALS AND METHODS : EC9706 and Eca109 cells were treated @ @ @ @ @ @ @ 20 , 40 μM ) for 24 h. The cell viability , cell cycle , reactive oxygen species ( ROS ) , mitochondrial membrane potential ( MMP ) , apoptosis rate , caspase-3 activity , autophagic flux , lysosomal function were examined .
Cell cycle , apoptotic , autophagy and mTOR signalpathway related proteins such as P53 , Cyclin B1 , CytoC , PARP , Beclin-1 , P62 , LC3 , PI3K , AKT and mTOR were analyzed by Western blot approach .
RESULTS : GAD inhibited cell proliferation and induced both apoptosis @ @ @ @ @ @ @ , we found that in the early stage of the autophagic process , GAD could initiate and enhance the autophagy signal while in the late stage it on the contrary could block the autophagic flux by impairing the autophagosome-lysosome fusion and inhibited the lysosomal degradation .
Besides the autophagic cell death , GAD also induced the apoptosis mediated by caspase-related process in parallel .
The mechanism involved for the synergistic apoptotic and autophagic cell death was also explored .
We found that GAD down-regulated the expression of PI3K , AKT and mTOR phosphorylated @ @ @ @ @ @ @ thus led to the synergistic effect on apoptosis and autophagic cell death in the ESCC cells .
CONCLUSIONS : In summary , this study has documented that GAD may inhibit cell proliferation through the mTOR pathway in ESCC cells , and induce synergistic apoptosis and autophagic cell death by disrupting the autophagic flux .
This work therefore also suggests that GAD may be used as an efficient anticancer adjuvant for ESCC cancer therapy .

ETHNOPHAMACOLOGICAL RELEVANCE: Ganoderma lucidum has been used as a medicinal mushroom for more than 2000 years in China. Ganoderic acid D (GAD) as a representative active triterpenoid from Ganoderma lucidum is known to possess anticancer activity. However, the mechanism involved in its anticancer cell process is still largely elusive.
AIM OF THE STUDY: Our study aimed to investigate the anticancer effects of GAD on the esophageal squamous cell carcinoma (ESCC) cells and the underlying mechanisms at the cell level.
MATERIALS AND METHODS: EC9706 and Eca109 cells were treated with GAD (0, 10, 20, 40 μM) for 24 h. The cell viability, cell cycle, reactive oxygen species (ROS), mitochondrial membrane potential (MMP), apoptosis rate, caspase-3 activity, autophagic flux, lysosomal function were examined. Cell cycle, apoptotic, autophagy and mTOR signalpathway related proteins such as P53, Cyclin B1, CytoC, PARP, Beclin-1, P62, LC3, PI3K, AKT and mTOR were analyzed by Western blot approach.
RESULTS: GAD inhibited cell proliferation and induced both apoptosis and autophagic cell death. In particular, we found that in the early stage of the autophagic process, GAD could initiate and enhance the autophagy signal while in the late stage it on the contrary could block the autophagic flux by impairing the autophagosome-lysosome fusion and inhibited the lysosomal degradation. Besides the autophagic cell death, GAD also induced the apoptosis mediated by caspase-related process in parallel. The mechanism involved for the synergistic apoptotic and autophagic cell death was also explored. We found that GAD down-regulated the expression of PI3K, AKT and mTOR phosphorylated proteins in the mTOR signaling pathway which thus led to the synergistic effect on apoptosis and autophagic cell death in the ESCC cells.
CONCLUSIONS: In summary, this study has documented that GAD may inhibit cell proliferation through the mTOR pathway in ESCC cells, and induce synergistic apoptosis and autophagic cell death by disrupting the autophagic flux. This work therefore also suggests that GAD may be used as an efficient anticancer adjuvant for ESCC cancer therapy.


greenmedinfo--2020-10-16--Ganoderma lucidum spore ethanol extract attenuates atherosclerosis.

CONTEXT : ( Leyss.ex Fr . )
Karst ( Ganodermataceae ) is a fungus that has been used in traditional Chinese medicine .
OBJECTIVE : This is the first investigation of the lipid-lowering and anti-atherosclerotic effects ofspore ethanol extract ( EEG ) in hyperlipidemic rabbits .
MATERIALS AND METHODS : Fifty-four Japanese rabbits were randomly divided into six groups ( = 9 ) : control , model , atorvastatin and three EEG groups ( 6 , 24 and 96 mg/kg/day , p.o. )
.
Control group was administered a normal diet and other groups were administered a high-fat diet to @ @ @ @ @ @ @ .
During this time , lipid profiles were recorded ; lipid testing and histopathological examination of aorta and liver were conducted .
LXRα and its downstream genes expression in the liver and small intestine were examined .
The effect of EEG on macrophage cholesterol efflux and ABCA1/G1 expression was observed under silenced LXRα expression .
RESULTS : EEG reduced serum cholesterol ( 20.33 ± 3.62 mmol/L vs 34.56 ± 8.27 mmol/L for the model group ) and LDL-C , reduced the area of arterial plaques ( 24.8 ± 10 % vs 53.9 ± @ @ @ @ @ @ @ and Intima/Medium thickness ratio , increased faecal bile acid content , upregulated LXRα , CYP7A1 , ABCA1/G1 , ABCG5/G8 expression in the liver , small intestine and macrophages .
After silencing LXRα in macrophages , the ability of EEG to promote cholesterol efflux was inhibited .
DISCUSSION AND CONCLUSION : EEG exert lipid-lowering and anti-atherosclerotic effects via upregulating expression of LXRα and downstream genes associated with reverse cholesterol transport and metabolism .
However , whether PPARα/γ are involved in the up-regulation of LXR expression by EEG remains to be elucidated .

CONTEXT: (Leyss.ex Fr.) Karst (Ganodermataceae) is a fungus that has been used in traditional Chinese medicine.
OBJECTIVE: This is the first investigation of the lipid-lowering and anti-atherosclerotic effects ofspore ethanol extract (EEG) in hyperlipidemic rabbits.
MATERIALS AND METHODS: Fifty-four Japanese rabbits were randomly divided into six groups ( = 9): control, model, atorvastatin and three EEG groups (6, 24 and 96 mg/kg/day, p.o.). Control group was administered a normal diet and other groups were administered a high-fat diet to induce hyperlipidaemia and atherosclerosis for 14 weeks. During this time, lipid profiles were recorded;lipid testing and histopathological examination of aorta and liver were conducted. LXRα and its downstream genes expression in the liver and small intestine were examined. The effect of EEG on macrophage cholesterol efflux and ABCA1/G1 expression was observed under silenced LXRα expression.
RESULTS: EEG reduced serum cholesterol (20.33 ± 3.62 mmol/L vs 34.56 ± 8.27 mmol/L for the model group) and LDL-C, reduced the area of arterial plaques (24.8 ± 10% vs 53.9 ± 15.2% for the model group) and Intima/Medium thickness ratio, increased faecal bile acid content, upregulated LXRα, CYP7A1, ABCA1/G1, ABCG5/G8 expression in the liver, small intestine and macrophages. After silencing LXRα in macrophages, the ability of EEG to promote cholesterol efflux was inhibited.
DISCUSSION AND CONCLUSION: EEG exert lipid-lowering and anti-atherosclerotic effects via upregulating expression of LXRα and downstream genes associated with reverse cholesterol transport and metabolism. However, whether PPARα/γ are involved in the up-regulation of LXR expression by EEG remains to be elucidated.


greenmedinfo--2020-10-16--A proteoglycan extract from Ganoderma Lucidum protects pancreatic beta-cells against STZ-induced apo

A proteoglycan extract from Ganoderma Lucidum protects pancreatic beta-cells against STZ-induced apoptosis.

: The pancreaticβ-cell death or dysfunction induced by oxidative stress plays an important effect on the development and progression of @ @ @ @ @ our previous findings , a natural proteoglycan extracted from , named , could treat T2DM @ @ @ @ @ we investigated the effects ofon STZ-induced apoptosis of INS-1 cells and its underlying mechanisms .
@ @ @ @ @ the cell viability and alleviated the apoptosis in STZ-treated INS-1 cells .
Moreover , markedly @ @ @ @ @ and NO release , and deactivated NF-κB , JNK , and p38 MAPK signaling pathways @ @ @ @ @ Furthermore , improved the insulin secretion through inhibiting the activation of JNK and improving the @ @ @ @ @ cells damaged by STZ .
These results indicated thatcould protect pancreaticβ-cells against apoptosis and dysfunction @ @ @ @ @ a promising pharmacological medicine for diabetes management .

: The pancreaticβ-cell death or dysfunction induced by oxidative stress plays an important effect on the development and progression of diabetes mellitus. Based on our previous findings, a natural proteoglycan extracted from, named, could treat T2DM. In this study, we investigated the effects ofon STZ-induced apoptosis of INS-1 cells and its underlying mechanisms. The results showed thatsignificantly improved the cell viability and alleviated the apoptosis in STZ-treated INS-1 cells. Moreover,markedly decreased the intracellular ROS accumulation and NO release, and deactivated NF-κB, JNK, and p38 MAPK signaling pathways in STZ-induced INS-1 cells. Furthermore,improved the insulin secretion through inhibiting the activation of JNK and improving the expression of Pdx-1 in INS-1 cells damaged by STZ. These results indicated thatcould protect pancreaticβ-cells against apoptosis and dysfunction, and be used as a promising pharmacological medicine for diabetes management.
ABBREVIATIONS: T2DM: type 2 diabetes mellitus;: Fudan-Yueyang; ROS: reactive oxygen species; NO: reactive oxygen species; NF-κB: nuclear factor kappa beta; JNK: c-jun N-terminal kinase; MAPK: mitogen-activated protein kinase; Pdx-1: Pancreatic duodenal homeobox 1.


greenmedinfo--2020-10-16--Ganoderma lucidum ameliorates neurobehavioral changes and oxidative stress induced by ethanol binge

Ganoderma lucidum ameliorates neurobehavioral changes and oxidative stress induced by ethanol binge drinking.

, mushroom used for centuries by Asian peoples as food supplement , has been shown interesting biological activities , including over the Central Nervous System .
Besides , these mushroom bioactive compounds present antioxidant and anti-inflammatory activities .
On the side , binge drinking paradigm consists of ethanol exposure that reflects the usual consumption of adolescents , which elicits deleterious effects , determined by high ethanol consumption , in a short period .
In this study , we investigated whether the Aqueous Extract of ( AEGl ) reduces the behavioral disorders induced by alcohol .
Male ( = 30 ) @ @ @ @ @ @ @ ) , seventy-two days old , were used for behavioral/biochemical and oral toxicity test , respectively .
Animals were exposed to 5 binges ( beginning at 35 days old ) of ethanol ( 3 g/kg/day ) or distilled water .
Twenty-four hours after the last binge administration , animals received AEGl ( 100 mg/kg/day ) or distilled water for three consecutive days .
After treatment protocol , open field , elevated plus maze , forced swim , and step-down inhibitory avoidance tests were performed .
Oxidative stress parameters were measured to evaluate the @ @ @ @ @ @ @ AEGl elicited the recovery of spontaneous horizontal exploration capacity , anxiogenic- and depressive-profile , as well as short-term memory damage induced by binge-ethanol exposure .
The behavioral effects of the extract were associated to the reequilibrium of the animals ' REDOX balance .
Thus , AEGl , a medicinal mushroom , ameliorates behavioral alteration on a model of motor , cognitive and psychiatric-like disorders induced by binge drinking paradigm and emerges as a useful tool as a food supplement in the management of disorders of alcoholic origin .

, mushroom used for centuries by Asian peoples as food supplement, has been shown interesting biological activities, including over the Central Nervous System. Besides, these mushroom bioactive compounds present antioxidant and anti-inflammatory activities. On the side, binge drinking paradigm consists of ethanol exposure that reflects the usual consumption of adolescents, which elicits deleterious effects, determined by high ethanol consumption, in a short period. In this study, we investigated whether the Aqueous Extract of(AEGl) reduces the behavioral disorders induced by alcohol. Male (= 30) and female Wistar rats (= 40), seventy-two days old, were used for behavioral/biochemical and oral toxicity test, respectively. Animals were exposed to 5 binges (beginning at 35 days old) of ethanol (3 g/kg/day) or distilled water. Twenty-four hours after the last binge administration, animals received AEGl (100 mg/kg/day) or distilled water for three consecutive days. After treatment protocol, open field, elevated plus maze, forced swim, and step-down inhibitory avoidance tests were performed. Oxidative stress parameters were measured to evaluate the REDOX balance. Our results demonstrated that AEGl elicited the recovery of spontaneous horizontal exploration capacity, anxiogenic- and depressive-profile, as well as short-term memory damage induced by binge-ethanol exposure. The behavioral effects of the extract were associated to the reequilibrium of the animals' REDOX balance. Thus, AEGl, a medicinal mushroom, ameliorates behavioral alteration on a model of motor, cognitive and psychiatric-like disorders induced by binge drinking paradigm and emerges as a useful tool as a food supplement in the management of disorders of alcoholic origin.


greenmedinfo--2020-10-16--Ganoderma lucidum ethanol extracts enhance re-epithelialization and prevent keratinocytes from free-

Ganoderma lucidum ethanol extracts enhance re-epithelialization and prevent keratinocytes from free-radical injury.

or Reishi is recognized as the most potent adaptogen present in nature , and its anti-inflammatory , antioxidant , immunomodulatory and anticancer activities are well known .
Moreover , lately , there has been an increasing interest from pharmaceutical companies in antiaging-extract-based formulations .
Nevertheless , the pharmacological mechanisms of such adaptogenic and regenerative actions remain unclear .
The present investigation aimed to explore its molecular and cellular effects in vitro in epidermal keratinocyte cultures by applying liquid chromatography coupled to ion trap time-of-flight mass spectrometry ( LCMS-IT-TOF ) for analysis of ethanol extracts using ganoderic acid-A as a reference @ @ @ @ @ @ @ induction accompanied by an increase of cyclic kinase protein expressions , such as CDK2 and CDK6 .
Furthermore , a noteworthy migration rate increase and activation of tissue remodelling factors , such as matrix metalloproteinases 2 and 9 ( MMP-2 and MMP-9 ) , were observed .
Finally , the extract showed an antioxidant effect , protecting from HO-induced cytotoxicity ; preventing activation of AKT ( protein kinase B ) , ERK ( extracellular signal-regulated kinase ) , p53 and p21 ; and reducing the number of apoptotic cells .
Our study paves @ @ @ @ @ @ @ its potential development as cosmeceutical skin products , providing the first evidence of its capability to accelerate the healing processes enhancing re-epithelialization and to protect cells from free-radical action .

or Reishi is recognized as the most potent adaptogen present in nature, and its anti-inflammatory, antioxidant, immunomodulatory and anticancer activities are well known. Moreover, lately, there has been an increasing interest from pharmaceutical companies in antiaging-extract-based formulations. Nevertheless, the pharmacological mechanisms of such adaptogenic and regenerative actions remain unclear. The present investigation aimed to explore its molecular and cellular effects in vitro in epidermal keratinocyte cultures by applying liquid chromatography coupled to ion trap time-of-flight mass spectrometry (LCMS-IT-TOF) for analysis of ethanol extracts using ganoderic acid-A as a reference compound. Theextract showed a keratinocyte proliferation induction accompanied by an increase of cyclic kinase protein expressions, such as CDK2 and CDK6. Furthermore, a noteworthy migration rate increase and activation of tissue remodelling factors, such as matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9), were observed. Finally, the extract showed an antioxidant effect, protecting from HO-induced cytotoxicity; preventing activation of AKT (protein kinase B), ERK (extracellular signal-regulated kinase), p53 and p21; and reducing the number of apoptotic cells. Our study paves the path for elucidating pharmacological properties ofand its potential development as cosmeceutical skin products, providing the first evidence of its capability to accelerate the healing processes enhancing re-epithelialization and to protect cells from free-radical action.


greenmedinfo--2020-10-16--Ganoderma Lucidum from red mushroom attenuates formaldehyde-induced liver damage.

The majority of liver-related illnesses are caused by occupational and domestic exposure to toxic chemicals like formaldehyde ( FA ) , which is widely common in Africa and the world at large .
Hence , measures should be taken to protect humans from its hazardous effects .
This study , therefore , examines the protective potential of ( 100 mg/kg body weight ) on formaldehyde-induced ( 40 % ) liver oxido-inflammation in male rats .
Male Wistar rats , 150-200 g , were allotted into four groups of 10 animals as follows : Group 1 was orally treated with 1 @ @ @ @ @ @ @ exposed to a 40 % formaldehyde vapor environment for 30 min per day , Group 3 was orally treated with 100 mg/kg ethanol extract of , and Group 4 was co-administered formaldehyde and 100 mg/kg ethanol extract of .
Rats were then sacrificed 24 h after administering the last dose of treatment , and the livers were excised.significantly reversed the formaldehyde-mediated reduction in body and organ weight.administration significantly prevented oxido-inflammation by reducing the levels of hydrogen peroxide and malondialdehyde and increasing the activity of antioxidant enzymes and glutathione contents , as well as @ @ @ @ @ @ @ production in FA-treated rats .
Additionally , reversed a large decline in proinflammatory markers in formaldehyde .
Furthermore , restores formaldehyde-induced histological alterations in the liver .
Collectively , our results provide valuable information on the protective potential ofin protecting formaldehyde-induced liver oxido-inflammation in male rats .

The majority of liver-related illnesses are caused by occupational and domestic exposure to toxic chemicals like formaldehyde (FA), which is widely common in Africa and the world at large. Hence, measures should be taken to protect humans from its hazardous effects. This study, therefore, examines the protective potential of(100 mg/kg body weight) on formaldehyde-induced (40%) liver oxido-inflammation in male rats. Male Wistar rats, 150-200 g, were allotted into four groups of 10 animals as follows: Group 1 was orally treated with 1 mg/mL distilled water, Group 2 was exposed to a 40% formaldehyde vapor environment for 30 min per day, Group 3 was orally treated with 100 mg/kg ethanol extract of, and Group 4 was co-administered formaldehyde and 100 mg/kg ethanol extract of. Rats were then sacrificed 24 h after administering the last dose of treatment, and the livers were excised.significantly reversed the formaldehyde-mediated reduction in body and organ weight.administration significantly prevented oxido-inflammation by reducing the levels of hydrogen peroxide and malondialdehyde and increasing the activity of antioxidant enzymes and glutathione contents, as well as the normal level of nitrite and myeloperoxidase production in FA-treated rats. Additionally,reversed a large decline in proinflammatory markers in formaldehyde. Furthermore,restores formaldehyde-induced histological alterations in the liver. Collectively, our results provide valuable information on the protective potential ofin protecting formaldehyde-induced liver oxido-inflammation in male rats.


greenmedinfo--2020-10-16--Ganoderma lucidum put forth anti-tumor activity against PC-3 prostate cancer cells.

Background : Prostate cancer ( PCA ) is a frequent cancer that mainly affects the men .
Studying growth feature pathways modified during PCA development may facilitate researchers to expand embattled therapeutic strategies for prostate cancer .
In present study , we examined the anticancer potentials ofagainst the prostate cancer ( PC-3 ) cells by inflection of JAK-1/STAT-3 signalling pathway .
Methods : The cytotoxicity ofagainst the PC-3 cells was examined by MTT assay .
The ROS production was monitored by using DCFH-DA staining .
The apoptotic morphological alterations stimulatory potential ofon PC-3 cells was inspected through the dual staining @ @ @ @ @ @ @ , STAT3 , Bax and CyclinD1 proteins were measured by western blotting .
The caspase-3 and 9 functions were condensed by assay kit .
Results : Findings demonstrates theconvince cytotoxicity , accretion of ROS , and apoptosis stimulation in PC-3 cells .
In addition , signal transducer and activating transcription ( STAT-3 ) is a successive oncogenic transcriptional factor that regularizes multiplication and apoptosis in cells .
Discretion of STAT-3 transcription deliberated as original approach to hinder prostate cell growth .
In present exploration , we ascertain thathold back STAT-3 translocation , in @ @ @ @ @ @ @ , BCL-2 , cyclin-D1 and declined the Bax , caspase-3 and 9 expressions in PC-3 cells .
Conclusion : In the end our finding concluded thathinder prostate cell development and convinces apoptosis via hampering the translocation STAT-3 .

Background: Prostate cancer (PCA) is a frequent cancer that mainly affects the men. Studying growth feature pathways modified during PCA development may facilitate researchers to expand embattled therapeutic strategies for prostate cancer. In present study, we examined the anticancer potentials ofagainst the prostate cancer (PC-3) cells by inflection of JAK-1/STAT-3 signalling pathway.
Methods: The cytotoxicity ofagainst the PC-3 cells was examined by MTT assay. The ROS production was monitored by using DCFH-DA staining. The apoptotic morphological alterations stimulatory potential ofon PC-3 cells was inspected through the dual staining. The expression of Bcl-2, JAK-1, STAT3, Bax and CyclinD1 proteins were measured by western blotting. The caspase-3 and 9 functions were condensed by assay kit.
Results: Findings demonstrates theconvince cytotoxicity, accretion of ROS, and apoptosis stimulation in PC-3 cells. In addition, signal transducer and activating transcription (STAT-3) is a successive oncogenic transcriptional factor that regularizes multiplication and apoptosis in cells. Discretion of STAT-3 transcription deliberated as original approach to hinder prostate cell growth. In present exploration, we ascertain thathold back STAT-3 translocation, in that way dropping the eminent expression of, BCL-2, cyclin-D1 and declined the Bax, caspase-3 and 9 expressions in PC-3 cells.
Conclusion: In the end our finding concluded thathinder prostate cell development and convinces apoptosis via hampering the translocation STAT-3.


greenmedinfo--2020-10-16--Effects of WSG, a polysaccharide from Ganoderma lucidum, on suppressing cell growth and mobility of

Effects of WSG, a polysaccharide from Ganoderma lucidum, on suppressing cell growth and mobility of lung cancer.

WSG is a water soluble polysaccharides isolated from Ganoderma lucidum .
In this study , we showed that WSG , @ @ @ @ @ average molecular mass of approximately 1000 kDa , effectively inhibited cell viability and mobility of @ @ @ @ @ studies revealed that WSG reduced phosphorylation of ERK1/2 in cells upon either EGF or TGFβ @ @ @ @ @ phosphorylation of multiple intracellular signaling molecules such as FAK , AKT andSmad2 .
Mechanistically , @ @ @ @ @ degradation of TGFβ and EGF receptors via proteasome and lysosome , respectively .
Moreover , @ @ @ @ @ suppressed lung tumor growth , reduced the size of metastatic nodules in the lungs and @ @ @ @ @ mice .
Our findings suggested that WSG may have potential as a therapeutic intervention for @ @ @ @ @

WSG is a water soluble polysaccharides isolated from Ganoderma lucidum. In this study, we showed that WSG, a glucose-rich polysaccharide with an average molecular mass of approximately 1000 kDa, effectively inhibited cell viability and mobility of lung cancer cells. Functional studies revealed that WSG reduced phosphorylation of ERK1/2 in cells upon either EGF or TGFβ stimulation. WSG also inhibited phosphorylation of multiple intracellular signaling molecules such as FAK, AKT andSmad2. Mechanistically, we demonstrated that WSG induced degradation of TGFβ and EGF receptors via proteasome and lysosome, respectively. Moreover, we found that WSG significantly suppressed lung tumor growth, reduced the size of metastatic nodules in the lungs and prolonged the survival of LLC1-bearing mice. Our findings suggested that WSG may have potential as a therapeutic intervention for treatment of lung cancer.


greenmedinfo--2020-10-16--Yogurt consumption was associated with a reduced risk of proximal colon cancer with a long latency p

Yogurt consumption was associated with a reduced risk of proximal colon cancer with a long latency period.

BACKGROUND : Yogurt is a commonly consumed fermented food .
Regular yogurt consumption may contribute to a favorable gut microbiome and gut health , but few epidemiologic studies have considered the relation between regular yogurt consumption and the incidence of and mortality from colorectal cancer .
OBJECTIVES : We used data from 2 large , prospective cohort studies , the Nurses ' Health Study and the Health Professionals Follow-Up Study , to examine the role of yogurt consumption on colorectal cancer incidence and mortality .
METHODS : During 32 years of follow-up in 83,054 women ( mean age at baseline @ @ @ @ @ @ @ of follow-up in 43,269 men ( mean age at baseline , 52.3 years ) , we documented a total of 2666 newly diagnosed cases of colorectal cancer in these cohorts .
We modeled yogurt consumption at baseline and cumulatively updated it throughout follow-up .
Results : Baseline yogurt consumption was associated with a reduced risk of colon cancer in age-adjusted analyses ( P for trend CONCLUSIONS : In these large cohorts , the frequency of yogurt consumption was associated with a reduced risk of proximal colon cancer with a long latency period .
@ @ @ @ @ @ @ colorectal cancer mortality .

BACKGROUND: Yogurt is a commonly consumed fermented food. Regular yogurt consumption may contribute to a favorable gut microbiome and gut health, but few epidemiologic studies have considered the relation between regular yogurt consumption and the incidence of and mortality from colorectal cancer.
OBJECTIVES: We used data from 2 large, prospective cohort studies, the Nurses' Health Study and the Health Professionals Follow-Up Study, to examine the role of yogurt consumption on colorectal cancer incidence and mortality.
METHODS: During 32 years of follow-up in 83,054 women (mean age at baseline, 45.7 years) and 26 years of follow-up in 43,269 men (mean age at baseline, 52.3 years), we documented a total of 2666 newly diagnosed cases of colorectal cancer in these cohorts. We modeled yogurt consumption at baseline and cumulatively updated it throughout follow-up. Results: Baseline yogurt consumption was associated with a reduced risk of colon cancer in age-adjusted analyses (P for trend < 0.001). Associations remained statistically significant after adjusting for potential confounders, including calcium and fiber intake (P for trend = 0.03), and were restricted to proximal colon cancer. The consumption of 1 + servings per week of yogurt at baseline, compared to no yogurt consumption, was associated with a multivariable HR of 0.84 (95% CI, 0.70-0.99; P trend = 0.04) for the proximal colon cancer incidence. Latency analyses suggested that the most important window of opportunity for regular yogurt consumption to prevent colorectal cancer was 16-20 years in the past. Whenyogurt consumption was cumulatively updated, associations attenuated and were no longer significant. No statistically significant inverse trend was observed between yogurt consumption and the colorectal cancer mortality.
CONCLUSIONS: In these large cohorts, the frequency of yogurt consumption was associated with a reduced risk of proximal colon cancer with a long latency period. No significant inverse trend was observed for colorectal cancer mortality.


greenmedinfo--2020-10-16--Bacopa monnieri alleviates aluminium chloride-induced anxiety.

Objectives Aluminium is present in food preparations , antacids and many medications .
It causes neurodegeneration thereby resulting in a spectrum of neurological disorders such as dementia , Alzheimer 's disease and anxiety .
Bacopa monnieri ( BM ) is widely used in ayurvedic medicine to improve memory functions .
Its anxiolytic property was investigated in this study by using elevated plus maze ( EPM ) and plasma corticosterone level .
Methods Thirty rats were assigned into five groups .
Control group received distilled water , and 0.5 % tween 80 , AlCl3 group received Aluminium Chloride ( AlCl3 ) @ @ @ @ @ @ @ group and BM200 + AlCl3 group ) received AlCl3 and BM at two different doses , and the BM200 group received BM .
The EPM experiment was performed at the end of the 4th week of oral administration of BM and AlCl3 followed by the measurement of plasma corticosterone .
Results Oral administration of AlCl3 to rats increases the levels of anxiety as seen in a decrease in the percentage of entries into the open arms of EPM , an increase in grooming frequency and defecation index .
However , the rats in @ @ @ @ @ @ @ the percentage of open arm entries and rearing frequency , and decreased grooming frequency and defecation index .
AlCl3 alone treated group showed a significant increase in the plasma corticosterone levels compared to the control group .
Whereas the protective groups have shown a significant decrease in the plasma corticosterone levels than the AlCl3 alone treated group .
Conclusions Hence the BM has potential role in reverting the anxiogenic effect of AlCl3 in the amygdala as it is evident from the plasma corticosterone levels and the EPM parameters of different groups under study @

Objectives Aluminium is present in food preparations, antacids and many medications. It causes neurodegeneration thereby resulting in a spectrum of neurological disorders such as dementia, Alzheimer's disease and anxiety. Bacopa monnieri (BM) is widely used in ayurvedic medicine to improve memory functions. Its anxiolytic property was investigated in this study by using elevated plus maze (EPM) and plasma corticosterone level. Methods Thirty rats were assigned into five groups. Control group received distilled water, and 0.5% tween 80, AlCl3 group received Aluminium Chloride (AlCl3), Protective groups (BM100 + AlCl3 group and BM200 + AlCl3 group) received AlCl3 and BM at two different doses, and the BM200 group received BM. The EPM experiment was performed at the end of the 4th week of oral administration of BM and AlCl3 followed by the measurement of plasma corticosterone. Results Oral administration of AlCl3 to rats increases the levels of anxiety as seen in a decrease in the percentage of entries into the open arms of EPM, an increase in grooming frequency and defecation index. However, the rats in the protective groups shown an increase in the percentage of open arm entries and rearing frequency, and decreased grooming frequency and defecation index. AlCl3 alone treated group showed a significant increase in the plasma corticosterone levels compared to the control group. Whereas the protective groups have shown a significant decrease in the plasma corticosterone levels than the AlCl3 alone treated group. Conclusions Hence the BM has potential role in reverting the anxiogenic effect of AlCl3 in the amygdala as it is evident from the plasma corticosterone levels and the EPM parameters of different groups under study.


greenmedinfo--2020-10-16--Cryptotanshinone could be developed as a potential therapeutic agent for the treatment of chronic di

Cryptotanshinone could be developed as a potential therapeutic agent for the treatment of chronic diabetic wound healing.

CONTEXT : Cryptotanshinone ( CT ) is a diterpene quinone compound fromBge .
Labiatae has been widely used in cardio-cerebral vascular diseases , which could be potentially effective in treating diabetic wounds .
OBJECTIVE : This study evaluates the wound healing activity of CT by employing an excisional wound splinting model in db/db mice .
MATERIALS AND METHODS : Wounds were induced at the dorsum of non-diabetic ( db/+ ) and diabetic ( db/db ) mice and treated with sodium carboxymethyl cellulose ( CMC-Na ) or 300 mg/kg/d CT for 16 days .
Wound closure was measured every two days @ @ @ @ @ @ @ , re-epithelialization , granulation , leukocyte infiltration , capillary density , collagen deposition and expressions of CXCL1 , CXCL2 , VEGF , Ang-1 , p-eNOS , eNOS , α-SMA , MMP2 and MMP9 were analysed .
Expression of VEGF and tube formation was measuredwith human umbilical vein endothelial cells ( HUVECs ) .
RESULTS : CT significantly accelerated rate of wound closure , as the contraction ratio increased from 68 % ( non-treated group ) to 83 % ( CT-treated group ) at days 16 post-injury .
A significant increase was observed in @ @ @ @ @ @ @ , CT suppressed leukocyte infiltration and CXCL1 and CXCL2 expression .
CT treatment also increased blood vessel density and expression level of VEGF , Ang-1 and p-eNOS.
, CT boosted expression of VEGF and tube formation of endothelial cells .
Moreover , extracellular matrix ( ECM ) remodelling was enhanced by CT via promoting fibroblast transformation and inhibiting MMP2 and MMP9 .
CONCLUSIONS : Our study provides evidence that CT could be developed as a potential therapeutic agent for the treatment of chronic diabetic wound healing .

CONTEXT: Cryptotanshinone (CT) is a diterpene quinone compound fromBge. Labiatae has been widely used in cardio-cerebral vascular diseases, which could be potentially effective in treating diabetic wounds.
OBJECTIVE: This study evaluates the wound healing activity of CT by employing an excisional wound splinting model in db/db mice.
MATERIALS AND METHODS: Wounds were induced at the dorsum of non-diabetic (db/+) and diabetic (db/db) mice and treated with sodium carboxymethyl cellulose (CMC-Na) or 300 mg/kg/d CT for 16 days. Wound closure was measured every two days. Body weight, fasting blood glucose, re-epithelialization, granulation, leukocyte infiltration, capillary density, collagen deposition and expressions of CXCL1, CXCL2, VEGF, Ang-1, p-eNOS, eNOS, α-SMA, MMP2 and MMP9 were analysed. Expression of VEGF and tube formation was measuredwith human umbilical vein endothelial cells (HUVECs).
RESULTS: CT significantly accelerated rate of wound closure, as the contraction ratio increased from 68% (non-treated group) to 83% (CT-treated group) at days 16 post-injury. A significant increase was observed in re-epithelialization and granulation tissue formation. Mechanistically, CT suppressed leukocyte infiltration and CXCL1 and CXCL2 expression. CT treatment also increased blood vessel density and expression level of VEGF, Ang-1 and p-eNOS., CT boosted expression of VEGF and tube formation of endothelial cells. Moreover, extracellular matrix (ECM) remodelling was enhanced by CT via promoting fibroblast transformation and inhibiting MMP2 and MMP9.
CONCLUSIONS: Our study provides evidence that CT could be developed as a potential therapeutic agent for the treatment of chronic diabetic wound healing.


greenmedinfo--2020-10-16--Overview of Salvia miltiorrhiza as a potential therapeutic agent for various diseases.

Bunge ( ) is a medicinal herb that has been used for the treatment for various diseases such as cardiovascular @ @ @ @ @ Asia including Korea .
Considering its extensive usage as a therapeutic agent for multiple diseases @ @ @ @ @ to review previous research regarding its therapeutic benefits and their mechanisms .
Therefore , we @ @ @ @ @ for articles reporting its therapeutic effects on certain disease groups including cancers , cardiovascular , @ @ @ @ @ diseases .
This review provides an overview of therapeutic benefits and targets of , including @ @ @ @ @ stress , and apoptosis .
The findings on multi-functional properties ofdiscussed in this article support @ @ @ @ @ diseases , but also call for further research on the multiple mechanisms that mediate its @ @ @

Bunge () is a medicinal herb that has been used for the treatment for various diseases such as cardiovascular and cerebrovascular diseases in East Asia including Korea. Considering its extensive usage as a therapeutic agent for multiple diseases, there is a need to review previous research regarding its therapeutic benefits and their mechanisms. Therefore, we searched PubMed and PubMed Central for articles reporting its therapeutic effects on certain disease groups including cancers, cardiovascular, liver, and nervous system diseases. This review provides an overview of therapeutic benefits and targets of, including inflammation, fibrosis, oxidative stress, and apoptosis. The findings on multi-functional properties ofdiscussed in this article support the efficacy ofextract on various diseases, but also call for further research on the multiple mechanisms that mediate its therapeutic effects.


greenmedinfo--2020-10-16--Combination of Danshen and ligustrazine has dual anti-inflammatory effect on macrophages and endothe

Combination of Danshen and ligustrazine has dual anti-inflammatory effect on macrophages and endothelial cells.

ETHNOPHARMACOLOGICAL RELEVANCE : Salvia Miltiorrhiza Radix et Rhizoma ( Danshen ) and Chuanxiong Rhizoma ( Chuanxiong ) are both traditional Chinese medicines with vascular protective effects , and their combination is widely used in China to treat occlusive or ischemic diseases of the cerebrovascular or cardiovascular system .
Although it is widely accepted that these diseases have high relevance to inflammation , little is known about the anti-inflammatory effect of Danshen , Chuanxiong , and their combination .
AIM OF STUDY : We aimed to investigate the complex mode of action of Danshen , Chuanxiong , and their combination and @ @ @ @ @ @ @ .
Specifically , toll-like receptor ( TLR1/2 , 3 , and 4 ) -triggered macrophages and endothelial cells , the two major cell players in atherosclerosis as well as in related cardiovascular and cerebrovascular injuries , were emphasized .
METHODS : TLR1/2- , TLR3- , and TLR4-induced bone marrow macrophages ( BMMs ) and human umbilical vein endothelial cells ( HUVECs ) were treated with Danshen extract ( S. miltiorrhiza extract , SME ) , ligustrazine ( 2 , 3 , 5 , 6-tetramethylpyrazine , TMP ) , and their combination ( S. @ @ @ @ @ @ @ , respectively .
The proinflammatory cytokines interleukin 6 ( IL-6 ) , IL-12 , and tumor necrosis factor alpha ( TNF-α ) were detected as the preliminary indicators of inflammation .
In addition , RNA sequencing ( RNA-seq ) -based transcriptional profiling analyses were conducted for TLR2-activated BMMs to determine the molecular mode of action of SLI as well as the contribution of SME to SLI activity .
RESULTS : SLI mitigated inflammation in both BMMs and HUVECs .
Refer to the combination , SME had pronounced anti-inflammatory effect on BMMs but had @ @ @ @ @ @ @ In contrast , TMP had considerable anti-inflammatory effect on HUVECs but not on BMMs .
Bioinformatic analysis identified a broad spectrum of regulatory genes , in addition to IL-6 gene , and C-X-C motif chemokine ligand 10 ( CXCL10 ) appeared to be another key molecule involved in the mechanism underlying SLI and SME effects .
At the molecular level , SME was a major contributor of the anti-inflammatory activity of SLI .
CONCLUSIONS : In TLR-activated inflammation , SLI exhibits a '' multiple ingredient-multiple target '' effect , with SME primarily affecting @ @ @ @ @ @ @ study provides evidence for the clinical application of SLI in treating complex diseases involving inflammation-induced injury of both macrophages and epithelial cells .
Further bioinformatics studies are required to reveal the entire molecular network involved in TMP , SME , and SLI activity .

ETHNOPHARMACOLOGICAL RELEVANCE: Salvia Miltiorrhiza Radix et Rhizoma (Danshen) and Chuanxiong Rhizoma (Chuanxiong) are both traditional Chinese medicines with vascular protective effects, and their combination is widely used in China to treat occlusive or ischemic diseases of the cerebrovascular or cardiovascular system. Although it is widely accepted that these diseases have high relevance to inflammation, little is known about the anti-inflammatory effect of Danshen, Chuanxiong, and their combination.
AIM OF STUDY: We aimed to investigate the complex mode of action of Danshen, Chuanxiong, and their combination and the molecular mechanisms underlying their anti-inflammatory activity. Specifically, toll-like receptor (TLR1/2, 3, and 4)-triggered macrophages and endothelial cells, the two major cell players in atherosclerosis as well as in related cardiovascular and cerebrovascular injuries, were emphasized.
METHODS: TLR1/2-, TLR3-, and TLR4-induced bone marrow macrophages (BMMs) and human umbilical vein endothelial cells (HUVECs) were treated with Danshen extract (S. miltiorrhiza extract, SME), ligustrazine (2, 3, 5, 6-tetramethylpyrazine, TMP), and their combination (S. miltiorrhiza and TMP injection, SLI), respectively. The proinflammatory cytokines interleukin 6 (IL-6), IL-12, and tumor necrosis factor alpha (TNF-α) were detected as the preliminary indicators of inflammation. In addition, RNA sequencing (RNA-seq)-based transcriptional profiling analyses were conducted for TLR2-activated BMMs to determine the molecular mode of action of SLI as well as the contribution of SME to SLI activity.
RESULTS: SLI mitigated inflammation in both BMMs and HUVECs. Refer to the combination, SME had pronounced anti-inflammatory effect on BMMs but had only a slight effect on HUVECs. In contrast, TMP had considerable anti-inflammatory effect on HUVECs but not on BMMs. Bioinformatic analysis identified a broad spectrum of regulatory genes, in addition to IL-6 gene, and C-X-C motif chemokine ligand 10 (CXCL10) appeared to be another key molecule involved in the mechanism underlying SLI and SME effects. At the molecular level, SME was a major contributor of the anti-inflammatory activity of SLI.
CONCLUSIONS: In TLR-activated inflammation, SLI exhibits a"multiple ingredient-multiple target"effect, with SME primarily affecting macrophages and TMP affecting HUVECs. Our study provides evidence for the clinical application of SLI in treating complex diseases involving inflammation-induced injury of both macrophages and epithelial cells. Further bioinformatics studies are required to reveal the entire molecular network involved in TMP, SME, and SLI activity.


greenmedinfo--2020-10-16--Modulatory effects of triphala and manjistha dietary supplementation on human gut microbiota.

Triphala ( which containsand ) and manjistha ( ) , have received increased clinical attention .
The aim of the study was to evaluate the effects of triphala , manjistha , or placebo dietary supplementation on gut microbiota as such studies in humans are lacking.This was a 4-week randomized , double-blind , placebo-controlled pilot trial.This trial was conducted at the University of California Davis , Department of Dermatology.A total of 31 healthy human subjects were randomized to 3 groups.The 3 groups were instructed to take 2,000 mg of either triphala , manjistha or placebo daily for 4 weeks.The impact of @ @ @ @ @ @ @ following a 4-week dietary intervention by profiling fecal communities with 16S rRNA profiling in triphala ( = 9 ) , manjistha ( = 9 ) , or placebo ( = 11 ) treated subjects that completed the intervention.An average of 336 phylotypes were detected in each sample ( range : 161 to 648 ) .
The analysis of gut microbiota in placebo control and herb-supplemented participants indicated that responses were highly personalized , and no taxa were uniformly altered by the medicinal herb supplementation protocol .
Subjects in both treatment groups displayed a @ @ @ @ @ @ @ and increased relative abundance of .
Both medicinal herb treatments reduced the relative abundance of Rikenellaceae , primarily reflecting changes inspp.Dietary supplementation with medicinal herbs altered fecal microbial communities .
Despite the lack of a clear response signature , a group of bacterial taxa were identified that were more commonly altered in herb-supplemented participants compared to placebo controls .
Clinicaltrials.gov identifier NCT03477825 .

Triphala (which containsand) and manjistha (), have received increased clinical attention. The aim of the study was to evaluate the effects of triphala, manjistha, or placebo dietary supplementation on gut microbiota as such studies in humans are lacking.This was a 4-week randomized, double-blind, placebo-controlled pilot trial.This trial was conducted at the University of California Davis, Department of Dermatology.A total of 31 healthy human subjects were randomized to 3 groups.The 3 groups were instructed to take 2,000 mg of either triphala, manjistha or placebo daily for 4 weeks.The impact of treatment on gut microbiota composition was evaluated following a 4-week dietary intervention by profiling fecal communities with 16S rRNA profiling in triphala ( = 9), manjistha ( = 9), or placebo ( = 11) treated subjects that completed the intervention.An average of 336 phylotypes were detected in each sample (range: 161 to 648). The analysis of gut microbiota in placebo control and herb-supplemented participants indicated that responses were highly personalized, and no taxa were uniformly altered by the medicinal herb supplementation protocol. Subjects in both treatment groups displayed a trend toward decreased Firmicutes to Bacteroidetes ratio and increased relative abundance of. Both medicinal herb treatments reduced the relative abundance of Rikenellaceae, primarily reflecting changes inspp.Dietary supplementation with medicinal herbs altered fecal microbial communities. Despite the lack of a clear response signature, a group of bacterial taxa were identified that were more commonly altered in herb-supplemented participants compared to placebo controls. Clinicaltrials.gov identifier NCT03477825.


greenmedinfo--2020-10-16--A standardized Terminalia chebula fruit extract alters the expression of genes associated with skin

A standardized Terminalia chebula fruit extract alters the expression of genes associated with skin architecture and barrier formation.

BACKGROUND : Terminalia chebula ( TC ) is a deciduous tree of which extracts have demonstrated efficacy for treatment of photodamage , skin aging , and wound healing .
However , molecular and cellular mechanisms underlying these benefits remain unclear .
MATERIALS AND METHODS : Microarrays were used to evaluate gene expression in three-dimensional reconstituted human skin cultures .
RESULTS : Genome-wide expression responses to TC were the opposite to those observed in cells exposed to oxidative stress , solar-simulated UV radiation , and wounding , with increased expression of genes associated with water homeostasis , skin barrier establishment , @ @ @ @ @ @ @ .
TC also increased expression of extracellular matrix components , such as collagens ( COL1A1 , COL1A2 ) and proteoglycans ( PRELP , OGN ) , and in separate assays , we showed that TC inhibits MMP enzymes ( MMP-1 , MMP-2 , MMP-3 , MMP-9 , MMP-12 ) and microbial activity ( S. aureus , P. acnes ) .
Unexpectedly , mRNA and protein levels of late keratinocyte ( KC ) differentiation markers ( FLG , LOR ) were increased by TC , and expression responses in skin cultures broadly resembled those @ @ @ @ @ @ @ with these results , TC increased expression of transcription factors regulating KC differentiation ( FOS , GHRL3 , PPARG ) and we noted enrichment of AP-1 binding sites in regions upstream of TC-increased genes .
CONCLUSION : These results demonstrate that functionally important TC extract responses occur in the epidermis and are therefore not restricted to the dermal layer .
Our findings thus suggest mechanisms by which TC may strengthen full-thickness skin architecture for treatment of skin aging and/or chronic wounds .

BACKGROUND: Terminalia chebula (TC) is a deciduous tree of which extracts have demonstrated efficacy for treatment of photodamage, skin aging, and wound healing. However, molecular and cellular mechanisms underlying these benefits remain unclear.
OBJECTIVES: To profile dermal expression responses to a standardized tannin-enriched TC fruit extract (SynastolTC).
MATERIALS AND METHODS: Microarrays were used to evaluate gene expression in three-dimensional reconstituted human skin cultures.
RESULTS: Genome-wide expression responses to TC were the opposite to those observed in cells exposed to oxidative stress, solar-simulated UV radiation, and wounding, with increased expression of genes associated with water homeostasis, skin barrier establishment, blood vessel development, and circadian rhythms. TC also increased expression of extracellular matrix components, such as collagens (COL1A1, COL1A2) and proteoglycans (PRELP, OGN), and in separate assays, we showed that TC inhibits MMP enzymes (MMP-1, MMP-2, MMP-3, MMP-9, MMP-12) and microbial activity (S. aureus, P. acnes). Unexpectedly, mRNA and protein levels of late keratinocyte (KC) differentiation markers (FLG, LOR) were increased by TC, and expression responses in skin cultures broadly resembled those that occur with KC differentiation. Consistent with these results, TC increased expression of transcription factors regulating KC differentiation (FOS, GHRL3, PPARG) and we noted enrichment of AP-1 binding sites in regions upstream of TC-increased genes.
CONCLUSION: These results demonstrate that functionally important TC extract responses occur in the epidermis and are therefore not restricted to the dermal layer. Our findings thus suggest mechanisms by which TC may strengthen full-thickness skin architecture for treatment of skin aging and/or chronic wounds.


greenmedinfo--2020-10-16--Potent anti-inflammatory Terminalia chebula fruit showed in vitro anticancer activity on lung and br

Potent anti-inflammatory Terminalia chebula fruit showed in vitro anticancer activity on lung and breast carcinoma cells.

The present study was aimed to investigate the anticancer and anti-inflammatory activities of Terminalia chebula fruit ( TCME ) .
The TCME was evaluated for in vitro anticancer activity on A549 and MCF-7 cells .
TCME showed cytotoxicity toward A549 ( IC- 359.06 ± 20.04 µg/ml ) , and MCF-7 ( IC- 61.02 ± 5.55 µg/ml ) cells .
The flow-cytometer analysis revealed increase in sub G1 population and apoptotic population , which were observed through cell cycle analysis and annexin-V-FLUOS staining .
Confocal microscopy showed DNA fragmentation in both the cell lines upon TCME treatment .
Moreover , TCME @ @ @ @ @ @ @ in both the cell lines .
TCME treatment on RAW 264.7 cells revealed the anti-inflammatory properties by regulating nitrite and TNF-α production ; iNOS , COX-2 levels , and translocation of NF-κB protein .
Finally , HPLC analysis revealed the bioactive phytocompounds present in TCME .
In conclusion , the combined results showed the potent anticancer and anti-inflammatory properties of T. chebula fruit .
PRACTICAL APPLICATIONS : Lung cancer is a leading cause of death in men with 35.5 % incidences and 30.8 % mortality rate worldwide .
On the contrary , breast @ @ @ @ @ @ @ % mortality rate among the female worldwide .
The present findings revealed the anti-lung and -breast cancer activity along with the potent anti-inflammatory potentials of Terminalia chebula fruit .
These findings will helpful to isolate the active drug molecules from the Terminalia chebula fruit and mark them as an anticancer and anti-inflammatory agent .

The present study was aimed to investigate the anticancer and anti-inflammatory activities of Terminalia chebula fruit (TCME). The TCME was evaluated for in vitro anticancer activity on A549 and MCF-7 cells. TCME showed cytotoxicity toward A549 (IC- 359.06 ± 20.04 µg/ml), and MCF-7 (IC- 61.02 ± 5.55 µg/ml) cells. The flow-cytometer analysis revealed increase in sub G1 population and apoptotic population, which were observed through cell cycle analysis and annexin-V-FLUOS staining. Confocal microscopy showed DNA fragmentation in both the cell lines upon TCME treatment. Moreover, TCME treatment induces activation of apoptosis-related caspase-cascade pathways in both the cell lines. TCME treatment on RAW 264.7 cells revealed the anti-inflammatory properties by regulating nitrite and TNF-α production; iNOS, COX-2 levels, and translocation of NF-κB protein. Finally, HPLC analysis revealed the bioactive phytocompounds present in TCME. In conclusion, the combined results showed the potent anticancer and anti-inflammatory properties of T. chebula fruit. PRACTICAL APPLICATIONS: Lung cancer is a leading cause of death in men with 35.5% incidences and 30.8% mortality rate worldwide. On the contrary, breast cancer possesses 55.2% incidences and 16.6% mortality rate among the female worldwide. The present findings revealed the anti-lung and -breast cancer activity along with the potent anti-inflammatory potentials of Terminalia chebula fruit. These findings will helpful to isolate the active drug molecules from the Terminalia chebula fruit and mark them as an anticancer and anti-inflammatory agent.


greenmedinfo--2020-10-17--Recombinant Ganoderma lucidum immunomodulatory protein improves the treatment for chemotherapy-induc

Recombinant Ganoderma lucidum immunomodulatory protein improves the treatment for chemotherapy-induced neutropenia.

, also known as LINGZHI , has a long tradition of use in folk medicine of the Far East , @ @ @ @ @ oldest Chinese pharmacopoeia , declaring it a superior medicine .
LINGZHI-8 ( LZ-8 ) is @ @ @ @ @ from the fruiting body of .
Neutropenia is a condition with an abnormally low levels @ @ @ @ @ , which is caused by numerous medical conditions or medications , such as chemotherapy .
@ @ @ @ @ recombinant LZ-8 ( rLZ-8 ) from Pichia promoted the differentiation of bone marrow hematopoietic stem @ @ @ @ @ granulocytes in a neutropenia mouse model induced by cyclophosphamide .
Also , it regulated the @ @ @ @ @ mobilization of HSCs and the release of neutrophils from the bone marrow to peripheral blood @ @ @ @ @ the colony stimulating factor 1 receptor ( CSF1R ) promotes the differentiation of HSCs into @ @ @ @ @ results suggested that rLZ-8 has a potential effect in the treatment of chemotherapy-induced neutropenia .

, also known as LINGZHI, has a long tradition of use in folk medicine of the Far East, which is documented in the oldest Chinese pharmacopoeia, declaring it a superior medicine. LINGZHI-8 (LZ-8) is an immunoregulatory fungal protein isolated from the fruiting body of. Neutropenia is a condition with an abnormally low levels of neutrophils in the blood, which is caused by numerous medical conditions or medications, such as chemotherapy. The current study demonstrated that recombinant LZ-8 (rLZ-8) from Pichia promoted the differentiation of bone marrow hematopoietic stem cells (HSCs) into granulocytes in a neutropenia mouse model induced by cyclophosphamide. Also, it regulated the CXCR4-SDF1 axis to promote the mobilization of HSCs and the release of neutrophils from the bone marrow to peripheral blood. Binding of rLZ-8 to the colony stimulating factor 1 receptor (CSF1R) promotes the differentiation of HSCs into primitive CFU colonies. These results suggested that rLZ-8 has a potential effect in the treatment of chemotherapy-induced neutropenia.