greenmedinfo--2020-07-11--Oligo-fucoidan enhances the immune system and protects hepatocytes.

Oligo-fucoidan , a sulfated polysaccharide extracted from brown seaweed , exhibits anti-inflammatory and anti-tumor effects .
However , the knowledge concerning the detailed mechanism of oligo-fucoidan on liver cells is obscure .
In this study , we investigate the effect of oligo-fucoidan in normal hepatocytes by transcriptomic analysis .
Using an oligo-fucoidan oral gavage in wild-type adult zebrafish , we find that oligo-fucoidan pretreatment enhances the immune system and anti-viral genes in hepatocytes .
Oligo-fucoidan pretreatment also decreases the expression of lipogenic enzymes and liver fibrosis genes .
Using pathway analysis , we identify hepatocyte nuclear factor 4 alpha ( @ @ @ @ @ @ @ gene .
We further investigate whether hepatocyte nuclear factor 4 alpha ( HNF4A ) could be induced by oligo-fucoidan and the underlying mechanism .
Therefore , a normal hepatocyte clone 9 cell as an in vitro model was used .
We demonstrate that oligo-fucoidan increases cell viability , Cyp3a4 activity , and Hnf4a expression in clone 9 cells .
We further demonstrate that oligo-fucoidan might bind to asialoglycoprotein receptors ( ASGPR ) in normal hepatocytes through both in vitro and in vivo competition assays .
This binding , consequently activating the signal transducer @ @ @ @ @ @ @ ) , increases the expression of the P1 isoform of HNF4A .
According to our data , we suggest that oligo-fucoidan not only enhances the gene expression associated with anti-viral ability and immunity , but also increases P1-HNF4A levels through ASGPR/STAT3 axis , resulting in protecting hepatocytes .

Oligo-fucoidan, a sulfated polysaccharide extracted from brown seaweed, exhibits anti-inflammatory and anti-tumor effects. However, the knowledge concerning the detailed mechanism of oligo-fucoidan on liver cells is obscure. In this study, we investigate the effect of oligo-fucoidan in normal hepatocytes by transcriptomic analysis. Using an oligo-fucoidan oral gavage in wild-type adult zebrafish, we find that oligo-fucoidan pretreatment enhances the immune system and anti-viral genes in hepatocytes. Oligo-fucoidan pretreatment also decreases the expression of lipogenic enzymes and liver fibrosis genes. Using pathway analysis, we identify hepatocyte nuclear factor 4 alpha (HNF4A) to be the potential driver gene. We further investigate whether hepatocyte nuclear factor 4 alpha (HNF4A) could be induced by oligo-fucoidan and the underlying mechanism. Therefore, a normal hepatocyte clone 9 cell as an in vitro model was used. We demonstrate that oligo-fucoidan increases cell viability, Cyp3a4 activity, and Hnf4a expression in clone 9 cells. We further demonstrate that oligo-fucoidan might bind to asialoglycoprotein receptors (ASGPR) in normal hepatocytes through both in vitro and in vivo competition assays. This binding, consequently activating the signal transducer and activator of transcription 3 (STAT3), increases the expression of the P1 isoform of HNF4A. According to our data, we suggest that oligo-fucoidan not only enhances the gene expression associated with anti-viral ability and immunity, but also increases P1-HNF4A levels through ASGPR/STAT3 axis, resulting in protecting hepatocytes.


greenmedinfo--2020-07-12--Sulforaphane inhibits autophagy and induces exosome-mediated paracrine senescence via regulating mTO

Sulforaphane inhibits autophagy and induces exosome-mediated paracrine senescence via regulating mTOR/TFE3.

SCOPE : The development of novel compounds that trigger non-apoptotic cell death may represent alternative therapeutic strategies for esophageal squamous cell carcinoma ( ESCC ) treatment .
Cellular senescence suppresses tumorigenesis by halting the proliferation of tumor cells , implying the induction of senescence as a promising anticancer strategy , especially when combined with senolytic agents that specially kill senescent cells .
This study is designed to screen novel anti-ESCC compounds from a natural product resource and identify its mechanism-of-action .
METHODS AND RESULTS : Identified are the significant anti-cancer effect and underlying mechanism of SFN , an isothiocyanate derived @ @ @ @ @ @ @ , western blot , and immunofluorescent assays .
It is found that SFN inhibits proliferation of ESCC cells through inducing senescence .
Mechanistically , SFN induces reactive oxygen species ( ROS ) via disrupting the balance between glutathione and oxidized glutathione , leading to DNA damage .
In addition , ROS deregulates autophagy and promotes lysosome abnormal biogenesis through regulating mTOR/TFE3 axis .
Finally , the inhibited autophagic flux facilitates exosome production , resulting in exosome-mediated paracrine senescence .
CONCLUSIONS : This study suggests the important roles of autophagy and exosome-mediated paracrine senescence @ @ @ @ @ @ @ a potent anti-ESCC drug candidate .

SCOPE: The development of novel compounds that trigger non-apoptotic cell death may represent alternative therapeutic strategies for esophageal squamous cell carcinoma (ESCC) treatment. Cellular senescence suppresses tumorigenesis by halting the proliferation of tumor cells, implying the induction of senescence as a promising anticancer strategy, especially when combined with senolytic agents that specially kill senescent cells. This study is designed to screen novel anti-ESCC compounds from a natural product resource and identify its mechanism-of-action.
METHODS AND RESULTS: Identified are the significant anti-cancer effect and underlying mechanism of SFN, an isothiocyanate derived from cruciferous vegetables, through RNA sequencing, western blot, and immunofluorescent assays. It is found that SFN inhibits proliferation of ESCC cells through inducing senescence. Mechanistically, SFN induces reactive oxygen species (ROS) via disrupting the balance between glutathione and oxidized glutathione, leading to DNA damage. In addition, ROS deregulates autophagy and promotes lysosome abnormal biogenesis through regulating mTOR/TFE3 axis. Finally, the inhibited autophagic flux facilitates exosome production, resulting in exosome-mediated paracrine senescence.
CONCLUSIONS: This study suggests the important roles of autophagy and exosome-mediated paracrine senescence in cancer therapy and highlights SFN as a potent anti-ESCC drug candidate.


greenmedinfo--2020-07-12--Inhibitory effects of phytochemicals on NLRP3 inflammasome activation.

BACKGROUND : The NLRP3 inflammasome formation and following cytokine secretion is a crucial step in innate immune responses .
Internal and external factors may trigger inflammasome activation and result in inflammatory cytokine secretion .
Inflammasome formation and activity play critical roles in several disease pathologies such as cardiovascular , metabolic , renal , digestive , and CNS diseases .
Underlying pathways are not yet clear , but phytochemicals as alternative therapies have been extensively used for suppression of inflammatory responses .
PURPOSE : In this review , we aimed to summarize in vivo and in vitro effects on NLRP3 inflammasome @ @ @ @ @ @ @ Three phytochemicals ; Sulforaphane , Curcumin , and Resveratrol were selected , and studies were reviewed to clarify their intracellular signaling mechanism in NLRP3 inflammasome activity .
PubMed and Scopus databases are used for the search .
For sulforaphane , 8 articles , for curcumin , 25 articles , and for resveratrol , 41 articles were included in the review .
CONCLUSION : In vitro and in vivo studies pointed out that the selected phytochemicals have inhibitory properties on NLRP3 inflammasome activity .
However , neither the mechanism is clear , nor the @ @ @ @ @ @ @

BACKGROUND: The NLRP3 inflammasome formation and following cytokine secretion is a crucial step in innate immune responses. Internal and external factors may trigger inflammasome activation and result in inflammatory cytokine secretion. Inflammasome formation and activity play critical roles in several disease pathologies such as cardiovascular, metabolic, renal, digestive, and CNS diseases. Underlying pathways are not yet clear, but phytochemicals as alternative therapies have been extensively used for suppression of inflammatory responses.
PURPOSE: In this review, we aimed to summarize in vivo and in vitro effects on NLRP3 inflammasome activation of selected phytochemicals.
METHOD: Three phytochemicals; Sulforaphane, Curcumin, and Resveratrol were selected, and studies were reviewed to clarify their intracellular signaling mechanism in NLRP3 inflammasome activity. PubMed and Scopus databases are used for the search. For sulforaphane, 8 articles, for curcumin, 25 articles, and for resveratrol, 41 articles were included in the review.
CONCLUSION: In vitro and in vivo studies pointed out that the selected phytochemicals have inhibitory properties on NLRP3 inflammasome activity. However, neither the mechanism is clear, nor the study designs and doses are standardized.


greenmedinfo--2020-07-12--Sulforaphane may hold potential for treating bladder carcinoma in patients with resistance to an mTO

Sulforaphane may hold potential for treating bladder carcinoma in patients with resistance to an mTOR inhibitor.

Progressive bladder cancer growth is associated with abnormal activation of the mammalian target of the rapamycin ( mTOR ) pathway , but treatment with an mTOR inhibitor has not been as effective as expected .
Rather , resistance develops under chronic drug use , prompting many patients to lower their relapse risk by turning to natural , plant-derived products .
The present study was designed to evaluate whether the natural compound , sulforaphane ( SFN ) , combined with the mTOR inhibitor everolimus , could block the growth and proliferation of bladder cancer cells in the short- and long-term .
@ @ @ @ @ @ @ UMUC3 , and TCCSUP were exposed short- ( 24 h ) or long-term ( 8 weeks ) to everolimus ( 0.5 nM ) or SFN ( 2.5µM ) alone or in combination .
Cell growth , proliferation , apoptosis , cell cycle progression , and cell cycle regulating proteins were evaluated .
siRNA blockade was used to investigate the functional impact of the proteins .
Short-term application of SFN and/or everolimus resulted in significant tumorgrowth suppression , with additive inhibition on clonogenic tumor growth .
Long-term everolimus treatment resulted in resistance development characterized @ @ @ @ @ @ @ with elevated Akt-mTOR signaling and cyclin-dependent kinase ( CDK ) 1 phosphorylation and down-regulation ofp19 and p27 .
In contrast , SFN alone or SFN+everolimus reduced cell growth and proliferation .
Akt and Rictor signaling remained low , and p19 and p27 expressions were high under combined drug treatment .
Long-term exposure to SFN+everolimus also induced acetylation of the H3 and H4 histones .
Phosphorylation of CDK1 was diminished , whereby down-regulation of CDK1 and its binding partner , Cyclin B , inhibited tumor growth .
In conclusion , the addition of SFN @ @ @ @ @ @ @ development in bladder cancer cells in vitro .
Therefore , sulforaphane may hold potential for treating bladder carcinoma in patients with resistance to an mTOR inhibitor .

Progressive bladder cancer growth is associated with abnormal activation of the mammalian target of the rapamycin (mTOR) pathway, but treatment with an mTOR inhibitor has not been as effective as expected. Rather, resistance develops under chronic drug use, prompting many patients to lower their relapse risk by turning to natural, plant-derived products. The present study was designed to evaluate whether the natural compound, sulforaphane (SFN), combined with the mTOR inhibitor everolimus, could block the growth and proliferation of bladder cancer cells in the short- and long-term. The bladder cancer cell lines RT112, UMUC3, and TCCSUP were exposed short- (24 h) or long-term (8 weeks) to everolimus (0.5 nM) or SFN (2.5µM) alone or in combination. Cell growth, proliferation, apoptosis, cell cycle progression, and cell cycle regulating proteins were evaluated. siRNA blockade was used to investigate the functional impact of the proteins. Short-term application of SFN and/or everolimus resulted in significant tumorgrowth suppression, with additive inhibition on clonogenic tumor growth. Long-term everolimus treatment resulted in resistance development characterized by continued growth, and was associated with elevated Akt-mTOR signaling and cyclin-dependent kinase (CDK)1 phosphorylation and down-regulation ofp19 and p27. In contrast, SFN alone or SFN+everolimus reduced cell growth and proliferation. Akt and Rictor signaling remained low, and p19 and p27 expressions were high under combined drug treatment. Long-term exposure to SFN+everolimus also induced acetylation of the H3 and H4 histones. Phosphorylation of CDK1 was diminished, whereby down-regulation of CDK1 and its binding partner, Cyclin B, inhibited tumor growth. In conclusion, the addition of SFN to the long-term everolimus application inhibits resistance development in bladder cancer cells in vitro. Therefore, sulforaphane may hold potential for treating bladder carcinoma in patients with resistance to an mTOR inhibitor.


greenmedinfo--2020-07-12--Sulforaphane exerts anticancer effects on human liver cancer cells.

PURPOSE : This study was undertaken to investigate the anticancer effects of Sulforaphane against liver cancer and to elucidate the underlying molecular mechanisms .
METHODS : WST-1 assay was used to monitor the proliferation rate .
DAPI and annexin V/propidium iodide ( PI ) staining was used for apoptosis .
Flow cytometry was used for cell cycle analysis .
Wound heal and transwell assays were used to monitor cell migration and invasion .
The protein expression was determined by western blot analysis .
RESULTS : It was found that Sulforaphane decreased the viability of the liver cancer HepG2 cells and @ @ @ @ @ @ @ , Sulforaphane ( µM ) exerted very low toxic effects on the normal AML12 hepatocytes and exhibited an IC50 of 100 µM .
Flow cytometery analysis showed that Sulforaphane triggered G2/M arrest of the liver HepG2 cancer cells .
DAPI staining revealed that Sulforaphane triggered the apoptotic cell death of HepG2 cells which was accompanied with activation of caspases 3 and 9 , upregulation of Bax and downregulation of Bcl-2 .
Transwell assays showed that Sulforaphane inhibited the migration and invasion of the HepG2 liver cancer cells in a dose dependent manner .
@ @ @ @ @ @ @ on the MAPK7 signalling pathway and it was found that Sulforaphane could block this pathway in HepG2 cells .
CONCLUSION : Taken together , Sulforaphane may prove essential in the development of chemotherapy for liver cancers .

PURPOSE: This study was undertaken to investigate the anticancer effects of Sulforaphane against liver cancer and to elucidate the underlying molecular mechanisms.
METHODS: WST-1 assay was used to monitor the proliferation rate. DAPI and annexin V/propidium iodide (PI) staining was used for apoptosis. Flow cytometry was used for cell cycle analysis. Wound heal and transwell assays were used to monitor cell migration and invasion. The protein expression was determined by western blot analysis.
RESULTS: It was found that Sulforaphane decreased the viability of the liver cancer HepG2 cells and exhibited an IC50 of 9µM. Nonetheless, Sulforaphane (µM) exerted very low toxic effects on the normal AML12 hepatocytes and exhibited an IC50 of 100 µM. Flow cytometery analysis showed that Sulforaphane triggered G2/M arrest of the liver HepG2 cancer cells. DAPI staining revealed that Sulforaphane triggered the apoptotic cell death of HepG2 cells which was accompanied with activation of caspases 3 and 9, upregulation of Bax and downregulation of Bcl-2. Transwell assays showed that Sulforaphane inhibited the migration and invasion of the HepG2 liver cancer cells in a dose dependent manner. The effects of Sulforaphane were also investigated on the MAPK7 signalling pathway and it was found that Sulforaphane could block this pathway in HepG2 cells.
CONCLUSION: Taken together, Sulforaphane may prove essential in the development of chemotherapy for liver cancers.


greenmedinfo--2020-07-14--These findings enhance the understanding of the biological mechanisms behind the observed antidepres

These findings enhance the understanding of the biological mechanisms behind the observed antidepressant effects of ayahuasca.

BACKGROUND : Ayahuasca is a traditional Amazon brew and its potential antidepressant properties have recently been explored in scientific settings .
We conducted a double-blind placebo-controlled trial of ayahuasca with treatment-resistant depression patients ( = 28 ) and healthy controls ( = 45 ) .
AIMS : We are evaluating the blood inflammatory biomarkers : C-reactive protein and interleukin 6 , as a potential consequence of ayahuasca intake and their correlation with serum cortisol and brain-derived neurotrophic factor levels .
Blood samples were collected at pre-treatment and 48 hours after substance ingestion to assess the concentration of inflammatory biomarkers , @ @ @ @ @ @ @ Rating Scale .
RESULTS : At pre-treatment , patients showed higher C-reactive protein levels than healthy controls and a significant negative correlation between C-reactive protein and serum cortisol levels was revealed ( = -0.40 , = 14 ) .
C-reactive protein in those patients was not correlated with Montgomery-Åsberg Depression Rating Scale scores .
We observed a significant reduction of C-reactive protein levels across time in both patients and controls treated with ayahuasca , but not with placebo .
Patients treated with ayahuasca showed a significant correlation ( = + 0.57 ) between @ @ @ @ @ @ @ depressive symptoms at 48 hours after substance ingestion ( Montgomery-Åsberg Depression Rating Scale ) .
No significant result with respect to interleukin 6 and brain-derived neurotrophic factor was found .
Furthermore , these biomarkers did not predict the antidepressant response or remission rates observed .
CONCLUSIONS : These findings enhance the understanding of the biological mechanisms behind the observed antidepressant effects of ayahuasca and encourage further clinical trials in adults with depression .

BACKGROUND: Ayahuasca is a traditional Amazon brew and its potential antidepressant properties have recently been explored in scientific settings. We conducted a double-blind placebo-controlled trial of ayahuasca with treatment-resistant depression patients (= 28) and healthy controls (= 45).
AIMS: We are evaluating the blood inflammatory biomarkers: C-reactive protein and interleukin 6, as a potential consequence of ayahuasca intake and their correlation with serum cortisol and brain-derived neurotrophic factor levels. Blood samples were collected at pre-treatment and 48 hours after substance ingestion to assess the concentration of inflammatory biomarkers, together with administration of the Montgomery-Åsberg Depression Rating Scale.
RESULTS: At pre-treatment, patients showed higher C-reactive protein levels than healthy controls and a significant negative correlation between C-reactive protein and serum cortisol levels was revealed (= -0.40,= 14). C-reactive protein in those patients was not correlated with Montgomery-Åsberg Depression Rating Scale scores. We observed a significant reduction of C-reactive protein levels across time in both patients and controls treated with ayahuasca, but not with placebo. Patients treated with ayahuasca showed a significant correlation (= + 0.57) between larger reductions of C-reactive protein and lower depressive symptoms at 48 hours after substance ingestion (Montgomery-Åsberg Depression Rating Scale). No significant result with respect to interleukin 6 and brain-derived neurotrophic factor was found. Furthermore, these biomarkers did not predict the antidepressant response or remission rates observed.
CONCLUSIONS: These findings enhance the understanding of the biological mechanisms behind the observed antidepressant effects of ayahuasca and encourage further clinical trials in adults with depression.


greenmedinfo--2020-07-14--Heavy metals induce antibiotic resistance and dandelion root extracts and taraxasterol could be used

Heavy metals induce antibiotic resistance and dandelion root extracts and taraxasterol could be used to help reverse bacterial resistance to antibiotics.

Metal exposure is an important factor for inducing antibiotic resistance in bacteria .
Dandelion extracts have been used for centuries in traditional Chinese and Native American medicine.We assessed the effects of dandelion water extracts and taraxasterol on heavy metal-induced antibiotic resistance inas well as the underlying mechanisms.Dandelion extracts were obtained through 4 h of boiling in distilled water .
Bacterial growth was monitored with a spectrophotometer .
Biochemical assays were performed to assess the activities and gene transcriptions of β-lactamase and acetyltransferase .
Oxidative stress was determined using an oxidation-sensitive probe , HDCFDA.The present study demonstrated that higher concentrations of @ @ @ @ @ @ @ cadmium ( > 0.1µg ml ) , arsenic ( > 0.1µg ml ) and copper ( > 5µg ml ) significantly inhibited the growth of .
Lower concentrations of nickel ( 0.5µg ml ) , cadmium ( 0.05µg ml ) and arsenic ( 0.05µg ml ) had no effect on bacterial growth , but helped the bacteria become resistant to two antibiotics , kanamycin and ampicillin .
The addition of dandelion root extracts and taraxasterol significantly reversed the antibiotic resistance induced by these heavy metals .
The supplements of antibiotics and cadmium generated @ @ @ @ @ @ @ acetyltransferase ( two antibiotic resistance-related proteins ) , which were significantly blocked by either dandelion root extract or taraxasterol .
In contrast , oxidative stress was not involved in the preventative roles of dandelion root extracts and taraxasterol in heavy metal-induced antibiotic resistance.This study suggests that heavy metals induce bacterial antibiotic resistance and dandelion root extracts and taraxasterol could be used to help reverse bacterial resistance to antibiotics .

Metal exposure is an important factor for inducing antibiotic resistance in bacteria. Dandelion extracts have been used for centuries in traditional Chinese and Native American medicine.We assessed the effects of dandelion water extracts and taraxasterol on heavy metal-induced antibiotic resistance inas well as the underlying mechanisms.Dandelion extracts were obtained through 4 h of boiling in distilled water. Bacterial growth was monitored with a spectrophotometer. Biochemical assays were performed to assess the activities and gene transcriptions of β-lactamase and acetyltransferase. Oxidative stress was determined using an oxidation-sensitive probe, HDCFDA.The present study demonstrated that higher concentrations of nickel (>5µg ml), cadmium (>0.1µg ml), arsenic (>0.1µg ml) and copper (>5µg ml) significantly inhibited the growth of. Lower concentrations of nickel (0.5µg ml), cadmium (0.05µg ml) and arsenic (0.05µg ml) had no effect on bacterial growth, but helped the bacteria become resistant to two antibiotics, kanamycin and ampicillin. The addition of dandelion root extracts and taraxasterol significantly reversed the antibiotic resistance induced by these heavy metals. The supplements of antibiotics and cadmium generated synergistic effects on the activities ofβ-lactamase and acetyltransferase (two antibiotic resistance-related proteins), which were significantly blocked by either dandelion root extract or taraxasterol. In contrast, oxidative stress was not involved in the preventative roles of dandelion root extracts and taraxasterol in heavy metal-induced antibiotic resistance.This study suggests that heavy metals induce bacterial antibiotic resistance and dandelion root extracts and taraxasterol could be used to help reverse bacterial resistance to antibiotics.


greenmedinfo--2020-07-14--Taraxasterol protects hippocampal neurons from oxygen-glucose deprivation-induced injury.

Cerebral ischemia/reperfusion ( I/R ) injury is a brain injury following ischaemic stroke that is associated with oxidative stress .
Taraxasterol , a natural product , has been shown to have anti-oxidative and neuro-protective effects .
However , the role of taraxasterol in cerebral I/R injury remains unknown .
Primary hippocampal neurons were subjected to oxygen-glucose deprivation/reperfusion ( OGD/R ) to induce cerebral I/R injury .
Cell viability of hippocampal neurons was measured CCK-8 assay .
Reactive oxygen species ( ROS ) production and MDA generation were measured to reflect oxidative stress .
Western blotting was performed to evaluate the @ @ @ @ @ @ @ factor 2 ( Nrf2 ) , haem oxygenase ( HO-1 ) , NAD ( P ) H : quinone oxidoreductase 1 ( NQO-1 ) and GPx-3 .
Caspase-3 activity was measured to assess cell apoptosis .
Hippocampal neurons were treated with ML385 to inhibit Nrf2 signalling pathway .
Our results showed that taraxasterol improved OGD/R-caused decrease in cell viability of hippocampal neurons .
In addition , taraxasterol significantly suppressed ROS production and MDA generation in OGD/R-induced hippocampal neurons .
Taraxasterol resulted in a significant decrease in caspase-3 activity and bcl-2 expression , as @ @ @ @ @ @ @ Furthermore , taraxasterol induced the Nrf2 nuclear accumulation and expressions of HO-1 , NQO-1 and GPx-3 in OGD/R-induced hippocampal neurons .
Notably , inhibition of Nrf2 signalling reversed the protective effects of taraxasterol on OGD/R-induced hippocampal neurons injury .
In conclusion , these findings indicated that taraxasterol protected hippocampal neurons from OGD/R-induced oxidative stress and cell apoptosisregulating the Nrf2 signalling pathway .

Cerebral ischemia/reperfusion (I/R) injury is a brain injury following ischaemic stroke that is associated with oxidative stress. Taraxasterol, a natural product, has been shown to have anti-oxidative and neuro-protective effects. However, the role of taraxasterol in cerebral I/R injury remains unknown. Primary hippocampal neurons were subjected to oxygen-glucose deprivation/reperfusion (OGD/R) to induce cerebral I/R injury. Cell viability of hippocampal neurons was measured CCK-8 assay. Reactive oxygen species (ROS) production and MDA generation were measured to reflect oxidative stress. Western blotting was performed to evaluate the expressions of bax, bcl-2, NF-E2-related factor 2 (Nrf2), haem oxygenase (HO-1), NAD(P)H:quinone oxidoreductase 1 (NQO-1) and GPx-3. Caspase-3 activity was measured to assess cell apoptosis. Hippocampal neurons were treated with ML385 to inhibit Nrf2 signalling pathway. Our results showed that taraxasterol improved OGD/R-caused decrease in cell viability of hippocampal neurons. In addition, taraxasterol significantly suppressed ROS production and MDA generation in OGD/R-induced hippocampal neurons. Taraxasterol resulted in a significant decrease in caspase-3 activity and bcl-2 expression, as well as increase in bax expression. Furthermore, taraxasterol induced the Nrf2 nuclear accumulation and expressions of HO-1, NQO-1 and GPx-3 in OGD/R-induced hippocampal neurons. Notably, inhibition of Nrf2 signalling reversed the protective effects of taraxasterol on OGD/R-induced hippocampal neurons injury. In conclusion, these findings indicated that taraxasterol protected hippocampal neurons from OGD/R-induced oxidative stress and cell apoptosisregulating the Nrf2 signalling pathway.


greenmedinfo--2020-07-14--Busted: 11 COVID Assumptions Based on Fear Not Fact

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By providing the information contained herein we are not diagnosing , treating @ @ @ @ @ or preventing any type of disease or medical condition .
Before beginning any type of @ @ @ @ @ treatment regimen , it is advisable to seek the advice of a licensed healthcare professional @

This website is for information purposes only. By providing the information contained herein we are not diagnosing, treating, curing, mitigating, or preventing any type of disease or medical condition. Before beginning any type of natural, integrative or conventional treatment regimen, it is advisable to seek the advice of a licensed healthcare professional.
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greenmedinfo--2020-07-16--Ellagic acid is a potent dual-target inhibitor against hepatitis C virus genotype 3 (HCV G3) NS3 enz

Ellagic acid is a potent dual-target inhibitor against hepatitis C virus genotype 3 (HCV G3) NS3 enzymes.

Structure-based virtual screening ( SBVS ) has served as a popular strategy for rational drug discovery .
In this study @ @ @ @ @ novel benzopyran-based inhibitors that targeted the NS3 enzymes ( NS3/4A protease and NS3 helicase ) @ @ @ @ @ combination of in silico and in vitro approaches .
With the aid of SBVS , @ @ @ @ @ to inhibit HCV G3 NS3/4A protease and two phytochemicals ( ellagic acid and myricetin ) @ @ @ @ @ that inhibited both NS3/4A protease and NS3 helicase in vitro ( IC= 40.37± 5.47 nM @ @ @ @ @ respectively ) .
Inhibitory activities against the replication of HCV G3 replicons were further assessed @ @ @ @ @ four compounds showed dose-dependent inhibition .
Compound P8 was determined to be the most potent @ @ @ @ @ withan ECof 19.05µM .
The dual-target inhibitor , ellagic acid was determined as the second @ @ @ @ @ ) and the most selective in its inhibitory activity against the replication of HCV replicons @ @ @ @ @ viability of the host cells ( selectivity index = 6.18 ) .

Structure-based virtual screening (SBVS) has served as a popular strategy for rational drug discovery. In this study, we aimed to discover novel benzopyran-based inhibitors that targeted the NS3 enzymes (NS3/4A protease and NS3 helicase) of HCV G3 using a combination of in silico and in vitro approaches. With the aid of SBVS, six novel compounds were discovered to inhibit HCV G3 NS3/4A protease and two phytochemicals (ellagic acid and myricetin) were identified as dual-target inhibitors that inhibited both NS3/4A protease and NS3 helicase in vitro (IC= 40.37± 5.47 nM and 6.58 ± 0.99 µM respectively). Inhibitory activities against the replication of HCV G3 replicons were further assessed in a cell-based system with four compounds showed dose-dependent inhibition. Compound P8 was determined to be the most potent compound from the cell-based assay withan ECof 19.05µM. The dual-target inhibitor, ellagic acid was determined as the second most potent (EC= 32.37µM) and the most selective in its inhibitory activity against the replication of HCV replicons, without severely affecting the viability of the host cells (selectivity index = 6.18).


greenmedinfo--2020-07-15--The COVID-19 Curve Has Been Flattened

The COVID-19 Curve Has Been Flattened


greenmedinfo--2020-07-15--Metabolomics revealing the response of rice exposed to polystyrene microplastics.

Large amounts of microplastics accumulate in the agricultural soil .
Microplastics would stress the crops but the underlying mechanism remains unclear .
Herein , a laboratory exposure and field trials were carried out to investigate the response of rice ( Oryza sativa L. II You .
900 ) to stress induced by polystyrene microplastics ( PS-MPs ) using a metabolomic approach .
After laboratory exposure for 21 days , the decreases in shoot biomass of rice exposed to low , medium and high doses of PS-MPs were 13.1 % ( CV = 4.1 % ) , 18.8 % ( CV @ @ @ @ @ @ @ % ( CV = 9.2 % ) , respectively , while the antioxidant enzymes showed an inverted upper-U shape when exposed to PS-MPs .
A total of 24 samples from three exposure dose levels were included in the metabolic analysis .
The metabolites of 12 amino acids , 16 saccharides , 26 organic acids and 17 others ( lipids and polyols ) in leaves decreased after the exposure to both 50 mg Land 250 mg LPS-MPs doses with hydroponically-cultured .
The inhibition of perturbed biological pathway causes the biosynthesis of amino acids , @ @ @ @ @ @ @ secondary metabolites decreased which indicate that the energy expenditure exceeded the substance accumulation .
In order to further validate the effects of PS-MPs on rice leaves obtained from the laboratory-scale experiments , a field-trial experiment was conducted .
After 142 days of cultivation in farmland , the results with a maximum of 25.9 % lower biomass in the crops exposed with PS-MPs .
As such , the presence of PS-MPs may affect rice production by altering the metabolic systems of rice .
Long-term exposure of PS-MPs to rice might be a potential risk @ @ @ @ @ @

Large amounts of microplastics accumulate in the agricultural soil. Microplastics would stress the crops but the underlying mechanism remains unclear. Herein, a laboratory exposure and field trials were carried out to investigate the response of rice (Oryza sativa L. II You. 900) to stress induced by polystyrene microplastics (PS-MPs) using a metabolomic approach. After laboratory exposure for 21 days, the decreases in shoot biomass of rice exposed to low, medium and high doses of PS-MPs were 13.1% (CV = 4.1%), 18.8% (CV = 3.7%), and 40.3% (CV = 9.2%), respectively, while the antioxidant enzymes showed an inverted upper-U shape when exposed to PS-MPs. A total of 24 samples from three exposure dose levels were included in the metabolic analysis. The metabolites of 12 amino acids, 16 saccharides, 26 organic acids and 17 others (lipids and polyols) in leaves decreased after the exposure to both 50 mg Land 250 mg LPS-MPs doses with hydroponically-cultured. The inhibition of perturbed biological pathway causes the biosynthesis of amino acids, nucleic acids, fatty acids and some secondary metabolites decreased which indicate that the energy expenditure exceeded the substance accumulation. In order to further validate the effects of PS-MPs on rice leaves obtained from the laboratory-scale experiments, a field-trial experiment was conducted. After 142 days of cultivation in farmland, the results with a maximum of 25.9% lower biomass in the crops exposed with PS-MPs. As such, the presence of PS-MPs may affect rice production by altering the metabolic systems of rice. Long-term exposure of PS-MPs to rice might be a potential risk to rice safety and quality.


greenmedinfo--2020-07-15--Dill powder supplementation can be effective in controlling the glycemic, lipid, stress oxidative an

BACKGROUND : The objective of this study was to investigate the effects of Anethum graveolens ( dill ) powder supplementation @ @ @ @ @ profile , some antioxidants and inflammatory markers , and gastrointestinal symptoms in patients with type @ @ @ @ @ METHODS : In this study , 42 patients with type 2 diabetes were randomly allocated @ @ @ @ @ and received either 3 g/day dill powder or placebo ( 3 capsules/day , 1 g @ @ @ @ @ sugar , insulin , homeostatic model assessment of insulin resistance , lipid profile , high-sensitivity @ @ @ @ @ capacity , malondialdehyde and gastrointestinal symptoms were measured in all of the subjects at baseline @ @ @ @ @ The dill powder supplementation significantly decreased the mean serum levels of insulin , homeostatic model @ @ @ @ @ low-density lipoprotein cholesterol , total cholesterol and malondialdehyde in the intervention group in comparison with @ @ @ @ @ CONCLUSION : Dill powder supplementation can be effective in controlling the glycemic , lipid , @ @ @ @ @ in patients with type 2 diabetes .

BACKGROUND: The objective of this study was to investigate the effects of Anethum graveolens (dill) powder supplementation on glycemic control, lipid profile, some antioxidants and inflammatory markers, and gastrointestinal symptoms in patients with type 2 diabetes.
MATERIALS AND METHODS: In this study, 42 patients with type 2 diabetes were randomly allocated to intervention and control groups and received either 3 g/day dill powder or placebo (3 capsules/day, 1 g each). Fasting blood sugar, insulin, homeostatic model assessment of insulin resistance, lipid profile, high-sensitivity C-reactive protein, total antioxidant capacity, malondialdehyde and gastrointestinal symptoms were measured in all of the subjects at baseline and postintervention.
RESULTS: The dill powder supplementation significantly decreased the mean serum levels of insulin, homeostatic model assessment of insulin resistance, low-density lipoprotein cholesterol, total cholesterol and malondialdehyde in the intervention group in comparison with the baseline measurements (P < 0.05). Furthermore, the mean serum levels of high-density lipoprotein and total antioxidant capacity were significantly increased in the intervention group in comparison with the baseline measurement (P < 0.05). Colonic motility disorder was the only gastrointestinal symptom whose frequency was significantly reduced by supplementation (P = 0.01). The mean changes in insulin, low-density lipoprotein cholesterol, total cholesterol and malondialdehyde were significantly lower in the interventiongroup than in the control group (P < 0.05). In addition, the mean changes in high-density lipoprotein were significantly higher in the intervention group than in the control group (P < 0.05).
CONCLUSION: Dill powder supplementation can be effective in controlling the glycemic, lipid, stress oxidative and gastrointestinal symptoms in patients with type 2 diabetes.
TRIAL REGISTRATION: Iran Clinical Trials Registry: IRCT20120704010181N12. Registered on 12 May 2018.


greenmedinfo--2020-07-15--The present findings demonstrate the potentials of Pimpinella anisum extract to relax pregnant uteri

The present findings demonstrate the potentials of Pimpinella anisum extract to relax pregnant uterine contractions.

ETHNOPHARMACOLOGY RELEVANCE : Pimpinella anisum is a well-known traditional medicinal herb which has been used in folk medicine as an antiulcer , anticancer , antibacterial and as a muscle relaxant .
AIM OF THE STUDY : This study was performed to explore the modulatory effects of Pimpinella anisum on term-pregnant rat uterine contractility and to investigate its possible underlying mechanisms .
MATERIAL AND METHODS : Intact uterine strips without endometrial layer were isolated from female term-pregnant Wistar rats ( 22 days of gestation ) and mounted in a tissue bath apparatus for in vitro isometric force recording .
The effects @ @ @ @ @ @ @ ( PAE ) ( 1 , 3 , 5 , and 7 mg/mL ) were examined on uterine contractions generated spontaneously or induced with oxytocin ( 5 nmol/L ) , Bay K8644 ( 1 μmol/L ) , and carbachol ( 10 μmol/L ) .
In some experiments , PAE was applied on depolarized myometrium in the presence of high-KCl solution ( 60 mmol/L ) .
The effect on Carelease was also examined .
RESULTS : Application of PAE significantly reduced uterine contractions generated spontaneously or induced with oxytocin , Bay K8644 , and @ @ @ @ @ @ @ = 7 ; P CONCLUSION : The present findings demonstrate the potentials of PAE to relax pregnant uterine contractions possibly by blocking Caentry via L-type calcium channels and inhibiting Carelease from the internal store .
The tocolytic effects of PAE may be a potential adjuvant against strong premature uterine contractions which threaten early pregnancy although clinical studies are required .

ETHNOPHARMACOLOGY RELEVANCE: Pimpinella anisum is a well-known traditional medicinal herb which has been used in folk medicine as an antiulcer, anticancer, antibacterial and as a muscle relaxant.
AIM OF THE STUDY: This study was performed to explore the modulatory effects of Pimpinella anisum on term-pregnant rat uterine contractility and to investigate its possible underlying mechanisms.
MATERIAL AND METHODS: Intact uterine strips without endometrial layer were isolated from female term-pregnant Wistar rats (22 days of gestation) and mounted in a tissue bath apparatus for in vitro isometric force recording. The effects of different concentrations of Pimpinella anisum extract (PAE) (1, 3, 5, and 7 mg/mL) were examined on uterine contractions generated spontaneously or induced with oxytocin (5 nmol/L), Bay K8644 (1 μmol/L), and carbachol (10 μmol/L). In some experiments, PAE was applied on depolarized myometrium in the presence of high-KCl solution (60 mmol/L). The effect on Carelease was also examined.
RESULTS: Application of PAE significantly reduced uterine contractions generated spontaneously or induced with oxytocin, Bay K8644, and carbachol in a concentration-dependent manner (n = 7; P < 0.01). In depolarized myometrium, PAE significantly reduced the tonic force induced by high-KCl solution (n = 7; P < 0.01). PAE prevented oxytocin-induced transient contraction in the entire absence of external calcium (n = 7; P < 0.01).
CONCLUSION: The present findings demonstrate the potentials of PAE to relax pregnant uterine contractions possibly by blocking Caentry via L-type calcium channels and inhibiting Carelease from the internal store. The tocolytic effects of PAE may be a potential adjuvant against strong premature uterine contractions which threaten early pregnancy although clinical studies are required.


greenmedinfo--2020-07-16--Top 10 Natural Cough and Lung Remedies

Top 10 Natural Cough and Lung Remedies


greenmedinfo--2020-07-16--Asiaticoside attenuates bleomycin-induced pulmonary fibrosis.

Idiopathic Pulmonary fibrosis ( PF ) is a chronic progressive disease , which is a lack of effective treatment , and the pathogenesis of IPF is not fully elucidated .
Asiaticoside ( AS ) is isolated from Centella asiatica and has the effect of promoting scar healing and reducing scar formation .
However , its possible role in idiopathic pulmonary fibrosis remains unclear .
Adenosine A2A receptor ( A2AR ) is reported a protective factor in pulmonary fibrosis , and the bone morphogenetic protein 7 ( BMP7 ) signaling pathway plays a crucial role in fibrosis in multiple organs .
@ @ @ @ @ @ @ BMP7 pathway has not yet been reported .
Therefore , we hypothesized AS may promote the expression of A2AR , and then influence the BMP7/Smad1/5 pathway to alleviate pulmonary fibrosis .
A2ARmice and wild-type ( WT ) mice were administered bleomycin ( BLM ) by intratracheal injection .
AS ( 50 mg/kg/d ) was given daily for 28 days .
AS reduced collagen deposition in lung tissue , interstitial lung inflammation .
Furthermore , AS promoted A2AR expression and BMP7 pathway .
Collectively , AS may attenuate BLM-induced pulmonary fibrosis by upregulating the @ @ @ @ @ @

Idiopathic Pulmonary fibrosis(PF)is a chronic progressive disease, which is a lack of effective treatment,and the pathogenesis of IPF is not fully elucidated. Asiaticoside(AS) is isolated from Centella asiatica and has the effect of promoting scar healing and reducing scar formation. However,its possible role in idiopathic pulmonary fibrosis remains unclear. Adenosine A2A receptor (A2AR) is reported a protective factor in pulmonary fibrosis, and the bone morphogenetic protein 7 (BMP7) signaling pathway plays a crucial role in fibrosis in multiple organs. But the impact of A2AR on the BMP7 pathway has not yet been reported. Therefore, we hypothesized AS may promote the expression of A2AR, and then influence the BMP7/Smad1/5 pathway to alleviate pulmonary fibrosis. A2ARmice and wild-type (WT) mice were administered bleomycin (BLM) by intratracheal injection. AS (50 mg/kg/d) was given daily for 28 days. AS reduced collagen deposition in lung tissue, interstitial lung inflammation. Furthermore, AS promoted A2AR expression and BMP7 pathway. Collectively, AS may attenuate BLM-induced pulmonary fibrosis by upregulating the BMP7 signaling pathway through A2AR.


greenmedinfo--2020-07-16--Centella asiatica extract prevents visual impairment by promoting the production of rhodopsin in the

Centella asiatica extract prevents visual impairment by promoting the production of rhodopsin in the retina.

BACKGROUND/OBJECTIVE : , also known as Gotu kola , is a tropical medicinal plant native to Madagascar , Southeast Asia , and South Africa .
It is well known to have biological activities , including wound healing , anti-inflammatory , antidiabetic , cytotoxic , and antioxidant effects .
The purpose of this study was to determine the efficacy of extracts ofagainst age-related eye degeneration and to examine their physiological activities .
MATERIALS/METHODS : To determine the effects of CA-HE50 ( 50 % EtOH extract ) on retinal pigment cells , we assessed the cytotoxicity of CoCland oxidized-A2E in ARPE-19 cells @ @ @ @ @ @ @ against-methyl -- nitrosourea ( MNU ) -induced retinal damage in C57BL/6 mice .
In particular , we measured factors related to apoptosis and anti-oxidation and the protein levels of rhodopsin/opsin .
We also measured glucose uptake to characterize glucose metabolism , a major factor in cell protection .
RESULTS : Induction of cytotoxicity with CoCland oxidized-A2E inhibited decreases in the viability of ARPE-19 cells when CA-HE50 was administered , and promoted glucose uptake under normal conditions ( < 0.05 ) .
In addition , CA-HE50 inhibited degeneration/apoptosis of the retina in the context @ @ @ @ @ @ @ .
In particular , CA-HE50 at 200 mg/kg inhibited the cleavage of pro-caspase-3 and pro-poly ( ADP-ribose ) -polymerase and maintained the expressions of nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 similar to normal control levels .
Rhodopsin/opsin expression was maintained at a higher level than in normal controls .
CONCLUSION : A series of experiments confirmed that CA-HE50 was effective for inhibiting or preventing age-related eye damage/degeneration .
Based on these results , we believe it is worthwhile to develop drugs or functional foods related to age-related eye degeneration using @ @

BACKGROUND/OBJECTIVE: , also known as Gotu kola, is a tropical medicinal plant native to Madagascar, Southeast Asia, and South Africa. It is well known to have biological activities, including wound healing, anti-inflammatory, antidiabetic, cytotoxic, and antioxidant effects. The purpose of this study was to determine the efficacy of extracts ofagainst age-related eye degeneration and to examine their physiological activities.
MATERIALS/METHODS: To determine the effects of CA-HE50 (50% EtOH extract) on retinal pigment cells, we assessed the cytotoxicity of CoCland oxidized-A2E in ARPE-19 cells and observed the protective effects of CA-HE50 against-methyl--nitrosourea (MNU)-induced retinal damage in C57BL/6 mice. In particular, we measured factors related to apoptosis and anti-oxidation and the protein levels of rhodopsin/opsin. We also measured glucose uptake to characterize glucose metabolism, a major factor in cell protection.
RESULTS: Induction of cytotoxicity with CoCland oxidized-A2E inhibited decreases in the viability of ARPE-19 cells when CA-HE50 was administered, and promoted glucose uptake under normal conditions (<0.05). In addition, CA-HE50 inhibited degeneration/apoptosis of the retina in the context of MNU-induced toxicity (<0.05). In particular, CA-HE50 at 200 mg/kg inhibited the cleavage of pro-caspase-3 and pro-poly (ADP-ribose)-polymerase and maintained the expressions of nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 similar to normal control levels. Rhodopsin/opsin expression was maintained at a higher level than in normal controls.
CONCLUSION: A series of experiments confirmed that CA-HE50 was effective for inhibiting or preventing age-related eye damage/degeneration. Based on these results, we believe it is worthwhile to develop drugs or functional foods related to age-related eye degeneration using CA-HE50.


greenmedinfo--2020-07-16--Effects of compound centella on oxidative stress and keap1-Nrf2-ARE pathway expression in diabetic k

Effects of compound centella on oxidative stress and keap1-Nrf2-ARE pathway expression in diabetic kidney disease.

The formula of Compound Centella mainly contains 3 traditional Chinese herbs : ( L. ) Urb .
( JiXueCao ) , Fish .
( HuangQi ) , andHook .
f. ( LeiGongTeng ) .
Though this formula is effective for treating diabetic kidney disease ( DKD ) in clinic , the exact mechanism is still unclear .
This study aims to investigate the effect and antioxidant mechanism of Compound Centella on DKD rats .
High-performance liquid chromatography ( HPLC ) was applied to analyse 3 herbs in Compound Centella .
Sprague-Dawley rats were divided into the normal group ( NG @ @ @ @ @ @ @ , Compound Centella group ( CCG ) , and losartan group ( LG ) , with 8 rats in each group .
On the first day of the experiment , rats in the NG were fed with ordinary -feed , while the other groups were fed with high-fat and high-sugar feed .
On the 29day , except the NG , the other 3 groups received a single intraperitoneal injection of streptozocin ( STZ , 35 mg/kg ) .
Fasting blood glucose ( FBG ) was measured on the 1day , 32day , 46day @ @ @ @ @ @ @ .
Total protein/creatinine ratio of urine was determined by the phenol red assay on the 1day and 112day .
Serum creatinine ( Scr ) was determined by an automatic biochemical analyser on the 112day .
Kidneys were collected on the 112day for analysis and evaluation .
Periodic acid-Schiff ( PAS ) staining , hematoxylin-eosin ( HE ) staining , and transmission electron microscopy were used to observe kidney pathological changes .
The mRNA and protein expressions of Kelch-like ECH-associated protein 1 ( Keap1 ) and nuclear factor-erythroid 2-related factor 2 ( Nrf2 ) @ @ @ @ @ @ @ , Western blot , and immunohistochemistry .
Oxidative stress was evaluated by detecting the levels of malondialdehyde ( MDA ) and heme oxidase-1 ( HO-1 ) .
The results showed that the content of asiaticoside , astragaloside , and triptolide in the herb was 5960 , 809 , and 2.42 g/g and in the Compound Centella was 340 , 64 , and 0.1403 g/mL by HPLC .
Compound Centella reduced the urine protein/creatinine ratio and improved renal pathology in the kidneys of DKD rats .
In addition , the mRNA and protein expressions @ @ @ @ @ @ @ upregulated by Compound Centella .
The expressions of MDA were downregulated but HO-1 were upregulated by Compound Centella .
Therefore , the protective effect of Compound Centella in the kidney of DKD rats may be related to regulating the Keap1-Nrf2-ARE pathway under oxidative stress , suggesting Compound Centella as a promising treatment against DKD .

The formula of Compound Centella mainly contains 3 traditional Chinese herbs:(L.) Urb. (JiXueCao),Fish. (HuangQi), andHook. f. (LeiGongTeng). Though this formula is effective for treating diabetic kidney disease (DKD) in clinic, the exact mechanism is still unclear. This study aims to investigate the effect and antioxidant mechanism of Compound Centella on DKD rats. High-performance liquid chromatography (HPLC) was applied to analyse 3 herbs in Compound Centella. Sprague-Dawley rats were divided into the normal group (NG), DKD group (DKDG), Compound Centella group (CCG), and losartan group (LG), with 8 rats in each group. On the first day of the experiment, rats in the NG were fed with ordinary -feed, while the other groups were fed with high-fat and high-sugar feed. On the 29day, except the NG, the other 3 groups received a single intraperitoneal injection of streptozocin (STZ, 35 mg/kg). Fasting blood glucose (FBG) was measured on the 1day, 32day, 46day, 56day, 84day, and 112day. Total protein/creatinine ratio of urine was determined by the phenol red assay on the 1day and 112day. Serum creatinine (Scr) was determined by an automatic biochemical analyser on the 112day. Kidneys were collected on the 112day for analysis and evaluation. Periodic acid-Schiff (PAS) staining, hematoxylin-eosin (HE) staining, and transmission electron microscopy were used to observe kidney pathological changes. The mRNA and protein expressions of Kelch-like ECH-associated protein 1 (Keap1) and nuclear factor-erythroid 2-related factor 2 (Nrf2) in renal tissues were detected by RT-qPCR, Western blot, and immunohistochemistry. Oxidative stress was evaluated by detecting the levels of malondialdehyde (MDA) and heme oxidase-1 (HO-1). The results showed that the content of asiaticoside, astragaloside, and triptolide in the herb was 5960, 809, and 2.42 g/g and in the Compound Centella was 340, 64, and 0.1403 g/mL by HPLC. Compound Centella reduced the urine protein/creatinine ratio and improved renal pathology in the kidneys of DKD rats. In addition, the mRNA and protein expressions of Keap1 and Nrf2 in kidneys were upregulated by Compound Centella. The expressions of MDA were downregulated but HO-1 were upregulated by Compound Centella. Therefore, the protective effect of Compound Centella in the kidney of DKD rats may be related to regulating the Keap1-Nrf2-ARE pathway under oxidative stress, suggesting Compound Centella as a promising treatment against DKD.


greenmedinfo--2020-07-16--C. asiatica treatment helps to prevent cerebral damage and maintain near normal cerebral function in

Centella asiatica is claimed to have a neuroprotective effect ; however , its ability to protect the cerebrum against damage in diabetes has never been identified .
The aims were to identify the possibility that C. asiatica ameliorates inflammation , oxidative stress , and apoptosis in the cerebrum in diabetes .
C. asiatica leave aqueous extract ( C. asiatica ) ( 50 , 100 , and 200 mg/kg/b.w . )
were given to diabetic rats for 28 days .
Changes in rats ' body weight , food and water intakes , and insulin and FBG levels were monitored .
Following @ @ @ @ @ @ @ for histological , biochemical , and molecular biological analyses .
The results revealed treatment with C. asiatica was able to ameliorate the loss in body weight , the increase in food and water intakes , the decrease in insulin , and the increase in FBG levels in diabetic rats .
Additionally , histopathological changes in the cerebrum and levels of p38 , ERK , JNK , cytosolic Nrf2 , Keap-1 , LPO , RAGE , and AGE levels decreased ; however , PI3K , AKT , IR , IRS , GLUT-1 , nuclear @ @ @ @ @ @ @ ( SOD , CAT , and GPx ) levels increased in diabetic rats receiving C. asiatica .
Furthermore , C. asiatica treatment also caused cerebral inflammation and apoptosis to decrease as indicated by decreased inflammatory markers ( cytosolic NF-κB p65 , p-Ikkβ , Ikkβ , iNOS , COX-2 , TNF-α , IL-6 , and IL-1β ) , decreased pro-apoptosis markers ( Casp-3 , 9 , and Bax ) , but increased anti-apoptosis marker , Bcl-2 .
Activity level of Na/K , Mg , and Ca-ATPases in the cerebrum also increased by C. asiatica @ @ @ @ @ @ @ helps to prevent cerebral damage and maintain near normal cerebral function in diabetes .

Centella asiatica is claimed to have a neuroprotective effect; however, its ability to protect the cerebrum against damage in diabetes has never been identified. The aims were to identify the possibility that C. asiatica ameliorates inflammation, oxidative stress, and apoptosis in the cerebrum in diabetes. C. asiatica leave aqueous extract (C. asiatica) (50, 100, and 200 mg/kg/b.w.) were given to diabetic rats for 28 days. Changes in rats' body weight, food and water intakes, and insulin and FBG levels were monitored. Following sacrificed, cerebrum was harvested and subjected for histological, biochemical, and molecular biological analyses. The results revealed treatment with C. asiatica was able to ameliorate the loss in body weight, the increase in food and water intakes, the decrease in insulin, and the increase in FBG levels in diabetic rats. Additionally, histopathological changes in the cerebrum and levels of p38, ERK, JNK, cytosolic Nrf2, Keap-1, LPO, RAGE, and AGE levels decreased; however, PI3K, AKT, IR, IRS, GLUT-1, nuclear NrfNqo-1, Ho-1, and anti-oxidative enzymes (SOD, CAT, and GPx) levels increased in diabetic rats receiving C. asiatica. Furthermore, C. asiatica treatment also caused cerebral inflammation and apoptosis to decrease as indicated by decreased inflammatory markers (cytosolic NF-κB p65, p-Ikkβ, Ikkβ, iNOS, COX-2, TNF-α, IL-6, and IL-1β), decreased pro-apoptosis markers (Casp-3, 9, and Bax), but increased anti-apoptosis marker, Bcl-2. Activity level of Na/K, Mg, and Ca-ATPases in the cerebrum also increased by C. asiatica treatment. Conclusions: C. asiatica treatment helps to prevent cerebral damage and maintain near normal cerebral function in diabetes.


greenmedinfo--2020-07-16--Centella asiatica potential in alleviating the alterations caused by diabetes in testes.

The in vivo effects of Centella asiatica L. Urban ( Family : Apiaceae ; CA ) on diabetes-induced testicular fatty acid misdistribution and oxidative injury were investigated .
Diabetic rats were treated with vehicle , CA or metformin daily for 14 days by oral gavage .
Fatty acid ( FA ) content in testis was analysed using gas chromatography-flame ionisation detection while redox indices were measured as peroxide value ( PV ) , malondialdehyde ( MDA ) , oxygen radical antioxidant capacity ( ORAC ) , reduced glutathione ( GSH ) , glutathione S-transferase ( GST ) and glutathione peroxidase @ @ @ @ @ @ @ omega-6 ( 61 % ) , and decreased omega-3 ( 23 % ) and monounsaturated fatty acids ( MUFA ; 18 % ) compared to non-diabetic controls .
Oxidative injury in diabetic rats was confirmed by increases in PV ( 112 % ) and MDA ( 77 % ) in addition to decreases in GSH ( 41 % ) and activities of GST ( 19 % ) & GPx ( 24 % ) compared to non-diabetic controls .
CA treatment led to 17 % reduction in omega-6 and 33 % rise in MUFA @ @ @ @ @ @ @ CA ameliorated the oxidative injury and improved antioxidant capacity by increasing GSH ( 49 % ) , GST ( 16 % ) and GPx ( 23 % ) when compared to diabetic controls .
Data suggest CA potential in alleviating the alterations caused by diabetes in testes through effects on omega-6 and MUFA ; and via increased GSH level and dependent enzyme activities .

The in vivo effects of Centella asiatica L. Urban (Family: Apiaceae; CA) on diabetes-induced testicular fatty acid misdistribution and oxidative injury were investigated. Diabetic rats were treated with vehicle, CA or metformin daily for 14 days by oral gavage. Fatty acid (FA) content in testis was analysed using gas chromatography-flame ionisation detection while redox indices were measured as peroxide value (PV), malondialdehyde (MDA), oxygen radical antioxidant capacity (ORAC), reduced glutathione (GSH), glutathione S-transferase(GST) and glutathione peroxidase (GPx) activities. Diabetes increased omega-6 (61%), and decreased omega-3 (23%) and monounsaturated fatty acids (MUFA; 18%) compared to non-diabetic controls. Oxidative injury in diabetic rats was confirmed by increases in PV (112%) and MDA (77%) in addition to decreases in GSH (41%) and activities of GST (19%)&GPx (24%) compared to non-diabetic controls. CA treatment led to 17% reduction in omega-6 and 33% rise in MUFA compared to diabetic controls. Additionally, CA ameliorated the oxidative injury and improved antioxidant capacity by increasing GSH (49%), GST (16%) and GPx (23%) when compared to diabetic controls. Data suggest CA potential in alleviating the alterations caused by diabetes in testes through effects on omega-6 and MUFA; and via increased GSH level and dependent enzyme activities.


greenmedinfo--2020-07-16--Myricetin diminishes myocardial injury as well as lethality in heat stroke by up-regulating HSP-72.

BACKGROUND : Heat stroke-induced mortality is rising across the globe .
So , the design of prophylactic and/or therapeutic modalities for heat stroke is pressing need .
The common plant derived flavonoid exhibits strong anti-oxidant and anti-inflammatory activities ; however , its effects in heat stroke remain unknown .
The study aimed to investigate the cardioprotective effects of myricetin on heat stroke induced acute myocardial injury as well as lethality in rats and to explore the underlying mechanisms .
METHODS : Myocardial injury was induced by subjecting the anesthetized rats to a high ambient temperature of 43°C for 70 min @ @ @ @ @ @ @ 5-25 mg/kg body weight ) was given to rats once per day for one week prior to the start of heat stress .
Heat shock protein 72 antibodies was given intraperitoneally to rats 24 h before the start of heat stress .
Myocardial injury severity was estimated by determing myocardial damage scores , myocardial injury indicators , myocardial oxidative and inflammatory factors .
Western blot analysis was used for cardiac expression of heat shock protein ( HSP ) 72 .
RESULTS : Significant ( P < 0.05 ) up-regulation of HSP-72 after chronic @ @ @ @ @ @ @ P < 0.05 ) reduction in hyperthermia , hypotension , cardiac inflammatory and oxidative damage and lethality .
Inhibition of HSP-72 showed a significant ( P < 0.05 ) reversal in the cardiaprotection as well as survival .
CONCLUSIONS : Our results indicate that myricetin diminishes myocardial injury as well as lethality in heat stroke by up-regulating HSP-72 and show promise as a novel prevention therapeutic for heat stroke .

BACKGROUND: Heat stroke-induced mortality is rising across the globe. So, the design of prophylactic and/or therapeutic modalities for heat stroke is pressing need. The common plant derived flavonoid exhibits strong anti-oxidant and anti-inflammatory activities; however, its effects in heat stroke remain unknown. The study aimed to investigate the cardioprotective effects of myricetin on heat stroke induced acute myocardial injury as well as lethality in rats and to explore the underlying mechanisms.
METHODS: Myocardial injury was induced by subjecting the anesthetized rats to a high ambient temperature of 43°C for 70 min. An intragastrical dose of myricetin (5-25 mg/kg body weight) was given to rats once per day for one week prior to the start of heat stress. Heat shock protein 72 antibodies was given intraperitoneally to rats 24 h before the start of heat stress. Myocardial injury severity was estimated by determing myocardial damage scores, myocardial injury indicators, myocardial oxidative and inflammatory factors. Western blot analysis was used for cardiac expression of heat shock protein (HSP)72.
RESULTS: Significant (P<0.05) up-regulation of HSP-72 after chronic administration of myricetin coincided with significant (P<0.05) reduction in hyperthermia, hypotension, cardiac inflammatory and oxidative damage and lethality. Inhibition of HSP-72 showed a significant (P<0.05) reversal in the cardiaprotection as well as survival.
CONCLUSIONS: Our results indicate that myricetin diminishes myocardial injury as well as lethality in heat stroke by up-regulating HSP-72 and show promise as a novel prevention therapeutic for heat stroke.


greenmedinfo--2020-07-16--The present findings suggest that myricetin could be further explored as a therapeutic agent for S.

The present findings suggest that myricetin could be further explored as a therapeutic agent for S. japonicum.

Schistosomiasis is a zoonotic and debilitating parasitic disease caused by .
Praziquantel remains the choice for treating schistosomiasis , but its efficacy could be hampered by emergence of resistance .
In this study , using large-scale drug screening , we selected out myricetin , a natural flavonol compound , having a good anti-schistosome effect .
We found that myricetin exhibited dose and time-dependent insecticidal effect on , with an LCof 600μM for 24 h , and inhibited female spawning .
The drug mainly destroyed the body structure of the worms and induced apoptosis of the worm cells , which in @ @ @ @ @ @ @ , oral administration of myricetin in mice infected withshowed a deworming effect , as evidenced by a significant reduction in the liver egg load .
H & E staining , quantitative RT-PCR , and Western blotting assays showed that myricetin significantly alleviated liver fibrosis in mice infected with .
Myricetin also effectively inhibited the expression of TGFβ1 , Smad2 , phospho-Smad2 , Smad3 , phospho-Smad3 , ERK , phospho-ERK , Akt , and phospho-Akt in the liver of infected mice , suggesting that myricetin attenuated liver fibrosis in micemodulating TGFβ1 and Akt signaling @ @ @ @ @ @ @ ( Th1/Th2/Th17/Treg ) in the mouse spleen further revealed that myricetin significantly increased the percentage Th1 cells in infected mice and reduced the proportion of Th2 cells and Th17 cells .
Immunology multiplex assay further showed that myricetin attenuated-induced rise in the plasma levels of IL-4 , IL-5 , IL-10 , IL-13 , and IL-17A in infected mice while increasing the plasma contents of IFN-γ , IL-12 , and IL-7 .
In conclusion , our study provides the first direct evidence that myricin possesses potent anti-schistosome activitiesand , and offers new insights into @ @ @ @ @ @ @ The present findings suggest that myricetin could be further explored as a therapeutic agent for .

Schistosomiasis is a zoonotic and debilitating parasitic disease caused by. Praziquantel remains the choice for treating schistosomiasis, but its efficacy could be hampered by emergence of resistance. In this study, using large-scale drug screening, we selected out myricetin, a natural flavonol compound, having a good anti-schistosome effect. We found that myricetin exhibited dose and time-dependent insecticidal effect on, with an LCof 600μM for 24 h, and inhibited female spawning. The drug mainly destroyed the body structure of the worms and induced apoptosis of the worm cells, which in turn led to death. In addition, oral administration of myricetin in mice infected withshowed a deworming effect, as evidenced by a significant reduction in the liver egg load. H&E staining, quantitative RT-PCR, and Western blotting assays showed that myricetin significantly alleviated liver fibrosis in mice infected with. Myricetin also effectively inhibited the expression of TGFβ1, Smad2, phospho-Smad2, Smad3, phospho-Smad3, ERK, phospho-ERK, Akt, and phospho-Akt in the liver of infected mice, suggesting that myricetin attenuated liver fibrosis in micemodulating TGFβ1 and Akt signaling. Flow cytometric analysis of Th subtypes (Th1/Th2/Th17/Treg) in the mouse spleen further revealed that myricetin significantly increased the percentage Th1 cells in infected mice and reduced the proportion of Th2 cells and Th17 cells. Immunology multiplex assay further showed that myricetin attenuated-induced rise in the plasma levels of IL-4, IL-5, IL-10, IL-13, and IL-17A in infected mice while increasing the plasma contents of IFN-γ, IL-12, and IL-7. In conclusion, our study provides the first direct evidence that myricin possesses potent anti-schistosome activitiesand, and offers new insights into the mechanisms of action by myricetin. The present findings suggest that myricetin could be further explored as a therapeutic agent for.


greenmedinfo--2020-07-16--Protective effects of myricetin on benzo[a]pyrene-induced 8-hydroxy-2′-deoxyguanosine and BPDE-DNA a

Protective effects of myricetin on benzo[a]pyrene-induced 8-hydroxy-2′-deoxyguanosine and BPDE-DNA adduct.

Benzo [ a ] pyrene ( B [ a ] P ) , a group 1 carcinogen , induces mutagenic DNA adducts .
Myricetin is present in many natural foods with diverse biological activities , such as anti-oxidative and anti-cancer activities .
The aim of this study was to investigate the protective effects of myricetin against B [ a ] P-induced toxicity .
Treatment of B [ a ] P induced cytotoxicity on HepG2 cells , whereas co-treatment of myricetin with B [ a ] P reduced the formation of the B [ a ] P-7,8-dihydrodiol-9,10-epoxide ( BPDE ) -DNA @ @ @ @ @ @ @ Furthermore , we found a protective effect of myricetin against B [ a ] P-induced genotoxicity in rats , via myricetin-induced inhibition of 8-hydroxy-2'-deoxyguanosine ( 8-OHdG ) and BPDE-DNA adduct formation in the liver , kidney , colon , and stomach tissue .
This inhibition was more prominent in the liver than in other tissues .
Correspondingly , myricetin regulated the phase I and II enzymes that inhibit B [ a ] P metabolism and B [ a ] P metabolites conjugated with DNA by reducing and inducing CYP1A1 and glutathione S-transferase ( @ @ @ @ @ @ @ together , this showed that myricetin attenuated B [ a ] P-induced genotoxicity via regulation of phase I and II enzymes .
Our results suggest that myricetin is anti-genotoxic , and prevents oxidative DNA damage and BPDE-DNA adduct formation via regulation of phase I and II enzymes .

Benzo[a]pyrene (B[a]P), a group 1 carcinogen, induces mutagenic DNA adducts. Myricetin is present in many natural foods with diverse biological activities, such as anti-oxidative and anti-cancer activities. The aim of this study was to investigate the protective effects of myricetin against B[a]P-induced toxicity. Treatment of B[a]P induced cytotoxicity on HepG2 cells, whereas co-treatment of myricetin with B[a]P reduced the formation of the B[a]P-7,8-dihydrodiol-9,10-epoxide (BPDE)-DNA adduct, which recovered cell viability. Furthermore, we found a protective effect of myricetin against B[a]P-induced genotoxicity in rats, via myricetin-induced inhibition of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and BPDE-DNA adduct formation in the liver, kidney, colon, and stomach tissue. This inhibition was more prominent in the liver than in other tissues. Correspondingly, myricetin regulated the phase I and II enzymes that inhibit B[a]P metabolism and B[a]P metabolites conjugated with DNA by reducing and inducing CYP1A1 and glutathione S-transferase (GST) expression, respectively. Taken together, this showed that myricetin attenuated B[a]P-induced genotoxicity via regulation of phase I and II enzymes. Our results suggest that myricetin is anti-genotoxic, and prevents oxidative DNA damage and BPDE-DNA adduct formation via regulation of phase I and II enzymes.


greenmedinfo--2020-07-16--Myricetin ameliorates bleomycin-induced pulmonary fibrosis in mice by inhibiting TGF-β signaling via

Myricetin ameliorates bleomycin-induced pulmonary fibrosis in mice by inhibiting TGF-β signaling via targeting HSP90β.

Idiopathic pulmonary fibrosis is a progressive-fibrosing lung disease with high mortality and limited therapy , which characterized by myofibroblasts proliferation and extracellular matrix deposition .
Myricetin , a natural flavonoid , has been shown to possess a variety of biological characteristics including anti-inflammatory and anti-tumor .
In this study we explored the potential effect and mechanisms of myricetin on pulmonary fibrosis in vivo and vitro .
The in vivo studies showed that myricetin effectively alleviated bleomycin ( BLM ) -induced pulmonary fibrosis .
KEGG analysis of RNA-seq data indicated that myricetin could regulate the transforming growth factor ( TGF ) @ @ @ @ @ @ @ indicated that myricetin could dose-dependently suppress TGF-β1/Smad signaling and attenuate TGF-β1-induced fibroblast activation and epithelial-mesenchymal transition ( EMT ) .
Molecular docking indicated that heat shock protein ( HSP ) 90β may be a potential target of myricetin , and MST assay demonstrated that the dissociation constant ( Kd ) of myricetin and HSP90β was 331.59 nM .
We demonstrated that myricetin interfered with the binding of HSP90β and TGF-β receptor II and impeded fibroblast activation and EMT .
In conclusion , myricetin impedes TGF-β1-induced lung fibroblast activation and EMT via targeting HSP90β @ @ @ @ @ @ @ .

Idiopathic pulmonary fibrosis is a progressive-fibrosing lung disease with high mortality and limited therapy, which characterized by myofibroblasts proliferation and extracellular matrix deposition. Myricetin, a natural flavonoid, has been shown to possess a variety of biological characteristics including anti-inflammatory and anti-tumor. In this study we explored the potential effect and mechanisms of myricetin on pulmonary fibrosis in vivo and vitro. The in vivo studies showed that myricetin effectively alleviated bleomycin (BLM)-induced pulmonary fibrosis. KEGG analysis of RNA-seq data indicated that myricetin could regulate the transforming growth factor (TGF)-β signaling pathway. In vitro studies indicated that myricetin could dose-dependently suppress TGF-β1/Smad signaling and attenuate TGF-β1-induced fibroblast activation and epithelial-mesenchymal transition (EMT). Molecular docking indicated that heat shock protein (HSP) 90β may be a potential target of myricetin, and MST assay demonstrated that the dissociation constant (Kd) of myricetin and HSP90β was 331.59 nM. We demonstrated that myricetin interfered with the binding of HSP90β and TGF-β receptor II and impeded fibroblast activation and EMT. In conclusion, myricetin impedes TGF-β1-induced lung fibroblast activation and EMT via targeting HSP90β and attenuates BLM-induced pulmonary fibrosis in mice.


greenmedinfo--2020-07-16--Myricetin induces apoptosis and autophagy by inhibiting PI3K/Akt/mTOR signalling in human colon canc

Myricetin induces apoptosis and autophagy by inhibiting PI3K/Akt/mTOR signalling in human colon cancer cells.

BACKGROUND : The compound 3,3',4',5,5',7-hexahydroxyflavone ( myricetin ) is a natural flavonoid with antitumour activity .
Most of the studies on myricetin have focused on the induction of tumour cell apoptosis , and little is known about the regulatory effects of myricetin on autophagy in colorectal cancer .
METHODS : Here , we studied the effects of myricetin on colon cancer cell proliferation , apoptosis and autophagy .
We detected colon cancer cell apoptosis induced by myricetin via flow cytometry and Hoechst 33258 staining .
Transmission electron microscopy was performed to observe the morphological changes associated with autophagy .
The @ @ @ @ @ @ @ PI3K/Akt/mTOR signalling-related proteins were measured by Western blot analysis .
RESULTS : This study confirmed that myricetin inhibits the proliferation of 4 kinds of colon cancer cell lines .
Myricetin induced cell apoptosis and autophagy by inhibiting PI3K/Akt/mTOR signalling pathway .
In addition , the inhibition of autophagy with 3-methyladenine ( 3-MA ) promoted the apoptosis of myricetin-treated colon cancer cells .
CONCLUSIONS : Considering that myricetin induces apoptosis and autophagy in colon cancer cells , myricetin may become a viable candidate for chemotherapy ; it could be used to exert tumour inhibitory @ @ @ @ @ @ @ inhibit autophagy .
These studies may provide further evidence for the potential use of myricetin in the treatment of colon cancer .

BACKGROUND: The compound 3,3',4',5,5',7-hexahydroxyflavone (myricetin) is a natural flavonoid with antitumour activity. Most of the studies on myricetin have focused on the induction of tumour cell apoptosis, and little is known about the regulatory effects of myricetin on autophagy in colorectal cancer.
METHODS: Here, we studied the effects of myricetin on colon cancer cell proliferation, apoptosis and autophagy. We detected colon cancer cell apoptosis induced by myricetin via flow cytometry and Hoechst 33258 staining. Transmission electron microscopy was performed to observe the morphological changes associated with autophagy. The expression levels of apoptosis-, autophagy- and PI3K/Akt/mTOR signalling-related proteins were measured by Western blot analysis.
RESULTS: This study confirmed that myricetin inhibits the proliferation of 4 kinds of colon cancer cell lines. Myricetin induced cell apoptosis and autophagy by inhibiting PI3K/Akt/mTOR signalling pathway. In addition, the inhibition of autophagy with 3-methyladenine (3-MA) promoted the apoptosis of myricetin-treated colon cancer cells.
CONCLUSIONS: Considering that myricetin induces apoptosis and autophagy in colon cancer cells, myricetin may become a viable candidate for chemotherapy; it could be used to exert tumour inhibitory effects alone or as adjuvant chemotherapy to inhibit autophagy. These studies may provide further evidence for the potential use of myricetin in the treatment of colon cancer.


greenmedinfo--2020-07-16--The effect of ellagic acid on spinal cord and sciatica function in a mice model of multiple sclerosi

The effect of ellagic acid on spinal cord and sciatica function in a mice model of multiple sclerosis.

Multiple sclerosis ( MS ) is a well-known neurodegenerative disorder , causing toxicity in different organs , such as spinal cord tissue .
The goal of this study was to investigate the protective effect of ellagic acid ( EA ) against spinal cord and sciatica function in cuprizone ( Cup ) -induced demyelination model .
Animals were divided into six equal groups .
The first group received tap water as the control .
Cup group was treated with Cup ( 0.2 % w/w in fed ) .
EA 100 group was orally treated with EA ( 100 mg/kg ) .
@ @ @ @ @ @ @ with three doses of 5 , 50 , and 100 mg/kg of EA plus Cup ( 0.2 % w/w ) .
All groups received treatment for 42 days .
Open field , rotarod , and gait tests were done to evaluate the behavioral changes following Cup and/or EA treatment .
Also , lipid peroxidation , reactive oxygen species ( ROS ) content , antioxidant capacity , superoxide dismutase ( SOD ) , and catalase enzymes activity in spinal cord was evaluated .
Luxol fast blue ( LFB ) staining also the behavioral tests @ @ @ @ @ @ @ Cup increased ROS levels and oxidative stress intheir spinal cord tissues .
Also , Cup reduced antioxidant capacity , SOD , and catalase activity .
EA ( especially at 100 mg/kg ) prevented these abnormal changes .
EA co-treatment dose-dependently was able to ameliorate behavioral impairments in mice that received Cup .
EA might act as a protective agent in MS by modulating spinal cord function .

Multiple sclerosis (MS) is a well-known neurodegenerative disorder, causing toxicity in different organs, such as spinal cord tissue. The goal of this study was to investigate the protective effect of ellagic acid (EA) against spinal cord and sciatica function in cuprizone (Cup)-induced demyelination model. Animals were divided into six equal groups. The first group received tap water as the control. Cup group was treated with Cup (0.2% w/w in fed). EA 100 group was orally treated with EA (100 mg/kg). EA + Cup groups were orally treated with three doses of 5, 50, and 100 mg/kg of EA plus Cup (0.2% w/w). All groups received treatment for 42 days. Open field, rotarod, and gait tests were done to evaluate the behavioral changes following Cup and/or EA treatment. Also, lipid peroxidation, reactive oxygen species (ROS) content, antioxidant capacity, superoxide dismutase (SOD), and catalase enzymes activity in spinal cord was evaluated. Luxol fast blue (LFB) staining also the behavioral tests were performed to evaluate the model. Cup increased ROS levels and oxidative stress intheir spinal cord tissues. Also, Cup reduced antioxidant capacity, SOD, and catalase activity. EA (especially at 100 mg/kg) prevented these abnormal changes. EA co-treatment dose-dependently was able to ameliorate behavioral impairments in mice that received Cup. EA might act as a protective agent in MS by modulating spinal cord function.


greenmedinfo--2020-07-16--Optimized ellagic acid-ca pectinate floating beads for gastroprotection against indomethacin-induced

Optimized ellagic acid-ca pectinate floating beads for gastroprotection against indomethacin-induced gastric injury.

A peptic ulcer is an alimentary tract injury that leads to a mucosal defect reaching the submucosa .
This work @ @ @ @ @ ellagic acid ( EA ) loading in Ca pectinate floating beads to maximize the release @ @ @ @ @ were selected : Ca pectinate concentration ( X1 , 1-3 w/v % ) , EA @ @ @ @ @ w/v % ) and the dropping time ( X3 , 10-30 min ) .
The @ @ @ @ @ .
The optimized EA-Ca pectinate formulation was evaluated for the gastric ulcer index and the @ @ @ @ @ gastric mucosa .
The results indicated that the optimum EA-Ca pectinate formula significantly improved the @ @ @ @ @ with raw EA .
The protective effect of the optimized EA-Ca pectinate formula was further @ @ @ @ @ of the stomach .
The results of the study indicate that an EA formulation in @ @ @ @ @ beads would be effective for protection against gastric ulcers because of Nonsteroidal anti-inflammatory drugs ( @ @ @ @

A peptic ulcer is an alimentary tract injury that leads to a mucosal defect reaching the submucosa. This work aimed to optimize and maximize ellagic acid (EA) loading in Ca pectinate floating beads to maximize the release for 24 h. Three factors were selected: Ca pectinate concentration (X1, 1-3 w/v %), EA concentration (X2, 1-3 w/v %) and the dropping time (X3, 10-30 min). The factorial design proposed eight formulations. The optimized EA-Ca pectinate formulation was evaluated for the gastric ulcer index and the oxidative stress parameter determination of gastric mucosa. The results indicated that the optimum EA-Ca pectinate formula significantly improved the gastric ulcer index in comparison with raw EA. The protective effect of the optimized EA-Ca pectinate formula was further indicated by the histopathological features of the stomach. The results of the study indicate that an EA formulation in the form of Ca pectinate beads would be effective for protection against gastric ulcers because of Nonsteroidal anti-inflammatory drugs (NSAID) administration.


greenmedinfo--2020-07-16--Chitosan-based microparticles enhance ellagic acid's colon targeting and proapoptotic activity.

This study aimed at improving the targeting and cytotoxic effect of ellagic acid ( EA ) on colon cancer cells .
EA was encapsulated in chitosan ( CHIT ) polymers then coated by eudragit S100 ( ES100 ) microparticles .
The release of EA double-coated microparticles ( MPs ) was tested at simulative pH values .
Maximum release was observed at 24 h and pH 7.4 .
The cytotoxicity of EA MPs on HCT 116 colon cancer cells was synergistically improved as compared with raw EA .
Cell-cycle analysis by flow cytometry suggested enhanced G2-M phase colon cancer cell accumulation @ @ @ @ @ @ @ cell fraction was observed in the pre-G phase , which highlighted the enhancement of the proapoptotic activity of EA formulated in the double-coat mixture .
Annexin-V staining was used for substantiation of the observed cell-death-inducing activity .
Cell fractions were significantly increased in early , late , and total cell death .
This was backed by high elevation in cellular content of caspase 3 .
Effectiveness of the double-coated EA to target colonic tissues was confirmed using real-time iohexol dye X-ray radiography .
In conclusion , CHIT loaded with EA and coated with @ @ @ @ @ @ @ well as enhanced cytotoxic and proapoptotic activity against HCT 116 colon cancer when compared with the administration of raw EA .

This study aimed at improving the targeting and cytotoxic effect of ellagic acid (EA) on colon cancer cells. EA was encapsulated in chitosan (CHIT) polymers then coated by eudragit S100 (ES100) microparticles. The release of EA double-coated microparticles (MPs) was tested at simulative pH values. Maximum release was observed at 24 h and pH 7.4. The cytotoxicity of EA MPs on HCT 116 colon cancer cells was synergistically improved as compared with raw EA. Cell-cycle analysis by flow cytometry suggested enhanced G2-M phase colon cancer cell accumulation. In addition, a significantly higher cell fraction was observed in the pre-G phase, which highlighted the enhancement of the proapoptotic activity of EA formulated in the double-coat mixture. Annexin-V staining was used for substantiation of the observed cell-death-inducing activity. Cell fractions were significantly increased in early, late, and total cell death. This was backed by high elevation in cellular content of caspase 3. Effectiveness of the double-coated EA to target colonic tissues was confirmed using real-time iohexol dye X-ray radiography. In conclusion, CHIT loaded with EA and coated with ES100 formula exhibits improved colon targeting as well as enhanced cytotoxic and proapoptotic activity against HCT 116 colon cancer when compared with the administration of raw EA.


greenmedinfo--2020-07-16--Corilagin ameliorates sleep deprivation-induced memory impairments by inhibiting NOX2 and activating

Corilagin ameliorates sleep deprivation-induced memory impairments by inhibiting NOX2 and activating Nrf2.

Sleep deprivation ( SD ) can induce cognitive and memory impairments .
This impairment is in part due to oxidative stress damage in the hippocampus region of the brain .
Corilagin ( CL ) , a polyphenol belonging to the tannin family and extracted from Terminalia chebula and Phyllanthus emblica , shows strong antioxidant and neuroprotective effects .
NF-E2-related factor ( Nrf2 ) /heme oxygenase-1 ( HO-1 ) and NADPH oxidase ( NOX ) are critical targets involved in cellular defense mechanisms against oxidative injury .
Thus , we hypothesized that CL could be a preventive treatment for SD-induced memory @ @ @ @ @ @ @ .
The results from behavioral tests showed that administration of CL resulted in significantly better performance compared to the SD mice .
CL significantly normalized the elevated MDA level and the reduced activity of GPx and SOD ( P < 0.05 , p < 0.01 ) caused by SD .
In hippocampal tissues , CL effectively activated Nrf2/HO-1 signaling and downregulated NOX2 protein expression compared with SD ( P < 0.05 , P < 0.01 ) .
Meanwhile , in vitro findings showed that knockdown of Nrf2 blocked the protective effect of CL @ @ @ @ @ @ @ of CL was enhanced in NOX2 siRNA-transfected neurons .
Overall , these findings provided evidence that CL ameliorates SD-induced memory impairments in mice by inhibiting NOX2 and activating Nrf2 .

Sleep deprivation (SD) can induce cognitive and memory impairments. This impairment is in part due to oxidative stress damage in the hippocampus region of the brain. Corilagin (CL), a polyphenol belonging to the tannin family and extracted from Terminalia chebula and Phyllanthus emblica, shows strong antioxidant and neuroprotective effects. NF-E2-related factor (Nrf2)/heme oxygenase-1 (HO-1) and NADPH oxidase (NOX) are critical targets involved in cellular defense mechanisms against oxidative injury. Thus, we hypothesized that CL could be a preventive treatment for SD-induced memory impairments by inhibiting NOX2 and activating Nrf2. The results from behavioral tests showed that administration of CL resulted in significantly better performance compared to the SD mice. CL significantly normalized the elevated MDA level and the reduced activity of GPx and SOD (P<0.05, p<0.01) caused by SD. In hippocampal tissues, CL effectively activated Nrf2/HO-1 signaling and downregulated NOX2 protein expression compared with SD (P<0.05, P<0.01). Meanwhile, in vitro findings showed that knockdown of Nrf2 blocked the protective effect of CL versus Glu-induced toxicity, while the effect of CL was enhanced in NOX2 siRNA-transfected neurons. Overall, these findings provided evidence that CL ameliorates SD-induced memory impairments in mice by inhibiting NOX2 and activating Nrf2.


greenmedinfo--2020-07-16--The role of mTOR and oral intervention of combined Zingiber officinale-Terminalia chebula extract in

The role of mTOR and oral intervention of combined Zingiber officinale-Terminalia chebula extract in type 2 diabetes models.

The present study examined the potential of Zingiber officinale-Terminalia chebula extract alone ( ZO and TC ) and in combination ( ZOTC ) against type 2 diabetes via downregulation of mechanistic target of rapamycin ( mTOR ) .
The 1:4 ( ZOTC ) ratio showed high cell survival percentage against the rat insulinoma cell line ( RIN-5F ) when compared to other possible ratios of ZOTC .
Oral administration of ZO alone , TC alone , combined ZOTC ( 1:4 ) , and the positive control metformin ( Met ) in fructose-streptozotocin ( STZ ) -induced diabetic rats showed reduced @ @ @ @ @ @ @ ( HOMA-IR ) , increased insulin levels , and increased pancreatic beta cell function ( HOMA-β ) .
ZOTC treatment in diabetic rats ameliorated the antioxidant status without affecting liver and serum parameters .
Histological evaluation of the pancreas was performed to find pathological changes ; the transcriptional and immunohistochemistry results showed reduced mTOR expression in the pancreas during ZOTC treatment .
Conclusively , the results obtained suggest that ZOTC treatment against fructose-STZ-induced type 2 diabetes rat models can help regulate blood glucose , insulin levels , and normalize pancreatic β cell damage @ @ @ @ @ @ @ is a chronic metabolic disorder that affects a large number of populations worldwide .
Zingiber officinale ( ZO ) and Terminalia chebula ( TC ) has been used in traditional medicine since ancient times against various ailments , including diabetes .
In this study , we reported the effect of the combined ZOTC that showed significantblood glucose reduction and increased insulin levels via mTOR when compared to individual treatments .
This finding is valuable for food technologists and alternative medicine practitioners to know the antidiabetic effect of the ZOTC combination .

The present study examined the potential of Zingiber officinale-Terminalia chebula extract alone (ZO and TC) and in combination (ZOTC) against type 2 diabetes via downregulation of mechanistic target of rapamycin (mTOR). The 1:4 (ZOTC) ratio showed high cell survival percentage against the rat insulinoma cell line (RIN-5F) when compared to other possible ratios of ZOTC. Oral administration of ZO alone, TC alone, combined ZOTC (1:4), and the positive control metformin (Met) in fructose-streptozotocin (STZ) -induced diabetic rats showed reduced blood glucose levels, reduced insulin resistance (HOMA-IR), increased insulin levels, and increased pancreatic beta cell function (HOMA-β). ZOTC treatment in diabetic rats ameliorated the antioxidant status without affecting liver and serum parameters. Histological evaluation of the pancreas was performed to find pathological changes; the transcriptional and immunohistochemistry results showed reduced mTOR expression in the pancreas during ZOTC treatment. Conclusively, the results obtained suggest that ZOTC treatment against fructose-STZ-induced type 2 diabetes rat models can help regulate blood glucose, insulin levels, and normalize pancreatic β cell damage. PRACTICAL APPLICATIONS: Type 2 diabetes is a chronic metabolic disorder that affects a large number of populations worldwide. Zingiber officinale (ZO) and Terminalia chebula (TC) has been used in traditional medicine since ancient times against various ailments, including diabetes. In this study, we reported the effect of the combined ZOTC that showed significantblood glucose reduction and increased insulin levels via mTOR when compared to individual treatments. This finding is valuable for food technologists and alternative medicine practitioners to know the antidiabetic effect of the ZOTC combination.


greenmedinfo--2020-07-16--Effect of an aqueous extract of Terminalia chebula on endothelial dysfunction, systemic inflammation

Effect of an aqueous extract of Terminalia chebula on endothelial dysfunction, systemic inflammation, and lipid profile in type 2 diabetes mellitus.

Endothelial dysfunction is a crucial complication in type 2 diabetic patients , related to cardiovascular risk .
Terminalia chebula ( TC ) , a traditional ayurvedic herb , is known for its antioxidant and antihyperlipidemic activity .
A prospective , randomized , double-blind , placebo-controlled clinical study was undertaken to evaluate the effects of an aqueous extract of T. chebula 250 and 500 mg versus placebo on endothelial dysfunction and biomarkers of oxidative stress in type 2 diabetic patients .
A total of 60 eligible patients were randomized to receive either T. chebula 250 mg , T. chebula 500 mg @ @ @ @ @ @ @ weeks .
The subjects were assessed based on the endothelial function , the levels of nitric oxide , malondialdehyde , glutathione , high sensitivity C-reactive protein , glycosylated hemoglobin , and lipid profile at baseline and after 12 weeks of treatment .
Treatment with T. chebula 250 mg and T. chebula 500 mg for 12 weeks significantly improved the endothelial function ( reflection index ) compared to placebo ( absolute changes : - T. chebula 250 : -2.55 ± 1.82 % vs. T. chebula 500 : -5.21 ± 2.41 % vs. placebo : @ @ @ @ @ @ @ cardiovascular risk indicators were also significantly ameliorated in the treatment groups compared toplacebo .
In conclusion , T. chebula ( especially , 500 mg BID dose ) significantly minimized the cardiovascular risk factors in patients with type 2 diabetes compared to placebo .

Endothelial dysfunction is a crucial complication in type 2 diabetic patients, related to cardiovascular risk. Terminalia chebula (TC), a traditional ayurvedic herb, is known for its antioxidant and antihyperlipidemic activity. A prospective, randomized, double-blind, placebo-controlled clinical study was undertaken to evaluate the effects of an aqueous extract of T. chebula 250 and 500 mg versus placebo on endothelial dysfunction and biomarkers of oxidative stress in type 2 diabetic patients. A total of 60 eligible patients were randomized to receive either T. chebula 250 mg, T. chebula 500 mg, or placebo twice daily for 12 weeks. The subjects were assessed based on the endothelial function, the levels of nitric oxide, malondialdehyde, glutathione, high sensitivity C-reactive protein, glycosylated hemoglobin, and lipid profile at baseline and after 12 weeks of treatment. Treatment with T. chebula 250 mg and T. chebula 500 mg for 12 weeks significantly improved the endothelial function (reflection index) compared to placebo (absolute changes: - T. chebula 250: -2.55 ± 1.82% vs. T. chebula 500: -5.21 ± 2.41% vs. placebo: 1.40 ± 2.11%). Other cardiovascular risk indicators were also significantly ameliorated in the treatment groups compared toplacebo. In conclusion, T. chebula (especially, 500 mg BID dose) significantly minimized the cardiovascular risk factors in patients with type 2 diabetes compared to placebo.


greenmedinfo--2020-07-16--Combined Zingiber officinale and Terminalia chebula induces apoptosis and modulates mTOR and hTERT g

Combined Zingiber officinale and Terminalia chebula induces apoptosis and modulates mTOR and hTERT gene expressions in MCF-7 cell line.

In this study , we evaluated the cytotoxicity and apoptotic activity of ( ZO ) , ( TC ) alone @ @ @ @ @ ZO : TC-1:4 ) .
The presence of major bioactive compounds in ZO ( 6-gingerol @ @ @ @ @ ( gallic acid , ellagic acid , and chebulinic acid ) were evaluated by high @ @ @ @ @ IC50 values of ZO , TC , and ZOTC ( 1:4 ) was estimated to @ @ @ @ @ and 53.5 μg/mL , respectively .
The cell death and cytomorphology changes upon treatment were @ @ @ @ @ , ZO , TC , and ZOTC showed reduced mitochondrial membrane potential , increased reactive @ @ @ @ @ activities .
It was also reported to downregulate mTOR and hTERTgene expression levels which are @ @ @ @ @ proliferation and growth .
This first report on ZOTC combination has the potential to develop @ @ @ @ @ breast cancer .

In this study, we evaluated the cytotoxicity and apoptotic activity of(ZO),(TC) alone, and in combination (ZO:TC-1:4). The presence of major bioactive compounds in ZO (6-gingerol and 6-shogaol) and TC (gallic acid, ellagic acid, and chebulinic acid) were evaluated by high performance liquid chromatography. The IC50 values of ZO, TC, and ZOTC (1:4) was estimated to be 88.5, 108.5, and 53.5 μg/mL, respectively. The cell death and cytomorphology changes upon treatment were observed. At these concentrations, ZO, TC, and ZOTC showed reduced mitochondrial membrane potential, increased reactive oxygen species, and apoptotic activities. It was also reported to downregulate mTOR and hTERTgene expression levels which are the primary genes for cell proliferation and growth. This first report on ZOTC combination has the potential to develop as a therapeutic agent for breast cancer.