greenmedinfo--2020-06-05--Genistein prevents single prolonged stress-induced cognitive Impairment in a post-traumatic stress d

Genistein prevents single prolonged stress-induced cognitive Impairment in a post-traumatic stress disorder model.

Post-traumatic stress disorder ( PTSD ) is a stress-associated mental disorder characterized by an imbalance of neurotransmitters in response to @ @ @ @ @ Genistein ( GEN ) , a natural isoflavone , has been shown to exhibit neuroprotective @ @ @ @ @ used the Morris water maze ( MWM ) and object recognition task ( ORT ) @ @ @ @ @ of GEN on cognitive impairment in rats after exposure to single prolonged stress ( SPS @ @ @ @ @ with the serotonergic system .
After exposure to SPS , male rats received GEN ( @ @ @ @ @ 10 mg/kg , i.p . )
for 14 days .
Daily GEN administration significantly improved @ @ @ @ @ and MWM tests .
GEN treatment also inhibited SPS-induced decreases in serotonin ( 5-HT ) @ @ @ @ @ cortex and hippocampus .
These increased 5-HT concentrations in response toGEN treatment could be partially @ @ @ @ @ 5-hydroxyindoleacetic acid/5-HT in the hippocampus .
Our findings suggest that GEN significantly attenuates SPS-induced memory @ @ @ @ @ represent an effective therapeutic option for the treatment of PTSD .

Post-traumatic stress disorder (PTSD) is a stress-associated mental disorder characterized by an imbalance of neurotransmitters in response to traumatic events or fear. Genistein (GEN), a natural isoflavone, has been shown to exhibit neuroprotective effects. Here, we used the Morris water maze (MWM) and object recognition task (ORT) tests to examine the effects of GEN on cognitive impairment in rats after exposure to single prolonged stress (SPS), and its interaction with the serotonergic system. After exposure to SPS, male rats received GEN (2, 4, and 10 mg/kg, i.p.) for 14 days. Daily GEN administration significantly improved cognitive function in the ORT and MWM tests. GEN treatment also inhibited SPS-induced decreases in serotonin (5-HT) levels in the medial prefrontal cortex and hippocampus. These increased 5-HT concentrations in response toGEN treatment could be partially attributed to the ratio of 5-hydroxyindoleacetic acid/5-HT in the hippocampus. Our findings suggest that GEN significantly attenuates SPS-induced memory deficits in rats and may represent an effective therapeutic option for the treatment of PTSD.


greenmedinfo--2020-06-05--Genistein may be a promising alternative adjuvant therapy for patients with esophageal carcinoma.

Esophageal carcinoma ( EsC ) is a clinically challenging neoplastic disease .
Genistein , a natural isoflavone product , has anti-tumor properties .
Throughandstudies , we found that genistein suppressed EsC cell proliferation in a time- and concentration-dependent manner .
In addition , genistein markedly promoted apoptosis and arrested cell cycle at the G0/G1 phase in a concentration-dependent manner .
Furthermore , high concentrations of genistein have no adverse effect on normal esophageal epithelial cells .
Mechanistically , genistein treatment strikingly reduced the expression of cell cycle-associated genes , and up-regulated the expression of cell apoptosis-related genes in EsC cells @ @ @ @ @ @ @ growth factor receptor ( EGFR ) expression and attenuated its down-stream signaling molecules STAT3 , MDM2 , Akt and JAK1/2 phosphorylation , resulting in inhibited nuclear translocation of STAT3 and MDM2 , thereby inhibiting the JAK1/2-STAT3 and AKT/MDM2/p53 signaling pathways .
In xenograft nude mice , genistein administration strikingly impaired tumor growth in a dose-dependent manner .
Moreover , similar disturbances in molecular mechanisms were observed .
Taken together , genistein suppressed the JAK1/2-STAT3 and AKT/MDM2/p53 signaling pathways by decreasing EGFR expression , leading to cell apoptosis , cell cycle arrest , and @ @ @ @ @ @ @ findings suggest that genistein may be a promising alternative adjuvant therapy for patients with EsC .

Esophageal carcinoma (EsC) is a clinically challenging neoplastic disease. Genistein, a natural isoflavone product, has anti-tumor properties. Throughandstudies, we found that genistein suppressed EsC cell proliferation in a time- and concentration-dependent manner. In addition, genistein markedly promoted apoptosis and arrested cell cycle at the G0/G1 phase in a concentration-dependent manner. Furthermore, high concentrations of genistein have no adverse effect on normal esophageal epithelial cells. Mechanistically, genistein treatment strikingly reduced the expression of cell cycle-associated genes, and up-regulated the expression of cell apoptosis-related genes in EsC cells. Additionally, genistein dramatically decreased epidermal growth factor receptor (EGFR) expression and attenuated its down-stream signaling molecules STAT3, MDM2, Akt and JAK1/2 phosphorylation, resulting in inhibited nuclear translocation of STAT3 and MDM2, thereby inhibiting the JAK1/2-STAT3 and AKT/MDM2/p53 signaling pathways. In xenograft nude mice, genistein administration strikingly impaired tumor growth in a dose-dependent manner. Moreover, similar disturbances in molecular mechanisms were observed. Taken together, genistein suppressed the JAK1/2-STAT3 and AKT/MDM2/p53 signaling pathways by decreasing EGFR expression, leading to cell apoptosis, cell cycle arrest, and proliferation inhibition in EsC cells. Our findings suggest that genistein may be a promising alternative adjuvant therapy for patients with EsC.


greenmedinfo--2020-06-05--N. sativa might be used for its anti-cancer and anti-metastatic properties and as an immune system a

BACKGROUND : In the last decade there have been accumulating data that the use of medicinal plants could bring additional benefits to the supportive treatment of various diseases .
Nigella sativa ( N. sativa , family Ranunculaceae ) is one of these plants that has attracted considerable interest .
The extracts and seeds of N. sativa and its active component thymoquinone have been studied extensively and the results suggest that N. sativa might carry some therapeutic potential for many diseases , including cancer .
METHODS : The selection criteria for references were applied through Pubmed with '' N. sativa and @ @ @ @ @ @ @ breast cancer '' , '' N. sativa and metastasis '' , '' N. sativa and cytotoxicity of natural killer cells '' .
The pathway analysis was performed using the PANTHER tool by using five randomly selected N. sativa affected genes ( Cyclin D1 , P53 , p21 protein ( Cdc42/Rac ) activated kinase 1 ( PAK1 ) , B-cell lymphoma 2 ( Bcl-2 ) and vascular endothelial growth factor ( VEGF ) ) in order to elucidate further potentially affected signaling pathways .
RESULTS AND CONCLUSION : The aim of this review was @ @ @ @ @ @ @ N. sativa in cancer generally , with a focus on breast cancer , its anti-metastatic effects , and how N. sativa modulates the cytotoxicity of Natural Killer cells that play a crucial role in tumor surveillance .
In summary , the data suggest that N. sativa might be used for its anti-cancer and anti-metastatic properties and as an immune system activator against cancer .

BACKGROUND: In the last decade there have been accumulating data that the use of medicinal plants could bring additional benefits to the supportive treatment of various diseases. Nigella sativa (N. sativa, family Ranunculaceae) is one of these plants that has attracted considerable interest. The extracts and seeds of N. sativa and its active component thymoquinone have been studied extensively and the results suggest that N. sativa might carry some therapeutic potential for many diseases, including cancer.
METHODS: The selection criteria for references were applied through Pubmed with"N. sativa and cancer","N. sativa and breast cancer","N. sativa and metastasis","N. sativa and cytotoxicity of natural killer cells". The pathway analysis was performed using the PANTHER tool by using five randomly selected N. sativa affected genes (Cyclin D1, P53, p21 protein (Cdc42/Rac) activated kinase 1 (PAK1), B-cell lymphoma 2 (Bcl-2) and vascular endothelial growth factor (VEGF)) in order to elucidate further potentially affected signaling pathways.
RESULTS AND CONCLUSION: The aim of this review was to summarize studies regarding the effects of N. sativa in cancer generally, with a focus on breast cancer, its anti-metastatic effects, and how N. sativa modulates the cytotoxicity of Natural Killer cells that play a crucial role in tumor surveillance. In summary, the data suggest that N. sativa might be used for its anti-cancer and anti-metastatic properties and as an immune system activator against cancer.


greenmedinfo--2020-06-05--Thymoquinone could be protective against valproic acid-induced testicular toxicity.

Although valproic acid ( VPA ) is a low-cost and effective drug , it is known to cause organ toxicity via oxidative stress and related process .
In present study , we aimed to evaluate the possible protective effects of thymoquinone ( TMQ ) on VPA-induced testicular toxicity .
Male Sprague-Dawley rats were divided into three as control , VPA ( 500 mg kg day ) for 14 days and VPA plus TMQ ( 50 mg kg dayfor 14 days ) with seven rats in .
Spermatic and interstitial degenerations induced by VPA were ameliorated with TMQ .
In VPA @ @ @ @ @ @ @ , and decreased TAS level were seen .
TMQ reversed these oxidative stress parameters significantly .
In Western analysis , VPA was found to increase the expressions of phospho-nuclear factor kappa beta ( p-Nf-kB ) and Caspase-3 .
These expressions were decreased by TMQ significantly .
Intense immunostaining for p-Nf-kB , Caspase-3 and NADPH oxidase 2 induced by VPA were transformed to moderate immunostaining by TMQ .
VPA-induced inflammation and apoptosis that were developed mainly by p-Nf-kB pathway were attenuated by TMQ .
TMQ can be a candidate supportive treatment for patients who @ @ @ @ @ @ @ TMQ inhibits the Nf-kB activation , and in addition to antioxidant property , it shows anti-inflammatory feature on VPA-induced testicular toxicity .

Although valproic acid (VPA) is a low-cost and effective drug, it is known to cause organ toxicity via oxidative stress and related process. In present study, we aimed to evaluate the possible protective effects of thymoquinone (TMQ) on VPA-induced testicular toxicity. Male Sprague-Dawley rats were divided into three as control, VPA (500 mg kg day) for 14 days and VPA plus TMQ (50 mg kg dayfor 14 days) with seven rats in. Spermatic and interstitial degenerations induced by VPA were ameliorated with TMQ. In VPA group, increased TOS and OSI levels, and decreased TAS level were seen. TMQ reversed these oxidative stress parameters significantly. In Western analysis, VPA was found to increase the expressions of phospho-nuclear factor kappa beta (p-Nf-kB) and Caspase-3. These expressions were decreased by TMQ significantly. Intense immunostaining for p-Nf-kB, Caspase-3 and NADPH oxidase 2 induced by VPA were transformed to moderate immunostaining by TMQ. VPA-induced inflammation and apoptosis that were developed mainly by p-Nf-kB pathway were attenuated by TMQ. TMQ can be a candidate supportive treatment for patients who need long-term and high-dose VPA therapy. TMQ inhibits the Nf-kB activation, and in addition to antioxidant property, it shows anti-inflammatory feature on VPA-induced testicular toxicity.


greenmedinfo--2020-06-05--Thymoquinone can be used as a protective agent to reduce the toxic effects of doxorubicin.

BACKGROUND : Doxorubicin ( DOX ) is used for treatment of many cancer types .
Thymoquinone ( THQ ) is a powerful antioxidant agent used for reducing side effects of several drugs .
The aim of this study is to determine possible therapeutic effects of THQ on doxorubicin-induced testicular toxicity in rats .
METHODS : Rats were divided into five groups ( = 8 ) : control , THQ , olive oil , DOX ( a single dose of 15 mg/kg intraperitoneally ( i.p . )
on seventh day of the experiment ) , and DOX + THQ ( 10 @ @ @ @ @ @ @ DOX i.p .
on seventh day ) .
Animals were euthanized , and testis tissues were evaluated histopathologically .
Caspase 3 and HSP90 immunostaining were performed to determine the expression levels of these proteins among groups .
Terminal deoxynucleotidyl transferase 2'-deoxyuridine , 5'-triphosphate nick-end labeling method was used for evaluation of apoptotic index .
Moreover , serum testosterone levels and total antioxidant status ( TAS ) and total oxidant status ( TOS ) in testicular tissue were measured by ELISA assay .
RESULTS : The DOX group had histopathological deterioration compared to the @ @ @ @ @ @ @ in apoptotic index , caspase 3 and HSP90 expressions in the DOX group .
While TAS level of the DOX group decreased , TOS level increased when compared with the other groups .
Serum testosterone levels in the DOX group decreased compared to the control group .
However , there was improvement in testicular tissue in DOX + THQ group compared to the DOX group .
There was a decrease in apoptotic index , caspase 3 , and HSP90 expressions in DOX + THQ group compared to the DOX group .
Testosterone level @ @ @ @ @ @ @ to the DOX group .
CONCLUSION : We suggest that THQ can be used as a protective agent to reduce the toxic effects of DOX .

BACKGROUND: Doxorubicin (DOX) is used for treatment of many cancer types. Thymoquinone (THQ) is a powerful antioxidant agent used for reducing side effects of several drugs. The aim of this study is to determine possible therapeutic effects of THQ on doxorubicin-induced testicular toxicity in rats.
METHODS: Rats were divided into five groups (= 8): control, THQ, olive oil, DOX (a single dose of 15 mg/kg intraperitoneally (i.p.) on seventh day of the experiment), and DOX + THQ (10 mg/kg THQ per day and 15 mg/kg DOX i.p. on seventh day). Animals were euthanized, and testis tissues were evaluated histopathologically. Caspase 3 and HSP90 immunostaining were performed to determine the expression levels of these proteins among groups. Terminal deoxynucleotidyl transferase 2'-deoxyuridine, 5'-triphosphate nick-end labeling method was used for evaluation of apoptotic index. Moreover, serum testosterone levels and total antioxidant status (TAS) and total oxidant status (TOS) in testicular tissue were measured by ELISA assay.
RESULTS: The DOX group had histopathological deterioration compared to the control group. There was an increase in apoptotic index, caspase 3 and HSP90 expressions in the DOX group. While TAS level of the DOX group decreased, TOS level increased when compared with the other groups. Serum testosterone levels in the DOX group decreased compared to the control group. However, there was improvement in testicular tissue in DOX + THQ group compared to the DOX group. There was a decrease in apoptotic index, caspase 3, and HSP90 expressions in DOX + THQ group compared to the DOX group. Testosterone level of DOX + THQ significantly increased compared to the DOX group.
CONCLUSION: We suggest that THQ can be used as a protective agent to reduce the toxic effects of DOX.


greenmedinfo--2020-06-05--Thymoquinone inhibits biofilm formation and virulence properties of periodontal bacteria.

OBJECTIVES : To evaluate the effects of thymoquinone ( TQ ) on biofilm formation , hemolysis , hydrogen sulfide ( HS ) production and expression of virulence factors of Fusobacterium nucleatum and Porphyromonas gingivalis .
MATERIALS AND METHODS : Reference strains of F. nucleatum ATCC 25586 and P. gingivalis A7436 were tested in our study .
The minimum inhibitory concentration ( MIC ) of TQ was determined by broth microdilution method .
The impacts of TQ on virulence properties of the periodontal bacteria including biofilm formation , hemolysis and HS activities were studied .
Quantitative RT-PCR was performed to evaluate @ @ @ @ @ @ @ including outer membrane proteins ( aim-1 , fadA ) in F. nucleatum as well as cysteine proteinases or gingipains ( rgpA , rgpB , kgp ) and fimbriae ( fimA , mfa1 ) in P. gingivalis .
RESULTS : The MIC of TQ were 12.5 and 1.56 μg/mL in F. nucleatum and P. gingivalis , respectively .
The sub-MIC concentrations of TQ could prevent biofilm formation and hemolysis activities of both bacteria .
TQ also inhibited HS production which is highly associated with oral malodour .
Scanning electron microscopy revealed that TQ could @ @ @ @ @ @ @ lysis .
Furthermore , TQ reduced the expression of major virulence factors tested in F. nucleatum and P. gingivalis .
CONCLUSIONS : The TQ had potent antibacterial effect and could attenuate virulence properties of F. nucleatum and P. gingivalis .
Therefore , TQ has the potential to be developed and used in periodontal treatments , especially to prevent the progression of periodontitis .

OBJECTIVES: To evaluate the effects of thymoquinone (TQ) on biofilm formation, hemolysis, hydrogen sulfide (HS) production and expression of virulence factors of Fusobacterium nucleatum and Porphyromonas gingivalis.
MATERIALS AND METHODS: Reference strains of F. nucleatum ATCC 25586 and P. gingivalis A7436 were tested in our study. The minimum inhibitory concentration (MIC) of TQ was determined by broth microdilution method. The impacts of TQ on virulence properties of the periodontal bacteria including biofilm formation, hemolysis and HS activities were studied. Quantitative RT-PCR was performed to evaluate the expression levels of key virulence factors including outer membrane proteins (aim-1, fadA) in F. nucleatum as well as cysteine proteinases or gingipains (rgpA, rgpB, kgp) and fimbriae (fimA, mfa1) in P. gingivalis.
RESULTS: The MIC of TQ were 12.5 and 1.56 μg/mL in F. nucleatum and P. gingivalis, respectively. The sub-MIC concentrations of TQ could prevent biofilm formation and hemolysis activities of both bacteria. TQ also inhibited HS production which is highly associated with oral malodour. Scanning electron microscopy revealed that TQ could disrupt bacterial membrane and led to cell lysis. Furthermore, TQ reduced the expression of major virulence factors tested in F. nucleatum and P. gingivalis.
CONCLUSIONS: The TQ had potent antibacterial effect and could attenuate virulence properties of F. nucleatum and P. gingivalis. Therefore, TQ has the potential to be developed and used in periodontal treatments, especially to prevent the progression of periodontitis.


greenmedinfo--2020-06-05--Thymoquinone potentiates miR-16 and miR-375 expressions in hepatocellular carcinoma.

AIMS : MicroRNAs ( miRNAs ) are non-coding RNAs that control post-transcriptional gene expression .
Recently , miRNAs were confirmed to be promising biomarkers for different pathological conditions .
This study assessed the role of serum miR-16 and miR-375 in HCC development in chronic liver disease patients such as cirrhosis .
Moreover , miR-16 and miR-375 levels were estimated in HCC cell lines ( HepG2 and Huh7 ) after treatment with doxorubicin ( DOX ) , thymoquinone ( TQ ) and their combination .
MAIN METHODS : Serum miR-16 and miR-375 were analyzed in 30 HCC patients , 20 cirrhosis @ @ @ @ @ @ @ .
Moreover , HepG2 and Huh7 cells were incubated with DOX , TQ or TQ/DOX combination for 24 h and the levels of miR-16 , miR-375 and gene expression of anti-apoptotic protein BCL-2 were determined in cell lysates using RT- PCR .
Moreover , the ability of DOX , TQ and TQ/DOX combination to induce apoptosis were analyzed by measuring caspase-3 expression using ELISA method .
KEY FINDINGS : Serum miR-16 and miR-375 levels were significantly decreased in HCC patients as compared to cirrhosis and healthy control group .
Also , combined use @ @ @ @ @ @ @ better predictive ability than each alone .
Moreover , the expression level of miR-16 and miR-375 in HepG2 and Huh7 cells increased significantly after treatment with DOX and TQ .
Also , TQ/DOX combination improved apoptosis by increasing caspase-3 expression and decreasing of BCL-2 expression .
SIGNIFICANCE : This study proved that the combined use of serum miR-16 and miR-375 was better than each alone for HCC detection .
Moreover , TQ induced apoptosis and upregulatedmiR-16 and miR-375 expression in HCC cells that may explain its anticancer activity .

AIMS: MicroRNAs (miRNAs) are non-coding RNAs that control post-transcriptional gene expression. Recently, miRNAs were confirmed to be promising biomarkers for different pathological conditions. This study assessed the role of serum miR-16 and miR-375 in HCC development in chronic liver disease patients such as cirrhosis. Moreover, miR-16 and miR-375 levels were estimated in HCC cell lines (HepG2 and Huh7) after treatment with doxorubicin (DOX), thymoquinone (TQ) and their combination.
MAIN METHODS: Serum miR-16 and miR-375 were analyzed in 30 HCC patients, 20 cirrhosis patients and 10 healthy volunteers using RT-PCR. Moreover, HepG2 and Huh7 cells were incubated with DOX, TQ or TQ/DOX combination for 24 h and the levels of miR-16, miR-375 and gene expression of anti-apoptotic protein BCL-2 were determined in cell lysates using RT- PCR. Moreover, the ability of DOX, TQ and TQ/DOX combination to induce apoptosis were analyzed by measuring caspase-3 expression using ELISA method.
KEY FINDINGS: Serum miR-16 and miR-375 levels were significantly decreased in HCC patients as compared to cirrhosis and healthy control group. Also, combined use of serum miR-16 and miR-375 showed a better predictive ability than each alone. Moreover, the expression level of miR-16 and miR-375 in HepG2 and Huh7 cells increased significantly after treatment with DOX and TQ. Also, TQ/DOX combination improved apoptosis by increasing caspase-3 expression and decreasing of BCL-2 expression.
SIGNIFICANCE: This study proved that the combined use of serum miR-16 and miR-375 was better than each alone for HCC detection. Moreover, TQ induced apoptosis and upregulatedmiR-16 and miR-375 expression in HCC cells that may explain its anticancer activity.


greenmedinfo--2020-06-05--Delivery of thymoquinone to cancer cells with as1411-conjugated nanodroplets.

Systemic delivery of conventional chemotherapies can cause negative systemic toxicity , including reduced immunity and damage to organs such as the heart and kidneys-limiting the maximum dose that can be administered .
Targeted therapies appear to address this problem by having a specific target while mitigating off-target effects .
Biocompatible perfluorocarbon-based nanodroplet emulsions encapsulated by a phospholipid shell are in development for delivery of molecular compounds and hold promise as vehicles for targeted delivery of chemotherapeutics to tumors .
When ultrasound is applied , perfluorocarbon will undergo a phase change-ultimately inducing transient perforation of the cell membrane when in close @ @ @ @ @ @ @ as '' sonoporation .
`` Sonoporation allows enhanced intracellular delivery of molecular compounds and will reseal to encapsulate the molecular compound intracellularly .
In this study , we investigated delivery of thymoquinone ( TQ ) , a natural hydrophobic phytochemical compound with bioactivity in cancer cells .
In addition , we conjugated a G-quadruplex aptamer , 'AS1411 ' , to TQ-loaded nanodroplets and explored their effects on multiple human cancer cell lines .
AS1411 binds nucleolin , which is over-expressed on the surface of cancer cells , and in addition to its tumor-targeting @ @ @ @ @ @ @ induce anti-cancer effects .
Thymoquinone was loaded onto AS1411-conjugated nanodroplet emulsion to assess activity against cancer cells .
Confocal microscopy indicated uptake of AS1411-conjugated nanodroplets by cancer cells .
Furthermore , AS1411-conjugated nanoemulsions loaded with TQ significantly enhanced cytotoxicity in cancer cells compared to free compound .
These results demonstrate that AS1411 can be conjugated onto nanodroplet emulsions for targeted delivery to human cancer cells .
This novel formulation offers significant potential for targeted delivery of hydrophobic chemotherapeutics to tumors for cancer treatment .

Systemic delivery of conventional chemotherapies can cause negative systemic toxicity, including reduced immunity and damage to organs such as the heart and kidneys-limiting the maximum dose that can be administered. Targeted therapies appear to address this problem by having a specific target while mitigating off-target effects. Biocompatible perfluorocarbon-based nanodroplet emulsions encapsulated by a phospholipid shell are in development for delivery of molecular compounds and hold promise as vehicles for targeted delivery of chemotherapeutics to tumors. When ultrasound is applied, perfluorocarbon will undergo a phase change-ultimately inducing transient perforation of the cell membrane when in close proximity, which is more commonly known as"sonoporation."Sonoporation allows enhanced intracellular delivery of molecular compounds and will reseal to encapsulate the molecular compound intracellularly. In this study, we investigated delivery of thymoquinone (TQ), a natural hydrophobic phytochemical compound with bioactivity in cancer cells. In addition, we conjugated a G-quadruplex aptamer, 'AS1411', to TQ-loaded nanodroplets and explored their effects on multiple human cancer cell lines. AS1411 binds nucleolin, which is over-expressed on the surface of cancer cells, and in addition to its tumor-targeting properties AS1411 has also been shown to induce anti-cancer effects. Thymoquinone was loaded onto AS1411-conjugated nanodroplet emulsion to assess activity against cancer cells. Confocal microscopy indicated uptake of AS1411-conjugated nanodroplets by cancer cells. Furthermore, AS1411-conjugated nanoemulsions loaded with TQ significantly enhanced cytotoxicity in cancer cells compared to free compound. These results demonstrate that AS1411 can be conjugated onto nanodroplet emulsions for targeted delivery to human cancer cells. This novel formulation offers significant potential for targeted delivery of hydrophobic chemotherapeutics to tumors for cancer treatment.


greenmedinfo--2020-06-05--This meta-analysis suggests that Nigella sativa supplementation in humans may benefit as an antioxid

This meta-analysis suggests that Nigella sativa supplementation in humans may benefit as an antioxidant.

Introduction : is a commonly used traditional medicine which has been shown to have antioxidant properties .
However , its supplementation in patients of clinical trials showed conflicting results..
Relevant articles were searched through PubMed/Medline , SCOPUS , and Google Scholar databases using '' '' or '' black seed '' or '' black caraway '' or '' thymoquinone '' and '' oxidative stress '' or '' antioxidant '' and '' clinical trial '' keywords .
Randomized , placebo-controlled human interventions usingwere included in this study .
The methodological quality of studies was assessed using Jadad 's quality scales .
Results @ @ @ @ @ @ @ the inclusion criteria .
The overall quality of all included trials was determined based on the low risk of bias and the high quality of reported information ( Jadad score ≥ 3 ) .
Meta-analysis of 293 eligible subjects showed that treatment withimproved the superoxide dismutase ( SOD ) level ( 48.18 ; 95 % CI 30.29 to 66.08 ; < 0.01 ) , but there was no significant effect on the malondialdehyde ( MDA ) level ( -5.32 ; 95 % CI -1.19 to 0.128 ; =0.114 ) and total antioxidant capacity @ @ @ @ @ @ @ 95 % CI -0.136 to 0.573 ; = 0.227 ) .
Conclusion : This meta-analysis suggests thatsupplementation in humans may benefit as an antioxidant by increasing SOD levels but has no significant effect on the MDA level and TAC level .

Introduction: is a commonly used traditional medicine which has been shown to have antioxidant properties. However, its supplementation in patients of clinical trials showed conflicting results.. Relevant articles were searched through PubMed/Medline, SCOPUS, and Google Scholar databases using""or"black seed"or"black caraway"or"thymoquinone"and"oxidative stress"or"antioxidant"and"clinical trial"keywords. Randomized, placebo-controlled human interventions usingwere included in this study. The methodological quality of studies was assessed using Jadad's quality scales.
Results: Five studies using 293 subjects met the inclusion criteria. The overall quality of all included trials was determined based on the low risk of bias and the high quality of reported information (Jadad score ≥ 3). Meta-analysis of 293 eligible subjects showed that treatment withimproved the superoxide dismutase (SOD) level (48.18; 95% CI 30.29 to 66.08;<0.01), but there was no significant effect on the malondialdehyde (MDA) level (-5.32; 95% CI -1.19 to 0.128;=0.114) and total antioxidant capacity (TAC) level (0.219; 95% CI -0.136 to 0.573; = 0.227).
Conclusion: This meta-analysis suggests thatsupplementation in humans may benefit as an antioxidant by increasing SOD levels but has no significant effect on the MDA level and TAC level.


greenmedinfo--2020-06-05--Thymoquinone-chemotherapeutic combinations: new regimen to combat cancer and cancer stem cells.

Cancer is a worldwide disease that causes millions of cases of mortality and morbidity .
The major problem associated with the cancer is its resistance to conventional therapy and a high relapse rate .
The use of chemotherapy to treat cancer began at the start of the twentieth century with attempts to control cancer .
In time advance , many cancer chemotherapeutic agents have been developed for cancer treatment with different mechanisms of action including the alkylating agents , antimetabolites , antimicrotubule , topoisomerase inhibitors , and cytotoxic antibiotics , all of which have toxic effects toward normal cells in @ @ @ @ @ @ @ chemotherapeutics ' anticancer role potentiation and safety by thymoquinone ( TQ ) alone or in combination with the most common therapeutic drugs .
Our search was done through PubMed , Science Direct , Springer Link , Taylor & Francis Online , Wiley Online Library , Nature publication group , SAGE Journals , and Web of Science databases .
We recognized that TQ-chemotherapeutics combination increased chemo-modulation to the anticancer effect of different chemotherapeutics and protected the normal body cells from the toxic injuries that are induced by chemotherapeutics based on its antioxidant power .
@ @ @ @ @ @ @ possible combinatory effect of TQ and chemotherapeutics to control cancer stem cells through molecular docking targeting of wingless/integrated ( Wnt ) and Hedgehog ( Hh ) .
We found that TQ modulates the Wnt and Hh pathways , by binding with tankyrase-2 and smoothened 7TM receptor , respectively , more efficiently than most chemotherapeutics drugs , while methotrexate showed high-binding affinity compared with TQ .
Therefore , we encourage researchers to investigate the chemo-modulatory potential and protective effects of TQ in combination with chemotherapeutics for either cancer or cancer stem cell treatment .

Cancer is a worldwide disease that causes millions of cases of mortality and morbidity. The major problem associated with the cancer is its resistance to conventional therapy and a high relapse rate. The use of chemotherapy to treat cancer began at the start of the twentieth century with attempts to control cancer. In time advance, many cancer chemotherapeutic agents have been developed for cancer treatment with different mechanisms of action including the alkylating agents, antimetabolites, antimicrotubule, topoisomerase inhibitors, and cytotoxic antibiotics, all of which have toxic effects toward normal cells in the body. Here, we reviewed chemotherapeutics' anticancer role potentiation and safety by thymoquinone (TQ) alone or in combination with the most common therapeutic drugs. Our search was done through PubMed, Science Direct, Springer Link, Taylor&Francis Online, Wiley Online Library, Nature publication group, SAGE Journals, and Web of Science databases. We recognized that TQ-chemotherapeutics combination increased chemo-modulation to the anticancer effect of different chemotherapeutics and protected the normal body cells from the toxic injuries that are induced by chemotherapeutics based on its antioxidant power. Moreover, the current study investigates the possible combinatory effect of TQ and chemotherapeutics to control cancer stem cells through molecular docking targeting of wingless/integrated (Wnt) and Hedgehog (Hh). We found that TQ modulates the Wnt and Hh pathways, by binding with tankyrase-2 and smoothened 7TM receptor, respectively, more efficiently than most chemotherapeutics drugs, while methotrexate showed high-binding affinity compared with TQ. Therefore, we encourage researchers to investigate the chemo-modulatory potential and protective effects of TQ in combination with chemotherapeutics for either cancer or cancer stem cell treatment.


greenmedinfo--2020-06-05--Natural products may interfere With SARS-CoV-2 attachment to the host cell.

SARS-CoV-2 has been emerged in December 2019 in China , causing deadly ( 5 % mortality ) pandemic pneumonia , termed COVID-19 .
More than one host-cell receptor is reported to be recognized by the viral spike protein , among them is the cell-surface Heat Shock Protein A5 ( HSPA5 ) , also termed GRP78 or BiP .
Upon viral infection , HSPA5 is upregulated , then translocating to the cell membrane where it is subjected to be recognized by the SARS-CoV-2 spike .
In this study , some natural product compounds are tested against the HSPA5 substrate-binding domainβ ( @ @ @ @ @ @ @ the recognition site for the SARS-CoV-2 spike .
Molecular docking and molecular dynamics simulations are used to test some natural compounds binding to HSPA5 SBDβ .
The results show high to a moderate binding affinity for the phytoestrogens ( Diadiazin , Genistein , Formontein , and Biochanin A ) , chlorogenic acid , linolenic acid , palmitic acid , caffeic acid , caffeic acid phenethyl ester , hydroxytyrosol , cis-p-Coumaric acid , cinnamaldehyde , thymoquinone , and some physiological hormones such as estrogens , progesterone , testosterone , and cholesterol to the HSPA5 @ @ @ @ @ @ @ phytoestrogens and estrogens are the best in binding HSPA5 , hence may interfere with SARS-CoV-2 attachment to the stressed cells .
These compounds can be successful as anti-COVID-19 agents for people with a high risk of cell stress like elders , cancer patients , and front-line medical staff.Communicated by Ramaswamy H. Sarma .

SARS-CoV-2 has been emerged in December 2019 in China, causing deadly (5% mortality) pandemic pneumonia, termed COVID-19. More than one host-cell receptor is reported to be recognized by the viral spike protein, among them is the cell-surface Heat Shock Protein A5 (HSPA5), also termed GRP78 or BiP. Upon viral infection, HSPA5 is upregulated, then translocating to the cell membrane where it is subjected to be recognized by the SARS-CoV-2 spike. In this study, some natural product compounds are tested against the HSPA5 substrate-binding domainβ (SBDβ), which reported to be the recognition site for the SARS-CoV-2 spike. Molecular docking and molecular dynamics simulations are used to test some natural compounds binding to HSPA5 SBDβ. The results show high to a moderate binding affinity for the phytoestrogens (Diadiazin, Genistein, Formontein, and Biochanin A), chlorogenic acid, linolenic acid, palmitic acid, caffeic acid, caffeic acid phenethyl ester, hydroxytyrosol, cis-p-Coumaric acid, cinnamaldehyde, thymoquinone, and some physiological hormones such as estrogens, progesterone, testosterone, and cholesterol to the HSPA5 SBDβ.Based on its binding affinities, the phytoestrogens and estrogens are the best in binding HSPA5, hence may interfere with SARS-CoV-2 attachment to the stressed cells. These compounds can be successful as anti-COVID-19 agents for people with a high risk of cell stress like elders, cancer patients, and front-line medical staff.Communicated by Ramaswamy H. Sarma.


greenmedinfo--2020-06-05--Genistin: a novel potent anti-adipogenic and anti-lipogenic agent.

Soy isoflavones are popular ingredients with anti-adipogenic and anti-lipogenic properties .
The anti-adipogenic and anti-lipogenic properties of genistein are well-known , but those of genistin and glycitein remain unknown , and those of daidzein are characterized by contrasting data .
Therefore , the purpose of our study was to investigate the effects of daidzein , glycitein , genistein , and genistin on adipogenesis and lipogenesis in 3T3-L1 cells .
Proliferation of 3T3-L1 preadipocytes was unaffected by genistin and glycitein , but it was affected by 50 and 100µM genistein and 100 µM daidzein for 48 h. Among the four isoflavones @ @ @ @ @ @ @ and genistein markedly suppressed lipid accumulation during adipogenesis in 3T3-L1 cells through a similar signaling pathway in a dose-dependent manner .
Genistin and genistein suppress adipocyte-specific proteins and genes , such as peroxisome proliferator-activated receptor γ ( PPARγ ) , CCAAT-enhancer-binding protein α ( C/EBPα ) , and adipocyte binding protein 2 ( aP2 ) /fatty acid-binding protein 4 ( FABP4 ) , and lipogenic enzymes such as ATP citrate lyase ( ACL ) , acetyl-CoA carboxylase 1 ( ACC1 ) , and fatty acid synthase ( FAS ) .
Both isoflavones also @ @ @ @ @ @ @ ) , an essential factor in adipocyte differentiation , and inhibited sterol regulatory element-binding transcription factor 1c ( SREBP-1c ) .
These results indicate that genistin is a potent anti-adipogenic and anti-lipogenic agent .

Soy isoflavones are popular ingredients with anti-adipogenic and anti-lipogenic properties. The anti-adipogenic and anti-lipogenic properties of genistein are well-known, but those of genistin and glycitein remain unknown, and those of daidzein are characterized by contrasting data. Therefore, the purpose of our study was to investigate the effects of daidzein, glycitein, genistein, and genistin on adipogenesis and lipogenesis in 3T3-L1 cells. Proliferation of 3T3-L1 preadipocytes was unaffected by genistin and glycitein, but it was affected by 50 and 100µM genistein and 100 µM daidzein for 48 h. Among the four isoflavones, only 50 and 100 µM genistin and genistein markedly suppressed lipid accumulation during adipogenesis in 3T3-L1 cells through a similar signaling pathway in a dose-dependent manner. Genistin and genistein suppress adipocyte-specific proteins and genes, such as peroxisome proliferator-activated receptor γ (PPARγ), CCAAT-enhancer-binding protein α (C/EBPα), and adipocyte binding protein 2 (aP2)/fatty acid-binding protein 4 (FABP4), and lipogenic enzymes such as ATP citrate lyase (ACL), acetyl-CoA carboxylase 1 (ACC1), and fatty acid synthase (FAS). Both isoflavones also activate AMP-activated protein kinase α (AMPKα), an essential factor in adipocyte differentiation, and inhibited sterol regulatory element-binding transcription factor 1c (SREBP-1c). These results indicate that genistin is a potent anti-adipogenic and anti-lipogenic agent.


greenmedinfo--2020-06-05--Genistein inhibited the migration and invasion of cervical cancer HeLa cells.

OBJECTIVE : Genistein obviously inhibits the migration and invasion of various tumor cells .
However , its effects on cervical cancer cells have seldom been referred .
We aimed to evaluate the effects of genistein on the proliferation , migration and invasion of cervical cancer HeLa cells , the expressions and phosphorylations of proteins related with FAK-paxillin and MAPKs signaling pathways , as well as the expressions of related key genes .
MATERIALS AND METHODS : HeLa cells were stimulated with genistein for 24 h and 48 h respectively .
After adherence for 2 h , 0 μM , 12.5 @ @ @ @ @ @ @ and 100 μM genistein solutions were added in DMEM .
Cell proliferation was tested by the CCK-8 assay .
After treatment with 100 μM genistein , the migration ability was detected by the scratch assay .
Transwellassay was used to detect cell migration and invasion abilities .
Western blot and qRT-PCR were used to detect the expressions of proteins and mRNAs related with FAK-paxillin and MAPKs signaling pathways respectively .
RESULTS : The effect of genistein on the proliferation of HeLa cells was proportional to treatment time and drug dose , and the @ @ @ @ @ @ @ 48 h at 100 μM .
After treatment with 100 μM genistein , the scratch migration rate was significantly lower than that of the control group at 24 h and 48 h ( P CONCLUSION : Genistein inhibited the migration and invasion of cervical cancer HeLa cells by regulating FAK-paxillin and MAPK signaling pathways in dose-dependent manners .

OBJECTIVE: Genistein obviously inhibits the migration and invasion of various tumor cells. However, its effects on cervical cancer cells have seldom been referred. We aimed to evaluate the effects of genistein on the proliferation, migration and invasion of cervical cancer HeLa cells, the expressions and phosphorylations of proteins related with FAK-paxillin and MAPKs signaling pathways, as well as the expressions of related key genes.
MATERIALS AND METHODS: HeLa cells were stimulated with genistein for 24 h and 48 h respectively. After adherence for 2 h, 0 μM, 12.5 μM, 25 μM, 50 μM and 100 μM genistein solutions were added in DMEM. Cell proliferation was tested by the CCK-8 assay. After treatment with 100 μM genistein, the migration ability was detected by the scratch assay. Transwellassay was used to detect cell migration and invasion abilities. Western blot and qRT-PCR were used to detect the expressions of proteins and mRNAs related with FAK-paxillin and MAPKs signaling pathways respectively.
RESULTS: The effect of genistein on the proliferation of HeLa cells was proportional to treatment time and drug dose, and the proliferation was inhibited after 24 h and 48 h at 100 μM. After treatment with 100 μM genistein, the scratch migration rate was significantly lower than that of the control group at 24 h and 48 h (P < 0.05). Genistein also inhibited the invasion of tumor cells through the upper chamber and Matrigel. The number of invasive cells was significantly lower than that of the control group (P < 0.05). Genistein significantly inhibited the phosphorylations of FAK, paxillin, p38 and p42/44. Compared to the control group, 100 μM genistein significantly suppressed the mRNA expressions of FAK, paxillin, Snail and twist.
CONCLUSION: Genistein inhibited the migration and invasion of cervical cancer HeLa cells by regulating FAK-paxillin and MAPK signaling pathways in dose-dependent manners.


greenmedinfo--2020-06-05--Genistein inhibits angiogenesis developed during rheumatoid arthritis.

Background : Angiogenesis plays an important role in the development of rheumatoid arthritis ( RA ) , which increases the supply of nutrients , cytokines , and inflammatory cells to the synovial membrane .
Genistein ( GEN ) , a soy-derived isoflavone , has been validated that can effectively inhibit the angiogenesis of several tumours .
We thus carried out a study in vitro to investigate the effect of GEN in vascular endothelial growth factor ( VEGF ) expression and angiogenesis induced by the inflammatory environment of RA .
Methods : MH7A cells were used to verify whether GEN can @ @ @ @ @ @ @ cells under inflammatory conditions and demonstrate the mechanism .
EA.hy926 cells were used to verify whether GEN can inhibit the migration and tube formation of vascular endothelial cells in inflammatory environment .
Results : GEN dose-dependently inhibited the expression and secretion of interleukin ( IL ) -6 and VEGF , as well as the nucleus translocation of Signal transducer and activator of transcription 3 ( STAT3 ) in MH7A .
Furthermore , GEN inhibited IL-6-induced vascular endothelial cell migration and tube formation in vitro .
Conclusion : GEN inhibits IL-6-induced VEGF expression and @ @ @ @ @ @ @ ( JAK2 ) /STAT3 pathway in RA , which has provided a novel insight into the antiangiogenic activity of GEN in RA .
The translational potential of this article : Our study provides scientific guidance for the clinical translational research of GEN in the RA treatment .

Background: Angiogenesis plays an important role in the development of rheumatoid arthritis (RA), which increases the supply of nutrients, cytokines, and inflammatory cells to the synovial membrane. Genistein (GEN), a soy-derived isoflavone, has been validated that can effectively inhibit the angiogenesis of several tumours. We thus carried out a study in vitro to investigate the effect of GEN in vascular endothelial growth factor (VEGF) expression and angiogenesis induced by the inflammatory environment of RA.
Methods: MH7A cells were used to verify whether GEN can inhibit the expression of VEGF in MH7A cells under inflammatory conditions and demonstrate the mechanism. EA.hy926 cells were used to verify whether GEN can inhibit the migration and tube formation of vascular endothelial cells in inflammatory environment.
Results: GEN dose-dependently inhibited the expression and secretion of interleukin (IL)-6 and VEGF, as well as the nucleus translocation of Signal transducer and activator of transcription 3 (STAT3) in MH7A. Furthermore, GEN inhibited IL-6-induced vascular endothelial cell migration and tube formation in vitro.
Conclusion: GEN inhibits IL-6-induced VEGF expression and angiogenesis partially through the Janus kinase 2 (JAK2)/STAT3 pathway in RA, which has provided a novel insight into the antiangiogenic activity of GEN in RA.
The translational potential of this article: Our study provides scientific guidance for the clinical translational research of GEN in the RA treatment.


greenmedinfo--2020-06-05--Protective effect of genistein in a rat model of ischemic acute kidney injury.

BACKGROUND : This study determined the possible anti-inflammatory and antioxidant renal protective effect of genistein , a soy isoflavone , against kidney damage and functional disorders following renal ischemia/reperfusion ( I/R ) in male rats .
MATERIALS AND METHODS : The animals were dedicated to five groups ( n = 7 per group ) : Sham , Sham + Geni ( genistein , 15 mg/kg in 1 ml 1 % DMSO , i.p . )
, Sham + DMSO ( 1 ml 1 % DMSO , i.p . )
, I/R ( bilateral renal ischemia for 45 min followed by @ @ @ @ @ @ @ Geni ( genistein , 15 mg/kg ) .
24-h urine samples , blood and tissue samples of the kidney were collected at the end of 24 h reperfusion period .
RESULTS : Compared to sham , sham + Geni and sham + DMSO groups , IR injury ( IRI ) ended in kidney dysfunction ( decreased creatinine clearance , and increased fractional excretion of sodium ) , increased levels of malondialdehyde , decreased activities of antioxidant enzymes ( superoxide dismutase , gluthatione peroxidase , and catalase ) , increased gene expression levels of @ @ @ @ @ @ @ TNF-α ( tumor necrosis factor-alpha ) , as well as histological damages in kidney tissue .
Genistein administration decreased all the changes .
Therefore , genistein apparently protects the kidney against IRI by mitigating both oxidative stress and inflammation .
The antioxidant and anti-inflammatory properties of genistein probably exert important roles in improving functional disorders and offer renal protection against IRI .

BACKGROUND: This study determined the possible anti-inflammatory and antioxidant renal protective effect of genistein, a soy isoflavone, against kidney damage and functional disorders following renal ischemia/reperfusion (I/R) in male rats.
MATERIALS AND METHODS: The animals were dedicated to five groups (n = 7 per group): Sham, Sham + Geni (genistein, 15 mg/kg in 1 ml 1% DMSO, i.p.), Sham + DMSO (1 ml 1% DMSO, i.p.), I/R (bilateral renal ischemia for 45 min followed by 24 h reperfusion), I/R + Geni (genistein, 15 mg/kg). 24-h urine samples, blood and tissue samples of the kidney were collected at the end of 24 h reperfusion period.
RESULTS: Compared to sham, sham + Geni and sham + DMSO groups, IR injury (IRI) ended in kidney dysfunction (decreased creatinine clearance, and increased fractional excretion of sodium), increased levels of malondialdehyde, decreased activities of antioxidant enzymes (superoxide dismutase, gluthatione peroxidase, and catalase), increased gene expression levels of TLR4 (Toll-like receptor 4) and TNF-α (tumor necrosis factor-alpha), as well as histological damages in kidney tissue. Genistein administration decreased all the changes. Therefore, genistein apparently protects the kidney against IRI by mitigating both oxidative stress and inflammation. The antioxidant and anti-inflammatory properties of genistein probably exert important roles in improving functional disorders and offer renal protection against IRI.


greenmedinfo--2020-06-06--These results support use of the Malus sp. extract and rutin as skin photochemopreventive agents for

These results support use of the Malus sp. extract and rutin as skin photochemopreventive agents for topical application.

The skin is exposed to the solar ultraviolet B ( UVB ) radiation , which leads to the formation of several types of skin damage responsible for cancer initiation and aging.sp .
is a genus of apples , which are a good source of polyphenolic compounds.sp .
and more precisely one of its components , rutin , have preventive effects on many diseases caused by reactive oxygen species .
In addition , previous studies have suggested the topical usage of the extract as a cosmetic product to prevent skin damage caused by oxidative stress .
In this study , we @ @ @ @ @ @ @ containing 1.25 % ofsp .
extract and the equivalent amount of rutin ( 0.75 % ) .
The photochemopreventive effect was assessed on two three-dimensional ( 3D ) skin models , that is , skin explants and 3D tissue-engineered skin to compare the models .
Both formulations protected against the UVB-induced increase in sunburn cell formation , as well as caspase-3 activation and cyclobutane pyrimidine dimer formation in both skin models .
Furthermore , the formulations inhibited the lipid peroxidation and the metalloproteinase formation induced by UVB radiation .
The tissue-engineered skins and @ @ @ @ @ @ @ assess the UVB-induced damages .
These results support use of thesp .
extract and rutin as skin photochemopreventive agents for topical application .

The skin is exposed to the solar ultraviolet B (UVB) radiation, which leads to the formation of several types of skin damage responsible for cancer initiation and aging.sp. is a genus of apples, which are a good source of polyphenolic compounds.sp. and more precisely one of its components, rutin, have preventive effects on many diseases caused by reactive oxygen species. In addition, previous studies have suggested the topical usage of the extract as a cosmetic product to prevent skin damage caused by oxidative stress. In this study, we evaluated the efficacy of two topical formulations containing 1.25% ofsp. extract and the equivalent amount of rutin (0.75%). The photochemopreventive effect was assessed on two three-dimensional (3D) skin models, that is,skin explants and 3D tissue-engineered skin to compare the models. Both formulations protected against the UVB-induced increase in sunburn cell formation, as well as caspase-3 activation and cyclobutane pyrimidine dimer formation in both skin models. Furthermore, the formulations inhibited the lipid peroxidation and the metalloproteinase formation induced by UVB radiation. The tissue-engineered skins and the skin explants provided effective tools to assess the UVB-induced damages. These results support use of thesp. extract and rutin as skin photochemopreventive agents for topical application.


greenmedinfo--2020-06-06--Continuous administration of apple polyphenol for 12 weeks alleviated ultraviolet irradiation induce

Continuous administration of apple polyphenol for 12 weeks alleviated ultraviolet irradiation induced skin pigmentation.

This clinical study was performed to evaluate the effects of continuous apple polyphenol ( AP ) administration on facial skin @ @ @ @ @ ultraviolet ( UV ) irradiation in healthy women participants .
Participants ( n = 65 @ @ @ @ @ were randomized to receive tablets containing AP ( 300 or 600 mg/day ) or placebo @ @ @ @ @ clinical trial .
Continuous administration of AP for 12 weeks significantly prevented UV irradiation induced @ @ @ @ @ , melanin value , L value ) , although a dose-dependent relationship was not clearly @ @ @ @ @ no significant differences were detected between the groups with regard to water content and trans-epidermal @ @ @ @ @ demonstrated that APs and their major active compounds , procyanidins , have several health benefits @ @ @ @ @ that continuous administration of AP for 12 weeks alleviated UV irradiation induced skin pigmentation , @ @ @ @ @ in healthy women .

This clinical study was performed to evaluate the effects of continuous apple polyphenol (AP) administration on facial skin conditions and pigmentation induced by ultraviolet (UV) irradiation in healthy women participants. Participants (n = 65, age 20-39 years) were randomized to receive tablets containing AP (300 or 600 mg/day) or placebo in a double-blinded, placebo-controlled clinical trial. Continuous administration of AP for 12 weeks significantly prevented UV irradiation induced skin pigmentation (erythema value, melanin value, L value), although a dose-dependent relationship was not clearly observed. In contrast, no significant differences were detected between the groups with regard to water content and trans-epidermal water loss. Our study demonstrated that APs and their major active compounds, procyanidins, have several health benefits. Here, we report that continuous administration of AP for 12 weeks alleviated UV irradiation induced skin pigmentation, when compared with placebo, in healthy women.


greenmedinfo--2020-06-06--Protective effect of Apple polyphenols on chronic ethanol exposure.

Apple polyphenols ( AP ) have attracted much attention due to their various bioactivities .
In this study , the protective effect of AP against chronic ethanol exposure-induced neural injury as well as the possible mechanisms were investigated .
Body weight , daily average food intake and daily average fluid intake were measured and daily average ethanol consumption was calculated .
The influences of AP on motor behavior and memory were detected by locomotor activity test , rotarod test , beam walking test , and Y maze test and novel object recognition test , respectively .
The changes of blood @ @ @ @ @ @ @ also measured .
AP improved chronic ethanol exposure-induced the inhibition of body weight and the decrease of daily average food intake , but did not influence the daily average fluid intake and the daily average ethanol intake , indicating that the improve effect of AP did not result from the decrease of ethanol intake .
Motor activity and motor coordination were not influenced after chronic ethanol exposure though the blood ethanol concentration was higher than that in control group .
AP improved significantly chronic ethanol-induced the memory impairment and the hippocampal CA1 neurons @ @ @ @ @ @ @ decreased the contents of NO and MDA and increased the levels of T-AOC and GSH in the hippocampus of rats .
These results suggest that AP exerts a protective effect against chronic ethanol-induced memory impairment through improving the oxidative stress in the hippocampus .

Apple polyphenols (AP) have attracted much attention due to their various bioactivities. In this study, the protective effect of AP against chronic ethanol exposure-induced neural injury as well as the possible mechanisms were investigated. Body weight, daily average food intake and daily average fluid intake were measured and daily average ethanol consumption was calculated. The influences of AP on motor behavior and memory were detected by locomotor activity test, rotarod test, beam walking test, and Y maze test and novel object recognition test, respectively. The changes of blood ethanol concentration and the oxidative stress were also measured. AP improved chronic ethanol exposure-induced the inhibition of body weight and the decrease of daily average food intake, but did not influence the daily average fluid intake and the daily average ethanol intake, indicating that the improve effect of AP did not result from the decrease of ethanol intake. Motor activity and motor coordination were not influenced after chronic ethanol exposure though the blood ethanol concentration was higher than that in control group. AP improved significantly chronic ethanol-induced the memory impairment and the hippocampal CA1 neurons damage. Further studies found that AP decreased the contents of NO and MDA and increased the levels of T-AOC and GSH in the hippocampus of rats. These results suggest that AP exerts a protective effect against chronic ethanol-induced memory impairment through improving the oxidative stress in the hippocampus.


greenmedinfo--2020-06-06--Shikonin relieves osteoporosis of ovariectomized mice.

Postmenopausal osteoporosis is very common in women .
Currently , many kinds of new drugs are being developed for this disease .
Postmenopausal osteoporosis is closely related to overactivity of osteoclasts in body .
Shikonin is purple red naphthoquinone pigment extracted from lithospermum , which has anti-inflammation , antivirus , anticancer and other bioactivities .
At the same time , it has been proved that shikonin can promote the proliferation and differentiation of osteoblasts , but its influence on osteoclasts and molecular mechanism are unknown .
Our study showed that shikonin could inhibit the activity and formation of RANKL-mediated osteoclasts @ @ @ @ @ @ @ of bone marrow macrophages ( BMM ) .
In addition , we have also found that shikonin can inhibit the expression of specific marker gene of osteoclasts , including nuclear factor of activated T cells cytoplasmic 1 ( NFATc1 ) , cathepsin K ( Ctsk ) , tartrate resistant acid phosphatase ( TRAcP ) and calcitonin receptor .
Shikonin also could promote the proliferation of MC3T3-E1 , increasing the expression of mRNA related to osteogenesis , like the expression of bone morphogenetic protein-2 ( BMP-2 ) , alkaline phosphatase ( ALP ) , @ @ @ @ @ @ @ and osteocalcin ( OCN ) .
Luciferase reporter gene assay and Western blot analysis further indicated that shikonin could inhibit the activity of RANKL-induced NF-κB and NFAT receptors .
Moreover , shikonin can also slow down bone loss of ovariectomized ( OVX ) mice by inhibiting the activity of osteoclasts .
This work explains the molecular mechanism of shikonin in RANKL-mediated formation of osteoclasts , and reveals the potential of further developing shikonininto a new drug for prevention and treatment of postmenopausal osteoporosis .

Postmenopausal osteoporosis is very common in women. Currently, many kinds of new drugs are being developed for this disease. Postmenopausal osteoporosis is closely related to overactivity of osteoclasts in body. Shikonin is purple red naphthoquinone pigment extracted from lithospermum, which has anti-inflammation, antivirus, anticancer and other bioactivities. At the same time, it has been proved that shikonin can promote the proliferation and differentiation of osteoblasts, but its influence on osteoclasts and molecular mechanism are unknown. Our study showed that shikonin could inhibit the activity and formation of RANKL-mediated osteoclasts depending on dose without affecting the activity of bone marrow macrophages (BMM). In addition, we have also found that shikonin can inhibit the expression of specific marker gene of osteoclasts, including nuclear factor of activated T cells cytoplasmic 1 (NFATc1), cathepsin K (Ctsk), tartrate resistant acid phosphatase (TRAcP) and calcitonin receptor. Shikonin also could promote the proliferation of MC3T3-E1, increasing the expression of mRNA related to osteogenesis, like the expression of bone morphogenetic protein-2 (BMP-2), alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx2) and osteocalcin (OCN). Luciferase reporter gene assay and Western blot analysis further indicated that shikonin could inhibit the activity of RANKL-induced NF-κB and NFAT receptors. Moreover, shikonin can also slow down bone loss of ovariectomized (OVX) mice by inhibiting the activity of osteoclasts. This work explains the molecular mechanism of shikonin in RANKL-mediated formation of osteoclasts, and reveals the potential of further developing shikonininto a new drug for prevention and treatment of postmenopausal osteoporosis.


greenmedinfo--2020-06-06--Anti-angiogenic effect of shikonin in rheumatoid arthritis.

ETHNOPHARMACOLOGICAL RELEVANCE : Zicao is the dried root of Lithospermum erythrorhizon Sieb , et Zucc , Arnebia euchroma ( Royle ) Johnst , or Arnebia guttata Bunge and commonly used to treat viral infection , inflammation , arthritis and cancer in China.Shikonin ( SKN ) is a major active chemical component isolated from zicao .
Previous reseach showed that SKN has anti-inflammatory , immunomodulatory and analgesic effects , and inhibits the development of arthritis and the condition of collagen arthritis ( CIA ) mice ; nevertheless , its role in the angiogenesis of rheumatoid arthritis ( RA ) has not @ @ @ @ @ @ @ : The purpose of this study was to investigate the antiangiogenic activity of SKN in CIA rats and various angiogenesis models .
MATERIAL AND METHODS : The anti-arthritic effect of SKN on CIA rats was tested by arthritis score , arthritis incidence , radiological observation and histopathology evaluation of inflamed joints .
Vessel density evaluated with CD31 immunohistochemistry/immunofluorescence in joint synovial membrane tissues of CIA rats , chick chorioallantoic membrane assay , rat aortic ring assay , and the migration , invasion , adhesion and tube formation of HUVEC induced by TNF-α were @ @ @ @ @ @ @ SKN .
Moreover , the effect of SKN on the expression of angiogenic mediators , such as VEGF , VEGFR2 , TNF-α , IL-1β , PDGF and TGF-β in sera and joint synovia of rats , and in TNF-α-induced MH7A/HUVEC cells were measured by immunohistochemistry , enzyme linked immunosorbent assay , Western blot and/or real-time PCR .
Through the analysis of protein and mRNA levels of PI3K , Akt and PTEN , and the autophosphorylation of ERK1/2 , JNK and p38 in joint synovia of rats and in TNF-α-induced HUVEC cells , the @ @ @ @ @ @ @ by using Western blot and/or real-time PCR .
RESULTS : SKN significantly reduced the arthritis score and arthritis incidence , and inhibited inflammation , pannus formation , cartilage and bone destruction of inflamed joints in CIA rats .
Partially , SKN remarkably decreased the immature blood vessels in synovial membrane tissues of inflamed joints from CIA rats .
It also suppressed in vivo angiogenesis in chick embryo and VEGF-induced microvessel sprout formation ex vivo .
Meanwhile , SKN inhibited TNF-α-induced migration , invasion , adhesion and tube formation of HUVEC cells .
Moreover @ @ @ @ @ @ @ angiogenic activators including VEGF , VEGFR2 , TNF-α , IL-1β , PDGF and TGF-β in synovia of CIA rats and/or in MH7A/HUVEC cells .
More interestingly , SKN downregulated PI3K and Akt , and simultaneously upregulated PTEN both at protein and mRNA levels in synovia tissues and/or in TNF-α-induced HUVEC cells .
It also suppressed the phosphorylation and gene level of TNF-α-induced signaling molecules , as ERK1/2 , JNK , and p38 in synovium and/or in TNF-α-induced HUVEC cells .
CONCLUSION : These findings indicate for the first time that SKN has the @ @ @ @ @ @ @ ex vivo and in vitro by interrupting the PI3K/AKT and MAPKs signaling pathways .

ETHNOPHARMACOLOGICAL RELEVANCE: Zicao is the dried root of Lithospermum erythrorhizon Sieb, et Zucc, Arnebia euchroma (Royle) Johnst, or Arnebia guttata Bunge and commonly used to treat viral infection, inflammation, arthritis and cancer in China.Shikonin (SKN) is a major active chemical component isolated from zicao. Previous reseach showed that SKN has anti-inflammatory, immunomodulatory and analgesic effects, and inhibits the development of arthritis and the condition of collagen arthritis (CIA) mice; nevertheless, its role in the angiogenesis of rheumatoid arthritis (RA) has not been elucidated.
AIM OF THE STUDY: The purpose of this study was to investigate the antiangiogenic activity of SKN in CIA rats and various angiogenesis models.
MATERIAL AND METHODS: The anti-arthritic effect of SKN on CIA rats was tested by arthritis score, arthritis incidence, radiological observation and histopathology evaluation of inflamed joints. Vessel density evaluated with CD31 immunohistochemistry/immunofluorescence in joint synovial membrane tissues of CIA rats, chick chorioallantoic membrane assay, rat aortic ring assay, and the migration, invasion, adhesion and tube formation of HUVEC induced by TNF-α were used to measured the antiangiogenenic activity of SKN. Moreover, the effect of SKN on the expression of angiogenic mediators, such as VEGF, VEGFR2, TNF-α, IL-1β, PDGF and TGF-β in sera and joint synovia of rats, and in TNF-α-induced MH7A/HUVEC cells were measured by immunohistochemistry,enzyme linked immunosorbent assay, Western blot and/or real-time PCR. Through the analysis of protein and mRNA levels of PI3K, Akt and PTEN, and the autophosphorylation of ERK1/2, JNK and p38 in joint synovia of rats and in TNF-α-induced HUVEC cells, the molecular mechanism of its inhibition was elucidated by using Western blot and/or real-time PCR.
RESULTS: SKN significantly reduced the arthritis score and arthritis incidence, and inhibited inflammation, pannus formation, cartilage and bone destruction of inflamed joints in CIA rats. Partially, SKN remarkably decreased the immature blood vessels in synovial membrane tissues of inflamed joints from CIA rats. It also suppressed in vivo angiogenesis in chick embryo and VEGF-induced microvessel sprout formation ex vivo. Meanwhile, SKN inhibited TNF-α-induced migration, invasion, adhesion and tube formation of HUVEC cells. Moreover, SKN significantly decreased the expression of angiogenic activators including VEGF, VEGFR2, TNF-α, IL-1β, PDGF and TGF-β in synovia of CIA rats and/or in MH7A/HUVEC cells. More interestingly, SKN downregulated PI3K and Akt, and simultaneously upregulated PTEN both at protein and mRNA levels in synovia tissues and/or in TNF-α-induced HUVEC cells. It also suppressed the phosphorylation and gene level of TNF-α-induced signaling molecules, as ERK1/2, JNK, and p38 in synovium and/or in TNF-α-induced HUVEC cells.
CONCLUSION: These findings indicate for the first time that SKN has the anti-angiogenic effect in RA in vivo, ex vivo and in vitro by interrupting the PI3K/AKT and MAPKs signaling pathways.


greenmedinfo--2020-06-06--Quercetin blocks ebola virus infection by counteracting the VP24 interferon inhibitory function

Ebola Virus ( EBOV ) is among the most devastating pathogens causing fatal hemorrhagic fever in humans .
The 2013-2016 epidemics resulted in over 11000 deaths , while another outbreak is currently ongoing .
Since there is no FDA-approved drug so far to fight EBOV infection , there is an urgent need to focus on drug discovery .
Considering the tight correlation between the high EBOV virulence and its ability to suppress the type-I Interferon ( IFN-I ) system , identifying molecules targeting viral protein VP24 , one of the main virulence determinants blocking IFN response , is a promising @ @ @ @ @ @ @ in the effort of finding novel EBOV inhibitors , a screening of a small set of flavonoids was performed , showing that Quercetin and Wogonin can suppress the VP24 effect on IFN-I signaling inhibition .
The mechanism of action of the most active compound , Quercetin , showing an ICvalue of 7.4μM , was characterized to significantly restore the IFN-I signaling cascade , blocked by VP24 , by directly interfering with the VP24 binding to karyopherin-α and thus restoring P-STAT1 nuclear transport and IFN genes transcription .
Quercetin significantly blocked viral infection , @ @ @ @ @ @ @ Overall , Quercetin is the first identified inhibitor of the EBOV VP24 anti-IFN function , representing a molecule interacting with a viral binding site that is very promising for further drug development aiming to block EBOV infection at the early steps .

Ebola Virus (EBOV) is among the most devastating pathogens causing fatal hemorrhagic fever in humans. The 2013-2016 epidemics resulted in over 11000 deaths, while another outbreak is currently ongoing. Since there is no FDA-approved drug so far to fight EBOV infection, there is an urgent need to focus on drug discovery. Considering the tight correlation between the high EBOV virulence and its ability to suppress the type-I Interferon (IFN-I) system, identifying molecules targeting viral protein VP24, one of the main virulence determinants blocking IFN response, is a promising novel anti-EBOV therapy approach. Hence, in the effort of finding novel EBOV inhibitors, a screening of a small set of flavonoids was performed, showing that Quercetin and Wogonin can suppress the VP24 effect on IFN-I signaling inhibition. The mechanism of action of the most active compound, Quercetin, showing an ICvalue of 7.4μM, was characterized to significantly restore the IFN-I signaling cascade, blocked by VP24, by directly interfering with the VP24 binding to karyopherin-α and thus restoring P-STAT1 nuclear transport and IFN genes transcription. Quercetin significantly blocked viral infection, specifically targeting EBOV VP24 anti-IFN-I function. Overall, Quercetin is the first identified inhibitor of the EBOV VP24 anti-IFN function, representing a molecule interacting with a viral binding site that is very promising for further drug development aiming to block EBOV infection at the early steps.


greenmedinfo--2020-06-06--Inhibitory effect of wogonin on human colorectal cancer cell SW480.

Wogonin is a main effective component of Scutellaria baicalensis , with a significant anti-cancer activity .
Recently , extensive studies focused on anti-cancer pharmacological effects of wogonin , but there were still a few studies on its molecular mechanism .
Therefore , the molecular targets of its anti-cancer activity were still unclear .
In this study , network pharmacology was applied to investigate the potential targets and molecular pathway of wogonin in inhibiting the growth of colorectal cancer .
It indicated that Wnt/β-catenin was a key pathway of wogonin on colorectal cancer .
Then , pharmacology and molecular mechanism studies @ @ @ @ @ @ @ .
Pharmacological results revealed that wogonin inhibited significantly the proliferation of SW480 ( P < 0.001 ) , with a concentration-dependent regularity in the range of 12.5-50μmol·L~ ( -1 ) .
Additionally , wogonin could induce G_1 phase blocking of SW480 cells .
Western blot was used to investigate the effect of wogonin on four characteristic proteins of Wnt/β-catenin pathway .
CTNNB1 ( β-catenin ) , BIRC5 ( survivin ) and GSK3 B were down-regulated significantly , while the expression level of BAX was up-regulated ( P < 0.05 ) .
In conclusion @ @ @ @ @ @ @ SW480 cells through Wnt/β-catenin pathway .
The feature protein CTNNB1 ( β-catenin ) , BIRC5 ( survivin ) , GSK3 B and BAX were identified as the potential targets .
This study illuminated the anti-cancer molecular mechanism and drug targets of wogonin , which provided a theoretical basis for anti-colon cancer drug discovery and clinical application .

Wogonin is a main effective component of Scutellaria baicalensis, with a significant anti-cancer activity. Recently, extensive studies focused on anti-cancer pharmacological effects of wogonin, but there were still a few studies on its molecular mechanism. Therefore, the molecular targets of its anti-cancer activity were still unclear. In this study, network pharmacology was applied to investigate the potential targets and molecular pathway of wogonin in inhibiting the growth of colorectal cancer. It indicated that Wnt/β-catenin was a key pathway of wogonin on colorectal cancer. Then, pharmacology and molecular mechanism studies were performed according to network pharmacological results. Pharmacological results revealed that wogonin inhibited significantly the proliferation of SW480(P<0.001), with a concentration-dependent regularity in the range of 12.5-50μmol·L~(-1). Additionally, wogonin could induce G_1 phase blocking of SW480 cells. Western blot was used to investigate the effect of wogonin on four characteristic proteins of Wnt/β-catenin pathway. CTNNB1(β-catenin), BIRC5(survivin) and GSK3 B were down-regulated significantly, while the expression level of BAX was up-regulated(P<0.05). In conclusion, wogonin could inhibit the proliferation of SW480 cells through Wnt/β-catenin pathway. The feature protein CTNNB1(β-catenin), BIRC5(survivin), GSK3 B and BAX were identified as the potential targets. This study illuminated the anti-cancer molecular mechanism and drug targets of wogonin, which provided a theoretical basis for anti-colon cancer drug discovery and clinical application.


greenmedinfo--2020-06-06--These results showed that cucurbitacin B may be a new agent that can support conventional treatment

These results showed that cucurbitacin B may be a new agent that can support conventional treatment in bladder cancer.

Alternative agents that will increase the effectiveness of cisplatin , which are widely used in the advanced stage and metastatic @ @ @ @ @ investigated .
In previous studies , Cucurbitacin B ( CuB ) , which is a @ @ @ @ @ family has been shown to inhibit the proliferation of tumor cells and create synergistic effects @ @ @ @ @ study , we investigated the synergistic effect of CuB with cisplatin for the first time @ @ @ @ @ findings showed that CuB treatment with cisplatin reduced cell proliferation , and reduced tumor development @ @ @ @ @ via PI3K/AKT/mTOR signaling pathway .
Our results showed that CuB may be a new agent @ @ @ @ @ in bladder cancer .
Our study is important in terms of enlightening new pathways and @ @ @ @ @ the treatment of bladder cancer .

Alternative agents that will increase the effectiveness of cisplatin, which are widely used in the advanced stage and metastatic bladder cancer, are being investigated. In previous studies, Cucurbitacin B (CuB), which is a natural compound from the Cucurbitaceae family has been shown to inhibit the proliferation of tumor cells and create synergistic effects with cisplatin. In this study, we investigated the synergistic effect of CuB with cisplatin for the first time in bladder cancerandmodels. Our findings showed that CuB treatment with cisplatin reduced cell proliferation, and reduced tumor development through activating apoptosis and autophagy via PI3K/AKT/mTOR signaling pathway. Our results showed that CuB may be a new agent that can support conventional treatment in bladder cancer. Our study is important in terms of enlightening new pathways and developing new treatment methods in the treatment of bladder cancer.


greenmedinfo--2020-06-06--Cucurbitacin B could significantly suppress releases of inflammatory cytokines and improve liver fib

Cucurbitacin B could significantly suppress releases of inflammatory cytokines and improve liver fibrosis induced by concanavalin A.

The present study investigated the improving effect of cucurbitacin B on liver fibrosis induced by concanavalin A in mice and explored its possible mechanism .
AST , ALT and TB were detected by kits .
ELISA was performed to detect the levels of IL 5 , IL 6 , IL 13 and TNF-α in serum .
HE staining and Masson 's trichrome staining were used to evaluate pathological changes .
Western blotting was performed to observe expression levels of sirtuin ( SIRT ) 1 , insulin-like growth factor binding protein-related protein 1 ( IGFBPrP1 ) and TGF β1 .
The @ @ @ @ @ @ @ .
Results showed that cucurbitacin B could effectively improve the abnormal liver function , inhibit liver fibrosis and suppress releases of inflammatory factors in mice induced by concanavalin A .
Furthermore , cucurbitacin B could down-regulate the expressions of TGF β1 and IGFBPrP1 , increasethe expression and activity of SIRT 1 .
Interestingly , when SIRT1 activity was inhibited by EX 527 , a selective inhibitor of SIRT 1 , the preventive effect of cucurbitacin B was significantly attenuated .
Taken together , the above results showed that cucurbitacin B could significantly suppress @ @ @ @ @ @ @ fibrosis induced by concanavalin A in mice , and those may be achieved through SIRT1/IGFBPrP1/TGF β1 axis .

The present study investigated the improving effect of cucurbitacin B on liver fibrosis induced by concanavalin A in mice and explored its possible mechanism. AST, ALT and TB were detected by kits. ELISA was performed to detect the levels of IL 5, IL 6, IL 13 and TNF-α in serum. HE staining and Masson's trichrome staining were used to evaluate pathological changes. Western blotting was performed to observe expression levels of sirtuin (SIRT) 1, insulin-like growth factor binding protein-related protein 1 (IGFBPrP1) and TGF β1. The activity of SIRT 1 also was detected. Results showed that cucurbitacin B could effectively improve the abnormal liver function, inhibit liver fibrosis and suppress releases of inflammatory factors in mice induced by concanavalin A. Furthermore, cucurbitacin B could down-regulate the expressions of TGF β1 and IGFBPrP1, increasethe expression and activity of SIRT 1. Interestingly, when SIRT1 activity was inhibited by EX 527, a selective inhibitor of SIRT 1, the preventive effect of cucurbitacin B was significantly attenuated. Taken together, the above results showed that cucurbitacin B could significantly suppress releases of inflammatory cytokines and improve liver fibrosis induced by concanavalin A in mice, and those may be achieved through SIRT1/IGFBPrP1/TGF β1 axis.


greenmedinfo--2020-06-06--Anthocyanins in red clover are the potential candidates to reduce inflammation and oxidative stress.

Red clover ( ) possesses various dietary compounds that improve human health .
However , the functions of anthocyanins in red clover remain unclear .
Here we examined anti-inflammatory and antioxidant effects of red clover extract ( RC ) and red clover anthocyanins fraction ( RCA ) using lipopolysaccharide ( LPS ) -treated RAW 264.7 macrophages and identified dietary compounds .
RC and RCA suppressed LPS-induced expression of genes such as tumor necrosis factor ( ) , interleukin ( ) , inducible nitric oxide synthase ( ) , monocyte chemoattractant protein ( ) 1 , and cyclooxygenase ( ) .
@ @ @ @ @ @ @ ) production also was prevented by both RC and RCA .
NADPH oxidase 1 ( NOX1 ) gene and phosphorylation of p47of NOX1 that were increased by LPS were inhibited in the cells treated with RCA .
LPS-stimulated nuclear factor erythroid 2-related factor 2 ( ) gene expression and nuclear translocation of nuclear factor kappa B ( NF-kB ) subunit p65 were suppressed together with reduced iNOS and COX2 proteins by RCA .
Additionally , 27 polyphenols and 7 anthocyanins from RC were identified and quantified .
In conclusion , RC , especially @ @ @ @ @ @ @ in vitro by regulating NF-κB and NRF2 signaling pathways , suggesting that anthocyanins in red clover are the potential candidates to reduce inflammation and oxidative stress .

Red clover () possesses various dietary compounds that improve human health. However, the functions of anthocyanins in red clover remain unclear. Here we examined anti-inflammatory and antioxidant effects of red clover extract (RC) and red clover anthocyanins fraction (RCA) using lipopolysaccharide (LPS)-treated RAW 264.7 macrophages and identified dietary compounds. RC and RCA suppressed LPS-induced expression of genes such as tumor necrosis factor (), interleukin (), inducible nitric oxide synthase (), monocyte chemoattractant protein ()1, and cyclooxygenase (). LPS-stimulated intracellular reactive oxygen species (ROS) production also was prevented by both RC and RCA. NADPH oxidase 1 (NOX1) gene and phosphorylation of p47of NOX1 that were increased by LPS were inhibited in the cells treated with RCA. LPS-stimulated nuclear factor erythroid 2-related factor 2 () gene expression and nuclear translocation of nuclear factor kappa B (NF-kB) subunit p65 were suppressed together with reduced iNOS and COX2 proteins by RCA. Additionally, 27 polyphenols and 7 anthocyanins from RC were identified and quantified. In conclusion, RC, especially RCA, exerted anti-inflammatory and anti-oxidative activities in vitro by regulating NF-κB and NRF2 signaling pathways, suggesting that anthocyanins in red clover are the potential candidates to reduce inflammation and oxidative stress.


greenmedinfo--2020-06-06--Red clover sprout prevents metabolic syndrome.

We examined the prevention effect of red clover ( Trifolium pratense L. ) sprout on metabolic syndrome using a high-carbohydrate @ @ @ @ @ diet ; WD ) -induced male C57BL/6J obese model mouse .
Red clover sprout-lyophilized powder @ @ @ @ @ mg/g dry-weight of formononetin as a major phenolic compound , as analyzed by high performance @ @ @ @ @ 0.3 % ( w/w ) RC in a WD ( WD+RC ) showed an anti-obesity @ @ @ @ @ in the obese model mice .
Additionally , fasting plasma glucose levels were significantly reduced @ @ @ @ @ Administration of 0.1 mg/kg formononetin reduced the postprandial blood glucose level , as assessed using @ @ @ @ @ .
However , no significant formononetin intake effect was observed on the plasma insulin level @ @ @ @ @ the formononetin contained in red clover sprout inhibitsα-glucosidase and thereby contributes to reducing the postprandial @ @ @ @ @ .

We examined the prevention effect of red clover (Trifolium pratense L.) sprout on metabolic syndrome using a high-carbohydrate and high-fat diet (Western diet; WD)-induced male C57BL/6J obese model mouse. Red clover sprout-lyophilized powder (RC) contained 3.5 mg/g dry-weight of formononetin as a major phenolic compound, as analyzed by high performance liquid chromatography. Supplementation of 0.3% (w/w) RC in a WD (WD+RC) showed an anti-obesity effect and ameliorated lipid metabolism in the obese model mice. Additionally, fasting plasma glucose levels were significantly reduced in the WD+RC group. Administration of 0.1 mg/kg formononetin reduced the postprandial blood glucose level, as assessed using the oral maltose tolerance test. However, no significant formononetin intake effect was observed on the plasma insulin level. These results suggest that the formononetin contained in red clover sprout inhibitsα-glucosidase and thereby contributes to reducing the postprandial blood glucose response in mice.


greenmedinfo--2020-06-06--Formononetin ameliorates myocardial ischemia/reperfusion injury.

Formononetin ( FN ) , a methoxy isoflavone abundant in many plants and herbs , has been evidently proven to possess multiple medicinal properties .
Our study aimed to clarify the impact of FN on myocardial ischemia/reperfusion ( I/R ) injury ( MIRI ) and the involved mechanism .
A rat model of MIRI was produced by ligation and loosening of the left anterior descending ( LAD ) branch of the coronary artery .
Rats received 10 and 30 mg/kg of FN when the reperfusion started .
At 24 h after surgery , cardiac function , infarct size , and @ @ @ @ @ @ @ inflammatory mediators were measured .
To mimic the inflammasome activation in cardiomyocytes , neonatal rat cardiomyocytes ( NRCMs ) were cultured and treated with lipopolysaccharide ( LPS ) plus nigericin .
Cell death and reactive oxygen species ( ROS ) were determined .
Myocardial expression and activation of the nucleotide-binding domain and leucine-rich repeat-containing protein 3 ( NLRP3 ) inflammasome in rats were examined by western blotting .
The level of thioredoxin interacting protein ( TXNIP ) -NLRP3 interaction was assessed .
FN notably attenuated cardiac dysfunction , infarct size , release of @ @ @ @ @ @ @ , IL-1β , and IL-6 .
FN alleviated LPS plus nigericin-induced injury and ROS increase in NRCMs .
Western blotting revealedthat FN suppressed the activation of NLRP3 inflammasome and TXNIP-NLRP3 interaction in rats .
These findings indicate that FN ameliorated MIRI in rats and inhibited the activation of the NLRP3 inflammasome , at least partially , attributable to suppression of the ROS-TXNIP-NLRP3 pathway .

Formononetin (FN), a methoxy isoflavone abundant in many plants and herbs, has been evidently proven to possess multiple medicinal properties. Our study aimed to clarify the impact of FN on myocardial ischemia/reperfusion (I/R) injury (MIRI) and the involved mechanism. A rat model of MIRI was produced by ligation and loosening of the left anterior descending (LAD) branch of the coronary artery. Rats received 10 and 30 mg/kg of FN when the reperfusion started. At 24 h after surgery, cardiac function, infarct size, and sera levels of the cardiac markers and inflammatory mediators were measured. To mimic the inflammasome activation in cardiomyocytes, neonatal rat cardiomyocytes (NRCMs) were cultured and treated with lipopolysaccharide (LPS) plus nigericin. Cell death and reactive oxygen species (ROS) were determined. Myocardial expression and activation of the nucleotide-binding domain and leucine-rich repeat-containing protein 3 (NLRP3) inflammasome in rats were examined by western blotting. The level of thioredoxin interacting protein (TXNIP)-NLRP3 interaction was assessed. FN notably attenuated cardiac dysfunction, infarct size, release of cardiac markers, and elevation of TNF-α, IL-1β, and IL-6. FN alleviated LPS plus nigericin-induced injury and ROS increase in NRCMs. Western blotting revealedthat FN suppressed the activation of NLRP3 inflammasome and TXNIP-NLRP3 interaction in rats. These findings indicate that FN ameliorated MIRI in rats and inhibited the activation of the NLRP3 inflammasome, at least partially, attributable to suppression of the ROS-TXNIP-NLRP3 pathway.


greenmedinfo--2020-06-06--Formononetin inhibits tumor growth by suppression of EGFR-Akt-Mcl-1 axis in non-small cell lung canc

Formononetin inhibits tumor growth by suppression of EGFR-Akt-Mcl-1 axis in non-small cell lung cancer.

BACKGROUND : Epidermal growth factor receptor ( EGFR ) activating mutations play crucial roles in the tumorigenesis of human non-small cell lung cancer ( NSCLC ) .
The mechanism regarding how EGFR signaling regulates myeloid cell leukemia sequence 1 ( Mcl-1 ) protein stability and ubiquitination remains undefined .
METHODS : MTS assay was used for natural product library screening .
The effect of formononetin ( Formo ) on NSCLC cells was determined by MTS assay and soft agar assay .
Molecular modeling was performed to analyze the potential different binding modes between Formo and EGFR WT or mutants .
@ @ @ @ @ @ @ of Formo on EGFR signaling were examined by immunoblot , in vitro kinase assay , in vitro pulldown and ATP competition assays , co-immunoprecipitation assay , ubiquitination analysis , in vivo xenograft model , and immunohistochemical staining .
RESULTS : Formo was identified as an EGFR inhibitor by a 98 commercially available natural product screening .
Formo suppresses WT and mutant EGFR kinases activity in vitro , ex vivo , and in vivo .
Molecular modeling indicates that Formo docks into the ATP-binding pocket of both WT and mutant EGFR .
Formo inhibits @ @ @ @ @ @ @ GSK3β and promotes Mcl-1 phosphorylation in NSCLC cells .
Treatment with Formo enhances the interaction between Mcl-1 and SCF , which eventually promotes Mcl-1 ubiquitination and degradation .
Depletion of either GSK3β or SCFcompromised Formo-induced Mcl-1 downregulation .
Finally , Formo inhibits the in vivo tumor growth in a xenograft mouse model .
CONCLUSION : This study highlights the importance of promoting ubiquitination-dependent Mcl-1 turnover might be an alternative strategy to enhance the anti-tumor efficacy of EGFR-TKI .

BACKGROUND: Epidermal growth factor receptor (EGFR) activating mutations play crucial roles in the tumorigenesis of human non-small cell lung cancer (NSCLC). The mechanism regarding how EGFR signaling regulates myeloid cell leukemia sequence 1 (Mcl-1) protein stability and ubiquitination remains undefined.
METHODS: MTS assay was used for natural product library screening. The effect of formononetin (Formo) on NSCLC cells was determined by MTS assay and soft agar assay. Molecular modeling was performed to analyze the potential different binding modes between Formo and EGFR WT or mutants. Mcl-1 protein level and the inhibitory effect of Formo on EGFR signaling were examined by immunoblot, in vitro kinase assay, in vitro pulldown and ATP competition assays, co-immunoprecipitation assay, ubiquitination analysis, in vivo xenograft model, and immunohistochemical staining.
RESULTS: Formo was identified as an EGFR inhibitor by a 98 commercially available natural product screening. Formo suppresses WT and mutant EGFR kinases activity in vitro, ex vivo, and in vivo. Molecular modeling indicates that Formo docks into the ATP-binding pocket of both WT and mutant EGFR. Formo inhibits EGFR-Akt signaling, which in turn activates GSK3β and promotes Mcl-1 phosphorylation in NSCLC cells. Treatment with Formo enhances the interaction between Mcl-1 and SCF, which eventually promotes Mcl-1 ubiquitination and degradation. Depletion of either GSK3β or SCFcompromised Formo-induced Mcl-1 downregulation. Finally, Formo inhibits the in vivo tumor growth in a xenograft mouse model.
CONCLUSION: This study highlights the importance of promoting ubiquitination-dependent Mcl-1 turnover might be an alternative strategy to enhance the anti-tumor efficacy of EGFR-TKI.


greenmedinfo--2020-06-06--Formononetin ameliorates diabetic neuropathy.

Diabetic neuropathy is commonly observed complication in more than 50 % of type 2 diabetic patients .
Histone deacetylases including SIRT1 have significant role to protect neuron from hyperglycemia induced damage .
Formononetin ( FMNT ) is known for its effect to control hyperglycemia and also activate SIRT1 .
In present study , we evaluated effect of FMNT as SIRT1 activator in type 2 diabetic neuropathy .
Type 2 diabetic neuropathy was induced in rats by modification of diet for 15 days using high fat diet and administration of streptozotocin ( 35 mg/kg/day , i. p. ) .
FMNT treatment @ @ @ @ @ @ @ diabetes .
Treatment was given for 16weeks at 10 , 20 and 40 mg/kg/day dose orally .
FMNT treatment-controlled hypoglycemia and reduced insulin resistance significantly in diabetic animals .
FMNT treatment reduced oxidative stress in sciatic nerve tissue .
FMNT treatment also reduced thermal hyperalgesia and mechanical allodynia significantly .
It improved conduction velocity in nerve and unregulated SIRT1 and NGF expression in sciatic nerve tissue .
Results of present study indicate that continuous administration of FMNT protected diabetic animals from hyperglycemia induced neuronal damage by controlling hyperglycemia and increasingSIRT1 and NGF expression @ @ @ @ @ @ @ can be an effective candidate for treatment of type 2 diabetic neuropathy .

Diabetic neuropathy is commonly observed complication in more than 50 % of type 2 diabetic patients. Histone deacetylases including SIRT1 have significant role to protect neuron from hyperglycemia induced damage. Formononetin (FMNT) is known for its effect to control hyperglycemia and also activate SIRT1. In present study, we evaluated effect of FMNT as SIRT1 activator in type 2 diabetic neuropathy. Type 2 diabetic neuropathy was induced in rats by modification of diet for 15 days using high fat diet and administration of streptozotocin (35 mg/kg/day, i. p.). FMNT treatment was initiated after confirmation of type 2 diabetes. Treatment was given for 16weeks at 10, 20 and 40 mg/kg/day dose orally. FMNT treatment-controlled hypoglycemia and reduced insulin resistance significantly in diabetic animals. FMNT treatment reduced oxidative stress in sciatic nerve tissue. FMNT treatment also reduced thermal hyperalgesia and mechanical allodynia significantly. It improved conduction velocity in nerve and unregulated SIRT1 and NGF expression in sciatic nerve tissue. Results of present study indicate that continuous administration of FMNT protected diabetic animals from hyperglycemia induced neuronal damage by controlling hyperglycemia and increasingSIRT1 and NGF expression in nerve tissue. Thus, FMNT can be an effective candidate for treatment of type 2 diabetic neuropathy.


greenmedinfo--2020-06-06--Formononetin significantly increased plant height, ear height, and grain yield 22% - 76% when no pho

Formononetin significantly increased plant height, ear height, and grain yield 22% - 76% when no phosphorus fertilizer was applied.

Abstract : The formononetin biostimulant may be an option for reducing P fertilization once it stimulates mycelial growth of arbuscular mycorrhizal fungi and increases plant ability to take up nutrients through the roots , especially phosphorus .
The objective of this study was to evaluate the effect of formononetin associated with phosphorus fertilization in maize .
Field experiments were conducted in a randomized block design with a 3× 4 factorial arrangement ( 0 , 50 or 70 , and 140 kg ha-1 P2O5 ; and formononetin application rates : 0 , 25 , 50 , and 100 g ha-1 ) @ @ @ @ @ @ @ 100 g ha-1 ) increased the mycorrhizal colonization rate up to 30 % in maize in the first four weeks after emergence when no P fertilizerwas applied , and to 17 % when 50 or 70 kg ha-1 of P2O5 were applied .
The application of 50 and 100 g ha-1 of formononetin significantly increased plant height , ear height , and grain yield ( 22 % - 76 % ) when no P fertilizer was applied .
The use of formononetin in the field stimulates mycorrhizal colonization , has a positive effect @ @ @ @ @ @ @ need for P fertilizer application in maize .
However , this effect was evident only at low P soil contents .

Abstract: The formononetin biostimulant may be an option for reducing P fertilization once it stimulates mycelial growth of arbuscular mycorrhizal fungi and increases plant ability to take up nutrients through the roots, especially phosphorus. The objective of this study was to evaluate the effect of formononetin associated with phosphorus fertilization in maize. Field experiments were conducted in a randomized block design with a 3× 4 factorial arrangement (0, 50 or 70, and 140 kg ha-1 P2O5; and formononetin application rates: 0, 25, 50, and 100 g ha-1), with four replications. Formononetin (100 g ha-1) increased the mycorrhizal colonization rate up to 30% in maize in the first four weeks after emergence when no P fertilizerwas applied, and to 17% when 50 or 70 kg ha-1 of P2O5 were applied. The application of 50 and 100 g ha-1 of formononetin significantly increased plant height, ear height, and grain yield (22% - 76%) when no P fertilizer was applied. The use of formononetin in the field stimulates mycorrhizal colonization, has a positive effect on maize yield, and reduces the need for P fertilizer application in maize. However, this effect was evident only at low P soil contents.


greenmedinfo--2020-06-06--Eight Reasons to Consume Bee Propolis

Eight Reasons to Consume Bee Propolis

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Before beginning any type of @ @ @ @ @ treatment regimen , it is advisable to seek the advice of a licensed healthcare professional @

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greenmedinfo--2020-06-07--NAC enhances the effect of selenium nanoparticles on cancer cytotoxicity by increasing the productio

NAC enhances the effect of selenium nanoparticles on cancer cytotoxicity by increasing the production of selenium-induced reactive oxygen species.

Peritoneal carcinomatosis ( PC ) has an extremely poor prognosis , which leads to a significantly decreased overall survival in patients with peritoneal implantation of cancer cells .
Administration of sodium selenite by intraperitoneal injection is highly effective in inhibiting PC .
Our previous study found that selenium nanoparticles ( SeNPs ) have higher redox activity and safety than sodium selenite .
In the present study , we examined the therapeutic effect of SeNPs on PC and elucidated the potential mechanism .
Our results revealed that intraperitoneal delivery of SeNPs to cancer cells in the peritoneal cavity of mice at @ @ @ @ @ @ @ the survival time of mice , even better than the optimal dose of cisplatin .
The underlying mechanism involved in SeNP-induced reactive oxygen species ( ROS ) production caused protein degradation and apoptotic response in cancer cells .
Interestingly , -acetyl-l-cysteine ( NAC ) , recognized as a ROS scavenger , without reducing the efficacy of SeNPs , enhanced ROS production and cytotoxicity .
The effect of NAC was associated with the following mechanisms : ( 1 ) the thiol groups in NAC can increase the biosynthesis of endogenous glutathione ( GSH ) @ @ @ @ @ @ @ ROS and cytotoxicity and ( 2 ) redox cycling of SeNPs was directly driven by thiol groups in NAC to produce ROS .
Moreover , NAC , without increasing the systematic toxicity of SeNPs , decreased SeNP-induced lethality in healthy mice .
Overall , we demonstrated that SeNPs exert a potential cytotoxicity effect by inducing ROS production in cancer cells ; NAC effectively heightens the property of SeNPsand .

Peritoneal carcinomatosis (PC) has an extremely poor prognosis, which leads to a significantly decreased overall survival in patients with peritoneal implantation of cancer cells. Administration of sodium selenite by intraperitoneal injection is highly effective in inhibiting PC. Our previous study found that selenium nanoparticles (SeNPs) have higher redox activity and safety than sodium selenite. In the present study, we examined the therapeutic effect of SeNPs on PC and elucidated the potential mechanism. Our results revealed that intraperitoneal delivery of SeNPs to cancer cells in the peritoneal cavity of mice at a tolerable dose was beneficial for prolonging the survival time of mice, even better than the optimal dose of cisplatin. The underlying mechanism involved in SeNP-induced reactive oxygen species (ROS) production caused protein degradation and apoptotic response in cancer cells. Interestingly,-acetyl-l-cysteine (NAC), recognized as a ROS scavenger, without reducing the efficacy of SeNPs, enhanced ROS production and cytotoxicity. The effect of NAC was associated with the following mechanisms: (1) the thiol groups in NAC can increase the biosynthesis of endogenous glutathione (GSH), thus increasing the production of SeNP-induced ROS and cytotoxicity and (2) redox cycling of SeNPs was directly driven by thiol groups in NAC to produce ROS. Moreover, NAC, without increasing the systematic toxicity of SeNPs, decreased SeNP-induced lethality in healthy mice. Overall, we demonstrated that SeNPs exert a potential cytotoxicity effect by inducing ROS production in cancer cells; NAC effectively heightens the property of SeNPsand.