greenmedinfo--2020-10-09--The protective effect of vitexinin septic encephalopathy by reducing leukocyte-endothelial adhesion

The protective effect of vitexinin septic encephalopathy by reducing leukocyte-endothelial adhesion and inflammatory response.

BACKGROUND : Despite advances in therapeutic strategies and critical care management , septic encephalopathy ( SE ) is still a leading cause of infection-associated death in intensive care units ( ICUs ) .
Vitexin , a flavonoids compound , exerts and anti-inflammatory effect through inhibition of proinflammatory cytokines and signaling pathways .
This study aimed to explore the anti-inflammatory effects of vitexin in SE and the underlying mechanisms .
METHODS : An SE-inducedC57BL/6 mouse model was established via cecal ligation and puncture ( CLP ) .
Western blotting was performed to evaluate the protein expression levels of Chemokine ( C-X-C @ @ @ @ @ @ @ , fractalkine ( CX3CL1 ) , intercellular adhesion molecule-1 ( ICAM-1 ) , vascular cell adhesion molecule-1 ( VCAM-1 ) , E-selectin , NF-κB p65 , p-NF-κB p65 , and tumor necrosis factor-α ( TNF-α ) .
Flow cytometry was used to detect the expressions ofCD11a/CD18 , CD11b/CD18 , ICAM-1 , and adherent leukocyte .
The expression of ICAM-1 was detected by immunohistochemistry .
An enzyme-linked immunosorbent assay was performed to evaluate theexpression of monocyte chemotactic protein-1 ( MCP-1 ) , Interleukin ( IL ) -6 , IL-8 , and IL-10 .
RESULTS @ @ @ @ @ @ @ that vitexin significantly downregulated the expression of brain endothelial chemokines CXCL1 and CX3CL1 in CLP mice , exerting a potential anti-inflammatory against SE .
Our data also showed that vitexin alleviated SE primarily by relying on reducing leukocyte-endothelial adhesion via the mediation of adhesion molecules .
Moreover , vitexin suppressed the expression of proinflammatory cytokines , such as MCP-1 , IL-6 , IL-8 , TNF-α , and NF-κB p65 , in the CLP mice , while the expression of the anti-inflammatory cytokine IL-10 was elevated .
CONCLUSIONS : Overall , our study demonstrated @ @ @ @ @ @ @ by reducing leukocyte-endothelial adhesion and inflammatory response .
These findings offer a molecular basis for the potential application of vitexin in the treatment of SE and other inflammatory-mediated and immunemediated disorders .

BACKGROUND: Despite advances in therapeutic strategies and critical care management, septic encephalopathy (SE) is still a leading cause of infection-associated death in intensive care units (ICUs). Vitexin, a flavonoids compound, exerts and anti-inflammatory effect through inhibition of proinflammatory cytokines and signaling pathways. This study aimed to explore the anti-inflammatory effects of vitexin in SE and the underlying mechanisms.
METHODS: An SE-inducedC57BL/6 mouse model was established via cecal ligation and puncture (CLP). Western blotting was performed to evaluate the protein expression levels of Chemokine (C-X-C motif) ligand 1 (CXCL1), fractalkine (CX3CL1), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, NF-κB p65, p-NF-κB p65, and tumor necrosis factor-α (TNF-α). Flow cytometry was used to detect the expressions ofCD11a/CD18, CD11b/CD18, ICAM-1, and adherent leukocyte. The expression of ICAM-1 was detected by immunohistochemistry. An enzyme-linked immunosorbent assay was performed to evaluate theexpression of monocyte chemotactic protein-1 (MCP-1), Interleukin (IL)-6, IL-8, and IL-10.
RESULTS: In this study, we found that vitexin significantly downregulated the expression of brain endothelial chemokines CXCL1 and CX3CL1 in CLP mice, exerting a potential anti-inflammatory against SE. Our data also showed that vitexin alleviated SE primarily by relying on reducing leukocyte-endothelial adhesion via the mediation of adhesion molecules. Moreover, vitexin suppressed the expression of proinflammatory cytokines, such as MCP-1, IL-6, IL-8, TNF-α, and NF-κB p65, in the CLP mice, while the expression of the anti-inflammatory cytokine IL-10 was elevated.
CONCLUSIONS: Overall, our study demonstrated the protective effect vitexin exerts in SE by reducing leukocyte-endothelial adhesion and inflammatory response. These findings offer a molecular basis for the potential application of vitexin in the treatment of SE and other inflammatory-mediated and immunemediated disorders.


greenmedinfo--2020-10-09--Antiviral properties of flavonoids and delivery strategies.

This review summarizes the latest advancements in phytochemicals as functional antiviral agents .
We focused on flavonoids , like apigenin @ @ @ @ @ rutin and naringenin , which have shown a wide range of biological effects including antiviral @ @ @ @ @ of their antiviral effects mainly consist in the inhibition of viral neuraminidase , proteases and @ @ @ @ @ as in the modification of various viral proteins .
Mixtures of different flavonoids or combination @ @ @ @ @ drugs provide an enhancement of their antiviral effects .
Recent strategies in drug delivery significantly @ @ @ @ @ bioavailability of flavonoids .
Frequent viral infections worldwide have led to the need for new @ @ @ @ @ can be identified among the various phytochemicals .
In this light , screening the antiviral @ @ @ @ @ flavonoids would be advantageous in order to prevent viral infections and improve current antiviral therapies @

This review summarizes the latest advancements in phytochemicals as functional antiviral agents. We focused on flavonoids, like apigenin, vitexin, quercetin, rutin and naringenin, which have shown a wide range of biological effects including antiviral activities. The molecular mechanisms of their antiviral effects mainly consist in the inhibition of viral neuraminidase, proteases and DNA/RNA polymerases, as well as in the modification of various viral proteins. Mixtures of different flavonoids or combination of flavonoids with antiviral synthetic drugs provide an enhancement of their antiviral effects. Recent strategies in drug delivery significantly contribute to overcoming the low bioavailability of flavonoids. Frequent viral infections worldwide have led to the need for new effective antiviral agents, which can be identified among the various phytochemicals. In this light, screening the antiviral activities of a cocktail of flavonoids would be advantageous in order to prevent viral infections and improve current antiviral therapies.


greenmedinfo--2020-10-09--Vitexin possesses anticonvulsant and anxiolytic-like effects in murine animal models.

Different types of epilepsy and forms of pathological anxiety have been described as significant neurological disorders that may exist as comorbidities .
Some of those disorders share the association of affected limbic areas/neuropathological triggers as well as the use of drugs for their clinical management .
The aim of this work was to investigate the anticonvulsant and anxiolytic properties of the vitexin ( apigenin-8-C-glucoside ) , since this compound is a flavonoid usually found as one of the major constituents in several medicinal plants claimed as anxiolytics and/or anticonvulsants .
This investigation was performed by the use of a series @ @ @ @ @ @ @ induced-seizures and of anxiety-related tests ( open-field , elevated plus-maze , and light-dark box tests ) .
Here , we show that the systemic administration of vitexin ( 1.25 ; 2.5 and 5 mg/kg ; i.p . )
exhibited selective protection against chemically-induced seizures .
Vitexin did not block seizures evoked by glutamate receptors agonists ( NMDA and kainic acid ) , and it did not interfere with the latencies for these seizures .
Conversely , the same treatments protected the animals in a dose-dependent manner against the seizures evoked by the Gabaergic @ @ @ @ @ @ @ latency time for the first seizure on non-protected animals .
The higher dose of vitexin protected 100 % of animals against the tonic-clonic seizures triggered by GABA antagonists .
The results from open-field , elevated plus-maze , and light-dark box tests indicated the anxiolytic properties of vitexin at similar range of doses described for the anticonvulsant action screening .
Furthermore , these results pointed that vitexin did not cause sedation or locomotor impairment on animals .
The selective action of vitexin against picrotoxin and PTZ may reinforce the hypothesis by which this compound @ @ @ @ @ @ @ neurotransmission and/or related pathways .
This could be useful to explain the dual activity of vitexin as anticonvulsant and anxiolytic , and highlight the pharmacological interest on this promising flavonoid .

Different types of epilepsy and forms of pathological anxiety have been described as significant neurological disorders that may exist as comorbidities. Some of those disorders share the association of affected limbic areas/neuropathological triggers as well as the use of drugs for their clinical management. The aim of this work was to investigate the anticonvulsant and anxiolytic properties of the vitexin (apigenin-8-C-glucoside), since this compound is a flavonoid usually found as one of the major constituents in several medicinal plants claimed as anxiolytics and/or anticonvulsants. This investigation was performed by the use of a series of classical murine animal models of chemically induced-seizures and of anxiety-related tests (open-field, elevated plus-maze, and light-dark box tests). Here, we show that the systemic administration of vitexin (1.25; 2.5 and 5 mg/kg; i.p.) exhibited selective protection against chemically-induced seizures. Vitexin did not block seizures evoked by glutamate receptors agonists (NMDA and kainic acid), and it did not interfere with the latencies for these seizures. Conversely, the same treatments protected the animals in a dose-dependent manner against the seizures evoked by the Gabaergic antagonists picrotoxin and PTZ and rise the latency time for the first seizure on non-protected animals. The higher dose of vitexin protected 100% of animals against the tonic-clonic seizures triggered by GABA antagonists. The results from open-field, elevated plus-maze, and light-dark box tests indicated the anxiolytic properties of vitexin at similar range of doses described for the anticonvulsant action screening. Furthermore, these results pointed that vitexin did not cause sedation or locomotor impairment on animals. The selective action of vitexin against picrotoxin and PTZ may reinforce the hypothesis by which this compound acts mainly by the modulation of GABAergic neurotransmission and/or related pathways. This could be useful to explain the dual activity of vitexin as anticonvulsant and anxiolytic, and highlight the pharmacological interest on this promising flavonoid.


greenmedinfo--2020-10-09--Vitexin suppresses renal cell carcinoma by regulating mTOR pathways.

Background : Renal cell carcinoma ( RCC ) is one of the most common malignant tumors in the world .
Vitexin ( apigenin-8-C-D-glucopyranoside ) , a bioactive compound isolated from a variety of plants , has multiple protective effects on human health .
The purpose of this study was to investigate the role of vitexin in RC and the related molecular mechanism .
Methods : Proliferation was tested with Cell Counting Kit-8 and Edu staining .
Apoptosis was studied with flow cytometry .
Immunofluorescent was applied to show LC3 spots .
BALB/c nude mice bearing ACHN cells were established and @ @ @ @ @ @ @ in vivo effects of vitexin .
All the effects and possible signaling pathways involved were validated with western blotting .
Results : Seventy micromole of vitexin started to show significant effect on the growth of normal renal tubular epithelial cells ( HK-2 ) , so 0 , 10 , 20 and 40µM of vitexin were used in later experiments .
Vitexin inhibited growth and induced apoptosis of ACHN and OS-RC-2 cells in a dose-dependent manner , and promoted excessive autophagy by reducing p62 levels and increasing Beclin1 and LC3II levels .
Western blotting @ @ @ @ @ @ @ levels of Adenosine Monophosphate Activated Protein Kinase ( AMPK ) and c-Jun N-terminal kinase ( JNK ) in ACHN and OS-RC-2 cells , while decreasing the phosphorylation levels of phosphatidylinositol 3-kinase/activates protein kinase/mammalian target of rapamycin ( PI3K/AKT/mTOR ) .
In BALB/c nude mice bearing ACHN cells , vitexin inhibited tumor growth , reduced Ki67 and increased caspase-3 levels in the tumor tissues .
Conclusions : The results indicated that the tumor suppressive role of vitexin in ACHN and OS-RC-2 cells involved AMPK/mTOR , PI3K/AKT/mTOR , and JNK pathways .
Therefore , vitexin @ @ @ @ @ @ @ treatment of RCC .

Background: Renal cell carcinoma (RCC) is one of the most common malignant tumors in the world. Vitexin (apigenin-8-C-D-glucopyranoside), a bioactive compound isolated from a variety of plants, has multiple protective effects on human health. The purpose of this study was to investigate the role of vitexin in RC and the related molecular mechanism.
Methods: Proliferation was tested with Cell Counting Kit-8 and Edu staining. Apoptosis was studied with flow cytometry. Immunofluorescent was applied to show LC3 spots. BALB/c nude mice bearing ACHN cells were established and immunohistochemical staining was applied to validate the in vivo effects of vitexin. All the effects and possible signaling pathways involved were validated with western blotting.
Results: Seventy micromole of vitexin started to show significant effect on the growth of normal renal tubular epithelial cells (HK-2), so 0, 10, 20 and 40µM of vitexin were used in later experiments. Vitexin inhibited growth and induced apoptosis of ACHN and OS-RC-2 cells in a dose-dependent manner, and promoted excessive autophagy by reducing p62 levels and increasing Beclin1 and LC3II levels. Western blotting revealed that vitexin significantly increased the phosphorylation levels of Adenosine Monophosphate Activated Protein Kinase (AMPK) and c-Jun N-terminal kinase (JNK) in ACHN and OS-RC-2 cells, while decreasing the phosphorylation levels of phosphatidylinositol 3-kinase/activates protein kinase/mammalian target of rapamycin (PI3K/AKT/mTOR). In BALB/c nude mice bearing ACHN cells, vitexin inhibited tumor growth, reduced Ki67 and increased caspase-3 levels in the tumor tissues.
Conclusions: The results indicated that the tumor suppressive role of vitexin in ACHN and OS-RC-2 cells involved AMPK/mTOR, PI3K/AKT/mTOR, and JNK pathways. Therefore, vitexin may be a promising drug for the treatment of RCC.


greenmedinfo--2020-10-09--Vitexin restores pancreatic β-cell function and insulin signaling through Nrf2 and NF-κB signaling p

Vitexin restores pancreatic β-cell function and insulin signaling through Nrf2 and NF-κB signaling pathways.

Chronic hyperglycemia induces pancreaticβ-cell dysfunction through several cell signaling pathways .
The β-cell loss by apoptosis appears to play a crucial role in the onset and progression of diabetes .
This study was aimed to investigate the role of vitexin against high glucose-induced β-cells apoptosis and the underlying mechanisms involved therein .
INS-1 cells were pretreated with vitexin ( 20 and 40 μM ) followed by high glucose ( 33 mM ) exposure and the cytotoxicity was assessed by MTT .
The effect of vitexin on nuclear factor erythroid 2-related factor 2 ( Nrf2 ) and NF-kB signaling molecules have @ @ @ @ @ @ @ was assessed .
Vitexin protected the cells against high glucose toxicity in a concentration-dependent manner .
Vitexin improved insulin signaling as analyzed by the levels of functional proteins in the insulin pathways , viz.
, insulin receptor ( IR ) , insulin receptor substrate ( IRS ) -1 and IRS-2 , glucose transporter -2 , and glucose-stimulated insulin secretion .
Vitexin improved the high glucose-induced nuclear transcription factor system by suppressing Rel A , Rel B , P50/p105 , and IκB expression resulting in decreased cell apoptosis , further confirmed by the reduction @ @ @ @ @ @ @ .
Our data suggest that vitexin improves insulin secretion by activating key proteins , including NF-κB and Nrf2 in β-cells regulating apoptosis .

Chronic hyperglycemia induces pancreaticβ-cell dysfunction through several cell signaling pathways. The β-cell loss by apoptosis appears to play a crucial role in the onset and progression of diabetes. This study was aimed to investigate the role of vitexin against high glucose-induced β-cells apoptosis and the underlying mechanisms involved therein. INS-1 cells were pretreated with vitexin (20 and 40 μM) followed by high glucose (33 mM) exposure and the cytotoxicity was assessed by MTT. The effect of vitexin on nuclear factor erythroid 2-related factor 2 (Nrf2) and NF-kB signaling molecules have been studied. Vitexin-mediated stimulation of Nrf2 was assessed. Vitexin protected the cells against high glucose toxicity in a concentration-dependent manner. Vitexin improved insulin signaling as analyzed by the levels of functional proteins in the insulin pathways, viz., insulin receptor (IR), insulin receptor substrate (IRS)-1 and IRS-2, glucose transporter -2, and glucose-stimulated insulin secretion. Vitexin improved the high glucose-induced nuclear transcription factor system by suppressing Rel A, Rel B, P50/p105, and IκB expression resulting in decreased cell apoptosis, further confirmed by the reduction in the percentage of Annexin-V positive cells. Our data suggest that vitexin improves insulin secretion by activating key proteins, including NF-κB and Nrf2 in β-cells regulating apoptosis.


greenmedinfo--2020-10-09--The results show that vitexin acts as a neuroprotective agent.

Alzheimer 's disease ( AD ) accounts for an estimated 60 % to 80 % of all dementia cases .
@ @ @ @ @ at evaluating the neuroprotective efficacy of vitexin , an apigenin flavone glycoside using transgenic Caenorhabditis @ @ @ @ @ of AD .
The neuroprotective effect of vitexin was determined using physiological assays , quantitative @ @ @ @ @ Western blotting .
The results of survival and paralysis assay indicate that vitexin ( 200 @ @ @ @ @ lifespan of the nematodes .
Vitexin-treated nematodes showed a significant reduction in the expression of @ @ @ @ @ ace-2 genes when compared to control .
Further , vitexin significantly upregulated the expression of @ @ @ @ @ increased the lifespanof the nematodes .
Vitexin was also found to modulate the unfolded protein @ @ @ @ @ pek-1 , ire-1 , and xbp-1 ) and suppress the expression of Aβ .
Overall @ @ @ @ @ vitexin acts as a neuroprotective agent and protects transgenic C. elegans strains from Aβ proteotoxicity @

Alzheimer's disease (AD) accounts for an estimated 60% to 80% of all dementia cases. The present study is aimed at evaluating the neuroprotective efficacy of vitexin, an apigenin flavone glycoside using transgenic Caenorhabditis elegans strain (CL2006) of AD. The neuroprotective effect of vitexin was determined using physiological assays, quantitative polymerase chain reaction, and Western blotting. The results of survival and paralysis assay indicate that vitexin (200 μM) significantly extended the lifespan of the nematodes. Vitexin-treated nematodes showed a significant reduction in the expression of Aβ, ace-1, and ace-2 genes when compared to control. Further, vitexin significantly upregulated the expression of acr-8 and dnj-14, and increased the lifespanof the nematodes. Vitexin was also found to modulate the unfolded protein response genes (hsp-4, pek-1, ire-1, and xbp-1) and suppress the expression of Aβ. Overall, the results show that vitexin acts as a neuroprotective agent and protects transgenic C. elegans strains from Aβ proteotoxicity.


greenmedinfo--2020-10-09--Apigenin mitigates iintervertebral disc degeneration.

BACKGROUND Intervertebral disc degeneration ( IDD ) is a common spinal disease affected by environmental and lifestyle factors that has a significant pathological cascade toward inflammation and partial disability .
There is currently no therapy that can completely restore the cellular derangement in IDD .
Hence , in this study , the therapeutic effects of apigenin on IDD were evaluated using a rat model .
MATERIAL AND METHODS Animals were separated into 4 groups : Grp 1 , sham-operated control ; Grp 2 , IDD-induced ; Grp 3 , IDD-induced+apigenin treatment ; Grp 4 , apigenin control .
The animals @ @ @ @ @ @ @ , and prostaglandin signaling .
RESULTS There were significant increases in the inflammatory cytokines IL-1ß , IL-2 , IL-6 , IL-8 and IL-17 in the IDD-induced group compared to that of control .
Moreover , with increased levels of MMP-3 , MMP-9 , ADAMTS-4 , and syndecan-4 , the levels of TNF-alpha , IFN-γ , prostaglandin E2 , and cyclooxygenase 2 were directly increased in the IDD-induced group .
In contrast , apigenin protectively restored levels of prostaglandin signaling and reduced cytokine levels .
In addition , nucleus pulposus cells cultured separately with @ @ @ @ @ @ @ the levels of extracellular matrix proteins .
CONCLUSIONS The reduction of cytokine levels under apigenin treatment suggests it may be a promising target drug therapy for the treatment of deleterious IDD conditions .

BACKGROUND Intervertebral disc degeneration (IDD) is a common spinal disease affected by environmental and lifestyle factors that has a significant pathological cascade toward inflammation and partial disability. There is currently no therapy that can completely restore the cellular derangement in IDD. Hence, in this study, the therapeutic effects of apigenin on IDD were evaluated using a rat model. MATERIAL AND METHODS Animals were separated into 4 groups: Grp 1, sham-operated control; Grp 2, IDD-induced; Grp 3, IDD-induced+apigenin treatment; Grp 4, apigenin control. The animals were assessed for inflammatory cytokines, chemokines, and prostaglandin signaling. RESULTS There were significant increases in the inflammatory cytokines IL-1ß, IL-2, IL-6, IL-8 and IL-17 in the IDD-induced group compared to that of control. Moreover, with increased levels of MMP-3, MMP-9, ADAMTS-4, and syndecan-4, the levels of TNF-alpha, IFN-γ, prostaglandin E2, and cyclooxygenase 2 were directly increased in the IDD-induced group. In contrast, apigenin protectively restored levels of prostaglandin signaling and reduced cytokine levels. In addition, nucleus pulposus cells cultured separately with either TNF-alpha inhibitor or apigenin significantly attenuated the levels of extracellular matrix proteins. CONCLUSIONS The reduction of cytokine levels under apigenin treatment suggests it may be a promising target drug therapy for the treatment of deleterious IDD conditions.


greenmedinfo--2020-10-09--Apigenin and hesperidin downregulate DNA repair genes in MCF-7 breast cancer cells and augment doxor

Apigenin and hesperidin downregulate DNA repair genes in MCF-7 breast cancer cells and augment doxorubicin toxicity.

A number of studies have confirmed anti-tumor activity of flavonoids and their ability to enhance the effectiveness of classical anticancer drugs .
The mechanism of this phenomenon is difficult to explain because of the ambivalent nature of these compounds .
Many therapeutic properties of these compounds are attributed to their antioxidant activity ; however , it is known that they can act as oxidants .
The aim of this study was to assess the influence of apigenin and hesperidin on MCF-7 breast cancer cells with doxorubicin .
The cytotoxic effect was determined using an MTT test and cell cycle analysis @ @ @ @ @ @ @ , reduced glutathione levels , as well as the DNA oxidative damage and the double strand breaks , were evaluated .
Additionally , mRNA expression of genes related to DNA repair was assessed .
It was demonstrated that flavonoids intensified the cytotoxic effect of doxorubicin despite flavonoids reduced oxidative damage caused by the drug .
At the same time , the number of double strand breaks significantly increased and expression of tested genes was downregulated .
In conclusion , both apigenin and hesperidin enhance the cytotoxic effects of doxorubicin on breast cancer cells @ @ @ @ @ @ @ oxidative stress but is accompanied by disorders of DNA damage response mechanisms .

A number of studies have confirmed anti-tumor activity of flavonoids and their ability to enhance the effectiveness of classical anticancer drugs. The mechanism of this phenomenon is difficult to explain because of the ambivalent nature of these compounds. Many therapeutic properties of these compounds are attributed to their antioxidant activity; however, it is known that they can act as oxidants. The aim of this study was to assess the influence of apigenin and hesperidin on MCF-7 breast cancer cells with doxorubicin. The cytotoxic effect was determined using an MTT test and cell cycle analysis. To evaluate the possible interaction mechanism, reduced glutathione levels, as well as the DNA oxidative damage and the double strand breaks, were evaluated. Additionally, mRNA expression of genes related to DNA repair was assessed. It was demonstrated that flavonoids intensified the cytotoxic effect of doxorubicin despite flavonoids reduced oxidative damage caused by the drug. At the same time, the number of double strand breaks significantly increased and expression of tested genes was downregulated. In conclusion, both apigenin and hesperidin enhance the cytotoxic effects of doxorubicin on breast cancer cells, and this phenomenon occurs regardless of oxidative stress but is accompanied by disorders of DNA damage response mechanisms.


greenmedinfo--2020-10-09--Neuroprotective effect of apigenin against cerebral ischemia/reperfusion injury.

OBJECTIVE : The therapeutic efficacy of apigenin in PC12 cells and rats remains uncertain .
The aim of this study was to investigate the neuroprotective effects of apigenin against cerebral ischemia/reperfusion injury , bothand .
METHODS : We first treated PC12 cells with cobalt chloride ( CoCl ) to create a model of oxidative stress injury .
Cell viability was then determined using a multifunctional microplate reader .
In addition , reactive oxygen species ( ROS ) levels , apoptosis , and mitochondrial membrane potentials ( MMPs ) were examined using high-content cytometer analysis .
The efficacy of apigenin treatment @ @ @ @ @ @ @ cerebral artery occlusion ( MCAO ) model using TTC staining and neurological deficit scores .
RESULTS : The half-inhibitory concentration of CoClwas 1.2 mM .
Pretreatment with 10µg ⋅ mLapigenin significantly enhanced cell viability , reduced ROS levels , alleviated apoptosis , and improved MMP in PC12 cells with CoCl-induced injury .
In addition , apigenin treatmentsignificantly improved neurological deficit scores and reduced infarct areas in MCAO rats .
These results suggest that the neuroprotective mechanisms of apigenin may be related to mitochondrial activation .
CONCLUSIONS : Apigenin had excellent neuroprotective effects for @ @ @ @ @ @

OBJECTIVE: The therapeutic efficacy of apigenin in PC12 cells and rats remains uncertain. The aim of this study was to investigate the neuroprotective effects of apigenin against cerebral ischemia/reperfusion injury, bothand.
METHODS: We first treated PC12 cells with cobalt chloride (CoCl) to create a model of oxidative stress injury. Cell viability was then determined using a multifunctional microplate reader. In addition, reactive oxygen species (ROS) levels, apoptosis, and mitochondrial membrane potentials (MMPs) were examined using high-content cytometer analysis. The efficacy of apigenin treatment was also analyzed in a rat middle cerebral artery occlusion (MCAO) model using TTC staining and neurological deficit scores.
RESULTS: The half-inhibitory concentration of CoClwas 1.2 mM. Pretreatment with 10µg ⋅ mLapigenin significantly enhanced cell viability, reduced ROS levels, alleviated apoptosis, and improved MMP in PC12 cells with CoCl-induced injury. In addition, apigenin treatmentsignificantly improved neurological deficit scores and reduced infarct areas in MCAO rats. These results suggest that the neuroprotective mechanisms of apigenin may be related to mitochondrial activation.
CONCLUSIONS: Apigenin had excellent neuroprotective effects for the treatment of cerebral ischemia/reperfusion injuryand


greenmedinfo--2020-10-09--Apigenin by targeting hnRNPA2 sensitizes triple-negative breast cancer spheroids to doxorubicin-indu

Apigenin by targeting hnRNPA2 sensitizes triple-negative breast cancer spheroids to doxorubicin-induced apoptosis.

Acquired resistance to doxorubicin is a major hurdle in triple-negative breast cancer ( TNBC ) therapy , emphasizing the need to identify improved strategies .
Apigenin and other structurally related dietary flavones are emerging as potential chemo-sensitizers , but their effect on three-dimensional TNBC spheroid models has not been investigated .
We previously showed that apigenin associates with heterogeneous ribonuclear protein A2/B1 ( hnRNPA2 ) , an RNA-binding protein involved in mRNA and co-transcriptional regulation .
However , the role of hnRNPA2 in apigenin chemo-sensitizing activity has not been investigated .
Here , we show that apigenin induced apoptosis in @ @ @ @ @ @ @ owing to higher cellular uptake .
Moreover , apigenin inhibited the growth of TNBC patient-derived organoids at an in vivo achievable concentration .
Apigenin sensitized spheroids to doxorubicin-induced DNA damage , triggering caspase-9-mediated intrinsic apoptotic pathway and caspase-3 activity .
Silencing of hnRNPA2 decreased apigenin-induced sensitization to doxorubicin in spheroids by diminishing apoptosis and partly abrogated apigenin-mediated reduction of ABCC4 and ABCG2 efflux transporters .
Together these findings provide novel insights into the critical role of hnRNPA2 in mediating apigenin-induced sensitization of TNBC spheroids to doxorubicin by increasing the expression of efflux transporters @ @ @ @ @ @ @ using dietary compounds as a chemotherapeutic adjuvant .

Acquired resistance to doxorubicin is a major hurdle in triple-negative breast cancer (TNBC) therapy, emphasizing the need to identify improved strategies. Apigenin and other structurally related dietary flavones are emerging as potential chemo-sensitizers, but their effect on three-dimensional TNBC spheroid models has not been investigated. We previously showed that apigenin associates with heterogeneous ribonuclear protein A2/B1 (hnRNPA2), an RNA-binding protein involved in mRNA and co-transcriptional regulation. However, the role of hnRNPA2 in apigenin chemo-sensitizing activity has not been investigated. Here, we show that apigenin induced apoptosis in TNBC spheroids more effectively than apigenin-glycoside, owing to higher cellular uptake. Moreover, apigenin inhibited the growth of TNBC patient-derived organoids at an in vivo achievable concentration. Apigenin sensitized spheroids to doxorubicin-induced DNA damage, triggering caspase-9-mediated intrinsic apoptotic pathway and caspase-3 activity. Silencing of hnRNPA2 decreased apigenin-induced sensitization to doxorubicin in spheroids by diminishing apoptosis and partly abrogated apigenin-mediated reduction of ABCC4 and ABCG2 efflux transporters. Together these findings provide novel insights into the critical role of hnRNPA2 in mediating apigenin-induced sensitization of TNBC spheroids to doxorubicin by increasing the expression of efflux transporters and apoptosis, underscoring the relevance of using dietary compounds as a chemotherapeutic adjuvant.


greenmedinfo--2020-10-09--Effect of apigenin on surface-associated characteristics and adherence of Streptococcus mutans.

Apigenin is a type of flavonols that exhibits anti-caries properties .
Bacterial adherence is the initial step in the forming @ @ @ @ @ leads to caries .
Bacterial adherence is affected by surface characteristics , including hydrophobicity and @ @ @ @ @ the effect of apigenin on surface characteristics of cariogenic bacteria has not been reported .
@ @ @ @ @ effects of apigenin on adherence and biofilm formation of Streptococcus mutans UA159 .
Hydrophobicity and @ @ @ @ @ gbpC gene expressions , and cytotoxicity on human dental pulp cells were also determined .
@ @ @ @ @ and biofilm formation of S. mutans .
Hydrophobicity decreased , whereas the aggregation rate was @ @ @ @ @ control .
Apigenin significantly suppressed pac and gbpC gene expressions .
Apigenin exhibited acceptable biocompatibility @ @ @ @ @ apigeinin may affect adherence and biofilm formation by altering the surface properties of S. mutans @ @ @ @ @ hDPCs .

Apigenin is a type of flavonols that exhibits anti-caries properties. Bacterial adherence is the initial step in the forming of a stable biofilm that leads to caries. Bacterial adherence is affected by surface characteristics, including hydrophobicity and bacterial aggregation. However, the effect of apigenin on surface characteristics of cariogenic bacteria has not been reported. We aimed to examine the effects of apigenin on adherence and biofilm formation of Streptococcus mutans UA159. Hydrophobicity and bacterial aggregation, pac and gbpC gene expressions, and cytotoxicity on human dental pulp cells were also determined. Apigenin significantly inhibited the adherence and biofilm formation of S. mutans. Hydrophobicity decreased, whereas the aggregation rate was significantly increased compared with the control. Apigenin significantly suppressed pac and gbpC gene expressions. Apigenin exhibited acceptable biocompatibility on hDPCs. Thus, apigeinin may affect adherence and biofilm formation by altering the surface properties of S. mutans without obvious adverse effect on hDPCs.


greenmedinfo--2020-10-09--Niacinamide mitigates SASP-related inflammation induced by environmental stressors in human epiderma

Niacinamide mitigates SASP-related inflammation induced by environmental stressors in human epidermal keratinocytes and skin.

OBJECTIVE : To evaluate whether niacinamide ( Nam ) can mitigate production of inflammatory and senescence-related biomarkers induced by environmental stressors .
METHODS : Human epidermal keratinocytes were exposed to UVB , urban dust , diesel exhaust and cigarette smoke extract and treated with Nam or vehicle control .
Full thickness 3-D skin organotypic models were exposed to a combination of UVB and PMand treated with Nam or vehicle control .
Quantitation of the SASP-related inflammatory mediators PGE , IL-6 and IL-8 was performed on cultured media .
UVB-exposed keratinocytes treated with and without Nam were immunostained for the senescence @ @ @ @ @ @ @ Transcriptomics profiling of cigarette smoke extract effects on keratinocytes was performed .
A double-blind , placebo-controlled clinical was conducted on 40 female panellists that were pretreated on back sites for two weeks with 5 % Nam or vehicle and then exposed to 1.5 minimal erythemal dose ( MED ) solar-simulated radiation ( SSR ) .
Treated sites were compared with non-treated exposed sites for erythema and the skin surface IL-1αRA/IL-1α inflammatory biomarkers .
RESULTS : Ultraviolet B induced synthesis of PGE , IL-8 and IL-6 and reduced LmnB1 levels in keratinocytes .
Urban @ @ @ @ @ @ @ of IL-8 whereas cigarette smoke extract only stimulated levels of PGE .
In all exposures , treatment with Nam significantly mitigated synthesis of the inflammatory mediators and restored levels of UVB-reduced LmnB1 .
In the 3D skin equivalent model , Nam reduced IL-8 levels stimulated by a combination of topical PMand UV exposure .
In a UV challenge clinical , pretreatment with 5 % Nam reduced erythema and skin surface IL-1αRA/IL-1α inflammatory biomarkers that were induced by SSR .
CONCLUSION : Since it is known that Nam has anti-inflammatory properties , we tested @ @ @ @ @ @ @ and senescence-associated secretory phenotype ( SASP ) biomarkers .
We show Nam can reduce PGE , IL-6 and IL-8 levels induced by environmental stressors .
Additionally , in vivo pretreatment with Nam can reduce UV-induced erythema and skin surface inflammatory biomarkers .
These findings add to the body of evidence that Nam can mitigate the skin 's inflammatory response elicited by environmental stressors .
This supports Nam can potentially inhibit senescence and premature ageing and thereby maintain skin 's functionality and appearance .

OBJECTIVE: To evaluate whether niacinamide (Nam) can mitigate production of inflammatory and senescence-related biomarkers induced by environmental stressors.
METHODS: Human epidermal keratinocytes were exposed to UVB, urban dust, diesel exhaust and cigarette smoke extract and treated with Nam or vehicle control. Full thickness 3-D skin organotypic models were exposed to a combination of UVB and PMand treated with Nam or vehicle control. Quantitation of the SASP-related inflammatory mediators PGE, IL-6 and IL-8 was performed on cultured media. UVB-exposed keratinocytes treated with and without Nam were immunostained for the senescence biomarker Lamin B1 (LmnB1). Transcriptomics profiling of cigarette smoke extract effects on keratinocytes was performed. A double-blind, placebo-controlled clinical was conducted on 40 female panellists that were pretreated on back sites for two weeks with 5% Nam or vehicle and then exposed to 1.5 minimal erythemal dose (MED) solar-simulated radiation (SSR). Treated sites were compared with non-treated exposed sites for erythema and the skin surface IL-1αRA/IL-1α inflammatory biomarkers.
RESULTS: Ultraviolet B induced synthesis of PGE, IL-8 and IL-6 and reduced LmnB1 levels in keratinocytes. Urban dust and diesel exhaust only stimulated synthesis of IL-8 whereas cigarette smoke extract only stimulated levels of PGE. In all exposures, treatment with Nam significantly mitigated synthesis of the inflammatory mediators and restored levels of UVB-reduced LmnB1. In the 3D skin equivalent model, Nam reduced IL-8 levels stimulated by a combination of topical PMand UV exposure. In a UV challenge clinical, pretreatment with 5% Nam reduced erythema and skin surface IL-1αRA/IL-1α inflammatory biomarkers that were induced by SSR.
CONCLUSION: Since it is known that Nam has anti-inflammatory properties, we tested whether Nam can inhibit environmental stress-induced inflammation and senescence-associated secretory phenotype (SASP) biomarkers. We show Nam can reduce PGE, IL-6 and IL-8 levels induced by environmental stressors. Additionally, in vivo pretreatment with Nam can reduce UV-induced erythema and skin surface inflammatory biomarkers. These findings add to the body of evidence that Nam can mitigate the skin's inflammatory response elicited by environmental stressors. This supports Nam can potentially inhibit senescence and premature ageing and thereby maintain skin's functionality and appearance.


greenmedinfo--2020-10-09--Inhibitory effects of ethanolic, methanolic, and hydroalcoholic extracts of olive leaf on growth, ac

Inhibitory effects of ethanolic, methanolic, and hydroalcoholic extracts of olive leaf on growth, acid production, and adhesion of Streptococcus mutans.

Background : Usage of chemical mouthwashes for controlling dental caries can end to some side effects such as oral biological imbalance .
Recently , using natural derivatives such as herbs , presented to overcome such adverse effects .
Due to antibacterial property of olive leaf extracts ( ) , this study conducted in order to evaluate bacteriocidal , anti-acid production , and anti-adhesion effects of olive leaf ethanolic , methanolic , and hydroalcoholic extracts on .
Materials and Methods : In thisstudy , nine strains of ( PTCC1683 ) were used .
Maceration methods were done in order to provide @ @ @ @ @ @ @ and hydroalcoholic extracts .
The antibacterial activities evaluated by macrodilution and disc diffusion method in different concentrations ( 3.25 % -100 % ) .
Acid production and adhesion of bacterial strains also were evaluated .
The obtained data were analyzed by analysis of variance method using SPSS software.
< 0.05 was considered as statistically significant .
Results : The minimum inhibitory concentration and minimum bactericidal concentration for ethanolic , methanolic , and hydroalcoholic olive leaf extracts onare 12 % -25 % , 50 % -75 % , and 12 % -25 % , @ @ @ @ @ @ @ ofsignificantly increased in higher concentration ( ethanolic and methanolic extracts : = 0.004 ; hydroalcoholic extract : = 0.003 ) .
The acid production and adhesion significantly decreased by increase in the concentration ( < 0.001 ) .
Conclusion : In general , olive leaf ethanolic , methanolic , and hydroalcoholic extracts induce growth inhibition , acid production , and adhesion of .
Consequently , it can be used as a natural preservative in the food industry , as well as in the production of commercial products such as chewing gum , chocolate @ @ @ @ @ @ @ .

Background: Usage of chemical mouthwashes for controlling dental caries can end to some side effects such as oral biological imbalance. Recently, using natural derivatives such as herbs, presented to overcome such adverse effects. Due to antibacterial property of olive leaf extracts (), this study conducted in order to evaluate bacteriocidal, anti-acid production, and anti-adhesion effects of olive leaf ethanolic, methanolic, and hydroalcoholic extracts on.
Materials and Methods: In thisstudy, nine strains of(PTCC1683) were used. Maceration methods were done in order to provide the olive leaf ethanolic, methanolic, and hydroalcoholic extracts. The antibacterial activities evaluated by macrodilution and disc diffusion method in different concentrations (3.25%-100%). Acid production and adhesion of bacterial strains also were evaluated. The obtained data were analyzed by analysis of variance method using SPSS software.<0.05 was considered as statistically significant.
Results: The minimum inhibitory concentration and minimum bactericidal concentration for ethanolic, methanolic, and hydroalcoholic olive leaf extracts onare 12%-25%, 50%-75%, and 12%-25%, respectively. In addition, inhibition zone ofsignificantly increased in higher concentration (ethanolic and methanolic extracts:= 0.004; hydroalcoholic extract:= 0.003). The acid production and adhesion significantly decreased by increase in the concentration (<0.001).
Conclusion: In general, olive leaf ethanolic, methanolic, and hydroalcoholic extracts induce growth inhibition, acid production, and adhesion of. Consequently, it can be used as a natural preservative in the food industry, as well as in the production of commercial products such as chewing gum, chocolate, and toothpaste to prevent dental caries.


greenmedinfo--2020-10-09--Olive leaf polyphenols may be an effective therapeutic approach for treating multiple sclerosis and

Olive leaf polyphenols may be an effective therapeutic approach for treating multiple sclerosis and other neurodegenerative diseases.

Numerous evidences suggest that plant polyphenols may have therapeutic benefits in regulating oxidative stress and providing neuroprotection in many neurodegenerative diseases , including multiple sclerosis ( MS ) .
However , these mechanisms are not yet completely understood .
In this study , we investigated the effect of olive leaf polyphenols on oxidative stress through oxidation marker level and activity ( TBARS , SOD , and GPX ) and their protein expression ( SOD1 , SOD2 , and GPX1 ) , as well as the protein expression of Sirtuin 1 ( SIRT1 ) and microglia markers ( Iba-1 , CD206 @ @ @ @ @ @ @ ( proteolipid protein expression ) in the brain of rats with induced experimental autoimmune encephalomyelitis ( EAE ) and subjected to olive leaf therapy .
Experiments were performed in male EAE DA rats , which were randomly divided into 2 main groups : EAE groups treated with the therapy of olive leaf ( EAE+TOL ) and untreated EAE control groups .
The EAE treated groups consumed olive leaf tea instead of drinking water ( ) from the beginning to the end of the experiment .
In addition , olive leaf extract was injected @ @ @ @ @ @ @ continuous days and started on the 8day after EAE induction .
The clinical course was monitored in both groups until the 30day after EAE induction .
Our results demonstrated that TOL attenuated the clinical course of EAE ; reduced the oxidative stress ( by decreasing the concentration of MDA ) ; upregulated antioxidant enzymes ( SOD1 , SOD2 , and GPX1 ) , SIRT1 ( overall and microglial ) , and anti-inflammatory M2 microglia ; downregulated proinflammatory M1 type ; and preserved myelin integrity .
These data support the idea that TOL may @ @ @ @ @ @ @ MS and other neurodegenerative diseases .

Numerous evidences suggest that plant polyphenols may have therapeutic benefits in regulating oxidative stress and providing neuroprotection in many neurodegenerative diseases, including multiple sclerosis (MS). However, these mechanisms are not yet completely understood. In this study, we investigated the effect of olive leaf polyphenols on oxidative stress through oxidation marker level and activity (TBARS, SOD, and GPX) and their protein expression (SOD1, SOD2, and GPX1), as well as the protein expression of Sirtuin 1 (SIRT1) and microglia markers (Iba-1, CD206, and iNOS) and myelin integrity (proteolipid protein expression) in the brain of rats with induced experimental autoimmune encephalomyelitis (EAE) and subjected to olive leaf therapy. Experiments were performed in male EAE DA rats, which were randomly divided into 2 main groups: EAE groups treated with the therapy of olive leaf (EAE+TOL) and untreated EAE control groups. The EAE treated groups consumed olive leaf tea instead of drinking water () from the beginning to the end of the experiment. In addition, olive leaf extract was injected intraperitoneally (.) for the 10 continuous days and started on the 8day after EAE induction. The clinical course was monitored in both groups until the 30day after EAE induction. Our results demonstrated that TOL attenuated the clinical course of EAE; reduced the oxidative stress (by decreasing the concentration of MDA); upregulated antioxidant enzymes (SOD1, SOD2, and GPX1), SIRT1 (overall and microglial), and anti-inflammatory M2 microglia; downregulated proinflammatory M1 type; and preserved myelin integrity. These data support the idea that TOL may be an effective therapeutic approach for treating MS and other neurodegenerative diseases.


greenmedinfo--2020-10-09--Phytochemical profile, cytotoxic, antioxidant, and allelopathic potentials of aqueous leaf extracts

Phytochemical profile, cytotoxic, antioxidant, and allelopathic potentials of aqueous leaf extracts of Olea europaea.

Although bioactivities of ( OEhave been widely described , most of them were related to its methanolic extracts or its essential oils , While data related to aqueous extracts still very scarce .
Thus , in this study , the phytochemical composition , the antioxidant activity , the cytotoxic potential , and the allelopathic potential of aqueous leaf extracts from two varieties of were investigated and compared .
High-performance liquid chromatography ( HPLC ) was used to identify and quantify the constituents of the tested plants , and spectrophotometric methods to evaluate antioxidant activities .
The cytotoxic potential was investigated @ @ @ @ @ @ @ germination seeds ' test was used for allelopathic activity .
HPLC analysis showed the presence of 10 phenolic compounds in both extracts .
Chemlali variety showed the highest antioxidant and allelopathic activities .
Regarding the cytotoxicity effect , a significant increase in cell viability was observed with both of our extracts compared to untreated cells .
These results confirm that aqueous extracts from OE produce a range of substances with potential antioxidant , antifungal , and allelopathic effects without toxic effects .
Thus , they could be used as an alternative of chemical @ @

Although bioactivities of(OEhave been widely described, most of them were related to its methanolic extracts or its essential oils, While data related to aqueous extracts still very scarce. Thus, in this study, the phytochemical composition, the antioxidant activity, the cytotoxic potential, and the allelopathic potential of aqueous leaf extracts from two varieties of were investigated and compared. High-performance liquid chromatography (HPLC) was used to identify and quantify the constituents of the tested plants, and spectrophotometric methods to evaluate antioxidant activities. The cytotoxic potential was investigated using murine oligodendrocytes (158N) while germination seeds' test was used for allelopathic activity. HPLC analysis showed the presence of 10 phenolic compounds in both extracts. Chemlali variety showed the highest antioxidant and allelopathic activities. Regarding the cytotoxicity effect, a significant increase in cell viability was observed with both of our extracts compared to untreated cells. These results confirm that aqueous extracts from OE produce a range of substances with potential antioxidant, antifungal, and allelopathic effects without toxic effects. Thus, they could be used as an alternative of chemical compounds.


greenmedinfo--2020-10-09--Nuciferine inhibits the progression of glioblastoma.

BACKGROUND : Nuciferine ( NF ) , extracted from the leaves of N. nucifera Gaertn , has been shown to exhibit anti-tumor and anti-viral pharmacological properties .
It can also penetrate the blood brain barrier ( BBB ) .
However , the mechanism by which NF inhibits glioblastoma ( GBM ) progression is not well understood .
We aimed to determine the anti-tumor effect of NF on GBM cell lines and clarify the potential molecular mechanism involved .
METHODS : U87MG and U251 cell lines were used in vitro to assess the anti-tumor efficacy of NF .
Cytotoxicity , viability @ @ @ @ @ @ @ and colony formation assay .
After Annexin V-FITC and PI staining , flow cytometry was performed to evaluate apoptosis and cell cycle changes in NF-treated GBM cells .
Wound healing and Transwell assays were used to assess migration and invasion of GBM cells .
Western blot analysis , immunofluorescence staining , immunohistochemistry , and bioinformatics were used to gain insights into the molecular mechanisms .
Preclinical therapeutic efficacy was mainly estimated by ultrasound and MRI in xenograft nude mouse models .
RESULTS : NF inhibited the proliferation , mobility , stemness , angiogenesis @ @ @ @ @ @ @ of GBM cells .
Additionally , NF induced apoptosis and G2 cell cycle arrest .
Slug expression was also decreased by NF via the AKT and STAT3 signaling pathways .
Interestingly , we discovered that NF affected GBM cells partly by targeting SOX2 , which may be upstream of the AKT and STAT3 pathways .
Finally , NF led to significant tumor control in GBM xenograft models .
CONCLUSIONS : NF inhibited the progression of GBM via the SOX2-AKT/STAT3-Slug signaling pathway .
SOX2-targeting with NF may offer a novel therapeutic approach for GBM @ @

BACKGROUND: Nuciferine (NF), extracted from the leaves of N. nucifera Gaertn, has been shown to exhibit anti-tumor and anti-viral pharmacological properties. It can also penetrate the blood brain barrier (BBB). However, the mechanism by which NF inhibits glioblastoma (GBM) progression is not well understood. We aimed to determine the anti-tumor effect of NF on GBM cell lines and clarify the potential molecular mechanism involved.
METHODS: U87MG and U251 cell lines were used in vitro to assess the anti-tumor efficacy of NF. Cytotoxicity, viability, and proliferation were evaluated by MTT and colony formation assay. After Annexin V-FITC and PI staining, flow cytometry was performed to evaluate apoptosis and cell cycle changes in NF-treated GBM cells. Wound healing and Transwell assays were used to assess migration and invasion of GBM cells. Western blot analysis, immunofluorescence staining, immunohistochemistry, and bioinformatics were used to gain insights into the molecular mechanisms. Preclinical therapeutic efficacy was mainly estimated by ultrasound and MRI in xenograft nude mouse models.
RESULTS: NF inhibited the proliferation, mobility, stemness, angiogenesis, and epithelial-to-mesenchymal transition (EMT) of GBM cells. Additionally, NF induced apoptosis and G2 cell cycle arrest. Slug expression was also decreased by NF via the AKT and STAT3 signaling pathways. Interestingly, we discovered that NF affected GBM cells partly by targeting SOX2, which may be upstream of the AKT and STAT3 pathways. Finally, NF led to significant tumor control in GBM xenograft models.
CONCLUSIONS: NF inhibited the progression of GBM via the SOX2-AKT/STAT3-Slug signaling pathway. SOX2-targeting with NF may offer a novel therapeutic approach for GBM treatment.


greenmedinfo--2020-10-09--Extra virgin olive oil modulates vasodilator enzyme level by repairing angiogenesis function in rat

Extra virgin olive oil modulates vasodilator enzyme level by repairing angiogenesis function in rat model of preeclampsia.

This study aimed to determine the effect of Extra Virgin Olive Oil ( EVOO ) on vasodilator enzyme by repairing angiogenic function in rat model of preeclampsia.This research consisted of five groups ; negative control ( normal pregnant rats ) group , positive control ( preeclampsia rat model ) group , preeclampsia rat model groups given EVOO in 3 different doses ( 0.5 ml/day , 1 ml/day , and 2 ml/day , respectively ) .
Blood pressure measurements were carried out on day 12 , 15 , and 19 of pregnancy .
After the rats were sacrificed , the placentas @ @ @ @ @ @ @ Synthase ( eNOS ) level of maternal plasma to determine soluble Fms-like Tyrosine Kinase 1 ( sFlt-1 ) and Vascular Endothelial Growth Factor ( VEGF ) level.There were significant higher sFlt-1 level ( p < 0.001 ) , lower VEGF level ( p = 0.009 ) , and lower eNOS level ( p = 0.034 ) between negative and positive control groups .
After EVOO administration , sFlt-1 level was lower in dose 1 and 2 groups but higher in dose 3 group in accordance with VEGF and eNOS levels that were increasing @ @ @ @ @ @ @ groups but decreasing in dose 3 .
There were significant differences between positive control and dose 1 ( p = 0.015 ) and dose 2 ( p = 0.001 ) in sFlt-1 level .
None of all dose groups were statistically different with positive control group in VEGF level ( dose 1 p = 0.601 ; dose 2 p = 0.297 ; dose 3 p = 0.805 ) .
eNOS levels of all dose groups were statistically different from that of the positive control group ( dose 1 p = 0.014 ; dose @ @ @ @ @ @ @ p = 0.024 ) .Administration of EVOO modulates eNOS as vasodilator enzyme by repairing the angiogenic function indicated by decreased sFlt-1 level and increased VEGF in rat model of preeclampsia .

This study aimed to determine the effect of Extra Virgin Olive Oil (EVOO) on vasodilator enzyme by repairing angiogenic function in rat model of preeclampsia.This research consisted of five groups; negative control (normal pregnant rats) group, positive control (preeclampsia rat model) group, preeclampsia rat model groups given EVOO in 3 different doses (0.5 ml/day, 1 ml/day, and 2 ml/day, respectively). Blood pressure measurements were carried out on day 12, 15, and 19 of pregnancy. After the rats were sacrificed, the placentas were collected to determine endothelial Nitric Oxide Synthase (eNOS) level of maternal plasma to determine soluble Fms-like Tyrosine Kinase 1 (sFlt-1) and Vascular Endothelial Growth Factor (VEGF) level.There were significant higher sFlt-1 level (p<0.001), lower VEGF level (p = 0.009), and lower eNOS level (p = 0.034) between negative and positive control groups. After EVOO administration, sFlt-1 level was lower in dose 1 and 2 groups but higher in dose 3 group in accordance with VEGF and eNOS levels that were increasing both in dose 1 and dose 2 groups but decreasing in dose 3. There were significant differences between positive control and dose 1 (p = 0.015) and dose 2 (p = 0.001) in sFlt-1 level. None of all dose groups were statistically different with positive control group in VEGF level (dose 1 p = 0.601; dose 2 p = 0.297; dose 3 p = 0.805). eNOS levels of all dose groups were statistically different from that of the positive control group (dose 1 p = 0.014; dose 2 p = 0.001; dose 3 p = 0.024).Administration of EVOO modulates eNOS as vasodilator enzyme by repairing the angiogenic function indicated by decreased sFlt-1 level and increased VEGF in rat model of preeclampsia.


greenmedinfo--2020-10-09--Ameliorative effect of virgin olive oil against nephrotoxicity following sub-chronic administration

Ameliorative effect of virgin olive oil against nephrotoxicity following sub-chronic administration of ethephon.

Background : Ethephon ( EP ) is the most famous plant growth regulator with different adverse effects on kidney function .
Virgin Olive Oil ( VOO ) is considered as a natural source of antioxidant with beneficial effects .
Thus , this study was conducted to investigate the effects of VOO on nephrotoxicity induced by EP in rats .
Methods and materials : In this study , 80 male rats ( weighing 200-250 g ) were divided into four groups including : control group received normal saline as vehicle , received VOO , received EP ( 150 mg/kg/day ) for @ @ @ @ @ @ @ mg/kg/day for 2 months , after 2-month pretreatment with VOO .
VOO ( 2 mL/kg/day ) and vehicle were administered by gastric gavage for 2 months .
At the end , the animals were sacrificed , and their blood and kidneys were used for examinations .
Isolated kidneys were used for histopathological and oxidative stress studies .
Results : Significant increases were recorded in blood ( neutrophils , monocytes ) and urinary parameters as well as malondialdehyde ( MDA ) content in the group III compared to groups II and I ( P˂0.05 @ @ @ @ @ @ @ histopathological alterations increased in the group III .
In the group IV , significant decreases were recorded in blood and urinary parameters , MDA , and histopathological alterations and a significant increase were found in antioxidant enzymescompared to group III ( P˂0.05 ) .
Conclusions : Findings of the present study demonstrated protective effects of VOO in prevention of kidneys against EP -induced toxicity in albino rats .

Background: Ethephon (EP) is the most famous plant growth regulator with different adverse effects on kidney function. Virgin Olive Oil (VOO) is considered as a natural source of antioxidant with beneficial effects. Thus, this study was conducted to investigate the effects of VOO on nephrotoxicity induced by EP in rats.
Methods and materials: In this study, 80 male rats (weighing 200-250 g) were divided into four groups including: control group received normal saline as vehicle,received VOO,received EP (150 mg/kg/day) for 2 months,received EP (150 mg/kg/day for 2 months, after 2-month pretreatment with VOO. VOO (2 mL/kg/day) and vehicle were administered by gastric gavage for 2 months. At the end, the animals were sacrificed, and their blood and kidneys were used for examinations. Isolated kidneys were used for histopathological and oxidative stress studies.
Results: Significant increases were recorded in blood (neutrophils, monocytes) and urinary parameters as well as malondialdehyde (MDA) content in the group III compared to groups II and I (P˂0.05). Antioxidant enzymes significantly declined and histopathological alterations increased in the group III. In the group IV, significant decreases were recorded in blood and urinary parameters, MDA, and histopathological alterations and a significant increase were found in antioxidant enzymescompared to group III (P˂0.05).
Conclusions: Findings of the present study demonstrated protective effects of VOO in prevention of kidneys against EP -induced toxicity in albino rats.


greenmedinfo--2020-10-09--A review on management of cardiovascular diseases by olive polyphenols.

Noncommunicable diseases have increasingly grown the cause of morbidities and mortalities worldwide .
Among them , cardiovascular diseases ( CVDs ) continue to be the major contributor to deaths .
CVDs are common in the urban community population due to the substandard living conditions , which have a significant impact on the healthcare system , and over 23 million human beings are anticipated to suffer from the CVDs before 2030 .
At the moment , CVD physicians are immediately advancing both primary and secondary prevention modalities in high-risk populations .
The cornerstone of CVD prevention is a healthy lifestyle that @ @ @ @ @ @ @ disease onset .
In fact , in the present scenario , comprehensive research conducted on food plant components is potentially efficacious in reducing some highly prevalent CVD risk factors , such as hypercholesterolemia , hypertension , and atherosclerosis .
Polyphenols of olive oil ( OO ) , virgin olive oil ( VOO ) , and extra virgin olive oil contribute an essential role for the management of CVDs .
Olive oil induces cardioprotective effects due to the presence of a plethora of polyphenolic compounds , for example , oleuropein ( OL ) , @ @ @ @ @ @ @ study examines the bioavailability and absorption of major olive bioactive compounds , for instance , oleacein , oleocanthal , OL , and tyrosol .
This review also elucidates the snobbish connection of olive polyphenols ( OP ) and the potential mechanism involved in combating various CVD results taken up from the in vitro and in vivo studies , such as animal and human model studies .

Noncommunicable diseases have increasingly grown the cause of morbidities and mortalities worldwide. Among them, cardiovascular diseases (CVDs) continue to be the major contributor to deaths. CVDs are common in the urban community population due to the substandard living conditions, which have a significant impact on the healthcare system, and over 23 million human beings are anticipated to suffer from the CVDs before 2030. At the moment, CVD physicians are immediately advancing both primary and secondary prevention modalities in high-risk populations. The cornerstone of CVD prevention is a healthy lifestyle that is more cost-effective than the treatments after disease onset. In fact, in the present scenario, comprehensive research conducted on food plant components is potentially efficacious in reducing some highly prevalent CVD risk factors, such as hypercholesterolemia, hypertension, and atherosclerosis. Polyphenols of olive oil (OO),virgin olive oil (VOO), and extra virgin olive oil contribute an essential role for the management of CVDs. Olive oil induces cardioprotective effects due to the presence of a plethora of polyphenolic compounds, for example, oleuropein (OL), tyrosol, and hydroxytyrosol. The present study examines the bioavailability and absorption of major olive bioactive compounds, for instance, oleacein, oleocanthal, OL, and tyrosol. This review also elucidates the snobbish connection of olive polyphenols (OP) and the potential mechanism involved in combating various CVD results taken up from the in vitro and in vivo studies, such as animal and human model studies.


greenmedinfo--2020-10-10--Curcumin and hesperetin attenuate D-galactose-induced brain senescence in vitro and in vivo

BACKGROUND/OBJECTIVES : Brain senescence causes cognitive impairment and neurodegeneration .
It has also been demonstrated that curcumin ( Cur ) and hesperetin ( Hes ) , both antioxidant polyphenolic compounds , mediate anti-aging and neuroprotective effects .
Therefore , the objective of this study was to investigate whether Cur , Hes , and/or their combination exert anti-aging effects in D-galactose ( Dg ) -induced aged neuronal cells and rats .
MATERIALS/METHODS : SH-SY5Y cells differentiated in response to retinoic acid were treated with Cur ( 1μM ) , Hes ( 1 μM ) , or a combination of both , @ @ @ @ @ @ @ loss was subsequently evaluated by measuring average neurite length and analyzing expression of β-tubulin III , phosphorylated extracellular signal-regulated kinases , and neurofilament heavy polypeptide .
Cellular senescenceand related proteins , p16 and p21 , were also investigated , including their regulation of antioxidant enzymes.
, brain aging was induced by injecting 250 mg/kg body weight ( b.w . )
Dg .
The effects of supplementing this model with 50 mg/kg b.w .
Cur , 50 mg/kg b.w .
Hes , or a combination of both for 3 months were subsequently evaluated .
@ @ @ @ @ @ @ passive avoidance test and apoptosis markers were analyzed in brain cortex tissues .
RESULTS : Cur , Hes , and their combination improved neuron length and cellular senescence by decreasing the number ofβ-gal stained cells , down-regulated expression of p16 and p21 , and up-regulated expression of antioxidant enzymes , including superoxide dismutase 1 , glutathione peroxidase 1 , and catalase .
Administration of Cur , Hes , or their combination also tended to ameliorate cognitive impairment and suppress apoptosis in the cerebral cortex by down-regulating Bax and poly ( ADP-ribose ) polymerase @ @ @ @ @ @ @ : Cur and Hes appear to attenuate Dg-induced brain aging via regulation of antioxidant enzymes and apoptosis .
These results suggest that Cur and Hes may mediate neuroprotective effects in the aging process , and further study of these antioxidant polyphenolic compounds is warranted .

BACKGROUND/OBJECTIVES: Brain senescence causes cognitive impairment and neurodegeneration. It has also been demonstrated that curcumin (Cur) and hesperetin (Hes), both antioxidant polyphenolic compounds, mediate anti-aging and neuroprotective effects. Therefore, the objective of this study was to investigate whether Cur, Hes, and/or their combination exert anti-aging effects in D-galactose (Dg)-induced aged neuronal cells and rats.
MATERIALS/METHODS: SH-SY5Y cells differentiated in response to retinoic acid were treated with Cur (1μM), Hes (1 μM), or a combination of both, followed by 300 mM Dg. Neuronal loss was subsequently evaluated by measuring average neurite length and analyzing expression of β-tubulin III, phosphorylated extracellular signal-regulated kinases, and neurofilament heavy polypeptide. Cellular senescenceand related proteins, p16 and p21, were also investigated, including their regulation of antioxidant enzymes., brain aging was induced by injecting 250 mg/kg body weight (b.w.) Dg. The effects of supplementing this model with 50 mg/kg b.w. Cur, 50 mg/kg b.w. Hes, or a combination of both for 3 months were subsequently evaluated. Brain aging was examined with a step-through passive avoidance test and apoptosis markers were analyzed in brain cortex tissues.
RESULTS: Cur, Hes, and their combination improved neuron length and cellular senescence by decreasing the number ofβ-gal stained cells, down-regulated expression of p16 and p21, and up-regulated expression of antioxidant enzymes, including superoxide dismutase 1, glutathione peroxidase 1, and catalase. Administration of Cur, Hes, or their combination also tended to ameliorate cognitive impairment and suppress apoptosis in the cerebral cortex by down-regulating Bax and poly (ADP-ribose) polymerase expression and increasing Bcl-2 expression.
CONCLUSIONS: Cur and Hes appear to attenuate Dg-induced brain aging via regulation of antioxidant enzymes and apoptosis. These results suggest that Cur and Hes may mediate neuroprotective effects in the aging process, and further study of these antioxidant polyphenolic compounds is warranted.


greenmedinfo--2020-10-10--A dihydroflavonoid naringin extends the lifespan of C. elegans and delays the progression of aging-r

A dihydroflavonoid naringin extends the lifespan of C. elegans and delays the progression of aging-related diseases.

Naringin is a dihydroflavonoid , which is rich in several plant species used for herbal medicine .
It has a wide range of biological activities , including antineoplastic , anti-inflammatory , antiphotoaging , and antioxidative activities .
So it would be interesting to know if naringin has an effect on aging and aging-related diseases .
We examined the effect of naringin on the aging of ( . )
.
Our results showed that naringin could extend the lifespan of..
Moreover , naringin could also increase the thermal and oxidative stress tolerance , reduce the accumulation of lipofuscin , and delay @ @ @ @ @ @ @ AD and PD .
Naringin could not significantly extend the lifespan of long-lived mutants from genes in insulin/IGF-1 signaling ( IIS ) and nutrient-sensing pathways , such as- , - , - , - , -.
, and- .
Naringin treatment prolonged the lifespan of long-lived-mutants , which have decreased reproductive stem cells .
Naringin could not extend the lifespan of a null mutant of the fox-head transcription factor DAF-16 .
Moreover , naringin could increase the mRNA expression of genes regulated by-and itself .
In conclusion , we show that a natural @ @ @ @ @ @ @ delay the progression of aging-related diseases in.models via DAF-16 .

Naringin is a dihydroflavonoid, which is rich in several plant species used for herbal medicine. It has a wide range of biological activities, including antineoplastic, anti-inflammatory, antiphotoaging, and antioxidative activities. So it would be interesting to know if naringin has an effect on aging and aging-related diseases. We examined the effect of naringin on the aging of(.). Our results showed that naringin could extend the lifespan of.. Moreover, naringin could also increase the thermal and oxidative stress tolerance, reduce the accumulation of lipofuscin, and delay the progress of aging-related diseases in.models of AD and PD. Naringin could not significantly extend the lifespan of long-lived mutants from genes in insulin/IGF-1 signaling (IIS) and nutrient-sensing pathways, such as-,-,-,-,-., and-. Naringin treatment prolonged the lifespan of long-lived-mutants, which have decreased reproductive stem cells. Naringin could not extend the lifespan of a null mutant of the fox-head transcription factor DAF-16. Moreover, naringin could increase the mRNA expression of genes regulated by-and itself. In conclusion, we show that a natural product naringin could extend the lifespan of.and delay the progression of aging-related diseases in.models via DAF-16.


greenmedinfo--2020-10-10--Naringin and bone marrow mesenchymal stem cells repair articular cartilage defects.

The present study aimed to assess the effect of a combination of naringin and rabbit bone marrow mesenchymal stem cells ( BMSCs ) on the repair of cartilage defects in rabbit knee joints and to assess possible involvement of the transforming growth factor-β ( TGF-β ) signaling pathway in this process .
After establishing an articular cartilage defect model in rabbit knees , 20 New Zealand rabbits were divided into a sham operation group ( Sham ) , a model group ( Mod ) , a naringin treatment group ( Nar ) , a BMSC group ( BMSCs ) and @ @ @ @ @ @ @ ) .
At 12 weeks after treatment , the cartilage was evaluated using the International Cartilage Repair Society ( ICRS ) 's macroscopic evaluation of cartilage repair scale , the ICRS 's visual histological assessment scale , the Modified O'Driscoll grading system , histological staining ( hematoxylin andeosin staining , toluidine blue staining and safranin O staining ) and immunohistochemical staining ( type-II collagen , TGF-β3 and SOX-9 immunostaining ) .
Using the above grading systems to quantify the extent of repair , histological quantification and macro quantification of joint tissue repair showed @ @ @ @ @ @ @ treatment in comparison to the untreated Mod group .
Among the injury model groups ( Mod , Nar , BMSCs and Nar/BMSCs ) , the Nar/BMSCs group displayed the highest degree of morphological repair .
The results of histological and immunohistochemical stainingof the repaired region of the joint defect indicated that the BMSCs had a satisfactory effect on the repair of the joint structure but had a poor effect on the repair of cartilage quality .
The Nar/BMSCs group displayed satisfactory therapeutic effects on both repair of the joint structure and cartilage quality @ @ @ @ @ @ @ was high in the Nar/BMSCs group .
Additionally , staining of TGF-β3 and SOX-9 in the Nar/BMSCs group was the strongest compared with that of any other group in the present study .
Naringin and/BMSCs together demonstrated a more efficient repair effect on articular cartilage defects in rabbit knees than the use of either treatment alone in terms of joint structure and cartilage quality .
One potential mechanism of naringin action may be through activation and continuous regulation of the TGF-β superfamily signaling pathway , which can promote BMSCs to differentiate into chondrocytes @

The present study aimed to assess the effect of a combination of naringin and rabbit bone marrow mesenchymal stem cells (BMSCs) on the repair of cartilage defects in rabbit knee joints and to assess possible involvement of the transforming growth factor-β (TGF-β) signaling pathway in this process. After establishing an articular cartilage defect model in rabbit knees, 20 New Zealand rabbits were divided into a sham operation group (Sham), a model group (Mod), a naringin treatment group (Nar), a BMSC group (BMSCs) and a naringin + BMSC group (Nar/BMSCs). At 12 weeks after treatment, the cartilage was evaluated using the International Cartilage Repair Society (ICRS)'s macroscopic evaluation of cartilage repair scale, the ICRS's visual histological assessment scale, the Modified O'Driscoll grading system, histological staining (hematoxylin andeosin staining, toluidine blue staining and safranin O staining) and immunohistochemical staining (type-II collagen, TGF-β3 and SOX-9 immunostaining). Using the above grading systems to quantify the extent of repair, histological quantification and macro quantification of joint tissue repair showed that the Nar/BMSCs group displayed repair after treatment in comparison to the untreated Mod group. Among the injury model groups (Mod, Nar, BMSCs and Nar/BMSCs), the Nar/BMSCs group displayed the highest degree of morphological repair. The results of histological and immunohistochemical stainingof the repaired region of the joint defect indicated that the BMSCs had a satisfactory effect on the repair of the joint structure but had a poor effect on the repair of cartilage quality. The Nar/BMSCs group displayed satisfactory therapeutic effects on both repair of the joint structure and cartilage quality. The expression level of type-II collagen was high in the Nar/BMSCs group. Additionally, staining of TGF-β3 and SOX-9 in the Nar/BMSCs group was the strongest compared with that of any other group in the present study. Naringin and/BMSCs together demonstrated a more efficient repair effect on articular cartilage defects in rabbit knees than the use of either treatment alone in terms of joint structure and cartilage quality. One potential mechanism of naringin action may be through activation and continuous regulation of the TGF-β superfamily signaling pathway, which can promote BMSCs to differentiate into chondrocytes.


greenmedinfo--2020-10-10--Naringin combined with tunicamycin+BAY 11-7082 efficiently induced apoptotic cell death in HT29 colo

Naringin combined with tunicamycin+BAY 11-7082 efficiently induced apoptotic cell death in HT29 colon cancer cells.

Currently , combination therapy is considered the most effective solution for a selective chemotherapeutic effect in the treatment of colon cancer .
This study investigated the death of both colon cancer HT29 cells and healthy vascular smooth muscle TG-Ha-VSMC cells ( VSMCs ) induced by naringin combined with endoplasmic reticulum ( ER ) stress and NF-κB inhibition .
Naringin combined with tunicamycin and BAY 11-7082 suppressed the proliferation of HT29 cells in a dose-dependent manner and induced particularly apoptotic death without significantly affecting healthy VSMCs according to Annexin V/PI staining and AO/EB staining analyses .
Insufficientantioxidant defense and heat shock @ @ @ @ @ @ @ were observed in HT29 cells following combination therapy .
Quantitative real-time PCR and western blot analysis demonstrated that drug combination-induced mitochondrial apoptosis was activated through the ROS-mediated PERK/eIF2α/ATF4/CHOP pathway .
Additionally , naringin combination significantly reduced the sXBP expression induced by tunicamycin+BAY 11-7082 in a dose-dependent manner .
In conclusion , this study found that naringin combined with tunicamycin+BAY 11-7082 efficiently induced apoptotic cell death in HT29 colon cancer cells via oxidative stress and the PERK/eIF2α/ATF4/CHOP pathway , suggesting that naringin combined with tunicamycin plus BAY 11-7082 could be a new combination therapy @ @ @ @ @ @ @ minimal side effects on healthy cells .

Currently, combination therapy is considered the most effective solution for a selective chemotherapeutic effect in the treatment of colon cancer. This study investigated the death of both colon cancer HT29 cells and healthy vascular smooth muscle TG-Ha-VSMC cells (VSMCs) induced by naringin combined with endoplasmic reticulum (ER) stress and NF-κB inhibition. Naringin combined with tunicamycin and BAY 11-7082 suppressed the proliferation of HT29 cells in a dose-dependent manner and induced particularly apoptotic death without significantly affecting healthy VSMCs according to Annexin V/PI staining and AO/EB staining analyses. Insufficientantioxidant defense and heat shock response as well as excessive ROS generation were observed in HT29 cells following combination therapy. Quantitative real-time PCR and western blot analysis demonstrated that drug combination-induced mitochondrial apoptosis was activated through the ROS-mediated PERK/eIF2α/ATF4/CHOP pathway. Additionally, naringin combination significantly reduced the sXBP expression induced by tunicamycin+BAY 11-7082 in a dose-dependent manner. In conclusion, this study found that naringin combined with tunicamycin+BAY 11-7082 efficiently induced apoptotic cell death in HT29 colon cancer cells via oxidative stress and the PERK/eIF2α/ATF4/CHOP pathway, suggesting that naringin combined with tunicamycin plus BAY 11-7082 could be a new combination therapy strategy for effective colon cancer treatment with minimal side effects on healthy cells.


greenmedinfo--2020-10-10--Nobiletin inhibits cell growth through restraining aerobic glycolysis via PKA-CREB pathway in oral s

Nobiletin inhibits cell growth through restraining aerobic glycolysis via PKA-CREB pathway in oral squamous cell carcinoma.

Background/Aim : Nobiletin is a polymethoxylated flavone enriched in Citrus and is used as an important drug in traditional Chinese medicine for various kinds of diseases .
Among its multiple functions , it has shown that nobiletin inhibits proliferation of various cancer cells .
However , it is unclear whether nobiletin inhibits the growth of oral squamous cell carcinoma ( OSCC ) cells .
Materials and Methods : We explored the antitumor effects of nobiletin in TCA-8113 and CAL-27 oral squamous cells .
The Cell Counting Kit-8 ( CCK8 ) assay was used to measure cell vitality .
Flow cytometry @ @ @ @ @ @ @ cells in the various phases of the cell cycle .
PCR and Western blot were applied to determine mRNA and protein expression , respectively .
Results : Nobiletin inhibited proliferation of TCA-8113 and CAL-27 cells via inducing cell cycle arrest at the G1 phase .
In addition , the levels of phosphorylated-PKA and phosphorylated-CREB were reduced in nobiletin-treated TCA-8113 and CAL-27 cells .
Importantly , our results showed that nobiletin treatment resulted in impaired mitochondrial function and altered glucose consumption , and pyruvate and lactate production .
Lastly , nobiletin was found to @ @ @ @ @ @ @ .
Interestingly , administration of 50 μmol/L Sp-cAMP , a potent PKA activator , rescued all phenotypes caused by nobiletin .
Conclusions : Nobiletin inhibits OSCC cell proliferation in a mitochondria-dependent manner , indicating that it may have a promising role in cancer treatment and attenuation of drug resistance .

Background/Aim: Nobiletin is a polymethoxylated flavone enriched in Citrus and is used as an important drug in traditional Chinese medicine for various kinds of diseases. Among its multiple functions, it has shown that nobiletin inhibits proliferation of various cancer cells. However, it is unclear whether nobiletin inhibits the growth of oral squamous cell carcinoma (OSCC) cells.
Materials and Methods: We explored the antitumor effects of nobiletin in TCA-8113 and CAL-27 oral squamous cells. The Cell Counting Kit-8 (CCK8) assay was used to measure cell vitality. Flow cytometry was performed to measure the number of cells in the various phases of the cell cycle. PCR and Western blot were applied to determine mRNA and protein expression, respectively.
Results: Nobiletin inhibited proliferation of TCA-8113 and CAL-27 cells via inducing cell cycle arrest at the G1 phase. In addition, the levels of phosphorylated-PKA and phosphorylated-CREB were reduced in nobiletin-treated TCA-8113 and CAL-27 cells. Importantly, our results showed that nobiletin treatment resulted in impaired mitochondrial function and altered glucose consumption, and pyruvate and lactate production. Lastly, nobiletin was found to inhibit the generation of xenografts in vivo. Interestingly, administration of 50 μmol/L Sp-cAMP, a potent PKA activator, rescued all phenotypes caused by nobiletin.
Conclusions: Nobiletin inhibits OSCC cell proliferation in a mitochondria-dependent manner, indicating that it may have a promising role in cancer treatment and attenuation of drug resistance.


greenmedinfo--2020-10-10--These results suggest that nobiletin attenuates high fat diet-induced vascular and renal alterations

These results suggest that nobiletin attenuates high fat diet-induced vascular and renal alterations.

AIMS : We investigate the effect of nobiletin on vascular and renal alterations and possible mechanisms involved in high-fat diet ( HFD ) -fed rats .
MAIN METHODS : Male Sprague-Dawley rats were fed a HFD with fructose 15 % in drinking water for 16 weeks .
HFD-fed rats were treated with nobiletin ( 20 or 40 mg/kg/day ) or vehicle for the last 4 weeks .
KEY FINDINGS : HFD-fed rats treated with nobiletin was significantly reduced obesity , hypertension , dyslipidemia and hyperinsulinemia .
Nobiletin improved vascular endothelial function , restored creatinine clearance , and reduced plasma urea @ @ @ @ @ @ @ urinary protein excretion .
Nobiletin markedly alleviated vascular medial cross-sectional area ( CSA ) and collagen deposition , glomerular extracellular matrix ( ECM ) accumulation , and renal fibrosis .
Nobiletin significantly elevated plasma adiponectin levels , together with upregulated adiponectin receptor 1 ( AdipoR1 ) and suppressed transforming growth factor-β1 ( TGF-β1 ) expression in kidney .
In addition , an increase of plasma tumor necrosis factor alpha ( TNF-α ) and interleukin 6 ( IL-6 ) was significantly attenuated after nobiletin treatment .
SIGNIFICANCE : Our results suggest that nobiletin attenuates @ @ @ @ @ @ @ , which is possibly related to the modulation of AdipoR1 and TGF-β1expression , and suppression of inflammation .

AIMS: We investigate the effect of nobiletin on vascular and renal alterations and possible mechanisms involved in high-fat diet (HFD)-fed rats.
MAIN METHODS: Male Sprague-Dawley rats were fed a HFD with fructose 15% in drinking water for 16 weeks. HFD-fed rats were treated with nobiletin (20 or 40 mg/kg/day) or vehicle for the last 4 weeks.
KEY FINDINGS: HFD-fed rats treated with nobiletin was significantly reduced obesity, hypertension, dyslipidemia and hyperinsulinemia. Nobiletin improved vascular endothelial function, restored creatinine clearance, and reduced plasma urea and creatinine levels, as well as urinary protein excretion. Nobiletin markedly alleviated vascular medial cross-sectional area (CSA) and collagen deposition, glomerular extracellular matrix (ECM) accumulation, and renal fibrosis. Nobiletin significantly elevated plasma adiponectin levels, together with upregulated adiponectin receptor 1 (AdipoR1) and suppressed transforming growth factor-β1 (TGF-β1) expression in kidney. In addition, an increase of plasma tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) was significantly attenuated after nobiletin treatment.
SIGNIFICANCE: Our results suggest that nobiletin attenuates HFD-induced vascular and renal alterations in rats, which is possibly related to the modulation of AdipoR1 and TGF-β1expression, and suppression of inflammation.


greenmedinfo--2020-10-10--Diosmin ameliorates inflammation, insulin resistance, and fibrosis in an experimental model of non-a

Diosmin ameliorates inflammation, insulin resistance, and fibrosis in an experimental model of non-alcoholic steatohepatitis.

Non-alcoholic steatohepatitis ( NASH ) is becoming of increasing significance due to its growing global prevalence and risk of progression to end-stage liver disease .
This study was carried out to investigate the potential anti-inflammatory , insulin sensitizing , and antifibrotic effects of diosmin in an experimental model of NASH induced in rats using high-fat diet ( HFD ) and 30 mg/kg streptozotocin ( STZ ) .
Diosmin was administered orally at dose of 100 mg/kg for 8 weeks .
Stained tissue sections were examined for histopathological signs of NASH , collagen deposition , and alpha smooth muscle actin ( @ @ @ @ @ @ @ insulin resistance , dyslipidemia , inflammation , and fibrosis markers were assessed .
HFD/STZ successfully induced different NASH features such as insulin resistance seen by elevated fasting blood glucose levels and homeostasis model assessment for insulin resistance .
Moreover , induced rats demonstrated dyslipidemia , a significant elevation in tumor necrosis factor alpha ( TNF-α ) and interleukin-6 levels , and an imbalance in the oxidative status of the liver .
Those events altogether precipitated initiation of liver fibrosis as confirmed by elevated transforming growth factor beta ( TGF-β ) levels .
Treatment @ @ @ @ @ @ @ it significantly ameliorated histopathological NASH findings , lowered TNF-α , interleukin-6 , and malondialdehyde levels , improved lipid and glucose metabolism , and lowered hepatic TGF-β , α-SMA , and collagen content compared to untreated rats .
The present study representsa drug repositioning scenario as diosmin is widely used for management of blood vessel disorders and is known to be well tolerated .
This encourages the extension of our study to the clinical setting to explore diosmin effects in NASH patients .

Non-alcoholic steatohepatitis (NASH) is becoming of increasing significance due to its growing global prevalence and risk of progression to end-stage liver disease. This study was carried out to investigate the potential anti-inflammatory, insulin sensitizing, and antifibrotic effects of diosmin in an experimental model of NASH induced in rats using high-fat diet (HFD) and 30 mg/kg streptozotocin (STZ). Diosmin was administered orally at dose of 100 mg/kg for 8 weeks. Stained tissue sections were examined for histopathological signs of NASH, collagen deposition, and alpha smooth muscle actin (α-SMA) expression. In addition, insulin resistance, dyslipidemia, inflammation, and fibrosis markers were assessed. HFD/STZ successfully induced different NASH features such as insulin resistance seen by elevated fasting blood glucose levels and homeostasis model assessment for insulin resistance. Moreover, induced rats demonstrated dyslipidemia, a significant elevation in tumor necrosis factor alpha (TNF-α) and interleukin-6 levels, and an imbalance in the oxidative status of the liver. Those events altogether precipitated initiation of liver fibrosis as confirmed by elevated transforming growth factor beta (TGF-β) levels. Treatment with diosmin demonstrated multiple beneficial effects as it significantly ameliorated histopathological NASH findings, lowered TNF-α, interleukin-6, and malondialdehyde levels, improved lipid and glucose metabolism, and lowered hepatic TGF-β, α-SMA, and collagen content compared to untreated rats. The present study representsa drug repositioning scenario as diosmin is widely used for management of blood vessel disorders and is known to be well tolerated. This encourages the extension of our study to the clinical setting to explore diosmin effects in NASH patients.


greenmedinfo--2020-10-10--Hesperetin promotes cisplatin-induced apoptosis of gastric cancer.

As one of the most common malignant gastrointestinal tumors , gastric cancer ( GC ) has a high incidence and poor prognosis .
Cisplatin ( DDP ) is often used as chemotherapy for advanced GC ; however , the high incidence of drug resistance remains a problem .
The use of several anti-tumor drugs as combined chemotherapy is an effective strategy .
Hesperetin has anti-tumor abilityits pro-apoptotic effect on various human cancers , bothand , with no significant toxicity .
However , a combination of DDP and hesperetin in GC has not been reported .
The present study aimed to @ @ @ @ @ @ @ DDP-induced apoptosis of GC .
The proliferation of GC ty -60cells was inhibited significantly in a time and dose-dependent manner by combined treatment of DDP with hesperetin .
Hesperetin markedly increased DDP-induced apoptosis of GC cell lines .
In a xenograft tumor mouse model , markedly better tumor suppression was observed after treatment with DDP plus hesperetin compared with that of either agent alone .
Additionally , the combination of DDP and hesperetin remarkably increased the expression levels of phosphatase and tensin homolog ( PTEN ) and Cytochrome C ( Cyt C ) @ @ @ @ @ @ @ phosphorylated protein kinase B ( p-AKT ) and CyclinD1 .
DDP and hesperetin also induced significant increases in apoptosis inducing factor ( AIF ) , BCL2 associated X , apoptosis regulator ( BAX ) , cleaved caspase-9 , and cleaved caspase-3 , and decreased B-cell lymphoma 2 ( BCL2 ) , caspase-9 , and caspase-3 levels .
Thus , we demonstrated that hesperetin could inhibit the phosphatidylinositol-4,5-bisphosphate 3-kinase ( PI3K ) /AKT signaling pathway and induce the mitochondrial pathwayupregulating PTEN expression , thereby significantly enhancing DDP 's anti-tumor effect on GC .
Hesperetin @ @ @ @ @ @ @ and merits further clinical investigation .

As one of the most common malignant gastrointestinal tumors, gastric cancer (GC) has a high incidence and poor prognosis. Cisplatin (DDP) is often used as chemotherapy for advanced GC; however, the high incidence of drug resistance remains a problem. The use of several anti-tumor drugs as combined chemotherapy is an effective strategy. Hesperetin has anti-tumor abilityits pro-apoptotic effect on various human cancers, bothand, with no significant toxicity. However, a combination of DDP and hesperetin in GC has not been reported. The present study aimed to investigate theandchemosensitization effect and mechanism of hesperetin-augmented DDP-induced apoptosis of GC. The proliferation of GC ty -60cells was inhibited significantly in a time and dose-dependent manner by combined treatment of DDP with hesperetin. Hesperetin markedly increased DDP-induced apoptosis of GC cell lines. In a xenograft tumor mouse model, markedly better tumor suppression was observed after treatment with DDP plus hesperetin compared with that of either agent alone. Additionally, the combination of DDP and hesperetin remarkably increased the expression levels of phosphatase and tensin homolog (PTEN) and Cytochrome C (Cyt C), and significantly decreased the levels of phosphorylated protein kinase B (p-AKT) and CyclinD1. DDP and hesperetin also induced significant increases in apoptosis inducing factor (AIF), BCL2 associated X, apoptosis regulator (BAX), cleaved caspase-9, and cleaved caspase-3, and decreased B-cell lymphoma 2 (BCL2), caspase-9, and caspase-3 levels. Thus, we demonstrated that hesperetin could inhibit the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/AKT signaling pathway and induce the mitochondrial pathwayupregulating PTEN expression, thereby significantly enhancing DDP's anti-tumor effect on GC. Hesperetin is a potential chemotherapeutic agent for GC and merits further clinical investigation.


greenmedinfo--2020-10-10--Origanum Syriacum essential oils have an antimicrobial activity.

This research has several purposes : First to assess the bacterial and fungal minimum inhibitory concentration of Origanum Syriacum essential @ @ @ @ @ its bactericidal and fungicidal minimal concentration against S. aureus , S. mutans , and C. @ @ @ @ @ .
The third purpose is to look at the influence of three different soils ( @ @ @ @ @ ) on the essential oils composition .
Three essential oils were extracted by hydro-distillation from @ @ @ @ @ origins .
Bioassays were conducted using a broth microdilution methods .
Gas Chromatography analysis was @ @ @ @ @ of most components in each essential oil .
Post hoc tests assessed antimicrobial effects between @ @ @ @ @ correlated the different components and their antimicrobial efficiency ( α

This research has several purposes: First to assess the bacterial and fungal minimum inhibitory concentration of Origanum Syriacum essential oil. Second to quantify its bactericidal and fungicidal minimal concentration against S. aureus, S. mutans, and C. albicans found in denture stomatitis. The third purpose is to look at the influence of three different soils (Annaya, Bhanin and Michrif) on the essential oils composition. Three essential oils were extracted by hydro-distillation from three different Origanum Syriacum plant origins. Bioassays were conducted using a broth microdilution methods. Gas Chromatography analysis was used to calculate the abundance of most components in each essential oil. Post hoc tests assessed antimicrobial effects between ecotypes while Pearson's test correlated the different components and their antimicrobial efficiency (α < 0.05). All tested essential oils were efficient against all microorganisms. Origanum Syriacum essential oils derived from Annaya and Bhanin soils showed a superior antimicrobial activity compared to the Michrif one. The most abundant component and most efficient among all essential oils constituents was carvacrol. It can be concluded that Origanum Syriacum essential oils have an antimicrobial activity, which depends on the ecotype, its origin and its composition. They might be used to start a clinical trial for the treatment of denture stomatitis.


greenmedinfo--2020-10-10--Origanum vulgare essential oil is an effective counteractive treatment against cypermethrin-induced

Origanum vulgare essential oil is an effective counteractive treatment against cypermethrin-induced damage in exposed common carp.

The study was designed to evaluate the possible protective roles of dietary Origanum vulgare essential oil ( OVEO ) against cypermethrin ( CP ) -induced serum biochemical changes and oxidative stress of common carp ( Cyprinus carpio ) .
Moreover , histopathological alterations , apoptosis , cell proliferation , and DNA damage in the gills and hepatic tissues were also assessed .
Briefly , fish were allotted into six groups with three triplicates whereas a group fed on basal diet and did not exposed to CP and served as control ( CTR ) , two groups were fed on diets @ @ @ @ @ @ @ 0.5 % and 1.0 % ) , a group exposed to sub-lethal concentration of CP ( 1/10 of 96 h-LC= 0.4134μg/L ) , and two other groups exposed to the same concentration of CP and fed on diets supplemented with both levels of OVEO ( CP + 0.5 % OVEO , and CP + 1.0 % OVEO ) , respectively , for 30 days .
CP induced significant elevation of serum alanine transaminase ( ALT ) , aspartate transaminase ( AST ) , alkalinephosphatase ( ALP ) , urea , and creatinine levels @ @ @ @ @ @ @ ) .
Besides , there was a significant decrease in serum catalase ( CAT ) and superoxide dismutase ( SOD ) activities ( P < 0.05 ) .
Moreover , CP induced significant histopathologic alterations in gills , anterior kidneys , and hepatic tissues with activation of apoptosis ( Caspase-3 ) and proliferating cell nuclear antigen ( PCNA ) .
Comet assay demonstrated significant DNA damage in gills and liver tissues of the CP-exposed group .
Interestingly , a significant attenuation of serum ALT , AST , ALP , urea , creatinine , @ @ @ @ @ @ @ < 0.05 ) was noticed in CP-exposed fish and concurrently fed diets supplemented with either 0.5 % or 1.0 % OVEO .
Moreover , histopathologic alterations and apoptosis were significantly reduced along with a concomitant significant decrease in DNA damage ( P < 0.05 ) which indicated the mitigation of DNA damage .
Conclusively , the study showed that OVEO is an effective counteractive treatment against CP-induced damage in exposed common carp and is recommended during the formulation of fish rations .

The study was designed to evaluate the possible protective roles of dietary Origanum vulgare essential oil (OVEO) against cypermethrin (CP)-induced serum biochemical changes and oxidative stress of common carp (Cyprinus carpio). Moreover, histopathological alterations, apoptosis, cell proliferation, and DNA damage in the gills and hepatic tissues were also assessed. Briefly, fish were allotted into six groups with three triplicates whereas a group fed on basal diet and did not exposed to CP and served as control (CTR), two groups were fed on diets supplemented with two levels of OVEO (0.5 % and 1.0 %), a group exposed to sub-lethal concentration of CP (1/10 of 96 h-LC= 0.4134μg/L), and two other groups exposed to the same concentration of CP and fed on diets supplemented with both levels of OVEO (CP + 0.5 % OVEO, and CP + 1.0 % OVEO), respectively, for 30 days. CP induced significant elevation of serum alanine transaminase (ALT), aspartate transaminase (AST), alkalinephosphatase (ALP), urea, and creatinine levels indicating hepato-renal toxicity (P<0.05). Besides, there was a significant decrease in serum catalase (CAT) and superoxide dismutase (SOD) activities (P<0.05). Moreover, CP induced significant histopathologic alterations in gills, anterior kidneys, and hepatic tissues with activation of apoptosis (Caspase-3) and proliferating cell nuclear antigen (PCNA). Comet assay demonstrated significant DNA damage in gills and liver tissues of the CP-exposed group. Interestingly, a significant attenuation of serum ALT, AST, ALP, urea, creatinine, CAT, and SOD levels (P<0.05) was noticed in CP-exposed fish and concurrently fed diets supplemented with either 0.5 % or 1.0 % OVEO. Moreover, histopathologic alterations and apoptosis were significantly reduced along with a concomitant significant decrease in DNA damage (P<0.05) which indicated the mitigation of DNA damage. Conclusively, the study showed that OVEO is an effective counteractive treatment against CP-induced damage in exposed common carp and is recommended during the formulation of fish rations.