greenmedinfo--2020-06-27--Nobiletin prevents against acute liver injury.

Acute liver injury resulting from several factors such as medication , food toxin and herbal supplementation , often leads to a severe health condition and difficult treatment , thereby prevention of acute liver injury remains a critical issue and is of great importance .
In this study , we investigated the preventive effects of nobiletin ( NOB ) on a mouse model of concanavalin A ( ConA ) -induced acute liver injury .
We observed that NOB ( 10 mg/kg ) pretreatment of ConA treated mice significantly lowered the levels of liver enzymes including alanine aminotransferase ( ALT ) and @ @ @ @ @ @ @ the intracellular generation of reactive oxygen species ( ROS ) and suppressed the release of inflammatory cytokines such as tumor necrosis factor-α ( TNF-α ) and interferon-γ ( IFN-γ ) .
Pathological data suggested that pretreatment with NOB ameliorated ConA-induced liver damage through promoting proliferation and alleviating apoptosis of hepatocytes .
Furthermore , significant suppression of c-Jun activating kinase ( JNK ) signal was also observed in NOB-pretreated liver tissues compared with that of ConA treatment only .
In addition , in vitro mechanism study confirmed that addition of NOB protected hepatocytes via @ @ @ @ @ @ @ alleviation of JNK-induced apoptosis of hepatocytes is correlated with NOB protection in acute liver injury .

Acute liver injury resulting from several factors such as medication, food toxin and herbal supplementation, often leads to a severe health condition and difficult treatment, thereby prevention of acute liver injury remains a critical issue and is of great importance. In this study, we investigated the preventive effects of nobiletin (NOB) on a mouse model of concanavalin A (ConA)-induced acute liver injury. We observed that NOB (10 mg/kg) pretreatment of ConA treated mice significantly lowered the levels of liver enzymes including alanine aminotransferase (ALT) and aspartate aminotransferase (AST), decreased the intracellular generation of reactive oxygen species (ROS) and suppressed the release of inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). Pathological data suggested that pretreatment with NOB ameliorated ConA-induced liver damage through promoting proliferation and alleviating apoptosis of hepatocytes. Furthermore, significant suppression of c-Jun activating kinase (JNK) signal was also observed in NOB-pretreated liver tissues compared with that of ConA treatment only. In addition, in vitro mechanism study confirmed that addition of NOB protected hepatocytes via inhibition of JNK activation, manifested that alleviation of JNK-induced apoptosis of hepatocytes is correlated with NOB protection in acute liver injury.


greenmedinfo--2020-06-27--Tangeretin may be a potential natural compound that targets breast cancer cells and cancer stem cell

Tangeretin may be a potential natural compound that targets breast cancer cells and cancer stem cells.

Breast cancer stem cells ( BCSCs ) are responsible for tumor chemoresistance and recurrence .
Targeting CSCs using natural compounds @ @ @ @ @ cancer therapy .
A CSC-inhibiting compound was purified from citrus extracts using silica gel , @ @ @ @ @ chromatography .
The purified compound was identified as tangeretin by using nuclear magnetic resonance ( @ @ @ @ @ cell proliferation , CSC formation and tumor growth , and modestly induced apoptosis in CSCs @ @ @ @ @ subpopulation with a CSC phenotype ( CD44/CD24 ) was reduced by tangeretin .
Tangeretin reduced @ @ @ @ @ nuclear level of signal transducer and activator of transcription 3 ( Stat3 ) .
Our @ @ @ @ @ that tangeretin inhibits the Stat3 signaling pathway and induces CSC death , indicating that tangeretin @ @ @ @ @ compound that targets breast cancer cells and CSCs .

Breast cancer stem cells (BCSCs) are responsible for tumor chemoresistance and recurrence. Targeting CSCs using natural compounds is a novel approach for cancer therapy. A CSC-inhibiting compound was purified from citrus extracts using silica gel, gel filtration and high-pressure liquid chromatography. The purified compound was identified as tangeretin by using nuclear magnetic resonance (NMR). Tangeretin inhibited cell proliferation, CSC formation and tumor growth, and modestly induced apoptosis in CSCs. The frequency of a subpopulation with a CSC phenotype (CD44/CD24) was reduced by tangeretin. Tangeretin reduced the total level and phosphorylated nuclear level of signal transducer and activator of transcription 3 (Stat3). Our results in this study show that tangeretin inhibits the Stat3 signaling pathway and induces CSC death, indicating that tangeretin may be a potential natural compound that targets breast cancer cells and CSCs.


greenmedinfo--2020-06-27--Essential oil from Citrus aurantium alleviates anxiety of patients undergoing coronary angiography.

OBJECTIVE : To determine the effectiveness and safety of essential oil from Citrus aurantium on anxiety in patients undergoing coronary angiography .
METHODS : A single-blind , randomized controlled trial was conducted in 80 patients experiencing coronary angiography in Imam Ali Hospital in Kermanshah , Iran from April to November in 2016 .
All patients were randomly divided into intervention and control groups by a random number table , 40 cases in each group .
The patients in the intervention group inhaled Citrus aurantium essential oil for 15-20 min about 60 min before angiography .
Following the same procedure , @ @ @ @ @ @ @ aurantium in the control group .
Spielbergers State-Trait Anxiety Inventory ( STAI ) was filled in and vital signs including systolic blood pressure ( SBP ) , diastolic blood pressure ( DBP ) , respiratory and pulse rate were recorded before and 20 min after the intervention .
Adverse reactions after intervention were observed .
RESULTS : In the intervention group , the mean scores of STAI , SBP , DBP , respiratory and pulse rate were 53.30± 10.13 , 134.82 ± 11.75 mm Hg , 84.49 ± 6.99 mm Hg , 17.87 @ @ @ @ @ @ @ 12.55 beats/min at baseline and significantly decreased to 42.37 ± 10.15 , 124.49 ± 10.48 mm Hg , 79.23 ± 6.62 mm Hg , 14.54 ± 1.43 times/min , and 70.03 ± 13.66 beats/min respectively 20 min after intervention ( all P < 0.05 ) ; however , in the control group , neither anxiety scores nor vital signs changed significantly ( P > 0.05 ) .
All subjects reported no adverse reactions .
CONCLUSION : Inhalation of the essential oil from Citrus aurantium was effective in reducing anxiety and stress levels in @ @ @ @ @

OBJECTIVE: To determine the effectiveness and safety of essential oil from Citrus aurantium on anxiety in patients undergoing coronary angiography.
METHODS: A single-blind, randomized controlled trial was conducted in 80 patients experiencing coronary angiography in Imam Ali Hospital in Kermanshah, Iran from April to November in 2016. All patients were randomly divided into intervention and control groups by a random number table, 40 cases in each group. The patients in the intervention group inhaled Citrus aurantium essential oil for 15-20 min about 60 min before angiography. Following the same procedure, distilled water was used instead of Citrus aurantium in the control group. Spielbergers State-Trait Anxiety Inventory (STAI) was filled in and vital signs including systolic blood pressure (SBP), diastolic blood pressure (DBP), respiratory and pulse rate were recorded before and 20 min after the intervention. Adverse reactions after intervention were observed.
RESULTS: In the intervention group, the mean scores of STAI, SBP, DBP, respiratory and pulse rate were 53.30± 10.13, 134.82 ± 11.75 mm Hg, 84.49 ± 6.99 mm Hg, 17.87 ± 1.73 times/min, and 76.48 ± 12.55 beats/min at baseline and significantly decreased to 42.37 ± 10.15, 124.49 ± 10.48 mm Hg, 79.23 ± 6.62 mm Hg, 14.54 ± 1.43 times/min, and 70.03 ± 13.66 beats/min respectively 20 min after intervention (all P<0.05); however, in the control group, neither anxiety scores nor vital signs changed significantly (P>0.05). All subjects reported no adverse reactions.
CONCLUSION: Inhalation of the essential oil from Citrus aurantium was effective in reducing anxiety and stress levels in patients undergoing coronary angiography.
TRIAL REGISTRATION: IRCT2016040816797N2 (retrospectively registered on 21 April 2016, https://en.irct.ir/trial/15600).


greenmedinfo--2020-06-27--Dietary immature Citrus unshiu alleviates UVB- induced photoaging.

Ultraviolet ( UV ) irradiation induces physiological and morphological skin damage , resulting in skin dryness , wrinkle formation , @ @ @ @ @ The basement membrane ( BM ) has been shown to play crucial roles in binding @ @ @ @ @ regulating cell differentiation and proliferation , and signaling protein production .
Dietary flavonoids have been @ @ @ @ @ caused by UV exposure .
Immatureis known to contain high concentrations of flavonoids such as @ @ @ @ @ this study , the effects of immaturepowder ( ICP ) on photoaged skin were demonstrated @ @ @ @ @ .
Oral administration of ICP improved loss of skin hydration and increase of transepidermal water @ @ @ @ @ of hairless mice dorsal skin revealed that oral administration of ICP improved UVB-induced overgrowth of @ @ @ @ @ cell mortality and BM destruction .
Therefore , the administration of ICP could improve photoaging @ @ @ @ @ BM .

Ultraviolet (UV) irradiation induces physiological and morphological skin damage, resulting in skin dryness, wrinkle formation, and loss of elasticity. The basement membrane (BM) has been shown to play crucial roles in binding epidermis to dermis tightly, regulating cell differentiation and proliferation, and signaling protein production. Dietary flavonoids have been revealed to improve the damage caused by UV exposure. Immatureis known to contain high concentrations of flavonoids such as hesperidin and narirutin. In this study, the effects of immaturepowder (ICP) on photoaged skin were demonstrated using UVB irradiated hairless mice. Oral administration of ICP improved loss of skin hydration and increase of transepidermal water loss. The histological analyses of hairless mice dorsal skin revealed that oral administration of ICP improved UVB-induced overgrowth of epidermal cell, suppressed epidermal cell mortality and BM destruction. Therefore, the administration of ICP could improve photoaging by protecting the tissues around BM.


greenmedinfo--2020-06-27--Citrus reticulata peel extract ameliorates hepatic steatosis, oxidative stress and inflammation.

Excessive lipid deposition , oxidative stress and inflammation in liver tissues are regarded as crucial inducers of nonalcoholic steatohepatitis ( @ @ @ @ @ the most frequent chronic liver disease and closely related to obesity and insulin resistance .
@ @ @ @ @ preventive and therapeutic effects of Citrus reticulata Blanco ( Jizigan ) peel extract ( JZE @ @ @ @ @ high fat ( HF ) diet and methionine choline-deficient ( MCD ) diet in C57BL/6 @ @ @ @ @ found that daily supplementation of JZE with an HF diet effectively ameliorated glucose tolerance and @ @ @ @ @ , the key indexes of lipid profiles , oxidative stress , hepatic steatosis and inflammatory @ @ @ @ @ both NASH mouse models .
Furthermore , JZE treatment activated nuclear factor erythroid-2-related factor 2 @ @ @ @ @ livers of diet- induced NASH mice .
Our study suggests that JZE might alleviate NASH @ @ @ @ @ signaling and that citrus Jizigan could be used as a dietary therapy for NASH and @ @ @ @

Excessive lipid deposition, oxidative stress and inflammation in liver tissues are regarded as crucial inducers of nonalcoholic steatohepatitis (NASH), which is the most frequent chronic liver disease and closely related to obesity and insulin resistance. In this work, the preventive and therapeutic effects of Citrus reticulata Blanco (Jizigan) peel extract (JZE) on NASH induced by high fat (HF) diet and methionine choline-deficient (MCD) diet in C57BL/6 mice were investigated. We found that daily supplementation of JZE with an HF diet effectively ameliorated glucose tolerance and insulin resistance. In addition, the key indexes of lipid profiles, oxidative stress, hepatic steatosis and inflammatory factors were also ameliorated in both NASH mouse models. Furthermore, JZE treatment activated nuclear factor erythroid-2-related factor 2 (Nrf2) in the livers of diet- induced NASH mice. Our study suggests that JZE might alleviate NASH via the activation of Nrf2 signaling and that citrus Jizigan could be used as a dietary therapy for NASH and related metabolic syndrome.


greenmedinfo--2020-06-27--Nootkatone inhibits acute and chronic inflammatory responses.

Nootkatone ( NTK ) is a sesquiterpenoid found in essential oils of many species of ( Rutaceae ) .
Considering previous reports demonstrating that NTK inhibited inflammatory signaling pathways , this study aimed to investigate the effects of this compound in mice models of acute and chronic inflammation .
Murine models of paw edema induced by carrageenan , dextran , histamine , and arachidonic acid , as well as carrageenan-induced peritonitis and pleurisy , were used to evaluate the effects of NTK on acute inflammation .
A murine model of granuloma induced by cotton pellets was used to access the @ @ @ @ @ @ @ .
In the acute inflammation models , NTK demonstrated antiedematogenic effects and inhibited leukocyte recruitment , which was associated with decreased vascular permeability , inhibition of myeloperoxidase ( MPO ) , interleukin ( IL ) 1-β , and tumor necrosis factor ( TNF ) -α production .
In silico analysis suggest that NTZ anti-inflammatory effects may also occur due to inhibition of cyclooxygenase ( COX ) -2 activity and antagonism of the histamine receptor type 1 ( H ) .
These mechanisms might have contributed to the reduction of granuloma weight and protein @ @ @ @ @ @ @ the chronic inflammation model .
In conclusion , NTK exerted anti-inflammatory effects that are associated with inhibition of IL1-β and TNF-α production , possibly due to inhibition of COX-2 activity and antagonism of the H1 receptor .
However , further studies are required to characterize the effects of this compound on chronic inflammation .

Nootkatone (NTK) is a sesquiterpenoid found in essential oils of many species of(Rutaceae). Considering previous reports demonstrating that NTK inhibited inflammatory signaling pathways, this study aimed to investigate the effects of this compound in mice models of acute and chronic inflammation. Murine models of paw edema induced by carrageenan, dextran, histamine, and arachidonic acid, as well as carrageenan-induced peritonitis and pleurisy, were used to evaluate the effects of NTK on acute inflammation. A murine model of granuloma induced by cotton pellets was used to access the impact of NTK treatment on chronic inflammation. In the acute inflammation models, NTK demonstrated antiedematogenic effects and inhibited leukocyte recruitment, which was associated with decreased vascular permeability, inhibition of myeloperoxidase (MPO), interleukin (IL)1-β, and tumor necrosis factor (TNF)-α production. In silico analysis suggest that NTZ anti-inflammatory effects may also occur due to inhibition of cyclooxygenase (COX)-2 activity and antagonism of the histamine receptor type 1 (H). These mechanisms might have contributed to the reduction of granuloma weight and protein concentration in the homogenates, observed in the chronic inflammation model. In conclusion, NTK exerted anti-inflammatory effects that are associated with inhibition of IL1-β and TNF-α production, possibly due to inhibition of COX-2 activity and antagonism of the H1 receptor. However, further studies are required to characterize the effects of this compound on chronic inflammation.


greenmedinfo--2020-06-27--Tanshinone IIA may reverse depressive-like behaviours in CUMS-exposed mice by regulating RasGRF1.

Tanshinone IIA ( Tan IIA ) is reported to have neuroprotective effects to suppress cell apoptosis of cortical neurons induced by Aβthrough inhibiting oxidative stress .
Nevertheless , few studies have investigated the effects of Tan IIA on depressive disorder .
Here , we aimed to measure the effects of Tan IIA on chronic unpredictable mild stress ( CUMS ) induced mouse model and its underlying mechanism .
For 28 days , mice were subjected to CUMS while Tan IIA was administered once daily at doses of 0 , 1 , 2.5 , 5 , or 10 mg/kg .
CUMS @ @ @ @ @ @ @ by increased immobility time in the forced swim and tail suspension tests , decreased sucrose preference in the sucrosepreference test , and reduced exploratory behavior in the open field test .
All of these behaviors were reversed dose-dependently by Tan IIA treatment .
Oxidative stress was determined by measuring malondialdehyde , glutathione peroxidase , and superoxide dismutase activity and total antioxidant capacity .
Levels of pro-inflammatory factors IL-1β and IL-18 , cAMP response element binding protein and brain derived neurotrophic factor were detected by ELISA and western blot assay , respectively .
The @ @ @ @ @ @ @ and pro-inflammatory factors and decreased levels of cAMP response element binding protein and brain-derived neurotrophic factor .
Tan IIA treatment again reversed these effects .
Importantly , RasGRF1 expression increased in CUMS-exposed mice but decreased after Tan IIA administration .
Using RasGRF1mice to determine the role of RasGRF1 in mice exposed to CUMS , we found that knockdown of RasGRF1 reversed the effects of CUMS on mice , just like Tan IIA .
These results indicate that Tan IIA may reverse depressive-like behaviors in CUMS-exposed mice by regulating RasGRF1 .

Tanshinone IIA (Tan IIA) is reported to have neuroprotective effects to suppress cell apoptosis of cortical neurons induced by Aβthrough inhibiting oxidative stress. Nevertheless, few studies have investigated the effects of Tan IIA on depressive disorder. Here, we aimed to measure the effects of Tan IIA on chronic unpredictable mild stress (CUMS) induced mouse model and its underlying mechanism. For 28 days, mice were subjected to CUMS while Tan IIA was administered once daily at doses of 0, 1, 2.5, 5, or 10 mg/kg. CUMS exposure increased depressive-like behaviors, as indicated by increased immobility time in the forced swim and tail suspension tests, decreased sucrose preference in the sucrosepreference test, and reduced exploratory behavior in the open field test. All of these behaviors were reversed dose-dependently by Tan IIA treatment. Oxidative stress was determined by measuring malondialdehyde, glutathione peroxidase, and superoxide dismutase activity and total antioxidant capacity. Levels of pro-inflammatory factors IL-1β and IL-18, cAMP response element binding protein and brain derived neurotrophic factor were detected by ELISA and western blot assay, respectively. The results showed that CUMS increased oxidative stress and pro-inflammatory factors and decreased levels of cAMP response element binding protein and brain-derived neurotrophic factor. Tan IIA treatment again reversed these effects. Importantly, RasGRF1 expression increased in CUMS-exposed mice but decreased after Tan IIA administration. Using RasGRF1mice to determine the role of RasGRF1 in mice exposed to CUMS, we found that knockdown of RasGRF1 reversed the effects of CUMS on mice, just like Tan IIA. These results indicate that Tan IIA may reverse depressive-like behaviors in CUMS-exposed mice by regulating RasGRF1.


greenmedinfo--2020-06-27--Tanshinone IIA restrained the gastric cancer progression by miR-874/HMGB2/β-catenin signalling in vi

Tanshinone IIA restrained the gastric cancer progression by miR-874/HMGB2/β-catenin signalling in vitro.

Gastric cancer ( GC ) is the second leading cause of cancer-associated deaths worldwide .
Tanshinone IIA ( TSN ) is the pure extract from the root of red-rooted salvia and has been reported to inhibit the progression of GC cells .
In this study , we investigated the microRNA ( miRNA ) mediated gene repression mechanism in TSN-administrated GC condition .
The cell viability of GC was determined by 3- ( 4,5-dimethyl-2-thiazolyl ) -2,5-diphenyl-2-H-tetrazolium bromide ( MTT ) assay .
Cell migration and invasion were detected by transwell assays .
The expression levels of epithelial-mesenchymal transition ( EMT ) @ @ @ @ @ @ @ E-cadherin ) , High-mobility group box proteins 2 ( HMGB2 ) , β-catenin pathway-related proteins ( β-catenin , c-myc , cyclin D1 ) were detected by western blot analysis in TSN/GC .
The expression patterns of miR-874 and HMGB2 in GC were determined by quantitative real-time polymerase chain reaction ( qRT-PCR ) .
The potential miR-874-targeted HMGB2 was searched viabioinformatic methods and identified by dual-luciferase reporter assays , and RNA immunoprecipitation ( RIP ) assays , and RNA Pull-down assays .
Xenograft tumor model was used to evaluate biological function in vivo .
@ @ @ @ @ @ @ invasion , EMT progression in GC , and these results could be inverted by silencing of miR-874 .
Moreover , the putative binding sites between miR-874 and HMGB2 were predicted by starBase software online .
Meanwhile , enforced expression of HMGB2 , negatively correlated with that of miR-874 , reversed the positive effects of TSN administration on cells .
Mechanically , TSN restrained the GC progression by miR-874/HMGB2/β-catenin signaling in vitro .
Additionally , in vivo experiments confirmed that TSN inhibited the GC progression as well .
TSN restrained the GC progression by @ @ @ @ @ @ @ vivo .

Gastric cancer (GC) is the second leading cause of cancer-associated deaths worldwide. Tanshinone IIA (TSN) is the pure extract from the root of red-rooted salvia and has been reported to inhibit the progression of GC cells. In this study, we investigated the microRNA (miRNA) mediated gene repression mechanism in TSN-administrated GC condition. The cell viability of GC was determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Cell migration and invasion were detected by transwell assays. The expression levels of epithelial-mesenchymal transition (EMT)-associated proteins (N-cadherin, vimentin, E-cadherin), High-mobility group box proteins 2 (HMGB2),β-catenin pathway-related proteins (β-catenin, c-myc, cyclin D1) were detected by western blot analysis in TSN/GC. The expression patterns of miR-874 and HMGB2 in GC were determined by quantitative real-time polymerase chain reaction (qRT-PCR). The potential miR-874-targeted HMGB2 was searched viabioinformatic methods and identified by dual-luciferase reporter assays, and RNA immunoprecipitation (RIP) assays, and RNA Pull-down assays. Xenograft tumor model was used to evaluate biological function in vivo. TSN limited the proliferation, migration, invasion, EMT progression in GC, and these results could be inverted by silencing of miR-874. Moreover, the putative binding sites between miR-874 and HMGB2 were predicted by starBase software online. Meanwhile, enforced expression of HMGB2, negatively correlated with that of miR-874, reversed the positive effects of TSN administration on cells. Mechanically, TSN restrained the GC progression by miR-874/HMGB2/β-catenin signaling in vitro. Additionally, in vivo experiments confirmed that TSN inhibited the GC progression as well. TSN restrained the GC progression by regulating miR-874/HMGB2/β-catenin pathways in vitro and in vivo.


greenmedinfo--2020-06-27--Tanshinone IIA had a protective effect on hypoxia-induced cell damage.

BACKGROUND : The aim of the present study was to investigate the protective effects of Tanshinone IIA ( Tan IIA ) on hypoxia induced injury in medial vestibular nucleus ( MVN ) cells .
METHODS : An in vitro hypoxia model was established using MVN cells exposed to hypoxia .
The hypoxia-induced cell damage was confirmed by assessing cell viability , apoptosis and expression of apoptosis-associated proteins .
Oxidative stress and related indicators were also measured following hypoxia modeling and Tan IIA treatment , and the genes potentially involved in the response were predicted using multiple GEO datasets .
RESULTS @ @ @ @ @ @ @ showed that Tan IIA significantly increased cell viability , decreased cell apoptosis and decreased the ratio of Bax/Bcl-2 in hypoxia treated cells .
In addition , hypoxia treatment increased oxidative stress in MVN cells , and treatment with Tan IIA reduced the oxidative stress .
The expression of S-Phase Kinase Associated Protein 2 ( SKP2 ) was upregulated in hypoxia treated cells , and Tan IIA treatment reduced the expression of SKP2 .
Mechanistically , SKP2 interacted with large conductance Ca2+ -activated K+ channels ( BKCa ) , regulating its expression , and @ @ @ @ @ @ @ Tan IIA on hypoxia induced cell apoptosis .
CONCLUSION : The results of the present study suggested that Tan IIA had a protective effect on hypoxia-induced cell damage through its anti-apoptotic and anti-oxidative activity via a SKP2/BKCa axis .
These findings suggest that Tan IIA may be a potential therapeutic for treatment of hypoxia induced vertigo .

BACKGROUND: The aim of the present study was to investigate the protective effects of Tanshinone IIA (Tan IIA) on hypoxia induced injury in medial vestibular nucleus (MVN) cells.
METHODS: An in vitro hypoxia model was established using MVN cells exposed to hypoxia. The hypoxia-induced cell damage was confirmed by assessing cell viability, apoptosis and expression of apoptosis-associated proteins. Oxidative stress and related indicators were also measured following hypoxia modeling and Tan IIA treatment, and the genes potentially involved in the response were predicted using multiple GEO datasets.
RESULTS: The results of the present study showed that Tan IIA significantly increased cell viability, decreased cell apoptosis and decreased the ratio of Bax/Bcl-2 in hypoxia treated cells. In addition, hypoxia treatment increased oxidative stress in MVN cells, and treatment with Tan IIA reduced the oxidative stress. The expression of S-Phase Kinase Associated Protein 2 (SKP2) was upregulated in hypoxia treated cells, and Tan IIA treatment reduced the expression of SKP2. Mechanistically, SKP2 interacted with large conductance Ca2+ -activated K+ channels (BKCa), regulating its expression, and BKCa knockdown alleviated the protective effects of Tan IIA on hypoxia induced cell apoptosis.
CONCLUSION: The results of the present study suggested that Tan IIA had a protective effect on hypoxia-induced cell damage through its anti-apoptotic and anti-oxidative activity via a SKP2/BKCa axis. These findings suggest that Tan IIA may be a potential therapeutic for treatment of hypoxia induced vertigo.


greenmedinfo--2020-06-27--Tanshinone IIA inhibits osteosarcoma growth.

Tanshinone IIA ( Tan IIA ) is a member of the major lipophilic components extracted from the root ofBunge .
Osteosarcomas are primary malignant tumors of bone .
The aim of our study is to explore the role of Tan IIA in osteosarcomas survival , migration , and proliferation .
MG63 osteosarcoma cell line was culturedand treated with different concentrations of Tan IIA .
Then , ELISA , immunofluorescence , qPCR , western blots , and pathway analysis were conducted to verify whether Tan II modulated osteosarcoma survival , migration , and proliferation through the AMPK/Nrf2 signaling pathway .
Our @ @ @ @ @ @ @ MG63 osteosarcoma cell survival , migration , and proliferation .
Mechanistically , Tan IIA reduced cell viability and inhibited the transcriptions of migratory factors .
In addition , the number of proliferative MG63 osteosarcoma cell was also reduced by Tan IIA .
Molecular investigations demonstrated that Tan IIA treatment caused a drop in the transcriptions and activities of AMPK and Nrf2 .
Interestingly , knockdown of AMPK and Nrf2 markedly attenuated MG63 osteosarcoma cell survival , migration , and proliferation .
Altogether , our results indicate that Tan IIA could be used as @ @ @ @ @ @ @ proliferation through affecting its survival , migration , and proliferation .

Tanshinone IIA (Tan IIA) is a member of the major lipophilic components extracted from the root ofBunge. Osteosarcomas are primary malignant tumors of bone. The aim of our study is to explore the role of Tan IIA in osteosarcomas survival, migration, and proliferation. MG63 osteosarcoma cell line was culturedand treated with different concentrations of Tan IIA. Then, ELISA, immunofluorescence, qPCR, western blots, and pathway analysis were conducted to verify whether Tan II modulated osteosarcoma survival, migration, and proliferation through the AMPK/Nrf2 signaling pathway. Our results indicated that Tan IIA dose-dependently inhibited MG63 osteosarcoma cell survival, migration, and proliferation. Mechanistically, Tan IIA reduced cell viability and inhibited the transcriptions of migratory factors. In addition, the number of proliferative MG63 osteosarcoma cell was also reduced by Tan IIA. Molecular investigations demonstrated that Tan IIA treatment caused a drop in the transcriptions and activities of AMPK and Nrf2. Interestingly, knockdown of AMPK and Nrf2 markedly attenuated MG63 osteosarcoma cell survival, migration, and proliferation. Altogether, our results indicate that Tan IIA could be used as an effective anticancer drug to control osteosarcoma proliferation through affecting its survival, migration, and proliferation.


greenmedinfo--2020-06-27--Tanshinone IIA suppresses proliferation and inflammatory cytokine production of synovial fibroblasts

Tanshinone IIA suppresses proliferation and inflammatory cytokine production of synovial fibroblasts from rheumatoid arthritis patients.

Rheumatoid arthritis ( RA ) is a chronic and progressive autoimmune disease in which activated RA fibroblast-1ike synoviocytes ( RA-FLSs ) are one of the main factors responsible for inducing morbidity .
Previous reports have shown that RA-FLSs have proliferative features similar to cancer cells , in addition to causing cartilage erosion that eventually causes joint damage .
Thus , new therapeutic strategies and drugs that can effectively contain the abnormal hyperplasia of RA-FLSs and restrain RA development are necessary for the treatment of RA .
Tanshinone IIA ( Tan IIA ) , one of the main phytochemicals isolated fromBunge @ @ @ @ @ @ @ and inhibiting arthritis in an AIA mouse model .
In addition , RA patients treated at our clinic with Tan IIA showed significant improvements in their clinical symptoms .
However , the details of the molecular mechanism by which Tan IIA effects RA are unknown .
To clarify this mechanism , we evaluated the antiproliferative and inhibitory effects of proinflammatory factor production caused by Tan IIA to RA-FLSs .
We demonstrated that Tan IIA can restrict the proliferation , migration , and invasion of RA-FLSs in a time- and dose-dependent manner .
Moreover @ @ @ @ @ @ @ in mRNA expression of some matrix metalloproteinases and proinflammatory factors induced by TNF-α in RA-FLSs , resulting in inflammatory reactivity inhibition and blocking the destruction of the knee joint .
Through the integration of network pharmacology analyses with the experimental data obtained , it is revealed that the effects of Tan IIA on RA can be attributed to its influence on different signaling pathways , including MAPK , AKT/mTOR , HIF-1 , and NF-kB .
Taken together , these data suggest that the compound Tan IIA has great therapeutic potential for RA treatment @

Rheumatoid arthritis (RA) is a chronic and progressive autoimmune disease in which activated RA fibroblast-1ike synoviocytes (RA-FLSs) are one of the main factors responsible for inducing morbidity. Previous reports have shown that RA-FLSs have proliferative features similar to cancer cells, in addition to causing cartilage erosion that eventually causes joint damage. Thus, new therapeutic strategies and drugs that can effectively contain the abnormal hyperplasia of RA-FLSs and restrain RA development are necessary for the treatment of RA. Tanshinone IIA (Tan IIA), one of the main phytochemicals isolated fromBunge, is capable of promoting RA-FLS apoptosis and inhibiting arthritis in an AIA mouse model. In addition, RA patients treated at our clinic with Tan IIA showed significant improvements in their clinical symptoms. However, the details of the molecular mechanism by which Tan IIA effects RA are unknown. To clarify this mechanism, we evaluated the antiproliferative and inhibitory effects of proinflammatory factor production caused by Tan IIA to RA-FLSs. We demonstrated that Tan IIA can restrict the proliferation, migration, and invasion of RA-FLSs in a time- and dose-dependent manner. Moreover, Tan IIA effectively suppressed the increase in mRNA expression of some matrix metalloproteinases and proinflammatory factors induced by TNF-α in RA-FLSs, resulting in inflammatory reactivity inhibition and blocking the destruction of the knee joint. Through the integration of network pharmacology analyses with the experimental data obtained, it is revealed that the effects of Tan IIA on RA can be attributed to its influence on different signaling pathways, including MAPK, AKT/mTOR, HIF-1, and NF-kB. Taken together, these data suggest that the compound Tan IIA has great therapeutic potential for RA treatment.


greenmedinfo--2020-06-27--Tanshinone IIA alleviates brain damage in a mouse model of neuromyelitis optica spectrum disorder.

BACKGROUND : Neuromyelitis optica spectrum disorder ( NMOSD ) , an autoimmune astrocytopathic disease associated with the anti-aquaporin-4 ( AQP4 ) antibody , is characterized by extensive necrotic lesions primarily located on the optic nerves and spinal cord .
Tanshinone IIA ( TSA ) , an active natural compound extracted from Salvia miltiorrhiza Bunge , has profound immunosuppressive effects on neutrophils .
OBJECTIVE : The present study aimed to evaluate the effect of TSA on NMOSD mice and explore the underlying mechanisms .
Mice were initially administered TSA ( pre-TSA group , n = 20 ) or vehicle ( vehicle @ @ @ @ @ @ @ 8 h for 3 days , and then NMOSD model was induced by intracerebral injection of NMOSD-immunoglobulin G ( NMO-IgG ) and human complement ( hC ) .
In addition , post-TSA mice ( n = 10 ) were administered equal dose of TSA at 8 h and 16 h after model induction .
At 24 h after intracerebral injection , histological analysis was performed to assess the inhibitory effects of TSA on astrocyte damage , demyelination , and neuroinflammation in NMOSD mice , and western blotting was conducted to clarify the effect @ @ @ @ @ @ @ signaling pathways .
Furthermore , flow cytometry and western blottingwere conducted to verify the proapoptotic effects of TSA on neutrophils in vitro .
RESULTS : There was a profound reduction in astrocyte damage and demyelination in the pre-TSA group and post-TSA group .
However , prophylactic administration of TSA induced a better effect than therapeutic treatment .
The number of infiltrated neutrophils was also decreased in the lesions of NMOSD mice that were pretreated with TSA .
We confirmed that prophylactic administration of TSA significantly promoted neutrophil apoptosis in NMOSD lesions in vivo @ @ @ @ @ @ @ by modulating the caspase pathway in the presence of inflammatory stimuli in vitro .
In addition , TSA restricted activation of the NF-κB signaling pathway in vivo .
CONCLUSION : Our data provide evidence that TSA can act as a prophylactic agent that reduces NMO-IgG-induced damage in the mouse brain by enhancing the resolution of inflammation by inducing neutrophil apoptosis , and TSA may serve as a promising therapeutic agent for neutrophil-associated inflammatory disorders , such as NMOSD .

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD), an autoimmune astrocytopathic disease associated with the anti-aquaporin-4 (AQP4) antibody, is characterized by extensive necrotic lesions primarily located on the optic nerves and spinal cord. Tanshinone IIA (TSA), an active natural compound extracted from Salvia miltiorrhiza Bunge, has profound immunosuppressive effects on neutrophils.
OBJECTIVE: The present study aimed to evaluate the effect of TSA on NMOSD mice and explore the underlying mechanisms. Mice were initially administered TSA (pre-TSA group, n = 20) or vehicle (vehicle group, n = 20) every 8 h for 3 days, and then NMOSD model was induced by intracerebral injection of NMOSD-immunoglobulin G (NMO-IgG) and human complement (hC). In addition, post-TSA mice (n = 10) were administered equal dose of TSA at 8 h and 16 h after model induction. At 24 h after intracerebral injection, histological analysis was performed to assess the inhibitory effects of TSA on astrocyte damage, demyelination, and neuroinflammation in NMOSD mice, and western blotting was conducted to clarify the effect of TSA on the NF-κB and MAPK signaling pathways. Furthermore, flow cytometry and western blottingwere conducted to verify the proapoptotic effects of TSA on neutrophils in vitro.
RESULTS: There was a profound reduction in astrocyte damage and demyelination in the pre-TSA group and post-TSA group. However, prophylactic administration of TSA induced a better effect than therapeutic treatment. The number of infiltrated neutrophils was also decreased in the lesions of NMOSD mice that were pretreated with TSA. We confirmed that prophylactic administration of TSA significantly promoted neutrophil apoptosis in NMOSD lesions in vivo, and this proapoptotic effect was mediated by modulating the caspase pathway in the presence of inflammatory stimuli in vitro. In addition, TSA restricted activation of the NF-κB signaling pathway in vivo.
CONCLUSION: Our data provide evidence that TSA can act as a prophylactic agent that reduces NMO-IgG-induced damage in the mouse brain by enhancing the resolution of inflammation by inducing neutrophil apoptosis, and TSA may serve as a promising therapeutic agent for neutrophil-associated inflammatory disorders, such as NMOSD.


greenmedinfo--2020-06-27--The present study revealed rutin administration prevents the progression of diabetic nephropathy and

The present study revealed rutin administration prevents the progression of diabetic nephropathy and cardiomyopathy.

Diabetic nephropathy and cardiomyopathy are two major causes of mortality among patients with diabetes mellitus ( DM ) .
Since current diabetic medications are associated with various side effects , the naturally occurring plant-derived compounds are in demand .
Bioflavonoids originating from vegetables and medicinal plants have beneficial effects on diabetes by improving glycemic control , lipid metabolism , and anti-oxidant status .
The present study is focused on the effect of rutin against alloxan induced diabetic nephropathy and cardiomyopathy .
Male albino Wistar rats were divided into four groups , each of six rats .
Group I control rats @ @ @ @ @ @ @ dose intraperitoneally .
Group II rats were induced diabetes with a single dose of alloxan monohydrate ( 150 mg/kg body weight in 0.9 % saline ) intraperitoneally .
Group III rats received 0.28 M of NHCl in drinking water for 3 days for the experimental induction of metabolic acidosis .
Group IV rats were injected with a single dose of alloxan monohydrate ( 150 mg/kg bodyweight ) and administered rutin hydrate ( 100 mg/kg ) for a period of 4 weeks by oral gavage .
Administration of rutin prevented urinary ketone body formation @ @ @ @ @ @ @ in alloxan induced diabetic rats .
Rutin supplementation reduced the levels of serum triglycerides and cholesterol in diabetic rats .
Gene expression profiling of metabolic acidosis related genes ( AQP2 , AQP3 and V2R ) and also histopathological resultsdemonstrated the protective effect of rutin against diabetic ketoacidodis and fibrosis .
The results of the present study revealed rutin administration prevents the progression of diabetic nephropathy and cardiomyopathy through amelioration of fibrosis and metabolic acidosis .

Diabetic nephropathy and cardiomyopathy are two major causes of mortality among patients with diabetes mellitus (DM). Since current diabetic medications are associated with various side effects, the naturally occurring plant-derived compounds are in demand. Bioflavonoids originating from vegetables and medicinal plants have beneficial effects on diabetes by improving glycemic control, lipid metabolism, and anti-oxidant status. The present study is focused on the effect of rutin against alloxan induced diabetic nephropathy and cardiomyopathy. Male albino Wistar rats were divided into four groups, each of six rats. Group I control rats received 0.9% saline as a single dose intraperitoneally. Group II rats were induced diabetes with a single dose of alloxan monohydrate (150 mg/kg body weight in 0.9% saline) intraperitoneally. Group III rats received 0.28 M of NHCl in drinking water for 3 days for the experimental induction of metabolic acidosis. Group IV rats were injected with a single dose of alloxan monohydrate (150 mg/kg bodyweight) and administered rutin hydrate (100 mg/kg) for a period of 4 weeks by oral gavage. Administration of rutin prevented urinary ketone body formation and decreased serum creatinine and urea levels in alloxan induced diabetic rats. Rutin supplementation reduced the levels of serum triglycerides and cholesterol in diabetic rats. Gene expression profiling of metabolic acidosis related genes (AQP2, AQP3 and V2R) and also histopathological resultsdemonstrated the protective effect of rutin against diabetic ketoacidodis and fibrosis. The results of the present study revealed rutin administration prevents the progression of diabetic nephropathy and cardiomyopathy through amelioration of fibrosis and metabolic acidosis.


greenmedinfo--2020-06-27--Effects of endurance exercise and Urtica dioica on the functional, histological and molecular aspect

Effects of endurance exercise and Urtica dioica on the functional, histological and molecular aspects of the hippocampus in STZ-induced diabetes.

ETHNOPHARMACOLOGICAL RELEVANCE : Many body systems and organs , including the hippocampus , are affected by diabetes , and undergo changes that may increase the risk of cognitive decline .
Urtica dioica ( UD ) has long been recognized as a medicinal plant with beneficial effects on blood glucose control in diabetes .
AIM OF THE STUDY : The present study aimed to investigate the effect of endurance exercise ( Ex ) , along with Urtica dioica ( UD ) hydro-alcoholic extract on some functional , histological , and molecular aspects of the hippocampus in streptozotocin ( STZ ) -induced @ @ @ @ @ @ @ 60 male Wistar rats were divided into five groups ( N = 12 ) : healthy control ( H-C ) , diabetes control ( D-C ) , diabetes exercise ( D-Ex ) , diabetes Urtica dioica ( D-UD ) , and diabetes exercise Urtica dioica ( D-Ex-UD ) .
Diabetes was induced intraperitoneally by STZ ( 45 mg/kg ) injection .
Two weeks after the injection by STZ , Ex ( moderate intensity/5day/week ) and gavage of UD extract ( 50mg/kg/day ) was performed for six weeks .
Cognitive functions were evaluated by @ @ @ @ @ @ @ histological examination , and molecular studies were done via Hematoxylin & Eosin stain , and Western blot .
RESULTS : Diabetic rats showed spatial learning and memory deficits , as well as negatively affects to the tissue and structure of the hippocampus in the dentate gyrus ( DG ) and cornu ammonis ( CA ) areas .
Ex + UD treatment caused a decrease of neural disorganization , an increase of neural-microglial density , and thickness of the pyramidal-molecular layer in the hippocampus .
In addition , Ex + UD caused a rise @ @ @ @ @ @ @ of CAP-1 protein levels , improved hippocampal structure , and improved learning and memory function .
CONCLUSIONS : These results show that Ex , along with the UD extract , may decrease levels of the central neural complications of diabetes .
Given the importance of recognizing non-pharmacological complementary therapies in this field , future studies are warranted .

ETHNOPHARMACOLOGICAL RELEVANCE: Many body systems and organs, including the hippocampus, are affected by diabetes, and undergo changes that may increase the risk of cognitive decline. Urtica dioica (UD) has long been recognized as a medicinal plant with beneficial effects on blood glucose control in diabetes.
AIM OF THE STUDY: The present study aimed to investigate the effect of endurance exercise (Ex), along with Urtica dioica (UD) hydro-alcoholic extract on some functional, histological, and molecular aspects of the hippocampus in streptozotocin (STZ)-induced diabetic rats.
MATERIALS AND METHODS: 60 male Wistar rats were divided into five groups (N = 12): healthy control (H-C), diabetes control (D-C), diabetes exercise (D-Ex), diabetes Urtica dioica (D-UD), and diabetes exercise Urtica dioica (D-Ex-UD). Diabetes was induced intraperitoneally by STZ (45 mg/kg) injection. Two weeks after the injection by STZ, Ex (moderate intensity/5day/week) and gavage of UD extract (50mg/kg/day) was performed for six weeks. Cognitive functions were evaluated by the Morris Water Maze test, routine histological examination, and molecular studies were done via Hematoxylin&Eosin stain, and Western blot.
RESULTS: Diabetic rats showed spatial learning and memory deficits, as well as negatively affects to the tissue and structure of the hippocampus in the dentate gyrus (DG) and cornu ammonis (CA) areas. Ex + UD treatment caused a decrease of neural disorganization, an increase of neural-microglial density, and thickness of the pyramidal-molecular layer in the hippocampus. In addition, Ex + UD caused a rise of GAP-43 protein levels, a reduction of CAP-1 protein levels, improved hippocampal structure, and improved learning and memory function.
CONCLUSIONS: These results show that Ex, along with the UD extract, may decrease levels of the central neural complications of diabetes. Given the importance of recognizing non-pharmacological complementary therapies in this field, future studies are warranted.


greenmedinfo--2020-06-27--U. dioica vegetable protects against diet induced obesity.

The shoot ofis used in several cultures as a vegetable or herb .
However , not much has been studied about the potential of this plant when consumed as a whole food/vegetable rather than an extract for dietary supplements .
In a 12-week dietary intervention study , we tested the effect ofvegetable on high fat diet induced obesity and insulin resistance in C57BL/6J mice .
Mice were fed ad libitum with isocaloric diets containing 10 % fat or 45 % fat with or without .
The diet supplemented withattenuated high fat diet induced weight gain ( < 0.005 ; = @ @ @ @ @ @ @ tissue ( < 0.005 ; = 9 ) , and whole-body insulin resistance ( HOMA-IR index ) ( < 0.001 ; = 9 ) .
Analysis of gene expression in skeletal muscle showed no effect on the constituents of the insulin signaling pathway ( AKT , IRS proteins , PI3K , GLUT4 , and insulin receptor ) .
Notable genes that impact lipid or glucose metabolism and whose expression was changed byinclude fasting induced adipocyte factor ( FIAF ) in adipose and skeletal muscle , peroxisome proliferator-activated receptor-α ( Ppar-α ) and forkhead @ @ @ @ @ @ @ and liver , and Carnitine palmitoyltransferase I ( Cpt1 ) in liver ( < 0.01 ) .
We conclude thatvegetable protects against diet induced obesity through mechanisms involving lipid accumulation and glucose metabolism in skeletal muscle , liver , and adipose tissue .

The shoot ofis used in several cultures as a vegetable or herb. However, not much has been studied about the potential of this plant when consumed as a whole food/vegetable rather than an extract for dietary supplements. In a 12-week dietary intervention study, we tested the effect ofvegetable on high fat diet induced obesity and insulin resistance in C57BL/6J mice. Mice were fed ad libitum with isocaloric diets containing 10% fat or 45% fat with or without. The diet supplemented withattenuated high fat diet induced weight gain (<0.005;= 9), fat accumulation in adipose tissue (<0.005;= 9), and whole-body insulin resistance (HOMA-IR index) (<0.001;= 9). Analysis of gene expression in skeletal muscle showed no effect on the constituents of the insulin signaling pathway (AKT, IRS proteins, PI3K, GLUT4, and insulin receptor). Notable genes that impact lipid or glucose metabolism and whose expression was changed byinclude fasting induced adipocyte factor (FIAF) in adipose and skeletal muscle, peroxisome proliferator-activated receptor-α (Ppar-α) and forkhead box protein (FOXO1) in muscle and liver, and Carnitine palmitoyltransferase I (Cpt1) in liver (<0.01). We conclude thatvegetable protects against diet induced obesity through mechanisms involving lipid accumulation and glucose metabolism in skeletal muscle, liver, and adipose tissue.


greenmedinfo--2020-06-27--Ameliorative effect of cotreatment with the methanolic leaf extract of Urtica dioica on acute kidney

Ameliorative effect of cotreatment with the methanolic leaf extract of Urtica dioica on acute kidney injury induced by gentamicin.

Objective : Effects of cotreatment with ( UD ) methanolic leaf extract on gentamicin ( GM ) -induced acute kidney injury were evaluated in rats .
Materials and Methods : Male Wistar rats ( n=32 ) were separated into four groups .
Gentamicin ( 100 mg/kg/day , IP ) was injected for eight days with or without UD methanolic extract ( 200 mg/kg/day , gavage ) .
The renal blood flow ( RBF ) and systolic blood pressure of rats were recorded .
Concentration of creatinine , blood urea nitrogen ( BUN ) , sodium , and potassium and osmolarity @ @ @ @ @ @ @ samples .
Oxidative stress level was determined by assessment of the levels of antioxidant power ( FRAP ) and lipid peroxidation ( MDA ) in the renal tissue .
The renal injury and histopathological changes in the kidney were determined by microscopic evaluations .
Results : Administration of UD extract along with GM , compared to GM group , significantly decreased the amounts of plasma creatinine and BUN , urinary sodium excretion , fractional excretion of sodium and potassium , and MDA levels but significantly increased creatinine clearance , urine osmolarity , renal @ @ @ @ @ @ @ : The cotreatment of UD extract can attenuate renal injury of GM by reduction of oxidative stress , lipid peroxidation , and oxygen free radicals .
The potential nephroprotective effects of UD extract are probably mediated via its antioxidant and anti-inflammatory activity .

Objective: Effects of cotreatment with(UD) methanolic leaf extract on gentamicin (GM)-induced acute kidney injury were evaluated in rats.
Materials and Methods: Male Wistar rats (n=32) were separated into four groups. Gentamicin (100 mg/kg/day, IP) was injected for eight days with or without UD methanolic extract (200 mg/kg/day, gavage). The renal blood flow (RBF) and systolic blood pressure of rats were recorded. Concentration of creatinine, blood urea nitrogen (BUN), sodium, and potassium and osmolarity were measured in the urine and plasma samples. Oxidative stress level was determined by assessment of the levels of antioxidant power (FRAP) and lipid peroxidation (MDA) in the renal tissue. The renal injury and histopathological changes in the kidney were determined by microscopic evaluations.
Results: Administration of UD extract along with GM, compared to GM group, significantly decreased the amounts of plasma creatinine and BUN, urinary sodium excretion, fractional excretion of sodium and potassium, and MDA levels but significantly increased creatinine clearance, urine osmolarity, renal blood flow and FRAP levels.
Conclusion: The cotreatment of UD extract can attenuate renal injury of GM by reduction of oxidative stress, lipid peroxidation, and oxygen free radicals. The potential nephroprotective effects of UD extract are probably mediated via its antioxidant and anti-inflammatory activity.


greenmedinfo--2020-06-27--Role of rutin in 5-fluorouracil-induced intestinal mucositis.

Intestinal mucositis , characterized by inflammatory and/or ulcerative processes in the gastrointestinal tract , occurs due to cellular and tissue damage following treatment with 5-fluorouracil ( 5-FU ) .
Rutin ( RUT ) , a natural flavonoid extracted from , exhibits antioxidant , anti-inflammatory , cytoprotective , and gastroprotective properties .
However , the effect of RUT on inflammatory processes in the intestine , especially on mucositis promoted by antineoplastic agents , has not yet been reported .
In this study , we investigated the role of RUT on 5-FU-induced experimental intestinal mucositis .
Swiss mice were randomly divided into @ @ @ @ @ @ @ RUT-50 , RUT-100 , RUT-200 , Celecoxib ( CLX ) , and CLX + RUT-200 groups .
The mice were weighed daily .
After treatment , the animals were euthanized and segments of the small intestine were collected to evaluate histopathological alterations ( morphometric analysis ) ; malondialdehyde ( MDA ) , myeloperoxidase ( MPO ) , and glutathione ( GSH ) concentrations ; mast and goblet cell counts ; and cyclooxygenase-2 ( COX-2 ) activity , as well as to perform immunohistochemical analyses .
RUT treatment ( 200 mg/kg ) prevented 5-FU-induced @ @ @ @ @ @ @ decreasing MDA concentrations and increasing GSH concentrations .
RUT attenuated the inflammatory response by decreasing MPO activity , intestinal mastocytosis , and COX-2 expression .
These results suggest that the COX-2 pathway is one of the underlying protective mechanisms of RUT against 5-FU-induced intestinal mucositis .

Intestinal mucositis, characterized by inflammatory and/or ulcerative processes in the gastrointestinal tract, occurs due to cellular and tissue damage following treatment with 5-fluorouracil (5-FU). Rutin (RUT), a natural flavonoid extracted from, exhibits antioxidant, anti-inflammatory, cytoprotective, and gastroprotective properties. However, the effect of RUT on inflammatory processes in the intestine, especially on mucositis promoted by antineoplastic agents, has not yet been reported. In this study, we investigated the role of RUT on 5-FU-induced experimental intestinal mucositis. Swiss mice were randomly divided into seven groups: Saline, 5-FU, RUT-50, RUT-100, RUT-200, Celecoxib (CLX), and CLX + RUT-200 groups. The mice were weighed daily. After treatment, the animals were euthanized and segments of the small intestine were collected to evaluate histopathological alterations (morphometric analysis); malondialdehyde (MDA), myeloperoxidase (MPO), and glutathione (GSH) concentrations; mast and goblet cell counts; and cyclooxygenase-2 (COX-2) activity, as well as to perform immunohistochemical analyses. RUT treatment (200 mg/kg) prevented 5-FU-induced histopathological changes and reduced oxidative stress by decreasing MDA concentrations and increasing GSH concentrations. RUT attenuated the inflammatory response by decreasing MPO activity, intestinal mastocytosis, and COX-2 expression. These results suggest that the COX-2 pathway is one of the underlying protective mechanisms of RUT against 5-FU-induced intestinal mucositis.


greenmedinfo--2020-06-27--Six Healthiest Vegetables to Plant in Your Garden

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greenmedinfo--2020-06-27--These findings are suggestive of hypolipidaemic and atherosclerosis prevention roles of Jihel and Ma

ETHNOPHARMACOLOGICAL RELEVANCE : Date seeds are widely used in Moroccan traditional medicine for treating obesity and related diseases .
AIM @ @ @ @ @ date seed varieties ( Jihel and Majhoul ) were assessed for their phenolic profile and @ @ @ @ @ METHODS : The polyphenolic profile was determined using HPLC-DAD .
Triton-WR-1339 and high-fat diet ( @ @ @ @ @ were used to evaluate the hypolipidaemic effect of date seeds extracts .
Serum lipid profile @ @ @ @ @ analyser .
RESULTS : Rutin , quercetin , p-coumaric and caffeic acids were the most @ @ @ @ @ phenolic compounds .
Serum lipids : Total cholesterol , triglycerides , low-density lipoprotein-cholesterol were lowered @ @ @ @ @ by date seed methanolic extract ( at 200 mg/kg ) in triton WR1339 -induced hyperlipidaemia @ @ @ @ @ feeding of these extracts ( at 200 mg/kg ) , to animals concurrently fed with @ @ @ @ @ ) for three weeks , caused a significant ( p CONCLUSIONS : These findings are @ @ @ @ @ prevention roles of Jihel and Majhoul date seeds .

ETHNOPHARMACOLOGICAL RELEVANCE: Date seeds are widely used in Moroccan traditional medicine for treating obesity and related diseases.
AIM OF THE STUDY: Two date seed varieties (Jihel and Majhoul) were assessed for their phenolic profile and lipid-lowering activity.
MATERIALS AND METHODS: The polyphenolic profile was determined using HPLC-DAD. Triton-WR-1339 and high-fat diet (HFD)-induced hyperlipidaemic rats were used to evaluate the hypolipidaemic effect of date seeds extracts. Serum lipid profile was measured using automatic biochemical analyser.
RESULTS: Rutin, quercetin, p-coumaric and caffeic acids were the most prevalent chemical among the analysed phenolic compounds. Serum lipids: Total cholesterol, triglycerides, low-density lipoprotein-cholesterol were lowered and high-density lipoprotein-cholesterol were increased by date seed methanolic extract (at 200 mg/kg) in triton WR1339 -induced hyperlipidaemia in experimental rats. Chronic feeding of these extracts (at 200 mg/kg), to animals concurrently fed with high fat diet (HFD) for three weeks, caused a significant (p < 0.05) decrease in serum total cholesterol, triglycerides, low-density lipoprotein-cholesterol levels and atherogenic index, while it increased serum HDL-C. Furthermore, the supplementation of date seed extract was effective in preventing body weight gain.
CONCLUSIONS: These findings are suggestive of hypolipidaemic and atherosclerosis prevention roles of Jihel and Majhoul date seeds.


greenmedinfo--2020-06-27--Ruta graveolens and rutin, as its major compound: investigating their effect on spatial memory and p

Ruta graveolens and rutin, as its major compound: investigating their effect on spatial memory and passive avoidance memory.

There are numerous pharmacological activities forand its bioactive constituent , rutin , on learning and memory.This study aimed to examine @ @ @ @ @ memory in rats.In this study animals were treated with the hydroalcholic extract ofand rutin by @ @ @ @ @ .
Behavioural and biochemical tests as well as HPLC analysis and antioxidant activity of extract @ @ @ @ @ significantly increased learning and improved spatial memory , as well as secondary latency ; moreover @ @ @ @ @ in the serum and brain antioxidant capacity as well as the level of TBARS in @ @ @ @ @ Results also showed thathas significant DPPH radical scavenging effect ( IC : 159.17 ± 1.56 @ @ @ @ @ analysis of extract showed that caffeic acid ( 19.92 ± 0.01 ) , rutin ( @ @ @ @ @ and apigenin ( 0.84 ± 0.01 ) mg/g of dry extract are the main components @ @ @ @ @ of.extract and rutin on animal brain cells , memory function , and learning , additional @ @ @ @ @ , might be beneficial in producing natural supplementary drugs from this herb .

There are numerous pharmacological activities forand its bioactive constituent, rutin, on learning and memory.This study aimed to examine the effect ofand rutin on memory in rats.In this study animals were treated with the hydroalcholic extract ofand rutin by IP injection for 10 days. Behavioural and biochemical tests as well as HPLC analysis and antioxidant activity of extract have been evaluated.extract and rutin significantly increased learning and improved spatial memory, as well as secondary latency; moreover, there were significant increases in the serum and brain antioxidant capacity as well as the level of TBARS in serum and brain tissues. Results also showed thathas significant DPPH radical scavenging effect (IC: 159.17 ± 1.56 μg/mL). The HPLC analysis of extract showed that caffeic acid (19.92 ± 0.01), rutin (40.15 ± 0.01), and apigenin (0.84 ± 0.01) mg/g of dry extract are the main components of the extract.Regarding the effects of.extract and rutin on animal brain cells, memory function, and learning, additional studies, including clinical trials, might be beneficial in producing natural supplementary drugs from this herb.


greenmedinfo--2020-06-27--Effect of rutin on oxidative DNA damage in PC12 neurons cultured in nutrients deprivation condition

Objectives : Rutin is a flavonoid with potent antioxidant property , which exhibited cytoprotective effects in several models of neuronal injury .
This work aimed to examine whether rutin can protect neurons against oxidative DNA damage caused by serum/glucose deprivation ( SGD ) as an in vitro model of neurodegeneration and ischemia .
Materials and Methods : The PC12 cells were cultured for 2 hr in normal culture medium containing different concentrations of rutin orα-tocopherol ( positive control ) and then further incubated for 12 hr in SGD condition .
Then , cell viability , DNA fragmentation , lipid peroxidation @ @ @ @ @ @ @ ROS ) , and the expression of proteins involved in apoptosis were determined .
Results : The SGD condition significantly decreased viability of the cells , which was accompanied by a significant rise in the generation of ROS and lipid peroxidation .
Rutin enhanced the viability of PC12 cells in SGD condition and reduced the production of ROS and lipid peroxidation .
In addition , rutin decreased DNA damage and inhibited apoptotic cell death by decreasing the levels of proapoptotic proteins ( Bax , caspase-3 , caspase-9 ) and increasing the level of @ @ @ @ @ @ @ study demonstrated that rutin inhibits oxidative DNA damage and neuronal death induced by nutrients deprivation condition .
Further studies may warrant the use of rutin as an appropriate neuroprotective agent for ischemic attacks and other neurodegenerative disorders .

Objectives: Rutin is a flavonoid with potent antioxidant property, which exhibited cytoprotective effects in several models of neuronal injury. This work aimed to examine whether rutin can protect neurons against oxidative DNA damage caused by serum/glucose deprivation (SGD) as an in vitro model of neurodegeneration and ischemia.
Materials and Methods: The PC12 cells were cultured for 2 hr in normal culture medium containing different concentrations of rutin orα-tocopherol (positive control) and then further incubated for 12 hr in SGD condition. Then, cell viability, DNA fragmentation, lipid peroxidation, generation of reactive oxygen species (ROS), and the expression of proteins involved in apoptosis were determined.
Results: The SGD condition significantly decreased viability of the cells, which was accompanied by a significant rise in the generation of ROS and lipid peroxidation. Rutin enhanced the viability of PC12 cells in SGD condition and reduced the production of ROS and lipid peroxidation. In addition, rutin decreased DNA damage and inhibited apoptotic cell death by decreasing the levels of proapoptotic proteins (Bax, caspase-3, caspase-9) and increasing the level of anti-apoptotic protein Bcl-2.
Conclusion: This study demonstrated that rutin inhibits oxidative DNA damage and neuronal death induced by nutrients deprivation condition. Further studies may warrant the use of rutin as an appropriate neuroprotective agent for ischemic attacks and other neurodegenerative disorders.


greenmedinfo--2020-06-27--Are You Getting Enough Dietary Sulfur?

Are You Getting Enough Dietary Sulfur?


greenmedinfo--2020-06-27--Green coffee extract modifies body weight, serum lipids and TNF-α in high-fat diet-induced obesity.

OBJECTIVE : Currently , there are many efforts to find functional nutrients for obesity management , and the green coffee @ @ @ @ @ .
This study aimed to examine the effect of low dose administration of green coffee @ @ @ @ @ serum lipids , and TNF-α level in high-fat diet-induced obese rats .
RESULTS : Administration @ @ @ @ @ high-fat diet-induced obese male Wistar rats ( Rattus norvegicus ) reduced body weight , total @ @ @ @ @ at the dose of 10 , 20 , and 40 mg/kg BW/day ; lowered serum @ @ @ @ @ of 20 mg/kg BW/day ( p

OBJECTIVE: Currently, there are many efforts to find functional nutrients for obesity management, and the green coffee extract is a potential candidate. This study aimed to examine the effect of low dose administration of green coffee extract on body weight, serum lipids, and TNF-α level in high-fat diet-induced obese rats.
RESULTS: Administration of green coffee extract to high-fat diet-induced obese male Wistar rats (Rattus norvegicus) reduced body weight, total serum cholesterol, and triglyceride at the dose of 10, 20, and 40 mg/kg BW/day; lowered serum LDL-cholesterol at the treatment dose of 20 mg/kg BW/day (p < 0.05). The effective dose to decrease serum TNF-α level was 40 mg/kg BW/day, while the effective dose to improve the lipid profile was 10 mg/kg BW/day. These results support the potential use of green coffee extract as a functional nutrient in the management of obesity.


greenmedinfo--2020-06-27--Green coffee extract provides a cost-effective and safe alternative for the treatment of obesity.

BACKGROUND AND AIM : Two meta-analyses summarized data on the effects of green coffee extract ( GCE ) supplementation on anthropometric measures .
However , the accuracy of those meta-analyses is uncertain due to several methodological limitations .
Therefore , we aimed to conduct a comprehensive systematic review and dose-response meta-analysis to summarize all available evidence on the effects of GCE supplementation on anthropometric measures by considering the main limitations in the previous meta-analyses .
METHODS : We searched available online databases for relevant publications up to January 2020 , using relevant keywords .
All randomized clinical trials ( RCTs @ @ @ @ @ @ @ , compared with a control group , on anthropometric measures [ including body weight , body mass index ( BMI ) , body fat percentage , waist circumference ( WC ) and waist-to-hip ratio ( WHR ) ] were included .
RESULTS : After identifying 1871 studies from our initial search , 15 RCTs with a total sample size of 897 participants were included in the systematic review and meta-analysis .
We found a significant reducing effect of GCE supplementation on body weight ( weighted mean difference ( WMD ) : -1.23 , @ @ @ @ @ @ @ kg , P < 0.001 ) , BMI ( WMD : -0.48 , 95 % CI : -0.78 , -0.18 kg/m , P = 0.001 ) , and WC ( WMD : -1.00 , 95 % CI : -1.70 , -0.29 cm , P = 0.006 ) .
No significant effect of GCE supplementation on body fat percentage and WHR was seen .
In the dose-response analyses , there was no significant association between chlorogenic acid ( CGA ) dosage , as the main polyphenol in green coffee , and changes in anthropometric @ @ @ @ @ @ @ GCE supplementation had a beneficial effect on body weight , BMI and WC .
It provides a cost-effective and safe alternative for the treatment of obesity .
Additional well-designed studies are required to further confirm our findings .

BACKGROUND AND AIM: Two meta-analyses summarized data on the effects of green coffee extract (GCE) supplementation on anthropometric measures. However, the accuracy of those meta-analyses is uncertain due to several methodological limitations. Therefore, we aimed to conduct a comprehensive systematic review and dose-response meta-analysis to summarize all available evidence on the effects of GCE supplementation on anthropometric measures by considering the main limitations in the previous meta-analyses.
METHODS: We searched available online databases for relevant publications up to January 2020, using relevant keywords. All randomized clinical trials (RCTs) investigating the effects of GCE supplementation, compared with a control group, on anthropometric measures [including body weight, body mass index (BMI), body fat percentage, waist circumference (WC) and waist-to-hip ratio (WHR)] were included.
RESULTS: After identifying 1871 studies from our initial search, 15 RCTs with a total sample size of 897 participants were included in the systematic review and meta-analysis. We found a significant reducing effect of GCE supplementation on body weight (weighted mean difference (WMD): -1.23, 95 % CI: -1.64, -0.82 kg,P<0.001), BMI (WMD: -0.48, 95 % CI: -0.78, -0.18 kg/m, P = 0.001), and WC (WMD: -1.00, 95 % CI: -1.70, -0.29 cm, P = 0.006). No significant effect of GCE supplementation on body fat percentage and WHR was seen. In the dose-response analyses, there was no significant association between chlorogenic acid (CGA) dosage, as the main polyphenol in green coffee, and changes in anthropometric measures.
CONCLUSION: We found that GCE supplementation had a beneficial effect on body weight, BMI and WC. It provides a cost-effective and safe alternative for the treatment of obesity. Additional well-designed studies are required to further confirm our findings.


greenmedinfo--2020-06-27--Neuromodulatory effects of green coffee bean extract against brain damage in male albino rats with e

Neuromodulatory effects of green coffee bean extract against brain damage in male albino rats with experimentally induced diabetes.

Diabetes mellitus is an increasing metabolic disease worldwide associated with central nervous system disorders .
Coffee is a widely consumed beverage that enriched with antioxidants with numerous medicinal applications .
Accordingly , the present study aimed to investigate the therapeutic potential of orally administered green coffee bean water extract ( GCBWE ) against cortical damage induced by high fat diet ( HFD ) followed by a single injection of streptozotocin ( STZ ) in rats .
Metformin ( Met ) was used as standard antidiabetic drug .
Animals were allocated into six groups : control , GCBWE ( 100 mg/kg @ @ @ @ @ @ @ , HFD/STZ + GCBWE ( 50 mg/kg ) , HFD/STZ + GCBWE ( 100 mg/kg ) and HFD/STZ + Met ( 200 mg/kg ) which were treated daily for 28 days .
Compared to control rats , HFD/STZ-treated rats showed decreased levels of cortical dopamine , norepinephrine and serotonin with marked increases in their metabolites .
Further , HFD/STZ treatment resulted in notable elevations in malondialdehyde , protein carbonyl and total nitrite levels paralleled with declines in antioxidant markers ( SOD , CAT , GPx , GR and GSH ) and down-regulations of @ @ @ @ @ @ @ gene expression .
Neuroinflammation was evident in diabetic animals by marked elevations in TNF-α , IL-1β and up-regulation of inducible nitric oxide synthase .
Significant rises incaspase-3 and Bax with decline in Bcl-2 level were noticed in diabetic rats together with similar results in their gene expressions .
Cortical histopathological examination supported the biochemical and molecular findings .
GCBWE administration achieved noteworthy neuroprotection in diabetic animals in most assessed parameters .
The overall results suggested that antioxidant , anti-inflammatory ; anti-apoptotic activities of GCBWE restoredthe cortical neurochemistry in diabetic rats .

Diabetes mellitus is an increasing metabolic disease worldwide associated with central nervous system disorders. Coffee is a widely consumed beverage that enriched with antioxidants with numerous medicinal applications. Accordingly, the present study aimed to investigate the therapeutic potential of orally administered green coffee bean water extract (GCBWE) against cortical damage induced by high fat diet (HFD) followed by a single injection of streptozotocin (STZ) in rats. Metformin (Met) was used as standard antidiabetic drug. Animals were allocated into six groups: control, GCBWE (100 mg/kg), HFD/STZ (40 mg/kg), HFD/STZ + GCBWE (50 mg/kg), HFD/STZ + GCBWE (100 mg/kg) and HFD/STZ + Met (200 mg/kg) which were treated daily for 28 days. Compared to control rats, HFD/STZ-treated rats showed decreased levels of cortical dopamine, norepinephrine and serotonin with marked increases in their metabolites. Further, HFD/STZ treatment resulted in notable elevations in malondialdehyde, protein carbonyl and total nitrite levels paralleled with declines in antioxidant markers (SOD, CAT, GPx, GR and GSH) and down-regulations of Sod2, Cat, GPx1 and Gsr gene expression. Neuroinflammation was evident in diabetic animals by marked elevations in TNF-α, IL-1β and up-regulation of inducible nitric oxide synthase. Significant rises incaspase-3 and Bax with decline in Bcl-2 level were noticed in diabetic rats together with similar results in their gene expressions. Cortical histopathological examination supported the biochemical and molecular findings. GCBWE administration achieved noteworthy neuroprotection in diabetic animals in most assessed parameters. The overall results suggested that antioxidant, anti-inflammatory; anti-apoptotic activities of GCBWE restoredthe cortical neurochemistry in diabetic rats.


greenmedinfo--2020-06-27--Beneficial effects of green coffee and green tea extract combination on metabolic syndrome improveme

Beneficial effects of green coffee and green tea extract combination on metabolic syndrome improvement.

Effect of green coffee and green tea extract on metabolic syndrome .
To explore green coffee and green tea extract combination effect on metabolic profile and blood pressure improvement through adenosine monophosphate-activated protein kinase ( AMPK ) and Peroxisome Proliferator-Activated Receptorα ( PPARα ) gene expression modulation .
Experimental laboratory research with pre- and post-control group design .
Twenty-five metabolic syndrome rats model were grouped into five groups ( = 5 ) : standard control ( normal ) , metabolic syndrome ( SM ) , green coffee extract ( GC ) , green tea extract ( GT ) , and @ @ @ @ @ @ @ ( CM ) .
The extract was given during 9 weeks .
Serum glucose , triglyceride , high-density lipoprotein , and systolic blood pressure level were analyzed before and after the extract administration .
At the end of the study , PPAR-α and AMPK-α2 gene were analyzed .
Independent-test .
CM group had significantly higher PPAR-α , and AMPK-α2 gene expression compared to those of SM , GC , and GT group .
Green coffee and green tea extract combination administration improved metabolic profile and blood pressure on metabolic syndrome through affecting PPAR-α @ @ @ @ @

Effect of green coffee and green tea extract on metabolic syndrome. To explore green coffee and green tea extract combination effect on metabolic profile and blood pressure improvement through adenosine monophosphate-activated protein kinase (AMPK) and Peroxisome Proliferator-Activated Receptorα (PPARα) gene expression modulation. Experimental laboratory research with pre- and post-control group design. Twenty-five metabolic syndrome rats model were grouped into five groups (= 5): standard control (normal), metabolic syndrome (SM), green coffee extract (GC), green tea extract (GT), and combination green coffee and green tea extract (CM). The extract was given during 9 weeks. Serum glucose, triglyceride, high-density lipoprotein, and systolic blood pressure level were analyzed before and after the extract administration. At the end of the study, PPAR-α and AMPK-α2 gene were analyzed. Independent-test. CM group had significantly higher PPAR-α, and AMPK-α2 gene expression compared to those of SM, GC, and GT group. Green coffee and green tea extract combination administration improved metabolic profile and blood pressure on metabolic syndrome through affecting PPAR-α and AMPK-α2 gene expression.


greenmedinfo--2020-06-27--Nuclear-targeted gold nanoparticles enhance cancer cell radiosensitization.

Radiation therapy aims to kill or inhibit proliferation of cancer cells while sparing normal cells .
To enhance radiosensitization , @ @ @ @ @ nanoparticles targeting the nucleus .
We exploited a strategy that combined RGD and NLS peptides @ @ @ @ @ the nucleus to initiate cell-death activated by X-ray irradiation .
We observed that the modified @ @ @ @ @ in the nuclei or accumulated in the vicinity of the nuclei .
We demonstrated that @ @ @ @ @ energy reduced cell proliferation by 3.8-fold when the nuclear targeted gold nanoparticles were used .
@ @ @ @ @ dose to have a 10 % survival fraction was reduced from 11.0 Gy to 7.1 @ @ @ @ @ NLS/RGD/PEG-AuNP was incubated with A549 cancer cells .
We conclude that the peptide-modified gold nanoparticles @ @ @ @ @ radiosensitization .

Radiation therapy aims to kill or inhibit proliferation of cancer cells while sparing normal cells. To enhance radiosensitization, we developed 40 nm-sized gold nanoparticles targeting the nucleus. We exploited a strategy that combined RGD and NLS peptides respectively targeting cancer cell and the nucleus to initiate cell-death activated by X-ray irradiation. We observed that the modified gold nanoparticles were either translocated in the nuclei or accumulated in the vicinity of the nuclei. We demonstrated that X-ray irradiation at 225 kVp energy reduced cell proliferation by 3.8-fold when the nuclear targeted gold nanoparticles were used. We determined that the radiation dose to have a 10% survival fraction was reduced from 11.0 Gy to 7.1 Gy when 10.0g/mL of the NLS/RGD/PEG-AuNP was incubated with A549 cancer cells. We conclude that the peptide-modified gold nanoparticles targeting the nucleus significantly enhance radiosensitization.


greenmedinfo--2020-06-27--Nobiletin may serve as a beneficial anti-leukemic agent for differentiation therapy.

Differentiation therapy is an alternative strategy used to induce the differentiation of blast cells toward mature cells and to inhibit tumor cell proliferation for cancer treatment .
Nobiletin ( NOB ) , a polymethoxyflavone phytochemical , is present abundantly in citrus peels and has been reported to possess anti-cancer activity .
In this study , we investigated the anti-leukemic effects of NOB on cell differentiation and its underlying mechanisms in human chronic myeloid leukemia ( CML ) K562 cells .
NOB ( 100μM ) treatment for 24 and 48 h significantly decreased viability of K562 cells to 54.4 ± 5.3 @ @ @ @ @ @ @ respectively .
NOB ( 10-100 μM ) significantly inhibited cell growth in K562 cells .
Flow cytometry analysis and immunoblotting data showed that NOB ( 40 and 80 μM ) could modulate the cell cycle regulators including p21 , p27 , and cyclin D2 , and induce G1 phase arrest .
NOB also increased the messenger RNA ( mRNA ) and protein expression of megakaryocytic differentiation markers , such as CD61 , CD41 , and CD42 as well as the formation of large cells with multi-lobulated nuclei in K562 cells.These results suggested that @ @ @ @ @ @ @ .
Furthermore , microarray analysis showed that expression of EGR1 , a gene associated with promotion of megakaryocytic differentiation , was markedly elevated in NOB-treated K562 cells .
The knockdown of EGR1expression by small interference RNA ( siRNA ) could significantly attenuate NOB-mediated cell differentiation .
We further elucidated that NOB induced EGR1 expression and CD61 expression through increases in MAPK/ERK phosphorylation in K562 cells .
These results indicate that NOB promotes megakaryocytic differentiation through the MAPK/ERK pathway-dependent EGR1 expression in human CML cells .
In addition , NOB when combined with imatinib @ @ @ @ @ @ @ cells .
Our findings suggest that NOB may serve as a beneficial anti-leukemic agent for differentiation therapy .

Differentiation therapy is an alternative strategy used to induce the differentiation of blast cells toward mature cells and to inhibit tumor cell proliferation for cancer treatment. Nobiletin (NOB), a polymethoxyflavone phytochemical, is present abundantly in citrus peels and has been reported to possess anti-cancer activity. In this study, we investigated the anti-leukemic effects of NOB on cell differentiation and its underlying mechanisms in human chronic myeloid leukemia (CML) K562 cells. NOB (100μM) treatment for 24 and 48 h significantly decreased viability of K562 cells to 54.4 ± 5.3% and 46.2 ± 9.9%, respectively. NOB (10-100 μM) significantly inhibited cell growth in K562 cells. Flow cytometry analysis and immunoblotting data showed that NOB (40 and 80 μM) could modulate the cell cycle regulators including p21, p27, and cyclin D2, and induce G1 phase arrest. NOB also increased the messenger RNA (mRNA) and protein expression of megakaryocytic differentiation markers, such as CD61, CD41, and CD42 as well as the formation of large cells with multi-lobulated nuclei in K562 cells.These results suggested that NOB facilitated K562 cells toward megakaryocytic differentiation. Furthermore, microarray analysis showed that expression of EGR1, a gene associated with promotion of megakaryocytic differentiation, was markedly elevated in NOB-treated K562 cells. The knockdown of EGR1expression by small interference RNA (siRNA) could significantly attenuate NOB-mediated cell differentiation. We further elucidated that NOB induced EGR1 expression and CD61 expression through increases in MAPK/ERK phosphorylation in K562 cells. These results indicate that NOB promotes megakaryocytic differentiation through the MAPK/ERK pathway-dependent EGR1 expression in human CML cells. In addition, NOB when combined with imatinib could synergistically reduce the viability of K562 cells. Our findings suggest that NOB may serve as a beneficial anti-leukemic agent for differentiation therapy.


greenmedinfo--2020-06-27--Hemp seed extract acted on U-87 cells by inducing the apoptosis machinery and suppressing the autoph

Hemp seed extract acted on U-87 cells by inducing the apoptosis machinery and suppressing the autophagic cell death.

The weak but noteworthy presence of ( poly ) phenols in hemp seeds has been long overshadowed by the essential polyunsaturated fatty acids and digestible proteins , considered responsible for their high nutritional benefits .
Instead , lignanamides and their biosynthetic precursors , phenylamides , seem to display interesting and diverse biological activities only partially clarified in the last decades .
Herein , negative mode HR-MS/MS techniques were applied to the chemical investigation of a ( poly ) phenol-rich fraction , obtained from hemp seeds after extraction/fractionation steps .
This extract contained phenylpropanoid amides and their random oxidative coupling derivatives @ @ @ @ @ @ @ abundant compounds and showed a high chemical diversity , deeply unraveled through high resolution tandem mass spectrometry ( HR-MS/MS ) tools .
The effect of different doses of the lignanamides-rich extract ( LnHS ) on U-87 glioblastoma cell line and non-tumorigenic human fibroblasts was evaluated .
Thus , cell proliferation , genomic DNA damage , colony forming and wound repair capabilities were assessed , as well as LnHS outcome on the expression levels of pro-inflammatory cytokines .
LnHS significantly inhibited U-87 cancer cell proliferation , but not that of fibroblasts , and was @ @ @ @ @ @ @ inducing further DNA damage .
No modification in cytokines ' expression level was found .
Data acquired suggested that LnHS acted in U-87 cells by inducing the apoptosis machinery and suppressing the autophagic cell death .

The weak but noteworthy presence of (poly)phenols in hemp seeds has been long overshadowed by the essential polyunsaturated fatty acids and digestible proteins, considered responsible for their high nutritional benefits. Instead, lignanamides and their biosynthetic precursors, phenylamides, seem to display interesting and diverse biological activities only partially clarified in the last decades. Herein, negative mode HR-MS/MS techniques were applied to the chemical investigation of a (poly)phenol-rich fraction, obtained from hemp seeds after extraction/fractionation steps. This extract contained phenylpropanoid amides and their random oxidative coupling derivatives, lignanamides, which were the most abundant compounds and showed a high chemical diversity, deeply unraveled through high resolution tandem mass spectrometry (HR-MS/MS) tools. The effect of different doses of the lignanamides-rich extract (LnHS) on U-87 glioblastoma cell line and non-tumorigenic human fibroblasts was evaluated. Thus, cell proliferation, genomic DNA damage, colony forming and wound repair capabilities were assessed, as well as LnHS outcome on the expression levels of pro-inflammatory cytokines. LnHS significantly inhibited U-87 cancer cell proliferation, but not that of fibroblasts, and was able to reduce U-87 cell migration, inducing further DNA damage. No modification in cytokines' expression level was found. Data acquired suggested that LnHS acted in U-87 cells by inducing the apoptosis machinery and suppressing the autophagic cell death.


greenmedinfo--2020-06-27--Dietary hemp seeds more effectively attenuate metabolic disorders in genetically obese rats than the

Dietary hemp seeds more effectively attenuate metabolic disorders in genetically obese rats than the oil extracted from them.

BACKGROUND : Hemp seeds are rich in PUFAs and other bioactives that can attenuate the development of obesity-related disorders ; however , the extent to which their lipid fraction is responsible for this effect is unknown .
OBJECTIVE : We hypothesized that hemp seed or hemp oil supplementation can attenuate genetically determined disorders and that the former are more effective in doing so .
METHODS : Lean and obese male Zucker rats , aged 8 wk , weighing 174 ± 4.2 g and 223 ± 3.8 g , respectively , were allocated to 4 groups .
The lean ( LC @ @ @ @ @ @ @ were fed a standard diet , whereas the other 2 obese groups were fed a modified diet in which hemp oil ( 4 % diet ; O + HO ) or hemp seeds ( 12 % diet ; O + HS ) were included .
All diets hadthe same proportions of protein ( 18 % ) , fat ( 8 % ) , and fiber ( 5 % ) and a similar carbohydrate proportion ( ∼52 % ) .
Diets fed to O + HO and O + HS had similar fatty acid @ @ @ @ @ @ @ of gut and liver function , antioxidant status , and lipid metabolism were measured .
RESULTS : The total SCFA concentration in the cecal digesta was lower in OC ( 64.8 ± 4.21 µmol/g ) compared with LC ( 78.1 ± 2.83 µmol/g ) ( P ≤ 0.05 ) , whereas it was greater in O + HS ( 89 ± 4.41 µmol/g ) compared with LC , OC , and O + HO ( 69.7 ± 2.68 µmol/g ) ( P ≤ 0.05 ) .
Plasma total cholesterol was greater in OC @ @ @ @ @ @ @ O + HO ( 5.60 ± 0.084 mmol/L ) compared with LC ( 2.71 ± 0.094 mmol/L ) ( P ≤ 0.05 ) ; in O + HS , the concentration did not differ from the other groups ( 5.16 ± 0.278 mmol/L ) .
The liver cholesterol concentration was greater in OC ( 1.79 ± 0.379 mg/g ) compared with the other groups ( 1.28-1.43 mg/g ) ( P ≤ 0.05 ) .
Hepatic expression of peroxisome proliferator-activated receptor γ was lower in OC ( 11.9 ± 0.93 units ) compared with @ @ @ @ @ @ @ ( P ≤ 0.05 ) , whereas it was greater in O + HS ( 19.2 ± 1.04 units ) compared with OC and O + HO ( 14.0 ± 1.33 units ) ( P ≤ 0.05 ) .
CONCLUSIONS : Dietary hemp seeds more effectively attenuate metabolic disorders in genetically obese rats than the oil extracted from them , which suggests that the lipid fraction is only partly responsible for these effects .

BACKGROUND: Hemp seeds are rich in PUFAs and other bioactives that can attenuate the development of obesity-related disorders; however, the extent to which their lipid fraction is responsible for this effect is unknown.
OBJECTIVE: We hypothesized that hemp seed or hemp oil supplementation can attenuate genetically determined disorders and that the former are more effective in doing so.
METHODS: Lean and obese male Zucker rats, aged 8 wk, weighing 174 ± 4.2 g and 223 ± 3.8 g, respectively, were allocated to 4 groups. The lean (LC) and obese controls (OC) were fed a standard diet, whereas the other 2 obese groups were fed a modified diet in which hemp oil (4% diet; O + HO) or hemp seeds (12% diet; O + HS) were included. All diets hadthe same proportions of protein (18%), fat (8%), and fiber (5%) and a similar carbohydrate proportion (∼52%). Diets fed to O + HO and O + HS had similar fatty acid profiles. After 4 wk, markers of gut and liver function, antioxidant status, and lipid metabolism were measured.
RESULTS: The total SCFA concentration in the cecal digesta was lower in OC (64.8 ± 4.21 µmol/g) compared with LC (78.1 ± 2.83 µmol/g) (P ≤ 0.05), whereas it was greater in O + HS (89 ± 4.41 µmol/g) compared with LC, OC, and O + HO (69.7 ± 2.68 µmol/g) (P ≤ 0.05). Plasma total cholesterol was greater in OC (6.20 ± 0.198 mmol/L) and O + HO (5.60 ± 0.084 mmol/L) compared with LC (2.71 ± 0.094 mmol/L) (P ≤ 0.05); in O + HS, the concentration did not differ from the other groups (5.16 ± 0.278 mmol/L). The liver cholesterol concentration was greater in OC (1.79 ± 0.379 mg/g) compared with the other groups (1.28-1.43 mg/g) (P ≤ 0.05). Hepatic expression of peroxisome proliferator-activated receptor γ was lower in OC (11.9 ± 0.93 units) compared with LC (17.3 ± 1.3 units) (P ≤ 0.05), whereas it was greater in O + HS (19.2 ± 1.04 units) compared with OC and O + HO (14.0 ± 1.33 units) (P ≤ 0.05).
CONCLUSIONS: Dietary hemp seeds more effectively attenuate metabolic disorders in genetically obese rats than the oil extracted from them, which suggests that the lipid fraction is only partly responsible for these effects.


greenmedinfo--2020-06-27--Hemp protein hydrolysates promote anti-inflammatory response in primary human monocytes.

Hemp seeds have a wide variety of chemical compounds which present biological activity .
Specifically , the focus on proteins and bioactive peptides are increasing as alternative sources of nutraceutical uses .
In the literature , hemp protein products ( HPPs ) have reported antioxidant and anti-inflammatory properties .
This study aimed to determine the inflammation-related modulatory effects of HPPs on lipopolysaccharide ( LPS ) -activated primary human monocytes .
CD14cells were immunomagnetically isolated from buffy coats and the anti-inflammatory activity of hemp protein isolate ( HPI ) and hydrolysates ( HPHs ) was evaluated on LPS-stimulated human primary monocytes @ @ @ @ @ @ @ polarization , and chemoattraction were measured by RT-qPCR and ELISA assays .
Our results showed that HPPs decreased the pro-inflammatory mediators ( , , and ) and increased the anti-inflammatory mediators ( and ) .
In addition , M1 polarization marker gene expression ( and ) was downregulated by HPPs and , M2 polarization marker gene expression ( and ) was upregulated .
Finally , the mRNA expression of chemotaxis genes ( and ) was downregulated by HPPs .
In conclusion , this study suggests that HPPs may improve chronic inflammatory states and @ @ @ @ @ @ @ M2 polarization phenotype .

Hemp seeds have a wide variety of chemical compounds which present biological activity. Specifically, the focus on proteins and bioactive peptides are increasing as alternative sources of nutraceutical uses. In the literature, hemp protein products (HPPs) have reported antioxidant and anti-inflammatory properties. This study aimed to determine the inflammation-related modulatory effects of HPPs on lipopolysaccharide (LPS)-activated primary human monocytes. CD14cells were immunomagnetically isolated from buffy coats and the anti-inflammatory activity of hemp protein isolate (HPI) and hydrolysates (HPHs) was evaluated on LPS-stimulated human primary monocytes. The specific markers of inflammation, polarization, and chemoattraction were measured by RT-qPCR and ELISA assays. Our results showed that HPPs decreased the pro-inflammatory mediators (,, and) and increased the anti-inflammatory mediators (and). In addition, M1 polarization marker gene expression (and) was downregulated by HPPs and, M2 polarization marker gene expression (and) was upregulated. Finally, the mRNA expression of chemotaxis genes (and) was downregulated by HPPs. In conclusion, this study suggests that HPPs may improve chronic inflammatory states and promote regenerative processes by reprogramming monocytes toward M2 polarization phenotype.


greenmedinfo--2020-06-27--Both curcumin and Hypericum perforatum oil are effective in burn wound healing.

Background : For centuries , medicinal plants have been extensively used in wound healing of burn injuries .
The aim of this study is to analyze comparatively the effects of curcumin and ( HP ) on second-degree burn wounds in rats..
This experimental study was conducted on 24 male Sprague-Dawley rats with second-degree burns .
The animals were randomly divided into three groups .
The burns were treated with curcumin ( Group B ) and ( HP ) on second-degree burn wounds in rats .
Results : All histological parameters of the control group showed statistically significant difference than the @ @ @ @ @ @ @ There was no statistically significant difference between Groups B and C in terms of reepithelization and inflammation ( < 0.05 ) .
There was no statistically significant difference between Groups B and C in terms of reepithelization and inflammation ( < 0.05 ) .
There was no statistically significant difference between Groups B and C in terms of reepithelization and inflammation ( < 0.05 ) .
There was no statistically significant difference between Groups B and C in terms of reepithelization and inflammation ( .
Conclusion : Both curcumin andoil are effective in @ @ @ @ @ @ @ a better quality of healing in curcumin-treated rats .
( HP ) on second-degree burn wounds in rats .

Background: For centuries, medicinal plants have been extensively used in wound healing of burn injuries. The aim of this study is to analyze comparatively the effects of curcumin and(HP) on second-degree burn wounds in rats.. This experimental study was conducted on 24 male Sprague-Dawley rats with second-degree burns. The animals were randomly divided into three groups. The burns were treated with curcumin (Group B) and(HP) on second-degree burn wounds in rats.
Results: All histological parameters of the control group showed statistically significant difference than the other groups (<0.05). There was no statistically significant difference between Groups B and C in terms of reepithelization and inflammation (<0.05). There was no statistically significant difference between Groups B and C in terms of reepithelization and inflammation (<0.05). There was no statistically significant difference between Groups B and C in terms of reepithelization and inflammation (<0.05). There was no statistically significant difference between Groups B and C in terms of reepithelization and inflammation (.
Conclusion: Both curcumin andoil are effective in burn wound healing. Our findings showed a better quality of healing in curcumin-treated rats.(HP) on second-degree burn wounds in rats.


greenmedinfo--2020-06-27--Potential protective effect of Achillea fragrantissima against adriamycin-induced cardiotoxicity.

Adriamycin ( Adr ) is a cytotoxic anthracycline agent that is utilized to manage many types of tumors , but its clinical use is undesirable due to severe cardiotoxicity .
The present study aimed to investigate the cardioprotective effect of ( ) against Adr-induced cardiotoxicity through the antioxidant and anti-inflammatory metabolic pathways .
A single dose of Adr was injected in rats to induce cardiotoxicity .
Rats are divided into 5 groups , control,800 , Adr,400 + Adr , and800 + Adr .
72 h after Adr administration , electrocardiographic ( ECG ) study was performed for all rats .
@ @ @ @ @ @ @ biochemical and histopathological studies.ameliorated Adr-induced ST-segment elevation .
It reduced Adr-induced elevation in lactate dehydrogenase ( LDH ) , creatine kinase-MB ( CK-MB ) , thiobarbituric acid reactive substance ( TBARS ) , tumor necrosis factor-alpha ( TNF- ) , interleukin-1 beta ( IL-1 ) , and IL-6 .
It also protected against Adr-induced histopathological changes .
Pretreatment with the extract increased heart tissue contents of glutathione peroxidase ( GSH-PX ) and reduced glutathione ( GSH ) .
Phytochemical analysis of the extract revealed that it is rich in phenolic and flavonoid active @ @ @ @ @ @ @ revealed thatextract ameliorates Adr-induced cardiotoxicityan antioxidant and anti-inflammatory mechanisms .
Further studies are warranted in order to recognize the precise active constituents of this natural extract which are responsible for the antioxidant and anti-inflammatory actions .

Adriamycin (Adr) is a cytotoxic anthracycline agent that is utilized to manage many types of tumors, but its clinical use is undesirable due to severe cardiotoxicity. The present study aimed to investigate the cardioprotective effect of() against Adr-induced cardiotoxicity through the antioxidant and anti-inflammatory metabolic pathways. A single dose of Adr was injected in rats to induce cardiotoxicity. Rats are divided into 5 groups, control,800, Adr,400 + Adr, and800 + Adr. 72 h after Adr administration, electrocardiographic (ECG) study was performed for all rats. Serum and hearts were then collected for biochemical and histopathological studies.ameliorated Adr-induced ST-segment elevation. It reduced Adr-induced elevation in lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), thiobarbituric acid reactive substance (TBARS), tumor necrosis factor-alpha (TNF-), interleukin-1 beta (IL-1), and IL-6. It also protected against Adr-induced histopathological changes. Pretreatment with the extract increased heart tissue contents of glutathione peroxidase (GSH-PX) and reduced glutathione (GSH). Phytochemical analysis of the extract revealed that it is rich in phenolic and flavonoid active constituents. The results of this study revealed thatextract ameliorates Adr-induced cardiotoxicityan antioxidant and anti-inflammatory mechanisms. Further studies are warranted in order to recognize the precise active constituents of this natural extract which are responsible for the antioxidant and anti-inflammatory actions.