greenmedinfo--2020-05-26--Fucoxanthin alleviates palmitate-induced inflammation in RAW 264.7 cells through improving lipid met

Fucoxanthin alleviates palmitate-induced inflammation in RAW 264.7 cells through improving lipid metabolism and attenuating mitochondrial dysfunction.

In this study , we aimed to examine the effects of fucoxanthin on inflammation triggered by palmitate in macrophages .
@ @ @ @ @ with palmitate with or without fucoxanthin co-treatment .
Fucoxanthin greatly alleviated palmitate-induced decrease in cell @ @ @ @ @ membrane potential .
Fucoxanthin also significantly attenuated the palmitate-induced transcriptional expression of Il-6 , Il-1β @ @ @ @ @ and increased the expression of Tgfb .
In addition , fucoxanthin decreased triglyceride accumulation induced @ @ @ @ @ expression of Cpt1a , Pparg and other lipid metabolism genes .
Inhibition of CPT1a by @ @ @ @ @ of fucoxanthin .
Furthermore , fucoxanthin increased AMPK phosphorylation and AMPKa1 knockdown by its specific @ @ @ @ @ In addition , fucoxanthin restored palmitate-mediated mitochondrial dysfunction and improved mitophagy-related gene expression .
These @ @ @ @ @ attenuate free fatty acid-induced inflammation in macrophages through modulating lipid metabolism and mitigating mitochondrial dysfunction @

In this study, we aimed to examine the effects of fucoxanthin on inflammation triggered by palmitate in macrophages. Raw 264.7 cells were treated with palmitate with or without fucoxanthin co-treatment. Fucoxanthin greatly alleviated palmitate-induced decrease in cell viability and loss of mitochondrial membrane potential. Fucoxanthin also significantly attenuated the palmitate-induced transcriptional expression of Il-6, Il-1β, Tnfα and Nlrp3 inflammasomes and increased the expression of Tgfb. In addition, fucoxanthin decreased triglyceride accumulation induced by palmitate through enhancing the expression of Cpt1a, Pparg and other lipid metabolism genes. Inhibition of CPT1a by etomoxir attenuated the anti-inflammatory effect of fucoxanthin. Furthermore, fucoxanthin increased AMPK phosphorylation and AMPKa1 knockdown by its specific siRNA diminished protective function. In addition, fucoxanthin restored palmitate-mediated mitochondrial dysfunction and improved mitophagy-related gene expression. These findings suggest that fucoxanthin could attenuate free fatty acid-induced inflammation in macrophages through modulating lipid metabolism and mitigating mitochondrial dysfunction.


greenmedinfo--2020-05-26--Fucoxanthin ameliorates atopic dermatitis symptoms by regulating keratinocytes and regulatory innate

Fucoxanthin ameliorates atopic dermatitis symptoms by regulating keratinocytes and regulatory innate lymphoid cells.

Fucoxanthin ( FX ) is a xanthophyll that is contained abundantly in marine plants .
The biological action of FX @ @ @ @ @ activities , while the precise action of its mechanisms on skin cells has not yet @ @ @ @ @ study examined the effect of FX in comparison with tacrolimus ( TAC ) on NC/Nga @ @ @ @ @ atopic dermatitis ( AD ) model .
FX topical treatment dramatically ameliorated itching behavior over @ @ @ @ @ was insufficient for improvement of AD symptoms .
In Nc/Nga mice , FX or TAC @ @ @ @ @ eosinophil infiltration with decreased expression of Il-33 .
FX also stimulated Il-2 , Il-5 , @ @ @ @ @ TGF-β expression levels , and Sca1Il-10TGF-βregulatory innate lymphoid cells ( ILCreg ) were dominantly observed @ @ @ @ @ keratinocytes and dermal layers .
This combined evidence demonstrated that FX exerts anti-inflammatory effects on @ @ @ @ @ by regulating ILCreg to normalize immune responses in an atopic dermatitis model .

Fucoxanthin (FX) is a xanthophyll that is contained abundantly in marine plants. The biological action of FX includes its antioxidant and anti-lipogenic activities, while the precise action of its mechanisms on skin cells has not yet been clarified. The current study examined the effect of FX in comparison with tacrolimus (TAC) on NC/Nga mice, which are an atopic dermatitis (AD) model. FX topical treatment dramatically ameliorated itching behavior over the TAC treatment, which was insufficient for improvement of AD symptoms. In Nc/Nga mice, FX or TAC applied to the skin inhibited eosinophil infiltration with decreased expression of Il-33. FX also stimulated Il-2, Il-5, Il-13, Il-10, and TGF-β expression levels, and Sca1Il-10TGF-βregulatory innate lymphoid cells (ILCreg) were dominantly observed in FX treated skin epidermal keratinocytes and dermal layers. This combined evidence demonstrated that FX exerts anti-inflammatory effects on keratinocytes and ameliorates AD symptoms by regulating ILCreg to normalize immune responses in an atopic dermatitis model.


greenmedinfo--2020-05-26--Spent hops extract as modulator of the inflammatory response in lipopolysaccharide stimulated RAW 26

Spent hops extract as modulator of the inflammatory response in lipopolysaccharide stimulated RAW 264.7 macrophages.

Macrophages play important roles in acute and chronic inflammation .
Upon their activation , they secrete a variety of mediators , including eicosanoids , nitric oxide and cytokines , which play different roles in the stimulation and resolution of inflammatory processes .
There is a continuous search for selective modulators of these processes .
Natural polyphenols and polyphenol-rich extracts have been found to possess preventive and therapeutic potential , including by their anti-inflammatory effects .
In this study , the inhibition of the formation of inflammatory mediators by the spent hops extract ( SHE ) , a polyphenol-rich extract from @ @ @ @ @ @ @ lipopolysaccharide ( LPS ) - activated murine macrophages ( RAW 264.7 ) .
The SHE suppressed inter alia the interleukin-6 ( IL-6 ) mRNA expression to 32 % in LPS-activated macrophages and to 61 % at a protein level ( at 25μg/mL ) .
SHE reduced both the cyclooxygenase-2 ( COX-2 ) mRNA expression to 47 % and their protein expression to 32 % .
Not only did SHE inhibit the IL-6 and COX-2 levels but also decreased both inducible nitric oxide synthase ( iNOS ) protein expression to 2 % at 25 @ @ @ @ @ @ @ productionfor all tested concentrations .
The inhibited expression of these inflammatory molecules was likely caused by the reduced activity of nuclear factor-κB ( NF-κB ) .
Both mRNA and protein expression of NF-κB was decreased to 38 % and 42 % , respectively .
These results provide the first evidence that SHE decreases the expression of proinflammatory cytokines and inflammatory mediators , which merits further studies to investigate the potential of SHE as anti-inflammatory preparation .

Macrophages play important roles in acute and chronic inflammation. Upon their activation, they secrete a variety of mediators, including eicosanoids, nitric oxide and cytokines, which play different roles in the stimulation and resolution of inflammatory processes. There is a continuous search for selective modulators of these processes. Natural polyphenols and polyphenol-rich extracts have been found to possess preventive and therapeutic potential, including by their anti-inflammatory effects. In this study, the inhibition of the formation of inflammatory mediators by the spent hops extract (SHE), a polyphenol-rich extract from Humulus Lupulus L., was examined using lipopolysaccharide (LPS)- activated murine macrophages (RAW 264.7). The SHE suppressed inter alia the interleukin-6 (IL-6) mRNA expression to 32% in LPS-activated macrophages and to 61% at a protein level (at 25μg/mL). SHE reduced both the cyclooxygenase-2 (COX-2) mRNA expression to 47% and their protein expression to 32%. Not only did SHE inhibit the IL-6 and COX-2 levels but also decreased both inducible nitric oxide synthase (iNOS) protein expression to 2% at 25 μg/mL and nitric oxide (NO) productionfor all tested concentrations. The inhibited expression of these inflammatory molecules was likely caused by the reduced activity of nuclear factor-κB (NF-κB). Both mRNA and protein expression of NF-κB was decreased to 38% and 42%, respectively. These results provide the first evidence that SHE decreases the expression of proinflammatory cytokines and inflammatory mediators, which merits further studies to investigate the potential of SHE as anti-inflammatory preparation.


greenmedinfo--2020-05-26--Anti-rheumatic activity of phenethyl isothiocyanate via inhibition of histone deacetylase-1.

Rheumatoid Arthritis ( RA ) affects approximately 1 % of the total world population .
Despite incessant research and development of new therapeutic agents , management of RA is still a troublesome affair .
Histone Deacetylase 1 ( HDAC1 ) is an epigenetic regulator which play important role in pathogenesis of RA .
In present study , we hypothesized that Phenethyl isothiocyanate ( PEITC ) , a potent inhibitor of HDAC1 , may ameliorate RA .
Efficacy of PEITC was evaluated in Complete Freund 's Adjuvant ( CFA ) induced arthritis model in rats .
CFA ( 0.1 ml ) @ @ @ @ @ @ @ paw on day 0 to all the groups except normal control .
The administration of test drug PEITC ( 10 , 24 & 50 mg/kg ) and standard drug Ibuprofen started simultaneously and was continued for 21 days .
Paw edema , total arthritic index , mobility score , stair climbing ability , behavioral parameters , and bone erosion were evaluated .
Further , radiographic studies , TNF-alpha as well as HDAC1 levels in synovial tissue homogenate and histological analysis were performed .
Prophylactic treatment of PEITC attenuated paw edema , total arthritic @ @ @ @ @ @ @ ability , behavioral parameters , and bone erosion in dose dependent manner .
Furthermore , there was significant decrease in TNF-alpha aswell as HDAC1 levels in synovial tissue homogenate .
Histological analysis revealed no cartilage damage , bone erosion , hyperplasia at synovial lining as well as infiltration of inflammatory cells in treatment group .
Results of this study suggest potent anti-rheumatoid arthritis activity of Phenethylisothiocyanate in CFA induced RA model in rats .

Rheumatoid Arthritis (RA) affects approximately 1% of the total world population. Despite incessant research and development of new therapeutic agents, management of RA is still a troublesome affair. Histone Deacetylase 1 (HDAC1) is an epigenetic regulator which play important role in pathogenesis of RA. In present study, we hypothesized that Phenethyl isothiocyanate (PEITC), a potent inhibitor of HDAC1, may ameliorate RA. Efficacy of PEITC was evaluated in Complete Freund's Adjuvant (CFA) induced arthritis model in rats. CFA (0.1 ml) was injected subplantarly in the left hind paw on day 0 to all the groups except normal control. The administration of test drug PEITC (10, 24&50 mg/kg) and standard drug Ibuprofen started simultaneously and was continued for 21 days. Paw edema, total arthritic index, mobility score, stair climbing ability, behavioral parameters, and bone erosion were evaluated. Further, radiographic studies, TNF-alpha as well as HDAC1 levels in synovial tissue homogenate and histological analysis were performed. Prophylactic treatment of PEITC attenuated paw edema, total arthritic index, mobility score, stair climbing ability, behavioral parameters, and bone erosion in dose dependent manner. Furthermore, there was significant decrease in TNF-alpha aswell as HDAC1 levels in synovial tissue homogenate. Histological analysis revealed no cartilage damage, bone erosion, hyperplasia at synovial lining as well as infiltration of inflammatory cells in treatment group. Results of this study suggest potent anti-rheumatoid arthritis activity of Phenethylisothiocyanate in CFA induced RA model in rats.


greenmedinfo--2020-05-26--β-phenethyl isothiocyanate induces cell death in human osteosarcoma.

Osteosarcoma is the most common primary malignancy of the skeleton in children and adults .
The outcomes of people with osteosarcomas are unsatisfied.-Phenethyl isothiocyanate ( PEITC ) exhibits chemoprevention and chemotherapeutic activities against many human cancers .
The molecular mechanism underlying its action on osteosarcoma is still unknown .
This study was aimed at investigating the effect of PEITC on human osteosarcoma bothand .
The results showed that PEITC reduced cell viability , inhibited proliferation , and caused G/M cell cycle arrest in four human osteosarcoma cell lines ( MNNG/HOS , U-2 OS , MG-63 , and 143B ) .
@ @ @ @ @ @ @ iron metabolism related to the processes of iron import , storage , and export , which resulted in increased labile iron .
Expectedly , PEITC caused oxidative stress as a consequence of GSH depletion-inducing ROS generation and lipid peroxidation .
Multiple cell death modalities , including ferroptosis , apoptosis , and autophagy , were triggered in human osteosarcoma cells .
Three MAPKs ( ERK , p38 , and JNK ) were all activated after PEITC treatment ; however , they presented different responses among the four human osteosarcoma cell lines .
ROS generation @ @ @ @ @ @ @ of PEITC-induced decreased proliferative potential , altered iron metabolism , cell death , and activated MAPKs in human osteosarcoma cells .
In addition , PEITC also significantly delayed tumor growth in a xenograft osteosarcoma mouse model with a 30 mg/kg administration dose .
In conclusion , this study reveals that PEITC simultaneously triggers ferroptosis , apoptosis , and autophagy in human osteosarcoma cells by inducing oxidative stress .

Osteosarcoma is the most common primary malignancy of the skeleton in children and adults. The outcomes of people with osteosarcomas are unsatisfied.-Phenethyl isothiocyanate (PEITC) exhibits chemoprevention and chemotherapeutic activities against many human cancers. The molecular mechanism underlying its action on osteosarcoma is still unknown. This study was aimed at investigating the effect of PEITC on human osteosarcoma bothand. The results showed that PEITC reduced cell viability, inhibited proliferation, and caused G/M cell cycle arrest in four human osteosarcoma cell lines (MNNG/HOS, U-2 OS, MG-63, and 143B). Then, we found that PEITC altered iron metabolism related to the processes of iron import, storage, and export, which resulted in increased labile iron. Expectedly, PEITC caused oxidative stress as a consequence of GSH depletion-inducing ROS generation and lipid peroxidation. Multiple cell death modalities, including ferroptosis, apoptosis, and autophagy, were triggered in human osteosarcoma cells. Three MAPKs (ERK, p38, and JNK) were all activated after PEITC treatment; however, they presented different responses among the four human osteosarcoma cell lines. ROS generation was proved to be the major cause of PEITC-induced decreased proliferative potential, altered iron metabolism, cell death, and activated MAPKs in human osteosarcoma cells. In addition, PEITC also significantly delayed tumor growth in a xenograft osteosarcoma mouse model with a 30 mg/kg administration dose. In conclusion, this study reveals that PEITC simultaneously triggers ferroptosis, apoptosis, and autophagy in human osteosarcoma cells by inducing oxidative stress.


greenmedinfo--2020-05-26--Xanthohumol protects neuron from cerebral ischemia injury in experimental stroke.

Treatment of antioxidants is necessary to protect ischemic stroke associated neuronal damage .
Xanthohumol ( XN ) , a natural @ @ @ @ @ has been reported to have potential function as an antioxidant and can be used for @ @ @ @ @ the role of XN in ischemic stroke remains unclear .
Here , we studied the @ @ @ @ @ experimental stroke models .
Middle cerebral artery occlusion ( MCAO ) and oxygen-glucose deprivation ( @ @ @ @ @ in vivo and in vitro model , respectively .
We found that the treatment of @ @ @ @ @ by reducing infarct size , improving neurological deficits , reversing neuronal damage , reducing oxidative @ @ @ @ @ .
Further experimental studies showed that XN could revive neuronal apoptosis induced by OGD by @ @ @ @ @ In addition , our study suggested that these effects were related to the inhibition of @ @ @ @ @ mediation of nuclear Nrf2 activation .
In conclusion , the neuroprotective effects of XN showed @ @ @ @ @ a promising supplement for ischemic stroke protection .

Treatment of antioxidants is necessary to protect ischemic stroke associated neuronal damage. Xanthohumol (XN), a natural flavonoid extracted from hops, has been reported to have potential function as an antioxidant and can be used for neuro protection. However, the role of XN in ischemic stroke remains unclear. Here, we studied the neuroprotective effects of XN through experimental stroke models. Middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation (OGD) was used as in vivo and in vitro model, respectively. We found that the treatment of XN improved MCAO-induced brain injury by reducing infarct size, improving neurological deficits, reversing neuronal damage, reducing oxidative stress injury and cell apoptosis. Further experimental studies showed that XN could revive neuronal apoptosis induced by OGD by preventing oxidative stress injury. In addition, our study suggested that these effects were related to the inhibition of phosphorylation of p38-MAPK and the mediation of nuclear Nrf2 activation. In conclusion, the neuroprotective effects of XN showed in this study make XN a promising supplement for ischemic stroke protection.


greenmedinfo--2020-05-27--Protective effect of crocin on electromagnetic field-induced testicular damage.

Objectives : Exposure to electromagnetic fields ( EMF ) emitted from mobile phones may cause a deleterious effect on human health and may affect the male reproductive system.
, a carotenoid isolated from , is a phar¬macologically active component of saffron .
So , this study was conducted to investigate the protective effect ofon the male reproductive system of 60 day old mice after EMF exposure .
Materials and Methods : Twenty-four male BALB/c mice were randomly divided into 4 groups : 1 .
Em group ( 2100 MHZ ) ; 2 .
Cr group ( 50 mg/kg ) ; @ @ @ @ @ @ @ mg/kg ) , and 4 .
Control group .
Sperm parameters ( count , and abnormal percent ) , testis weight index , testis volume , seminiferous tubule diam¬eter , germinal epithelium thickness , LH , FSH and testosterone serum level , testicular Heat shock protein A2 ( HspA2 ) immunoreactivity , and apoptosis were evaluated .
Results : HspA2 immunoreactivity , apoptosis in the germinal epithelium and abnormal sperm were increased in Em group compared with the control group ( < 0.05 ) .
Sperm count , LH , and testosterone serum @ @ @ @ @ @ @ compared with the control group ( < 0.05 ) .
These parameters were improved in the Em+Cr group compared with Em group significantly ( < 0.05 ) .
Conclusion : our findings revealed that EMF exposure leads to harmful impressions on the male reproductive system , while crocin can attenuate EMF-induced destructive effects .

Objectives: Exposure to electromagnetic fields (EMF) emitted from mobile phones may cause a deleterious effect on human health and may affect the male reproductive system., a carotenoid isolated from, is a phar¬macologically active component of saffron. So, this study was conducted to investigate the protective effect ofon the male reproductive system of 60 day old mice after EMF exposure.
Materials and Methods: Twenty-four male BALB/c mice were randomly divided into 4 groups: 1. Em group (2100 MHZ); 2. Cr group (50 mg/kg); 3. Em+Cr group (2100 MHZ+50 mg/kg), and 4. Control group. Sperm parameters (count, and abnormal percent), testis weight index, testis volume, seminiferous tubule diam¬eter, germinal epithelium thickness, LH, FSH and testosterone serum level, testicular Heat shock protein A2 (HspA2) immunoreactivity, and apoptosis were evaluated.
Results: HspA2 immunoreactivity, apoptosis in the germinal epithelium and abnormal sperm were increased in Em group compared with the control group (<0.05). Sperm count, LH, and testosterone serum level were decreased in the Em group compared with the control group (<0.05). These parameters were improved in the Em+Cr group compared with Em group significantly (<0.05).
Conclusion: our findings revealed that EMF exposure leads to harmful impressions on the male reproductive system, while crocin can attenuate EMF-induced destructive effects.


greenmedinfo--2020-05-27--Saffron may have a favourable effect on fasting blood glucose.

BACKGROUND : Experimental studies demonstrated a positive effect of administration ofL .
( saffron ) and its bioactive ingredients on metabolic profile through their antioxidant capacity .
PURPOSE : To determine if the use of saffron in humans is beneficial to patients with diabetes mellitus ( DM ) or metabolic syndrome ( MS ) .
METHODS : This systematic review includes 14randomized control trials that investigated the impact of saffron administration and its bioactive ingredient crocin on the metabolic profile of patients with DM , MS , prediabetes , and coronary artery disease .
We documented the following clinical outcomes @ @ @ @ @ @ @ , glycated haemoglobin ( HbA1c ) , total cholesterol , low-density lipoprotein ( LDL ) cholesterol , high-density lipoprotein ( HDL ) cholesterol , triglycerides , systolic , and diastolic blood pressure .
RESULTS : Eight studies examined the efficacy of saffron in patients with DM , four with the metabolic syndrome , one with prediabetes and one with coronary artery disease .
A favorable effect on FBG was observed .
The results regarding blood lipids and blood pressure were inconclusive in the current review .
CONCLUSIONS : According to the available limited @ @ @ @ @ @ @ effect on FBG .
Many of the studies in the reviewed literature are of poor quality , and more research is needed in this direction to confirm and establish the above findings .

BACKGROUND: Experimental studies demonstrated a positive effect of administration ofL. (saffron) and its bioactive ingredients on metabolic profile through their antioxidant capacity.
PURPOSE: To determine if the use of saffron in humans is beneficial to patients with diabetes mellitus (DM) or metabolic syndrome (MS).
METHODS: This systematic review includes 14randomized control trials that investigated the impact of saffron administration and its bioactive ingredient crocin on the metabolic profile of patients with DM, MS, prediabetes, and coronary artery disease. We documented the following clinical outcomes: fasting blood glucose (FBG), glycated haemoglobin (HbA1c), total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, systolic, and diastolic blood pressure.
RESULTS: Eight studies examined the efficacy of saffron in patients with DM, four with the metabolic syndrome, one with prediabetes and one with coronary artery disease. A favorable effect on FBG was observed. The results regarding blood lipids and blood pressure were inconclusive in the current review.
CONCLUSIONS: According to the available limited evidence, saffron may have a favorable effect on FBG. Many of the studies in the reviewed literature are of poor quality, and more research is needed in this direction to confirm and establish the above findings.


greenmedinfo--2020-05-27--Effects of saffron on cognitive function.

INTRODUCTION : Improvement of cognitive function may be desirable for healthy individuals and clinically beneficial for those with cognitive impairment such as from Alzheimer 's disease ( AD ) or mild cognitive impairment ( MCI ) .
The aim of this systematic review is to investigate the cognitive effects of oral saffron intake , in patients with MCI/AD and/or in non-demented individuals , by following the PRISMA guidelines .
METHODS : We performed a literature search on MedLine , Cochrane library , and ClinicalTrials.gov to identify randomized controlled trials ( RCTs ) investigating the effects of oral saffron administration in @ @ @ @ @ @ @ .
RESULTS : Five studies ( enrolling 325 individuals ) met our inclusion criteria .
Four studies included patients with MCI/AD , and one study included cognitively normal individuals .
Saffron was well-tolerated in all groups .
Regarding cognitively impaired patients , scores on Alzheimer 's Disease Assessment Scale-cognitive subscale or Mini mental state examination were significantly better when saffron was compared with placebo and did not differ significantly when saffron was compared with donepezil or memantine .
Saffron effects on functional status were similar with its effects on cognition .
CONCLUSIONS : @ @ @ @ @ @ @ to common symptomatic drugs for MCI/AD and resulted in no difference in the incidence of side effects , when compared with placebo or drugs .
The promising results should be seen cautiously , since the evidence was derived from studies with potentially high risk of bias ( ROB ) .
RCTs with larger sample sizes and low ROB are required to definitively assess the potential role of saffron as an MCI/AD treatment .

INTRODUCTION: Improvement of cognitive function may be desirable for healthy individuals and clinically beneficial for those with cognitive impairment such as from Alzheimer's disease (AD) or mild cognitive impairment (MCI). The aim of this systematic review is to investigate the cognitive effects of oral saffron intake, in patients with MCI/AD and/or in non-demented individuals, by following the PRISMA guidelines.
METHODS: We performed a literature search on MedLine, Cochrane library, and ClinicalTrials.gov to identify randomized controlled trials (RCTs) investigating the effects of oral saffron administration in patients with MCI/AD and/or in non-demented individuals.
RESULTS: Five studies (enrolling 325 individuals) met our inclusion criteria. Four studies included patients with MCI/AD, and one study included cognitively normal individuals. Saffron was well-tolerated in all groups. Regarding cognitively impaired patients, scores on Alzheimer's Disease Assessment Scale-cognitive subscale or Mini mental state examination were significantly better when saffron was compared with placebo and did not differ significantly when saffron was compared with donepezil or memantine. Saffron effects on functional status were similar with its effects on cognition.
CONCLUSIONS: Saffron was shown to be equally effective to common symptomatic drugs for MCI/AD and resulted in no difference in the incidence of side effects, when compared with placebo or drugs. The promising results should be seen cautiously, since the evidence was derived from studies with potentially high risk of bias (ROB). RCTs with larger sample sizes and low ROB are required to definitively assess the potential role of saffron as an MCI/AD treatment.


greenmedinfo--2020-05-27--Crocetin might halt or delay disease progression in age-related macular degeneration.

Age-related macular degeneration ( AMD ) is a leading cause for visual impairment in aging populations with limited established therapeutic interventions available .
Oxidative stress plays an essential role in the pathogenesis of AMD , damaging the retinal pigment epithelium ( RPE ) , which is essential for the function and maintenance of the light-sensing photoreceptors .
This study aimed to evaluate the effects of crocetin , one of the main components of Saffron , on an in vitro RPE model of tert-butyl hydroperoxide ( TBHP ) induced oxidative stress using ARPE19 cells .
The effects of crocetin were assessed @ @ @ @ @ @ @ ATP assays , as well as immunocytochemistry for cell morphology , junctional integrity , and nuclear morphology .
The mechanism of crocetin action was determined via assessment of energy production pathways , including mitochondrial respiration and glycolysis in real-time as well as investigation of extracellular signal-regulated kinase 1/2 ( ERK1/2 ) activation and distribution .
Our results show that crocetin pre-treatment protects ARPE19 cells from TBHP-induced LDH release , intracellular ATP depletion , nuclear condensation , and disturbance of junctional integrity and cytoskeleton .
The protective effect of crocetin is mediated via the @ @ @ @ @ @ @ of ERK1/2 in the first minutes of TBHP exposure to potentiate survival pathways .
The combined data suggest that a natural antioxidant , such as crocetin , represents a promising candidate to prevent oxidative stress in RPE cells and might halt or delay disease progression in AMD .

Age-related macular degeneration (AMD) is a leading cause for visual impairment in aging populations with limited established therapeutic interventions available. Oxidative stress plays an essential role in the pathogenesis of AMD, damaging the retinal pigment epithelium (RPE), which is essential for the function and maintenance of the light-sensing photoreceptors. This study aimed to evaluate the effects of crocetin, one of the main components of Saffron, on an in vitro RPE model of tert-butyl hydroperoxide (TBHP) induced oxidative stress using ARPE19 cells. The effects of crocetin were assessed using lactate de-hydrogenase (LDH) and ATP assays, as well as immunocytochemistry for cell morphology, junctional integrity, and nuclear morphology. The mechanism of crocetin action was determined via assessment of energy production pathways, including mitochondrial respiration and glycolysis in real-time as well as investigation of extracellular signal-regulated kinase 1/2 (ERK1/2) activation and distribution. Our results show that crocetin pre-treatment protects ARPE19 cells from TBHP-induced LDH release, intracellular ATP depletion, nuclear condensation, and disturbance of junctional integrity and cytoskeleton. The protective effect of crocetin is mediated via the preservation of energy production pathways and activation of ERK1/2 in the first minutes of TBHP exposure to potentiate survival pathways. The combined data suggest that a natural antioxidant, such as crocetin, represents a promising candidate to prevent oxidative stress in RPE cells and might halt or delay disease progression in AMD.


greenmedinfo--2020-05-27--Saffron and its main ingredients such as crocin could be a potential candidate for the treatment of

Saffron and its main ingredients such as crocin could be a potential candidate for the treatment of ocular disease.

INTRODUCTION : Some medicinal plants have shown promising therapeutic potential for management of the diseases .
We aimed to systematically review the literature wherein the therapeutic effects of saffron have been studied on eye disorders .
METHODS : A systematic literature search was performed in PubMed , Scopus , Web of Science , Google scholar and other databases using eye disorders , and saffron as key terms .
No strict inclusion criteria were defined , and almost all clinical studies , as well as in vivo and in vitro studies were included .
The reported data in each study were @ @ @ @ @ @ @ : Finally , 78 articles were found but only 29 relevant articles were included .
Nine articles are clinical trials and 20 articles were done on cellular and molecular aspects of saffron on eye disorders .
According to the included studies , crocin prevented the pro-inflammatory response in retinal cells and decreased glucose level in diabetic mice .
Also , crocetin prevented retinal degeneration and saffron protected photoreceptors from light-induced damage in retinal cells .
Saffron also improved visual function in age-related macular edema and decreased intraocular pressure in patients with glaucoma .
@ @ @ @ @ @ @ crocin can improve best corrected visual acuity and decreased central macular thickness in patients with diabetic maculopathy .
CONCLUSION : The results of this review indicated that saffron and its main ingredients such as crocin could be a potential candidate for the treatment of ocular disease especially eye inflammation ; however , further clinical studies are needed to confirm such efficiency .

INTRODUCTION: Some medicinal plants have shown promising therapeutic potential for management of the diseases. We aimed to systematically review the literature wherein the therapeutic effects of saffron have been studied on eye disorders.
METHODS: A systematic literature search was performed in PubMed, Scopus, Web of Science, Google scholar and other databases using eye disorders, and saffron as key terms. No strict inclusion criteria were defined, and almost all clinical studies, as well as in vivo and in vitro studies were included. The reported data in each study were extracted and then qualitatively described.
RESULTS: Finally, 78 articles were found but only 29 relevant articles were included. Nine articles are clinical trials and 20 articles were done on cellular and molecular aspects of saffron on eye disorders. According to the included studies, crocin prevented the pro-inflammatory response in retinal cells and decreased glucose level in diabetic mice. Also, crocetin prevented retinal degeneration and saffron protected photoreceptors from light-induced damage in retinal cells. Saffron also improved visual function in age-related macular edema and decreased intraocular pressure in patients with glaucoma. In addition, it was shown that crocin can improve best corrected visual acuity and decreased central macular thickness in patients with diabetic maculopathy.
CONCLUSION: The results of this review indicated that saffron and its main ingredients such as crocin could be a potential candidate for the treatment of ocular disease especially eye inflammation; however, further clinical studies are needed to confirm such efficiency.


greenmedinfo--2020-05-27--Saffron carotenoids change the superoxide dismutase activity in breast cancer.

Superoxide dismutase ( SOD ) is an important member of the antioxidant defense system and is proposed as a therapeutic agent against the ROS-mediated diseases , and a therapeutic target for cancer treatment .
Saffron carotenoids , crocin ( Cro ) and crocetin ( Crt ) , are antioxidants with anticancer activity .
In the present study , we investigated the effects of Cro/Crt on the SOD activity in both in vivo and in vitro models of breast cancer .
Both Cro and Crt showed strong radical scavenging activity and SOD inhibition in the MCF-7 breast cancer cell line .
@ @ @ @ @ @ @ studies proposed the binding of both Cro and Crt with SOD ; theΔG° of binding at 310 °K was -8.6 and -4.4 kcal/mol , respectively .
The docking analysis predicted the Cro/Crt binding near the active site channel , but in different sites .
According to the obtained data , Cro inhibits SOD activity by scavenging superoxide radical ( O ) , while Crt inhibits SOD by affecting the copper-binding site .
In contrast to the in vitro data , both Cro and Crt effectively increased SOD activity in breast tumors of BALB/c @ @ @ @ @ @ @ .
The mechanism that is important to compensate for the SOD decreased activity in cancer .

Superoxide dismutase (SOD) is an important member of the antioxidant defense system and is proposed as a therapeutic agent against the ROS-mediated diseases, and a therapeutic target for cancer treatment. Saffron carotenoids, crocin (Cro) and crocetin (Crt), are antioxidants with anticancer activity. In the present study, we investigated the effects of Cro/Crt on the SOD activity in both in vivo and in vitro models of breast cancer. Both Cro and Crt showed strong radical scavenging activity and SOD inhibition in the MCF-7 breast cancer cell line. The UVVis, circular dichroism and fluorometry studies proposed the binding of both Cro and Crt with SOD; theΔG° of binding at 310 °K was -8.6 and -4.4 kcal/mol, respectively. The docking analysis predicted the Cro/Crt binding near the active site channel, but in different sites. According to the obtained data, Cro inhibits SOD activity by scavenging superoxide radical (O), while Crt inhibits SOD by affecting the copper-binding site. In contrast to the in vitro data, both Cro and Crt effectively increased SOD activity in breast tumors of BALB/c mice, after one month of treatment. The mechanism that is important to compensate for the SOD decreased activity in cancer.


greenmedinfo--2020-05-27--Flavolignans from silymarin as Nrf2 bioactivators and their therapeutic applications.

Silymarin ( SM ) is a mixture of flavolignans extracted from the seeds of species derived from , commonly known as milk thistle or St. Mary'sthistle .
These species have been widely used in the treatment of liver disorders in traditional medicine since ancient times .
Several properties had been attributed to the major SM flavolignans components , identified as silybin , isosilybin , silychristin , isosilychristin , and silydianin .
Previous research reported antioxidant and protective activities , which are probably related to the activation of the nuclear factor erythroid 2 ( NFE2 ) -related factor 2 ( Nrf2 @ @ @ @ @ @ @ of the cytoprotector response .
Nrf2 is a redox-sensitive nuclear transcription factor able to induce the downstream-associated genes .
The disruption of Nrf2 signaling has been associated with different pathological conditions .
Some identified phytochemicals from SM had shown to participate in the Nrf2 signaling pathway ; in particular , they have been suggested as activators that disrupt interactions in the Keap1-Nrf2 system , but also as antioxidants or with additional actions regarding Nrf2 regulation .
Thus , the study of these molecules makes them appear attractive as novel targets for the treatment @ @ @ @ @ @

Silymarin (SM) is a mixture of flavolignans extracted from the seeds of species derived from, commonly known as milk thistle or St. Mary'sthistle. These species have been widely used in the treatment of liver disorders in traditional medicine since ancient times. Several properties had been attributed to the major SM flavolignans components, identified as silybin, isosilybin, silychristin, isosilychristin, and silydianin. Previous research reported antioxidant and protective activities, which are probably related to the activation of the nuclear factor erythroid 2 (NFE2)-related factor 2 (Nrf2), known as a master regulator of the cytoprotector response. Nrf2 is a redox-sensitive nuclear transcription factor able to induce the downstream-associated genes. The disruption of Nrf2 signaling has been associated with different pathological conditions. Some identified phytochemicals from SM had shown to participate in the Nrf2 signaling pathway; in particular, they have been suggested as activators that disrupt interactions in the Keap1-Nrf2 system, but also as antioxidants or with additional actions regarding Nrf2 regulation. Thus, the study of these molecules makes them appear attractive as novel targets for the treatment or prevention of several diseases.


greenmedinfo--2020-05-27--Op-Ed: COVID-19 Vaccination: What the Plan Looks Like

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

This website is for information purposes only. By providing the information contained herein we are not diagnosing, treating, curing, mitigating, or preventing any type of disease or medical condition. Before beginning any type of natural, integrative or conventional treatment regimen, it is advisable to seek the advice of a licensed healthcare professional.
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greenmedinfo--2020-05-27--In vitro antimicrobial activity of frankincense oils from Boswellia sacra.

Frankincense essential oils fromhave been commonly used to treat microbial infections from as early as the 11th century .
The main feature of the plant is its gum resin , from which it is possible to obtain essential oils .
In the present study , we focused on the comparative study of the oils extracted from the resins of three differentcultivars ( Najdi , Sahli and Houjri ) .
From each of frankincense resin three successive essential oil samples ( Grade 1 , Grade 2 , Grade 3 ) were obtained .
Houjri gum resin gave the lowest percentage ( @ @ @ @ @ @ @ content but showed the maximum number of volatile components in all three grades .
Najdi Grade 2 essential oil showed a minimum inhibitory concentration ( MIC ) of 52 mg/mL toward relevant pathogensand , and samples from Grade 2 of Sahily and Houjiri were particularly active against a dermatological strain , displaying MIC values of 0.264 and 0.66 mg/mL , respectively .
Data obtained from in vitro studies showed that all essential oils had a significant antifungal effect againstand , showing MIC values ranging from 54.56 to 0.246 mg/mL .
This work aims @ @ @ @ @ @ @ in the fight against pathogens and to combat the phenomenon of antibiotic resistance , encouraging the use of alternative resources , especially in non-clinical settings ( farms , food processing , etc . )
.

Frankincense essential oils fromhave been commonly used to treat microbial infections from as early as the 11th century. The main feature of the plant is its gum resin, from which it is possible to obtain essential oils. In the present study, we focused on the comparative study of the oils extracted from the resins of three differentcultivars (Najdi, Sahli and Houjri). From each of frankincense resin three successive essential oil samples (Grade 1, Grade 2, Grade 3) were obtained. Houjri gum resin gave the lowest percentage (5%) of total essential oil content but showed the maximum number of volatile components in all three grades. Najdi Grade 2 essential oil showed a minimum inhibitory concentration (MIC) of 52 mg/mL toward relevant pathogensand, and samples from Grade 2 of Sahily and Houjiri were particularly active against a dermatological strain, displaying MIC values of 0.264 and 0.66 mg/mL, respectively. Data obtained from in vitro studies showed that all essential oils had a significant antifungal effect againstand, showing MIC values ranging from 54.56 to 0.246 mg/mL. This work aims to increase the number of substances available in the fight against pathogens and to combat the phenomenon of antibiotic resistance, encouraging the use of alternative resources, especially in non-clinical settings (farms, food processing, etc.).


greenmedinfo--2020-05-27--Silymarin, boswellic acid and curcumin enriched dietetic formulation reduces the growth of inherited

Silymarin, boswellic acid and curcumin enriched dietetic formulation reduces the growth of inherited intestinal polyps.

BACKGROUND : Some substances of plant origin have been reported to exert an effect in reducing intestinal neoplasm development , especially in animal models .
Adenomatous polyposis coli multiple intestinal neoplasia - Apcis the most studied murine model of genetic intestinal carcinogenesis .
AIM : To assess whether an enriched nutritional formulation ( silymarin , boswellic acid and curcumin ) with provenandanti-carcinogenetic properties may prevent inherited intestinal cancer in animal model .
METHODS : Forty adenomatous polyposis coli multiple intestinal neoplasia - Apcmice were used for the study of cancer prevention .
They were divided into two groups : 20 @ @ @ @ @ @ @ At the 110d animals were sacrificed .
In each group , four subgroups received intraperitoneal bromodeoxyuridine injection at different times ( 24 , 48 , 72 and 96 h before the sacrifice ) in order to assess epithelial turnover .
Moreover , we evaluated the following parameters : Intestinal polypoid lesion number and size on autoptic tissue , dysplasia and neoplasia areas by histological examination of the whole small intestine , inflammation by histology and cytokine mRNA expression by real-time polymerase chain reaction , bromodeoxyuridine and TUNEL immuno-fluorescence for epithelial turnover and apoptosis @ @ @ @ @ @ @ western blotting analysis for the expression of estrogen alpha and beta receptors , cyclin D1 and cleaved caspase 3 in normal and polypoid tissues .
RESULTS : Compared to standard , enriched diet reduced the total number ( 203416 ) and the mean± SD/animal ( 12.6 ± 5.026.0± 8.8 ; < 0.001 ) of polypoid lesions .
In enriched diet group a reduction in polyp size was observed ( < 0.001 ) .
Histological inflammation and pro-inflammatory cytokine expression were similar in both groups .
Areas of low-grade dysplasia ( < 0.001 ) @ @ @ @ @ @ @ 0.001 ) were significantly decreased in enriched diet group .
IC was observed in 100 % in standard and 85 % in enriched formulation assuming animals .
Enriched diet showed a faster epithelial migration and an increased apoptosis in normal mucosa and low-grade dysplasia areas ( < 0.001 ) .
At western blotting , estrogen receptor beta protein was well expressed in normal mucosa of enriched and standard groups , with a more marked trend associated to the first one .
Estrogen receptor alpha was similarly expressed in normal and polypoid mucosa of @ @ @ @ @ @ @ caspase 3 showed in normal mucosa a stronger signal in enriched than in standard diet .
Cyclin D1 was more expressed in standard than enriched diet group of both normal and polypoid tissue .
CONCLUSION : Our results are suggestive of a chemo-preventive synergic effect of the components ( silymarin , boswellic acid and curcumin ) of an enriched formulation in inherited IC .
This effect may be mediated by the reduction of epithelial proliferation , the increase of apoptosis and the acceleration of villous cell renewal due to dietary formulation intake .

BACKGROUND: Some substances of plant origin have been reported to exert an effect in reducing intestinal neoplasm development, especially in animal models. Adenomatous polyposis coli multiple intestinal neoplasia - Apcis the most studied murine model of genetic intestinal carcinogenesis.
AIM: To assess whether an enriched nutritional formulation (silymarin, boswellic acid and curcumin) with provenandanti-carcinogenetic properties may prevent inherited intestinal cancer in animal model.
METHODS: Forty adenomatous polyposis coli multiple intestinal neoplasia - Apcmice were used for the study of cancer prevention. They were divided into two groups: 20 assumed standard and 20 enriched diet. At the 110d animals were sacrificed. In each group, four subgroups received intraperitoneal bromodeoxyuridine injection at different times (24, 48, 72 and 96 h before the sacrifice) in order to assess epithelial turnover. Moreover, we evaluated the following parameters: Intestinal polypoid lesion number and size on autoptic tissue, dysplasia and neoplasia areas by histological examination of the whole small intestine, inflammation by histology and cytokine mRNA expression by real-time polymerase chain reaction, bromodeoxyuridine and TUNEL immuno-fluorescence for epithelial turnover and apoptosis, respectively. Additionally, we performed western blotting analysis for the expression of estrogen alpha and beta receptors, cyclin D1 and cleaved caspase 3 in normal and polypoid tissues.
RESULTS: Compared to standard, enriched diet reduced the total number (203416) and the mean± SD/animal (12.6 ± 5.026.0± 8.8;<0.001) of polypoid lesions. In enriched diet group a reduction in polyp size was observed (<0.001). Histological inflammation and pro-inflammatory cytokine expression were similar in both groups. Areas of low-grade dysplasia (<0.001) and intestinal carcinoma (IC;<0.001) were significantly decreased in enriched diet group. IC was observed in 100% in standard and 85% in enriched formulation assuming animals. Enriched diet showed a faster epithelial migration and an increased apoptosis in normal mucosa and low-grade dysplasia areas (<0.001). At western blotting, estrogen receptor beta protein was well expressed in normal mucosa of enriched and standard groups, with a more marked trend associated to the first one. Estrogen receptor alpha was similarly expressed in normal and polypoid mucosa of standard and enriched diet group. Cleaved caspase 3 showed in normal mucosa a stronger signal in enriched than in standard diet. Cyclin D1 was more expressed in standard than enriched diet group of both normal and polypoid tissue.
CONCLUSION: Our results are suggestive of a chemo-preventive synergic effect of the components (silymarin, boswellic acid and curcumin) of an enriched formulation in inherited IC. This effect may be mediated by the reduction of epithelial proliferation, the increase of apoptosis and the acceleration of villous cell renewal due to dietary formulation intake.


greenmedinfo--2020-05-27--Triterpenic acids as non-competitive α-glucosidase inhibitors from Boswellia elongate.

Fourteen triterpene acids , viz.
, three tirucallane-type ( - ) , eight ursane-type ( - ) , two oleanane-type ( , ) and one lupane type ( ) , along with boswellic aldehyde ( ) , α-amyrine ( ) , epi-amyrine ( ) , straight chain acid ( ) , sesquiterpene ( ) and two cembrane-type diterpenes ( , ) were isolated , first time , from the methanol extract ofresin .
Compound ( ) was isolated for first time as a natural product , while the remaining compounds ( ‒ ) were reported for first time fromThe structures @ @ @ @ @ @ @ spectroscopic techniques including mass spectrometry and also by comparison with the reported literature .
Eight compounds ( -and ) were further screened for in vitroα-glucosidase inhibitory activity .
Compounds-andshowed significant activity againstα-glucosidase with ICvalues ranging from 9.9-56.8μM .
Compound ( IC= 9.9± 0.48 μM ) demonstrated higher inhibition followed by ( IC= 14.9± 1.31 μM ) , ( IC= 20.9± 0.05 μM ) and ( IC= 56.8± 1.30 μM ) , indicating that carboxylic acid play a key role in α-glucosidase inhibition .
Kinetics studies on the active compounds-andwere carried out to investigate @ @ @ @ @ @ @ dissociation constants ) .
All compounds were found to be non-competitive inhibitors withvalues in the range of 7.05± 0.17-51.15 ± 0.25 µM .
Moreover , in silico docking was performed to search the allosteric hotspot for ligand binding which is targeted by our active compounds investigates the binding mode of active compounds and it was identified that compounds preferentially bind in the allosteric binding sites of α-glucosidase .
The results obtained from docking study suggested that the carboxylic group is responsible for their biologic activities .
Furthermore , the α-glucosidase inhibitory potential of @ @ @ @ @ @ @ the first time .

Fourteen triterpene acids, viz., three tirucallane-type (-), eight ursane-type (-), two oleanane-type (,) and one lupane type (), along with boswellic aldehyde (),α-amyrine (), epi-amyrine (), straight chain acid (), sesquiterpene () and two cembrane-type diterpenes (,) were isolated, first time, from the methanol extract ofresin. Compound () was isolated for first time as a natural product, while the remaining compounds (‒) were reported for first time fromThe structures of all compounds were confirmed by advanced spectroscopic techniques including mass spectrometry and also by comparison with the reported literature. Eight compounds (-and) were further screened for in vitroα-glucosidase inhibitory activity. Compounds-andshowed significant activity againstα-glucosidase with ICvalues ranging from 9.9-56.8μM. Compound(IC= 9.9± 0.48 μM) demonstrated higher inhibition followed by(IC= 14.9± 1.31 μM),(IC= 20.9± 0.05 μM) and(IC= 56.8± 1.30 μM), indicating that carboxylic acid play a key role in α-glucosidase inhibition. Kinetics studies on the active compounds-andwere carried out to investigate their mechanism (mode of inhibition and dissociation constants). All compounds were found to be non-competitive inhibitors withvalues in the range of 7.05± 0.17-51.15 ± 0.25 µM. Moreover, in silico docking was performed to search the allosteric hotspot for ligand binding which is targeted by our active compounds investigates the binding mode of active compounds and it was identified that compounds preferentially bind in the allosteric binding sites of α-glucosidase. The results obtained from docking study suggested that the carboxylic group is responsible for their biologic activities. Furthermore, the α-glucosidase inhibitory potential of the active compounds is reported here for the first time.


greenmedinfo--2020-05-27--Genus Boswellia as a new candidate for neurodegenerative disorders.

Neurodegenerative diseases , characterized by progressive loss of neurons , share common mechanisms such as apoptotic cell death , mitochondrial dysfunction , inflammation , and oxidative stress .
Genusis a genus in the Burseraceae family .
It comprises several species traditionally used for treatment of chronic inﬂammatory diseases , cerebral edema , chronic pain syndrome , gastrointestinal diseases , tumors , as well as enhancing intelligence .
Many studies have been carried out to discover therapeutic approaches for neurodegenerative diseases such as Alzheimer 's diseases , Parkinson 's disease , Huntington 's disease , multiple sclerosis and amyotrophic lateral sclerosis @ @ @ @ @ @ @ .
However , no curative treatment has been developed .
This paper provides an overview of evidence about the potential of the Boswellia species and their main constituents , boswellic acids , as modulators of several mechanisms involved in the pathology of the neurodegenerative diseases.
, animal , and clinical studies have confirmed that Boswellia species contain bioactive components that may enhance cognitive activity and protect against neurodegeneration .
They exert the beneficial effects via targeting multiple pathological causes by antioxidative , anti-inflammatory , antiamyloidogenic , and anti-apoptotic properties .
The Boswellia species @ @ @ @ @ @ @ a promising candidate to cure or prevent the neurodegenerative disorders .

Neurodegenerative diseases, characterized by progressive loss of neurons, share common mechanisms such as apoptotic cell death, mitochondrial dysfunction, inflammation, and oxidative stress. Genusis a genus in the Burseraceae family. It comprises several species traditionally used for treatment of chronic inﬂammatory diseases, cerebral edema, chronic pain syndrome, gastrointestinal diseases, tumors, as well as enhancing intelligence. Many studies have been carried out to discover therapeutic approaches for neurodegenerative diseases such as Alzheimer's diseases, Parkinson's disease, Huntington's disease, multiple sclerosis and amyotrophic lateral sclerosis, stroke, and concomitant cognitive deficits. However, no curative treatment has been developed. This paper provides an overview of evidence about the potential of the Boswellia species and their main constituents, boswellic acids, as modulators of several mechanisms involved in the pathology of the neurodegenerative diseases., animal, and clinical studies have confirmed that Boswellia species contain bioactive components that may enhance cognitive activity and protect against neurodegeneration. They exert the beneficial effects via targeting multiple pathological causes by antioxidative, anti-inflammatory, antiamyloidogenic, and anti-apoptotic properties. The Boswellia species, having neuroprotective potential, makes them a promising candidate to cure or prevent the neurodegenerative disorders.


greenmedinfo--2020-05-27--Licochalcone A selectively resensitizes ABCG2-overexpressing multidrug-resistant cancer cells to che

Licochalcone A selectively resensitizes ABCG2-overexpressing multidrug-resistant cancer cells to chemotherapeutic drugs.

The overexpression of the ATP-binding cassette ( ABC ) transporter ABCG2 has been linked to clinical multidrug resistance in solid tumors and blood cancers , which remains a significant obstacle to successful cancer chemotherapy .
For years , the potential modulatory effect of bioactive compounds derived from natural sources on ABCG2-mediated multidrug resistance has been investigated , as they are inherently well tolerated and offer a broad range of chemical scaffolds .
Licochalcone A ( LCA ) , a natural chalcone isolated from the root of , is known to possess a broad spectrum of biological and pharmacological activities , @ @ @ @ @ @ @ cancer cell lines .
In this study , the chemosensitization effect of LCA was examined in ABCG2-overexpressing multidrug-resistant cancer cells .
Experimental data demonstrated that LCA inhibits the drug transport function of ABCG2 and reverses ABCG2-mediated multidrug resistance in human multidrug-resistant cancer cell lines in a concentration-dependent manner .
Results of LCA-stimulated ABCG2 ATPase activity and the in silico docking analysis of LCA to the inward-open conformation of human ABCG2 suggest that LCA binds ABCG2 in the transmembrane substrate-binding pocket .
This study provides evidence that LCA should be further evaluated as a @ @ @ @ @ @ @ trials against ABCG2-expressing drug-resistant tumors .

The overexpression of the ATP-binding cassette (ABC) transporter ABCG2 has been linked to clinical multidrug resistance in solid tumors and blood cancers, which remains a significant obstacle to successful cancer chemotherapy. For years, the potential modulatory effect of bioactive compounds derived from natural sources on ABCG2-mediated multidrug resistance has been investigated, as they are inherently well tolerated and offer a broad range of chemical scaffolds. Licochalcone A (LCA), a natural chalcone isolated from the root of, is known to possess a broad spectrum of biological and pharmacological activities, including pro-apoptotic and antiproliferative effects in various cancer cell lines. In this study, the chemosensitization effect of LCA was examined in ABCG2-overexpressing multidrug-resistant cancer cells. Experimental data demonstrated that LCA inhibits the drug transport function of ABCG2 and reverses ABCG2-mediated multidrug resistance in human multidrug-resistant cancer cell lines in a concentration-dependent manner. Results of LCA-stimulated ABCG2 ATPase activity and the in silico docking analysis of LCA to the inward-open conformation of human ABCG2 suggest that LCA binds ABCG2 in the transmembrane substrate-binding pocket. This study provides evidence that LCA should be further evaluated as a modulator of ABCG2 in drug combination therapy trials against ABCG2-expressing drug-resistant tumors.


greenmedinfo--2020-05-27--Vasorelaxation effect of 18β-glycyrrhetinic acid on the thoracic aorta of rats.

18β-Glycyrrhetinic acid ( 18β-GA ) is an effective component extracted from the traditional Chinese medicine ( Leguminosae ) and has various biological activities .
This study was performed to investigate the vasodilatory effects of 18β-GA on isolated rat thoracic aortic rings and explore the underlying mechanisms .
The rings were obtained from normal Sprague-Dawley rats and then precontracted with norepinephrine ( NE ) ( 1 μM ) or KCl ( 60 mM ) .
18β-GA ( 1.883-11.297mg/L ) was added successively by cumulative dosing to observe and record the changes in the tension of the vascular ring .
The effects @ @ @ @ @ @ @ indomethacin ( INDO ) , barium chloride ( BaCl₂ ) , 4-aminopyridine ( 4-AP ) , tetraethylammonium ( TEA ) , and glibenclamide on the vascular diastolic function of 18β-GA were determined .
18β-GA substantially exhibited a dose-dependent vasorelaxant effect on the NE-induced and KCl-induced contractions of the rings .
The integrity of the vascular endothelium had no influence on the 18β-GA-induced vasorelaxation effect in the rings .
L-NAME and IDON showed no significant differences in their effects on this vasorelaxation process in the rings precontracted with NE .
This result suggests that @ @ @ @ @ @ @ independent of the vascular endotheliumBaCl₂ and 4-AP antagonized the vasorelaxation effect of 18β-GA , but TEA and glibenclamide showed no remarkable effect on the vasodilation of 18β-GA .
Findings suggest that 18β-GA induces vasorelaxation in thoracic aortic rings via the receptor-operated Cachannels and voltage-operated Cachannels and the opening of inward rectifier potassium channels and voltage-operated potassium .

18β-Glycyrrhetinic acid (18β-GA) is an effective component extracted from the traditional Chinese medicine(Leguminosae) and has various biological activities. This study was performed to investigate the vasodilatory effects of 18β-GA on isolated rat thoracic aortic rings and explore the underlying mechanisms. The rings were obtained from normal Sprague-Dawley rats and then precontracted with norepinephrine (NE) (1 μM) or KCl (60 mM). 18β-GA (1.883-11.297mg/L) was added successively by cumulative dosing to observe and record the changes in the tension of the vascular ring. The effects of NG-nitro-l-arginine methylester (L-NAME), indomethacin (INDO), barium chloride (BaCl₂), 4-aminopyridine(4-AP), tetraethylammonium (TEA), and glibenclamide on the vascular diastolic function of 18β-GA were determined. 18β-GA substantially exhibited a dose-dependent vasorelaxant effect on the NE-induced and KCl-induced contractions of the rings. The integrity of the vascular endothelium had no influence on the 18β-GA-induced vasorelaxation effect in the rings. L-NAME and IDON showed no significant differences in their effects on this vasorelaxation process in the rings precontracted with NE. This result suggests that the vasorelaxation mechanism of 18β-GA may be independent of the vascular endotheliumBaCl₂ and 4-AP antagonized the vasorelaxation effect of 18β-GA, but TEA and glibenclamide showed no remarkable effect on the vasodilation of 18β-GA. Findings suggest that 18β-GA induces vasorelaxation in thoracic aortic rings via the receptor-operated Cachannels and voltage-operated Cachannels and the opening of inward rectifier potassium channels and voltage-operated potassium.


greenmedinfo--2020-05-27--18α-glycyrrhetinic acid ameliorates fructose-induced nephropathy.

Excessive fructose ( FRU ) intake can result in insulin resistance and metabolic disorder , which are related to renal injury.18α-Glycyrrhetinic acid ( GA ) is a bioactive component mainly extracted from Glycyrrhiza radix , and has anti-oxidant and anti-inflammatory activities .
However , its effects on FRU-induced renal injury still remain unclear .
In this study , we found that 18α-GA treatments could significantly ameliorate the cell viability in FRU-treated tubule epithelial cells , accompanied with improved mitochondrial membrane potential .
Furthermore , reactive oxygen species ( ROS ) accumulation in FRU-stimulated cells was markedly reduced by 18α-GA , @ @ @ @ @ @ @ nuclear factor ( erythroid-derived-2 ) -like 2 ( Nrf-2 ) and the blockage of MAPKs signaling .
Additionally , dyslipidemia detected in FRU-treated cells was greatly inhibited by 18α-GA. We also found that 18α-GA significantly ameliorated FRU-induced inflammation in cells through reducing the expression of pro-inflammatory cytokines and chemokine .
The anti-inflammatory effects regulated by 18α-GA were mainly related to the repression of nuclear factor-κB ( NF-κB ) signaling .
Furthermore , the protective effects of 18α-GA against ROS production , lipid accumulation and inflammation were verified in renal tissues from FRU-challenged mice @ @ @ @ @ @ @ injury .
Taken together , these findings demonstrated that 18α-GA exerted renal protective effects through reducing oxidative stress , lipid deposition and inflammatory response , and thus could be considered as a promising therapeuticstrategy for metabolic stress-induced kidney injury .

Excessive fructose (FRU) intake can result in insulin resistance and metabolic disorder, which are related to renal injury.18α-Glycyrrhetinic acid (GA) is a bioactive component mainly extracted from Glycyrrhiza radix, and has anti-oxidant and anti-inflammatory activities. However, its effects on FRU-induced renal injury still remain unclear. In this study, we found that 18α-GA treatments could significantly ameliorate the cell viability in FRU-treated tubule epithelial cells, accompanied with improved mitochondrial membrane potential. Furthermore, reactive oxygen species (ROS) accumulation in FRU-stimulated cells was markedly reduced by 18α-GA, which were associated with the activation of nuclear factor (erythroid-derived-2)-like 2 (Nrf-2) and the blockage of MAPKs signaling. Additionally, dyslipidemia detected in FRU-treated cells was greatly inhibited by 18α-GA. We also found that 18α-GA significantly ameliorated FRU-induced inflammation in cells through reducing the expression of pro-inflammatory cytokines and chemokine. The anti-inflammatory effects regulated by 18α-GA were mainly related to the repression of nuclear factor-κB(NF-κB) signaling. Furthermore, the protective effects of 18α-GA against ROS production, lipid accumulation and inflammation were verified in renal tissues from FRU-challenged mice, consequently improving metabolic disorder and kidney injury. Taken together, these findings demonstrated that 18α-GA exerted renal protective effects through reducing oxidative stress, lipid deposition and inflammatory response, and thus could be considered as a promising therapeuticstrategy for metabolic stress-induced kidney injury.


greenmedinfo--2020-05-27--18β-glycyrrhetinic acid acts through hepatocyte nuclear factor 4 alpha to modulate lipid and carbohy

18β-glycyrrhetinic acid acts through hepatocyte nuclear factor 4 alpha to modulate lipid and carbohydrate metabolism.

Hepatocyte nuclear factor 4 alpha ( HNF4α ) regulates the expression of essential genes involved in very-low-density lipoprotein ( VLDL ) homeostasis and gluconeogenesis .
18β-glycyrrhetinic acid ( GA ) is an active ingredient of Glycyrrhiza uralensis an herbal medicine used for treating liver aliments .
In this study , we established that GAfunctions as a partial antagonist of HNF4α through HNF4α-driven reporter luciferase assay and co-immunoprecipitation experiments with co-activator PGC1α .
By virtual docking and site-directed mutagenesis analysis , we confirmed that serine 190 and arginine 235 of HNF4α are both essential for GA to exert its antagonistic action @ @ @ @ @ @ @ the expression of HNF4α target genes such as apolipoprotein B ( ApoB ) , microsomal triglyceride transfer protein ( MTP ) and phospholipase AG12B ( PLA2G12B ) modulating hepatic VLDL secretion in mice fed on a high fat diet .
In addition , GA also suppressed gluconeogenesis and ameliorated glucose intolerance via down-regulating the expression of HNF4α target genes glucose-6-phosphatase ( G6pc ) and phosphoenolpyruvate carboxykinase ( Pepck ) .
Furthermore , GA significantly lowered blood glucose and improved insulin resistance in db/db mice .
In all , we established that GA acts @ @ @ @ @ @ @ and carbohydrate metabolism .

Hepatocyte nuclear factor 4 alpha (HNF4α) regulates the expression of essential genes involved in very-low-density lipoprotein (VLDL) homeostasis and gluconeogenesis. 18β-glycyrrhetinic acid (GA) is an active ingredient of Glycyrrhiza uralensis an herbal medicine used for treating liver aliments. In this study, we established that GAfunctions as a partial antagonist of HNF4α through HNF4α-driven reporter luciferase assay and co-immunoprecipitation experiments with co-activator PGC1α. By virtual docking and site-directed mutagenesis analysis, we confirmed that serine 190 and arginine 235 of HNF4α are both essential for GA to exert its antagonistic action on HNF4α. Importantly, GA suppressed the expression of HNF4α target genes such as apolipoprotein B (ApoB), microsomal triglyceride transfer protein (MTP) and phospholipase AG12B (PLA2G12B) modulating hepatic VLDL secretion in mice fed on a high fat diet. In addition, GA also suppressed gluconeogenesis and ameliorated glucose intolerance via down-regulating the expression of HNF4α target genes glucose-6-phosphatase (G6pc) and phosphoenolpyruvate carboxykinase (Pepck). Furthermore, GA significantly lowered blood glucose and improved insulin resistance in db/db mice. In all, we established that GA acts as a partial HNF4α antagonist modulating lipid and carbohydrate metabolism.


greenmedinfo--2020-05-27--COVID-19 Fact Sheet - Face Masks

COVID-19 Fact Sheet - Face Masks


greenmedinfo--2020-05-27--The effects of licorice containing diphenhydramine solution on recurrent aphthous stomatitis.

OBJECTIVES : The aim of this study was to compare the efficacy of the diphenhydramine solution ( DS ) and diphenhydramine-containing glycyrrhiza glabra ( DSG ) in the treatment of recurrent aphthous stomatitis ( RAS ) .
DESIGN : It was a double-blind randomized clinical trial that was conducted from July to September 2018 at the Faculty of Dentistry , Birjand University of Medical Sciences , Birjand , Iran .
INTERVENTION : DSG was made by adding 5 % hydroethanolic extract of licorice to the diphenhydramine elixir .
A total of 70 patients diagnosed with RSA were randomly assigned to @ @ @ @ @ @ @ containing 35 patients .
Participants were instructed to swish 3 ml of either solution around their mouth for about three minutes four times a day ( at least 20 min before each meal and before bedtime ) until the complete healing of the oral lesions .
MAIN OUTCOME MEASURES : The primary outcome of this study was to assess the severity of pain prior to the intervention and on the first , third , and fifth days of it .
This was done using the visual analog scale ( VAS ) .
The @ @ @ @ @ @ @ through photography .
The secondary outcome was to record the adverse effects of the intervention .
This trial was registered at the Iranian Registry of Clinical Trials under numberIRCT20180407039213N1 .
RESULTS : The average pain score before the treatment in the DS and DSG groups was 8 .
1 ± 1.17 and 7.97 ± 1.72 , respectively , and there was apparently no significant difference between them .
However , there was a significant difference between the two groups in terms of the average pain scores on the first ( 7 ± 1.28 @ @ @ @ @ @ @ ( 4.02 ± 1.8 vs. 2.86 ± 1.56 ) and fifth days ( 1.71 ± 1.69 vs. 0.54 ± 1.31 ) of the intervention .
Indeed , DSG significantly reduced the average wound healing duration by 1.5 days , as compared to DS ( P = 0.0001 ) .
No adverse effects were observed with the intervention .
CONCLUSION : According to our results , DSG appeared to be more effective in treating RAS than DS alone .
TRIAL REGISTRATION : The trial was registered at Iranian Registry of Clinical Trials before the @ @ @ @ @ @ @ 29 , 2019 ( registration no : IRCT20180407039213N1 , https : //www.irct.ir/trial/31497 ) .

OBJECTIVES: The aim of this study was to compare the efficacy of the diphenhydramine solution (DS) and diphenhydramine-containing glycyrrhiza glabra (DSG) in the treatment of recurrent aphthous stomatitis (RAS).
DESIGN: It was a double-blind randomized clinical trial that was conducted from July to September 2018 at the Faculty of Dentistry, Birjand University of Medical Sciences, Birjand, Iran.
INTERVENTION: DSG was made by adding 5% hydroethanolic extract of licorice to the diphenhydramine elixir. A total of 70 patients diagnosed with RSA were randomly assigned to the DS and DSG groups, each containing 35 patients. Participants were instructed to swish 3 ml of either solution around their mouth for about three minutes four times a day (at least 20 min before each meal and before bedtime) until the complete healing of the oral lesions.
MAIN OUTCOME MEASURES: The primary outcome of this study was to assess the severity of pain prior to the intervention and on the first, third, and fifth days of it. This was done using the visual analog scale (VAS). The duration of wound healing was also measured through photography. The secondary outcome was to record the adverse effects of the intervention. This trial was registered at the Iranian Registry of Clinical Trials under numberIRCT20180407039213N1.
RESULTS: The average pain score before the treatment in the DS and DSG groups was 8. 1 ± 1.17 and 7.97 ± 1.72, respectively, and there was apparently no significant difference between them. However, there was a significant difference between the two groups in terms of the average pain scores on the first (7 ± 1.28 versus 5.31 ± 1.28), third (4.02 ± 1.8 vs. 2.86 ± 1.56) and fifth days (1.71 ± 1.69 vs. 0.54 ± 1.31) of the intervention. Indeed, DSG significantly reduced the average wound healing duration by 1.5 days, as compared to DS (P = 0.0001). No adverse effects were observed with the intervention.
CONCLUSION: According to our results, DSG appeared to be more effective in treating RAS than DS alone.
TRIAL REGISTRATION: The trial was registered at Iranian Registry of Clinical Trials before the enrolment of the first patient on June 29, 2019 (registration no: IRCT20180407039213N1, https://www.irct.ir/trial/31497).


greenmedinfo--2020-05-27--Antihyperglycemic activity of bacosine.

Antihyperglycemic activity of bacosine.

This article describes the antihyperglycemic activity , in vivo antioxidant potential , effect on hemoglobin glycosylation , estimation of liver glycogen content , and in vitro peripheral glucose utilization of bacosine , a triterpene isolated from the ethyl acetate fraction ( EAF ) of the ethanolic extract of Bacopa monnieri .
Bacosine produced a significant decrease in the blood glucose level when compared with the diabetic control rats both in the single administration as well as in the multiple administration study .
It was observed that the compound reversed the weight loss of the diabetic rats , returning the values @ @ @ @ @ @ @ elevation of glycosylated hemoglobin in vitro with an IC₅₀ value of 7.44 µg/mL , comparable with the one for the reference drug α-tocopherol .
Administration of bacosine and glibenclamide significantly decreased the levels of malondialdehyde ( MDA ) , and increased the levels of reduced glutathione ( GSH ) and the activities of superoxide dismutase ( SOD ) and catalase ( CAT ) in the liver of diabetic rats .
Bacosine increased glycogen content in the liver of diabetic rats and peripheral glucose utilization in the diaphragm of diabetic rats in vitro , @ @ @ @ @ @ @ insulin .
Thus , bacosine might have insulin-like activity and its antihyperglycemic effect might be due to an increase in peripheral glucose consumption as well as protection against oxidative damage in alloxanized diabetes .

This article describes the antihyperglycemic activity, in vivo antioxidant potential, effect on hemoglobin glycosylation, estimation of liver glycogen content, and in vitro peripheral glucose utilization of bacosine, a triterpene isolated from the ethyl acetate fraction (EAF) of the ethanolic extract of Bacopa monnieri. Bacosine produced a significant decrease in the blood glucose level when compared with the diabetic control rats both in the single administration as well as in the multiple administration study. It was observed that the compound reversed the weight loss of the diabetic rats, returning the values to near normal. Bacosine also prevented elevation of glycosylated hemoglobin in vitro with an IC₅₀ value of 7.44 µg/mL, comparable with the one for the reference drug α-tocopherol. Administration of bacosine and glibenclamide significantly decreased the levels of malondialdehyde (MDA), and increased the levels of reduced glutathione (GSH) and the activities of superoxide dismutase (SOD)and catalase (CAT) in the liver of diabetic rats. Bacosine increased glycogen content in the liver of diabetic rats and peripheral glucose utilization in the diaphragm of diabetic rats in vitro, which is comparable with the action of insulin. Thus, bacosine might have insulin-like activity and its antihyperglycemic effect might be due to an increase in peripheral glucose consumption as well as protection against oxidative damage in alloxanized diabetes.


greenmedinfo--2020-05-27--Bacopa monnieri and their bioactive compounds inferred multi-target treatment strategy for neurologi

Bacopa monnieri and their bioactive compounds inferred multi-target treatment strategy for neurological diseases.

Neurological diseases ( NDs ) , especially Alzheimer 's and Spinocerebellar ataxia ( SCA ) , can severely cause biochemical abnormalities in the brain , spinal cord and other nerves of human beings .
Their ever-increasing prevalence has led to a demand for new drug development .
Indian traditional and Ayurvedic medicine used to combat the complex diseases from a holistic and integrative point of view has shown efficiency and effectiveness in the treatment of NDs.is a potent Indian medicinal herb used for multiple ailments , but is significantly known as a nootropic or brain tonic and memory enhancer .
@ @ @ @ @ @ @ and acts as an alternative and complementary medicine in various countries .
However , system-level insights of the molecular mechanism of a multiscale treatment strategy for NDs is still a bottleneck .
Considering its prominence , we used cheminformatics and system pharmacological approaches , with the aim to unravel the various molecular mechanisms represented by Bacopa-derived compounds in identifying the active human targets when treating NDs .
First , using cheminformatics analysis combined with the drug target mining process , 52 active compounds and their corresponding 780 direct receptors were retrieved and computationally @ @ @ @ @ @ @ , bioactive scores and comparative analysis with commercially available drugs , novel and active compounds such as asiatic acid ( ASTA ) and loliolide ( LLD ) to treat the Alzheimer 's and SCA were identified .
According to the interactions among the active compounds , the targets and diseases were further analyzed to decipher the deeper pharmacological actions of the drug .
NDs consist of complex regulatory modules that are integrated to dissect the therapeutic effects of compounds derived from Bacopa in various pathological features and their encoding biological processes .
All @ @ @ @ @ @ @ curative activities in regulating the various biological processes of NDs and also pave the way for the treatment of various diseases in modern medicine .

Neurological diseases (NDs), especially Alzheimer's and Spinocerebellar ataxia (SCA), can severely cause biochemical abnormalities in the brain, spinal cord and other nerves of human beings. Their ever-increasing prevalence has led to a demand for new drug development. Indian traditional and Ayurvedic medicine used to combat the complex diseases from a holistic and integrative point of view has shown efficiency and effectiveness in the treatment of NDs.is a potent Indian medicinal herb used for multiple ailments, but is significantly known as a nootropic or brain tonic and memory enhancer. This annual herb has various active compounds and acts as an alternative and complementary medicine in various countries. However, system-level insights of the molecular mechanism of a multiscale treatment strategy for NDs is still a bottleneck. Considering its prominence, we used cheminformatics and system pharmacological approaches, with the aim to unravel the various molecular mechanisms represented by Bacopa-derived compounds in identifying the active human targets when treating NDs. First, using cheminformatics analysis combined with the drug target mining process, 52 active compounds and their corresponding 780 direct receptors were retrieved and computationally validated. Based on the molecular properties, bioactive scores and comparative analysis with commercially available drugs, novel and active compounds such as asiatic acid (ASTA) and loliolide (LLD) to treat the Alzheimer's and SCA were identified. According to the interactions among the active compounds, the targets and diseases were further analyzed to decipher the deeper pharmacological actions of the drug. NDs consist of complex regulatory modules that are integrated to dissect the therapeutic effects of compounds derived from Bacopa in various pathological features and their encoding biological processes. All these revealed that Bacopa compounds have several curative activities in regulating the various biological processes of NDs and also pave the way for the treatment of various diseases in modern medicine.


greenmedinfo--2020-05-27--Bacopa monnieri inhibits apoptosis and senescence through mitophagy in human astrocytes.

Benzo [ a ] pyrene ( B [ a ] P ) , a polycyclic aromatic hydrocarbon , is a potent neurotoxic agent that is responsible for impaired neuronal development and is associated with aging .
Here , it was demonstrated that extracts of Bacopa monnieri ( BM ) , a traditional Ayurvedic medicine , diminished the B [ a ] P-induced apoptosis and senescence in human astrocytes .
BM was demonstrated to protect the immortalized primary fetal astrocytes ( IMPHFA ) from B [ a ] P-induced apoptosis and senescence by reducing the damaged mitochondria that produced reactive oxygen @ @ @ @ @ @ @ it was shown that B [ a ] P-triggered G2 arrest could be altered by BM , thus indicating that BM could reverse the cell cycle arrest and mediate a normal cell cycle in IMPHFA cells .
In addition , the lifespan of Caenorhabditis elegans was assessed , which confirmed these effects in the presence of BM , compared to the B [ a ] P-treated group .
Furthermore , the anti-senescence and anti-apoptotic activities of BM were observed to be mediated through the protective effect of mitophagy , and inhibition of mitophagy @ @ @ @ @ @ @ ROS-induced apoptosis and senescence in BM-treated cells .
Moreover , it was revealed that BM induced Parkin-dependent mitophagy to exert its cytoprotective activity in IMPHFA cells .
In conclusion , the anti-senescence and anti-apoptotic effects of BM in astrocytes could combat pollution and aging-related neurological disorders .

Benzo[a]pyrene (B[a]P), a polycyclic aromatic hydrocarbon, is a potent neurotoxic agent that is responsible for impaired neuronal development and is associated with aging. Here, it was demonstrated that extracts of Bacopa monnieri (BM), a traditional Ayurvedic medicine, diminished the B[a]P-induced apoptosis and senescence in human astrocytes. BM was demonstrated to protect the immortalized primary fetal astrocytes (IMPHFA) from B[a]P-induced apoptosis and senescence by reducing the damaged mitochondria that produced reactive oxygen species (ROS). Furthermore, it was shown that B[a]P-triggered G2 arrest could be altered by BM, thus indicating that BM could reverse the cell cycle arrest and mediate a normal cell cycle in IMPHFA cells. In addition, the lifespan of Caenorhabditis elegans was assessed, which confirmed these effects in the presence of BM, compared to the B[a]P-treated group. Furthermore, the anti-senescence and anti-apoptotic activities of BM were observed to be mediated through the protective effect of mitophagy, and inhibition of mitophagy could not protect the astrocytes from mitochondrial ROS-induced apoptosis and senescence in BM-treated cells. Moreover, it was revealed that BM induced Parkin-dependent mitophagy to exert its cytoprotective activity in IMPHFA cells. In conclusion, the anti-senescence and anti-apoptotic effects of BM in astrocytes could combat pollution and aging-related neurological disorders.


greenmedinfo--2020-05-27--Bacopa monnieri extract improves memory performance.

L. Wettst .
( BM ) is a botanical component of Ayurvedic medicines and of dietary supplements used worldwide for cognitive health and function .
We previously reported that administration of BM alcoholic extract ( BME ) prevents trimethyltin ( TMT ) -induced cognitive deficits and hippocampal cell damage and promotes TMT-induced hippocampal neurogenesis .
In this study , we demonstrate that administration of BME improves spatial working memory in adolescent ( 5-week- old ) healthy mice but not adult ( 8-week-old ) mice .
Moreover , improved spatial working memory was retained even at 4 weeks after terminating 1-week @ @ @ @ @ @ @ treatment of adolescent mice significantly enhanced hippocampal BrdU incorporation and expression of genes involved in neurogenesis determined by RNAseq analysis .
Cell death , as detected by histochemistry , appeared not to be significant .
A significant increase in neurogenesis was observed in the dentate gyrus region 4 weeks after terminating 1-week treatment of adolescent mice with BME .
Bacopaside I , an active component of BME , promoted the proliferation of neural progenitor cells in vitro in a concentration-dependent manner via the facilitation of the Akt and ERK1/2 signaling .
These results @ @ @ @ @ @ @ in healthy adolescent mice by promoting hippocampal neurogenesis and that the effects of BME are due , in significant amounts , to bacopaside I .

L. Wettst. (BM) is a botanical component of Ayurvedic medicines and of dietary supplements used worldwide for cognitive health and function. We previously reported that administration of BM alcoholic extract (BME) prevents trimethyltin (TMT)-induced cognitive deficits and hippocampal cell damage and promotes TMT-induced hippocampal neurogenesis. In this study, we demonstrate that administration of BME improves spatial working memory in adolescent (5-week- old) healthy mice but not adult (8-week-old) mice. Moreover, improved spatial working memory was retained even at 4 weeks after terminating 1-week treatment of adolescent mice. One-week BME treatment of adolescent mice significantly enhanced hippocampal BrdU incorporation and expression of genes involved in neurogenesis determined by RNAseq analysis. Cell death, as detected by histochemistry, appeared not to be significant. A significant increase in neurogenesis was observed in the dentate gyrus region 4 weeks after terminating 1-week treatment of adolescent mice with BME. Bacopaside I, an active component of BME, promoted the proliferation of neural progenitor cells in vitro in a concentration-dependent manner via the facilitation of the Akt and ERK1/2 signaling. These results suggest that BME enhances spatial working memory in healthy adolescent mice by promoting hippocampal neurogenesis and that the effects of BME are due, in significant amounts, to bacopaside I.


greenmedinfo--2020-05-27--Astaxanthin modulates apoptotic molecules to induce death of SKBR3 breast cancer cells.

Astaxanthin ( AST ) is related to apoptosis but the details of the mechanism of how AST makes apoptosis is not clear .
The present study investigated apoptotic effects of AST to SKBR3 , a breast cancer cell line in detail .
Cell viability assay showed cellular proliferation and morphological changes of the cells were observed under AST treatment .
FACS analysis indicated that AST blocked cell cycle progression at G0/G1 , suppressed proliferation dose-dependently , and induced apoptosis of the cells .
The apoptosis of the cells by AST was further demonstrated through the decreased expression level of mutp53 @ @ @ @ @ @ @ .
In addition , AST induced the intrinsic apoptosis of the cells by activation of Bax/Bcl2 , cleaved caspase-3 , and cleaved caspase-9 as well as the phosphorylation of ERK1/2 , JNK , and p38 .
Furthermore , AST decreased production of intracellular reactive oxygen species as well as modulated expressions of superoxide dismutases and Pontin , an anti-apoptotic factor .
Co-immunoprecipitation assay revealed AST reduced interaction between Pontin and mutant p53 .
Taken together , these studies proved that AST regulates the expression of apoptotic molecules to induce intrinsic apoptosis of the @ @ @ @ @ @ @ an alternative for improving the efficacies of other anti-cancer therapies for breast cancer .

Astaxanthin (AST) is related to apoptosis but the details of the mechanism of how AST makes apoptosis is not clear. The present study investigated apoptotic effects of AST to SKBR3, a breast cancer cell line in detail. Cell viability assay showed cellular proliferation and morphological changes of the cells were observed under AST treatment. FACS analysis indicated that AST blocked cell cycle progression at G0/G1, suppressed proliferation dose-dependently, and induced apoptosis of the cells. The apoptosis of the cells by AST was further demonstrated through the decreased expression level of mutp53 and cleaved a PARP-1 fragment, respectively. In addition, AST induced the intrinsic apoptosis of the cells by activation of Bax/Bcl2, cleaved caspase-3, and cleaved caspase-9 as well as the phosphorylation of ERK1/2, JNK, and p38. Furthermore, AST decreased production of intracellular reactive oxygen species as well as modulated expressions of superoxide dismutases and Pontin, an anti-apoptotic factor. Co-immunoprecipitation assay revealed AST reduced interaction between Pontin and mutant p53. Taken together, these studies proved that AST regulates the expression of apoptotic molecules to induce intrinsic apoptosis of the cells, suggesting AST therapy might provide an alternative for improving the efficacies of other anti-cancer therapies for breast cancer.


greenmedinfo--2020-05-27--Astaxanthin attenuates hepatic damages and mitochondrial dysfunction in nonalcoholic fatty liver dis

Astaxanthin attenuates hepatic damages and mitochondrial dysfunction in nonalcoholic fatty liver disease.

BACKGROUND AND PURPOSE : Non-alcoholic fatty liver disease ( NAFLD ) is considered to be one of the most common chronic liver diseases across worldwide .
Astaxanthin ( Ax ) is a type of carotenoid , and beneficial effects of Ax , including anti-oxidative , anti-inflammatory , and anti-tumor activity , have been identified .
The present study aimed to elucidate the protective effect of Ax against NAFLD and its underlying mechanism .
EXPERIMENTAL APPROACH : Mice were fed either a high fat or chow diet , with or without AX , for up to 12 weeks .
L02 cells @ @ @ @ @ @ @ with different doses of Ax for 48 h. Histopathology , expression of lipid metabolism , inflammation , apoptosis , and fibrosis-related gene expression were assessed .
And the function of mitochondria were also evaluated .
KEY RESULTS : The results indicated that Ax attenuated HFD- and FFA-induced lipid accumulation and its associated oxidative stress , cell apoptosis , inflammation , and fibrosis both in vivo and in vitro .
Ax upregulated FGF21 and PGC-1α expression in damaged hepatocytes , which suggested an unrecognized mechanism of Ax on ameliorating NAFLD .
CONCLUSION AND IMPLICATIONS @ @ @ @ @ @ @ dysfunction in NAFLD by upregulating FGF21/PGC-1α pathway .
Our studies verified that Ax may become a promising drug to treat or relieve NAFLD .

BACKGROUND AND PURPOSE: Non-alcoholic fatty liver disease (NAFLD) is considered to be one of the most common chronic liver diseases across worldwide. Astaxanthin (Ax) is a type of carotenoid,and beneficial effects of Ax,including anti-oxidative, anti-inflammatory, and anti-tumor activity, have been identified. The present study aimed to elucidate the protective effect of Ax against NAFLD and its underlying mechanism.
EXPERIMENTAL APPROACH: Mice were fed either a high fat or chow diet, with or without AX, for up to 12 weeks. L02 cells were treated with free fatty acids combined with different doses of Ax for 48 h. Histopathology, expression of lipid metabolism, inflammation, apoptosis, and fibrosis-related gene expression were assessed. And the function of mitochondria were also evaluated.
KEY RESULTS: The results indicated that Ax attenuated HFD- and FFA-induced lipid accumulation and its associated oxidative stress, cell apoptosis, inflammation, and fibrosis both in vivo and in vitro. Ax upregulated FGF21 and PGC-1α expression in damaged hepatocytes, which suggested an unrecognized mechanism of Ax on ameliorating NAFLD.
CONCLUSION AND IMPLICATIONS: Ax attenuated hepatocyte damage and mitochondrial dysfunction in NAFLD by upregulating FGF21/PGC-1α pathway. Our studies verified that Ax may become a promising drug to treat or relieve NAFLD.


greenmedinfo--2020-05-27--Astaxanthin improves osteopenia caused by aldehyde-stress resulting from Aldh2 mutation due to impai

Astaxanthin improves osteopenia caused by aldehyde-stress resulting from Aldh2 mutation due to impaired osteoblastogenesis.

Aldehyde dehydrogenase 2 ( ALDH2 ) plays major roles in aldehyde detoxification and in the catalysis of amino acids .
ALDH2∗2 , a dominant-negative transgenic expressing aldehyde dehydrogenase 2 ( ALDH2 ) protein , is produced by a single nucleotide polymorphism ( rs671 ) and is involved in the development of osteoporosis and hip fracture with aging .
In a previous study , transgenic mice expressing Aldh2∗2 ( Aldh2∗2 Tg ) osteoblastic cells or acetaldehyde -treated MC3T3-E1 showed impaired osteoblastogenesis and caused osteoporosis [ 1 ] .
In this study , we demonstrated the effects of astaxanthin for differentiation to @ @ @ @ @ @ @ acetaldehyde and Aldh2∗2 Tg mesenchymal stem cells in bone marrow .
Astaxanthin restores the inhibited osteoblastogenesis by acetaldehyde in MC 3T3-E1 and in bone marrow mesenchymal stem cells of Aldh2∗2 Tg mice .
Additionally , astaxanthin administration improved femur bone density in Aldh2∗2 Tg mice .
Furthermore , astaxanthin improved cell survival and mitochondrial function in acetaldehyde-treated MC 3T3-E1 cells .
Our results suggested that astaxanthin had restorative effects on osteoblast formation and provide new insight into the regulation of osteoporosis and suggest a novel strategy to promote bone formation in osteopenic diseases @ @ @ @ @

Aldehyde dehydrogenase 2 (ALDH2) plays major roles in aldehyde detoxification and in the catalysis of amino acids. ALDH2∗2, a dominant-negative transgenic expressing aldehyde dehydrogenase 2 (ALDH2) protein, is produced by a single nucleotide polymorphism (rs671) and is involved in the development of osteoporosis and hip fracture with aging. In a previous study, transgenic mice expressing Aldh2∗2(Aldh2∗2 Tg) osteoblastic cells or acetaldehyde -treated MC3T3-E1 showed impaired osteoblastogenesis and caused osteoporosis [1]. In this study, we demonstrated the effects of astaxanthin for differentiation to osteoblasts of MC3T3-E1 by the addition of acetaldehyde and Aldh2∗2 Tg mesenchymal stem cells in bone marrow. Astaxanthin restores the inhibited osteoblastogenesis by acetaldehyde in MC 3T3-E1 and in bone marrow mesenchymal stem cells of Aldh2∗2 Tg mice. Additionally, astaxanthin administration improved femur bone density in Aldh2∗2 Tg mice. Furthermore, astaxanthin improved cell survival and mitochondrial function in acetaldehyde-treated MC 3T3-E1 cells. Our results suggested that astaxanthin had restorative effects on osteoblast formation and provide new insight into the regulation of osteoporosis and suggest a novel strategy to promote bone formation in osteopenic diseases caused byimpaired acetaldehyde metabolism.


greenmedinfo--2020-05-27--Neuroprotective activities of bacopa, lycopene, astaxanthin, and vitamin B12 combination on oxidativ

Neuroprotective activities of bacopa, lycopene, astaxanthin, and vitamin B12 combination on oxidative stress-dependent neuronal death.

Oxidative stress is considered the common effector of the cascade of degenerative events in many neurological conditions .
Thus , @ @ @ @ @ different nutraceuticals in HOin vitro model to understand if could represent an adjuvant treatment for @ @ @ @ @ study , nutraceuticals bacopa , lycopene , astaxanthin , and vitamin B12 were used alone @ @ @ @ @ neuronal differentiated SH-SY5Y cells upon hydrogen peroxide-induced injury and neuroprotective , neuronal death pathways were @ @ @ @ @ were able to protect HOcytotoxic effects , through increasing cell viability and proteins involved in @ @ @ @ @ involved in cell death pathways .
On this basis , it is possible to propose @ @ @ @ @ as dietary supplement for the prevention or as adjuvant to the only symptomatic treatments so @ @ @ @ @ .

Oxidative stress is considered the common effector of the cascade of degenerative events in many neurological conditions. Thus, in this paper we tested different nutraceuticals in HOin vitro model to understand if could represent an adjuvant treatment for neurological diseases. In this study, nutraceuticals bacopa, lycopene, astaxanthin, and vitamin B12 were used alone or in combination in human neuronal differentiated SH-SY5Y cells upon hydrogen peroxide-induced injury and neuroprotective, neuronal death pathways were analyzed. The nutraceuticals analyzed were able to protect HOcytotoxic effects, through increasing cell viability and proteins involved in neuroprotection pathways and restoring proteins involved in cell death pathways. On this basis, it is possible to propose the use of these compounds as dietary supplement for the prevention or as adjuvant to the only symptomatic treatments so far available for neurodegenerative diseases.


greenmedinfo--2020-05-27--The anti-cancer effects of fucoidan: a review of both in vivo and in vitro investigations.

Fucoidan is a kind of the polysaccharide , which comes from brown algae and comprises of sulfated fucose residues .
It has shown a large range of biological activities in basic researches , including many elements like anti-inflammatory , anti-cancer , anti-viral , anti-oxidation , anticoagulant , antithrombotic , anti-angiogenic and anti-Helicobacter pylori , etc .
Cancer is a multifactorial disease of multiple causes .
Most of the current chemotherapy drugs for cancer therapy are projected to eliminate the ordinary deregulation mechanisms in cancer cells .
Plenty of wholesome tissues , however , are also influenced by these chemical cytotoxic @ @ @ @ @ @ @ fucoidan can directly exert the anti-cancer actions through cell cycle arrest , induction of apoptosis , etc.
, and can also indirectly kill cancer cells by activating natural killer cells , macrophages , etc .
Fucoidan is used as a new anti-tumor drug or as an adjuvant in combination with an anti-tumor drug because of its high biological activity , wide source , low resistance to drug resistance and low side effects .
This paper reviews the mechanism by which fucoidan can eliminate tumor cells , delay tumor growth and synergize with anticancer @ @ @ @ @ @ @ and in clinical trials .

Fucoidan is a kind of the polysaccharide, which comes from brown algae and comprises of sulfated fucose residues. It has shown a large range of biological activities in basic researches, including many elements like anti-inflammatory, anti-cancer, anti-viral, anti-oxidation, anticoagulant, antithrombotic, anti-angiogenic and anti-Helicobacter pylori, etc. Cancer is a multifactorial disease of multiple causes. Most of the current chemotherapy drugs for cancer therapy are projected to eliminate the ordinary deregulation mechanisms in cancer cells. Plenty of wholesome tissues, however, are also influenced by these chemical cytotoxic effects. Existing researches have demonstrated that fucoidan can directly exert the anti-cancer actions through cell cycle arrest, induction of apoptosis, etc., and can also indirectly kill cancer cells by activating natural killer cells, macrophages, etc. Fucoidan is used as a new anti-tumor drug or as an adjuvant in combination with an anti-tumor drug because of its high biological activity, wide source, low resistance to drug resistance and low side effects. This paper reviews the mechanism by which fucoidan can eliminate tumor cells, delay tumor growth and synergize with anticancer chemotherapy drugs in vitro, in vivo and in clinical trials.