greenmedinfo--2020-06-19--Frankincense and myrrh and their bioactive compounds inhibit proliferation of U266 multiple myeloma

Frankincense and myrrh and their bioactive compounds inhibit proliferation of U266 multiple myeloma cells.

BACKGROUND : Frankincense and myrrh are used as traditional anti-inflammatory and analgesic medicines in China .
It has been reported that frankincense and myrrh have significant anti-tumor activities .
The present study was designed to investigate the inhibitory efficacy of frankincense ethanol extracts ( RXC ) , myrrh ethanol extracts ( MYC ) , frankincense -myrrh ethanol extracts ( YDC ) , frankincense -myrrh water extracts ( YDS ) and their main compounds on U266 human multiple myeloma cell line .
METHODS : The inhibition effects of cell proliferation was evaluated by MTT assays .
Cell culture supernatant was collected @ @ @ @ @ @ @ analysis was designed to investigate the regulatory of JAK/STAT signal pathway .
In addition , cell metabolomics based on the ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry ( UPLC/Q-TOF-MS ) had been established to investigate the holistic efficacy of frankincense and myrrh on U266 cells .
Acquired data were processed by partial least-squares discriminant analysis ( PLS-DA ) and orthogonal projection to latent structures squares-discriminant analysis ( OPLS-DA ) to identify potential biomarkers .
RESULTS : RXC , MYC significantly inhibited the proliferation of U266 cells at dose of 25-400 μg/mL @ @ @ @ @ @ @ of 12.5-400 μg/mL .
3-O-acetyl-α-boswellic acid , 3-acetyl-11 keto-boswellic acid and 11-keto-boswellic acid had the most significant anti- multiple myeloma activities in the 10 compounds investigated , therefore these 3 compounds were selected as representativesfor Elisa assay and western blotting experiments .
All the extracts and active compounds ameliorated the secretion of cytokines and down-regulated the expression of JAK/STAT signaling pathway-related proteins .
Comparing RXC , MYC , YDC and YDS-treated U266 cells with vehicle control ( DMSO ) , 13 , 8 , 7 , 7distinct metabolites and 2 , 2 , @ @ @ @ @ @ @ in amino acid metabolism , lipid metabolism , vitamin metabolism , arachidonic acid were identified , respectively .
CONCLUSIONS : Taken together our results suggest that the frankincense and myrrh and their bioactive compounds inhibit proliferation of U266 multiple myeloma cells by regulating JAK/STAT signaling pathway and cellular metabolic profile .

BACKGROUND: Frankincense and myrrh are used as traditional anti-inflammatory and analgesic medicines in China. It has been reported that frankincense and myrrh have significant anti-tumor activities. The present study was designed to investigate the inhibitory efficacy of frankincense ethanol extracts (RXC), myrrh ethanol extracts (MYC), frankincense -myrrh ethanol extracts (YDC), frankincense -myrrh water extracts (YDS) and their main compounds on U266 human multiple myeloma cell line.
METHODS: The inhibition effects of cell proliferation was evaluated by MTT assays. Cell culture supernatant was collected for estimation of cytokines. Western blot analysis was designed to investigate the regulatory of JAK/STAT signal pathway. In addition, cell metabolomics based on the ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS) had been established to investigate the holistic efficacy of frankincense and myrrh on U266 cells. Acquired data were processed by partial least-squares discriminant analysis (PLS-DA) and orthogonal projection to latent structures squares-discriminant analysis (OPLS-DA) to identify potential biomarkers.
RESULTS: RXC, MYC significantly inhibited the proliferation of U266 cells at dose of 25-400 μg/mL, YDC and YDS at the dose of 12.5-400 μg/mL. 3-O-acetyl-α-boswellic acid, 3-acetyl-11 keto-boswellic acid and 11-keto-boswellic acid had the most significant anti- multiple myeloma activities in the 10 compounds investigated, therefore these 3 compounds were selected as representativesfor Elisa assay and western blotting experiments. All the extracts and active compounds ameliorated the secretion of cytokines and down-regulated the expression of JAK/STAT signaling pathway-related proteins. Comparing RXC, MYC, YDC and YDS-treated U266 cells with vehicle control (DMSO), 13, 8, 7, 7distinct metabolites and 2, 2, 3, 0 metabolic target pathways involved in amino acid metabolism, lipid metabolism, vitamin metabolism, arachidonic acid were identified, respectively.
CONCLUSIONS: Taken together our results suggest that the frankincense and myrrh and their bioactive compounds inhibit proliferation of U266 multiple myeloma cells by regulating JAK/STAT signaling pathway and cellular metabolic profile.


greenmedinfo--2020-06-19--Acetyl-11-keto-β-boswellic acid could be a promising chemotherapy treatment for glioblastoma.

Glioblastoma is the most common and aggressive primary tumor in the central nervous system , accounting for 12 % -15 % of all brain tumors .
3 -- Acetyl-11-keto -- boswellic acid ( AKBA ) , one of the most active ingredients of gum resin fromBirdw.
, was reported to inhibit the growth of glioblastoma cells and subcutaneous glioblastoma .
However , whether AKBA has antitumor effects on orthotopic glioblastoma and the underlying mechanisms are still unclear .
An orthotopic mouse model was used to evaluate the anti-glioblastoma effects of AKBA .
The effects of AKBA on tumor growth were @ @ @ @ @ @ @ the alteration of metabolic landscape were detected by MALDI-MSI .
The underlying mechanisms of autophagy reducing by AKBA treatment were determined by immunoblotting and immunofluorescence , respectively .
Transmission electron microscope was used to check morphology of cells treated by AKBA .
Our results showed that AKBA ( 100 mg/kg ) significantly inhibited the growth of orthotopic U87-MG gliomas .
Results from MALDI-MSI showed that AKBA improved the metabolic profile of mice with glioblastoma , while immunoblot assays revealed that AKBA suppressed the expression of ATG5 , p62 , LC3B , p-ERK/ERK , @ @ @ @ @ @ @ of p-mTOR/mTOR .
Taken together , these results suggested that the antitumor effects of AKBA were related to the normalization of aberrant metabolism in the glioblastoma and the inhibition of autophagy .
AKBA could be a promising chemotherapy drug for glioblastoma .

Glioblastoma is the most common and aggressive primary tumor in the central nervous system, accounting for 12%-15% of all brain tumors. 3--Acetyl-11-keto--boswellic acid (AKBA), one of the most active ingredients of gum resin fromBirdw., was reported to inhibit the growth of glioblastoma cells and subcutaneous glioblastoma. However, whether AKBA has antitumor effects on orthotopic glioblastoma and the underlying mechanisms are still unclear. An orthotopic mouse model was used to evaluate the anti-glioblastoma effects of AKBA. The effects of AKBA on tumor growth were evaluated using MRI. The effects on the alteration of metabolic landscape were detected by MALDI-MSI. The underlying mechanisms of autophagy reducing by AKBA treatment were determined by immunoblotting and immunofluorescence, respectively. Transmission electron microscope was used to check morphology of cells treated by AKBA. Our results showed that AKBA (100 mg/kg) significantly inhibited the growth of orthotopic U87-MG gliomas. Results from MALDI-MSI showed that AKBA improved the metabolic profile of mice with glioblastoma, while immunoblot assays revealed that AKBA suppressed the expression of ATG5, p62, LC3B, p-ERK/ERK, and P53, and increased the ratio of p-mTOR/mTOR. Taken together, these results suggested that the antitumor effects of AKBA were related to the normalization of aberrant metabolism in the glioblastoma and the inhibition of autophagy. AKBA could be a promising chemotherapy drug for glioblastoma.


greenmedinfo--2020-06-19--Acetyl-11-keto-β-boswellic acid ameliorates cognitive deficits and reduces amyloid-β levels.

Alzheimer 's disease ( AD ) is a complex disease involved oxidative stress and inflammation in its pathogenesis .
Acetyl-11-keto-β-boswellic acid ( AKBA ) is an active triterpenoid compound from extracts of Boswellia serrata , which has been widely used as an antioxidant and anti-inflammatory agent .
The present study was to determine whether AKBA , a novel candidate , could protect against cognitive and neuropathological impairments in AD .
We found that AKBA treatment resulted in a significant improvement of learning and memory deficits , a dramatic decrease in cerebral amyloid-β ( Aβ ) levels and plaque burden , @ @ @ @ @ @ @ inflammation , and a marked reduction in activated glial cells and synaptic defects in the APPswe/PS1dE9 mice .
Furthermore , amyloid precursor protein ( APP ) processing was remarkably suppressed with AKBA treatment by inhibiting beta-site APP cleaving enzyme 1 ( BACE1 ) protein expression to produce Aβ in the APPswe/PS1dE9 mice brains .
Mechanistically , AKBA modulated antioxidant and anti-inflammatory pathways via increasing nuclear erythroid 2-related factor 2 ( Nrf2 ) and heme oxygenase-1 ( HO-1 ) expression , and via declining phosphorylation of inhibitor of nuclear factor-kappa B alpha ( IκBα @ @ @ @ @ @ @ findings provide evidence that AKBA protectsneurons against oxidative stress and inflammation in AD , and this neuroprotective effect involves the Nrf2/HO-1 and nuclear factor-kappa B ( NF-κB ) signaling pathways .

Alzheimer's disease (AD) is a complex disease involved oxidative stress and inflammation in its pathogenesis. Acetyl-11-keto-β-boswellic acid (AKBA) is an active triterpenoid compound from extracts of Boswellia serrata, which has been widely used as an antioxidant and anti-inflammatory agent. The present study was to determine whether AKBA, a novel candidate, could protect against cognitive and neuropathological impairments in AD. We found that AKBA treatment resulted in a significant improvement of learning and memory deficits, a dramatic decrease in cerebral amyloid-β (Aβ) levels and plaque burden, a profound alleviation in oxidative stress and inflammation, and a marked reduction in activated glial cells and synaptic defects in the APPswe/PS1dE9 mice. Furthermore, amyloid precursor protein (APP) processing was remarkably suppressed with AKBA treatment by inhibiting beta-site APP cleaving enzyme 1 (BACE1) protein expression to produce Aβ in the APPswe/PS1dE9 mice brains. Mechanistically, AKBA modulated antioxidant and anti-inflammatory pathways via increasing nuclear erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression, and via declining phosphorylation of inhibitor of nuclear factor-kappa B alpha (IκBα) and p65. Collectively, our findings provide evidence that AKBA protectsneurons against oxidative stress and inflammation in AD, and this neuroprotective effect involves the Nrf2/HO-1 and nuclear factor-kappa B (NF-κB) signaling pathways.


greenmedinfo--2020-06-19--Acetyl-11-keto-β-boswellic acid exerts the anti-cancer effects via cell cycle arrest, apoptosis indu

Acetyl-11-keto-β-boswellic acid exerts the anti-cancer effects via cell cycle arrest, apoptosis induction, and autophagy suppression in NSCLC cells.

Objective : Acetyl-11-keto-β-boswellic acid ( AKBA ) is a triterpenoid , which is the main component of boswellic acid from Boswellia Serrata , a medicinal plant that has shown immense potential in anti-cancer therapy .
This study aims to explore the roles and molecular mechanisms of AKBA on cell behavior in non-small cell lung cancer ( NSCLC ) cells .
Materials and Methods : The effects of AKBA on the cell viability in A549 , H460 , H1299 , and BEAS-2B cells were determined by the CCK-8 assay .
The colony formation assay was used to identify the effects of @ @ @ @ @ @ @ of AKBA in regulating the cell cycle , apoptosis , and autophagy in A549 were evaluated by flow cytometry , Western blotting , reverse transcription-polymerase chain reaction ( PCR ) and immunofluorescence ( IF ) .
Results : AKBA reduced cell viability in A549 , H460 , H1299 , and BEAS-2B .
In A549 cells , AKBA suppressed the clone formation , arrested the cell cycle at the G/Gphase , induced cellular apoptosis .
We found that AKBA suppressed the formation of autolysosome , and decreased the expression levels of Beclin-1 , LC3A/B-I @ @ @ @ @ @ @ AKBA also inhibited the expression levels of PI3K/Akt signaling pathway proteins .
Conclusion : AKBA exerts the anti-cancer effects via cell cycle arrest , apoptosis induction , and autophagy suppression in NSCLC cells .
This body of evidence supports the potential of AKBA as a promising drug in the treatment of NSCLC .

Objective: Acetyl-11-keto-β-boswellic acid (AKBA) is a triterpenoid, which is the main component of boswellic acid from Boswellia Serrata, a medicinal plant that has shown immense potential in anti-cancer therapy. This study aims to explore the roles and molecular mechanisms of AKBA on cell behavior in non-small cell lung cancer (NSCLC) cells.
Materials and Methods: The effects of AKBA on the cell viability in A549, H460, H1299, and BEAS-2B cells were determined by the CCK-8 assay. The colony formation assay was used to identify the effects of AKBA on cell proliferation. Potential roles of AKBA in regulating the cell cycle, apoptosis, and autophagy in A549 were evaluated by flow cytometry, Western blotting, reverse transcription-polymerase chain reaction (PCR) and immunofluorescence (IF).
Results: AKBA reduced cell viability in A549, H460, H1299, and BEAS-2B. In A549 cells, AKBA suppressed the clone formation, arrested the cell cycle at the G/Gphase, induced cellular apoptosis. We found that AKBA suppressed the formation of autolysosome, and decreased the expression levels of Beclin-1, LC3A/B-I, and LC3A/B-II proteins. Furthermore, AKBA also inhibited the expression levels of PI3K/Akt signaling pathway proteins.
Conclusion: AKBA exerts the anti-cancer effects via cell cycle arrest, apoptosis induction, and autophagy suppression in NSCLC cells. This body of evidence supports the potential of AKBA as a promising drug in the treatment of NSCLC.


greenmedinfo--2020-06-19--Acetyl-11-keto-β-boswellic acid inhibits precancerous breast lesion MCF-10AT cells.

Purpose : Acetyl-11-keto-β-boswellic acid ( AKBA ) has therapeutic effects on a range of diseases , including tumours .
lncRNAs , as competing endogenous RNAs ( ceRNAs ) , can interact with miRNAs to regulate the expression of target genes , which can affect the development of tumors .
Here , we examined the effects of AKBA on breastprecancerous lesions MCF-10AT cells .
Methods : The expression profiles of breast cancer ( BC ) tissue were collated from The Cancer Genome Atlas ( TCGA ) , and the lncRNA-miRNA-mRNA ceRNA network was constructed .
AKBA targets were predicted by network @ @ @ @ @ @ @ nonprotein-coding RNA 707 ( LINC00707 ) , miR-206 and ER-α was determined by qRT-PCR .
Cell viability , apoptosis and cycle were assessed by CCK-8 and flow cytometry .
Protein levels were measured by Western blotting .
Results : A total of 3205 differentially expressed mRNAs , 104 miRNAs , and 605 lncRNAs were identified .
The ceRNA network consisting of 9 lncRNAs , 15 miRNAs and 82 mRNAs was constructed .
We found that LINC00707 was up-regulated and miR-206 was down-regulated in MCF-10AT cells .
Transfected si-LINC00707 could inhibit cell proliferation , @ @ @ @ @ @ @ MCF-10AT cells .
In addition , network pharmacology predicted that AKBA may regulate the ESR1 in the treatment of BC .
Our research demonstrated that AKBA could induce cell apoptosis and G1-phase arrest and inhibit ER-α expression via LINC00707/miR-206 in MCF-10AT cells .
Conclusion : AKBA inhibited MCF-10AT cells via regulation of LINC00707/miR-206 that reduces ER-α .

Purpose: Acetyl-11-keto-β-boswellic acid (AKBA) has therapeutic effects on a range of diseases, including tumours. lncRNAs, as competing endogenous RNAs (ceRNAs), can interact with miRNAs to regulate the expression of target genes, which can affect the development of tumors. Here, we examined the effects of AKBA on breastprecancerous lesions MCF-10AT cells.
Methods: The expression profiles of breast cancer (BC) tissue were collated from The Cancer Genome Atlas (TCGA), and the lncRNA-miRNA-mRNA ceRNA network was constructed. AKBA targets were predicted by network pharmacology. The expression of long intergenic nonprotein-coding RNA 707 (LINC00707), miR-206 and ER-α was determined by qRT-PCR. Cell viability, apoptosis and cycle were assessed by CCK-8 and flow cytometry. Protein levels were measured by Western blotting.
Results: A total of 3205 differentially expressed mRNAs, 104 miRNAs, and 605 lncRNAs were identified. The ceRNA network consisting of 9 lncRNAs, 15 miRNAs and 82 mRNAs was constructed. We found that LINC00707 was up-regulated and miR-206 was down-regulated in MCF-10AT cells. Transfected si-LINC00707 could inhibit cell proliferation, induce cell apoptosis and cycle arrest of MCF-10AT cells. In addition, network pharmacology predicted that AKBA may regulate the ESR1 in the treatment of BC. Our research demonstrated that AKBA could induce cell apoptosis and G1-phase arrest and inhibit ER-α expression via LINC00707/miR-206 in MCF-10AT cells.
Conclusion: AKBA inhibited MCF-10AT cells via regulation of LINC00707/miR-206 that reduces ER-α.


greenmedinfo--2020-06-19--Structural and mechanistic insights into 5-lipoxygenase inhibition by natural products.

Leukotrienes ( LT ) are lipid mediators of the inflammatory response that are linked to asthma and atherosclerosis .
LT @ @ @ @ @ ( 5-LOX ) with the assistance of the substrate-binding 5-LOX-activating protein at the nuclear membrane @ @ @ @ @ the structural and functional consequences of the binding of two natural product inhibitors of 5-LOX @ @ @ @ @ acid ( NDGA ) is lodged in the 5-LOX active site , now fully exposed @ @ @ @ @ that caps it in the apo-enzyme .
In contrast , the allosteric inhibitor 3-acetyl-11-keto-beta-boswellic acid @ @ @ @ @ wedges between the membrane-binding and catalytic domains of 5-LOX , some 30 Å from the @ @ @ @ @ inhibition by NDGA is robust , AKBA promotes a shift in the regiospecificity , evident @ @ @ @ @ cells and in primary immune cells expressing 5-LOX .
Our results suggest a new approach @ @ @ @ @ through exploitation of an allosteric site in 5-LOX .

Leukotrienes (LT) are lipid mediators of the inflammatory response that are linked to asthma and atherosclerosis. LT biosynthesis is initiated by 5-lipoxygenase (5-LOX) with the assistance of the substrate-binding 5-LOX-activating protein at the nuclear membrane. Here, we contrast the structural and functional consequences of the binding of two natural product inhibitors of 5-LOX. The redox-type inhibitor nordihydroguaiaretic acid (NDGA) is lodged in the 5-LOX active site, now fully exposed by disordering of the helix that caps it in the apo-enzyme. In contrast, the allosteric inhibitor 3-acetyl-11-keto-beta-boswellic acid (AKBA) from frankincense wedges between the membrane-binding and catalytic domains of 5-LOX, some 30 Å from the catalytic iron. While enzyme inhibition by NDGA is robust, AKBA promotes a shift in the regiospecificity, evident in human embryonic kidney 293 cells and in primary immune cells expressing 5-LOX. Our results suggest a new approach to isoform-specific 5-LOX inhibitor development through exploitation of an allosteric site in 5-LOX.


greenmedinfo--2020-06-19--The effects of acetyl-11-keto-β-boswellic acid on brain cytokines and memory impairment induced by l

The effects of acetyl-11-keto-β-boswellic acid on brain cytokines and memory impairment induced by lipopolysaccharide.

The therapeutic effects of the olibanum , the resin of Boswellia serrata on inflammatory diseases have been reported .
There @ @ @ @ @ ingredients in this resin including acetyl-11-keto-β-boswellic acid ( AKBA ) .
We proposed that AKBA @ @ @ @ @ by cerebral inflammation following the administration of lipopolysaccharide ( LPS ) .
Forty male rats @ @ @ @ @ following treatments : Control ( diluted DMSO + saline ) , LPS ( diluted DMSO @ @ @ @ @ , LPS- AKBA 5 and LPS- AKBA 10 ( 5 or 10 mg/ kg AKBA @ @ @ @ @ water maze ( MWM ) , passive avoidance ( PA ) and biochemical tests were @ @ @ @ @ both doses of AKBA improved memory performance in MWM and PA tests ( P

The therapeutic effects of the olibanum, the resin of Boswellia serrata on inflammatory diseases have been reported. There are more than 200 active ingredients in this resin including acetyl-11-keto-β-boswellic acid (AKBA). We proposed that AKBA can improve memory impairment induced by cerebral inflammation following the administration of lipopolysaccharide (LPS). Forty male rats were grouped and received the following treatments: Control (diluted DMSO + saline), LPS (diluted DMSO + 1 mg/kg LPS), LPS- AKBA 5 and LPS- AKBA 10 (5 or 10 mg/ kg AKBA before LPS). Morris water maze (MWM), passive avoidance (PA) and biochemical tests were carried out. Pre-treatment with both doses of AKBA improved memory performance in MWM and PA tests (P < 0.05 to P < 0.001). Pre-treatment by AKBA improved the levels of hippocampal IL-10 (P < 0.001), BDNF (P < 0.001), CAT (P < 0.05 and P < 0.001), SOD P < 0.001 and thiols (P < 0.01 and P < 0.001) while reduced IL-6 (P < 0.001), TNF-α (P < 0.001), NO (P < 0.05 and P < 0.001), GFAP (P < 0.001) and MDA (P < 0.001) levels. AKBA effectively ameliorated LPS-induced learning and memory impairments and improved BDNF in a neuroinflammation animal model. The effects seem to be due to setting a positive balance between pro-inflammatory to inflammatory cytokines and reinvigorate the antioxidant system.


greenmedinfo--2020-06-19--Lipid mediator profiles predict response to therapy with an oral frankincense extract in relapsing-r

Lipid mediator profiles predict response to therapy with an oral frankincense extract in relapsing-remitting multiple sclerosis.

Lipid mediators ( LMs ) are a unique class of immunoregulatory signalling molecules and known to be affected by frankincense extracts .
We performed LM profiling by metabololipidomics in plasma samples from 28 relapsing-remitting multiple sclerosis ( RR-MS ) patients who took a standardised frankincense extract ( SFE ) daily for eight months in a clinical phase IIa trial ( NCT01450124 ) and in 28 age- and gender-matched healthy controls .
Magnetic resonance imaging , immunological outcomes and serum neurofilament light chain levels were correlated to changes in the LM profiles of the RR-MS cohort .
Eight out of 44 @ @ @ @ @ @ @ eight-month treatment period by the SFE and seven of these eight significant LM derive from the 5-lipoxygenase ( 5-LO ) pathway .
Baseline levels of 12- and 15-LO products were elevated in patients who exhibited disease activity ( EDA ) during SFE treatment compared to no-evidence-of-disease-activity ( NEDA ) patients and could predict treatment response to the SFE in a prediction model at baseline .
Oral treatment with an SFE significantly reduces 5-LO-derived LMs in RR-MS patients during an eight-month treatment period .
Treatment response to an SFE , however , seems to @ @ @ @ @ @ @ levels before SFE exposure .
Further studies should confirm their biomarker potential in RR-MS and SFE treatment .

Lipid mediators (LMs) are a unique class of immunoregulatory signalling molecules and known to be affected by frankincense extracts. We performed LM profiling by metabololipidomics in plasma samples from 28 relapsing-remitting multiple sclerosis (RR-MS) patients who took a standardised frankincense extract (SFE) daily for eight months in a clinical phase IIa trial (NCT01450124) and in 28 age- and gender-matched healthy controls. Magnetic resonance imaging, immunological outcomes and serum neurofilament light chain levels were correlated to changes in the LM profiles of the RR-MS cohort. Eight out of 44 analysed LMs were significantly reduced during an eight-month treatment period by the SFE and seven of these eight significant LM derive from the 5-lipoxygenase (5-LO) pathway. Baseline levels of 12- and 15-LO products were elevated in patients who exhibited disease activity (EDA) during SFE treatment compared to no-evidence-of-disease-activity (NEDA) patients and could predict treatment response to the SFE in a prediction model at baseline. Oral treatment with an SFE significantly reduces 5-LO-derived LMs in RR-MS patients during an eight-month treatment period. Treatment response to an SFE, however, seems to be related to 12-,15-LO and cyclooxygenase product levels before SFE exposure. Further studies should confirm their biomarker potential in RR-MS and SFE treatment.


greenmedinfo--2020-06-19--Double-blind trial of solid lipid Boswellia serrata particles vs. standardized Boswellia serrata gum

Double-blind trial of solid lipid Boswellia serrata particles vs. standardized Boswellia serrata gum extract for osteoarthritis of knee.

Present study was planned to investigate the efficacy of SLBSP vs. standardized BSE for symptomatic knee osteoarthritis ( OA ) @ @ @ @ @ , randomized , double-blind , double-dummy , placebo-controlled , and single-centre clinical trial for symptomatic @ @ @ @ @ were randomized to receive SLBSP capsule + BSE Placebo or BSE tablet + SLBSP placebo @ @ @ @ @ were allowed to take rescue analgesics ( Acelofenac 100 mg ) .
Improvement in pain @ @ @ @ @ WOMAC , VAS .
Level of CTX-II in urine and serum levels of inflammatory cytokines @ @ @ @ @ IL-6 , TNF-α , and IFN-γ were measured initially and at end of treatment .
@ @ @ @ @ markedly in SLBSP as well as in BSE arm ( p

Present study was planned to investigate the efficacy of SLBSP vs. standardized BSE for symptomatic knee osteoarthritis (OA) treatment. It was prospective, randomized, double-blind, double-dummy, placebo-controlled, and single-centre clinical trial for symptomatic osteoarthritis of knee. Subjects were randomized to receive SLBSP capsule + BSE Placebo or BSE tablet + SLBSP placebo for two months. Patients were allowed to take rescue analgesics (Acelofenac 100 mg). Improvement in pain and function was assessed utilizing WOMAC, VAS. Level of CTX-II in urine and serum levels of inflammatory cytokines including IL-2, IL-4, IL-6, TNF-α, and IFN-γ were measured initially and at end of treatment. WOMAC and VAS score improved markedly in SLBSP as well as in BSE arm (p < 0.05). Difference in VAS and WOMAC scores between the two arms was not statistically significant. Most significant effect was observed in the need for rescue analgesics. SLBSP caused marked lowering of pro-inflammatory cytokines levels whereas a several fold increase was noted in the BSE arm (p < 0.05). Both groups showed marked improvement in pain, SLBSP being superior to BSE with respect to reducing the need for rescue analgesics in addition to modulating inflammatory cytokines.


greenmedinfo--2020-06-19--Effect of Boswellia ovalifoliolata on glycoproteins proportions in diabetes induced hepatic and rena

Effect of Boswellia ovalifoliolata on glycoproteins proportions in diabetes induced hepatic and renal injury.

Purpose : Chronic hyperglycemia and deficiency of insulin are peculiar features of diabetes mellitus alters glycoprotein levels in various tissues leads to impaired metabolism of glycoproteins which play a major role in the pathogenesis of diabetic complications.is a medicinal plant known for its many medicinal properties including diabetes .
In this background our study was aimed to evaluate the effect of aqueous extract of stem bark of ( AESBBO ) on antidiabetic and glycoprotein metabolism .
Methods : Diabetes was induced in rats by intraperitoneal administration of streptozotocin at a dose of 50 mg/kg bw .
After induction of diabetes @ @ @ @ @ @ @ of 200 mg/kg for a long term treatment of 40 days .
Finally , by the end of study all the rats were dissected blood , liver , and kidney tissue samples were collected to investigate the long term effects of AESBBO on diabetes and glycoprotein metabolism .
Results : Treatment with AESBBO significantly reduced the fasting blood glucose levels whereas the levels of insulin and hemoglobin were increased with decreased levels of glycosylated hemoglobin .
The long term treatment of AESBBO significantly decreased the levels of plasma , liver and kidney tissue @ @ @ @ @ @ @ hexosamine and sialic acid .
Conclusions : This study concludes that the aqueous extract of stem bark ofpossesses a protective role on abnormal glycoprotein metabolism in addition to its antihyperglycemic activity .

Purpose: Chronic hyperglycemia and deficiency of insulin are peculiar features of diabetes mellitus alters glycoprotein levels in various tissues leads to impaired metabolism of glycoproteins which play a major role in the pathogenesis of diabetic complications.is a medicinal plant known for its many medicinal properties including diabetes. In this background our study was aimed to evaluate the effect of aqueous extract of stem bark of(AESBBO) on antidiabetic and glycoprotein metabolism.
Methods: Diabetes was induced in rats by intraperitoneal administration of streptozotocin at a dose of 50 mg/kg bw. After induction of diabetes rats were treated with AESBBO at dosage of 200 mg/kg for a long term treatment of 40 days. Finally, by the end of study all the rats were dissected blood, liver, and kidney tissue samples were collected to investigate the long term effects of AESBBO on diabetes and glycoprotein metabolism.
Results: Treatment with AESBBO significantly reduced the fasting blood glucose levels whereas the levels of insulin and hemoglobin were increased with decreased levels of glycosylated hemoglobin. The long term treatment of AESBBO significantly decreased the levels of plasma, liver and kidney tissue glycoproteins such as fucose, hexose, hexosamine and sialic acid.
Conclusions: This study concludes that the aqueous extract of stem bark ofpossesses a protective role on abnormal glycoprotein metabolism in addition to its antihyperglycemic activity.


greenmedinfo--2020-06-19--Anti-inflammatory and anti-cancer activities of frankincense.

The oleogum resins of Boswellia species known as frankincense have been used for ages in traditional medicine in India , China and the Arabian world independent of its use for cultural and religious rituals in Europe .
During the past two decades , scientific investigations provided mounting evidence for the therapeutic potential of frankincense .
We conducted a systematic review on the anti-inflammatory and anti-cancer activities of Boswellia species and their chemical ingredients ( e.g .
3-O-acetyl-11-keto-β boswellic acid , α- and β-boswellic acids , 11-keto-β-boswellic acid and other boswellic acids , lupeolic acids , incensole , cembrenes , triterpenediol @ @ @ @ @ @ @ .
Frankincense acts by multiple mechanisms , e.g .
by the inhibition of leukotriene synthesis , of cyclooxygenase 1/2 and 5-lipoxygenase , of oxidative stress , and by regulation of immune cells from the innate and acquired immune systems .
Furthermore , frankincense modulates signaling transduction responsible for cell cycle arrest and inhibition of proliferation , angiogenesis , invasion and metastasis .
Clinical trials showed the efficacy of frankincense and its phytochemicals against osteoarthritis , multiple sclerosis , asthma , psoriasis and erythematous eczema , plaque-induced gingivitis and pain .
Frankincense revealed beneficial @ @ @ @ @ @ @ did not reduce glioma size .
Even if there is no treatment effect on brain tumors itself , the management of glioma-associated edema may represent a desirable improvement .
The therapeutic potential against other tumor types is still speculative .
Experimental toxicology and clinical trials revealed only mild adverse side effects .
Morerandomized clinical trials are required to estimate the full clinical potential of frankincense for cancer therapy .

The oleogum resins of Boswellia species known as frankincense have been used for ages in traditional medicine in India, China and the Arabian world independent of its use for cultural and religious rituals in Europe. During the past two decades, scientific investigations provided mounting evidence for the therapeutic potential of frankincense. We conducted a systematic review on the anti-inflammatory and anti-cancer activities of Boswellia species and their chemical ingredients (e.g. 3-O-acetyl-11-keto-β boswellic acid, α- and β-boswellic acids, 11-keto-β-boswellic acid and other boswellic acids, lupeolic acids, incensole, cembrenes, triterpenediol, tirucallic acids, and olibanumols). Frankincense acts by multiple mechanisms, e.g. by the inhibition of leukotriene synthesis, of cyclooxygenase 1/2 and 5-lipoxygenase, of oxidative stress, and by regulation of immune cells from the innate and acquired immune systems. Furthermore, frankincense modulates signaling transduction responsible for cell cycle arrest and inhibition of proliferation, angiogenesis, invasion and metastasis. Clinical trials showed the efficacy of frankincense and its phytochemicals against osteoarthritis, multiple sclerosis, asthma, psoriasis and erythematous eczema, plaque-induced gingivitis and pain. Frankincense revealed beneficial effects towards brain tumor-related edema, but did not reduce glioma size. Even if there is no treatment effect on brain tumors itself, the management of glioma-associated edema may represent a desirable improvement. The therapeutic potential against other tumor types is still speculative. Experimental toxicology and clinical trials revealed only mild adverse side effects. Morerandomized clinical trials are required to estimate the full clinical potential of frankincense for cancer therapy.


greenmedinfo--2020-06-19--The findings highlight the ability of kaffir lime leaves extract to inhibit S. mutans activity.

OBJECTIVES : Although kaffir lime has been reported to exhibit antioxidant and antileukemic activity , little is known about the antimicrobial effect of kaffir lime extract .
Because Streptococcus mutans has been known to cause biofilm formation , it has been considered the most important causative pathogen of dental caries .
Thus , the effective control of its effects on the oral biofilm is the key to the prevention of dental caries .
The aims of the present study were to investigate the effect of kaffir lime leaves extract on biofilm formation and its antibacterial activity on S. mutans .
@ @ @ @ @ @ @ kaffir lime leaves extract on growth and biofilm formation of S. mutans .
For the investigation we used a kaffir lime extract with high phenolic content .
The minimum inhibitory concentration of the extract was determined by broth microdilution assay .
The inhibitory effect of the test substances on biofilm formation was also investigated by biofilm formation assay and qRT-PCR of biofilm formation-associated genes .
RESULTS : Kaffir lime leaves extract inhibits the growth of S. mutans , corresponding to the activity of an antibiotic , ampicillin .
Formation of biofilm by S. @ @ @ @ @ @ @ .
These results were confirmed by the down-regulation of genes associated with the biofilm formation .
CONCLUSIONS : The findings highlight the ability of kaffir lime leaves extract to inhibit S. mutans activity , which may be beneficial in the prevention of biofilm formation on dental surface , reducing dental plaque and decreasing the chance of dental carries .

OBJECTIVES: Although kaffir lime has been reported to exhibit antioxidant and antileukemic activity, little is known about the antimicrobial effect of kaffir lime extract. Because Streptococcus mutans has been known to cause biofilm formation, it has been considered the most important causative pathogen of dental caries. Thus, the effective control of its effects on the oral biofilm is the key to the prevention of dental caries. The aims of the present study were to investigate the effect of kaffir lime leaves extract on biofilm formation and its antibacterial activity on S. mutans.
METHODS: We examined the effect of kaffir lime leaves extract on growth and biofilm formation of S. mutans. For the investigation we used a kaffir lime extract with high phenolic content. The minimum inhibitory concentration of the extract was determined by broth microdilution assay. The inhibitory effect of the test substances on biofilm formation was also investigated by biofilm formation assay and qRT-PCR of biofilm formation-associated genes.
RESULTS: Kaffir lime leaves extract inhibits the growth of S. mutans, corresponding to the activity of an antibiotic, ampicillin. Formation of biofilm by S. mutans was also inhibited by the extract. These results were confirmed by the down-regulation of genes associated with the biofilm formation.
CONCLUSIONS: The findings highlight the ability of kaffir lime leaves extract to inhibit S. mutans activity, which may be beneficial in the prevention of biofilm formation on dental surface, reducing dental plaque and decreasing the chance of dental carries.


greenmedinfo--2020-06-19--Antileukemic cell proliferation of active compounds from kaffir lime.

Kaffir lime ( ) is a plant member of family Rutaceae , and its leaves are commonly used in folk medicine .
The present study explores antileukemic effects of the extracts and purified active compounds from the leaves .
The antileukemic activity was investigated via inhibition of Wilms ' tumor 1 ( WT1 ) , which is a protein that involves in leukemic cell proliferation .
In addition , the compounds were investigated for their effects ongene expression using real time RT-PCR and Western blotting .
Cell cycle arrest and total cell number were investigated using flow cytometry and trypan @ @ @ @ @ @ @ results demonstrated that the hexane fractionated extract had the greatest inhibitory effect ongene expression of many leukemic cell lines and significantly decreased WT1 protein levels of K562 cells ( representative of the leukemic cells ) , in a dose- and time-dependent manner .
Subfraction No .
9 ( F9 ) after partial purification of hexane fractioned extract showed the highest suppression on WT1 protein and suppressed cell cycle at G2/M .
The organic compounds were isolated from F9 and identified as phytol and lupeol .
The bioassays confirmed antiproliferative activities of natural products @ @ @ @ @ @ @ anticancer activity of the isolated phytol and lupeol to decrease leukemic cell proliferation .

Kaffir lime () is a plant member of family Rutaceae, and its leaves are commonly used in folk medicine. The present study explores antileukemic effects of the extracts and purified active compounds from the leaves. The antileukemic activity was investigated via inhibition of Wilms' tumor 1 (WT1), which is a protein that involves in leukemic cell proliferation. In addition, the compounds were investigated for their effects ongene expression using real time RT-PCR and Western blotting. Cell cycle arrest and total cell number were investigated using flow cytometry and trypan blue exclusion method, respectively. The results demonstrated that the hexane fractionated extract had the greatest inhibitory effect ongene expression of many leukemic cell lines and significantly decreased WT1 protein levels of K562 cells (representative of the leukemic cells), in a dose- and time-dependent manner. Subfraction No. 9 (F9) after partial purification of hexane fractioned extract showed the highest suppression on WT1 protein and suppressed cell cycle at G2/M. The organic compounds were isolated from F9 and identified as phytol and lupeol. The bioassays confirmed antiproliferative activities of natural products phytol and lupeol. The results demonstrated anticancer activity of the isolated phytol and lupeol to decrease leukemic cell proliferation.


greenmedinfo--2020-06-19--Moringa oleifera leaves extract modulates toxicity, sperms alterations, oxidative stress, and testic

Moringa oleifera leaves extract modulates toxicity, sperms alterations, oxidative stress, and testicular damage induced by tramadol.

Tramadol is a synthetic opioid analgesic used for moderate-to-severe pain structurally related to codeine and morphine , where their analgesic mechanism is a result of opioid and non-opioid mechanisms .
This study was designed to evaluate the effects ofleaves extract ( MLE ) on tramadol-induced testicular toxicity , sperm changes , testicular damage , and oxidative stress in male rats .
Forty male albino rats were divided into four groups and treated for 4 weeks ( group 1 , as control ; group 2 , MLE ; group 3 , tramadol ; group 4 , MLE + tramadol ) .
@ @ @ @ @ @ @ weight , serum total testosterone , luteinizing hormone , follicle-stimulating hormone , sperm counts , vitality , total sperm motility , catalase , and superoxide dismutase activities were significantly decreased in tramadol-treated group when compared with the control group .
In contrast , sperm abnormality , immotile sperm percent , testicular injury , and TBARS concentration in testes were significantly increased in the tramadol-treated group .
In addition , histopathological examination for the tramadol-treated group has shown incomplete spermatogenesis , moderate degeneration in some seminiferous tubules with a significant decrease in the number @ @ @ @ @ @ @ cells .
The administration of MLE with tramadol ameliorates the testicular toxicity , injury , sperm count , abnormalities , and oxidative stress induced by tramadol .

Tramadol is a synthetic opioid analgesic used for moderate-to-severe pain structurally related to codeine and morphine, where their analgesic mechanism is a result of opioid and non-opioid mechanisms. This study was designed to evaluate the effects ofleaves extract (MLE) on tramadol-induced testicular toxicity, sperm changes, testicular damage, and oxidative stress in male rats. Forty male albino rats were divided into four groups and treated for 4 weeks (group 1, as control; group 2, MLE; group 3, tramadol; group 4, MLE + tramadol). The relative body weight, relative testes weight, serum total testosterone, luteinizing hormone, follicle-stimulating hormone, sperm counts, vitality, total sperm motility, catalase, and superoxide dismutase activities were significantly decreased in tramadol-treated group when compared with the control group. In contrast, sperm abnormality, immotile sperm percent, testicular injury, and TBARS concentration in testes were significantly increased in the tramadol-treated group. In addition, histopathological examination for the tramadol-treated group has shown incomplete spermatogenesis, moderate degeneration in some seminiferous tubules with a significant decrease in the number of spermatogenic cells and depletion of Leydig cells. The administration of MLE with tramadol ameliorates the testicular toxicity, injury, sperm count, abnormalities, and oxidative stress induced by tramadol.


greenmedinfo--2020-06-20--Yogurt Improves Immune System in the Elderly

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

This website is for information purposes only. By providing the information contained herein we are not diagnosing, treating, curing, mitigating, or preventing any type of disease or medical condition. Before beginning any type of natural, integrative or conventional treatment regimen, it is advisable to seek the advice of a licensed healthcare professional.
© Copyright 2008-2023 GreenMedInfo.com, Journal Articles copyright of original owners, MeSH copyright NLM.


greenmedinfo--2020-06-20--Caffeine supplementation showed a significant ergogenic effect on muscle endurance and maximum stren

This study aimed to determine the effects of caffeine supplementation on muscle endurance , maximum strength , and ratings of perceived exertion ( RPE ) in individuals undergoing strength training with external resistance exercises .
A search of three databases ( PubMed , LiLACS , and CENTRAL ) and gray literature was carried out to find randomized controlled trials , with a double-blind design , which investigated the effects of caffeine supplementation in healthy adults .
Meta-analyses of weighted mean differences ( WMD ) and standardized mean differences ( SMD ) between caffeine and placebo groups from individual studies were @ @ @ @ @ @ @ studies were included in the quantitative synthesis .
Only the bench press and the leg press exercises were assessed in a sufficient number of studies to be included in meta-analyses .
In the bench press exercise , caffeine supplementation improved strength resistance ( WMD 0.87 ( 95 % confidence interval ( CI ) : 0.33 , 1.41 ) repetitions , P = 0.001 ; 15 studies ) , and maximum strength ( WMD 2.01 ( 95 % CI : 0.20 , 3.80 ) kg , P = 0.02 ; 7 studies ) , @ @ @ @ @ @ @ SMD -0.45 ( 95 % CI : -1.40 , 0.48 ) , P = 0.34 , 7 studies ) In the leg press exercise , no significant improvement were observed in muscle endurance ( WMD : 1.24 ( 95 % CI : -0.21 , 2.70 ) repetitions , P = 0.09 , 8 studies ) , maximum strength ( WMD 8.49 ( 95 % CI : -11.91 , 28.90 ) kg , P = 0.415 , 3 studies ) , and in RPE ( SMD -0.17 ( 95 % CI : -1.62 , @ @ @ @ @ @ @ 3 studies ) .
Caffeine supplementation showed a significant ergogenic effect on muscle endurance and maximum strength in the bench press exercise .
More investigations are needed to clarify the contradictions in its effects regarding lower-body exercises .

This study aimed to determine the effects of caffeine supplementation on muscle endurance, maximum strength, and ratings of perceived exertion (RPE) in individuals undergoing strength training with external resistance exercises. A search of three databases (PubMed, LiLACS, and CENTRAL) and gray literature was carried out to find randomized controlled trials, with a double-blind design, which investigated the effects of caffeine supplementation in healthy adults. Meta-analyses of weighted mean differences (WMD) and standardized mean differences (SMD) between caffeine and placebo groups from individual studies were performed using a random-effects model. Nineteen studies were included in the quantitative synthesis. Only the bench press and the leg press exercises were assessed in a sufficient number of studies to be included in meta-analyses. In the bench press exercise, caffeine supplementation improved strength resistance (WMD 0.87 (95% confidence interval (CI): 0.33, 1.41) repetitions, P = 0.001; 15 studies), and maximum strength (WMD 2.01 (95% CI: 0.20, 3.80) kg, P = 0.02; 7 studies), but showed no effect in RPE (SMD -0.45 (95% CI: -1.40, 0.48), P = 0.34, 7 studies) In the leg press exercise, no significant improvement were observed in muscle endurance (WMD: 1.24 (95%CI: -0.21, 2.70) repetitions, P = 0.09, 8 studies), maximum strength (WMD 8.49 (95% CI: -11.91, 28.90) kg, P = 0.415, 3 studies), and in RPE (SMD -0.17 (95% CI: -1.62, 1.27), P = 0.812, 3 studies). Caffeine supplementation showed a significant ergogenic effect on muscle endurance and maximum strength in the bench press exercise. More investigations are needed to clarify the contradictions in its effects regarding lower-body exercises.


greenmedinfo--2020-06-20--Protective effect of caffeic acid phenethyl ester against imidacloprid-induced hepatotoxicity.

Imidacloprid ( IMI ) is a widely used neonicotinoid pesticide in the world , its environmental and human health risk has particularly attracted the attention of researchers .
Caffeic acid phenethyl ester ( CAPE ) , an active polyphenol of propolis , has many pharmacological activities including free radical scavenger , anti-inflammatory , and anti-oxidant .
In this study , protective effect of CAPE against IMI induced liver injury in mice was performed .
Administration of 1 and 2.5 mg/kg CAPE markedly prevented serum AST and ALT increase in 5 mg/kg IMI-induced mice .
CAPE significantly downregulated liver NO generation @ @ @ @ @ @ @ , catalase , superoxide dismutase and glutathione peroxidase in a dose-dependent manner in liver of IMI-induced mice .
Endoplasmic reticulum stress represented by the swelling of endoplasmic reticulum was observed by transmission electron microscope in IMI group .
Pretreatment of 2.5 mg/kg CAPE significantly attenuated the endoplasmic reticulum stress induced by IMI in liver .
Western blot analysis illustrated that pretreatment of CAPE downregulated the upregulation of TNF-α and IFN-γ induced by IMI in liver of mice .
Moreover , the increase of positive apoptotic hepatocytes further suggested apoptosis might be involved in @ @ @ @ @ @ @ 2.5 mg/kg CAPE significantlydecreased positive apoptotic hepatocytes , suggested that CAPE prevented apoptosis in liver of IMI-induced mice .
In conclusion , CAPE prevented liver injury in IMI-induced mice via attenuation of oxidative stress , endoplasmic reticulum stress , inflammation and apoptosis .
Our findings may have broad biological and environmental implications for future research on the therapeutic strategy to prevent liver injury induced by pesticides .

Imidacloprid (IMI) is a widely used neonicotinoid pesticide in the world, its environmental and human health risk has particularly attracted the attention of researchers. Caffeic acid phenethyl ester (CAPE), an active polyphenol of propolis, has many pharmacological activities including free radical scavenger, anti-inflammatory, and anti-oxidant. In this study, protective effect of CAPE against IMI induced liver injury in mice was performed. Administration of 1 and 2.5 mg/kg CAPE markedly prevented serum AST and ALT increase in 5 mg/kg IMI-induced mice. CAPE significantly downregulated liver NO generation and lipid peroxidation, and upregulated glutathione, catalase, superoxide dismutase and glutathione peroxidase in a dose-dependent manner in liver of IMI-induced mice. Endoplasmic reticulum stress represented by the swelling of endoplasmic reticulum was observed by transmission electron microscope in IMI group. Pretreatment of 2.5 mg/kg CAPE significantly attenuated the endoplasmic reticulum stress induced by IMI in liver. Western blot analysis illustrated that pretreatment of CAPE downregulated the upregulation of TNF-α and IFN-γ induced by IMI in liver of mice. Moreover, the increase of positive apoptotic hepatocytes further suggested apoptosis might be involved in IMI-induced hepatotoxicity. Pretreatment of 1 and 2.5 mg/kg CAPE significantlydecreased positive apoptotic hepatocytes, suggested that CAPE prevented apoptosis in liver of IMI-induced mice. In conclusion, CAPE prevented liver injury in IMI-induced mice via attenuation of oxidative stress, endoplasmic reticulum stress, inflammation and apoptosis. Our findings may have broad biological and environmental implications for future research on the therapeutic strategy to prevent liver injury induced by pesticides.


greenmedinfo--2020-06-20--Caffeic acid phenethyl ester against cadmium induced toxicity mediated by circRNA modulates autophag

Caffeic acid phenethyl ester against cadmium induced toxicity mediated by circRNA modulates autophagy in HepG2 cells.

Cadmium pollution and poisoning are serious environmental and pharmacological concerns , and effective drugs can alleviate or offset cadmium-induced toxicity @ @ @ @ @ this study , Caffeic acid phenethyl ester ( CAPE ) , a major active component @ @ @ @ @ effect against CdCl-induced toxicology by suppressing autophagy in HepG2 cells .
CircRNAs are increasingly perceived @ @ @ @ @ process of autophagy .
However , it remain unclear whether circRNAs are involved in CAPE @ @ @ @ @ .
Under this context , the roles of CircRNA ( hsa_circ_0040768 ) in CAPE 's @ @ @ @ @ investigated by PCR and Western blot .
Results showed that CAPE significantly ( P

Cadmium pollution and poisoning are serious environmental and pharmacological concerns, and effective drugs can alleviate or offset cadmium-induced toxicity are badly needed. In this study, Caffeic acid phenethyl ester (CAPE), a major active component of propolis, showed protective effect against CdCl-induced toxicology by suppressing autophagy in HepG2 cells. CircRNAs are increasingly perceived as vital regulators in the process of autophagy. However, it remain unclear whether circRNAs are involved in CAPE's protection against CdCl-induced autophagy. Under this context, the roles of CircRNA (hsa_circ_0040768) in CAPE's protection against CdCl-induced damage were investigated by PCR and Western blot. Results showed that CAPE significantly (P < 0.05) increased cell viability via inhibiting CdCl-induced autophagy, and this process was regulated by hsa_circ_0040768/MAP1LC3B axis. Overexpressing hsa_circ_0040768 led to reduced cell viability and increased autophagy in CAPE-treated HepG2 cells exposed to CdCl. In contrast, silencing hsa_circ_0040768 showed similar protective effect to CAPE. These results show for the first time the involvement of the hsa_circ_0040768/MAP1LC3B axis in the CAPE's protection against CdCl-induced autophagy, and provide novel insights into the pathogenesis and potential prevention/treatment of cadmium-associated diseases.


greenmedinfo--2020-06-20--Biochanin A ameliorates ovalbumin-induced airway inflammation.

OBJECTIVE : Asthma is an inflammatory airway disease affecting most of the population in the world .
The current medication for asthma relieves airway inflammation but it has serious adverse effects .
Biochanin A ( BCA ) , a phytoestrogen , is an active component present in red clover , alfalfa , soy having anti-oxidant and anti-inflammatory properties .
BCA was identified as a natural activator of peroxisome proliferator-activated receptor-gamma ( PPARγ ) .
METHODS : The study aims to evaluate the effects of BCA in ovalbumin ( OVA ) -induced murine model of asthma and to study the role @ @ @ @ @ @ @ that BCA administration reduced the severity of murine allergic asthma as evidenced histologically , and measurement of allergen-specific IgE levels in serum as well as in BAL fluid .
BCA also reversed the elevated levels of inflammatory cytokines , cell infiltration , protein leakage into the airways and expression of hemoxygenase-1 in OVA-induced lungs .
Further , we confirmed that BCA mediated inhibitory effects are mediated through PPARγ as assessed by treatment with PPARγ antagonist GW9662 .
CONCLUSION : Our results suggest that BCA is efficacious in a preclinical model of asthma and @ @ @ @ @ @ @ of asthma in humans .

OBJECTIVE: Asthma is an inflammatory airway disease affecting most of the population in the world. The current medication for asthma relieves airway inflammation but it has serious adverse effects. Biochanin A (BCA), a phytoestrogen, is an active component present in red clover, alfalfa, soy having anti-oxidant and anti-inflammatory properties. BCA was identified as a natural activator of peroxisome proliferator-activated receptor-gamma (PPARγ).
METHODS: The study aims to evaluate the effects of BCA in ovalbumin (OVA)-induced murine model of asthma and to study the role of PPARγ.
RESULTS: We found that BCA administration reduced the severity of murine allergic asthma as evidenced histologically, and measurement of allergen-specific IgE levels in serum as well as in BAL fluid. BCA also reversed the elevated levels of inflammatory cytokines, cell infiltration, protein leakage into the airways and expression of hemoxygenase-1 in OVA-induced lungs. Further, we confirmed that BCA mediated inhibitory effects are mediated through PPARγ as assessed by treatment with PPARγ antagonist GW9662.
CONCLUSION: Our results suggest that BCA is efficacious in a preclinical model of asthma and may have the potential for the treatment of asthma in humans.


greenmedinfo--2020-06-20--Biochanin A induces relaxation of the coronary artery.

The dietary intake of flavonoids seems to be inversely related to cardiovascular mortality .
The consumption of isoflavonoids is increasing in the general population , especially due to the use of food supplements and a variety of isoflavonoid-rich foods .
However , detailed studies on the vascular influence of individual pure isoflavonoids are mostly missing .
For this study , 16 isoflavonoids were initially screened for their vasorelaxant properties on rat aortas .
The 2 most potent of them , biochanin A and glycitein , were further tested for the mechanism of action on porcine coronary arteries .
They both @ @ @ @ @ @ @ with ECbelow 6 and 17 µM , respectively .
Biochanin A , but not glycitein , was able to block the vasoconstriction caused by KCl , CaCl , serotonin , and U46619 in a dose-dependent manner .
Another series of experiments suggested that the major mechanism of action of biochanin A was the inhibition of L-type calcium channels .
Moreover , biochanin A in relatively small concentrations ( 2 - 4 µM ) interfered with the cGMP , but not cAMP , pathway in isolated coronary arteries .
These results indicate that some @ @ @ @ @ @ @ are able to have vasodilatory effects in micromolar concentrations , which is of potential clinical interest for the management ofcardiovascular pathologies .

The dietary intake of flavonoids seems to be inversely related to cardiovascular mortality. The consumption of isoflavonoids is increasing in the general population, especially due to the use of food supplements and a variety of isoflavonoid-rich foods. However, detailed studies on the vascular influence of individual pure isoflavonoids are mostly missing. For this study, 16 isoflavonoids were initially screened for their vasorelaxant properties on rat aortas. The 2 most potent of them, biochanin A and glycitein, were further tested for the mechanism of action on porcine coronary arteries. They both induced an endothelium independent vascular relaxation, with ECbelow 6 and 17 µM, respectively. Biochanin A, but not glycitein, was able to block the vasoconstriction caused by KCl, CaCl, serotonin, and U46619 in a dose-dependent manner. Another series of experiments suggested that the major mechanism of action of biochanin A was the inhibition of L-type calcium channels. Moreover, biochanin A in relatively small concentrations (2 - 4 µM) interfered with the cGMP, but not cAMP, pathway in isolated coronary arteries. These results indicate that some isoflavonoids, in particular biochanin A, are able to have vasodilatory effects in micromolar concentrations, which is of potential clinical interest for the management ofcardiovascular pathologies.


greenmedinfo--2020-06-20--Prophylactic effect of biochanin A in lipopolysaccharide-stimulated BV2 microglial cells.

Inhibition of microglial activation using phytochemicals may be a potential candidate for the prevention of neurodegenerative diseases caused by neuroinflammation and oxidative stress .
The goal of this study was to investigate the protective role of Biochanin A on lipopolysaccharide ( LPS ) -stimulated BV2 microglial cells .
BV2 microglial cells were treated with LPS in the presence and absence of Biochanin A.For this aim , nitric oxide production , nuclear factor kappa B ( NF-κB ) , tumor necrosis factor alpha ( TNF-α ) , interleukin-1 beta ( IL-1β ) , IL-6 , Prostaglandin E2 ( PGE2 ) , @ @ @ @ @ @ @ levels , inducible nitric oxide synthase ( iNOS ) , cyclooxygenase-2 ( COX-2 ) , myeloid differentiation factor-88 ( MyD88 ) , and toll like receptor-4 ( TLR-4 ) protein expressions , Akt and ERK1/2 phosphorylation levels were measured.Biochanin A pretreatment resulted in significant and concentration-dependently reduced the LPS-induced production of nitric oxide , NF-κB p65 , TNF-α , IL-1β , IL-6 , PGE2 , and ROS compared to the untreated group .
Biochanin A prophylaxis exerted an anti-inflammatory effect by suppressing iNOS , COX-2 , MyD88 , and TLR-4 protein expressions and @ @ @ @ @ @ @ these results show that Biochanin A exerts antioxidant and anti-inflammatory activities , thus may be beneficial for preventing neurodegenerative diseases mediated by microglial cells .

Inhibition of microglial activation using phytochemicals may be a potential candidate for the prevention of neurodegenerative diseases caused by neuroinflammation and oxidative stress. The goal of this study was to investigate the protective role of Biochanin A on lipopolysaccharide (LPS)-stimulated BV2 microglial cells. BV2 microglial cells were treated with LPS in the presence and absence of Biochanin A.For this aim, nitric oxide production, nuclear factor kappa B (NF-κB), tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), IL-6, Prostaglandin E2 (PGE2), and reactive oxygen species (ROS) levels, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), myeloid differentiation factor-88 (MyD88), and toll like receptor-4 (TLR-4) protein expressions, Akt and ERK1/2 phosphorylation levels were measured.Biochanin A pretreatment resulted in significant and concentration-dependently reduced the LPS-induced production of nitric oxide, NF-κB p65, TNF-α, IL-1β, IL-6, PGE2, and ROS compared to the untreated group. Biochanin A prophylaxis exerted an anti-inflammatory effect by suppressing iNOS, COX-2, MyD88, and TLR-4 protein expressions and Akt and ERK1/2 pathway activation.Taken together, these results show that Biochanin A exerts antioxidant and anti-inflammatory activities, thus may be beneficial for preventing neurodegenerative diseases mediated by microglial cells.


greenmedinfo--2020-06-20--Caffeic acid phenethyl ester prevents colitis-associated cancer by inhibiting NLRP3 inflammasome.

Long-lasting inflammation in the intestinal tract renders individuals susceptible to colitis-associated cancer ( CAC ) .
The NOD-like receptor protein 3 ( NLRP3 ) inflammasome plays a key role in the progression of inflammatory bowel disease and CAC .
Therefore , identifying effective drugs that prevent CAC by targeting NLRP3 inflammasome is of great interest .
Here , we aimed to evaluate the anti-inflammatory effect of caffeic acid phenethyl ester ( CAPE ) on bone marrow-derived macrophages ( BMDMs ) , THP-1 cells , and azoxymethane/dextran sulfate sodium ( AOM/DSS ) -induced colon cancer mouse model .
We also investigated @ @ @ @ @ @ @ found that CAPE decreased NLRP3 inflammasome activation in BMDMs and THP-1 cells and protected mice from colorectal cancer induced by AOM/DSS .
CAPE regulated NLRP3 at the post-transcriptional level by inhibiting reactive oxygen species ( ROS ) production .
However , CAPE did not affect NLRP3 or IL-1β transcription , but instead enhanced NLRP3 binding to ubiquitin molecules , promoting NLRP3 ubiquitination , and contributing to the anti-tumor effect in the AOM/DSS mouse model .
Moreover , CAPE suppressed the interaction between NLRP3 and CSN5 but enhanced that between NLRP3 and Cullin1 bothand @ @ @ @ @ @ @ CAPE prevents CAC by post-transcriptionally inhibiting NLRP3 inflammasome .
Thus , CAPE may be an effective candidate for reducing the risk of CAC in patients with inflammatory bowel disease .

Long-lasting inflammation in the intestinal tract renders individuals susceptible to colitis-associated cancer (CAC). The NOD-like receptor protein 3 (NLRP3) inflammasome plays a key role in the progression of inflammatory bowel disease and CAC. Therefore, identifying effective drugs that prevent CAC by targeting NLRP3 inflammasome is of great interest. Here, we aimed to evaluate the anti-inflammatory effect of caffeic acid phenethyl ester (CAPE) on bone marrow-derived macrophages (BMDMs), THP-1 cells, and azoxymethane/dextran sulfate sodium (AOM/DSS)-induced colon cancer mouse model. We also investigated the anti-tumor mechanism of CAPE. We found that CAPE decreased NLRP3 inflammasome activation in BMDMs and THP-1 cells and protected mice from colorectal cancer induced by AOM/DSS. CAPE regulated NLRP3 at the post-transcriptional level by inhibiting reactive oxygen species (ROS) production. However, CAPE did not affect NLRP3 or IL-1β transcription, but instead enhanced NLRP3 binding to ubiquitin molecules, promoting NLRP3 ubiquitination, and contributing to the anti-tumor effect in the AOM/DSS mouse model. Moreover, CAPE suppressed the interaction between NLRP3 and CSN5 but enhanced that between NLRP3 and Cullin1 bothand. Altogether, our findings demonstrate that CAPE prevents CAC by post-transcriptionally inhibiting NLRP3 inflammasome. Thus, CAPE may be an effective candidate for reducing the risk of CAC in patients with inflammatory bowel disease.


greenmedinfo--2020-06-20--Caffeic acid phenethyl ester assisted by reversible electroporation - in vitro study on human melano

Caffeic acid phenethyl ester assisted by reversible electroporation - in vitro study on human melanoma cells.

Melanoma is one of the most serious skin cancers .
The incidence of this malignant skin lesion is continuing to increase worldwide .
Melanoma is resistant to chemotherapeutic drugs and highly metastatic .
Surgical resection can only be used to treat melanoma in the early stages , while chemotherapy is limited due to melanoma multi-drug resistance .
The overexpression of glutathione-transferase ( GST ) may have a critical role in this resistance .
Caffeic acid phenethyl ester ( CAPE ) is a natural phenolic compound , which occurs in many plants .
Previous studies demonstrated that CAPE suppresses the growth @ @ @ @ @ @ @ species generation .
It is also known that bioactivation of CAPE to its corresponding quinone metabolite by tyrosinase would lead to GST inhibition and selective melanoma cell death .
We investigated the biochemical toxicity of CAPE in combination with microsecond electropermeabilization in two human melanoma cell lines .
Our results indicate that electroporation of melanoma cells in the presence of CAPE induced high oxidative stress , which correlates with high cytotoxicity .
Moreover , it can disrupt the metabolism of cancer cells by inducing apoptotic cell death .
Electroporation of melanoma cells may @ @ @ @ @ @ @ enabling the application of this compound , while reducing its dose and exposure time .

Melanoma is one of the most serious skin cancers. The incidence of this malignant skin lesion is continuing to increase worldwide. Melanoma is resistant to chemotherapeutic drugs and highly metastatic. Surgical resection can only be used to treat melanoma in the early stages, while chemotherapy is limited due to melanoma multi-drug resistance. The overexpression of glutathione-transferase (GST) may have a critical role in this resistance. Caffeic acid phenethyl ester (CAPE) is a natural phenolic compound, which occurs in many plants. Previous studies demonstrated that CAPE suppresses the growth of melanoma cells and induces reactive oxygen species generation. It is also known that bioactivation of CAPE to its corresponding quinone metabolite by tyrosinase would lead to GST inhibition and selective melanoma cell death. We investigated the biochemical toxicity of CAPE in combination with microsecond electropermeabilization in two human melanoma cell lines. Our results indicate that electroporation of melanoma cells in the presence of CAPE induced high oxidative stress, which correlates with high cytotoxicity. Moreover, it can disrupt the metabolism of cancer cells by inducing apoptotic cell death. Electroporation of melanoma cells may be an efficient CAPE delivery system, enabling the application of this compound, while reducing its dose and exposure time.


greenmedinfo--2020-06-20--Caffeic acid protects against iron-induced cardiotoxicity.

The protective effects of caffeic acid on angiotensin-converting enzyme (ACE) and purinergic enzyme activities, as well as gluconeogenesis was investigated in iron-induced cardiotoxicity. Cardiotoxicity was induced in heart tissues harvested from healthy male SD rats by 0.1 mM FeSO. Treatment was carried out by co-incubating hearts tissues with caffeic acid and 0.1 mM FeSO. Cardiotoxicity induction significantly (p < 0.05) depleted GSH level, SOD, catalase, and ENTPDase activities, with concomitant elevation of the levels of malondialdehyde (MDA), nitric oxide, ACE, ATPase, glycogen phosphorylase, glucose 6-phosphatase, fructose 6-biphsophatase, and lipase activities. There was significant (p < 0.05) reversion in these levels and activities on treatment with caffeic acid. Caffeic acid also caused depletion in cardiac levels of cholesterol, triglyceride, LDL-c, while elevating HDL-c level. Our results suggest the protective effect of caffeic acid against iron-mediated cardiotoxicity as indicated by its ability to suppress oxidative imbalance and ACE activity, while concomitantly modulating nucleotide hydrolysis and metabolic switch.


greenmedinfo--2020-06-20--The antibacterial effect of caffeic acid phenethyl ester on cariogenic bacteria and streptococcus mu

The antibacterial effect of caffeic acid phenethyl ester on cariogenic bacteria and streptococcus mutans biofilms.

Dental caries is the most common disease in the human mouth.is the primary cariogenic bacteria .
Propolis is a nontoxic natural product with a strong inhibitory effect on oral cariogenic bacteria .
The polyphenol-rich extract from propolis inhibitgrowth and biofilm formation , as well as the genes involved in virulence and adherence , through the inhibition of glucosyltransferases .
However , because the chemical composition of propolis is highly variable and complex , the mechanism of its antimicrobial action and the active compound are controversial and not completely understood .
Caffeic acid phenethyl ester ( CAPE ) is abundant in @ @ @ @ @ @ @ it has many pharmacological effects .
In this study , we investigated the antibacterial effects of CAPE on common oral cariogenic bacteria ( , ,and ) and its effects on the biofilm-forming and cariogenic abilities ofCAPE shows remarkable antimicrobial activity against cariogenic bacteria .
Moreover , CAPE also inhibits the formation ofbiofilms and its metabolic activity in mature biofilms .
Furthermore , CAPE can inhibit the key virulence factors ofassociated with cariogenicity , including acid production , acid tolerance and its ability to produce extracellular polysaccharides without affecting bacterial viability at subinhibitory levels @ @ @ @ @ @ @ be a new agent with anticariogenic potential , not only via inhibition of the growth of cariogenic bacteria .

Dental caries is the most common disease in the human mouth.is the primary cariogenic bacteria. Propolis is a nontoxic natural product with a strong inhibitory effect on oral cariogenic bacteria. The polyphenol-rich extract from propolis inhibitgrowth and biofilm formation, as well as the genes involved in virulence and adherence, through the inhibition of glucosyltransferases. However, because the chemical composition of propolis is highly variable and complex, the mechanism of its antimicrobial action and the active compound are controversial and not completely understood. Caffeic acid phenethyl ester (CAPE) is abundant in the polyphenolic compounds from propolis, and it has many pharmacological effects. In this study, we investigated the antibacterial effects of CAPE on common oral cariogenic bacteria (,,and) and its effects on the biofilm-forming and cariogenic abilities ofCAPE shows remarkable antimicrobial activity against cariogenic bacteria. Moreover, CAPE also inhibits the formation ofbiofilms and its metabolic activity in mature biofilms. Furthermore, CAPE can inhibit the key virulence factors ofassociated with cariogenicity, including acid production, acid tolerance and its ability to produce extracellular polysaccharides without affecting bacterial viability at subinhibitory levels. In conclusion, CAPE appears to be a new agent with anticariogenic potential, not only via inhibition of the growth of cariogenic bacteria.


greenmedinfo--2020-06-20--Natural compounds attenuate heavy metal-induced PC12 cell damage.

OBJECTIVES : To investigate the neuroprotective effects of six natural compounds ( caffeine , gallic acid , resveratrol , epigallocatechin @ @ @ @ @ L-ascorbic acid and alpha tocopherol [ Vitamin E ] on heavy metal-induced cell damage in @ @ @ @ @ : In thisexperiment , rat PC12 cells were exposed to four heavy metals ( CdCl @ @ @ @ @ ) at different concentrations and cell apoptosis , necrosis and oxidative stress were assessed with @ @ @ @ @ the six natural compounds .
RESULTS : The metals decreased cell viability but the natural @ @ @ @ @ apoptosis , necrosis and reactive oxygen species ( ROS ) levels .
Mitochondrial protein changes @ @ @ @ @ .
CONCLUSION : Overall , the natural compounds did provide protection against the metal-induced PC12 @ @ @ @ @ suggest that natural compounds may have therapeutic potential against metal-induced neurodegenerative disease .

OBJECTIVES: To investigate the neuroprotective effects of six natural compounds (caffeine, gallic acid, resveratrol, epigallocatechin gallate [EGCG], L-ascorbic acid and alpha tocopherol [Vitamin E] on heavy metal-induced cell damage in rat PC12 cells.
METHODS: In thisexperiment, rat PC12 cells were exposed to four heavy metals (CdCl, HgCl, CoCland PbCl) at different concentrations and cell apoptosis, necrosis and oxidative stress were assessed with and without the addition of the six natural compounds.
RESULTS: The metals decreased cell viability but the natural compounds attenuated their effects on apoptosis, necrosis and reactive oxygen species (ROS) levels. Mitochondrial protein changes were involved in the regulation.
CONCLUSION: Overall, the natural compounds did provide protection against the metal-induced PC12 cell damage. These data suggest that natural compounds may have therapeutic potential against metal-induced neurodegenerative disease.


greenmedinfo--2020-06-20--Patients with community acquired pneumonia exhibit depleted vitamin C status and elevated oxidative

Patients with community acquired pneumonia exhibit depleted vitamin C status and elevated oxidative stress.

Pneumonia is a severe lower respiratory tract infection that is a common complication and a major cause of mortality of the vitamin C-deficiency disease scurvy .
This suggests an important link between vitamin C status and lower respiratory tract infections .
Due to the paucity of information on the vitamin C status of patients with pneumonia , we assessed the vitamin C status of 50 patients with community-acquired pneumonia and compared these with 50 healthy community controls .
The pneumonia cohort comprised 44 patients recruited through the Acute Medical Assessment Unit ( AMAU ) and 6 patients recruited through the @ @ @ @ @ @ @ mean age 68± 17 years , 54 % male .
Clinical , microbiological and hematological parameters were recorded .
Blood samples were tested for vitamin C status using HPLC with electrochemical detection and protein carbonyl concentrations , an established marker of oxidative stress , using ELISA .
Patients with pneumonia had depleted vitamin C status compared with healthy controls ( 23 ± 14 µmol/L vs. 56 ± 24 µmol/L , < 0.001 ) .
The more severe patients in the ICU had significantly lower vitamin C status than those recruited through AMAU ( @ @ @ @ @ @ @ µmol/L , = 0.02 ) .
The pneumonia cohort comprised 62 % with hypovitaminosis C and 22 % with deficiency , compared with only 8 % hypovitaminosis C and no cases of deficiency in the healthy controls .
The pneumonia cohort also exhibited significantly elevated protein carbonyl concentrations compared with the healthy controls ( < 0.001 ) , indicating enhanced oxidative stress in the patients .
We were able to collect subsequent samples from 28 % of the cohort ( mean 2.7± 1.7 days ; range 1-7 days ) .
These showed no @ @ @ @ @ @ @ protein carbonyl concentrations compared with baseline values ( = 0.6 ) .
Overall , the depleted vitamin C status and elevated oxidative stress observed in the patients with pneumonia indicates an enhanced requirement for the vitamin during their illness .
Therefore , these patients would likely benefit from additional vitamin C supplementation to restore their blood and tissue levels to optimal .
This may decrease excessive oxidative stress and aid in their recovery .

Pneumonia is a severe lower respiratory tract infection that is a common complication and a major cause of mortality of the vitamin C-deficiency disease scurvy. This suggests an important link between vitamin C status and lower respiratory tract infections. Due to the paucity of information on the vitamin C status of patients with pneumonia, we assessed the vitamin C status of 50 patients with community-acquired pneumonia and compared these with 50 healthy community controls. The pneumonia cohort comprised 44 patients recruited through the Acute Medical Assessment Unit (AMAU) and 6 patients recruited through the Intensive Care Unit (ICU); mean age 68± 17 years, 54% male. Clinical, microbiological and hematological parameters were recorded. Blood samples were tested for vitamin C status using HPLC with electrochemical detection and protein carbonyl concentrations, an established marker of oxidative stress, using ELISA. Patients with pneumonia had depleted vitamin C status compared with healthy controls (23 ± 14 µmol/L vs. 56 ± 24 µmol/L,<0.001). The more severe patients in the ICU had significantly lower vitamin C status than those recruited through AMAU (11± 3 µmol/L vs. 24 ± 14 µmol/L,= 0.02). The pneumonia cohort comprised 62% with hypovitaminosis C and 22% with deficiency, compared with only 8% hypovitaminosis C and no cases of deficiency in the healthy controls. The pneumonia cohort also exhibited significantly elevated protein carbonyl concentrations compared with the healthy controls (<0.001), indicating enhanced oxidative stress in the patients. We were able to collect subsequent samples from 28% of the cohort (mean 2.7± 1.7 days; range 1-7 days). These showed no significant differences in vitamin C status or protein carbonyl concentrations compared with baseline values (= 0.6). Overall, the depleted vitamin C status and elevated oxidative stress observed in the patients with pneumonia indicates an enhanced requirement for the vitamin during their illness. Therefore, these patients would likely benefit from additional vitamin C supplementation to restore their blood and tissue levels to optimal. This may decrease excessive oxidative stress and aid in their recovery.


greenmedinfo--2020-06-20--Vitamin C deficiency mimicking inflammatory bone disease of the hand.

BACKGROUND : Severe vitamin C deficiency , or scurvy , encompasses a syndrome of multisystem abnormalities due to defective collagen synthesis and antioxidative functions .
Among the more common presentations is a combination of oral or subcutaneous hemorrhage with lower extremity pain , the latter often exhibiting inflammatory bone changes on magnetic resonance imaging ( MRI ) .
CASE PRESENTATION : A 12-year-old male with anorexia nervosa presented with asymmetric painful swelling of multiple fingers of both hands .
Imaging demonstrated soft tissue and bone marrow edema of several phalanges , without arthritis , concerning for an inflammatory process .
@ @ @ @ @ @ @ unrevealing , with the exception of a severely low vitamin C level and a moderately low vitamin D level .
A diagnosis of scurvy was made and supplementation was initiated .
Within 3 weeks of treatment , serum levels of both vitamins normalized and the digital abnormalities resolved on physical exam .
CONCLUSIONS : This represents the first description of scurvy manifesting with bone and soft tissue changes limited to the hands .
There must be a high index of suspicion for scurvy in children with restricted dietary intake or malabsorption who have @ @ @ @ @ @ @ the lesions .

BACKGROUND: Severe vitamin C deficiency, or scurvy, encompasses a syndrome of multisystem abnormalities due to defective collagen synthesis and antioxidative functions. Among the more common presentations is a combination of oral or subcutaneous hemorrhage with lower extremity pain, the latter often exhibiting inflammatory bone changes on magnetic resonance imaging (MRI).
CASE PRESENTATION: A 12-year-old male with anorexia nervosa presented with asymmetric painful swelling of multiple fingers of both hands. Imaging demonstrated soft tissue and bone marrow edema of several phalanges, without arthritis, concerning for an inflammatory process. Extensive imaging and laboratory evaluations were largely unrevealing, with the exception of a severely low vitamin C level and a moderately low vitamin D level. A diagnosis of scurvy was made and supplementation was initiated. Within 3 weeks of treatment, serum levels of both vitamins normalized and the digital abnormalities resolved on physical exam.
CONCLUSIONS: This represents the first description of scurvy manifesting with bone and soft tissue changes limited to the hands. There must be a high index of suspicion for scurvy in children with restricted dietary intake or malabsorption who have bone pain, irrespective of location of the lesions.


greenmedinfo--2020-06-20--The neuropsychiatric effects of vitamin C deficiency.

BACKGROUND : Vitamin C deficiency may be more common than is generally assumed , and the association between vitamin C deficiency and adverse psychiatric effects has been known for centuries .
This paper aims to systematically review the evidence base for the neuropsychiatric effects of vitamin C deficiency .
RESULTS : Nine studies of vitamin C deficiency , including subjects both with and without the associated physical manifestations of scurvy , were included in this review .
Vitamin C deficiency , including scurvy , has been linked to depression and cognitive impairment .
No effect on affective or non-affective psychosis @ @ @ @ @ @ @ techniques for vitamin C , and differing definitions of vitamin C deficiency were apparent , complicating comparisons between studies .
However , there is evidence suggesting that vitamin C deficiency is related to adverse mood and cognitive effects .
The vitamin C blood levels associated with depression and cognitive impairment are higher than those implicated in clinical manifestations of scurvy .
While laboratory testing for ascorbic acid can be practically difficult , these findings nonetheless suggest that mental health clinicians should be alerted to the possibility of vitamin C deficiency in patients with @ @ @ @ @ @ @ replacement is inexpensive and easy to deliver , although as of yet there are no outcome studies investigating the neuropsychiatric impact of vitamin C replacement in those who are deficient .

BACKGROUND: Vitamin C deficiency may be more common than is generally assumed, and the association between vitamin C deficiency and adverse psychiatric effects has been known for centuries. This paper aims to systematically review the evidence base for the neuropsychiatric effects of vitamin C deficiency.
METHODS: Relevant studies were identified via systematic literature review.
RESULTS: Nine studies of vitamin C deficiency, including subjects both with and without the associated physical manifestations of scurvy, were included in this review. Vitamin C deficiency, including scurvy, has been linked to depression and cognitive impairment. No effect on affective or non-affective psychosis was identified.
CONCLUSIONS: Disparate measurement techniques for vitamin C, and differing definitions of vitamin C deficiency were apparent, complicating comparisons between studies. However, there is evidence suggesting that vitamin C deficiency is related to adverse mood and cognitive effects. The vitamin C blood levels associated with depression and cognitive impairment are higher than those implicated in clinical manifestations of scurvy. While laboratory testing for ascorbic acid can be practically difficult, these findings nonetheless suggest that mental health clinicians should be alerted to the possibility of vitamin C deficiency in patients with depression or cognitive impairment. Vitamin C replacement is inexpensive and easy to deliver, although as of yet there are no outcome studies investigating the neuropsychiatric impact of vitamin C replacement in those who are deficient.


greenmedinfo--2020-06-20--High dose vitamin C can inhibit the proliferation and promote the apoptosis of acute myeloid leukemi

High dose vitamin C can inhibit the proliferation and promote the apoptosis of acute myeloid leukemia cells.

OBJECTIVE : To investigate the effects of high dose vitamin C on proliferation and apoptosis of acute myeloid leukemia ( AML ) cell lines including HL-60 , U937 and primary CD34leukemia cells in AML .
METHODS : CD34cells were sorted by using immunomagnetic cell sorting system , then the primary CD34leukemia cells , including HL-60 and U937 cell lines were cultured in vitro .
Cells in each group were treated with different concentrations of vitamin C , the survival rate of cells was determined by MTT assay , the apoptosis rate of cells was evaluated by Annexin V/PI double staining @ @ @ @ @ @ @ caspase 3 , cleaved caspase-9 and cleaved PARP were detected by Western blot .
RESULTS : The proliferation of HL-60 and U937 cells could be inhibited by high dose vitamin C , which showed a concentration-dependent manner ( r=-0.9664 ; r=-0.9796 ) .
HL-60 and U937 cells were treated with different concentrations of vitamin C ( 8 and 20 mmol/L ) for 24 hours , respectively , it was found that with the increasing of vitamin C concentration , cell apoptosis rate was significantly increased ( r=0.9905 ; r=0.9971 ) , and the @ @ @ @ @ @ @ caspase 3 , cleaved caspase-9 and cleaved PARP was aslo significantly increased with the increasing of concentration .
In addition , it was found that with or without the mutation of TET2 , high dose vitamin C could inhibit the proliferation ( r=-0.9719 ; r=-0.9699 ) and promote the apoptosis ( r=0.9998 ; r=0.9901 ) of primary CD34leukemia cells in AML , which showed a dose-dependent manner , but it showed no effect on the proliferation ( r=-0.2032 ) and apoptosis ( r=0.1912 ) of normal CD34cells .
CONCLUSION : High dose vitamin @ @ @ @ @ @ @ the apoptosis of acute myeloid leukemia cells , and selectively kill primary CD34leukemia cells in AML .

OBJECTIVE: To investigate the effects of high dose vitamin C on proliferation and apoptosis of acute myeloid leukemia (AML) cell lines including HL-60, U937 and primary CD34leukemia cells in AML.
METHODS: CD34cells were sorted by using immunomagnetic cell sorting system, then the primary CD34leukemia cells, including HL-60 and U937 cell lines were cultured in vitro. Cells in each group were treated with different concentrations of vitamin C, the survival rate of cells was determined by MTT assay, the apoptosis rate of cells was evaluated by Annexin V/PI double staining, the expression of apoptotic proteins-including cleaved caspase 3, cleaved caspase-9 and cleaved PARP were detected by Western blot.
RESULTS: The proliferation of HL-60 and U937 cells could be inhibited by high dose vitamin C, which showed a concentration-dependent manner (r=-0.9664; r=-0.9796). HL-60 and U937 cells were treated with different concentrations of vitamin C (8 and 20 mmol/L) for 24 hours, respectively, it was found that with the increasing of vitamin C concentration, cell apoptosis rate was significantly increased (r=0.9905; r=0.9971), and the expression of apoptosis related proteins including cleaved caspase 3, cleaved caspase-9 and cleaved PARP was aslo significantly increased with the increasing of concentration. In addition, it was found that with or without the mutation of TET2, high dose vitamin C could inhibit the proliferation (r=-0.9719; r=-0.9699) and promote the apoptosis (r=0.9998; r=0.9901) of primary CD34leukemia cells in AML, which showed a dose-dependent manner, but it showed no effect on the proliferation (r=-0.2032) and apoptosis (r=0.1912) of normal CD34cells.
CONCLUSION: High dose vitamin C can inhibit the proliferation and promote the apoptosis of acute myeloid leukemia cells, and selectively kill primary CD34leukemia cells in AML.


greenmedinfo--2020-06-20--Nigella sativa seeds can be considered as a therapeutic agent in management of Hashimoto-related met

Nigella sativa seeds can be considered as a therapeutic agent in management of Hashimoto-related metabolic abnormalities.

OBJECTIVE : Oxidative stress plays an important role in the pathogenesis of Hashimoto 's thyroiditis .
Because of the major anti-oxidant properties of black cumin , the current study aimed to evaluate the effect of powdered Nigella sativa seeds on markers of oxidative stress , endothelial dysfunction and serum lipids in patients with Hashimoto 's thyroiditis .
METHODS : Forty patients with Hashimoto 's thyroiditis , aged between 22 and 50 years old , participated in the trial and were randomly allocated into two groups of intervention and control receiving powdered N. sativa or placebo daily for 8 weeks .
@ @ @ @ @ @ @ including total anti-oxidant capacity ( TAC ) , malondialdehyde ( MDA ) , superoxide dismutase ( SOD ) , glutathione peroxidase ( GPX ) , and biomarkers of endothelial dysfunction including Intracellular Adhesion Molecule ( ICAM ) -1 , Vascular Cell Adhesion Molecule ( VCAM ) -1 and serum lipids were also evaluated .
RESULTS : Treatment with N. sativa , significantly increased serum TAC , SOD and reduced MDA concentrations with no significant change in GPX ( P CONCLUSIONS : Giving attention to the potent beneficial effects of powdered black cumin seeds @ @ @ @ @ @ @ , serum lipids and anthropometric features in patients with Hashimoto 's thyroiditis , this medicinal plant can be considered as a therapeutic agent in management of Hashimoto-related metabolic abnormalities .

OBJECTIVE: Oxidative stress plays an important role in the pathogenesis of Hashimoto's thyroiditis. Because of the major anti-oxidant properties of black cumin, the current study aimed to evaluate the effect of powdered Nigella sativa seeds on markers of oxidative stress, endothelial dysfunction and serum lipids in patients with Hashimoto's thyroiditis.
METHODS: Forty patients with Hashimoto's thyroiditis, aged between 22 and 50 years old, participated in the trial and were randomly allocated into two groups of intervention and control receiving powdered N. sativa or placebo daily for 8 weeks. Changes in markers of oxidative stress, including total anti-oxidant capacity (TAC), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPX), and biomarkers of endothelial dysfunction including Intracellular Adhesion Molecule (ICAM)-1, Vascular Cell Adhesion Molecule (VCAM)-1 and serum lipids were also evaluated.
RESULTS: Treatment with N. sativa, significantly increased serum TAC, SOD and reduced MDA concentrations with no significant change in GPX (P < 0.05). A significant reduction in VCAM-1 (P = 0.0012), body mass index (P = 0.002), serum concentrations of low density lipoprotein cholesterol (P = 0.002) and triglyceride (P = 0.02) were also reported in N. sativa-treated group after 8 weeks; while serum high density lipoprotein cholesterol (HDL) also significantly increased (P < 0.05). No change in other parameters were reported.
CONCLUSIONS: Giving attention to the potent beneficial effects of powdered black cumin seeds in improving oxidative stress, endothelial dysfunction, serum lipids and anthropometric features in patients with Hashimoto's thyroiditis, this medicinal plant can be considered as a therapeutic agent in management of Hashimoto-related metabolic abnormalities.
TRIAL REGISTRATION NUMBER: Iranian registry of clinical trials (registration number IRCT2015021719082N4).


greenmedinfo--2020-06-20--A new oleanane type saponin from the aerial parts of Nigella sativa with anti-oxidant and anti-diabe

A new oleanane type saponin from the aerial parts of Nigella sativa with anti-oxidant and anti-diabetic potential.

Natural product studies explore potential and interesting new compounds to discover innovative drugs .
( ( Ranunculaceae ) is traditionally used to treat diabetes .
Flavonoids and triterpenoid mostly show anti-diabetic activity .
The current study aim to identify new compounds by a systematic study of the anti-oxidant and anti-diabetic activity of aerial parts ofconcerning .
Phytochemicals were isolated from the methanolic extract of aerial parts of the plant by column chromatography and identified by nuclear magnetic resonance spectroscopy and mass spectroscopy .
A new triterpenoid saponin glycoside was isolated along with flavonoids .
The anti-diabetic study was carried out @ @ @ @ @ @ @ , and protein tyrosine phosphatase 1B assays at doses of 12.5 to 250 µM .
The isolated phytochemicals were identified as 3-O- ( β-d-xylopyranosyl- ( 1-3 ) -α-l-rhamnopyrnaosyl- ( 1-2 ) -α-l-arabinopyranosyl ] -28-O- ( α-l-rhamno-pyranosyl- ( 1-4 ) -β-d-glucopyranosyl- ( 1-6 ) -β-d-glucopyranosyl ] hederagenin ( ) , flaccidoside III ( ) , catechol ( ) , quercetin-3-gentiobiosides ( ) , magnoflorine ( ) , nigelflavonoside B ( ) , nigelloside ( ) , quercetin sphorotrioside ( ) , kaempferol-3 , 7-diglucoside ( ) , kaempferol 3-O-rutinoside ( ) , rutin ( @ @ @ @ @ @ @ ) -α-l-arabinopyranpsylhederagenin ( ) , 3β,23,28-trihydroxyolean-12-ene-3-O-α-l-arabinopyranoside ( 1→4 ) -a-rhamnopyranosyl , ( 1→4 ) -β-d-gluco-pyranoside ( ) , 3-O-α-l-rhamnopyranosyl- ( 1→2 ) -α-l-arabinopyranpsyl ] -28-O-β-d-gluco-pyranosyl hederagenin ( ) , andα-hederin ( ) .
These were isolated and are reported for the first time in this study .
Comparedwas identified as a new compound .
Compoundwas isolated for first time from the genus .
Compoundwas found to be the most active in the DPPH , and ABTS assays and compoundwas found to be the most active in theα-glucosidase assay , with IC32.7± 0.1 , @ @ @ @ @ @ @ µΜ , respectively .
Compound , at a dose of 125µΜ , showed anti-diabetic activity in a PTP1B assay with IC91.30± 2.5 µΜ .
In conclusion , the anti-diabetic activity ofis due to its flavonoids and TTSGs .
Therefore , our studies suggest that the aerial parts ofare also a valuable and alternate source of valuable phytochemicals that could be used to develop anti-oxidant and anti-diabetic medicines .

Natural product studies explore potential and interesting new compounds to discover innovative drugs.((Ranunculaceae) is traditionally used to treat diabetes. Flavonoids and triterpenoid mostly show anti-diabetic activity. The current study aim to identify new compounds by a systematic study of the anti-oxidant and anti-diabetic activity of aerial parts ofconcerning. Phytochemicals were isolated from the methanolic extract of aerial parts of the plant by column chromatography and identified by nuclear magnetic resonance spectroscopy and mass spectroscopy. A new triterpenoid saponin glycoside was isolated along with flavonoids. The anti-diabetic study was carried out by DPPH, ABTS,α -glucosidase, and protein tyrosine phosphatase 1B assays at doses of 12.5 to 250 µM. The isolated phytochemicals were identified as 3-O-(β-d-xylopyranosyl-(1-3)-α-l-rhamnopyrnaosyl-(1-2)-α-l-arabinopyranosyl]-28-O-(α-l-rhamno-pyranosyl-(1-4)-β-d-glucopyranosyl-(1-6)-β-d-glucopyranosyl] hederagenin (), flaccidoside III (), catechol (), quercetin-3-gentiobiosides (), magnoflorine (), nigelflavonoside B (), nigelloside (), quercetin sphorotrioside (), kaempferol-3, 7-diglucoside (), kaempferol 3-O-rutinoside (), rutin (), 3-O-[α-l-rhamnopyranosyl-(1→2)-α-l-arabinopyranpsylhederagenin (), 3β,23,28-trihydroxyolean-12-ene-3-O-α-l-arabinopyranoside(1→4)-a-rhamnopyranosyl,(1→4)-β-d-gluco-pyranoside (), 3-O-α-l-rhamnopyranosyl-(1→2)-α-l-arabinopyranpsyl]-28-O-β-d-gluco-pyranosyl hederagenin (), andα-hederin (). These were isolated and are reported for the first time in this study. Comparedwas identified as a new compound. Compoundwas isolated for first time from the genus. Compoundwas found to be the most active in the DPPH, and ABTS assays and compoundwas found to be the most active in theα-glucosidase assay, with IC32.7± 0.1, 95.18 ± 0.9, 214.5 ± 0.0 µΜ, respectively. Compound, at a dose of 125µΜ, showed anti-diabetic activity in a PTP1B assay with IC91.30± 2.5 µΜ. In conclusion, the anti-diabetic activity ofis due to its flavonoids and TTSGs. Therefore, our studies suggest that the aerial parts ofare also a valuable and alternate source of valuable phytochemicals that could be used to develop anti-oxidant and anti-diabetic medicines.