greenmedinfo--2020-12-03--Low concentrations of silver nanoparticles and silver ions perturb the antioxidant defense system an

Low concentrations of silver nanoparticles and silver ions perturb the antioxidant defense system and nitrogen metabolism in N 2-Fixing cyanobacteria.

Although toxic effects of silver nanoparticles ( AgNPs ) on aquatic organisms have been extensively reported , responses of nitrogen-fixing cyanobacteria to AgNPs/Agunder environmentally relevant concentrations are largely unknown .
Here , cyanobacteria were exposed to different concentrations of AgNPs ( 0.01 , 0.1 , and 1 mg/L ) or Ag ( 0.1 , 1 , and 10μg/L ) for 96 h. The impacts of AgNPs and Agon photosynthesis and Nfixation in cyanobacteria ( ) were evaluated .
In addition , gas chromatography-mass spectrometry ( GC-MS ) -based metabolomics was employed to give an instantaneous snapshot of the physiological status @ @ @ @ @ @ @ to high doses of AgNPs ( 1 mg/L ) or Ag ( 10μg/L ) caused growth inhibition , reactive oxygen species overproduction , malondialdehyde accumulation , and decreased Nfixation .
In contrast , low doses of AgNPs ( 0.01 and 0.1 mg/L ) and Ag ( 0.1 and 1μg/L ) did not induce observable responses .
However , metabolomics revealed that metabolic reprogramming occurred even at low concentrations of AgNP and Agexposure .
Levels of a number of antioxidant defense-related metabolites , especially phenolic acid and polyphenols ( gallic acid , resveratrol , @ @ @ @ @ @ @ acid , 3-hydroxybenzoic acid , epicatechin , catechin , and ferulic acid ) , significantly decreased in response to AgNPs or Ag .
This indicates that AgNPs and Agcan disrupt the antioxidant defense system and disturb nitrogen metabolism even at low-dose exposure .
Metabolomics was shown to be a powerful tool to detect '' invisible '' changes , not observable by typical phenotypic-based endpoints .

Although toxic effects of silver nanoparticles (AgNPs) on aquatic organisms have been extensively reported, responses of nitrogen-fixing cyanobacteria to AgNPs/Agunder environmentally relevant concentrations are largely unknown. Here, cyanobacteria were exposed to different concentrations of AgNPs (0.01, 0.1, and 1 mg/L) or Ag(0.1, 1, and 10μg/L) for 96 h. The impacts of AgNPs and Agon photosynthesis and Nfixation in cyanobacteria () were evaluated. In addition, gas chromatography-mass spectrometry (GC-MS)-based metabolomics was employed to give an instantaneous snapshot of the physiological status of the cells under AgNP/Agexposure. Exposure to high doses of AgNPs (1 mg/L) or Ag(10μg/L) caused growth inhibition, reactive oxygen species overproduction, malondialdehyde accumulation, and decreased Nfixation. In contrast, low doses of AgNPs (0.01 and 0.1 mg/L) and Ag(0.1 and 1μg/L) did not induce observable responses. However, metabolomics revealed that metabolic reprogramming occurred even at low concentrations of AgNP and Agexposure. Levels of a number of antioxidant defense-related metabolites, especially phenolic acid and polyphenols (gallic acid, resveratrol, isochlorogenic acid, chlorogenic acid, cinnamic acid, 3-hydroxybenzoic acid, epicatechin, catechin, and ferulic acid), significantly decreased in response to AgNPs or Ag. This indicates that AgNPs and Agcan disrupt the antioxidant defense system and disturb nitrogen metabolism even at low-dose exposure. Metabolomics was shown to be a powerful tool to detect"invisible"changes, not observable by typical phenotypic-based endpoints.


greenmedinfo--2020-12-03--Chlorogenic acid depresses cellular bioenergetics to suppress pancreatic carcinoma.

Pancreatic ductal adenocarcinoma ( PDAC ) is severe malignant tumor in human , the outcomes of PDAC is extremely poor @ @ @ @ @ the potential anti-tumor activity of chlorogenic Acid ( CA ) in PDAC .
Here , @ @ @ @ @ to suppress PDAC cell growth in vitro and in vivo .
Importantly , we found @ @ @ @ @ significantly decreased in CA dose-dependent manner .
We also found glycolysis reverse was decreased in @ @ @ @ @ glycolysis and glycolytic capacity were not significantly changed .
Mechanistically , we demonstrated TFR1 could @ @ @ @ @ of CA , which is essential for PDAC cell growth and cellular bioenergetics maintenance .
@ @ @ @ @ CA-reduced c-Myc resulted to down-regulation of TFR1 , which contributes to mitochondrial respiration dysfunction and @ @ @ @ @ , this study indicates that CA suppresses PDAC cell growth through targeting c-Myc-TFR1 axis and @ @ @ @ @ as a promising compound for PDAC treatment .

Pancreatic ductal adenocarcinoma (PDAC) is severe malignant tumor in human, the outcomes of PDAC is extremely poor. Here, we evaluated the potential anti-tumor activity of chlorogenic Acid (CA) in PDAC. Here, we found CA was effective to suppress PDAC cell growth in vitro and in vivo. Importantly, we found overall oxygen consumption rate was significantly decreased in CA dose-dependent manner. We also found glycolysis reverse was decreased in CA-treated cells, while basal glycolysis and glycolytic capacity were not significantly changed. Mechanistically, we demonstrated TFR1 could be a novel downstream target of CA, which is essential for PDAC cell growth and cellular bioenergetics maintenance. Furthermore, we validated that CA-reduced c-Myc resulted to down-regulation of TFR1, which contributes to mitochondrial respiration dysfunction and cell growth delay. Together, this study indicates that CA suppresses PDAC cell growth through targeting c-Myc-TFR1 axis and suggests CA could be considered as a promising compound for PDAC treatment.


greenmedinfo--2020-12-03--Chlorogenic acid enriched Green Coffee Ameliorated Renal Injury

The incidence of acute kidney injury ( AKI ) during the treatment with gentamicin ( GM ) is very common in hospitalized patients .
Green coffee bean , containing chlorogenic acid ( CGA ) has been reported to improve non communicable diseases .
In the present study , CGA enriched fraction of green coffee bean was evaluated on GM induced nephrotoxicity in rats .
It was a preclinical case-controlled experimental intervention conducted in the Department of Pharmacology , R G Kar Medical College , Kolkata , India from 2016-2019 using animal model .
CGA content of green coffee bean extract @ @ @ @ @ @ @ by high performance thin layer chromatography ( HPTLC ) ( 6.426 % ) .
The rats were treated with GCBE at the dose of 100 , 200 and 400mg/kg in gentamicin ( GM ) induced AKI for five consecutive days .
At day 6 , the renal function was assessed through analysing urine , blood and renal tissues .
GCBE dose dependently and significantly ( p < 0.001 ) lowered blood urea , creatinine and potassium while , enhanced sodium compared to AKI control .
Moreover , it showed significant elevation in glutathione @ @ @ @ @ @ @ SOD ) and catalase ( CAT ) and reduction in lipid peroxides ( p < 0.001 ) .
It was suggested that chlorogenic acid of green coffee seed can protect kidney through down regulation of p53 transcription factor and thereby attenuation of oxidative stress , inflammation and apoptotic process in renal tubules .

The incidence of acute kidney injury (AKI) during the treatment with gentamicin (GM) is very common in hospitalized patients. Green coffee bean, containing chlorogenic acid (CGA) has been reported to improve non communicable diseases. In the present study, CGA enriched fraction of green coffee bean was evaluated on GM induced nephrotoxicity in rats. It was a preclinical case-controlled experimental intervention conducted in the Department of Pharmacology, R G Kar Medical College, Kolkata, India from 2016-2019 using animal model. CGA content of green coffee bean extract (GCBE) was isolated and quantified by high performance thin layer chromatography (HPTLC) (6.426%). The rats were treated with GCBE at the dose of 100, 200 and 400mg/kg in gentamicin (GM) induced AKI for five consecutive days. At day 6, the renal function was assessed through analysing urine, blood and renal tissues. GCBE dose dependently and significantly (p<0.001) lowered blood urea, creatinine and potassium while, enhanced sodium compared to AKI control. Moreover, it showed significant elevation in glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) and reduction in lipid peroxides (p<0.001). It was suggested that chlorogenic acid of green coffee seed can protect kidney through down regulation of p53 transcription factor and thereby attenuation of oxidative stress, inflammation and apoptotic process in renal tubules.


greenmedinfo--2020-12-03--This review suggests that caffeine consumption, especially moderate quantities consumed through coff

This review suggests that caffeine consumption, especially moderate quantities consumed through coffee or green tea.

BACKGROUND : Epidemiologic studies have provided inconclusive evidence for a protective effect of caffeine consumption on risk of dementia and cognitive decline .
OBJECTIVE : To summarize literature on the association between caffeine and 1 ) the risk of dementia and/or cognitive decline , and 2 ) cognitive performance in individuals with mild cognitive impairment ( MCI ) or dementia , and 3 ) to examine the effect of study characteristics by categorizing studies based on caffeine source , quantity and other possible confounders .
METHODS : We performed a systematic review of caffeine effects by assessing overall study outcomes @ @ @ @ @ @ @ .
Our literature search identified 61 eligible studies performed between 1990 and 2020 .
RESULTS : For studies analyzing the association between caffeine and the risk of dementia and/or cognitive decline , 16/57 ( 28 % ) studies including a total of 40,707/153,070 ( 27 % ) subjects reported positive study outcomes , and 30/57 ( 53 % ) studies including 71,219/153,070 ( 47 % ) subjects showed positive results that were dependent on study characteristics .
Caffeine effects were more often positive when consumed in moderate quantities ( 100-400 mg/d ) , @ @ @ @ @ @ @ and in women .
Furthermore , four studies evaluated the relationship between caffeine consumption and cognitive function in cognitively impaired individuals and the majority ( 3/4 [ 75 % ] ) of studies including 272/289 subjects ( 94 % ) reported positive outcomes .
CONCLUSION : This review suggests that caffeine consumption , especially moderate quantities consumed through coffee or green tea and in women , may reduce the risk of dementia and cognitive decline , and may ameliorate cognitive decline in cognitively impaired individuals .

BACKGROUND: Epidemiologic studies have provided inconclusive evidence for a protective effect of caffeine consumption on risk of dementia and cognitive decline.
OBJECTIVE: To summarize literature on the association between caffeine and 1) the risk of dementia and/or cognitive decline, and 2) cognitive performance in individuals with mild cognitive impairment (MCI) or dementia, and 3) to examine the effect of study characteristics by categorizing studies based on caffeine source, quantity and other possible confounders.
METHODS: We performed a systematic review of caffeine effects by assessing overall study outcomes; positive, negative or no effect. Our literature search identified 61 eligible studies performed between 1990 and 2020.
RESULTS: For studies analyzing the association between caffeine and the risk of dementia and/or cognitive decline, 16/57 (28%) studies including a total of 40,707/153,070 (27%) subjects reported positive study outcomes, and 30/57 (53%) studies including 71,219/153,070 (47%) subjects showed positive results that were dependent on study characteristics. Caffeine effects were more often positive when consumed in moderate quantities (100-400 mg/d), consumed in coffee or green tea, and in women. Furthermore, four studies evaluated the relationship between caffeine consumption and cognitive function in cognitively impaired individuals and the majority (3/4 [75% ]) of studies including 272/289 subjects (94%) reported positive outcomes.
CONCLUSION: This review suggests that caffeine consumption, especially moderate quantities consumed through coffee or green tea and in women, may reduce the risk of dementia and cognitive decline, and may ameliorate cognitive decline in cognitively impaired individuals.


greenmedinfo--2020-12-03--Orthosiphon stamineus proteins alleviate pentylenetetrazol-induced seizures.

The anticonvulsive potential of proteins extracted fromleaves ( OSLP ) has never been elucidated in zebrafish ( ) .
This study thus aims to elucidate the anticonvulsive potential of OSLP in pentylenetetrazol ( PTZ ) -induced seizure model .
Physical changes ( seizure score and seizure onset time , behavior , locomotor ) and neurotransmitter analysis were elucidated to assess the pharmacological activity .
The protective mechanism of OSLP on brain was also studied using mass spectrometry-based label-free proteomic quantification ( LFQ ) and bioinformatics .
OSLP was found to be safe up to 800µg/kg and pre-treatment with OSLP ( @ @ @ @ @ @ @ ) decreased the frequency of convulsive activities ( lower seizure score and prolonged seizure onset time ) , improved locomotor behaviors ( reduced erratic swimming movements and bottom-dwelling habit ) , and lowered the excitatory neurotransmitter ( glutamate ) .
Pre-treatment with OSLP increased protein Complexin 2 ( Cplx 2 ) expression in the zebrafish brain .
Cplx2 is an important regulator in the trans-SNARE complex which is required during the vesicle priming phase in the calcium-dependent synaptic vesicle exocytosis .
Findings in this study collectively suggests that OSLP could be regulating the @ @ @ @ @ @ @ exocytosis mediated by the '' Synaptic Vesicle Cycle '' pathway .
OSLP 's anticonvulsive actions could be acting differently from diazepam ( DZP ) and with that , it might not produce the similar cognitive insults such as DZP .

The anticonvulsive potential of proteins extracted fromleaves (OSLP) has never been elucidated in zebrafish (). This study thus aims to elucidate the anticonvulsive potential of OSLP in pentylenetetrazol (PTZ)-induced seizure model. Physical changes (seizure score and seizure onset time, behavior, locomotor) and neurotransmitter analysis were elucidated to assess the pharmacological activity. The protective mechanism of OSLP on brain was also studied using mass spectrometry-based label-free proteomic quantification (LFQ) and bioinformatics. OSLP was found to be safe up to 800µg/kg and pre-treatment with OSLP (800 µg/kg, i.p., 30 min) decreased the frequency of convulsive activities (lower seizure score and prolonged seizure onset time), improved locomotor behaviors (reduced erratic swimming movements and bottom-dwelling habit), and lowered the excitatory neurotransmitter (glutamate). Pre-treatment with OSLP increased protein Complexin 2 (Cplx 2) expression in the zebrafish brain. Cplx2 is an important regulator in the trans-SNARE complex which is required during the vesicle priming phase in the calcium-dependent synaptic vesicle exocytosis. Findings in this study collectively suggests that OSLP could be regulating the release of neurotransmitters via calcium-dependent synaptic vesicle exocytosis mediated by the"Synaptic Vesicle Cycle"pathway. OSLP's anticonvulsive actions could be acting differently from diazepam (DZP) and with that, it might not produce the similar cognitive insults such as DZP.


greenmedinfo--2020-12-03--Ethanolic extract of Orthosiphon stamineus improves memory in scopolamine-induced amnesia model.

Alzheimer 's disease ( AD ) is a chronic neurodegenerative brain disease which is characterized by impairment in cognitive functioning .
( OS ) Benth .
( Lamiaceae ) is a medicinal plant found around Southeast Asia that has been employed as treatments for various diseases .
OS extract contains many active compounds that have been shown to possess various pharmacological properties wherebystudies have demonstrated neuroprotective as well as cholinesterase inhibitory effects .
This study , therefore aimed at determining whether this Malaysian plant derived flavonoid can reverse scopolamine induced learning and memory dysfunction in the novel object recognition ( @ @ @ @ @ @ @ maze ( EPM ) test .
In the present study , rats were treated once daily with OS 50 mg/kg , 100 mg/kg , 200 mg/kg and donepezil 1 mg/kgoral dosing and were given intraperitoneal ( ip ) injection of scopolamine 1 mg/kg daily to induce cognitive deficits .
Rats were subjected to behavioral analysis to assess learning and memory functions and hippocampal tissues were extracted for gene expression and immunohistochemistry studies .
All the three doses demonstrated improved scopolamine-induced impairment by showing shortened transfer latency as well as the higher inflexion ratio @ @ @ @ @ @ @ .
OS extract also exhibited memory-enhancing activity against chronic scopolamine-induced memory deficits in the long-term memory novel object recognition performance as indicated by an increase in the recognition index .
OS extract was observed to have modulated the mRNA expression of CREB1 , BDNF , and TRKB genes and pretreatment with OS extract were observed to have increased the immature neurons against hippocampal neurogenesis suppressed by scopolamine , which was confirmed by the DCX-positive stained cells .
These research findings suggest that the OS ethanolic extract demonstrated an improving effect on memory and @ @ @ @ @ @ @ target for the treatment of neurodegenerative diseases like AD .

Alzheimer's disease (AD) is a chronic neurodegenerative brain disease which is characterized by impairment in cognitive functioning.(OS) Benth. (Lamiaceae) is a medicinal plant found around Southeast Asia that has been employed as treatments for various diseases. OS extract contains many active compounds that have been shown to possess various pharmacological properties wherebystudies have demonstrated neuroprotective as well as cholinesterase inhibitory effects. This study, therefore aimed at determining whether this Malaysian plant derived flavonoid can reverse scopolamine induced learning and memory dysfunction in the novel object recognition (NOR) test and the elevated plus maze (EPM) test. In the present study, rats were treated once daily with OS 50 mg/kg, 100 mg/kg, 200 mg/kg and donepezil 1 mg/kgoral dosing and were given intraperitoneal (ip) injection of scopolamine 1 mg/kg daily to induce cognitive deficits. Rats were subjected to behavioral analysis to assess learning and memory functions and hippocampal tissues were extracted for gene expression and immunohistochemistry studies. All the three doses demonstrated improved scopolamine-induced impairment by showing shortened transfer latency as well as the higher inflexion ratio when compared to the negative control group. OS extract also exhibited memory-enhancing activity against chronic scopolamine-induced memory deficits in the long-term memory novel object recognition performance as indicated by an increase in the recognition index. OS extract was observed to have modulated the mRNA expression of CREB1, BDNF, and TRKB genes and pretreatment with OS extract were observed to have increased the immature neurons against hippocampal neurogenesis suppressed by scopolamine, which was confirmed by the DCX-positive stained cells. These research findings suggest that the OS ethanolic extract demonstrated an improving effect on memory and hence could serve as a potential therapeutic target for the treatment of neurodegenerative diseases like AD.


greenmedinfo--2020-12-03--Java Tea (Orthosiphon stamineus) protected against osteoarthritis.

The effect of Orthosiphon stamineus aqueous ( OSA ) extract against osteoarthritis ( OA ) was investigated in explant cartilage culture and in postmenopausal OA rat model .
Female rats were bilaterally ovariectomized ( OVX ) .
Osteoarthritis was induced after surgical recovery , by intra-articular injection of monosodium iodoacetate ( MIA ) into the right knee .
Rats were grouped ( n = 8 ) into : healthy sham control ; non-treated OA ; OA + diclofenac ( positive control 5 mg/kg ) ; and two doses OSA ( 150-300 mg/kg ) .
After 4 weeks ' treatment , @ @ @ @ @ @ @ biomarkers .
The OSA reduced proteoglycan and ROS release from the cartilage explants under inflammatory ( IL-1b ) conditions .
In the OA-induced rats ' cartilages , the OSA downregulated the mRNA expressions for IL-1β , IL-6 , IL-10 , TNF-α , NF-κβ , NOS2 , PTGS2 , PTGER2 , ACAN , COL2A1 , MMP1 , MMP13 , ADAMTS4 , ADAMTS5 and TIMP1 , mostly dose-dependently .
The OSA reduced the OA rats ' serum levelsfor PGE , CTX-II , TNF-α , MMP1 , MMP13 , PIINP , OPG , RANKL , OC @ @ @ @ @ @ @ The OSA contained polyphenols and flavonoids ( tetramethoxyflavone ) .
The OSA alleviated articular cartilage degradation , inflammation , collagenase/aggrecanase activities , to improve joint and subchondral bone structure .
O. stamineus mitigated osteoarthritis by downregulating inflammation , peptidases and aggrecanases , at a dose equivalent to about 30 mg/kg for humans .

The effect of Orthosiphon stamineus aqueous (OSA) extract against osteoarthritis (OA) was investigated in explant cartilage culture and in postmenopausal OA rat model. Female rats were bilaterally ovariectomized (OVX). Osteoarthritis was induced after surgical recovery, by intra-articular injection of monosodium iodoacetate (MIA) into the right knee. Rats were grouped (n = 8) into: healthy sham control; non-treated OA; OA + diclofenac (positive control 5 mg/kg); and two doses OSA (150-300 mg/kg). After 4 weeks' treatment, rats were evaluated for OA-related parameters and biomarkers. The OSA reduced proteoglycan and ROS release from the cartilage explants under inflammatory (IL-1b) conditions. In the OA-induced rats' cartilages, the OSA downregulated the mRNA expressions for IL-1β, IL-6, IL-10, TNF-α, NF-κβ, NOS2, PTGS2, PTGER2, ACAN, COL2A1, MMP1, MMP13, ADAMTS4, ADAMTS5 and TIMP1, mostly dose-dependently. The OSA reduced the OA rats' serum levelsfor PGE, CTX-II, TNF-α, MMP1, MMP13, PIINP, OPG, RANKL, OC and BALP, but not dose-dependently. The OSA contained polyphenols and flavonoids (tetramethoxyflavone). The OSA alleviated articular cartilage degradation, inflammation, collagenase/aggrecanase activities, to improve joint and subchondral bone structure. O. stamineus mitigated osteoarthritis by downregulating inflammation, peptidases and aggrecanases, at a dose equivalent to about 30 mg/kg for humans.


greenmedinfo--2020-12-03--O. stamineus could be a potential source of a specific oral hypoglycaemic agent to treat glucose int

O. stamineus could be a potential source of a specific oral hypoglycaemic agent to treat glucose intolerance in pregnancy.

Background : Maternal hyperglycemia is associated with increased risk of adverse outcomes for both mother and offspring .
Insulin is the standard treatment of hyperglycemia with the aim to reduce risks of complications , however , due to several restrictions , the search for more effective drugs from traditional medicinal plants continues .
Methods : The antidiabetic effects of ( in non-pregnant and pregnant streptozotocin-induced Sprague Dawley rats were identified .
The effect of different concentrations ofon insulin level using isolated pancreatic islets in response to low and high concentrations of glucose was identified .
Oral glucose tolerance test was @ @ @ @ @ @ @ prior to and after treatment with ( 0.1 g/100 g of body weight ) .was given orally daily for 2 weeks in non-pregnant and 10 days in pregnant rats .
Results : Oral glucose tolerance test indicated that treatment within non-pregnant and pregnant rats significantly reduced blood glucose level and stimulated glucose-induced insulin secretion .
No mortality was recorded throughout the study and no signs of toxicity during the experimental period including in both mother and foetus .
For plasma analysis , the interactions of peptides such as GLP-1 and ghrelin level might @ @ @ @ @ @ @ stimulation of insulin .
The incubation of islets showed thatsignificantly stimulated insulin release in response to high glucose .
Conclusion : could be a potential source of a specific oral hypoglycaemic agent to treat glucose intolerance in pregnancy .

Background: Maternal hyperglycemia is associated with increased risk of adverse outcomes for both mother and offspring. Insulin is the standard treatment of hyperglycemia with the aim to reduce risks of complications, however, due to several restrictions, the search for more effective drugs from traditional medicinal plants continues.
Methods: The antidiabetic effects of(in non-pregnant and pregnant streptozotocin-induced Sprague Dawley rats were identified. The effect of different concentrations ofon insulin level using isolated pancreatic islets in response to low and high concentrations of glucose was identified. Oral glucose tolerance test was performed in both pregnant and non-pregnant rats prior to and after treatment with(0.1 g/100 g of body weight).was given orally daily for 2 weeks in non-pregnant and 10 days in pregnant rats.
Results: Oral glucose tolerance test indicated that treatment within non-pregnant and pregnant rats significantly reduced blood glucose level and stimulated glucose-induced insulin secretion. No mortality was recorded throughout the study and no signs of toxicity during the experimental period including in both mother and foetus. For plasma analysis, the interactions of peptides such as GLP-1 and ghrelin level might contribute to the glucose lowering effect byvia stimulation of insulin. The incubation of islets showed thatsignificantly stimulated insulin release in response to high glucose.
Conclusion: could be a potential source of a specific oral hypoglycaemic agent to treat glucose intolerance in pregnancy.


greenmedinfo--2020-12-03--Orthosiphon stamineus: traditional uses, phytochemistry, pharmacology, and toxicology.

Orthosiphon stamineus Benth .
( Lambiaceae ) is an important plant in traditional folk medicine .
This review is a @ @ @ @ @ available chemical , pharmacological , and toxicological investigations as well as the traditional and therapeutic @ @ @ @ @ Different in vitro and in vivo models have been addressed along with a survey of @ @ @ @ @ plant , including flavonoids , terpenoids , and essential oils .
Previous studies revealed that @ @ @ @ @ activities , which are attributed to its phytochemical content .
It was found that O.
@ @ @ @ @ , renal protective , antioxidant , anti-inflammatory , hepatoprotective , gastroprotective , antihypertensive , antidiabetic @ @ @ @ @ and anorexic activities .
In conclusion , O. stamineus has wide traditional and pharmacological uses @ @ @ @ @ Therefore , it is an attractive subject for further experimental and clinical investigations .

Orthosiphon stamineus Benth. (Lambiaceae) is an important plant in traditional folk medicine. This review is a comprehensive summary of the currently available chemical, pharmacological, and toxicological investigations as well as the traditional and therapeutic uses of this plant. Different in vitro and in vivo models have been addressed along with a survey of all phytochemicals identified in this plant, including flavonoids, terpenoids, and essential oils. Previous studies revealed that O. stamineus possesses several pharmacological activities, which are attributed to its phytochemical content. It was found that O. stamineus exhibits diuretic, hypouricemic, renal protective, antioxidant, anti-inflammatory, hepatoprotective, gastroprotective, antihypertensive, antidiabetic, antihyperlipidemic, antimicrobial, and anorexic activities. In conclusion, O. stamineus has wide traditional and pharmacological uses in various pathophysiological conditions. Therefore, it is an attractive subject for further experimental and clinical investigations.


greenmedinfo--2020-12-03--Orthosiphon pallidus, a potential treatment for patients with breast cancer.

Objective : , which belongs to thefamily , is a popular garden plant that is widely used for the treatment of various diseases , such as urinary lithiasis , fever , hepatitis , cancer and jaundice .
The objective of the present work was to investigate the antioxidant free-radical scavenging and the anticancer activities ofagainst human breast-cancer cell lines .
Methods : The antioxidant activity ofaqueous extract ( OPAE ) was investigated using different models , such as the 1,1-diphenyl-2-picrylhydrazyl ( DPPH ) and the 2 , 2'-azinobis- ( 3-ethylbenzothiazoline-6-sulfonic acid ) ( ABTS ) models , as were the @ @ @ @ @ @ @ radical scavenging , and total reducing power activities .
The anticancer activities of the extract were determined by using the 3- ( 4 , 5- dimethylthiazolyl-2 ) -2 , 5-diphenyltetrazolium bromide ( MTT ) and the sulforhodamine ( SRB ) assays on the MCF-7 and the MDA-MB-231 cancer cell lines .
Results : The aqueousextract showed potent activity inmodels .
It significantly inhibited the scavenging of hydroxyl and superoxide radicals , but induced a remarkable Fechelation activity .
For both cell lines , the percent cytotoxicity was found to increase steadily with increasing @ @ @ @ @ @ @ : These results suggest thathas excellent antioxidant , antimicrobial , and anticancer activities against human breast-cancer cell lines .

Objective: , which belongs to thefamily, is a popular garden plant that is widely used for the treatment of various diseases, such as urinary lithiasis, fever, hepatitis, cancer and jaundice. The objective of the present work was to investigate the antioxidant free-radical scavenging and the anticancer activities ofagainst human breast-cancer cell lines.
Methods: The antioxidant activity ofaqueous extract (OPAE) was investigated using different models, such as the 1,1-diphenyl-2-picrylhydrazyl (DPPH) and the 2, 2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) models, as were the Fechelation, the hydroxyl radical and superoxide radical scavenging, and total reducing power activities. The anticancer activities of the extract were determined by using the 3-(4, 5- dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) and the sulforhodamine (SRB) assays on the MCF-7 and the MDA-MB-231 cancer cell lines.
Results: The aqueousextract showed potent activity inmodels. It significantly inhibited the scavenging of hydroxyl and superoxide radicals, but induced a remarkable Fechelation activity. For both cell lines, the percent cytotoxicity was found to increase steadily with increasing OPAE concentration up to 240μg/mL.
Conclusion: These results suggest thathas excellent antioxidant, antimicrobial, and anticancer activities against human breast-cancer cell lines.


greenmedinfo--2020-12-03--Quercetin may have promising potential in ameliorating atherosclerotic pathophysiology.

Inflammation and oxidative stress serve interrelated roles in the development of atherosclerosis and other vascular diseases .
Quercetin has been previously reported to exhibit numerous beneficial properties towards several metabolic conditions and cardiovascular disease .
The present study aimed to evaluate the effects of quercetin on the 5'adenosine monophosphate-activated protein kinase ( AMPK ) /sirtuin 1 ( SIRT1 ) /NF-κB signaling pathway and inflammatory/oxidative stress response in diabetic-induced atherosclerosis in the carotid artery of rats .
Male Wistar rats were used to create a diabetes-induced atherosclerosis model by the administration of high fat diet ( HFD ) with streptozotocin , @ @ @ @ @ @ @ and diabetic rats received quercetin ( 30 mg/kg/day ; orally ) for the last 2 weeks of the diabetic period .
Plasma lipid profile and vascular levels of oxidative stress markers , inflammatory cytokines , NF-κB signaling proteins and SIRT1 expression were evaluated using ELISA and western blotting .
Quercetin treatment in HFD diabetic rats was reported to improve the lipid profile and reduce the number of atherosclerotic lesions , atherogenic index and malondialdehyde levels , whilst increasing the activity of enzymatic antioxidants in the carotid artery .
Additionally , the inflammatory response @ @ @ @ @ @ @ indicated by the reduced NF-κB and IL-1β levels , and increased IL-10 levels .
Furthermore , SIRT1 expression was revealed to be significantly increased in response to quercetin treatment compared with non-treated HFD rats .
However , these effects ofquercetin were abolished or reversed by the administration of compound-C ( 0.2 mg/kg ) , a specific AMPK blocker , in HFD rats .
Therefore , quercetin may have promising potential in ameliorating atherosclerotic pathophysiology in the rat carotid artery by inhibiting oxidative stress and inflammatory responses mechanistically by modulating the AMPK/SIRT1/NF-κB signaling pathway @

Inflammation and oxidative stress serve interrelated roles in the development of atherosclerosis and other vascular diseases. Quercetin has been previously reported to exhibit numerous beneficial properties towards several metabolic conditions and cardiovascular disease. The present study aimed to evaluate the effects of quercetin on the 5'adenosine monophosphate-activated protein kinase (AMPK)/sirtuin 1 (SIRT1)/NF-κB signaling pathway and inflammatory/oxidative stress response in diabetic-induced atherosclerosis in the carotid artery of rats. Male Wistar rats were used to create a diabetes-induced atherosclerosis model by the administration of high fat diet (HFD) with streptozotocin, which lasted for 8 weeks. Control and diabetic rats received quercetin (30 mg/kg/day; orally) for the last 2 weeks of the diabetic period. Plasma lipid profile and vascular levels of oxidative stress markers, inflammatory cytokines, NF-κB signaling proteins and SIRT1 expression were evaluated using ELISA and western blotting. Quercetin treatment in HFD diabetic rats was reported to improve the lipid profile and reduce the number of atherosclerotic lesions, atherogenic index and malondialdehyde levels, whilst increasing the activity of enzymatic antioxidants in the carotid artery. Additionally, the inflammatory response was suppressed by quercetin administration, as indicated by the reduced NF-κB and IL-1β levels, and increased IL-10 levels. Furthermore, SIRT1 expression was revealed to be significantly increased in response to quercetin treatment compared with non-treated HFD rats. However, these effects ofquercetin were abolished or reversed by the administration of compound-C (0.2 mg/kg), a specific AMPK blocker, in HFD rats. Therefore, quercetin may have promising potential in ameliorating atherosclerotic pathophysiology in the rat carotid artery by inhibiting oxidative stress and inflammatory responses mechanistically by modulating the AMPK/SIRT1/NF-κB signaling pathway.


greenmedinfo--2020-12-03--COVID-911: From Homeland Security to Biosecurity

9/11 , as we were told repeatedly in the days , weeks , and months after the attack , was @ @ @ @ @ .
And now a new event has come along to once again throw the world @ @ @ @ @ the post-9/11 era introduced America to the concept of homeland security , the COVID-19 era @ @ @ @ @ an altogether more abstract concept : biosecurity .
This is the story of the COVID-911 @ @ @ @ @ by using the Stand for Health Freedom digital advocacy platform here : https : //www.standforhealthfreedom.com

Visit our Re-post guidelines This article is copyrighted by GreenMedInfo LLC, 2020
9/11, as we were told repeatedly in the days, weeks, and months after the attack, was the day that changed everything. And now a new event has come along to once again throw the world into chaos. But whereas the post-9/11 era introduced America to the concept of homeland security, the COVID-19 era is introducing the world to an altogether more abstract concept: biosecurity. This is the story of the COVID-911 security state.
TRANSCRIPT AND SOURCES: https://www.corbettreport.com/covid911/
Take action by using the Stand for Health Freedom digital advocacy platform here: https://www.standforhealthfreedom.com


greenmedinfo--2020-12-04--Puerarin alleviates the progression of non-small cell lung cancer by regulating the miR-342/CCND1 ax

Puerarin alleviates the progression of non-small cell lung cancer by regulating the miR-342/CCND1 axis.

Puerarin has recently been demonstrated to play anti-cancer roles in a series of human cancers , including non-small cell lung cancer ( NSCLC ) , possibly through regulation of cancer-related microRNAs ( miRNAs ) .
The purpose of the present study was to further investigate the detailed role and underlying mechanism of puerarin on NSCLC progression .
Cell viability and apoptosis were assessed using the Cell Counting kit-8 ( CCK-8 ) assay and flow cytometry , respectively .
Transwell assays were performed to determine cell migration and invasion abilities .
The qRT-PCR assay was employed to detect the expression of @ @ @ @ @ @ @ mRNA , and CCND1 protein expression was evaluated by western blotting .
The targeted interaction between miR-342 and CCND1 was verified by dual-luciferase reporter assay and RNA immunoprecipitation ( RIP ) assay .
We found that our data demonstrated that puerarin repressed cell viability , migration , invasion , and cell cycle progression , and enhanced the apoptosis of NSCLC cells .
miR-342 overexpression hindered the migration , invasion and cell cycle progression , and accelerated the apoptosis of NSCLC cells .
miR-342 inhibited CCND1 expression by directly binding to the 3'-UTR of @ @ @ @ @ @ @ , anti-invasion , anti-cell cycle progression , and pro-apoptotic effects were abated by co-transfection of pcDNA-CCND1 .
More importantly , puerarin inhibited CCND1 expression by upregulating miR-342 .
Additionally , puerarin hampered NSCLC cell progression in vitro and tumor growth in vivo by upregulating miR-342 .
In conclusion , our study suggested that puerarin hampered NSCLC progression in vitro and in vivo at least partly through regulating miR-342/CCND1 axis , highlighting a novel mechanism of puerarin exerting anti-cancer property in NSCLC .

Puerarin has recently been demonstrated to play anti-cancer roles in a series of human cancers, including non-small cell lung cancer (NSCLC), possibly through regulation of cancer-related microRNAs (miRNAs). The purpose of the present study was to further investigate the detailed role and underlying mechanism of puerarin on NSCLC progression. Cell viability and apoptosis were assessed using the Cell Counting kit-8 (CCK-8) assay and flow cytometry, respectively. Transwell assays were performed to determine cell migration and invasion abilities. The qRT-PCR assay was employed to detect the expression of miR-342 and cyclin D1 (CCND1) mRNA, and CCND1 protein expression was evaluated by western blotting. The targeted interaction between miR-342 and CCND1 was verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. We found that our data demonstrated that puerarin repressed cell viability, migration, invasion, and cell cycle progression, and enhanced the apoptosis of NSCLC cells. miR-342 overexpression hindered the migration, invasion and cell cycle progression, and accelerated the apoptosis of NSCLC cells. miR-342 inhibited CCND1 expression by directly binding to the 3'-UTR of CCND1. Moreover, miR-342 overexpression-mediated anti-migration, anti-invasion, anti-cell cycle progression, and pro-apoptotic effects were abated by co-transfection of pcDNA-CCND1. More importantly, puerarin inhibited CCND1 expression by upregulating miR-342. Additionally, puerarin hampered NSCLC cell progression in vitro and tumor growth in vivo by upregulating miR-342. In conclusion, our study suggested that puerarin hampered NSCLC progression in vitro and in vivo at least partly through regulating miR-342/CCND1 axis, highlighting a novel mechanism of puerarin exerting anti-cancer property in NSCLC.


greenmedinfo--2020-12-04--Rosmarinic Acid as a Potent Influenza Neuraminidase Inhibitor.

BACKGROUND : Neuraminidase ( NA ) , a major glycoprotein found on the surface of the influenza virus , is an important target for the prophylaxis and treatment of influenza virus infections .
Recently , several plant-derived polyphenols , especially caffeic acid analogs , have been reported to exert the inhibitory activity against NA .
OBJECTIVE : Herein , we aimed to investigate the anti-influenza NA activity of caffeic acid and its hydroxycinnamate analogues , rosmarinic acid and salvianolic acid A , in comparison to a known NA inhibitor , oseltamivir .
METHODS : In vitro MUNANA-based NA inhibitory assay @ @ @ @ @ @ @ of the three interested hydroxycinnamic compounds towards the influenza NA enzyme .
Subsequently , allatom molecular dynamics ( MD ) simulations and binding free energy calculations were employed to elucidate the structural insights into the protein-ligand complexations .
RESULTS : Rosmarinic acid showed the highest inhibitory activity against NA with the IC50 of 0.40μM compared to caffeic acid ( IC50 of 0.81 μM ) and salvianolic acid A ( IC50 of > 1μM ) .
From 100-ns MD simulations , the binding affinity , hot-spot residues , and H-bond formations of rosmarinic acid/NA @ @ @ @ @ @ @ acid/NA model , in which their molecular complexations was driven mainly by electrostatic attractions and H-bond formations from several charged residues ( R118 , E119 , D151 , R152 , E227 , E277 , and R371 ) .
Notably , the two hydroxyl groups on both phenyl and phenylacetic rings of rosmarinic acid play a crucial role in stabilizing NA through a strongly formed Hbond ( s ) .
CONCLUSION : Our findings shed light on the potentiality of rosmarinic acid as a lead compound for further development of a potential influenza NA @ @

BACKGROUND: Neuraminidase (NA), a major glycoprotein found on the surface of the influenza virus, is an important target for the prophylaxis and treatment of influenza virus infections. Recently, several plant-derived polyphenols, especially caffeic acid analogs, have been reported to exert the inhibitory activity against NA.
OBJECTIVE: Herein, we aimed to investigate the anti-influenza NA activity of caffeic acid and its hydroxycinnamate analogues, rosmarinic acid and salvianolic acid A, in comparison to a known NA inhibitor, oseltamivir.
METHODS: In vitro MUNANA-based NA inhibitory assay was used to evaluate the inhibitory activity of the three interested hydroxycinnamic compounds towards the influenza NA enzyme. Subsequently, allatom molecular dynamics (MD) simulations and binding free energy calculations were employed to elucidate the structural insights into the protein-ligand complexations.
RESULTS: Rosmarinic acid showed the highest inhibitory activity against NA with the IC50 of 0.40μM compared to caffeic acid (IC50 of 0.81 μM) and salvianolic acid A (IC50 of>1μM). From 100-ns MD simulations, the binding affinity, hot-spot residues, and H-bond formations of rosmarinic acid/NA complex were higher than those of caffeic acid/NA model, in which their molecular complexations was driven mainly by electrostatic attractions and H-bond formations from several charged residues (R118, E119, D151, R152, E227, E277, and R371). Notably, the two hydroxyl groups on both phenyl and phenylacetic rings of rosmarinic acid play a crucial role in stabilizing NA through a strongly formed Hbond( s).
CONCLUSION: Our findings shed light on the potentiality of rosmarinic acid as a lead compound for further development of a potential influenza NA inhibitor.


greenmedinfo--2020-12-04--Antiviral activity of puerarin as potent inhibitor of influenza virus neuraminidase.

Puerarin is a major isofiavone compound isolated from the root of Pueraria lobata .
It was reported that puerarin had antioxidant , antiinflammatory , antitumor , cholesterol lowering , liver protective , and neuroprotective properties .
However , few studies have explored the antiviral effect of puerarin and its target mechanism related to influenza virus .
Here , the antiinfluenza activity of puerarin in vitro and in vivo and its mode of action on the potential inhibition of neuraminidase ( NA ) were investigated .
Puerarin displayed an inhibitory effect on A/FM/1/1947 ( H1N1 ) ( EC= 52.06 μM ) @ @ @ @ @ @ @ puerarin blocked the nuclear export of viral NP .
The inhibition of NA activity confirmed that puerarin can block the release of newly formed virus particles from infected cells .
Puerarin ( 100 and 200 mg/kg/d ) exhibited effective antiviral activity in mice , conferring 50 % and 70 % protection from death against H1N1 , reducing virus titers , and effectively alleviating inflammation in the lungs .
The molecular docking results showed that puerarin had a strong binding affinity with NA from H1N1 .
The results of the molecular dynamics simulation revealed @ @ @ @ @ @ @ the 150-loop region of the NA protein .
These results demonstrated that puerarin acts as a NA blocker to inhibit influenza A virus both in cellular and animal models .
Thus , puerarin has potential utility for the treatment of the influenza virus infection .

Puerarin is a major isofiavone compound isolated from the root of Pueraria lobata. It was reported that puerarin had antioxidant, antiinflammatory, antitumor, cholesterol lowering, liver protective, and neuroprotective properties. However, few studies have explored the antiviral effect of puerarin and its target mechanism related to influenza virus. Here, the antiinfluenza activity of puerarin in vitro and in vivo and its mode of action on the potential inhibition of neuraminidase (NA) were investigated. Puerarin displayed an inhibitory effect on A/FM/1/1947(H1N1) (EC= 52.06 μM). An indirect immunofluorescence assay indicated that puerarin blocked the nuclear export of viral NP. The inhibition of NA activity confirmed that puerarin can block the release of newly formed virus particles from infected cells. Puerarin (100 and 200 mg/kg/d) exhibited effective antiviral activity in mice, conferring 50% and 70% protection from death against H1N1, reducing virus titers, and effectively alleviating inflammation in the lungs. The molecular docking results showed that puerarin had a strong binding affinity with NA from H1N1. The results of the molecular dynamics simulation revealed that puerarin had higher stable binding at the 150-loop region of the NA protein. These results demonstrated that puerarin acts as a NA blocker to inhibit influenza A virus both in cellular and animal models. Thus, puerarin has potential utility for the treatment of the influenza virus infection.


greenmedinfo--2020-12-04--Puerarin suppresses MPP +/MPTP-induced oxidative stress through an Nrf2-dependent mechanism.

In this study , we hypothesized that anti-parkinsonian effect of puerarin is attributable to its antioxidant properties via Nrf2-dependent glutathione ( GSH ) biosynthesis mechanism .
Experimentally , we found that puerarin attenuated 1-methyl-4-phenylpyridinium ( MPP ) -induced oxidative stress through elevating biosynthetic capacity of GSH in PC12 cells .
Mechanistically , puerarin suppressed Fyn phosphorylation by GSK-3β-dependent mechanism in MPP-challenged PC12 cells .
Furthermore , puerarin induced accumulation of Nrf2 in the nucleus via inhibiting its nuclear exclusion .
In parallel , puerarin up-regulated antioxidant response element ( ARE ) -driven catalytic subunits from glutamate cysteine ligase ( GCLc @ @ @ @ @ @ @ translation .
Most interestingly , pharmacological inhibitor of GSK-3β or Fyn shRNA blocked puerarin-induced Nrf2 activation in MPP-challenged PC12 cells .
Concomitantly , puerarin ameliorated motor deficits and inhibited oxidative stress in the ventral midbrain in MPTP-intoxicated wild-type ( WT ) mice , but failed to attenuate MPTP neurotoxicity and up-regulate GCLc gene in Nrf2-knockout ( Nrf2 ) mice , suggesting that anti-parkinsonian effect of puerarin was dependent on Nrf2 .
Additionally , puerarin regulated Fyn and GSK-3β phosphorylation in the ventral midbrain in MPTP-intoxicated WT mice .
Collectively , the results of @ @ @ @ @ @ @ potential therapeutic action of puerarin in Parkinson 's disease , suggesting that puerarin may be a promising candidate for the treatment of Parkinson 's disease .

In this study, we hypothesized that anti-parkinsonian effect of puerarin is attributable to its antioxidant properties via Nrf2-dependent glutathione (GSH) biosynthesis mechanism. Experimentally, we found that puerarin attenuated 1-methyl-4-phenylpyridinium (MPP)-induced oxidative stress through elevating biosynthetic capacity of GSH in PC12 cells. Mechanistically, puerarin suppressed Fyn phosphorylation by GSK-3β-dependent mechanism in MPP-challenged PC12 cells. Furthermore, puerarin induced accumulation of Nrf2 in the nucleus via inhibiting its nuclear exclusion. In parallel, puerarin up-regulated antioxidant response element (ARE)-driven catalytic subunits from glutamate cysteine ligase (GCLc) expression at levels of transcription and translation. Most interestingly, pharmacological inhibitor of GSK-3β or Fyn shRNA blocked puerarin-induced Nrf2 activation in MPP-challenged PC12 cells. Concomitantly, puerarin ameliorated motor deficits and inhibited oxidative stress in the ventral midbrain in MPTP-intoxicated wild-type (WT) mice, but failed to attenuate MPTP neurotoxicity and up-regulate GCLc gene in Nrf2-knockout (Nrf2) mice, suggesting that anti-parkinsonian effect of puerarin was dependent on Nrf2. Additionally, puerarin regulated Fyn and GSK-3β phosphorylation in the ventral midbrain in MPTP-intoxicated WT mice. Collectively, the results of the study provide molecular insights into the potential therapeutic action of puerarin in Parkinson's disease, suggesting that puerarin may be a promising candidate for the treatment of Parkinson's disease.


greenmedinfo--2020-12-04--This study emphasizes the renal-protective effects of puerarin in diabetic nephropathy.

Background and Purpose : Autophagy is the main protective mechanism against aging in podocytes , which are terminally differentiated cells that have a very limited capacity for mitosis and self-renewal .
Here , a streptozotocin-induced DN C57BL/6 mouse model was used to investigate the effects of puerarin on the modulation of autophagy under conditions associated with endoplasmic reticulum stress ( ERS ) .
In addition , this study aimed to identify the potential underlying molecular mechanisms .
Methods and Results : DN C57BL/6 mouse model was induced by streptozotocin ( 150 mg/kg ) injection .
The mice were administered rapamycin @ @ @ @ @ @ @ up to 8 weeks .
After the serum and kidney samples were collected , the fasting blood glucose ( FBG ) , parameters of renal function , histomorphology , and the podocyte functional proteins were analyzed .
Moreover , the autophagy markers and the expressions of PERK/ATF4 pathway were studied in kidney .
Results found that the FBG level in DN mice was significantly higher than in normal mice .
Compared with DN model mice , puerarin-treated mice showed an increased expression of podocyte functional proteins , including nephrin , podocin , and @ @ @ @ @ @ @ structure alterations were improved by treatment with rapamycin and puerarin compared with the DN control .
The results indicated an elevated level of autophagy in rapamycin and puerarin groups compared with the DN model , as demonstrated by the upregulated expression of autophagy markers Beclin-1 , LC3II , and Atg5 , and downregulated p62 expression .
In addition , the levels of PERK , eIF2α , and ATF4 were reduced in the DN model , which was partially , but significantly , prevented by rapamycin and puerarin .
Conclusion : This study emphasizes @ @ @ @ @ @ @ mice , particularly in the modulation of autophagy under ERS conditions , which may be associated with activation of the PERK/eIF2α/ATF4 signaling pathway .
Therefore , PERK may be a potential target for DN treatment .

Background and Purpose: Autophagy is the main protective mechanism against aging in podocytes, which are terminally differentiated cells that have a very limited capacity for mitosis and self-renewal. Here, a streptozotocin-induced DN C57BL/6 mouse model was used to investigate the effects of puerarin on the modulation of autophagy under conditions associated with endoplasmic reticulum stress (ERS). In addition, this study aimed to identify the potential underlying molecular mechanisms.
Methods and Results: DN C57BL/6 mouse model was induced by streptozotocin (150 mg/kg) injection. The mice were administered rapamycin and puerarin, respectively, daily for up to 8 weeks. After the serum and kidney samples were collected, the fasting blood glucose (FBG), parameters of renal function, histomorphology, and the podocyte functional proteins were analyzed. Moreover, the autophagy markers and the expressions of PERK/ATF4 pathway were studied in kidney. Results found that the FBG level in DN mice was significantly higher than in normal mice. Compared with DN model mice, puerarin-treated mice showed an increased expression of podocyte functional proteins, including nephrin, podocin, and podocalyxin. Furthermore, the pathology and structure alterations were improved by treatment with rapamycin and puerarin compared with the DN control. The results indicated an elevated level of autophagy in rapamycin and puerarin groups compared with the DN model, as demonstrated by the upregulated expression of autophagy markers Beclin-1, LC3II, and Atg5, and downregulated p62 expression. In addition, the levels of PERK, eIF2α, and ATF4 were reduced in the DN model, which was partially, but significantly, prevented by rapamycin and puerarin.
Conclusion: This study emphasizes the renal-protective effects of puerarin in DN mice, particularly in the modulation of autophagy under ERS conditions, which may be associated with activation of the PERK/eIF2α/ATF4 signaling pathway. Therefore, PERK may be a potential target for DN treatment.


greenmedinfo--2020-12-04--Puerarin alleviates cisplatin-induced acute renal damage.

Cisplatin ( DDP ) is a commonly used chemotherapy drug ; however , the side effects associated with its use , particularly acute kidney injury ( AKI ) , limit its clinical application .
Puerarin is a natural flavonoid extracted from the Chinese medical herb , which has been reported to alleviate DDP-induced nephrotoxicity .
However , the mechanisms underlying puerarin regulation on microRNA ( miR ) -31-mediated signaling pathways in AKI remain unknown .
Thus , the present study aimed to investigate the function of puerarin in a DDP-induced AKI rat model via reverse transcription-quantitative PCR and western blot @ @ @ @ @ @ @ upregulated the levels of miR-31 in a concentration-dependent manner , bothand .
Furthermore , DDP significantly increased blood urea nitrogen and malondialdehyde content , serum creatinine and histopathological changes , while significantly decreasing the expression levels of superoxide dismutase , catalase and glutathione S-transferase in kidney tissues .
TUNEL and western blot analyses indicated that DDP increased the expression levels of apoptotic proteins and affected the Numb/Notch1 signaling pathway , which is downstream of miR-31 .
The effects induced by DDP were counteracted following treatment with puerarin .
Taken together , the results @ @ @ @ @ @ @ exhibits a renal protective effect against DDP-induced AKI by upregulating miR-31 expression and inhibiting the Numb/Notch1 signaling pathway .

Cisplatin (DDP) is a commonly used chemotherapy drug; however, the side effects associated with its use, particularly acute kidney injury (AKI), limit its clinical application. Puerarin is a natural flavonoid extracted from the Chinese medical herb, which has been reported to alleviate DDP-induced nephrotoxicity. However, the mechanisms underlying puerarin regulation on microRNA (miR)-31-mediated signaling pathways in AKI remain unknown. Thus, the present study aimed to investigate the function of puerarin in a DDP-induced AKI rat model via reverse transcription-quantitative PCR and western blot analyses. The results demonstrated that DDP upregulated the levels of miR-31 in a concentration-dependent manner, bothand. Furthermore, DDP significantly increased blood urea nitrogen and malondialdehyde content, serum creatinine and histopathological changes, while significantly decreasing the expression levels of superoxide dismutase, catalase and glutathione S-transferase in kidney tissues. TUNEL and western blot analyses indicated that DDP increased the expression levels of apoptotic proteins and affected the Numb/Notch1 signaling pathway, which is downstream of miR-31. The effects induced by DDP were counteracted following treatment with puerarin. Taken together, the results of the present study suggest that puerarin exhibits a renal protective effect against DDP-induced AKI by upregulating miR-31 expression and inhibiting the Numb/Notch1 signaling pathway.


greenmedinfo--2020-12-04--Puerarin attenuates the endothelial-mesenchymal transition induced by oxidative stress in human coro

Puerarin attenuates the endothelial-mesenchymal transition induced by oxidative stress in human coronary artery endothelial cells.

Endothelial-mesenchymal transition ( EndMT ) is a process in which endothelial cells lose their specific morphology/markers and undergo a dramatic remodeling of the cytoskeleton .
It has been implicated in the progression of cardiovascular diseases such as cardiac fibrosis and cardiac dysfunction .
Recent study indicated that puerarin could inhibit EndMT against cardiac fibrosis .
However , the precise role of puerarin in EndMT and the underlying molecular mechanisms remain unclear .
EndMT was induced by HO ( 150 μM ) in human coronary artery endothelial cells ( HCAECs ) .
HCAECs were exposed to HOfor six days with or @ @ @ @ @ @ @ changes of EndMT markers ( CD31 , VE-cadherin , FSP1 and α-SMA ) in HCAECs were detected .
The levels of phosphoinositide-3-kinase ( PI3K ) and protein kinase B ( AKT ) proteins were analyzed by Western Blot .
Wound healing and transwell assay were carried out to examine cell chemotaxis .
Puerarin mitigated HO-induced EndMT as indicated by alleviating the reduced expression of CD31 and VE-cadherin and inhibiting the upregulation ofα-SMA and FSP1 .
Furthermore , the mechanisms study showed that puerarin activated the PI3K/AKT pathway by inhibiting reactive oxygen species and @ @ @ @ @ @ @ hand , PI3K inhibitor LY294002 reversed this effect imposed by puerarin .
Puerarin alleviated the migration of mesenchymal-like cells through reducing MMPs protein expression .
These results implicated that puerarin exhibited cytoprotective effects against HO-induced EndMT in HCAECs through alleviating oxidative stress , activating the PI3K/AKT pathway and limiting cell migration .

Endothelial-mesenchymal transition (EndMT) is a process in which endothelial cells lose their specific morphology/markers and undergo a dramatic remodeling of the cytoskeleton. It has been implicated in the progression of cardiovascular diseases such as cardiac fibrosis and cardiac dysfunction. Recent study indicated that puerarin could inhibit EndMT against cardiac fibrosis. However, the precise role of puerarin in EndMT and the underlying molecular mechanisms remain unclear. EndMT was induced by HO(150 μM) in human coronary artery endothelial cells (HCAECs). HCAECs were exposed to HOfor six days with or without puerarin pretreated 2 h. The protein changes of EndMT markers (CD31, VE-cadherin, FSP1 and α-SMA) in HCAECs were detected. The levels of phosphoinositide-3-kinase (PI3K) and protein kinase B (AKT) proteins were analyzed by Western Blot. Wound healing and transwell assay were carried out to examine cell chemotaxis. Puerarin mitigated HO-induced EndMT as indicated by alleviating the reduced expression of CD31 and VE-cadherin and inhibiting the upregulation ofα-SMA and FSP1. Furthermore, the mechanisms study showed that puerarin activated the PI3K/AKT pathway by inhibiting reactive oxygen species and further attenuated EndMT. On the other hand, PI3K inhibitor LY294002 reversed this effect imposed by puerarin. Puerarin alleviated the migration of mesenchymal-like cells through reducing MMPs protein expression. These results implicated that puerarin exhibited cytoprotective effects against HO-induced EndMT in HCAECs through alleviating oxidative stress, activating the PI3K/AKT pathway and limiting cell migration.


greenmedinfo--2020-12-04--Puerarin rebuilding the mucus layer and regulating mucin-utilizing bacteria to relieve ulcerative co

Puerarin rebuilding the mucus layer and regulating mucin-utilizing bacteria to relieve ulcerative colitis.

The colonic mucus barrier serves as a primary defense against enteric pathogens ; destruction of this mucus layer has been @ @ @ @ @ .
This study aims to investigate the possibility of rebuilding the colon mucus layer through @ @ @ @ @ stimulate mucin secretion and goblet cells differentiation .
After puerarin supplementation , the thickness of @ @ @ @ @ and the permeability was reduced .
The erosion of intestinal epithelium by bacteria was blocked @ @ @ @ @ epithelial integrity was alleviated .
Puerarin also altered the composition of mucin-utilizing bacteria , which @ @ @ @ @ Levels of short-chain fatty acids ( SCFAs ) were increased after puerarin supplementation , which @ @ @ @ @ energy for the proliferation of epithelia and goblet cells .
This study demonstrated that enhancement @ @ @ @ @ ulcerative colitis ( UC ) by puerarin supplementation is feasible , and the regulation of @ @ @ @ @ levels of SCFAs may be the main reasons .

The colonic mucus barrier serves as a primary defense against enteric pathogens; destruction of this mucus layer has been observed in ulcerative colitis patients. This study aims to investigate the possibility of rebuilding the colon mucus layer through puerarin supplementation, which can stimulate mucin secretion and goblet cells differentiation. After puerarin supplementation, the thickness of colon mucus layer was increased and the permeability was reduced. The erosion of intestinal epithelium by bacteria was blocked, and the loss of epithelial integrity was alleviated. Puerarin also altered the composition of mucin-utilizing bacteria, which influenced the mucus permeability. Levels of short-chain fatty acids (SCFAs) were increased after puerarin supplementation, which as a direct source of energy for the proliferation of epithelia and goblet cells. This study demonstrated that enhancement of mucin secretion to relieve ulcerative colitis (UC) by puerarin supplementation is feasible, and the regulation of mucin-utilizing bacteria and the increased levels of SCFAs may be the main reasons.


greenmedinfo--2020-12-04--Cannabis Cuts OCD Symptoms in Half

Cannabis Cuts OCD Symptoms in Half

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--2020-12-04--Puerarin inhibits titanium particle-induced osteolysis and RANKL-induced osteoclastogenesis.

Osteolysis around the prosthesis and subsequent aseptic loosening are the main causes of prosthesis failure .
Inflammation due to wear particles and osteoclast activation are the key factors in osteolysis and are also potential targets for the treatment of osteolysis .
However , it is not clear whether puerarin can inhibit chronic inflammation and alleviate osteolysis .
In this study , we investigated the effect of puerarin on Ti particle-induced inflammatory osteolysis in vivo in rat femoral models and in vitro in receptor activator of nuclear factor kappa-B ligand ( RANKL ) -induced osteoclast activation models .
Our in vivo @ @ @ @ @ @ @ particle-induced osteolysis and the expression of matrix metallopeptidase 9 ( MMP-9 ) , nuclear factor of activated T cells 1 ( NFATc1 ) , tumour necrosis factor ( TNF ) -α and interleukin ( IL ) -6 .
In vitro , puerarin prevented RANKL-induced osteoclast differentiation , bone resorption and F-actin ring formation in a concentration-dependent manner .
Furthermore , puerarin decreased the phosphorylation of p65 and prevented p65 moving from the cytoplasm to the nucleus .
Puerarin also reduced the expression of osteoclast-specific factors and inhibited the inflammatory response .
In conclusion @ @ @ @ @ @ @ block the NF-κB signalling pathway to inhibit osteoclast activation and inflammatory processes , which provides a new direction for the treatment of osteolysis-related diseases .

Osteolysis around the prosthesis and subsequent aseptic loosening are the main causes of prosthesis failure. Inflammation due to wear particles and osteoclast activation are the key factors in osteolysis and are also potential targets for the treatment of osteolysis. However, it is not clear whether puerarin can inhibit chronic inflammation and alleviate osteolysis. In this study, we investigated the effect of puerarin on Ti particle-induced inflammatory osteolysis in vivo in rat femoral models and in vitro in receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclast activation models. Our in vivo results showed that puerarin significantly inhibited Ti particle-induced osteolysis and the expression of matrix metallopeptidase 9 (MMP-9), nuclear factor of activated T cells 1 (NFATc1), tumour necrosis factor (TNF)-α and interleukin (IL)-6. In vitro, puerarin prevented RANKL-induced osteoclast differentiation, bone resorption and F-actin ring formation in a concentration-dependent manner. Furthermore, puerarin decreased the phosphorylation of p65 and prevented p65 moving from the cytoplasm to the nucleus. Puerarin also reduced the expression of osteoclast-specific factors and inhibited the inflammatory response. In conclusion, our study proves that puerarin can block the NF-κB signalling pathway to inhibit osteoclast activation and inflammatory processes, which provides a new direction for the treatment of osteolysis-related diseases.


greenmedinfo--2020-12-04--Anti-inflammatory activities of puerarin in high-fat diet-fed rats with streptozotocin-induced gesta

Anti-inflammatory activities of puerarin in high-fat diet-fed rats with streptozotocin-induced gestational diabetes mellitus.

To investigate the effect of puerarin on insulin resistance and inflammation in rats with gestational diabetes mellitus ( GDM ) .
Gestational diabetic model rats were established by intraperitoneal injection of streptozotocin ( 25 mg/kg ) combined with high-fat feeding and were randomly assigned to three groups : the control group , the GDM group , and the puerarin-treated group .
Puerarin was intragastrically administered to rats daily until the offspring were born .
The rats in both the GDM group and control group were administered the same volume of normal saline .
Serum total cholesterol , triglycerides , high-density @ @ @ @ @ @ @ in all groups of rats were measured .
Haematoxylin and eosin staining was used to evaluate morphological changes in the liver , pancreas , and adipose tissues around the reproductive organs .
Western blotting was carried out to measure the protein expression of IRS-1 and inflammatory factors , including TNF-α , TLR4 , MyD88 and phosphorylated NF-κB , in the adipose tissues around the reproductive organs .
Puerarin had preventive effects on GDM-induced pathological changes and ameliorated glucose and lipid metabolism disorders in GDM rats .
Puerarin upregulated IRS-1 expression and decreased the @ @ @ @ @ @ @ and MyD88 as well as the levels of phosphorylated NF-κB in adipose tissues around the reproductive organs in GDMrats .
This study indicated that puerarin exerts anti-inflammatory effects by downregulating the important TLR4/MyD88/NF-κB inflammatory signalling pathway .
Therefore , puerarin can decrease the expression of TNF-α and ameliorate insulin resistance in GDM rats , suggesting the potential efficacy ofpuerarin in GDM treatment .

To investigate the effect of puerarin on insulin resistance and inflammation in rats with gestational diabetes mellitus (GDM). Gestational diabetic model rats were established by intraperitoneal injection of streptozotocin (25 mg/kg) combined with high-fat feeding and were randomly assigned to three groups: the control group, the GDM group, and the puerarin-treated group. Puerarin was intragastrically administered to rats daily until the offspring were born. The rats in both the GDM group and control group were administered the same volume of normal saline. Serum total cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol in all groups of rats were measured. Haematoxylin and eosin staining was used to evaluate morphological changes in the liver, pancreas, and adipose tissues around the reproductive organs. Western blotting was carried out to measure the protein expression of IRS-1 and inflammatory factors, including TNF-α, TLR4, MyD88 and phosphorylated NF-κB, in the adipose tissues around the reproductive organs. Puerarin had preventive effects on GDM-induced pathological changes and ameliorated glucose and lipid metabolism disorders in GDM rats. Puerarin upregulated IRS-1 expression and decreased the protein expression of TNF-α, TLR4, and MyD88 as well as the levels of phosphorylated NF-κB in adipose tissues around the reproductive organs in GDMrats. This study indicated that puerarin exerts anti-inflammatory effects by downregulating the important TLR4/MyD88/NF-κB inflammatory signalling pathway. Therefore, puerarin can decrease the expression of TNF-α and ameliorate insulin resistance in GDM rats, suggesting the potential efficacy ofpuerarin in GDM treatment.


greenmedinfo--2020-12-04--Puerarin may improve the survival of female reproductive stem cells and play a protective role again

Puerarin may improve the survival of female reproductive stem cells and play a protective role against premature ovarian failure.

This study was designed to investigate the protective effects of puerarin ( PUE ) , which work via the Wnt/β-catenin @ @ @ @ @ stress in the premature ovarian failure ( POF ) model .
Two-month-old female mice were @ @ @ @ @ .
One group was used as the control , and the other three groups were @ @ @ @ @ to create POF models .
TwoPOF treatment groups were gavaged with 100 or 200 mg/kg @ @ @ @ @ Next , the ovaries were fixed , and the numbers of different stage follicles were @ @ @ @ @ surface epithelium ( OSE ) was collected .
Oct4 and Mvh expression , Wnt/β-catenin signaling @ @ @ @ @ stress factors SOD2 and Nrf2 , and the apoptosis-related proteins Bcl-2 and Bax were detected @ @ @ @ @ and western blotting .
We found that the number of follicles , Oct4 and Mvh @ @ @ @ @ were reduced in the POF groups ( p

This study was designed to investigate the protective effects of puerarin (PUE), which work via the Wnt/β-catenin signaling pathway, and oxidative stress in the premature ovarian failure (POF) model. Two-month-old female mice were randomly divided into four groups. One group was used as the control, and the other three groups were injected with cyclophosphamide and busulfan to create POF models. TwoPOF treatment groups were gavaged with 100 or 200 mg/kg PUE for 28 days. Next, the ovaries were fixed, and the numbers of different stage follicles were measured, and the ovarian surface epithelium (OSE) was collected. Oct4 and Mvh expression, Wnt/β-catenin signaling pathway activity, the oxidative stress factors SOD2 and Nrf2, and the apoptosis-related proteins Bcl-2 and Bax were detected by IHC, RT-QPCR, and western blotting. We found that the number of follicles, Oct4 and Mvh expression, and Wnt/β-catenin-signaling activity were reduced in the POF groups (p < 0.05 or p < 0.001). After PUE treatment, the follicle number and the primordial follicle ratio increased (p < 0.01), while the atresia ratio decreased (p < 0.01). In addition, the expression levels of Oct4, Mvh, Wnt1, β-catenin, cyclin D1, SOD2, and Nrf2 showed obvious recovery compared with levels in the POF group (p < 0.01, p < 0.05, or p < 0.001). The Bcl-2/Bax ratio in the POF model had reduced by about 60% compared with the control group (p < 0.001) and improved by about 50% after PUE treatment (p < 0.001). In conclusion, PUE may improve the survival of female reproductive stem cells (FGSCs) and play a protective role against POF via a mechanism involving the Wnt/β-catenin signaling pathway, as well as relieving oxidative stress. Further investigations should focus on the culture of oocytesand FGSCs in vitro in a PUE environment with inhibitors or agonists of the Wnt signaling pathway.


greenmedinfo--2020-12-04--Puerarin inhibits the progression of bladder cancer.

Previous studies have shown puerarin to be a potential therapeutic drug for treatment of bladder cancer .
But the role and possible molecular mechanism of puerarin remain unknown.Cell viability , apoptosis , migration , and invasion were assessed by Cell Counting Kit-8 ( CCK-8 ) , flow cytometry , and transwell assays , respectively .
Western blot was used to measure the levels of all protein .
Glucose consumption and lactate production were detected using a glucose and lactate assay kit .
Circular RNA_0020394 ( ) , microRNA-328-3p ( ) , and nuclear receptor binding protein 1 ( ) levels @ @ @ @ @ @ @ reaction ( qRT-PCR ) .
The interaction between miRNA and circRNA or mRNA was confirmed using dual-luciferase reporter assay.experiments were performed to examine the effect of puerarin on tumor growth.Puerarin suppressed cell viability , migration , invasion , and glycolysis , and induced apoptosis in bladder cancer.was downregulated in puerarin-treated bladder cancer cells , andoverexpression attenuated the inhibitory effect of puerarin on cell progression .
Moreover , could bind to , anddirectly targeted .
Functionally , could reverse the promotion effect ofoverexpression on the progression of puerarin-treated cells , and silencingcounteracted the effects @ @ @ @ @ @ @ could increaseexpression by acting assponge in puerarin-treated bladder cancer cells .
Besides , puerarin inhibited tumorigenesisby increasingand decreasing the levels ofand.Puerarin impedes cell viability , migration , invasion , and glycolysis , and promoted apoptosis in bladder cancer by regulating//axis .

Previous studies have shown puerarin to be a potential therapeutic drug for treatment of bladder cancer. But the role and possible molecular mechanism of puerarin remain unknown.Cell viability, apoptosis, migration, and invasion were assessed by Cell Counting Kit-8 (CCK-8), flow cytometry, and transwell assays, respectively. Western blot was used to measure the levels of all protein. Glucose consumption and lactate production were detected using a glucose and lactate assay kit. Circular RNA_0020394 (), microRNA-328-3p (), and nuclear receptor binding protein 1 () levels were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The interaction between miRNA and circRNA or mRNA was confirmed using dual-luciferase reporter assay.experiments were performed to examine the effect of puerarin on tumor growth.Puerarin suppressed cell viability, migration, invasion, and glycolysis, and induced apoptosis in bladder cancer.was downregulated in puerarin-treated bladder cancer cells, andoverexpression attenuated the inhibitory effect of puerarin on cell progression. Moreover,could bind to, anddirectly targeted. Functionally,could reverse the promotion effect ofoverexpression on the progression of puerarin-treated cells, and silencingcounteracted the effects of anti-on puerarin-treated cells. Mechanically,could increaseexpression by acting assponge in puerarin-treated bladder cancer cells. Besides, puerarin inhibited tumorigenesisby increasingand decreasing the levels ofand.Puerarin impedes cell viability, migration, invasion, and glycolysis, and promoted apoptosis in bladder cancer by regulating//axis.


greenmedinfo--2020-12-04--Puerarin alleviates vincristine-induced neuropathic pain and neuroinflammation.

Chemotherapy-induced neuropathic pain harms the quality of life patients .
Vincristine is an often used chemotherapeutic drug that evokes neuralgia via inflammation .
Puerarin ( Pue ) extracted from Puerariae Lobatae Radix has analgesic and anti-inflammatory effects ; however , its possible effect and mechanism in vincristine ( Vin ) -induced neuropathic pain has not been investigated .
The present research aimed to explore whether Pue could relieve chemotherapy-evoked neuropathic pain and the underlying mechanism actions .
Rat neuropathic pain was established by intraperitoneal injection of vincristine .
Pue was orally administered in two dose levels ( 25 or 50 @ @ @ @ @ @ @ paw withdrawal latency and paw withdrawal threshold were performed to evaluate the pain behaviors .
Inflammatory cytokines in the spinal cord and dorsal root ganglion were measured by ELISA kits .
qRT-PCR , western blot , and immunofluorescence staining were employed to measure the level and expression feature of inflammatory cytokines .
Our findings showed that Pue improved hyperalgesia and allodynia .
Treatment with Pue restored the levels of tumor necrosis factor-α ( TNF-α ) , and IL-1β and increased the levels of transforming growth factor-β ( TGF-β ) , and interleukin-10 ( @ @ @ @ @ @ @ , treatment with Pue down-regulated the protein levels of IL-1β , and NF-κBp65 and up-regulated the protein levels of TGF-β , p-Smad2 , and p-Smad3 ( TGF-β/Smad ) in the spinal cord and DRG .
Immunofluorescence staining further demonstrated that Pue decreased theNF-κBp65 protein .
Our findings imply that Pue relieved chemotherapy-induced neuropathic pain might be attributable to the suppression of inflammation cytokines .
The anti-inflammation action of Pue might be associated with the activation of the TGF-β/Smad pathway , a novel mechanism exploring its prophylactic effect in vincristine-induced neuropathic pain .

Chemotherapy-induced neuropathic pain harms the quality of life patients. Vincristine is an often used chemotherapeutic drug that evokes neuralgia via inflammation. Puerarin (Pue) extracted from Puerariae Lobatae Radix has analgesic and anti-inflammatory effects; however, its possible effect and mechanism in vincristine (Vin)-induced neuropathic pain has not been investigated. The present research aimed to explore whether Pue could relieve chemotherapy-evoked neuropathic pain and the underlying mechanism actions. Rat neuropathic pain was established by intraperitoneal injection of vincristine. Pue was orally administered in two dose levels (25 or 50 mg/kg/d) for three weeks. The paw withdrawal latency and paw withdrawal threshold were performed to evaluate the pain behaviors. Inflammatory cytokines in the spinal cord and dorsal root ganglion were measured by ELISA kits. qRT-PCR, western blot, and immunofluorescence staining were employed to measure the level and expression feature of inflammatory cytokines. Our findings showed that Pue improved hyperalgesia and allodynia. Treatment with Pue restored the levels of tumor necrosis factor-α (TNF-α), and IL-1β and increased the levels of transforming growth factor-β (TGF-β), and interleukin-10 (IL-10). On the molecular level, treatment with Pue down-regulated the protein levels of IL-1β, and NF-κBp65 and up-regulated the protein levels of TGF-β, p-Smad2, and p-Smad3 (TGF-β/Smad) in the spinal cord and DRG. Immunofluorescence staining further demonstrated that Pue decreased theNF-κBp65 protein. Our findings imply that Pue relieved chemotherapy-induced neuropathic pain might be attributable to the suppression of inflammation cytokines. The anti-inflammation action of Pue might be associated with the activation of the TGF-β/Smad pathway, a novel mechanism exploring its prophylactic effect in vincristine-induced neuropathic pain.


greenmedinfo--2020-12-04--These results suggest that puerarin may be a novel candidate for the treatment of ischemic heart dis

AIMS : The purpose of this study was to investigate the protective effects of puerarin and elucidate the underlying mechanisms of puerarin in myocardial ischemia/reperfusion ( MI/R ) injury .
MAIN METHODS : C57BL/6 mice were exposed to puerarin ( 100 mg/kg ) with or without the SIRT1 inhibitor nicotinamide ( 500 mg/kg ) and then subjected to MI/R operation .
Myocardial infarct size , serum creatine kinase-MB ( CK-MB ) activity , apoptotic cell death , and cardiac structure and function were examined to evaluate MI/R injury .
RT-PCR and western blottingwere used to determine the inflammatory response and @ @ @ @ @ @ @ of SIRT1/NF-κB pathway .
RESULTS : Puerarin significantly reduced myocardial infarct size , serum CK-MB activity , and apoptotic cell death , and improved cardiac structural damage and dysfunction .
Moreover , puerarin notably decreased the mRNA and protein levels of TNF-α , IL-6 , and IL-1β , indicating that puerarin attenuated MI/R-induced inflammation .
Furthermore , puerarin markedly decreased the protein levels of Ac-NF-κB , NLRP3 , cleaved caspase-1 , cleaved IL-1β , and cleaved IL-18 and increased the protein level of SIRT1 .
More importantly , the SIRT1 inhibitor nicotinamide prevented @ @ @ @ @ @ @ the SIRT1/NF-κB pathway , as well as the NLRP3 inflammasome activation .
CONCLUSION : Puerarin protected against MI/R injury by inhibiting inflammatory responses probably via the SIRT1/NF-κB pathway , and inhibition of the NLRP3 inflammasome was also involved in puerarin-induced cardioprotective effects .
These results suggest that puerarin may be a novel candidate for the treatment of ischemic heart disease .

AIMS: The purpose of this study was to investigate the protective effects of puerarin and elucidate the underlying mechanisms of puerarin in myocardial ischemia/reperfusion (MI/R) injury.
MAIN METHODS: C57BL/6 mice were exposed to puerarin (100 mg/kg) with or without the SIRT1 inhibitor nicotinamide (500 mg/kg) and then subjected to MI/R operation. Myocardial infarct size, serum creatine kinase-MB (CK-MB) activity, apoptotic cell death, and cardiac structure and function were examined to evaluate MI/R injury. RT-PCR and western blottingwere used to determine the inflammatory response and inflammasome activation, as well as activation of SIRT1/NF-κB pathway.
RESULTS: Puerarin significantly reduced myocardial infarct size, serum CK-MB activity, and apoptotic cell death, and improved cardiac structural damage and dysfunction. Moreover, puerarin notably decreased the mRNA and protein levels of TNF-α, IL-6, and IL-1β, indicating that puerarin attenuated MI/R-induced inflammation. Furthermore, puerarin markedly decreased the protein levels of Ac-NF-κB, NLRP3, cleaved caspase-1, cleaved IL-1β, and cleaved IL-18 and increased the protein level of SIRT1. More importantly, the SIRT1 inhibitor nicotinamide prevented these puerarin-induced cardioprotective effects and regulation of the SIRT1/NF-κB pathway, as well as the NLRP3 inflammasome activation.
CONCLUSION: Puerarin protected against MI/R injury by inhibiting inflammatory responses probably via the SIRT1/NF-κB pathway, and inhibition of the NLRP3 inflammasome was also involved in puerarin-induced cardioprotective effects. These results suggest that puerarin may be a novel candidate for the treatment of ischemic heart disease.


greenmedinfo--2020-12-04--Puerarin promotes neuronal survival and neurite outgrowth.

Background : Progesterone receptor ( PR ) modulates neuroprotective and regenerative responses in Parkinson 's disease and related neurological diseases .
Objectives : The present study was designed to determine whether botanical drug puerarin could exhibit neuroprotective and neurorestorative activities via PR signaling .
Methods : The neuroprotective and neurotrophic activities of puerarin were investigated in MPTP-lesioned mice and MPP-challenged primary rat midbrain neurons .
Rotarod performance test and tail suspension test were used to assess motor functions .
Tyrosine hydroxylase ( TH ) and PR were determined by immunostaining , Western blotting , and luciferase reporter assays .
Neurite @ @ @ @ @ @ @ immunostaining .
Results : Puerarin effectively ameliorated the MPTP-induced motor abnormalities in MPTP-lesioned mice and protected primary rat midbrain neurons against MPP-induced toxicity via PR signaling although progesterone exhibited the neuroprotection .
PR antagonist mifepristone ( RU486 ) diminished the neuroprotection of puerarin in MPTP-lesioned mice and MPP-induced primary rat midbrain neurons .
Moreover , puerarin promoted the differentiation of primary rat midbrain neurons and potentiated NGF to induce neuritogenesis in PC12 cells .
RU486 and PR-siRNA could inhibit the effect of puerarin .
Puerarin and progesterone could enhance the PR promoter .
@ @ @ @ @ @ @ toxicity and potentiated neurite outgrowth via PR .
These results suggested that puerarin may become an alternative hormone for suppressing MPTP- and MPP-induced toxicity in neurodegenerative diseases .

Background: Progesterone receptor (PR) modulates neuroprotective and regenerative responses in Parkinson's disease and related neurological diseases.
Objectives: The present study was designed to determine whether botanical drug puerarin could exhibit neuroprotective and neurorestorative activities via PR signaling.
Methods: The neuroprotective and neurotrophic activities of puerarin were investigated in MPTP-lesioned mice and MPP-challenged primary rat midbrain neurons. Rotarod performance test and tail suspension test were used to assess motor functions. Tyrosine hydroxylase (TH) and PR were determined by immunostaining, Western blotting, and luciferase reporter assays. Neurite outgrowth was assessed by fluorescence staining and immunostaining.
Results: Puerarin effectively ameliorated the MPTP-induced motor abnormalities in MPTP-lesioned mice and protected primary rat midbrain neurons against MPP-induced toxicity via PR signaling although progesterone exhibited the neuroprotection. PR antagonist mifepristone (RU486) diminished the neuroprotection of puerarin in MPTP-lesioned mice and MPP-induced primary rat midbrain neurons. Moreover, puerarin promoted the differentiation of primary rat midbrain neurons and potentiated NGF to induce neuritogenesis in PC12 cells. RU486 and PR-siRNA could inhibit the effect of puerarin. Puerarin and progesterone could enhance the PR promoter.
Conclusion: Puerarin attenuated MPTP- and MPP-induced toxicity and potentiated neurite outgrowth via PR. These results suggested that puerarin may become an alternative hormone for suppressing MPTP- and MPP-induced toxicity in neurodegenerative diseases.


greenmedinfo--2020-12-04--Wogonin ameliorates renal inflammation and fibrosis in diabetic nephropathy.

Introduction : Diabetic nephropathy ( DN ) has become an increasing threat to health , and inflammation and fibrosis play important roles in its progression .
Wogonin , a flavonoid , has been proven to suppress inflammation and fibrosis in various diseases , including acute kidney injury .
This study aimed at investigating the effect of wogonin on diabetes-induced renal inflammation and fibrosis .
Materials and Methods : Streptozotocin ( STZ ) -induced diabetic mouse models received gavage doses of wogonin ( 10 , 20 , and 40 mg/kg ) for 12 weeks .
Metabolic indices from blood and urine @ @ @ @ @ @ @ diabetic model were assessed .
Glomerular mesangial cells SV40 were cultured in high glucose ( HG ) medium containing wogonin at concentrations of 1.5825 , 3.125 , and 6.25μg/mL for 24 h. Inflammation and fibrosis indices were evaluated by histopathological , Western blotting , and PCR analyses .
Results : Wogonin treatment ameliorated albuminuria and histopathological lesions in diabetic mice .
Inflammatory cytokines , such as monocyte chemotactic protein-1 ( MCP-1 ) , tumor necrosis factor-α ( TNF-α ) , interleukin-1β ( IL-1β ) , and related signaling pathway NF-κB were downregulated after @ @ @ @ @ @ @ in vitro .
Furthermore , wogonin reduced the expression of extracellular matrix ( ECM ) , including fibronectin ( FN ) , collagen IV ( Col-IV ) , α-smooth muscle actin ( α-SMA ) , and transforming growth factor-β1 ( TGF-β1 ) in the kidneys of diabetic mice and HG-induced mesangial cells .
Moreover , the inhibition of TGF-β1/Smad3 pathway might be responsible for these changes .
Conclusion : Wogonin may ameliorate renal inflammation and fibrosis in diabetic nephropathy by inhibiting the NF-κB and TGF-β1/Smad3 signaling pathways .

Introduction: Diabetic nephropathy (DN) has become an increasing threat to health, and inflammation and fibrosis play important roles in its progression. Wogonin, a flavonoid, has been proven to suppress inflammation and fibrosis in various diseases, including acute kidney injury. This study aimed at investigating the effect of wogonin on diabetes-induced renal inflammation and fibrosis.
Materials and Methods: Streptozotocin (STZ)-induced diabetic mouse models received gavage doses of wogonin (10, 20, and 40 mg/kg) for 12 weeks. Metabolic indices from blood and urine and pathological damage of glomerulus in the diabetic model were assessed. Glomerular mesangial cells SV40 were cultured in high glucose (HG) medium containing wogonin at concentrations of 1.5825, 3.125, and 6.25μg/mL for 24 h. Inflammation and fibrosis indices were evaluated by histopathological, Western blotting, and PCR analyses.
Results: Wogonin treatment ameliorated albuminuria and histopathological lesions in diabetic mice. Inflammatory cytokines, such as monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and related signaling pathway NF-κB were downregulated after the administration of wogonin in vivo and in vitro. Furthermore, wogonin reduced the expression of extracellular matrix (ECM), including fibronectin (FN), collagen IV (Col-IV), α-smooth muscle actin(α-SMA), and transforming growth factor-β1 (TGF-β1) in the kidneys of diabetic mice and HG-induced mesangial cells. Moreover, the inhibition of TGF-β1/Smad3 pathway might be responsible for these changes.
Conclusion: Wogonin may ameliorate renal inflammation and fibrosis in diabetic nephropathy by inhibiting the NF-κB and TGF-β1/Smad3 signaling pathways.


greenmedinfo--2020-12-04--Wogonoside attenuates cutaneous squamous cell carcinoma.

Purpose : Cutaneous squamous cell carcinoma ( cSCC ) is the most common second basal cell carcinoma in our population .
Wogonoside , the main in vivo metabolite of wogonin , possesses anti-inflammatory , anti-angiogenesis and anti-cancer activities .
Nevertheless , the effectiveness of wogonoside therapy on cSCC has not been clarified .
Methods : In this study , we investigated the effects of wogonoside on cell proliferation , invasion , epithelial-mesenchymal transition ( EMT ) and cancer stem-like cell ( CSC ) properties of SCL-1 and SCC12 cell lines , and the effects on tumor formation in vivo .
@ @ @ @ @ @ @ 0 , 25 , 50 and 100μM wogonoside for 48 h. In vivo , SCL-1 cells were subcutaneously injected into the right thigh of mice to form xenograft tumors .
Animals were randomly divided into two groups ( n=10 ) : the control group and the 80 mg/kg wogonoside group .
Results : The results showed that wogonoside attenuated proliferation , invasion and EMT of SCL-1 and SCC12 cell lines , and enhanced the rate of apoptosis .
Meanwhile , wogonoside efficiently abolished the CSC traits of cSCC ; the expression of CSC @ @ @ @ @ @ @ and CD44 ) and the percentage of CD133cells were remarkably downregulated .
In addition , we found that wogonoside repressed the activation of both PI3K/AKT and Wnt/β-catenin pathways .
In vivo , wogonoside significantly inhibited tumor formation .
Conclusion : The results indicated that wogonoside could attenuate cSCC by reducing EMT , invasion and CSC properties .
The efficacy of intervention may be related to inhibition of the PI3K/Akt and Wnt/β-catenin pathways .
These novel findings could furnish new ideas on the potential therapeutic application of wogonoside in cSCC cancellation and cancer intervention @

Purpose: Cutaneous squamous cell carcinoma (cSCC) is the most common second basal cell carcinoma in our population. Wogonoside, the main in vivo metabolite of wogonin, possesses anti-inflammatory, anti-angiogenesis and anti-cancer activities. Nevertheless, the effectiveness of wogonoside therapy on cSCC has not been clarified.
Methods: In this study, we investigated the effects of wogonoside on cell proliferation, invasion, epithelial-mesenchymal transition (EMT) and cancer stem-like cell (CSC) properties of SCL-1 and SCC12 cell lines, and the effects on tumor formation in vivo. In vitro, cells were treated with 0, 25, 50 and 100μM wogonoside for 48 h. In vivo, SCL-1 cells were subcutaneously injected into the right thigh of mice to form xenograft tumors. Animals were randomly divided into two groups (n=10): the control group and the 80 mg/kg wogonoside group.
Results: The results showed that wogonoside attenuated proliferation, invasion and EMT of SCL-1 and SCC12 cell lines, and enhanced the rate of apoptosis. Meanwhile, wogonoside efficiently abolished the CSC traits of cSCC; the expression of CSC markers (ALDH1, SOX-2, Oct4 and CD44) and the percentage of CD133cells were remarkably downregulated. In addition, we found that wogonoside repressed the activation of both PI3K/AKT and Wnt/β-catenin pathways. In vivo, wogonoside significantly inhibited tumor formation.
Conclusion: The results indicated that wogonoside could attenuate cSCC by reducing EMT, invasion and CSC properties. The efficacy of intervention may be related to inhibition of the PI3K/Akt and Wnt/β-catenin pathways. These novel findings could furnish new ideas on the potential therapeutic application of wogonoside in cSCC cancellation and cancer intervention.


greenmedinfo--2020-12-04--When Cancer Spontaneously Disappears

When Cancer Spontaneously Disappears


greenmedinfo--2020-12-04--Prophylactic melatonin treatment ameliorated propofol-induced cognitive dysfunction.

Considering the fact that melatonin acts as protective agent in various cognitive impairment , we decided to explore the precise effect of pretreatment with melatonin on cognitive function , mitochondrial activity , apoptosis and synaptic integrity in aged rats anesthetized by propofol .
We first randomly allocated the thirty Sprague Dawley rats into three groups : Control vehicle-treated group ( Con ) , Propofol-treated group ( Pro ) and Melatonin + Propofol group ( Mel + Pro ) .
The Barnes maze , open field and contextual fear conditioning test were employed to evaluate spatial memory , exploratory behavior and @ @ @ @ @ @ @ and memory ability , respectively .
Moreover , mitochondrial function ( including reactive oxygen species , mitochondrial membrane potential and ATP levels ) and apoptosis were detected in the regions of hippocampus ( HIP ) and prefrontal cortex ( PFC ) .
The results of behavioral tests suggested that melatonin improved propofol-induced memory impairment in aged rats .
Melatonin mitigated mitochondrial dysfunction and decreased the apoptotic cell counts in the regions of HIP and PFC .
Furthermore , prophylactic melatonin treatment also reversed the propofol-induced inactivation of PKA/CREB/BDNF signaling and synaptic dysfunction .
@ @ @ @ @ @ @ thatmelatonin ameliorated the propofol-induced cognitive disorders via attenuating mitochondrial dysfunction , apoptosis , inactivation of PKA/CREB/BDNF signaling and synaptic dysfunction .

Considering the fact that melatonin acts as protective agent in various cognitive impairment, we decided to explore the precise effect of pretreatment with melatonin on cognitive function, mitochondrial activity, apoptosis and synaptic integrity in aged rats anesthetized by propofol. We first randomly allocated the thirty Sprague Dawley rats into three groups: Control vehicle-treated group (Con), Propofol-treated group (Pro) and Melatonin + Propofol group (Mel + Pro). The Barnes maze, open field and contextual fear conditioning test were employed to evaluate spatial memory, exploratory behavior and general locomotor activity, and hippocampus-dependent learning and memory ability, respectively. Moreover, mitochondrial function (including reactive oxygen species, mitochondrial membrane potential and ATP levels) and apoptosis were detected in the regions of hippocampus (HIP) and prefrontal cortex (PFC). The results of behavioral tests suggested that melatonin improved propofol-induced memory impairment in aged rats. Melatonin mitigated mitochondrial dysfunction and decreased the apoptotic cell counts in the regions of HIP and PFC. Furthermore, prophylactic melatonin treatment also reversed the propofol-induced inactivation of PKA/CREB/BDNF signaling and synaptic dysfunction. On the whole, our results indicated thatmelatonin ameliorated the propofol-induced cognitive disorders via attenuating mitochondrial dysfunction, apoptosis, inactivation of PKA/CREB/BDNF signaling and synaptic dysfunction.


greenmedinfo--2020-12-04--Melatonin and regulation of autophagy: Mechanisms and therapeutic implications

Mitochondria are essential subcellular units that generate basic energy for the cell , as well as influence Caflux , apoptosis @ @ @ @ @ Mitophagy can selectively remove impaired mitochondria to preserve mitochondrial function , which is crucial for @ @ @ @ @ dysfunction and mitophagy are widely reported to be linked to various pathogeneses .
In addition @ @ @ @ @ regarding the beneficial role of melatonin in the regulation and intervention of mitophagy progression .
@ @ @ @ @ focus on specific pathological conditions , including ischemia/reperfusion injury ( IRI ) , cancer and @ @ @ @ @ the essential role of melatonin in the modulation of mitophagy in each of these distinct @ @

Mitochondria are essential subcellular units that generate basic energy for the cell, as well as influence Caflux, apoptosis, and cell signaling. Mitophagy can selectively remove impaired mitochondria to preserve mitochondrial function, which is crucial for normal cellular maintenance. Mitochondrial dysfunction and mitophagy are widely reported to be linked to various pathogeneses. In addition, there is increasing evidence regarding the beneficial role of melatonin in the regulation and intervention of mitophagy progression. In this review, we focus on specific pathological conditions, including ischemia/reperfusion injury (IRI), cancer and neurodegenerative diseases, and elucidate the essential role of melatonin in the modulation of mitophagy in each of these distinct disorders.