greenmedinfo--2020-08-09--Targeting foam cell formation and macrophage polarization in atherosclerosis: The therapeutic potent

Targeting foam cell formation and macrophage polarization in atherosclerosis: The therapeutic potential of rhubarb.

Atherosclerosis , a chronic inflammatory disease associated with high morbidity and mortality , is characterized by the accumulation of foam cells in the arterial wall .
It has long been acknowledged that the formation of foam cells is caused by excess lipid uptake and abnormal cholesterol metabolism function .
And increasing evidence shows that inhibiting foam cell formation is a promising way to suppress the development of atherosclerotic lesions .
In addition to excess foam cells accumulation , inflammation is another major contributor of atherosclerotic lesions .
Recently , macrophage polarization has been demonstrated to play a vital role in @ @ @ @ @ @ @ , macrophages mainly polarized into two phenotypes : either classically activated pro-inflammatory M1 or alternatively activated anti-inflammatory M2 .
And targeting macrophage polarization has been considered as a feasible approach to prevent the development of atherosclerosis .
At present , the anti-atherosclerosis drugs mainly classified into two types : lipid-lowering drugs and anti-inflammatory drugs .
A large part of those drugs belong to western medicine , and various side effects are unavoidable .
Interestingly , in recent years , Traditional Chinese medicine has attracted growing attention because of its good efficacy and low @ @ @ @ @ @ @ Huang in Chinese ) is a famous folk medicine with a wide spectrum of pharmacological effects , such as lipid-lowering and anti-inflammatory effects .
In this review , we summarized current findings about the regulatory effects of Rhubarb on foam cell formation and macrophage polarization , with emphasis on the molecular mechanisms of action that have been revealed during the past two decades , to better understand its pivotal role in the treatment and prevention of atherosclerosis .

Atherosclerosis, a chronic inflammatory disease associated with high morbidity and mortality, is characterized by the accumulation of foam cells in the arterial wall. It has long been acknowledged that the formation of foam cells is caused by excess lipid uptake and abnormal cholesterol metabolism function. And increasing evidence shows that inhibiting foam cell formation is a promising way to suppress the development of atherosclerotic lesions. In addition to excess foam cells accumulation, inflammation is another major contributor of atherosclerotic lesions. Recently, macrophage polarization has been demonstrated to play a vital role in the regulation of inflammatory response. Generally, macrophages mainly polarized into two phenotypes: either classically activated pro-inflammatory M1 or alternatively activated anti-inflammatory M2. And targeting macrophage polarization has been considered as a feasible approach to prevent the development of atherosclerosis. At present, the anti-atherosclerosis drugs mainly classified into two types: lipid-lowering drugs and anti-inflammatory drugs. A large part of those drugs belong to western medicine, and various side effects are unavoidable. Interestingly, in recent years, Traditional Chinese medicine has attracted growing attention because of its good efficacy and low negative effects. Rhubarb (called Da Huang in Chinese) is a famous folk medicine with a wide spectrum of pharmacological effects, such as lipid-lowering and anti-inflammatory effects. In this review, we summarized current findings about the regulatory effects of Rhubarb on foam cell formation and macrophage polarization, with emphasis on the molecular mechanisms of action that have been revealed during the past two decades, to better understand its pivotal role in the treatment and prevention of atherosclerosis.


greenmedinfo--2020-08-09--Emodin exerts a protective effect in CVB3-mediated encephalitis in HFMD by inhibiting the TLR3 pathw

BACKGROUND : Encephalitis in hand , foot , and mouth disease ( HFMD ) is a serious threat to children 's health and life .
Toll-like receptor 3 ( TLR3 ) is an innate immune-recognition receptor that can recognize virus and initiate innate immune responses .
Emodin has the effects of anti-inflammatory and regulating immune function , but the mechanism is not very clear .
METHODS : Cells and mice were pretreated with coxsackievirus B3m ( CVB3 ) and treated with emodin .
The messenger ribonucleic acid ( mRNA ) and protein levels of TLR3 and downstream molecules were detected @ @ @ @ @ @ @ western blotting analysis , respectively .
TLR3 expression was also downregulated by anti-TLR3 antibody ( TLR3Ab ) or small interfering RNA ( siRNA ) .
Pathological changes were assessed with hematoxylin and eosin staining .
Immunohistochemistry was used to examine the expression of TLR3 in brain tissues .
The expression of interleukin ( IL ) -6 , nuclear factor ( NF ) -κB , and interferon ( IFN ) -β in serum were tested with enzyme-linked immunosorbent assay .
RESULTS : Emodin decreased the mRNA and protein levels of TLR3 and downstream molecules @ @ @ @ @ @ @ downregulating TLR3 using anti-TLR3Ab or siRNA , emodin could still decrease the mRNA and protein levels of TLR3 and downstream molecules .
Emodin also displayed notable effects on pathology , TLR3 protein in brain tissues , and expression of IL-6 , NF-κB , IFN-β , in serum .
CONCLUSIONS : Emodin exerts a protective effect in CVB3-mediated encephalitis in HFMD by inhibiting the TLR3 pathway .

BACKGROUND: Encephalitis in hand, foot, and mouth disease (HFMD) is a serious threat to children's health and life. Toll-like receptor 3 (TLR3) is an innate immune-recognition receptor that can recognize virus and initiate innate immune responses. Emodin has the effects of anti-inflammatory and regulating immune function, but the mechanism is not very clear.
METHODS: Cells and mice were pretreated with coxsackievirus B3m (CVB3) and treated with emodin. The messenger ribonucleic acid (mRNA) and protein levels of TLR3 and downstream molecules were detected by quantitative real-time polymearse chain reaction and western blotting analysis, respectively. TLR3 expression was also downregulated by anti-TLR3 antibody (TLR3Ab) or small interfering RNA (siRNA). Pathological changes were assessed with hematoxylin and eosin staining. Immunohistochemistry was used to examine the expression of TLR3 in brain tissues. The expression of interleukin (IL)-6, nuclear factor (NF)-κB, and interferon (IFN)-β in serum were tested with enzyme-linked immunosorbent assay.
RESULTS: Emodin decreased the mRNA and protein levels of TLR3 and downstream molecules in vitro and in vivo. After downregulating TLR3 using anti-TLR3Ab or siRNA, emodin could still decrease the mRNA and protein levels of TLR3 and downstream molecules. Emodin also displayed notable effects on pathology, TLR3 protein in brain tissues, and expression of IL-6, NF-κB, IFN-β, in serum.
CONCLUSIONS: Emodin exerts a protective effect in CVB3-mediated encephalitis in HFMD by inhibiting the TLR3 pathway.


greenmedinfo--2020-08-09--Emodin protected against synaptic impairment and oxidative stress induced by fluoride in SH-SY5Y cel

Emodin protected against synaptic impairment and oxidative stress induced by fluoride in SH-SY5Y cells.

Excessive fluoride exposure contributes to neurotoxic effects .
Emodin exhibits antioxidative functions in the central nervous system ( CNS ) @ @ @ @ @ mechanism against fluoride remains to be elucidated .
Our aim was to explore the neuroprotective @ @ @ @ @ of emodin .
In our study , synaptic proteins and oxidative stress damage were examined @ @ @ @ @ were treated with high doses of NaF for 24 hours .
Moreover , pretreatment with @ @ @ @ @ light on the neuroprotective effects in NaF-induced toxicity in SH-SY5Y cells .
We found that @ @ @ @ @ expressions of SNAP 25 , synaptophysin and PSD 95 in SH-SY5Y cells .
In addition @ @ @ @ @ expression of p-ERK1/2 and decreased the protein expressions of Nrf2 and HO-1 , as well @ @ @ @ @ 4-hydroxynonenal ( 4-HNE ) , and 8-Hydroxy-2'-deoxyguanosine ( 8-OHdG ) .
Pretreatment with emodin significantly @ @ @ @ @ NaF .
These data implied thatthe neuroprotective effects of emodin and pointed to the promising @ @ @ @ @ induced by fluoride .

Excessive fluoride exposure contributes to neurotoxic effects. Emodin exhibits antioxidative functions in the central nervous system (CNS); however, its neuroprotective mechanism against fluoride remains to be elucidated. Our aim was to explore the neuroprotective efficacy and the possible mechanisms of emodin. In our study, synaptic proteins and oxidative stress damage were examined after human neuroblastoma SH-SY5Y cells were treated with high doses of NaF for 24 hours. Moreover, pretreatment with emodin was used to shed light on the neuroprotective effects in NaF-induced toxicity in SH-SY5Y cells. We found that NaF significantly lowered the protein expressions of SNAP 25, synaptophysin and PSD 95 in SH-SY5Y cells. In addition, NaF exposure increased theprotein expression of p-ERK1/2 and decreased the protein expressions of Nrf2 and HO-1, as well as facilitated increasing ROS, 4-hydroxynonenal (4-HNE), and 8-Hydroxy-2'-deoxyguanosine (8-OHdG). Pretreatment with emodin significantly recovered these alterations caused by NaF. These data implied thatthe neuroprotective effects of emodin and pointed to the promising utilization for protecting against neurotoxicity induced by fluoride.


greenmedinfo--2020-08-09--Emodin in Rheum undulatum inhibits oxidative stress in the liver.

Emodin is a compound inLinne ( Polygonaceae ) that has been reported to exert anti-inflammatory , antibacterial , and antiallergic effects.Oxidative stress is a causative agent of liver inflammation that may lead to fibrosis and hepato-carcinoma .
In this study , we investigated the antioxidant effects of emodin and its mechanism.We used the hepatocyte stimulated by arachidonic acid ( AA ) + iron cotreatment and the C57B/6 mice orally injected with acetaminophen ( APAP , 500 mg/kg , 6 h ) , as assessed by immunoblot and next generation sequencing ( NGS ) .
Emodin was pre-treated in hepatocyte ( @ @ @ @ @ @ @ h before AA + iron , and in mice ( 10 and 30 m/kg , P.O . )
for 3 days before APAP.
, emodin treatment inhibited the cell death induced by AA + iron maximally at a dose of 10 μM ( EC > 3 μM ) .
In addition , emodin attenuated the decrease of anti-apoptotic proteins , and restored mitochondria membrane potential as mediated by the liver kinase B1 ( LKB1 ) -AMP-activated protein kinase ( AMPK ) pathway .
LKB1 mediated AMPK activation was verified using the LKB1 deficient @ @ @ @ @ @ @ 10 μM ; after 10 min ) also induced the phosphorylation of Yes-associated protein 1 ( YAP1 ) , the main downstream target of the Hippo signalling pathway that mediated oxidative stress or the ROS-initiated signalling pathway.the oral treatment of emodin ( 10 and 30 m/kg , 3 days ) decreased APAP-induced hepatic damage , as indicated by decreases in antioxidant genes as well as tissue damage.Our results show that emodin inhibits oxidative liver injury via the AMPK/YAP mediated pathway .

Emodin is a compound inLinne (Polygonaceae) that has been reported to exert anti-inflammatory, antibacterial, and antiallergic effects.Oxidative stress is a causative agent of liver inflammation that may lead to fibrosis and hepato-carcinoma. In this study, we investigated the antioxidant effects of emodin and its mechanism.We used the hepatocyte stimulated by arachidonic acid (AA) + iron cotreatment and the C57B/6 mice orally injected with acetaminophen (APAP, 500 mg/kg, 6 h), as assessed by immunoblot and next generation sequencing (NGS). Emodin was pre-treated in hepatocyte (3 ∼ 30 μM) for 1 h before AA + iron, and in mice (10 and 30 m/kg, P.O.) for 3 days before APAP., emodin treatment inhibited the cell death induced by AA + iron maximally at a dose of 10 μM (EC>3 μM). In addition, emodin attenuated the decrease of anti-apoptotic proteins, and restored mitochondria membrane potential as mediated by the liver kinase B1 (LKB1)-AMP-activated protein kinase (AMPK) pathway. LKB1 mediated AMPK activation was verified using the LKB1 deficient cell line, HeLa. Emodin (10 μM; after 10 min) also induced the phosphorylation of Yes-associated protein 1 (YAP1), the main downstream target of the Hippo signalling pathway that mediated oxidative stress or the ROS-initiated signalling pathway.the oral treatment of emodin (10 and 30 m/kg, 3 days) decreased APAP-induced hepatic damage, as indicated by decreases in antioxidant genes as well as tissue damage.Our results show that emodin inhibits oxidative liver injury via the AMPK/YAP mediated pathway.


greenmedinfo--2020-08-09--Neuroprotective effects of emodin against ischemia/reperfusion injury.

BACKGROUND : Stroke is one of the leading causes of death and disability worldwide and places a heavy burden on the economy in our society .
Current treatments , such as the use of thrombolytic agents , are often limited by a narrow therapeutic time window .
However , the regeneration of the brain after damage is still active days , even weeks , after stroke occurs , which might provide a second window for treatment .
Emodin , a traditional Chinese medicinal herb widely used to treat acute hepatitis , has been reported to possess antioxidative capabilities and protective @ @ @ @ @ @ @ , the underlying mechanisms and neuroprotective functions of Emodin in a rat middle cerebral artery occlusion ( MCAO ) model of ischemic stroke remain unknown .
This study investigates neuroprotective effects of Emodin in ischemia both in vitro and in vivo .
METHODS : PC12 cells were exposed to oxygen-glucose deprivation to simulate hypoxic injury , and the involved signaling pathways and results of Emodin treatment were evaluated .
The therapeutic effects of Emodin in ischemia animals were further investigated .
RESULTS : Emodin reduced infarct volume and cell death following focal cerebral @ @ @ @ @ @ @ cell viability and reduced reactive oxygen species ( ROS ) production and glutamate release under conditions of ischemia/hypoxia .
Emodin increased Bcl-2 and glutamate transporter-1 ( GLT-l ) expression but suppressed activated-caspase 3 levels through activating the extracellular signal-regulated kinase ( ERK ) -1/2 signaling pathway .
CONCLUSION : Emodin induced Bcl-2 and GLT-1 expression to inhibit neuronal apoptosis and ROS generation while reducing glutamate toxicity via the ERK-1/2 signaling pathway .
Furthermore , Emodin alleviated nerve cell injury following ischemia/reperfusion in a rat MCAO model .
Emodin has neuroprotective effects against ischemia/reperfusion @ @ @ @ @ @ @ , which may be through activating the ERK-1/2 signaling pathway .

BACKGROUND: Stroke is one of the leading causes of death and disability worldwide and places a heavy burden on the economy in our society. Current treatments, such as the use of thrombolytic agents, are often limited by a narrow therapeutic time window. However, the regeneration of the brain after damage is still active days, even weeks, after stroke occurs, which might provide a second window for treatment. Emodin, a traditional Chinese medicinal herb widely used to treat acute hepatitis, has been reported to possess antioxidative capabilities and protective effects against myocardial ischemia/reperfusion injury. However, the underlying mechanisms and neuroprotective functions of Emodin in a rat middle cerebral artery occlusion (MCAO) model of ischemic stroke remain unknown. This study investigates neuroprotective effects of Emodin in ischemia both in vitro and in vivo.
METHODS: PC12 cells were exposed to oxygen-glucose deprivation to simulate hypoxic injury, and the involved signaling pathways and results of Emodin treatment were evaluated. The therapeutic effects of Emodin in ischemia animals were further investigated.
RESULTS: Emodin reduced infarct volume and cell death following focal cerebral ischemia injury. Emodin treatment restored PC12 cell viability and reduced reactive oxygen species (ROS) production and glutamate release under conditions of ischemia/hypoxia. Emodin increased Bcl-2 and glutamate transporter-1 (GLT-l) expression but suppressed activated-caspase 3 levels through activating the extracellular signal-regulated kinase (ERK)-1/2 signaling pathway.
CONCLUSION: Emodin induced Bcl-2 and GLT-1 expression to inhibit neuronal apoptosis and ROS generation while reducing glutamate toxicity via the ERK-1/2 signaling pathway. Furthermore, Emodin alleviated nerve cell injury following ischemia/reperfusion in a rat MCAO model. Emodin has neuroprotective effects against ischemia/reperfusion injury both in vitro and in vivo, which may be through activating the ERK-1/2 signaling pathway.


greenmedinfo--2020-08-09--Emodin reverses 5-Fu resistance in human colorectal cancer via downregulation of PI3K/Akt signaling

Emodin reverses 5-Fu resistance in human colorectal cancer via downregulation of PI3K/Akt signaling pathway.

BACKGROUND : 5-Fu resistance is a major obstacle in the treatment of malignant tumors .
Therefore , combination therapy is employed to overcome this limitation .
Since it was demonstrated that emodin could resensitize breast cancer to 5-Fu treatment , we aimed to investigate if emodin could reverse 5-Fu resistant colorectal cancer ( CRC ) in the current study .
METHODS : For the aim to explore the effect of emodin on 5-Fu resistant CRC , 5-Fu-resistant cell line ( SW480/5-Fu ) was established .
CCK-8 assay and Ki67 staining were performed to evaluate the effects of emodin in combination @ @ @ @ @ @ @ cytometry was used to detect the apoptosis of SW480/5-Fu cells .
Additionally , the invasion and migration of SW480/5-Fu cells were tested by transwell assay and wound healing , respectively .
Western-blot was performed to examine the protein expressions in SW480/5-Fu cells .
Moreover , xenograft mice model was established to test the anti-tumor effect of emodin in combination with 5-Fu .
RESULTS : Emodin notably increased the anti-proliferation effect of 5-Fu in SW480/5-Fu cells .
Similarly , the invasion and migration of SW480/5-Fu cells were further inhibited in the presence of emodin @ @ @ @ @ @ @ ( emodin plus 5-Fu ) induced cell apoptosis via inhibiting Bcl-2 and activating cleaved caspase3 and Bax .
Moreover , emodin reduced 5-Fu resistant in CRC via downregulation of PI3K/Akt signaling .
Finally , study indicated that emodin could notably reverse 5-Fu resistance in CRC xenograft .
CONCLUSION : Our research revealed that emodin could reverse 5-Fu resistance in CRC through inactivating PI3K/Akt signaling pathwayand .
Thus , this finding might provide a molecular basis for treating 5-Fu resistant CRC .

BACKGROUND: 5-Fu resistance is a major obstacle in the treatment of malignant tumors. Therefore, combination therapy is employed to overcome this limitation. Since it was demonstrated that emodin could resensitize breast cancer to 5-Fu treatment, we aimed to investigate if emodin could reverse 5-Fu resistant colorectal cancer (CRC) in the current study.
METHODS: For the aim to explore the effect of emodin on 5-Fu resistant CRC, 5-Fu-resistant cell line (SW480/5-Fu) was established. CCK-8 assay and Ki67 staining were performed to evaluate the effects of emodin in combination with 5-Fu on cell proliferation. Flow cytometry was used to detect the apoptosis of SW480/5-Fu cells. Additionally, the invasion and migration of SW480/5-Fu cells were tested by transwell assay and wound healing, respectively. Western-blot was performed to examine the protein expressions in SW480/5-Fu cells. Moreover, xenograft mice model was established to test the anti-tumor effect of emodin in combination with 5-Fu.
RESULTS: Emodin notably increased the anti-proliferation effect of 5-Fu in SW480/5-Fu cells. Similarly, the invasion and migration of SW480/5-Fu cells were further inhibited in the presence of emodin. In addition, the combination treatment (emodin plus 5-Fu) induced cell apoptosis via inhibiting Bcl-2 and activating cleaved caspase3 and Bax. Moreover, emodin reduced 5-Fu resistant in CRC via downregulation of PI3K/Akt signaling. Finally,study indicated that emodin could notably reverse 5-Fu resistance in CRC xenograft.
CONCLUSION: Our research revealed that emodin could reverse 5-Fu resistance in CRC through inactivating PI3K/Akt signaling pathwayand. Thus, this finding might provide a molecular basis for treating 5-Fu resistant CRC.


greenmedinfo--2020-08-09--Emodin protects against acute pancreatitis-associated lung injury.

Aim : Lung injury is a common complication of acute pancreatitis ( AP ) , which leads to the development of acute respiratory distress syndrome and causes high mortality .
In the present study , we investigated the therapeutic effect of emodin on AP-induced lung injury and explored the molecular mechanisms involved .
Materials and Methods : Thirty male Sprague-Dawley rats were randomly divided into AP ( n=24 ) and normal ( n=6 ) groups .
Rats in the AP group received a retrograde injection of 5 % sodium taurocholate into the biliary-pancreatic duct and then randomly assigned to untreated @ @ @ @ @ @ @ , and dexamethasone ( DEX ) groups .
Pancreatic and pulmonary injury was assessed using H & E staining .
In in vitro study , rat alveolar epithelial cell line L2 cells were exposed to lipopolysaccharide and treated with emodin .
Nrf2 siRNA pool was applied for the knockdown of Nrf2 .
The contents of the pro-inflammatory cytokines in the bronchoalveolar lavage fluid and lung were determined using enzyme-linked immunosorbent assay .
The expressions of related mRNAs and proteins in the lung or L2 cells were detected using real-time polymerase chain reaction , @ @ @ @ @ @ @ Key Findings : Emodin administration alleviated pancreatic and pulmonary injury of rats with AP .
Emodin administration suppressed the production of proinflammatory cytokines , downregulated NLRP3 , ASC and caspase-1 expressions and inhibited NF-κB nuclear accumulation in the lung .
In addition , Emodin increased Nrf2 nuclear translocation and upregulated HO-1 expression .
Moreover , the anti-inflammatory effect of emodin was blocked by Nrf2 inhibitor ML385 .
Conclusion : Emodin effectively protects rats against AP-associated lung injury by inhibiting NLRP3 inflammasome activation via Nrf2/HO-1 signaling .

Aim: Lung injury is a common complication of acute pancreatitis (AP), which leads to the development of acute respiratory distress syndrome and causes high mortality. In the present study, we investigated the therapeutic effect of emodin on AP-induced lung injury and explored the molecular mechanisms involved.
Materials and Methods: Thirty male Sprague-Dawley rats were randomly divided into AP (n=24) and normal (n=6) groups. Rats in the AP group received a retrograde injection of 5% sodium taurocholate into the biliary-pancreatic duct and then randomly assigned to untreated, emodin, combined emodin and ML385, and dexamethasone (DEX) groups. Pancreatic and pulmonary injury was assessed using H&E staining. In in vitro study, rat alveolar epithelial cell line L2 cells were exposed to lipopolysaccharide and treated with emodin. Nrf2 siRNA pool was applied for the knockdown of Nrf2. The contents of the pro-inflammatory cytokines in the bronchoalveolar lavage fluid and lung were determined using enzyme-linked immunosorbent assay. The expressions of related mRNAs and proteins in the lung or L2 cells were detected using real-time polymerase chain reaction, Western blot, immunohistochemistry and immunofluorescence.
Key Findings: Emodin administration alleviated pancreatic and pulmonary injury of rats with AP. Emodin administration suppressed the production of proinflammatory cytokines, downregulated NLRP3, ASC and caspase-1 expressions and inhibited NF-κB nuclear accumulation in the lung. In addition, Emodin increased Nrf2 nuclear translocation and upregulated HO-1 expression. Moreover, the anti-inflammatory effect of emodin was blocked by Nrf2 inhibitor ML385.
Conclusion: Emodin effectively protects rats against AP-associated lung injury by inhibiting NLRP3 inflammasome activation via Nrf2/HO-1 signaling.


greenmedinfo--2020-08-09--Herb-sourced emodin inhibits angiogenesis of breast cancer by targeting VEGFA transcription.

Anti-angiogenesis is an important and promising strategy in cancer therapy .
However , the current methods using anti-vascular endothelial growth factor A ( VEGFA ) antibodies or inhibitors targeting VEGFA receptors are not as efficient as expected partly due to their low efficiencies in blocking VEGFA signaling .
Until now , there is still no method to effectively block VEGFA production in cancer cells from the very beginning , i.e.
, from the transcriptional level .
Here , we aimed to find bioactive small molecules to block VEGFA transcription.We screened our natural compound pool containing 330 small molecules derived from @ @ @ @ @ @ @ the expression of seryl-tRNA synthetase ( SerRS ) , which is a newly identified potent transcriptional repressor of VEGFA , by a cell-based screening system in MDA-MB-231 cell line .
The activities of the candidate molecules on regulating SerRS and VEGFA expression were first tested in breast cancer cells .
We next investigated the antiangiogenic activityby testing the effects of candidate drugs on the vascular development in zebrafish and by matrigel plug angiogenesis assay in mice .
We further examined the antitumor activities of candidate drugs in two triple-negative breast cancer ( TNBC @ @ @ @ @ @ @ streptavidin-biotin affinity pull-down assay , coimmunoprecipitation assays , docking analysis and chromatin immunoprecipitation were performed to identify the direct targets of candidate drugs.We identified emodin that could greatly increase SerRS expression in TNBC cells , consequently reducing VEGFA transcription .
Emodin potently inhibited vascular development of zebrafish and blocked tumor angiogenesis in TNBC-bearing mice , greatly improving the survival .
We also identified nuclear receptor corepressor 2 ( NCOR2 ) to be the direct target of emodin .
Once bound by emodin , NCOR2 got released from SerRS promoter , resulting in the @ @ @ @ @ @ @ suppression of VEGFA transcription.We discovered a herb-sourced small molecule emodin with the potential for the therapy of TNBC by targeting transcriptional regulators NCOR2 and SerRS to suppress VEGFA transcription and tumor angiogenesis .

Anti-angiogenesis is an important and promising strategy in cancer therapy. However, the current methods using anti-vascular endothelial growth factor A (VEGFA) antibodies or inhibitors targeting VEGFA receptors are not as efficient as expected partly due to their low efficiencies in blocking VEGFA signaling. Until now, there is still no method to effectively block VEGFA production in cancer cells from the very beginning, i.e., from the transcriptional level. Here, we aimed to find bioactive small molecules to block VEGFA transcription.We screened our natural compound pool containing 330 small molecules derived from Chinese traditional herbs for small molecules activating the expression of seryl-tRNA synthetase (SerRS), which is a newly identified potent transcriptional repressor of VEGFA, by a cell-based screening system in MDA-MB-231 cell line. The activities of the candidate molecules on regulating SerRS and VEGFA expression were first tested in breast cancer cells. We next investigated the antiangiogenic activityby testing the effects of candidate drugs on the vascular development in zebrafish and by matrigel plug angiogenesis assay in mice. We further examined the antitumor activities of candidate drugs in two triple-negative breast cancer (TNBC)-bearing mouse models. Furthermore, streptavidin-biotin affinity pull-down assay, coimmunoprecipitation assays, docking analysis and chromatin immunoprecipitation were performed to identify the direct targets of candidate drugs.We identified emodin that could greatly increase SerRS expression in TNBC cells, consequently reducing VEGFA transcription. Emodin potently inhibited vascular development of zebrafish and blocked tumor angiogenesis in TNBC-bearing mice, greatly improving the survival. We also identified nuclear receptor corepressor 2 (NCOR2) to be the direct target of emodin. Once bound by emodin, NCOR2 got released from SerRS promoter, resulting in the activation of SerRS expression and eventually the suppression of VEGFA transcription.We discovered a herb-sourced small molecule emodin with the potential for the therapy of TNBC by targeting transcriptional regulators NCOR2 and SerRS to suppress VEGFA transcription and tumor angiogenesis.


greenmedinfo--2020-08-09--The effect of emodin on liver disease - comprehensive advances in molecular mechanisms.

Liver injury could be caused by a variety of causes , including alcohol , drug poisoning , autoimmune overreaction , etc .
In the period of liver injury , hepatic stellate cells ( HSCs ) will be activated and produce excessive extracellular matrix ( ECM ) .
If injury can not be suppressed , liver injury will develop into fibrosis , even cirrhosis and liver cancer .
It is reported that some monomer components extracted from traditional Chinese medicine have better effects on protecting liver .
Emodin , an anthraquinone compound extracted from the traditional Chinese medicine RHEI RADIX ET @ @ @ @ @ @ @ liver protection and anti-cancer effects , and can prevent liver injury induced by a variety of factors .
By searching literatures related to the liver protection of emodin in PUBMED , SINOMED , EBM and CNKI databases , it was found that emodin could inhibit the production and promote the secretion of bile acids , and have a protective effect on intrahepatic cholestasis .
Also , emodin reduce collagen synthesis and anti-hepatic fibrosis by inhibiting oxidative stress , TGF-β/Smad pathway and HSCs proliferation , and promoting apoptosis of HSCs .
Emodin can also @ @ @ @ @ @ @ and oxidation of lipids and cholesterol to protect the nonalcoholic fatty liver .
Besides , emodin can induce the apoptosis of hepatocellular carcinoma cells byacting on the death receptor pathway and mitochondrial apoptosis pathway , thus inhibiting the development of hepatocellular carcinoma .
Moreover , emodin can modulate immunity and improve immune rejection in liver transplantation animals .
In conclusion , emodin has a good effect on liver protection , but further experimental data are needed to verify it .

Liver injury could be caused by a variety of causes, including alcohol, drug poisoning, autoimmune overreaction, etc. In the period of liver injury, hepatic stellate cells (HSCs) will be activated and produce excessive extracellular matrix (ECM). If injury cannot be suppressed, liver injury will develop into fibrosis, even cirrhosis and liver cancer. It is reported that some monomer components extracted from traditional Chinese medicine have better effects on protecting liver. Emodin, an anthraquinone compound extracted from the traditional Chinese medicine RHEI RADIX ET RHIZOMA, has anti-inflammatory, antioxidant, liver protection and anti-cancer effects, and can prevent liver injury induced by a variety of factors. By searching literatures related to the liver protection of emodin in PUBMED, SINOMED, EBM and CNKI databases, it was found that emodin could inhibit the production and promote the secretion of bile acids, and have a protective effect on intrahepatic cholestasis. Also, emodin reduce collagen synthesis and anti-hepatic fibrosis by inhibiting oxidative stress, TGF-β/Smad pathway and HSCs proliferation, and promoting apoptosis of HSCs. Emodin can also regulate lipid metabolism and regulate the synthesis and oxidation of lipids and cholesterol to protect the nonalcoholic fatty liver. Besides, emodin can induce the apoptosis of hepatocellular carcinoma cells byacting on the death receptor pathway and mitochondrial apoptosis pathway, thus inhibiting the development of hepatocellular carcinoma. Moreover, emodin can modulate immunity and improve immune rejection in liver transplantation animals. In conclusion, emodin has a good effect on liver protection, but further experimental data are needed to verify it.


greenmedinfo--2020-08-09--Emodin could regulate Notch1 and RhoA/ROCK pathways by regulating the miR-218a-5p expression in the

Emodin could regulate Notch1 and RhoA/ROCK pathways by regulating the miR-218a-5p expression in the intestine.

Emodin is an effective component in rhubarb to cure intestinal dysfunction , but the specific mechanism remains unknown .
This study aimed to evaluate the protective effects of emodin on intestinal dysfunction caused by acute severe pancreatitis and reveal the functional mechanism of emodin in the treatment of this condition .
An acute severe pancreatitis model was prepared using taurocholate .
In the treatment group , 50 mg/kg emodin was injected intravenously 2 h before the induction of acute severe pancreatitis at an interval of 8 h. After 24 h , the gene expression and protein levels of miR-218a-5p , @ @ @ @ @ @ @ , Bax , Bcl-2 , Fas , FasL , caspase-3 , and caspase-9 were determined through reverse transcription polymerase chain reaction and Western blot analysis .
The protein levels of occludin , zonula occludens-1 ( ZO-1 ) , and E-cadherin in the intestinal tract were also determined through Western blot analysis .
The effects of miR-218a-5p on the apoptosis of rat intestinal epithelial cell-18 were observed through flow cytometry .
The effects of emodin on intestinal cell apoptosis induced by acute severe pancreatitis were observed via TUNEL ( terminal deoxynucleotidyl transferase dUTP nick-end @ @ @ @ @ @ @ pancreas and intestine of rats in each group were observed through hematoxylin and eosin staining .
After 24 h of acute severe pancreatitis induced by taurocholate , emodin reduced the expression of miR-218a-5p in the intestinal tract ; increased the expression of Notch1 and Bcl-2 ; decreased the expression levels of RhoA , ROCK1 , Akt , Bax , Fas , FasL , caspase-3 , and caspase-9 ; inhibited the intestinal cell apoptosis caused by acute severe pancreatitis ; increased the protein expression levels of occludin , zonula occludens-1 ( ZO-1 ) , @ @ @ @ @ @ @ and alleviated intestinal dysfunction caused by acute severe pancreatitis .
Emodin couldregulate Notch1 and RhoA/ROCK pathways by regulating the miR-218a-5p expression in the intestine .
It could also inhibit intestinal cell apoptosis induced by acute severe pancreatitis and improve the intestinal dysfunction caused by severe acute pancreatitis .

Emodin is an effective component in rhubarb to cure intestinal dysfunction, but the specific mechanism remains unknown. This study aimed to evaluate the protective effects of emodin on intestinal dysfunction caused by acute severe pancreatitis and reveal the functional mechanism of emodin in the treatment of this condition. An acute severe pancreatitis model was prepared using taurocholate. In the treatment group, 50 mg/kg emodin was injected intravenously 2 h before the induction of acute severe pancreatitis at an interval of 8 h. After 24 h, the gene expression and protein levels of miR-218a-5p, RhoA, ROCK1, Akt, Notch1, Bax, Bcl-2, Fas, FasL, caspase-3, and caspase-9 were determined through reverse transcription polymerase chain reaction and Western blot analysis. The protein levels of occludin, zonula occludens-1 (ZO-1), and E-cadherin in the intestinal tract were also determined through Western blot analysis. The effects of miR-218a-5p on the apoptosis of rat intestinal epithelial cell-18 were observed through flow cytometry. The effects of emodin on intestinal cell apoptosis induced by acute severe pancreatitis were observed via TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling). Pathological changes in the pancreas and intestine of rats in each group were observed through hematoxylin and eosin staining. After 24 h of acute severe pancreatitis induced by taurocholate, emodin reduced the expression of miR-218a-5p in the intestinal tract; increased the expression of Notch1 and Bcl-2; decreased the expression levels of RhoA, ROCK1, Akt, Bax, Fas, FasL, caspase-3,and caspase-9; inhibited the intestinal cell apoptosis caused by acute severe pancreatitis; increased the protein expression levels of occludin, zonula occludens-1 (ZO-1), and E-cadherin in the intestinal tract; and alleviated intestinal dysfunction caused by acute severe pancreatitis. Emodin couldregulate Notch1 and RhoA/ROCK pathways by regulating the miR-218a-5p expression in the intestine. It could also inhibit intestinal cell apoptosis induced by acute severe pancreatitis and improve the intestinal dysfunction caused by severe acute pancreatitis.


greenmedinfo--2020-08-09--Emodin reduces breast cancer lung metastasis.

Our previous studies demonstrated that the natural compound emodin blocks the tumor-promoting feedforward interactions between cancer cells and macrophages , and thus ameliorates the immunosuppressive state of the tumor microenvironment .
Since tumor-associated macrophages ( TAMs ) also affect epithelial mesenchymal-transition ( EMT ) and cancer stem cell ( CSC ) formation , here we aimed to test if emodin as a neoadjuvant therapy halts breast cancer metastasis by attenuating TAM-induced EMT and CSC formation of breast cancer cells.Bioinformatical analysis was performed to examine the correlation between macrophage abundance and EMT/CSC markers in human breast tumors .
Cell culture and @ @ @ @ @ @ @ emodin suppresses TGF-β1 or macrophage-induced EMT and CSC formation of breast cancer cells , and if it inhibits breast cancer cell migration and invasion .
Using mouse models , we tested if short-term administration of emodin before surgical removal of breast tumors halts breast cancer post-surgery metastatic recurrence in the lungs .
The effects of emodin on TGF-β1 signaling pathways in breast cancer cells were examined by western blots and immunofluorescent imaging.Macrophage abundance positively correlates with EMT and CSC markers in human breast tumors .
Emodin suppressed TGF-β1 production in breast cancer cells @ @ @ @ @ @ @ EMT and CSC formation of breast cancer cells .
Short-term administration of emodin before surgery halted breast cancer post-surgery metastatic recurrence in the lungs by reducing tumor-promoting macrophages and suppressing EMT and CSC formation in the primary tumors .
Mechanistic studies revealed that emodin inhibited both canonical and noncanonical TGF-β1 signaling pathways in breast cancer cells and suppressed transcription factors key to EMT and CSC.Natural compound emodin suppresses EMT and CSC formation of breast cancer cells by blocking TGF-β1-mediated crosstalk between TAMs and breast cancer cells .
Our study provides evidence suggesting that @ @ @ @ @ @ @ as a new effective and safe agent to halt metastatic recurrence of breast cancer .

Our previous studies demonstrated that the natural compound emodin blocks the tumor-promoting feedforward interactions between cancer cells and macrophages, and thus ameliorates the immunosuppressive state of the tumor microenvironment. Since tumor-associated macrophages (TAMs) also affect epithelial mesenchymal-transition (EMT) and cancer stem cell (CSC) formation, here we aimed to test if emodin as a neoadjuvant therapy halts breast cancer metastasis by attenuating TAM-induced EMT and CSC formation of breast cancer cells.Bioinformatical analysis was performed to examine the correlation between macrophage abundance and EMT/CSC markers in human breast tumors. Cell culture and co-culture studies were performed to test if emodin suppresses TGF-β1 or macrophage-induced EMT and CSC formation of breast cancer cells, and if it inhibits breast cancer cell migration and invasion. Using mouse models, we tested if short-term administration of emodin before surgical removal of breast tumors halts breast cancer post-surgery metastatic recurrence in the lungs. The effects of emodin on TGF-β1 signaling pathways in breast cancer cells were examined by western blots and immunofluorescent imaging.Macrophage abundance positively correlates with EMT and CSC markers in human breast tumors. Emodin suppressed TGF-β1 production in breast cancer cells and macrophages and attenuated TGF-β1 or macrophage-induced EMT and CSC formation of breast cancer cells. Short-term administration of emodin before surgery halted breast cancer post-surgery metastatic recurrence in the lungs by reducing tumor-promoting macrophages and suppressing EMT and CSC formation in the primary tumors. Mechanistic studies revealed that emodin inhibited both canonical and noncanonical TGF-β1 signaling pathways in breast cancer cells and suppressed transcription factors key to EMT and CSC.Natural compound emodin suppresses EMT and CSC formation of breast cancer cells by blocking TGF-β1-mediated crosstalk between TAMs and breast cancer cells. Our study provides evidence suggesting that emodin harbors the potential for clinical development as a new effective and safe agent to halt metastatic recurrence of breast cancer.


greenmedinfo--2020-08-09--Berberine and Emodin abrogates breast cancer growth and facilitates apoptosis.

Salt-inducible kinases 3 ( SIK3 ) belong to the AMPK-related family of kinases , which have been implicated in the regulation of cell metabolism , cell polarity remodelling , and epithelial-mesenchymal transition .
Elevated SIK3 expressions in breast cancer cells are shown to contribute to tumorigenesis ; however , the underlying mechanism remains to be elucidated .
In this study , we demonstrate that SIK3 expression is upregulated and concurrently high expression of SIK3 is associated with poor survival in breast cancer .
Specifically , SIK3 knockdown revealed that SIK3 is required for the mTOR/Akt signaling pathway and proliferation of @ @ @ @ @ @ @ findings showed that Emodin ( EMO ) combined with Berberine ( BBR ) significantly inhibited SIK3 activity , leading to reduced cell growth , increased cell cycle arrest and apoptosis in breast cancer cells , but not in non-malignant breast epithelial cell line .
Mechanistic studies further reveal that EMO and BBR in combined treatment inhibited SIK3-potentiated mTOR-mediated aerobic glycolysis and cell growth in breast cancer cells .
Moreover , combination treatments attenuate Akt signaling , thereby inducing G0/G1 phase cell cycle arrest and apoptosis of breast cancer cells in a SIK3-dependent manner @ @ @ @ @ @ @ an opposite trend in both the luminal and basal-like breast cancer .
Collectively , our findings reveal that combination of EMO and BBR attenuates SIK3-driven tumor growth in breast cancer , and thus , EMO and BBR might be a novel SIK3 inhibitor explored into the prevention of breast cancer .

Salt-inducible kinases 3 (SIK3) belong to the AMPK-related family of kinases, which have been implicated in the regulation of cell metabolism, cell polarity remodelling, and epithelial-mesenchymal transition. Elevated SIK3 expressions in breast cancer cells are shown to contribute to tumorigenesis; however, the underlying mechanism remains to be elucidated. In this study, we demonstrate that SIK3 expression is upregulated and concurrently high expression of SIK3 is associated with poor survival in breast cancer. Specifically, SIK3 knockdown revealed that SIK3 is required for the mTOR/Akt signaling pathway and proliferation of breast cancer cells. Furthermore, our findings showed that Emodin (EMO) combined with Berberine (BBR) significantly inhibited SIK3 activity, leading to reduced cell growth, increased cell cycle arrest and apoptosis in breast cancer cells, but not in non-malignant breast epithelial cell line. Mechanistic studies further reveal that EMO and BBR in combined treatment inhibited SIK3-potentiated mTOR-mediated aerobic glycolysis and cell growth in breast cancer cells. Moreover, combination treatments attenuate Akt signaling, thereby inducing G0/G1 phase cell cycle arrest and apoptosis of breast cancer cells in a SIK3-dependent manner. CRISPR/Cas9 or siRNA-mediated SIK3 knockout/knockdown showed an opposite trend in both the luminal and basal-like breast cancer. Collectively, our findings reveal that combination of EMO and BBR attenuates SIK3-driven tumor growth in breast cancer, and thus, EMO and BBR might be a novel SIK3 inhibitor explored into the prevention of breast cancer.


greenmedinfo--2020-08-09--This meta-analysis found a significant reduction of body weight, BMI, WC and CRP levels associated w

This meta-analysis found a significant reduction of body weight, BMI, WC and CRP levels associated with berberine intake.

INTRODUCTION : So far , no study has summarized the findings on the effects of berberine intake on anthropometric parameters @ @ @ @ @ ) and liver enzymes .
This systematic review and meta-analysis were done based upon randomized @ @ @ @ @ to analyze the effects of berberine on anthropometric parameters , CRP and liver enzymes .
@ @ @ @ @ searched for eligible studies published from inception to 30 July 2019 : MEDLINE , EMBASE @ @ @ @ @ Cochrane Library , PubMed and Google scholar .
Necessary data were extracted .
Data were @ @ @ @ @ method and expressed as mean difference with 95 % Confidence Intervals ( 95 % CI @ @ @ @ @ meta-analysis found a significant reduction of body weight , BMI , WC and CRP levels @ @ @ @ @ may have played an indirect role in improved clinical symptoms in diseases with metabolic disorders @ @ @ @ @ significant effect on ALT and AST levels .

INTRODUCTION: So far, no study has summarized the findings on the effects of berberine intake on anthropometric parameters, C-reactive protein (CRP) and liver enzymes. This systematic review and meta-analysis were done based upon randomized controlled trials (RCTs) to analyze the effects of berberine on anthropometric parameters, CRP and liver enzymes.
METHOD: Following databases were searched for eligible studies published from inception to 30 July 2019: MEDLINE, EMBASE, Web of Science, Cochrane Library, PubMed and Google scholar. Necessary data were extracted. Data were pooled by the inverse variance method and expressed as mean difference with 95% Confidence Intervals (95% CI).
RESULT: 12 studies were included. Berberine treatment moderately but significantly decreased body weight (WMD = -2.07 kg, 95% CI -3.09, -1.05, P < 0.001), body mass index (BMI) (WMD = -0.47 kg/m, 95% CI -0.70, -0.23, P < 0.001), waist circumference (WC) (WMD = -1.08 cm, 95% CI -1.97, -0.19, P = 0.018) and C-reactive protein (CRP) concentrations (WMD = -0.42 mg/L, 95% CI -0.82, -0.03, P = 0.034). However, berberine intake did not affect liver enzymes, including alanine aminotransferase (ALT) (WMD = -1.66 I/U, 95% CI -3.98, 0.65, P = 0.160) and aspartate aminotransferase (AST) (WMD = -0.87 I/U, 95% CI -2.56, 0.82, P = 0.311).
CONCLUSION: This meta-analysis found a significant reduction of body weight, BMI, WC and CRP levels associated with berberine intake which may have played an indirect role in improved clinical symptoms in diseases with metabolic disorders. Berberine administration had no significant effect on ALT and AST levels.


greenmedinfo--2020-08-09--Berberine inhibits cancer cells growth by suppressing fatty acid synthesis and biogenesis of extrace

Berberine inhibits cancer cells growth by suppressing fatty acid synthesis and biogenesis of extracellular vesicles.

AIMS : Berberine is an isoquinoline alkaloid extracted from the root , rhizome and stem bark of Coptidis Rhizoma .
Previous studies have revealed the anti-tumor potential of berberine against various types of cancer cells .
However , the underlying mechanisms are not yet fully understood .
In this study , we focused on the effects of berberine on fatty acid synthesis and extracellular vesicles formation in cancer cells , and revealed the internal mechanism of berberine inhibition on cancer cell proliferation .
MATERIALS AND METHODS : Anti-proliferative activity of berberine was determined by cell counting and microscope observation and @ @ @ @ @ @ @ and ACC , expression of extracellular vesicles markers were detected by western blotting.C labeling metabolic flux analysis was used for determination of de novo synthesis of fatty acids .
The excreted extracellular vesicles in culture mediums were separated by both polyethylene glycol enrichment of extracellular vesicles and differential centrifugation separation .
KEY FINDINGS : Among our early experiments , 5-10 μmol/L berberine exhibited the substantial anti-proliferative effect against human colon cancer cell line HCT116 , cervical cancer cell line HeLa and other cancer cells .
It was also revealed that , through activating @ @ @ @ @ @ @ suppressed intracellular fatty acid synthesis , finally decreased the biogenesis of extracellular vesicles .
Moreover , supplement with citrate acid , palmitic acid , as well as exogenous extracellular vesicles , could rescue the inhibitory effect of berberine on cell proliferation , suggesting that inhibited ACC activity , suppressed fatty acid synthesis and decreased extracellular vesicles production were important mechanisms account for berberine inhibiting cancer cell proliferation .
SIGNIFICANCE : Our study indicates that berberine suppresses cancer cell proliferation through inhibiting the synthesis of fatty acids and decreasing biogenesis and secretion of extracellular @ @ @ @ @ @ @ promising candidate for the development of new therapies for cancer .

AIMS: Berberine is an isoquinoline alkaloid extracted from the root, rhizome and stem bark of Coptidis Rhizoma. Previous studies have revealed the anti-tumor potential of berberine against various types of cancer cells. However, the underlying mechanisms are not yet fully understood. In this study, we focused on the effects of berberine on fatty acid synthesis and extracellular vesicles formation in cancer cells, and revealed the internal mechanism of berberine inhibition on cancer cell proliferation.
MATERIALS AND METHODS: Anti-proliferative activity of berberine was determined by cell counting and microscope observation and cell cycle analysis. Activities of AMPK and ACC, expression of extracellular vesicles markers were detected by western blotting.C labeling metabolic flux analysis was used for determination of de novo synthesis of fatty acids. The excreted extracellular vesicles in culture mediums were separated by both polyethylene glycol enrichment of extracellular vesicles and differential centrifugation separation.
KEY FINDINGS: Among our early experiments, 5-10 μmol/L berberine exhibited the substantial anti-proliferative effect against human colon cancer cell line HCT116, cervical cancer cell line HeLa and other cancer cells. It was also revealed that, through activating AMPK, berberine inhibited ACC activity then suppressed intracellular fatty acid synthesis, finally decreased the biogenesis of extracellular vesicles. Moreover, supplement with citrate acid, palmitic acid, as well as exogenous extracellular vesicles, could rescue the inhibitory effect of berberine on cell proliferation, suggesting that inhibited ACC activity, suppressed fatty acid synthesis and decreased extracellular vesicles production were important mechanisms account for berberine inhibiting cancer cell proliferation.
SIGNIFICANCE: Our study indicates that berberine suppresses cancer cell proliferation through inhibiting the synthesis of fatty acids and decreasing biogenesis and secretion of extracellular vesicles, suggests that berberine is a promising candidate for the development of new therapies for cancer.


greenmedinfo--2020-08-09--Synergistic effect of berberine hydrochloride and fluconazole against Candida albicans resistant iso

Synergistic effect of berberine hydrochloride and fluconazole against Candida albicans resistant isolates.

The emergence of resistanthas made clinical fluconazole ( FLC ) treatment difficult .
Improving sensitivity to FLC is an effective way to treat resistant isolates .
Berberine hydrochloride ( BBH ) is a commonly used traditional Chinese medicine with antimicrobial effects , especially in resistant isolates .
We investigated the molecular mechanisms underlying BBH and FLC synergism on biofilm-positive FLC-resistantinhibition .
Checkerboard microdilution assays and time-kill assays showed a strong synergistic effect between BBH and FLC in resistantisolates , causing a significant 32-512-fold reduction in minimum inhibitory concentrations .
BBH combined with FLC inhibited intracellular FLC efflux due to key @ @ @ @ @ @ @ induced hightranscription in resistant strains .
Further , BBH + FLC inhibited yeast adhesion , morphological hyphae transformation , and biofilm formation by downregulating the hyphal-specific genes , , and .
BBH caused cytoplasmic Cainflux , while FLC alone did not induce high intracellular Calevels .
The vacuolar calcium channel genewas upregulated , while the vacuolar calcium pump genewas downregulated in the BBH + FLC and BBH alone groups .
However , vacuolar calcium gene expression after FLC treatment was opposite in biofilm-positive FLC-resistant , which might explain why BBH induces Cainflux .
@ @ @ @ @ @ @ exerts synergistic effects to increase FLC sensitivity by regulating multiple targets in FLC-resistant .
These findings further show that traditional Chinese medicines have multi-target antimicrobial effects that may inhibit drug-resistant strains .
This study also found that the vacuolar calcium regulation genesandare key BBH + FLC targets which increase cytoplasmic Cain resistant isolates , which might be critical for reversing biofilm-positive FLC-resistant .

The emergence of resistanthas made clinical fluconazole (FLC) treatment difficult. Improving sensitivity to FLC is an effective way to treat resistant isolates. Berberine hydrochloride (BBH) is a commonly used traditional Chinese medicine with antimicrobial effects, especially in resistant isolates. We investigated the molecular mechanisms underlying BBH and FLC synergism on biofilm-positive FLC-resistantinhibition. Checkerboard microdilution assays and time-kill assays showed a strong synergistic effect between BBH and FLC in resistantisolates, causing a significant 32-512-fold reduction in minimum inhibitory concentrations. BBH combined with FLC inhibited intracellular FLC efflux due to key efflux pump genedownregulation, whereas FLC alone induced hightranscription in resistant strains. Further, BBH + FLC inhibited yeast adhesion, morphological hyphae transformation, and biofilm formation by downregulating the hyphal-specific genes,, and. BBH caused cytoplasmic Cainflux, while FLC alone did not induce high intracellular Calevels. The vacuolar calcium channel genewas upregulated, while the vacuolar calcium pump genewas downregulated in the BBH + FLC and BBH alone groups. However, vacuolar calcium gene expression after FLC treatment was opposite in biofilm-positive FLC-resistant, which might explain why BBH induces Cainflux. These results demonstrate that BBH + FLC exerts synergistic effects to increase FLC sensitivity by regulating multiple targets in FLC-resistant. These findings further show that traditional Chinese medicines have multi-target antimicrobial effects that may inhibit drug-resistant strains. This study also found that the vacuolar calcium regulation genesandare key BBH + FLC targets which increase cytoplasmic Cain resistant isolates, which might be critical for reversing biofilm-positive FLC-resistant.


greenmedinfo--2020-08-09--Berberine attenuates severity of chronic pancreatitis and fibrosis.

Berberine ( BR ) acts as an AMP-activated protein kinase ( AMPK ) activator which possesses antioxidant and anti-inflammatory properties .
In this study , we have investigated the effects of BR against cerulein-induced chronic pancreatitis ( CP ) via inhibition of TGF-β/Smad signaling and M2 macrophages polarization in AMPK dependent manner .
Cerulein-induced CP mice were treated with BR ( 3 and 10 mg/kg ) , intraperitoneally every day for 21 days .
Our results indicated that , BR treatment ( 10 mg/kg ) significantly reduced oxidative-nitrosative stress , histologicalalterations , inflammatory cells infiltration and collagen deposition in pancreatic @ @ @ @ @ @ @ pancreatic stellate cells ( PSCs ) activation and extracellular matrix ( ECM ) deposition via downregulation of α-SMA , collagen1a , collagen3a and fibronectin expression .
Mechanistically , treatment with BR significantly activated AMPK signaling as compared to cerulein-challenged mice .
Further , administration of BR also inhibited TGF-β/Smad signaling and macrophages polarization in cerulein-induced CP in-vivo models and TGF-β1 stimulated RAW 264.7 macrophages in-vitro .
Together , our results strongly suggest that BR treatment protected against cerulein-induced CP and associated fibrosis progression by inhibiting TGF-β1/Smad signaling and M2 macrophages polarization in an @ @ @ @

Berberine (BR) acts as an AMP-activated protein kinase (AMPK) activator which possesses antioxidant and anti-inflammatory properties. In this study, we have investigated the effects of BR against cerulein-induced chronic pancreatitis (CP) via inhibition of TGF-β/Smad signaling and M2 macrophages polarization in AMPK dependent manner. Cerulein-induced CP mice were treated with BR (3 and 10 mg/kg), intraperitoneally every day for 21 days. Our results indicated that, BR treatment (10 mg/kg) significantly reduced oxidative-nitrosative stress, histologicalalterations, inflammatory cells infiltration and collagen deposition in pancreatic tissue. BR treatment also prevented cerulein-induced pancreatic stellate cells (PSCs) activation and extracellular matrix (ECM) deposition via downregulation of α-SMA, collagen1a, collagen3a and fibronectin expression. Mechanistically, treatment with BR significantly activated AMPK signaling as compared to cerulein-challenged mice. Further, administration of BR also inhibited TGF-β/Smad signaling and macrophages polarization in cerulein-induced CP in-vivo models and TGF-β1 stimulated RAW 264.7 macrophages in-vitro. Together, our results strongly suggest that BR treatment protected against cerulein-induced CP and associated fibrosis progression by inhibiting TGF-β1/Smad signaling and M2 macrophages polarization in an AMPK dependent manner.


greenmedinfo--2020-08-09--Berberine: A novel therapeutic strategy for cancer.

Cancer , even currently , is one of the main reasons for mortality and morbidity , worldwide .
In recent @ @ @ @ @ of effort has been made to find efficient therapeutic strategies for cancer , however , @ @ @ @ @ effects and the possibility of complete remission .
Berberine ( BBR ) is a nature-driven @ @ @ @ @ plant groups such as Berberis vulgaris , Berberis aquifolium , and Berberis aristata .
BBR @ @ @ @ @ of its wide range of pharmacological activities including anti-inflammatory , antidiabetic , antibacterial , antiparasitic @ @ @ @ @ hypolipidemic , and fungicide .
In addition , it exhibits inhibitory effects on multiple types @ @ @ @ @ review , we have elaborated on the anticancer effects of BBR through the regulation of @ @ @ @ @ : inducing apoptosis , autophagy , arresting cell cycle , and inhibiting metastasis and invasion @

Cancer, even currently, is one of the main reasons for mortality and morbidity, worldwide. In recent years, a great deal of effort has been made to find efficient therapeutic strategies for cancer, however, particularly with regards to side effects and the possibility of complete remission. Berberine (BBR) is a nature-driven phytochemical component originated from different plant groups such as Berberis vulgaris, Berberis aquifolium, and Berberis aristata. BBR is a well-known nutraceutical because of its wide range of pharmacological activities including anti-inflammatory, antidiabetic, antibacterial, antiparasitic, antidiarrheal, antihypertensive, hypolipidemic, and fungicide. In addition, it exhibits inhibitory effects on multiple types of cancers. In this review, we have elaborated on the anticancer effects of BBR through the regulation of different molecular pathways such as: inducing apoptosis, autophagy, arresting cell cycle, and inhibiting metastasis and invasion.


greenmedinfo--2020-08-09--Anti-arthritis effect of berberine associated with regulating energy metabolism of macrophages.

Berberine ( BBR ) is the effective constituent of Cortex phellodendri and was characterized as an excellent anti-microbial agent with significant anti-inflammatory effects .
Previously , we had demonstrated that BBR alleviated the inflammatory response in adjuvant-induced arthritis ( AA ) rats by regulating polarization of macrophages .
However , the exact mechanics by which BBR regulates macrophage polarization remained unclear .
Here , we showed that BBR treatment had little influence on total number of macrophages in joints of AA rats , but increased the proportion of M2 macrophages and decreased the proportion of M1 macrophages .
Meanwhile , @ @ @ @ @ @ @ AMP-activated protein kinase phosphorylation ( p-AMPK ) and down-regulated the expression of Hypoxia inducible factor 1α ( HIF-1α ) in synovial macrophages of AA rats .
In vitro , using LPS-stimulated peritoneal macrophages from normal rats , we also verified that pretreatment with BBR promoted transition from M1 to M2 by up-regulating the expression of p-AMPK and suppressing the expression of HIF-1α .
Compound C ( an AMPK inhibitor ) could abrogate the inhibition of BBR on migration of macrophages .
Glycolysis of M1 suppressed by BBR through decreasing lactate export , glucose @ @ @ @ @ @ @ , which was remarkably reversed by Compound C. These findings indicated that anti-arthritis effect of BBR is associated with regulating energy metabolism of macrophages through AMPK/HIF-1α pathway .

Berberine (BBR) is the effective constituent of Cortex phellodendri and was characterized as an excellent anti-microbial agent with significant anti-inflammatory effects. Previously, we had demonstrated that BBR alleviated the inflammatory response in adjuvant-induced arthritis (AA) rats by regulating polarization of macrophages. However, the exact mechanics by which BBR regulates macrophage polarization remained unclear. Here, we showed that BBR treatment had little influence on total number of macrophages in joints of AA rats, but increased the proportion of M2 macrophages and decreased the proportion of M1 macrophages. Meanwhile, we found BBR up-regulated the expression of AMP-activated protein kinase phosphorylation (p-AMPK) and down-regulated the expression of Hypoxia inducible factor 1α (HIF-1α) in synovial macrophages of AA rats. In vitro, using LPS-stimulated peritoneal macrophages from normal rats, we also verified that pretreatment with BBR promoted transition from M1 to M2 by up-regulating the expression of p-AMPK and suppressing the expression of HIF-1α. Compound C (an AMPK inhibitor) could abrogate the inhibition of BBR on migration of macrophages. Glycolysis of M1 suppressed by BBR through decreasing lactate export, glucose consumption, and increasing intracellular ATP content, which was remarkably reversed by Compound C. These findings indicated that anti-arthritis effect of BBR is associated with regulating energy metabolism of macrophages through AMPK/HIF-1α pathway.


greenmedinfo--2020-08-09--Berberine attenuates the abnormal ectopic lipid deposition in skeletal muscle.

BACKGROUND : Lipid deposition in non-adipose tissue is associated with a propensity to obesity .
Skeletal muscle mitochondrial dysfunction , evidenced by incomplete beta oxidation may contribute to ectopic lipid deposition during high fat diet-induced obesity .
Berberine ( BBR ) has been proved to possess the properties of improving metabolic disorders in patients with obesity or type 2 diabetes mellitus .
However , the precise mechanism remains obscure .
METHODS : Mice were treated with berberine and metabolic profile were analyzed .
Mitochondrial number and function were detected after berberine treatment in vitro and in vivo .
The role @ @ @ @ @ @ @ ) /peroxisome proliferator-activated receptor-γ coactivator 1α ( PGC-1α ) was verified after RNA interference or adenovirus infection .
RESULTS : In the current study , we investigated the influence of berberine on the lipid deposition of skeletal muscle and found that berberine could increase the mitochondrial number and function both in vivo and in vitro .
Furthermore , berberine promoted the expression of PGC-1α , the crucial transcriptional coactivator related to mitochondrial biogenesis and function , through AMPK pathway .
Berberine reduced the basal oxygen consumption rates ( OCR ) but increased the @ @ @ @ @ @ @ indicated that berberine could increase the potential function of mitochondria .
CONCLUSION : Our results proved that berberine can protect the lean body mass from excessive lipid accumulation , by promoting the mitochondrial biogenesis and improving fatty acid oxidation in an AMPK/PGC-1α dependent manner .

BACKGROUND: Lipid deposition in non-adipose tissue is associated with a propensity to obesity. Skeletal muscle mitochondrial dysfunction, evidenced by incomplete beta oxidation may contribute to ectopic lipid deposition during high fat diet-induced obesity. Berberine (BBR) has been proved to possess the properties of improving metabolic disorders in patients with obesity or type 2 diabetes mellitus. However, the precise mechanism remains obscure.
METHODS: Mice were treated with berberine and metabolic profile were analyzed. Mitochondrial number and function were detected after berberine treatment in vitro and in vivo. The role of Adenosine 5'-monophosphate-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) was verified after RNA interference or adenovirus infection.
RESULTS: In the current study, we investigated the influence of berberine on the lipid deposition of skeletal muscle and found that berberine could increase the mitochondrial number and function both in vivo and in vitro. Furthermore, berberine promoted the expression of PGC-1α, the crucial transcriptional coactivator related to mitochondrial biogenesis and function, through AMPK pathway. Berberine reduced the basal oxygen consumption rates (OCR) but increased the maximal OCR in C2C12 myocytes, which indicated that berberine could increase the potential function of mitochondria.
CONCLUSION: Our results proved that berberine can protect the lean body mass from excessive lipid accumulation, by promoting the mitochondrial biogenesis and improving fatty acid oxidation in an AMPK/PGC-1α dependent manner.


greenmedinfo--2020-08-10--Pea lectin inhibits growth of Ehrlich ascites carcinoma cells by inducing apoptosis and G2/M cell cy

Pea lectin inhibits growth of Ehrlich ascites carcinoma cells by inducing apoptosis and G2/M cell cycle arrest in vivo.

Pea ( Pisum sativum L. ) lectin is known to have interesting pharmacological activities and of great interest on biomedical research .
In the current research pea lectin was purified followed by ion exchange chromatography on DEAE column and affinity chromatography on glucose-sepharose column .
The lectin shown 11.7-84 % inhibitory effect against Ehrlich ascites carcinoma ( EAC ) cells at the concentration range of 8-120μg/ml in RPMI 1640 medium as determined by MTT assay .
Pea lectin was also shown 63 % and 44 % growth inhibition against EAC cells in vivo in mice when administered 2.8 mg/kg/day and @ @ @ @ @ @ @ for five consequent days .
When Pea lectin injected into the EAC bearing mice for 10 days its significantly increased the hemoglobin and RBC with the decreased of WBC levels toward the normal .
Apoptotic cell morphological change of the treated EAC cells of mice was determined by fluorescence and optical microscope .
Interestingly , cell growth inhibition of the lectin was significantlyreduced in the presence of caspase inhibitors .
Treatment with the lectin caused the cell cycle arrest at G2/M phase of EAC cells which was determined by flow cytometry .
The @ @ @ @ @ @ @ Bcl-X and Bax was evaluated by reverse transcriptase polymerase chain reaction ( RT-PCR ) .
Intensive increase of Bax gene expression and totally despaired of Bcl-2 and Bcl-X gene expression were observed in the cells treated with Pea lectin for five consecutive days .

Pea (Pisum sativum L.) lectin is known to have interesting pharmacological activities and of great interest on biomedical research. In the current research pea lectin was purified followed by ion exchange chromatography on DEAE column and affinity chromatography on glucose-sepharose column. The lectin shown 11.7-84% inhibitory effect against Ehrlich ascites carcinoma (EAC) cells at the concentration range of 8-120μg/ml in RPMI 1640 medium as determined by MTT assay. Pea lectin was also shown 63% and 44% growth inhibition against EAC cells in vivo in mice when administered 2.8 mg/kg/day and 1.4 mg/kg/day (i.p.) respectively for five consequent days. When Pea lectin injected into the EAC bearing mice for 10 days its significantly increased the hemoglobin and RBC with the decreased of WBC levels toward the normal. Apoptotic cell morphological change of the treated EAC cells of mice was determined by fluorescence and optical microscope. Interestingly, cell growth inhibition of the lectin was significantlyreduced in the presence of caspase inhibitors. Treatment with the lectin caused the cell cycle arrest at G2/M phase of EAC cells which was determined by flow cytometry. The expression of apoptosis-related genes, Bcl-2, Bcl-X and Bax was evaluated by reverse transcriptase polymerase chain reaction (RT-PCR). Intensive increase of Bax gene expression and totally despaired of Bcl-2 and Bcl-X gene expression were observed in the cells treated with Pea lectin for five consecutive days.


greenmedinfo--2020-08-10--Pea lectin inhibits cell growth by inducing apoptosis in SW480 and SW48 cell lines.

Globally , colorectal cancer is the third most common type of malignant tumor , after lung and breast .
Here anticancer property of pea lectin was evaluated against colorectal cancer cell lines SW480 and SW48 .
The cells were treated with different doses of lectin for 3 days in vitro and the inhibitory effects were found in a dose dependent manner .
At the high dose ( 1.0 mg/ml ) 62 % and 63 % cell growth inhibitions were observed for SW48 and SW480 cell lines , respectively .
Cell growth inhibition was further studied by colony formation of the @ @ @ @ @ @ @ in SW480and SW48cells were noted significantly lower in comparison to that of control cells .
Cell morphological study revealed that pea lectin induced apoptosis both in SW48 and SW480 cell lines , which was further confirmed by caspase inhibitors .
Involvement of intrinsic mitochondrial pathway in the apoptosis progression was confirmed by caspase inhibitors and increased of caspase-3 & -9 proteins expressions .
Expression levels of p53 and p21 protein were also increased significantly in both cell lines with the decreased of PARP1 protein expression .
G/M and G/Gcell cycle arrested was noted @ @ @ @ @ @ @ respectively , after treatment with pea lectin .

Globally, colorectal cancer is the third most common type of malignant tumor, after lung and breast. Here anticancer property of pea lectin was evaluated against colorectal cancer cell lines SW480 and SW48. The cells were treated with different doses of lectin for 3 days in vitro and the inhibitory effects were found in a dose dependent manner. At the high dose(1.0 mg/ml) 62% and 63% cell growth inhibitions were observed for SW48 and SW480 cell lines, respectively. Cell growth inhibition was further studied by colony formation of the cell lines and the numbers of colonies in SW480and SW48cells were noted significantly lower in comparison to that of control cells. Cell morphological study revealed that pea lectin induced apoptosis both in SW48 and SW480 cell lines, which was further confirmed by caspase inhibitors. Involvement of intrinsic mitochondrial pathway in the apoptosis progression was confirmed by caspase inhibitors and increased of caspase-3&-9 proteins expressions. Expression levels of p53 and p21 protein were also increased significantly in both cell lines with the decreased of PARP1 protein expression. G/M and G/Gcell cycle arrested was noted in SW48 and SW480 cell lines, respectively, after treatment with pea lectin.


greenmedinfo--2020-08-10--Lepidium sativum extract that accelerated bone healing by increasing osteoblastic proliferation.

India is a land of spices and medicinal plants .
Ayurvedic medications and methods are commonly practised in India for curing several ailments .
Lepidium sativum ( garden cress ) is an important herb that belongs to Brassicaceae family .
It is believed that the plant has its origin in Ethiopia but is now cultivated throughout the world .
The plant is well-known in Ayurveda for its beneficial properties it holds .
The present study describes the fracture healing property of the methanolic and aqueous extract of Lepidium sativum seeds .
For the study , 21 Charles foster rats were @ @ @ @ @ @ @ groups each containing seven rats : control , methanolic , and aqueous group .
Rats were anesthetized using ether vapors and fractures were induced in each rat from all the three groups using hand held three-point bending technique .
The broken bone fragments were then stabilized using splints .
The control group was administered with normal saline , along with food and water , post-fracture .
The methanolic group was administered with the methanolic extract of Lepidium sativum seeds at dose of 400 mg/kg given orally , post-fracture along with food and water @ @ @ @ @ @ @ of the seeds in doses of 550 mg/kg orally , along with daily food and water intake for a period of 8 weeks .
The results were evaluated both radiologically and biochemically .
X-rays were done on day 0 , 2week , and 4week post-fractures to look for the callus formation and serum levels for calcium , phosphorus , and alkaline phosphatases were evaluated on 0 day , 1 week , 2week , 4week , 6week , 8week , and 10week post-injury .
It was observed at the end of the study period @ @ @ @ @ @ @ formation starting at the 2week itself post-fracture .
The serum levels of calcium , phosphorus , and alkaline phosphatases at 4 , 6 , and 8weeks had significantvalues in the methanolic group rats .

India is a land of spices and medicinal plants. Ayurvedic medications and methods are commonly practised in India for curing several ailments. Lepidium sativum (garden cress) is an important herb that belongs to Brassicaceae family. It is believed that the plant has its origin in Ethiopia but is now cultivated throughout the world. The plant is well-known in Ayurveda for its beneficial properties it holds. The present study describes the fracture healing property of the methanolic and aqueous extract of Lepidium sativum seeds. For the study, 21 Charles foster rats were used. They were grouped into three groups each containing seven rats: control, methanolic, and aqueous group. Rats were anesthetized using ether vapors and fractures were induced in each rat from all the three groups using hand held three-point bending technique. The broken bone fragments were then stabilized using splints. The control group was administered with normal saline, along with food and water, post-fracture. The methanolic group was administered with the methanolic extract of Lepidium sativum seeds at dose of 400 mg/kg given orally, post-fracture along with food and water. The third group received aqueous extract of the seeds in doses of 550 mg/kg orally, along with daily food and water intake for a period of 8 weeks. The results were evaluated both radiologically and biochemically. X-rays were done on day 0, 2week, and 4week post-fractures to look for the callus formation and serum levels for calcium, phosphorus, and alkaline phosphatases were evaluated on 0 day, 1 week, 2week, 4week, 6week, 8week, and 10week post-injury. It was observed at the end of the study period that the methanolic group had significant callus formation starting at the 2week itself post-fracture. The serum levels of calcium, phosphorus, and alkaline phosphatases at 4, 6, and 8weeks had significantvalues in the methanolic group rats.


greenmedinfo--2020-08-10--L. sativum ameliorates ovariectomy-induced bone injury in rats.

seeds are used traditionally to accelerate healing of bone fracture in addition to its culinary uses .
This study aimed to characterize the osteoprotective effect ofin an ovariectomized rat model at two dose levels ( 50 and 100 mg/kg ) using 17β-estradiol as a positive reference standard .
Moreover , a complete metabolite profile ofvia UHPLC/PDA/ESI-MS , as well as headspace solid-phase microextraction ( SPME ) -GC/MS is presented .
Results revealed thatextract exhibited significant anti-osteoporotic actions as evidenced by mitigating the decrease in relative bone weight concurrent with improved longitudinal and perpendicular femur compression strength .
Further , the @ @ @ @ @ @ @ lactate dehydrogenase ( LDH ) activity and osteocalcin levels .
The extract also inhibited exhaustion of superoxide dismutase ( SOD ) as well as glutathione peroxidase ( GPx ) activities and accumulation of lipid peroxides in bone tissues .
This is in addition to ameliorating the rise in the markers of bone resorption carboxyterminal telopeptide , type I ( CTXI ) and tartrate-resistant acid phosphatase ( TRAP ) and modulating receptor activator of nuclear factor kappa-Β ligand ( ) / osteoprotegerin ( ) expression .
Metabolite characterization suggests that glucosinolates , lignans , @ @ @ @ @ @ @ mediate these anti-osteoporotic effects in a synergistic manner .

seeds are used traditionally to accelerate healing of bone fracture in addition to its culinary uses. This study aimed to characterize the osteoprotective effect ofin an ovariectomized rat model at two dose levels (50 and 100 mg/kg) using 17β-estradiol as a positive reference standard. Moreover, a complete metabolite profile ofvia UHPLC/PDA/ESI-MS, as well as headspace solid-phase microextraction (SPME)-GC/MS is presented. Results revealed thatextract exhibited significant anti-osteoporotic actions as evidenced by mitigating the decrease in relative bone weight concurrent with improved longitudinal and perpendicular femur compression strength. Further, the extract enhanced the serum bone formation biomarkers lactate dehydrogenase (LDH) activity and osteocalcin levels. The extract also inhibited exhaustion of superoxide dismutase (SOD) as well as glutathione peroxidase (GPx) activities and accumulation of lipid peroxides in bone tissues. This is in addition to ameliorating the rise in the markers of bone resorption carboxyterminal telopeptide, type I (CTXI) and tartrate-resistant acid phosphatase (TRAP) and modulating receptor activator of nuclear factor kappa-Β ligand ()/ osteoprotegerin () expression. Metabolite characterization suggests that glucosinolates, lignans, coumarins, phenolic acids, and alkaloids mediate these anti-osteoporotic effects in a synergistic manner.


greenmedinfo--2020-08-11--Anti-quorum sensing and biofilm inhibitory activity of Apium graveolens L. oleoresin.

L. ( Apiaceae ) is a dietary herb used as a spice , condiment and medicine .
( Celery ) @ @ @ @ @ antimicrobial property and for its application as flavours in food industry .
The present study @ @ @ @ @ sensing and antibiofilm agent .
The quorum sensing and biofilm inhibition study was carried out @ @ @ @ @ The MIC of celery oleoresin againstCV12472 andPAO1 was 10 and 25 % v/v , respectively @ @ @ @ @ biofilm formation was tested at concentrations of oleoresins ranging from 1.56 and 50 % v/v @ @ @ @ @ concentration dependent QS inhibitory activity and at sub-MIC of 6.25 and 12.5 % v/v , @ @ @ @ @ production and biofilm formation (

L. (Apiaceae) is a dietary herb used as a spice, condiment and medicine.(Celery) has been studied for its antimicrobial property and for its application as flavours in food industry. The present study investigated theoleoresin as an anti-quorum sensing and antibiofilm agent. The quorum sensing and biofilm inhibition study was carried out using biosensor strainsCV12472 andPAO1. The MIC of celery oleoresin againstCV12472 andPAO1 was 10 and 25% v/v, respectively. Inhibition of violacein and biofilm formation was tested at concentrations of oleoresins ranging from 1.56 and 50% v/v. The oleoresins showed a concentration dependent QS inhibitory activity and at sub-MIC of 6.25 and 12.5% v/v, the oleoresins significantly inhibited violacein production and biofilm formation ( < 0.05). Similarly, the celery oleoresin had significant QS modulatory effect on swimming, swarming and twitching motility inPAO1 at 12.5% v/v ( < 0.05). The major phytoconstituents present in celery oleoresin as analysed by GC-MS were eicosadiene, benzenemethanol and methyl ester which have not been previously reported. The findings suggest that celery has QS and biofilm inhibitory potential against gram negative pathogens and can find application as food intervention techniques.


greenmedinfo--2020-08-11--Chokeberry extract dietary supplement induced a wide range of beneficial effects in active handball

Chokeberry extract dietary supplement induced a wide range of beneficial effects in active handball players.

The aim of our study was to investigate the influence of twelve-week consumption of chokeberry extract on redox status , body composition , lipid profile and biochemical parameters in active handball players .
The study included 16 handball players , aged 16-24 years ( 20.26±2.86 years ) .
Every morning before training players received 30mL of liquid chokeberry extract for 12 weeks , during regular competition season .
The research consisted of morphofunctional and biochemical testing , which was performed at three points ( at the beginning of the study , 6 and 12 weeks after extract consumption ) .
@ @ @ @ @ @ @ noticed significant changes in three main aspects .
The 12-week supplementation with chokeberry extract decreased the levels of pro-oxidants ( TBARS and nitrites ) and increased catalase activity .
Analyzing the dynamic of body composition showed a decrease in body fat ( 9.4±0.5 vs. 7.3±0.6kg ) , as well as its percent in a body ( 11.4±0.4 vs. 8.8±0.4 % ) .
On the other hand , the analysis showed an increase of high-density lipoprotein ( 1.3±0.3 vs. 1.6±0.2mmol/L ) and hemoglobin ( 144.4±11.7 vs. 151.7±9.9g/L ) after 6-week treatment.At the same time @ @ @ @ @ @ @ vs. 6.5±1.2 109/L ) and an increase in red blood cells count ( 4.9±0.4 vs. 5.5±0.5 109/L ) were noticed .
Overall , these results emphatically show that the use of chokeberry extract dietary supplement induced a wide range of beneficial effects in the examined group of athletes .

The aim of our study was to investigate the influence of twelve-week consumption of chokeberry extract on redox status, body composition, lipid profile and biochemical parameters in active handball players. The study included 16 handball players, aged 16-24 years (20.26±2.86 years). Every morning before training players received 30mL of liquid chokeberry extract for 12 weeks, during regular competition season. The research consisted of morphofunctional and biochemical testing, which was performed at three points (at the beginning of the study, 6 and 12 weeks after extract consumption). After the chokeberry extract treatment, we noticed significant changes in three main aspects. The 12-week supplementation with chokeberry extract decreased the levels of pro-oxidants (TBARS and nitrites) and increased catalase activity. Analyzing the dynamic of body composition showed a decrease in body fat (9.4±0.5 vs. 7.3±0.6kg), as well as its percent in a body (11.4±0.4 vs. 8.8±0.4%). On the other hand, the analysis showed an increase of high-density lipoprotein (1.3±0.3 vs. 1.6±0.2mmol/L) and hemoglobin (144.4±11.7 vs. 151.7±9.9g/L) after 6-week treatment.At the same time, a decrease in leukocytes (7.2±2.8 vs. 6.5±1.2 109/L) and an increase in red blood cells count (4.9±0.4 vs. 5.5±0.5 109/L) were noticed. Overall, these results emphatically show that the use of chokeberry extract dietary supplement induced a wide range of beneficial effects in the examined group of athletes.


greenmedinfo--2020-08-11--Mulberry fruit cultivar 'Chiang Mai' prevents beta-amyloid toxicity in PC12 neuronal cells.

Alzheimer 's disease ( AD ) is the most common form of dementia , characterized by chronic neuron loss and cognitive problems .
Aggregated amyloid beta ( Aβ ) peptides , a product of cleaved amyloid precursor protein ( APP ) by beta-secretase 1 ( BACE-1 ) , have been indicated for the progressive pathogenesis of AD .
Currently , screening for anti-AD compounds in foodstuffs is increasing , with promising results .
Hence , the purpose of this study was to investigate the extraction conditions , phytochemical contents , and anti-AD properties , targeting Aβ peptides ofcf .
'Chiang @ @ @ @ @ @ @ vitro and in vivo .
Data showed that the aqueous extract of MNCM contained high amounts of cyanidin , keracyanin , and kuromanin as anthocyanidin and anthocyanins .
The extract also strongly inhibited cholinesterases and BACE-1 in vitro .
Moreover , MNCM extract prevented Aβ-induced neurotoxicity and promoted neurite outgrowth in neuronal cells .
Interestingly , MNCM extract reduced Aβpeptides and improved locomotory coordination ofco-expressing human APP and BACE-1 , specifically in the brain .
These findings suggest that MNCM may be useful as an AD preventive agent by targeting Aβ formation .

Alzheimer's disease (AD) is the most common form of dementia, characterized by chronic neuron loss and cognitive problems. Aggregated amyloid beta (Aβ) peptides, a product of cleaved amyloid precursor protein (APP) by beta-secretase 1 (BACE-1), have been indicated for the progressive pathogenesis of AD. Currently, screening for anti-AD compounds in foodstuffs is increasing, with promising results. Hence, the purpose of this study was to investigate the extraction conditions, phytochemical contents, and anti-AD properties, targeting Aβ peptides ofcf.'Chiang Mai' (MNCM) both in vitro and in vivo. Data showed that the aqueous extract of MNCM contained high amounts of cyanidin, keracyanin, and kuromanin as anthocyanidin and anthocyanins. The extract also strongly inhibited cholinesterases and BACE-1 in vitro. Moreover, MNCM extract prevented Aβ-induced neurotoxicity and promoted neurite outgrowth in neuronal cells. Interestingly, MNCM extract reduced Aβpeptides and improved locomotory coordination ofco-expressing human APP and BACE-1, specifically in the brain. These findings suggest that MNCM may be useful as an AD preventive agent by targeting Aβ formation.


greenmedinfo--2020-08-11--The lozenge of black mulberry leaf extract possesses activity as a α-glucosidase inhibitor.

Background : Diabetes mellitus is a chronic metabolic disease , which possibly leads to kidney , brain , heart failure , and other organ complications , subsequently harming human health .
These symptoms have been prevented using the leaf of black mulberry ( BM ) , as a traditional medicine , because the phenolic compounds contained are able to decrease blood glucose concentration .
Meanwhile , previous reports have shown that BM contains 1-deoxynojirimycin , with strong activity as anα-glucosidase inhibitor .
The aim of this study , therefore , was to formulate and evaluate BM leaf extract in lozenge @ @ @ @ @ @ @ Materials and Methods : The leaves of BM were extracted using the maceration method , where ethanol ( 70 % ) served as a solvent , and the inhibitory activity of the sourcedα-glucosidase enzyme was determined throughstudy .
Subsequently , the extract was formulated into lozenge dosage form and evaluated for physical stability and also the effect ofα-glucosidase enzyme .
Results : The result showed an inhibitory activity of BM leaf extract against the enzymeα-glucosidase , with a half maximal inhibitory concentration ( IC ) value of 357.6μg/mL , whereas the lozenge formulation @ @ @ @ @ @ @ as 5 % polyvinylpyrrolidone showed the best physical stability as compared to other formulas .
However , the lozenge inhibits α-glucosidase enzyme with an ICvalue of 549.7μg/mL .
Conclusion : It was established that the lozenge of BM leaf extract possesses activity as anα-glucosidase inhibitor .

Background: Diabetes mellitus is a chronic metabolic disease, which possibly leads to kidney, brain, heart failure, and other organ complications, subsequently harming human health. These symptoms have been prevented using the leaf of black mulberry (BM), as a traditional medicine, because the phenolic compounds contained are able to decrease blood glucose concentration. Meanwhile, previous reports have shown that BM contains 1-deoxynojirimycin, with strong activity as anα-glucosidase inhibitor. The aim of this study, therefore, was to formulate and evaluate BM leaf extract in lozenge dosage form as an α-glucosidase inhibitor.
Materials and Methods: The leaves of BM were extracted using the maceration method, where ethanol (70%) served as a solvent, and the inhibitory activity of the sourcedα-glucosidase enzyme was determined throughstudy. Subsequently, the extract was formulated into lozenge dosage form and evaluated for physical stability and also the effect ofα-glucosidase enzyme.
Results: The result showed an inhibitory activity of BM leaf extract against the enzymeα-glucosidase, with a half maximal inhibitory concentration (IC) value of 357.6μg/mL, whereas the lozenge formulation containing 43% of extract as well as 5% polyvinylpyrrolidone showed the best physical stability as compared to other formulas. However, the lozenge inhibits α-glucosidase enzyme with an ICvalue of 549.7μg/mL.
Conclusion: It was established that the lozenge of BM leaf extract possesses activity as anα-glucosidase inhibitor.


greenmedinfo--2020-08-11--Black mulberry fruit extract alleviates streptozotocin-induced diabetic nephropathy.

OBJECTIVES : This study was designed to investigate the effect of Morus nigra fruit extract in retarding the progression of diabetic nephropathy in streptozotocin ( STZ ) -induced diabetic rats .
METHODS : Diabetic male Wistar rats were injected with black mulberry fruit extract ( BMFE ) at doses of 150 and 300 mg/kg body weight .
After 4 weeks , microalbuminuria was estimated in addition to serum concentrations of glucose , insulin , creatinine and albumin .
KEY FINDINGS : The study revealed a significant amelioration of all the measured parameters in diabetic animals .
In addition , MDA @ @ @ @ @ @ @ were also improved .
The histopathological examination of kidney tissues revealed significant improvement of the pathological changes and glomerular sclerosis in diabetic rats treated with BMFE .
Treated rats showed downregulation of TNF-α , vascular cell adhesion molecule-1 ( VCAM-1 ) and fibronectin mRNA expression .
CONCLUSION : The ameliorative effect of BMFE on diabetic nephropathy is not only through its potent antioxidant and hypoglycaemic effects but also through its downregulation of TNF-α , VCAM-1 and fibronectin mRNA expression in renal tissues of diabetic-treated rats .
Therefore , BMFE as dietary supplement could @ @ @ @ @ @ @ nephropathy .

OBJECTIVES: This study was designed to investigate the effect of Morus nigra fruit extract in retarding the progression of diabetic nephropathy in streptozotocin (STZ)-induced diabetic rats.
METHODS: Diabetic male Wistar rats were injected with black mulberry fruit extract (BMFE) at doses of 150 and 300 mg/kg body weight. After 4 weeks, microalbuminuria was estimated in addition to serum concentrations of glucose, insulin, creatinine and albumin.
KEY FINDINGS: The study revealed a significant amelioration of all the measured parameters in diabetic animals. In addition, MDA, lipid peroxide levels and catalase activity were also improved. The histopathological examination of kidney tissues revealed significant improvement of the pathological changes and glomerular sclerosis in diabetic rats treated with BMFE. Treated rats showed downregulation of TNF-α, vascular cell adhesion molecule-1 (VCAM-1) and fibronectin mRNA expression.
CONCLUSION: The ameliorative effect of BMFE on diabetic nephropathy is not only through its potent antioxidant and hypoglycaemic effects but also through its downregulation of TNF-α, VCAM-1 and fibronectin mRNA expression in renal tissues of diabetic-treated rats. Therefore, BMFE as dietary supplement could be a promising agent in improving diabetic nephropathy.


greenmedinfo--2020-08-11--Mulberry fruit and ginger is a potential neuroprotectant candidate against ischemic stroke in the me

Mulberry fruit and ginger is a potential neuroprotectant candidate against ischemic stroke in the metabolic syndrome condition.

The prevalence of ischemic stroke in metabolic syndrome ( MetS ) is continually increasing and produces a great impact on both qualities of life and annual healthcare budget .
Due to the efficiency limitation of the current therapeutic strategy , the poor availability of polyphenol substances induced by the first pass effect and the beneficial effects of mulberry fruit and ginger on brain and MetS-related diseases together with the synergistic concept , the neuroprotective effect against ischemic stroke in MetS condition of phytosome containing the combined extract of mulberry fruit and ginger ( PMG ) has been considered .
To @ @ @ @ @ @ @ mechanism of PMG on brain damage in cerebral ischemic rat with MetS , male Wistar rats were induced MetS by high-carbohydrate high-fat diet ( HCHF ) for 16 weeks and subjected to the cerebral ischemia/reperfusion injury ( CIRI ) at the right middle cerebral artery ( Rt .
MCAO ) .
PMG at doses of 50 , 100 , and 200 mg/kg were orally fed with for 21 days , and they were assessed brain damage , neurological deficit score , and the changes of oxidative stress markers , inflammatory markers , PPARexpression @ @ @ @ @ @ @ performed .
All doses of PMG significantly improved brain infarction , brain edema , and neurological deficit score .
In addition , the reduction in DNMT-1 , MDA level , NF-B , TNF , and C-reactive protein together with the increase in SOD , CAT , and GPH-Px activities , and PPARexpression in the lesion brain were also observed .
The current data clearly revealed the neuroprotective effect against cerebral ischemia with MetS condition .
The possible underlying mechanism might occur partly via the suppression of DNMT-1 giving rise to the improvement of @ @ @ @ @ @ @ of inflammation and oxidative stress .
In conclusion , PMG is the potential neuroprotectant candidate against ischemic stroke in the MetS condition .
However , the clinical trial is still essential .

The prevalence of ischemic stroke in metabolic syndrome (MetS) is continually increasing and produces a great impact on both qualities of life and annual healthcare budget. Due to the efficiency limitation of the current therapeutic strategy, the poor availability of polyphenol substances induced by the first pass effect and the beneficial effects of mulberry fruit and ginger on brain and MetS-related diseases together with the synergistic concept, the neuroprotective effect against ischemic stroke in MetS condition of phytosome containing the combined extract of mulberry fruit and ginger (PMG) has been considered. To explore the neuroprotective effect and possible underlying mechanism of PMG on brain damage in cerebral ischemic rat with MetS, male Wistar rats were induced MetS by high-carbohydrate high-fat diet (HCHF) for 16 weeks and subjected to the cerebral ischemia/reperfusion injury (CIRI) at the right middle cerebral artery (Rt. MCAO). PMG at doses of 50, 100, and 200 mg/kg were orally fed with for 21 days, and they were assessed brain damage, neurological deficit score, and the changes of oxidative stress markers, inflammatory markers, PPARexpression, and epigenetic modification via DNMT-1 were performed. All doses of PMG significantly improved brain infarction, brain edema, and neurological deficit score. In addition, the reduction in DNMT-1, MDA level, NF-B, TNF, and C-reactive protein together with the increase in SOD, CAT, and GPH-Px activities, and PPARexpression in the lesion brain were also observed. The current data clearly revealed the neuroprotective effect against cerebral ischemia with MetS condition. The possible underlying mechanism might occur partly via the suppression of DNMT-1 giving rise to the improvement of signal transduction via PPARresulting in the decreasing of inflammation and oxidative stress. In conclusion, PMG is the potential neuroprotectant candidate against ischemic stroke in the MetS condition. However, the clinical trial is still essential.