greenmedinfo--2020-08-21--Cannabis Use Leads to Fewer, Less Painful Migraines

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greenmedinfo--2020-08-21--Cabbage and fermented vegetables: from death rate heterogeneity in countries to candidates for mitig

Cabbage and fermented vegetables: from death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19.

Large differences in COVID-19 death rates exist between countries and between regions of the same country .
Some very low death rate countries such as Eastern Asia , Central Europe or the Balkans have a common feature of eating large quantities of fermented foods .
Although biases exist when examining ecological studies , fermented vegetables or cabbage were associated with low death rates in European countries .
SARS-CoV-2 binds to its receptor , the angiotensin converting enzyme 2 ( ACE2 ) .
As a result of SARS-Cov-2 binding , ACE2 downregulation enhances the angiotensin II receptor type 1 ( ATR @ @ @ @ @ @ @ This leads to insulin resistanceas well as lung and endothelial damage , two severe outcomes of COVID-19 .
The nuclear factor ( erythroid-derived 2 ) -like 2 ( Nrf2 ) is the most potent antioxidant in humans and can block the ATR axis .
Cabbage contains precursors of sulforaphane , the most active natural activator of Nrf2 .
Fermented vegetables contain many lactobacilli , which are also potent Nrf2 activators .
Three examples are given : Kimchi in Korea , westernized foods and the slum paradox .
It is proposed that fermented cabbage @ @ @ @ @ @ @ may enhance Nrf2-associated antioxidant effects helpful in mitigating COVID-19 severity .

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage were associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin converting enzyme 2 (ACE2). As a result of SARS-Cov-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (ATR) axis associated with oxidative stress. This leads to insulin resistanceas well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block the ATR axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are given: Kimchi in Korea, westernized foods and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects helpful in mitigating COVID-19 severity.


greenmedinfo--2020-08-22--Honokiol ameliorates angiotensin II-induced hypertension and endothelial dysfunction by inhibiting H

Honokiol ameliorates angiotensin II-induced hypertension and endothelial dysfunction by inhibiting HDAC6-mediated cystathionine γ-lyase degradation.

Hypertension and endothelial dysfunction are associated with various cardiovascular diseases .
Hydrogen sulphide ( HS ) produced by cystathionineγ-lyase ( CSE ) promotes vascular relaxation and lowers hypertension .
Honokiol ( HNK ) , a natural compound in the Magnolia plant , has been shown to retain multifunctional properties such as anti-oxidative and anti-inflammatory activities .
However , a potential role of HNK in regulating CSE and hypertension remains largely unknown .
Here , we aimed to demonstrate that HNK co-treatment attenuated the vasoconstriction , hypertension and HS reduction caused by angiotensin II ( AngII ) , a well-established inducer @ @ @ @ @ @ @ histone deacetylase 6 ( HDAC6 ) mediates AngII-induced deacetylation of CSE , which facilitates its ubiquitination and proteasomal degradation .
Our current results indicated that HNK increased endothelial CSE protein levels by enhancing its stability in a sirtuin-3-independent manner .
Notably , HNK could increase CSE acetylation levels by inhibiting HDAC6 catalytic activity , thereby blocking the AngII-induced degradative ubiquitination of CSE .
CSE acetylation and ubiquitination occurred mainly on the lysine 73 ( K73 ) residue .
Conversely , its mutant ( K73R ) was resistant to both acetylation and ubiquitination , @ @ @ @ @ @ @ wild-type CSE .
Collectively , our findings suggested that HNK treatment protects CSE against HDAC6-mediated degradation and may constitute an alternative for preventing endothelial dysfunction and hypertensive disorders .

Hypertension and endothelial dysfunction are associated with various cardiovascular diseases. Hydrogen sulphide (HS) produced by cystathionineγ-lyase (CSE) promotes vascular relaxation and lowers hypertension. Honokiol (HNK), a natural compound in the Magnolia plant, has been shown to retain multifunctional properties such as anti-oxidative and anti-inflammatory activities. However, a potential role of HNK in regulating CSE and hypertension remains largely unknown. Here, we aimed to demonstrate that HNK co-treatment attenuated the vasoconstriction, hypertension and HS reduction caused by angiotensin II (AngII), a well-established inducer of hypertension. We previously found that histone deacetylase 6 (HDAC6) mediates AngII-induced deacetylation of CSE, which facilitates its ubiquitination and proteasomal degradation. Our current results indicated that HNK increased endothelial CSE protein levels by enhancing its stability in a sirtuin-3-independent manner. Notably, HNK could increase CSE acetylation levels by inhibiting HDAC6 catalytic activity, thereby blocking the AngII-induced degradative ubiquitination of CSE. CSE acetylation and ubiquitination occurred mainly on the lysine 73 (K73) residue. Conversely, its mutant (K73R) was resistant to both acetylation and ubiquitination, exhibiting higher protein stability than that of wild-type CSE. Collectively, our findings suggested that HNK treatment protects CSE against HDAC6-mediated degradation and may constitute an alternative for preventing endothelial dysfunction and hypertensive disorders.


greenmedinfo--2020-08-22--Apoptotic and antihepatofibrotic effect of honokiol via activation of GSK3β and suppression of Wnt/β

Apoptotic and antihepatofibrotic effect of honokiol via activation of GSK3β and suppression of Wnt/β-catenin pathway in hepatic stellate cells.

Though honokiol , derived from the Magnolia tree , was known to suppress renal fibrosis , pulmonary fibrosis , non-alcoholic steatoheptitis , inflammation and cancers , the underlying antifibrotic mechanisms of honokiol are not fully understood in hepatic stellate cells until now .
Thus , in the present study , inhibitory mechanism of honokiol on liver fibrosis was elucidated mainly in hepatic stellate cells ( HSCs ) by 3- ( 4 , 5-dimethylthiazol-2-yl ) -2,5-diphenyltetrazolium bromide ( MTT ) assay , cell cycle analysis and western-blotting .
Honokiol exerted cytotoxicity in LX-2 , HSC-T6 and Hep-G2 cells .
Honokiol increased @ @ @ @ @ @ @ and cleaved poly ( ADP-ribose ) polymerase ( PARP ) in HSCs .
Moreover , honokiol attenuated the expression of alpha smooth muscle actin ( α-SMA ) , transforming growth factor beta 1 ( TGF-β1 ) , phospho-Smad3 , phospho-AKT , cyclin D1 , c-Myc , Wnt3a , β-catenin , and activated phosphorylation of glycogen synthase kinase 3 beta ( GSK3β ) in HSCs .
Conversely , GSK3β inhibitor SB216763 reversed the effect of honokiol on PARP , α-SMA , phospho-GSK3β , β-catenin and sub G1 population in LX-2 cells .
Overall , @ @ @ @ @ @ @ activation of GSK3β and inhibition of Wnt3a/β-catenin signalling pathway .

Though honokiol, derived from the Magnolia tree, was known to suppress renal fibrosis, pulmonary fibrosis, non-alcoholic steatoheptitis, inflammation and cancers, the underlying antifibrotic mechanisms of honokiol are not fully understood in hepatic stellate cells until now. Thus, in the present study, inhibitory mechanism of honokiol on liver fibrosis was elucidated mainly in hepatic stellate cells (HSCs) by 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, cell cycle analysis and western-blotting. Honokiol exerted cytotoxicity in LX-2, HSC-T6 and Hep-G2 cells. Honokiol increased sub G1 population and activated caspase 3 and cleaved poly (ADP-ribose) polymerase (PARP) in HSCs. Moreover, honokiol attenuated the expression of alpha smooth muscle actin (α-SMA), transforming growth factor beta 1 (TGF-β1), phospho-Smad3, phospho-AKT, cyclin D1, c-Myc, Wnt3a, β-catenin, and activated phosphorylation of glycogen synthase kinase 3 beta (GSK3β) in HSCs. Conversely, GSK3β inhibitor SB216763 reversed the effect of honokiol on PARP, α-SMA, phospho-GSK3β, β-catenin and sub G1 population in LX-2 cells. Overall, honokiol exerts apoptotic and antifibrotic effects via activation of GSK3β and inhibition of Wnt3a/β-catenin signalling pathway.


greenmedinfo--2020-08-22--Counteracting cisplatin-induced testicular damages by natural polyphenol constituent honokiol.

Cisplatin , despite its anti-cancer ability , exhibits severe testicular toxicities when applied systemically .
Due to its wide application @ @ @ @ @ of its damages to normal tissue is an imminent clinical need .
Here we evaluated @ @ @ @ @ a natural lipophilic polyphenol compound , on cisplatin-induced testicular injury .
We showed in-vitro and @ @ @ @ @ cisplatin-induced DNA oxidative stress by suppressing intracellular reactive oxygen species production and elevating gene expressions @ @ @ @ @ Nanosome honokiol also mitigated endoplasmic reticulum stress through down regulation of Bip-ATF4-CHOP signaling pathway .
@ @ @ @ @ compound diminished cisplatin-induced DNA breaks and cellular apoptosis .
The reduced type I collagen accumulation @ @ @ @ @ from inhibition of TGFβ1 , αSMA and ER protein TXNDC5 protein expression .
The combinatorial @ @ @ @ @ layers and facilitate repopulation of sperm cells .
Our study renders opportunity for re-introducing cisplatin @ @ @ @ @ reduced testicular toxicity and restored fertility .

Cisplatin, despite its anti-cancer ability, exhibits severe testicular toxicities when applied systemically. Due to its wide application in cancer treatment, reduction of its damages to normal tissue is an imminent clinical need. Here we evaluated the effects of honokiol, a natural lipophilic polyphenol compound, on cisplatin-induced testicular injury. We showed in-vitro and in-vivo that nanosome-encapsulated honokiol attenuated cisplatin-induced DNA oxidative stress by suppressing intracellular reactive oxygen species production and elevating gene expressions of mitochondrial antioxidation enzymes. Nanosome honokiol also mitigated endoplasmic reticulum stress through down regulation of Bip-ATF4-CHOP signaling pathway. Additionally, this natural polyphenol compound diminished cisplatin-induced DNA breaks and cellular apoptosis. The reduced type I collagen accumulation in the testis likely attributed from inhibition of TGFβ1, αSMA and ER protein TXNDC5 protein expression. The combinatorial beneficial effects better preserve spermatogenic layers and facilitate repopulation of sperm cells. Our study renders opportunity for re-introducing cisplatin to systemic anti-cancer therapy with reduced testicular toxicity and restored fertility.


greenmedinfo--2020-08-22--Evaluation of anticancer activity of honokiol by complexation with hydroxypropyl-β-cyclodextrin.

Honokiol ( HK ) , an active compound derived from Magnolia officinalis Rehd .
et Wils , possesses many beneficial @ @ @ @ @ .
However , its poor solubility and low bioavailability severely limits its application .
In @ @ @ @ @ the pharmaceutical properties , the HK was complexed in hydroxypropyl-β-cyclodextrin ( HP-β-CD ) and its @ @ @ @ @ were evaluated .
The HK/HP-β-CD inclusion complex ( 1:1 ) was prepared by saturated aqueous @ @ @ @ @ complex ( HK-HP-β-CD ) obtained had a higher solubility , about 1497 times that of @ @ @ @ @ dissolution rate and the oral bioavailability of HK was also significantly higher from inclusion complex @ @ @ @ @ Furthermore , the HK-HP-β-CD exhibited higher antitumor activity against Human Hepatoma Cell Line ( HepG2 @ @ @ @ @ More cells were arrested in the sub-G1 phase of the cell cycle and were induced @ @ @ @ @ treated with the HK-HP-β-CD than when treated with free HK .

Honokiol (HK), an active compound derived from Magnolia officinalis Rehd. et Wils, possesses many beneficial biological activities for human beings. However, its poor solubility and low bioavailability severely limits its application. In this way, to improve the pharmaceutical properties, the HK was complexed in hydroxypropyl-β-cyclodextrin (HP-β-CD) and its oral bioavailability and antitumor effects were evaluated. The HK/HP-β-CD inclusion complex (1:1) was prepared by saturated aqueous solution method. The inclusion complex (HK-HP-β-CD) obtained had a higher solubility, about 1497 times that of the free HK. The dissolution rate and the oral bioavailability of HK was also significantly higher from inclusion complex than from free HK. Furthermore, the HK-HP-β-CD exhibited higher antitumor activity against Human Hepatoma Cell Line (HepG2) than free HK. More cells were arrested in the sub-G1 phase of the cell cycle and were induced to undergo late apoptosis when treated with the HK-HP-β-CD than when treated with free HK.


greenmedinfo--2020-08-22--Honokiol-chlorambucil co-prodrugs selectively enhance the killing effect through STAT3 binding on ly

Honokiol-chlorambucil co-prodrugs selectively enhance the killing effect through STAT3 binding on lymphocytic leukemia cells.

The broad-spectrum DNA alkylating therapeutic , chlorambucil ( CBL ) , has limited safety and shows lower therapy effect because of a short half-life while used in the clinic .
Therefore , it is very necessary to develop a more efficient and safer type of CBL derivate against tumors with selective targeting of cancer cells .
In addition , the natural product of honokiol ( HN ) , the novel potent chemo-preventive or therapeutic entity/carrier , can target the mitochondria of cancer cells through STAT3 to prevent cancer from spreading and metastasizing .
In this study , we designed and @ @ @ @ @ @ @ through carbonate ester linkage conjugating with the targeted delivery help of the HN skeleton in cancer cells .
Biological evaluation indicated that HN-CBL can remarkably enhance the antiproliferation of human leukemic cell lines CCRF-CEM , Jurkat , U937 , MV4-11 , and K562 .
Furthermore , HN-CBL can also selectively inhibit the lymphocytic leukemia ( LL ) cell survival compared to those mononuclear cells derived from healthy donors ( PBMCs ) , enhance mitochondrial activity in leukemia cells , and induce LL cell apoptosis .
Molecular docking and western blot study showed that @ @ @ @ @ @ @ protein at some hydrophobic residues and downregulate the phosphorylation level of STAT3-like HN .
Significantly , HN-CBL could dramatically delay leukemia growthwith no observable physiological toxicity .
Thus , HN-CBL may provide a novel and effective targeting therapeutic against LL with fewer side effects .

The broad-spectrum DNA alkylating therapeutic, chlorambucil (CBL), has limited safety and shows lower therapy effect because of a short half-life while used in the clinic. Therefore, it is very necessary to develop a more efficient and safer type of CBL derivate against tumors with selective targeting of cancer cells. In addition, the natural product of honokiol (HN), the novel potent chemo-preventive or therapeutic entity/carrier, can target the mitochondria of cancer cells through STAT3 to prevent cancer from spreading and metastasizing. In this study, we designed and synthesized the honokiol-chlorambucil (HN-CBL) co-prodrugs through carbonate ester linkage conjugating with the targeted delivery help of the HN skeleton in cancer cells. Biological evaluation indicated that HN-CBL can remarkably enhance the antiproliferation of human leukemic cell lines CCRF-CEM, Jurkat, U937, MV4-11, and K562. Furthermore, HN-CBL can also selectively inhibit the lymphocytic leukemia (LL) cell survival compared to those mononuclear cells derived from healthy donors (PBMCs), enhance mitochondrial activity in leukemia cells, and induce LL cell apoptosis. Molecular docking and western blot study showed that HN-CBL can also bind with the STAT3 protein at some hydrophobic residues and downregulate the phosphorylation level of STAT3-like HN. Significantly, HN-CBL could dramatically delay leukemia growthwith no observable physiological toxicity. Thus, HN-CBL may provide a novel and effective targeting therapeutic against LL with fewer side effects.


greenmedinfo--2020-08-22--Synergistic therapy with tangeretin and 5-fluorouracil accelerates the ROS/JNK mediated apoptotic pa

Synergistic therapy with tangeretin and 5-fluorouracil accelerates the ROS/JNK mediated apoptotic pathway in human colorectal cancer cells.

Synergistic therapy is emerging as a promising strategy for improving the chemotherapeutic efficacy of anticancer drugs .
Addition of adjuvants with standard anticancer drugs has shown successful reduction of adverse side effects .
The synthetic drug 5-Fluorouracil ( 5-FU ) shows several side effects upon prolonged chemotherapy , thereby restricting its long-term clinical application .
Several studies have reported anticancer potential and anti-inflammatory activity of tangeretin ( TAN ) towards mammalian cells .
Therefore , we investigate whether the combination of TAN with 5-FU increases their anticancer potential against colorectal cancer .
In this study , we examined the synergistic @ @ @ @ @ @ @ viability of several human cancer and normal cells .
Several possible mechanistic pathways were screened , and found that co-exposure of TAN and 5-FU accelerates oxidative-stress and increases endogenous-ROS generation , which sequentially triggers the DNA damage response and activates the apoptotic pathway , by down-regulating autophagy and DNA repair system in HCT-116 cells .
TAN and 5-FU co-treatment also remarkably reduces the mitochondrial membrane potential , and sequentially decreases ATPase activity .
Collectively , results indicate that combination of TAN and 5-FU significantly accelerates apoptosis via JNK mediated pathway .
To our @ @ @ @ @ @ @ is the first to describe synergistic activity of TAN and 5-FU against colorectal cancer cells .

Synergistic therapy is emerging as a promising strategy for improving the chemotherapeutic efficacy of anticancer drugs. Addition of adjuvants with standard anticancer drugs has shown successful reduction of adverse side effects. The synthetic drug 5-Fluorouracil (5-FU) shows several side effects upon prolonged chemotherapy, thereby restricting its long-term clinical application. Several studies have reported anticancer potential and anti-inflammatory activity of tangeretin (TAN) towards mammalian cells. Therefore, we investigate whether the combination of TAN with 5-FU increases their anticancer potential against colorectal cancer. In this study, we examined the synergistic activity of TAN and 5-FU on the viability of several human cancer and normal cells. Several possible mechanistic pathways were screened, and found that co-exposure of TAN and 5-FU accelerates oxidative-stress and increases endogenous-ROS generation, which sequentially triggers the DNA damage response and activates the apoptotic pathway, by down-regulating autophagy and DNA repair system in HCT-116 cells. TAN and 5-FU co-treatment also remarkably reduces the mitochondrial membrane potential, and sequentially decreases ATPase activity. Collectively, results indicate that combination of TAN and 5-FU significantly accelerates apoptosis via JNK mediated pathway. To our knowledge gained from literature, this study is the first to describe synergistic activity of TAN and 5-FU against colorectal cancer cells.


greenmedinfo--2020-08-22--Perillaldehyde prevents the formations of atherosclerotic plaques through recoupling endothelial nit

Perillaldehyde prevents the formations of atherosclerotic plaques through recoupling endothelial nitric oxide synthase.

BACKGROUNDS : Nitric oxide ( NO ) produced by endothelial NO synthase ( eNOS ) is essential for cardiovascular homeostasis owing to its anti-inflammatory , antithrombotic , antiproliferative , and antioxidant effects .
Perillaldehyde ( PAH ) , one of the major oil components in Perilla frutescens , has anti-inflammatory effects .
AIM : This study was designed to explore whether PAH prevents atherosclerosis through normalizing eNOS functions .
METHODS : The model of atherosclerosis was induced by feeding rats and mice with high-fat diet or plus balloon injury .
Oil red and hematoxylin-eosin ( HE ) stainings were used @ @ @ @ @ @ @ : Pretreatment of PAH for 30 minutes concentration-dependently increased tetrahydrobiopterin ( BH4 ) levels , NO generations , and improved cell viabilities in cultured human umbilicus vessel endothelial cells ( HUVEC ) incubated with oxidized ( OX ) low-density lipoprotein ( LDL ) , in which all protective effects of PAH were abolished by guanosinetriphosphate ( GTP ) cyclohydrolase 1 inhibitor 2,4-Diamino-6-hydroxypyrimidine ( DAHP ) or eNOS inhibitor L-NAME in those cells .
In rats , high-fat diet plus balloon injury induced the formation of atherosclerotic plaque in carotid arteries .
Administration of @ @ @ @ @ @ @ plaque in rats and improved the responses of aortic rings to acetylcholine isolated from rats , accompanied with increased BH4 content and NO generations .
In Apoemice feeding with normal diet or high-fat diet , PAH ( 150 mg/kg ) reduced the size of atherosclerotic plaque in aortic arteries , prevented endothelial dysfunctions , and increased both BH4 and NO generations in carotid arteries .
CONCLUSION : PAH prevents the growth of atherosclerosis through increasing BH4 generation and subsequent eNOS recouping .
Clinically , PAH should be considered as a new medicine to @ @ @ @ @

BACKGROUNDS: Nitric oxide (NO) produced by endothelial NO synthase (eNOS) is essential for cardiovascular homeostasis owing to its anti-inflammatory, antithrombotic, antiproliferative, and antioxidant effects. Perillaldehyde (PAH), one of the major oil components in Perilla frutescens, has anti-inflammatory effects.
AIM: This study was designed to explore whether PAH prevents atherosclerosis through normalizing eNOS functions.
METHODS: The model of atherosclerosis was induced by feeding rats and mice with high-fat diet or plus balloon injury. Oil red and hematoxylin-eosin (HE) stainings were used to assess the atherosclerotic plaque.
RESULTS: Pretreatment of PAH for 30 minutes concentration-dependently increased tetrahydrobiopterin (BH4) levels, NO generations, and improved cell viabilities in cultured human umbilicus vessel endothelial cells (HUVEC) incubated with oxidized (OX) low-density lipoprotein (LDL), in which all protective effects of PAH were abolished by guanosinetriphosphate (GTP) cyclohydrolase 1 inhibitor 2,4-Diamino-6-hydroxypyrimidine (DAHP) or eNOS inhibitor L-NAME in those cells. In rats, high-fat diet plus balloon injury induced the formation of atherosclerotic plaque in carotid arteries. Administration of PAH or lovastatin reduced thesize of atherosclerotic plaque in rats and improved the responses of aortic rings to acetylcholine isolated from rats, accompanied with increased BH4 content and NO generations. In Apoemice feeding with normal diet or high-fat diet, PAH (150 mg/kg) reduced the size of atherosclerotic plaque in aortic arteries, prevented endothelial dysfunctions, and increased both BH4 and NO generations in carotid arteries.
CONCLUSION: PAH prevents the growth of atherosclerosis through increasing BH4 generation and subsequent eNOS recouping. Clinically, PAH should be considered as a new medicine to treat patients with atherosclerosis.


greenmedinfo--2020-08-22--Perillaldehyde: a promising antifungal agent to treat oropharyngeal candidiasis.

Perillaldehyde ( PAE ) , a natural monoterpenoid agent extracted from Perilla frutescence leaves , PAE has been reported to @ @ @ @ @ such as anti-inflammation , anti-oxidative and anti-fungal .
In this study , we show that @ @ @ @ @ against C. albicans .
Candida albicans , a fungal pathogen with high incidence of antifungal @ @ @ @ @ is the major cause of oropharyngeal candidiasis ( OPC ) .
OPC is characterized by @ @ @ @ @ infections .
Our in vitro results show PAE inhibited several virulence attributes of C. albicans @ @ @ @ @ transition and SAPs ( secreted aspartic proteinases ) gene expression .
Using an experimental murine @ @ @ @ @ found that PAE inhibited NLRP3 inflammasome assembly , reduced the excessive accumulation of ROS and @ @ @ @ @ nuclear ; processes all leading to reduced inflammation burden in the host .
Together , @ @ @ @ @ use PAE as a promising new agent to improve OPC .

Perillaldehyde (PAE), a natural monoterpenoid agent extracted from Perilla frutescence leaves, PAE has been reported to present various physiological capabilities, such as anti-inflammation, anti-oxidative and anti-fungal. In this study, we show that PAE exhibits strong antifungal activity against C. albicans. Candida albicans, a fungal pathogen with high incidence of antifungal resistance in clinical settings, is the major cause of oropharyngeal candidiasis (OPC). OPC is characterized by inflammatory immunological responses to fungal infections. Our in vitro results show PAE inhibited several virulence attributes of C. albicans including biofilm formation, yeast-to-hyphal transition and SAPs (secreted aspartic proteinases) gene expression. Using an experimental murine model of OPC, we found that PAE inhibited NLRP3 inflammasome assembly, reduced the excessive accumulation of ROS and prevented the p65 transfer in nuclear; processes all leading to reduced inflammation burden in the host. Together, this supports edible perilla or use PAE as a promising new agent to improve OPC.


greenmedinfo--2020-08-22--Coix seed oil prolongs lifespan and enhances stress resistance in Caenorhabditis elegans.

Coix seed oil ( CSO ) has many beneficial effects , but there is limited research on its influence on @ @ @ @ @ to senescence .
Here , we used Caenorhabditis elegans as an in vivo model to @ @ @ @ @ longevity .
CSO ( 1 mg/mL ) significantly extended the mean lifespan of C. elegans @ @ @ @ @ markedly improved stress resistance .
Gene-specific mutant studies showed that the CSO-mediated increase in life @ @ @ @ @ , hsf-1 and daf-16 , but not daf-2 .
Furthermore , CSO significantly upregulated stress-inducible @ @ @ @ @ its downstream genes ( sod-3 , hsp-16.2 and gst-4 ) .
In addition , four @ @ @ @ @ , oleic , palmitic and stearic , played leading roles in C. elegans ' extended @ @ @ @ @ increased the life expectancy of , and enhanced the stressresistance in , C. elegans mainly @ @ @ @ @ genes , but not through the insulin/insulin-like growth factor 1 signaling pathway .

Coix seed oil (CSO) has many beneficial effects, but there is limited research on its influence on the processes and mechanisms related to senescence. Here, we used Caenorhabditis elegans as an in vivo model to investigate CSO's bioeffects on longevity. CSO (1 mg/mL) significantly extended the mean lifespan of C. elegans by over 22.79% and markedly improved stress resistance. Gene-specific mutant studies showed that the CSO-mediated increase in life expectancy was dependent on mev-1, hsf-1 and daf-16, but not daf-2. Furthermore, CSO significantly upregulated stress-inducible genes, including daf-16 and its downstream genes (sod-3, hsp-16.2 and gst-4). In addition, four major fatty acids, linoleic, oleic, palmitic and stearic, played leading roles in C. elegans' extended lifespan. Thus, CSO increased the life expectancy of, and enhanced the stressresistance in, C. elegans mainly through daf-16 and its downstream genes, but not through the insulin/insulin-like growth factor 1 signaling pathway.


greenmedinfo--2020-08-22--Coixol decreased PMA-induced MUC5AC mucin secretion from NCI-H292 cells.

In this study , we investigated whether natural products including coixol derived from Coix Lachryma-Jobi var .
ma-yuen affect MUC5AC mucin gene expression , production and secretion from airway epithelial cells .
Confluent NCI-H292 cells were pretreated with oleic acid , linoleic acid , glyceryl trilinoleate , beta-stigmasterol or coixol for 30 min and then stimulated with PMA ( phorbol 12-myristate 13-acetate ) , EGF ( epidermal growth factor ) or TNF-α ( tumor necrosis factor-α ) for 24 h. The MUC5AC mucin gene expression , mucin protein production and secretion were measured by RT-PCR and ELISA .
The results @ @ @ @ @ @ @ Oleic acid , linoleic acid , glyceryl trilinoleate , beta-stigmasterol and coixol inhibited the expression of MUC5AC mucin gene induced by PMA from NCI-H292 cells ; ( 2 ) Oleic acid , linoleic acid , glyceryl trilinoleate , beta-stigmasterol and coixol also inhibited the production of MUC5AC mucin protein induced by the same inducers from NCI-H292 cells ; ( 3 ) Coixol inhibited the expression of MUC5AC mucin gene and production of MUC5AC mucin protein , induced by EGF or TNF-α from NCI-H292 cells ; ( 4 ) Coixol decreased PMA-induced MUC5AC mucin @ @ @ @ @ @ @ suggests that coixol , the characteristic component among the examined five natural products derived from C. Lachryma-Jobi var .
ma-yuen , can regulate gene expression , production and secretion of mucin , by directly acting on airway epithelial cells .

In this study, we investigated whether natural products including coixol derived from Coix Lachryma-Jobi var. ma-yuen affect MUC5AC mucin gene expression, production and secretion from airway epithelial cells. Confluent NCI-H292 cells were pretreated with oleic acid, linoleic acid, glyceryl trilinoleate, beta-stigmasterol or coixol for 30 min and then stimulated with PMA (phorbol 12-myristate 13-acetate), EGF (epidermal growth factor) or TNF-α (tumor necrosis factor-α) for 24 h. The MUC5AC mucin gene expression, mucin protein production and secretion were measured by RT-PCR and ELISA. The results were as follows: (1) Oleic acid, linoleic acid, glyceryl trilinoleate, beta-stigmasterol and coixol inhibited the expression of MUC5AC mucin gene induced by PMA from NCI-H292 cells; (2) Oleic acid, linoleic acid, glyceryl trilinoleate, beta-stigmasterol and coixol also inhibited the production of MUC5AC mucin protein induced by the same inducers from NCI-H292 cells; (3) Coixol inhibited the expression of MUC5AC mucin gene and production of MUC5AC mucin protein, induced by EGF or TNF-α from NCI-H292 cells; (4) Coixol decreased PMA-induced MUC5AC mucin secretion from NCI-H292 cells. This result suggests that coixol, the characteristic component among the examined five natural products derived from C. Lachryma-Jobi var. ma-yuen, can regulate gene expression, production and secretion of mucin, by directly acting on airway epithelial cells.


greenmedinfo--2020-08-22--Coixol suppresses NF-κB, MAPK pathways and NLRP3 inflammasome activation in lipopolysaccharide-induc

Coixol suppresses NF-κB, MAPK pathways and NLRP3 inflammasome activation in lipopolysaccharide-induced RAW 264.7 cells.

Coixol , a plant polyphenol extracted from coix ( L.var.Stapf ) , has not been investigated for its anti-inflammatory effect @ @ @ @ @ using a lipopolysaccharide ( LPS ) -induced macrophage cell model , we observed that coixol @ @ @ @ @ of interleukin ( IL ) -1β , IL-6 , IL-18 , tumor necrosis factor ( @ @ @ @ @ oxide ( NO ) , inducible nitric oxide synthases ( iNOS ) , and cyclooxygenase @ @ @ @ @ but had no effect on the expression of the anti-inflammatory mediator IL-10 .
Furthermore , @ @ @ @ @ mitogen-activated protein kinases ( MAPKs ) , nuclear transcription factor κ B ( NF-κB ) @ @ @ @ @ protein ( NLRP ) 3 inflammasome activation .
In conclusion , the present study demonstrates @ @ @ @ @ effects by inhibiting the expression of pro-inflammatory mediators in vitro .
The mechanism of this @ @ @ @ @ to its ability to inhibit the activation of NF-κB , MAPKs pathways , and NLRP3 @ @

Coixol, a plant polyphenol extracted from coix (L.var.Stapf), has not been investigated for its anti-inflammatory effect. In this study, using a lipopolysaccharide (LPS)-induced macrophage cell model, we observed that coixol can effectively reduce the expression of interleukin (IL)-1β, IL-6, IL-18, tumor necrosis factor (TNF)-α, nitric oxide (NO), inducible nitric oxide synthases (iNOS), and cyclooxygenase (COX)-2, but had no effect on the expression of the anti-inflammatory mediator IL-10. Furthermore, we found that coixol inhibits mitogen-activated protein kinases (MAPKs),nuclear transcription factor κ B (NF-κB) pathways, and NOD-like receptor protein (NLRP) 3 inflammasome activation. In conclusion, the present study demonstrates that coixol exerts certain anti-inflammatory effects by inhibiting the expression of pro-inflammatory mediators in vitro. The mechanism of this effect was in part related to its ability to inhibit the activation of NF-κB, MAPKs pathways, and NLRP3 inflammasome.


greenmedinfo--2020-08-22--Adlay seed extracts exhibit a prophylactic effect on diet-induced metabolic dysfunction and nonalcoh

Adlay seed extracts exhibit a prophylactic effect on diet-induced metabolic dysfunction and nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease ( NAFLD ) is common worldwide and closely associated with metabolic dysfunction .
NAFLD leads to a higher risk of development of severe liver diseases , such as nonalcoholic steatohepatitis ( NASH ) , liver cirrhosis , and hepatocellular carcinoma ( HCC ) .
To date , no pharmacotherapy targeting NAFLD has received general approval .
Adlay is a plant that has been used as traditional herbal medicine in Asia and is a promising candidate to solve this global issue .
We have established a mouse model of NAFLD by feeding a high-fat diet ( HFD @ @ @ @ @ @ @ ethanolic or water extracts of adlay seed ( ASE and ASW , respectively ) , mixed with HFD , were fed to the mice for 10 weeks .
The ASE and ASW treatment ameliorated hyperglycemia and improved the glucose tolerance and insulin resistance in the HFD mice .
Hyperlipidemia in HFD mice was prevented by the ASE and ASW diet .
In addition , the ASE and ASW supplementation attenuated hepatic steatosis and inflammation , improved liver function , and caused no harm to the kidneys .
Moreover , the mechanism of the @ @ @ @ @ @ @ hepatic lipogenesis and inducing fatty acid-oxidation was certified by the simulated human fatty liver cell model .
Our study showed the regulatory potential of the extracts of adlay seeds for alleviating NAFLD , as well as related liver and metabolic diseases .

Nonalcoholic fatty liver disease (NAFLD) is common worldwide and closely associated with metabolic dysfunction. NAFLD leads to a higher risk of development of severe liver diseases, such as nonalcoholic steatohepatitis (NASH), liver cirrhosis, and hepatocellular carcinoma (HCC). To date, no pharmacotherapy targeting NAFLD has received general approval. Adlay is a plant that has been used as traditional herbal medicine in Asia and is a promising candidate to solve this global issue. We have established a mouse model of NAFLD by feeding a high-fat diet (HFD) for 10 weeks. Here, ethanolic or water extracts of adlay seed (ASE and ASW, respectively), mixed with HFD, were fed to the mice for 10 weeks. The ASE and ASW treatment ameliorated hyperglycemia and improved the glucose tolerance and insulin resistance in the HFD mice. Hyperlipidemia in HFD mice was prevented by the ASE and ASW diet. In addition, the ASE and ASW supplementation attenuated hepatic steatosis and inflammation, improved liver function, and caused no harm to the kidneys. Moreover, the mechanism of the effect of ASE and ASW on inhibiting hepatic lipogenesis and inducing fatty acid-oxidation was certified by the simulated human fatty liver cell model. Our study showed the regulatory potential of the extracts of adlay seeds for alleviating NAFLD, as well as related liver and metabolic diseases.


greenmedinfo--2020-08-22--Ayahuasca blocks the reinstatement of methylphenidate-induced conditioned place preference in mice.

RATIONALE : Accumulating evidence suggests that ayahuasca , a hallucinogenic beverage used in traditional Amazonian communities for ritualistic and curative purposes , has been associated with reduced rates of substance use disorders .
However , the brain mechanisms underlying the therapeutic effects of ayahuasca have not yet been fully elucidated .
OBJECTIVES : The aim of the present study was to investigate the effects of treatment with ayahuasca on the rewarding properties of the psychostimulant methylphenidate .
METHODS : The rewarding properties of ayahuasca ( 100 mg/kg , orally ) and methylphenidate ( 10 mg/kg , i.p . )
were @ @ @ @ @ @ @ CPP ) model .
Furthermore , we evaluated the effects of repeated treatment with ayahuasca on the reinstatement of methylphenidate-induced CPP .
Fos expression was evaluated in different limbic structures ( cingulate cortex-area 1 , prelimbic cortex , infralimbic cortex , orbitofrontal cortex-lateral orbital area , nucleus accumbens core and shell , ventral tegmental area , dorsal striatum , and basolateral amygdala ) upon each experimental phase .
RESULTS : Both ayahuasca and methylphenidate induced CPP in mice .
However , ayahuasca had limited effects on Fos expression , while methylphenidate altered Fos @ @ @ @ @ @ @ the behavioral effects of drugs of abuse .
Treatment with ayahuasca after conditioning with methylphenidate blocked the reinstatement of methylphenidate-induced CPP .
Those behavioral effects were accompanied by changes in Fos expression patterns , with ayahuasca generally blocking the changes in Fos expression induced by conditioning with methylphenidate and/or reexposure to methylphenidate .
CONCLUSIONS : Our findings suggest that ayahuasca restored normal brain function in areas associated with the long-term expression of drug wanting/seeking in animals conditioned to methylphenidate .

RATIONALE: Accumulating evidence suggests that ayahuasca, a hallucinogenic beverage used in traditional Amazonian communities for ritualistic and curative purposes, has been associated with reduced rates of substance use disorders. However, the brain mechanisms underlying the therapeutic effects of ayahuasca have not yet been fully elucidated.
OBJECTIVES: The aim of the present study was to investigate the effects of treatment with ayahuasca on the rewarding properties of the psychostimulant methylphenidate.
METHODS: The rewarding properties of ayahuasca (100 mg/kg, orally) and methylphenidate (10 mg/kg, i.p.) were investigated using the conditioned place preference (CPP) model. Furthermore, we evaluated the effects of repeated treatment with ayahuasca on the reinstatement of methylphenidate-induced CPP. Fos expression was evaluated in different limbic structures (cingulate cortex-area 1, prelimbic cortex, infralimbic cortex, orbitofrontal cortex-lateral orbital area, nucleus accumbens core and shell, ventral tegmental area, dorsal striatum, and basolateral amygdala) upon each experimental phase.
RESULTS: Both ayahuasca and methylphenidate induced CPP in mice. However, ayahuasca had limited effects on Fos expression, while methylphenidate altered Fos expression in several brain regions associated with the behavioral effects of drugs of abuse. Treatment with ayahuasca after conditioning with methylphenidate blocked the reinstatement of methylphenidate-induced CPP. Those behavioral effects were accompanied by changes in Fos expression patterns, with ayahuasca generally blocking the changes in Fos expression induced by conditioning with methylphenidate and/or reexposure to methylphenidate.
CONCLUSIONS: Our findings suggest that ayahuasca restored normal brain function in areas associated with the long-term expression of drug wanting/seeking in animals conditioned to methylphenidate.


greenmedinfo--2020-08-22--Modulatory effects of ayahuasca on personality structure in a traditional framework.

: Ayahuasca is a psychoactive plant brew containing dimethyltryptamine ( DMT ) and monoamine oxidase inhibitors ( MAOIs ) .
It originates from the Amazon basin , where it is used primarily for ceremonial purposes .
Ayahuasca tourists are now entering certain communities seeking alternative physical or psychological healing , as well as spiritual growth .
RATIONALE : Recent evidence has shown that the similar acting psychedelic compound , psilocybin , facilitated long-term increases in trait openness following a single administration .
OBJECTIVES : This paper assesses the impact of ayahuasca on personality in a traditional framework catering for ayahuasca @ @ @ @ @ @ @ design , we examined the effect of ayahuasca on participants ' personality ( measured by the NEO Personality Inventory 3 questionnaire ) across time ( pre- to post-ayahuasca administration , and 6-month follow-up ) , relative to a comparison group ( who did not ingest ayahuasca ) .
RESULTS : The results demonstrated significant increases in agreeableness pre- and post-ayahuasca administration and significant reductions in neuroticism in 24 participants , relative to the comparison group .
Both of these changes were sustained at 6-month follow-up , and trait level increases were also observed @ @ @ @ @ @ @ , greater perceived mystical experience ( measured using the Mystical Experience Questionnaire 30 ) was associated with increased reductions in neuroticism .
CONCLUSIONS : These findings , which indicate a positive mediating effect of ayahuasca on personality , support the growing literature suggesting potential therapeutic avenues for serotonergic psychedelics .

: Ayahuasca is a psychoactive plant brew containing dimethyltryptamine (DMT) and monoamine oxidase inhibitors (MAOIs). It originates from the Amazon basin, where it is used primarily for ceremonial purposes. Ayahuasca tourists are now entering certain communities seeking alternative physical or psychological healing, as well as spiritual growth.
RATIONALE: Recent evidence has shown that the similar acting psychedelic compound, psilocybin, facilitated long-term increases in trait openness following a single administration.
OBJECTIVES: This paper assesses the impact of ayahuasca on personality in a traditional framework catering for ayahuasca tourists.
METHOD: Within a mixed design, we examined the effect of ayahuasca on participants' personality (measured by the NEO Personality Inventory 3 questionnaire) across time (pre- to post-ayahuasca administration, and 6-month follow-up), relative to a comparison group (who did not ingest ayahuasca).
RESULTS: The results demonstrated significant increases in agreeableness pre- and post-ayahuasca administration and significant reductions in neuroticism in 24 participants, relative to the comparison group. Both of these changes were sustained at 6-month follow-up, and trait level increases were also observed in openness at this stage. Additionally, greater perceived mystical experience (measured using the Mystical Experience Questionnaire 30) was associated with increased reductions in neuroticism.
CONCLUSIONS: These findings, which indicate a positive mediating effect of ayahuasca on personality, support the growing literature suggesting potential therapeutic avenues for serotonergic psychedelics.


greenmedinfo--2020-08-22--Ayahuasca - potential therapeutic properties in psychiatry. Research review

Ayahuasca , also known as '' the liana of the soul '' and '' the vine of the soul '' is a ritual psychedelic traditionally administered in the form of plant decoction , used by the indigenous people of South America for centuries , and in the last 25 years also in Europe , Asia , Africa , Australia , Canada , and the United States .
Its biological activity results from the content of N , N-dimethyltryptamine ( DMT ) , acting mainly as a non-selective agonist of serotonin receptors and beta-carboline alkaloids , which are strong and short-acting @ @ @ @ @ @ @ inhibitors .
For many years there have been reports of both the anti-anxiety and antidepressant effects of ayahuasca , as well as indications of the possibility of its use in the treatment of addictions .
The results of studies of its effectiveness in drug-resistant depression seem to be promising , comparable in the opinion of some authors with the effect of therapeutic action of ketamine .
In the article , we try to explain the complex profile of action and the resulting potential benefits , but also the risk of interaction and adverse @ @ @ @ @ @ @ , which is important given the high variability of herbal mixtures used to produce the decoction .

Ayahuasca, also known as"the liana of the soul"and"the vine of the soul"is a ritual psychedelic traditionally administered in the form of plant decoction, used by the indigenous people of South America for centuries, and in the last 25 years also in Europe, Asia, Africa, Australia, Canada, and the United States. Its biological activity results from the content of N,N-dimethyltryptamine (DMT), acting mainly as a non-selective agonist of serotonin receptors and beta-carboline alkaloids, which are strong and short-acting monoamine oxidase type A(MAOI-A) inhibitors. For many years there have been reports of both the anti-anxiety and antidepressant effects of ayahuasca, as well as indications of the possibility of its use in the treatment of addictions. The results of studies of its effectiveness in drug-resistant depression seem to be promising, comparable in the opinion of some authors with the effect of therapeutic action of ketamine. In the article, we try to explain the complex profile of action and the resulting potential benefits, but also the risk of interaction and adverse effects associated with the taking of ayahuasca, which is important given the high variability of herbal mixtures used to produce the decoction.


greenmedinfo--2020-08-22--A review of psychedelic treatments for psychiatric disorders.

INTRODUCTION : Interest in the use of psychedelic substances for the treatment of mental disorders is increasing .
Processes that may affect therapeutic change are not yet fully understood .
Qualitative research methods are increasingly used to examine patient accounts ; however , currently , no systematic review exists that synthesizes these findings in relation to the use of psychedelics for the treatment of mental disorders .
OBJECTIVE : To provide an overview of salient themes in patient experiences of psychedelic treatments for mental disorders , presenting both common and diverging elements in patients ' accounts , and elucidating how @ @ @ @ @ @ @ : We systematically searched the PubMed , MEDLINE , PsycINFO , and Embase databases for English-language qualitative literature without time limitations .
Inclusion criteria were qualitative research design ; peer-reviewed studies ; based on verbalized patient utterances ; and a level of abstraction or analysis of the results .
Thematic synthesis was used to analyze and synthesize results across studies .
A critical appraisal of study quality and methodological rigor was conducted using the Critical Appraisal Skills Programme ( CASP ) .
RESULTS : Fifteen research articles , comprising 178 patient experiences , @ @ @ @ @ @ @ heterogeneity in terms of substance , mental disorder , treatment context , and qualitative methodology .
Substances included psilocybin , lysergic acid diethylamide ( LSD ) , ibogaine , ayahuasca , ketamine and 3,4-methylenedioxymethamphetamine ( MDMA ) .
Disorders included anxiety , depression , eating disorders , post-traumatic stress disorder , and substance use disorders .
While the included compounds were heterogeneous in pharmacology and treatment contexts , patients reported largely comparable experiences across disorders , which included phenomenological analogous effects , perspectives on the intervention , therapeutic processes and treatment outcomes .
@ @ @ @ @ @ @ self-perception , increased connectedness , transcendental experiences , and an expanded emotional spectrum , which patients reported contributed to clinically and personally relevant responses .
CONCLUSIONS : This review demonstrates how qualitative research of psychedelic treatments can contribute to distinguishing specific features of specific substances , and carry otherwise undiscovered implications for the treatment of specific psychiatric disorders .

INTRODUCTION: Interest in the use of psychedelic substances for the treatment of mental disorders is increasing. Processes that may affect therapeutic change are not yet fully understood. Qualitative research methods are increasingly used to examine patient accounts; however, currently, no systematic review exists that synthesizes these findings in relation to the use of psychedelics for the treatment of mental disorders.
OBJECTIVE: To provide an overview of salient themes in patient experiences of psychedelic treatments for mental disorders, presenting both common and diverging elements in patients' accounts, and elucidating how these affect the treatment process.
METHODS: We systematically searched the PubMed, MEDLINE, PsycINFO, and Embase databases for English-language qualitative literature without time limitations. Inclusion criteria were qualitative research design; peer-reviewed studies; based on verbalized patient utterances; and a level of abstraction or analysis of the results. Thematic synthesis was used to analyze and synthesize results across studies. A critical appraisal of study quality and methodological rigor was conducted using the Critical Appraisal Skills Programme (CASP).
RESULTS: Fifteen research articles, comprising 178 patient experiences, were included. Studies exhibited a broad heterogeneity in terms of substance, mental disorder, treatment context, and qualitative methodology. Substances included psilocybin, lysergic acid diethylamide (LSD), ibogaine, ayahuasca, ketamine and 3,4-methylenedioxymethamphetamine (MDMA). Disorders included anxiety, depression, eating disorders, post-traumatic stress disorder, and substance use disorders. While the included compounds were heterogeneous in pharmacology and treatment contexts, patients reported largely comparable experiences across disorders, which included phenomenological analogous effects, perspectives on the intervention, therapeutic processes and treatment outcomes. Comparable therapeutic processes included insights, altered self-perception, increased connectedness, transcendental experiences, and an expanded emotional spectrum, which patients reported contributed to clinically and personally relevant responses.
CONCLUSIONS: This review demonstrates how qualitative research of psychedelic treatments can contribute to distinguishing specific features of specific substances, and carry otherwise undiscovered implications for the treatment of specific psychiatric disorders.


greenmedinfo--2020-08-22--Citrus flavone tangeretin is a potential insulin sensitizer.

BACKGROUND : Tangeretin , a flavonoid derived from citrus peel , showed anti-diabetic effects .
However , the role of tangeretin on liver , the organ that act as target of insulin and play the central role in maintaining the blood glucose level control , is still largely unknown .
The current study was designed to assess the effect of tangeretin on liver insulin sensitivity in vitro and in vivo .
METHODS : Primary hepatocytes and mice were treated with different dose of tangeretin , parameters of insulin sensitivity , such as blood glucose levels , serum insulin levels , @ @ @ @ @ @ @ insulin tolerate test ( ITT ) , insulin stimulated IR-AKT pathway were analyzed .
RESULTS : Primary hepatocytes treated with 10/20 μM tangeretin showed up-regulated insulin signaling pathway as well as the glycogen content , while the glucose output were reduced .
Intragastric administration of tangeretin ( 25/50 mg/kg ) also ameliorated the liver insulin sensitivity and improved the glucose homeostasis , both in wild type C57 mice and in db/db mice , a diabetic model .
Tangeretin treatment dose-dependently suppressed the MEK-ERK1/2 pathway , while forced activation of p-ERK1/2 reversed the insulin @ @ @ @ @ @ @ These results indicated that tangeretin enhanced the liver insulin sensitivity in vitro and in vivo , through suppressing the MEK-ERK1/2 pathway .

BACKGROUND: Tangeretin, a flavonoid derived from citrus peel, showed anti-diabetic effects. However, the role of tangeretin on liver, the organ that act as target of insulin and play the central role in maintaining the blood glucose level control, is still largely unknown. The current study was designed to assess the effect of tangeretin on liver insulin sensitivity in vitro and in vivo.
METHODS: Primary hepatocytes and mice were treated with different dose of tangeretin, parameters of insulin sensitivity, such as blood glucose levels, serum insulin levels, glucose tolerate test (GTT), insulin tolerate test (ITT), insulin stimulated IR-AKT pathway were analyzed.
RESULTS: Primary hepatocytes treated with 10/20 μM tangeretin showed up-regulated insulin signaling pathway as well as the glycogen content, while the glucose output were reduced. Intragastric administration of tangeretin (25/50 mg/kg) also ameliorated the liver insulin sensitivity and improved the glucose homeostasis, both in wild type C57 mice and in db/db mice, a diabetic model. Tangeretin treatment dose-dependently suppressed the MEK-ERK1/2 pathway, while forced activation of p-ERK1/2 reversed the insulin sensitized effect of tangeretin.
CONCLUSION: These results indicated that tangeretin enhanced the liver insulin sensitivity in vitro and in vivo, through suppressing the MEK-ERK1/2 pathway.


greenmedinfo--2020-08-22--The result clearly showed tangeretin neuro-protective and anti-inflammatory effect against ischemia/

The result clearly showed tangeretin neuro-protective and anti-inflammatory effect against ischemia/reperfusion injury.

The neuro-inflammation is well known to be an inflammatory response in the brain tissue .
Anti-inflammatory therapy in ischemia/reperfusion ( @ @ @ @ @ potential therapeutic strategy for post-I/R injury .
Currently , we made attempt to scrutinize the @ @ @ @ @ I/R injury in the brain of experimental rats .
I/R injury is induced in the @ @ @ @ @ artery occlusion ( 2 h ) and reperfusion ( 20 h ) .
The infarction @ @ @ @ @ and neurofunctional parameters were also estimated .
Inflammatory cytokines and brain injury markers were scrutinized @ @ @ @ @ study .
mRNA expression of interleukin 6 ( IL-6 ) , toll-like receptor-4 ( TLR-4 @ @ @ @ @ IL-1β ) , tumor necrosis factor-α ( TNF-α ) , interferon-γ ( IFNG-γ ) , @ @ @ @ @ TGF-β1 ) was estimated using the qRT-PCR .
Tangeretin significantly ( P

The neuro-inflammation is well known to be an inflammatory response in the brain tissue. Anti-inflammatory therapy in ischemia/reperfusion (I/R) pathogenesis is a potential therapeutic strategy for post-I/R injury. Currently, we made attempt to scrutinize the neuro-protective effect of tangeretin against I/R injury in the brain of experimental rats. I/R injury is induced in the brain via transient middle cerebral artery occlusion (2 h) and reperfusion (20 h). The infarction area, brain water content and neurofunctional parameters were also estimated. Inflammatory cytokines and brain injury markers were scrutinized at the end of the study. mRNA expression of interleukin 6 (IL-6), toll-like receptor-4 (TLR-4), interleukin 1β(IL-1β), tumor necrosis factor-α (TNF-α), interferon-γ (IFNG-γ), and transforming growth factor-β1 (TGF-β1) was estimated using the qRT-PCR. Tangeretin significantly (P < 0.001) decreased brain water content, infarct volume, neurological score, brain edema, and Evans blue leakage. Tangeretin significantly (P < 0.001) down-regulated the inflammatory and pro-inflammatory cytokines and oxidative stress parameters in the serum and brain tissue of experimental rats. qRT-PCR data demonstrated that rats treated with tangeretin could significantly (P < 0.001) suppress the IL-1β, TLR-4 TNF-α, IFNG-γ, and IL-6 and boost the expression of TGF-β1 compared with I/R injury rats. The result clearly showed tangeretin neuro-protective and anti-inflammatory effect against I/R injury in rats through suppressed inflammatory reaction.


greenmedinfo--2020-08-22--Synergistic effect of tangeretin and atorvastatin for colon cancer combination therapy.

Purpose : Colorectal cancer ( CRC ) is the third most frequently diagnosed cancer and the fourth leading cause of cancer death over the world .
Nano-sized drug delivery systems are used for the treatment of cancers .
The aim of this study was to develop a tangeretin ( TAGE ) and atorvastatin ( ATST ) combined nano-system decorated with RGD ( RGD-ATST/TAGE CNPs ) for colon cancer combination therapy .
Materials and Methods : In this study , cyclized arginine-glycine-aspartic acid sequences ( RGD ) contained ligand was synthesized by conjugating cyclo ( Arg-Gly-Asp-d-Phe-Lys ) ( cRGDfK ) with @ @ @ @ @ @ @ ) using polyethylene glycol ( PEG ) as a linker to obtain cRGDfK-PEG-TOSD .
ATST and TAGE combined nano-systems : RGD-ATST/TAGE CNPs were prepared .
The combination effects as well as antitumor effects of these two agents were evaluated on colon cancer cells and mice bearing cancer models .
Results : Drug entrapment efficiencies of nano-systems were high ( around 90 % ) , suggesting the good loading capacity .
The release profiles of ATST or TAGE from RGD-ATST/TAGE CNPs followed Higuchi model .
The RGD-decorated nano-system showed more obvious cytotoxicity on HT-29 @ @ @ @ @ @ @ no obvious difference was found on normal CCD-18 cells .
The strongest synergism was observed when the weight ratio of ATST to TAGE was 1:1 .
In vivo biodistribution of RGD-ATST/TAGE CNPs in the tumor site is high and prominently inhibited the in vivo tumor growth .
Conclusion : The results demonstrated that RGD-ATST/TAGE CNPs showed the most significant synergistic therapeutic efficacy , exhibited no significant toxicity to major organs and tissues , and body weight of the treated mice was stable .
Therefore , the combination nano-system is a promising platform for @ @ @ @

Purpose: Colorectal cancer (CRC) is the third most frequently diagnosed cancer and the fourth leading cause of cancer death over the world. Nano-sized drug delivery systems are used for the treatment of cancers. The aim of this study was to develop a tangeretin (TAGE) and atorvastatin (ATST) combined nano-system decorated with RGD (RGD-ATST/TAGE CNPs) for colon cancer combination therapy.
Materials and Methods: In this study, cyclized arginine-glycine-aspartic acid sequences (RGD) contained ligand was synthesized by conjugating cyclo (Arg-Gly-Asp-d-Phe-Lys) (cRGDfK) with D--tocopheryl succinate dichloromethane (TOSD) using polyethylene glycol (PEG) as a linker to obtain cRGDfK-PEG-TOSD. ATST and TAGE combined nano-systems: RGD-ATST/TAGE CNPs were prepared. The combination effects as well as antitumor effects of these two agents were evaluated on colon cancer cells and mice bearing cancer models.
Results: Drug entrapment efficiencies of nano-systems were high (around 90%), suggesting the good loading capacity. The release profiles of ATST or TAGE from RGD-ATST/TAGE CNPs followed Higuchi model. The RGD-decorated nano-system showed more obvious cytotoxicity on HT-29 cells than the undecorated nano-system, but no obvious difference was found on normal CCD-18 cells. The strongest synergism was observed when the weight ratio of ATST to TAGE was 1:1. In vivo biodistribution of RGD-ATST/TAGE CNPs in the tumor site is high and prominently inhibited the in vivo tumor growth.
Conclusion: The results demonstrated that RGD-ATST/TAGE CNPs showed the most significant synergistic therapeutic efficacy, exhibited no significant toxicity to major organs and tissues, and body weight of the treated mice was stable. Therefore, the combination nano-system is a promising platform for colon cancer therapy.


greenmedinfo--2020-08-22--Anti- Helicobacter pylori activity and inhibition of gastritis by Allium hookeri extract.

is widely consumed plant as a vegetable and herbal medicine in southeastern Asia.has been reported antioxidant , improvement of bone health and antidiabetic effects .
In the present study , we investigated the potential inhibitory effect ofextract ( AHE ) on .
Theanti-bacterial activities of AHE were determined by disk agar diffusion method .
Also , the inhibition effect of the AHE oninfection was investigated using a mouse model.colonization was confirmed by rapid urease tests , as described previously .
Mucosal damage was evaluated grossly and histologically according to previously described criteria .
As the results of the disk agar @ @ @ @ @ @ @ MTZ inhibited the bacterial growth with inhibition zone of 19.2 , 15.2 and 7.5 mm , respectively .
AHE 100µg/mL showed an inhibition zone value of 20.6 mm .
Rapid urease tests of the mice stomachs demonstrated a significant reduction incolonization .
In addition to the therapeutic effect againstinfection , the AHE reduced mucosal inflammation and epithelial damages in the stomach of-infected mice .
These results demonstrate that the AHE successfully cured aninfection and treated theinfection .
This AHE could be a promising treatment for patients with gastric complaints including gastritis caused by @

is widely consumed plant as a vegetable and herbal medicine in southeastern Asia.has been reported antioxidant, improvement of bone health and antidiabetic effects. In the present study, we investigated the potential inhibitory effect ofextract (AHE) on. Theanti-bacterial activities of AHE were determined by disk agar diffusion method. Also, the inhibition effect of the AHE oninfection was investigated using a mouse model.colonization was confirmed by rapid urease tests, as described previously. Mucosal damage was evaluated grossly and histologically according to previously described criteria. As the results of the disk agar diffusion assay, CLR, AMX and MTZ inhibited the bacterial growth with inhibition zone of 19.2, 15.2 and 7.5 mm, respectively. AHE 100µg/mL showed an inhibition zone value of 20.6 mm. Rapid urease tests of the mice stomachs demonstrated a significant reduction incolonization. In addition to the therapeutic effect againstinfection, the AHE reduced mucosal inflammation and epithelial damages in the stomach of-infected mice. These results demonstrate that the AHE successfully cured aninfection and treated theinfection. This AHE could be a promising treatment for patients with gastric complaints including gastritis caused by.


greenmedinfo--2020-08-23--Nobiletin could be used as a potential therapeutic to counter the nonylphenol-prompted oxidative str

Nobiletin could be used as a potential therapeutic to counter the nonylphenol-prompted oxidative stress and apoptotic damages in testes.

Nonylphenol ( NP ) is an environmental contaminant , which adversely affects the male fertility due to endocrine disruption and generation of oxidative stress .
The current research was planned to assess the effects of nobiletin ( NOB ) , a polymethoxyflavone , on NP-induced testicular damages .
Twenty-four male rats were divided into 4 groups : control ( 0.1 % DMSo ) , NP group ( 50 mg/kg ) , NP+NOB group ( 50 mg/kg + 25 mg/kg ) , and NOB group ( 25 mg/kg ) .
Our results revealed that NP brought down the activities of catalase @ @ @ @ @ @ @ SOD ) , glutathione peroxidase ( GPx ) and glutathione reductase ( GSR ) , while elevated the level of thiobarbituric acid reactive substances ( TBARS ) .
Additionally , NP decreased the level of follicle-stimulating hormone ( FSH ) , luteinizing hormone ( LH ) , plasma testosterone , daily sperm production ( DSP ) , epididymal sperm count , viability , motility , gene expression of testicular steroidogenic enzymes ( StAR , 3β-HSD and 17β-HSD ) and anti-apoptotic protein ( Bcl-2 ) , as well as number of spermatogenic cells belonging @ @ @ @ @ @ @ ( head , mid-piece/neck and tail ) abnormalities , expression of apoptotic proteins ( Bax and caspase-3 ) , and histopathological damages were increased .
However , NOB remarkably reversed all the damages caused by NP .
Therefore , it is deduced that NOB could be used as a potential therapeutic to counter the NP-prompted oxidative stress and apoptotic damages in testes .

Nonylphenol (NP) is an environmental contaminant, which adversely affects the male fertility due to endocrine disruption and generation of oxidative stress. The current research was planned to assess the effects of nobiletin (NOB), a polymethoxyflavone, on NP-induced testicular damages. Twenty-four male rats were divided into 4 groups: control (0.1% DMSo), NP group (50 mg/kg), NP+NOB group (50 mg/kg + 25 mg/kg), and NOB group (25 mg/kg). Our results revealed that NP brought down the activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GSR), while elevated the level of thiobarbituric acid reactive substances (TBARS). Additionally, NP decreased the level of follicle-stimulating hormone (FSH), luteinizing hormone (LH), plasma testosterone, daily sperm production (DSP), epididymal sperm count, viability, motility, gene expression of testicular steroidogenic enzymes (StAR, 3β-HSD and 17β-HSD) and anti-apoptotic protein (Bcl-2), as well as number of spermatogenic cells belonging to various stages. Whereas, sperm (head, mid-piece/neck and tail) abnormalities, expression of apoptotic proteins (Bax and caspase-3), and histopathological damages were increased. However, NOB remarkably reversed all the damages caused by NP. Therefore, it is deduced that NOB could be used as a potential therapeutic to counter the NP-prompted oxidative stress and apoptotic damages in testes.


greenmedinfo--2020-08-23--Naringenin inhibited TLR4 expression and p65 phosphorylation in Wilms tumor xenograft tumors.

BACKGROUND : Nuclear factor kappa B ( NF-κB ) is usually activated in Wilms tumor ( WT ) cells and plays a critical role in WT development .
OBJECTIVE : The study purpose was to screen a NF-κB inhibitor from natural product library and explore its effects on WT development .
METHODS : Luciferase assay was employed to assess the effects of natural chemical son NF-κB activity .
CCK-8 assay was conducted to assess cell growth in response to naringenin .
WT xenograft model was established to analyze the effect of naringenin in vivo .
Quantitative real-time PCR and Western @ @ @ @ @ @ @ and protein levels of relative genes , respectively .
RESULTS : Naringenin displayed significant inhibitory effect on NF-κB activation in SK-NEP-1 cells .
In SK-NEP-1 and G-401 cells , naringenin inhibited p65 phosphorylation .
Moreover , naringenin suppressed TNF-α-induced p65 phosphorylation in WT cells .
Naringenin inhibited TLR4 expression at both mRNA and protein levels in WT cells .
CCK-8 staining showed that naringenin inhibited cell growth of the two above WT cells in dose-and time-dependent manner , whereas Toll-like receptor 4 ( TLR4 ) over expression partially reversed the above phenomena .
@ @ @ @ @ @ @ in dose-and time-dependent manner in vivo .
Western blot found that naringenin inhibited TLR4 expression and p65 phosphorylation in WT xenograft tumors .

BACKGROUND: Nuclear factor kappa B (NF-κB) is usually activated in Wilms tumor (WT) cells and plays a critical role in WT development.
OBJECTIVE: The study purpose was to screen a NF-κB inhibitor from natural product library and explore its effects on WT development.
METHODS: Luciferase assay was employed to assess the effects of natural chemical son NF-κB activity. CCK-8 assay was conducted to assess cell growth in response to naringenin. WT xenograft model was established to analyze the effect of naringenin in vivo. Quantitative real-time PCR and Western blot were performed to examine the mRNA and protein levels of relative genes, respectively.
RESULTS: Naringenin displayed significant inhibitory effect on NF-κB activation in SK-NEP-1 cells. In SK-NEP-1 and G-401 cells, naringenin inhibited p65 phosphorylation. Moreover, naringenin suppressed TNF-α-induced p65 phosphorylation in WT cells. Naringenin inhibited TLR4 expression at both mRNA and protein levels in WT cells. CCK-8 staining showed that naringenin inhibited cell growth of the two above WT cells in dose-and time-dependent manner, whereas Toll-like receptor 4 (TLR4) over expression partially reversed the above phenomena. Besides, naringenin suppressed WT tumor growth in dose-and time-dependent manner in vivo. Western blot found that naringenin inhibited TLR4 expression and p65 phosphorylation in WT xenograft tumors.
CONCLUSION: Naringenin inhibits WT development viasuppressing TLR4/NF-κB signaling.


greenmedinfo--2020-08-22--Defective insulin receptor signaling in patients with gestational diabetes is related to dysregulate

Defective insulin receptor signaling in patients with gestational diabetes is related to dysregulated miR-140 which can be improved by naringenin.

Gestational diabetes ( GDM ) affects about 20 % of pregnancies globally .
Defective insulin receptor ( IR ) signaling has been found in the placenta from patients with GDM , but the underly mechanism is still unclear .
In the present study , the mRNA and protein levels of IR-α , insulin receptor substrate 1 ( IRS-1 ) and inulin like growth factor 1 receptor ( IGF1R ) were detected in the placenta tissue samples from 33 GDM patients and 20 healthy controls .
Reduced IR-α protein level was observed in both obese and non-obese GDM patients , and @ @ @ @ @ @ @ GDM patients .
However , the IR-α and IGF1R mRNAs level was not significantly altered in GDM patients .
Subsequently , the expression of 10 miRNAs that have the potential targeting IR-α and IGF1R was examined by qRT-PCR in the placenta , and miR-140-3p was found overexpressed .
Through dual-luciferase assay and immunoblotting , miR-140-3p was confirmed to suppress IR-α and IGF1R expression via targeting the 3'UTRs .
As a treatment candidate , naringenin downregulated miR-140-3p level in trophoblasts and endothelial cells .
Meanwhile , IR-α and IGF1R expression was upregulated by naringenin @ @ @ @ @ @ @ in naringenin treated trophoblasts and endothelial cells .
Finally , naringenin upregulated cell viability , migration capacity of HTR-8/SVneo and HUVEC cells , and increased HUVEC cells angiogenesis in high glucose condition .
In conclusion , miR-140-3p overexpression contributes to the defective placental IR signaling in patients with GDM .
Naringenin treatment protects trophoblasts and endothelial cells from the harmful high glucose environment which have the potential for GDM treatment .

Gestational diabetes (GDM) affects about 20 % of pregnancies globally. Defective insulin receptor (IR) signaling has been found in the placenta from patients with GDM, but the underly mechanism is still unclear. In the present study, the mRNA and protein levels of IR-α, insulin receptor substrate 1(IRS-1) and inulin like growth factor 1 receptor (IGF1R) were detected in the placenta tissue samples from 33 GDM patients and 20 healthy controls. Reduced IR-α protein level was observed in both obese and non-obese GDM patients, and decreased IGF1R protein level wasfound in obese GDM patients. However, the IR-α and IGF1R mRNAs level was not significantly altered in GDM patients. Subsequently, the expression of 10 miRNAs that have the potential targeting IR-α and IGF1R was examined by qRT-PCR in the placenta, and miR-140-3p was found overexpressed. Through dual-luciferase assay and immunoblotting, miR-140-3p was confirmed to suppress IR-α and IGF1R expression via targeting the 3'UTRs. As a treatment candidate, naringenin downregulated miR-140-3p level in trophoblasts and endothelial cells. Meanwhile, IR-α and IGF1R expression was upregulated by naringenin, and the glucose uptake was increased in naringenin treated trophoblasts and endothelial cells. Finally, naringenin upregulated cell viability, migration capacity of HTR-8/SVneo and HUVEC cells, and increased HUVEC cells angiogenesis in high glucose condition. In conclusion, miR-140-3p overexpression contributes to the defective placental IR signaling in patients with GDM. Naringenin treatment protects trophoblasts and endothelial cells from the harmful high glucose environment which have the potential for GDM treatment.


greenmedinfo--2020-08-23--MDM2 as a target for ellagic acid‑mediated suppression of prostate cancer cells in vitro.

Prostate cancer ( PCa ) is the most common cancer in men .
Despite the available treatments for PCa , a significant number of patients relapse as the disease becomes hormonal‑independent .
p53 is a common tumor suppressor ; however , its activity is diminished via the overexpression of murine double minute‑2 ( MDM2 ) .
The pomegranate , walnuts , and blueberries are widely consumed fruits and nuts that contain several polyphenolic compounds , mainly ellagic acid ( EA ) .
The present study focused on the influence of EA on the p53/MDM2 pathway in PCa cell lines .
@ @ @ @ @ @ @ ( p53+/+ ) , 22RV1 ( p53-/+ ) , and PC3 ( p53-/- ) harboring different p53 genotypes were used in this research .
We found that EA downregulated the gene and protein expression levels ofMDM2 and increased the protein expression of p53 as determined by qPCR and western blot analyses .
Moreover , by using western blot analysis , we determined that EA increased the protein expression of the p53 target proteins p21 , p53 upregulated modulator of apoptosis ( PUMA ) [ also known as Bcl‑2‑binding component 3 ( BBC3 ) @ @ @ @ @ @ @ ) .
Furthermore , we found that EA induced apoptosis in the absence of p53 by downregulating MDM2 and X‑linked inhibitor of apoptosis protein ( XIAP ) protein expressions as determined by western blot analysis .
We conclude that EA suppressed PCa cells in vitro partly by downregulating MDM2 .

Prostate cancer (PCa) is the most common cancer in men. Despite the available treatments for PCa, a significant number of patients relapse as the disease becomes hormonal‑independent. p53 is a common tumor suppressor; however, its activity is diminished via the overexpression of murine double minute‑2 (MDM2). The pomegranate, walnuts, and blueberries are widely consumed fruits and nuts that contain several polyphenolic compounds, mainly ellagic acid (EA). The present study focused on the influence of EA on the p53/MDM2 pathway in PCa cell lines. Three human PCa cell lines PCa LNCaP (p53+/+), 22RV1 (p53-/+), and PC3 (p53-/-) harboring different p53 genotypes were used in this research. We found that EA downregulated the gene and protein expression levels ofMDM2 and increased the protein expression of p53 as determined by qPCR and western blot analyses. Moreover, by using western blot analysis, we determined that EA increased the protein expression of the p53 target proteins p21, p53 upregulated modulator of apoptosis (PUMA) [also known as Bcl‑2‑binding component 3 (BBC3)] and Phorbol‑12‑myristate‑13‑acetate‑induced protein 1 (NOXA). Furthermore, we found that EA induced apoptosis in the absence of p53 by downregulating MDM2 and X‑linked inhibitor of apoptosis protein (XIAP) protein expressions as determined by western blot analysis. We conclude that EA suppressed PCa cells in vitro partly by downregulating MDM2.


greenmedinfo--2020-08-23--Punicalagin is a neuraminidase inhibitor of influenza viruses.

Influenza A virus ( IAV ) causes great morbidity and mortality worldwide every year .
However , there are only a limited number of drugs clinically available against IAV infection .
Further , emergence of drug resistant strains can render those drugs ineffective .
Thus there is an unmet medical need to develop new anti-influenza agents .
In this study , we show that punicalagin from plants possesses strong anti-influenza activity with a low micromolar ICvalue in tissue culture .
Using a battery of bioassays such as single-cycle replication assay , neuraminidase ( NA ) inhibition assay , and virus @ @ @ @ @ @ @ the primary mechanism of action ( MOA ) of punicalagin is the NA-mediated viral release .
Moreover , punicalagin can inhibit replication of different strains of influenza A and B viruses , including oseltamivir-resistant virus ( NA/H274Y ) , indicating that punicalagin is a broad spectrum antiviral against both IAV and IBV .
Further , although punicalagin targets NA like oseltamivir , it has a different MOA .
These results suggest that punicalagin is an influenza NA inhibitor that may be further developed as a novel antiviral against influenza viruses .
This article @ @ @ @ @ @ @ reserved .

Influenza A virus (IAV) causes great morbidity and mortality worldwide every year. However, there are only a limited number of drugs clinically available against IAV infection. Further, emergence of drug resistant strains can render those drugs ineffective. Thus there is an unmet medical need to develop new anti-influenza agents. In this study, we show that punicalagin from plants possesses strong anti-influenza activity with a low micromolar ICvalue in tissue culture. Using a battery of bioassays such as single-cycle replication assay, neuraminidase (NA) inhibition assay, and virus yield reduction assay, we demonstrate that the primary mechanism of action (MOA) of punicalagin is the NA-mediated viral release. Moreover, punicalagin can inhibit replication of different strains of influenza A and B viruses, including oseltamivir-resistant virus (NA/H274Y), indicating that punicalagin is a broad spectrum antiviral against both IAV and IBV. Further, although punicalagin targets NA like oseltamivir, it has a different MOA. These results suggest that punicalagin is an influenza NA inhibitor that may be further developed as a novel antiviral against influenza viruses. This article is protected by copyright. All rights reserved.


greenmedinfo--2020-08-23--Punicalagin regulates apoptosis-autophagy switch via modulation of annexin A1 in colorectal cancer.

Punicalagin ( PU ) , a polyphenol extracted from pomegranate ( ) husk is proven to have anti-cancer effects on different types of cancer including colorectal cancer ( CRC ) .
Its role in modulating endogenous protein as a means of eliciting its anti-cancer effects , however , has not been explored to date .
Hence , this study aimed to investigate the role of PU in modulating the interplay between apoptosis and autophagy by regulating Annexin A1 ( Anx-A1 ) expression in HCT 116 colorectal adenocarcinoma cells .
In the study , selective cytotoxicity , pro-apoptotic , autophagic and @ @ @ @ @ @ @ which indicate therapeutic potential that this polyphenol has against CRC .
Autophagy flux analysis via flow cytometry showed significant autophagosomes degradation in treated cells , proving the involvement of autophagy .
Proteome profiling of 35 different proteins in the presence and absence of Anx-A1 antagonists in PU-treated cells demonstrated a complex interplay that happens between apoptosis and autophagy that suggests the possible simultaneous induction and inhibition of these two cell death mechanisms by PU .
Overall , this study suggests that PU induces autophagy while maintaining basal level of apoptosis as the main @ @ @ @ @ @ @ Anx-A1 expression in HCT 116 cells , and thus has a promising translational potential .

Punicalagin (PU), a polyphenol extracted from pomegranate () husk is proven to have anti-cancer effects on different types of cancer including colorectal cancer (CRC). Its role in modulating endogenous protein as a means of eliciting its anti-cancer effects, however, has not been explored to date. Hence, this study aimed to investigate the role of PU in modulating the interplay between apoptosis and autophagy by regulating Annexin A1 (Anx-A1) expression in HCT 116 colorectal adenocarcinoma cells. In the study, selective cytotoxicity, pro-apoptotic, autophagic and Anx-A1 downregulating properties of PU were shown which indicate therapeutic potential that this polyphenol has against CRC. Autophagy flux analysis via flow cytometry showed significant autophagosomes degradation in treated cells, proving the involvement of autophagy. Proteome profiling of 35 different proteins in the presence and absence of Anx-A1 antagonists in PU-treated cells demonstrated a complex interplay that happens between apoptosis and autophagy that suggests the possible simultaneous induction and inhibition of these two cell death mechanisms by PU. Overall, this study suggests that PU induces autophagy while maintaining basal level of apoptosis as the main mechanisms of cytotoxicity via the modulation of Anx-A1 expression in HCT 116 cells, and thus has a promising translational potential.


greenmedinfo--2020-08-23--Dietary Intake of rosmarinic acid increases serum inhibitory activity in amyloid A aggregation.

Serum amyloid A ( SAA ) is one of the most important precursor amyloid proteins and plays a vital step in AA amyloidosis , although the underlying aggregation mechanism has not been elucidated .
Since SAA aggregation is a key step in this pathogenesis , inhibitors are useful to prevent and treat AA amyloidosis , serving as tools to investigate the pathogenic mechanism .
In this study , we showed that rosmarinic acid ( RA ) , which is a well-known inhibitor of the aggregation of amyloidβ ( Aβ ) , displayed inhibitory activity against SAA aggregation in vitro using @ @ @ @ @ @ @ system with quantum-dot nanoprobes .
Therefore , we evaluated the amyloid aggregation inhibitory activity of blood and the deposition of SAA in organs by feeding mice withextract ( ME ) containing RA as an active substance .
Interestingly , the inhibitory activity of ME-fed mice sera for SAA and Aβ aggregation , measured with the MSHTS system , was higher than that of the control group .
The amount of amyloid deposition in the organs of ME-fed mice was lower than that in the control group , suggesting that the SAA aggregation inhibitory @ @ @ @ @ @ @ deposition .
Theseresults suggest that dietary intake of RA-containing ME enhanced amyloid aggregation inhibitory activity of blood and suppressed SAA deposition in organs .
This study also demonstrated that the MSHTS system could be applied to in vitro screening and to monitor comprehensive activity of metabolized foods adsorbed by blood .

Serum amyloid A (SAA) is one of the most important precursor amyloid proteins and plays a vital step in AA amyloidosis, although the underlying aggregation mechanism has not been elucidated. Since SAA aggregation is a key step in this pathogenesis, inhibitors are useful to prevent and treat AA amyloidosis, serving as tools to investigate the pathogenic mechanism. In this study, we showed that rosmarinic acid (RA), which is a well-known inhibitor of the aggregation of amyloidβ (Aβ), displayed inhibitory activity against SAA aggregation in vitro using a microliter-scale high-throughput screening (MSHTS) system with quantum-dot nanoprobes. Therefore, we evaluated the amyloid aggregation inhibitory activity of blood and the deposition of SAA in organs by feeding mice withextract (ME) containing RA as an active substance. Interestingly, the inhibitory activity of ME-fed mice sera for SAA and Aβ aggregation, measured with the MSHTS system, was higher than that of the control group. The amount of amyloid deposition in the organs of ME-fed mice was lower than that in the control group, suggesting that the SAA aggregation inhibitory activity of serum is associated with SAA deposition. Theseresults suggest that dietary intake of RA-containing ME enhanced amyloid aggregation inhibitory activity of blood and suppressed SAA deposition in organs. This study also demonstrated that the MSHTS system could be applied to in vitro screening and to monitor comprehensive activity of metabolized foods adsorbed by blood.


greenmedinfo--2020-08-23--Allicin suppresses growth and metastasis of gastric carcinoma.

Allicin is a natural product suppressing the progression of gastric carcinoma ( GC ) .
In the current study , @ @ @ @ @ effect of allicin was explored by focusing on the role of miR-383-5p/ERBB4 signaling .
Two @ @ @ @ @ with allicin and the effects on viability , apoptosis , migration , invasion , and @ @ @ @ @ were assessed .
The interaction between allicin and miR-383-5p was further explored by inhibiting the @ @ @ @ @ cell viability and induced apoptosis in both GC cell lines .
The compound also inhibited @ @ @ @ @ cells , which was associated with the up-regulation miR-383-5p and down-regulation of ERBB4 .
The @ @ @ @ @ inhibitor blocked the anti-GC effect of allicin .
Our results demonstrated that allicin contributed to @ @ @ @ @ potentials in GC cell lines .
The effect was accompanied by an increased level of @ @ @ @ @ ERBB4 .

Allicin is a natural product suppressing the progression of gastric carcinoma (GC). In the current study, the mechanism underlying the anti-GC effect of allicin was explored by focusing on the role of miR-383-5p/ERBB4 signaling. Two GC cell lines were treated with allicin and the effects on viability, apoptosis, migration, invasion, and miR-383-5p/ERBB4 activity in the cells were assessed. The interaction between allicin and miR-383-5p was further explored by inhibiting the miR-383-5p level. Allicin suppressed cell viability and induced apoptosis in both GC cell lines. The compound also inhibited migration and invasion of GC cells, which was associated with the up-regulation miR-383-5p and down-regulation of ERBB4. The inhibition of miR-383-5p by specific inhibitor blocked the anti-GC effect of allicin. Our results demonstrated that allicin contributed to the suppressed growth and metastasis potentials in GC cell lines. The effect was accompanied by an increased level of miR-383-5p and subsequent inhibition of ERBB4.


greenmedinfo--2020-08-23--Allicin‐induced host‐gut microbe interactions improves energy homeostasis.

Allicin ( diallylthiosulfinate ) is a natural food compound with multiple biological and pharmacological functions .
However , the mechanism of beneficial role of Allicin on energy homeostasis is not well studied .
Gut microbiota ( GM ) profoundly affects host metabolism via microbiota-host interactions and coevolution .
Here , we investigated the interventions of beneficial microbiome induced by Allicin on energy homeostasis , particularly obesity , and related complications .
Interestingly , Allicin treatment significantly improved GM composition and induced the most significant alteration enrichment of Bifidobacterium and Lactobacillus .
Importantly , transplantation of the Allicin-induced GM to HFD @ @ @ @ @ @ @ role in decreasing adiposity , maintaining glucose homeostasis , and ameliorating hepatic steatosis .
Furthermore , AGMT was effective in modulating lipid metabolism , activated brown adipose tissues ( BATs ) , induced browning in sWAT , reduced inflammation , and inhibited the degradation of intestinal villi .
Mechanically , AGMT significantly increased Blautia [ short-chain fatty acids ( SCFAs ) -producing microbiota ] and Bifidobacterium in HFD mice , also increased the SCFAs in the cecum , which has been proved many beneficial effects on energy homeostasis .
Our study highlights that @ @ @ @ @ @ @ role in regulating energy homeostasis , which provides a promising potential therapy for obesity and metabolic disorders based on host-microbe interactions .

Allicin (diallylthiosulfinate) is a natural food compound with multiple biological and pharmacological functions. However, the mechanism of beneficial role of Allicin on energy homeostasis is not well studied. Gut microbiota (GM) profoundly affects host metabolism via microbiota-host interactions and coevolution. Here, we investigated the interventions of beneficial microbiome induced by Allicin on energy homeostasis, particularly obesity, and related complications. Interestingly, Allicin treatment significantly improved GM composition and induced the most significant alteration enrichment of Bifidobacterium and Lactobacillus. Importantly, transplantation of the Allicin-induced GM to HFD mice (AGMT) played a remarkable role in decreasing adiposity, maintaining glucose homeostasis, and ameliorating hepatic steatosis. Furthermore, AGMT was effective in modulating lipid metabolism, activated brown adipose tissues (BATs), induced browning in sWAT, reduced inflammation, and inhibited the degradation of intestinal villi. Mechanically, AGMT significantly increased Blautia [short-chain fatty acids (SCFAs)-producing microbiota] and Bifidobacterium in HFD mice, also increased the SCFAs in the cecum, which has been proved many beneficial effects on energy homeostasis. Our study highlights that Allicin-induced host-gut microbe interactions plays an important role in regulating energy homeostasis, which provides a promising potential therapy for obesity and metabolic disorders based on host-microbe interactions.


greenmedinfo--2020-08-23--Allicin was found to be potentially effective on wound healing.

OBJECTIVE : The aim of this study was to investigate the effect of allicin on wound healing in an experimental diabetes model .
METHOD : In this randomised controlled study , 50 Wistar albino rats ( 25 females , 25 males ) each weighing 200-300g were used .
To develop the diabetes model , 30 rats were induced with 50mg/kg streptozotocin ( STZ ) ; 20 rats were not induced in order to compare diabetic and nondiabetic rats .
The diabetic rats were divided into three groups , according to dressing material used ( allicin , physiological serum and control @ @ @ @ @ @ @ , and the nondiabetic rats were divided into two groups ( allicin and control , where no dressing was used ) .
The wound area was calculated and recorded on days 0 , 7 , 14 and 21 .
In addition , biopsies were taken from the wound area on days 0 , 7 , 14 and 21 and used for microscopic examination .
Day 0 was used as a reference to calculate wound healing percentage .
RESULTS : On days 7 and 14 , there were statistically significant differences between groups .
@ @ @ @ @ @ @ allicin group than in other groups on days 7 and 14 .
There were no statistically significant differences between the groups on day 21 .
In addition , it was determined that neutrophil , mononuclear cell , intraepithelial oedema and dermal oedema density were lower and fibroblast , angiogenesis and collagen density were higher in the allicin groups on days 7 and 14 .
CONCLUSION : In this study , allicin was found to be potentially effective on wound healing .
Future research should be conducted in order to clarify how it affects @ @ @

OBJECTIVE: The aim of this study was to investigate the effect of allicin on wound healing in an experimental diabetes model.
METHOD: In this randomised controlled study, 50 Wistar albino rats (25 females, 25 males) each weighing 200-300g were used. To develop the diabetes model, 30 rats were induced with 50mg/kg streptozotocin (STZ); 20 rats were not induced in order to compare diabetic and nondiabetic rats. The diabetic rats were divided into three groups, according to dressing material used (allicin, physiological serum and control, where no dressing was used), and the nondiabetic rats were divided into two groups (allicin and control, where no dressing was used). The wound area was calculated and recorded on days 0, 7, 14 and 21. In addition, biopsies were taken from the wound area on days 0, 7, 14 and 21 and used for microscopic examination. Day 0 was used as a reference to calculate wound healing percentage.
RESULTS: On days 7 and 14, there were statistically significant differences between groups. Wound surface areas were smaller in the allicin group than in other groups on days 7 and 14. There were no statistically significant differences between the groups on day 21. In addition, it was determined that neutrophil, mononuclear cell, intraepithelial oedema and dermal oedema density were lower and fibroblast, angiogenesis and collagen density were higher in the allicin groups on days 7 and 14.
CONCLUSION: In this study, allicin was found to be potentially effective on wound healing. Future research should be conducted in order to clarify how it affects wound healing.


greenmedinfo--2020-08-23--Allicin reduces inflammation by regulating ROS/NLRP3 and autophagy in the context of A. fumigatus in

Allicin reduces inflammation by regulating ROS/NLRP3 and autophagy in the context of A. fumigatus infection in mice.

OBJECTIVES : Inhibitory effect of allicin with broad-spectrum antimicrobial activity on A. fumigatus and the regulation mechanism of inflammation and autophagy in vitro and in vivo .
METHODS : The corresponding concentration of allicin was prepared according to the needs of the experiment .
In vitro , 2 ml 5 × 10of fungal spores suspension was added to the 6-well plate per hole , and different final concentrations of allicin ( 1 μl/ml , 2.5 μl/ml , 5 μl/ml , 10 μl/ml , 20 μl/ml , 30 μl/ml ) were added .
The fungal spores were stained by fluorescent dye @ @ @ @ @ @ @ , and the spore germination inhibition was detected by flow cytometry in different PH .
RAW264.7 cells were cultured and stimulated by A. fumigatus spores for 3 h , then allicin solution was added .
Then some cells were stained with ROS probe ( green ) and hochest33342 ( blue ) .
The effect of allicin on ROS was observed by fluorescence microscope .
The other part of cells extracted protein from cell lysate and detected the effect of allicin on inflammatory factors and autophagy by Western-blotting .
The green and red spots @ @ @ @ @ @ @ were observed by fluorescence microscopy .
In vivo , A. fumigatus spore was injected intratracheally into mice , then allicin was injected intravenously at a concentrationof 5 mg/kg/day for 7 consecutive days .
The survival status , pulmonary fungal load and weight of mice was recorded continuously for 30 days and detected the changes of lung by pathological examination and immunohistochemistry .
RESULTS : In vitro , allicin significantly inhibited the spore germination of A. fumigatus within 24 h in a dose-dependent manner and it had a stable inhibition on the spore germination @ @ @ @ @ @ @ Cell experiments showed that allicin inhibited intracellular spore germination by inhibiting ROS production , inflammation and autophagy .
In the animal experiment , the survival rate and body weight of allicin injection group were higher than that of non injection group , while the spore load of lung was lower than that of non injection group ( P CONCLUSIONS : These results support that allicin reduces inflammation and autophagy resistance to A. fumigatus infection , It also provides a possible treatment for Aspergillus infectious diseases , i.e .
early anti-inflammation , antibiotics or @ @ @ @ @ @

OBJECTIVES: Inhibitory effect of allicin with broad-spectrum antimicrobial activity on A. fumigatus and the regulation mechanism of inflammation and autophagy in vitro and in vivo.
METHODS: The corresponding concentration of allicin was prepared according to the needs of the experiment. In vitro, 2 ml 5 × 10of fungal spores suspension was added to the 6-well plate per hole, and different final concentrations of allicin (1 μl/ml, 2.5 μl/ml, 5 μl/ml, 10 μl/ml, 20 μl/ml, 30 μl/ml) were added. The fungal spores were stained by fluorescent dye SYTO 9 (green) every day, and the spore germination inhibition was detected by flow cytometry in different PH. RAW264.7 cells were cultured and stimulated by A. fumigatus spores for 3 h, then allicin solution was added. Then some cells were stained with ROS probe (green) and hochest33342 (blue). The effect of allicin on ROS was observed by fluorescence microscope. The other part of cells extracted protein from cell lysate and detected the effect of allicin on inflammatory factors and autophagy by Western-blotting. The green and red spots of RAW264.7 cells stably transfected with GFP-RFP-LC3 were observed by fluorescence microscopy. In vivo, A. fumigatus spore was injected intratracheally into mice, then allicin was injected intravenously at a concentrationof 5 mg/kg/day for 7 consecutive days. The survival status, pulmonary fungal load and weight of mice was recorded continuously for 30 days and detected the changes of lung by pathological examination and immunohistochemistry.
RESULTS: In vitro, allicin significantly inhibited the spore germination of A. fumigatus within 24 h in a dose-dependent manner and it had a stable inhibition on the spore germination of A. fumigatus in acidic environment. Cell experiments showed that allicin inhibited intracellular spore germination by inhibiting ROS production, inflammation and autophagy. In the animal experiment, the survival rate and body weight of allicin injection group were higher than that of non injection group, while the spore load of lung was lower than that of non injection group (P < 0.05).
CONCLUSIONS: These results support that allicin reduces inflammation and autophagy resistance to A. fumigatus infection, It also provides a possible treatment for Aspergillus infectious diseases, i.e. early anti-inflammation, antibiotics or drugs that inhibit excessive autophagy.