greenmedinfo--2020-08-14--This study shows that melatonin has a protective effect on the glyphosate exposed E. sinensis.

Glyphosate is one of the most widely used pesticides , which can cause toxicity to aquatic animals .
In this @ @ @ @ @ , immune response , digestive enzyme activities , and the intestinal microbiota diversity of Chinese @ @ @ @ @ ) were evaluated after 14 days of exposure to glyphosate ( 48.945 mg/L from 50 @ @ @ @ @ and melatonin feeding ( 80 mg/kg ) .
The results showed that MT significantly improved @ @ @ @ @ capacity of E. sinensis ( P

Glyphosate is one of the most widely used pesticides, which can cause toxicity to aquatic animals. In this study, the survival rate, immune response, digestive enzyme activities, and the intestinal microbiota diversity of Chinese mitten crab (Eriocheir sinensis) were evaluated after 14 days of exposure to glyphosate (48.945 mg/L from 50% 96 h LCvalue) and melatonin feeding (80 mg/kg). The results showed that MT significantly improved the survival rate, antibacterial capacity of E. sinensis (P < 0.05). After exposure to glyphosate, the expression of Hsp60, Hsp70 and Hsp90 in cranial ganglia and thoracic ganglia was decreased significantly, but MT significantly raised the expression of these proteins (P < 0.05). Glyphosate significantly decreased lipase activity compared with the control group (P < 0.05), while melatonin significantly increased the lipase, amylase and trypsin activities (P < 0.05). Melatonin significantly increased the Chao1 and Shannon index and the relative abundance of Proteobacteria and Bacteroidetes (P < 0.05). This study shows that melatonin has a protective effect on the glyphosate exposed E. sinensis.


greenmedinfo--2020-08-14--Toxicity of pesticides toward human immune cells U-937 and HL-60.

The industrialization of the agricultural sector has significantly increased the use of chemicals such as pesticides .
Therefore , exposure to them is unavoidable , which makes it necessary to assess their safety for humans at actual exposure doses .
This paper aims to determine toxicity of three types of pesticides toward human immune cells ( HL-60 and U-937 ) : glyphosate ( GLY ) , deltamethrin ( DEL ) , and chlorothalonil ( CHL ) .
Cell viability , membrane integrity , inflammation induction , and antioxidant activity were evaluated to determine differences in cellular response to the tested @ @ @ @ @ @ @ , all tested substances caused increased mortality of cells after only 24 h. Cell membrane damage was recorded under DEL and CHL influences .
The largest disintegration of the cell membrane was due to the action of 100 μg/mL DEL for U-937 and CHL at 1 μg/mL for HL-60 .
GLY at a concentration of 3,600 μg/mL caused significant peroxidation of U-937 cells ' lipids.CHL-induced inflammation in both types of cells tested .
DEL and GLY also induced antioxidant activity in cells .
These results lead to the conclusion that the tested pesticides @ @ @ @ @ @ @ human immune system in doses to which both farmers and consumers are exposed .

The industrialization of the agricultural sector has significantly increased the use of chemicals such as pesticides. Therefore, exposure to them is unavoidable, which makes it necessary to assess their safety for humans at actual exposure doses. This paper aims to determine toxicity of three types of pesticides toward human immune cells (HL-60 and U-937): glyphosate (GLY), deltamethrin (DEL), and chlorothalonil (CHL). Cell viability, membrane integrity, inflammation induction, and antioxidant activity were evaluated to determine differences in cellular response to the tested plant protection agents. In experimental models, all tested substances caused increased mortality of cells after only 24 h. Cell membrane damage was recorded under DEL and CHL influences. The largest disintegration of the cell membrane was due to the action of 100 μg/mL DEL for U-937 and CHL at 1 μg/mL for HL-60. GLY at a concentration of 3,600 μg/mL caused significant peroxidation of U-937 cells' lipids.CHL-induced inflammation in both types of cells tested. DEL and GLY also induced antioxidant activity in cells. These results lead to the conclusion that the tested pesticides act cytotoxically to the cells of the human immune system in doses to which both farmers and consumers are exposed.


greenmedinfo--2020-08-14--Glyphosate-based herbicide has soil-mediated effects on potato glycoalkaloids and oxidative status o

Glyphosate-based herbicide has soil-mediated effects on potato glycoalkaloids and oxidative status of a potato pest.

Glyphosate is the most used herbicide worldwide , targeting physiological pathways in plants .
Recent studies have shown that glyphosate can also cause toxic effects in animals .
We investigated the glyphosate-based herbicide ( GBH ) -induced changes in potato ( Solanum tuberosum ) plant chemistry and the effects of a GBH on the survival rate and oxidative status of the Colorado potato beetle ( Leptinotarsa decemlineata ) .
The beetles were reared on potato plants grown in pots containing soil treated with a GBH ( Roundup Gold , 450 g/l ) or untreated soil ( water control ) .
@ @ @ @ @ @ @ the potato plants and then collected in 2 phases : as 4th instar larvae and as adults .
The main glycoalkaloids of the potato plants , α-solanine and α-chaconine , were measured twice during the experiment .
The α-solanine was reduced in potato plants grown in GBH-treated soil , which can be detrimental to plant defenses against herbivores .
GBH treatment had no effect on the survival rate or body mass of the larvae or the adult beetles .
In the larvae , total glutathione ( tGSH ) concentration and the enzyme activity @ @ @ @ @ @ @ dismutase , and glutathione-S-transferase were increased in the GBH treatment group .
In the adult beetles , CAT activity and tGSH levels were affected by the interactive effect of GBH treatment and the body mass .
To conclude , environmentally relevant concentrations of a GBH can affect the potato plant 's glycoalkaloid concentrations , but are not likely to directly affect the survival rate of the Colorado potato beetle , but instead , modify the antioxidant defense of the beetles via diet .

Glyphosate is the most used herbicide worldwide, targeting physiological pathways in plants. Recent studies have shown that glyphosate can also cause toxic effects in animals. We investigated the glyphosate-based herbicide (GBH)-induced changes in potato (Solanum tuberosum) plant chemistry and the effects of a GBH on the survival rate and oxidative status of the Colorado potato beetle (Leptinotarsa decemlineata). The beetles were reared on potato plants grown in pots containing soil treated with a GBH (Roundup Gold, 450 g/l) or untreated soil (water control). The 2nd instar larvae were introduced to the potato plants and then collected in 2 phases: as 4th instar larvae and as adults. The main glycoalkaloids of the potato plants, α-solanine and α-chaconine, were measured twice during the experiment. The α-solanine was reduced in potato plants grown in GBH-treated soil, which can be detrimental to plant defenses against herbivores. GBH treatment had no effect on the survival rate or body mass of the larvae or the adult beetles. In the larvae, total glutathione (tGSH) concentration and the enzyme activity of catalase (CAT), superoxide dismutase, and glutathione-S-transferase were increased in the GBH treatment group. In the adult beetles, CAT activity and tGSH levels were affected by the interactive effect of GBH treatment and the body mass. To conclude, environmentally relevant concentrations of a GBH can affect the potato plant's glycoalkaloid concentrations, but are not likely to directly affect the survival rate of the Colorado potato beetle, but instead, modify the antioxidant defense of the beetles via diet.


greenmedinfo--2020-08-14--Neonatal exposure to a glyphosate-based herbicide alters the uterine differentiation of prepubertal

Neonatal exposure to a glyphosate-based herbicide alters the uterine differentiation of prepubertal ewe lambs.

The exposure to endocrine-disrupting compounds ( EDCs ) , such as glyphosate-based herbicides ( GBHs ) , during early life might alter female fertility .
The aim of the present study was to evaluate the effects of neonatal exposure to a GBH on sheep uterine development .
To achieve this , Friesian ewe lambs were exposed to GBH ( 2 mg/kg of body weight/day ; n = 12 ) or vehicle ( controls ; n = 10 ) through s.c. injections , from postnatal day ( PND ) 1 to PND14 ; on PND45 , the uteri were obtained to @ @ @ @ @ @ @ parameters were determined by picrosirius-hematoxylin staining.Protein expression of Ki67 ( as a cell proliferation marker ) , p27 , and molecules involved in uterine organogenetic differentiation was measured by immunohistochemistry .
We also determined the mRNA expression of the IGF molecular pathway by RT-PCR .
Although histomorphology was not modified , the uteriof GBH-exposed ewe lambs showed lower cell proliferation , together with higher p27 protein expression .
In addition , the uteri of GBH-exposed ewe lambs showed increased gene expression of insulin-like growth factor binding protein 3 ( IGFBP-3 ) , decreased @ @ @ @ @ @ @ LE ) and glandular ( GE ) epithelia and in the subepithelial stroma ( SS ) , and lower PR expression in the LE but higher in the GE and SS .
In addition , GBH treatment decreased the uterine expression of Wnt5a in the GE , of Wnt7a in the SS , of β-catenin in the LE and GE , of Hoxa10 in the SS , and of Foxa2 in the GE as compared with controls .
In conclusion , neonatal exposure to GBH decreased cell proliferation and altered the expression of @ @ @ @ @ @ @ the uterus .
All these changes might have adverse consequences on uterine differentiation and functionality , affecting the female reproductive health of sheep .
GBH may be responsible for uterine subfertility , acting as an EDC .

The exposure to endocrine-disrupting compounds (EDCs), such as glyphosate-based herbicides (GBHs), during early life might alter female fertility. The aim of the present study was to evaluate the effects of neonatal exposure to a GBH on sheep uterine development. To achieve this, Friesian ewe lambs were exposed to GBH (2 mg/kg of body weight/day; n = 12) or vehicle (controls; n = 10) through s.c. injections, from postnatal day (PND) 1 to PND14; on PND45, the uteri were obtained to evaluate histomorphological and molecular parameters. Morphological parameters were determined by picrosirius-hematoxylin staining.Protein expression of Ki67 (as a cell proliferation marker), p27, and molecules involved in uterine organogenetic differentiation was measured by immunohistochemistry. We also determined the mRNA expression of the IGF molecular pathway by RT-PCR. Although histomorphology was not modified, the uteriof GBH-exposed ewe lambs showed lower cell proliferation, together with higher p27 protein expression. In addition, the uteri of GBH-exposed ewe lambs showed increased gene expression of insulin-like growth factor binding protein 3 (IGFBP-3), decreased expression of ERα in the luminal (LE) and glandular (GE) epithelia and in the subepithelial stroma (SS), and lower PR expression in the LE but higher in the GE and SS. In addition, GBH treatment decreased the uterine expression of Wnt5a in the GE, of Wnt7a in the SS, of β-catenin in the LE and GE, of Hoxa10 in the SS, and of Foxa2 in the GE as compared with controls. In conclusion, neonatal exposure to GBH decreased cell proliferation and altered the expression of molecules that control proliferation and development in the uterus. All these changes might have adverse consequences on uterine differentiation and functionality, affecting the female reproductive health of sheep. GBH may be responsible for uterine subfertility, acting as an EDC.


greenmedinfo--2020-08-14--Effects of Roundup and its main component, glyphosate, upon mammalian sperm function and survival.

The wide use of glyphosate-based herbicides ( GBHs ) has become a matter of concern due to its potential harmful @ @ @ @ @ including men fertility .
This study sought to investigate , using the pig as a @ @ @ @ @ pure glyphosate and its most known commercial formulation , Roundup , on sperm function and @ @ @ @ @ , fresh commercial semen doses were incubated with different concentrations ( 0-360 µg/mL ) of @ @ @ @ @ .
1 ) or Roundup , at the equivalent GLY concentration ( exp .
2 @ @ @ @ @ for 3 h. Glyphosate at 360 µg/mL significantly ( P

The wide use of glyphosate-based herbicides (GBHs) has become a matter of concern due to its potential harmful effects on human health, including men fertility. This study sought to investigate, using the pig as a model, the impact of pure glyphosate and its most known commercial formulation, Roundup, on sperm function and survival. With this purpose, fresh commercial semen doses were incubated with different concentrations (0-360 µg/mL) of glyphosate (GLY; exp. 1) or Roundup, at the equivalent GLY concentration (exp. 2), at 38 °C for 3 h. Glyphosate at 360 µg/mL significantly (P < 0.05) decreased sperm motility, viability, mitochondrial activity and acrosome integrity but had no detrimental effect at lower doses. On the other hand, Roundup did significantly (P < 0.05) reduce sperm motility at ≥ 5 µg/mL GLY-equivalent concentration; mitochondrial activity at ≥ 25 µg/mL GLY-equivalent concentration; and sperm viability and acrosome integrity at ≥ 100 µg/mL GLY-equivalent concentration as early as 1 h of incubation. In a similar fashion, GLY and Roundup did not inflict any detrimental effect on sperm DNA integrity. Taken together, these data indicate that, while both glyphosate and Roundup exert a negative impact on male gametes, Roundup is more toxic than its main component, glyphosate.


greenmedinfo--2020-08-15--Melatonin supplementation in elderly could be beneficial in COVID-19 treatment.

The aim of this review is to summarize current studies on the relationship between melatonin and aging .
Nowadays , @ @ @ @ @ , and identifying age-related changes and developing proper therapeutic approaches are counted in major issues @ @ @ @ @ is the main hormone of the pineal gland .
Melatonin is known to influence many @ @ @ @ @ , including circadian rhythms , immune system , neuroendocrine and cardiovascular functions .
Melatonin rhythms @ @ @ @ @ of aging .
Aging is an extremely complex and multifactorial process .
Melatonin levels decline @ @ @ @ @ loss is associated with several age-related diseases .
Aging is closely associated with oxidative damage @ @ @ @ @ radical reactions initiated by the mitochondria constitute the inherent aging process .
Melatonin plays a @ @ @ @ @ age-related oxidative stress .
COVID-19 fatality rates increase with chronic diseases and age , where @ @ @ @ @ .
For this reason , melatonin supplementation in elderly could be beneficial in COVID-19 treatment @ @ @ @ @ usage of melatonin in COVID-19 treatment are needed .

The aim of this review is to summarize current studies on the relationship between melatonin and aging. Nowadays, age-related diseases come into prominence, and identifying age-related changes and developing proper therapeutic approaches are counted in major issues of community health. Melatonin is the main hormone of the pineal gland. Melatonin is known to influence many biological processes in the body, including circadian rhythms, immune system, neuroendocrine and cardiovascular functions. Melatonin rhythms also reflect the biological process of aging. Aging is an extremely complex and multifactorial process. Melatonin levels decline considerably with aging and its loss is associated with several age-related diseases. Aging is closely associated with oxidative damage and mitochondrial dysfunction. Free radical reactions initiated by the mitochondria constitute the inherent aging process. Melatonin plays a pivotal role to prevent the age-related oxidative stress. COVID-19 fatality rates increase with chronic diseases and age, where melatonin levels are also decrease. For this reason, melatonin supplementation in elderly could be beneficial in COVID-19 treatment. Therefore, studies on usage of melatonin in COVID-19 treatment are needed.


greenmedinfo--2020-08-15--Zerumbone inhibited enterotoxigenic Bacteroides fragilis-promoted colon carcinogenesis.

Chronic inflammation has been linked to colitis-associated colorectal cancer in humans .
The human symbiont enterotoxigenic Bacteroides fragilis ( ETBF ) , a pro-carcinogenic bacterium , has the potential to initiate and/or promote colorectal cancer .
Antibiotic treatment of ETBF has shown promise in decreasing colonic polyp formation in murine models of colon cancer .
However , there are no reported natural products that have shown efficacy in decreasing polyp burden .
In this study , we investigated the chemopreventive effects of oral administration of zerumbone in ETBF-colonized mice with azoxymethane ( AOM ) /dextran sulfate sodium ( DSS ) @ @ @ @ @ @ @ severity of disease activity index ( DAI ) scores as well as several parameters of colonic inflammation ( i.e.
, colon weight , colon length , cecum weight and spleen weight ) .
In addition , inflammation of the colon and cecum as well as hyperplasia was reduced .
Zerumbone treatment significantly inhibited colonic polyp numbers and prevented macroadenoma progression .
Taken together , these findings suggest that oral treatment with zerumbone inhibited ETBF-promoted colon carcinogenesis in mice indicating that zerumbone could be employed as a promising protective agent against ETBF-mediated colorectal cancer @

Chronic inflammation has been linked to colitis-associated colorectal cancer in humans. The human symbiont enterotoxigenic Bacteroides fragilis (ETBF), a pro-carcinogenic bacterium, has the potential to initiate and/or promote colorectal cancer. Antibiotic treatment of ETBF has shown promise in decreasing colonic polyp formation in murine models of colon cancer. However, there are no reported natural products that have shown efficacy in decreasing polyp burden. In this study, we investigated the chemopreventive effects of oral administration of zerumbone in ETBF-colonized mice with azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced tumorigenesis. Zerumbone significantly reduced the severity of disease activity index (DAI) scores as well as several parameters of colonic inflammation (i.e., colon weight, colon length, cecum weight and spleen weight). In addition, inflammation of the colon and cecum as well as hyperplasia was reduced. Zerumbone treatment significantly inhibited colonic polyp numbers and prevented macroadenoma progression. Taken together, these findings suggest that oral treatment with zerumbone inhibited ETBF-promoted colon carcinogenesis in mice indicating that zerumbone could be employed as a promising protective agent against ETBF-mediated colorectal cancer.


greenmedinfo--2020-08-15--Zerumbone was clearly identified as a unique dual acetylcholinesterase and butyrylcholinesterase inh

Zerumbone was clearly identified as a unique dual acetylcholinesterase and butyrylcholinesterase inhibitor.

Acetylcholinesterase ( AChE ) and butyrylcholinesterase ( BChE ) mediate the degradation of acetylcholine ( ACh ) , a primary neurotransmitter in the brain .
Cholinergic deficiency occurs during the progression of Alzheimer 's disease ( AD ) , resulting in widespread cognitive dysfunction and decline .
We evaluated the potential effect of a natural cholinesterase inhibitor , zerumbone , using in vitro target enzyme assays , as well as in silico docking and ADMET ( absorption , distribution , metabolism , excretion , and toxicity ) simulation .
Zerumbone showed a predominant cholinesterase inhibitory property with ICvalues of 2.74± @ @ @ @ @ @ @ for AChE and BChE , respectively ; however , the modes of inhibition were different .
Computational docking simulation indicated that Van der Waals interactions between zerumbone and both the cholinesterases were the main forces responsible for its inhibitory effects .
Furthermore , zerumbone showed the best physicochemical properties for both bioavailability and blood-brain barrier ( BBB ) permeability .
Together , in the present study , zerumbone was clearly identified as a unique dual AChE and BChE inhibitor with high permeability across the BBB , suggesting a strong potential for its physiological @ @ @ @ @ @ @ of AD .

Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) mediate the degradation of acetylcholine (ACh), a primary neurotransmitter in the brain. Cholinergic deficiency occurs during the progression of Alzheimer's disease (AD), resulting in widespread cognitive dysfunction and decline. We evaluated the potential effect of a natural cholinesterase inhibitor, zerumbone, using in vitro target enzyme assays, as well as in silico docking and ADMET (absorption, distribution, metabolism, excretion, and toxicity) simulation. Zerumbone showed a predominant cholinesterase inhibitory property with ICvalues of 2.74± 0.48 µM and 4.12 ± 0.42 µM for AChE and BChE, respectively; however, the modes of inhibition were different. Computational docking simulation indicated that Van der Waals interactions between zerumbone and both the cholinesterases were the main forces responsible for its inhibitory effects. Furthermore, zerumbone showed the best physicochemical properties for both bioavailability and blood-brain barrier (BBB) permeability. Together, in the present study, zerumbone was clearly identified as a unique dual AChE and BChE inhibitor with high permeability across the BBB, suggesting a strong potential for its physiological benefits and/or pharmacological eﬃcacy in the prevention of AD.


greenmedinfo--2020-08-15--Zerumbone promotes cytotoxicity in human malignant glioblastoma cells.

Glioblastoma multiforme ( GBM ) is the most hostile tumor in the central nervous system .
Unfortunately , the prognosis of GBM patients is poor following surgical interventions , chemotherapy , and radiotherapy .
Consequently , more efficient and effective treatment options for the treatment of GBM need to be explored .
Zerumbone , as a sesquiterpene derived fromSmith , has substantial cytotoxic and antiproliferative activities in some types of cancer .
Here , we show that exposure of GBM cells ( U-87 MG ) to Zerumbone demonstrated significant growth inhibition in a concentration-dependent manner .
Zerumbone also induced apoptosis @ @ @ @ @ @ @ GBM U-87 MG cells in the G2/M phase of the cell cycle .
In detail , the apoptotic process triggered by Zerumbone involved the upregulation of proapoptotic Bax and the suppression of antiapoptotic Bcl-2 genes expression as determined by qRT-PCR .
Moreover , Zerumbone enhanced the generation of reactive oxygen species ( ROS ) , and N-acetyl cysteine ( NAC ) , as an antioxidant , reversed the ROS-induced cytotoxicity of U-87 MG cells .
The Western blot analysis suggested that Zerumbone activated the NF-B p65 , which was partly inhibited by NAC @ @ @ @ @ @ @ that Zerumbone induces cytotoxicity by ROS generation .
Thus , the study raises the possibility of Zerumbone as a potential natural agent for treating GBM due to its ability to induce cytotoxicity .

Glioblastoma multiforme (GBM) is the most hostile tumor in the central nervous system. Unfortunately, the prognosis of GBM patients is poor following surgical interventions, chemotherapy, and radiotherapy. Consequently, more efficient and effective treatment options for the treatment of GBM need to be explored. Zerumbone, as a sesquiterpene derived fromSmith, has substantial cytotoxic and antiproliferative activities in some types of cancer. Here, we show that exposure of GBM cells (U-87 MG) to Zerumbone demonstrated significant growth inhibition in a concentration-dependent manner. Zerumbone also induced apoptosis and caused cell cycle arrest of human GBM U-87 MG cells in the G2/M phase of the cell cycle. In detail, the apoptotic process triggered by Zerumbone involved the upregulation of proapoptotic Bax and the suppression of antiapoptotic Bcl-2 genes expression as determined by qRT-PCR. Moreover, Zerumbone enhanced the generation of reactive oxygen species (ROS), and N-acetyl cysteine (NAC), as an antioxidant, reversed the ROS-induced cytotoxicity of U-87 MG cells. The Western blot analysis suggested that Zerumbone activated the NF-B p65, which was partly inhibited by NAC treatment. Collectively, our results confirmed that Zerumbone induces cytotoxicity by ROS generation. Thus, the study raises the possibility of Zerumbone as a potential natural agent for treating GBM due to its ability to induce cytotoxicity.


greenmedinfo--2020-08-15--Anti-biofilm and anti-virulence effects of zerumbone against Acinetobacter baumannii.

is a multidrug-resistant opportunistic pathogen that affects patients with a compromised immune system and is becoming increasingly important as a @ @ @ @ @ is difficult to treat owing to its intrinsic multidrug resistance and ability to form antimicrobial-tolerant @ @ @ @ @ study , we aimed to assess the potential use of zerumbone as a novel anti-biofilm @ @ @ @ @ The results showed that zerumbone at sub-inhibitory doses decreased biofilm formation and disrupted establishedbiofilms .
@ @ @ @ @ formation was dose-dependent based on the results of microtitre plate biofilm assays and confocal laser @ @ @ @ @ , our data validated the anti-virulence efficacy of zerumbone , wherein it significantly interfered with @ @ @ @ @ support these phenotypic results , transcriptional analysis revealed that zerumbone downregulated the expression of biofilm- @ @ @ @ @ ,and ) in .
Overall , our findings suggested that zerumbone might be a promising @ @ @ @ @ of biofilm- and virulence-related infections caused by multidrug-resistant .

is a multidrug-resistant opportunistic pathogen that affects patients with a compromised immune system and is becoming increasingly important as a hospital-derived infection. This pathogen is difficult to treat owing to its intrinsic multidrug resistance and ability to form antimicrobial-tolerant biofilms. In the present study, we aimed to assess the potential use of zerumbone as a novel anti-biofilm and/or anti-virulence agent against. The results showed that zerumbone at sub-inhibitory doses decreased biofilm formation and disrupted establishedbiofilms. The zerumbone-induced decrease in biofilm formation was dose-dependent based on the results of microtitre plate biofilm assays and confocal laser scanning microscopy. In addition, our data validated the anti-virulence efficacy of zerumbone, wherein it significantly interfered with the motility of. To support these phenotypic results, transcriptional analysis revealed that zerumbone downregulated the expression of biofilm- and virulence-associated genes (,,and) in. Overall, our findings suggested that zerumbone might be a promising bioactive agent for the treatment of biofilm- and virulence-related infections caused by multidrug-resistant.


greenmedinfo--2020-08-15--Advances on anti-tumor mechanisms of zerumbone.

Zerumbone ( ZER ) , one of humulane-type sesquiterpenoids , showed its unique advantage against tumor activities .
The main @ @ @ @ @ growth and proliferation of cancer cells , inducing apoptosis of cancer cells and differentiation of @ @ @ @ @ function , inhibiting invasion and metastasis of cancer cells , and reversing multidrug resistance of @ @ @ @ @ ZER focusing its cytotoxic or anti-tumor is one of hot topic .
Currently , with @ @ @ @ @ , the clarified mechanisms are getting rich .
The present paper describes a summary of @ @ @ @ @ and helps to provide significant reference to more in-depth research .

Zerumbone(ZER), one of humulane-type sesquiterpenoids, showed its unique advantage against tumor activities. The main underlying mechanisms include inhibiting the growth and proliferation of cancer cells, inducing apoptosis of cancer cells and differentiation of cancer cells, regulating immune function, inhibiting invasion and metastasis of cancer cells, and reversing multidrug resistance of cancer cells. Studies on ZER focusing its cytotoxic or anti-tumor is one of hot topic. Currently, with the increasing studies on ZER, the clarified mechanisms are getting rich. The present paper describes a summary of its anti-tumor mechanism of action and helps to provide significant reference to more in-depth research.


greenmedinfo--2020-08-15--Study on the effect of regulation of Cordyceps militaris polypeptide on the immune function.

BACKGROUND : The pathogenesis of the abnormality of the immune system is still not clear at present .
Chemosynthetic drugs , human or animal immune products and microbiological drugs are used as the main drugs in clinics currently , but these drugs have different side effects .
So researchers turned to safer natural products in order to find immunomodulatory active substances from natural products and their extracts .
METHODS : Immunosuppressed mice were induced by cyclophosphamide and administered with Cordyceps militaris polypeptide ( CMP ) for the study on the effect of CMP on the immune function of mice and @ @ @ @ @ @ @ differential gene sets selected in our previous work , the transcription factors and their corresponding target genes were screened by integrating the TRED ( Transcriptional Regulatory Element Database ) , a transcriptional factor-target gene regulatory network was constructed , then the role of transcription factors in the regulatory network was elucidated by statistically analyzing the key nodes , and finally , the correlation of network genes with diseases was analyzed by using the DAVID database .
RESULTS : The results of animal experiments showed that CMP could increase the immune organ indexes , @ @ @ @ @ @ @ the degree of delayed allergy and the content of hemolysin in the serum of mice .
CMP was found to be involved in the regulation of immune function in mice through genes Kdr , Spp1 , Ptgs2 , Rel , and Smad3 , and transcription factors Ets1 , E2f2 and E2f1 .
E2F2 and E2F1 are members of the E2F family , so we speculated that the E2F family might play an important role , and its main regulatory pathways were the PI3K-Akt signaling pathway and TNF signaling pathway .
CONCLUSION : CMP @ @ @ @ @ @ @ CMP can regulate the immune function of mice through multiple genes and transcription factors , and may also play a role in immune-related diseases , such as cancer .

BACKGROUND: The pathogenesis of the abnormality of the immune system is still not clear at present. Chemosynthetic drugs, human or animal immune products and microbiological drugs are used as the main drugs in clinics currently, but these drugs have different side effects. So researchers turned to safer natural products in order to find immunomodulatory active substances from natural products and their extracts.
METHODS: Immunosuppressed mice were induced by cyclophosphamide and administered with Cordyceps militaris polypeptide (CMP) for the study on the effect of CMP on the immune function of mice and its mechanism. Based on the 1748 differential gene sets selected in our previous work, the transcription factors and their corresponding target genes were screened by integrating the TRED (Transcriptional Regulatory Element Database), a transcriptional factor-target gene regulatory network was constructed, then the role of transcription factors in the regulatory network was elucidated by statistically analyzing the key nodes, and finally, the correlation of network genes with diseases was analyzed by using the DAVID database.
RESULTS: The results of animal experiments showed that CMP could increase the immune organ indexes, the number of white blood cells, the degree of delayed allergy and the content of hemolysin in the serum of mice. CMP was found to be involved in the regulation of immune function in mice through genes Kdr, Spp1, Ptgs2, Rel, and Smad3, and transcription factors Ets1, E2f2 and E2f1. E2F2 and E2F1 are members of the E2F family, so we speculated that the E2F family might play an important role, and its main regulatory pathways were the PI3K-Akt signaling pathway and TNF signaling pathway.
CONCLUSION: CMP can improve the immunity of mice. CMP can regulate the immune function of mice through multiple genes and transcription factors, and may also play a role in immune-related diseases, such as cancer.


greenmedinfo--2020-08-15--Polysaccharides from Cordyceps miltaris cultured at different pH: Sugar composition and antioxidant

Polysaccharides from Cordyceps miltaris cultured at different pH: Sugar composition and antioxidant activity.

In the study , theβ-glucan content , the primary structure and the antioxidant capacity of polysaccharides in Cordyceps militaris cultivated @ @ @ @ @ were evaluated .
Meanwhile , the mechanism of β-glucan biosynthesis was investigated by RNA-Seq .
@ @ @ @ @ C. militaris growing at aninitial growth pH of 5-7 ( CMsA ) was distinguished from @ @ @ @ @ initial growth pH of 8-9 ( CMsB ) and their unigenes showed the comparable expression @ @ @ @ @ content of CMsB group was 32.7 % ( w/w ) , 10 % higher than @ @ @ @ @ results of RNA-seq showed 1088 differentially expressed genes between CMsA and CMsB groups .
Furthermore @ @ @ @ @ terms were up-regulated in CMsB groups .
In addition , the results of structural analysis @ @ @ @ @ composition , periodate oxidation ) and bioactivity evaluation speculated that C. militaris polysaccharides possessed higher @ @ @ @ @ ) -glucan content and antioxidant activities in CMsB groups .

In the study, theβ-glucan content, the primary structure and the antioxidant capacity of polysaccharides in Cordyceps militaris cultivated with different initial growth pH were evaluated. Meanwhile, the mechanism of β-glucan biosynthesis was investigated by RNA-Seq. Based on the results, C. militaris growing at aninitial growth pH of 5-7 (CMsA) was distinguished from C. militaris growing at an initial growth pH of 8-9 (CMsB) and their unigenes showed the comparable expression. The mean of β-glucan content of CMsB group was 32.7% (w/w), 10% higher than that of CMsA. The results of RNA-seq showed 1088 differentially expressed genes between CMsA and CMsB groups. Furthermore, oxidative phosphorylation-related Gene ontology terms were up-regulated in CMsB groups. In addition, the results of structural analysis (FTIR spectrum, monosaccharide composition, periodate oxidation) and bioactivity evaluation speculated that C. militaris polysaccharides possessed higher β-(1 → 6)-glucan content and antioxidant activities in CMsB groups.


greenmedinfo--2020-08-15--Regulation of autophagy in cardiovascular diseases by natural products.

Several major cardiovascular diseases , such as heart failure ( HF ) and atherosclerosis ( AS ) , have been @ @ @ @ @ The influence of autophagy on the occurrence and development of cardiovascular diseases has two sides @ @ @ @ @ of autophagy at a low level can provide energy and nutrients for cells through degradation @ @ @ @ @ cardiomyocytes and vascular endothelial cells , and stabilize atherosclerotic plaques .
However , excessive autophagy @ @ @ @ @ endothelial cells and even cause cell death .
Therefore , the study on the role @ @ @ @ @ the pathogenesis of cardiovascular diseases may not only provide new targets for the treatment of @ @ @ @ @ and reperfusion injury , atherosclerosis and heart failure , but also provide clues for the @ @ @ @ @ and treatment of clinical cardiovascular diseases .
In this chapter , we reviewed the research @ @ @ @ @ , epigallocatechin-3-gallate , and cordyceps sinensis on their recent research progress for cardiovascular diseases .
@ @ @ @ @ effective strategy for the treatment of cardiovascular diseases in the future .

Several major cardiovascular diseases, such as heart failure (HF) and atherosclerosis (AS), have been linked to autophagy dysfunction. The influence of autophagy on the occurrence and development of cardiovascular diseases has two sides. Generally, the induction of autophagy at a low level can provide energy and nutrients for cells through degradation of damaged organelles, protect cardiomyocytes and vascular endothelial cells, and stabilize atherosclerotic plaques. However, excessive autophagy may damage cardiomyocytes and vascular endothelial cells and even cause cell death. Therefore, the study on the role and mechanism of autophagy in the pathogenesis of cardiovascular diseases may not only provide new targets for the treatment of cardiac remodeling, myocardial ischemia and reperfusion injury, atherosclerosis and heart failure, but also provide clues for the developing new drugs on prevention and treatment of clinical cardiovascular diseases. In this chapter, we reviewed the research progress on resveratrol, curcumin, epigallocatechin-3-gallate, and cordyceps sinensis on their recent research progress for cardiovascular diseases. Regulating autophagy may be an effective strategy for the treatment of cardiovascular diseases in the future.


greenmedinfo--2020-08-15--Study Finds Fenugreek Increases Strength and Lean Muscle Mass

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greenmedinfo--2020-08-15--Zyflamend inhibits adipocyte differentiation through the activation of the PKA and JNK pathways.

: The prevalence of obesity and its comorbidities has sparked a worldwide concern to address rates of adipose tissue accrual .
Recent studies have demonstrated a novel role of Zyflamend , a blend of natural herbal extracts , in regulating lipid metabolism in several cancer cell lines through the activation of the AMPK signalling pathway .
Yet , the role of Zyflamend in adipogenic differentiation and lipid metabolism remains largely unexplored .
The objective of this study is to investigate the effects of Zyflamend on white 3T3-MBX pre-adipocyte differentiation and elucidate the molecular mechanisms .
We demonstrate that Zyflamend treatment @ @ @ @ @ @ @ , and increased cell death of 3T3-MBX pre-adipocytes .
In addition , treatment with Zyflamend inhibited lipid accumulation during the differentiation of 3T3-MBX cells , consistent with decreased expression of lipogenic genes and increased lipolysis .
Mechanistically , Zyflamend-induced alterations in adipogenesis were mediated , at least in part , through the activation of AMPK , PKA , and JNK .
Inhibition of AMPK partially reversed Zyflamend-induced inhibition of differentiation , whereas the inhibition of either JNK or PKA fully restored adipocyte differentiation and decreased lipolysis .
Taken together , the present study @ @ @ @ @ @ @ anti-adipogenic bioactive mix , inhibits adipocyte differentiation through the activation of the PKA and JNK pathways .
ABBREVIATION : 7-AAD : 7-amino-actinomycin D ; ACC : acetyl-CoA carboxylase ; AKT : protein kinase B ; AMPK : AMP-activated protein kinase ; ATGL : adipose triglyceride lipase ; C/EBPα : CCAAT-enhancer binding protein alpha ; DMEM : Dulbecco 's Modified Eagle Medium ; DMSO : dimethyl sulphoxide ; DTT : dithiothreitol ; EGTA : ethylene glycol-bis- ( 2-aminoethyl ) -N , N , N ' , N'-tetraacetic acid ; ERK : extracellular signal-regulated kinases @ @ @ @ @ @ @ FBS : foetal bovine serum ; GLUT : glucose transporter ; HSL : hormone-sensitive lipase ; IR : insulin receptor ; IRS : insulin receptor substrate ; JNK : c-JUN N-terminal kinase ; MGL : monoacylglycerol lipase ; NaF : sodium fluoride ; NF-κB : nuclear factor kappa-light-chain-enhancer of activated B cells ; PBS : phosphate buffered- saline ; PCB : pyruvate carboxylase ; PDE : phosphodiesterase ; PKA : protein kinase cAMP-dependent ; PMSF : phenylmethylsulfonyl fluoride ; PPARγ : perilipin peroxisome proliferator-activated receptor gamma ; PREF-1 : pre-adipocyte factor 1 ; @ @ @ @ @ @ @ radio-immunoprecipitation assay ; SDS-PAGE : sodium dodecyl sulphate polyacrylamide gel electrophoresis ; SEM : standard error of the mean ; SOX9 : suppressor of cytokine signalling 9 ; TGs : triacylglycerols .

: The prevalence of obesity and its comorbidities has sparked a worldwide concern to address rates of adipose tissue accrual. Recent studies have demonstrated a novel role of Zyflamend, a blend of natural herbal extracts, in regulating lipid metabolism in several cancer cell lines through the activation of the AMPK signalling pathway. Yet, the role of Zyflamend in adipogenic differentiation and lipid metabolism remains largely unexplored. The objective of this study is to investigate the effects of Zyflamend on white 3T3-MBX pre-adipocyte differentiation and elucidate the molecular mechanisms. We demonstrate that Zyflamend treatment altered cell cycle progression, attenuated proliferation, and increased cell death of 3T3-MBX pre-adipocytes. In addition, treatment with Zyflamend inhibited lipid accumulation during the differentiation of 3T3-MBX cells, consistent with decreased expression of lipogenic genes and increased lipolysis. Mechanistically, Zyflamend-induced alterations in adipogenesis were mediated, at least in part, through the activation of AMPK, PKA, and JNK. Inhibition of AMPK partially reversed Zyflamend-induced inhibition of differentiation, whereas the inhibition of either JNK or PKA fully restored adipocyte differentiation and decreased lipolysis. Taken together, the present study demonstrates that Zyflamend, as a novel anti-adipogenic bioactive mix, inhibits adipocyte differentiation through the activation of the PKA and JNK pathways.
ABBREVIATION: 7-AAD: 7-amino-actinomycin D; ACC: acetyl-CoA carboxylase; AKT: protein kinase B; AMPK: AMP-activated protein kinase; ATGL: adipose triglyceride lipase; C/EBPα: CCAAT-enhancer binding protein alpha; DMEM: Dulbecco's Modified Eagle Medium; DMSO: dimethyl sulphoxide; DTT: dithiothreitol; EGTA: ethylene glycol-bis-(2-aminoethyl)-N,N,N',N'-tetraacetic acid; ERK: extracellular signal-regulated kinases; FASN: fatty acid synthase; FBS: foetal bovine serum; GLUT: glucose transporter; HSL: hormone-sensitive lipase; IR: insulin receptor; IRS: insulin receptor substrate; JNK: c-JUN N-terminal kinase; MGL: monoacylglycerol lipase; NaF: sodium fluoride; NF-κB: nuclear factor kappa-light-chain-enhancer of activated B cells; PBS: phosphate buffered- saline; PCB: pyruvate carboxylase; PDE: phosphodiesterase; PKA: protein kinase cAMP-dependent; PMSF: phenylmethylsulfonyl fluoride; PPARγ: perilipin peroxisome proliferator-activated receptor gamma; PREF-1: pre-adipocyte factor 1; PVDF: polyvinylidene fluoride; RIPA: radio-immunoprecipitation assay; SDS-PAGE:sodium dodecyl sulphate polyacrylamide gel electrophoresis; SEM: standard error of the mean; SOX9: suppressor of cytokine signalling 9; TGs: triacylglycerols.


greenmedinfo--2020-08-15--Effects of three drying methods on polyphenol composition and antioxidant activities of Litchi chine

Effects of three drying methods on polyphenol composition and antioxidant activities of Litchi chinensis Sonn.

The aim of this study was to investigate the effects of three different drying methods , freeze drying ( FD @ @ @ @ @ VD ) and oven drying ( OD ) on phenolic contents and antioxidant activities of @ @ @ @ @ were exactly identified in the litchi fruits by UPLC-QqQ/MS .
Significant losses were observed in @ @ @ @ @ and antioxidant activities in the dried litchi when compared with the fresh litchi .
Principle @ @ @ @ @ was significant difference of phenolic component between the use of thermal drying ( VD and @ @ @ @ @ Our results suggest that FD is the optimum drying method for litchi fruits considering the @ @ @ @ @ antioxidant activities .

The aim of this study was to investigate the effects of three different drying methods, freeze drying (FD), vacuum drying (VD) and oven drying (OD) on phenolic contents and antioxidant activities of litchi fruits. 20 polyphenols were exactly identified in the litchi fruits by UPLC-QqQ/MS. Significant losses were observed in the contents of total polyphenols and antioxidant activities in the dried litchi when compared with the fresh litchi. Principle component analysis indicated that there was significant difference of phenolic component between the use of thermal drying (VD and OD) and FD. Our results suggest that FD is the optimum drying method for litchi fruits considering the content of total polyphenols and antioxidant activities.


greenmedinfo--2020-08-15--Lychee seed polyphenol inhibits Aβ-induced activation of NLRP3 inflammasome.

Emerging evidence indicates that the enhancement of microglial autophagy inhibits the NLRP3 inflammasome mediated neuroinflammation in Alzheimer 's disease ( AD ) .
Meanwhile , low density lipoprotein receptor-related protein 1 ( LRP1 ) highly expressed in microglia is able to negatively regulate neuroinflammation and positively regulate autophagy .
In addition , we have previously reported that an active lychee seed fraction enriching polyphenol ( LSP ) exhibits anti-neuroinflammation in Aβ-induced BV-2 cells .
However , its molecular mechanism of action is still unclear .
In this study , we aim to investigate whether LSP inhibits the NLRP3 inflammasome mediated @ @ @ @ @ @ @ Aβ-induced BV-2 cells and APP/PS1 mice .
The results showed that LSPdose- and time-dependently activated autophagy by increasing the expression of Beclin 1 and LC3II in BV-2 cells , which was regulated by the upregulation of LRP1 and its mediated AMPK signaling pathway .
In addition , both the Western blotting and fluorescence microscopic results demonstrated that LSPcould significantly suppress the activation of NLRP3 inflammasome by inhibiting the expression of NLRP3 , ASC , the cleavage of caspase-1 , and the release of IL-1β in Aβ ( 1-42 ) -induced BV-2 cells .
@ @ @ @ @ @ @ abolished the effect of LSP on the activation of AMPK and its mediated autophagy , as well as the inhibition of NLRP3 inflammasome .
Furthermore , LSP rescued PC-12 cells which were induced by the conditioned medium from Aβ ( 1-42 ) -treated BV-2 cells .
Moreover , LSP improved the cognitive function and inhibited the NLRP3 inflammasome in APP/PS1 mice .
Taken together , LSP inhibited the NLRP3 inflammasome-mediated neuroinflammation in the in vitro and in vivo models of AD , which was closely associated with the LRP1/AMPK-mediated autophagy .
Thus , @ @ @ @ @ @ @ evidences for LSP serving as a potential drug for the treatment of AD in the future .

Emerging evidence indicates that the enhancement of microglial autophagy inhibits the NLRP3 inflammasome mediated neuroinflammation in Alzheimer's disease (AD). Meanwhile, low density lipoprotein receptor-related protein 1 (LRP1) highly expressed in microglia is able to negatively regulate neuroinflammation and positively regulate autophagy. In addition, we have previously reported that an active lychee seed fraction enriching polyphenol (LSP) exhibits anti-neuroinflammation in Aβ-induced BV-2 cells. However, its molecular mechanism of action is still unclear. In this study, we aim to investigate whether LSP inhibits the NLRP3 inflammasome mediated neuroinflammation and clarify its molecular mechanism in Aβ-induced BV-2 cells and APP/PS1 mice. The results showed that LSPdose- and time-dependently activated autophagy by increasing the expression of Beclin 1 and LC3II in BV-2 cells, which was regulated by the upregulation of LRP1 and its mediated AMPK signaling pathway. In addition, both the Western blotting and fluorescence microscopic results demonstrated that LSPcould significantly suppress the activation of NLRP3 inflammasome by inhibiting the expression of NLRP3, ASC, the cleavage of caspase-1, and the release of IL-1β in Aβ(1-42)-induced BV-2 cells. In addition, the siRNA LRP1 successfully abolished the effect of LSP on the activation of AMPK and its mediated autophagy, as well as the inhibition of NLRP3 inflammasome. Furthermore, LSP rescued PC-12 cells which were induced by the conditioned medium from Aβ(1-42)-treated BV-2 cells. Moreover, LSP improved the cognitive function and inhibited the NLRP3 inflammasome in APP/PS1 mice. Taken together,LSP inhibited the NLRP3 inflammasome-mediated neuroinflammation in the in vitro and in vivo models of AD, which was closely associated with the LRP1/AMPK-mediated autophagy. Thus, the findings from this study further provide evidences for LSP serving as a potential drug for the treatment of AD in the future.


greenmedinfo--2020-08-15--Oligonol modulates cholesterol metabolism in animals.

There is growing research interest in the hypocholesterolemic effect of various food components such as polyphenols .
In this study @ @ @ @ @ of oligonol-a low-molecular weight polyphenol extracted from lychee fruit-on cholesterol metabolism in rats under short-term @ @ @ @ @ for 3 days significantly increased cecum weight and decreased cecal n-butyric acid concentrations in rats @ @ @ @ @ the levels of hepatic cholesterol and increased the levels of total neutral steroids excreted in @ @ @ @ @ increased fecalβ-muricholic acid significantly , whereas the levels of total acidic steroids remained unchanged .
@ @ @ @ @ ( cytochrome P450 family 7 subfamily A member 1 ) significantly increased following the administration @ @ @ @ @ could be ascribed to changes in the expression of farnesoid X receptor , small heterodimer @ @ @ @ @ factor 15 in ileum .
Our data suggest that oligonol induces hypocholesterolemic effects through the @ @ @ @ @ from the intestine and the upregulation of cholesterol catabolism in rats even following short-term administration @ @ @ @ @ be an important food component for reducing cholesterol level .

There is growing research interest in the hypocholesterolemic effect of various food components such as polyphenols. In this study, we examined the effects of oligonol-a low-molecular weight polyphenol extracted from lychee fruit-on cholesterol metabolism in rats under short-term administration. Administration of oligonol for 3 days significantly increased cecum weight and decreased cecal n-butyric acid concentrations in rats. Oligonol also significantly lowered the levels of hepatic cholesterol and increased the levels of total neutral steroids excreted in the feces. It also increased fecalβ-muricholic acid significantly, whereas the levels of total acidic steroids remained unchanged. Gene expression of hepatic CYP7A1 (cytochrome P450 family 7 subfamily A member 1) significantly increased following the administration of oligonol. This increase could be ascribed to changes in the expression of farnesoid X receptor, small heterodimer partner, and fibroblast growth factor 15 in ileum. Our data suggest that oligonol induces hypocholesterolemic effects through the inhibition of biliary cholesterol absorption from the intestine and the upregulation of cholesterol catabolism in rats even following short-term administration. Therefore, oligonol may be an important food component for reducing cholesterol level.


greenmedinfo--2020-08-15--Ascorbic acid supplementation attenuates schizophrenia-like symptoms in an animal model induced by k

Ascorbic acid supplementation attenuates schizophrenia-like symptoms in an animal model induced by ketamine.

Schizophrenia is a chronic neuropsychiatric disorder with a poorly understood pathophysiology .
The theories about the disorder are mainly about dysregulation in one or more systems of neurotransmitters , and the progression triggers the presence of inflammatory markers indicates the possibility that the disorder is initially an inflammatory disease .
The objective was to evaluate the ascorbic acid supplementation in an animal model of schizophrenia , on behavioral parameters , and cytokines involved in inflammation IL-1β , IL-10 .
Wistar rats with 60 days of age were used which were supplemented with ascorbic acid at 0.1 , 1 , and @ @ @ @ @ @ @ via orogastric gavage .
Subsequently , 4 groups were given ketamine ( 25mg/kg ) and 4 groups received intraperitoneal saline from the 9th-15th day of the experiment .
After 30 minutes of the last administration of ketamine/saline , and behavioral test , rats were killed by guillotine decapitation and the brain structures were carefully dissected for biochemical analysis .
Results showed that ascorbic acid supplementation prevented motor sensory loss but nor alter other parameters evaluated .
We concluded that ascorbic acid may be used as a therapeutic adjuvant in schizophrenia and may help @ @ @ @ @ @ @ quality .

Schizophrenia is a chronic neuropsychiatric disorder with a poorly understood pathophysiology. The theories about the disorder are mainly about dysregulation in one or more systems of neurotransmitters, and the progression triggers the presence of inflammatory markers indicates the possibility that the disorder is initially an inflammatory disease. The objective was to evaluate the ascorbic acid supplementation in an animal model of schizophrenia, on behavioral parameters, and cytokines involved in inflammation IL-1β, IL-10. Wistar rats with 60 days of age were used which were supplemented with ascorbic acid at 0.1, 1, and 10 mg/kg or saline for 14 days via orogastric gavage. Subsequently, 4 groups were given ketamine (25mg/kg) and 4 groups received intraperitoneal saline from the 9th-15th day of the experiment. After 30 minutes of the last administration of ketamine/saline, and behavioral test, rats were killed by guillotine decapitation and the brain structures were carefully dissected for biochemical analysis. Results showed that ascorbic acid supplementation prevented motor sensory loss but nor alter other parameters evaluated. We concluded that ascorbic acid may be used as a therapeutic adjuvant in schizophrenia and may help to improve the schizophrenic patient's life quality.


greenmedinfo--2020-08-15--Plasma vitamin C concentrations were negatively associated with tingling, prickling or pins and need

Plasma vitamin C concentrations were negatively associated with tingling, prickling or pins and needles sensation in patients with postherpetic neuralgia.

Vitamin C deficiency increases the risk of postherpetic neuralgia ( PHN ) .
In this cross-sectional study , the relationships among plasma vitamin C concentrations , pain and Leeds assessment of neuropathic symptoms and signs ( LANSS ) items were investigated during their first pain clinic visit of 120 PHN patients .
The factors associated with vitamin C deficiency were determined .
Independent predictors of vitamin C deficiency were presented as adjusted odds ratios ( AOR ) and 95 % confidence intervals ( CI ) .
The patients had a high prevalence ( 52.5 % ) of vitamin C deficiency @ @ @ @ @ @ @ negatively associated with spontaneous pain and tingling , prickling or pins and needles sensation according to the LANSS questionnaire .
Based on the receiver operator characteristic curve , the cutoffs for plasma vitamin C to predict moderate-to-severe and severe symptoms of sharp sensation were < 7.05 and < 5.68 mg/L , respectively .
By comparison , the patients well-nourished with vitamin C had lower incidences of sharp sensations , sharp pain , and reddish skin .
Multivariate analyses revealed that vitamin C deficiency was associated with the low intake of fruit/vegetables ( AOR @ @ @ @ @ @ @ = 0.032 ) , peptic ulcer disease ( AOR 3.25 , 95 % CI 1.28-8.28 , = 0.014 ) , and smoking ( AOR 3.60 , 95 % CI 1.33-9.77 , = 0.010 ) .
Future studies are needed to substantiate these findings .

Vitamin C deficiency increases the risk of postherpetic neuralgia (PHN). In this cross-sectional study, the relationships among plasma vitamin C concentrations, pain and Leeds assessment of neuropathic symptoms and signs (LANSS) items were investigated during their first pain clinic visit of 120 PHN patients. The factors associated with vitamin C deficiency were determined. Independent predictors of vitamin C deficiency were presented as adjusted odds ratios (AOR) and 95% confidence intervals (CI). The patients had a high prevalence (52.5%) of vitamin C deficiency. Their plasma vitamin C concentrations were negatively associated with spontaneous pain and tingling, prickling or pins and needles sensation according to the LANSS questionnaire. Based on the receiver operator characteristic curve, the cutoffs for plasma vitamin C to predict moderate-to-severe and severe symptoms of sharp sensation were<7.05 and<5.68 mg/L, respectively. By comparison, the patients well-nourished with vitamin C had lower incidences of sharp sensations, sharp pain, and reddish skin. Multivariate analyses revealed that vitamin C deficiency was associated with the low intake of fruit/vegetables (AOR 2.66, 95% CI 1.09-6.48,= 0.032), peptic ulcer disease (AOR 3.25, 95% CI 1.28-8.28,= 0.014), and smoking (AOR 3.60, 95% CI 1.33-9.77,= 0.010). Future studies are needed to substantiate these findings.


greenmedinfo--2020-08-15--The role of vitamin C in osteoporosis development and treatment.

Osteoporosis and associated low energy fractures are a significant clinical problem , especially in the elderly population .
The occurrence of a hip fracture is associated with significant mortality and a high risk of disability .
For this , apart from the treatment of osteoporosis , effective prevention of both the development of the disease and related fractures is extremely important .
One aspect of osteoporosis prevention is proper dietary calcium intake and normal vitamin D3 levels .
However , there is some evidence for a potential role of vitamin C in osteoporosis and fracture prevention , too .
This @ @ @ @ @ @ @ about the role of vitamin C in osteoporosis development , prevention and treatment .
The PubMed/Medline search on the role of vitamin C in bone metabolism database was performed for articles between 2000 and May 2020 .
Reports from in vitro and animal studies seem promising .
Epidemiological studies also indicate the positive effect of high vitamin C content in the daily diet on bone mineral density .
Despite promising observations , there are still few observational and intervention studies and their results do not allow for unequivocal determination of the benefits of @ @ @ @ @ @ @ its long-term supplementation .

Osteoporosis and associated low energy fractures are a significant clinical problem, especially in the elderly population. The occurrence of a hip fracture is associated with significant mortality and a high risk of disability. For this, apart from the treatment of osteoporosis, effective prevention of both the development of the disease and related fractures is extremely important. One aspect of osteoporosis prevention is proper dietary calcium intake and normal vitamin D3 levels. However, there is some evidence for a potential role of vitamin C in osteoporosis and fracture prevention, too. This review aims to summarize the current knowledge about the role of vitamin C in osteoporosis development, prevention and treatment. The PubMed/Medline search on the role of vitamin C in bone metabolism database was performed for articles between 2000 and May 2020. Reports from in vitro and animal studies seem promising. Epidemiological studies also indicate the positive effect of high vitamin C content in the daily diet on bone mineral density. Despite promising observations, there are still few observational and intervention studies and their results do not allow for unequivocal determination of the benefits of high daily intake of vitamin C or its long-term supplementation.


greenmedinfo--2020-08-15--Vitamin A and C showed a protective effect against cataract.

Oxidative stress in eye lens is one of the main causes of the cataract .
Dietary antioxidants including vitamin A and C are therefore known to be associated with the risk of the disease .
However , evidences are still lacking in Koreans .
This study aimed to examine whether dietary vitamin A and C levels are associated with the cataract , using data of Korea National Health and Nutrition Examination Survey 2012 .
A total of 3,344 individuals ( 599 cases and 2,745 controls ) were analyzed in the study .
Dietary data was classified into 3 groups following @ @ @ @ @ @ @ 1 ) ≤ estimated average requirements ( EAR ) , 2 ) EAR-recommended nutrient intake ( RNI ) , and 3 ) ≥ RNI .
Findings suggested normal subjects ( controls ) had better vitamin A and C nutritional status .
Vitamin A and C intakes of normal subjects were significantly higher than those of cataract cases ( p < 0.001 , respectively ) .
Ratio of subjects who consumed vitamin A and C lower than EAR was higher in cataract cases compared to normal subjects ( p < 0.001 , respectively ) @ @ @ @ @ @ @ having lower level of vitamins lower than EAR increased the odd ratios ( ORs ) for cataract [ for vitamin A : OR , 1.89 ; 95 % confidence interval ( CI ) , 1.55-2.31 and for vitamin C : OR , 2.06 ; 95 % CI , 1.69-2.51 ] .
However , such associations were not retained , when the subjects ' demographic and lifestyle factor were adjusted .
In conclusion , vitamin A and C showed a protective effect against cataract .
However , subjects ' life style and demographic factors @ @ @ @ @ @ @ required to verify the true association between dietary antioxidants and risk of cataract in Koreans .

Oxidative stress in eye lens is one of the main causes of the cataract. Dietary antioxidants including vitamin A and C are therefore known to be associated with the risk of the disease. However, evidences are still lacking in Koreans. This study aimed to examine whether dietary vitamin A and C levels are associated with the cataract, using data of Korea National Health and Nutrition Examination Survey 2012. A total of 3,344 individuals (599 cases and 2,745 controls) were analyzed in the study. Dietary data was classified into 3 groups following Dietary Reference Intakes for Koreans 2015: 1)≤ estimated average requirements (EAR), 2) EAR-recommended nutrient intake (RNI), and 3) ≥ RNI. Findings suggested normal subjects (controls) had better vitamin A and C nutritional status. Vitamin A and C intakes of normal subjects were significantly higher than those of cataract cases (p<0.001, respectively). Ratio of subjects who consumed vitamin A and C lower than EAR was higher in cataract cases compared to normal subjects (p<0.001, respectively). These antioxidant intake levels predicted that having lower level of vitamins lower than EAR increased the odd ratios (ORs) for cataract [for vitamin A: OR, 1.89; 95% confidence interval (CI), 1.55-2.31 and for vitamin C: OR, 2.06; 95% CI, 1.69-2.51]. However, such associations were not retained, when the subjects' demographic and lifestyle factor were adjusted. In conclusion, vitamin A and C showed a protective effect against cataract. However, subjects' life style and demographic factors nullified the association. More studies are required to verify the true association between dietary antioxidants and risk of cataract in Koreans.


greenmedinfo--2020-08-15--High-dose vitamin C alleviates pancreatic injury.

Background : Oxidative stress plays a pivotal role in the progress of severe acute pancreatitis ( SAP ) .
Vitamin C ( VC ) is the most important antioxidant in plasma .
However , the effects of an intravenous administration of high-dose VC and the mechanisms by which it exerts its antioxidant function in an experimental model of SAP have not been determined .
Methods : Sodium taurocholate was used to induce rat pancreatic injury and AR42J cells injury .
After the establishment of SAP model , SAP rat and injured AR42J cells were treated with VC .
For the @ @ @ @ @ @ @ knockdown of NRF2 was conducted after VC treatment .
The histopathological characteristics , the apoptosis of pancreatic acinar cells , oxidative stress markers and levels of enzymes , biochemical indicators , and inflammatory cytokines were examinedand .
Furthermore , the mortality of rats was assessed .
Results : andresults demonstrated that VC treatment ameliorated apoptosis of pancreatic acinar cells , as evidenced by the increase in Bcl-2 , Bcl-XL , and MCL-1 expressions and decrease in Bax and cleaved caspase-3 expression along with decreased TUNEL-positive cells .
Also , we found that the @ @ @ @ @ @ @ , GPx , GSH/GSSG , and T-AOC induced by SAP were reversed by VC treatmentand , and VC treatment increased expressions of Nrf2 , NQO1 , and HO-1 in SAP model at protein and gene level , indicating that VC attenuated oxidative stress via the NRF2/NQO1/HO-1 pathway .
Meanwhile , it was found that sodium taurocholate significantly induced the release of amylase , lipase , IL-1β , and IL-6 in rat plasma and AR42J cells , which were declined by VC treatment.results also revealed that these alterations in sodium taurocholate-injured AR42J cells due @ @ @ @ @ @ @ knockdown .
In addition , VC at a dose of 500 mg/kg decreased the levels of lactic acid , Cre , NGAL , AST , and ALT in the plasma of SAP rats , suggesting the improvement of renal and pancreatic injury and liver function of SAP rats .
Furthermore , the mortality of SAP rats was 50 % , which declined to 30 % after VC treatment .
Conclusions : The present study suggests that high-dose of VC ameliorate pancreatic injury of SAP via the NRF2/NQO1/HO-1 pathway to inhibit oxidative stress .

Background: Oxidative stress plays a pivotal role in the progress of severe acute pancreatitis (SAP). Vitamin C (VC) is the most important antioxidant in plasma. However, the effects of an intravenous administration of high-dose VC and the mechanisms by which it exerts its antioxidant function in an experimental model of SAP have not been determined.
Methods: Sodium taurocholate was used to induce rat pancreatic injury and AR42J cells injury. After the establishment of SAP model, SAP rat and injured AR42J cells were treated with VC. For the injured AR42J cells, small interfering RNA-mediated knockdown of NRF2 was conducted after VC treatment. The histopathological characteristics, the apoptosis of pancreatic acinar cells, oxidative stress markers and levels of enzymes, biochemical indicators, and inflammatory cytokines were examinedand. Furthermore, the mortality of rats was assessed.
Results: andresults demonstrated that VC treatment ameliorated apoptosis of pancreatic acinar cells, as evidenced by the increase in Bcl-2, Bcl-XL, and MCL-1 expressions and decrease in Bax and cleaved caspase-3 expression along with decreased TUNEL-positive cells. Also, we found that the elevation of MDA and decrease of SOD, GPx, GSH/GSSG, and T-AOC induced by SAP were reversed by VC treatmentand, and VC treatment increased expressions of Nrf2, NQO1, and HO-1 in SAP model at protein and gene level, indicating that VC attenuated oxidative stress via the NRF2/NQO1/HO-1 pathway. Meanwhile, it was found that sodium taurocholate significantly induced the release of amylase, lipase, IL-1β, and IL-6 in rat plasma and AR42J cells, which were declined by VC treatment.results also revealed that these alterations in sodium taurocholate-injured AR42J cells due to VC treatment was attenuated by NRF2 knockdown. In addition, VC at a dose of 500 mg/kg decreased the levels of lactic acid, Cre, NGAL, AST, and ALT in the plasma of SAP rats, suggesting the improvement of renal and pancreatic injury and liver function of SAP rats. Furthermore, the mortality of SAP rats was 50%, which declined to 30% after VC treatment.
Conclusions: The present study suggests that high-dose of VC ameliorate pancreatic injury of SAP via the NRF2/NQO1/HO-1 pathway to inhibit oxidative stress.


greenmedinfo--2020-08-15--Flavonoids-rich Ziziphus jujuba extract can inhibit biofilm formation.

BACKGROUND : To evaluate the in vitro antibacterial effect of flavonoids-rich Ziziphus jujuba Mill .
extract ( FZM ) against @ @ @ @ @ ( BBFs ) in Staphylococcus aureus .
RESULTS : FZM can effectively inhibit the formation @ @ @ @ @ vitro .
Morphological observation showed a decrease in both biofilm adhesion and thickness .
Results @ @ @ @ @ used to detect the thickness of the BBFs showed that FZM treatment reduced the thickness @ @ @ @ @ , after the Image-Pro Plus v.6.0 analysis of the fluorescence intensity , FZM treatment reduced @ @ @ @ @ as well as the proportion of green fluorescence .
Scanning electron microscopy showed that FZM @ @ @ @ @ for substance exchange in the biofilm , thus exposing the bacterial cells and damaging its @ @ @ @ @ FZM can inhibit biofilm formation , improve the bacterial pH environment , and eliminate the @ @ @ @ @ species and flavonoids .

BACKGROUND: To evaluate the in vitro antibacterial effect of flavonoids-rich Ziziphus jujuba Mill. extract (FZM) against the formation of bacterial biofilms (BBFs) in Staphylococcus aureus.
RESULTS: FZM can effectively inhibit the formation of S. aureus biofilms in vitro. Morphological observation showed a decrease in both biofilm adhesion and thickness. Results of confocal laser scanning microscopy used to detect the thickness of the BBFs showed that FZM treatment reduced the thickness of the BBFs. Furthermore, after the Image-Pro Plus v.6.0 analysis of the fluorescence intensity, FZM treatment reduced the thickness of the BBFs as well as the proportion of green fluorescence. Scanning electron microscopy showed that FZM can disrupt the channels available for substance exchange in the biofilm, thus exposing the bacterial cells and damaging its three-dimensional structures.
CONCLUSION: FZM can inhibit biofilm formation, improve the bacterial pH environment, and eliminate the hydrophobic effect of reactive oxygen species and flavonoids.


greenmedinfo--2020-08-15--The results of the present study showed that aqueous and ethyl acetate fractions of Ziziphus jujube

The results of the present study showed that aqueous and ethyl acetate fractions of Ziziphus jujube prevented the development of hypertension.

Background : ( ZJ ) is a plant with anti-hypertensive property .
In this regard , the present study investigated the effect of aqueous and ethyl acetate fractions of ZJ extract on acute hypertension ( HTN ) induced by nitro-L-arginine methyl ester ( L-NAME ) .
Methods : The current study was carried on 49 hypertensive rats divided into seven groups , including i ) control ; ii ) L-NAME ( 10 mg/kg ) ; iii ) sodium nitroprusside ( SNP ) ( 50μg/kg ) plus L-NAME ; iv and v ) aqueous fraction of ZJ ( 150 mg/kg and @ @ @ @ @ @ @ ) and vii ) ethyl acetate fractions of ZJ ( 150 mg/kg and 300 mg/kg ) plus L-NAME .
The rats were orally treated with both fractions for four weeks and received intravenous L-NAME on the 28th day .
The mean arterial pressure ( MAP ) , systolic blood pressure ( SBP ) and heart rate ( HR ) of the rats were recorded then maximal changes ( Δ ) of MAP , SBP and HR were calculated and compared with changes of control and L-NAME .
Results : According to the obtained @ @ @ @ @ @ @ was shown that the administration of L-NAME significantly increasedΔMAP , ΔSBP and ΔHR , and these effects were significantly attenuated by administration of SNP .
The pre-treatment with both doses ( 150 mg/kg and 300 mg/kg ) of aqueous and ethyl acetate fractions could significantly reduce cardiovascular responses induced by L-NAME that comparable with SNP .
However , a lower dose of aqueous fractions and higher dose of ethyl acetate fractions were reported with stronger effects .
Conclusion : The results of the current study showed that both the aqueous and ethyl acetate @ @ @ @ @ @ @ nitric oxide system can prevent the development of HTN induced by L-NAME .

Background: (ZJ) is a plant with anti-hypertensive property. In this regard, the present study investigated the effect of aqueous and ethyl acetate fractions of ZJ extract on acute hypertension (HTN) induced by nitro-L-arginine methyl ester (L-NAME).
Methods: The current study was carried on 49 hypertensive rats divided into seven groups, including i) control; ii) L-NAME (10 mg/kg); iii) sodium nitroprusside (SNP) (50μg/kg) plus L-NAME; iv and v) aqueous fraction of ZJ (150 mg/kg and 300 mg/kg) plus L-NAME; vi) and vii) ethyl acetate fractions of ZJ (150 mg/kg and 300 mg/kg) plus L-NAME. The rats were orally treated with both fractions for four weeks and received intravenous L-NAME on the 28th day. The mean arterial pressure (MAP), systolic blood pressure (SBP) and heart rate (HR) of the rats were recorded then maximal changes (Δ) of MAP, SBP and HR were calculated and compared with changes of control and L-NAME.
Results: According to the obtained results of the present study, it was shown that the administration of L-NAME significantly increasedΔMAP, ΔSBP and ΔHR, and these effects were significantly attenuated by administration of SNP. The pre-treatment with both doses (150 mg/kg and 300 mg/kg) of aqueous and ethyl acetate fractions could significantly reduce cardiovascular responses induced by L-NAME that comparable with SNP. However,a lower dose of aqueous fractions and higher dose of ethyl acetate fractions were reported with stronger effects.
Conclusion: The results of the current study showed that both the aqueous and ethyl acetate fractions of ZJ through the effect on nitric oxide system can prevent the development of HTN induced by L-NAME.


greenmedinfo--2020-08-15--Dietary hydrolyzed jujube extract can reduce benzo(a)pyrene-induced lung inflammation.

The fruit of Ziziphus jujuba , commonly called jujube , has long been consumed for its health benefits .
The aim of this study was to examine the protective effect of dietary supplementation of enzymatically hydrolyzed jujube against lung inflammation in mice .
The macerated flesh of jujube was extracted with aqueous ethanol before and after Viscozyme treatment .
The extract of enzyme-treated jujube , called herein hydrolyzed jujube extract ( HJE ) , contained higher levels of quercetin , total phenolics , and flavonoids , and exhibited more effective radical-scavenging abilities in comparison to non-hydrolyzed jujube extract ( NHJE @ @ @ @ @ @ @ inflammation-associated molecules , including nitric oxide and pro-inflammatory cytokines from activated Raw 264.7 or differentiated THP-1 cells .
HJE treatment also reduced expression of nuclear factor-κB and its downstream proteins in A549 human lung epithelial cells .
Moreover , oral supplementation of 1.5 g of HJE per kg of body weight ( BW ) attenuated histological lung damage , decreased plasma cytokines , and inhibited expression of inflammatory proteins and oxidative stress mediators in the lungs of mice exposed to benzo ( a ) pyrene at 50 mg/kg BW .
Expression levels of @ @ @ @ @ @ @ nuclear factor erythroid-derived 2-related factor 2 and heme oxygenase-1 , were increased in lung and liver tissues from mice treated with HJE , compared to mice fed NHJE .
These findings indicate that dietary HJE can reduce benzo ( a ) pyrene-induced lung inflammation by inhibiting cytokine release from macrophages and promoting antioxidant defenses in vivo .

The fruit of Ziziphus jujuba, commonly called jujube, has long been consumed for its health benefits. The aim of this study was to examine the protective effect of dietary supplementation of enzymatically hydrolyzed jujube against lung inflammation in mice. The macerated flesh of jujube was extracted with aqueous ethanol before and after Viscozyme treatment. The extract of enzyme-treated jujube, called herein hydrolyzed jujube extract (HJE), contained higher levels of quercetin, total phenolics, and flavonoids, and exhibited more effective radical-scavenging abilities in comparison to non-hydrolyzed jujube extract (NHJE). HJE treatment decreased production of inflammation-associated molecules, including nitric oxide and pro-inflammatory cytokines from activated Raw 264.7 or differentiated THP-1 cells. HJE treatment also reduced expression of nuclear factor-κB and its downstream proteins in A549 human lung epithelial cells. Moreover, oral supplementation of 1.5 g of HJE per kg of body weight (BW) attenuated histological lung damage, decreased plasma cytokines, and inhibited expression of inflammatory proteins and oxidative stress mediators in the lungs of mice exposed to benzo(a)pyrene at 50 mg/kg BW. Expression levels of antioxidant and cytoprotective factors, such as nuclear factor erythroid-derived 2-related factor 2 and heme oxygenase-1, were increased in lung and liver tissues from mice treated with HJE, compared to mice fed NHJE. These findings indicate that dietary HJE can reduce benzo(a)pyrene-induced lung inflammation by inhibiting cytokine release from macrophages and promoting antioxidant defenses in vivo.


greenmedinfo--2020-08-15--Molecular mechanisms of polysaccharides from Ziziphus jujuba Mill var. spinosa seeds regulating the

Molecular mechanisms of polysaccharides from Ziziphus jujuba Mill var. spinosa seeds regulating the bioavailability of spinosin and preventing colitis.

In this study , the effect of Ziziphus jujuba Mill var .
spinosa seeds ( ZSS ) polysaccharides on the @ @ @ @ @ and its molecular mechanism were investigated .
After continuously fed with ZSS polysaccharides 100 mg/kg·dfor @ @ @ @ @ C57BL/6 mice absorbed spinosin at an obvious lower level compared with the control group .
@ @ @ @ @ , MRP2 and Occludin in the colon were significantly increased .
ZSS polysaccharides significantly regulated @ @ @ @ @ microbiota , reducing the abundance of Bacteroidetes , and increasing the richness of Firmicutes and @ @ @ @ @ polysaccharides can significantly regulate the expression levels of tight junction proteins and efflux transporters in @ @ @ @ @ the gut microbiota culture supernatant showed no obvious biological activity in this regard .
Furthermore @ @ @ @ @ polysaccharides can alleviate TNBS-induced colitis , reduced inflammatory cell infiltration in mice .
This immune @ @ @ @ @ NF-κB and MAPK pathways in RAW264.7 cells .

In this study, the effect of Ziziphus jujuba Mill var. spinosa seeds (ZSS) polysaccharides on the bioavailability of spinosin in mice and its molecular mechanism were investigated. After continuously fed with ZSS polysaccharides 100 mg/kg·dfor 28 consecutive days, the C57BL/6 mice absorbed spinosin at an obvious lower level compared with the control group. The expression levels of P-gp, MRP2 and Occludin in the colon were significantly increased. ZSS polysaccharides significantly regulated the composition of the gut microbiota, reducing the abundance of Bacteroidetes, and increasing the richness of Firmicutes and Verrucomicrobia. Moreover, ZSS polysaccharides can significantly regulate the expression levels of tight junction proteins and efflux transporters in Caco-2 cells. However, the gut microbiota culture supernatant showed no obvious biological activity in this regard. Furthermore, histopathological analysis revealed ZSS polysaccharides can alleviate TNBS-induced colitis, reduced inflammatory cell infiltration in mice. This immune regulation was related to the NF-κB and MAPK pathways in RAW264.7 cells.


greenmedinfo--2020-08-17--Paeonol alleviates dextran sodium sulfate induced colitis involving Candida albicans-associated dysb

Paeonol alleviates dextran sodium sulfate induced colitis involving Candida albicans-associated dysbiosis.

: Inflammatory bowel disease ( IBD ) , which consists of ulcerative colitis ( UC ) and Crohn 's disease ( CD ) , is a chronic inflammatory disorder of the gastrointestinal tract .
Occurrence and development of UC have been associated with multiple potential causative factors , which include fungal dysbiosis .
Growing evidence reveals that Candida albicans-associated dysbiosis is correlated with clinical deterioration in UC .
Paeonol ( PAE ) is a commonly used traditional medicine with multiple reported properties including effective alleviation of UC .
In this study , a murine UC model was established by colonizing @ @ @ @ @ @ @ prior to dextran sodium sulfate ( DSS ) administration .
Effects of PAE treatment were also assessed at initiation and in preestablished C. albicans-associated colitis .
The results showed that C. albicans supplementation could aggravate disease activity index ( DAI ) , compromise mucosal integrity , exacerbate fecal and tissue fungal burdens , increase serumβ-glucan and anti-Saccharomyces cerevisiae antibody ( ASCA ) levels , promote serum and colonic tissue pro-inflammatory cytokine secretion ( tumor necrosis factor ( TNF ) -α , interleukin ( IL ) -1β , IL-6 , and IL-8 ) and @ @ @ @ @ @ @ It also stimulated Dectin-1 , TLR2 and TLR4 as well as expression of their downstream effector NF-κB in colonic tissue .
After PAE treatment , the adverse impacts of C. albicans on colitis were relieved , via decreased receptor-associated local and systemic inflammation .
Our study suggests that PAE should be a candidate for treatment offungal dysbiosis-associated UC and may act through the Dectin-1/NF-κB pathway in collaboration with TLR2 and TLR4 .
LAY SUMMARY : Candida albicans is believed to be an important stimulator in ulcerative colitice ( UC ) development .
Suppressing @ @ @ @ @ @ @ be contributory to the amelioration of UC .
Paeonol ( PAE ) is a commonly used traditional medicine with multiple biological functions .
In this study , we observed that PAE could alleviate symptoms in mice UC model accompanying with burden reduction of C. albicans .
Therefore , we suppose that PAE can be a candidate in the treatment of C. albicans-associated UC .

: Inflammatory bowel disease (IBD), which consists of ulcerative colitis (UC) and Crohn's disease (CD), is a chronic inflammatory disorder of the gastrointestinal tract. Occurrence and development of UC have been associated with multiple potential causative factors, which include fungal dysbiosis. Growing evidence reveals that Candida albicans-associated dysbiosis is correlated with clinical deterioration in UC. Paeonol (PAE) is a commonly used traditional medicine with multiple reported properties including effective alleviation of UC. In this study, a murine UC model was established by colonizing mice with additional C. albicans via gavage prior to dextran sodium sulfate (DSS) administration. Effects of PAE treatment were also assessed at initiation and in preestablished C. albicans-associated colitis. The results showed that C. albicans supplementation could aggravate disease activity index (DAI), compromise mucosal integrity, exacerbate fecal and tissue fungal burdens, increase serumβ-glucan and anti-Saccharomyces cerevisiae antibody (ASCA) levels, promote serum and colonic tissue pro-inflammatory cytokine secretion (tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-8) and decrease the anti-inflammatory cytokine IL-10 level. It also stimulated Dectin-1, TLR2 and TLR4 as well as expression of their downstream effector NF-κB in colonic tissue. After PAE treatment, the adverse impacts of C. albicans on colitis were relieved, via decreased receptor-associated local and systemic inflammation. Our study suggests that PAE should be a candidate for treatment offungal dysbiosis-associated UC and may act through the Dectin-1/NF-κB pathway in collaboration with TLR2 and TLR4.
LAY SUMMARY: Candida albicans is believed to be an important stimulator in ulcerative colitice (UC) development. Suppressing the growth of intestinal C. albicans can be contributory to the amelioration of UC. Paeonol (PAE) is a commonly used traditional medicine with multiple biological functions. In this study, we observed that PAE could alleviate symptoms in mice UC model accompanying with burden reduction of C. albicans. Therefore, we suppose that PAE can be a candidate in the treatment of C. albicans-associated UC.


greenmedinfo--2020-08-16--Paeonol exerts anti‑tumor activity against colorectal cancer cells.

Paeonol is a simple phenolic compound isolated from herbal root bark , which has been reported to possess numerous biological and pharmacological characteristics , including a desirable anti‑tumor effect .
To date , the effect of paeonol against colorectal cancer ( CRC ) cells is yet to be fully elucidated .
Therefore , the present study aimed to identify the underlying mechanism via which paeonol exerts its anti‑tumor activity on HCT116 cells .
After incubation with various concentrations of paeonol ( 7.8125 , 15.625 , 31.25 , 62.5 , 125 , 250 and 500 µg/ml ) , the inhibitory effect @ @ @ @ @ @ @ using a Cell Counting Kit‑8 assay .
Cell apoptosis and cell cycle distribution were measured using flow cytometry .
Moreover , caspase activity was measured using a colorimetric caspase assay .
Luciferase assay was also used to determine the β‑catenin‑mediated transcriptional activity of T‑cell specific transcription factor/lymphoid‑enhancer binding factor ( TCF/LEF ) , and western blotting analysis was performed to measure the related expression of proteins .
The results indicated that paeonol exhibited a notable effect against HCT116 cells by inducing G0/G1‑phase arrest , as demonstrated by downregulation of the cell cycle regulators @ @ @ @ @ @ @ upregulation of p21Cip1 in a dose‑dependent manner .
Furthermore , paeonol dose‑dependently induced cell apoptosis , accompanied by an increase in the Bax/Bcl‑2 ratio , release of cytochrome c and further activation of caspases .
Paeonol also dose‑dependently blocked the activation of the Wnt/β‑catenin signaling pathway by suppressing the expression of β‑catenin , resulting in a decrease in β‑catenin‑mediated activity of TCF/LEF and downregulation of downstream target genes , including cyclin D1 , survivin and c‑Myc .
Therefore , the present results suggested that paeonol exerted its anti‑tumor effects on CRC cells , @ @ @ @ @ @ @ induction of cell cycle arrest and initiation of apoptosis , at least partly by suppressing the Wnt/β‑catenin pathway , which may offer a promising therapeutic strategy for CRC .

Paeonol is a simple phenolic compound isolated from herbal root bark, which has been reported to possess numerous biological and pharmacological characteristics, including a desirable anti‑tumor effect. To date, the effect of paeonol against colorectal cancer (CRC) cells is yet to be fully elucidated. Therefore, the present study aimed to identify the underlying mechanism via which paeonol exerts its anti‑tumor activity on HCT116 cells. After incubation with various concentrations of paeonol (7.8125, 15.625, 31.25, 62.5, 125, 250 and 500 µg/ml), the inhibitory effect of paeonol on cell viability was assessed using a Cell Counting Kit‑8 assay. Cell apoptosis and cell cycle distribution were measured using flow cytometry. Moreover, caspase activity was measured using a colorimetric caspase assay. Luciferase assay was also used to determine the β‑catenin‑mediated transcriptional activity of T‑cell specific transcription factor/lymphoid‑enhancer binding factor (TCF/LEF), and western blotting analysis was performed to measure the related expression of proteins. The results indicated that paeonol exhibited a notable effect against HCT116 cells by inducing G0/G1‑phase arrest, as demonstrated by downregulation of the cell cycle regulators cyclin‑dependent kinase 4 and cyclin D1 and upregulation of p21Cip1 in a dose‑dependent manner. Furthermore, paeonol dose‑dependently induced cell apoptosis, accompanied by an increase in the Bax/Bcl‑2 ratio, release of cytochrome c and further activation of caspases. Paeonol also dose‑dependently blocked the activation of the Wnt/β‑catenin signaling pathway by suppressing the expression of β‑catenin, resulting in a decrease in β‑catenin‑mediated activity of TCF/LEF and downregulation of downstream target genes, including cyclin D1, survivin and c‑Myc. Therefore, the present results suggested that paeonol exerted its anti‑tumor effects on CRC cells, including the inhibition of cell proliferation, induction of cell cycle arrest and initiation of apoptosis, at least partly by suppressing the Wnt/β‑catenin pathway, which may offer a promising therapeutic strategy for CRC.


greenmedinfo--2020-08-16--Paeonol inhibits proliferation and induces cell apoptosis of human T24 and 5637 bladder cancer cells

Paeonol inhibits proliferation and induces cell apoptosis of human T24 and 5637 bladder cancer cells.

PURPOSE : Paeonol is a natural chemical medicine derived from the bark of peony root , which has been found to inhibit tumor activity in various tumor cell lines , and can play a synergistic anti-tumor effect with chemotherapy or radiotherapy .
METHODS : We used paeonol to act on human bladder cancer T24 and 5637 cells , and established xenograft tumor in nude mice by subcutaneous injection of T24 cells .
RESULTS : CCK-8 assay and plate cloning experiments showed that paeonol could inhibit the proliferation of T24 and 5637 cells in vitro .
The results of flow cytometry @ @ @ @ @ @ @ and Caspase-3 proteins suggested that paeonol can induce apoptosis of T24 and 5637 cells in vitro .
Tumor formation , TUNEL detection and immunohistochemical results of Ki67 , BAX , Bcl-2 and Caspase-3 in nude mice showed that paeonol could inhibit T24 cell proliferation and induce apoptosis in vivo , thus inhibiting tumor growth .
Further research revealed that paeonol could reduce phosphorylation expression of PI3K and AKT in T24 and 5637 cells .
CONCLUSION : We confirmed that paeonol could inhibit proliferation and induce apoptosis of human bladder cancer T24 and 5637 @ @ @ @ @ @ @ inhibit the growth of T24 tumor-forming nude mice , and possibly play a role by inhibiting the PI3K/AKT signaling pathway , so as to provide a potential therapeutic drug for bladder cancer .

PURPOSE: Paeonol is a natural chemical medicine derived from the bark of peony root, which has been found to inhibit tumor activity in various tumor cell lines, and can play a synergistic anti-tumor effect with chemotherapy or radiotherapy.
METHODS: We used paeonol to act on human bladder cancer T24 and 5637 cells, and established xenograft tumor in nude mice by subcutaneous injection of T24 cells.
RESULTS: CCK-8 assay and plate cloning experiments showed that paeonol could inhibit the proliferation of T24 and 5637 cells in vitro. The results of flow cytometry and the detection of BAX, Bcl-2 and Caspase-3 proteins suggested that paeonol can induce apoptosis of T24 and 5637 cells in vitro. Tumor formation, TUNEL detection and immunohistochemical results of Ki67, BAX, Bcl-2 and Caspase-3 in nude mice showed that paeonol could inhibit T24 cell proliferation and induce apoptosis in vivo, thus inhibiting tumor growth. Further research revealed that paeonol could reduce phosphorylation expression of PI3K and AKT in T24 and 5637 cells.
CONCLUSION: We confirmed that paeonol could inhibit proliferation and induce apoptosis of human bladder cancer T24 and 5637 cells in vitro and in vivo, inhibit the growth of T24 tumor-forming nude mice, and possibly play a role by inhibiting the PI3K/AKT signaling pathway, so as to provide a potential therapeutic drug for bladder cancer.


greenmedinfo--2020-08-16--Paeonol impeded cell viability, migration and invasion and triggered apoptosis by regulating miR-21-

Background : Hepatocellular carcinoma ( HCC ) is one of the most common tumors with high mortality .
MicroRNAs ( miRNAs ) were reported as crucial markers for the diagnosis of HCC .
Paeonol exerted many pharmacological effects on tumor progression .
This study aimed to elucidate the underlying molecular mechanism of paeonol in HCC progression .
Methods : Cell viability was determined by Cell Counting Kit-8 ( CCK-8 ) assay .
Cell apoptosis was examined by flow cytometry .
The levels of Cyclin D1 , cyclin-dependent kinase 4 ( CDK4 ) , B-cell lymphoma-2 ( Bcl-2 ) and Bcl-2 @ @ @ @ @ @ @ detected by Western blot assay .
Cell migration and invasion were assessed by transwell assay .
The levels of matrix metalloproteinase-2 ( MMP2 ) and matrix metalloproteinase-9 ( MMP9 ) were measured by Western blot .
The expression of miR-21-5p and kruppel-like factor 6 ( KLF6 ) was detected by quantitative real-time PCR ( qRT-PCR ) or Western blot assay , respectively .
Dual-luciferase reporter assay was performed to analyze the interaction between miR-21-5p and KLF6 .
The enrichment of miR-21-5p was determined by RNA pull-down assay .
Xenograft assay was conducted to @ @ @ @ @ @ @ : The results demonstrated that cell viability of Hep3B and Huh-7 cells was inhibited , while cell apoptosis was promoted after treatment with paeonol .
Transwell assay indicated that cell migration and invasion were blocked in paeonol-treated cells .
Moreover , miR-21-5p expression was markedly decreased in paeonol-treated cells and its knockdown suppressed cell viability , migration and invasion , but contributed to cell apoptosis .
MiR-21-5p targeted KLF6 and its silencing prominently elevated KLF6 level .
Furthermore , the restoration experiment determined that miR-21-5p and KLF6 were antagonisms on cell viability , @ @ @ @ @ @ @ , paeonol abated the decrease in KLF6 level caused by miR-21-5p up-regulation .
Besides , paeonol suppressed tumor growth in vivo .
Conclusion : Paeonol impeded cell viability , migration and invasion and triggered apoptosis by regulating miR-21-5p/KLF6 axis in HCC cells .
Xenograft assay confirmed that paeonol inhibited tumor growth through miR-21-5p/KLF6 axis in HCC in vivo .

Background: Hepatocellular carcinoma (HCC) is one of the most common tumors with high mortality. MicroRNAs (miRNAs) were reported as crucial markers for the diagnosis of HCC. Paeonol exerted many pharmacological effects on tumor progression. This study aimed to elucidate the underlying molecular mechanism of paeonol in HCC progression.
Methods: Cell viability was determined by Cell Counting Kit-8 (CCK-8) assay. Cell apoptosis was examined by flow cytometry. The levels of Cyclin D1, cyclin-dependent kinase 4 (CDK4), B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax) were detected by Western blot assay. Cell migration and invasion were assessed by transwell assay. The levels of matrix metalloproteinase-2 (MMP2) and matrix metalloproteinase-9 (MMP9) were measured by Western blot. The expression of miR-21-5p and kruppel-like factor 6 (KLF6) was detected by quantitative real-time PCR (qRT-PCR) or Western blot assay, respectively. Dual-luciferase reporter assay was performed to analyze the interaction between miR-21-5p and KLF6. The enrichment of miR-21-5p was determined by RNA pull-down assay. Xenograft assay was conducted to analyze tumor growth in vivo.
Results: The results demonstrated that cell viability of Hep3B and Huh-7 cells was inhibited, while cell apoptosis was promoted after treatment with paeonol. Transwell assay indicated that cell migration and invasion were blocked in paeonol-treated cells. Moreover, miR-21-5p expression was markedly decreased in paeonol-treated cells and its knockdown suppressed cell viability, migration and invasion, but contributed to cell apoptosis. MiR-21-5p targeted KLF6 and its silencing prominently elevated KLF6 level. Furthermore, the restoration experiment determined that miR-21-5p and KLF6 were antagonisms on cell viability, apoptosis, migration and invasion. Also, paeonol abated the decrease in KLF6 level caused by miR-21-5p up-regulation. Besides, paeonol suppressed tumor growth in vivo.
Conclusion: Paeonol impeded cell viability, migration and invasion and triggered apoptosis by regulating miR-21-5p/KLF6 axis in HCC cells. Xenograft assay confirmed that paeonol inhibited tumor growth through miR-21-5p/KLF6 axis in HCC in vivo.