greenmedinfo--2020-11-20--Berberine inhibits proliferation and induces G0/G1 phase arrest in colorectal cancer cells.

AIMS : Berberine ( BBR ) is one of isoquinoline alkaloids from Coptidis Rhizoma and possesses extensive pharmacological activities , @ @ @ @ @ ) activity .
However , the detailed mechanisms remain to be determined .
The current @ @ @ @ @ ability and the potential mechanism of BBR against CRC .
MAIN METHODS : By mining @ @ @ @ @ results of cells and tumors treated with BBR for perform bioinformatics analysis to find key @ @ @ @ @ knockdown of IGF2BP3 assays were used to explore the biological role of IGF2BP3 in the @ @ @ @ @ .
KEY FINDINGS : Our results showed that BBR inhibits proliferation and induces G0/G1 phase @ @ @ @ @ downregulating IGF2BP3 .
Specifically , Knockdown of IGF2BP3 could suppress the PI3K/AKT pathway to inhibit @ @ @ @ @ .
The negative effects of BBR in CRC cells could be rescued by overexpressing IGF2BP3 @ @ @ @ @ might provide a theoretical basis for the future use of BBR in colorectal cancer prevention @

AIMS: Berberine (BBR) is one of isoquinoline alkaloids from Coptidis Rhizoma and possesses extensive pharmacological activities, including anti-colorectal cancer (CRC) activity. However, the detailed mechanisms remain to be determined. The current study aims to investigate the ability and the potential mechanism of BBR against CRC.
MAIN METHODS: By mining recognized CRC datasets and RNA-seq results of cells and tumors treated with BBR for perform bioinformatics analysis to find key targets IGF2BP3. Overexpression and knockdown of IGF2BP3 assays were used to explore the biological role of IGF2BP3 in the process of BBR against CRC.
KEY FINDINGS: Our results showed that BBR inhibits proliferation and induces G0/G1 phase arrest in CRC cells by downregulating IGF2BP3. Specifically, Knockdown of IGF2BP3 could suppress the PI3K/AKT pathway to inhibit cell proliferation and cycle transition. The negative effects of BBR in CRC cells could be rescued by overexpressing IGF2BP3.
SIGNIFICANCE: Our data might provide a theoretical basis for the future use of BBR in colorectal cancer prevention.


greenmedinfo--2020-11-20--These results demonstrated that berberine could alleviate symptoms in type 2 diabetes.

OBJECTIVE : Berberine ( BBR ) , which is extracted from traditional Chinese herb , is abundant in Coptis chinensis and Berberis vulgaris , with a treatment on type 2 diabetes mellitus ( T2DM ) .
However , its oral bioavailability is poor .
Therefore , the ability of BBR to regulate gut microbiota and intestinal metabolites might exist .
This study aimed to investigate changes in gut microbiota and intestinal metabolites , and to reveal the potential mechanism of BBR .
METHODS : To observe the role of gut microbiota in the treatment of T2DM by BBR , antibiotics @ @ @ @ @ @ @ study , and the therapeutic effects of BBR were evaluated .
A 16S rRNA gene sequencing approach was utilized to analyze gut microbiota alterations , and UHPLC-QTOF/MS-based untargeted metabolomics analysis of colon contents was used to identity differential intestinal metabolites .
Finally , serum aromatic amino acids ( AAAs ) were absolutely quantified using LC/MS .
RESULTS : Inhibition of the blood glucose levels , and improvements in glucose tolerance and serum lipid parameters were observed in the BBR treated group .
Type 2 diabetic symptoms in rats in the BA group ( @ @ @ @ @ @ @ alleviated .
However , the therapeutical effects are weaker in the BA group compared with the BBR group , indicating that BBR can be used to treat type 2 diabetic rats immediately , and modulation of gut microbiota is related to the mechanism of BBR in the treatment of T2DM .
The community richness and diversity of the gut microbiota were significantly increased by BBR , and the relative abundance of Bacteroidetes was increased in the BBR group , which was accompanied by a decreased relative abundance of Proteobacteria and Verrucomicrobia at the @ @ @ @ @ @ @ , a probiotic Lactobacillaceae was significantly upregulated not only in the BBR group but also in the BA group and was negatively associated with the risk of T2DM .
Metabolomic analysis of colon contents identified 55 differential intestinal metabolites between the BBR group and the model group .
AAAs , including tyrosine , tryptophan and phenylalanine , were obviously decreased in the BBR group not only in the colon contents but also in the serum .
CONCLUSIONS : These results demonstrated that BBR could alleviate symptoms in type 2 diabetic rats by affecting @ @ @ @ @ @ @ of AAAs .

OBJECTIVE: Berberine (BBR), which is extracted from traditional Chinese herb, is abundant in Coptis chinensis and Berberis vulgaris, with a treatment on type 2 diabetes mellitus (T2DM). However, its oral bioavailability is poor. Therefore, the ability of BBR to regulate gut microbiota and intestinal metabolites might exist. This study aimed to investigate changes in gut microbiota and intestinal metabolites, and to reveal the potential mechanism of BBR.
METHODS: To observe the role of gut microbiota in the treatment of T2DM by BBR, antibiotics intervened gut microbiota was used in this study, and the therapeutic effects of BBR were evaluated. A 16S rRNA gene sequencing approach was utilized to analyze gut microbiota alterations, and UHPLC-QTOF/MS-based untargeted metabolomics analysis of colon contents was used to identity differential intestinal metabolites. Finally, serum aromatic amino acids (AAAs) were absolutely quantified using LC/MS.
RESULTS: Inhibition of the blood glucose levels, and improvements in glucose tolerance and serum lipid parameters were observed in the BBR treated group. Type 2 diabetic symptoms in rats in the BA group (treated with antibotics and BBR) were alleviated. However, the therapeutical effects are weaker in the BA group compared with the BBR group, indicating that BBR can be used to treat type 2 diabetic rats immediately, and modulation of gut microbiota is related to the mechanism of BBR in the treatment of T2DM. The community richness and diversity of the gut microbiota were significantly increased by BBR, and the relative abundance of Bacteroidetes was increased in the BBR group, which was accompanied by a decreased relative abundance of Proteobacteria and Verrucomicrobia at the phylum level. At the family level, a probiotic Lactobacillaceae was significantly upregulated not only in the BBR group but also in the BA group and was negatively associated with the risk of T2DM. Metabolomic analysis of colon contents identified 55 differential intestinal metabolites between the BBR group and the model group. AAAs, including tyrosine, tryptophan and phenylalanine, were obviously decreased in the BBR group not only in the colon contents but also in the serum.
CONCLUSIONS: These results demonstrated that BBR could alleviate symptoms in type 2 diabetic rats by affecting gut microbiota composition and reducing the concentration of AAAs.


greenmedinfo--2020-11-20--Berberine alleviates cisplatin-induced acute kidney injury.

Background : To study the protective effect of berberine ( BBR ) on cisplatin-induced acute kidney injury ( AKI ) and its effect on mitophagy .
Methods : ( I ) Male C57BL/6 mice aged 6-8 weeks were randomly divided into control group ( saline ) , cisplatin group ( cisplatin ) , and cisplatin + BBR ( 5 , 10 mg/kg ) groups .
In the cisplatin group and BBR groups , mice were injected intraperitoneally with 15 mg/kg of cisplatin .
Mice in BBR groups were given BBR at 72 , 48 , 24 , 0.5 h before @ @ @ @ @ @ @ injection .
Mice were sacrificed 72 h after cisplatin injection , and blood were collected for detecting serum creatinine ( SCr ) and blood urea nitrogen ( BUN ) levels .
Kidneys were collected for detecting protein expression levels of Kidney injury molecule 1 ( KIM-1 ) , LC3 II/LC3 I , p62 , PINK 1 , Parkin in the renal tissue by Western blotting .
The pathological changes in renal tissues were observed using periodic acid-Schiff ( PAS ) staining .
( II ) Renal tubular epithelial cells ( RTECs ) were @ @ @ @ @ @ @ 2 , and 4µM ) of BBR , and then incubated with cisplatin .
Changes in autophagy proteins LC3 II/LC3 I , p62 , PINK 1 , and Parkin were detected by Western blotting , and changes in cellular reactive oxygen species ( ROS ) and mitochondrial membrane potential ( MMP ) were detected by flow cytometry .
Results : ( I ) Mice treated with BBR at dosage of 5 and 10 mg/kg for 6 days showed significant reduction in SCr and BUN compared to that in mice treated with cisplatin .
@ @ @ @ @ @ @ ameliorated cisplatin-induced nephrotoxicity and reduced cisplatin-induced increase in protein expression levels of KIM-1 .
Compared to cisplatin-treated mice , the mice treated with BBR showed increased LC3 II/LC3 I , PINK 1 , and Parkin , and decreased p62 protein expression .
( II ) Compared to cisplatin-incubated RTECs , cells pretreated with BBR for 24 h exhibited increased protein expressions of LC3 II/LC3 I , PINK1 , and Parkin and decreased protein expression of p62 .
BBR reversed cellular ROS and cell MMP level induced by cisplatin .
Conclusions : BBR plays @ @ @ @ @ @ @ up-regulating mitophagy in RTECs .

Background: To study the protective effect of berberine (BBR) on cisplatin-induced acute kidney injury (AKI) and its effect on mitophagy.
Methods: (I) Male C57BL/6 mice aged 6-8 weeks were randomly divided into control group (saline), cisplatin group (cisplatin), and cisplatin + BBR (5, 10 mg/kg) groups. In the cisplatin group and BBR groups, mice were injected intraperitoneally with 15 mg/kg of cisplatin. Mice in BBR groups were given BBR at 72, 48, 24, 0.5 h before and 24, 48 h after cisplatin injection. Mice were sacrificed 72 h after cisplatin injection, and blood were collected for detecting serum creatinine (SCr) and blood urea nitrogen (BUN) levels. Kidneys were collected for detecting protein expression levels of Kidney injury molecule 1 (KIM-1), LC3 II/LC3 I, p62, PINK 1, Parkin in the renal tissue by Western blotting. The pathological changes in renal tissues were observed using periodic acid-Schiff (PAS) staining. (II) Renal tubular epithelial cells (RTECs) were pretreated with different concentrations (1, 2, and 4µM) of BBR, and then incubated with cisplatin. Changes in autophagy proteins LC3 II/LC3 I, p62, PINK 1, and Parkin were detected by Western blotting, and changes in cellular reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were detected by flow cytometry.
Results: (I) Mice treated with BBR at dosage of 5 and 10 mg/kg for 6 days showed significant reduction in SCr and BUN compared to that in mice treated with cisplatin. PAS staining and immunohistochemistry showed that BBR ameliorated cisplatin-induced nephrotoxicity and reduced cisplatin-induced increase in protein expression levels of KIM-1. Compared to cisplatin-treated mice, the mice treated with BBR showed increased LC3 II/LC3 I, PINK 1, and Parkin, and decreased p62 protein expression. (II) Compared to cisplatin-incubated RTECs, cells pretreated with BBR for 24 h exhibited increased protein expressions of LC3 II/LC3 I, PINK1, and Parkin and decreased protein expression of p62. BBR reversed cellular ROS and cell MMP level induced by cisplatin.
Conclusions: BBR plays a protective role in cisplatin-induced AKI by up-regulating mitophagy in RTECs.


greenmedinfo--2020-11-20--Berberine inhibits colorectal tumor growth by suppressing SHH secretion.

Hedgehog plays an important role in a wide range of physiological and pathological conditions .
Paracrine activation of Hedgehog pathway in stromal cells increases the expression of VEGF , which promotes neovascularization in colorectal cancer and ultimately the growth of colorectal cancer .
Berberine ( BBR ) has anticancer activity .
In this study we investigated whether BBR inhibited the growth of colon cancer through suppressing the paracrine sonic hedgehog ( SHH ) signaling in vitro and in vivo .
We showed that BBR ( 1-10 μM ) dose-dependently inhibited the secretion and expression of SHH protein in HT-29 and @ @ @ @ @ @ @ the transcription of SHH , but promoted the degradation of SHH mRNA , thus decreased the SHH mRNA expression in the colorectal cancer cells .
In nude mice bearing HT-29 xenograft , oral administration of BBR ( 100 mg · kg · d ) or a positive control drug GDC-0449 ( 100 mg · kg · d ) for 4 weeks markedly suppressed the growth of HT-29 tumor with BBR exhibiting a better antitumor efficacy .
The tumor growth inhibition caused by BBR or GDC-0449 was comparable to their respective inhibitory effect on @ @ @ @ @ @ @ tumor .
However , BBR ( 20μM ) did not affect the expression of human transcription factor Gli1 mRNA in HT-29 and SW480 cells .
In conclusion , BBR promotes the degradation of SHH mRNA in colorectal cancer cells , interrupting the paracrine Hedgehog signaling pathway activity thus suppresses the colorectal cancer growth .
This study reveals a novel molecular mechanism underlying the anticancer action of BBR .

Hedgehog plays an important role in a wide range of physiological and pathological conditions. Paracrine activation of Hedgehog pathway in stromal cells increases the expression of VEGF, which promotes neovascularization in colorectal cancer and ultimately the growth of colorectal cancer. Berberine (BBR) has anticancer activity. In this study we investigated whether BBR inhibited the growth of colon cancer through suppressing the paracrine sonic hedgehog (SHH) signaling in vitro and in vivo. We showed that BBR (1-10 μM) dose-dependently inhibited the secretion and expression of SHH protein in HT-29 and SW480 cells. BBR did not influence the transcription of SHH, but promoted the degradation of SHH mRNA, thus decreased the SHH mRNA expression in the colorectal cancer cells. In nude mice bearing HT-29 xenograft, oral administration of BBR (100 mg · kg · d) or a positive control drug GDC-0449 (100 mg · kg · d) for 4 weeks markedly suppressed the growth of HT-29 tumor with BBR exhibiting a better antitumor efficacy. The tumor growth inhibition caused by BBR or GDC-0449 was comparable to their respective inhibitory effect on the mouse-specific Gli mRNA expression in the tumor. However, BBR (20μM) did not affect the expression of human transcription factor Gli1 mRNA in HT-29 and SW480 cells. In conclusion, BBR promotes the degradation of SHH mRNA in colorectal cancer cells, interrupting the paracrine Hedgehog signaling pathway activity thus suppresses the colorectal cancer growth. This study reveals a novel molecular mechanism underlying the anticancer action of BBR.


greenmedinfo--2020-11-20--Immunomodulatory effects of berberine on the inflamed joint reveal new therapeutic targets for rheum

Immunomodulatory effects of berberine on the inflamed joint reveal new therapeutic targets for rheumatoid arthritis management.

Rheumatoid arthritis ( RA ) is a chronic inflammatory syndrome designated by synovial joint inflammation leading to cartilage degradation and @ @ @ @ @ progressive disability .
Synovial inflammation is promoted through the infiltration of mononuclear immune cells , @ @ @ @ @ macrophages and dendritic cells ( DCs ) , together with fibroblast-like synoviocytes ( FLS ) @ @ @ @ @ .
Berberine is a bioactive isoquinoline alkaloid compound showing various pharmacological properties that are mainly @ @ @ @ @ effects .
Several lines of experimental study have recently investigated the therapeutic potential of berberine @ @ @ @ @ treating RA condition .
The present review aimed to clarify determinant cellular and molecular targets @ @ @ @ @ found that berberine through modulating several signalling pathways involved in the joint inflammation , including @ @ @ @ @ and LPA/LPA/ERK/p38 MAPK can inhibit inflammatory proliferation of FLS cells , suppress DC activation and @ @ @ @ @ prevent cartilage and bone destruction .
Importantly , these molecular targets may explore new therapeutic @ @ @ @ @

Rheumatoid arthritis (RA) is a chronic inflammatory syndrome designated by synovial joint inflammation leading to cartilage degradation and bone damage as well as progressive disability. Synovial inflammation is promoted through the infiltration of mononuclear immune cells, dominated by CD4T cells, macrophages and dendritic cells (DCs), together with fibroblast-like synoviocytes (FLS), into the synovial compartment. Berberine is a bioactive isoquinoline alkaloid compound showing various pharmacological properties that are mainly attributed to immunomodulatory and anti-inflammatory effects. Several lines of experimental study have recently investigated the therapeutic potential of berberine and its underlying mechanisms in treating RA condition. The present review aimed to clarify determinant cellular and molecular targets of berberine in RA and found that berberine through modulating several signalling pathways involved in the joint inflammation, including PI3K/Akt, Wnt1/β-catenin, AMPK/lipogenesis and LPA/LPA/ERK/p38 MAPK can inhibit inflammatory proliferation of FLS cells, suppress DC activation and modulate Th17/Treg balance and thus prevent cartilage and bone destruction. Importantly, these molecular targets may explore new therapeutic targets for RA treatment.


greenmedinfo--2020-11-20--Berberine can improve myocardial injury and cardiac function in sepsis.

To investigated whether berberine could ameliorate septic cardiomyopathy in a rat model of sepsis and it 's mechanisms.SD rats were divided into 3 groups : sepsis group ( LPS group ) , rats were intraperitoneal injected of LPS ( 10 mg/kg ) ; Berberine intervention group ( Ber group ) , Ber ( 50 mg/kg , one time per day ) was gavage fed 3 days before intraperitoneally injection of lipopolysaccharides ( LPS ) ; control group ( Con group ) , rats were gavage fed with double distilled water ( 2 ml/100 g , one time per day ) @ @ @ @ @ @ @ saline ( 1 ml/100 g ) .
LPS group and the Ber group was further divided into 3 subgroups ( 6 ) , and the follow-up experiments were conducted at 6 h , 24 h and 48 h after LPS injection ( of which 48 h subgroup rats were gavage fed with Ber/saline at 24 h ) .
Left ventricular systolic pressure ( LVSP ) , left ventricular end-diastolic pressure ( LVEDP ) , and the maximum rate of change of left ventricular pressure ( ±dp/dtmax ) were monitored , the level of @ @ @ @ @ @ @ tumor necrosis factor ( TNF ) -α and interleukin ( IL ) -1β was detected by ELISA method , HE staining of myocardial tissues was done to observe myocardial injury ; Western blotting method was used to detect the expression of toll-like receptor 4 ( TLR4 ) protein in rat myocardial tissue , the level of myocardial cell nucleus protein p65 was detected to reflects the degree of NF-κB activation .
The correlation of factors was analyzed with Pearson correlation analysis.Pre-treatment with berberine stabilized cardiac hemodynamics and improved the systolic function and diastolic @ @ @ @ @ @ @ , as evidenced by the partial recovery of the reduced±dp/dtmax and LVSP , as well as the decreased LVEDP .
Compared with the LPS group , the Ber group showed improved myocardial injury , as demonstrated by decreased cTnT at each time point .
HE staining results showed that berberine decreased inflammatory cell infiltration and LPS-induced cell swelling .
These effects were observed early at 6 hours , severe at 24 hours , and become more serious at 48 hours after LPS injection .
Further , TLR4 and NF-κB p65 subunits , which @ @ @ @ @ @ @ TLR4/NF-κB signaling , were upregulated in the LPS group and attenuated in the Ber group .
Consistently , the expression levels of the downstream cytokines TNF-α and IL-1β were lower in the Ber group than those in the LPS group ( all0.05 ) .
Myocardial injury markers were positively correlated with the markers of TLR4/NF-κB signals and the downstream host inflammatory factors ( all0.05 ) .Berberine can improve myocardial injury and cardiac function in sepsis rats , the mechanism is considered to be related to that it can inhibit the activation of TLR4/NF-κB @ @ @ @ @ @ @ reducing the production of TNF-α and IL-1β .

To investigated whether berberine could ameliorate septic cardiomyopathy in a rat model of sepsis and it's mechanisms.SD rats were divided into 3 groups: sepsis group (LPS group), rats were intraperitoneal injected of LPS (10 mg/kg); Berberine intervention group (Ber group), Ber (50 mg/kg, one time per day) was gavage fed 3 days before intraperitoneally injection of lipopolysaccharides (LPS); control group (Con group), rats were gavage fed with double distilled water (2 ml/100 g, one time per day) 3 days before intraperitoneal injection of normal saline (1 ml/100 g). LPS group and the Ber group was further divided into 3 subgroups (6), and the follow-up experiments were conducted at 6 h, 24 h and 48 h after LPS injection (of which 48 h subgroup rats were gavage fed with Ber/saline at 24 h). Left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), and the maximum rate of change of left ventricular pressure (±dp/dtmax) were monitored, the level of cardiac troponin T (cTnT), tumor necrosis factor (TNF)-α and interleukin (IL)-1β was detected by ELISA method, HE staining of myocardial tissues was done to observe myocardial injury; Western blotting method was used to detect the expression of toll-like receptor 4(TLR4) protein in rat myocardial tissue, the level of myocardial cell nucleus protein p65 was detected to reflects the degree of NF-κB activation. The correlation of factors was analyzed with Pearson correlation analysis.Pre-treatment with berberine stabilized cardiac hemodynamics and improved the systolic function and diastolic function in the heart of LPS-induced rats, as evidenced by the partial recovery of the reduced±dp/dtmax and LVSP, as well as the decreased LVEDP. Compared with the LPS group, the Ber group showed improved myocardial injury, as demonstrated by decreased cTnT at each time point. HE staining results showed that berberine decreased inflammatory cell infiltration and LPS-induced cell swelling. These effects were observed early at 6 hours, severe at 24 hours, and become more serious at 48 hours after LPS injection. Further, TLR4 and NF-κB p65 subunits, which were the two key factors of the TLR4/NF-κB signaling, were upregulated in the LPS group and attenuated in the Ber group. Consistently, the expression levels of the downstream cytokines TNF-α and IL-1β were lower in the Ber group than those in the LPS group (all0.05). Myocardial injury markers were positively correlated with the markers of TLR4/NF-κB signals and the downstream host inflammatory factors (all0.05).Berberine can improve myocardial injury and cardiac function in sepsis rats, the mechanism is considered to be related to that it can inhibit the activation of TLR4/NF-κB signaling pathway induced by LPS and further reducing the production of TNF-α and IL-1β.


greenmedinfo--2020-11-20--Berberine exerts anti-cancer activity by modulating adenosine monophosphate-activated protein kinase

Berberine exerts anti-cancer activity by modulating adenosine monophosphate-activated protein kinase.

BACKGROUND : The antagonistic relationship between adenosine monophosphate-activated protein kinase ( AMPK ) and phosphatidylinositol 3-kinase/protein kinase B ( PI3K/AKT ) signaling play a vital role in cancer development .
The anti-cancer effects of berberine have been reported as a main component of the traditional Chinese medicine Rhizoma coptidis , although the roles of these signaling pathways in these effects have not been systematically reviewed .
METHODS : We searched the PubMed database for studies with keywords including [ `` berberine '' ] and [ `` tumor '' or '' cancer '' ] and [ `` AMPK '' ] or @ @ @ @ @ @ @ January 2010 and July 2020 , to elucidate the roles of the AMPK and PI3K/AKT pathways and their upstream and downstream targets in the anti-cancer effects of berberine .
RESULTS : The anti-cancer effects of berberine include inhibition of cancer cell proliferation , promotion of apoptosis and autophagy in cancer cells , and prevention of metastasis and angiogenesis .
The mechanism of these effects involves multiple cell kinases and signaling pathways , including activation of AMPK and forkhead box transcription factor O3a ( FOXO3a ) , accumulation of reactive oxygen species ( ROS @ @ @ @ @ @ @ of PI3K/AKT , rapamycin ( mTOR ) and nuclear factor-κB ( NF-κB ) .
Most of these mechanisms converge on regulation of the balance of AMPK and PI3K/AKT signaling by berberine .
CONCLUSION : This evidence supports the possibility that berberine is a promising anti-cancer natural product , with pharmaceutical potential in inhibiting cancer growth , metastasis and angiogenesis via multiple pathways , particularly by regulating the balance of AMPK and PI3K/AKT signaling .
However , systematic preclinical studies are still required to provide scientific evidence for further clinical studies .

BACKGROUND: The antagonistic relationship between adenosine monophosphate-activated protein kinase (AMPK) and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling play a vital role in cancer development. The anti-cancer effects of berberine have been reported as a main component of the traditional Chinese medicine Rhizoma coptidis, although the roles of these signaling pathways in these effects have not been systematically reviewed.
METHODS: We searched the PubMed database for studies with keywords including ["berberine"] and ["tumor"or"cancer"] and ["AMPK"] or ["AKT"] published between January 2010 and July 2020, to elucidate the roles of the AMPK and PI3K/AKT pathways and their upstream and downstream targets in the anti-cancer effects of berberine.
RESULTS: The anti-cancer effects of berberine include inhibition of cancer cell proliferation, promotion of apoptosis and autophagy in cancer cells, and prevention of metastasis and angiogenesis. The mechanism of these effects involves multiple cell kinases and signaling pathways, including activation of AMPK and forkhead box transcription factor O3a (FOXO3a), accumulation of reactive oxygen species (ROS), and inhibition of the activity of PI3K/AKT, rapamycin (mTOR) and nuclear factor-κB (NF-κB). Most of these mechanisms converge on regulation of the balance of AMPK and PI3K/AKT signaling by berberine.
CONCLUSION: This evidence supports the possibility that berberine is a promising anti-cancer natural product, with pharmaceutical potential in inhibiting cancer growth, metastasis and angiogenesis via multiple pathways, particularly by regulating the balance of AMPK and PI3K/AKT signaling. However, systematic preclinical studies are still required to provide scientific evidence for further clinical studies.


greenmedinfo--2020-11-20--Enhanced in vitro antimicrobial activity of amphotericin B with berberine against dual-species biofi

Enhanced in vitro antimicrobial activity of amphotericin B with berberine against dual-species biofilms of Candida albicans and Staphylococcus aureus.

AIMS : Multi-species biofilms formed by fungi and bacteria are clinically common and confer the commensal micro-organisms with protection against antimicrobial therapies .
Previously , the plant alkaloid berberine was reported to show antimicrobial efficacy to eliminate bacterial and fungal biofilms .
In this study , the combination of berberine and amphotericin B , an antifungal agent , was evaluated against dual-species Candida albicans/Staphylococcus aureus biofilms .
METHODS AND RESULTS : Combinatorial treatment by berberine and amphotericin B significantly reduced the biomass and viability of residing species in biofilms .
Moreover , morphological examination revealed hyphal filamentation of C. albicans @ @ @ @ @ @ @ were considerably impaired by the treatment .
These effects coincided with the reduced expression of cell surface components and quorum-sensing-related genes in both C. albicans and S. aureus .
Additionally , in C. albicans , the core transcription factors for controlling biofilm formation together with a crucial component of dual-species biofilms were also downregulated .
CONCLUSIONS : These results demonstrated synergistic effects of berberine and amphotericin B against C. albicans/S .
aureus dual-species biofilms .
SIGNIFICANCE AND IMPACT OF THE STUDY : This study confirms the potential of berberine and amphotericin B for @ @ @ @ @ @ @ related infections and reveals molecular basis for the efficacy of combinatorial treatment .

AIMS: Multi-species biofilms formed by fungi and bacteria are clinically common and confer the commensal micro-organisms with protection against antimicrobial therapies. Previously, the plant alkaloid berberine was reported to show antimicrobial efficacy to eliminate bacterial and fungal biofilms. In this study, the combination of berberine and amphotericin B, an antifungal agent, was evaluated against dual-species Candida albicans/Staphylococcus aureus biofilms.
METHODS AND RESULTS: Combinatorial treatment by berberine and amphotericin B significantly reduced the biomass and viability of residing species in biofilms. Moreover, morphological examination revealed hyphal filamentation of C. albicans and coadhesion between C. albicans/S. aureus were considerably impaired by the treatment. These effects coincided with the reduced expression of cell surface components and quorum-sensing-related genes in both C. albicans and S. aureus. Additionally, in C. albicans, the core transcription factors for controlling biofilm formation together with a crucial component of dual-species biofilms were also downregulated.
CONCLUSIONS: These results demonstrated synergistic effects of berberine and amphotericin B against C. albicans/S. aureus dual-species biofilms.
SIGNIFICANCE AND IMPACT OF THE STUDY: This study confirms the potential of berberine and amphotericin B for treating the C. albicans/S. aureus biofilms related infections and reveals molecular basis for the efficacy of combinatorial treatment.


greenmedinfo--2020-11-21--Apigenin significantly inhibits the proliferation, migration, and invasion of Tca8113 cells.

OBJECTIVE : This study aimed to examine the effects of apigenin ( API ) on the proliferation , migration , and invasion of human tongue squamous cell carcinoma Tca8113 cells and explore its probable mechanisms .
METHODS : After treating Tca8113 cells with API , the cell proliferation , migration , and invasivecapacities were identified by te-trazolium salt colorimetry ( MTT ) assay , cell scratch test , and Transwell chamber test .
Cellular immunofluorescence staining was used to localize mitogen-activated protein kinase 1 ( MAPK1 ) and extracellular regulated protein kinase ( ERK ) 1/2 proteins .
Western blot @ @ @ @ @ @ @ the related protein expression levels .
RESULTS : ① Through the MTT assay , API significantly inhibited cell proliferation ( P < 0.01 ) .②In the cell scratch test , the dis-tance of lateral migration after the API treatment was significantly shorter compared to the control group ( P < 0.01 ) .③The inva-sion rate in the lower chamber of the Transwell chamber was lower in the API group ( P < 0.01 ) .④ Cellular immunofluores-cence staining presented that the total-MEKK1 was localized in the cytoplasm , p-MEKK1 was localized in the @ @ @ @ @ @ @ was localized in the cytoplasm and nucleus .
⑤ After API was applied to cells , the expres-sions of p-MEKK1 and p-ERK1/2proteins significantly reduced ( P < 0.01 ) .
CONCLUSION : Apigenin ( API ) significantly inhibits the proliferation , migration , and invasion of Tca8113 cells and its mecha-nism may be associatedwith the MAPK signaling pathway .

OBJECTIVE: This study aimed to examine the effects of apigenin (API) on the proliferation, migration, and invasion of human tongue squamous cell carcinoma Tca8113 cells and explore its probable mechanisms.
METHODS: After treating Tca8113 cells with API, the cell proliferation, migration, and invasivecapacities were identified by te-trazolium salt colorimetry(MTT) assay, cell scratch test, and Transwell chamber test. Cellular immunofluorescence staining was used to localize mitogen-activated protein kinase 1 (MAPK1) and extracellular regulated protein kinase (ERK) 1/2 proteins. Western blot was used to detect the variations of the related protein expression levels.
RESULTS: ① Through the MTT assay, API significantly inhibited cell proliferation (P<0.01).②In the cell scratch test, the dis-tance of lateral migration after the API treatment was significantly shorter compared to the control group (P<0.01).③The inva-sion rate in the lower chamber of the Transwell chamber was lower in the API group (P<0.01).④ Cellular immunofluores-cence staining presented that the total-MEKK1 was localized in the cytoplasm, p-MEKK1 was localized in the nuclear mem-brane and cytoplasm, and p-ERK1/2 was localized in the cytoplasm and nucleus. ⑤ After API was applied to cells, the expres-sions of p-MEKK1 and p-ERK1/2proteins significantly reduced (P<0.01).
CONCLUSION: Apigenin(API) significantly inhibits the proliferation, migration, and invasion of Tca8113 cells and its mecha-nism may be associatedwith the MAPK signaling pathway.


greenmedinfo--2020-11-21--Apigenin 7-O-glucoside promotes cell apoptosis through the PTEN/PI3K/AKT pathway and inhibits cell m

Apigenin 7-O-glucoside promotes cell apoptosis through the PTEN/PI3K/AKT pathway and inhibits cell migration in cervical cancer HeLa cells.

Epidemiologic evidence promote the inclusion of flavones in diet due to their inhibitory effects on certain types of cancers , particularly in women .
Among the naturally occurring plant flavonoids , Apigenin 7-O-glucoside ( AGL ) is endowed with anti-inflammatory , anti-oxidant , and anti-cancer activities .
However , its mechanism of action on cervical cancer , the fourth largest cancer in women , has not yet been clarified .
In the current study , we have determined the effect of AGL on human cervical cancer cells and studied its molecular mechanism against cervical cancer .
The results showed that @ @ @ @ @ @ @ ( ICwas 47.26 μM at 48 h ) by inducing apoptosis .
Furthermore , AGL treatment caused G0/G1 phase arrest , reduced mitochondrial membrane potential ( MMP ) , and upgraded intracellular ROS production .
AGL could promote the release of cytochrome c by regulating Bcl-2 family proteins , and then activated caspase 9/3 to promote cell apoptosis .
Moreover , AGL treatment promoted the expression of p16 INK4A , while inhibited the expression of Cyclin A/D/E and CDK2/6 .
At the same time in HeLa cells treated with AGL , the PTEN/PI3K/AKT @ @ @ @ @ @ @ , and cell migration was alsoimpeded correspondingly through the matrix metalloproteinase 2 and 9 .
Our study may provide a new research direction for harnessing the novel natural compounds in cervical cancer treatment .

Epidemiologic evidence promote the inclusion of flavones in diet due to their inhibitory effects on certain types of cancers, particularly in women. Among the naturally occurring plant flavonoids, Apigenin 7-O-glucoside (AGL) is endowed with anti-inflammatory, anti-oxidant, and anti-cancer activities. However, its mechanism of action on cervical cancer, the fourth largest cancer in women, has not yet been clarified. In the current study, we have determined the effect of AGL on human cervical cancer cells and studied its molecular mechanism against cervical cancer. The results showed that AGL inhibited the proliferation of HeLa cells (ICwas 47.26 μM at 48 h) by inducing apoptosis. Furthermore, AGL treatment caused G0/G1 phase arrest, reduced mitochondrial membrane potential (MMP), and upgraded intracellular ROS production. AGL could promote the release of cytochrome c by regulating Bcl-2 family proteins, and then activated caspase 9/3 to promote cell apoptosis. Moreover, AGL treatment promoted the expression of p16 INK4A, while inhibited the expression of Cyclin A/D/E and CDK2/6. At the same time in HeLa cells treated with AGL, the PTEN/PI3K/AKT pathway was inhibited in a concentration-dependent manner, and cell migration was alsoimpeded correspondingly through the matrix metalloproteinase 2 and 9. Our study may provide a new research direction for harnessing the novel natural compounds in cervical cancer treatment.


greenmedinfo--2020-11-21--This study highlights that apigenin may be employed as a promising chemopreventive agent against can

This study highlights that apigenin may be employed as a promising chemopreventive agent against cancers in smokers with an HPV infection.

Tobacco smoke and human papillomavirus ( HPV ) are both crucial causes of cancer , and their cooperative carcinogenesis has drawn more attention in recent years .
Apigenin ( AP ) , a typical flavonoid abundantly found in flowers of plants , vegetables , and fruits , has been demonstrated to exert an anti-carcinogenic effect on various types of cancer .
In this study , we investigated the capability of AP against malignant transformation and DNA damage of immortalized human esophageal epithelial ( SHEE ) cells induced by the synergism of HPV18 and 4- ( methylnitrosamino ) -1- ( 3-pyridyl @ @ @ @ @ @ @ results indicated that the enhancement of migration , invasion , and proliferation ability of SHEE cells induced by HPV and NNK could be effectively inhibited by AP .
Moreover , the levels of pyridyloxybutylated ( POB ) -DNA adducts induced by NNK via P450-catalyzed metabolic activation could also be significantly suppressed by AP .
Further analyses on the molecular mechanism revealed that AP inhibited the synergistic carcinogenesis of NNK and HPV on SHEE cells by reducing the expression of mutp53 , CDK4 , Cyclin D1 , and p-Rb ( Ser 780 ) , @ @ @ @ @ @ @ cell cycle at G1 phase and promoting apoptosis of SHEE cells .
We hypothesize that the decrease in NNK-induced POB-DNA adduct levels is related to the deactivation of P450 by AP , which needs to be confirmed in future studies .
This study highlights that AP may be employed as a promising chemopreventive agent against cancers in smokers with an HPV infection .

Tobacco smoke and human papillomavirus (HPV) are both crucial causes of cancer, and their cooperative carcinogenesis has drawn more attention in recent years. Apigenin (AP), a typical flavonoid abundantly found in flowers of plants, vegetables, and fruits, has been demonstrated to exert an anti-carcinogenic effect on various types of cancer. In this study, we investigated the capability of AP against malignant transformation and DNA damage of immortalized human esophageal epithelial (SHEE) cells induced by the synergism of HPV18 and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). The results indicated that the enhancement of migration, invasion, and proliferation ability of SHEE cells induced by HPV and NNK could be effectively inhibited by AP. Moreover, the levels of pyridyloxybutylated (POB)-DNA adducts induced by NNK via P450-catalyzed metabolic activation could also be significantly suppressed by AP. Further analyses on the molecular mechanism revealed that AP inhibited the synergistic carcinogenesis of NNK and HPV on SHEE cells by reducing the expression of mutp53, CDK4, Cyclin D1, and p-Rb (Ser 780), increasing caspase-3 activity, thereby arresting the cell cycle at G1 phase and promoting apoptosis of SHEE cells. We hypothesize that the decrease in NNK-induced POB-DNA adduct levels is related to the deactivation of P450 by AP, which needs to be confirmed in future studies. This study highlights that AP may be employed as a promising chemopreventive agent against cancers in smokers with an HPV infection.


greenmedinfo--2020-11-21--Apigenin induces apoptosis by regulating Akt and MAPK pathways in human melanoma cell A375SM.

Apigenin , an aromatic compound , exhibits antioxidant , anti‑inflammatory and anti‑viral effects .
The present study aimed to investigate the effects of apigenin on cell proliferation and apoptosis of human melanoma cells A375P and A375SM .
Therefore , melanoma cells were treated with apigenin to determine its anti‑proliferative and survival effects , using wound healing and MTT assays .
The results revealed that melanoma cell viability was decreased in a dose‑dependent manner .
Furthermore , chromatin condensation , indicating apoptosis , was significantly increased in a dose‑dependent manner , as demonstrated by DAPI staining .
In addition , increasedapoptosis @ @ @ @ @ @ @ by Annexin V‑propidium iodide staining .
The changes in the expression levels of apoptosis‑related proteins in A375P and A375SM melanoma cells were subsequently detected using western blot analysis .
The results demonstrated that theprotein expression levels of Bcl‑2 were decreased , whereas those of Bax , cleaved poly ADP‑ribose polymerase , cleaved caspase‑9 and p53 were upregulated in a dose‑dependent manner in apigenin‑treated cells compared with those noted in untreated cells .
In addition , in apigenin‑treated A375P cells , phosphorylated ( p ) ‑p38 was upregulated and p‑extracellular signal‑regulated kinase ( ERK @ @ @ @ @ @ @ ) and p‑protein kinase B ( Akt ) were downregulated .
However , in A375SM cells , apigenin treatment increased p‑ERK and p‑JNK and decreased p‑p38 and p‑Akt protein expression levels .
Subsequently , the inhibitory effect of apigenin on tumor growth was investigated in vivo .
Tumor volume was significantly reduced in the 25 and 50 mg/kg apigenin‑treated groups compared with the control group .
Additionally , a TUNEL assay was performed to detect apoptotic cells .
Immunohistochemical staining also revealed elevated p‑ERK expression in the apigenin‑treated group compared with the control @ @ @ @ @ @ @ the present study indicated that apigenin attenuated the growth of A375SM melanoma cells by inducing apoptosis via regulating the Akt and mitogen‑activated protein kinase signaling pathways .

Apigenin, an aromatic compound, exhibits antioxidant, anti‑inflammatory and anti‑viral effects. The present study aimed to investigate the effects of apigenin on cell proliferation and apoptosis of human melanoma cells A375P and A375SM. Therefore, melanoma cells were treated with apigenin to determine its anti‑proliferative and survival effects, using wound healing and MTT assays. The results revealed that melanoma cell viability was decreased in a dose‑dependent manner. Furthermore, chromatin condensation, indicating apoptosis, was significantly increased in a dose‑dependent manner, as demonstrated by DAPI staining. In addition, increasedapoptosis rate following treatment with apigenin was confirmed by Annexin V‑propidium iodide staining. The changes in the expression levels of apoptosis‑related proteins in A375P and A375SM melanoma cells were subsequently detected using western blot analysis. The results demonstrated that theprotein expression levels of Bcl‑2 were decreased, whereas those of Bax, cleaved poly ADP‑ribose polymerase, cleaved caspase‑9 and p53 were upregulated in a dose‑dependent manner in apigenin‑treated cells compared with those noted in untreated cells. In addition, in apigenin‑treated A375P cells, phosphorylated (p)‑p38 was upregulated and p‑extracellular signal‑regulated kinase (ERK), p‑c‑Jun N‑terminal kinase (JNK) and p‑protein kinase B (Akt) were downregulated. However, in A375SM cells, apigenin treatment increased p‑ERK and p‑JNK and decreased p‑p38 and p‑Akt protein expression levels. Subsequently, the inhibitory effect of apigenin on tumor growth was investigated in vivo. Tumor volume was significantly reduced in the 25 and 50 mg/kg apigenin‑treated groups compared with the control group. Additionally, a TUNEL assay was performed to detect apoptotic cells. Immunohistochemical staining also revealed elevated p‑ERK expression in the apigenin‑treated group compared with the control group. Overall, the findings of the present study indicated that apigenin attenuated the growth of A375SM melanoma cells by inducing apoptosis via regulating the Akt and mitogen‑activated protein kinase signaling pathways.


greenmedinfo--2020-11-21--Astaxanthin protects cognitive function of vascular dementia.

OBJECTIVE : The purpose of this study was to evaluate the effect of astaxanthin ( AST ) on cognition function , inflammatory response and oxidative stress in vascular dementia ( VD ) mice .
METHOD : VD mice model was established by left unilateral common carotid arteries occlusion ( LUCCAO ) .
Following LUCCAO , AST was intragastrically administered for 30 days .
Object recognition test and morris water maze test were used to evaluate cognitive function .
Hematoxylin and eosin staining was performed to observe the hippocampal neuron structure .
Enzyme-linked immunosorbent assay kit and bicinchoninic acid kit were @ @ @ @ @ @ @ expression and superoxide dismutase ( SOD ) activity and malondialdehyde ( MDA ) content in hippocampus and prefrontal cortex .
RESULTS : AST improved the discrimination ability of VD mice .
The escape latency and path length of VD mice treated with AST were dramatically reduced .
Besides , AST 200 mg/kg enhanced crossing platform time and the number of times crossing the platform quadrant , and alleviated the morphological impairment in VD mice .
Moreover , we found that AST inhibited IL-1β expression and MDA content , whereas promoted IL-4 expression and @ @ @ @ @ @ @ CONCLUSION : AST could improve cognitive impairment and hippocampal neurons in VD mice , which may be related to suppression of inflammatory response and oxidative stress .

OBJECTIVE: The purpose of this study was to evaluate the effect of astaxanthin (AST) on cognition function, inflammatory response and oxidative stress in vascular dementia (VD) mice.
METHOD: VD mice model was established by left unilateral common carotid arteries occlusion (LUCCAO). Following LUCCAO, AST was intragastrically administered for 30 days. Object recognition test and morris water maze test were used to evaluate cognitive function. Hematoxylin and eosin staining was performed to observe the hippocampal neuron structure. Enzyme-linked immunosorbent assay kit and bicinchoninic acid kit were respectively adopted to measure IL-1βand IL-4 protein expression and superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in hippocampus and prefrontal cortex.
RESULTS: AST improved the discrimination ability of VD mice. The escape latency and path length of VD mice treated with AST were dramatically reduced. Besides, AST 200 mg/kg enhanced crossing platform time and the number of times crossing the platform quadrant, and alleviated the morphological impairment in VD mice. Moreover, we found that AST inhibited IL-1β expression and MDA content, whereas promoted IL-4 expression and SOD activity in a dose-dependent manner.
CONCLUSION: AST could improve cognitive impairment and hippocampal neurons in VD mice, which may be related to suppression of inflammatory response and oxidative stress.


greenmedinfo--2020-11-21--Astaxanthin protects mesenchymal stem cells from oxidative stress by direct scavenging of free radic

Astaxanthin protects mesenchymal stem cells from oxidative stress by direct scavenging of free radicals and modulation of cell signaling.

Recent evidence has shown that mesenchymal stem cells ( MSCs ) play vital roles in cell therapies of ischemia/hypoxia damaged tissues .
However , after transplantation , they might undergo apoptosis due to oxidative stress .
Thus , recent strategies have developed to support stem cells in harsh conditions , including pre-treatment with antioxidants .
Of the various antioxidants , in this study , astaxanthin ( ATX ) was used to protect adipose-derived MSCs ( ADMSCs ) against oxidative stress .
The MSCs were exposed to different doses of hydrogen peroxide , and then the expression of key genes involved @ @ @ @ @ @ @ , including Nuclear factor erythroid 2-related factor 2 ( Nrf2 ) , Heme oxygenase-1 ( HO-1 ) , and NADPH quinine oxidoreductase 1 ( NQO1 ) .
The balance of intracellular ROS was detected with the H2DCFDA molecular probe .
Additionally , for the detection of apoptosis and protective effect of ATX , the DAPI/Phallacidin and Annexin V cell staining were performed .
The results of cellular studies showed that ATX reduced HO-induced cell apoptosis and oxidative stress .
Furthermore , after the induction of oxidative stress , the cells ' native antioxidants @ @ @ @ @ @ @ they were modulated with ATX treatments ( p˂0.023 ) .
Based on our findings , ATX could increase the expression of Nrf2 as a key transcription factor of antioxidant enzymes ( p˂0.05 ) .
This finding supports the notion that ATX can act as an attractive antioxidant candidate for the pre-treatment of MSCs before cell therapy to enhance the viability of stem cells after transplantation in harsh conditions and result in an improved cell therapy output .

Recent evidence has shown that mesenchymal stem cells (MSCs) play vital roles in cell therapies of ischemia/hypoxia damaged tissues. However, after transplantation, they might undergo apoptosis due to oxidative stress. Thus, recent strategies have developed to support stem cells in harsh conditions, including pre-treatment with antioxidants. Of the various antioxidants, in this study, astaxanthin (ATX) was used to protect adipose-derived MSCs (ADMSCs) against oxidative stress. The MSCs were exposed to different doses of hydrogen peroxide, and then the expression of key genes involved in the redox signaling pathway was studied, including Nuclear factor erythroid 2-related factor 2 (Nrf2), Heme oxygenase-1 (HO-1), and NADPH quinine oxidoreductase 1 (NQO1). The balance of intracellular ROS was detected with the H2DCFDA molecular probe. Additionally, for the detection of apoptosis and protective effect of ATX, the DAPI/Phallacidin and Annexin V cell staining were performed. The results of cellular studies showed that ATX reduced HO-induced cell apoptosis and oxidative stress. Furthermore, after the induction of oxidative stress, the cells' native antioxidants including HO-1 and NQO1 were overexpressed but they were modulated with ATX treatments (p˂0.023). Based on our findings, ATX could increase the expression of Nrf2 as a key transcription factor of antioxidant enzymes (p˂0.05). This finding supports the notion that ATX can act as an attractive antioxidant candidate for the pre-treatment of MSCs before cell therapy to enhance the viability of stem cells after transplantation in harsh conditions and result in an improved cell therapy output.


greenmedinfo--2020-11-21--Anti-inflammatory effects of astaxanthin against fungal keratitis

AIM : To characterize effect of astaxanthin ( ASX ) in ( ) induced keratitis in mouse model .
METHODS @ @ @ @ @ model was established in C57BL/6 mice using , followed by ASX or dimethyl sulfoxide ( @ @ @ @ @ responses were evaluated by clinical score and myeloperoxidase ( MPO ) assay .
Inflammatory cytokines @ @ @ @ @ chain reaction ( RT-PCR ) , Western blot , immunofluorescence , and enzyme-linked immuno sorbent @ @ @ @ @ RESULTS : In animal model , ASX improved corneal transparency and clinical response , suppressed @ @ @ @ @ like IL-1β , TNF-α , and HMGB-1 .
Neutrophil levels have been shown to decrease @ @ @ @ @ and MPO .
TLR2 and TLR4 levels were lower in ASX-treated group than DMSO-treated .
@ @ @ @ @ inflammatory response and reduce inflammatory cytokine production in mice model withkeratitis .

AIM: To characterize effect of astaxanthin (ASX) in() induced keratitis in mouse model.
METHODS: , fungal keratitis mouse model was established in C57BL/6 mice using, followed by ASX or dimethyl sulfoxide (DMSO) treatment. Clinical responses were evaluated by clinical score and myeloperoxidase (MPO) assay. Inflammatory cytokines were assessed by reverse-transcription polymerase chain reaction (RT-PCR), Western blot, immunofluorescence, and enzyme-linked immuno sorbent assay (ELISA).
RESULTS: In animal model, ASX improved corneal transparency and clinical response, suppressed the expression of inflammatory cytokine like IL-1β, TNF-α, and HMGB-1. Neutrophil levels have been shown to decrease in ASX-treated cornea by immunofluorescence and MPO. TLR2 and TLR4 levels were lower in ASX-treated group than DMSO-treated.
CONCLUSION: ASX can suppress inflammatory response and reduce inflammatory cytokine production in mice model withkeratitis.


greenmedinfo--2020-11-21--Therapeutic effect of curcumin on oral diseases.

Curcumin ( diferuloylmethane ) is a polyphenol compound extracted from the rhizome of the plant Curcuma longa .
It has @ @ @ @ @ yellow or orange pigment with a variety of biological properties , including anti-inflammation , antioxidation @ @ @ @ @ anti-fungus , and wound healing .
Previous studies have reported the role of curcumin in @ @ @ @ @ tumors in vitro and in vivo .
Recently , it has been demonstrated that curcumin @ @ @ @ @ mucosal diseases , periodontal diseases , and mouth neoplasms .
In this review , we @ @ @ @ @ effects of curcumin on oral diseases .

Curcumin (diferuloylmethane) is a polyphenol compound extracted from the rhizome of the plant Curcuma longa. It has the feature of being a yellow or orange pigment with a variety of biological properties, including anti-inflammation, antioxidation, anti-tumor, anti-bacteria, anti-fungus, and wound healing. Previous studies have reported the role of curcumin in treating different inflammatory diseases and tumors in vitro and in vivo. Recently, it has been demonstrated that curcumin has therapeutic benefits in oral mucosal diseases, periodontal diseases, and mouth neoplasms. In this review, we will focus on the therapeutic effects of curcumin on oral diseases.


greenmedinfo--2020-11-21--Effects of grape polyphenols on the Life span and neuroinflammatory alterations related to neurodege

Effects of grape polyphenols on the Life span and neuroinflammatory alterations related to neurodegenerative disease-like disturbances.

Functional nutrition is a valuable supplementation to dietary therapy .
Functional foods are enriched with biologically active substances .
Plant polyphenols attract particular attention due to multiple beneficial properties attributed to their high antioxidant and other biological activities .
We assessed the effect of grape polyphenols on the life span of C57BL/6 mice and on behavioral and neuroinflammatory alterations in a transgenic mouse model of Parkinson disease ( PD ) with overexpression of the A53T-mutant humanα-synuclein .
C57BL/6 mice were given a dietary supplement containing grape polyphenol concentrate ( GPC-1.5 mL/kg/day ) with drinking water from the age of 6-8 @ @ @ @ @ @ @ received GPC beginning at the age of 10 weeks for four months .
GPC significantly influenced the cumulativeproportion of surviving and substantially augmented the average life span in mice .
In the transgenic PD model , the grape polyphenol ( GP ) diet enhanced memory reconsolidation and diminished memory extinction in a passive avoidance test .
Behavioral effects of GP treatment were accompanied by a decrease in α-synuclein accumulation in the frontal cortex and a reduction in the expression of neuroinflammatory markers ( IBA1 and CD54 ) in the frontal cortex and hippocampus @ @ @ @ @ @ @ recommended as promising functional nutrition for aging people and patients with neurodegenerative disorders .

Functional nutrition is a valuable supplementation to dietary therapy. Functional foods are enriched with biologically active substances. Plant polyphenols attract particular attention due to multiple beneficial properties attributed to their high antioxidant and other biological activities. We assessed the effect of grape polyphenols on the life span of C57BL/6 mice and on behavioral and neuroinflammatory alterations in a transgenic mouse model of Parkinson disease (PD) with overexpression of the A53T-mutant humanα-synuclein. C57BL/6 mice were given a dietary supplement containing grape polyphenol concentrate (GPC-1.5 mL/kg/day) with drinking water from the age of 6-8 weeks for life. Transgenic PD mice received GPC beginning at the age of 10 weeks for four months. GPC significantly influenced the cumulativeproportion of surviving and substantially augmented the average life span in mice. In the transgenic PD model, the grape polyphenol (GP) diet enhanced memory reconsolidation and diminished memory extinction in a passive avoidance test. Behavioral effects of GP treatment were accompanied by a decrease in α-synuclein accumulation in the frontal cortex and a reduction in the expression of neuroinflammatory markers (IBA1 and CD54) in the frontal cortex and hippocampus. Thus, a GP-rich diet is recommended as promising functional nutrition for aging people and patients with neurodegenerative disorders.


greenmedinfo--2020-11-21--Osteoprotective roles of green tea catechins.

Osteoporosis is the second most common disease only secondary to cardiovascular disease , with the risk of fracture increasing with age .
Osteoporosis is caused by an imbalance between osteoblastogenesis and osteoclastogenesis processes .
Osteoclastogenesis may be enhanced , osteoblastogenesis may be reduced , or both may be evident .
Inflammation and high reactive oxygen enhance osteoclastogenesis while reducing osteoblastogenesis by inducing osteoblast apoptosis and suppressing osteoblastic proliferation and differentiation .
Catechins , the main polyphenols found in green tea with potent anti-oxidant and anti-inflammatory properties , can counteract the deleterious effects of the imbalance of osteoblastogenesis and osteoclastogenesis caused @ @ @ @ @ @ @ attenuate osteoclastogenesis by enhancing apoptosis of osteoclasts , hampering osteoclastogenesis , and prohibiting bone resorption in vitro .
Catechin effects can be directly exerted on pre-osteoclasts/osteoclasts or indirectly exerted via the modulation of mesenchymal stem cells ( MSCs ) /stromal cell regulation of pre-osteoclasts through activation of the nuclear factor kB ( RANK ) /RANK ligand ( RANKL ) /osteoprotegerin ( OPG ) system .
Catechins also can enhance osteoblastogenesis by enhancing osteogenic differentiation of MSCs and increasing osteoblastic survival , proliferation , differentiation , and mineralization .
The in vitro effects of @ @ @ @ @ @ @ several animal models , as well as in epidemiological observational studies on human subjects .
Even though randomized control trials have not shown that catechins provide anti-fracture efficacy , safety data in the trials are promising .
A large-scale , placebo-controlled , long-term randomized trial with a tea regimen intervention of optimal duration is required to determine anti-fracture efficacy .

Osteoporosis is the second most common disease only secondary to cardiovascular disease, with the risk of fracture increasing with age. Osteoporosis is caused by an imbalance between osteoblastogenesis and osteoclastogenesis processes. Osteoclastogenesis may be enhanced, osteoblastogenesis may be reduced, or both may be evident. Inflammation and high reactive oxygen enhance osteoclastogenesis while reducing osteoblastogenesis by inducing osteoblast apoptosis and suppressing osteoblastic proliferation and differentiation. Catechins, the main polyphenols found in green tea with potent anti-oxidant and anti-inflammatory properties, can counteract the deleterious effects of the imbalance of osteoblastogenesis and osteoclastogenesis caused by osteoporosis. Green tea catechins can attenuate osteoclastogenesis by enhancing apoptosis of osteoclasts, hampering osteoclastogenesis, and prohibiting bone resorption in vitro. Catechin effects can be directly exerted on pre-osteoclasts/osteoclasts or indirectly exerted via the modulation of mesenchymal stem cells (MSCs)/stromal cell regulation of pre-osteoclasts through activation of the nuclear factor kB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) system. Catechins also can enhance osteoblastogenesis by enhancing osteogenic differentiation of MSCs and increasing osteoblastic survival, proliferation, differentiation, and mineralization. The in vitro effects of catechins on osteogenesis have been confirmed in several animal models, as well as in epidemiological observational studies on human subjects. Even though randomized control trials have not shown that catechins provide anti-fracture efficacy, safety data in the trials are promising. A large-scale, placebo-controlled, long-term randomized trial with a tea regimen intervention of optimal duration is required to determine anti-fracture efficacy.


greenmedinfo--2020-11-21--The anti-neuroinflammatory role of anthocyanins and their metabolites for the prevention and treatme

The anti-neuroinflammatory role of anthocyanins and their metabolites for the prevention and treatment of brain disorders.

Anthocyanins are naturally occurring polyphenols commonly found in fruits and vegetables .
Numerous studies have described that anthocyanin-rich foods may @ @ @ @ @ the prevention and treatment of different pathological conditions , which have encouraged their consumption around @ @ @ @ @ a significant neuroprotective role , mainly due to their well-recognized antioxidant and anti-inflammatory properties .
@ @ @ @ @ relevant in both homeostatic and pathological circumstances .
Since the progression of several neurological disorders @ @ @ @ @ targeting brain inflammation has been considered a promising strategy in those conditions .
Recent data @ @ @ @ @ of many anthocyanins and of their metabolites in the onset and development of several neurological @ @ @ @ @ , it will be discussed the importance and the applicability of these polyphenolic compounds as @ @ @ @ @ be also scrutinized the molecular mechanisms underlying the modulation of neuroinflammation by these natural compounds @ @ @ @ @ brain diseases .

Anthocyanins are naturally occurring polyphenols commonly found in fruits and vegetables. Numerous studies have described that anthocyanin-rich foods may play a crucial role in the prevention and treatment of different pathological conditions, which have encouraged their consumption around the world. Anthocyanins exhibit a significant neuroprotective role, mainly due to their well-recognized antioxidant and anti-inflammatory properties. Neuroinflammation is an intricate process relevant in both homeostatic and pathological circumstances. Since the progression of several neurological disorders relies on neuroinflammatory process, targeting brain inflammation has been considered a promising strategy in those conditions. Recent data have shown the anti-neuroinflammatory abilities of many anthocyanins and of their metabolites in the onset and development of several neurological disorders. In this review, it will be discussed the importance and the applicability of these polyphenolic compounds as neuroprotective agents and it will be also scrutinized the molecular mechanisms underlying the modulation of neuroinflammation by these natural compounds in the context of several brain diseases.


greenmedinfo--2020-11-21--Anti-neuroinflammatory potential of polyphenols by inhibiting NF-κB to halt Alzheimer's disease.

Alzheimer 's disease ( AD ) is an irrevocable chronic brain disorder featured by neuronal loss , microglial accumulation , and progressive cognitive impairment .
The proper pathophysiology of this life-threatening disorder is not completely understood and no exact remedies are found yet .
Over the last few decades , research on AD has mainly highlighted in pathomechanisms linked to a couple of the major pathological hallmarks , including extracellular senile plaques , made of amyloid-β ( Aβ ) peptides , and intracellular neurofibrillary tangles ( NFTs ) , made of tau proteins .
Aβ can induce apoptosis , trigger @ @ @ @ @ @ @ synaptic plasticity of the hippocampus , which ultimately contributes to reducing cognitive functions and memory impairment .
Recently , a third disease hallmark , the neuroinflammatory reaction that is mediated by cerebral innate immune cells , has become a spotlight in the current research area , assured by pre-clinical , clinical , and genetic investigations .
Nuclear factor kappa-light-chain-enhancer of activated B cells ( NF-κB ) , a cytokine producer , is significantly associated with physiological inflammatory proceedings and thus showing a promising candidate for inflammation-based AD therapy .
Recent data reveal that @ @ @ @ @ @ @ functions and it may be consideredas a vital resource for discovering several drug candidates against AD .
Interestingly , phytochemicals can easily interfere with the signaling pathway of NF-κB .
This review represents the anti-neuroinflammatory potential of polyphenols as inhibitors of NF-κB to combat AD pathogenesis .

Alzheimer's disease (AD) is an irrevocable chronic brain disorder featured by neuronal loss, microglial accumulation, and progressive cognitive impairment. The proper pathophysiology of this life-threatening disorder is not completely understood and no exact remedies are found yet. Over the last few decades, research on AD has mainly highlighted in pathomechanisms linked to a couple of the major pathological hallmarks, including extracellular senile plaques, made of amyloid-β (Aβ) peptides, and intracellular neurofibrillary tangles (NFTs), made of tau proteins. Aβ can induce apoptosis, trigger an inflammatory response, and inhibit the synaptic plasticity of the hippocampus, which ultimately contributes to reducing cognitive functions and memory impairment. Recently,a third disease hallmark, the neuroinflammatory reaction that is mediated by cerebral innate immune cells, has become a spotlight in the current research area, assured by pre-clinical, clinical, and genetic investigations. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), a cytokine producer, is significantly associated with physiological inflammatory proceedings and thus showing a promising candidate for inflammation-based AD therapy. Recent data reveal that phytochemicals mainly polyphenols compounds exhibit potential neuroprotective functions and it may be consideredas a vital resource for discovering several drug candidates against AD. Interestingly, phytochemicals can easily interfere with the signaling pathway of NF-κB. This review represents the anti-neuroinflammatory potential of polyphenols as inhibitors of NF-κB to combat AD pathogenesis.


greenmedinfo--2020-11-21--Resveratrol alleviates alveolar epithelial cell injury induced by hyperoxia by reducing apoptosis an

Resveratrol alleviates alveolar epithelial cell injury induced by hyperoxia by reducing apoptosis and mitochondrial dysfunction.

Bronchopulmonary dysplasia is a severe and long-term pulmonary disease in premature infants .
Hyperoxia-induced acute lung injury plays a critical role in bronchopulmonary dysplasia .
Resveratrol is a polyphenolic phytoalexin and a natural agonist of Sirtuin 1 .
Many studies have shown that resveratrol has a protective effect on hyperoxia-induced lung damage , but its specific protective mechanism is still not clear .
Further exploration of the possible protective mechanism of resveratrol was the main goal of this study .
In this study , human alveolar epithelial cells were used to establish a hyperoxia-induced acute lung injury cell model , @ @ @ @ @ @ @ , the Sirtuin 1 activator SRT1720 ( S ) and the Sirtuin 1 inhibitor EX-527 ( E ) were administered to alveolar epithelial cells , which were then exposed to hyperoxia to investigate the role of Res in mitochondrial function and apoptosis .
We divided human alveolar epithelial cells into the following groups : ( 1 ) the control group , ( 2 ) hyperoxia group , ( 3 ) hyperoxia+Res20 group , ( 4 ) hyperoxia+Res20+E5 group , ( 5 ) hyperoxia+Res20+E10 group , ( 6 ) hyperoxia+S2 group , ( 7 @ @ @ @ @ @ @ ) hyperoxia+S2+E10 group .
Hyperoxia-induced cell apoptosis and mitochondrial dysfunction were alleviated by Res and SRT1720 .
Res and SRT1720 upregulated Sirtuin 1 , PGC-1α , NRF1 , and TFAM but decreased the expression of acetyl-p53 in human alveolar epithelial cells that were exposed to hyperoxia .
These findings revealed that Res may alleviated hyperoxia-induced mitochondrial dysfunction and apoptosis in alveolar epithelial cells through the SIRT1/PGC-1a signaling pathway .
Thus , Sirtuin 1 upregulation plays an important role in lung protection .

Bronchopulmonary dysplasia is a severe and long-term pulmonary disease in premature infants. Hyperoxia-induced acute lung injury plays a critical role in bronchopulmonary dysplasia. Resveratrol is a polyphenolic phytoalexin and a natural agonist of Sirtuin 1. Many studies have shown that resveratrol has a protective effect on hyperoxia-induced lung damage, but its specific protective mechanism is still not clear. Further exploration of the possible protective mechanism of resveratrol was the main goal of this study. In this study, human alveolar epithelial cells were used to establish a hyperoxia-induced acute lung injury cell model, and resveratrol (Res or R), the Sirtuin 1 activator SRT1720 (S) and the Sirtuin 1 inhibitor EX-527 (E) were administered to alveolar epithelial cells, which were then exposed to hyperoxia to investigate the role of Res in mitochondrial function and apoptosis. We divided human alveolar epithelial cells into the following groups: (1) the control group, (2) hyperoxia group, (3) hyperoxia+Res20 group, (4) hyperoxia+Res20+E5 group, (5) hyperoxia+Res20+E10 group, (6) hyperoxia+S2 group, (7) hyperoxia+S2+E5 group, and (8) hyperoxia+S2+E10 group. Hyperoxia-induced cell apoptosis and mitochondrial dysfunction were alleviated by Res and SRT1720. Res and SRT1720 upregulated Sirtuin 1, PGC-1α, NRF1, and TFAM but decreased the expression of acetyl-p53 in human alveolar epithelial cells that were exposed to hyperoxia. These findings revealed that Res may alleviated hyperoxia-induced mitochondrial dysfunction and apoptosis in alveolar epithelial cells through the SIRT1/PGC-1a signaling pathway. Thus, Sirtuin 1 upregulation plays an important role in lung protection.


greenmedinfo--2020-11-21--Protection of polyphenols against glyco-oxidative stress.

Chronic high glucose ( HG ) exposure increases methylglyoxal ( MGO ) -derived advanced glycation end-products ( AGEs ) and is involved in the onset of pathological conditions , such as diabetes , atherosclerosis and chronic-degenerative diseases .
Under physiologic conditions the harmful effects of MGO are contrasted by glyoxalase system that is implicated in the detoxification of Reactive Carbonyl Species ( RCS ) and maintain the homeostasis of the redox environment of the cell .
Polyphenols are the most abundant antioxidants in the diet and present various health benefits .
Aims of the study were to investigate the effects @ @ @ @ @ @ @ system in intestinal cells , using CaCo-2 cells .
Moreover , we studied the effect of apple polyphenols on glyco-oxidative stress .
Our data demonstrated that HG-treatment triggers glyco-oxidation stress with a significant increase in intracellular Reactive Oxygen Species ( ROS ) , lipid peroxidation , AGEs , and increase of Glyoxalase I ( GlxI ) activity .
On the contrary , Glyoxalase II ( GlxII ) activity was lower in HG-treated cells .
We demonstrate that apple polyphenols exert a protective effect against oxidative stress and dicarbonyl stress .
The increase of @ @ @ @ @ @ @ ) levels in HG-treated cells in the presence of apple polyphenols was associated with a decrease of GlxI activity .

Chronic high glucose (HG) exposure increases methylglyoxal (MGO)-derived advanced glycation end-products (AGEs) and is involved in the onset of pathological conditions, such as diabetes, atherosclerosis and chronic-degenerative diseases. Under physiologic conditions the harmful effects of MGO are contrasted by glyoxalase system that is implicated in the detoxification of Reactive Carbonyl Species (RCS) and maintain the homeostasis of the redox environment of the cell. Polyphenols are the most abundant antioxidants in the diet and present various health benefits. Aims of the study were to investigate the effects of HG-chronic exposure on glyco-oxidation and glyoxalase system in intestinal cells, using CaCo-2 cells. Moreover, we studied the effect of apple polyphenols on glyco-oxidative stress. Our data demonstrated that HG-treatment triggers glyco-oxidation stress with a significant increase in intracellular Reactive Oxygen Species (ROS), lipid peroxidation, AGEs, and increase of Glyoxalase I (GlxI) activity. On the contrary, Glyoxalase II (GlxII) activity was lower in HG-treated cells. We demonstrate that apple polyphenols exert a protective effect against oxidative stress and dicarbonyl stress. The increase of total antioxidant capacity and glutathione (GSH) levels in HG-treated cells in the presence of apple polyphenols was associated with a decrease of GlxI activity.


greenmedinfo--2020-11-21--Young persimmon fruit extract suppresses obesity.

Young persimmon fruit ( YPF ) has recently been reported to have a regulatory effect on lipid metabolism .
The aim of this study was to investigate whether the YPF aqueous extract ( YPFE ) exert an antiobesity effect by modulating lipid metabolism in the white adipose tissue ( WAT ) of obese C57BLKS/Jmice .
YPFE ( 100 or 200 mg/kg body weight/day ) or distilled water as a vehicle was orally administered by gavage to 12-week-old obese malemice for 3 weeks ( = 7 for each group ) .
YPFE administration significantly reduced body weight and WAT size .
@ @ @ @ @ @ @ cholesterol concentrations in serum and WAT .
Obese vehicle treated mice exhibited an enhanced protein expression of adipogenic and lipogenic genes .
However , this increased expression was alleviated in the YPFE-fed groups , resulting in inhibition of adipogenesis and downregulation of fatty acid synthesis .
In addition , there was an increase in the level of transcription factors associated with fatty acid oxidation in the YPFE-treated group .
In obese mice , the expression of proteins associated with cholesterol metabolism was augmented .
YPFE did not affect cholesterol synthesis , but cholesterol @ @ @ @ @ @ @ exerts beneficial effects on obesity by inhibiting adipogenesis and reducing lipid synthesisand accumulation by regulation of lipid-related transcription factors in the WAT of obese mice .

Young persimmon fruit (YPF) has recently been reported to have a regulatory effect on lipid metabolism. The aim of this study was to investigate whether the YPF aqueous extract (YPFE) exert an antiobesity effect by modulating lipid metabolism in the white adipose tissue (WAT) of obese C57BLKS/Jmice. YPFE (100 or 200 mg/kg body weight/day) or distilled water as a vehicle was orally administered by gavage to 12-week-old obese malemice for 3 weeks ( = 7 for each group). YPFE administration significantly reduced body weight and WAT size. Furthermore, YPFE considerably reduced triglyceride and cholesterol concentrations in serum and WAT. Obese vehicle treated mice exhibited an enhanced protein expression of adipogenic and lipogenic genes. However, this increased expression was alleviated in the YPFE-fed groups, resulting in inhibition of adipogenesis and downregulation of fatty acid synthesis. In addition, there was an increase in the level of transcription factors associated with fatty acid oxidation in the YPFE-treated group. In obese mice, the expression of proteins associated with cholesterol metabolism was augmented. YPFE did not affect cholesterol synthesis, but cholesterol efflux-related proteins were significantly upregulated. YPF exerts beneficial effects on obesity by inhibiting adipogenesis and reducing lipid synthesisand accumulation by regulation of lipid-related transcription factors in the WAT of obese mice.


greenmedinfo--2020-11-21--Persimmon highly galloylated-tannins in vitro mitigated α-amylase and α-glucosidase.

Reticence ofα-amylase ( α-Amy ) and α-glucosidase ( α-Glu ) is needed due to their mitigation potency on the glucose absorption .
In this study , the anti-amylolytic effects of persimmon tannins ( PT ) on α-Amy and α-Glu and their interaction mechanisms were investigated .
It was found that PT inhibited α-Amy andα-Glu with the half inhibitory concentration ( IC ) values of 0.35 and 0.24 mg/ml , respectively .
Fluorescence and FT-IR spectrometry results showed that PT could bind to enzymes and alter their conformations .
Molecular docking showed that the structural units of PT interacted with the @ @ @ @ @ @ @ Asp197 , and Asp300 ) of α-Amy by H-bonds and π-π interactions , while they bound to the residues closed to the active sites of α-Glu .
The whole results implied that PT was a promising mitigator of α-Amy and α-Glu .
It might help to understand mechanisms of glycemic response inhibition of PT and develop certain therapeutic strategies against diabetes .
PRACTICAL APPLICATIONS : α-Amy and α-Glu are the crucial starch digestive enzymes associated with type II diabetes mellitus in humans .
Persimmon is an excellent source of bio-functional tannins which potentially @ @ @ @ @ @ @ study showed that PT beneficially decreased the action of the carbohydrate digestion-related enzymes , namely α-Amy and α-Glu via interaction simultaneously , which could be used to formulate a functional food and natural medicine .

Reticence ofα-amylase (α-Amy) and α-glucosidase (α-Glu) is needed due to their mitigation potency on the glucose absorption. In this study, the anti-amylolytic effects of persimmon tannins (PT) on α-Amy and α-Glu and their interaction mechanisms were investigated. It was found that PT inhibited α-Amy andα-Glu with the half inhibitory concentration (IC) values of 0.35 and 0.24 mg/ml, respectively. Fluorescence and FT-IR spectrometry results showed that PT could bind to enzymes and alter their conformations. Molecular docking showed that the structural units of PT interacted with the key sites (amino acids Glu233, Asp197, and Asp300) of α-Amy by H-bonds and π-π interactions, while they bound to the residues closed to the active sites of α-Glu. The whole results implied that PT was a promising mitigator of α-Amy and α-Glu. It might help to understand mechanisms of glycemic response inhibition of PT and develop certain therapeutic strategies against diabetes. PRACTICAL APPLICATIONS: α-Amy and α-Glu are the crucial starch digestive enzymes associated with type II diabetes mellitus in humans. Persimmon is an excellent source of bio-functional tannins which potentially mitigate the type II diabetes. This study showed that PT beneficially decreased the action of the carbohydrate digestion-related enzymes, namely α-Amy and α-Glu via interaction simultaneously, which could be used to formulate a functional food and natural medicine.


greenmedinfo--2020-11-21--Antioxidant activity and mechanism of commercial Rama Forte persimmon fruits.

This study aimed to characterize the antioxidant properties of Rama Forte persimmon , a tannin-rich fruit variety produced in Brazil .
Extracts prepared with lyophilized pulps from fruits obtained in local markets were analyzed individually to evaluate the extent of antioxidant protection and investigate the antioxidant mechanism .
Iron-mediated hydroxylation of 5,5-dimethyl-1-pirrolidine-N-oxide , determined by electron paramagnetic resonance ( EPR ) , and oxidative degradation of 2-deoxyribose ( 2-DR ) were inhibited by fruit extracts in a dose-dependent manner .
There was a considerable individual variability in inhibition of 2-DR degradation by individual fruits .
Higher protection of 2-DR degradation @ @ @ @ @ @ @ in Fe ( III ) -citrate/ascorbate in comparison with Fe ( III ) -EDTA/ascorbate system ; however , antioxidant effectiveness of fruit extracts was not diminished by increasing EDTA concentration by 10-fold .
Other competition experiments using the 2-DR assay ( varying pre-incubation time and 2-DR concentration ) indicated that protection comes mainly from free radical scavenging , rather that metal chelation antioxidant activity .
Persimmon extracts prevented iron-mediated lipid peroxidation in rat liver homogenates , which correlated significantly with the inhibition of 2-DR oxidation .
Finally , sugar content of individual fruits @ @ @ @ @ @ @ , which could indicate that maturation decreases soluble antioxidant concentration or efficiency .
In conclusion , lipid peroxidation , 2-DR and EPR experiments indicated that extracts from commercial fruits showed mainly radical-scavenger activity and relevant antioxidant activity .

This study aimed to characterize the antioxidant properties of Rama Forte persimmon, a tannin-rich fruit variety produced in Brazil. Extracts prepared with lyophilized pulps from fruits obtained in local markets were analyzed individually to evaluate the extent of antioxidant protection and investigate the antioxidant mechanism. Iron-mediated hydroxylation of 5,5-dimethyl-1-pirrolidine-N-oxide, determined by electron paramagnetic resonance (EPR), and oxidative degradation of 2-deoxyribose (2-DR) were inhibited by fruit extracts in a dose-dependent manner. There was a considerable individual variability in inhibition of 2-DR degradation by individual fruits. Higher protection of 2-DR degradation (by the extracts) was observed in Fe(III)-citrate/ascorbate in comparison with Fe(III)-EDTA/ascorbate system; however, antioxidant effectiveness of fruit extracts was not diminished by increasing EDTA concentration by 10-fold. Other competition experiments using the 2-DR assay (varying pre-incubation time and 2-DR concentration) indicated that protection comes mainly from free radical scavenging, rather that metal chelation antioxidant activity. Persimmon extracts prevented iron-mediated lipid peroxidation in rat liver homogenates, which correlated significantly with the inhibition of 2-DR oxidation. Finally, sugar content of individual fruits correlated inversely with inhibition of 2-DR degradation, which could indicate that maturation decreases soluble antioxidant concentration or efficiency. In conclusion, lipid peroxidation, 2-DR and EPR experiments indicated that extracts from commercial fruits showed mainly radical-scavenger activity and relevant antioxidant activity.


greenmedinfo--2020-11-21--Antitumor and immunomodulatory activities of total flavonoids extract from persimmon leaves in H 22

Antitumor and immunomodulatory activities of total flavonoids extract from persimmon leaves in H 22 liver tumor-bearing mice.

Persimmon ( Diospyros kaki L. ) leaves are commonly used in Asia as tea infusion and as an agent in @ @ @ @ @ study aims to explore the antitumor and immunomodulatory effects of total flavonoids extract from persimmon @ @ @ @ @ Hliver tumor-bearing mice .
We found that the PLF showed significant inhibition on the liver @ @ @ @ @ a tumor inhibition rate of up to 49.35 % .
In contrast to the severe @ @ @ @ @ CTX ) , the PLF exhibited anti-cachexia effect and showed no alternation in the body @ @ @ @ @ mice .
Moreover , compared with the vehicle control and CTX group , the PLF @ @ @ @ @ spleen indices , level of serum interleukin-18 ( IL-18 ) , monocyte/macrophage phagocytosis , level @ @ @ @ @ activity of natural killer ( NK ) cells .
This study demonstrated that the PLF @ @ @ @ @ growth in vivo via enhancement of the immune function in mice , and it displayed @ @ @ @ @ safe and effective anticancer agent or functional immune-enhancing agent .

Persimmon (Diospyros kaki L.) leaves are commonly used in Asia as tea infusion and as an agent in traditional medicine. The present study aims to explore the antitumor and immunomodulatory effects of total flavonoids extract from persimmon leaves (PLF) in Hliver tumor-bearing mice. We found that the PLF showed significant inhibition on the liver tumor growth in mice with a tumor inhibition rate of up to 49.35%. In contrast to the severe side effects of cyclophosphamide (CTX), the PLF exhibited anti-cachexia effect and showed no alternation in the body weight and food intake in mice. Moreover, compared with the vehicle control and CTX group, the PLF significantly enhanced the thymus and spleen indices, level of serum interleukin-18 (IL-18), monocyte/macrophage phagocytosis, level of serum hemolysin, and activity of natural killer (NK) cells. This study demonstrated that the PLF could effectively inhibit liver tumor growth in vivo via enhancement of the immune function in mice, and it displayed the potential to be a safe and effective anticancer agent or functional immune-enhancing agent.


greenmedinfo--2020-11-21--Anti-osteoporotic effects of polysaccharides isolated from persimmon leaves via osteoclastogenesis i

Anti-osteoporotic effects of polysaccharides isolated from persimmon leaves via osteoclastogenesis inhibition.

Persimmon ( L.f. ) leaves have traditionally been used as a phytomedicine , in health beverages to treat cardiovascular and respiratory disease and to promote maternal health in East Asia .
In particular , polysaccharides from persimmon are known to have anti-coagulant , anti-oxidant , and immune-stimulatory activities .
However , their beneficial effects against osteoporosis have not been reported .
In the present study , we investigated the anti-osteoporotic effects of polysaccharides from persimmon leaves ( PLE0 ) using an in vivo model of ovariectomy ( OVX ) -induced bone loss and an in vitro system of receptor activator @ @ @ @ @ @ @ -induced osteoclast differentiation .
In the OVX mouse model , PLE0 remarkably improved OVX-induced trabecular bone loss by suppressing osteoclast activity .
In primary bone marrow-derived macrophages ( BMMs ) , PLE0 dose-dependently inhibited osteoclast differentiation .
In addition , PLE0 down-regulated RANKL-induced activation of mitogen-activated protein kinases ( MAPKs ) such as p38 , ERK , and JNK resulting in suppression of nuclear factor of activated T cells cytoplasmic 1 ( NFATc1 ) expression .
Our results indicate that PLE0 has anti-osteoporotic effects in OVX-induced bone loss via inhibition of osteoclast differentiation @ @ @ @ @ @ @ may prevent postmenopausal bone loss and osteoporotic bone fragility .

Persimmon (L.f.) leaves have traditionally been used as a phytomedicine, in health beverages to treat cardiovascular and respiratory disease and to promote maternal health in East Asia. In particular, polysaccharides from persimmon are known to have anti-coagulant, anti-oxidant, and immune-stimulatory activities. However, their beneficial effects against osteoporosis have not been reported. In the present study, we investigated the anti-osteoporotic effects of polysaccharides from persimmon leaves (PLE0) using an in vivo model of ovariectomy (OVX)-induced bone loss and an in vitro system of receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation. In the OVX mouse model, PLE0 remarkably improved OVX-induced trabecular bone loss by suppressing osteoclast activity. In primary bone marrow-derived macrophages (BMMs), PLE0 dose-dependently inhibited osteoclast differentiation. In addition, PLE0 down-regulated RANKL-induced activation of mitogen-activated protein kinases (MAPKs) such as p38, ERK, and JNK resulting in suppression of nuclear factor of activated T cells cytoplasmic 1 (NFATc1) expression. Our results indicate that PLE0 has anti-osteoporotic effects in OVX-induced bone loss via inhibition of osteoclast differentiation. Taken together, PLE0 from persimmon may prevent postmenopausal bone loss and osteoporotic bone fragility.


greenmedinfo--2020-11-21--Antioxidant activities of ethanolic and acidic ethanolic extracts of astringent persimmon in H 2 O 2

Antioxidant activities of ethanolic and acidic ethanolic extracts of astringent persimmon in H 2 O 2-stimulated Caco-2 human colonic epithelial cells.

The aim of this study was to investigate the protective effects of ethanol ( EAP ) and acidic ethanol extracts @ @ @ @ @ persimmon fruits ( ) against hydrogen peroxide ( HO ) -induced oxidative stress in Caco-2 @ @ @ @ @ reactive oxygen species ( ROS ) and reduced glutathione ( GSH ) , activities of @ @ @ @ @ and catalase ( CAT ) , as well as protein and DNA damage were measured @ @ @ @ @ stress in Caco-2 cells but had no effect on SOD activity .
Both EAP and @ @ @ @ @ oxidative damage and exhibited similar effects on cellular ROS scavenging activity and protein carbonyl levels @ @ @ @ @ more potent than EAP in normalizing CAT activity and cytosolic GSH level , and in @ @ @ @ @ These results demonstrated that astringent persimmon fruit extracts were biologically active , and that the @ @ @ @ @ possesses stronger protective activity against HO-induced oxidative stress in Caco-2 cells .

The aim of this study was to investigate the protective effects of ethanol (EAP) and acidic ethanol extracts (AEAP) of astringent persimmon fruits () against hydrogen peroxide (HO)-induced oxidative stress in Caco-2 epithelial cells. Levels of reactive oxygen species (ROS) and reduced glutathione (GSH), activities of superoxide dismutase (SOD) and catalase (CAT), as well as protein and DNA damage were measured. Treatment with HOinduced oxidative stress in Caco-2 cells but had no effect on SOD activity. Both EAP and AEAP protected the cells against oxidative damage and exhibited similar effects on cellular ROS scavenging activity and protein carbonyl levels. However, AEAP was more potent than EAP in normalizing CAT activity and cytosolic GSH level, and in protecting against DNA damage. These results demonstrated that astringent persimmon fruit extracts were biologically active, and that the tannin-rich fraction (AEAP) possesses stronger protective activity against HO-induced oxidative stress in Caco-2 cells.


greenmedinfo--2020-11-21--Ethanol extract from the leaves of Diospyros kaki may be a potential therapeutic strategy for preven

Ethanol extract from the leaves of Diospyros kaki may be a potential therapeutic strategy for preventing and treating age-related neurodegenerative diseases.

Aging is a major factor that contributes to neurological impairment and neuropathological changes , such as inflammation , oxidative stress , neuronal apoptosis , and synaptic dysfunction .
Flavonoids act as protective antioxidant and anti-inflammatory agents against various age-related neurodegenerative diseases .
Here , we investigated the protective effect and mechanisms of the flavonoid-rich ethanol extract from the leaves of ( FELDK ) in the cortex and hippocampus of D-galactose- ( gal- ) aged mice .
Our results showed that FELDK treatment restored memory impairment in mice as determined by the Y-maze and Morris water maze tests .
FELDK decreased @ @ @ @ @ @ @ species ( ROS ) and malondialdehyde ( MDA ) production and elevating antioxidative enzymes .
FELDK also alleviated D-gal-induced neuroinflammation via suppressing the expression of advanced glycation end products ( AGEs ) and receptor for AGEs ( RAGE ) and activating microgliosis and astrocytosis , nuclear factor kappa B ( NF-B ) nuclear translocation , and downstream inflammatory mediators .
Moreover , FELDK inhibited the phosphatidylinositol 3-kinase ( PI3K ) /Akt and C-jun N-terminal kinase ( JNK ) apoptotic signaling pathways and ameliorated the impairment of synapse-related proteins .
Hence , these results @ @ @ @ @ @ @ D-gal-induced brain aging .
Thus , FELDK may be a potential therapeutic strategy for preventing and treating age-related neurodegenerative diseases such as Alzheimer 's disease .

Aging is a major factor that contributes to neurological impairment and neuropathological changes, such as inflammation, oxidative stress, neuronal apoptosis, and synaptic dysfunction. Flavonoids act as protective antioxidant and anti-inflammatory agents against various age-related neurodegenerative diseases. Here, we investigated the protective effect and mechanisms of the flavonoid-rich ethanol extract from the leaves of(FELDK) in the cortex and hippocampus of D-galactose- (gal-) aged mice. Our results showed that FELDK treatment restored memory impairment in mice as determined by the Y-maze and Morris water maze tests. FELDK decreased oxidative stress levels via inhibiting reactive oxygen species (ROS) and malondialdehyde (MDA) production and elevating antioxidative enzymes. FELDK also alleviated D-gal-induced neuroinflammation via suppressing the expression of advanced glycation end products (AGEs) and receptor for AGEs (RAGE) and activating microgliosis and astrocytosis, nuclear factor kappa B (NF-B) nuclear translocation, and downstream inflammatory mediators. Moreover, FELDK inhibited the phosphatidylinositol 3-kinase (PI3K)/Akt and C-jun N-terminal kinase (JNK) apoptotic signaling pathways and ameliorated the impairment of synapse-related proteins. Hence, these results indicate that FELDK exerts neuroprotective effects on D-gal-induced brain aging. Thus, FELDK may be a potential therapeutic strategy for preventing and treating age-related neurodegenerative diseases such as Alzheimer's disease.


greenmedinfo--2020-11-21--Chromatographic analysis and anti-oxidative property of Naoxinqing tablet, a proprietary preparation

Chromatographic analysis and anti-oxidative property of Naoxinqing tablet, a proprietary preparation of Diospyros Kaki leaves.

The Naoxinqing ( NXQ ) tablet is a standardised proprietary herbal product containing an extract of persimmon leaves ( ) for the management of cardio- and cerebrovascular diseases .
Although previous reports suggested that the efficacy of NXQ is at least partly mediated by its anti-oxidative property , the anti-oxidative effect of the major components of NXQ has not been studied systematically .
For quality control purposes , only analytical methods limited to 3 marker analytes have been reported , the extent to which the other components affect efficacy has not been explored .
In this study , we developed @ @ @ @ @ @ @ UPLC MS/MS ) method for the identification of seven analytes ( kaempferol-3 -- glucoside ( astragalin ) , quercetin-3 -- galactoside ( hypericin ) , quercetin-3 -- glucoside ( isoquercitin ) , kaempferol , 3,4-dihydroxybenzoic acid ( protocatechuic acid ) , and furan-2-carboxylic acid ( pyromucic acid ) and quercetin ) in the NXQ .
This is the first method reported and validated for the quantification of the seven major secondary metabolites in NXQ .
The results for the quantified analytes were then compared in 15 different batches of NXQ .
The variation @ @ @ @ @ @ @ need to quantify key bioactive components to ensure product consistency .
Radical scavenging activity and abundance was used to rank the analytes .
The anti-oxidative effects of NXQ were examined using cultured human vascular endothelial cells ( EA.hy926 ) .
Corrected 2,2-di ( 4-tert-octylphenyl ) -1-picrylhydrazyl ( DPPH ) activity results revealed that quercetin and kaempferol have the strongest anti-oxidant capacity in the extract .
Both quercetin and kaempferol significantly inhibited the hydrogen peroxide ( H₂O₂ ) -induced EA.hy926 cell injury and intracellular reactive oxygen species ( ROS ) generation .
In conclusion @ @ @ @ @ @ @ method for the analysis of major bioactive components in the NXQ and demonstrated that its anti-oxidative property may play a critical role in cerebrovascular protection .

The Naoxinqing (NXQ) tablet is a standardised proprietary herbal product containing an extract of persimmon leaves () for the management of cardio- and cerebrovascular diseases. Although previous reports suggested that the efficacy of NXQ is at least partly mediated by its anti-oxidative property, the anti-oxidative effect of the major components of NXQ has not been studied systematically. For quality control purposes, only analytical methods limited to 3 marker analytes have been reported, the extent to which the other components affect efficacy has not been explored. In this study, we developed an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC MS/MS) method for the identification of seven analytes (kaempferol-3--glucoside (astragalin), quercetin-3--galactoside (hypericin), quercetin-3--glucoside (isoquercitin), kaempferol, 3,4-dihydroxybenzoic acid (protocatechuic acid), and furan-2-carboxylic acid (pyromucic acid) and quercetin) in the NXQ. This is the first method reported and validated for the quantification of the seven major secondary metabolites in NXQ. The results for the quantified analytes were then compared in 15 different batches of NXQ. The variation observed in the seven components highlights the need to quantify key bioactive components to ensure product consistency. Radical scavenging activity and abundance was used to rank the analytes. The anti-oxidative effects of NXQ were examined using cultured human vascular endothelial cells (EA.hy926). Corrected 2,2-di(4-tert-octylphenyl)-1-picrylhydrazyl (DPPH) activity results revealed that quercetin and kaempferol have the strongest anti-oxidant capacity in the extract. Both quercetin and kaempferol significantly inhibited the hydrogen peroxide (H₂O₂)-induced EA.hy926 cell injury and intracellular reactive oxygen species (ROS) generation. In conclusion, we established and validated an UPLC-MS/MC method for the analysis of major bioactive components in the NXQ and demonstrated that its anti-oxidative property may play a critical role in cerebrovascular protection.