greenmedinfo--2020-08-23--Allicin can reduce oxidative stress damage and cardiomyocyte apoptosis in a model of myocardial infa

Allicin can reduce oxidative stress damage and cardiomyocyte apoptosis in a model of myocardial infarction.

OBJECTIVE : This research was aimed to explore protective effects of allicin on rat model of myocardial infarction via JNK signaling pathway .
METHODS : Rat myocardial ischemia model was established with subcutaneous injection of isoproterenol ( ISO ) .
Seventy-five rats were randomly divided into 5 groups ( n = 15 ) : sham group , ISO group , low-dose group ( 1.2 mg/kg/days for 7 days ) , medium-dose group ( 1.8 mg/kg/days for 7 days ) , and high-dose group ( 3.6 mg/kg/days for 7 days ) .
Routine HE staining and Masson staining were performed to @ @ @ @ @ @ @ oxidative stress-related indicators , heart tissue apoptosis-related proteins , and JNK and p-JNK proteins were measured for different groups .
RESULTS : Compared with the sham group , the T wave value of the ISO group was significantly increased ( p < 0.01 ) .
When allicin was administered , the T wave values at different time points in all groups were all decreased .
Compared with the sham group , the ratio of eNOS , Bcl-2/Bax was significantly decreased , and p-eNOS , iNOS , caspase-3 , caspase-9 , and Cyt-c were @ @ @ @ @ @ @ p < 0.05 ) .
After allicin was administered , significant changes in these proteins were observed in the medium- and high-dose groups .
There was no significant change in the expression of JNK protein in the ISO group compared with the sham group ; however , the expression of eNOS and p-JNK protein were significantly upregulated ( p < 0.01 ) and the expression of p-eNOS and iNOS were significantly downregulated ( p < 0.01 ) .
When allicin was administered , expression of p-JNK protein was significantly downregulated .
CONCLUSION : @ @ @ @ @ @ @ cardiomyocyte apoptosis in rat model of myocardial infarction and can significantly regulate JNK signaling pathway .

OBJECTIVE: This research was aimed to explore protective effects of allicin on rat model of myocardial infarction via JNK signaling pathway.
METHODS: Rat myocardial ischemia model was established with subcutaneous injection of isoproterenol (ISO). Seventy-five rats were randomly divided into 5 groups (n = 15): sham group, ISO group, low-dose group (1.2 mg/kg/days for 7 days), medium-dose group (1.8 mg/kg/days for 7 days), and high-dose group (3.6 mg/kg/days for 7 days). Routine HE staining and Masson staining were performed to observe myocardial histopathology. The expression of oxidative stress-related indicators, heart tissue apoptosis-related proteins, and JNK and p-JNK proteins were measured for different groups.
RESULTS: Compared with the sham group, the T wave value of the ISO group was significantly increased (p<0.01). When allicin was administered, the T wave values at different time points in all groups were all decreased. Compared with the sham group, the ratio of eNOS, Bcl-2/Bax was significantly decreased, and p-eNOS, iNOS, caspase-3, caspase-9, and Cyt-c were significantly elevated in the ISO group (p<0.05). After allicin was administered, significant changes in these proteins were observed in the medium- and high-dose groups. There was no significant change in the expression of JNK protein in the ISO group compared with the sham group; however, the expression of eNOS and p-JNK protein were significantly upregulated (p<0.01) and the expression of p-eNOS and iNOS were significantly downregulated (p<0.01). When allicin was administered, expression of p-JNK protein was significantly downregulated.
CONCLUSION: Allicin can reduce oxidative stress damage and cardiomyocyte apoptosis in rat model of myocardial infarction and can significantly regulate JNK signaling pathway.


greenmedinfo--2020-08-23--Allicin, a potent new ornithine decarboxylase inhibitor in neuroblastoma cells.

The natural product allicin is a reactive sulfur species ( RSS ) from garlic ( L. ) .
Neuroblastoma ( NB ) is an early childhood cancer arising from the developing peripheral nervous system .
Ornithine decarboxylase ( ODC ) is a rate-limiting enzyme in the biosynthesis of polyamines , which are oncometabolites that contribute to cell proliferation in NB and other c-MYC/MYCN-driven cancers .
Both c-MYC and MYCN directly transactivate the E-box gene , a validated anticancer drug target .
We identified allicin as a potent ODC inhibitor in a specific radioactiveassay using purified human ODC .
Allicin was∼23 @ @ @ @ @ @ @ ) than DFMO ( IC= 252μM ) , under identicalassay conditions .
ODC is a homodimer with 12 cysteines per monomer , and allicin reversibly-thioallylates cysteines .
In actively proliferating human NB cells allicin inhibited ODC enzyme activity , reduced cellular polyamine levels , inhibited cell proliferation ( IC9-19μM ) , and induced apoptosis .
The natural product allicin is a new ODC inhibitor and could be developed for use in conjunction with other anticancer treatments , the latter perhaps at a lower than usual dosage , to achieve drug synergism with good @ @ @ @ @ @

The natural product allicin is a reactive sulfur species (RSS) from garlic (L.). Neuroblastoma (NB) is an early childhood cancer arising from the developing peripheral nervous system. Ornithine decarboxylase (ODC) is a rate-limiting enzyme in the biosynthesis of polyamines, which are oncometabolites that contribute to cell proliferation in NB and other c-MYC/MYCN-driven cancers. Both c-MYC and MYCN directly transactivate the E-box gene, a validated anticancer drug target. We identified allicin as a potent ODC inhibitor in a specific radioactiveassay using purified human ODC. Allicin was∼23 000-fold more potent (IC= 11 nM) than DFMO (IC= 252μM), under identicalassay conditions. ODC is a homodimer with 12 cysteines per monomer, and allicin reversibly-thioallylates cysteines. In actively proliferating human NB cells allicin inhibited ODC enzyme activity, reduced cellular polyamine levels, inhibited cell proliferation (IC9-19μM), and induced apoptosis. The natural product allicin is a new ODC inhibitor and could be developed for use in conjunction with other anticancer treatments, the latter perhaps at a lower than usual dosage, to achieve drug synergism with good prognosis and reduced adverse effects.


greenmedinfo--2020-08-23--Allicin overcomes hypoxia mediated cisplatin resistance in lung cancer cells.

BACKGROUND/AIMS : The hypoxic microenvironment in NSCLC has been widely accepted as a contributor to both therapeutic resistance and tumor progression .
In this study , we have explored Allicin , a key organosulfur compound present in garlic for its previously unreported effectiveness in the heterogeneous hypoxic tumor microenvironment of NSCLC .
METHODS : The effect of Allicin on the viability of NSCLC cells was determined by MTT assay .
To determine the migration rate of treated cells compared to the control , scratch and transwell migration assays were performed .
Flowcytometry was done to explore cell cycle distribution , @ @ @ @ @ @ @ Fluorescence microscopy was used to examine autophagy and DNA damage in cells .
Dot blot was done to check genome wide methylation .
RNA expression was detected by RT-PCR and protein expression by western blotting .
RESULTS : Allicin significantly decreases cell viability , proliferation and migration of NSCLC cells in both normoxia and hypoxia .
It elicits both apoptosis and autophagy pathway in A549 cells by ROS accumulation and facilitating S/G2-M phase arrest in both normoxia as well as hypoxia .
We suggest that ROS/MAPK and ROS/JNK signaling pathway together govern the @ @ @ @ @ @ @ .
Notably , allicin suppresses the expression of HIF-1α and HIF-2α in hypoxic cells , pointing towards a mechanism of its effectiveness in hypoxia .
A long term passive demethylation was observed , with decreased mC and no change in TET expression , thereby ruling out active demethylation by allicin .
Furthermore , allicin synergistically enhances growth inhibitory activity of low dose cisplatin to effectively overcome hypoxia induced cisplatin resistance in A549 cells .
CONCLUSION : Altogether , our results elucidate a potential use of allicin in sensitizing hypoxic and chemoresistant NSCLC to @ @ @ @ @ @ @ therapeutic strategy with reduced side effects .

BACKGROUND/AIMS: The hypoxic microenvironment in NSCLC has been widely accepted as a contributor to both therapeutic resistance and tumor progression. In this study, we have explored Allicin, a key organosulfur compound present in garlic for its previously unreported effectiveness in the heterogeneous hypoxic tumor microenvironment of NSCLC.
METHODS: The effect of Allicin on the viability of NSCLC cells was determined by MTT assay. To determine the migration rate of treated cells compared to the control, scratch and transwell migration assays were performed. Flowcytometry was done to explore cell cycle distribution, apoptosis and ROS production in cells. Fluorescence microscopy was used to examine autophagy and DNA damage in cells. Dot blot was done to check genome wide methylation. RNA expression was detected by RT-PCR and protein expression by western blotting.
RESULTS: Allicin significantly decreases cell viability, proliferation and migration of NSCLC cells in both normoxia and hypoxia. It elicits both apoptosis and autophagy pathway in A549 cells by ROS accumulation and facilitating S/G2-M phase arrest in both normoxia as well as hypoxia. We suggest that ROS/MAPK and ROS/JNK signaling pathway together govern the cytotoxic effect of allicin in NSCLC cells. Notably, allicin suppresses the expression of HIF-1α and HIF-2α in hypoxic cells, pointing towards a mechanism of its effectiveness in hypoxia. A long term passive demethylation was observed, with decreased mC and no change in TET expression, thereby ruling out active demethylation by allicin. Furthermore, allicin synergistically enhances growth inhibitory activity of low dose cisplatin to effectively overcome hypoxia induced cisplatin resistance in A549 cells.
CONCLUSION: Altogether, our results elucidate a potential use of allicin in sensitizing hypoxic and chemoresistant NSCLC to cisplatin-based chemotherapy and provide new, affordable therapeutic strategy with reduced side effects.


greenmedinfo--2020-08-23--Aloin promotes cell apoptosis by targeting HMGB1-TLR4-ERK axis in human melanoma cells.

Aloin ( ALO ) is the major anthraquinone glycoside purified from the Aloe species .
It is well known for @ @ @ @ @ , the protective effects of ALO in melanoma cancer and underlying molecular mechanism remain unclear @ @ @ @ @ ( HMGB1 ) is an intracellular protein , which has closely association with cell survival @ @ @ @ @ various cancers .
In this study , we explored the effect of ALO on cell @ @ @ @ @ HMGB1 signal pathway .
We confirmed that ALO exerts a strong effect on promoting cell @ @ @ @ @ Furthermore , HMGB1 release was significantly inhibited in melanoma cancer cells treated with ALO .
@ @ @ @ @ melanoma cell death that is induced by ALO treatment .
Moreover , HMGB1 facilitated ALO @ @ @ @ @ binding to its receptor , Toll-like receptor 4 and activating extracellular regulated protein kinases ( @ @ @ @ @ Altogether , our study demonstrated that ALO plays an important role in promoting apoptosis of @ @ @ @ @ release and activation of downstream ERK signal pathway .

Aloin (ALO) is the major anthraquinone glycoside purified from the Aloe species. It is well known for its anti-tumor effects. However, the protective effects of ALO in melanoma cancer and underlying molecular mechanism remain unclear. High-mobility group protein B1 (HMGB1) is an intracellular protein, which has closely association with cell survival, proliferation and metastasis in various cancers. In this study, we explored the effect of ALO on cell survival and apoptosis by targeting HMGB1 signal pathway. We confirmed that ALO exerts a strong effect on promoting cell apoptosis of melanoma cells. Furthermore, HMGB1 release was significantly inhibited in melanoma cancer cells treated with ALO. Knockdown of HMGB1 could enhance melanoma cell death that is induced by ALO treatment. Moreover, HMGB1 facilitated ALO mediated melanoma cell apoptosis by binding to its receptor, Toll-like receptor 4 and activating extracellular regulated protein kinases (ERK) signal pathway. Altogether, our study demonstrated that ALO plays an important role in promoting apoptosis of melanoma cells by inhibiting HMGB1 release and activation of downstream ERK signal pathway.


greenmedinfo--2020-08-23--Antidiabetic activity of Aloe vera leaves.

This research evaluated the potential of using the methanol extract of ( L. ) Burm.f ( AVM ) to prevent @ @ @ @ @ means of the BSA/glucose assay , BSA-methylglyoxal assay , arginine-methylglyoxal assay , fructosamine , N- @ @ @ @ @ CML ) , thiol groups , and carbonyl protein .
The effect of AVM was @ @ @ @ @ inhibiting the enzymes-amylase , -glucosidase , and pancreatic lipase .
For this , the plant @ @ @ @ @ and subsequently macerated with methanol.methanol extract ( AVM ) significantly decreased the formation of AGEs @ @ @ @ @ formation of fructosamine , CML , and carbonyl protein .
The concentration of 5 mg/ml @ @ @ @ @ results .
AVM significantly inhibited the-amylase and-glucosidase enzymes .
As regards the content of thiol @ @ @ @ @ was observed during the four weeks of the experiment .
So , we can conclude @ @ @ @ @ of AGEs and may inhibit the increase in postprandial glucose , suggesting that AVM can @ @ @ @ @ AGE .

This research evaluated the potential of using the methanol extract of(L.) Burm.f (AVM) to prevent the formation of AGEs by means of the BSA/glucose assay, BSA-methylglyoxal assay, arginine-methylglyoxal assay, fructosamine, N-(carboxymethyl) lysine (CML), thiol groups, and carbonyl protein. The effect of AVM was also evaluated with regard to inhibiting the enzymes-amylase,-glucosidase, and pancreatic lipase. For this, the plant was dried, ground, and subsequently macerated with methanol.methanol extract (AVM) significantly decreased the formation of AGEs, as well as the formation of fructosamine, CML, and carbonyl protein. The concentration of 5 mg/ml of AVM presented the best results. AVM significantly inhibited the-amylase and-glucosidase enzymes. As regards the content of thiol groups, a significant increase was observed during the four weeks of the experiment. So, we can conclude thatmethanol extract decreases the formation of AGEs and may inhibit the increase in postprandial glucose, suggesting that AVM can prevent diabetes complications associated with AGE.


greenmedinfo--2020-08-23--Aloe vera and honey solution and their ethanolic extraction solution could act on metastasis-regulat

Aloe vera and honey solution and their ethanolic extraction solution could act on metastasis-regulating processes in Walker 256 tumor tissue.

Research has shown that bothand honey have anticancer and nutrition properties , including the inhibition of metastasis .
In order to evaluate the effect of a solution ofand honey ( A ) and their ethanolic fraction ( F ) on metastasis-regulating processes in primary tumors , Wistar rats were subcutaneously implanted with Walker 256 tumors and treated with A and F ( 670 µl/kg by gavage , daily for 21 days ) .
An analysis of the primary tumor tissues of these animals showed a decrease in N-cadherin expression in groups WA and WF , with a concomitant increase in @ @ @ @ @ @ @ the control group .
Cathepsin D activity was also decreased in the tumor tissues from groups WA and WF .
In addition , the number of blood vessels and their diameter significantly reduced in tumor tissues from groups WA and WF compared to those from control group .
UHPLC-ESI-MS/MS analysis of the samples A and F , suggested presence of molecules with verified antitumor activity , including caffeic acid , ferulic acid , mannose , aloin A , aloin B , pinocembrin , chrysin , and kaempferol .
These data showed that treatment @ @ @ @ @ @ @ metastatic propensity of tumors by modulating neoangiogenesis and the process of epithelial-to-mesenchymal transition .

Research has shown that bothand honey have anticancer and nutrition properties, including the inhibition of metastasis. In order to evaluate the effect of a solution ofand honey (A) and their ethanolic fraction (F) on metastasis-regulating processes in primary tumors, Wistar rats were subcutaneously implanted with Walker 256 tumors and treated with A and F (670 µl/kg by gavage, daily for 21 days). An analysis of the primary tumor tissues of these animals showed a decrease in N-cadherin expression in groups WA and WF, with a concomitant increase in E-cadherin expression in group WA compared to the control group. Cathepsin D activity was also decreased in the tumor tissues from groups WA and WF. In addition, the number of blood vessels and their diameter significantly reduced in tumor tissues from groups WA and WF compared to those from control group. UHPLC-ESI-MS/MS analysis of the samples A and F, suggested presence of molecules with verified antitumor activity, including caffeic acid, ferulic acid, mannose, aloin A, aloin B, pinocembrin, chrysin, and kaempferol. These data showed that treatment with A and F could reduce the metastatic propensity of tumors by modulating neoangiogenesis and the process of epithelial-to-mesenchymal transition.


greenmedinfo--2020-08-23--Aloe vera ethanol extract possesses concentration dependent activity against Candida albicans that i

Aimcan cause two major types of infections : superficial infections ( such as oral or vaginal candidiasis ) as well as life-threatening systemic infections , andextract is one of the potentially useful therapeutic options .
The aim of this study was to determine antifungal properties ofethanol extract on vulvovaginal candidiasis caused by .
Methodsethanol extract was prepared by the maceration method with 70 % ethanol and dissolved in DMSO into multiple concentrations ( 6.25 % , 12.5 % , 25 % , and 50 % ) .was cultured in Sabouraud dextrose agar for 72 hours and disc diffusion method was @ @ @ @ @ @ @ each concentration in comparison with fluconazole .
Zones of inhibition at 72 hours were measured and documented , then analysed to get the mean inhibition zone ( MIZ ) .
Results After 72 hours , all concentrations ofethanol extract showed inhibition effect againstwith mean inhibition zones of each concentration , 12.450±0.208 mm ( 6.25 % ) , 13.975±0.457 mm ( 12.5 % ) , 15.650±0.420 mm ( 25 % ) , and 17.225±0.512 mm ( 50 % ) , respectively .
Fluconazole revealed comparable antifungal effect with MIZ of 11.025±0.478 mm .
Oneway @ @ @ @ @ @ @ extract on inhibition zone ofgrowth ( p < 0.005 ) .
Conclusion Aloe vera ethanol extract possesses concentration dependent activity against Candida albicans that is comparable with standard antifungal agents .

Aimcan cause two major types of infections: superficial infections (such as oral or vaginal candidiasis) as well as life-threatening systemic infections, andextract is one of the potentially useful therapeutic options. The aim of this study was to determine antifungal properties ofethanol extract on vulvovaginal candidiasis caused by. Methodsethanol extract was prepared by the maceration method with 70% ethanol and dissolved in DMSO into multiple concentrations (6.25%, 12.5%, 25%, and 50%).was cultured in Sabouraud dextrose agar for 72 hours and disc diffusion method was used to evaluate the inhibitory effect of each concentration in comparison with fluconazole. Zones of inhibition at 72 hours were measured and documented, then analysed to get the mean inhibition zone (MIZ). Results After 72 hours, all concentrations ofethanol extract showed inhibition effect againstwith mean inhibition zones of each concentration, 12.450±0.208 mm (6.25%), 13.975±0.457 mm (12.5%), 15.650±0.420 mm (25%), and 17.225±0.512 mm (50%), respectively. Fluconazole revealed comparable antifungal effect with MIZ of 11.025±0.478 mm. Oneway ANOVA test showed a significant effect ofethanol extract on inhibition zone ofgrowth (p<0.005). Conclusion Aloe vera ethanol extract possesses concentration dependent activity against Candida albicans that is comparable with standard antifungal agents.


greenmedinfo--2020-08-23--Aloe vera gel could be used to improve the symptoms of ulcerative colitis.

Ulcerative colitis ( UC ) is a chronic intestinal inflammation .
Common clinical symptoms are weight loss , diarrhea , ulcers , and inflammation .
Aloe vera ( AV ) has several medicinal properties including antioxidant , anti-inflammatory analgesic , and improvement of gastric and skin ulcers .
This study aimed to investigate the protective and therapeutic effects of AV gel on acetic acid-induced UC in rats .
UC was induced in 48 rats by injection of 4 % acetic acid into the rectum .
Protective and treatment groups received treatments 7 days before and after the induction of colitis @ @ @ @ @ @ @ , the positive control group , and AV groups received distilled water , sulfasalazine , and 50 and 300 mg/kg of gel extract , respectively .
Water and food intake and body weight changes were recorded .
The extent of the mucosal ulcers , colon tissue thickening , and mucosal bleeding were scored by the Gerald classification system score ( microscopy observations ) .
Slides of tissues were prepared for pathologic assay using the modified Wallace method ( macroscopic observations ) .
The results of the macroscopic and microscopic examination showed protective and @ @ @ @ @ @ @ AV on acetic acid-induced colitis in rats which reduces the inflammation , ulcers and tissue damage compared with negative control ( p < 0.05 ) .
There were no significant changes in the amount of water and food intake , body weight changes , and colon weight in protective and treatment groups .
Based on the results , AV gel could be used to improve the symptoms of UC , as well as prevent people who are susceptible to the UC .

Ulcerative colitis (UC) is a chronic intestinal inflammation. Common clinical symptoms are weight loss, diarrhea, ulcers, and inflammation. Aloe vera (AV) has several medicinal properties including antioxidant, anti-inflammatory analgesic, and improvement of gastric and skin ulcers. This study aimed to investigate the protective and therapeutic effects of AV gel on acetic acid-induced UC in rats. UC was induced in 48 rats by injection of 4% acetic acid into the rectum. Protective and treatment groups received treatments 7 days before and after the induction of colitis, respectively. The negative control group, the positive control group, and AV groups received distilled water, sulfasalazine, and 50 and 300 mg/kg of gel extract, respectively. Water and food intake and body weight changes were recorded. The extent of the mucosal ulcers, colon tissue thickening, and mucosal bleeding were scored by the Gerald classification system score (microscopy observations). Slides of tissues were prepared for pathologic assay using the modified Wallace method (macroscopic observations). The results of the macroscopic and microscopic examination showed protective and therapeutic effects of 50 mg/kg dose of AV on acetic acid-induced colitis in rats which reduces the inflammation, ulcers and tissue damage compared with negative control (p<0.05). There were no significant changes in the amount of water and food intake, body weight changes, and colon weight in protective and treatment groups. Based on the results, AV gel could be used to improve the symptoms of UC, as well as prevent people who are susceptible to the UC.


greenmedinfo--2020-08-23--Aloin inhibits the proliferation and migration of gastric cancer cells.

Background : Aloin has been reported to have many pharmacological effects including anti-inflammatory , anti-oxidant and anti-tumour activities .
However , the precise molecular mechanisms underlying the anti-tumour properties of aloin are yet to be elucidated .
Methods : HGC-27 and BGC-823 gastric cancer cells were treated with aloin .
EdU and colony formation assays were used to detect the proliferation ability of cells .
The migration of cells was detected using wound healing and transwell assays .
Western blotting was used to detect the levels of cyclinD1 , cyclin E1 , MMPs , N-cadherin , E-cadherin and NOX2 .
@ @ @ @ @ @ @ P70S6K , S6 , Src , stat3 and IκBα were also detected by Western blotting .
Flow cytometry was used to detect the cell cycle distribution.The location of p65 in cells was determined by using a confocal microscopy assay .
The total amounts of ROS present in cells were measured using an ROS assay kit .
Results : Here , we found that aloin inhibited the proliferation and migration of HGC-27 and BGC-823 gastric cancer cells using a combination of EdU , colony formation , wound healing and transwell assays .
Further investigations @ @ @ @ @ @ @ levels of cyclin D1 , N-cadherin , and the matrix metalloproteinases ( MMP ) -2 and MMP-9 ; increased E-cadherin expression in a dose-dependent manner ; inhibited reactive oxygen species ( ROS ) generation ; and mediated the activation of Akt-mTOR , signal transducer and activator of transcription-3 ( Stat3 ) , and NF-κB signalling pathways .
Our results also indicated that aloin is able to attenuate the expression levels of the two regulatory proteins of nicotinamide adenine dinucleotide phosphate oxidase 2 ( NOX2 ) , p47and p22 , but had no effect @ @ @ @ @ @ @ treatment of gastric cancer cells inhibited ROS production and Akt-mTOR , Stat3 , and IκBα phosphorylation .
Taken together , our data suggest that aloin inhibits the proliferation and migration of gastric cancer cells by downregulating NOX2-ROS-mediated activation of the Akt-mTOR , Stat3 , and NF-κB signalling pathways .
Conclusion : Our findings suggest a potential role for aloin in the prevention of gastric cancer cell proliferation and migration and provide novel insights into the anti-cancer properties of aloin .

Background: Aloin has been reported to have many pharmacological effects including anti-inflammatory, anti-oxidant and anti-tumour activities. However, the precise molecular mechanisms underlying the anti-tumour properties of aloin are yet to be elucidated.
Methods: HGC-27 and BGC-823 gastric cancer cells were treated with aloin. EdU and colony formation assays were used to detect the proliferation ability of cells. The migration of cells was detected using wound healing and transwell assays. Western blotting was used to detect the levels of cyclinD1, cyclin E1, MMPs, N-cadherin, E-cadherin and NOX2. The phosphorylation of Akt, mTOR, P70S6K, S6, Src, stat3 and IκBα were also detected by Western blotting. Flow cytometry was used to detect the cell cycle distribution.The location of p65 in cells was determined by using a confocal microscopy assay. The total amounts of ROS present in cells were measured using an ROS assay kit.
Results: Here, we found that aloin inhibited the proliferation and migration of HGC-27 and BGC-823 gastric cancer cells using a combination of EdU, colony formation, wound healing and transwell assays. Further investigations revealed that aloin decreased the protein expression levels of cyclin D1, N-cadherin, and the matrix metalloproteinases (MMP)-2 and MMP-9; increased E-cadherin expression in a dose-dependent manner; inhibited reactive oxygen species (ROS) generation; and mediated the activation of Akt-mTOR, signal transducer and activator of transcription-3 (Stat3), and NF-κB signalling pathways. Our results also indicated that aloin is able to attenuate the expression levels of the two regulatory proteins of nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2), p47and p22, but had no effect on the level of gp91. N-acetylcysteine treatment of gastric cancer cells inhibited ROS production and Akt-mTOR, Stat3, and IκBα phosphorylation. Taken together, our data suggest that aloin inhibits the proliferation and migration of gastric cancer cells by downregulating NOX2-ROS-mediated activation of the Akt-mTOR, Stat3, and NF-κB signalling pathways.
Conclusion: Our findings suggest a potential role for aloin in the prevention of gastric cancer cell proliferation and migration and provide novel insights into the anti-cancer properties of aloin.


greenmedinfo--2020-08-23--Aloin protects against blood-brain barrier damage after traumatic brain injury in mice.

Aloin is a small-molecule drug well known for its protective actions in various models of damage .
Traumatic brain injury ( TBI ) -induced cerebral edema from secondary damage caused by disruption of the blood-brain barrier ( BBB ) often leads to an adverse prognosis .
Since the role of aloin in maintaining the integrity of the BBB after TBI remains unclear , we explored the protective effects of aloin on the BBB using in vivo and in vitro TBI models .
Adult male C57BL/6 mice underwent controlled cortical impact injury , and mouse brain capillary endothelial bEnd.3 cells underwent @ @ @ @ @ @ @ aloin treatment .
In the animal experiments , we found 20 mg/kg aloin to be the optimum concentration to decrease cerebral edema , decrease disruption of the BBB , and improve neurobehavioral performance after cortical impact injury .
In the cellular studies , the optimum concentration of 40 μg/mL aloin reduced apoptosis and reversed the loss of tight junctions by reducing the reactive oxygen species levels and changes in mitochondrial membrane potential after stretch injury .
The mechanisms may be that aloin downregulates the phosphorylation of p38 mitogen-activated protein kinase , the activation @ @ @ @ @ @ @ the ratios of B cell lymphoma ( Bcl ) -2-associated X protein/Bcl-2 and cleaved caspase-3/caspase-3 .
We conclude that aloin exhibits these protective effects on the BBB after TBI through its anti-oxidative stress and anti-apoptotic properties in mouse brain capillary endothelial cells .
Aloin may thus be a promising therapeutic drug for TBI .

Aloin is a small-molecule drug well known for its protective actions in various models of damage. Traumatic brain injury (TBI)-induced cerebral edema from secondary damage caused by disruption of the blood-brain barrier (BBB) often leads to an adverse prognosis. Since the role of aloin in maintaining the integrity of the BBB after TBI remains unclear, we explored the protective effects of aloin on the BBB using in vivo and in vitro TBI models. Adult male C57BL/6 mice underwent controlled cortical impact injury, and mouse brain capillary endothelial bEnd.3 cells underwent biaxial stretch injury, then both received aloin treatment. In the animal experiments, we found 20 mg/kg aloin to be the optimum concentration to decrease cerebral edema, decrease disruption of the BBB, and improve neurobehavioral performance after cortical impact injury. In the cellular studies, the optimum concentration of 40 μg/mL aloin reduced apoptosis and reversed the loss of tight junctions by reducing the reactive oxygen species levels and changes in mitochondrial membrane potential after stretch injury. The mechanisms may be that aloin downregulates the phosphorylation of p38 mitogen-activated protein kinase, the activation of p65 nuclear factor-kappa B, and the ratios of B cell lymphoma (Bcl)-2-associated X protein/Bcl-2 and cleaved caspase-3/caspase-3. We conclude that aloin exhibits these protective effects on the BBB after TBI through its anti-oxidative stress and anti-apoptotic properties in mouse brain capillary endothelial cells. Aloin may thus be a promising therapeutic drug for TBI.


greenmedinfo--2020-08-23--Aloin suppresses lipopolysaccharide-induced acute lung injury by inhibiting NLRP3/NF-κB via activati

Aloin suppresses lipopolysaccharide-induced acute lung injury by inhibiting NLRP3/NF-κB via activation of SIRT1 in mice.

OBJECTIVE : The purpose of this study was to explore the protective effects and potential mechanisms of aloin on lipopolysaccharide ( LPS ) -induced acute lung injury ( ALI ) .
METHODS : Mice were pretreatment with aloin 1 h before LPS administration .
The number of inflammatory cells and the levels of TNF-α and IL-1β was detected .
The lung histopathological changes , wet/dry ratio , MPO activity , GSH , MDA , SOD , and the expression of NF-κB and NLRP3 inflammasome were measured .
RESULTS : The results showed that aloin significantly inhibited the number of total @ @ @ @ @ @ @ as well as the levels of TNF-α and IL-1β in BALF induced by LPS .
In addition , pretreatment with aloin also inhibited LPS-induced lung histopathological injuries , lung wet/dry ratio , MPO activity , and MDA content .
The levels of GSH and SOD were decreased by LPS and treatment of aloin could increase the levels of GSH and SOD .
To study the protective mechanisms of alion on LPS-induced ALI , the expression of SIRT1 , NF-κB and NLRP3 inflammasome were tested .
We found that aloin significantly inhibited the activation @ @ @ @ @ @ @ induced by LPS .
Meanwhile , aloin was found to increase the expressionof SIRT1 and inhibition of SIRT1 by EX-527 reversed the protective effects of aloin .
CONCLUSIONS : These results suggest that aloin exerts its protective effects on LPS-induced ALI by activation SIRT1 , which subsequently results in the suppression of NF-κB and NLRP3 inflammasome .

OBJECTIVE: The purpose of this study was to explore the protective effects and potential mechanisms of aloin on lipopolysaccharide (LPS)-induced acute lung injury (ALI).
METHODS: Mice were pretreatment with aloin 1 h before LPS administration. The number of inflammatory cells and the levels of TNF-α and IL-1β was detected. The lung histopathological changes, wet/dry ratio, MPO activity, GSH, MDA, SOD, and the expression of NF-κB and NLRP3 inflammasome were measured.
RESULTS: The results showed that aloin significantly inhibited the number of total cells, neutrophils, and macrophages, as well as the levels of TNF-α and IL-1β in BALF induced by LPS. In addition, pretreatment with aloin also inhibited LPS-induced lung histopathological injuries, lung wet/dry ratio, MPO activity, and MDA content. The levels of GSH and SOD were decreased by LPS and treatment of aloin could increase the levels of GSH and SOD. To study the protective mechanisms of alion on LPS-induced ALI, the expression of SIRT1, NF-κB and NLRP3 inflammasome were tested. We found that aloin significantly inhibited the activation of NF-κB and NLRP3 inflammasome in ALI induced by LPS. Meanwhile, aloin was found to increase the expressionof SIRT1 and inhibition of SIRT1 by EX-527 reversed the protective effects of aloin.
CONCLUSIONS: These results suggest that aloin exerts its protective effects on LPS-induced ALI by activation SIRT1, which subsequently results in the suppression of NF-κB and NLRP3 inflammasome.


greenmedinfo--2020-08-23--Aloin alleviates doxorubicin-induced cardiotoxicity in rats by abrogating oxidative stress and pro-i

Aloin alleviates doxorubicin-induced cardiotoxicity in rats by abrogating oxidative stress and pro-inflammatory cytokines.

PURPOSE : Aloin , an anthraquinone present in the aloe species , possesses antiangiogenic , chemopreventive and antioxidant properties .
It exerts cytotoxicity against breast cancer and ovarian cancer cell lines .
These properties of aloin project it as a chemopreventive adjuvant to anticancer chemotherapy .
METHODS : We evaluated the effect of concurrent oral administration of aloin against doxorubicin ( DOX ) -induced cardiotoxicity in rats .
The protective effects of aloin against DOX-induced toxicity were evident as a statistically significant inhibition of a rise in the biochemical markers of myocardial damage including lactate dehydrogenase ( LDH ) , @ @ @ @ @ @ @ alanine aminotransferase ( ALT ) , and aspartate aminotransferase ( AST ) .
RESULTS : Aloin dose dependently inhibited the DOX-induced changes in ECG like increased ST-height and prolonged QT interval .
It protected heart against the lipid peroxidation and restored the levels of antioxidative defenses : reduced glutathione , catalase and superoxide dismutase .
Aloin prominently reduced the levels of proinflammatory cytokines- TNF-α , IL-1β and IL-6 .
Notably , the significant protective effects of aloin were evident even at the strikingly lower doses of 1 and 5 mg/kg per day .
@ @ @ @ @ @ @ to further investigate the chemopreventive effects of aloin against other chemotherapeutic agents .

PURPOSE: Aloin, an anthraquinone present in the aloe species, possesses antiangiogenic, chemopreventive and antioxidant properties. It exerts cytotoxicity against breast cancer and ovarian cancer cell lines. These properties of aloin project it as a chemopreventive adjuvant to anticancer chemotherapy.
METHODS: We evaluated the effect of concurrent oral administration of aloin against doxorubicin (DOX)-induced cardiotoxicity in rats. The protective effects of aloin against DOX-induced toxicity were evident as a statistically significant inhibition of a rise in the biochemical markers of myocardial damage including lactate dehydrogenase (LDH), creatinine kinase-myocardial band (CK-MB), alanine aminotransferase (ALT), and aspartate aminotransferase (AST).
RESULTS: Aloin dose dependently inhibited the DOX-induced changes in ECG like increased ST-height and prolonged QT interval. It protected heart against the lipid peroxidation and restored the levels of antioxidative defenses: reduced glutathione, catalase and superoxide dismutase. Aloin prominently reduced the levels of proinflammatory cytokines- TNF-α, IL-1β and IL-6. Notably, the significant protective effects of aloin were evident even at the strikingly lower doses of 1 and 5 mg/kg per day.
CONCLUSION: Our results highlight the necessity to further investigate the chemopreventive effects of aloin against other chemotherapeutic agents.


greenmedinfo--2020-08-23--Anti-inflammatory and anti-oxidant effects of aloe vera in rats with non-alcoholic steatohepatitis.

BACKGROUND : Aloe vera exerts several biological activities , such as , anti-inflammatory , antioxidant , and antimicrobial effects .
It was recently shown to reduce insulin resistance and triglyceride level .
We hypothesized that aloe vera would have beneficial effects in alleviating non-alcoholic steatohepatitis ( NASH ) in rats .
AIM : To examine the therapeutic effects of aloe vera in NASH rats .
METHODS : All rats were randomly divided into 3 groups ( = 6 in each group ) .
Rats in the control group were fed ad libitum with a standard diet for 8 wk .
@ @ @ @ @ @ @ ad libitum with a high-fat high-fructose diet ( HFHFD ) for 8 wk .
Rats in the aloe vera group were fed ad libitum with a HFHFD and aloe vera in dimethylsulfoxide ( 50 mg/kg ) by gavage daily for 8 wk .
Liver samples were collected at the end of the treatment period .
RESULTS : Hepatic malondialdehyde ( MDA ) levels increased significantly in the NASH group as compared with the control group ( 377± 77 nmol/mg129± 51 nmol/mg protein , respectively , < 0.001 ) .
Glutathione ( GSH ) @ @ @ @ @ @ @ group than the control group ( 9± 2 nmol/mg24± 8 nmol/mg protein , respectively , = 0.001 ) .
The expression of interleukin-18 ( IL-18 ) , nuclear factor-kappaβ , and caspase-3 increased , while peroxisome proliferator-activated receptor gamma decreased in the NASH group compared with the controls .
Following aloe vera administration , MDA levels decreased ( 199 ± 35 nmol/mg protein ) and GSH increased ( 18 ± 4 nmol/mg protein ) markedly .
Steatosis , hepatocyteballooning , lobular inflammation and increased hepatocyte apoptosis were observed in the NASH group .
@ @ @ @ @ @ @ liver histology .
CONCLUSION : Aloe vera attenuated oxidative stress , hepatic inflammation and hepatocyte apoptosis , thus improving liver pathology in rats with NASH .

BACKGROUND: Aloe vera exerts several biological activities, such as, anti-inflammatory, antioxidant, and antimicrobial effects. It was recently shown to reduce insulin resistance and triglyceride level. We hypothesized that aloe vera would have beneficial effects in alleviating non-alcoholic steatohepatitis (NASH) in rats.
AIM: To examine the therapeutic effects of aloe vera in NASH rats.
METHODS: All rats were randomly divided into 3 groups (= 6 in each group). Rats in the control group were fed ad libitum with a standard diet for 8 wk. Rats in the NASH group were fed ad libitum with a high-fat high-fructose diet (HFHFD) for 8 wk. Rats in the aloe vera group were fed ad libitum with a HFHFD and aloe vera in dimethylsulfoxide (50 mg/kg) by gavage daily for 8 wk. Liver samples were collected at the end of the treatment period.
RESULTS: Hepatic malondialdehyde (MDA) levels increased significantly in the NASH group as compared with the control group (377± 77 nmol/mg129± 51 nmol/mg protein, respectively,<0.001). Glutathione (GSH) levels were significantly lower in the NASH group than the control group (9± 2 nmol/mg24± 8 nmol/mg protein, respectively,= 0.001). The expression of interleukin-18 (IL-18), nuclear factor-kappaβ, and caspase-3 increased, while peroxisome proliferator-activated receptor gamma decreased in the NASH group compared with the controls. Following aloe vera administration, MDA levels decreased (199 ± 35 nmol/mg protein) and GSH increased (18 ± 4 nmol/mg protein) markedly. Steatosis, hepatocyteballooning, lobular inflammation and increased hepatocyte apoptosis were observed in the NASH group. Aloe vera treatment attenuated these changes in liver histology.
CONCLUSION: Aloe vera attenuated oxidative stress, hepatic inflammation and hepatocyte apoptosis, thus improving liver pathology in rats with NASH.


greenmedinfo--2020-08-23--Phytochemical analysis and in vitro anti-proliferative activity of Viscum album ethanolic extracts.

BACKGROUND : Viscum album L. ( Santalaceae ) , commonly known as mistletoe , is a hemiparasitic plant traditionally used in complementary cancer treatment .
Its antitumor potential is mostly attributed to the presence of aqueous soluble metabolites ; however , the use of ethanol as solvent also permits the extraction of pharmacological compounds with antitumor potential .
The clinical efficacy of mistletoe therapy inspired the present work , which focuses on ethanolic extracts ( V. album '' mother tinctures '' , MT ) prepared from different host trees .
METHODS : Samples from three European subspecies ( album , @ @ @ @ @ @ @ , and five different V. album-MT strains were prepared .
The following phytochemical analyses were performed : thin layer chromatography ( TLC ) , high-performance liquid chromatography ( HPLC ) and liquid chromatography-high resolution mass spectrometry ( LC-HRMS ) .
The proliferation assay was performed with WST-1 after incubation of tumor ( Yoshida and Molt-4 ) and fibroblast cell lines ( NIH/3 T3 ) with different MT concentrations ( 0.5 to 0.05 % v/v ) .
The cell death mechanism was investigated by flow cytometry ( FACS ) using Annexin V-7AAD .
RESULTS @ @ @ @ @ @ @ presence of phenolic acids , flavonoids and lignans .
The MT flavonoid and viscotoxin contents ( mg/g fresh weight ) were highest in Quercus robur ( 9.67 ± 0.85 mg/g ) and Malus domestica ( 3.95 ± 0.58 mg/mg ) , respectively .
The viscotoxin isoform proportions ( % total ) were also different among the VA subspecies with a higher content of A3 in V. album growing on Abies alba ( 60.57 ± 2.13 ) .
The phytochemical compounds as well as the viscotoxin contents are probably related to the antitumor effects @ @ @ @ @ @ @ evaluated by colorimetric and FACS methodologies involved necrotic damage , which was host tree- , time- and dose- dependent , with different selectivity to tumor cells .
Mother tincture from V. album ssp .
abietis was the most effective at inducing in vitro cellular effects , even when incubated at the smallest concentration tested , probably because of the higher content of VT A3 .
CONCLUSION : Our results indicate the promising antitumor potential of Viscum album ethanolic extracts and the importance of botanical and phytochemical characterization for in vitro anti-proliferative effects .

BACKGROUND: Viscum album L. (Santalaceae), commonly known as mistletoe, is a hemiparasitic plant traditionally used in complementary cancer treatment. Its antitumor potential is mostly attributed to the presence of aqueous soluble metabolites; however, the use of ethanol as solvent also permits the extraction of pharmacological compounds with antitumor potential. The clinical efficacy of mistletoe therapy inspired the present work, which focuses on ethanolic extracts (V. album"mother tinctures", MT) prepared from different host trees.
METHODS: Samples from three European subspecies (album, austriacum, and abietis) were harvested, and five different V. album-MT strains were prepared. The following phytochemical analyses were performed: thin layer chromatography (TLC), high-performance liquid chromatography (HPLC) and liquid chromatography-high resolution mass spectrometry (LC-HRMS). The proliferation assay was performed with WST-1 after incubation of tumor (Yoshida and Molt-4) and fibroblast cell lines (NIH/3 T3) with different MT concentrations (0.5 to 0.05% v/v). The cell death mechanism was investigated by flow cytometry (FACS) using Annexin V-7AAD.
RESULTS: Chemical analyses of MT showed the presence of phenolic acids, flavonoids and lignans. The MT flavonoid and viscotoxin contents (mg/g fresh weight) were highest in Quercus robur (9.67 ± 0.85 mg/g) and Malus domestica (3.95 ± 0.58 mg/mg), respectively. The viscotoxin isoform proportions (% total) were also different among the VA subspecies with a higher content of A3 in V. album growing on Abies alba (60.57 ± 2.13). The phytochemical compounds as well as the viscotoxin contents are probably related to the antitumor effects of MT. The cell death mechanisms evaluated by colorimetric and FACS methodologies involved necrotic damage, which was host tree-, time- and dose- dependent, with different selectivity to tumor cells. Mother tincture from V. album ssp. abietis was the most effective at inducing in vitro cellular effects, even when incubated at the smallest concentration tested, probably because of the higher content of VT A3.
CONCLUSION: Our results indicate the promising antitumor potential of Viscum album ethanolic extracts and the importance of botanical and phytochemical characterization for in vitro anti-proliferative effects.


greenmedinfo--2020-08-23--AbnobaVISCUM Fraxini has cell line dependent antitumoral effects in medulloblastoma models.

BACKGROUND : Mistletoe therapy is frequently administered as a supportive treatment in diverse pediatric cancer entities including brain tumors .
Medulloblastoma is the most common brain tumor in childhood .
Its high risk to metastasize and its long-term sequelae caused by aggressive chemo- or radiotherapies are still challenging .
MATERIAL AND METHODS : Effects of a lectin-rich mistletoe extract , abnobaVISCUM Fraxini , were investigated in two medulloblastoma cell lines ( Daoy and ONS-76 ) .
Responsiveness of tumor cells was assessed by cell viability assays and xCELLigence real-time analyses .
Moreover , impacts on proliferation , cell cycle and @ @ @ @ @ @ @ by staining of vital mitochondria and assessing the involvement of caspases .
In addition , effects on migration and invasion were analyzed .
RESULTS : Both medulloblastoma cell lines were more susceptible to treatment with the mistletoe extract than a nontumorigenic fibroblast cell line .
In mistletoe-sensitive Daoy cells , reduction of proliferation and induction of caspase-mediated apoptosis were observed upon administration of 0.05 and 0.5 mg/mL abnobaVISCUM Fraxini treatment , respectively .
Furthermore , mistletoe extract inhibited migration and invasion properties in Daoy and significantly impaired invasive capabilities of ONS-76 cells .
@ @ @ @ @ @ @ dependent antitumoral effects in medulloblastoma models .
These results call for further investigations , to reveal mechanistic insights into antitumorigenic properties of mistletoe extracts .

BACKGROUND: Mistletoe therapy is frequently administered as a supportive treatment in diverse pediatric cancer entities including brain tumors. Medulloblastoma is the most common brain tumor in childhood. Its high risk to metastasize and its long-term sequelae caused by aggressive chemo- or radiotherapies are still challenging.
MATERIAL AND METHODS: Effects of a lectin-rich mistletoe extract, abnobaVISCUM Fraxini, were investigated in two medulloblastoma cell lines (Daoy and ONS-76). Responsiveness of tumor cells was assessed by cell viability assays and xCELLigence real-time analyses. Moreover, impacts on proliferation, cell cycle and apoptosis were investigated. Apoptosis was studied by staining of vital mitochondria and assessing the involvement of caspases. In addition, effects on migration and invasion were analyzed.
RESULTS: Both medulloblastoma cell lines were more susceptible to treatment with the mistletoe extract than a nontumorigenic fibroblast cell line. In mistletoe-sensitive Daoy cells, reduction of proliferation and induction of caspase-mediated apoptosis were observed upon administration of 0.05 and 0.5 mg/mL abnobaVISCUM Fraxini treatment, respectively. Furthermore, mistletoe extract inhibited migration and invasion properties in Daoy and significantly impaired invasive capabilities of ONS-76 cells.
CONCLUSION: AbnobaVISCUM Fraxini has cell line dependent antitumoral effects in medulloblastoma models. These results call for further investigations, to reveal mechanistic insights into antitumorigenic properties of mistletoe extracts.


greenmedinfo--2020-08-23--Flavonoid and cannabinoid impact on the ocular surface.

PURPOSE OF REVIEW : To evaluate the impact of flavonoids and cannabinoids as anti-inflammatory and antiallergic treatments on the anterior surface of the eye .
RECENT FINDINGS : Allergic conjunctivitis and dry eye syndrome are common ocular surface diseases that have been treated with traditional pharmacological measures , e.g .
corticosteroids , antihistamines .
Given the side-effect profiles of these medications and the growing interest in complementary treatment modalities as part of integrative medical interventions , well known flavonoids , such as quercetin and catechin , are under investigation for topical and systemic application methods for relief .
As flavonoid @ @ @ @ @ @ @ alleviated dry eye symptoms , including lacrimal gland inflammation , tear secretion , and the stability of the tear film .
Research on ocular cannabinoid receptors and response to synthetic cannabinoids are also being considered for therapy of anterior ocular disorders .
The expansion of herbal formulations provides a framework for future treatment regimens for ocular surface disorders .
SUMMARY : Flavonoids and cannabinoids show promise as potential complementary treatment for allergic diseases because of their anti-inflammatory and antiallergic properties .
Several studies implementing ocular and systemic application of these compounds show potential @ @ @ @ @ @ @ quality of life while also managing ocular surface disease processes .

PURPOSE OF REVIEW: To evaluate the impact of flavonoids and cannabinoids as anti-inflammatory and antiallergic treatments on the anterior surface of the eye.
RECENT FINDINGS: Allergic conjunctivitis and dry eye syndrome are common ocular surface diseases that have been treated with traditional pharmacological measures, e.g. corticosteroids, antihistamines. Given the side-effect profiles of these medications and the growing interest in complementary treatment modalities as part of integrative medical interventions, well known flavonoids, such as quercetin and catechin, are under investigation for topical and systemic application methods for relief. As flavonoid derivatives, pycnogenol and epigallocatechin gallate have alleviated dry eye symptoms, including lacrimal gland inflammation, tear secretion, and the stability of the tear film. Research on ocular cannabinoid receptors and response to synthetic cannabinoids are also being considered for therapy of anterior ocular disorders. The expansion of herbal formulations provides a framework for future treatment regimens for ocular surface disorders.
SUMMARY: Flavonoids and cannabinoids show promise as potential complementary treatment for allergic diseases because of their anti-inflammatory and antiallergic properties. Several studies implementing ocular and systemic application of these compounds show potential in becoming adjuvant treatment strategies for improving quality of life while also managing ocular surface disease processes.


greenmedinfo--2020-08-23--Pycnogenol achieves neuroprotective effects in rats with spinal cord injury by stabilizing the mitoc

Pycnogenol achieves neuroprotective effects in rats with spinal cord injury by stabilizing the mitochondrial membrane potential.

OBJECTIVES : In this study , we aimed to verify the neuroprotective effects of pycnogenol ( PYC ) on spinal cord injury ( SCI ) and to determine the underlying mechanisms .
METHODS : Male Wistar rats were selected to establish a model of SCI in accordance with the Allen 's protocol .
The rats in the PYC group were treated with 100 mg/kg PYC by intraperitoneal injection 15 minutes after SCI .
The Basso , Beattie and Bresnahan ( BBB ) scale was used to evaluate locomotor activity .
The superoxide dismutase ( SOD ) activity and malondialdehyde ( @ @ @ @ @ @ @ .
The expression of Cleaved-caspase 3 , Bcl-2 , Bax and the levels of Cytochrome c ( Cyt-c ) wereanalysed by Western blot or Immunohistochemistry .
Furthermore , we used the JC-1 fluorescent probe to analyse the mitochondrial membrane potential ( ΔΨm ) .
RESULTS : The rats that received PYC had significantly higher BBB scores than the control lesion rats .
PYC treatment resulted in reduced bleeding in spinal cord tissue and proliferation of glial cells , greater numbers of anterior horn neurons , more complete structures of residual neurons , and @ @ @ @ @ @ @ In addition , PYC reduced MDA production and increased SOD activity .
The mitochondrial membrane potential ( MMP ) was significantly increased in the PYC treatment group compared with the SCI group .
In addition , PYC decreased the expression of Cleaved-caspase 3 and Bax and the release of Cyt-c and increased the expression of Bcl-2 in the SCI rats .
CONCLUSIONS : The above findings suggested that PYC can improve motor function and reduce neuronal apoptosis after SCI by stabilizing the MMP through the inhibition of oxidative stress .

OBJECTIVES: In this study, we aimed to verify the neuroprotective effects of pycnogenol (PYC) on spinal cord injury (SCI) and to determine the underlying mechanisms.
METHODS: Male Wistar rats were selected to establish a model of SCI in accordance with the Allen's protocol. The rats in the PYC group were treated with 100 mg/kg PYC by intraperitoneal injection 15 minutes after SCI. The Basso, Beattie and Bresnahan (BBB) scale was used to evaluate locomotor activity. The superoxide dismutase (SOD) activity and malondialdehyde (MDA) production were detected by ELISA. The expression of Cleaved-caspase 3, Bcl-2, Bax and the levels of Cytochrome c (Cyt-c) wereanalysed by Western blot or Immunohistochemistry. Furthermore, we used the JC-1 fluorescent probe to analyse the mitochondrial membrane potential (ΔΨm).
RESULTS: The rats that received PYC had significantly higher BBB scores than the control lesion rats. PYC treatment resulted in reduced bleeding in spinal cord tissue and proliferation of glial cells, greater numbers of anterior horn neurons, more complete structures of residual neurons, and significant improvement in Nissl body morphology. In addition, PYC reduced MDA production and increased SOD activity. The mitochondrial membrane potential (MMP) was significantly increased in the PYC treatment group compared with the SCI group. In addition, PYC decreased the expression of Cleaved-caspase 3 and Bax and the release of Cyt-c and increased the expression of Bcl-2 in the SCI rats.
CONCLUSIONS: The above findings suggested that PYC can improve motor function and reduce neuronal apoptosis after SCI by stabilizing the MMP through the inhibition of oxidative stress.
ABBREVIATIONS: DMSO: dimethyl sulfoxide; IHC: immunological histological chemistry; MDA: malondialdehyde; PBS: phosphate buffered saline; PMSF: phenylmethanesulfonyl fluoride; PVDF: polyvinylidene difluoride; PYC: Pycnogenol; RIPA: radio immunoprecipitation assay; SCI: spinal cord injury; SOD: superoxide dismutase.


greenmedinfo--2020-08-23--Pycnogenol supplementation attenuates memory deficits and protects hippocampal CA1 pyramidal neurons

Pycnogenol supplementation attenuates memory deficits and protects hippocampal CA1 pyramidal neurons.

Pycnogenol ( an extract of the bark of French maritime pine tree ) is used for dietary supplement and known to have excellent antioxidative efficacy .
However , there are few reports on neuroprotective effect of Pycnogenolsupplementation and its mechanisms against ischemic injury following transient forebrain ischemia ( TFI ) in gerbils .
Now , we examined neuroprotective effect and its mechanisms of Pycnogenolin the gerbils with 5-min TFI , which evokes a significant death ( loss ) of pyramidal cells located in the cornu ammonis ( CA1 ) region of gerbil hippocampus from 4-5 days post-TFI .
Gerbils were @ @ @ @ @ @ @ 50 mg/kg of Pycnogenolonce a day for 7 days before TFI surgery .
Treatment with 50 mg/kg , not 30 or 40 mg/kg , of Pycnogenolpotently protected learning and memory , as well as CA1 pyramidal cells , from ischemic injury .
Treatment with 50 mg/kg Pycnogenolsignificantly enhanced immunoreactivity of antioxidant enzymes ( superoxide dismutases and catalase ) in the pyramidal cells before and after TFI induction .
Furthermore , the treatment significantly reduced the generation of superoxide anion , ribonucleic acid oxidation and lipid peroxidation in the pyramidal cells .
Moreover , @ @ @ @ @ @ @ by administration of sodium azide ( a potent inhibitor of SODs and catalase activities ) .
Taken together , current results clearly indicate that Pycnogenolsupplementation can prevent neurons from ischemic stroke through its potent antioxidative role .

Pycnogenol(an extract of the bark of French maritime pine tree) is used for dietary supplement and known to have excellent antioxidative efficacy. However, there are few reports on neuroprotective effect of Pycnogenolsupplementation and its mechanisms against ischemic injury following transient forebrain ischemia (TFI) in gerbils. Now, we examined neuroprotective effect and its mechanisms of Pycnogenolin the gerbils with 5-min TFI, which evokes a significant death (loss) of pyramidal cells located in the cornu ammonis (CA1) region of gerbil hippocampus from 4-5 days post-TFI. Gerbils were pretreated with 30, 40, and 50 mg/kg of Pycnogenolonce a day for 7 days before TFI surgery. Treatment with 50 mg/kg, not 30 or 40 mg/kg, of Pycnogenolpotently protected learning and memory, as well as CA1 pyramidal cells, from ischemic injury. Treatment with 50 mg/kg Pycnogenolsignificantly enhanced immunoreactivity of antioxidant enzymes (superoxide dismutases and catalase) in the pyramidal cells before and after TFI induction. Furthermore, the treatment significantly reduced the generation of superoxide anion, ribonucleic acid oxidation and lipid peroxidation in the pyramidal cells. Moreover, interestingly, its neuroprotective effect was abolished by administration of sodium azide (a potent inhibitor of SODs and catalase activities). Taken together, current results clearly indicate that Pycnogenolsupplementation can prevent neurons from ischemic stroke through its potent antioxidative role.


greenmedinfo--2020-08-23--Grape seed polyphenol extract and cognitive function in healthy young adults.

Grapes are polyphenol-rich , and grape juice intake has shown cognitive benefits in middle-aged females and older adults with mild cognitive impairment .
Extracts obtained from grape seeds have similarly been associated with cognitive benefits in older adults .
The aim of this research was to investigate whether a highly purified grape seed-derived polyphenol extract was associated with cognitive benefits in healthy young adults following a single acute dose , and chronically following repeated daily dosage over 12 weeks .
Following an acute-on-chronic , parallel groups , randomised , double-blind , placebo-controlled design , sixty adults aged 18-30 consumed either @ @ @ @ @ @ @ ( GSPE , = 30 ) or a placebo ( = 30 ) .
Cognitive function was assessed acutely at baseline and 2 , 4 and 6 h post consumption , and chronically at 6 and 12 twelve weeks with a computerised battery of multiple cognitive tests .
Mood was assessed with the Positive and Negative Affect Schedule .
Linear marginal model analysis with baseline included as a covariate did not reveal a consistent pattern of cognitive benefits following the GSPE relative to the placebo either acutely or chronically when considering all outcome @ @ @ @ @ @ @ improvements in reaction time ( acutely ) and psychomotor skill ( chronically ) , however the placebo was also associated with some benefits to reaction time and memory .
Therefore , a 400 mg GSPE did not consistently improve cognitive function in healthy young adults .
These findings suggest that younger , healthy populations are perhaps less sensitive to polyphenol extract doses < 400mg relative to older , or cognitively compromised populations .

Grapes are polyphenol-rich, and grape juice intake has shown cognitive benefits in middle-aged females and older adults with mild cognitive impairment. Extracts obtained from grape seeds have similarly been associated with cognitive benefits in older adults. The aim of this research was to investigate whether a highly purified grape seed-derived polyphenol extract was associated with cognitive benefits in healthy young adults following a single acute dose, and chronically following repeated daily dosage over 12 weeks. Following an acute-on-chronic, parallel groups, randomised, double-blind, placebo-controlled design, sixty adults aged 18-30 consumed either a 400 mg grape seed polyphenol extract (GSPE,= 30) or a placebo (= 30). Cognitive function was assessed acutely at baseline and 2, 4 and 6 h post consumption, and chronically at 6 and 12 twelve weeks with a computerised battery of multiple cognitive tests. Mood was assessed with the Positive and Negative Affect Schedule. Linear marginal model analysis with baseline included as a covariate did not reveal a consistent pattern of cognitive benefits following the GSPE relative to the placebo either acutely or chronically when considering all outcome measures. GSPE was associated with some improvements in reaction time (acutely) and psychomotor skill (chronically), however the placebo was also associated with some benefits to reaction time and memory. Therefore, a 400 mg GSPE did not consistently improve cognitive function in healthy young adults. These findings suggest that younger, healthy populations are perhaps less sensitive to polyphenol extract doses<400mg relative to older, or cognitively compromised populations.


greenmedinfo--2020-08-24--Ellagic acid and urolithins A and B differentially regulate fat accumulation and inflammation in 3T3

Ellagic acid and urolithins A and B differentially regulate fat accumulation and inflammation in 3T3-L1 adipocytes.

Ellagic acid ( EA ) is a component of ellagitannins , present in crops such as pecans , walnuts , and many berries , which metabolized by the gut microbiota forms urolithins A , B , C , or D. In this study , ellagic acid , as well as urolithins A and B , were tested on 3T3-L1 preadipocytes for differentiation and lipid accumulation .
In addition , inflammation was studied in mature adipocytes challenged with lipopolysaccharide ( LPS ) .
Results indicated that EA and urolithins A and B did not affect differentiation ( adipogenesis ) and only @ @ @ @ @ @ @ ( lipogenesis ) , which seemed to be through gene regulation of glucose transporter type 4 ( GLUT4 ) and adiponectin .
On the other hand , gene expression of cytokines and proteins associated with the inflammation process indicate that urolithins and EA differentially inhibit tumor necrosis factor alpha ( TNFα ) , inducible nitric oxide synthase ( iNOS ) , interleukin 6 ( IL-6 ) , and monocyte chemoattractant protein-1 ( MCP-1 ) .
Urolithins A and B were found to reduce nuclear levels of phosphorylated nuclear factor κB ( p-NF-κB ) @ @ @ @ @ @ @ nuclear phosphorylated protein kinaseB ( p-AKT ) in challenged LPS cells when treated with insulin , indicating the fact that adipocytes remained insulin sensitive .
In general , urolithin A is a compound able to reduce lipid accumulation , without affecting the protein expression of peroxisome proliferator-activated receptor-γ ( PPARγ ) , CCAAT/enhancer binding protein-α ( c/EBPα ) , and PPARα , whereas EA and urolithin B were found to enhance PPARγ and c/EBPα protein expressions as well as fatty acid ( FA ) oxidation , and differentially affected lipid accumulation .

Ellagic acid (EA) is a component of ellagitannins, present in crops such as pecans, walnuts, and many berries, which metabolized by the gut microbiota forms urolithins A, B, C, or D. In this study, ellagic acid, as well as urolithins A and B, were tested on 3T3-L1 preadipocytes for differentiation and lipid accumulation. In addition, inflammation was studied in mature adipocytes challenged with lipopolysaccharide (LPS). Results indicated that EA and urolithins A and B did not affect differentiation (adipogenesis) and only EA and urolithin A attenuated lipid accumulation (lipogenesis), which seemed to be through gene regulation of glucose transporter type 4 (GLUT4) and adiponectin. On the other hand, gene expression of cytokines and proteins associated with the inflammation process indicate that urolithins and EA differentially inhibit tumor necrosis factor alpha (TNFα), inducible nitric oxide synthase (iNOS), interleukin 6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1). Urolithins A and B were found to reduce nuclear levels of phosphorylated nuclear factor κB (p-NF-κB), whereas all treatments showed expression of nuclear phosphorylated protein kinaseB (p-AKT) in challenged LPS cells when treated with insulin, indicating the fact that adipocytes remained insulin sensitive. In general, urolithin A is a compound able to reduce lipid accumulation, without affecting the protein expression of peroxisome proliferator-activated receptor-γ (PPARγ), CCAAT/enhancer binding protein-α (c/EBPα), and PPARα, whereas EA and urolithin B were found to enhance PPARγ and c/EBPα protein expressions as well as fatty acid (FA) oxidation, and differentially affected lipid accumulation.


greenmedinfo--2020-08-24--Urolithin a attenuates IL-1β-induced inflammatory responses and cartilage degradation via inhibiting

Urolithin a attenuates IL-1β-induced inflammatory responses and cartilage degradation via inhibiting the MAPK/NF-κB signaling pathways in rat articular chondrocytes.

Background : Osteoarthritis ( OA ) is characterized by inflammation and extracellular matrix ( ECM ) degradation and is one of the most common chronic degenerative joint diseases that causes pain and disability in adults .
Urolithin A ( UA ) has been widely reported for its anti-inflammatory properties in several chronic diseases .
However , the effects of UA on OA remain unclear .
The aim of the current study was to investigate the anti-inflammatory effects and mechanism of UA in interleukin-1β ( IL-1β ) -induced chondrocytes .
Results : No marked UA cytotoxicity was noted , and UA @ @ @ @ @ @ @ in micromasses .
Moreover , UA promoted the expression of anabolic factors including Sox-9 , Collagen II , and Aggrecan while inhibiting the expression of catabolic factors such as matrix metalloproteinases ( MMPs ) and a disintegrin and metalloproteinase with thrombospondin motifs 4 ( ADAMTS-4 ) in rat chondrocytes .
Protective effects of UA were also observed in ex vivo organ culture of articular cartilage .
Mechanistically , IL-1β significantly activated and upregulated the expression of p-ERK 1/2 , p-JNK , p-P38 , and p-P65 , while UA protected chondrocytes against IL-1β-induced injury @ @ @ @ @ @ @ ) /nuclear factor-κB ( NF-κB ) signaling pathways .
Conclusion : Our results provide the evidence that UA could attenuate IL-1β-induced cell injury in chondrocytes via its anti-inflammatory action .
UA may be a promising therapeutic agent in the treatment of OA .

Background: Osteoarthritis (OA) is characterized by inflammation and extracellular matrix (ECM) degradation and is one of the most common chronic degenerative joint diseases that causes pain and disability in adults. Urolithin A (UA) has been widely reported for its anti-inflammatory properties in several chronic diseases. However, the effects of UA on OA remain unclear. The aim of the current study was to investigate the anti-inflammatory effects and mechanism of UA in interleukin-1β (IL-1β)-induced chondrocytes.
Results: No marked UA cytotoxicity was noted, and UA protected cartilage from damage following IL-1β stimulation in micromasses. Moreover, UA promoted the expression of anabolic factors including Sox-9, Collagen II, and Aggrecan while inhibiting the expression of catabolic factors such as matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS-4) in rat chondrocytes. Protective effects of UA were also observed in ex vivo organ culture of articular cartilage. Mechanistically, IL-1β significantly activated and upregulated the expression of p-ERK 1/2, p-JNK, p-P38, and p-P65, while UA protected chondrocytes against IL-1β-induced injury by activating the mitogen-activated kinase (MAPK)/nuclear factor-κB (NF-κB) signaling pathways.
Conclusion: Our results provide the evidence that UA could attenuate IL-1β-induced cell injury in chondrocytes via its anti-inflammatory action. UA may be a promising therapeutic agent in the treatment of OA.


greenmedinfo--2020-08-24--Urolithin A exerts antiobesity effects through enhancing adipose tissue thermogenesis in mice.

Obesity leads to multiple health problems , including diabetes , fatty liver , and even cancer .
Here , we report that urolithin A ( UA ) , a gut-microflora-derived metabolite of pomegranate ellagitannins ( ETs ) , prevents diet-induced obesity and metabolic dysfunctions in mice without causing adverse effects .
UA treatment increases energy expenditure ( EE ) by enhancing thermogenesis in brown adipose tissue ( BAT ) and inducing browning of white adipose tissue ( WAT ) .
Mechanistically , UA-mediated increased thermogenesis is caused by an elevation of triiodothyronine ( T3 ) levels in BAT and inguinal @ @ @ @ @ @ @ in UA-treated white and brown adipocytes .
Consistent with this mechanism , UA loses its beneficial effects on activation of BAT , browning of white fat , body weight control , and glucose homeostasis when thyroid hormone ( TH ) production is blocked by its inhibitor , propylthiouracil ( PTU ) .
Conversely , administration of exogenous tetraiodothyronine ( T4 ) to PTU-treated mice restores UA-induced activation of BAT and browning of white fat and its preventive role on high-fat diet ( HFD ) -induced weight gain .
Together , these results suggest @ @ @ @ @ @ @ with potential for human clinical applications .

Obesity leads to multiple health problems, including diabetes, fatty liver, and even cancer. Here, we report that urolithin A (UA), a gut-microflora-derived metabolite of pomegranate ellagitannins (ETs), prevents diet-induced obesity and metabolic dysfunctions in mice without causing adverse effects. UA treatment increases energy expenditure (EE) by enhancing thermogenesis in brown adipose tissue (BAT) and inducing browning of white adipose tissue (WAT). Mechanistically, UA-mediated increased thermogenesis is caused by an elevation of triiodothyronine (T3) levels in BAT and inguinal fat depots. This is also confirmed in UA-treated white and brown adipocytes. Consistent with this mechanism, UA loses its beneficial effects on activation of BAT, browning of white fat, body weight control, and glucose homeostasis when thyroid hormone (TH) production is blocked by its inhibitor, propylthiouracil (PTU). Conversely, administration of exogenous tetraiodothyronine (T4) to PTU-treated mice restores UA-induced activation of BAT and browning of white fat and its preventive role on high-fat diet (HFD)-induced weight gain. Together, these results suggest that UA is a potent antiobesity agent with potential for human clinical applications.


greenmedinfo--2020-08-24--Urolithin A attenuated ox-LDL-induced cholesterol accumulation in macrophages partly through regulat

Urolithin A attenuated ox-LDL-induced cholesterol accumulation in macrophages partly through regulating miR-33a and ERK/AMPK/SREBP1 signaling pathways.

Promoting cholesterol efflux from foam cells represents one of the therapeutic strategies for ameliorating atherosclerosis .
Urolithin A ( UA ) has been shown before to attenuate ox-LDL induced endothelial dysfunction in endothelial cells with its anti-inflammatory properties .
The aim of this study was to investigate whether UA could promote cholesterol efflux via modulating related microRNA ( miR ) and signaling pathways .
RAW264.7 cells were treated with 50μg mLox-LDL to induce foam cell formation .
After treatment with UA at different concentrations , intercellular and extracellular cholesterol levels were determined .
Expression of Erk1/2 , AMPKα and their @ @ @ @ @ @ @ analyzed by western-blotting .
The effect of UA on miR-33a expression and the involvement of miR-33a in cholesterol efflux regulation were also investigated .
UA reduced ox-LDL induced cholesterol accumulation in macrophage cells and promoted cholesterol efflux from cells .
Compared with ox-LDL treated cells , UA treatment reduced the level of phosphorylated ERK1/2 , increased the expression of phosphorylated AMPKα and decreased the SREBP1 expression .
Moreover , UA decreased the miR-33a expression at the transcriptional level but increased the transcriptional expression of ATP-binding cassette transporter A1 ( ABCA1 ) and ABCG1 @ @ @ @ @ @ @ transport .
Furthermore , pre-miR-33a attenuated cholesterol efflux induced by UA .
Collectively , UA promoted the reverse cholesterol transport in macrophage-derived foam cells and interfered with cholesterol metabolism possibly through regulating the miRNA-33 expression and interaction with the ERK/AMPKα/SREBP1 signaling pathway .

Promoting cholesterol efflux from foam cells represents one of the therapeutic strategies for ameliorating atherosclerosis. Urolithin A (UA) has been shown before to attenuate ox-LDL induced endothelial dysfunction in endothelial cells with its anti-inflammatory properties. The aim of this study was to investigate whether UA could promote cholesterol efflux via modulating related microRNA (miR) and signaling pathways. RAW264.7 cells were treated with 50μg mLox-LDL to induce foam cell formation. After treatment with UA at different concentrations, intercellular and extracellular cholesterol levels were determined. Expression of Erk1/2, AMPKα and their phosphorylation forms, and SREBP1, was analyzed by western-blotting. The effect of UA on miR-33a expression and the involvement of miR-33a in cholesterol efflux regulation were also investigated. UA reduced ox-LDL induced cholesterol accumulation in macrophage cells and promoted cholesterol efflux from cells. Compared with ox-LDL treated cells, UA treatment reduced the level of phosphorylated ERK1/2, increased the expression of phosphorylated AMPKα and decreased the SREBP1 expression. Moreover, UA decreased the miR-33a expression at the transcriptional level but increased the transcriptional expression of ATP-binding cassette transporter A1 (ABCA1) and ABCG1, two genes contributing to reverse cholesterol transport. Furthermore, pre-miR-33a attenuated cholesterol efflux induced by UA. Collectively, UA promoted the reverse cholesterol transport in macrophage-derived foam cells and interfered with cholesterol metabolism possibly through regulating the miRNA-33 expression and interaction with the ERK/AMPKα/SREBP1 signaling pathway.


greenmedinfo--2020-08-24--Potential of the ellagic acid-derived gut microbiota metabolite - urolithin A in gastrointestinal pr

Potential of the ellagic acid-derived gut microbiota metabolite - urolithin A in gastrointestinal protection.

Urolithin A ( UA ) is a metabolic compound generated during the biotransformation of ellagitannins by the intestinal bacteria .
@ @ @ @ @ of UA , achieved in the plasma and gastrointestinal tract ( GI ) after consumption @ @ @ @ @ have been revealed to offer GI protection .
The health benefit has been demonstrated to @ @ @ @ @ and anti-inflammatory effects .
UA has been shown to possess the capability to regulate multiple @ @ @ @ @ and to modulate enzyme activity , including those involved in carcinogen biotransformation and antioxidant defense @ @ @ @ @ review is to gather evidence from bothandstudies showing the potential of UA in GI protection @ @ @ @ @ UA can protect against cancer and inflammatory diseases of the digestive tract .
The data @ @ @ @ @ studies on the pure compound andgenerated UA form its natural precursor , support the potential @ @ @ @ @ interventions against GI ailments .

Urolithin A (UA) is a metabolic compound generated during the biotransformation of ellagitannins by the intestinal bacteria. The physiologically relevant micromolar concentrations of UA, achieved in the plasma and gastrointestinal tract (GI) after consumption of its dietary precursors, have been revealed to offer GI protection. The health benefit has been demonstrated to be principally related to anticancer and anti-inflammatory effects. UA has been shown to possess the capability to regulate multiple tumor and inflammatory signaling pathways and to modulate enzyme activity, including those involved in carcinogen biotransformation and antioxidant defense. The purpose of this review is to gather evidence from bothandstudies showing the potential of UA in GI protection alongside suggested mechanisms by which UA can protect against cancer and inflammatory diseases of the digestive tract. The data presented herein, covering both studies on the pure compound andgenerated UA form its natural precursor, support the potential of this metabolite in treatment interventions against GI ailments.


greenmedinfo--2020-08-24--Urolithin A is a promising candidate for the development of therapies to prevent diabetes mellitus-a

Urolithin A is a promising candidate for the development of therapies to prevent diabetes mellitus-associated Alzheimer's disease pathogenesis.

Hyperglycemia in diabetes mellitus ( DM ) patients is a causative factor for amyloidogenesis and induces neuropathological changes , such as impaired neuronal integrity , neurodegeneration , and cognitive impairment .
Regulation of mitochondrial calcium influx from the endoplasmic reticulum ( ER ) is considered a promising strategy for the prevention of mitochondrial ROS ( mtROS ) accumulation that occurs in the Alzheimer 's disease ( AD ) -associated pathogenesis in DM patients .
Among the metabolites of ellagitannins that are produced in the gut microbiome , urolithin A has received an increasing amount of attention as a novel candidate @ @ @ @ @ @ @ .
Here , we investigated the effect of urolithin A on high glucose-induced amyloidogenesis caused by mitochondrial calcium dysregulation and mtROS accumulation resulting in neuronal degeneration .
We also identified the mechanism related to mitochondria-associated ER membrane ( MAM ) formation .
We found that urolithin A-lowered mitochondrial calcium influx significantly alleviated high glucose-induced mtROS accumulation and expression of amyloid beta ( Aβ ) -producing enzymes , such as amyloid precursor protein ( APP ) and β-secretase-1 ( BACE1 ) , as well as Aβ production .
Urolithin A injections in a streptozotocin @ @ @ @ @ @ @ alleviated APP and BACE1 expressions , Tau phosphorylation , Aβ deposition , and cognitive impairment .
In addition , high glucose stimulated MAM formation and transglutaminase type 2 ( TGM2 ) expression .
We first discovered that urolithin A significantly reduced high glucose-induced TGM2 expression .
In addition , disruption of the AIP-AhR complex was involved in urolithin A-mediated suppression of high glucose-induced TGM2 expression .
Markedly , TGM2 silencing inhibited inositol 1 , 4 , 5-trisphosphate receptor type 1 ( IP3R1 ) -voltage-dependent anion-selective channel protein 1 ( VDAC1 ) interactions and @ @ @ @ @ @ @ mtROS accumulation .
We also found that urolithin A or TGM2 silencing prevented Aβ-induced mitochondrial calcium influx , mtROS accumulation , Tau phosphorylation , and cell death in neuronal cells .
In conclusion , we suggest that urolithin A is a promising candidate for the development of therapies to prevent DM-associatedAD pathogenesis by reducing TGM2-dependent MAM formation and maintaining mitochondrial calcium and ROS homeostasis .

Hyperglycemia in diabetes mellitus (DM) patients is a causative factor for amyloidogenesis and induces neuropathological changes, such as impaired neuronal integrity, neurodegeneration, and cognitive impairment. Regulation of mitochondrial calcium influx from the endoplasmic reticulum (ER) is considered a promising strategy for the prevention of mitochondrial ROS (mtROS) accumulation that occurs in the Alzheimer's disease (AD)-associated pathogenesis in DM patients. Among the metabolites of ellagitannins that are produced in the gut microbiome, urolithin A has received an increasing amount of attention as a novel candidate with anti-oxidative and neuroprotective effects in AD. Here, we investigated the effect of urolithin A on high glucose-induced amyloidogenesis caused by mitochondrial calcium dysregulation and mtROS accumulation resulting in neuronal degeneration. We also identified the mechanism related to mitochondria-associated ER membrane (MAM) formation. We found that urolithin A-lowered mitochondrial calcium influx significantly alleviated high glucose-induced mtROS accumulation and expression of amyloid beta (Aβ)-producing enzymes, such as amyloid precursor protein (APP) and β-secretase-1 (BACE1), as well as Aβ production. Urolithin A injections in a streptozotocin (STZ)-induced diabetic mouse model alleviated APP and BACE1 expressions, Tau phosphorylation, Aβ deposition, and cognitive impairment. In addition, high glucose stimulated MAM formation and transglutaminase type 2 (TGM2) expression. We first discovered that urolithin A significantly reduced high glucose-induced TGM2 expression. In addition, disruption of the AIP-AhR complex was involved in urolithin A-mediated suppression of high glucose-induced TGM2 expression. Markedly, TGM2 silencing inhibited inositol 1, 4, 5-trisphosphate receptor type 1 (IP3R1)-voltage-dependent anion-selective channel protein 1 (VDAC1) interactions and prevented high glucose-induced mitochondrial calcium influx and mtROS accumulation. We also found that urolithin A or TGM2 silencing prevented Aβ-induced mitochondrial calcium influx, mtROS accumulation, Tau phosphorylation, and cell death in neuronal cells. In conclusion, we suggest that urolithin A is a promising candidate for the development of therapies to prevent DM-associatedAD pathogenesis by reducing TGM2-dependent MAM formation and maintaining mitochondrial calcium and ROS homeostasis.


greenmedinfo--2020-08-24--Ellagic acid and its microbial metabolite urolithin A alleviate diet-induced insulin resistance in m

Ellagic acid and its microbial metabolite urolithin A alleviate diet-induced insulin resistance in mice.

SCOPE : We aimed at evaluating the effect of dietary ellagic acid ( EA ) and its microbial metabolite urolithin A ( UA ) on glucose metabolism and insulin resistance ( IR ) in mice with diet-induced IR .
METHODS AND RESULTS : DBA2J mice were fed a high fat/high sucrose diet ( HF/HS ) for 8 weeks to induce IR and then 0.1 % EA , UA , or EA and UA combined ( EA+UA ) were added to the HF/HS-diet for another 8 weeks .
UA significantly decreased fasting glucose and increased serum adiponectin compared with HF/HS-controls .
@ @ @ @ @ @ @ significantly improved insulin-mediated glucose lowering effects at 15 and 120 min and reduced blood triglycerides compared with HF/HS-controls .
Serum free fatty acids were significantly decreased by EA , UA and EA+UA .
We observed differential expression of genes related to mitochondrial function by EA , UA and EA+UA in liver and skeletal muscle .
Primary hepatocytes from IR-mice had higher proton leak , basal and ATP-linked oxygen consumption rates compared with healthy controls .
EA and EA+UA but not UA reduced the proton leak in hepatocytes from IR-mice .
CONCLUSION : EA @ @ @ @ @ @ @ HF/HS diet induced IR mice .
The effects of EA and UA on mitochondrial function suggest a potentially novel mechanism modulating metabolism .
This article is protected by copyright .
All rights reserved .

SCOPE: We aimed at evaluating the effect of dietary ellagic acid (EA) and its microbial metabolite urolithin A (UA) on glucose metabolism and insulin resistance (IR) in mice with diet-induced IR.
METHODS AND RESULTS: DBA2J mice were fed a high fat/high sucrose diet (HF/HS) for 8 weeks to induce IR and then 0.1% EA, UA, or EA and UA combined (EA+UA) were added to the HF/HS-diet for another 8 weeks. UA significantly decreased fasting glucose and increased serum adiponectin compared with HF/HS-controls. During intraperitoneal insulin tolerance test, EA+UA significantly improved insulin-mediated glucose lowering effects at 15 and 120 min and reduced blood triglycerides compared with HF/HS-controls. Serum free fatty acids were significantly decreased by EA, UA and EA+UA. We observed differential expression of genes related to mitochondrial function by EA, UA and EA+UA in liver and skeletal muscle. Primary hepatocytes from IR-mice had higher proton leak, basal and ATP-linked oxygen consumption rates compared with healthy controls. EA and EA+UA but not UA reduced the proton leak in hepatocytes from IR-mice.
CONCLUSION: EA and UA induced different metabolic benefits in HF/HS diet induced IR mice. The effects of EA and UA on mitochondrial function suggest a potentially novel mechanism modulating metabolism. This article is protected by copyright. All rights reserved.


greenmedinfo--2020-08-24--An in-silico evaluation of dietary components for structural inhibition of SARS-Cov-2 main protease.

The main protease ( M ) of SARS-CoV-2 is responsible for the cleavage of viral replicase polyproteins 1a and 1ab @ @ @ @ @ is highly specific and exclusive in its activity .
Many studies have targeted this enzyme @ @ @ @ @ develop therapeutics against the highly infectious disease Covid-19 .
Our diet contains many natural antioxidants @ @ @ @ @ for proper growth and functioning of the body , pose additional health benefits .
Present @ @ @ @ @ antioxidants like sesamin , ellagic acid , capsaisin , and epicatechin along with galangin , @ @ @ @ @ catalytic site of the Menzyme .
They interacted with excellent efficiency with the chief active @ @ @ @ @ seem to possess the remarkable potential to act as drug candidates for the treatment of @ @ @ @ @ can be easily administered orally with least toxicity related concern and thus yell for urgent @ @ @ @ @ efficient therapies .
Communicated by Ramaswamy H. Sarma .

The main protease (M) of SARS-CoV-2 is responsible for the cleavage of viral replicase polyproteins 1a and 1ab into their mature form and is highly specific and exclusive in its activity. Many studies have targeted this enzyme by small molecule inhibitors to develop therapeutics against the highly infectious disease Covid-19. Our diet contains many natural antioxidants which along with providing support for proper growth and functioning of the body, pose additional health benefits. Present in-silico analysis depicted that natural antioxidants like sesamin, ellagic acid, capsaisin, and epicatechin along with galangin, exhibited significant binding at the catalytic site of the Menzyme. They interacted with excellent efficiency with the chief active site residue Cys145 and thus seem to possess the remarkable potential to act as drug candidates for the treatment of Covid-19. Such dietary compounds can be easily administered orally with least toxicity related concern and thus yell for urgent exhaustive research to develop into efficient therapies. Communicated by Ramaswamy H. Sarma.


greenmedinfo--2020-08-24--Select polyphenol-rich berry consumption to defer or deter diabetes and diabetes-related complicatio

Select polyphenol-rich berry consumption to defer or deter diabetes and diabetes-related complications.

Berries are considered '' promising functional fruits '' due to their distinct and ubiquitous therapeutic contents of anthocyanins , proanthocyanidins , phenolic acids , flavonoids , flavanols , alkaloids , polysaccharides , hydroxycinnamic , ellagic acid derivatives , and organic acids .
These polyphenols are part of berries and the human diet , and evidence suggests that their intake is associated with a reduced risk or the reversal of metabolic pathophysiologies related to diabetes , obesity , oxidative stress , inflammation , and hypertension .
This work reviewed and summarized both clinical and non-clinical findings that the consumption of berries @ @ @ @ @ @ @ juices , jams , jellies , and other berry byproducts aided in the prevention and or otherwise management of type 2 diabetes mellitus ( T2DM ) and related complications .
The integration of berries and berries-derived byproducts into high-carbohydrate ( HCD ) and high-fat ( HFD ) diets , also reversed/reduced the HCD/HFD-induced alterations in glucose metabolism-related pathways , and markers of oxidative stress , inflammation , and lipid oxidation in healthy/obese/diabetic subjects .
The berry polyphenols also modulate the intestinal microflora ecology by opposing the diabetic and obesity rendered symbolic reduction of @ @ @ @ @ @ @ bacteria , short-chain fatty acids , and organic acid producing microflora .
All studies proposed a number of potential mechanisms of action of respective berry bioactive compounds , although further mechanistic and molecular studies are warranted .
The metabolic profiling of each berry is also included to provide up-to-date information regarding the potential anti-oxidative/antidiabetic constituents of each berry .

Berries are considered"promising functional fruits"due to their distinct and ubiquitous therapeutic contents of anthocyanins, proanthocyanidins, phenolic acids, flavonoids, flavanols, alkaloids, polysaccharides, hydroxycinnamic, ellagic acid derivatives, and organic acids. These polyphenols are part of berries and the human diet, and evidence suggests that their intake is associated with a reduced risk or the reversal of metabolic pathophysiologies related to diabetes, obesity, oxidative stress, inflammation, and hypertension. This work reviewed and summarized both clinical and non-clinical findings that the consumption of berries, berry extracts, purified compounds, juices, jams, jellies, and other berry byproducts aided in the prevention and or otherwise management of type 2 diabetes mellitus (T2DM) and related complications. The integration of berries and berries-derived byproducts into high-carbohydrate (HCD) and high-fat (HFD) diets, also reversed/reduced the HCD/HFD-induced alterations in glucose metabolism-related pathways, and markers of oxidative stress, inflammation, and lipid oxidation in healthy/obese/diabetic subjects. The berry polyphenols also modulate the intestinal microflora ecology by opposing the diabetic and obesity rendered symbolic reduction of Bacteroidetes/Firmicutes ratio, intestinal mucosal barrier dysfunction-restoring bacteria, short-chain fatty acids, and organic acid producing microflora. All studies proposed a number of potential mechanisms of action of respective berry bioactive compounds, although further mechanistic and molecular studies are warranted. The metabolic profiling of each berry is also included to provide up-to-date information regarding the potential anti-oxidative/antidiabetic constituents of each berry.


greenmedinfo--2020-08-24--The protective effects of wine pomace products on the vascular endothelial barrier function.

Endothelial dysfunction is associated with cardiovascular diseases and involves a chronic inflammatory process that together with oxidative stress increases the permeability of the vascular endothelium .
The aim of this study was to evaluate the role of red and white wine pomace products ( rWPPs and wWPPs ) in the maintenance of endothelial integrity in hyperglycemia of EA.hy926 endothelial cells .
EA.hy926 endothelial cells exposed to hyperglycemia were treated with the in vitro digested fractions of rWPPs and wWPPs .
A Real Time Cellular Analysis ( RTCA ) system was used to evaluate the endothelial monolayer integrity after INF-γ stimulation @ @ @ @ @ @ @ fractions .
The changes in cell viability , NO , ROS and NOX4 were recorded and actin cytoskeleton and E-cadherin junctions were evaluated by immunofluorescence .
All digested fractions prevent the hyperglycemic actions in the cell viability and NO/ROS balance .
The inflammatory mediator INF-γ and hyperglycemia caused a decrease in RTCA adhesion of the EA.hy926 endothelial cell monolayer .
Pre-treatment with all digested fractions enhanced the EA.hy926 endothelial monolayer integrity and maintained actin cytoskeleton and E-cadherin junctions .
These in vitro studies elucidate that the anti-hyperglycemic and anti-inflammatory actions of wine pomace @ @ @ @ @ @ @ and the stabilization of junction proteins via modulation of VE-cadherin and actin cytoskeleton suggesting a potential prevention of endothelial damage by these natural products .

Endothelial dysfunction is associated with cardiovascular diseases and involves a chronic inflammatory process that together with oxidative stress increases the permeability of the vascular endothelium. The aim of this study was to evaluate the role of red and white wine pomace products (rWPPs and wWPPs) in the maintenance of endothelial integrity in hyperglycemia of EA.hy926 endothelial cells. EA.hy926 endothelial cells exposed to hyperglycemia were treated with the in vitro digested fractions of rWPPs and wWPPs. A Real Time Cellular Analysis (RTCA) system was used to evaluate the endothelial monolayer integrity after INF-γ stimulation of pre-treated endothelial cells with the digested fractions. The changes in cell viability, NO, ROS and NOX4 were recorded and actin cytoskeleton and E-cadherin junctions were evaluated by immunofluorescence. All digested fractions prevent the hyperglycemic actions in the cell viability and NO/ROS balance. The inflammatory mediator INF-γ and hyperglycemia caused a decrease in RTCA adhesion of the EA.hy926 endothelial cell monolayer. Pre-treatment with all digested fractions enhanced the EA.hy926 endothelial monolayer integrity and maintained actin cytoskeleton and E-cadherin junctions. These in vitro studies elucidate that the anti-hyperglycemic and anti-inflammatory actions of wine pomace products involve a decrease in ROS production and the stabilization of junction proteins via modulation of VE-cadherin and actin cytoskeleton suggesting a potential prevention of endothelial damage by these natural products.


greenmedinfo--2020-08-24--Piceatannol exerts anti-angiogenic efficiencies by blockage of vascular endothelial growth factor bi

Piceatannol exerts anti-angiogenic efficiencies by blockage of vascular endothelial growth factor binding to its receptor.

Piceatannol is also named as-3,4,3',5'-tetrahydroxy-stilbene , which is a natural analog of resveratrol and a polyphenol existing in red wine , grape and sugar cane .
Piceatannol has been proved to possess activities of immunomodulatory , anti-inflammatory , antiproliferative and anticancer .
However , the effect of piceatannol on VEGF-mediated angiogenesis is not known .
Here , the inhibitory effects of piceatannol on VEGF-induced angiogenesis were tested both in vitro and in vivo models of angiogenesis .
In human umbilical vein endothelial cells ( HUVECs ) , piceatannol markedly reduced the VEGF-induced cell proliferation , migration , invasion , as @ @ @ @ @ @ @ viability .
Furthermore , piceatannol significantly inhibited the formation of subintestinal vessel in zebrafish embryos in vivo .
In addition , we identified the underlying mechanism of piceatannol in triggering the anti-angiogenic functions .
Piceatannol was proposed to bind with VEGF , thus attenuating VEGF in activating VEGF receptor and blocking VEGF-mediated downstream signaling , including expressions of phosphorylated eNOS , Erk and Akt .
Furthermore , piceatannol visibly suppressed ROS formation , as triggered by VEGF .
Moreover , we further determined the outcome of piceatannol binding to VEGF in cancer cells @ @ @ @ @ @ @ proliferation and migration .
Thus , these lines of evidence supported the conclusion that piceatannol could down regulate the VEGF-mediated angiogenic functions with no cytotoxicity via decreasing the amount of VEGF binding to its receptors , thus affecting the related downstream signaling .
Piceatannol may be developed into therapeutic agents or health products to reduce the high incidence of angiogenesis-related diseases .

Piceatannol is also named as-3,4,3',5'-tetrahydroxy-stilbene, which is a natural analog of resveratrol and a polyphenol existing in red wine, grape and sugar cane. Piceatannol has been proved to possess activities of immunomodulatory, anti-inflammatory, antiproliferative and anticancer. However, the effect of piceatannol on VEGF-mediated angiogenesis is not known. Here, the inhibitory effects of piceatannol on VEGF-induced angiogenesis were tested both in vitro and in vivo models of angiogenesis. In human umbilical vein endothelial cells (HUVECs), piceatannol markedly reduced the VEGF-induced cell proliferation, migration, invasion, as well as tube formation without affecting cell viability. Furthermore, piceatannol significantly inhibited the formation of subintestinal vessel in zebrafish embryos in vivo. In addition, we identified the underlying mechanism of piceatannol in triggering the anti-angiogenic functions. Piceatannol was proposed to bind with VEGF, thus attenuating VEGF in activating VEGF receptor and blocking VEGF-mediated downstream signaling, including expressions of phosphorylated eNOS, Erk and Akt. Furthermore, piceatannol visibly suppressed ROS formation, as triggered by VEGF. Moreover, we further determined the outcome of piceatannol binding to VEGF in cancer cells: piceatannol significantly suppressed VEGF-induced colon cancer proliferation and migration. Thus, these lines of evidence supported the conclusion that piceatannol could down regulate the VEGF-mediated angiogenic functions with no cytotoxicity via decreasing the amount of VEGF binding to its receptors, thus affecting the related downstream signaling. Piceatannol may be developed into therapeutic agents or health products to reduce the high incidence of angiogenesis-related diseases.