greenmedinfo--2020-09-05--Ginsenoside Rd ameliorates auditory cortex injury associated with military aviation noise-induced he

Ginsenoside Rd ameliorates auditory cortex injury associated with military aviation noise-induced hearing loss.

Free radicals and oxidative stress play an important role in the pathogenesis of noise-induced hearing loss ( NIHL ) .
Some ginseng monomers showed certain therapeutic effects in NIHL by scavenging free radicals .
Therefore , we hypothesized that ginsenoside Rd ( GSRd ) may exert neuroprotective effects after noise-induced auditory system damage through a mechanism involving the SIRT1/PGC-1α signaling pathway .
Forty-eight guinea pigs were randomly divided into four equal groups ( normal control group , noise group , experimental group that received GSRd dissolved in glycerin through an intraperitoneal injection at a dose of 30 mg/kg body weight @ @ @ @ @ @ @ the end of the noise exposure period , and experimental control group ) .
Hearing levels were examined by auditory brainstem response ( ABR ) and distortion product otoacoustic emission ( DPOAE ) .
Hematoxylin-eosin and Nissl staining were used to examine neuron morphology .
RT-qPCR and western blotting analysis were used to examine SIRT1/PGC-1α signaling and apoptosis-related genes , including Bax and Bcl-2 , in the auditory cortex .
Bax and Bcl-2 expression was assessed via immunohistochemistry analysis .
Superoxide dismutase ( SOD ) , malondialdehyde ( MDA ) , and glutathione @ @ @ @ @ @ @ using a commercial testing kit .
Noise exposure was found to up-regulate ABR threshold and down-regulate DPOAE amplitudes , with prominent morphologic changes and apoptosis of the auditory cortex neurons ( < 0.01 ) .
GSRd treatment restored hearing loss and remarkably alleviated morphological changes or apoptosis ( < 0.01 ) , concomitantly increasing Bcl-2 expression and decreasing Bax expression ( < 0.05 ) .
Moreover , GSRd increased SOD and GSH-Px levels and decreased MDA levels , which alleviated oxidative stress damage and activated SIRT1/PGC-1α signaling pathway .
Taken together , our @ @ @ @ @ @ @ injury associated with military aviation NIHL by activating the SIRT1/PGC-1α signaling pathway , which can be an attractive pharmacological target for the development of novel drugs for NIHL treatment .

Free radicals and oxidative stress play an important role in the pathogenesis of noise-induced hearing loss (NIHL). Some ginseng monomers showed certain therapeutic effects in NIHL by scavenging free radicals. Therefore, we hypothesized that ginsenoside Rd (GSRd) may exert neuroprotective effects after noise-induced auditory system damage through a mechanism involving the SIRT1/PGC-1α signaling pathway. Forty-eight guinea pigs were randomly divided into four equal groups (normal control group, noise group, experimental group that received GSRd dissolved in glycerin through an intraperitoneal injection at a dose of 30 mg/kg body weight from 5 days before noise exposure until the end of the noise exposure period, and experimental control group). Hearing levels were examined by auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE). Hematoxylin-eosin and Nissl staining were used to examine neuron morphology. RT-qPCR and western blotting analysis were used to examine SIRT1/PGC-1α signaling and apoptosis-related genes, including Bax and Bcl-2, in the auditory cortex. Bax and Bcl-2 expression was assessed via immunohistochemistry analysis. Superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) levels were determined using a commercial testing kit. Noise exposure was found to up-regulate ABR threshold and down-regulate DPOAE amplitudes, with prominent morphologic changes and apoptosis of the auditory cortex neurons (<0.01). GSRd treatment restored hearing loss and remarkably alleviated morphological changes or apoptosis (<0.01), concomitantly increasing Bcl-2 expression and decreasing Bax expression (<0.05). Moreover, GSRd increased SOD and GSH-Px levels and decreased MDA levels, which alleviated oxidative stress damage and activated SIRT1/PGC-1α signaling pathway. Taken together, our findings suggest that GSRd ameliorates auditory cortex injury associated with military aviation NIHL by activating the SIRT1/PGC-1α signaling pathway, which can be an attractive pharmacological target for the development of novel drugs for NIHL treatment.


greenmedinfo--2020-09-05--Neuroprotective effect of ginsenoside Rb-1 on a rat model of Alzheimer's disease.

To investigate the protective mechanism of ginsenoside Rb-1 on the brain in a rat model of Alzheimer 's disease.Fifty-six male Sprague-Dawley rats were randomly divided into control group , model group , low-dose Rb-1 group ( Rb-1 : 25 mg•kg ( -1 ) •d ( -1 ) ) and high-dose Rb-1 group ( Rb-1:50 mg•kg ( -1 ) •d ( -1 ) ) .
Morris water maze was designed to observe the changes of learning and memory ability in rats .
Flow cytometry was used to detect the apoptosis of hippocampal neurons .
Immunohistochemistry and Western blot were employed to @ @ @ @ @ @ @ ( p53 , Bax , cytochrome C ( Cyto C ) , Caspase-3 and caspase-9 ) and anti-oxidative stress-associated genes ( nuclear Factor-E2-related factor 2 ( Nrf2 ) , kelch-like ECH-associated protein 1 ( keap-1 ) , heme oxygenase 1 ( HO-1 ) and NADPH quinone dehydrogenase 1 ( NQO1 ) ) .The activities of catalase ( CAT ) , glutathione peroxidase ( GSH-Px ) and superoxide dismutase ( SOD ) were detected by relevant kits .
ANOVA and Tukey-Kramer test were used for statistical analysis.The learning and memory ability of rats in @ @ @ @ @ @ @ of the control group ( < 0.01 ) .The learning and memory ability of rats in the high-dose Rb-1 treatment group was significantly higher than that of the model group [ ( 80±8 ) s vs ( 100±11 ) s , =5.390 , < 0.01 ] .
The expression levels of apoptosis-related genes ( p53 , Bax , Cyto C , caspase-3 and caspase-9 ) in the model group were significantly higher than those in the control group ( < 0.01 ) , while the expression levels of these genes in low-dose and @ @ @ @ @ @ @ those of the model group ( < 0.01 ) .
The expression levels of Nrf2 , HO-1 and NQO1 genes in the model group were significantly lower than those in the control group ( < 0.05 ) , while the expression of these genes in low-dose and high-dose Rb-1 groupswere significantly higher than those of the model group ( < 0.01 ) .
The activities of CAT , GSH-Px and SOD in the model group were lower than those in the control group ( < 0.01 ) , however the activities of CAT @ @ @ @ @ @ @ high-dose Rb-1 groups were higher than those of model group ( < 0.05 ) .Both low-dose and high-dose Rb-1 have protective effect on memory and cognitive function of Alzheimer 's disease rats by reducing the damage and apoptosis of hippocampal neurons , down-regulating the expression levels of p53 , Bax , Cyto C , caspase-3 and caspase-9 , up-regulating the expression of Nrf2 , HO-1 and NQO1 genes , and increasing the activities of CAT , GSH-Px and SOD .
Moreover , the protective effect of Rb-1 on rat brain may be dose-dependent @

To investigate the protective mechanism of ginsenoside Rb-1 on the brain in a rat model of Alzheimer's disease.Fifty-six male Sprague-Dawley rats were randomly divided into control group, model group, low-dose Rb-1 group (Rb-1: 25 mg•kg(-1)•d(-1)) and high-dose Rb-1 group (Rb-1:50 mg•kg(-1)•d(-1)). Morris water maze was designed to observe the changes of learning and memory ability in rats. Flow cytometry was used to detect the apoptosis of hippocampal neurons. Immunohistochemistry and Western blot were employed to detect the expression levels of apoptosis-related genes (p53, Bax, cytochrome C (Cyto C), Caspase-3 and caspase-9) and anti-oxidative stress-associated genes (nuclear Factor-E2-related factor 2 (Nrf2), kelch-like ECH-associated protein 1 (keap-1), heme oxygenase 1(HO-1) and NADPH quinone dehydrogenase 1(NQO1)).The activities of catalase (CAT), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were detected by relevant kits. ANOVA and Tukey-Kramer test were used for statistical analysis.The learning and memory ability of rats in the model group was lower than that of the control group (<0.01).The learning and memory ability of rats in the high-dose Rb-1 treatment group was significantly higher than that of the model group [(80±8) s vs (100±11) s,=5.390,<0.01]. The expression levels of apoptosis-related genes (p53, Bax, Cyto C, caspase-3 and caspase-9) in the model group were significantly higher than those in the control group (<0.01), while the expression levels of these genes in low-dose and high-dose Rb-1 groups were significantly lower than those of the model group (<0.01). The expression levels of Nrf2, HO-1 and NQO1 genes in the model group were significantly lower than those in the control group (<0.05), while the expression of these genes in low-dose and high-dose Rb-1 groupswere significantly higher than those of the model group (<0.01). The activities of CAT, GSH-Px and SOD in the model group were lower than those in the control group (<0.01), however the activities of CAT, GSH-Px and SOD in low-dose and high-dose Rb-1 groups were higher than those of model group (<0.05).Both low-dose and high-dose Rb-1 have protective effect on memory and cognitive function of Alzheimer's disease rats by reducing the damage and apoptosis of hippocampal neurons, down-regulating the expression levels of p53, Bax, Cyto C, caspase-3 and caspase-9, up-regulating the expression of Nrf2, HO-1 and NQO1 genes, and increasing the activities of CAT, GSH-Px and SOD. Moreover, the protective effect of Rb-1 on rat brain may be dose-dependent.


greenmedinfo--2020-09-06--Is the CDC's COVID Death Count Really "Evidence-Based"?  [VIDEO]

On Sept. 5th , Sayer Ji , founder of Greenmedinfo.com , interviewed former death records clerk , Joy M. Fritz , on the recent controversy over the CDC 's alleged admission that only 6 % of the estimated 181k decedents from Covid-19 died solely as a result of infection from the virus , the misunderstandings around the CDC 's reports on excess deaths , as well as long-standing problems with the way death certificates are coded and understood by the public .
In the interview , Joy reveals a hitherto undisclosed fact about `` excess deaths '' that has not @ @ @ @ @ @ @ 2014 to 2017 deaths increased by ~187,000 .
From 2017 to 2020 deaths are projected to increase by 5 % or ~141,000 .
Apparently having a pandemic saved 46,000 lives .
# ThanksCOVID # statisticalcontext https : //www.cdc.gov/nchs/nvss/vsrr/covid19/index.htm https : //www.cdc.gov/nchs/fastats/deaths.htm https : //www.cdc.gov/nchs/data/databriefs/db267.pdf According to Joy 's most recent update , submitted on Sept 6th , '' So it looks like the excess deaths are now being compared by week in the previous years , so it looks a little alarmist right now with it showing excess deaths at 111 % , @ @ @ @ @ @ @ ’ s total death number is still 952,398 shy of hitting 2017 death toll .
That ’ s 33.9 % left of the total to fulfill to hit even 100 % of 2017 numbers .
With 118 days left in the year which is 32.3 % of the year , we are pretty exactly on par with 2017 numbers . ''
Also , this interview discloses how the CDC 's provisional death counts are based 100 % on medical opinion/beliefs/thinking and not on scientific facts or medical evidence -- despite contrary perceptions and @ @ @ @ @ @ @ and even many government officials themselves .
To learn more , follow Joy M Fritz on the following platforms : The video that inspired this interview : COVID death recording manipulation on Facebook ( it got censored from YouTube ) : https : //www.facebook.com/454038888346437/posts/977684859315168/ ?
vh=e & d=n

Visit our Re-post guidelines This article is copyrighted by GreenMedInfo LLC, 2020
On Sept. 5th, Sayer Ji, founder of Greenmedinfo.com, interviewed former death records clerk, Joy M. Fritz, on the recent controversy over the CDC's alleged admission that only 6% of the estimated 181k decedents from Covid-19 died solely as a result of infection from the virus, the misunderstandings around the CDC's reports on excess deaths, as well as long-standing problems with the way death certificates are coded and understood by the public
In the interview, Joy reveals a hitherto undisclosed fact about "excess deaths" that has not been reported elsewhere. Namely, from 2014 to 2017 deaths increased by ~187,000. From 2017 to 2020 deaths are projected to increase by 5% or ~141,000. Apparently having a pandemic saved 46,000 lives. #ThanksCOVID #statisticalcontext https://www.cdc.gov/nchs/nvss/vsrr/covid19/index.htm, https://www.cdc.gov/nchs/fastats/deaths.htm, https://www.cdc.gov/nchs/data/databriefs/db267.pdf
According to Joy's most recent update, submitted on Sept 6th,
"So it looks like the excess deaths are now being compared by week in the previous years, so it looks a little alarmist right now with it showing excess deaths at 111%, but our total death number versus 2017's total death number is still 952,398 shy of hitting 2017 death toll. That's 33.9% left of the total to fulfill to hit even 100% of 2017 numbers. With 118 days left in the year which is 32.3% of the year, we are pretty exactly on par with 2017 numbers."
Also, this interview discloses how the CDC's provisional death counts are based 100% on medical opinion/beliefs/thinking and not on scientific facts or medical evidence -- despite contrary perceptions and claims by the public, media, and even many government officials themselves. To learn more, follow Joy M Fritz on the following platforms: www.facebook.com/TheUntrivialPursuit/
Support Joy here: https://www.patreon.com/TheUntrivialPursuit
The video that inspired this interview: COVID death recording manipulation on Facebook (it got censored from YouTube) : https://www.facebook.com/454038888346437/posts/977684859315168/?vh=e&d=n


greenmedinfo--2020-09-07--Oridonin inhibits the proliferation of human colon cancer cells by upregulating BMP7 to activate p38

Oridonin inhibits the proliferation of human colon cancer cells by upregulating BMP7 to activate p38 MAPK.

Oridonin ( ORI ) , a diterpenoid purified from Rabdosia rubescens , has been reported as a promising chemotherapy drug for colon cancer treatment ; yet , the precise mechanisms underlying this anticancer activity remain unclear .
In the present study , we investigated the anticancer effect of ORI in HCT116 cells , and dissected the possible molecular mechanisms underlying this activity .
With crystal violet staining , flow cytometry and western blot assay , we found that ORI effectively inhibited the proliferation and induced the apoptosis of HCT116 cells .
Further analysis of the results indicated that BMP7 was @ @ @ @ @ @ @ cells , but its endogenous expression in FHC cells was apparently lower than that in the colon cancer cell lines .
Exogenous expression of BMP7 inhibited the proliferation of the HCT116 cells , and substantially potentiated the anticancer effect of ORI .
However , the specific antibody of BMP7 nearly abolished this anticancer activity of ORI in the HCT116 cells .
Meanwhile , ORI exerted no significant effect on the level of phosphorylated Smad1/5/8 or total p38 MAPK , but greatly increased the level of phosphorylated p38 MAPK in the HCT116 cells .
@ @ @ @ @ @ @ antiproliferative effect of BMP7 in the HCT116 cells , but prominently promoted the effect of the BMP7 antibody on proliferation .
Exogenous expression of BMP7 increased the ORI-induced phosphorylation of p38 MAPK , while the BMP7 antibody almost abolished the ORI-elevated p38 MAPK phosphorylation .
Our findings suggest that ORI may be an efficacious drug for colon cancer treatment .
This anticancer activity of ORI may be mediated by upregulating BMP7 at least to increase the activation of p38 MAPK .

Oridonin (ORI), a diterpenoid purified from Rabdosia rubescens, has been reported as a promising chemotherapy drug for colon cancer treatment; yet, the precise mechanisms underlying this anticancer activity remain unclear. In the present study, we investigated the anticancer effect of ORI in HCT116 cells, and dissected the possible molecular mechanisms underlying this activity. With crystal violet staining, flow cytometry and western blot assay, we found that ORI effectively inhibited the proliferation and induced the apoptosis of HCT116 cells. Further analysis of the results indicated that BMP7 was greatly upregulated by ORI in the HCT116 cells, but its endogenous expression in FHC cells was apparently lower than that in the colon cancer cell lines. Exogenous expression of BMP7 inhibited the proliferation of the HCT116 cells, and substantially potentiated the anticancer effect of ORI. However, the specific antibody of BMP7 nearly abolished this anticancer activity of ORI in the HCT116 cells. Meanwhile, ORI exerted no significant effect on the level of phosphorylated Smad1/5/8 or total p38 MAPK, but greatly increased the level of phosphorylated p38 MAPK in the HCT116 cells. A p38 MAPK-specific inhibitor partly reversed the antiproliferative effect of BMP7 in the HCT116 cells, but prominently promoted the effect of the BMP7 antibody on proliferation. Exogenous expression of BMP7 increased the ORI-induced phosphorylation of p38 MAPK, while the BMP7 antibody almost abolished the ORI-elevated p38 MAPK phosphorylation. Our findings suggest that ORI may be an efficacious drug for colon cancer treatment. This anticancer activity of ORI may be mediated by upregulating BMP7 at least to increase the activation of p38 MAPK.


greenmedinfo--2020-09-07--Oridonin induces apoptosis through the mitochondrial pathway in human gastric cancer SGC-7901 cells.

Oridonin is one of the most important antitumor active ingredients of Rabdosia rubescens .
Recently published studies from our laboratory have demonstrated that oridonin was able to arrest human gastric cancer SGC-7901 cells at G2/M phase .
However , little is known about inducing apoptosis in gastric cancer .
The aim of this study was to investigate the effect of oridonin on antineoplastic capability of SGC-7901 cells and the detailed molecular mechanism of oridonin-mediated intrinsic pathway of apoptosis .
Cell proliferation was assessed by MTT assay while apoptosis induced by oridonin was determined by Hoechst 33342 staining assay and Annexin @ @ @ @ @ @ @ rate was stained by Annexin V/PI and detected by flow cytometry .
Apoptosis pathway was analyzed by western blot analysis of Bcl-2 , Bax , cytochrome c and caspase-3 expression .
The results showed that oridonin was able to inhibit the SGC-7901 cell proliferation , the 50 % growth inhibition ( IC50 ) was 22.74 µM .
Oridonin could induce cell apoptosis of SGC-7901 cells and the early apoptotic rates induced by 0 , 20 , 40 , 80 µmol/l oridonin were 1.53±0.67 , 3.33±0.29 , 84.80±0.82 and 96.43±0.51 % , respectively .
@ @ @ @ @ @ @ protein ( the anti-apoptotic factor ) and upregulated Bax protein ( pro-apoptotic factor ) , eventually leading to a reduction in the ratio of Bcl-2/Bax proteins .
Furthermore , oridonin induced the release of cytochrome c from the mitochondria tothe cytosol and the activation of caspase-3 .
Taken together , the current study suggested that oridonin induced apoptosis in SGC-7901 cells via the mitochondrial signal pathway , which may represent one of the major mechanisms of oridonin-mediated apoptosis in SGC-7901 cells .

Oridonin is one of the most important antitumor active ingredients of Rabdosia rubescens. Recently published studies from our laboratory have demonstrated that oridonin was able to arrest human gastric cancer SGC-7901 cells at G2/M phase. However, little is known about inducing apoptosis in gastric cancer. The aim of this study was to investigate the effect of oridonin on antineoplastic capability of SGC-7901 cells and the detailed molecular mechanism of oridonin-mediated intrinsic pathway of apoptosis. Cell proliferation was assessed by MTT assay while apoptosis induced by oridonin was determined by Hoechst 33342 staining assay and Annexin V/PI double staining assay. Early apoptotic rate was stained by Annexin V/PI and detected by flow cytometry. Apoptosis pathway was analyzed by western blot analysis of Bcl-2, Bax, cytochrome c and caspase-3 expression. The results showed that oridonin was able to inhibit the SGC-7901 cell proliferation, the 50% growth inhibition (IC50) was 22.74 µM. Oridonin could induce cell apoptosis of SGC-7901 cells and the early apoptotic rates induced by 0, 20, 40, 80 µmol/l oridonin were 1.53±0.67, 3.33±0.29, 84.80±0.82 and 96.43±0.51%, respectively. Westernblot analysis revealed that oridonin downregulated Bcl-2 protein (the anti-apoptotic factor) and upregulated Bax protein (pro-apoptotic factor), eventually leading to a reduction in the ratio of Bcl-2/Bax proteins. Furthermore, oridonin induced the release of cytochrome c from the mitochondria tothe cytosol and the activation of caspase-3. Taken together, the current study suggested that oridonin induced apoptosis in SGC-7901 cells via the mitochondrial signal pathway, which may represent one of the major mechanisms of oridonin-mediated apoptosis in SGC-7901 cells.


greenmedinfo--2020-09-07--Oridonin inhibits gefitinib-resistant lung cancer cells.

Oridonin ( Ori ) , a diterpenoid compound extracted from traditional medicinal herbs , elicits antitumor effects on many cancer types .
However , whether Ori can be used in gefitinib-resistant non-small cell lung cancer ( NSCLC ) cells remains unclear .
This study investigated the antitumor activity and underlying mechanisms of Ori .
Results demonstrated that this compound dose-dependently inhibited the proliferation , invasion , and migration of the gefitinib-resistant NSCLC cells in vitro .
Ori also significantly downregulated the phosphorylation of EGFR , ERK , Akt , expression levels of matrix metalloproteinase-12 ( MMP-12 ) , and the @ @ @ @ @ @ @ CIP2A ) .
In addition , Ori upregulated protein phosphatase 2A ( PP2A ) activity of gefitinib-resistant NSCLC cells .
Ori combined with docetaxel synergistically inhibited these cells .
Ori also inhibited tumor growth in murine models .
Immunohistochemistry results further revealed that Ori downregulated phospho-EGFR , MMP-12 , and CIP2A in vivo .
These findings indicated that Ori can inhibit the proliferation , invasion , and migration of gefitinib-resistant NSCLC cells by suppressing EGFR/ERK/MMP-12 and CIP2A/PP2A/Akt signaling pathways .
Thus , Ori may be a novel effective candidate to treat gefitinib-resistant NSCLC @

Oridonin (Ori), a diterpenoid compound extracted from traditional medicinal herbs, elicits antitumor effects on many cancer types. However, whether Ori can be used in gefitinib-resistant non-small cell lung cancer (NSCLC) cells remains unclear. This study investigated the antitumor activity and underlying mechanisms of Ori. Results demonstrated that this compound dose-dependently inhibited the proliferation, invasion, and migration of the gefitinib-resistant NSCLC cells in vitro. Ori also significantly downregulated the phosphorylation of EGFR, ERK, Akt, expression levels of matrix metalloproteinase-12 (MMP-12), and the cancerous inhibitor of protein phosphatase 2A (CIP2A). In addition, Ori upregulated protein phosphatase 2A (PP2A) activity of gefitinib-resistant NSCLC cells. Ori combined with docetaxel synergistically inhibited these cells. Ori also inhibited tumor growth in murine models. Immunohistochemistry results further revealed that Ori downregulated phospho-EGFR, MMP-12, and CIP2A in vivo. These findings indicated that Ori can inhibit the proliferation, invasion, and migration of gefitinib-resistant NSCLC cells by suppressing EGFR/ERK/MMP-12 and CIP2A/PP2A/Akt signaling pathways. Thus, Ori may be a novel effective candidate to treat gefitinib-resistant NSCLC.


greenmedinfo--2020-09-07--Oridonin alleviates visceral hyperalgesia in a rat model of post-inflammatory irritable bowel syndro

Oridonin alleviates visceral hyperalgesia in a rat model of post-inflammatory irritable bowel syndrome.

The aim of this present study was to investigate the effect of oridonin on visceral hyperalgesia and colonic serotonin availability in a rat model of trinitrobenzenesulfonic acid-induced postinflammatory irritable bowel syndrome ( PI-IBS ) .
Rats were randomly divided into five groups : normal control , PI-IBS model , PI-IBS+low-dose oridonin ( 5 mg/kg ) , PI-IBS+median-dose oridonin ( 10 mg/kg ) , and PI-IBS+high-dose oridonin ( 20 mg/kg ) .
Rats in control and model groups were orally administered with water by gavage , whereas rats in oridonin-treated groups were orally administered with different dosages of oridonin , and @ @ @ @ @ @ @ .
Compared with the control group , the pain threshold pressure was significantly reduced in PI-IBS rats .
The colonic enterochromaffin ( EC ) cell number , serotonin content , and the protein expression of tryptophan hydroxylase ( TPH ) were markedly increased and the protein expression of serotonin reuptake transporter was significantly decreased in PI-IBS rats .
The spleen index in PI-IBS rats was decreased , and the levels of tumor necrosis factor ( TNF ) -α , interferon ( IFN ) -γ , interleukin ( IL ) -4 , and IL-13 @ @ @ @ @ @ @ also markedly decreased .
Oridonin treatment dose dependently increased pain threshold pressure , and markedly decreased colon EC cell numbers , TPH expression , and serotonin content in PI-IBS rats .
Oridonin treatment also significantly increased the spleen index as well as the levels of TNF-α , IFN-γ , IL-4 , and IL-13 in the colon of PI-IBS rats .
Results of this study demonstrate that the analgesic effect of oridonin in PI-IBS rats is associated with reduced colonic EC cell hyperplasia and 5-HT availability , the regulatory effect of oridonin on colonic @ @ @ @ @ @ @ effect on colonic EC cell number .

The aim of this present study was to investigate the effect of oridonin on visceral hyperalgesia and colonic serotonin availability in a rat model of trinitrobenzenesulfonic acid-induced postinflammatory irritable bowel syndrome (PI-IBS). Rats were randomly divided into five groups: normal control, PI-IBS model, PI-IBS+low-dose oridonin (5 mg/kg), PI-IBS+median-dose oridonin (10 mg/kg), and PI-IBS+high-dose oridonin (20 mg/kg). Rats in control and model groups were orally administered with water by gavage, whereas rats in oridonin-treated groups were orally administered with different dosages of oridonin, and drugs were given for 14 consecutive days. Compared with the control group, the pain threshold pressure was significantly reduced in PI-IBS rats. The colonic enterochromaffin (EC) cell number, serotonin content, and the protein expression of tryptophan hydroxylase (TPH) were markedly increased and the protein expression of serotonin reuptake transporter was significantly decreased in PI-IBS rats. The spleen index in PI-IBS rats was decreased, and the levels of tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-4, and IL-13 in the colon of PI-IBS rats were also markedly decreased. Oridonin treatment dose dependently increased pain threshold pressure, and markedly decreased colon EC cell numbers, TPH expression, and serotonin content in PI-IBS rats. Oridonin treatment also significantly increased the spleen index as well as the levels of TNF-α, IFN-γ, IL-4, and IL-13 in the colon of PI-IBS rats. Results of this study demonstrate that the analgesic effect of oridonin in PI-IBS rats is associated with reduced colonic EC cell hyperplasia and 5-HT availability, the regulatory effect of oridonin on colonic cytokine production may be correlated with its effect on colonic EC cell number.


greenmedinfo--2020-09-07--Effects of Oridonin on growth performance and oxidative stress in broilers challenged with lipopolys

Effects of Oridonin on growth performance and oxidative stress in broilers challenged with lipopolysaccharide.

This study was conducted to investigate the effects of oridonin ( ORI ) on growth performance and antioxidant capacity in broiler chickens that were repeatedly challenged with lipopolysaccharide ( LPS ) .
A total of 384 one-day-old male Arbor Acre broiler chickens were randomly assigned to 8 treatments with 6 replicate cages per treatment and 8 birds per replicate .
There were 4 dietary treatments : the control group ( birds fed the basal diet ) , the ORI 50 group , the ORI 80 group , and the ORI 100 group ( the basal diet supplemented with 50 , @ @ @ @ @ @ @ respectively ) .
Broilers were intraperitoneally injected with either 250μg/kg BW LPS or an equivalent amount of sterile saline at 16 , 18 , and 20 d of age .
LPS decreased the average daily weight gain ( ADG ) , the average daily feed intake ( ADFI ) , and the feed conversion ratio ( FCR ) of broiler chickens ( P < 0.05 ) ; oridonin supplementation had no effects on performance whether before or after LPS injection ( P > 0.05 ) .
LPS stimulation increased the relative weight of @ @ @ @ @ @ @ 0.05 ) ; oridonin inclusion markedly attenuated the increased spleen index ( P < 0.05 ) .
Additionally , the LPS-induced increases in the concentrations of malondialdehyde ( MDA ) and decreases in activities of total superoxide dismutase ( T-SOD ) , total antioxidant capacity ( T-AOC ) and catalase ( CAT ) were dramatically attenuated by oridonin in both the serum and liver ( P < 0.05 ) .
Furthermore , LPS down-regulated the mRNA expressions of nuclear factor erythroid 2-related factor 2 ( Nrf2 ) , copper and zinc superoxide dismutase @ @ @ @ @ @ @ ( Mn-SOD ) , glutathione peroxidase ( GPx1 ) , and CAT in the liver ( P < 0.05 ) , However , oridonin inclusion increased the liver mRNA expression levels of Nrf2 , Cu/Zn-SOD , Mn-SOD , CAT , and GPx1 ( P < 0.05 ) .
It was concluded that the dietary oridonin supplementation at an optimum dose of 100 mg/kg improves the antioxidant capacity in broilers , as evidenced by the decrease in MDA and the increase in total SOD activities and mRNA expression levels of the liver antioxidant genes @ @ @ @ @ @ @ was negligible .

This study was conducted to investigate the effects of oridonin (ORI) on growth performance and antioxidant capacity in broiler chickens that were repeatedly challenged with lipopolysaccharide (LPS). A total of 384 one-day-old male Arbor Acre broiler chickens were randomly assigned to 8 treatments with 6 replicate cages per treatment and 8 birds per replicate. There were 4 dietary treatments: the control group (birds fed the basal diet), the ORI 50 group, the ORI 80 group, and the ORI 100 group (the basal diet supplemented with 50, 80, and 100 mg/kg oridonin, respectively). Broilers were intraperitoneally injected with either 250μg/kg BW LPS or an equivalent amount of sterile saline at 16, 18, and 20 d of age. LPS decreased the average daily weight gain (ADG), the average daily feed intake (ADFI), and the feed conversion ratio (FCR) of broiler chickens (P<0.05); oridonin supplementation had no effects on performance whether before or after LPS injection (P>0.05). LPS stimulation increased the relative weight of the spleen and bursa (P<0.05); oridonin inclusion markedly attenuated the increased spleen index (P<0.05). Additionally, the LPS-induced increases in the concentrations of malondialdehyde (MDA) and decreases in activities of total superoxide dismutase (T-SOD), total antioxidant capacity (T-AOC) and catalase (CAT) were dramatically attenuated by oridonin in both the serum and liver (P<0.05). Furthermore, LPS down-regulated the mRNA expressions of nuclear factor erythroid 2-related factor 2 (Nrf2), copper and zinc superoxide dismutase (Cu/Zn-SOD), manganese superoxide dismutase (Mn-SOD), glutathione peroxidase (GPx1), and CAT in the liver (P<0.05), However, oridonin inclusion increased the liver mRNA expression levels of Nrf2, Cu/Zn-SOD, Mn-SOD, CAT, and GPx1 (P<0.05). It was concluded that the dietary oridonin supplementation at an optimum dose of 100 mg/kg improves the antioxidant capacity in broilers, as evidenced by the decrease in MDA and the increase in total SOD activities and mRNA expression levels of the liver antioxidant genes, although the effects on growth performance was negligible.


greenmedinfo--2020-09-07--Oridonin enhances the anticancer activity of NVP-BEZ235 against neuroblastoma cells in vitro and in

Oridonin enhances the anticancer activity of NVP-BEZ235 against neuroblastoma cells in vitro and in vivo through autophagy.

The aberrant activation of PI3K/Akt/mTOR signaling pathway plays an important role in the oncogenesis , prognosis and chemotherapy resistance of neuroblastoma .
However , NVP-BEZ235 , a potent dual PI3K and mTOR inhibitor have not shown beneficial effects on neuroblastoma especially in terms of apoptosis induction as a single agent .
We therefore attempted to explore an effective combination regimen to enhance the anticancer activity of NVP-BEZ235 .
Interestingly , we found that oridonin , a natural biologically active compound extracted from the Chinese medicinal herb Rabdosia rubescens , combined with NVP-BEZ235 markedly induced apoptosis of neuroblastoma cells .
Notably @ @ @ @ @ @ @ pathway was accompanied with enhanced autophagy as evidenced by significant decreased p62 expression as well as upregulated conversion of LC3-II .
Suppression of the Beclin-1 , a core component of the autophagy machinery , by means of shRNA resulted in diminished synergistic antitumor effect .
Furthermore , the co-treatment with oridonin and NVP-BEZ235 was also much more effective than either agent alone in inhibiting the growth of neuroblastoma xenografts and in inducing tumor cells apoptosis .
Taken together , our results suggest that the combination of NVP-BEZ235 and oridonin is a novel and @ @ @ @ @ @

The aberrant activation of PI3K/Akt/mTOR signaling pathway plays an important role in the oncogenesis, prognosis and chemotherapy resistance of neuroblastoma. However, NVP-BEZ235, a potent dual PI3K and mTOR inhibitor have not shown beneficial effects on neuroblastoma especially in terms of apoptosis induction as a single agent. We therefore attempted to explore an effective combination regimen to enhance the anticancer activity of NVP-BEZ235. Interestingly, we found that oridonin, a natural biologically active compound extracted from the Chinese medicinal herb Rabdosia rubescens, combined with NVP-BEZ235 markedly induced apoptosis of neuroblastoma cells. Notably, the synergistic activation of the apoptotic pathway was accompanied with enhanced autophagy as evidenced by significant decreased p62 expression as well as upregulated conversion of LC3-II. Suppression of the Beclin-1, a core component of the autophagy machinery, by means of shRNA resulted in diminished synergistic antitumor effect. Furthermore, the co-treatment with oridonin and NVP-BEZ235 was also much more effective than either agent alone in inhibiting the growth of neuroblastoma xenografts and in inducing tumor cells apoptosis. Taken together, our results suggest that the combination of NVP-BEZ235 and oridonin is a novel and potential strategy for neuroblastoma therapy.


greenmedinfo--2020-09-07--Oridonin regulates Th1/Th2 balance in mice and exhibited anti‑asthmatic effects.

Oridonin is an extract obtained from a traditional Chinese medicinal herb , Xihuangcao .
Previous studies have demonstrated that Oridonin exerts various pharmaceutical effects , such as anti‑tumor and immunosuppressive effects , as well as modulating cytokine balance .
The present study identified that Oridonin could regulate the Th1/Th2 cytokine balance in mice .
However , as the anti‑asthmatic effect of Oridonin is currently unknown a mouse model of asthma was used in the present study .
BALB/c mice were sensitized using ovalbumin ( OVA ) , then the sensitized mice were treated with Oridonin prior to OVA challenge .
@ @ @ @ @ @ @ decreased the OVA‑induced airway hyper‑responsiveness significantly ( P < 0.05 ) .
In addition , the results indicated that in Oridonin‑treated mice , the eosinophil number and total inflammatory cell number in bronchoalveolar lavage ( BAL ) fluid decreased significantly in the Oridonin group when compared with the control group .
Further study indicated that Oridonin significantly decreased the level of inflammatory cytokines , whichwere induced by OVA , in BAL fluid .
Histological studies were performed to evaluate the effect of Oridonin on eosinophilia and mucus in the airway , the results @ @ @ @ @ @ @ and mucus production in the lungs .
Therefore the present study demonstratedthat Oridonin regulates Th1/Th2 balance in mice and exhibited anti‑asthmatic effects in a mouse model of asthma .
These findings indicate that Oridonin may serve as a potential therapeutic compound for the treatment of asthma in future .

Oridonin is an extract obtained from a traditional Chinese medicinal herb, Xihuangcao. Previous studies have demonstrated that Oridonin exerts various pharmaceutical effects, such as anti‑tumor and immunosuppressive effects, as well as modulating cytokine balance. The present study identified that Oridonin could regulate the Th1/Th2 cytokine balance in mice. However, as the anti‑asthmatic effect of Oridonin is currently unknown a mouse model of asthma was used in the present study. BALB/c mice were sensitized using ovalbumin (OVA), then the sensitized mice were treated with Oridonin prior to OVA challenge. The in vivo study indicated that Oridonin decreased the OVA‑induced airway hyper‑responsiveness significantly (P<0.05). In addition, the results indicated that in Oridonin‑treated mice, the eosinophil number and total inflammatory cell number in bronchoalveolar lavage (BAL) fluid decreased significantly in the Oridonin group when compared with the control group. Further study indicated that Oridonin significantly decreased the level of inflammatory cytokines, whichwere induced by OVA, in BAL fluid. Histological studies were performed to evaluate the effect of Oridonin on eosinophilia and mucus in the airway, the results indicated that Oridonin significantly inhibited the eosinophilia and mucus production in the lungs. Therefore the present study demonstratedthat Oridonin regulates Th1/Th2 balance in mice and exhibited anti‑asthmatic effects in a mouse model of asthma. These findings indicate that Oridonin may serve as a potential therapeutic compound for the treatment of asthma in future.


greenmedinfo--2020-09-07--Oridonin inhibits pancreatic cancer cell migration and epithelial-mesenchymal transition by suppress

Oridonin inhibits pancreatic cancer cell migration and epithelial-mesenchymal transition by suppressing Wnt/β-catenin signaling pathway.

BACKGROUND : Oridonin ( ORI ) can inhibit proliferation and migration in various types of cancer cell lines .
However , the exact mechanism remains unclear .
We investigated the migration inhibitory effect of ORI on human pancreatic cancer SW1990 cells and dissected the possible molecular mechanism ( s ) .
METHODS : CCK-8 assay was used to observe the cell viability .
Wound healing assay , transwell assay and spontaneous metastasis model were used to observe the migration activities .
Real-time PCR , immunofluorescence , western blot analysis and immunohistochemistry methods were used to observe the expression of genes @ @ @ @ @ @ @ the migration of SW1990 cells .
Real-time PCR and immuno-fluorescence analyses of epithelial-to-mesenchymal transition ( EMT ) markers were compared between control group and ORI group .
The expression of mesenchymal molecular markers , such as vimentin , snail and slug decreased .
The expression of epithelial-related marker E-cadherin increased .
Wnt/β-catenin signalling was inhibited by ORI using luciferase reporter assay .
ORI can decrease the β-catenin protein level not only in the nucleus , but also in the cytoplasm and the whole cell after the treatment with ORI and glycogen synthase kinase @ @ @ @ @ @ @ the ORI-treated group .
CHIR could attenuate the effects of ORI in SW1990 cells .
We established a mice model by injecting 1 × 10 ( 6 ) SW1990 cells into nude mice intraperitoneally to test whether ORI affects tumour metastasis .
Metastatic formation was inhibited by ORI ( 5 and 10 mg/kg ) compared with the control group.Tumour sections stained with anti-E-cadherin , anti-vimentin and anti-β-catenin antibodies revealed that ORI inhibited EMT , as well as the Wnt/β-catenin pathway in vivo .
CONCLUSIONS : ORI can inhibit pancreatic cancer cell SW1990 migration @ @ @ @ @ @ @ in vitro and in vivo .
Therefore , it can be potentially and effectively used in the clinical management of pancreatic cancer .

BACKGROUND: Oridonin (ORI) can inhibit proliferation and migration in various types of cancer cell lines. However, the exact mechanism remains unclear. We investigated the migration inhibitory effect of ORI on human pancreatic cancer SW1990 cells and dissected the possible molecular mechanism(s).
METHODS: CCK-8 assay was used to observe the cell viability. Wound healing assay, transwell assay and spontaneous metastasis model were used to observe the migration activities. Real-time PCR, immunofluorescence, western blot analysis and immunohistochemistry methods were used to observe the expression of genes or proteins.
RESULTS: ORI inhibited the migration of SW1990 cells. Real-time PCR and immuno-fluorescence analyses of epithelial-to-mesenchymal transition (EMT) markers were compared between control group and ORI group. The expression of mesenchymal molecular markers, such as vimentin, snail and slug decreased. The expression of epithelial-related marker E-cadherin increased. Wnt/β-catenin signalling was inhibited by ORI using luciferase reporter assay. ORI can decrease the β-catenin protein level not only in the nucleus, but also in the cytoplasm and the whole cell after the treatment with ORI and glycogen synthase kinase 3β (GSK3β) was increased in the ORI-treated group. CHIR could attenuate the effects of ORI in SW1990 cells. We established a mice model by injecting 1 × 10(6) SW1990 cells into nude mice intraperitoneally to test whether ORI affects tumour metastasis. Metastatic formation was inhibited by ORI (5 and 10 mg/kg) compared with the control group.Tumour sections stained with anti-E-cadherin, anti-vimentin and anti-β-catenin antibodies revealed that ORI inhibited EMT, as well as the Wnt/β-catenin pathway in vivo.
CONCLUSIONS: ORI can inhibit pancreatic cancer cell SW1990 migration and EMT by down-regulating Wnt/β-catenin signal transduction in vitro and in vivo. Therefore, it can be potentially and effectively used in the clinical management of pancreatic cancer.


greenmedinfo--2020-09-07--Synergistic effect of oridonin and a PI3K/mTOR inhibitor on the non-germinal center B cell-like subt

Synergistic effect of oridonin and a PI3K/mTOR inhibitor on the non-germinal center B cell-like subtype of diffuse large B cell lymphoma.

We demonstrate the synergistic antitumor effect of oridonin and the PI3K/mTOR inhibitor NVP-BEZ235 on the non-germinal center B cell-like subtype @ @ @ @ @ lymphoma ( non-GCB DLBCL ) both in vitro and in vivo .
The underlying mechanism @ @ @ @ @ apoptosis , AKT/mTOR and NF-kB inactivation , and ROS-mediated DNA damage response .
Our findings @ @ @ @ @ new potential treatment option for non-GCB DLBCL with the combination of oridonin and NVP-BEZ235 .

We demonstrate the synergistic antitumor effect of oridonin and the PI3K/mTOR inhibitor NVP-BEZ235 on the non-germinal center B cell-like subtype of diffuse large B cell lymphoma (non-GCB DLBCL) both in vitro and in vivo. The underlying mechanism may be multifunctional, involving apoptosis, AKT/mTOR and NF-kB inactivation, and ROS-mediated DNA damage response. Our findings pave the way for a new potential treatment option for non-GCB DLBCL with the combination of oridonin and NVP-BEZ235.


greenmedinfo--2020-09-08--Exosomes transport trace amounts of polyphenols.

( Poly ) phenols have varied biological activities that may account for the beneficial effects of fruits and vegetables as @ @ @ @ @ .
Although their cellular absorption and their many mechanisms of action have been partly elucidated @ @ @ @ @ systemic circulation , other than their binding to albumin , is poorly described .
We @ @ @ @ @ poly ) phenols can be transported by extracellular vesicles .
We supplemented rats with a @ @ @ @ @ ( GSPE ) and we quantified ( poly ) phenols and their metabolites at 3 @ @ @ @ @ After quantitative LC-MS/MS analysis of circulating aglycones , and microbial-derived , or phase II-derived metabolites @ @ @ @ @ modest transport of ( poly ) phenols in plasma exosomes when isolated by commercial ultracentrifugation @ @ @ @ @ data suggest that GSPE-derived ( poly ) phenols are minimally , if at all , @ @ @ @

(Poly)phenols have varied biological activities that may account for the beneficial effects of fruits and vegetables as part of a healthy diet. Although their cellular absorption and their many mechanisms of action have been partly elucidated, their transport through the systemic circulation, other than their binding to albumin, is poorly described. We aimed at determining whether (poly)phenols can be transported by extracellular vesicles. We supplemented rats with a dietary grape seed polyphenol extract (GSPE) and we quantified (poly)phenols and their metabolites at 3 and 7 h post-gavage. After quantitative LC-MS/MS analysis of circulating aglycones, and microbial-derived, or phase II-derived metabolites we recorded a quantitatively very modest transport of (poly)phenols in plasma exosomes when isolated by commercial ultracentrifugation or precipitation kits. Our data suggest that GSPE-derived (poly)phenols are minimally, if at all, transported by exosomes.


greenmedinfo--2020-09-08--Antifungal activity of phenolic and polyphenolic compounds from different matrices of Vitis vinifera

Antifungal activity of phenolic and polyphenolic compounds from different matrices of Vitis vinifera L. against human pathogens.

Phenolic compounds , the most widely distributed class of natural products in the plants , show several biological properties including @ @ @ @ @ in grapes can be classified in two main groups , flavonoids and non-flavonoids compounds .
@ @ @ @ @ phenolic and polyphenolic compounds from different matrices ofdepends of cultivar , climate , soil condition @ @ @ @ @ grapes , berry skins and seeds , leaves , canes and stems and not-fermented and @ @ @ @ @ and valuable wastes from agricultural and agro-industrial processes .
This review summarizes studies that examine @ @ @ @ @ characterization , and antifungal activity of phenolic and polyphenolic compounds from edible and non-ediblematrices against @ @ @ @ @ the world , around one billion people have fungal diseases related to skin , nail @ @ @ @ @ million have systemic diseases caused by fungi .
Few studies on antifungal activity of plant @ @ @ @ @ This review provides useful information for the application ofphenolics in the field of antifungals for @ @ @

Phenolic compounds, the most widely distributed class of natural products in the plants, show several biological properties including antifungal activity. Phenolics contained in grapes can be classified in two main groups, flavonoids and non-flavonoids compounds. Variability and yield extraction of phenolic and polyphenolic compounds from different matrices ofdepends of cultivar, climate, soil condition and process technology. Unripe grapes, berry skins and seeds, leaves, canes and stems and not-fermented and fermented pomaces represent large reusable and valuable wastes from agricultural and agro-industrial processes. This review summarizes studies that examine the extraction method, chemical characterization, and antifungal activity of phenolic and polyphenolic compounds from edible and non-ediblematrices against human fungal pathogens. In the world, around one billion people have fungal diseases related to skin, nail or hair and around 150 million have systemic diseases caused by fungi. Few studies on antifungal activity of plant extracts have been performed. This review provides useful information for the application ofphenolics in the field of antifungals for human use.


greenmedinfo--2020-09-08--Glutathione improves the antioxidant activity of vitamin C in human lens and retinal epithelial cell

Glutathione improves the antioxidant activity of vitamin C in human lens and retinal epithelial cells.

PURPOSE : Tissues in the eye are particularly susceptible to oxidative damage due to light exposure .
While vitamin C ( ascorbic acid ) has been noted as a vital antioxidant in the vitreous humor , its physiological concentration ( 1-2 mM ) has been shown to be toxic to retinal and lens epithelial cells incell culture .
We have explored adding vitamin C to hydrogel vitreous substitutes as a potential therapeutic to prevent oxidative damage to intraocular tissues after vitrectomy .
However , vitamin C degrades rapidly even when loaded at high concentrations , limiting its long-term effectiveness .
@ @ @ @ @ @ @ the lens at concentrations of 2-10 mM , was proposed to be used in conjunction with vitamin C. METHODS : Cell viability and reactive oxygen species activity of human retinal and lens epithelial cells treated with various combinations of vitamin C , glutathione , hydrogen peroxide , and a hydrogel vitreous substitute were determined using CellTiter-Glo luminescent cell viability assay and dichlorofluorescein assay , respectively .
The vitamin C remaining in hydrogel vitreous substitute or glutathione-vitamin C solutions was determined using a microplate reader at 265 nm wavelength , compared against standard solutions @ @ @ @ @ @ @ protected the lens and retinal cells from the negative effect of vitamin C on cell viability and prolonged the antioxidant effect of vitamin C. While the detected reading of pure vitamin C solution decreased rapidly from 100 % to 10 % by 3 days , glutathione provided a significant extension to vitamin C stability , with 70 % remaining after 14 days when the glutathione was used at physiological concentrations found in the lens ( 2-10 mM ) .
CONCLUSIONS : These results indicate glutathione might be an effective addition to vitamin C @ @ @ @ @ @ @ substitutes , and warrants additional studies on the effectiveness of the vitamin C - glutathione combination in preventing oxidative stress post-vitrectomy .

PURPOSE: Tissues in the eye are particularly susceptible to oxidative damage due to light exposure. While vitamin C (ascorbic acid) has been noted as a vital antioxidant in the vitreous humor, its physiological concentration (1-2 mM) has been shown to be toxic to retinal and lens epithelial cells incell culture. We have explored adding vitamin C to hydrogel vitreous substitutes as a potential therapeutic to prevent oxidative damage to intraocular tissues after vitrectomy. However, vitamin C degrades rapidly even when loaded at high concentrations, limiting its long-term effectiveness. Glutathione, another antioxidant found abundantly in the lens at concentrations of 2-10 mM, was proposed to be used in conjunction with vitamin C.
METHODS: Cell viability and reactive oxygen species activity of human retinal and lens epithelial cells treated with various combinations of vitamin C, glutathione, hydrogen peroxide, and a hydrogel vitreous substitute were determined using CellTiter-Glo luminescent cell viability assay and dichlorofluorescein assay, respectively. The vitamin C remaining in hydrogel vitreous substitute or glutathione-vitamin C solutions was determined using a microplate reader at 265 nm wavelength, compared against standard solutions with known concentrations.
RESULTS: Glutathione protected the lens and retinal cells from the negative effect of vitamin C on cell viability and prolonged the antioxidant effect of vitamin C. While the detected reading of pure vitamin C solution decreased rapidly from 100% to 10% by 3 days, glutathione provided a significant extension to vitamin C stability, with 70% remaining after 14 days when the glutathione was used at physiological concentrations found in the lens (2-10 mM).
CONCLUSIONS: These results indicate glutathione might be an effective addition to vitamin C in intraocular implants, including potential vitreous substitutes, and warrants additional studies on the effectiveness of the vitamin C - glutathione combination in preventing oxidative stress post-vitrectomy.


greenmedinfo--2020-09-08--Application of methylene blue -vitamin C -N-acetyl cysteine for treatment of critically ill COVID-19

Application of methylene blue -vitamin C -N-acetyl cysteine for treatment of critically ill COVID-19 patients.

COVID-19 is a global catastrophic event that causes severe acute respiratory syndrome .
The mechanism of the disease remains unclear , and hypoxia is one of the main complications .
There is no currently approved protocol for treatment .
The microbial threat as induced by COVID-19 causes the activation of macrophages to produce a huge amount of inflammatory molecules and nitric oxide ( NO ) .
Activation of macrophages population into a pro-inflammatory phenotype induces a self-reinforcing cycle .
Oxidative stress and NO contribute to this cycle , establishing a cascade inflammatory state that can kill the patient .
Interrupting @ @ @ @ @ @ @ may save critical patients ' lives .
Nitrite , nitrate ( the metabolites of NO ) , methemoglobin , and prooxidant-antioxidant-balance levels were measured in 25 ICU COVID-19 patients and 25 healthy individuals .
As the last therapeutic option , five patients were administered methylene blue-vitamin C-N-acetyl Cysteine ( MCN ) .
Nitrite , nitrate , methemoglobin , and oxidative stress were significantly increased in patients in comparison to healthy individuals .
Four of the five patients responded well to treatment .
In conclusion , NO , methemoglobin and oxidative stress may play @ @ @ @ @ @ @ critical COVID-19 disease .
MCN treatment seems to increase the survival rate of these patients .
Considering the vicious cycle of macrophage activation leading to deadly NO , oxidative stress , and cytokine cascade syndrome ; the therapeutic effect of MCN seems to be reasonable .
Accordingly , a wider clinical trial has been designed .
It should be noted that the protocol is using the low-cost drugs which the FDA approved for other diseases .
TRIAL REGISTRATION NUMBER : NCT04370288 .

COVID-19 is a global catastrophic event that causes severe acute respiratory syndrome. The mechanism of the disease remains unclear, and hypoxia is one of the main complications. There is no currently approved protocol for treatment. The microbial threat as induced by COVID-19 causes the activation of macrophages to produce a huge amount of inflammatory molecules and nitric oxide (NO). Activation of macrophages population into a pro-inflammatory phenotype induces a self-reinforcing cycle. Oxidative stress and NO contribute to this cycle, establishing a cascade inflammatory state that can kill the patient. Interrupting this vicious cycle by a simple remedy may save critical patients' lives. Nitrite, nitrate (the metabolites of NO), methemoglobin, and prooxidant-antioxidant-balance levels were measured in 25 ICU COVID-19 patients and 25 healthy individuals. As the last therapeutic option, five patients were administered methylene blue-vitamin C-N-acetyl Cysteine (MCN). Nitrite, nitrate, methemoglobin, and oxidative stress were significantly increased in patients in comparison to healthy individuals. Four of the five patients responded well to treatment. In conclusion, NO, methemoglobin and oxidative stress may play a central role in the pathogenesis of critical COVID-19 disease. MCN treatment seems to increase the survival rate of these patients. Considering the vicious cycle of macrophage activation leading to deadly NO, oxidative stress, and cytokine cascade syndrome; the therapeutic effect of MCN seems to be reasonable. Accordingly, a wider clinical trial has been designed. It should be noted that the protocol is using the low-cost drugs which the FDA approved for other diseases. TRIAL REGISTRATION NUMBER: NCT04370288.


greenmedinfo--2020-09-08--Efficacy and safety of vitamin C in the management of acute respiratory infection and disease.

Brief overview : Current evidence from published systematic reviews indicate that oral intake of vitamin C may assist with symptoms of acute viral respiratory infections ( ARI ) by reducing fever and chills , relieving chest pain and assist in reducing symptoms of common cold-induced asthma .
Intravenous ( IV ) vitamin C administration may reduce the need for vasopressor support and the duration of mechanical ventilations in critically ill patients in hospital .
COVID-19 has similar signs and symptoms of ARI .
Further studies involving patients with COVID-19 , either through administration of oral vitamin C in mild cases @ @ @ @ @ @ @ , would be advantageous to examine if it is safe and efficacious .
Verdict : Oral vitamin C may assist with the symptoms of acute respiratory viral infections ( ARI ) and common cold-induced asthma but no studies have been identified justifying oral vitamin C for the prevention or treatment of coronavirus infections including COVID-19 .
When taken at onset of ARI , oral vitamin C may reduce the duration of symptoms including fever , chest pain , chills and bodily aches and pains .
It may also reduce the incidence of hospital @ @ @ @ @ @ @ For individuals admitted to hospital with community-acquired pneumonia , vitamin C may improve respiratory function in more severe cases .
No major adverse events nor interactions were reported by either method of administration .
However , there is an absence of high quality , contemporary clinical research examining this topic .
Current evidence suggests further studies are needed to better understand the value of both oral and IV vitamin C for ARI , including COVID-19 .

Brief overview: Current evidence from published systematic reviews indicate that oral intake of vitamin C may assist with symptoms of acute viral respiratory infections (ARI) by reducing fever and chills, relieving chest pain and assist in reducing symptoms of common cold-induced asthma. Intravenous (IV) vitamin C administration may reduce the need for vasopressor support and the duration of mechanical ventilations in critically ill patients in hospital. COVID-19 has similar signs and symptoms of ARI. Further studies involving patients with COVID-19, either through administration of oral vitamin C in mild cases or IV vitamin C in critical cases, would be advantageous to examine if it is safe and efficacious.
Verdict: Oral vitamin C may assist with the symptoms of acute respiratory viral infections (ARI) and common cold-induced asthma but no studies have been identified justifying oral vitamin C for the prevention or treatment of coronavirus infections including COVID-19. When taken at onset of ARI, oral vitamin C may reduce the duration of symptoms including fever, chest pain, chills and bodily aches and pains. It may also reduce the incidence of hospital admission and duration of hospital stays. For individuals admitted to hospital with community-acquired pneumonia, vitamin C may improve respiratory function in more severe cases. No major adverse events nor interactions were reported by either method of administration. However, there is an absence of high quality, contemporary clinical research examining this topic. Current evidence suggests further studies are needed to better understand the value of both oral and IV vitamin C for ARI, including COVID-19.


greenmedinfo--2020-09-08--This suggests that dietary vitamin C intake may be useful for reducing age-related muscle loss.

BACKGROUND : Age-related loss of skeletal muscle mass contributes to poor outcomes including sarcopenia , physical disability , frailty , type 2 diabetes , and mortality .
Vitamin C has physiological relevance to skeletal muscle and may protect it during aging , but few studies have investigated its importance in older populations .
OBJECTIVES : We aimed to investigate cross-sectional associations of dietary and plasma vitamin C with proxy measures of skeletal muscle mass in a large cohort of middle- and older-aged individuals .
METHODS : We analyzed data from > 13,000 men and women in the European Prospective Investigation @ @ @ @ @ @ @ 42-82 y. Fat-free mass ( FFM ) , as a proxy for skeletal muscle mass , was estimated using bioelectrical impedance analysis and expressed as a percentage of total mass ( FFM % ) or standardized by BMI ( FFMBMI ) .
Dietary vitamin C intakes were calculated from 7-d food diary data , and plasma vitamin C was measured in peripheral blood .
Multivariable regression models , including relevant lifestyle , dietary , and biological covariates , were used to determine associations between FFM measures and quintiles of dietary vitamin C or @ @ @ @ @ @ @ ( < 50 μmol/L and ≥50 μmol/L ) .
RESULTS : Positive trends were found across quintiles of dietary vitamin C and FFM measures for both sexes , with interquintile differences in FFM % and FFMBMI of 1.0 % and 2.3 % for men and 1.9 % and 2.9 % for women , respectively ( all P CONCLUSIONS : Our findings of positive associations , of both dietary and circulating vitamin C with measures of skeletal muscle mass in middle- and older-aged men and women , suggest that dietary vitamin C intake may @ @ @ @ @ @ @ .

BACKGROUND: Age-related loss of skeletal muscle mass contributes to poor outcomes including sarcopenia, physical disability, frailty, type 2 diabetes, and mortality. Vitamin C has physiological relevance to skeletal muscle and may protect it during aging, but few studies have investigated its importance in older populations.
OBJECTIVES: We aimed to investigate cross-sectional associations of dietary and plasma vitamin C with proxy measures of skeletal muscle mass in a large cohort of middle- and older-aged individuals.
METHODS: We analyzed data from>13,000 men and women in the European Prospective Investigation into Cancer and Nutrition-Norfolk cohort, aged 42-82 y. Fat-free mass (FFM), as a proxy for skeletal muscle mass, was estimated using bioelectrical impedance analysis and expressed as a percentage of total mass (FFM%) or standardized by BMI (FFMBMI). Dietary vitamin C intakes were calculated from 7-d food diary data, and plasma vitamin C was measured in peripheral blood. Multivariable regression models, including relevant lifestyle, dietary, and biological covariates, were used to determine associations between FFM measures and quintiles of dietary vitamin C or insufficient compared with sufficient plasma vitamin C (<50 μmol/L and ≥50 μmol/L).
RESULTS: Positive trends were found across quintiles of dietary vitamin C and FFM measures for both sexes, with interquintile differences in FFM% and FFMBMI of 1.0% and 2.3% for men and 1.9% and 2.9% for women, respectively (all P< 0.001). Similarly, FFM% and FFMBMI measures were higher in participants with sufficient than with insufficient plasma vitamin C: by 1.6% and 2.0% in men, and 3.4% and 3.9% in women, respectively (all P< 0.001). Associations were also evident in analyses stratified into<65-y and≥65-y age groups.
CONCLUSIONS: Our findings of positive associations, of both dietary and circulating vitamin C with measures of skeletal muscle mass in middle- and older-aged men and women, suggest that dietary vitamin C intake may be useful for reducing age-related muscle loss.


greenmedinfo--2020-09-08--Will the Law Protect Health Freedom

Will the Law Protect Health Freedom

This website is for information purposes only .
By providing the information contained herein we are not diagnosing , treating @ @ @ @ @ or preventing any type of disease or medical condition .
Before beginning any type of @ @ @ @ @ treatment regimen , it is advisable to seek the advice of a licensed healthcare professional @

This website is for information purposes only. By providing the information contained herein we are not diagnosing, treating, curing, mitigating, or preventing any type of disease or medical condition. Before beginning any type of natural, integrative or conventional treatment regimen, it is advisable to seek the advice of a licensed healthcare professional.
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greenmedinfo--2020-09-08--The protective roles of ascorbic acid and α-tocopherol pyrethroid-induced organ Toxicity.

The pyrethroid toxicants , fatal at high doses , are found as remnants of crop pesticides and ingredients of commercially available insecticides .
The toxic effects of high-content insecticidal pyrethroid formulations are available in 0.05 g , 1.17 g , and 0.04 g pyrethroid-instilled products , namely burning coils , pyrethroid-soaked mats , and liquid formulations of pyrethroids that release pyrethroid vapor/smoke upon heating .
They provided 5.46 g/kg , 21.15 g/kg , and 4.24 g/kg of toxicants to the experimental animals over a total of 3 weeks/5 h per os ( p.o . )
administration , producing necrosis , @ @ @ @ @ @ @ liver ; fiber separation in cardiac muscles ; atrophy , lymphatic infiltration , blood vessel congestion , and hyperemia in the heart tissues of the experimental animals .
The glomerular tuft necrosis , cytoplasmic degeneration of renal tubular cells , necrotic tubules , congestion , and dilatation of blood vessels were observed in the kidney tissue of intoxicated animals .
Air-space enlargement , interstitial inflammation , lymphocyte infiltration aggregates , connective tissue infiltration by inflammatory cells , and hyperemia were found in the lung tissues .
The pyrethroid toxicants also produced nervous tissue @ @ @ @ @ @ @ , which were observed through histopathological examinations of the brain , lungs , heart , kidneys , and liver .
The protective effects of ascorbic acid ( AA/vitamin C ) andα-tocopherol ( E307/vitamin E ) at 100 mg/kg oral doses administered daily for the entire period of the toxicant exposure of three weeks to the experimental mice , aged between 3-4 months and weighing ≈30 g , ameliorated the tissue damage , as observed through the histopathological examinations .
The ascorbic acid caused recovery of the liver , kidney , brain , and @ @ @ @ @ @ @ effective at ameliorating the damage in the kidneys and lung tissue compared with the control groups .
The high levels of tissue damage recovery suggested a prophylactic effect of the concurrentuse of ascorbic acid and α-tocopherol for the subjects under the exposure of pyrethroids .

The pyrethroid toxicants, fatal at high doses, are found as remnants of crop pesticides and ingredients of commercially available insecticides. The toxic effects of high-content insecticidal pyrethroid formulations are available in 0.05 g, 1.17 g, and 0.04 g pyrethroid-instilled products, namely burning coils, pyrethroid-soaked mats, and liquid formulations of pyrethroids that release pyrethroid vapor/smoke upon heating. They provided 5.46 g/kg, 21.15 g/kg, and 4.24 g/kg of toxicants to the experimental animals over a total of 3 weeks/5 h per os (p.o.) administration, producing necrosis, hyperemia, and fatty changes in the liver; fiber separation in cardiac muscles; atrophy, lymphatic infiltration, blood vessel congestion, and hyperemia in the heart tissues of the experimental animals. The glomerular tuft necrosis, cytoplasmic degeneration of renal tubular cells, necrotic tubules, congestion, and dilatation of blood vessels were observed in the kidney tissue of intoxicated animals. Air-space enlargement, interstitial inflammation, lymphocyte infiltration aggregates, connective tissue infiltration by inflammatory cells, and hyperemia were found in the lung tissues. The pyrethroid toxicants also produced nervous tissue degeneration and decreased neurons in the brain, which were observed through histopathological examinations of the brain, lungs, heart, kidneys, and liver. The protective effects of ascorbic acid (AA/vitamin C) andα-tocopherol (E307/vitamin E) at 100 mg/kg oral doses administered daily for the entire period of the toxicant exposure of three weeks to the experimental mice, aged between 3-4 months and weighing ≈30 g, ameliorated the tissue damage, as observed through the histopathological examinations. The ascorbic acid caused recovery of the liver, kidney, brain, and heart tissue damage, while α-tocopherol was effective at ameliorating the damage in the kidneys and lung tissue compared with the control groups. The high levels of tissue damage recovery suggested a prophylactic effect of the concurrentuse of ascorbic acid and α-tocopherol for the subjects under the exposure of pyrethroids.


greenmedinfo--2020-09-08--Ascorbic acid, inflammatory cytokines or their combination's effect on stemness, proliferation, and

Ascorbic acid, inflammatory cytokines or their combination's effect on stemness, proliferation, and differentiation of gingival mesenchymal stem cells.

Objective : Ascorbic acid ( AA ) and controlled inflammatory stimuli are postulated to possess the ability to independently exert positive effects on a variety of proliferative , pluripotency , and differentiation attributes of gingival mesenchymal stem/progenitor cells ( G-MSCs ) .
The current study 's objective was to explore and compare for the first time the impact of the major inflammatory cytokines ( IL-1/TNF-/IFN- ) , AA , or their combination on multipotency/pluripotency , proliferative , and differentiation characteristics of G-MSCs .
Design : Human G-MSCs ( = 5 ) were isolated and cultured in basic medium ( control @ @ @ @ @ @ @ major inflammatory cytokines ; 1 ng/ml IL-1 , 10 ng/ml TNF- , and 100 ng/ml IFN- ( inflammatory group ) , in basic medium with 250 mol/l AA ( AA group ) and in inflammatory medium supplemented by AA ( inflammatory/AA group ) .
All media were renewed three times per week .
In stimulated G-MSCs intracellular-catenin at 1 hour , pluripotency gene expression at 1 , 3 , and 5 days , as well as colony-forming units ( CFUs ) ability and cellular proliferation over 14 days were examined .
Following a @ @ @ @ @ @ @ multilineage differentiation was assessed via qualitative and quantitative histochemistry as well as mRNA expression .
Results : -Catenin significantly decreased intracellularly in all experimental groups ( = 0.002 , Friedman ) .
AA group exhibited significantly higher cellular counts on days 3 , 6 , 7 , and 13 ( < 0.05 ) and the highest CFUs at 14 days [ median-CFUs ( Q25/Q75 ) ; 40 ( 15/50 ) , = 0.043 ] .
Significantly higher Nanog expression was noted in AA group [ median gene-copies/PGK1 ( Q25/Q75 ) ; 0.0006 ( @ @ @ @ @ @ @ ] .
Significant multilineage differentiation abilities , especially into osteogenic and chondrogenic directions , were further evident in the AA group .
Conclusions : AA stimulation enhances G-MSCs ' stemness , proliferation , and differentiation properties , effects which are associated with a Wnt/-catenin signaling pathway activation .
Apart from initially boosting cellular metabolism as well as Sox2 and Oct4A pluripotency marker expression , inflammation appeared to attenuate these AA-induced positive effects .
Current results reveal that for AA to exert its beneficial effects on G-MSCs ' cellular attributes , it requires to @ @ @ @ @ @

Objective: Ascorbic acid (AA) and controlled inflammatory stimuli are postulated to possess the ability to independently exert positive effects on a variety of proliferative, pluripotency, and differentiation attributes of gingival mesenchymal stem/progenitor cells (G-MSCs). The current study's objective was to explore and compare for the first time the impact of the major inflammatory cytokines (IL-1/TNF-/IFN-), AA, or their combination on multipotency/pluripotency, proliferative, and differentiation characteristics of G-MSCs.
Design: Human G-MSCs (= 5) were isolated and cultured in basic medium (control group), in basic medium with major inflammatory cytokines; 1 ng/ml IL-1, 10 ng/ml TNF-, and 100 ng/ml IFN-(inflammatory group), in basic medium with 250 mol/l AA (AA group) and in inflammatory medium supplemented by AA (inflammatory/AA group). All media were renewed three times per week. In stimulated G-MSCs intracellular-catenin at 1 hour, pluripotency gene expression at 1, 3, and 5 days, as well as colony-forming units (CFUs) ability and cellular proliferation over 14 days were examined. Following a five-days stimulation in the designated groups, multilineage differentiation was assessed via qualitative and quantitative histochemistry as well as mRNA expression.
Results: -Catenin significantly decreased intracellularly in all experimental groups (= 0.002, Friedman). AA group exhibited significantly higher cellular counts on days 3, 6, 7, and 13 (<0.05) and the highest CFUs at 14 days [median-CFUs (Q25/Q75); 40 (15/50),= 0.043]. Significantly higher Nanog expression was noted in AA group [median gene-copies/PGK1 (Q25/Q75); 0.0006 (0.0002/0.0007),<0.01, Wilcoxon-signed-rank]. Significant multilineage differentiation abilities, especially into osteogenic and chondrogenic directions, were further evident in the AA group.
Conclusions: AA stimulation enhances G-MSCs' stemness, proliferation, and differentiation properties, effects which are associated with a Wnt/-catenin signaling pathway activation. Apart from initially boosting cellular metabolism as well as Sox2 and Oct4A pluripotency marker expression, inflammation appeared to attenuate these AA-induced positive effects. Current results reveal that for AA to exert its beneficial effects on G-MSCs' cellular attributes, it requires to act in an inflammation-free microenvironment.


greenmedinfo--2020-09-08--These findings suggest that oridonin may have promising therapeutic application in diffuse large B c

These findings suggest that oridonin may have promising therapeutic application in diffuse large B cell lymphoma.

This study investigated the cytotoxic effect of oridonin ( ORI ) , a diterpenoid isolated from Rabdosia rubescens , in @ @ @ @ @ lymphoma ( DLBCL ) in vitro and in vivo and the potential molecular mechanisms for @ @ @ @ @ treatment caused reactive oxygen species ( ROS ) -mediated oxidative DNA damage response ( DDR @ @ @ @ @ kinase ( JNK ) pathway activation , leading to an induction of intrinsic apoptosis .
@ @ @ @ @ and attenuated the expression of phospho-histone H2AX and phospho-JNK , indicating that ROS-mediated DNA damage @ @ @ @ @ involved in ORI-induced apoptosis .
The systemic administration of ORI suppressed the growth of human @ @ @ @ @ toxicity .
These findings suggest that ORI may have promising therapeutic application in DLBCL .

This study investigated the cytotoxic effect of oridonin (ORI), a diterpenoid isolated from Rabdosia rubescens, in human diffuse large B cell lymphoma (DLBCL) in vitro and in vivo and the potential molecular mechanisms for ORI-induced cell apoptosis. ORI treatment caused reactive oxygen species (ROS)-mediated oxidative DNA damage response (DDR) and the c-Jun N-terminal kinase (JNK) pathway activation, leading to an induction of intrinsic apoptosis. ROS abolition blocked ORI-induced apoptosis and attenuated the expression of phospho-histone H2AX and phospho-JNK, indicating that ROS-mediated DNA damage and JNK pathway activation were involved in ORI-induced apoptosis. The systemic administration of ORI suppressed the growth of human DLBCL xenografts without showing significant toxicity. These findings suggest that ORI may have promising therapeutic application in DLBCL.


greenmedinfo--2020-09-08--A novel combination of oridonin and valproic acid in enhancement of apoptosis induction of HL-60 leu

A novel combination of oridonin and valproic acid in enhancement of apoptosis induction of HL-60 leukemia cells.

Oridonin , obtained from the traditional Chinese herbal medicine rabdosia rubescens , exerts potent antitumor activities in cancer cells .
Valproic acid ( VPA ) , as a potent histone deacetylase inhibitor ( HDACI ) , also plays an important role in inhibition of proliferation of tumor cells .
However , there are no reports so far on the cooperation between oridonin and VPA for anti-leukemic effect .
Therefore , in the present study , we undertook experiments to determine whether lower concentration of oridonin in conjunction with lower concentration of VPA would produce even more encouraging synergistic effect than @ @ @ @ @ @ @ clarify its molecular mechanism .
The results demonstrated that the lower concentration of oridonin in combination with lower concentration of VPA synergistically inhibited the proliferation of HL-60 cells , and induced obvious caspase-dependent apoptosis through activation of the intrinsic apoptosis pathway , which is involved in the downregulation of Bcl-2/Bax ratio , release of cytochrome c to cytosol and caspase-9 activation , as well as through the extrinsic apoptosis pathway mediated by Fas/FasL and caspase-8 activation .
In addition , MAPK signaling pathway was also involved in apoptosis induced by oridonin plus VPA @ @ @ @ @ @ @ vivo remarkably reduced the xenograft tumor size and triggered tumor cell apoptosis .
Taken together , the novel combination of oridonin plus VPA exerted synergistic anti-proliferative and apoptosis-inducing effects on human myeloid leukemia cells , and may serve as a potential promising anti-leukemia strategy .

Oridonin, obtained from the traditional Chinese herbal medicine rabdosia rubescens, exerts potent antitumor activities in cancer cells. Valproic acid (VPA), as a potent histone deacetylase inhibitor (HDACI), also plays an important role in inhibition of proliferation of tumor cells. However, there are no reports so far on the cooperation between oridonin and VPA for anti-leukemic effect. Therefore, in the present study, we undertook experiments to determine whether lower concentration of oridonin in conjunction with lower concentration of VPA would produce even more encouraging synergistic effect than each of them alone, and to clarify its molecular mechanism. The results demonstrated that the lower concentration of oridonin in combination with lower concentration of VPA synergistically inhibited the proliferation of HL-60 cells, and induced obvious caspase-dependent apoptosis through activation of the intrinsic apoptosis pathway, which is involved in the downregulation of Bcl-2/Bax ratio, release of cytochrome c to cytosol and caspase-9 activation, as well as through the extrinsic apoptosis pathway mediated by Fas/FasL and caspase-8 activation. In addition, MAPK signaling pathway was also involved in apoptosis induced by oridonin plus VPA. Furthermore, the combination treatment in vivo remarkably reduced the xenograft tumor size and triggered tumor cell apoptosis. Taken together, the novel combination of oridonin plus VPA exerted synergistic anti-proliferative and apoptosis-inducing effects on human myeloid leukemia cells, and may serve as a potential promising anti-leukemia strategy.