greenmedinfo--2020-03-14--The results indicated that S. chinensis might be a candidate cosmetic preservative for its good anti

The results indicated that S. chinensis might be a candidate cosmetic preservative for its good antibacterial activity and multiple targets on E. coli.

Schisandra chinensis ( Turcz . )
Baill ( S. chinensis ) , an edible traditional medicine herb , has a strong constitution , which extract has good antibacterial activity .
The study investigated its antibacterial properties on E. coli , to find a candidate for the development as new preservative .
In vitro antibacterial assay showed that S. chinensis extract ( SCE ) effectively inhibited the growth of test bacteria with MBC of 18 mg/mL .
In model cosmetic system of O/W emulsions , SCE possessed a great antibacterial capacity .
The growth curves of E. coli treated with SCE @ @ @ @ @ @ @ log phase .
Scanning electron microscopy showed that the treated E. coli cells exhibited wrinkled and witheredsurfaces , and disappearing outmost layer , suggesting S. chinensis extract can damage S. aureus cell member and wall , in addition , the leakage of periplasm enzyme AKPase and the increased activities of Na/K-ATPase and Ca-ATPase in cell membrane were also consistent with the microscopy results .
Moreover , the S. chinensis extract can decrease the activities of dehydrogenase and total ATPase and the content of intracellular proteins , and bind with S. aureus DNA by @ @ @ @ @ @ @ indicated that SCE might be a candidate cosmetic preservative for its good antibacterial activity and multiple targets on E. coli .

Schisandra chinensis (Turcz.) Baill (S. chinensis), an edible traditional medicine herb, has a strong constitution, which extract has good antibacterial activity. The study investigated its antibacterial properties on E. coli, to find a candidate for the development as new preservative. In vitro antibacterial assay showed that S. chinensis extract (SCE) effectively inhibited the growth of test bacteria with MBC of 18 mg/mL. In model cosmetic system of O/W emulsions, SCE possessed a great antibacterial capacity. The growth curves of E. coli treated with SCE exhibited an extended lag phase and restricted log phase. Scanning electron microscopy showed that the treated E. coli cells exhibited wrinkled and witheredsurfaces, and disappearing outmost layer, suggesting S. chinensis extract can damage S. aureus cell member and wall, in addition, the leakage of periplasm enzyme AKPase and the increased activities of Na/K-ATPase and Ca-ATPase in cell membrane were also consistent with the microscopy results. Moreover, the S. chinensis extract can decrease the activities of dehydrogenase and total ATPase and the content of intracellular proteins, and bind with S. aureus DNA by electrostatic and groove binding. The results indicated that SCE might be a candidate cosmetic preservative for its good antibacterial activity and multiple targets on E. coli.


greenmedinfo--2020-03-14--Schisantherin A causes endothelium-dependent and -independent vasorelaxation in isolated rat thoraci

Schisantherin A causes endothelium-dependent and -independent vasorelaxation in isolated rat thoracic aorta.

AIMS : Schisandra is a good choice in Traditional Chinese Medicine for the therapy of cardiovascular diseases , but whether it contains a or some specific component ( s ) responsible these effects are still unclear .
In the present study , we explored whether Schisantherin A ( SCA ) causes vasorelaxation in isolated rat thoracic aorta .
MAIN METHODS : We selected SCA , one of the main monomers of lignans from Schisandra , to examine its vasorelaxant effect on the isolated rat thoracic aorta and also exploited several tool inhibitors to probe its underlying mechanisms .
KEY FINDINGS @ @ @ @ @ @ @ endothelium-intact ( 43.56 ± 2.17 % ) and endothelium-denuded thoracic aorta strips ( 18.76 ± 3.95 % ) pre-contracted by phenylephrine ( PE ) .
However , after treated with indomethacin or L-NAME , SCA showed only partial vasorelaxant effects .
Whereas , this vasorelaxation by SCA was not changed with specific K-channel inhibitors , i.e .
barium chloride ( BaCl ) , 4-aminopyridine ( 4-AP ) , tetraethylamine ( TEA ) , and glibenclamide .
SCA had no effect on the aorta strips pre-contracted by PE in neither Ca-free nor CaClconditions .
@ @ @ @ @ @ @ Kenvironment , SCA partly abolished the vasocontraction induced by CaCl .
SIGNIFICANCE : It was the first report to demonstrate that SCA had endothelium-dependent and -independent vasorelaxant effects on the isolated rat thoracic aorta , and the underlying mechanisms might be involved into its promoting the production of nitric oxide ( NO ) and prostacyclin ( PGI ) , and inhibiting the voltage-dependent calcium channels ( VDCCs ) opening .
This study may partially explain the use of Schisandra in cardiovascular diseases and facilitate further drug development as well .

AIMS: Schisandra is a good choice in Traditional Chinese Medicine for the therapy of cardiovascular diseases, but whether it contains a or some specific component (s) responsible these effects are still unclear. In the present study, we explored whether Schisantherin A (SCA) causes vasorelaxation in isolated rat thoracic aorta.
MAIN METHODS: We selected SCA, one of the main monomers of lignans from Schisandra, to examine its vasorelaxant effect on the isolated rat thoracic aorta and also exploited several tool inhibitors to probe its underlying mechanisms.
KEY FINDINGS: SCA produced relaxation concentration-dependently on the endothelium-intact (43.56 ± 2.17%) and endothelium-denuded thoracic aorta strips (18.76 ± 3.95%) pre-contracted by phenylephrine (PE). However, after treated with indomethacin or L-NAME, SCA showed only partial vasorelaxant effects. Whereas, this vasorelaxation by SCA was not changed with specific K-channel inhibitors, i.e. barium chloride (BaCl), 4-aminopyridine (4-AP), tetraethylamine (TEA), and glibenclamide. SCA had no effect on the aorta strips pre-contracted by PE in neither Ca-free nor CaClconditions. But, in the Cafree and high Kenvironment, SCA partly abolished the vasocontraction induced by CaCl.
SIGNIFICANCE: It was the first report to demonstrate that SCA had endothelium-dependent and -independent vasorelaxant effects on the isolated rat thoracic aorta, and the underlying mechanisms might be involved into its promoting the production of nitric oxide (NO) and prostacyclin (PGI), and inhibiting the voltage-dependent calcium channels (VDCCs) opening. This study may partially explain the use of Schisandra in cardiovascular diseases and facilitate further drug development as well.


greenmedinfo--2020-03-14--Schisandrin A and B enhance the dentate gyrus neurogenesis in mouse hippocampus.

Schisandrin A and B ( Sch A and B ) are the main effective components of Schisandra chinensis ( S. chinensis ) , which is traditionally used to enhance mental and intellectual functions in eastern Asia .
Previously , we reported Sch A and B remarkably affect adult neurogenesis in the subventricular zone of mouse lateral ventricle .
Since the neurogenesis in the hippocampal dentate gyrus ( DG ) is more important to learning , memory and cognition , here we further examined their effects on the adult DG neurogenesis .
Phosphohistone H3 ( PHH3 ) immunostaining showed that Sch @ @ @ @ @ @ @ the DG .
Glial fibrillary acidic protein ( GFAP , mostly labels astrocytes and some stem cells ) staining was used to further identify the proliferating cell type .
Dramatically , increases of GFAPcells in both Sch A and B treated groups were observed .
What 's more , the total numbers of the mature neurons labeled by neuron-specific nuclear protein ( NeuN ) were also increased in both Sch A and B treated groups compared with the controls .
Together , Sch A and B enhance the adult DG neurogenesis by increasing @ @ @ @ @ @ @ maturation of DG neurons .
Our study shed a new light on the neuropharmacological functions of the herbal medicine S. chinensis .

Schisandrin A and B (Sch A and B) are the main effective components of Schisandra chinensis (S. chinensis), which is traditionally used to enhance mental and intellectual functions in eastern Asia. Previously, we reported Sch A and B remarkably affect adult neurogenesis in the subventricular zone of mouse lateral ventricle. Since the neurogenesis in the hippocampal dentate gyrus (DG) is more important to learning, memory and cognition, here we further examined their effects on the adult DG neurogenesis. Phosphohistone H3 (PHH3) immunostaining showed that Sch B significantly enhanced the cell proliferation in the DG. Glial fibrillary acidic protein (GFAP, mostly labels astrocytes and some stem cells) staining was used to further identify the proliferating cell type. Dramatically, increases of GFAPcells in both Sch A and B treated groups were observed. What's more, the total numbers of the mature neurons labeled by neuron-specific nuclear protein (NeuN) were also increased in both Sch A and B treated groups compared with the controls. Together, Sch A and B enhance the adult DG neurogenesis by increasing astrocytes/stem cells and improving the survival and maturation of DG neurons. Our study shed a new light on the neuropharmacological functions of the herbal medicine S. chinensis.


greenmedinfo--2020-03-14--Effect of gomisin A on osteoblast differentiation in high glucose-mediated oxidative stress.

BACKGROUND : Gomisin A is a lignan isolated from the hexane of Schisandra chinensis fruit extract with antioxidant properties .
Oxidative stress mediated by high glucose is one of the major complications of diabetes mellitus .
PURPOSE : This study investigates the role of gomisin A in osteoblast differentiation under high glucose-induced oxidative stress in MC3T3 E1 cells and determines its relationship with heme oxygenase-1 ( HO-1 ) and mitochondrial biogenesis .
METHODS : MC3T3 E1 cells were treated by gomisin A following induced by high glucose levels and glucose oxidase to investigate the inhibitory effect of gomisin A against @ @ @ @ @ @ @ analysis , alizarin red staining , alkaline phosphatase ( ALP ) activity , analysis of reactive oxygen species ( ROS ) and confocal microscopy were used to determine mitochondrial biogenesis , oxidative stress , osteoblast differentiation and mineralization .
To analyze the role of HO-1 , the MC3T3 E1 cells were treated with the HO-1 inhibitor zinc protoporphyrin IX ( ZnPP ) .
RESULTS : Gomisin A enhanced the expression of HO-1 , increased mitochondrial biogenesis factors ( peroxisome proliferator-activated receptor gamma coactivator 1-alpha , nuclear respiratory factor-1 , and mitochondrial transcription factor @ @ @ @ @ @ @ superoxide dismutases and manganese superoxide dismutase ) , osteoblast differentiation molecules ( bone morphogenic protein-2/7 , osteoprotegerin and Runt-related transcription factor-2 ) and mineralization by upregulation of ALP and alizarin red staining , which were decreased by ZnPP and high glucose oxidative stress .
Similarly , gomisin A inhibited ROS which was increased by ZnPP and the high glucose-mediated oxidative stress .
CONCLUSIONS : The findings demonstrated the antioxidative effects of gomisin A , and its role in mitochondrial biogenesis and osteoblast differentiation .
It potentially regulated osteoblast differentiation under high glucose-induced oxidative @ @ @ @ @ @ @ of mitochondrial homeostasis .
Thus , gomisin A may represent a potential therapeutic agent for prevention of bone fragility fractures and implant failure triggered by diabetes .

BACKGROUND: Gomisin A is a lignan isolated from the hexane of Schisandra chinensis fruit extract with antioxidant properties. Oxidative stress mediated by high glucose is one of the major complications of diabetes mellitus.
PURPOSE: This study investigates the role of gomisin A in osteoblast differentiation under high glucose-induced oxidative stress in MC3T3 E1 cells and determines its relationship with heme oxygenase-1 (HO-1) and mitochondrial biogenesis.
METHODS: MC3T3 E1 cells were treated by gomisin A following induced by high glucose levels and glucose oxidase to investigate the inhibitory effect of gomisin A against high glucose oxidative stress. Western blot analysis, alizarin red staining, alkaline phosphatase (ALP) activity, analysis of reactive oxygen species (ROS) and confocal microscopy were used to determine mitochondrial biogenesis, oxidative stress, osteoblast differentiation and mineralization. To analyze the role of HO-1, the MC3T3 E1 cells were treated with the HO-1 inhibitor zinc protoporphyrin IX (ZnPP).
RESULTS: Gomisin A enhanced the expression of HO-1, increased mitochondrial biogenesis factors (peroxisome proliferator-activated receptor gamma coactivator 1-alpha, nuclear respiratory factor-1, and mitochondrial transcription factor A), antioxidant enzymes (copper-zinc superoxide dismutases and manganese superoxide dismutase), osteoblast differentiation molecules (bone morphogenic protein-2/7, osteoprotegerin and Runt-related transcription factor-2) and mineralization by upregulation of ALP and alizarin red staining, which were decreased by ZnPP and high glucose oxidative stress. Similarly, gomisin A inhibited ROS which was increased by ZnPP and the high glucose-mediated oxidative stress.
CONCLUSIONS: The findings demonstrated the antioxidative effects of gomisin A, and its role in mitochondrial biogenesis and osteoblast differentiation. It potentially regulated osteoblast differentiation under high glucose-induced oxidative stress via upregulation of HO-1 and maintenance of mitochondrial homeostasis. Thus, gomisin A may represent a potential therapeutic agent for prevention of bone fragility fractures and implant failure triggered by diabetes.


greenmedinfo--2020-03-14--Gomisin A has the potential to reduce metastatic melanoma through its anti-proliferative and anti-me

Gomisin A has the potential to reduce metastatic melanoma through its anti-proliferative and anti-metastatic effects.

BACKGROUND : Gomisin A ( G.A ) , a lignan compound extracted from the fruits of Schisandra chinensis , is known to exert anti-tumor effects on hepatocarcinoma and colorectal cancer cells .
Suppression of proliferation and metastatic abilities of cancer cells are some effective cancer treatment methods .
PURPOSE : The objective of this study is to investigate the effects of G.A on metastatic melanoma , and the mechanism by which it affects metastatic melanoma .
STUDY DESIGN : The anti-proliferative and anti-metastatic effects of G.A were observed in in vitro and in vivo .
METHODS : WST assay and @ @ @ @ @ @ @ effect of G.A on proliferation , cell cycle arrest , and apoptosis in metastatic melanoma cell lines .
Migration and invasion abilities of G.A-treated melanoma cells were observed by wound healing and invasion assays .
RESULTS : G.A ( 25-100 μM ) decreased the viability of melanoma cells by inducing cell cycle arrest and apoptosis .
These anti-proliferative effects of G.A were found to be mediated by AMPK , ERK , and JNK activation .
G.A ( 5-20 μM ) decreased the migration and invasion of melanoma cells by suppressing epithelial-mesenchymal transition ( @ @ @ @ @ @ @ 2-50 mg/kg ) inhibited lung metastasis by suppressing EMT and inducing cell cycle arrest and apoptosis in melanoma cells .
CONCLUSION : These results conclude that G.A has the potential to reduce metastatic melanoma through its anti-proliferative and anti-metastatic effects .

BACKGROUND: Gomisin A (G.A), a lignan compound extracted from the fruits of Schisandra chinensis, is known to exert anti-tumor effects on hepatocarcinoma and colorectal cancer cells. Suppression of proliferation and metastatic abilities of cancer cells are some effective cancer treatment methods.
PURPOSE: The objective of this study is to investigate the effects of G.A on metastatic melanoma, and the mechanism by which it affects metastatic melanoma.
STUDY DESIGN: The anti-proliferative and anti-metastatic effects of G.A were observed in in vitro and in vivo.
METHODS: WST assay and flow cytometry were conducted to investigate the effect of G.A on proliferation, cell cycle arrest, and apoptosis in metastatic melanoma cell lines. Migration and invasion abilities of G.A-treated melanoma cells were observed by wound healing and invasion assays.
RESULTS: G.A (25-100 μM) decreased the viability of melanoma cells by inducing cell cycle arrest and apoptosis. These anti-proliferative effects of G.A were found to be mediated by AMPK, ERK, and JNK activation. G.A (5-20 μM) decreased the migration and invasion of melanoma cells by suppressing epithelial-mesenchymal transition (EMT). Consequently, G.A (2-50 mg/kg) inhibited lung metastasis by suppressing EMT and inducing cell cycle arrest and apoptosis in melanoma cells.
CONCLUSION: These results conclude that G.A has the potential to reduce metastatic melanoma through its anti-proliferative and anti-metastatic effects.


greenmedinfo--2020-03-14--Lignans and terpenoids from the leaves of Schisandra chinensis.

Fifteen constituents , include one new lignan ( schisandroside E , 1 ) and one new terpenoid ( schisandenoid A @ @ @ @ @ as nine known lignans and four known terpenoids , were isolated from Schisandra chinensis leaves @ @ @ @ @ 1-2 were established by entirely meticulous spectroscopic analysis ( NMR , MS , CD , @ @ @ @ @ All compounds were tested for cytotoxicity against MGC-803 , Caco-2 and Ishikawa cell lines .
@ @ @ @ @ against these three cancer cell lines with IC50﹤1 μM .

Fifteen constituents, include one new lignan (schisandroside E, 1) and one new terpenoid (schisandenoid A, 2) as well as nine known lignans and four known terpenoids, were isolated from Schisandra chinensis leaves. The structures of compounds 1-2 were established by entirely meticulous spectroscopic analysis (NMR, MS, CD, IR and UV). All compounds were tested for cytotoxicity against MGC-803, Caco-2 and Ishikawa cell lines. Some compounds showed strong cytotoxicity against these three cancer cell lines with IC50﹤1 μM.


greenmedinfo--2020-03-15--Effects of ayahuasca on mental health and quality of life in naïve users.

Ayahuasca is a hallucinogenic decoction used as a traditional medicine in several Amazonian regions .
The ritualistic use of ayahuasca has spread throughout many countries , making it necessary to study its risks and benefits .
Two sub-studies were designed for this investigation .
In sub-study 1 , a psychiatric interview and a battery of questionnaires were administered to subjects ( n = 40 ) before their first ayahuasca use .
Two follow-ups were conducted at 1 and 6 months .
In sub-study 2 , the same interview and battery of questionnaires were administered to long-term ayahuasca users ( n @ @ @ @ @ @ @ compared with those of the ayahuasca-naïve group .
In the first assessment , nearly half ( 45 % ) of the naïve users were found to meet the diagnostic criteria for a psychiatric disorder .
After the ayahuasca use , more than 80 % of those subjects showed clinical improvements that persisted at 6 months .
The questionnaires showed significant reductions in depression and psychopathology .
Regarding sub-study 2 , long-term users showed lower depression scores , and higher scores for self-transcendence and quality of life , as compared to their peers in @ @ @ @ @ @ @ naturalistic studies assessing the eventual risks and potentialbenefits of ayahuasca are warranted .

Ayahuasca is a hallucinogenic decoction used as a traditional medicine in several Amazonian regions. The ritualistic use of ayahuasca has spread throughout many countries, making it necessary to study its risks and benefits. Two sub-studies were designed for this investigation. In sub-study 1, a psychiatric interview and a battery of questionnaires were administered to subjects (n = 40) before their first ayahuasca use. Two follow-ups were conducted at 1 and 6 months. In sub-study 2, the same interview and battery of questionnaires were administered to long-term ayahuasca users (n = 23) and their scores were compared with those of the ayahuasca-naïve group. In the first assessment, nearly half (45%) of the naïve users were found to meet the diagnostic criteria for a psychiatric disorder. After the ayahuasca use, more than 80% of those subjects showed clinical improvements that persisted at 6 months. The questionnaires showed significant reductions in depression and psychopathology. Regarding sub-study 2, long-term users showed lower depression scores, and higher scores for self-transcendence and quality of life, as compared to their peers in sub-study 1. Further controlled and observational naturalistic studies assessing the eventual risks and potentialbenefits of ayahuasca are warranted.


greenmedinfo--2020-03-15--These results suggest that gomisin A protects the liver from injury after administration of acetamin

The preventive effect of gomisin A , a lignan component of shizandra fruits , on acetaminophen-induced hepatotoxicity in rats was @ @ @ @ @ analysis .
Acetaminophen at a dose of 750 mg/kg was administered to male Wistar rats @ @ @ @ @ 50 mg/kg of gomisin A. Gomisin A inhibited not only the elevation of serum aminotransferase @ @ @ @ @ , characteristic of acetaminophen administration , but also the appearance of histological changes such as @ @ @ @ @ .
However , gomisin A did not affect the decrease in liver glutathione content .
@ @ @ @ @ A protects the liver from injury after administration of acetaminophen through the suppression of lipid @ @

The preventive effect of gomisin A, a lignan component of shizandra fruits, on acetaminophen-induced hepatotoxicity in rats was examined by histological and biochemical analysis. Acetaminophen at a dose of 750 mg/kg was administered to male Wistar rats with or without pretreatment with 50 mg/kg of gomisin A. Gomisin A inhibited not only the elevation of serum aminotransferase activity and hepatic lipoperoxides content, characteristic of acetaminophen administration, but also the appearance of histological changes such as degeneration and necrosis of hepatocytes. However, gomisin A did not affect the decrease in liver glutathione content. These results suggest that gomisin A protects the liver from injury after administration of acetaminophen through the suppression of lipid peroxidation.


greenmedinfo--2020-03-15--Anti-HIV-1 activity of lignans from the fruits of Schisandra rubriflora.

This study investigated the 70 % aqueous acetone extract of the fruits of Schisandra rubriflora which led to the isolation @ @ @ @ @ a new isolate , rubrisandrin C ( 1 ) , and seven known lignans ( @ @ @ @ @ of 1 was established by extensive 1D and 2D NMR spectroscopy and its absolute stereochemistry @ @ @ @ @ .
Compounds 1-5 and 7-8 were evaluated for their anti-HIV-1 activity that showed inhibitory activity @ @ @ @ @ induced syncytium formation with EC ( 50 ) values in the range of 2.26 approximately @ @ @ @ @ and 7 exerted their obvious protection of HIV-1 ( IIIB ) inducted MT-4 host cells @ @ @ @ @ index of 15.4 and 24.6 , respectively .

This study investigated the 70% aqueous acetone extract of the fruits of Schisandra rubriflora which led to the isolation of eight lignans, including a new isolate, rubrisandrin C (1), and seven known lignans (2-8). The structure of 1 was established by extensive 1D and 2D NMR spectroscopy and its absolute stereochemistry was determined by CD spectrum. Compounds 1-5 and 7-8 were evaluated for their anti-HIV-1 activity that showed inhibitory activity on HIV-1(IIIB) induced syncytium formation with EC(50) values in the range of 2.26 approximately 20.4 microg/mL. Compounds 1 and 7 exerted their obvious protection of HIV-1(IIIB) inducted MT-4 host cells lytic effects with a selectivity index of 15.4 and 24.6, respectively.


greenmedinfo--2020-03-14--Protective effects of gomisin A isolated from Schisandra chinensis against CCl(4)-induced hepatic an

Protective effects of gomisin A isolated from Schisandra chinensis against CCl(4)-induced hepatic and renal injury.

The aim of the present study was to investigate the protective effects of gomisin A , a lignan compound isolated from Schisandra chinensis , against liver and kidney damage induced by CCl ( 4 ) exposure .
We assessed alterations in organ weights , levels of serum biochemical indicators , and activation of the caspase-3 and MAPK signaling pathways and carried out histological analysis of liver and kidney tissue in rats pretreated with gomisin A for four days .
In the gomisin A/CCl ( 4 ) -treated group , only the liver experienced a significant increase in weight , whereas @ @ @ @ @ @ @ changes .
Five biochemical indicators in serum indicated that liver and kidney toxicity dramatically decreased upon gomisin A pretreatment , although the decrease in ratios varied .
Upon histological analysis , the gomisin A/CCl ( 4 ) -treated group showed less hepatocellular necrosis , a poorly dilated central vein in the liver section , decreased diameter of the glomerulus , a lower number of capillaries , and a convoluted tubule in the kidney section .
Furthermore , the formation of active caspase-3 was inhibited by gomisin A pretreatment in the gomisin A/CCl ( @ @ @ @ @ @ @ expression level of Bax protein was slightly increased .
Western blot analysis revealed that there were differences between the liver and kidney in terms of activation of the MAPK signaling pathway .
In the liver , gomisin A pretreatment increased phosphorylation of three members of the MAPK pathway when compared to that in the vehicle pretreatment group .
However , in the kidney , only the phosphorylation level of p38 was elevated upon gomisin A pretreatment , whereas levels of the other two members were decreased .
These results suggest that gomisin A @ @ @ @ @ @ @ renal injury induced by CCl ( 4 ) exposure through differential regulation of the MAPK signal transduction pathway .

The aim of the present study was to investigate the protective effects of gomisin A, a lignan compound isolated from Schisandra chinensis, against liver and kidney damage induced by CCl(4) exposure. We assessed alterations in organ weights, levels of serum biochemical indicators, and activation of the caspase-3 and MAPK signaling pathways and carried out histological analysis of liver and kidney tissue in rats pretreated with gomisin A for four days. In the gomisin A/CCl(4)-treated group, only the liver experienced a significant increase in weight, whereas the other organs did not undergo any changes. Five biochemical indicators in serum indicated that liver and kidney toxicity dramatically decreased upon gomisin A pretreatment, although the decrease in ratios varied. Upon histological analysis, the gomisin A/CCl(4)-treated group showed less hepatocellular necrosis, a poorly dilated central vein in the liver section, decreased diameter of the glomerulus, a lower number of capillaries, and a convoluted tubule in the kidney section. Furthermore, the formation of active caspase-3 was inhibited by gomisin A pretreatment in the gomisin A/CCl(4)-treated group, whereas the expression level of Bax protein was slightly increased. Western blot analysis revealed that there were differences between the liver and kidney in terms of activation of the MAPK signaling pathway. In the liver, gomisin A pretreatment increased phosphorylation of three members of the MAPK pathway when compared to that in the vehicle pretreatment group. However, in the kidney, only the phosphorylation level of p38 was elevated upon gomisin A pretreatment, whereas levels of the other two members were decreased. These results suggest that gomisin A induces marked protective effects against hepatic and renal injury induced by CCl(4) exposure through differential regulation of the MAPK signal transduction pathway.


greenmedinfo--2020-03-14--Dibenzocyclooctadiene lignans from the fruits of Schisandra rubriflora and their anti-HIV-1 activiti

Dibenzocyclooctadiene lignans from the fruits of Schisandra rubriflora and their anti-HIV-1 activities.

Two new dibenzocyclooctadiene lignans , rubrilignans A and B ( 1 , 2 ) , together with 17 known ones @ @ @ @ @ fruits of Schisandra rubriflora .
The structures of 1 and 2 were elucidated by spectroscopic @ @ @ @ @ 2D NMR techniques .
Compounds 1 and 2 were also evaluated for their anti-HIV-1 activities @ @ @ @ @ with EC ( 50 ) values of 2.26 and 1.82μg/ml , and therapeutic index values @ @ @ @ @ respectively .

Two new dibenzocyclooctadiene lignans, rubrilignans A and B (1, 2), together with 17 known ones, were isolated from the fruits of Schisandra rubriflora. The structures of 1 and 2 were elucidated by spectroscopic methods including extensive 1D and 2D NMR techniques. Compounds 1 and 2 were also evaluated for their anti-HIV-1 activities and showed weak anti-HIV-1 activity with EC(50) values of 2.26 and 1.82μg/ml, and therapeutic index values of 35.5 and 18.6, respectively.


greenmedinfo--2020-03-14--Gomisin A inhibits lipopolysaccharide-induced inflammatory responses in N9 microglia.

Gomisin A , one of the major dibenzocyclooctadiene lignans isolated from Schisandra chinensis Baill.
, has proved to possess a variety of pharmacological effects .
The aim of the present study was to investigate the anti-inflammatory and neuroprotective effects of gomisin A as well as its potential molecular mechanisms .
It was found that gomisin A not only inhibited the production of NO and PGE2 in a concentration-dependent manner but also suppressed the expressions of iNOS and COX-2 in LPS-stimulated N9 microglia without observable cytotoxicity .
Gomisin A was also able to attenuate the mRNA expression and the production of @ @ @ @ @ @ @ .
Moreover , LPS induced reactive oxygen species ( ROS ) production , NADPH oxidase activation , and gp91phox expression , which were markedly inhibited by gomisin A in microglia .
Furthermore , the data showed that gomisin A significantly down-regulated the TLR4 protein expression , and inhibited nuclear transcription factor ( NF ) -κB and mitogen-activated protein kinases ( MAPKs ) signaling pathways .
Additionally , gomisin A alleviated the cell death of SH-SY5Y neuroblastoma , rat primary cortical and hippocampal neurons induced by the conditioned-media from activated microglia .
In summary @ @ @ @ @ @ @ by attenuating the microglia-mediated neuroinflammatory response via inhibiting the TLR4-mediated NF-κB and MAPKs signaling pathways .

Gomisin A, one of the major dibenzocyclooctadiene lignans isolated from Schisandra chinensis Baill., has proved to possess a variety of pharmacological effects. The aim of the present study was to investigate the anti-inflammatory and neuroprotective effects of gomisin A as well as its potential molecular mechanisms. It was found that gomisin A not only inhibited the production of NO and PGE2 in a concentration-dependent manner but also suppressed the expressions of iNOS and COX-2 in LPS-stimulated N9 microglia without observable cytotoxicity. Gomisin A was also able to attenuate the mRNA expression and the production of pro-inflammatory factors TNF-α, IL-1β and IL-6. Moreover, LPS induced reactive oxygen species (ROS) production, NADPH oxidase activation, and gp91phox expression, which were markedly inhibited by gomisin A in microglia. Furthermore, the data showed that gomisin A significantly down-regulated the TLR4 protein expression, and inhibited nuclear transcription factor (NF)-κB and mitogen-activated protein kinases (MAPKs) signaling pathways. Additionally, gomisin A alleviated the cell death of SH-SY5Y neuroblastoma, rat primary cortical and hippocampal neurons induced by the conditioned-media from activated microglia. In summary, gomisin A may exert neuroprotective effects by attenuating the microglia-mediated neuroinflammatory response via inhibiting the TLR4-mediated NF-κB and MAPKs signaling pathways.


greenmedinfo--2020-03-14--Schisandrol B protects against cholestatic liver injury through pregnane X receptors.

BACKGROUND AND PURPOSE : Currently , ursodeoxycholic acid and obeticholic acid are the only two FDA-approved drugs for cholestatic liver diseases .
Thus , new therapeutic approaches need to be developed .
Here we have evaluated the anti-cholestasis effects of Schisandrol B ( SolB ) , a bioactive compound isolated from Schisandra sphenanthera .
EXPERIMENTAL APPROACH : Hepatoprotective effect of SolB against intrahepatic cholestasis , induced by lithocholic acid ( LCA ) , was evaluated in mice .
Metabolomic analysis and gene analysis were used to assess involvement of pregnane X receptor ( PXR ) .
Molecular docking , cell-based @ @ @ @ @ @ @ used to demonstrate the critical role of the PXR pathway in the anti-cholestasis effects of SolB .
KEY RESULTS : SolB protected against LCA-induced intrahepatic cholestasis .
Furthermore , therapeutic treatment with SolB decreased mortality in cholestatic mice .
Metabolomics and gene analysis showed that SolB accelerated metabolism of bile acids , promoted bile acid efflux into the intestine , and induced hepatic expression of the PXR-target genes Cyp3a11 , Ugt1a1 , and Oatp2 , which are involved in bile acid homeostasis .
Mechanistic studies showed that SolB activated human PXR and up-regulated @ @ @ @ @ @ @ .
Additionally , SolB did not protect Pxr-null mice from liver injury induced by intrahepatic cholestasis , thus providing genetic evidence that the effect of SolB was PXR-dependent .
CONCLUSION AND IMPLICATIONS : These findings provide direct evidence for the hepatoprotective effects of SolB against cholestasis by activating PXR .
Therefore , SolB may provide a new and effective approach to the prevention and treatment of cholestatic liver diseases .

BACKGROUND AND PURPOSE: Currently, ursodeoxycholic acid and obeticholic acid are the only two FDA-approved drugs for cholestatic liver diseases. Thus, new therapeutic approaches need to be developed. Here we have evaluated the anti-cholestasis effects of Schisandrol B (SolB), a bioactive compound isolated from Schisandra sphenanthera.
EXPERIMENTAL APPROACH: Hepatoprotective effect of SolB against intrahepatic cholestasis, induced by lithocholic acid (LCA), was evaluated in mice. Metabolomic analysis and gene analysis were used to assess involvement of pregnane X receptor (PXR). Molecular docking, cell-based reporter gene analysis and knockout mice were used to demonstrate the critical role of the PXR pathway in the anti-cholestasis effects of SolB.
KEY RESULTS: SolB protected against LCA-induced intrahepatic cholestasis. Furthermore, therapeutic treatment with SolB decreased mortality in cholestatic mice. Metabolomics and gene analysis showed that SolB accelerated metabolism of bile acids, promoted bile acid efflux into the intestine, and induced hepatic expression of the PXR-target genes Cyp3a11, Ugt1a1, and Oatp2, which are involved in bile acid homeostasis. Mechanistic studies showed that SolB activated human PXR and up-regulated PXR target genes in human cell lines. Additionally, SolB did not protect Pxr-null mice from liver injury induced by intrahepatic cholestasis, thus providing genetic evidence that the effect of SolB was PXR-dependent.
CONCLUSION AND IMPLICATIONS: These findings provide direct evidence for the hepatoprotective effects of SolB against cholestasis by activating PXR. Therefore, SolB may provide a new and effective approach to the prevention and treatment of cholestatic liver diseases.


greenmedinfo--2020-03-14--Does the 2019 Coronavirus Exist?

Does the 2019 Coronavirus Exist?

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 @

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greenmedinfo--2020-03-14--Gomisin A modulates aging progress via mitochondrial biogenesis in human diploid fibroblast cells.

Gomisin A from the fruit of Schisandra chinensis has many pharmacological properties , including hepato-protective , anti-diabetic , and anti-oxidative stress .
However , the potential benefit of gomisin A is still not well understood , especially in aging progression .
Therefore , the aim of this study was to clarify whether the promotion of mitochondrial biogenesis and autophagy of gomisin A affects anti-aging progression , and its mechanism .
Intermediate ( PD32 ) human diploid fibroblast ( HDF ) cells were brought to stress-induced premature senescence ( SIPS ) using hydrogen peroxide .
Gomisin A inhibited reactive oxygen species @ @ @ @ @ @ @ Gomisin A was also able to attenuate the activity of senescence-associatedβ-galactosidase and the production of pro-inflammatory molecules in the SIPS as well as aged HDF cells .
The antioxidant activity of gomisin A was determined by recovering the Cu/Zn , Mn-SOD , and HO-1 expression in the SIPS-HDF cells .
In mechanistic aspect , gomisin A inhibited the mitogen-activated protein kinase pathway and the translocation of nuclear factor kappa B to the nucleus .
In addition , gomisin A promoted the autophagy and mitochondrial biogenesis factors through the translocation of nuclear factor erythroid @ @ @ @ @ @ @ in the SIPS-HDF cells .
Insummary , the enhanced properties of mitochondrial biogenesis and autophagy of gomisin A has a benefit to control age-related molecules against SIPS-induced chronic oxidative stress , and gomisin A may be a potential therapeutic compound for the enhancement of intracellular homeostasis to aging progression .

Gomisin A from the fruit of Schisandra chinensis has many pharmacological properties, including hepato-protective, anti-diabetic, and anti-oxidative stress. However, the potential benefit of gomisin A is still not well understood, especially in aging progression. Therefore, the aim of this study was to clarify whether the promotion of mitochondrial biogenesis and autophagy of gomisin A affects anti-aging progression, and its mechanism. Intermediate (PD32) human diploid fibroblast (HDF) cells were brought to stress-induced premature senescence (SIPS) using hydrogen peroxide. Gomisin A inhibited reactive oxygen species production even in the SIPS-HDF cells. Gomisin A was also able to attenuate the activity of senescence-associatedβ-galactosidase and the production of pro-inflammatory molecules in the SIPS as well as aged HDF cells. The antioxidant activity of gomisin A was determined by recovering the Cu/Zn, Mn-SOD, and HO-1 expression in the SIPS-HDF cells. In mechanistic aspect, gomisin A inhibited the mitogen-activated protein kinase pathway and the translocation of nuclear factor kappa B to the nucleus. In addition, gomisin A promoted the autophagy and mitochondrial biogenesis factors through the translocation of nuclear factor erythroid 2-related factor-2, and inhibited aging progression in the SIPS-HDF cells. Insummary, the enhanced properties of mitochondrial biogenesis and autophagy of gomisin A has a benefit to control age-related molecules against SIPS-induced chronic oxidative stress, and gomisin A may be a potential therapeutic compound for the enhancement of intracellular homeostasis to aging progression.


greenmedinfo--2020-03-14--Schisanhenol improves learning and memory in scopolamine-treated mice.

PURPOSE : Schisanhenol is a compound derived from the fruit of a traditional Chinese herb Schisandra rubriflora .
The aim of the present study was to evaluate the effect of Schisanhenol on the cognitive impairment induced by scopolamine .
MATERIAL AND METHODS : Male mice were randomly divided into three Schisanhenol groups ( 10 , 30 , 100 mg/kg ) , Galantamine group ( 3 mg/kg ) , model group ( 1mg/kg scopolamine ) , and vehicle control group ( normal saline ) .
The learning and memory ability of mice was monitored by water morris maze .
Hippocampus of @ @ @ @ @ @ @ the activity of SOD , MDA , GSH-px , AChE were measured with standard biochemical procedures .
Western blotting was used to analyze the expression of SIRT1 , PGC-1α , phosphorylated Tau proteins .
RESULTS : Intraperitoneal administration of Schisanhenol ( 10 , 30 or 100 mg/kg ) significantly attenuated scopolamine-induced cognitive impairment in water morris maze .
In addition , Schisanhenol increased the activity of SOD and GSH-px while decreased the content of AChE and MDA .
Furthermore , western blotting analysis revealed that Schisanhenol increased the levels of SIRT1 and PGC-1α @ @ @ @ @ @ @ protein ( Ser 396 ) significantly in the hippocampal tissues .
CONCLUSIONS : Our findings indicated that Schisanhenol can attenuate scopolamine-induced learning impairment and enhance cognitive function , the mechanism via improve the cholinergic system and antioxidant ability , activate SIRT1-PGC1α signaling , inhibit the phosphorylation of Tau , and would be an effective candidate against cognitive disorders , such as Alzheimer 's disease .

PURPOSE: Schisanhenol is a compound derived from the fruit of a traditional Chinese herb Schisandra rubriflora. The aim of the present study was to evaluate the effect of Schisanhenol on the cognitive impairment induced by scopolamine.
MATERIAL AND METHODS: Male mice were randomly divided into three Schisanhenol groups (10, 30, 100 mg/kg), Galantamine group (3 mg/kg), model group (1mg/kg scopolamine), and vehicle control group (normal saline). The learning and memory ability of mice was monitored by water morris maze. Hippocampus of mice were collected after behavioral testing and the activity of SOD, MDA, GSH-px, AChE were measured with standard biochemical procedures. Western blotting was used to analyze the expression of SIRT1, PGC-1α, phosphorylated Tau proteins.
RESULTS: Intraperitoneal administration of Schisanhenol (10, 30 or 100 mg/kg) significantly attenuated scopolamine-induced cognitive impairment in water morris maze. In addition, Schisanhenol increased the activity of SOD and GSH-px while decreased the content of AChE and MDA. Furthermore, western blotting analysis revealed that Schisanhenol increased the levels of SIRT1 and PGC-1α and decreased the level of phosphorylated Tau protein (Ser 396) significantly in the hippocampal tissues.
CONCLUSIONS: Our findings indicated that Schisanhenol can attenuate scopolamine-induced learning impairment and enhance cognitive function, the mechanism via improve the cholinergic system and antioxidant ability, activate SIRT1-PGC1α signaling, inhibit the phosphorylation of Tau, and would be an effective candidate against cognitive disorders, such as Alzheimer's disease.


greenmedinfo--2020-03-15--The effects of pomegranate supplementation on biomarkers of inflammation and endothelial dysfunction

The effects of pomegranate supplementation on biomarkers of inflammation and endothelial dysfunction.

OBJECTS : Cardiovascular disease ( CVD ) is one of the leading causes of death worldwide .
CVD is associated with increased levels of reactive oxygen species which are pro-inflammatory and can damage the endothelium .
The pomegranate fruit is a rich source of phytochemicals with a high antioxidant and anti-inflammatory activity , possessing thus health benefits .
This systematic review and meta-analysis aims to evaluate the effect of pomegranate juice on the biomarkers of inflammation and vascular dysfunction .
METHODS : Studies were identified using the PubMed/Medline and SCOPUS databases .
Screening of relevant articles and references was carried @ @ @ @ @ @ @ This systematic review and meta-analysis was performed using the Preferred Items for Reporting of Systematic Reviews and Meta-Analyses ( PRISMA ) guidelines .
RESULTS : Overall , 16 randomized controlled trials ( RCTs ) involving 572 subjects were included in this study .
Combining effect sizes from 16 studies , we recorded that pomegranate supplementation significantly reduced hs-CRP , IL-6 and TNF-α ( Weighted Mean Diﬀ ; erences ( WMD ) : -6.57 mg/L , 95 % CI : -10.04 to -3.10 , P = 0.000 ; WMD : -1.68 pg/mL , 95 @ @ @ @ @ @ @ P = 0.000 ; WMD : -2.37 pg/mL , 95 % CI : -3.67 , -1.07 , P = 0.00 , respectively ) levels , when compared to placebo .
No significant reduction was found in CRP ( WMD : 2.19 mg/dL,95 % CI : -3.28 , 7.67 , P = 0.61 ) , E-selectin ( WMD : 8.42 ng/mL , 95 % CI : -22.9 , 39.8 , P = 0.599 ) , ICAM ( WMD= -17.38 ng/mL , 95 % CI : -53.43 , 18.66 , P = 0.107 ) , @ @ @ @ @ @ @ 95 % CI : -229.26 , 90.61 , P = 0.396 ) or MDA ( WMD : 0.031 μmol/L , 95 % CI : -1.56 , 0.218 , P = 0.746 ) comparing pomegranate supplementation to placebo .
CONCLUSION : We found a significant effect of pomegranate supplementation on hs-CRP , IL-6 and TNF-α in adults .
However , the effects of pomegranate supplementation on CRP , E-selectin , ICAM , VCAM or MDA were not significant in this meta-analysis .

OBJECTS: Cardiovascular disease (CVD) is one of the leading causes of death worldwide. CVD is associated with increased levels of reactive oxygen species which are pro-inflammatory and can damage the endothelium. The pomegranate fruit is a rich source of phytochemicals with a high antioxidant and anti-inflammatory activity, possessing thus health benefits. This systematic review and meta-analysis aims to evaluate the effect of pomegranate juice on the biomarkers of inflammation and vascular dysfunction.
METHODS: Studies were identified using the PubMed/Medline and SCOPUS databases. Screening of relevant articles and references was carried out from inception until May 2019. This systematic review and meta-analysis was performed using the Preferred Items for Reporting of Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
RESULTS: Overall, 16 randomized controlled trials (RCTs) involving 572 subjects were included in this study. Combining effect sizes from 16 studies, we recorded that pomegranate supplementation significantly reduced hs-CRP, IL-6 and TNF-α (Weighted Mean Diﬀ ;erences (WMD): -6.57 mg/L, 95 % CI: -10.04 to -3.10, P = 0.000; WMD: -1.68 pg/mL, 95 % CI: -3.52, 0.157, P = 0.000; WMD: -2.37 pg/mL, 95 % CI: -3.67, -1.07, P = 0.00, respectively) levels, when compared to placebo. No significant reduction was found in CRP (WMD: 2.19 mg/dL,95 % CI: -3.28, 7.67, P = 0.61), E-selectin (WMD: 8.42 ng/mL, 95 % CI: -22.9, 39.8, P = 0.599), ICAM (WMD= -17.38 ng/mL, 95 % CI: -53.43, 18.66, P = 0.107), VCAM (WMD: -69.32 ng/mL, 95 % CI: -229.26, 90.61, P = 0.396) or MDA (WMD: 0.031 μmol/L, 95 % CI: -1.56, 0.218, P = 0.746) comparing pomegranate supplementation to placebo.
CONCLUSION: We found a significant effect of pomegranate supplementation on hs-CRP, IL-6 and TNF-α in adults. However, the effects of pomegranate supplementation on CRP, E-selectin, ICAM, VCAM or MDA were not significant in this meta-analysis.


greenmedinfo--2020-03-15--Antioxidant and anti-inflammatory effects of Schisandra chinensis baillon hot water extract fermente

Antioxidant and anti-inflammatory effects of Schisandra chinensis baillon hot water extract fermented using Lactobacilius paracasei.

Waste management is a major part of the food industry .
The present study was designed to utilize the discarded @ @ @ @ @ and anti-inflammatory effects of a 30 % ethanol fraction ( RPG-OM-30E ) from the fermented @ @ @ @ @ byproduct were investigated using RAW 264.7 cells and zebrafish larvae .
RPG-OM-30E reduced lipopolysaccharide ( @ @ @ @ @ production in the RAW 264.7 cells .
Additionally , RPG-OM-30E inhibited mRNA expression and protein @ @ @ @ @ such as interleukin-6 ( - ) and interleukin-1β ( - ) .
The anti-inflammatory effects @ @ @ @ @ larvae .
Neutrophil migration to a wound site was decreased by RPG-OM-30E .
Neutrophil aggregation @ @ @ @ @ after induction of an LPS-induced immune response in the yolk .
Finally , the antioxidant @ @ @ @ @ were examined in vivo .
Mice with induced oxidative damage recovered from the stress following @ @ @

Waste management is a major part of the food industry. The present study was designed to utilize the discarded byproduct ofBaillon. The antioxidant and anti-inflammatory effects of a 30% ethanol fraction (RPG-OM-30E) from the fermented hot water extraction of theBaillon byproduct were investigated using RAW 264.7 cells and zebrafish larvae. RPG-OM-30E reduced lipopolysaccharide (LPS)-induced nitric oxide production in the RAW 264.7 cells. Additionally, RPG-OM-30E inhibited mRNA expression and protein secretion of pro-inflammatory cytokines, such as interleukin-6 (-) and interleukin-1β (-). The anti-inflammatory effects of RPG-OM-30E were tested inzebrafish larvae. Neutrophil migration to a wound site was decreased by RPG-OM-30E. Neutrophil aggregation was also inhibited by RPG-OM-30E after induction of an LPS-induced immune response in the yolk. Finally, the antioxidant and hepatoprotective effects of RPG-OM-30E were examined in vivo. Mice with induced oxidative damage recovered from the stress following RPG-OM-30E treatment.


greenmedinfo--2020-03-15--Lentil protein hydrolysate and a mixed training protocol is an efficient lifestyle intervention to m

Lentil protein hydrolysate and a mixed training protocol is an efficient lifestyle intervention to manage cardiovascular and renal alterations in obesity.

PURPOSE : Functional and structural changes in cardiovascular and renal systems resulting from obesity and metabolic syndrome represent a severe risk to human health .
Lifestyle interventions such as combining healthy diet with adequate physical exercise protocols are good strategies to manage these pathologies .
In this research , the effects of lentil protein hydrolysate administration , combined or not with a mixed training protocol , on insulin resistance , cardiovascular and renal functionality were studied in the obese Zucker rat experimental model .
METHODS : Thirty-two rats ( 16 lean and 16 obese subdivided in sedentary and trained animals @ @ @ @ @ @ @ whereas another 32 subdivided in the same experimental design were administered placebo .
The experiment lasted for 8 weeks .
At the end of the experimental period , insulin resistance and different parameters of cardiovascular and renal functionality were measured .
RESULTS : The individual or combined interventions with lentil protein hydrolysate and mixed training protocol were efficient at counteracting some of the metabolic , cardiovascular and renal alterations characterizing the obese Zucker rat .
Specifically , lentil protein hydrolysate decreased hyperphagia , amplitude of QRS complex , plasma ACE and selectin E @ @ @ @ @ @ @ volume and pH .
Exercise showed beneficial actions on HOMA-IR , QRS amplitude , QTc interval , urinary volume , kidney weight and Mn-SOD activity .
Interestingly , most of the mentioned benefits of exercise were more consistent when protein hydrolysate was also administered .
CONCLUSION : The interesting synergies between the two interventions assessed qualify them as alternative therapeutic strategies to treat cardiovascular and kidney diseases associated to the metabolic syndrome .

PURPOSE: Functional and structural changes in cardiovascular and renal systems resulting from obesity and metabolic syndrome represent a severe risk to human health. Lifestyle interventions such as combining healthy diet with adequate physical exercise protocols are good strategies to manage these pathologies. In this research, the effects of lentil protein hydrolysate administration, combined or not with a mixed training protocol, on insulin resistance, cardiovascular and renal functionality were studied in the obese Zucker rat experimental model.
METHODS: Thirty-two rats (16 lean and 16 obese subdivided in sedentary and trained animals) were administered lentil protein hydrolysate, whereas another 32 subdivided in the same experimental design were administered placebo. The experiment lasted for 8 weeks. At the end of the experimental period, insulin resistance and different parameters of cardiovascular and renal functionality were measured.
RESULTS: The individual or combined interventions with lentil protein hydrolysate and mixed training protocol were efficient at counteracting some of the metabolic, cardiovascular and renal alterations characterizing the obese Zucker rat. Specifically, lentil protein hydrolysate decreased hyperphagia, amplitude of QRS complex, plasma ACE and selectin E expression in aorta, while increasing urinary volume and pH. Exercise showed beneficial actions on HOMA-IR, QRS amplitude, QTc interval, urinary volume, kidney weight and Mn-SOD activity. Interestingly, most of the mentioned benefits of exercise were more consistent when protein hydrolysate was also administered.
CONCLUSION: The interesting synergies between the two interventions assessed qualify them as alternative therapeutic strategies to treat cardiovascular and kidney diseases associated to the metabolic syndrome.


greenmedinfo--2020-03-15--Ginkgo biloba L. leaf extract may be able to improve the cognitive function in patients who suffered

Ginkgo biloba L. leaf extract may be able to improve the cognitive function in patients who suffered from mild dementia during long-term administration.

Alzheimer 's disease ( AD ) is a common neurodegenerative disease , mainly manifested by cognitive dysfunction .
It seriously @ @ @ @ @ , and there is no ideal treatment strategy in clinical practice .
Clinical studies on @ @ @ @ @ .
leaf extract ( EGb ) have been reported since 1980s , and many clinical @ @ @ @ @ during the following 30 years .
However , the benefits of EGb on the treatment @ @ @ @ @ .
In this review , we collected the clinical trial reports of EGb on cognitive @ @ @ @ @ , Europe PMC , and other database since the 1980s .
Through analysis and comparison @ @ @ @ @ may be able to improve the cognitive function in patients who suffered from mild dementia @ @ @ @ @ than 24 weeks ) and appropriate dosage ( 240 mg per day ) .
The @ @ @ @ @ of the negative and positive experimental results were summarized .

Alzheimer's disease (AD) is a common neurodegenerative disease, mainly manifested by cognitive dysfunction. It seriously reduces the quality of life, and there is no ideal treatment strategy in clinical practice. Clinical studies on the treatment of AD withL. leaf extract (EGb) have been reported since 1980s, and many clinical studies have been carried out during the following 30 years. However, the benefits of EGb on the treatment of AD are still controversial. In this review, we collected the clinical trial reports of EGb on cognitive function from Pubmed, Elsevier, Europe PMC, and other database since the 1980s. Through analysis and comparison, we consider that EGb may be able to improve the cognitive function in patients who suffered from mild dementia during long-term administration (more than 24 weeks) and appropriate dosage (240 mg per day). The main evidences and existing problems of the negative and positive experimental results were summarized.


greenmedinfo--2020-03-15--Neuroprotective effects of urolithin A on H2O2-induced oxidative stress-mediated apoptosis in SK-N-M

Neuroprotective effects of urolithin A on H2O2-induced oxidative stress-mediated apoptosis in SK-N-MC cells.

BACKGROUND/OBJECTIVES : Oxidative stress causes cell damage and death , which contribute to the pathogenesis of neurodegenerative diseases .
Urolithin A ( UA ) , a gut microbial-derived metabolite of ellagitannins and ellagic acid , has high bioavailability and various health benefits such as antioxidant and anti-inflammatory effects .
However , it is unknown whether it has protective effects against oxidative stress-induced cell death .
We investigated whether UA ameliorates HO-induced neuronal cell death .
MATERIALS/METHODS : We induced oxidative damage with 300µM HOafter UA pretreatment at concentrations of 1.25 , 2.5 , and 5µM in SK-N-MC cells .
Cytotoxicity @ @ @ @ @ @ @ CCK-8 assay .
The formation of reactive oxygen species ( ROS ) was measured using a 2,7-dichlorofluorescein diacetate assay .
Hoechst 33342 staining was used to characterize morphological changes in apoptotic cells .
The expressions of apoptosis proteins were measured using Western blotting .
RESULTS : UA significantly increased cell viability and decreased intracellular ROS production in a dose-dependent manner in SK-N-MC cells .
It also decreased the Bax/Bcl-2 ratio and the expressions of cytochrome c , cleaved caspase-9 , cleaved caspase-3 , and cleaved PARP .
In addition , it suppressed the @ @ @ @ @ @ @ ( MAPK ) pathway .
CONCLUSIONS : UA attenuates oxidative stress-induced apoptosis via inhibiting the mitochondrial-related apoptosis pathway and modulating the p38 MAPK pathway , suggesting that it may be an effective neuroprotective agent .

BACKGROUND/OBJECTIVES: Oxidative stress causes cell damage and death, which contribute to the pathogenesis of neurodegenerative diseases. Urolithin A (UA), a gut microbial-derived metabolite of ellagitannins and ellagic acid, has high bioavailability and various health benefits such as antioxidant and anti-inflammatory effects. However, it is unknown whether it has protective effects against oxidative stress-induced cell death. We investigated whether UA ameliorates HO-induced neuronal cell death.
MATERIALS/METHODS: We induced oxidative damage with 300µM HOafter UA pretreatment at concentrations of 1.25, 2.5, and 5µM in SK-N-MC cells. Cytotoxicity and cell viability were determined using the CCK-8 assay. The formation of reactive oxygen species (ROS) was measured using a 2,7-dichlorofluorescein diacetate assay. Hoechst 33342 staining was used to characterize morphological changes in apoptotic cells. The expressions of apoptosis proteins were measured using Western blotting.
RESULTS: UA significantly increased cell viability and decreased intracellular ROS production in a dose-dependent manner in SK-N-MC cells. It also decreased the Bax/Bcl-2 ratio and the expressions of cytochrome c, cleaved caspase-9, cleaved caspase-3, and cleaved PARP. In addition, it suppressed the phosphorylation of the p38 mitogen-activated protein kinase (MAPK) pathway.
CONCLUSIONS: UA attenuates oxidative stress-induced apoptosis via inhibiting the mitochondrial-related apoptosis pathway and modulating the p38 MAPK pathway, suggesting that it may be an effective neuroprotective agent.


greenmedinfo--2020-03-15--Urolithin A-induced mitophagy suppresses apoptosis and attenuates intervertebral disc degeneration.

Intervertebral disc degeneration ( IDD ) is a major cause of low back pain ( LBP ) , and effective @ @ @ @ @ Previous studies reported that mitochondrial dysfunction contributes to apoptosis , and urolithin A ( UA @ @ @ @ @ Herein , we aimed to investigate the protective effect of UA-induced mitophagy on tert-butyl hydroperoxide @ @ @ @ @ in nucleus pulposus ( NP ) cells in vitro and a rat model of IDD @ @ @ @ @ , apoptosis , and mitophagy were measured in UA-treated NP cells by western blotting and @ @ @ @ @ of UA on IDD were assessed in rats with puncture-induced IDD .
The results showed @ @ @ @ @ in primary NP cells , and UA treatment inhibited TBHP-induced mitochondrial dysfunction and the intrinsic @ @ @ @ @ we revealed that UA promoted mitophagy by activating AMPK signaling in TBHP-induced NP cells .
@ @ @ @ @ shown to effectively alleviate the progression of puncture-induced IDD in rats .
Taken together , @ @ @ @ @ could be a novel and effective therapeutic strategy for IDD .

Intervertebral disc degeneration (IDD) is a major cause of low back pain (LBP), and effective therapies are still lacking. Previous studies reported that mitochondrial dysfunction contributes to apoptosis, and urolithin A (UA) specifically induces mitophagy. Herein, we aimed to investigate the protective effect of UA-induced mitophagy on tert-butyl hydroperoxide (TBHP)-induced apoptosis in nucleus pulposus (NP) cells in vitro and a rat model of IDD in vivo. Mitochondrial function, apoptosis, and mitophagy were measured in UA-treated NP cells by western blotting and immunofluorescence; the therapeutic effects of UA on IDD were assessed in rats with puncture-induced IDD. The results showed that UA could activate mitophagy in primary NP cells, and UA treatment inhibited TBHP-induced mitochondrial dysfunction and the intrinsic apoptosis pathway. Mechanistically, we revealed that UA promoted mitophagy by activating AMPK signaling in TBHP-induced NP cells. In vivo, UA was shown to effectively alleviate the progression of puncture-induced IDD in rats. Taken together, our results suggest that UA could be a novel and effective therapeutic strategy for IDD.


greenmedinfo--2020-03-15--The metabolite urolithin-A ameliorates oxidative stress in neuro-2a cells.

Urolithin A is a metabolite generated from ellagic acid and ellagitannins by the intestinal microbiota after consumption of fruits such as pomegranates or strawberries .
The objective of this study was to determine the cytoprotective capacity of this polyphenol in Neuro-2a cells subjected to oxidative stress , as well as its direct radical scavenging activity and properties as an inhibitor of oxidases .
Cells treated with this compound and HOshowed a greater response to oxidative stress than cells only treated with HO , as mitochondrial activity ( MTT assay ) , redox state ( ROS formation , lipid peroxidation ) @ @ @ @ @ @ @ ( CAT : catalase , SOD : superoxide dismutase , GR : glutathione reductase , GPx : glutathione peroxidase ) were significantly ameliorated ; additionally , urolithin A enhanced the expression of cytoprotective peroxiredoxins 1 and 3 .
Urolithin A also acted as a direct radical scavenger , showing values of 13.2μM Trolox Equivalents for Oxygen Radical Absorbance Capacity ( ORAC ) and 5.01 µM and 152.66 µM ICvalues for superoxide and 2,2-diphenyss1-picrylhydrazyl ( DPPH ) radicals , respectively .
Finally , inhibition of oxidizing enzymes , such as monoamine oxidase A and @ @ @ @ @ @ @ dose-dependent manner .
The cytoprotective effects of urolithin A could be attributed to the improvement of the cellular antioxidant battery , but also to its role as a direct radical scavenger and enzyme inhibitor of oxidases .

Urolithin A is a metabolite generated from ellagic acid and ellagitannins by the intestinal microbiota after consumption of fruits such as pomegranates or strawberries. The objective of this study was to determine the cytoprotective capacity of this polyphenol in Neuro-2a cells subjected to oxidative stress, as well as its direct radical scavenging activity and properties as an inhibitor of oxidases. Cells treated with this compound and HOshowed a greater response to oxidative stress than cells only treated with HO, as mitochondrial activity (MTT assay), redox state (ROS formation, lipid peroxidation), and the activity of antioxidant enzymes (CAT: catalase, SOD: superoxide dismutase, GR: glutathione reductase, GPx: glutathione peroxidase) were significantly ameliorated; additionally, urolithin A enhanced the expression of cytoprotective peroxiredoxins 1 and 3. Urolithin A also acted as a direct radical scavenger, showing values of 13.2μM Trolox Equivalents for Oxygen Radical Absorbance Capacity (ORAC) and 5.01 µM and 152.66 µM ICvalues for superoxide and 2,2-diphenyss1-picrylhydrazyl (DPPH) radicals, respectively. Finally, inhibition of oxidizing enzymes, such as monoamine oxidase A and tyrosinase, was also detected in a dose-dependent manner. The cytoprotective effects of urolithin A could be attributed to the improvement of the cellular antioxidant battery, but also to its role as a direct radical scavenger and enzyme inhibitor of oxidases.


greenmedinfo--2020-03-15--Protective effect of tanshinone IIA on H2O2-induced oxidative stress injury.

To investigate the protective effect of tanshinone IIA on HO-induced oxidative stress injury in rat cardiomyocytes , and further to study its potential mechanisms .
H9C2 cells were used to establish HOinjury model .
The cell viability and apoptosis were detected by CCK-8 assay and flow cytometry , respectively .
ELISA was used to detect the levels of lactate dehydrogenase ( LDH ) , superoxide dismutase ( SOD ) , and glutathione peroxidase ( GSH-Px ) .
Moreover , the levels of malondialdehyde ( MDA ) and catalase ( CAT ) were tested by TBA and visible light methods , @ @ @ @ @ @ @ detected by Western blot .
To validate the protective effect of tanshinone IIA on rat cardiomyocytes is worked by regulating the Nrf2 pathway , we further silenced Nrf2 and the above experiments were repeated .
Tanshinone IIA could promote the proliferation , and reduce the apoptosis and ROS of rat cardiomyocytes induced by HO .
Tanshinone IIA also could increase the activity of SOD , CAT , and GSH-Px , and decreased the activity of MDA and LDH .
The protein expression of Nrf2 , HO-1 , and NQO1 was significantly up-regulated in @ @ @ @ @ @ @ expression of Keap1 was significantly down-regulated .
A further study has shown that silenced Nrf2 has completely opposite results .
All those results suggested that tanshinone IIA could protect HO-induced oxidative stress injury in rat cardiomyocytes by activating Nrf2 pathway .

To investigate the protective effect of tanshinone IIA on HO-induced oxidative stress injury in rat cardiomyocytes, and further to study its potential mechanisms. H9C2 cells were used to establish HOinjury model. The cell viability and apoptosis were detected by CCK-8 assay and flow cytometry, respectively. ELISA was used to detect the levels of lactate dehydrogenase (LDH), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px). Moreover, the levels of malondialdehyde (MDA) and catalase (CAT) were tested by TBA and visible light methods, respectively. The Nrf2 pathway-related proteins were detected by Western blot. To validate the protective effect of tanshinone IIA on rat cardiomyocytes is worked by regulating the Nrf2 pathway, we further silenced Nrf2 and the above experiments were repeated. Tanshinone IIA could promote the proliferation, and reduce the apoptosis and ROS of rat cardiomyocytes induced by HO. Tanshinone IIA also could increase the activity of SOD, CAT, and GSH-Px, and decreased the activity of MDA and LDH. The protein expression of Nrf2, HO-1, and NQO1 was significantly up-regulated in tanshinone IIA groups, while the protein expression of Keap1 was significantly down-regulated. A further study has shown that silenced Nrf2 has completely opposite results. All those results suggested that tanshinone IIA could protect HO-induced oxidative stress injury in rat cardiomyocytes by activating Nrf2 pathway.


greenmedinfo--2020-03-15--Tanshinone IIA attenuates silica-induced pulmonary fibrosis.

Silicosis is an occupational pulmonary fibrosis that is caused by inhalation of silica ( SiO ) , and there are no effective drugs to treat this disease .
Tanshinone IIA ( Tan IIA ) , a natural product , has been reported to possess antioxidant and anti-fibrotic properties in various diseases .
The purpose of the current study was to examine Tan IIA 's protective effects against silica-induced pulmonary fibrosis and to explore the underlying mechanisms .
We found that in vivo treatment with Tan IIA significantly relieved silica-induced lung fibrosis in a silicosis rat model by histological and immunohistochemical @ @ @ @ @ @ @ investigations , mainly using western blot and immunofluorescence analyses , revealed that Tan IIA administration markedly inhibited the silica-induced epithelial-mesenchymal transition ( EMT ) and transforming growth factor-β1 ( TGF-β1 ) /Smad signaling pathway and also reduced silica-induced oxidative stress and activated the nuclear factor erythroid 2-related factor-2 ( Nrf2 ) signaling pathway in A549 and human bronchial epithelial ( HBE ) cells .
Furthermore , through transfection with siRNA , we demonstrate that Nrf2 activation partially mediates the suppression effects of Tan IIA on EMT and TGF-β1/Smad signaling pathway activation induced by @ @ @ @ @ @ @ effects of Tan IIA against silica-induced pulmonary fibrosis .
In our study , Tan IIA has been identified as a possible anti-oxidative and anti-fibrotic drug for silicosis .

Silicosis is an occupational pulmonary fibrosis that is caused by inhalation of silica (SiO), and there are no effective drugs to treat this disease. Tanshinone IIA (Tan IIA), a natural product, has been reported to possess antioxidant and anti-fibrotic properties in various diseases. The purpose of the current study was to examine Tan IIA's protective effects against silica-induced pulmonary fibrosis and to explore the underlying mechanisms. We found that in vivo treatment with Tan IIA significantly relieved silica-induced lung fibrosis in a silicosis rat model by histological and immunohistochemical analyses. Further, in vitro mechanistic investigations, mainly using western blot and immunofluorescence analyses, revealed that Tan IIA administration markedly inhibited the silica-induced epithelial-mesenchymal transition (EMT) and transforming growth factor-β1 (TGF-β1)/Smad signaling pathway and also reduced silica-induced oxidative stress and activated the nuclear factor erythroid 2-related factor-2 (Nrf2) signaling pathway in A549 and human bronchial epithelial (HBE) cells. Furthermore, through transfection with siRNA, we demonstrate that Nrf2 activation partially mediates the suppression effects of Tan IIA on EMT and TGF-β1/Smad signaling pathway activation induced by silica exposure, thus mediating the anti-fibrotic effects of Tan IIA against silica-induced pulmonary fibrosis. In our study, Tan IIA has been identified as a possible anti-oxidative and anti-fibrotic drug for silicosis.


greenmedinfo--2020-03-15--These results suggest that tanshinone IIA protects against lung blast injury.

Although Tanshinone IIA ( Tan IIA ) has been associated with inflammation , oxidative stress and apoptosis , the effects of Tan IIA on lung blast injury remain uncertain .
In this study , we explored the effects of Tan IIA on lung blast injury , studied its possible molecular mechanisms .
Fifty C57BL/6 mice were randomly divided into the control , blast , blast + Tan IIA , blast + LY294002 ( a PI3K inhibitor ) , or blast + Tan IIA + LY294002 groups .
Serum and lung samples were collected 48 h after blast injury .
The @ @ @ @ @ @ @ blast-induced increases in the lung weight/body weight and wet/dry ( W/D ) weight ratios , decreased the CD44and CD163-positive inflammatory cell infiltration in the lungs , reduced the IL-1β , TNF-α and IL-6 expression , and enhanced IL-10 expression .
Tan IIA also significantly alleviated the increases in MDA5 and IRE-a and the decrease in SOD-1 and reversed the low Bcl-2 expression and the high Bax and Caspase-3 expressions .
Additionally , Tan IIA significantly decreased p-PI3K and p-Akt expression and increased p-FoxO1 expression .
More importantly , both LY294002 and Tan IIA @ @ @ @ @ @ @ oxidative stress and apoptosis in lung blast injury .
These results suggest that Tan IIA protects against lung blast injury , which may be partly mediated by inhibiting the PI3K/Akt/FoxO1 signaling pathway .

Although Tanshinone IIA (Tan IIA) has been associated with inflammation, oxidative stress and apoptosis, the effects of Tan IIA on lung blast injury remain uncertain. In this study, we explored the effects of Tan IIA on lung blast injury, studied its possible molecular mechanisms. Fifty C57BL/6 mice were randomly divided into the control, blast, blast + Tan IIA, blast + LY294002 (a PI3K inhibitor), or blast + Tan IIA + LY294002 groups. Serum and lung samples were collected 48 h after blast injury. The data showed that Tan IIA significantly inhibited blast-induced increases in the lung weight/body weight and wet/dry (W/D) weight ratios,decreased the CD44and CD163-positive inflammatory cell infiltration in the lungs, reduced the IL-1β, TNF-α and IL-6 expression, and enhanced IL-10 expression. Tan IIA also significantly alleviated the increases in MDA5 and IRE-a and the decrease in SOD-1 and reversed the low Bcl-2 expression and the high Bax and Caspase-3 expressions. Additionally, Tan IIA significantly decreased p-PI3K and p-Akt expression and increased p-FoxO1 expression. More importantly, both LY294002 and Tan IIA pretreatment markedly protected against blast-induced inflammation, oxidative stress and apoptosis in lung blast injury. These results suggest that Tan IIA protects against lung blast injury, which may be partly mediated by inhibiting the PI3K/Akt/FoxO1 signaling pathway.


greenmedinfo--2020-03-15--Tanshinone IIA pretreatment promotes cell survival in human lung epithelial cells under hypoxia.

Activator protein-1 ( AP-1 ) plays a decisive role in cell proliferation , apoptosis , and inflammation under hypoxia ; thus , AP-1 subunits or dimers could be modulated for a desired phenomenon in a cell using a suitable compound of therapeutic potential .
Herein , we used Tanshinone-IIA as an AP-1 ( subunits ) modulator , and the purpose of the study was to investigate the signaling mechanism exhibited by Tan-IIA in facilitating tolerance to hypoxia .
A549 cells were pretreated with Tan-IIA and exposed to hypoxia for 6 , 12 , 24 , and 48 h. Biochemical and @ @ @ @ @ @ @ trace the signaling pathway .
Tan-IIA attenuated hypoxia-induced oxidative stress by modulating the expression of AP-1 subunits ( via .
MAPK ) and Nrf2 transcription factor , which in turn were responsible for maintaining the higher levels of antioxidant enzymes and genes ( HO ) .
Tan-IIA increased the cell survival .
This could be attributed to an increased NO level via iNOS gene and activated JNK , ERK pathway that induced c-jun/c-fos , c-jun/fosB , junD/c-fos , and junD/fosB heterodimers .
This in turn leads to the cell cycle progressionby activating cyclins @ @ @ @ @ @ @ was further confirmed by the lower levels of p53 and their downstream genes ( p16 , p21 , p27 ) .
In addition , Tan-IIA decreased pro-inflammatory cytokine levels by inhibiting the formation of junB/fra-1 heterodimer regulated by p38 .
Tan-IIA increased cell survivalto hypoxia by maintaining the higher levels of cellular iNOS , HO-1 , jun-D , c-jun , fos B via Nrf2-AP-1 .

Activator protein-1 (AP-1) plays a decisive role in cell proliferation, apoptosis, and inflammation under hypoxia; thus, AP-1 subunits or dimers could be modulated for a desired phenomenon in a cell using a suitable compound of therapeutic potential. Herein, we used Tanshinone-IIA as an AP-1 (subunits) modulator, and the purpose of the study was to investigate the signaling mechanism exhibited by Tan-IIA in facilitating tolerance to hypoxia. A549 cells were pretreated with Tan-IIA and exposed to hypoxia for 6, 12, 24, and 48 h. Biochemical and molecular parameters were assessed in order to trace the signaling pathway. Tan-IIA attenuated hypoxia-induced oxidative stress by modulating the expression of AP-1 subunits (via. MAPK) and Nrf2 transcription factor, which in turn were responsible for maintaining the higher levels of antioxidant enzymes and genes (HO). Tan-IIA increased the cell survival. This could be attributed to an increased NO level via iNOS gene and activated JNK, ERK pathway that induced c-jun/c-fos, c-jun/fosB, junD/c-fos, and junD/fosB heterodimers. This in turn leads to the cell cycle progressionby activating cyclins (D and B). This was further confirmed by the lower levels of p53 and their downstream genes (p16, p21, p27). In addition, Tan-IIA decreased pro-inflammatory cytokine levels by inhibiting the formation of junB/fra-1 heterodimer regulated by p38. Tan-IIA increased cell survivalto hypoxia by maintaining the higher levels of cellular iNOS, HO-1, jun-D, c-jun, fos B via Nrf2-AP-1.


greenmedinfo--2020-03-15--miR-497 plays a key role in Tanshinone IIA-attenuated proliferation in OCI-AML3 cells via the MAPK/E

miR-497 plays a key role in Tanshinone IIA-attenuated proliferation in OCI-AML3 cells via the MAPK/ERK1/2 pathway.

Acute myelod leukemia ( AML ) , as a uncontrolled proliferation of cells , was arrested differentiation of progenitor cells @ @ @ @ @ to explore Tanshinone IIA ( TIIA ) effects on OCI-AML3 and the involvement of the @ @ @ @ @ in TIIA-mediated effects .
Cell growth percentage was detected using a cell counting kit .
@ @ @ @ @ by qPCR .
Phosphorylated ERK1/2 , JNK and p38 were assessed using western blot .
@ @ @ @ @ decreased and the effected time increased with increasing TIIA concentration .
The miR-497 was upregulated @ @ @ @ @ when the TIIA added .
TIIA can not influence the p-ERK1/2 .
Hence , the @ @ @ @ @ raising .
However , when the p-ERK1/2 was inhibited , there no influence on the @ @ @ @ @ .
TIIA upregulates miR-497 , and decrease the p-ERK1/2 expression , when TIIA simulated OCI-AML3 @ @ @ @ @ in miR-497 might be involved in the regulation of proliferation in this process .

Acute myelod leukemia (AML), as a uncontrolled proliferation of cells, was arrested differentiation of progenitor cells. The present study aimed to explore Tanshinone IIA (TIIA) effects on OCI-AML3 and the involvement of the MAPK signaling pathway and miR-497 in TIIA-mediated effects. Cell growth percentage was detected using a cell counting kit. Expression of miR-497 was detected by qPCR. Phosphorylated ERK1/2, JNK and p38 were assessed using western blot. The growth percentage of OCI-AML3 decreased and the effected time increased with increasing TIIA concentration. The miR-497 was upregulated and the p-ERK1/2 was decreased when the TIIA added. TIIA cannot influence the p-ERK1/2. Hence, the proliferation of OCI-AML3 cells was raising. However, when the p-ERK1/2 was inhibited, there no influence on the miR-497 expression after TIIA added. TIIA upregulates miR-497, and decrease the p-ERK1/2 expression, when TIIA simulated OCI-AML3 cell in vitro. And in miR-497 might be involved in the regulation of proliferation in this process.


greenmedinfo--2020-03-16--Allicin alleviates inflammation of diabetic macroangiopathy via the Nrf2 and NF-kB pathway.

As diabetic macroangiopathy is becoming increasingly prevalent , it is urgent to explore preventive and therapeutic drugs and study the mechanism .
Diabetic mice were induced by intraperitoneal injection of streptozotocin ( STZ ) for five consecutive days .
Diabetic mice were divided into diabetic and allicin groups .
After sacrifice , frozen aortic root sections were immunohistochemically stained for nuclear factor erythroid 2-related factor 2 ( Nrf2 ) and inflammation cytokine-tumor necrosis factorα ( TNF-α ) , and the remaining aortic tissues were analyzed by Western blot for the expression of proinflammation genes .
In vitro , Nrf2 and @ @ @ @ @ @ @ Umbilical Vein Endothelial Cells ( HUVECs ) were examined .
HUVECs proliferation and apoptosis were measured .
TNF-α expression was increased in diabetic group compared to that in control group ; this effect was alleviated in allicin-treated mice .
Inflammation relative protein expression of Vascular Cell Adhesion Molecule 1 ( VCAM-1 ) , Matrix metalloproteinase 2 ( MMP-2 ) , Inducible Nitric Oxide Synthase ( iNOS ) , and monocyte chemotactic protein 1 ( MCP-1 ) was higher in the diabetic group than in the control group ; however , allicin treatment inhibited @ @ @ @ @ @ @ allicin treatment reversed the hyperglycemia-induced reduction in proliferation , and decreased the apoptosis induced by high glucose .
Inflammation relative protein expression was consistent with that in vivo .
Additionally , the expression of nuclear factor kappa-B ( NF-κB ) and Nrf2 was increased in both DM mice and HUVECs ; allicin treatment induced a significant reduction in NF-κB level and improvement in Nrf2level .
Allicin alleviates inflammation caused by diabetic macroangiopathy , and the mechanism may occur via increasing Nrf2 and decreasing NF-κB .

As diabetic macroangiopathy is becoming increasingly prevalent, it is urgent to explore preventive and therapeutic drugs and study the mechanism. Diabetic mice were induced by intraperitoneal injection of streptozotocin (STZ)for five consecutive days. Diabetic mice were divided into diabetic and allicin groups. After sacrifice, frozen aortic root sections were immunohistochemically stained for nuclear factor erythroid 2-related factor 2 (Nrf2) and inflammation cytokine-tumor necrosis factorα (TNF-α), and the remaining aortic tissues were analyzed by Western blot for the expression of proinflammation genes. In vitro, Nrf2 and inflammatory relative protein expression levels in Human Umbilical Vein Endothelial Cells (HUVECs) were examined. HUVECs proliferation and apoptosis were measured. TNF-α expression was increased in diabetic group compared to that in control group; this effect was alleviated in allicin-treated mice. Inflammation relative protein expression of Vascular Cell Adhesion Molecule 1(VCAM-1), Matrix metalloproteinase 2 (MMP-2), Inducible Nitric Oxide Synthase (iNOS), and monocyte chemotactic protein 1 (MCP-1) was higher in the diabetic group than in the control group; however, allicin treatment inhibited these diabetes-induced increase. In vitro, allicin treatment reversed the hyperglycemia-induced reduction in proliferation, and decreased the apoptosis induced by high glucose. Inflammation relative protein expression was consistent with that in vivo. Additionally, the expression of nuclear factor kappa-B (NF-κB)and Nrf2 was increased in both DM mice and HUVECs; allicin treatment induced a significant reduction in NF-κB level and improvement in Nrf2level. Allicin alleviates inflammation caused by diabetic macroangiopathy, and the mechanism may occur via increasing Nrf2 and decreasing NF-κB.


greenmedinfo--2020-03-16--Improved cardioprotective effects of hesperidin solid lipid nanoparticles prepared by supercritical

Improved cardioprotective effects of hesperidin solid lipid nanoparticles prepared by supercritical antisolvent technology.

Doxorubicin ( DOX ) is commonly used for the treatment of many types of cancers but its cardiotoxicity , owing to free radical formation , limits its clinical use .
Hesperidin ( HES ) , a flavanone glycoside , has been shown to exert multiple pharmacological actions including cardioprotective effects .
Herein , we aim to formulate HES loaded solid lipid nanoparticles ( SLNs ) using supercritical antisolvent ( SAS ) technology to improve the oral delivery of HES .
Process parameters were optimized to produce small size ( 175.3 ± 3.6 nm ) HES-SLNs with high encapsulation efficiency ( @ @ @ @ @ @ @ and XRD showed that HES is amorphously dispersed in SLNs .
Compared to HES , HES-SLNs resulted in a nearly 20-fold increase in aqueous solubility and a nearly 5-fold increase in apparent permeability .
Pharmacokinetics in rats revealed nearly 4.5-fold higher bioavailability of HES from SLN formulation compared to HES suspension .
Data showed that HES-SLN significantly attenuated DOX-induced cardiotoxicity through lowering creatine kinase-muscle/brain , cardiac troponin I and improving histopathological scores ascompared to the DOX group .
HES-SLN also decreased malondialdehyde , increased catalase and superoxide dismutase of rats ' heart to @ @ @ @ @ @ @ reductions in caspase-3 were also observed following HES-SLN treatment .
Conclusively , these results describe a cardioprotective effect for HES-SLN against DOX-induced cardiotoxicity likely facilitated via suppression of oxidative stress and apoptosis .

Doxorubicin (DOX) is commonly used for the treatment of many types of cancers but its cardiotoxicity, owing to free radical formation, limits its clinical use. Hesperidin (HES), a flavanone glycoside, has been shown to exert multiple pharmacological actions including cardioprotective effects. Herein, we aim to formulate HES loaded solid lipid nanoparticles (SLNs) using supercritical antisolvent (SAS) technology to improve the oral delivery of HES. Process parameters were optimized to produce small size (175.3 ± 3.6 nm) HES-SLNs with high encapsulation efficiency (87.6 ± 3.8 %). DSC and XRD showed that HES is amorphously dispersed in SLNs. Compared to HES, HES-SLNs resulted in a nearly 20-fold increase in aqueous solubility and a nearly 5-fold increase in apparent permeability. Pharmacokinetics in rats revealed nearly 4.5-fold higher bioavailability of HES from SLN formulation compared to HES suspension. Data showed that HES-SLN significantly attenuated DOX-induced cardiotoxicity through lowering creatine kinase-muscle/brain, cardiac troponin I and improving histopathological scores ascompared to the DOX group. HES-SLN also decreased malondialdehyde, increased catalase and superoxide dismutase of rats' heart to levels relatively comparable to control. Marked reductions in caspase-3 were also observed following HES-SLN treatment. Conclusively, these results describe a cardioprotective effect for HES-SLN against DOX-induced cardiotoxicity likely facilitated via suppression of oxidative stress and apoptosis.


greenmedinfo--2020-03-16--Hesperidin could be considered as a dietary supplement to manage type 2 diabetes and to suppress oxi

Hesperidin could be considered as a dietary supplement to manage type 2 diabetes and to suppress oxidative stress mediated diabetic pathophysiology.

The present study investigates the in vitro antidiabetic and antioxidant potential of hesperidin and hesperetin under oxidative stress induced in L6 myotubes .
Also , the study attempts to reveal the effect of glycosylation ( hesperetin ) on the biological activities of hesperidin .
Oxidative stress is the leading cause of complications associated with diabetes .
Both hesperidin and hesperetin reduce oxidative stress directly by scavenging intracellular reactive oxygen species ( ROS ) and by up-regulating natural antioxidant defence system like glutathione .
Hesperidin and hesperetin at 10μM inhibited the non-enzymatic glycation of proteins ( 65.57 % and 35.6 % @ @ @ @ @ @ @ involved in the formation of advanced glycation end products ( AGEs ) which has a significant role in the pathogenesis of diabetes .
Additionally , these compounds induced glucose uptake in L6 myotubes following acute and chronic treatment .
The percentage 2-NBDG uptake shown by both the compounds was comparable with that of the antidiabetic drug , rosiglitazone ( 30.4 % ) .
Both the compounds downregulated PI3 kinase activity whereas GLUT4 , IRS , and AKT were upregulated in L6 myotubes pointingto the possible overlapping with the insulin signalling pathway .
SIGNIFICANCE @ @ @ @ @ @ @ oxidative stress occurs in diabetes and could have a role in the development of insulin resistance .
Oral hypoglycaemic agents which target on increasing insulin levels and improving insulin sensitivity or that reduce the rate of carbohydrate absorption from the gastrointestinal tract are used to manage type 2 diabetes .
But these therapies rarely target the real cause of type 2 diabetes and have severe adverse effects .
The observations from the present study provide significant evidence for hesperidin and hesperetin , to be considered as a dietary supplement to manage type 2 @ @ @ @ @ @ @ diabetic pathophysiology .

The present study investigates the in vitro antidiabetic and antioxidant potential of hesperidin and hesperetin under oxidative stress induced in L6 myotubes. Also, the study attempts to reveal the effect of glycosylation (hesperetin) on the biological activities of hesperidin. Oxidative stress is the leading cause of complications associated with diabetes. Both hesperidin and hesperetin reduce oxidative stress directly by scavenging intracellular reactive oxygen species (ROS) and by up-regulating natural antioxidant defence system like glutathione. Hesperidin and hesperetin at 10μM inhibited the non-enzymatic glycation of proteins (65.57% and 35.6%, respectively), the critical reaction involved in the formation of advanced glycation end products (AGEs) which has a significant role in the pathogenesis of diabetes. Additionally, these compounds induced glucose uptake in L6 myotubes following acute and chronic treatment. The percentage 2-NBDG uptake shown by both the compounds was comparable with that of the antidiabetic drug, rosiglitazone (30.4%). Both the compounds downregulated PI3 kinase activity whereas GLUT4, IRS, and AKT were upregulated in L6 myotubes pointingto the possible overlapping with the insulin signalling pathway. SIGNIFICANCE OF THE STUDY: Evidence suggest that oxidative stress occurs in diabetes and could have a role in the development of insulin resistance. Oral hypoglycaemic agents which target on increasing insulin levels and improving insulin sensitivity or that reduce the rate of carbohydrate absorption from the gastrointestinal tract are used to manage type 2 diabetes. But these therapies rarely target the real cause of type 2 diabetes and have severe adverse effects. The observations from the present study provide significant evidence for hesperidin and hesperetin, to be considered as a dietary supplement to manage type 2 diabetes and to suppress oxidative stress mediated diabetic pathophysiology.


greenmedinfo--2020-03-16--A review of hesperidin: A therapeutic agent for obesity.

Obesity is a chronic metabolic disease caused by multiple factors and is considered to be a risk factor for type @ @ @ @ @ , hypertension , stroke and various cancers .
Hesperidin , a flavanone glycoside , is @ @ @ @ @ a wide range of biological effects .
Mounting evidence has demonstrated that hesperidin possesses inhibitory @ @ @ @ @ Our review discusses mechanisms of hesperidin in the treatment of obesity .
Hesperidin regulates lipid @ @ @ @ @ mediating AMPK and PPAR signaling pathways , directly regulates antioxidant index and anti-apoptosis , and @ @ @ @ @ to regulate inflammation to play a role in the treatment of obesity .
In addition @ @ @ @ @ significantly improve symptoms such as postprandial hyperglycemia and hyperlipidemia .
Further clinical trials are also @ @ @ @ @ of this natural flavonoid and evaluating its safety profile .

Obesity is a chronic metabolic disease caused by multiple factors and is considered to be a risk factor for type 2 diabetes, cardiovascular disease, hypertension, stroke and various cancers. Hesperidin, a flavanone glycoside, is a natural phenolic compound with a wide range of biological effects. Mounting evidence has demonstrated that hesperidin possesses inhibitory effect against obesity diseases. Our review discusses mechanisms of hesperidin in the treatment of obesity. Hesperidin regulates lipid metabolism and glucose metabolism by mediating AMPK and PPAR signaling pathways, directly regulates antioxidant index and anti-apoptosis, and indirectly mediates NF-κB signaling pathway to regulate inflammation to play a role in the treatment of obesity. In addition, hesperidin-enriched dietary supplements can significantly improve symptoms such as postprandial hyperglycemia and hyperlipidemia. Further clinical trials are also required for confirming lipid-lowering efficacy of this natural flavonoid and evaluating its safety profile.


greenmedinfo--2020-03-16--Exosomes derived from epigallocatechin gallate-treated cardiomyocytes attenuated acute myocardial in

Exosomes derived from epigallocatechin gallate-treated cardiomyocytes attenuated acute myocardial infarction.

Background : Ischemia-derived exosomes can restrict excessive autophagy by transferring microRNA-30a ( miR30a ) to cells .
Reports have confirmed that epigallocatechin gallate ( EGCG ) alleviates acute myocardial infarction ( AMI ) by regulating autophagy ; however , research evaluating the communication with cardiomyocytes and exosomes is lacking .
This study aimed to explore whether exosomes derived from EGCG-treated cardiomyocytes mitigated AMI by adjusting miR30a to inactivate apoptosis and autophagy .
Methods : Exosomes were extracted from cardiomyocytes , cultured either in control or AMI condition , with or without EGCG pretreatment .
The exosome characteristics were analyzed by @ @ @ @ @ @ @ .
The change in miR30a in cells and exosomes was demonstrated by qRT-PCR .
H9c2 or stable miR30a knockdown ( miR30a ) cell lines were incubated with exosomes derived from EGCG-treated cardiomyocytesor .
The effect of EGCG and exosomes on I/R-induced cardiomyocyte apoptosis and autophagy was assessed .
Results : EGCG improved the activity of cardiomyocytes , and increased average diameter , concentration , miR30a mRNA level , and specific protein expression in AMI-derived exosomes produced by cardiomyocytes .
Moreover , the coincubation of AMI cells with EGCG or exosomes derived from EGCG-treated @ @ @ @ @ @ @ Conclusions : The findings showed that EGCG upregulates miR30a , which was efficiently transferredexosomes between cardiomyocytes , thereby contributing to the suppression of apoptosis and autophagy .
By focusing on the cardiomyocyte microenvironment , we identified a new target of EGCG alleviating AMI by regulating apoptosis and autophagy .

Background: Ischemia-derived exosomes can restrict excessive autophagy by transferring microRNA-30a (miR30a) to cells. Reports have confirmed that epigallocatechin gallate (EGCG) alleviates acute myocardial infarction (AMI) by regulating autophagy; however, research evaluating the communication with cardiomyocytes and exosomes is lacking. This study aimed to explore whether exosomes derived from EGCG-treated cardiomyocytes mitigated AMI by adjusting miR30a to inactivate apoptosis and autophagy.
Methods: Exosomes were extracted from cardiomyocytes, cultured either in control or AMI condition, with or without EGCG pretreatment. The exosome characteristics were analyzed by nanoparticle tracking analyses and transmission electron microscopy. The change in miR30a in cells and exosomes was demonstrated by qRT-PCR. H9c2 or stable miR30a knockdown (miR30a) cell lines were incubated with exosomes derived from EGCG-treated cardiomyocytesor. The effect of EGCG and exosomes on I/R-induced cardiomyocyte apoptosis and autophagy was assessed.
Results: EGCG improved the activity of cardiomyocytes, and increased average diameter, concentration, miR30a mRNA level, and specific protein expression in AMI-derived exosomes produced by cardiomyocytes. Moreover, the coincubation of AMI cells with EGCG or exosomes derived from EGCG-treated cardiomyocytes attenuated cardiomyocyte apoptosis and autophagy.
Conclusions: The findings showed that EGCG upregulates miR30a, which was efficiently transferredexosomes between cardiomyocytes, thereby contributing to the suppression of apoptosis and autophagy. By focusing on the cardiomyocyte microenvironment, we identified a new target of EGCG alleviating AMI by regulating apoptosis and autophagy.


greenmedinfo--2020-03-16--Inhibitory potential of EGCG on Streptococcus mutans biofilm: A new approach to prevent Cariogenesis

Inhibitory potential of EGCG on Streptococcus mutans biofilm: A new approach to prevent Cariogenesis.

Dental caries is a common cause for tooth loss and Streptococcus mutans is identified as the etiologic pathogen .
This @ @ @ @ @ of Epigallocatechin gallate ( EGCG ) on S.mutans glucansucrase enzyme and its biofilm .
Glucansucrase @ @ @ @ @ of EGCG was validated using AutoDock tool and enzyme inhibitory assay .
Biofilm inhibitory potential @ @ @ @ @ Electron Microscopic ( SEM ) analysis in human tooth samples .
Molecular docking revealed that @ @ @ @ @ and TRP 517 amino acids and binds to glucansucrase .
SEM analysis revealed inhibition of @ @ @ @ @ of EGCG on surfaces of tooth samples .
Bioinformatics and biological assays confirmed that EGCG @ @ @ @ @ mutans glucansucrase and inhibits its enzymatic activity .
Enzymatic inhibition of glucansucrase attenuated biofilm formation @ @ @ @ @ tooth surface .
Thus , we conclude that EGCG inhibitory potential of S. mutans biofilm @ @ @ @ @ a novel approach in prevention of dental caries .

Dental caries is a common cause for tooth loss and Streptococcus mutans is identified as the etiologic pathogen. This study evaluates the inhibitory potential of Epigallocatechin gallate (EGCG) on S.mutans glucansucrase enzyme and its biofilm. Glucansucrase binding and the inhibitory potential of EGCG was validated using AutoDock tool and enzyme inhibitory assay. Biofilm inhibitory potential was also confirmed using Scanning Electron Microscopic (SEM) analysis in human tooth samples. Molecular docking revealed that EGCG interacted with GLU 515 and TRP 517 amino acids and binds to glucansucrase. SEM analysis revealed inhibition of S.mutans biofilm by various concentrations of EGCG on surfaces of tooth samples. Bioinformatics and biological assays confirmed that EGCG potentially binds to the S. mutans glucansucrase and inhibits its enzymatic activity. Enzymatic inhibition of glucansucrase attenuated biofilm formation potential of S. mutans on tooth surface. Thus, we conclude that EGCG inhibitory potential of S. mutans biofilm on the tooth surface is a novel approach in prevention of dental caries.