greenmedinfo--2020-12-02--EGCG targeted Notch to attenuate renal fibrosis.

Renal fibrosis is a characteristic of diabetic nephropathy , which is a serious complication of diabetes .
It has been reported that ( - ) -epigallocatechin gallate ( EGCG ) attenuates renal fibrosis .
However , the molecular mechanism of regulation by EGCG in this process remains unclear .
Previous studies showed that abnormal activation of Notch signaling contributes to the development of renal fibrosis .
Previous studies have demonstrated that EGCG attenuates Notch1 expression .
In this study , we found that the levels of fibronectin and Notch1 expression were decreased in human embryonic kidney cells after treatment with @ @ @ @ @ @ @ type II transforming growth factor beta receptor ( TGFβRII ) and Smad3 pathway were inhibited in kidney cells by treatment with EGCG .
In the diabetic kidney , we found that the activation of Notch signaling was attenuated by administration of EGCG .
Moreover , TGFβRII and Smad3 phosphorylation could be inhibited by treatment with EGCG in the kidney .
These results indicated that EGCG may improve renal fibrosis by targeting Notch via inhibition of the TGFβ/Smad3 pathway in diabetic mice .
Our findings provide insight into the therapeutic strategy for diabetes-induced renal @ @ @ @ @ @ @ a novel potential medicine for the treatmentof chronic kidney disease in patients with diabetes .

Renal fibrosis is a characteristic of diabetic nephropathy, which is a serious complication of diabetes. It has been reported that (-)-epigallocatechin gallate (EGCG) attenuates renal fibrosis. However, the molecular mechanism of regulation by EGCG in this process remains unclear. Previous studies showed that abnormal activation of Notch signaling contributes to the development of renal fibrosis. Previous studies have demonstrated that EGCG attenuates Notch1 expression. In this study, we found that the levels of fibronectin and Notch1 expression were decreased in human embryonic kidney cells after treatment with EGCG. We also observed that the type II transforming growth factor beta receptor (TGFβRII) and Smad3 pathway were inhibited in kidney cells by treatment with EGCG. In the diabetic kidney, we found that the activation of Notch signaling was attenuated by administration of EGCG. Moreover, TGFβRII and Smad3 phosphorylation could be inhibited by treatment with EGCG in the kidney. These results indicated that EGCG may improve renal fibrosis by targeting Notch via inhibition of the TGFβ/Smad3 pathway in diabetic mice. Our findings provide insight into the therapeutic strategy for diabetes-induced renal fibrosis, and suggest EGCG to be a novel potential medicine for the treatmentof chronic kidney disease in patients with diabetes.


greenmedinfo--2020-12-02--Fuzhuan Brick-Tea may provide benefits in ameliorating disorders of glucose and lipid metabolism.

Fuzhuan Brick-Tea is a postfermented product with the hypoglycemic effect , which is prepared from the leaves of Camellia sinensis var .
sinensis .
However , the material basis associated with the hypoglycemic effect was not clear .
The present research was designed to explore the hypoglycemic effect of extract/fractions from Fuzhuan Brick-Tea in streptozotocin-induced type II diabetic mice .
Then an ultra-high pressure liquid chromatography along with quadrupole time of flight mass spectrometry was used to analyze the phytochemicals in Fuzhuan Brick-Tea fractions .
As a result , the hypoglycemic and hypolipidemic effects were evidently observed from the serum @ @ @ @ @ @ @ type II diabetic mice .
In addition , there were total of 20 major components including eight lysophosphatidylcholines ( Lyso-PCs ) , five fatty acids , and seven novel theophylline derivatives tentatively identified in the active fraction from water extract .
Therefore , these components were assumed to contribute partly to the hypoglycemic effect of Fuzhuan Brick-Tea .
These findings also give the evidence that the Lyso-PCs , fatty acids , and novel theophylline derivatives in Fuzhuan Brick-Tea may provide benefits in ameliorating disorders of glucose and lipid metabolism .
PRACTICAL APPLICATION : @ @ @ @ @ @ @ fatty acids , and novel theophylline derivatives in Fuzhuan Brick-Tea may provide benefits in ameliorating disorders of glucose and lipid metabolism .
It can be taken as a beneficial diet additive or nutraceutical .

Fuzhuan Brick-Tea is a postfermented product with the hypoglycemic effect, which is prepared from the leaves of Camellia sinensis var. sinensis. However, the material basis associated with the hypoglycemic effect was not clear. The present research was designed to explore the hypoglycemic effect of extract/fractions from Fuzhuan Brick-Tea in streptozotocin-induced type II diabetic mice. Then an ultra-high pressure liquid chromatography along with quadrupole time of flight mass spectrometry was used to analyze the phytochemicals in Fuzhuan Brick-Tea fractions. As a result, the hypoglycemic and hypolipidemic effects were evidently observed from the serum biochemical indexes and liver pathological examination in type II diabetic mice. In addition, there were total of 20 major components including eight lysophosphatidylcholines (Lyso-PCs), five fatty acids, and seven novel theophylline derivatives tentatively identified in the active fraction from water extract. Therefore, these components were assumed to contribute partly to the hypoglycemic effect of Fuzhuan Brick-Tea. These findings also give the evidence that the Lyso-PCs, fatty acids, and novel theophylline derivatives in Fuzhuan Brick-Tea may provide benefits in ameliorating disorders of glucose and lipid metabolism. PRACTICAL APPLICATION: This study suggests that the Lyso-PCs, fatty acids, and novel theophylline derivatives in Fuzhuan Brick-Tea may provide benefits in ameliorating disorders of glucose and lipid metabolism. It can be taken as a beneficial diet additive or nutraceutical.


greenmedinfo--2020-12-02--Combination effects of ellagic acid with erlotinib in a Ba/F3 cell line expressing EGFR H773_V774 in

Combination effects of ellagic acid with erlotinib in a Ba/F3 cell line expressing EGFR H773_V774 insH mutation.

BACKGROUND : Epidermal growth factor receptor H773_V774 insH ( EGFR-insH ) is an EGFR exon 20 insertion mutation in non-small cell lung cancer ( NSCLC ) , which is naturally resistant to available EGFR tyrosine kinase inhibitors ( TKIs ) and lacks a patient-derived cell line .
METHODS : A Ba/F3 cell line expressing EGFR-insH mutation ( Ba/F3-insH cell line ) was generated using an IL3-deprivation method .
A cell proliferation assay was performed to screen natural compounds that exhibit a synergistic effect with erlotinib .
Trypan blue staining was used to assess cell growth and crystal violate staining was @ @ @ @ @ @ @ cytometry was used to detect EGFR expression and cell apoptosis .
A xenograft model was created to evaluate the effect of ellagic acid ( EA ) with erlotinib on tumor growth .
RESULTS : EA was identified to synergistically inhibit the proliferation of Ba/F3-insH cells with erlotinib .
The growth and clonogenic potential of Ba/F3-insH cells were definitely constrained by EA with erlotinib , whereas , the apoptosis of Ba/F3-insH cells was dramatically promoted by the combination .
In a xenograft model of the Ba/F3-insH cell line , the combination treatment also exhibited @ @ @ @ @ @ @ CONCLUSIONS : In this study , we generated a Ba/F3 cell line expressing EGFR H773_V774 insH mutation and identified a synergistic treatment ( EA with erlotinib ) that markedly inhibited the viability of Ba/F3-insH cells in vitro and in vivo .
KEY POINTS : Our results indicated that the combination of ellagic acid with erlotinib has synergistic effects against EGFR H773_V774 insH mutation .

BACKGROUND: Epidermal growth factor receptor H773_V774 insH (EGFR-insH) is an EGFR exon 20 insertion mutation in non-small cell lung cancer (NSCLC), which is naturally resistant to available EGFR tyrosine kinase inhibitors (TKIs) and lacks a patient-derived cell line.
METHODS: A Ba/F3 cell line expressing EGFR-insH mutation (Ba/F3-insH cell line) was generated using an IL3-deprivation method. A cell proliferation assay was performed to screen natural compounds that exhibit a synergistic effect with erlotinib. Trypan blue staining was used to assess cell growth and crystal violate staining was recruited to evaluate clonogenic potential. Flow cytometry was used to detect EGFR expression and cell apoptosis. A xenograft model was created to evaluate the effect of ellagic acid (EA) with erlotinib on tumor growth.
RESULTS: EA was identified to synergistically inhibit the proliferation of Ba/F3-insH cells with erlotinib. The growth and clonogenic potential of Ba/F3-insH cells were definitely constrained by EA with erlotinib, whereas, the apoptosis of Ba/F3-insH cells was dramatically promoted by the combination. In a xenograft model of the Ba/F3-insH cell line, the combination treatment also exhibited a synergistic reduction in tumor growth.
CONCLUSIONS: In this study, we generated a Ba/F3 cell line expressing EGFR H773_V774 insH mutation and identified a synergistic treatment (EA with erlotinib) that markedly inhibited the viability of Ba/F3-insH cells in vitro and in vivo.
KEY POINTS: Our results indicated that the combination of ellagic acid with erlotinib has synergistic effects against EGFR H773_V774 insH mutation.


greenmedinfo--2020-12-02--Theacrine, a purine alkaloid from kucha, protects against Parkinson's disease through SIRT3 activati

Theacrine, a purine alkaloid from kucha, protects against Parkinson's disease through SIRT3 activation.

BACKGROUND : Oxidative damage of dopaminergic neurons is the fundamental causes of Parkinson 's disease ( PD ) that has no standard cure at present .
Theacrine , a purine alkaloid from Chinese tea Kucha , has been speculated to benefit the neurodegeneration in PD , through similar actions to its chemical analogue caffeine , albeit excluding side effects .
Theacrine has nowadays gained a lot of interest for its multiple benefits , while the investigations are weak and insufficient .
HYPOTHESIS/PURPOSE : It is well-known that tea has a wide range of functions , especially in the prevention and @ @ @ @ @ @ @ an active monomer compound in Camellia assamica var .
kucha Hung T. Chang & H.S.Wang ( Kucha ) , which appears to be effective and safe in PD therapy .
The aim of this study is to examine its actions in diverse PD models and explore the mechanisms .
STUDY DESIGN : For determination of theacrine 's effects , we employed diverse oxidative damage-associated PD models , including 6-OHDA-treated rats , MPTP-treated mice/zebrafish and MPP-treated SH-SY5Y cells , and using caffeine , selegiline and depranyl as positve control .
For investigation and verification @ @ @ @ @ @ @ testing mitochondrial function-related parameters and enzyme activity as well as applied gene knockdown and overexpression .
METHODS : We employed behavioral tests including spontaneous activity , pole , swimming , rotarod and gait , immunohistochemistry , HPLC , flow cytometry , immunohistochemistry , Western blot , gene knockdown by siRNA and overexpression by plasmid in this study .
RESULTS : Theacrine is demonstrated to retrieve the loss of dopaminergic neurons and the damages of behavioral performance in multiple animal models of PD ( 6-OHDA-treated rats and in MPTP-treated mice and zebrafish ) .
@ @ @ @ @ @ @ indicate that theacrine relieves apoptosis resulted from oxidative damage and mitochondrial dysfunction .
Further investigations illustrate that theacrine activates SIRT3 directly .
It is of advantage to prevent apoptosis through SIRT3-mediated SOD2 deacetylation that reduces ROS accumulation and restores mitochondrial function .
This concept is elaborated by 3TYP that inhibits SIRT3 enzyme activity and knockdown/overexpression of SIRT3 gene , demonstrating a crucial role of SIRT3 in theacrine-benefited dopaminergic neurons .
CONCLUSION : Theacrine prevents apoptosis of dopaminergic neurons through directly activating SIRT3 which deacetylating SOD2 and restoring mitochondrial functions .

BACKGROUND: Oxidative damage of dopaminergic neurons is the fundamental causes of Parkinson's disease (PD) that has no standard cure at present. Theacrine, a purine alkaloid from Chinese tea Kucha, has been speculated to benefit the neurodegeneration in PD, through similar actions to its chemical analogue caffeine, albeit excluding side effects. Theacrine has nowadays gained a lot of interest for its multiple benefits, while the investigations are weak and insufficient.
HYPOTHESIS/PURPOSE: It is well-known that tea has a wide range of functions, especially in the prevention and treatment of neurodegenerative diseases. Theacrine is an active monomer compound in Camellia assamica var. kucha Hung T. Chang&H.S.Wang (Kucha), which appears to be effective and safe in PD therapy. The aim of this study is to examine its actions in diverse PD models and explore the mechanisms.
STUDY DESIGN: For determination of theacrine's effects, we employed diverse oxidative damage-associated PD models, including 6-OHDA-treated rats, MPTP-treated mice/zebrafish and MPP-treated SH-SY5Y cells, and using caffeine, selegiline and depranyl as positve control. For investigation and verification of the mechanisms, we utilized approaches testing mitochondrial function-related parameters and enzyme activity as well as applied gene knockdown and overexpression.
METHODS: We employed behavioral tests including spontaneous activity, pole, swimming, rotarod and gait, immunohistochemistry, HPLC, flow cytometry, immunohistochemistry, Western blot, gene knockdown by siRNA and overexpression by plasmid in this study.
RESULTS: Theacrine is demonstrated to retrieve the loss of dopaminergic neurons and the damages of behavioral performance in multiple animal models of PD (6-OHDA-treated rats and in MPTP-treated mice and zebrafish). The followed data of MPP-treated SH-SY5Y cells indicate that theacrine relieves apoptosis resulted from oxidative damage and mitochondrial dysfunction. Further investigations illustrate that theacrine activates SIRT3 directly. It is of advantage to prevent apoptosis through SIRT3-mediated SOD2 deacetylation that reduces ROS accumulation and restores mitochondrial function. This concept is elaborated by 3TYP that inhibits SIRT3 enzyme activity and knockdown/overexpression of SIRT3 gene, demonstrating a crucial role of SIRT3 in theacrine-benefited dopaminergic neurons.
CONCLUSION: Theacrine prevents apoptosis of dopaminergic neurons through directly activating SIRT3 which deacetylating SOD2 and restoring mitochondrial functions.


greenmedinfo--2020-12-02--Theacrine and strictinin, two major ingredients for the anti-influenza activity of Yunnan Kucha tea.

ETHNOPHARMACOLOGICAL RELEVANCE : Kucha tea plant ( Camellia assamica var .
kucha Chang et Wang ) is regarded as a mutant variety of wild Pu'er tea plant found in few mountain areas of Yunnan , China .
Its fresh young leaves and shoots are picked by the indigenous aborigines in these local areas to prepare an herbal tea for the treatment of common cold empirically .
MATERIALS AND METHODS : Two extra compounds of relative abundance were detected in Kucha tea in comparison with Pu'er tea , and their chemical structures were identified as chlorogenic acid and theacrine .
These @ @ @ @ @ @ @ compounds , strictinin and caffeine , in Kucha tea were evaluated for their cytotoxicity and inhibitory effects on human influenza virus A/Puerto Rico/8/34 by analyzing viral protein expression and progeny production .
RESULTS : No or low cytotoxicity was detected for the four Kucha compounds when their concentrations were below 100 μM .
Expression of viral NS1 protein was significantly inhibited by chlorogenic acid , theacrine or strictinin , but not caffeine at a concentration of 100 μM .
The relative inhibitory potency was detected as chlorogenic acid CONCLUSION : It is suggested @ @ @ @ @ @ @ ingredients responsible for the anti-influenza activity of Yunnan Kucha tea traditionally used for the treatment of common cold .

ETHNOPHARMACOLOGICAL RELEVANCE: Kucha tea plant (Camellia assamica var. kucha Chang et Wang) is regarded as a mutant variety of wild Pu'er tea plant found in few mountain areas of Yunnan, China. Its fresh young leaves and shoots are picked by the indigenous aborigines in these local areas to prepare an herbal tea for the treatment of common cold empirically.
MATERIALS AND METHODS: Two extra compounds of relative abundance were detected in Kucha tea in comparison with Pu'er tea, and their chemical structures were identified as chlorogenic acid and theacrine. These two compounds as well as two major compounds, strictinin and caffeine, in Kucha tea were evaluated for their cytotoxicity and inhibitory effects on human influenza virus A/Puerto Rico/8/34 by analyzing viral protein expression and progeny production.
RESULTS: No or low cytotoxicity was detected for the four Kucha compounds when their concentrations were below 100 μM. Expression of viral NS1 protein was significantly inhibited by chlorogenic acid, theacrine or strictinin, but not caffeine at a concentration of 100 μM. The relative inhibitory potency was detected as chlorogenic acid < theacrine < strictinin, and both theacrine and strictinin displayed significant inhibition at a concentration of 50 μM. According to a plaque assay, viral progeny production was significantly reduced by theacrine or strictinin, but not by chlorogenic acid or caffeine under the same concentration of 100 μM.
CONCLUSION: It is suggested that theacrine and strictinin are two major ingredients responsible for the anti-influenza activity of Yunnan Kucha tea traditionally used for the treatment of common cold.


greenmedinfo--2020-12-02--Caffeine targets SIRT3 to enhance SOD2 activity in mitochondria.

Caffeine is chemically stable and not readily oxidized under normal physiological conditions but also has antioxidant effects , although the underlying molecular mechanism is not well understood .
Superoxide dismutase ( SOD ) 2 is a manganese-containing enzyme located in mitochondria that protects cells against oxidative stress by scavenging reactive oxygen species ( ROS ) .
SOD2 activity is inhibited through acetylation under conditions of stress such as exposure to ultraviolet ( UV ) radiation .
Sirtuin 3 ( SIRT3 ) is the major mitochondrial nicotinamide adenine dinucleotide ( NAD ) -dependent deacetylase , which deacetylates two critical lysine residues @ @ @ @ @ @ @ on SOD2 and promotes its antioxidative activity .
In this study , we investigated whether the antioxidant effect of caffeine involves modulation of SOD2 by SIRT3 usingandmodels .
The results show that caffeine interacts with SIRT3 and promotes direct binding of SIRT3 with its substrate , thereby enhancing its enzymatic activity .
Mechanistically , caffeine bound to SIRT3 with high affinity ( = 6.858× 10M ) ; the binding affinity between SIRT3 and its substrate acetylated p53 was also 9.03 ( without NAD ) or 6.87 ( with NAD ) times higher in @ @ @ @ @ @ @ protected skin cells from UV irradiation-induced oxidative stress .
More importantly , caffeine enhanced SIRT3 activity and reduced SOD2 acetylation , thereby leading to increased SOD2 activity , which could be reversed by treatment with the SIRT3 inhibitor 3- ( 1H-1,2,3-triazol-4-yl ) pyridine ( 3-TYP ) and .
Taken together , our results show that caffeine targets SIRT3 to enhance SOD2 activity and protect skin cells from UV irradiation-induced oxidative stress .
Thus , caffeine , as a small-molecule SIRT3 activator , could be a potential agent to protect human skin against UV @ @

Caffeine is chemically stable and not readily oxidized under normal physiological conditions but also has antioxidant effects, although the underlying molecular mechanism is not well understood. Superoxide dismutase (SOD) 2 is a manganese-containing enzyme located in mitochondria that protects cells against oxidative stress by scavenging reactive oxygen species (ROS). SOD2 activity is inhibited through acetylation under conditions of stress such as exposure to ultraviolet (UV) radiation. Sirtuin 3 (SIRT3) is the major mitochondrial nicotinamide adenine dinucleotide (NAD)-dependent deacetylase, which deacetylates two critical lysine residues (lysine 68 and lysine 122) on SOD2 and promotes its antioxidative activity. In this study, we investigated whether the antioxidant effect of caffeine involves modulation of SOD2 by SIRT3 usingandmodels. The results show that caffeine interacts with SIRT3 and promotes direct binding of SIRT3 with its substrate, thereby enhancing its enzymatic activity. Mechanistically, caffeine bound to SIRT3 with high affinity (= 6.858× 10M); the binding affinity between SIRT3 and its substrate acetylated p53 was also 9.03 (without NAD) or 6.87 (with NAD) times higher in the presence of caffeine. Caffeine effectively protected skin cells from UV irradiation-induced oxidative stress. More importantly, caffeine enhanced SIRT3 activity and reduced SOD2 acetylation, thereby leading to increased SOD2 activity, which could be reversed by treatment with the SIRT3 inhibitor 3-(1H-1,2,3-triazol-4-yl) pyridine (3-TYP)and. Taken together, our results show that caffeine targets SIRT3 to enhance SOD2 activity and protect skin cells from UV irradiation-induced oxidative stress. Thus, caffeine, as a small-molecule SIRT3 activator, could be a potential agent to protect human skin against UV radiation.


greenmedinfo--2020-12-02--Caffeine targets G6PDH to disrupt redox homeostasis and inhibit renal cell carcinoma proliferation.

Glucose-6-phosphate dehydrogenase ( G6PDH ) is the rate-limiting enzyme in the pentose phosphate pathway ( PPP ) and plays a crucial role in the maintenance of redox homeostasis by producing nicotinamide adenine dinucleotide phosphate ( NADPH ) , the major intracellular reductant .
G6PDH has been shown to be a biomarker and potential therapeutic target for renal cell carcinoma ( RCC ) .
Here , we report a previously unknown biochemical mechanism through which caffeine , a well-known natural small molecule , regulates G6PDH activity to disrupt cellular redox homeostasis and suppress RCC development and progression .
We found that @ @ @ @ @ @ @ Mechanistically , caffeine directly binds to G6PDH with high affinity ( = 0.1923μM ) and competes with the coenzyme NADPfor G6PDH binding , as demonstrated by the decreased binding affinities of G6PDH for its coenzyme and substrate .
Molecular docking studies revealed that caffeine binds to G6PDH at the structural NADPbinding site , and chemical cross-linking analysis demonstrated that caffeine inhibits the formation of dimeric G6PDH .
G6PDH inhibition abrogated the inhibitory effects of caffeine on RCC cell growth .
Moreover , inhibition of G6PDH activity by caffeine led to a reduction in @ @ @ @ @ @ @ oxygen species ( ROS ) , and altered the expression of redox-related proteins in RCC cells .
Accordingly , caffeine could inhibit tumor growth through inhibition of G6PDH activity .
Taken together , these results demonstrated that caffeine can target G6PDH to disrupt redox homeostasis and inhibit RCC tumor growth , and has potential as a therapeutic agent for the treatment of RCC .

Glucose-6-phosphate dehydrogenase (G6PDH) is the rate-limiting enzyme in the pentose phosphate pathway (PPP) and plays a crucial role in the maintenance of redox homeostasis by producing nicotinamide adenine dinucleotide phosphate (NADPH), the major intracellular reductant. G6PDH has been shown to be a biomarker and potential therapeutic target for renal cell carcinoma (RCC). Here, we report a previously unknown biochemical mechanism through which caffeine, a well-known natural small molecule, regulates G6PDH activity to disrupt cellular redox homeostasis and suppress RCC development and progression. We found that caffeine can inhibit G6PDH enzymatic activity. Mechanistically, caffeine directly binds to G6PDH with high affinity (= 0.1923μM) and competes with the coenzyme NADPfor G6PDH binding, as demonstrated by the decreased binding affinities of G6PDH for its coenzyme and substrate. Molecular docking studies revealed that caffeine binds to G6PDH at the structural NADPbinding site, and chemical cross-linking analysis demonstrated that caffeine inhibits the formation of dimeric G6PDH. G6PDH inhibition abrogated the inhibitory effects of caffeine on RCC cell growth. Moreover, inhibition of G6PDH activity by caffeine led to a reduction in the intracellular levels of NADPH and reactive oxygen species (ROS), and altered the expression of redox-related proteins in RCC cells. Accordingly, caffeine could inhibit tumor growth through inhibition of G6PDH activity. Taken together, these results demonstrated that caffeine can target G6PDH to disrupt redox homeostasis and inhibit RCC tumor growth, and has potential as a therapeutic agent for the treatment of RCC.


greenmedinfo--2020-12-02--Pu'er tea water extract protects against cognitive impairment in a mouse model of lipopolysaccharide

Pu'er tea water extract protects against cognitive impairment in a mouse model of lipopolysaccharide-induced neuroinflammation.

BACKGROUND : Pu'er tea , a type of post-fermented tea made from Camellia sinensis leaves , has long been widely used in East Asian countries .
It is mainly produced in southern China and is effective in preventing obesity due to its ability to break down fat .
However , the effects of Pu'er tea on cognitive impairment or neuroinflammation by endotoxin have not yet been studied .
PURPOSE : Here , we assessed the inhibitory activity of Pu'er tea hot water extract ( PTW ) on neuroinflammation and cognitive impairment and explored its mechanism .
STUDY DESIGN : The @ @ @ @ @ @ @ was investigated in a mouse model of lipopolysaccharide ( LPS ) -induced neuroinflammation and murine microglia BV2 cells .
METHODS : We examined whether oral administration of PTW prevented cognitive impairment and LPS-induced neuroinflammation using behavioral tests , Nissl staining , immunohistochemistry , western blotting , real-time reverse transcription-polymerase chain reaction ( real-time RT-PCR ) , Griess assay , and enzyme-linked immunosorbent assay ( ELISA ) .
RESULTS : First , Morris water maze ( MWM ) and passive avoidance ( PA ) tests demonstrated that oral administration of PTW effectively attenuated LPS-induced @ @ @ @ @ @ @ of mouse brains .
Histopathological analysis showed that PTW repressed LPS-induced expression of the activation markers ionized calcium-binding adaptor molecule-1 ( Iba-1 ) and glial fibrillary acidic protein ( GFAP ) .
Furthermore , PTW inhibited the expression of amyloidogenesis proteins such as amyloid-β precursor protein ( APP ) , C99 , and β-secretase-1 ( BACE-1 ) ; production of inflammatory proteins such as Iba-1 , GFAP , inducible nitric oxide synthase ( iNOS ) , and cyclooxygenase ( COX ) -2 ; activation of inflammatory pathways ; and expression of inflammatory mediator @ @ @ @ @ @ @ microglia , PTW treatment inhibited the generation of various inflammatory factors activated by LPS .
CONCLUSION : Our results in vivo and in vitro demonstrate that PTW effectively prevents cognitive impairment caused by neuroinflammation and is , therefore , a potential candidate for the development of a therapeutic agent for neurodegenerative diseases .

BACKGROUND: Pu'er tea, a type of post-fermented tea made from Camellia sinensis leaves, has long been widely used in East Asian countries. It is mainly produced in southern China and is effective in preventing obesity due to its ability to break down fat. However, the effects of Pu'er tea on cognitive impairment or neuroinflammation by endotoxin have not yet been studied.
PURPOSE: Here, we assessed the inhibitory activity of Pu'er tea hot water extract (PTW) on neuroinflammation and cognitive impairment and explored its mechanism.
STUDY DESIGN: The ability of PTW to inhibit cognitive impairment was investigated in a mouse model of lipopolysaccharide (LPS)-induced neuroinflammation and murine microglia BV2 cells.
METHODS: We examined whether oral administration of PTW prevented cognitive impairment and LPS-induced neuroinflammation using behavioral tests, Nissl staining, immunohistochemistry, western blotting, real-time reverse transcription-polymerase chain reaction (real-time RT-PCR), Griess assay, and enzyme-linked immunosorbent assay (ELISA).
RESULTS: First, Morris water maze (MWM) and passive avoidance (PA) tests demonstrated that oral administration of PTW effectively attenuated LPS-induced spatial memory loss and inhibited neuronal damage of mouse brains. Histopathological analysis showed that PTW repressed LPS-induced expression of the activation markers ionized calcium-binding adaptor molecule-1 (Iba-1) and glial fibrillary acidic protein (GFAP). Furthermore, PTW inhibited the expression of amyloidogenesis proteins such as amyloid-β precursor protein (APP), C99, and β-secretase-1 (BACE-1); production of inflammatory proteins such as Iba-1, GFAP, inducible nitric oxide synthase (iNOS), and cyclooxygenase (COX)-2; activation of inflammatory pathways; and expression of inflammatory mediator mRNAs in hippocampal tissue. In cultured microglia, PTW treatment inhibited the generation of various inflammatory factors activated by LPS.
CONCLUSION: Our results in vivo and in vitro demonstrate that PTW effectively prevents cognitive impairment caused by neuroinflammation and is, therefore, a potential candidate for the development of a therapeutic agent for neurodegenerative diseases.


greenmedinfo--2020-12-02--Shoumei polyphenols are high-quality natural products with liver-protective effects.

Shoumei is a kind of white tea ( slightly fermented ) that is rich in polyphenols .
In this study , polyphenols were extracted from Shoumei .
High-performance liquid chromatography ( HPLC ) showed that the polyphenols included mainly gallic acid , catechin , hyperoside , and sulfuretin .
In anexperiment , HOwas used to induce oxidative damage in human normal hepatic L-02 cells .
In an animal experiment , CClwas used to induce liver injury .
Theresults showed that Shoumei polyphenols inhibited oxidative damage in normal hepatic L-02 cells , and theresults showed that the polyphenols effectively reduced liver @ @ @ @ @ @ @ .
The polyphenols also decreased aspartate aminotransferase ( AST ) , alanine aminotransferase ( ALT ) , alkaline phosphatase ( ALP ) , triglyceride ( TG ) , total cholesterol ( TC ) , blood urea nitrogen ( BUN ) , nitric oxide ( NO ) , malondialdehyde ( MDA ) , interleukin 6 ( IL-6 ) , interleukin 12 ( IL-12 ) , tumour necrosis factor alpha ( TNF- ) , and interferon gamma ( IFN- ) levels and increased albumin ( ALB ) , superoxide dismutase ( SOD ) , catalase @ @ @ @ @ @ @ ( GSH-Px ) levels in the serum of mice with liver injury .
Furthermore , pathological observation showed that the Shoumei polyphenols reduced CCl-induced hepatocyte damage .
qRT-PCR and Western blotting showed that the polyphenols upregulated the mRNA and protein expression of neuronal nitric oxide synthase ( nNOS ) , endothelial nitric oxide synthase ( eNOS ) , manganese- ( Mn- ) SOD , copper/zinc- ( Cu/Zn- ) SOD , CAT , and inhibitor of nuclear factor kappa B ( NF-B ) alpha ( IB- ) and downregulated the expression of inducible nitric @ @ @ @ @ @ @ p65 .
The Shoumei polyphenols had a preventive effect against CCl-induced mouse liver injury equivalent to that of silymarin .
The four polyphenols identified as the key substances responsible for this effect mediated the effect through their antioxidant capacity .
These results suggest that Shoumei polyphenols are high-quality natural products with liver-protective effects .

Shoumei is a kind of white tea (slightly fermented) that is rich in polyphenols. In this study, polyphenols were extracted from Shoumei. High-performance liquid chromatography (HPLC) showed that the polyphenols included mainly gallic acid, catechin, hyperoside, and sulfuretin. In anexperiment, HOwas used to induce oxidative damage in human normal hepatic L-02 cells. In an animal experiment, CClwas used to induce liver injury. Theresults showed that Shoumei polyphenols inhibited oxidative damage in normal hepatic L-02 cells, and theresults showed that the polyphenols effectively reduced liver index values in mice with liver injury. The polyphenols also decreased aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), triglyceride (TG), total cholesterol (TC), blood urea nitrogen (BUN), nitric oxide (NO), malondialdehyde (MDA), interleukin 6 (IL-6), interleukin 12 (IL-12), tumour necrosis factor alpha (TNF-), and interferon gamma (IFN-) levels and increased albumin (ALB), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) levels in the serum of mice with liver injury. Furthermore, pathological observation showed that the Shoumei polyphenols reduced CCl-induced hepatocyte damage. qRT-PCR and Western blotting showed that the polyphenols upregulated the mRNA and protein expression of neuronal nitric oxide synthase (nNOS), endothelial nitric oxide synthase (eNOS), manganese- (Mn-) SOD, copper/zinc- (Cu/Zn-) SOD, CAT, and inhibitor of nuclear factor kappa B (NF-B) alpha (IB-) and downregulated the expression of inducible nitric oxide synthase (iNOS) and NF-B p65. The Shoumei polyphenols had a preventive effect against CCl-induced mouse liver injury equivalent to that of silymarin. The four polyphenols identified as the key substances responsible for this effect mediated the effect through their antioxidant capacity. These results suggest that Shoumei polyphenols are high-quality natural products with liver-protective effects.


greenmedinfo--2020-12-02--Former Pfizer Science Officer Reveals Great COVID-19 Scam

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greenmedinfo--2020-12-02--Messengers of Gates' Agenda: How the Cornell Alliance for Science Spreads Disinformation on Behalf o

Messengers of Gates' Agenda: How the Cornell Alliance for Science Spreads Disinformation on Behalf of the Bill and Melinda Gates Foundation


greenmedinfo--2020-12-02--Orthosiphon stamineus ameliorated postmenopausal osteoporosis.

OBJECTIVE : Orthosiphon stamineus ( OS ) or Misai Kucing ( Java tea ) is a popular herbal supplement from @ @ @ @ @ , age-related diseases .
This study investigated the potential use of OS leaf extracts to @ @ @ @ @ .
METHODS : Fifty-six female Sprague-Dawley rats were randomly allocated into eight groups ( n @ @ @ @ @ ( healthy sham control ) ; OVX ( ovarietomized ) nontreated rats ( negative control @ @ @ @ @ ( 100 mg/kg body weight ) , and 2 % green tea extract ( positive @ @ @ @ @ OS 50 % ethanolic and aqueous extracts , both at either 150 or 300 mg/kg @ @ @ @ @ the rats ' bones and blood were evaluated for osteoporosis indicators ( protein and mRNA @ @ @ @ @ for bone histomorphometry , and three-point bending test for tibia mechanical strength .
CONCLUSIONS : @ @ @ @ @ antiosteoporotic effects ( improving bone strength , flexibility , bone density , and bone morphometry @ @ @ @ @ the bone resorption biomarkers , while enhancing bone formation biomarkers and collagen synthesis .

OBJECTIVE: Orthosiphon stamineus (OS) or Misai Kucing (Java tea) is a popular herbal supplement from Southeast Asia for various metabolic, age-related diseases. This study investigated the potential use of OS leaf extracts to ameliorate osteoporosis in ovariectomized rats.
METHODS: Fifty-six female Sprague-Dawley rats were randomly allocated into eight groups (n = 7): SHAM (healthy sham control); OVX (ovarietomized) nontreated rats (negative control); OVX + Remifemin (100 mg/kg body weight), and 2% green tea extract (positive controls); OVX + OS 50% ethanolic and aqueous extracts, both at either 150 or 300 mg/kg. After 16 weeks, the rats' bones and blood were evaluated for osteoporosis indicators (protein and mRNA expressions), micro-computed tomography for bone histomorphometry, and three-point bending test for tibia mechanical strength.
RESULTS: The extracts dose-dependently and significantly (P < 0.05) improved bone strength and flexibility, bone mineral density, bone formation protein markers (P1NP), and bone histomorphometry. All extracts reduced the inflammation biomarker (interleukin-6). The extracts up-regulated osteoblastogenesis (bone morphogenetic protein-2) and collagen-1 synthesis (collagen type 1 alpha-1) mRNA expressions, and down-regulated bone resorption (TNFSF11 and nuclear factor-kappa B) mRNA expressions. Both the water and 50% ethanolic extract were effective. The effective dose is equivalent to 25 to 50 mg/kg extract for humans.
CONCLUSIONS: The extract showed bone-protective and antiosteoporotic effects (improving bone strength, flexibility, bone density, and bone morphometry) by reducing inflammation and the bone resorption biomarkers, while enhancing bone formation biomarkers and collagen synthesis.


greenmedinfo--2020-12-02--Orthosiphon stamineus is an outstanding food medicine.

Benth .
( Lamiaceae ) is a valued medicinal plant in traditional folk medicine .
Many pharmacological studies have demonstrated @ @ @ @ @ to exhibit antimicrobial , antioxidant , hepatoprotection , antigenotoxic , antiplasmodial , cytotoxic , cardioactive @ @ @ @ @ .
This review is a comprehensive summary of the presently available chemical , pharmacological investigations @ @ @ @ @ and therapeutic uses of this plant .
Important and different experimental data have been addressed @ @ @ @ @ all phytochemicals identified in this plant , including flavonoids , terpenoids , and essential oils.has @ @ @ @ @ in various pathophysiological conditions .
Therefore , it is an attractive subject for further experimental @ @ @ @

Benth. (Lamiaceae) is a valued medicinal plant in traditional folk medicine. Many pharmacological studies have demonstrated the ability of this plant to exhibit antimicrobial, antioxidant, hepatoprotection, antigenotoxic, antiplasmodial, cytotoxic, cardioactive, antidiabetic, anti-inflammatory activies. This review is a comprehensive summary of the presently available chemical, pharmacological investigations as well as the traditional and therapeutic uses of this plant. Important and different experimental data have been addressed along with a review of all phytochemicals identified in this plant, including flavonoids, terpenoids, and essential oils.has wide traditional and pharmacological uses in various pathophysiological conditions. Therefore, it is an attractive subject for further experimental and clinical investigations.


greenmedinfo--2020-12-02--The combination of D-mannose, inulin, cranberry, bearberry, Olea europaea, Orthosiphon and Lactobaci

The combination of D-mannose, inulin, cranberry, bearberry, Olea europaea, Orthosiphon and Lactobacillus acidophilus SGL 11 per os represents a useful therapy for recurrent UTIs.

Aim of the study : To evaluate the efficacy of a nutraceutical compound containing Uticlin® ( D-mannose , cranberry , bearberry , ) , inulin , and , in preventing recurrent urinary tract infections ( UTIs ) in menopausal women .
Material and methods : This was a prospective cohort study of menopausal women recruited with a history of recurrent UTIs in the previous twelve months and who intended to treat their bladder problem without the use of antibiotics and/or anti-inflammatories .
Women were proposed the use of an oral nutraceutical compound .
The drug was taken for ten days @ @ @ @ @ @ @ to two parallel cohorts : patients using ( group 1 ) or not using ( group 2 ) this nutraceutical compound .
The primary objective of the study was to evaluate the number of women with less than two infective episodes in the 6-month follow-up and less than three episodes in the 12-month follow-up .
The secondary endpoints were to evaluate the reduction of related symptoms at 12-month follow-up , according to the Visual Analog Scale ( VAS ) .
Results : At 6 months of therapy , the reduction in the number @ @ @ @ @ @ @ significant ( < 0.05 ) compared to baseline only in group 1 .
At 12 months , the number of patients who were disease-free was significantly higher ( < 0.05 ) in group 1 compared to group 2 .
Moreover , the improvement of related symptoms was statistically significant ( < 0.05 ) in group 1 , as shown by the reduction in the VAS scale value .
Conclusions : In menopausal women , the combination of D-mannose , inulin , cranberry , bearberry , andSGL 11 per os represents a useful therapy @ @ @ @ @ @ @ natural approach .

Aim of the study: To evaluate the efficacy of a nutraceutical compound containing Uticlin® (D-mannose, cranberry, bearberry,), inulin,and, in preventing recurrent urinary tract infections (UTIs) in menopausal women.
Material and methods: This was a prospective cohort study of menopausal women recruited with a history of recurrent UTIs in the previous twelve months and who intended to treat their bladder problem without the use of antibiotics and/or anti-inflammatories. Women were proposed the use of an oral nutraceutical compound. The drug was taken for ten days, every month. Women were assigned to two parallel cohorts: patients using (group 1) or not using (group 2) this nutraceutical compound. The primary objective of the study was to evaluate the number of women with less than two infective episodes in the 6-month follow-up and less than three episodes in the 12-month follow-up. The secondary endpoints were to evaluate the reduction of related symptoms at 12-month follow-up, according to the Visual Analog Scale (VAS).
Results: At 6 months of therapy, the reduction in the number of patients with≥ 2 UTIs was statistically significant (<0.05) compared to baseline only in group 1. At 12 months, the number of patients who were disease-free was significantly higher (<0.05) in group 1 compared to group 2. Moreover, the improvement of related symptoms was statistically significant (<0.05) in group 1, as shown by the reduction in the VAS scale value.
Conclusions: In menopausal women, the combination of D-mannose, inulin, cranberry, bearberry,andSGL 11 per os represents a useful therapy for recurrent UTIs in women wanting a natural approach.


greenmedinfo--2020-12-02--Epigallocatechin gallate decreases plasma triglyceride, blood pressure, and serum kisspeptin in obes

Epigallocatechin gallate decreases plasma triglyceride, blood pressure, and serum kisspeptin in obese human subjects.

Obesity is one of major risk factors increasing chronic diseases including type II diabetes , cardiovascular diseases , and hypertension @ @ @ @ @ gallate ( EGCG ) , the major active compound in green tea , on reduced @ @ @ @ @ are still controversial .
Furthermore , the effects of EGCG on human adipocyte lipolysis and @ @ @ @ @ not been elucidated .
This study aimed to investigate the effects of EGCG on obesity @ @ @ @ @ of human white adipocytes .
The results showed that , when compared to the baseline @ @ @ @ @ fasting plasma triglyceride levels ( P

Obesity is one of major risk factors increasing chronic diseases including type II diabetes, cardiovascular diseases, and hypertension. The effects of epigallocatechin gallate (EGCG), the major active compound in green tea, on reduced obesity and improved metabolic profiles are still controversial. Furthermore, the effects of EGCG on human adipocyte lipolysis and browning of white adipocytes have not been elucidated. This study aimed to investigate the effects of EGCG on obesity, lipolysis, and browning of human white adipocytes. The results showed that, when compared to the baseline values, EGCG significantly decreased fasting plasma triglyceride levels (P< 0.05), systolic blood pressure (P < 0.05), diastolic blood pressure (P < 0.05), and serum kisspeptin levels (P < 0.05) after 8 weeks of supplement. On the other hand, supplement of EGCG in obese human subjects for 4 or 8 weeks did not decrease body weight, body mass index, waist and hip circumferences, nor total body fat mass or percentage when compared to their baseline values. The study in human adipocytes showed that EGCG did not increase the glycerol release when compared to vehicle, suggesting that it had no lipolytic effect. Furthermore, treatment of EGCG did not enhance uncoupling protein 1 (UCP1) mRNA expression in human white adipocytes when compared with treatment of pioglitazone, the peroxisome proliferator-activated receptor γ (PPAR-γ) agonist, suggesting that EGCG did not augment the browning effect of PPAR-γ on white adipocytes. This study revealed that EGCG reduced 2 metabolic risk factors which are triglyceride and blood pressure in the human experiment. We also showed a novel evidence that EGCG decreased kisspeptin levels. However, EGCG had no effects on obesity reduction in humans, lipolysis, nor browning of human white adipocytes.


greenmedinfo--2020-12-03--O. stamineus extracts are able to inhibit proliferation and induced apoptosis of uterine fibroid cel

O. stamineus extracts are able to inhibit proliferation and induced apoptosis of uterine fibroid cells.

Objectives : The effects of water and 50 % ethanolic-water extracts of Orthosiphon stamineus Benth ( OS ) on cell @ @ @ @ @ uterine leiomyosarcoma ( SK-UT-1 ) cells were investigated .
Methods : Anti-proliferation effect was evaluated @ @ @ @ @ apoptotic activity was determined via screening and quantifying using fluorescence microscopy and flow cytometric analysis @ @ @ @ @ of extracts on molecular mechanism was studied using real-time reverse transcription polymerase chain reaction and @ @ @ @ @ Cell cycle flow cytometric analysis showed the induction of cell cycle arrests were behaves in @ @ @ @ @ examination using fluorescence microscopy and Annexin V flow cytometry revealed the presence of morphological features @ @ @ @ @ of anti-apoptotic gene ( Bcl-2 ) supports the apoptotic activity of OS extracts although poorly @ @ @ @ @ blot analysis .
The extracts also inhibit the SK-UT-1 growth by suppressing VEGF-A , TGF-β1 @ @ @ @ @ involved in angiogenesis and cell proliferation .
Conclusion : This study demonstrates that O. stamineus @ @ @ @ @ proliferation and induced apoptosis of uterine fibroid cells and is worth further investigation .

Objectives: The effects of water and 50% ethanolic-water extracts of Orthosiphon stamineus Benth (OS) on cell proliferation and apoptotic activity against uterine leiomyosarcoma (SK-UT-1) cells were investigated. Methods: Anti-proliferation effect was evaluated through cell cycle analysis whereas apoptotic activity was determined via screening and quantifying using fluorescence microscopy and flow cytometric analysis, respectively. The effect of extracts on molecular mechanism was studied using real-time reverse transcription polymerase chain reaction and Western blotting. Results: Cell cycle flow cytometric analysis showed the induction of cell cycle arrests were behaves in a p53-independent manner. The examination using fluorescence microscopy and Annexin V flow cytometry revealed the presence of morphological features of apoptotic bodies. Downregulation of anti-apoptotic gene (Bcl-2) supports the apoptotic activity of OS extracts although poorly induce PARP-1 cleavage in Western blot analysis. The extracts also inhibit the SK-UT-1 growth by suppressing VEGF-A, TGF-β1 and PCNA genes, which involved in angiogenesis and cell proliferation. Conclusion: This study demonstrates that O. stamineus extracts are able to inhibit proliferation and induced apoptosis of uterine fibroid cells and is worth further investigation.


greenmedinfo--2020-12-04--Wogonin reverses the drug resistance of chronic myelogenous leukemia cells to imatinib.

Background : In the current study , chronic myeloid leukemia ( CML ) cells ( K562 and KU812 ) co-cultured with human bone marrow stromal cells ( BMSCs ) were significantly less sensitive to imatinib ( IM ) .
The activation of the CXCL12-CXCR4/7 axis plays an important role in the protective effect of the bone marrow microenvironment ( BME ) on CML cells .
The aim of this study was to investigate whether Wogonin could increase the sensitivity of CML cells to IM when they were co-cultured with BME and explore its underlying mechanism .
Methods : A model @ @ @ @ @ @ @ applied .
Flow cytometric , western blotting , immunofluorescence , and RT-PCR assays were used to explore the protective effects of BME on CML cells .
Results : The results showed that Wogonin could reverse the resistance of CML cells to IM under co-culture conditions by inhibiting Transforming growth factor-β ( TGF-β ) secretion in the BME , preventing the translocation of Smad4 into nucleus and subsequently reducing the expression of CXCR4 and CXCR7 in CML cells .
Moreover , the reverse effect of Wogonin was demonstrated by inhibiting the activation of CXCL12-CXCR4/7 @ @ @ @ @ @ @ showed that Wogonin decreased the expression of CXCR4 and CXCR7 in mice bone marrow with low systemic toxicity , and the mechanism was consistent with thestudy .
Conclusions : Wogonin increases the sensitivity of CML cells to IM in BME by controlling the TGF-β/Smad4/Id3 pathway and decreasing the expression of CXCR4 and CXCR7 .
These results co-supported the point that Wogonin could be a potential candidate of reversal agents on treatment of IM-resistant CML .

Background: In the current study, chronic myeloid leukemia (CML) cells (K562 and KU812) co-cultured with human bone marrow stromal cells (BMSCs) were significantly less sensitive to imatinib (IM). The activation of the CXCL12-CXCR4/7 axis plays an important role in the protective effect of the bone marrow microenvironment (BME) on CML cells. The aim of this study was to investigate whether Wogonin could increase the sensitivity of CML cells to IM when they were co-cultured with BME and explore its underlying mechanism.
Methods: A model of CML cells co-cultured with BMSCs was applied. Flow cytometric, western blotting, immunofluorescence, and RT-PCR assays were used to explore the protective effects of BME on CML cells.
Results: The results showed that Wogonin could reverse the resistance of CML cells to IM under co-culture conditions by inhibiting Transforming growth factor-β (TGF-β) secretion in the BME, preventing the translocation of Smad4 into nucleus and subsequently reducing the expression of CXCR4 and CXCR7 in CML cells. Moreover, the reverse effect of Wogonin was demonstrated by inhibiting the activation of CXCL12-CXCR4/7 axis via restraining the TGF-β/Smad4/Id3 pathway.studies also showed that Wogonin decreased the expression of CXCR4 and CXCR7 in mice bone marrow with low systemic toxicity, and the mechanism was consistent with thestudy.
Conclusions: Wogonin increases the sensitivity of CML cells to IM in BME by controlling the TGF-β/Smad4/Id3 pathway and decreasing the expression of CXCR4 and CXCR7. These results co-supported the point that Wogonin could be a potential candidate of reversal agents on treatment of IM-resistant CML.


greenmedinfo--2020-12-04--Puerarin induces mouse mesenteric vasodilation and ameliorates hypertension involving endothelial TR

Puerarin induces mouse mesenteric vasodilation and ameliorates hypertension involving endothelial TRPV4 channels.

Puerarin ( Pue ) is an isoflavone derived from the root of Pueraria lobata , which has been widely used as food and a herb for treating cardiovascular and cerebrovascular diseases .
Transient receptor potential vanilloid 4 ( TRPV4 ) , a Ca2+-permeable channel with multiple modes of activation , plays an important role in vascular endothelial function and vasodilation .
However , no reports have shown the effects of Pue on TRPV4 channels and mouse small mesenteric arteries .
In the present study , we performed a molecular docking assay by using Discovery Studio 3.5 software to predict the @ @ @ @ @ @ @ The activation of TRPV4 by Pue was determined by intracellular Ca2+ concentration ( [ Ca2+ ] i ) , live-cell fluorescent Ca2+ imaging and patch clamp assays .
Molecular docking results indicated a high possibility of Pue-TPRV4 binding .
[ Ca2+ ] i and Ca2+ imaging assays showed that Pue activated TRPV4 channels and increased [ Ca2+ ] i in TRPV4-overexpressing HEK293 ( TRPV4-HEK293 ) cells and primary mouse mesenteric artery endothelial cells ( MAECs ) .
Patch clamp assay demonstrated that Pue stimulated the TRPV4-mediated cation currents .
Additionally , Pue relaxed @ @ @ @ @ @ @ K+ channel ( SKCa ) /intermediate-conductance Ca2+-activated K+ channel ( IKCa ) pathway , and reduced systolic blood pressure ( SBP ) in high-salt-induced hypertensive mice .
Our study found for the first time that Pue acts as a TRPV4 agonist , induces endothelium-dependent vasodilation in mouse mesenteric arteries , and attenuates blood pressure in high-salt-induced hypertensive mice , highlighting the beneficial effect of Pue in treating endothelial dysfunction-related cardiovascular diseases .

Puerarin (Pue) is an isoflavone derived from the root of Pueraria lobata, which has been widely used as food and a herb for treating cardiovascular and cerebrovascular diseases. Transient receptor potential vanilloid 4 (TRPV4), a Ca2+-permeable channel with multiple modes of activation, plays an important role in vascular endothelial function and vasodilation. However, no reports have shown the effects of Pue on TRPV4 channels and mouse small mesenteric arteries. In the present study, we performed a molecular docking assay by using Discovery Studio 3.5 software to predict the binding of Pue to TRPV4 protein. The activation of TRPV4 by Pue was determined by intracellular Ca2+ concentration ([Ca2+]i), live-cell fluorescent Ca2+ imaging and patch clamp assays. Molecular docking results indicated a high possibility of Pue-TPRV4 binding. [Ca2+]i and Ca2+ imaging assays showed that Pue activated TRPV4 channels and increased [Ca2+]i in TRPV4-overexpressing HEK293 (TRPV4-HEK293) cells and primary mouse mesenteric artery endothelial cells (MAECs). Patch clamp assay demonstrated that Pue stimulated the TRPV4-mediated cation currents. Additionally, Pue relaxed mouse mesenteric arteries involving the TRPV4-small-conductance Ca2+-activated K+ channel (SKCa)/intermediate-conductance Ca2+-activated K+ channel (IKCa) pathway, and reduced systolic blood pressure (SBP) in high-salt-induced hypertensive mice. Our study found for the first time that Pue acts as a TRPV4 agonist, induces endothelium-dependent vasodilation in mouse mesenteric arteries, and attenuates blood pressure in high-salt-induced hypertensive mice, highlighting the beneficial effect of Pue in treating endothelial dysfunction-related cardiovascular diseases.


greenmedinfo--2020-12-03--Puerarin treatment modulated the gut microbiota disorder to elicit the anti-osteoporosis effects in

Puerarin treatment modulated the gut microbiota disorder to elicit the anti-osteoporosis effects in OVX rats.

SCOPE : Half of women over the age of 50 will experience a fracture related osteoporosis in their lifetime .
The common treatment is estrogen replacement therapy , which can cause many side effects .
Puerarin as a phytoestrogen has been proven to improve postmenopausal osteoporosis .
However , the mechanisms of anti-osteoporosis remain unclear due to its low bioavailability .
The aim of this study is to investigate whether the anti-osteoporosis effects of puerarin are related to modulations in the gut microbiota and focus on the mechanism of gut / bone axis .
METHODS : We established ovariectomized ( @ @ @ @ @ @ @ The femur was analyzed by microcomputed tomography ( μ-CT ) and we measured serum biochemical indices and inflammatory factors .
16S rRNA sequencing was employed to evaluate the gut microbiota composition in the fecal samples .
Short-chain fatty acids ( SCFAs ) was analyzed by GC .
The expression of intestinal inflammatory factors and adhesion proteins wasconfirmed by western blotting and qPCR .
RESULTS : Puerarin increased the BMD and improved the intestinal mucosal integrity to reduce the systemic inflammation .
The disorder of gut microbiota was improved and its metabolites SCFAs were @ @ @ @ @ @ @ acid metabolism , LPS biosynthesis and butyrate metabolism were enriched .
CONCLUSION : Puerarin treatment modulated the gut microbiota disorder to elicit the anti-osteoporosis effects in OVX rats , by improving the bone micro-environment via regulating the SCFAs levels and repairing the intestinal mucosal integrity .

SCOPE: Half of women over the age of 50 will experience a fracture related osteoporosis in their lifetime. The common treatment is estrogen replacement therapy, which can cause many side effects. Puerarin as a phytoestrogen has been proven to improve postmenopausal osteoporosis. However, the mechanisms of anti-osteoporosis remain unclear due to its low bioavailability. The aim of this study is to investigate whether the anti-osteoporosis effects of puerarin are related to modulations in the gut microbiota and focus on the mechanism of gut / bone axis.
METHODS: We established ovariectomized (OVX) rats as osteoporosis model. The femur was analyzed by microcomputed tomography (μ-CT) and we measured serum biochemical indices and inflammatory factors. 16S rRNA sequencing was employed to evaluate the gut microbiota composition in the fecal samples. Short-chain fatty acids (SCFAs) was analyzed by GC. The expression of intestinal inflammatory factors and adhesion proteins wasconfirmed by western blotting and qPCR.
RESULTS: Puerarin increased the BMD and improved the intestinal mucosal integrity to reduce the systemic inflammation. The disorder of gut microbiota was improved and its metabolites SCFAs were elevated. Metabolic pathways such as amino acid metabolism, LPS biosynthesis and butyrate metabolism were enriched.
CONCLUSION: Puerarin treatment modulated the gut microbiota disorder to elicit the anti-osteoporosis effects in OVX rats, by improving the bone micro-environment via regulating the SCFAs levels and repairing the intestinal mucosal integrity.


greenmedinfo--2020-12-03--Standard puerarin prevents diabetic renal damage.

Aim : This study was designed to use in vivo and in vitro approaches to evaluate puerarin in diabetes-induced renal injury .
Materials and Methods : SD rats were divided into NC ( normal control ) , Model ( diabetic induced renal injury model ) , SP-L ( model rats treated with low-dose standard puerarin ) , SP-M ( model rats treated with middle-dose standard puerarin ) , and SP-H ( model rats treated with high-dose standard puerarin ) groups .
We evaluated fasting blood-glucose ( FBG ) , urinary albumin/creatinine ratio ( UACR ) , body weight , and @ @ @ @ @ @ @ different groups .
TNF-α , IL-1β , and IL-6 concentrations were measured using Elisa assays .
HE staining and TUNEL assays were used to evaluate pathology and apoptosis in kidney tissues , respectively .
Relative gene and protein expression was measured using RT-qPCR and Western blot assays .
Apoptosis was measured using flowcytometry .
The correlation between miRNA-145-5p and TLR4 was assessed using dual-luciferase reporter gene assays .
Results : The pathology and apoptosis cell number were deteriorate in Model group ; TNF-α , IL-1β and IL-6 concentrations , FGB , UACR and @ @ @ @ @ @ @ depressed ; meanwhile , relative gene and proteins expressions ( miRNA-145-5p , TLR4 , MyD88 and NF-κB p65 ) were significantly different in Model group in vivo and vitro study compared with NC group .
SP treatment significantly improved the pathology and apoptosis levels in the tissues , as well as TNF-α , IL-1β and IL-6 concentrations , FGB , UACR , body weight , and KI .
In vitro cell studies revealed that SP could prevent renal injury induced by diabetes through the miRNA-145-5p/TLR4 axis .
Conclusion : SP prevents diabetes-induced renal @ @ @ @ @ @ @ ( p65 ) pathway activation in vitro and in vivo .

Aim: This study was designed to use in vivo and in vitro approaches to evaluate puerarin in diabetes-induced renal injury.
Materials and Methods: SD rats were divided into NC (normal control), Model (diabetic induced renal injury model), SP-L (model rats treated with low-dose standard puerarin), SP-M (model rats treated with middle-dose standard puerarin), and SP-H (model rats treated with high-dose standard puerarin) groups. We evaluated fasting blood-glucose (FBG), urinary albumin/creatinine ratio (UACR), body weight, and kidney index (KI) in the different groups. TNF-α, IL-1β, and IL-6 concentrations were measured using Elisa assays. HE staining and TUNEL assays were used to evaluate pathology and apoptosis in kidney tissues, respectively. Relative gene and protein expression was measured using RT-qPCR and Western blot assays. Apoptosis was measured using flowcytometry. The correlation between miRNA-145-5p and TLR4 was assessed using dual-luciferase reporter gene assays.
Results: The pathology and apoptosis cell number were deteriorate in Model group; TNF-α, IL-1β and IL-6 concentrations, FGB, UACR and KI were increased and body weight was depressed; meanwhile, relative gene and proteins expressions (miRNA-145-5p, TLR4, MyD88 and NF-κB p65) were significantly different in Model group in vivo and vitro study compared with NC group. SP treatment significantly improved the pathology and apoptosis levels in the tissues, as well as TNF-α, IL-1β and IL-6 concentrations, FGB, UACR, body weight, and KI. In vitro cell studies revealed that SP could prevent renal injury induced by diabetes through the miRNA-145-5p/TLR4 axis.
Conclusion: SP prevents diabetes-induced renal damage via miRNA-145-5p overexpression and reduces TLR4/MyD88/NF-κB (p65) pathway activation in vitro and in vivo.


greenmedinfo--2020-12-03--Puerarin sensitized K562/ADR cells by inhibiting NF-κB pathway and inducing autophagy.

Puerarin is an isoflavone isolated from Pueraria lobata ( Willd . )
Ohwi .
In the present study , reversal effect and underlying mechanisms of puerarin on multidrug resistance ( MDR ) were investigated in K562/ADR cells .
K562/ADR cells exhibited adriamycin ( ADR ) resistance and higher levels of MDR1 expression compared with K562 cells .
Puerarin enhanced the chemosensitivity of K562/ADR cells and increased the ADR accumulation in K562/ADR cells .
The expression levels of MDR1 were down-regulated by puerarin in K562/ADR cells .
Luciferase reporter assay further demonstrated the inhibitory effect of puerarin on TNF-α-induced NF-κB activation @ @ @ @ @ @ @ suppressed by puerarin .
In silico docking analyses suggested that puerarin well matched with the active sites of IκB-α .
Moreover , a large number of autophagosomes were found in the cytoplasm of K562/ADR cells after puerarin treatment .
The significant increase in LC3-II and beclin-1 was also observed , indicating autophagy induction by puerarin in K562/ADR cells .
Puerarin induced cell cycle arrest and apoptosis in K562/ADR cells .
Finally , puerarin inhibited phosphorylation of Akt and JNK .
In conclusion , puerarin-sensitized K562/ADR cells by downregulating MDR1 expression via inhibition of @ @ @ @ @ @ @ inhibition .

Puerarin is an isoflavone isolated from Pueraria lobata (Willd.) Ohwi. In the present study, reversal effect and underlying mechanisms of puerarin on multidrug resistance (MDR) were investigated in K562/ADR cells. K562/ADR cells exhibited adriamycin (ADR) resistance and higher levels of MDR1 expression compared with K562 cells. Puerarin enhanced the chemosensitivity of K562/ADR cells and increased the ADR accumulation in K562/ADR cells. The expression levels of MDR1 were down-regulated by puerarin in K562/ADR cells. Luciferase reporter assay further demonstrated the inhibitory effect of puerarin on TNF-α-induced NF-κB activation. The phosphorylation of IκB-α was significantly suppressed by puerarin. In silico docking analyses suggested that puerarin well matched with the active sites of IκB-α. Moreover, a large number of autophagosomes were found in the cytoplasm of K562/ADR cells after puerarin treatment. The significant increase in LC3-II and beclin-1 was also observed, indicating autophagy induction by puerarin in K562/ADR cells. Puerarin induced cell cycle arrest and apoptosis in K562/ADR cells. Finally, puerarin inhibited phosphorylation of Akt and JNK. In conclusion, puerarin-sensitized K562/ADR cells by downregulating MDR1 expression via inhibition of NF-κB pathway and autophagy induction via Akt inhibition.


greenmedinfo--2020-12-03--Puerarin alleviates osteoporosis in the ovariectomy-induced changes.

In this study , we investigated the mechanisms by which puerarin alleviates osteoclast-related loss of bone mass in ovariectomy ( @ @ @ @ @ mice .
Puerarin-treated OVX mice exhibited higher bone density , fewer tartrate-resistant acid phosphatase ( @ @ @ @ @ and levels of lower reactive oxygen species ( ROS ) within bone tissues than vehicle-treated @ @ @ @ @ differentiation , hydroxyapatite resorption activity , and expression of osteoclastogenesis-related genes , such as NFATc1 @ @ @ @ @ Acp5 and c-Fos , in RANKL-induced bone marrow macrophages ( BMMs ) and RAW264.7 cells @ @ @ @ @ ROS levels by suppressing expression of TRAF6 and NADPH oxidase 1 ( NOX1 ) and @ @ @ @ @ such as heme oxygenase-1 ( HO-1 ) .
Puerarin inhibited TRAF6/ROS-dependent activation of the MAPK @ @ @ @ @ RANKL-induced RAW264.7 cells , and these effects were partially reversed by HO-1 silencing or TRAF6 @ @ @ @ @ puerarin alleviates loss of bone mass in the OVX-model mice by suppressing osteoclastogenesis via inhibition @ @ @ @ @ .

In this study, we investigated the mechanisms by which puerarin alleviates osteoclast-related loss of bone mass in ovariectomy (OVX)-induced osteoporosis model mice. Puerarin-treated OVX mice exhibited higher bone density, fewer tartrate-resistant acid phosphatase (TRAcP)-positive osteoclasts, and levels of lower reactive oxygen species (ROS) within bone tissues than vehicle-treated OVX mice. Puerarin suppressedosteoclast differentiation, hydroxyapatite resorption activity, and expression of osteoclastogenesis-related genes, such as NFATc1, MMP9, CTSK, Acp5 and c-Fos, in RANKL-induced bone marrow macrophages (BMMs) and RAW264.7 cells. It also reduced intracellular ROS levels by suppressing expression of TRAF6 and NADPH oxidase 1 (NOX1) and increasing expression of antioxidant enzymes such as heme oxygenase-1 (HO-1). Puerarin inhibited TRAF6/ROS-dependent activation of the MAPK and NF-κB signaling pathways in RANKL-induced RAW264.7 cells, and these effects were partially reversed by HO-1 silencing or TRAF6 overexpression. These findings suggest puerarin alleviates loss of bone mass in the OVX-model mice by suppressing osteoclastogenesis via inhibition of the TRAF6/ROS-dependentMAPK/NF-κB signaling pathway.


greenmedinfo--2020-12-03--Puerarin protects vascular smooth muscle cells from oxidized low-density lipoprotein-induced reducti

Puerarin protects vascular smooth muscle cells from oxidized low-density lipoprotein-induced reductions in viability.

Puerarin belongs to the family of flavonoids extracted from ( Wild . )
Ohwi , which exhibits antioxidative , anti-inflammatory , anti-hyperglycemic , antitumor , anti-hypertensive and anti-atherosclerotic activities .
In the present study , the effects of puerarin on oxidized low-density lipoprotein ( ox-LDL ) -stimulated vascular smooth muscle cells ( VSMCs ) were explored to understand the mechanisms underlying the anti-atherosclerotic effects of puerarin .
VSMCs were treated with various concentrations of puerarin ( 0 , 20 , 40 and 80µM ) prior to stimulation with ox-LDL ( 50 µg/ml ) .
VSMC viability was evaluated by performing @ @ @ @ @ @ @ Moreover , superoxide dismutase ( SOD ) and malondialdehyde ( MDA ) levels were measured by performing ELISAs .
The mRNA expression levels of interleukin-6 ( IL-6 ) and tumor necrosis factor-α ( TNF-α ) were determined via reverse transcription-quantitative PCR .
Western blotting was conducted to assess the levels of p38-MAPK and JNK phosphorylation .
The results indicated that puerarin inhibited ox-LDL-induced VSMC viability .
Moreover , puerarin significantly decreased the mRNA expression levels of IL-6 and TNF-α , significantly reduced the production of MDA and significantly increased SOD activity in ox-LDL-stimulated @ @ @ @ @ @ @ of p38 and JNK in VSMCs .
The results suggested that puerarin reduced ox-LDL-induced VSMC viability via inhibition of the p38 MAPK and JNK signaling pathways .
The present study provided theoretical evidence that puerarin may serve as a therapeutic agent to reduce the development of atherosclerosis .

Puerarin belongs to the family of flavonoids extracted from(Wild.) Ohwi, which exhibits antioxidative, anti-inflammatory, anti-hyperglycemic, antitumor, anti-hypertensive and anti-atherosclerotic activities. In the present study, the effects of puerarin on oxidized low-density lipoprotein (ox-LDL)-stimulated vascular smooth muscle cells (VSMCs) were explored to understand the mechanisms underlying the anti-atherosclerotic effects of puerarin. VSMCs were treated with various concentrations of puerarin (0, 20, 40 and 80µM) prior to stimulation with ox-LDL (50 µg/ml). VSMC viability was evaluated by performing MTT and Cell Counting Kit-8 assays. Moreover, superoxide dismutase (SOD) and malondialdehyde (MDA) levels were measured by performing ELISAs. The mRNA expression levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were determined via reverse transcription-quantitative PCR. Western blotting was conducted to assess the levels of p38-MAPK and JNK phosphorylation. The results indicated that puerarin inhibited ox-LDL-induced VSMC viability. Moreover, puerarin significantly decreased the mRNA expression levels of IL-6 and TNF-α, significantly reduced the production of MDA and significantly increased SOD activity in ox-LDL-stimulated VSMCs. Puerarin also inhibited ox-LDL-induced phosphorylation of p38 and JNK in VSMCs. The results suggested that puerarin reduced ox-LDL-induced VSMC viability via inhibition of the p38 MAPK and JNK signaling pathways. The present study provided theoretical evidence that puerarin may serve as a therapeutic agent to reduce the development of atherosclerosis.


greenmedinfo--2020-12-03--Reiki Improves Heart Attack Outcomes, Yale Study Confirms


greenmedinfo--2020-12-03--Anti-coronavirus disease 2019 (COVID-19) targets and mechanisms of puerarin.

The present study aimed to uncover the pharmacological function and underlying mechanism of puerarin as a potential treatment for COVID-19 , using an in silico methodology , including network pharmacology and molecular docking .
The pivotal targets of puerarin to treat COVID-19 were identified and included the epidermal growth factor receptor ( EGFR ) , tumour necrosis factor ( TNF ) , tumour protein p53 ( TP53 ) , caspase 3 ( CASP3 ) , RELA proto-oncogene ( RELA ) , Fos proto-oncogene ( FOS ) , caspase 8 ( CASP8 ) , prostaglandin-endoperoxide synthase 2 ( PTGS2 ) , @ @ @ @ @ @ @ kinase CB ( PRKCB ) , B cell lymphoma/leukaemia gene-2 ( BCL2 ) , protein kinase CA ( PRKCA ) , nitric oxide synthase 3 ( NOS3 ) and peroxisome proliferator-activated receptor gamma ( PPARG ) .
Functionally , the anti-COVID-19 action of puerarin was associated with the suppression of oxidative stress and inflammatory cascades , and cell apoptosis .
The signalling pathways of puerarin to treat COVID-19 included modulation of the pathways of apoptosis , IL-17 signalling , mitogen-activated protein kinase ( MAPK ) signalling and TNF signalling .
Molecular docking data @ @ @ @ @ @ @ COVID-19 and the effective anti-COVID-19 activity of puerarin .
Taken together , our current network pharmacology-based findings revealed the pharmacological role of puerarin in the treatment of COVID-19 .
Furthermore , the bioinformatic findings elucidated that some of these pivotal targets might serve as potential molecular markers for detecting COVID-19 .

The present study aimed to uncover the pharmacological function and underlying mechanism of puerarin as a potential treatment for COVID-19, using an in silico methodology, including network pharmacology and molecular docking. The pivotal targets of puerarin to treat COVID-19 were identified and included the epidermal growth factor receptor (EGFR), tumour necrosis factor (TNF), tumour protein p53 (TP53), caspase 3 (CASP3), RELA proto-oncogene (RELA), Fos proto-oncogene (FOS), caspase 8 (CASP8), prostaglandin-endoperoxide synthase 2 (PTGS2), interleukin 2 (IL2), protein kinase CB (PRKCB), B cell lymphoma/leukaemia gene-2 (BCL2), protein kinase CA (PRKCA), nitric oxide synthase 3 (NOS3) and peroxisome proliferator-activated receptor gamma (PPARG). Functionally, the anti-COVID-19 action of puerarin was associated with the suppression of oxidative stress and inflammatory cascades, and cell apoptosis. The signalling pathways of puerarin to treat COVID-19 included modulation of the pathways of apoptosis, IL-17 signalling, mitogen-activated protein kinase (MAPK) signalling and TNF signalling. Molecular docking data illustrated the binding capacity of puerarin with COVID-19 and the effective anti-COVID-19 activity of puerarin. Taken together, our current network pharmacology-based findings revealed the pharmacological role of puerarin in the treatment of COVID-19. Furthermore, the bioinformatic findings elucidated that some of these pivotal targets might serve as potential molecular markers for detecting COVID-19.


greenmedinfo--2020-12-03--Puerarin mitigated skeletal muscle wasting in type 1 diabetes.

Puerarin is an isoflavonoid extracted from Pueraria lobate with extensive pharmacological effects in traditional Chinese medicine .
The evidence implicates that puerarin mitigates hyperglycemia and various relevant complications .
Here , the effect of puerarin on skeletal muscle wasting induced by type 1 diabetes ( T1D ) was explored .
Streptozotocin ( STZ ) -induced T1D male Sprague Dawley ( SD ) rats were used in this study .
Muscle strength , weight and size were measured .
L6 rat skeletal muscle cells were applied for in vitro study .
Our results showed that eight-week oral puerarin administration ( 100 @ @ @ @ @ @ @ accompanied by enhanced skeletal muscle cross-sectional areas in diabetic rats .
Simultaneously , puerarin also reduced expressions of several muscle wasting marker genes including F-box only protein 32 ( Atrogin-1 ) and muscle-specific RING-finger 1 ( Murf-1 ) in diabetic group both in vitro and in vivo .
Transformation from type I fibers ( slow muscle ) to type II fibers ( fast muscle ) were also observed under puerarin administration in diabetic rats .
Puerarin promoted Akt/mTOR while inhibited LC3/p62 signaling pathway in skeletal muscle cells .
In conclusion , our study @ @ @ @ @ @ @ in T1D rats and closely related with Akt/mTOR activation and autophagy inhibition .
Whether this effect in murine applies to humans remains to be determined .

Puerarin is an isoflavonoid extracted from Pueraria lobate with extensive pharmacological effects in traditional Chinese medicine. The evidence implicates that puerarin mitigates hyperglycemia and various relevant complications. Here, the effect of puerarin on skeletal muscle wasting induced by type 1 diabetes (T1D) was explored. Streptozotocin (STZ)-induced T1D male Sprague Dawley (SD) rats were used in this study. Muscle strength, weight and size were measured. L6 rat skeletal muscle cells were applied for in vitro study. Our results showed that eight-week oral puerarin administration (100 mg/kg) increased muscle strengths and weights accompanied by enhanced skeletal muscle cross-sectional areas in diabetic rats. Simultaneously, puerarin also reduced expressions of several muscle wasting marker genes including F-box only protein 32 (Atrogin-1) and muscle-specific RING-finger 1 (Murf-1) in diabetic group both in vitro and in vivo. Transformation from type I fibers (slow muscle) to type II fibers (fast muscle) were also observed under puerarin administration in diabetic rats. Puerarin promoted Akt/mTOR while inhibited LC3/p62 signaling pathway in skeletal muscle cells. In conclusion, our study showed that puerarin mitigated skeletal muscle wasting in T1D rats and closely related with Akt/mTOR activation and autophagy inhibition. Whether this effect in murine applies to humans remains to be determined.


greenmedinfo--2020-12-03--The ameliorative effects of capsidiol isolated from elicited Capsicum annuum on mouse splenocyte imm

The ameliorative effects of capsidiol isolated from elicited Capsicum annuum on mouse splenocyte immune responses and neuroinflammation.

Capsidiol , is an anti-fungal phytoalexin produced by plants of Solanaceae .
Capsidiol was examined in cultures of primary splenocytes ( SPLCs ) isolated from healthy C57BL/6 mice and from those with induced experimental autoimmune encephalomyelitis ( EAE ) as a mouse model for autoimmune neurodegenerative multiple sclerosis ( MS ) .
We also examined the impact of capsidiol in IFN-γ-stimulated mouse BV2 microglial cells .
Capsidiol resulted in a significant reduction in the anti-CD3/CD28 ( αCD3/CD28 ) -induced IFN-γCD4 ( Th1 ) and IFN-γCD8 ( Tc1 ) populations as well as in the production of cytokines ( IFN-γ , @ @ @ @ @ @ @ , and IP-10 ) .
Specifically , the CD4and CD8populations ( T-betIFN-γ , T-betIFN-γ , and T-betIFN-γ ) and cytokine production mediated by Th1/Tc1 polarization were diminished by 25 μM capsidiol .
MOGrestimulation of SPLCs from EAE mice resulted in an increase in antigen-specific T cells , including Th1 , IL-17ACD4 ( Th17 ) , and IL-17ACD8 ( Tc17 ) populations .
By contrast , capsidiol resulted in a decrease in the proportions of Th17 and Tc17 cells ; MOG-specific cytokine production was also diminished by capsidiol .
Capsidiol treatment resulted in diminished @ @ @ @ @ @ @ ; expression of iNOS and COX-2 were suppressed by 50 μM capsidiol in IFN-γ-stimulated BV2 cells .
This is the first report of capsidiol-mediated immunomodulatory and antineuroinflammatory activities that may serve to prevent neurodegeneration .

Capsidiol, is an anti-fungal phytoalexin produced by plants of Solanaceae. Capsidiol was examined in cultures of primary splenocytes (SPLCs) isolated from healthy C57BL/6 mice and from those with induced experimental autoimmune encephalomyelitis (EAE) as a mouse model for autoimmune neurodegenerative multiple sclerosis (MS). We also examined the impact of capsidiol in IFN-γ-stimulated mouse BV2 microglial cells. Capsidiol resulted in a significant reduction in the anti-CD3/CD28 (αCD3/CD28)-induced IFN-γCD4(Th1) and IFN-γCD8(Tc1) populations as well as in the production of cytokines (IFN-γ, IL-17A, IL-6, IL-2, TNF-α, and IP-10). Specifically, the CD4and CD8populations (T-betIFN-γ, T-betIFN-γ, and T-betIFN-γ) and cytokine production mediated by Th1/Tc1 polarization were diminished by 25 μM capsidiol. MOGrestimulation of SPLCs from EAE mice resulted in an increase in antigen-specific T cells, including Th1, IL-17ACD4(Th17), and IL-17ACD8(Tc17) populations. By contrast, capsidiol resulted in a decrease in the proportions of Th17 and Tc17 cells; MOG-specific cytokine production was also diminished by capsidiol. Capsidiol treatment resulted in diminished levels of IFN-γ-induced nitric oxide and IL-6; expression of iNOS and COX-2 were suppressed by 50 μM capsidiol in IFN-γ-stimulated BV2 cells. This is the first report of capsidiol-mediated immunomodulatory and antineuroinflammatory activities that may serve to prevent neurodegeneration.


greenmedinfo--2020-12-03--C. annuum supplementation had significant effect on low density lipoprotein-cholesterol.

Metabolic syndrome ( MetS ) has increasingly gained importance as the main risk factor for cardiovascular diseases and type II diabetes mellitus .
Various natural compounds derived from plants are associated with beneficial effects on the incidence and progression of MetS .
This study aimed to evaluate the effects of Capsicum annuum on factors related to MetS by assessing randomized controlled trials ( written in English ) .
We searched the online databases of PubMed , Embase , Google scholar , and Cochrane Library up to April 2020 .
'Patient/Population , Intervention , Comparison and Outcomes ' format was used @ @ @ @ @ @ @ supplementation compared with placebo supplementation had any effect on the components of MetS among participants .
We considered standardized mean differences ( SMD ) with 95 % confidence intervals ( CI ) as effect size measures using random-effects model .
Analysis of the included 11 studies ( n = 609 ) showed that C. annuum supplementation had significant effect on low density lipoprotein-cholesterol [ SMD = - 0.39 ; 95 % CI - 0.72 , - 0.07 ; P = 0.02 ; prediction interval , - 1.28 to 0.50 ] and marginally significant @ @ @ @ @ @ @ - 0.19 ; 95 % CI - 0.40 , 0.03 ; P = 0.09 ] .
However , larger and well-designed clinical trials are needed to investigate the effects of C. annuum on MetS .

Metabolic syndrome (MetS) has increasingly gained importance as the main risk factor for cardiovascular diseases and type II diabetes mellitus. Various natural compounds derived from plants are associated with beneficial effects on the incidence and progression of MetS. This study aimed to evaluate the effects of Capsicum annuum on factors related to MetS by assessing randomized controlled trials (written in English). We searched the online databases of PubMed, Embase, Google scholar, and Cochrane Library up to April 2020. 'Patient/Population, Intervention, Comparison and Outcomes' format was used to determine whether intervention with C. annuum supplementation compared with placebo supplementation had any effect on the components of MetS among participants. We considered standardized mean differences (SMD) with 95% confidence intervals (CI) as effect size measures using random-effects model. Analysis of the included 11 studies (n = 609) showed that C. annuum supplementation had significant effect on low density lipoprotein-cholesterol [SMD = - 0.39; 95% CI - 0.72, - 0.07; P = 0.02; prediction interval, - 1.28 to 0.50] and marginally significant effect on body weight [SMD = - 0.19; 95% CI - 0.40, 0.03;P = 0.09]. However, larger and well-designed clinical trials are needed to investigate the effects of C. annuum on MetS.


greenmedinfo--2020-12-03--Paprika carotenoid extract supplementation suppresses bone resorption and contributes to maintaining

Paprika carotenoid extract supplementation suppresses bone resorption and contributes to maintaining bone quality in postmenopausal women.

Background : Paprika ( L. ) is a good source of carotenoids , including capsanthin , β-carotene , β-cryptoxanthin , and zeaxanthin .
Several epidemiological studies have shown a beneficial association of intake of these carotenoids or their blood concentration with bone mineral density ( BMD ) and fracture risk .
However , little information is available regarding the effect of intake ofthese carotenoids on bone metabolism in postmenopausal women .
Objective : The objective of the present study was to investigate the effects of paprika carotenoid extract ( PCE ) on bone turnover in healthy , postmenopausal women .
@ @ @ @ @ @ @ double-blind , placebo-controlled , parallel-group comparison study .
One hundred participants were randomly assigned to PCE or placebo groups .
Each group was given a 20 mg PCE ( equivalent to 1.4 mg of carotenoids ) a day or a placebo for 24 weeks .
We measured bone resorption markers ( tartrate-resistant acid phosphatase 5b [ TRACP-5b ] and serum type I collagen cross-linked N-telopeptide [ sNTX ] ) at 12 and 24 weeks and bone formation markers ( bone alkaline phosphatase and osteocalcin ) at 24 weeks .
Results : The percentage @ @ @ @ @ @ @ significantly higher for PCE than the placebo .
There were no significant differences in sNTX or bone formation markers , although PCE decreased each marker compared with the placebo .
Conclusion : Our findings suggest that PCE supplementation suppresses bone resorption and contributes to maintaining bone quality in postmenopausal women .

Background: Paprika (L.) is a good source of carotenoids, including capsanthin,β-carotene, β-cryptoxanthin, and zeaxanthin. Several epidemiological studies have shown a beneficial association of intake of these carotenoids or their blood concentration with bone mineral density (BMD) and fracture risk. However, little information is available regarding the effect of intake ofthese carotenoids on bone metabolism in postmenopausal women.
Objective: The objective of the present study was to investigate the effects of paprika carotenoid extract (PCE) on bone turnover in healthy, postmenopausal women.
Design: We conducted a randomized, double-blind, placebo-controlled, parallel-group comparison study. One hundred participants were randomly assigned to PCE or placebo groups. Each group was given a 20 mg PCE (equivalent to 1.4 mg of carotenoids) a day or a placebo for 24 weeks. We measured bone resorption markers (tartrate-resistant acid phosphatase 5b [TRACP-5b] and serum type I collagen cross-linked N-telopeptide [sNTX]) at 12 and 24 weeks and bone formation markers (bone alkaline phosphatase and osteocalcin) at 24 weeks.
Results: The percentage decrease of TRACP-5b at 24 weeks was significantly higher for PCE than the placebo. There were no significant differences in sNTX or bone formation markers, although PCE decreased each marker compared with the placebo.
Conclusion: Our findings suggest that PCE supplementation suppresses bone resorption and contributes to maintaining bone quality in postmenopausal women.


greenmedinfo--2020-12-03--β-carotene and epigallocatechin gallate significantly reduces plaque size and dissolves peptide aggr

β-carotene and epigallocatechin gallate significantly reduces plaque size and dissolves peptide aggregates.

SCOPE : Alzheimer 's disease is a neurodegenerative condition marked by the formation and aggregation of amyloid-β ( Aβ ) peptides .
There exists , to this day , no cure or effective prevention for the disease ; however , there is evidence that a healthy diet and certain food products can slow down first occurrence and progression .
To investigate if food ingredients can interact with peptide aggregates , synthetic membranes that contained aggregates consisting of cross-β sheets of the membrane active fragment Aare prepared .
METHODS AND RESULTS : The impact of resveratrol , found in grapes , @ @ @ @ @ @ @ coffee , β-carotene , found in orange fruits and vegetables , and epigallocatechin gallate ( EGCG ) , a component of green tea , on the size and volume fraction of Aβ aggregates is studied using optical and fluorescence microscopy , X-ray diffraction , UV-vis spectroscopy , and molecular dynamics simulations .
All compounds are membrane active and spontaneously partitioned in the synthetic brain membranes .
While resveratrol and caffeine lead to membrane thickening and reduced membrane fluidity , β-carotene and EGCG preserve or increase fluidity .
CONCLUSION : Resveratrol and caffeine do @ @ @ @ @ @ @ aggregates whileβ-carotene significantly reduces plaque size .
Interestingly , EGCG dissolves peptide aggregates and significantly decreases the corresponding cross-β and β-sheet signals .

SCOPE: Alzheimer's disease is a neurodegenerative condition marked by the formation and aggregation of amyloid-β (Aβ) peptides. There exists, to this day, no cure or effective prevention for the disease; however, there is evidence that a healthy diet and certain food products can slow down first occurrence and progression. To investigate if food ingredients can interact with peptide aggregates, synthetic membranes that contained aggregates consisting of cross-β sheets of the membrane active fragment Aare prepared.
METHODS AND RESULTS: The impact of resveratrol, found in grapes, caffeine, the main active ingredient in coffee,β-carotene, found in orange fruits and vegetables, and epigallocatechin gallate (EGCG), a component of green tea, on the size and volume fraction of Aβ aggregates is studied using optical and fluorescence microscopy, X-ray diffraction, UV-vis spectroscopy, and molecular dynamics simulations. All compounds are membrane active and spontaneously partitioned in the synthetic brain membranes. While resveratrol and caffeine lead to membrane thickening and reduced membrane fluidity, β-carotene and EGCG preserve or increase fluidity.
CONCLUSION: Resveratrol and caffeine do not reduce the volume fraction of peptide aggregates whileβ-carotene significantly reduces plaque size. Interestingly, EGCG dissolves peptide aggregates and significantly decreases the corresponding cross-β and β-sheet signals.


greenmedinfo--2020-12-03--Anti-cancer effects of green tea epigallocatchin-3-gallate and coffee chlorogenic acid.

Tea and coffee are consumed worldwide and epidemiological and clinical studies have shown their health beneficial effects , including anti-cancer effects .
Epigallocatechin gallate ( EGCG ) and chlorogenic acid ( CGA ) are the major components of green tea polyphenols and coffee polyphenols , respectively , and believed to be responsible for most of these effects .
Although a large number of cell-based and animal experiments have provided convincing evidence to support the anti-cancer effects of green tea , coffee , EGCG , and CGA , human studies are still controversial and some studies have suggested even an increased @ @ @ @ @ @ @ as esophageal and gynecological cancers with green tea consumption and bladder and lung cancers with coffee consumption .
The reason for these inconsistent results may have been arisen from various confounding factors .
Cell-based and animal studies have proposed several mechanisms whereby EGCG and CGA exert their anti-cancer effects .
These components appear to share the common mechanisms , among which one related to reactive oxygen species is perhaps the most attractive .
Meanwhile , EGCG and CGA have also different target molecules which might explain the site-specific differences of anti-cancer effects found @ @ @ @ @ @ @ be necessary to clarify what is the mechanism to cause such differences between green tea and coffee .

Tea and coffee are consumed worldwide and epidemiological and clinical studies have shown their health beneficial effects, including anti-cancer effects. Epigallocatechin gallate (EGCG) and chlorogenic acid (CGA) are the major components of green tea polyphenols and coffee polyphenols, respectively, and believed to be responsible for most of these effects. Although a large number of cell-based and animal experiments have provided convincing evidence to support the anti-cancer effects of green tea, coffee, EGCG, and CGA, human studies are still controversial and some studies have suggested even an increased risk for certain types of cancers such as esophageal and gynecological cancers with green tea consumption and bladder and lung cancers with coffee consumption. The reason for these inconsistent results may have been arisen from various confounding factors. Cell-based and animal studies have proposed several mechanisms whereby EGCG and CGA exert their anti-cancer effects. These components appear to share the common mechanisms, among which one related to reactive oxygen species is perhaps the most attractive. Meanwhile, EGCG and CGA have also different target molecules which might explain the site-specific differences of anti-cancer effects found in human studies. Further studies will be necessary to clarify what is the mechanism to cause such differences between green tea and coffee.


greenmedinfo--2020-12-03--Higher consumption of green tea and coffee was associated with reduced all-cause mortality.

INTRODUCTION : The impact of consuming green tea or coffee on mortality in patients with diabetes is controversial .
We prospectively investigated the impact of each beverage and their combination on mortality among Japanese patients with type 2 diabetes .
RESEARCH DESIGN AND METHODS : In all , 4923 patients ( 2790 men , 2133 women ) with type 2 diabetes ( mean age , 66 years ) were followed prospectively ( median , 5.3 years ; follow-up rate , 99.5 % ) .
We evaluated the amount of green tea and coffee consumed using self-administered questionnaires .
RESULTS : @ @ @ @ @ @ @ died .
The consumption of green tea , coffee , and a combination of the beverages was associated with reduced all-cause mortality .
Multivariable-adjusted hazard ratios ( 95 % CIs ) for green tea were as follows : none 1.0 ( referent ) ; 0.85 ( 0.60-1.22 ) for≤1 cup/day ; 0.73 ( 0.51-1.03 ) for 2-3 cups/day ; 0.60 ( 0.42-0.85 ) for ≥4 cups/day ; and P for trend , 0.002 .
For coffee , they were : none 1.0 ( referent ) ; 0.88 ( 0.66-1.18 ) for < 1 @ @ @ @ @ @ @ 1 cup/day ; 0.59 ( 0.42-0.82 ) for≥2 cups/day ; P for trend , 0.002 .
With the combination they were 1.0 ( referent ) for no consumption of green tea and coffee ; 0.49 ( 0.24-0.99 ) for 2-3 cups/day of green tea with ≥2 cups/day of coffee ; 0.42 ( 0.20-0.88 ) for ≥4 cups/day of green tea with 1 cup/day of coffee ; and 0.37 ( 0.18-0.77 ) for≥4 cups/day of green tea with ≥2 cups/day of coffee .
CONCLUSIONS : Higher consumption of green tea and coffee was associated @ @ @ @ @ @ @ effect appeared to be additive in patients with type 2 diabetes .

INTRODUCTION: The impact of consuming green tea or coffee on mortality in patients with diabetes is controversial. We prospectively investigated the impact of each beverage and their combination on mortality among Japanese patients with type 2 diabetes.
RESEARCH DESIGN AND METHODS: In all, 4923 patients (2790 men, 2133 women) with type 2 diabetes (mean age, 66 years) were followed prospectively (median, 5.3 years; follow-up rate, 99.5%). We evaluated the amount of green tea and coffee consumed using self-administered questionnaires.
RESULTS: During the follow-up period, 309 participants died. The consumption of green tea, coffee, and a combination of the beverages was associated with reduced all-cause mortality. Multivariable-adjusted hazard ratios (95% CIs) for green tea were as follows: none 1.0 (referent); 0.85 (0.60-1.22) for≤1 cup/day; 0.73 (0.51-1.03) for 2-3 cups/day; 0.60 (0.42-0.85) for ≥4 cups/day; and P for trend, 0.002. For coffee, they were: none 1.0 (referent); 0.88 (0.66-1.18) for<1 cup/day; 0.81 (0.58-1.13) for 1 cup/day; 0.59 (0.42-0.82) for≥2 cups/day; P for trend, 0.002. With the combination they were 1.0 (referent) for no consumption of green tea and coffee; 0.49 (0.24-0.99) for 2-3 cups/day of green tea with ≥2 cups/day of coffee; 0.42 (0.20-0.88) for ≥4 cups/day of green tea with 1 cup/day of coffee; and 0.37 (0.18-0.77) for≥4 cups/day of green tea with ≥2 cups/day of coffee.
CONCLUSIONS: Higher consumption of green tea and coffee was associated with reduced all-cause mortality: their combined effect appeared to be additive in patients with type 2 diabetes.


greenmedinfo--2020-12-03--Gold nanoparticles as radiosensitizers in cancer radiotherapy.

The rapid development of nanotechnology offers a variety of potential therapeutic strategies for cancer treatment .
High atomic element nanomaterials @ @ @ @ @ due to their unique photoelectric decay characteristics .
Among them , gold nanoparticles ( GNPs @ @ @ @ @ most widely investigated and are considered to be an ideal radiosensitizers for radiotherapy due to @ @ @ @ @ unique physicochemical properties .
Over the last few decades , multi-disciplinary studies have focused on @ @ @ @ @ GNPs to achieve greater dosing capability and higher therapeutic effects and highlight potential mechanisms for @ @ @ @ @ the radiosensitizing potential of GNPs has been widely recognized , its clinical translation still faces @ @ @ @ @ analyses the different roles of GNPs as radiosensitizers in cancer radiotherapy and summarizes recent advances @ @ @ @ @ underlying mechanisms of GNP radiosensitization , including physical , chemical and biological mechanisms are discussed @ @ @ @ @ directions for the optimization and clinical transformation of next-generation GNPs .

The rapid development of nanotechnology offers a variety of potential therapeutic strategies for cancer treatment. High atomic element nanomaterials are often utilized as radiosensitizers due to their unique photoelectric decay characteristics. Among them, gold nanoparticles (GNPs) are one of the most widely investigated and are considered to be an ideal radiosensitizers for radiotherapy due to their high X-ray absorption and unique physicochemical properties. Over the last few decades, multi-disciplinary studies have focused on the design and optimization of GNPs to achieve greater dosing capability and higher therapeutic effects and highlight potential mechanisms for radiosensitization of GNPs. Although the radiosensitizing potential of GNPs has been widely recognized, its clinical translation still faces many challenges. This review analyses the different roles of GNPs as radiosensitizers in cancer radiotherapy and summarizes recent advances. In addition, the underlying mechanisms of GNP radiosensitization, including physical, chemical and biological mechanisms are discussed, which may provide new directions for the optimization and clinical transformation of next-generation GNPs.