greenmedinfo--2020-06-17--The results encourage evaluation of lingonberries as a part of healthy diet against obesity and its

Obesity is a constantly increasing health problem worldwide .
It is associated with a systemic low-grade inflammation , which contributes to the development of metabolic disorders and comorbidities such as type 2 diabetes .
Diet has an important role in the prevention of obesity and its adverse health effects ; as a part of healthy diet , polyphenol-rich berries , such as lingonberry ( Vaccinium vitis-idaea L. ) have been proposed to have health-promoting effects .
In the present study , we investigated the effects of lingonberry supplementation on high-fat diet induced metabolic and inflammatory changes in a mouse model @ @ @ @ @ @ @ were divided into three groups ( n = 10/group ) to receive low-fat ( LF ) , high-fat ( HF ) and lingonberry-supplemented high-fat ( HF+LGB ) diet for six weeks .
Low-fat and high-fat diet contained 10 % and 46 % of energy from fat , respectively .
Lingonberry supplementation prevented the high-fat diet induced adverse changes in blood cholesterol and glucose levels and had a moderate effect on the weight and visceral fat gain , which were 26 % and 25 % lower , respectively , in the lingonberry group than @ @ @ @ @ @ @ Interestingly , lingonberry supplementation also restrained the high-fat diet induced increases in the circulating levels of the proinflammatory adipocytokine leptin ( by 36 % ) and the inflammatory acute phase reactant serum amyloid A ( SAA ; by 85 % ) .
Similar beneficial effects were discovered in the hepatic expression of the inflammatory factors CXCL-14 , S100A10 and SAA by lingonberry supplementation .
In conclusion , the present results indicate that lingonberry supplementation significantly prevents high-fat diet induced metabolic and inflammatory changes in a murine model of obesity .
The results encourage @ @ @ @ @ @ @ healthy diet against obesity and its comorbidities .

Obesity is a constantly increasing health problem worldwide. It is associated with a systemic low-grade inflammation, which contributes to the development of metabolic disorders and comorbidities such as type 2 diabetes. Diet has an important role in the prevention of obesity and its adverse health effects; as a part of healthy diet, polyphenol-rich berries, such as lingonberry (Vaccinium vitis-idaea L.) have been proposed to have health-promoting effects. In the present study, we investigated the effects of lingonberry supplementation on high-fat diet induced metabolic and inflammatory changes in a mouse model of obesity. Thirty male C57BL/6N mice were divided into three groups (n = 10/group) to receive low-fat (LF), high-fat (HF) and lingonberry-supplemented high-fat (HF+LGB) diet for six weeks. Low-fat and high-fat diet contained 10% and 46% of energy from fat, respectively. Lingonberry supplementation prevented the high-fat diet induced adverse changes in blood cholesterol and glucose levels and had a moderate effect on the weight and visceral fat gain, which were 26% and 25% lower, respectively, in the lingonberry group than in the high-fat diet control group. Interestingly, lingonberry supplementation also restrained the high-fat diet induced increases in the circulating levels of the proinflammatory adipocytokine leptin (by 36%) and the inflammatory acute phase reactant serum amyloid A (SAA; by 85%). Similar beneficial effects were discovered in the hepatic expression of the inflammatory factors CXCL-14, S100A10 and SAA by lingonberry supplementation. In conclusion, the present results indicate that lingonberry supplementation significantly prevents high-fat diet induced metabolic and inflammatory changes in a murine model of obesity. The results encourage evaluation of lingonberries as a part of healthy diet against obesity and its comorbidities.


greenmedinfo--2020-06-17--The present study showed that cranberry significantly attenuated NAFLD.

Background : Non-alcoholic fatty liver disease ( NAFLD ) is a pathological accumulation of triglycerides ( TGs ) in the hepatocyte in the absence of alcohol intake .
Untreated NAFLD is expected to progress into liver fibrosis .
Cranberry is rich in polyphenols with antioxidant and anti-inflammatory activities .
Hypothesis : The present study was performed to evaluate our hypothesis of the possible anti-fibrotic effect of cranberry nutraceuticals in a high fat cholesterol diet induced ( HFCD ) -NAFLD in rats , focusing on improving insulin sensitivity and modulating the expression of nuclear factor erythroid-2-related factor-2 ( Nrf2 ) ( @ @ @ @ @ @ @ redox balance ) .
Method : Male albino wistar rats ( 12 weeks ) received HFCD and/or cranberry ( 50 and 100 mg/kg/day , three times/week ) orally for 8 consecutive weeks .
Results : In comparison to the HFCD group , cranberry treated groups ( 50 and 100 mg/kg ) showed marked hepatoprotection , where it significantly decreased liver enzymes ( alanine transaminases by 49 and 64 % and aspartate transaminases by 45 and 64 % ; respectively ) , TGs , and ameliorated the histopathological alterations ( such as inflammatory cells @ @ @ @ @ @ @ HFCD .
Cranberry also alleviated oxidative stress ( malondialdehyde , glutathione , catalase and superoxide dismutase ) and inflammation ( tumor necrosis factor- alpha , interleukine-6 and nuclear factor kappa-b ) and significantly reduced the HOMA-IR and TyG index .
On the other hand , cranberry treated groups ( 50 and 100 mg/kg ) showed a marked increase in the expression of adiponectin , by 8 and 13-fold , insulin receptor substrate-2 by 21 and 79 % , and Nrf2 by 13 and 61 % , respectively .
Notably , cranberry significantly reduced @ @ @ @ @ @ @ expression and collagen deposition .
Conclusion : The present study showed that cranberry significantly attenuated NAFLD , in a dose dependent manner , which could be partially recognized by its antioxidant , anti-inflammatory activities , and its ability to improve insulin sensitivity .
Notably , our study proves for the first time that the anti-fibrotic activity of cranberry is promising .

Background: Non-alcoholic fatty liver disease (NAFLD) is a pathological accumulation of triglycerides (TGs) in the hepatocyte in the absence of alcohol intake. Untreated NAFLD is expected to progress into liver fibrosis. Cranberry is rich in polyphenols with antioxidant and anti-inflammatory activities.
Hypothesis: The present study was performed to evaluate our hypothesis of the possible anti-fibrotic effect of cranberry nutraceuticals in a high fat cholesterol diet induced (HFCD)-NAFLD in rats, focusing on improving insulin sensitivity and modulating the expression of nuclear factor erythroid-2-related factor-2 (Nrf2) (a transcription factor responsible for regulating cellular redox balance).
Method: Male albino wistar rats (12 weeks) received HFCD and/or cranberry (50 and 100 mg/kg/day, three times/week) orally for 8 consecutive weeks.
Results: In comparison to the HFCD group, cranberry treated groups (50 and 100 mg/kg) showed marked hepatoprotection, where it significantly decreased liver enzymes (alanine transaminases by 49 and 64% and aspartate transaminases by 45 and 64%; respectively), TGs, and ameliorated the histopathological alterations (such as inflammatory cells infiltration and ballooning degeneration) induced by HFCD. Cranberry also alleviated oxidative stress (malondialdehyde, glutathione, catalase and superoxide dismutase) and inflammation (tumor necrosis factor- alpha, interleukine-6 and nuclear factor kappa-b) and significantly reduced the HOMA-IR and TyG index. On the other hand, cranberry treated groups (50 and 100 mg/kg) showed a marked increase in the expression of adiponectin, by 8 and 13-fold, insulin receptor substrate-2 by 21 and 79%, and Nrf2 by 13 and 61%, respectively. Notably, cranberry significantly reduced the fibrotic markers, TGF-β and α-SMA expression and collagen deposition.
Conclusion: The present study showed that cranberry significantly attenuated NAFLD, in a dose dependent manner, which could be partially recognized by its antioxidant, anti-inflammatory activities, and its ability to improve insulin sensitivity. Notably, our study proves for the first time that the anti-fibrotic activity of cranberry is promising.


greenmedinfo--2020-06-17--Daily cranberry consumption may lower TAG and change certain oxidative stress biomarkers in individu

Daily cranberry consumption may lower TAG and change certain oxidative stress biomarkers in individuals with obesity and a proinflammatory state.

Cranberries are high in polyphenols , and epidemiological studies have shown that a high-polyphenol diet may reduce risk factors for diabetes and CVD .
The present study aimed to determine if short-term cranberry beverage consumption would improve insulin sensitivity and other cardiovascular risk factors .
Thirty-five individuals with obesity and with elevated fasting glucose or impaired glucose tolerance participated in a randomised , double-blind , placebo-controlled , parallel-designed pilot trial .
Participants consumed 450 ml of low-energy cranberry beverage or placebo daily for 8 weeks .
Changes in insulin sensitivity and cardiovascular risk factors including vascular reactivity , blood pressure @ @ @ @ @ @ @ profiles and oxidative stress biomarkers were evaluated .
Change in insulin sensitivity via hyperinsulinaemic-euglycaemic clamp was not different between the two groups .
Levels of 8-isoprostane ( biomarker of lipid peroxidation ) decreased in the cranberry group but increased in the placebo group ( -2·18 v. +20·81 pg/ml ; P = 0·02 ) .
When stratified by baseline C-reactive protein ( CRP ) levels , participants with high CRP levels ( > 4 mg/l ) benefited more from cranberry consumption .
In this group , significant differences in the mean change from baseline @ @ @ @ @ @ @ and the placebo groups ( n 7 ) in levels of TAG ( -13·75 v. +10·32 % ; P = 0·04 ) , nitrate ( +3·26 v. -6·28 µmol/l ; P = 0·02 ) and 8-isoprostane ( +0·32 v. +30·8 pg/ml ; P = 0·05 ) were observed .
These findings indicate that 8 weeks of daily cranberry beverage consumption may not impact insulin sensitivity but may be helpful in lowering TAG and changing certain oxidative stress biomarkers in individuals with obesity and a proinflammatory state .

Cranberries are high in polyphenols, and epidemiological studies have shown that a high-polyphenol diet may reduce risk factors for diabetes and CVD. The present study aimed to determine if short-term cranberry beverage consumption would improve insulin sensitivity and other cardiovascular risk factors. Thirty-five individuals with obesity and with elevated fasting glucose or impaired glucose tolerance participated in a randomised, double-blind, placebo-controlled, parallel-designed pilot trial. Participants consumed 450 ml of low-energy cranberry beverage or placebo daily for 8 weeks. Changes in insulin sensitivity and cardiovascular risk factors including vascular reactivity, blood pressure, RMR, glucose tolerance, lipid profiles and oxidative stress biomarkers were evaluated. Change in insulin sensitivity via hyperinsulinaemic-euglycaemic clamp was not different between the two groups. Levels of 8-isoprostane (biomarker of lipid peroxidation) decreased in the cranberry group but increased in the placebo group (-2·18 v. +20·81 pg/ml; P = 0·02). When stratified by baseline C-reactive protein (CRP) levels, participants with high CRP levels (>4 mg/l) benefited more from cranberry consumption. In this group, significant differences in the mean change from baseline between the cranberry (n 10) and the placebo groups (n 7) in levels of TAG (-13·75 v. +10·32 %; P = 0·04), nitrate (+3·26 v. -6·28 µmol/l; P = 0·02) and 8-isoprostane (+0·32 v. +30·8 pg/ml; P = 0·05) were observed. These findings indicate that 8 weeks of daily cranberry beverage consumption may not impact insulin sensitivity but may be helpful in lowering TAG and changing certain oxidative stress biomarkers in individuals with obesity and a proinflammatory state.


greenmedinfo--2020-06-17--B-ring substituted flavones and flavonols from cranberry contribute to the antiadhesive activity aga

B-ring substituted flavones and flavonols from cranberry contribute to the antiadhesive activity against uropathogenic E. coli

ETHNOPHARMACOLOGICAL RELEVANCE : Extracts from Cranberry fruits ( Vaccinium macrocarpon ) are traditionally used against urinary tract infections , mainly due to antiadhesive activity against uropathogenic E. coli ( UPEC ) , but the exact mode of action and compounds , responsible for the activity , are unknown .
AIM OF THE STUDY : i .
To investigate if cranberry extract acts only by a single component or must be assessed as a multi-active-compound preparation ; ii to screen isolated cranberry-related natural products under in vitro conditions to pinpoint natural products with antiadhesive effects against UPEC , followed by in @ @ @ @ @ @ @ potential antiadhesive compounds ; iii .
investigations by using urine samples from cranberry treated volunteers for evaluation on the bacterial transcriptome and the mannose-binding side of FimH , iv .
to investigate if besides Tamm Horsfall Protein induction in the kidney , the extract acts also directly against UPEC .
MATERIAL AND METHODS : Antiadhesive activity of 105 compounds was determined by flow cytometric adhesion assay ( UPEC UTI89 on T24 bladder cells ) .
Urine samples from 16 volunteers treated with cranberry extract ( p.o.
, 7 days , 900 mg/day ) @ @ @ @ @ @ @ influence on the bacterial transcriptome ( Illumina RNA-seq ) and interaction with the mannose binding domain of type-1 fimbriae .
RESULTS : i .
The antiadhesive effect of cranberry extract can not be attributed to a single compound or to a single fraction .
ii .
Unglycosylated flavones and flavonols with bulky substitution of the B ring contribute to the antiadhesive activity .
3'-8″-biflavones and flavolignans ( not related to cranberry fruits ) were identified as potent antiadhesive compounds against UPEC .
iii .
QSAR yielded a model with good statistical performance and @ @ @ @ @ @ @ iv .
Urine samples from male cranberry-treated volunteers indicated significant interaction with the mannose binding domain of type-1 fimbriae , which correlated with the amount of Tamm-Horsfall Protein in the test samples .
v Cranberry extract did not influence the UPEC transcriptome ; gene expression of bacterial adhesins ( P- , S-fimbrae , curli ) was not influenced by the urine samples , while a slight , but non-significant upregulation of type 1 fimbriae was observed .
CONCLUSIONS : B-ring substituted flavones and flavonols from cranberry contribute to the antiadhesive activity against UPEC @ @ @ @ @ @ @ the host cell bladder epithelium .

ETHNOPHARMACOLOGICAL RELEVANCE: Extracts from Cranberry fruits (Vaccinium macrocarpon) are traditionally used against urinary tract infections, mainly due to antiadhesive activity against uropathogenic E. coli (UPEC), but the exact mode of action and compounds, responsible for the activity, are unknown.
AIM OF THE STUDY: i. To investigate if cranberry extract acts only by a single component or must be assessed as a multi-active-compound preparation; ii to screen isolated cranberry-related natural products under in vitro conditions to pinpoint natural products with antiadhesive effects against UPEC, followed by in silico calculations (QSAR) to predict potential antiadhesive compounds; iii. investigations by using urine samples from cranberry treated volunteers for evaluation on the bacterial transcriptome and the mannose-binding side of FimH, iv. to investigate if besides Tamm Horsfall Protein induction in the kidney, the extract acts also directly against UPEC.
MATERIAL AND METHODS: Antiadhesive activity of 105 compounds was determined by flow cytometric adhesion assay (UPEC UTI89 on T24 bladder cells). Urine samples from 16 volunteers treated with cranberry extract (p.o., 7 days, 900 mg/day) were used for ex vivo testing concerning influence on the bacterial transcriptome (Illumina RNA-seq) and interaction with the mannose binding domain of type-1 fimbriae.
RESULTS: i. The antiadhesive effect of cranberry extract cannot be attributed to a single compound or to a single fraction. ii. Unglycosylated flavones and flavonols with bulky substitution of the B ring contribute to the antiadhesive activity. 3'-8″-biflavones and flavolignans (not related to cranberry fruits) were identified as potent antiadhesive compounds against UPEC. iii. QSAR yielded a model with good statistical performance and sufficient internal and external predictive ability. iv. Urine samples from male cranberry-treated volunteers indicated significant interaction with the mannose binding domain of type-1 fimbriae, which correlated with the amount of Tamm-Horsfall Protein in the test samples. v Cranberry extract did not influence the UPEC transcriptome; gene expression of bacterial adhesins (P-, S-fimbrae, curli) was not influenced by the urine samples, while a slight, but non-significant upregulation of type 1 fimbriae was observed.
CONCLUSIONS: B-ring substituted flavones and flavonols from cranberry contribute to the antiadhesive activity against UPEC by inhibition of the FimH-mediated interaction with the host cell bladder epithelium.


greenmedinfo--2020-06-17--Cranberry polyphenolic extract exhibits an antiobesity effect.

BACKGROUND : Although polyphenol-rich cranberry extracts reportedly have an antiobesity effect , the exact reason for this remains unclear .
OBJECTIVES : In light of the reported health benefits of the polyphenolic compounds in cranberry , we investigated the effects and mechanism of a cranberry polyphenolic extract ( CPE ) in high-fat diet ( HFD ) -fed obese mice .
METHODS : The distributions of individual CPE compounds were characterized by HPLC fingerprinting .
Male C57BL/6J mice ( 4 wk old ) were fed for 16 wk normal diet ( ND , 10 % fat energy ) or HFD ( @ @ @ @ @ @ @ without 0.75 % CPE in drinking water ( HFD + CPE ) .
Body and adipose depot weights , indices of glucose metabolism , energy expenditure ( EE ) , and expression of genes related to brown adipose tissue ( BAT ) thermogenesis , and inguinal/epididymal white adipose tissue ( iWAT/eWAT ) browning were measured .
RESULTS : After 16 wk , the body weight was 22.5 % lower in the CPE-treated mice than in the HFD group but remained 17.9 % higher than in the ND group .
CPE treatment significantly increased @ @ @ @ @ @ @ and HFD groups .
The elevated EE was linked with BAT thermogenesis , and iWAT/eWAT browning , shown by the induction of thermogenic genes , especially uncoupling protein 1 ( Ucp1 ) , and browning-related genes , including Cd137 , a member of the tumor necrosis factor receptor superfamily ( Tnfrsf9 ) .
The mRNA expression and abundance of uncoupling protein 1 in BAT of CPE-fed mice were 5.78 and 1.47 times higher than in the HFD group , and 0.61 and 1.12 times higher than in the ND group , respectively .
@ @ @ @ @ @ @ of CPE-fed mice were 2.35 and 3.13 times higher than in the HFD group , and 0.84 and 1.39 times higher than in the ND group , respectively .
CONCLUSIONS : Dietary CPE reduced but did not normalize HFD-induced body weight gain in male C57BL/6J mice , possibly by affecting energy metabolism .

BACKGROUND: Although polyphenol-rich cranberry extracts reportedly have an antiobesity effect, the exact reason for this remains unclear.
OBJECTIVES: In light of the reported health benefits of the polyphenolic compounds in cranberry, we investigated the effects and mechanism of a cranberry polyphenolic extract (CPE) in high-fat diet (HFD)-fed obese mice.
METHODS: The distributions of individual CPE compounds were characterized by HPLC fingerprinting. Male C57BL/6J mice (4 wk old) were fed for 16 wk normal diet (ND, 10% fat energy) or HFD (60% fat energy) with or without 0.75% CPE in drinking water (HFD + CPE). Body and adipose depot weights, indices of glucose metabolism, energy expenditure (EE), and expression of genes related to brown adipose tissue (BAT) thermogenesis, and inguinal/epididymal white adipose tissue (iWAT/eWAT) browning were measured.
RESULTS: After 16 wk, the body weight was 22.5% lower in the CPE-treated mice than in the HFD group but remained 17.9% higher than in the ND group. CPE treatment significantly increased EE compared with that of the ND and HFD groups. The elevated EE was linked with BAT thermogenesis, and iWAT/eWAT browning, shown by the induction of thermogenic genes, especially uncoupling protein 1 (Ucp1), and browning-related genes, including Cd137, a member of the tumor necrosis factor receptor superfamily (Tnfrsf9). The mRNA expression and abundance of uncoupling protein 1 in BAT of CPE-fed mice were 5.78 and 1.47 times higher than in the HFD group, and 0.61 and 1.12 times higher than in the ND group, respectively. Cd137 gene expression in iWAT and eWAT of CPE-fed mice were 2.35 and 3.13 times higher than in the HFD group, and 0.84 and 1.39 times higher than in the ND group, respectively.
CONCLUSIONS: Dietary CPE reduced but did not normalize HFD-induced body weight gain in male C57BL/6J mice, possibly by affecting energy metabolism.


greenmedinfo--2020-06-17--These findings suggest that supplementing cranberry or cherry juice might contribute to an improveme

PURPOSE : This review aims to compare the magnitude of the effects of chronic consumption of fruits ; specifically berries , citrus and cherries on cardiovascular disease ( CVD ) risk factors .
METHODS : PubMed , Web of Science , Scopus , and psycARTICLES were searched from inception until January 2020 .
Forty-five chronic ( ≥ 1 week ) randomised controlled trials assessing CVD risk factors including endothelial ( dys ) function , blood pressure ( BP ) , blood lipids and inflammatory biomarkers were included .
RESULTS : Investigated interventions reported improvements in endothelial function ( n = @ @ @ @ @ @ @ status ( n = 14 ) , and BP ( n = 10 ) .
Berries including juice of barberry , cranberry , grape , pomegranate , powder of blueberry , grape , raspberry and freeze-dried strawberry significantly reduced SBP by 3.68 mmHg ( 95 % CI - 6.79 to - 0.58 ; P = 0.02 ) and DBP by 1.52 mmHg ( 95 % CI - 2.87 to - 0.18 , P = 0.04 ) .
In subgroup analysis , these associations were limited to cranberry juice ( SBP by 1.52 mmHg @ @ @ @ @ @ @ - 0.07 ; P = 0.05 ] , DBP by 1.78 mmHg [ 95 % CI - 3.43 to - 0.12 , P = 0.04 ] and cherry juice ( SBP by 3.11 mmHg [ 95 % CI - 4.06 to - 2.15 ; P = 0.02 ] ) .
Berries also significantly elevated sVCAM-1 levels by 14.57 ng/mL ( 85 % CI 4.22 to 24.93 ; P = 0.02 ) .
CONCLUSION : These findings suggest that supplementing cranberry or cherry juice might contribute to an improvement in blood pressure .
No @ @ @ @ @ @ @ specified fruits .
More research is warranted comparing different classes of fruit and exploring the importance of fruit processing on their cardiovascular-protective effects .

PURPOSE: This review aims to compare the magnitude of the effects of chronic consumption of fruits; specifically berries, citrus and cherries on cardiovascular disease (CVD) risk factors.
METHODS: PubMed, Web of Science, Scopus, and psycARTICLES were searched from inception until January 2020. Forty-five chronic (≥ 1 week) randomised controlled trials assessing CVD risk factors including endothelial (dys)function, blood pressure (BP), blood lipids and inflammatory biomarkers were included.
RESULTS: Investigated interventions reported improvements in endothelial function (n = 8), inflammatory biomarkers and lipid status (n = 14), and BP (n = 10). Berries including juice of barberry, cranberry, grape, pomegranate, powder of blueberry, grape, raspberry and freeze-dried strawberry significantly reduced SBP by 3.68 mmHg (95% CI - 6.79 to - 0.58; P = 0.02) and DBP by 1.52 mmHg (95% CI - 2.87 to - 0.18, P = 0.04). In subgroup analysis, these associations were limited to cranberry juice (SBP by 1.52 mmHg [95% CI - 2.97 to - 0.07; P = 0.05], DBP by 1.78 mmHg [95% CI - 3.43 to - 0.12, P = 0.04] and cherry juice (SBP by 3.11 mmHg [95% CI - 4.06 to - 2.15; P = 0.02]). Berries also significantly elevated sVCAM-1 levels by 14.57 ng/mL (85% CI 4.22 to 24.93; P = 0.02).
CONCLUSION: These findings suggest that supplementing cranberry or cherry juice might contribute to an improvement in blood pressure. No other significant improvements were observed for other specified fruits. More research is warranted comparing different classes of fruit and exploring the importance of fruit processing on their cardiovascular-protective effects.


greenmedinfo--2020-06-17--Citrus hystrix leaf extract attenuated diabetic-cataract in STZ-rats.

Diabetic cataract causes severe vision loss .
This study evaluated the effects of hesperidin-standardized Citrus hystrix leaf flavonoids-rich extract ( CLE ) on diabetic-cataract development .
Streptozotocin-induced diabetic rats were orally given 150 and 300 mg CLE/kg body-weight .
These were compared with non-treated diabetic or healthy rats as controls , over 8 weeks .
The CLE gradually attenuated fasting blood glucose ( FBG ) , biomarkers for inflammation ( Tumor necrosis factor alpha TNF-α ; prostaglandin E2 PGE2 ) ; vascular permeability , ( Vascular endothelial growth factor VEGF ) ; and oxidative stress , ( malondialdehyde MDA ) @ @ @ @ @ @ @ by the 150 mg CLE/kg dose .
Good correlations were found between cataract incidence with FBG ( r = 0.90 ) , serum PGE2 ( r = 0.91 ) , MDA ( r = 0.99 ) , VEGF ( r = 0.71 ) , but not with TNF-α levels ( r = 0.49 ) suggesting the serum FBG , PGE2 , MDA , and possibly the VEGF levels may help to predict the cataract risks .
The CLE mitigated cataract probably by attenuating hyperglycaemia , inflammation , lens fluid influx , vascular leakage @ @ @ @ @ @ @ .
PRACTICAL APPLICATIONS : The study shows the flavonoids-rich Citrus hystrix leaf consumption , effectively attenuated diabetes ( fasting blood glucose ) and mitigated diabetic cataract .
It help reduce diabetes-related hyperglycaemia , oxidative stress , inflammation , and vascular leakage .
The evidences were the CLE consumptions reduced the serum biomarkers tumor necrosis factor-alpha TNF-α ; prostaglandin E2 PGE2 , vascular endothelial growth factor ( VEGF ) , and malondialdehyde ( MDA ) .
The C. hystrix leaf contains hesperidin , apiin , diosmin , saponarin , apigetrin , rutin and xanthotoxol @ @ @ @ @ @ @ study also showed good correlations between cataract incidence with fasting blood glucose FBG ( r = 0.90 ) , serum PGE2 ( r = 0.91 ) , and MDA ( r = 0.99 ) , and less closely with VEGF ( r = 0.71 ) suggesting these serum biomarkers may help predict cataract risks .
The CLE indicated cataract mitigation properties probably by attenuating FBG , inflammation , lens fluid influx , lens osmotic-imbalance , and fibers over-hydration .

Diabetic cataract causes severe vision loss. This study evaluated the effects of hesperidin-standardized Citrus hystrix leaf flavonoids-rich extract (CLE) on diabetic-cataract development. Streptozotocin-induced diabetic rats were orally given 150 and 300 mg CLE/kg body-weight. These were compared with non-treated diabetic or healthy rats as controls, over 8 weeks. The CLE gradually attenuated fasting blood glucose (FBG), biomarkers for inflammation (Tumor necrosis factor alpha TNF-α; prostaglandin E2 PGE2); vascular permeability, (Vascular endothelial growth factor VEGF); and oxidative stress, (malondialdehyde MDA). The diabetic cataract was significantly mitigated by the 150 mg CLE/kg dose. Good correlations were found between cataract incidence with FBG (r = 0.90), serum PGE2 (r = 0.91), MDA (r = 0.99), VEGF (r = 0.71), but not with TNF-α levels (r = 0.49) suggesting the serum FBG, PGE2, MDA, and possibly the VEGF levels may help to predict the cataract risks. The CLE mitigated cataract probably by attenuating hyperglycaemia, inflammation, lens fluid influx, vascular leakage, lens osmotic-imbalance, and fibers over-hydration. PRACTICAL APPLICATIONS: The study shows the flavonoids-rich Citrus hystrix leaf consumption, effectively attenuated diabetes (fasting blood glucose) and mitigated diabetic cataract. It help reduce diabetes-related hyperglycaemia, oxidative stress, inflammation, and vascular leakage. The evidences were the CLE consumptions reduced the serum biomarkers tumor necrosis factor-alpha TNF-α; prostaglandin E2 PGE2, vascular endothelial growth factor (VEGF), and malondialdehyde (MDA). The C. hystrix leaf contains hesperidin, apiin, diosmin, saponarin, apigetrin, rutin and xanthotoxol, and other flavonoid glucosides. The study also showed good correlations between cataract incidence with fasting blood glucose FBG (r = 0.90), serum PGE2 (r = 0.91), and MDA (r = 0.99), and less closely with VEGF (r = 0.71) suggesting these serum biomarkers may help predict cataract risks. The CLE indicated cataract mitigation properties probably by attenuating FBG, inflammation, lens fluid influx, lens osmotic-imbalance, and fibers over-hydration.


greenmedinfo--2020-06-17--Potent in vitro activity of Citrus aurantium essential oil and Vitis vinifera hydrolate against gut

Potent in vitro activity of Citrus aurantium essential oil and Vitis vinifera hydrolate against gut yeast isolates from irritable bowel syndrome patients.

BACKGROUND : Irritable bowel syndrome ( IBS ) is a functional disorder without any pathological alteration , in which the @ @ @ @ @ the gut microbiota , the balance of pro and anti-inflammatory cytokines and the brain-gut-microbiome axis @ @ @ @ @ and progression of IBS .
The aim of the study was to identify natural products @ @ @ @ @ hydrolates , which were contextually harmless for the gut beneficial strains ( e.g.spp . )
@ @ @ @ @ ones ( spp. )
.
METHODS : The effectiveness of 6 essential oils and 2 @ @ @ @ @ tests , carried out on 50 clinical isolates ( , andspecies ) and 9 probiotic @ @ @ @ @ and immunological and antioxidant assays .
RESULTS : The study led to a mixture based @ @ @ @ @ oil /cv Italia hydrolate able to contextually reduce , in a concentration-dependent manner , the @ @ @ @ @ filaments and have an interesting immunomodulatory and anti-oxidant action .
This mixture can potentially be @ @ @ @ @ promoting the restoration of the intestinal microbial and immunological balance .

BACKGROUND: Irritable bowel syndrome (IBS) is a functional disorder without any pathological alteration, in which the alterations of the/s ratio of the gut microbiota, the balance of pro and anti-inflammatory cytokines and the brain-gut-microbiome axis are important for the development and progression of IBS. The aim of the study was to identify natural products, including essential oils or hydrolates, which were contextually harmless for the gut beneficial strains (e.g.spp.) but inhibitory for the pathogenic ones (spp.).
METHODS: The effectiveness of 6 essential oils and 2 hydrolates was evaluated using microbiological tests, carried out on 50 clinical isolates (,andspecies) and 9 probiotic strains (,,and) and immunological and antioxidant assays.
RESULTS: The study led to a mixture based on a 1/100 ratio ofvar.essential oil /cv Italia hydrolate able to contextually reduce, in a concentration-dependent manner, the ability ofspecies to form hyphal filaments and have an interesting immunomodulatory and anti-oxidant action. This mixture can potentially be useful in the IBS treatment promoting the restoration of the intestinal microbial and immunological balance.


greenmedinfo--2020-06-17--Anthocyanin from the fruit of Vitis Coignetiae acts as a potent inhibitor of TNF-α effect by inhibit

Anthocyanin from the fruit of Vitis Coignetiae acts as a potent inhibitor of TNF-α effect by inhibiting NF-κB-regulated genes in human breast cancer cells.

( Meoru in Korea ) has been used in Korean folk medicine for the treatment of inflammatory diseases and cancers .
Evidence suggests that NF-κB activation is mainly involved in cancer cell proliferation , invasion , angiogenesis , and metastasis .
TNF-α also enhances the inflammatory process in tumor development .
Recently , flavonoids from plants have been reported to have inhibitory effects on NF-κB activities .
We investigated the effectsof anthocyanins extracted from the fruits of ( AIM , anthocyanins isolated from Meoru ( AIM ) ) on TNF-α-induced NF-κB activities in MCF-7 human breast cancer cells and the @ @ @ @ @ @ @ especially on cancer metastasis .
We performed cell viability assay , gelatin zymography , invasion assay , and western blot analysis to unravel the anti-NF-κB activity of AIMson MCF-7 cells .
AIM suppressed the TNF-α effects on the NF-κB-regulated proteins involved in cancer cell proliferation ( COX-2 , C-myc ) , invasion , and angiogenesis ( MMP-2 , MMP9 , ICAM-1 , and VEGF ) .
AIM also increased the expression of E-cadherin , which is one of the hallmarks of the epithelial-mesenchymal transition ( EMT ) process .
In conclusion , this @ @ @ @ @ @ @ the fruits ofacts as an inhibitor of TNF-α induced NF-κB activation , and subsequent downstream molecules involved in cancer proliferation , invasion , adhesion , angiogenesis , and thus have anti-metastatic activities in MCF-7 breast cancer cells .

(Meoru in Korea) has been used in Korean folk medicine for the treatment of inflammatory diseases and cancers. Evidence suggests that NF-κB activation is mainly involved in cancer cell proliferation, invasion, angiogenesis, and metastasis. TNF-α also enhances the inflammatory process in tumor development. Recently, flavonoids from plants have been reported to have inhibitory effects on NF-κB activities. We investigated the effectsof anthocyanins extracted from the fruits of(AIM, anthocyanins isolated from Meoru (AIM)) on TNF-α-induced NF-κB activities in MCF-7 human breast cancer cells and the molecules involved in AIM-induced anti-cancer effects, especially on cancer metastasis. We performed cell viability assay, gelatin zymography, invasion assay, and western blot analysis to unravel the anti-NF-κB activity of AIMson MCF-7 cells. AIM suppressed the TNF-α effects on the NF-κB-regulated proteins involved in cancer cell proliferation (COX-2, C-myc), invasion, and angiogenesis (MMP-2, MMP9, ICAM-1, and VEGF). AIM also increased the expression of E-cadherin, which is one of the hallmarks of the epithelial-mesenchymal transition (EMT) process. In conclusion, this study demonstrates that the anthocyanins isolated from the fruits ofacts as an inhibitor of TNF-α induced NF-κB activation, and subsequent downstream molecules involved in cancer proliferation, invasion, adhesion, angiogenesis, and thus have anti-metastatic activities in MCF-7 breast cancer cells.


greenmedinfo--2020-06-17--Percutaneous absorption of resveratrol and its oligomers to relieve psoriasiform lesions.

Resveratrol was shown to exert anti-inflammatory effects in experimental models of psoriasis .
Several natural oligomers of resveratrol have been extracted from plants .
We investigated the antipsoriatic activity of topical administration of resveratrol oligomers and explored the effect of the number of resveratrol subunits on skin absorption to establish the structure-permeation relationship ( SPR ) .
Three oligomers , ε-viniferin ( dimer ) , ampelopsin C ( trimer ) and vitisin A ( tetramer ) , extracted from Vitis thunbergii root were compared to the resveratrol glycoside polydatin .
Delivery to porcine skin was assessed in vitro using the @ @ @ @ @ @ @ ( IMQ ) were utilized to evaluatecytokine/chemokine inhibition .
Topical application of resveratrol and oligomers was characterized in vivo by assessing cutaneous absorption , skin physiology , proinflammatory mediator expression , and histopathology in IMQ-treated mice .
Skin deposition decreased as the molecular size and lipophilicity of the permeants increased .
Resveratrol exhibited highest absorption , followed by ε-viniferin .
The monomers resveratrol and polydatin exhibited higher flux across skin than the larger oligomers .
In silico modeling revealed the permeants that strongly interacted with stratum corneum ( SC ) lipids exhibited lower @ @ @ @ @ @ @ compartment .
In vitro , resveratrol and its derivatives had comparable ability to inhibit IMQ-induced IL-1β , IL-6 , and CXCL8 secretion in activated keratinocytes .
In vivo , topically applied ε-viniferin accumulated at higher levels than resveratrol ( 0.067 versus 0.029 nmol/mg ) in psoriasis-like mouse skin with impaired barrier capacity .
Topical ε-viniferin alleviated psoriasiform symptoms and reduced IL-23 secretion ( by 58 % vs. 37 % ) more effectively than resveratrol .
ε-Viniferin has potential as an anti-inflammatory agent to prevent ortreat psoriasis .

Resveratrol was shown to exert anti-inflammatory effects in experimental models of psoriasis. Several natural oligomers of resveratrol have been extracted from plants. We investigated the antipsoriatic activity of topical administration of resveratrol oligomers and explored the effect of the number of resveratrol subunits on skin absorption to establish the structure-permeation relationship (SPR). Three oligomers,ε-viniferin (dimer), ampelopsin C (trimer) and vitisin A (tetramer), extracted from Vitis thunbergii root were compared to the resveratrol glycoside polydatin. Delivery to porcine skin was assessed in vitro using the Franz cell. Keratinocytes activated with imiquimod (IMQ) were utilized to evaluatecytokine/chemokine inhibition. Topical application of resveratrol and oligomers was characterized in vivo by assessing cutaneous absorption, skin physiology, proinflammatory mediator expression, and histopathology in IMQ-treated mice. Skin deposition decreased as the molecular size and lipophilicity of the permeants increased. Resveratrol exhibited highest absorption, followed by ε-viniferin. The monomers resveratrol and polydatin exhibited higher flux across skin than the larger oligomers. In silico modeling revealed the permeants that strongly interacted with stratum corneum (SC) lipids exhibited lower transport to viable skin and the receptor compartment. In vitro, resveratrol and its derivatives had comparable ability to inhibit IMQ-induced IL-1β, IL-6, and CXCL8 secretion in activated keratinocytes. In vivo, topically applied ε-viniferin accumulated at higher levels than resveratrol (0.067 versus 0.029 nmol/mg) in psoriasis-like mouse skin with impaired barrier capacity. Topical ε-viniferin alleviated psoriasiform symptoms and reduced IL-23 secretion (by 58% vs. 37%) more effectively than resveratrol. ε-Viniferin has potential as an anti-inflammatory agent to prevent ortreat psoriasis.


greenmedinfo--2020-06-17--Quorum-quenching endophytic bacteria inhibit disease caused by Pseudomonas syringae Pv. in citrus cu

Quorum-quenching endophytic bacteria inhibit disease caused by Pseudomonas syringae Pv. in citrus cultivars.

Two strains of 64 endophytic bacteria , Bacillus cereus Si-Ps1 and Pseudomonas azotoformans La-Pot3-3 , isolated from Citrus sinensis and @ @ @ @ @ 's leaves , respectively , reduced N-acyl homoserine-based quorum sensing in bioindicator strain Pseudomonas syringae @ @ @ @ @ ) B728a and the biofilm production and swarming motility of field isolate Pss 3289 .
@ @ @ @ @ encoding an AHL-lactonase was found in B. cereus ( Si-Ps1 ) , suggesting that this @ @ @ @ @ signal molecules of Pss 3289 .
The crude extract of endophytic bacterium , B. cereus @ @ @ @ @ Pss 3289 biofilm formation after 48 and 96 h by 55 % and 58 % @ @ @ @ @ in biofilm formation were conferred by crude extracts of P. azotoformans ( La-Pot3-3 ) .
@ @ @ @ @ planktonic cells in cultures treated with these extracts was higher than in control cultures , @ @ @ @ @ biofilm formation and not on cell growth .
In greenhouse assays , the virulence of @ @ @ @ @ cultivars was decreased when coinoculated with these endophytic bacteria .

Two strains of 64 endophytic bacteria, Bacillus cereus Si-Ps1 and Pseudomonas azotoformans La-Pot3-3, isolated from Citrus sinensis and C. sinensis var. Thomson's leaves, respectively, reduced N-acyl homoserine-based quorum sensing in bioindicator strain Pseudomonas syringae pv. syringae (Pss) B728a and the biofilm production and swarming motility of field isolate Pss 3289. A homolog of aiiA gene encoding an AHL-lactonase was found in B. cereus (Si-Ps1), suggesting that this isolate can degrade the quorum-sensing signal molecules of Pss 3289. The crude extract of endophytic bacterium, B. cereus (Si-Ps1), inhibited Pss 3289 biofilm formation after 48 and 96 h by 55% and 58%, respectively. Similar reductions in biofilm formation were conferred by crude extracts of P. azotoformans (La-Pot3-3). Correspondingly, the number of planktonic cells in cultures treated with these extracts was higher than in control cultures, indicating a direct effect on biofilm formation and not on cell growth. In greenhouse assays, the virulence of Pss 3289 to different citrus cultivars was decreased when coinoculated with these endophytic bacteria.


greenmedinfo--2020-06-17--Citrus sinensis and Vitis vinifera protect cardiomyocytes from doxorubicin-induced oxidative stress.

The interest towards nutraceuticals able to counteract drug side effects is continuously growing in current chemotherapeutic protocols .
In the @ @ @ @ @ that smoothies containing mixtures ofandL .
cv .
Aglianico N , two typical fruits of @ @ @ @ @ bioactive polyphenols that protect cardiomyocytes against doxorubicin-induced oxidative stress .
The polyphenolic extracts isolated fromand-based @ @ @ @ @ by Liquid Chromatography-Mass Spectrometry methods .
Subsequently , the functional smoothies and relative mixtures were @ @ @ @ @ to affect cellular viability and oxidative stress parameters in embryonic cardiomyocyte cells ( H9c2 ) @ @ @ @ @ cell line ( MCF-7 ) exposed to doxorubicin .
Interestingly , we found that the @ @ @ @ @ 1:1 was able to reduce cardiomyocytes damage induced by anthracyclines , without significantly interfering with @ @ @ @ @ drug on breast cancer cells .
These results point out the potential use of vegetable @ @ @ @ @ for chemotherapeutic anticancer protocols .

The interest towards nutraceuticals able to counteract drug side effects is continuously growing in current chemotherapeutic protocols. In the present study, we demonstrated that smoothies containing mixtures ofandL. cv. Aglianico N, two typical fruits of the Mediterranean diet, possess bioactive polyphenols that protect cardiomyocytes against doxorubicin-induced oxidative stress. The polyphenolic extracts isolated fromand-based functional smoothies were deeply characterized by Liquid Chromatography-Mass Spectrometry methods. Subsequently, the functional smoothies and relative mixtures were tested to verify their ability to affect cellular viability and oxidative stress parameters in embryonic cardiomyocyte cells (H9c2), and human breast adenocarcinoma cell line (MCF-7) exposed to doxorubicin. Interestingly, we found that the mix resulting fromandassociation in ratio 1:1 was able to reduce cardiomyocytes damage induced by anthracyclines, without significantly interfering with the pro-apoptotic activity of the drug on breast cancer cells. These results point out the potential use of vegetable smoothies as adjuvants functional foods for chemotherapeutic anticancer protocols.


greenmedinfo--2020-06-17--Ginsenoside Rg1 can inhibit inflammatory reaction, regulate lipid metabolism, and alleviate liver in

Ginsenoside Rg1 can inhibit inflammatory reaction, regulate lipid metabolism, and alleviate liver injury in NAFLD.

To establish the molecular mechanism of ginsenoside Rg1 in nonalcoholic fatty liver disease ( NAFLD ) , Sprague Dawley ( SD ) rats ( 180-220 g ) were randomly divided into a control group , model group , ginsenoside Rg1 low-dose group ( 30 mg/ ( kg day ) ) , high-dose ( 60 mg/ ( kg day ) ) group , and simvastatin group ( 1 mg/ ( kg day ) ) , with 10 SD rats in each group .
The control group was given a normal diet .
The model group rats were given high-sugar and high-fat @ @ @ @ @ @ @ model of NAFLD was established successfully , ginsenoside Rg1 was administered orally for 4 or 8 weeks .
The results showed that ginsenoside Rg1 decreased the levels of glucose ( GLU ) , insulin ( INS ) , triglyceride ( TG ) , and total cholesterol ( TC ) and improved liver function .
Meanwhile , ginsenoside Rg1 inhibited the secretion of interleukin-1 ( IL-1 ) , IL-6 , IL-8 , IL-18 , and tumor necrosis factor-α ( TNF-α ) and improved hepatocyte morphology and lipid accumulation in the liver .
Furthermore , @ @ @ @ @ @ @ proliferator-activated receptor-α ( PPAR-α ) , carnitine palmitoyl transferase 1α ( CPT1A ) , carnitine palmitoyl transferase 2 ( CPT2 ) , and cholesterol7α-hydroxylase ( CYP-7A ) and inhibited the expression of sterol regulatory element binding proteins-1C ( SREBP-1C ) .
In conclusion , ginsenoside Rg1 can inhibit inflammatory reaction , regulate lipid metabolism , and alleviate liver injury in NAFLD model rats .

To establish the molecular mechanism of ginsenoside Rg1 in nonalcoholic fatty liver disease (NAFLD), Sprague Dawley (SD) rats (180-220 g) were randomly divided into a control group, model group, ginsenoside Rg1 low-dose group (30 mg/(kg day)), high-dose (60 mg/(kg day)) group, and simvastatin group (1 mg/(kg day)), with 10 SD rats in each group. The control group was given a normal diet. The model group rats were given high-sugar and high-fat diets for 14 weeks. After the model of NAFLD was established successfully, ginsenoside Rg1 was administered orally for 4 or 8 weeks. The results showed that ginsenoside Rg1 decreased the levels of glucose (GLU), insulin (INS), triglyceride (TG), and total cholesterol (TC) and improved liver function. Meanwhile, ginsenoside Rg1 inhibited the secretion of interleukin-1 (IL-1), IL-6, IL-8, IL-18, and tumor necrosis factor-α (TNF-α) and improved hepatocyte morphology and lipid accumulation in the liver. Furthermore, ginsenoside Rg1 promoted the expression of peroxisome proliferator-activated receptor-α (PPAR-α), carnitine palmitoyl transferase 1α (CPT1A), carnitine palmitoyl transferase 2 (CPT2), and cholesterol7α-hydroxylase (CYP-7A) and inhibited the expression of sterol regulatory element binding proteins-1C (SREBP-1C). In conclusion, ginsenoside Rg1 can inhibit inflammatory reaction, regulate lipid metabolism, and alleviate liver injury in NAFLD model rats.


greenmedinfo--2020-06-17--These results suggest that ginsenoside Rh2 dose-dependently inhibits adipogenesis through down-regul

These results suggest that ginsenoside Rh2 dose-dependently inhibits adipogenesis through down-regulating the PPAR-γ pathway.

Ginsenoside Rh2 , an intermediate metabolite of ginseng , but not naturally occurring , has recently drawn attention because of its anticancer effect .
However , it is not clear if and how Rh2 inhibits preadipocytes differentiation .
In the present study , we hypothesized that ginsenoside Rh2 attenuates adipogenesis through regulating the peroxisome proliferator-activated receptor gamma ( PPAR-γ ) pathway both in cells and obese mice .
Different concentrations of Rh2 were applied both in 3T3-L1 cells and human primary preadipocytes to determine if Rh2 inhibits cell differentiation .
Dietary Rh2 was administered to obese mice to determine if @ @ @ @ @ @ @ mRNA and proteinexpression of PPAR-γ pathway molecules in cells and tissues were measured by real-time polymerase chain reaction ( RT-PCR ) and Western blot , respectively .
Our results show that Rh2 dose-dependently ( 30-60 μM ) inhibited cell differentiation in 3T3-L1 cells ( 44.5 % ± 7.8 % of control at 60 μM ) .
Thisinhibitory effect is accompanied by the attenuation of the protein and/or mRNA expression of adipogenic markers including PPAR-γ and CCAAT/enhancer binding protein alpha , fatty acid synthase , fatty acid binding protein 4 , and perilipin significantly @ @ @ @ @ @ @ Rh2 significantly ( < 0.05 ) inhibited differentiation in human primary preadipocytes at much lower concentrations ( 5-15μM ) .
Furthermore , dietary intake of Rh2 ( 0.1 g Rh2/kg diet , w/w for eight weeks ) significantly ( < 0.05 ) reduced protein PPAR-γ expression in liver and hepatic glutathione reductase and lowered fasting blood glucose .
These results suggest that ginsenoside Rh2 dose-dependently inhibits adipogenesis through down-regulating the PPAR-γ pathway , and Rh2 may be a potential agent in preventing obesity in vivo .

Ginsenoside Rh2, an intermediate metabolite of ginseng, but not naturally occurring, has recently drawn attention because of its anticancer effect. However, it is not clear if and how Rh2 inhibits preadipocytes differentiation. In the present study, we hypothesized that ginsenoside Rh2 attenuates adipogenesis through regulating the peroxisome proliferator-activated receptor gamma (PPAR-γ) pathway both in cells and obese mice. Different concentrations of Rh2 were applied both in 3T3-L1 cells and human primary preadipocytes to determine if Rh2 inhibits cell differentiation. Dietary Rh2 was administered to obese mice to determine if Rh2 prevents obesity in vivo. The mRNA and proteinexpression of PPAR-γ pathway molecules in cells and tissues were measured by real-time polymerase chain reaction (RT-PCR) and Western blot, respectively. Our results show that Rh2 dose-dependently (30-60 μM) inhibited cell differentiation in 3T3-L1 cells (44.5% ± 7.8% of control at 60 μM). Thisinhibitory effect is accompanied by the attenuation of the protein and/or mRNA expression of adipogenic markers including PPAR-γ and CCAAT/enhancer binding protein alpha, fatty acid synthase, fatty acid binding protein 4, and perilipin significantly (<0.05). Moreover, Rh2 significantly (<0.05) inhibited differentiation in human primary preadipocytes at much lower concentrations (5-15μM). Furthermore, dietary intake of Rh2 (0.1 g Rh2/kg diet, w/w for eight weeks) significantly (<0.05) reduced protein PPAR-γ expression in liver and hepatic glutathione reductase and lowered fasting blood glucose. These results suggest that ginsenoside Rh2 dose-dependently inhibits adipogenesis through down-regulating the PPAR-γ pathway, and Rh2 may be a potential agent in preventing obesity in vivo.


greenmedinfo--2020-06-17--Ginsenoside 20(S)-protopanaxadiol attenuates depressive-like behaviour and neuroinflammation in chro

Ginsenoside 20(S)-protopanaxadiol attenuates depressive-like behaviour and neuroinflammation in chronic unpredictable mild stress.

20 ( S ) -protopanaxadiol ( PPD ) possesses a variety of biological activities , including antioxidant , antifatigue and anti-inflammatory properties .
This study was aimed to investigate the antidepressant-like effects of PPD and potential mechanisms in rats exposed to chronic unpredictable mild stress ( CUMS ) model .
Results showed that chronic treatment with PPD for 14 days ameliorated depressive-like behaviour , as indicated by the increase in sucrose preference in the sucrose preference test and decrease in immobility in the forced swim test and tail suspension test .
In addition , PPD decreased the elevated levels of @ @ @ @ @ @ @ IL-1β and TNF-α ) in the serum and neurotransmitters ( 5-HT and NE ) in the hippocampus and PFC induced by CUMS .
PPD suppressed the microglial activation in the DG induced by CUMS .
Furthermore , our results suggested that rats treated with PPD displayed decreased iNOS , COX2 , cleaved-caspase3 , cleaved-caspase9 , Bax , Bcl-2 , and ac-p65 levels and increased Sirt1 levels in the hippocampus .
In conclusion , this study indicated that PPD exerts promising antidepressant-like effects in CUMS rats that are mediated in part through alterations in @ @ @ @ @ @ @ the normalization of the levelsof neurotransmitters , and the suppression of neuronal apoptosis and neuroinflammation , possibly through the regulation of the SIRT1/NF-kB signalling pathway .

20 (S)-protopanaxadiol (PPD) possesses a variety of biological activities, including antioxidant, antifatigue and anti-inflammatory properties. This study was aimed to investigate the antidepressant-like effects of PPD and potential mechanisms in rats exposed to chronic unpredictable mild stress (CUMS) model. Results showed that chronic treatment with PPD for 14 days ameliorated depressive-like behaviour, as indicated by the increase in sucrose preference in the sucrose preference test and decrease in immobility in the forced swim test and tail suspension test. In addition, PPD decreased the elevated levels of CORT and proinflammatory cytokines (IL-6, IL-1β and TNF-α) in the serum and neurotransmitters (5-HT and NE) in the hippocampus and PFC induced by CUMS. PPD suppressed the microglial activation in the DG induced by CUMS. Furthermore, our results suggested that rats treated with PPD displayed decreased iNOS, COX2, cleaved-caspase3, cleaved-caspase9, Bax, Bcl-2, and ac-p65 levels and increased Sirt1 levels in the hippocampus. In conclusion, this study indicated that PPD exerts promising antidepressant-like effects in CUMS rats that are mediated in part through alterations in the dysfunction of the HPA axis, the normalization of the levelsof neurotransmitters, and the suppression of neuronal apoptosis and neuroinflammation, possibly through the regulation of the SIRT1/NF-kB signalling pathway.


greenmedinfo--2020-06-17--Ginsenoside Rd therapy improves histological and functional recovery in a model of inflammatory bowe

Ginsenoside Rd therapy improves histological and functional recovery in a model of inflammatory bowel disease.

Ginsenoside Rd ( GRd ) is a biologically active component of ginseng that stimulates the proliferation of endogenous stem cells @ @ @ @ @ research was to evaluate the utility of GRd in gastrointestinal mucosal regeneration in a rat @ @ @ @ @ ( IBD ) and to clarify whether GRd exerts its pharmacological effects by modulating endogenous @ @ @ @ @ IBD rat model was established via subcutaneous injection of indomethacin , and 10 , 20 @ @ @ @ @ or an equal volume of physiological saline was then administered orally to rats in different @ @ @ @ @ consecutive days .
We observed that GRd treatment , especially 20 mg/kg GRd , significantly @ @ @ @ @ that in the control group.By measuring the mRNA and protein levels of the intestinal stem @ @ @ @ @ and the intestinal epithelial cell marker CDX-2 as well as by double-labelling these markers with @ @ @ @ @ we inferred that GRd could stimulate the proliferation and differentiation of endogenous intestinal stem cells @ @ @ @ @ leading to improved recovery of intestinal function .

Ginsenoside Rd (GRd) is a biologically active component of ginseng that stimulates the proliferation of endogenous stem cells. The objective of our research was to evaluate the utility of GRd in gastrointestinal mucosal regeneration in a rat model of inflammatory bowel disease (IBD) and to clarify whether GRd exerts its pharmacological effects by modulating endogenous intestinal stem cells. The IBD rat model was established via subcutaneous injection of indomethacin, and 10, 20, or 40 mg/kg GRd or an equal volume of physiological saline was then administered orally to rats in different groups every day for seven consecutive days. We observed that GRd treatment, especially 20 mg/kg GRd, significantly reduced indomethacin-induced damage compared with that in the control group.By measuring the mRNA and protein levels of the intestinal stem cell markers Bmi and Msi-1 and the intestinal epithelial cell marker CDX-2 as well as by double-labelling these markers with 5-bromo-2-deoxyuridine (BrdU), we inferred that GRd could stimulate the proliferation and differentiation of endogenous intestinal stem cells in IBD model rats, leading to improved recovery of intestinal function.


greenmedinfo--2020-06-18--Licochalcone A reverses NNK-induced ectopic miRNA expression to elicit in vitro and in vivo chemopre

Licochalcone A reverses NNK-induced ectopic miRNA expression to elicit in vitro and in vivo chemopreventive effects.

BACKGROUND : Chemoprevention is the best cost-effective way regarding cancers .
MicroRNAs ( miRNAs ) have been reported to be differentially expressed during the development of lung cancer .
However , if lung cancer prevention can be achieved through modulating miRNAs expression so far remains unknown .
PURPOSE : To discover ectopically expressed miRNAs in NNK-induced lung cancer and clarify whether Licochalcone A ( lico A ) can prevent NNK-induced lung cancer by modulating miRNA expression .
STUDY DESIGN AND METHODS : A/J mice were used to construct a lung cancer model by intraperitoneal injection with physiological saline NNK ( @ @ @ @ @ @ @ lico A against lung cancer at 2 mg/kg and 20 mg/kg doses were evaluated in vivo .
MicroRNA array and RT-qPCR were used to assess the expression levels of miRNAs .
MLE-12 cells were treated with 0.1 mg/ml NNK , stimulating the ectopic expression pattern of miR-144-3p , miR-20a-5p , miR-29c-3p , let-7d-3p , and miR-328-3p .
miR-144-3p mimics and inhibitors were used to manipulate miR-144-3p levels .
The effects of lico A ( 10μM ) on cell cycle distribution , apoptosis , and the expression of CK19 , RASA1 , miR-144-3p , @ @ @ @ @ @ @ miR-328-3p in NNK-treated MLE-12 cells were studied .
RESULTS : The expression levels of miR-144-3p , miR-20a-5p , and miR-29c-3p increased , while those of let-7d-3p and miR-328-3p decreased in both NNK-induced A/J mice and MLE-12 cells .
Lico A could reverse the NNK-induced ectopic miRNA ( miR-144-3p , miR-20a-5p , miR-29c-3p , let-7d-3p , and miR-328-3p ) expression both in vivo and in vitro and elicit in vivo lung cancer chemopreventive effect against NNK .
In MLE-12 cells , the overexpression of miR-144-3p elicited the same effect as NNK regarding the expression @ @ @ @ @ @ @ silencing of miR-144-3p reversed the effect of NNK on cell cycle distribution and apoptosis .
Lico A could reverse the effect of NNK on the expression of miR-144-3p , CK19 , and RASA1 ( predicted target of miR-144-3p ) .
CONCLUSION : The present study suggests that miR-144-3p , miR-20a-5p , miR-29c-3p , let-7d-3p , and miR-328-3p were involved in the in vivo pathogenesis of NNK-induced lung cancer , and lico A could reverse the effect of NNK both in vivo and in vitro to elicit lung cancer chemopreventive effects through , at @ @ @ @ @ @ @ miRNAs , especially miR-144-3p .

BACKGROUND: Chemoprevention is the best cost-effective way regarding cancers. MicroRNAs (miRNAs) have been reported to be differentially expressed during the development of lung cancer. However, if lung cancer prevention can be achieved through modulating miRNAs expression so far remains unknown.
PURPOSE: To discover ectopically expressed miRNAs in NNK-induced lung cancer and clarify whether Licochalcone A (lico A) can prevent NNK-induced lung cancer by modulating miRNA expression.
STUDY DESIGN AND METHODS: A/J mice were used to construct a lung cancer model by intraperitoneal injection with physiological saline NNK (100 mg/kg). Chemopreventive effects of lico A against lung cancer at 2 mg/kg and 20 mg/kg doses were evaluated in vivo. MicroRNA array and RT-qPCR were used to assess the expression levels of miRNAs. MLE-12 cells were treated with 0.1 mg/ml NNK, stimulating the ectopic expression pattern of miR-144-3p, miR-20a-5p, miR-29c-3p, let-7d-3p, and miR-328-3p. miR-144-3p mimics and inhibitors were used to manipulate miR-144-3p levels. The effects of lico A (10μM) on cell cycle distribution, apoptosis, and the expression of CK19, RASA1, miR-144-3p, miR-20a-5p, miR-29c-3p, let-7d-3p, and miR-328-3p in NNK-treated MLE-12 cells were studied.
RESULTS: The expression levels of miR-144-3p, miR-20a-5p, and miR-29c-3p increased, while those of let-7d-3p and miR-328-3p decreased in both NNK-induced A/J mice and MLE-12 cells. Lico A could reverse the NNK-induced ectopic miRNA (miR-144-3p, miR-20a-5p, miR-29c-3p, let-7d-3p, and miR-328-3p) expression both in vivo and in vitro and elicit in vivo lung cancer chemopreventive effect against NNK. In MLE-12 cells, the overexpression of miR-144-3p elicited the same effect as NNK regarding the expression of lung cancer biomarker CK19; the silencing of miR-144-3p reversed the effect of NNK on cell cycle distribution and apoptosis. Lico A could reverse the effect of NNK on the expression of miR-144-3p, CK19, and RASA1 (predicted target of miR-144-3p).
CONCLUSION: The present study suggests that miR-144-3p, miR-20a-5p, miR-29c-3p, let-7d-3p, and miR-328-3p were involved in the in vivo pathogenesis of NNK-induced lung cancer, and lico A could reverse the effect of NNK both in vivo and in vitro to elicit lung cancer chemopreventive effects through, at least partially, these five ectopically expressed miRNAs, especially miR-144-3p.


greenmedinfo--2020-06-18--The results obtained reinforce the notion of lactoferrin potency as a remedy against atherosclerosis

The results obtained reinforce the notion of lactoferrin potency as a remedy against atherosclerosis.

Myeloperoxidase ( MPO ) is unique heme-containing peroxidase which can catalyze formation of hypochlorous acid ( HOCl ) .
Strong @ @ @ @ @ lipoproteins ( LDL ) promotes proatherogenic modification of LDL by HOCl .
The so-called MPO-modified @ @ @ @ @ in macrophages with formation of foam cells , which is the pathognomic symptom of atherosclerosis @ @ @ @ @ prophylaxis and therapy of atherosclerosis is searching for remedies preventing modification or accumulation of LDL @ @ @ @ @ LF ) has several application points in obesity pathogenesis .
We aimed to study LF @ @ @ @ @ accumulation in monocytes transformed into macrophages .
Using surface plasmon resonance and ELISA techniques we @ @ @ @ @ intact LDL , while Mox-LDL strongly interacted with LF .
Affinity of Mox-LDL to LF @ @ @ @ @ oxidative modification of LDL .
Moreover , an excess of MPO did not prevent interaction @ @ @ @ @ LF inhibits accumulation of cholesterol in macrophages exposed to Mox-LDL .
The results obtained reinforce @ @ @ @ @ as a remedy against atherosclerosis .

Myeloperoxidase (MPO) is unique heme-containing peroxidase which can catalyze formation of hypochlorous acid (HOCl). Strong interaction of MPO with low-density lipoproteins (LDL) promotes proatherogenic modification of LDL by HOCl. The so-called MPO-modified LDL (Mox-LDL) accumulates in macrophages with formation of foam cells, which is the pathognomic symptom of atherosclerosis. A promising approach to prophylaxis and therapy of atherosclerosis is searching for remedies preventing modification or accumulation of LDL in macrophages. Lactoferrin (LF) has several application points in obesity pathogenesis. We aimed to study LF binding to Mox-LDL and their accumulation in monocytes transformed into macrophages. Using surface plasmon resonance and ELISA techniques we observed no LF interaction with intact LDL, while Mox-LDL strongly interacted with LF. Affinity of Mox-LDL to LF increased with the degree of oxidative modification of LDL. Moreover, an excess of MPO did not prevent interaction of Mox-LDL with LF. LF inhibits accumulation of cholesterol in macrophages exposed to Mox-LDL. The results obtained reinforce the notion of LF potency as a remedy against atherosclerosis.


greenmedinfo--2020-06-18--How Fear of a Virus Changed Our World

How Fear of a Virus Changed Our World

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Before beginning any type of @ @ @ @ @ treatment regimen , it is advisable to seek the advice of a licensed healthcare professional @

This website is for information purposes only. By providing the information contained herein we are not diagnosing, treating, curing, mitigating, or preventing any type of disease or medical condition. Before beginning any type of natural, integrative or conventional treatment regimen, it is advisable to seek the advice of a licensed healthcare professional.
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greenmedinfo--2020-06-18--Lupeol suppresses plasminogen activator inhibitor-1-mediated macrophage recruitment and attenuates M

Lupeol suppresses plasminogen activator inhibitor-1-mediated macrophage recruitment and attenuates M2 macrophage polarization.

Tumor-associated macrophages ( TAMs ) are closely related with poor prognosis of cancers .
The current study investigated whether lupeol @ @ @ @ @ the recruitment and polarization of macrophages .
We found that lupeol suppressed the recruitment of @ @ @ @ @ differentiated into macrophages ) towards H1299 lung carcinoma cells by inhibiting plasminogen activator inhibitor-1 ( @ @ @ @ @ cells .
The reduced migration of THP-1 macrophages by lupeol was recovered by adding recombinant @ @ @ @ @ .
Knockdown of PAI-1 or treatment of tiplaxtinin , a PAI-1 inhibitor , in H1299 @ @ @ @ @ macrophages .
Furthermore , lupeol suppressed the interleukin ( IL ) -4- and IL-13-induced M2 @ @ @ @ @ expression of M2 macrophage markers and the phosphorylation of signal transducerand activator of transcription 6 @ @ @ @ @ decreased by lupeol in RAW264.7 cells .
In addition , lupeol-suppressed M2 macrophage polarization led @ @ @ @ @ Lewis lung carcinoma ( LLC ) cells .
Taken together , our results suggest that @ @ @ @ @ towards cancer cells and inhibits M2 macrophage polarization .

Tumor-associated macrophages (TAMs) are closely related with poor prognosis of cancers. The current study investigated whether lupeol regulates TAMs by focusing on the recruitment and polarization of macrophages. We found that lupeol suppressed the recruitment of THP-1 macrophages (THP-1 cells differentiated into macrophages) towards H1299 lung carcinoma cells by inhibiting plasminogen activator inhibitor-1 (PAI-1) production from H1299 cells. The reduced migration of THP-1 macrophages by lupeol was recovered by adding recombinant human PAI-1 as a chemoattractant. Knockdown of PAI-1 or treatment of tiplaxtinin, a PAI-1 inhibitor, in H1299 cells abrogated the chemotaxis of macrophages. Furthermore, lupeol suppressed the interleukin (IL)-4- and IL-13-induced M2 macrophage polarization. The mRNA expression of M2 macrophage markers and the phosphorylation of signal transducerand activator of transcription 6 (STAT6) were commonly decreased by lupeol in RAW264.7 cells. In addition, lupeol-suppressed M2 macrophage polarization led to the reduced migration of Lewis lung carcinoma (LLC) cells. Taken together, our results suggest that lupeol attenuates PAI-1-mediated macrophage recruitment towards cancer cells and inhibits M2 macrophage polarization.


greenmedinfo--2020-06-18--Total glucosides of paeony: A review of its phytochemistry, role in autoimmune diseases, and mechani

Total glucosides of paeony: A review of its phytochemistry, role in autoimmune diseases, and mechanisms of action.

ETHNOPHARMACOLOGICAL RELEVANCE : Paeoniae Radix Alba ( PRA , called baishao in China ) , the root of Paeonia lactiflora Pall.
, has shown a rich medicinal value for more than 2000 years .
PRA is used in local medicine and traditional medicine for autoimmune diseases associated with inflammation .
At present , total glucosides of paeony ( TGP ) , the main active ingredient of PRA , has been developed into a preparation for the treatment of autoimmune diseases , as TGP exhibits the effect of regulating immunity , anti-inflammatory , and analgesic effects .
AIM OF THE REVIEW @ @ @ @ @ @ @ inflammation-related autoimmune diseases in modern clinical practice .
Based on its application in traditional prescriptions , this article reviews PRA 's botany and phytochemistry ( including its extraction process and quality control ) , and discusses the clinical application and pharmacological research of TGP as an anti-inflammatory drug from the perspective of ethnopharmacology .
Additionally , we review modern pharmacological and molecular-target research on TGP and discuss the mechanisms of TGP in treating autoimmune diseases .
Through a systematic literature review , we also highlight the clinical efficacy of TGP in the treatment @ @ @ @ @ @ @ reference for the continued scientific development and quality control of TGP so that its wider application and clinical value can be fully realized .
MATERIALS AND METHODS : Literature search was conducted through the Web of Science , Baidu Scholar , ScienceDirect , PubMed , CNKI , and WanFang DATA using the keywords '' Total glucosides of paeony '' , '' Paeonia lactiflora Pall .
`` , '' Paeonia veitchii Lynch '' , '' Paeoniae Radix Alba or white peony '' , '' Paeoniae Radix Rubra or red peony '' , '' Paeoniflorin @ @ @ @ @ @ @ Autoimmune diseases '' , and their combinations .
In addition , information was collected from relevant textbooks , reviews , and documents .
RESULTS : Approximately 15 compounds have been identified in TGP , of which paeoniflorin and albiflorin are the most common constituents .
In recent years , studies have found that TGP and its main chemical components are effective in the treatment of autoimmune diseases , such as rheumatoid arthritis , psoriasis , oral lichen planus , and Sjogren 's syndrome .
TGP has a variety of pharmacological effects related to @ @ @ @ @ @ @ anti-inflammatory , analgesic , antioxidant , cardiovascular , and nervous-system protection .
Previously published reports on TGP treatment of autoimmune diseases have shown that TGP regulates intracellular pathways , such as the nuclear factor kappa-light-chain-enhancer of activated B cells ( NF-κB ) , mitogen-activated protein kinase ( MAPK ) , and phosphatidylinositol 3-kinase/protein kinase B ( PI3K/Akt ) signaling pathways .
However , there is no standardized preparation method for TGP , and there is insufficient quality control of formulations .
Many related pharmacological studies have not tested TGP components , and the @ @ @ @ @ @ @ verification .
CONCLUSIONS : Modern pharmacological research on TGP is based on the traditional usage of PRA , and its folk medicinal value in the treatment of autoimmune diseases has now been verified .
In particular , TGP has been developed into a formulation used clinically for the treatment of autoimmune diseases .
The combination of TGP capsules and chemicals to treat autoimmune diseases has the effect of increasing efficacy and reducing toxicity .
Based on further research on its preparation , quality control , and mechanisms of action , TGP is expected @ @ @ @ @ @ @ the treatment of autoimmune diseases .

ETHNOPHARMACOLOGICAL RELEVANCE: Paeoniae Radix Alba (PRA, called baishao in China), the root of Paeonia lactiflora Pall., has shown a rich medicinal value for more than 2000 years. PRA is used in local medicine and traditional medicine for autoimmune diseases associated with inflammation. At present, total glucosides of paeony (TGP), the main active ingredient of PRA, has been developed into a preparation for the treatment of autoimmune diseases, as TGP exhibits the effect of regulating immunity, anti-inflammatory, and analgesic effects.
AIM OF THE REVIEW: TGP was developed and applied to inflammation-related autoimmune diseases in modern clinical practice. Based on its application in traditional prescriptions, this article reviews PRA's botany and phytochemistry (including its extraction process and quality control), and discusses the clinical application and pharmacological research of TGP as an anti-inflammatory drug from the perspective of ethnopharmacology. Additionally, we review modern pharmacological and molecular-target research on TGP and discuss the mechanisms of TGP in treating autoimmune diseases. Through a systematic literature review, we also highlight the clinical efficacy of TGP in the treatment of immune diseases, and provide a reference for the continued scientific development and quality control of TGP so that its wider application and clinical value can be fully realized.
MATERIALS AND METHODS: Literature search was conducted through the Web of Science, Baidu Scholar, ScienceDirect, PubMed, CNKI, and WanFang DATA using the keywords"Total glucosides of paeony","Paeonia lactiflora Pall.","Paeonia veitchii Lynch","Paeoniae Radix Alba or white peony","Paeoniae Radix Rubra or red peony","Paeoniflorin","Albiflorin","Autoimmune diseases", and their combinations. In addition, information was collected from relevant textbooks, reviews, and documents.
RESULTS: Approximately 15 compounds have been identified in TGP, of which paeoniflorin and albiflorin are the most common constituents. In recent years, studies have found that TGP and its main chemical components are effective in the treatment of autoimmune diseases, such as rheumatoid arthritis, psoriasis, oral lichen planus, and Sjogren's syndrome. TGP has a variety of pharmacological effects related to PRA traditional effects, including anti-organ-damage, anti-inflammatory, analgesic, antioxidant, cardiovascular, and nervous-system protection. Previously published reports on TGP treatment of autoimmune diseases have shown that TGP regulates intracellular pathways, such as the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), mitogen-activated protein kinase (MAPK), and phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathways. However, there is no standardized preparation method for TGP, and there is insufficient quality control of formulations. Many related pharmacological studies have not tested TGP components, and the validity of such pharmacological results requires further verification.
CONCLUSIONS: Modern pharmacological research on TGP is based on the traditional usage of PRA, and its folk medicinal value in the treatment of autoimmune diseases has now been verified. In particular, TGP has been developed into a formulation used clinically for the treatment of autoimmune diseases. The combination of TGP capsules and chemicals to treat autoimmune diseases has the effect of increasing efficacy and reducing toxicity. Based on further research on its preparation, quality control, and mechanisms of action, TGP is expected to eventually play a greater role in the treatment of autoimmune diseases.


greenmedinfo--2020-06-18--Total glucosides of paeony alleviates blood-brain barrier disruption and cerebral ischemia/reperfusi

Total glucosides of paeony alleviates blood-brain barrier disruption and cerebral ischemia/reperfusion injury.

At present it remains uncertain as to whether total glucosides of paeony ( TGP ) are able to mediate neuroprotection @ @ @ @ @ ischemia/reperfusion ( CIR ) injury , and if so , what mechanisms underlie such protection @ @ @ @ @ model of middle cerebral artery occlusion and reperfusion , and then Evans blue ( EB @ @ @ @ @ , Nissl staining , TUNEL staining , ELISAs and immunohistochemistry were used .
We observed @ @ @ @ @ , neurological deficits , and CIR-associated histopathological changes following TGP treatment .
We further found @ @ @ @ @ restoration of the BBB integrity , a reduction in levels of cerebral IL-1β , IL-6 @ @ @ @ @ decrease in overall neuronal apoptotic death that coincided with reduced Cleaved Caspase-3 and Bax expression @ @ @ @ @ These results demonstrate that TGP treatment is capable of reducing neurons damage and associated BBB @ @ @ @ @ a rodent model of CIR injury .

At present it remains uncertain as to whether total glucosides of paeony (TGP) are able to mediate neuroprotection in the context of cerebral ischemia/reperfusion (CIR) injury, and if so, what mechanisms underlie such protection. We employed a rat model of middle cerebral artery occlusion and reperfusion, and then Evans blue (EB), hematoxylin and eosin, Nissl staining, TUNEL staining, ELISAs and immunohistochemistry were used. We observed marked reductions in infarct volume, neurological deficits, and CIR-associated histopathological changes following TGP treatment. We further found that TGP was associated with restoration of the BBB integrity, a reduction in levels of cerebral IL-1β, IL-6 and TNF-α, and a decrease in overall neuronal apoptotic death that coincided with reduced Cleaved Caspase-3 and Bax expression, and elevated Bcl-2. These results demonstrate that TGP treatment is capable of reducing neurons damage and associated BBB dysfunctionanti-apoptotic and anti-inflammatory mechanisms in a rodent model of CIR injury.


greenmedinfo--2020-06-18--Radix Paeoniae rubra ameliorates lupus nephritis.

OBJECTIVE : Vasculitis is the basic pathological change of systemic lupus erythematosus ( SLE ) .
Radix Paeoniae Rubra ( RPR ) , a traditional Chinese herb with the function of reducing blood stasis , has antiinflammatory and immunoregulatory properties .
This study explored the effects of RPR on the kidneys of lupus-like symptoms of mrl ( MRL/lpr ) mice from the perspective of intercellular cell adhesion molecule-1 ( ICAM-1 ) , vascular cell adhesion molecule-1 ( VCAM-1 ) and platelet endothelial cell adhesion molecule-1 ( PECAM-1 ) .
METHODS : Eighteen MRL/lpr lupus model mice were randomly divided into @ @ @ @ @ @ @ , prednisone-treated group , and RPR-treated group , and 6 C57BL/6mice were classified as a control group .
After the mice had been treated for 12 weeks , the expression of ICAM-1 , VCAM-1and PECAM-1in the kidney was determined by immunohistochemistry and Reverse TranscriptionPolymerase Chain Reaction ( RT-PCR ) .
RESULTS : After 12 weeks , there were significant differences in body weight in the model , prednisone and RPR groups compared with the normal group ( P < 0.05 ) .
Pathological observation : Compared with the model group , the proliferation @ @ @ @ @ @ @ cells in prednisone and RPR groups were reduced , and renal pathological damage was reduced .
Compared with the model group , urine protein level of prednisone and RPR groups were reduced with no significance ( P > 0.05 ) .
The mRNA expression levels of ICAM-1 and VCAM-1 were significantly reduced in the prednisone group and RPR group compared with the model group ( P < 0.05 or P < 0.01 ) .
Meanwhile , the immunohistochemistry expressions of ICAM-1 and VCAM-1 expressed in the kidney were significantly reduced in the prednisone @ @ @ @ @ @ @ 0.01 or P < 0.05 ) .
However , The mRNA expression level and the immunohistochemistry expressions of PECAM-1 expressed in the kidney were reduced in each treatment group ( prednisone group and RPR group ) , but these differences were not significant ( P＞0.05 ) .
CONCLUSIONS : ICAM-1 , VCAM-1 and PECAM-1 expression in the model group was significantly increased .
In addition , RPR could reduce the expression of ICAM-1 , VCAM-1 and PECAM-1 in MRL/lpr lupus mice as effectively as prednisone , which may result in the dosage reduction @ @ @ @ @ @ @ and improving the efficacy of prednisone -based treatment of SLE .

OBJECTIVE: Vasculitis is the basic pathological change of systemic lupus erythematosus(SLE). Radix Paeoniae Rubra (RPR), a traditional Chinese herb with the function of reducing blood stasis, has antiinflammatory and immunoregulatory properties. This study explored the effects of RPR on the kidneys of lupus-like symptoms of mrl (MRL/lpr) mice from the perspective of intercellular cell adhesion molecule-1(ICAM-1), vascular cell adhesion molecule-1(VCAM-1) and platelet endothelial cell adhesion molecule-1(PECAM-1).
METHODS: Eighteen MRL/lpr lupus model mice were randomly divided into three groups, the model control group, prednisone-treated group, and RPR-treated group, and 6 C57BL/6mice were classified as a control group. After the mice had been treated for 12 weeks, the expression of ICAM-1, VCAM-1and PECAM-1in the kidney was determined by immunohistochemistry and Reverse TranscriptionPolymerase Chain Reaction (RT-PCR).
RESULTS: After 12 weeks, there were significant differences in body weight in the model, prednisone and RPR groups compared with the normal group (P<0.05). Pathological observation: Compared with the model group, the proliferation of inflammatory cells infiltrated glomeruli and interstitial cells in prednisone and RPR groups were reduced, and renal pathological damage was reduced. Compared with the model group,urine protein level of prednisone and RPR groups were reduced with no significance(P>0.05). The mRNA expression levels of ICAM-1 and VCAM-1 were significantly reduced in the prednisone group and RPR group compared with the model group (P<0.05 or P<0.01). Meanwhile, the immunohistochemistry expressions of ICAM-1 and VCAM-1 expressed in the kidney were significantly reduced in the prednisone group and RPR group (P<0.01 or P<0.05). However, The mRNA expression level and the immunohistochemistry expressions of PECAM-1 expressed in the kidney were reduced in each treatment group (prednisone group and RPR group), but these differences were not significant (P＞0.05).
CONCLUSIONS: ICAM-1, VCAM-1 and PECAM-1 expression in the model group was significantly increased. In addition, RPR could reduce the expression of ICAM-1, VCAM-1 and PECAM-1 in MRL/lpr lupus mice as effectively as prednisone, which may result in the dosage reduction of prednisone, thus decreasing the toxicity and improving the efficacy of prednisone -based treatment of SLE.


greenmedinfo--2020-06-18--Total glucosides of herbaceous peony is promising as a therapeutic agent against hyperuricaemia.

ETHNOPHARMACOLOGICAL RELEVANCE : Herbaceous peony ( Paeonia lactiflora Pall . )
flower has been used widely in dietotherapy in China and other countries .
It has good ethnopharmacological value in the treatment of various metabolic diseases .
However , the molecular mechanisms by which it lowers serum uric acid are unknown .
The development of pharmaceutical resources is very important .
Here , we sought to elucidate the mode of action of herbaceous peony in terms of reducing uric acid levels .
AIM OF THE STUDY : In the present research , the effects of the total glucosides of herbaceous @ @ @ @ @ @ @ hyperuricaemia model .
Another aim of the study was to clarify the mechanism by which herbaceous peony flower ( TGPF ) lowers serum uric acid levels .
MATERIALS AND METHODS : A hyperuricaemic rat model was induced via intragastric administration of 100 mg/kg adenine and 250 mg/kg ethambutol hydrochloride ( EH ) for 23 d. Then TongFengShu 600 mg/kg , allopurinol 42 mg/kg , or TGPF ( 50 mg/kg , 100 mg/kg , or 200 mg/kg ) was administered 1 h after the adenine and EH treatments .
RESULTS : TGPF improved weight @ @ @ @ @ @ @ , MCP-1 , TNF-α , Cr , and BUN in the rats with hyperuricaemic nephropathy .
TGPF downregulated renal URAT1 and GLUT9 , upregulated renal OAT1 , and ameliorated histopathological changes in the thymus , spleen , and kidney .
CONCLUSION : TGPF is promising as a therapeutic agent against hyperuricaemia .
It regulates the uric acid transporters and diminished serum uric acid levels , and alleviates renal pathology associated with hyperuricaemia .

ETHNOPHARMACOLOGICAL RELEVANCE: Herbaceous peony (Paeonia lactiflora Pall.) flower has been used widely in dietotherapy in China and other countries. It has good ethnopharmacological value in the treatment of various metabolic diseases. However, the molecular mechanisms by which it lowers serum uric acid are unknown. The development of pharmaceutical resources is very important. Here, we sought to elucidate the mode of action of herbaceous peony in terms of reducing uric acid levels.
AIM OF THE STUDY: In the present research, the effects of the total glucosides of herbaceous peony flower were investigated in a rat hyperuricaemia model. Another aim of the study was to clarify the mechanism by which herbaceous peony flower (TGPF) lowers serum uric acid levels.
MATERIALS AND METHODS: A hyperuricaemic rat model was induced via intragastric administration of 100 mg/kg adenine and 250 mg/kg ethambutol hydrochloride (EH) for 23 d. Then TongFengShu 600 mg/kg, allopurinol 42 mg/kg, or TGPF (50 mg/kg, 100 mg/kg, or 200 mg/kg) was administered 1 h after the adenine and EH treatments.
RESULTS: TGPF improved weight loss and decreased serum UA, XOD, MCP-1, TNF-α, Cr, and BUN in the rats with hyperuricaemic nephropathy. TGPF downregulated renal URAT1 and GLUT9, upregulated renal OAT1, and ameliorated histopathological changes in the thymus, spleen, and kidney.
CONCLUSION: TGPF is promising as a therapeutic agent against hyperuricaemia. It regulates the uric acid transporters and diminished serum uric acid levels, and alleviates renal pathology associated with hyperuricaemia.


greenmedinfo--2020-06-18--Exploring and characterizing a novel combination of paeoniflorin and talatizidine for the treatment

Exploring and characterizing a novel combination of paeoniflorin and talatizidine for the treatment of rheumatoid arthritis.

Wutou Decoction ( WTD ) achieves favorable therapeutic response in treating rheumatoid arthritis ( RA ) , especially for wind-cold-dampness stimulating RA .
However , its material basis and molecular mechanisms remain unclear .
To address this problem , the main bioactive compounds ( BACs ) of WTD against RA and the candidate targets were identified in the current study via transcriptional regulatory network analysis , computational structure-based methods , as well as in vivo and in vitro experimental validations .
As a result , we successfully established a RA rat model named AIA-S , which simulated the clinical manifestations @ @ @ @ @ @ @ , and also displayed the distinctive characteristics and biological basis of inflammatory-immune system imbalance and abnormal energy metabolism changes .
In addition , ALOX15B-PPAR-γ-PTGS2-FGF2-IL-1β-c-JUN-MMP13-TGF-β1 signal axis , involved into thermogenesis and energy metabolism , as well as maintaining the balance of inflammation-immune system , was identified as a candidate target of WTD against RA , according to the transcriptional regulatory network analysis on '' RA-related gene-WTD-effective gene interaction network '' .
Moreover , Paeoniflorin ( PAE ) and Talatizidine ( TLT ) were demonstrated to be the main BACs of WTD against RA @ @ @ @ @ @ @ both PAE and TLT were the BACs of WTD according to ADME analysis in silico and the pharmacokinetics analysis in vivo .
Secondly , both PAE and TLT were able to bind with PPAR-γ , c-JUN , MMP13 and TGF-β1 , which were the candidate targets of WTD against RA , with the strong binding affinity .
Thirdly , the PAE and TLT combination exerted significant therapeutic effects on AIA-S rats through reversing the imbalance of inflammatory-immune system , and the disturbance of thermogenesis and energy metabolism , which were similar to WTD @ @ @ @ @ @ @ TLT or PAE alone did n't exert as prominently therapeutic effects as that of the two-BAC-combination did .
Fourthly , the PAE and TLT combination promoted adipogenesis and lipogenesis by upregulating the PPAR-γ-induced lipogenic proteins .
In conclusion , this study identified PAE and TLT as the main BACs of WTD in alleviating the severity of RA , and also developed a novel combination of PAE and TLT as a promising candidate drug for RA therapy .

Wutou Decoction (WTD) achieves favorable therapeutic response in treating rheumatoid arthritis (RA), especially for wind-cold-dampness stimulating RA. However, its material basis and molecular mechanisms remain unclear. To address this problem, the main bioactive compounds (BACs) of WTD against RA and the candidate targets were identified in the current study via transcriptional regulatory network analysis, computational structure-based methods, as well as in vivo and in vitro experimental validations. As a result, we successfully established a RA rat model named AIA-S, which simulated the clinical manifestations and pathological changes of wind-cold-dampness stimulating RA, and also displayed the distinctive characteristics and biological basis of inflammatory-immune system imbalance and abnormal energy metabolism changes. In addition, ALOX15B-PPAR-γ-PTGS2-FGF2-IL-1β-c-JUN-MMP13-TGF-β1 signal axis, involved into thermogenesis and energy metabolism, as well as maintaining the balance of inflammation-immune system, was identified as a candidate target of WTD against RA, according to the transcriptional regulatory network analysis on"RA-related gene-WTD-effective gene interaction network". Moreover, Paeoniflorin (PAE) and Talatizidine (TLT) were demonstrated to be the main BACs of WTD against RA for the following reasons: firstly, both PAE and TLT were the BACs of WTD according to ADME analysis in silico and the pharmacokinetics analysis in vivo. Secondly, both PAE and TLT were able to bind with PPAR-γ, c-JUN, MMP13 and TGF-β1, which were the candidate targets of WTD against RA, with the strong binding affinity. Thirdly, the PAE and TLT combination exerted significant therapeutic effects on AIA-S rats through reversing the imbalance of inflammatory-immune system, and the disturbance of thermogenesis and energy metabolism, which were similar to WTD. More importantly, the administration of TLT or PAE alone didn't exert as prominently therapeutic effects as that of the two-BAC-combination did. Fourthly, the PAE and TLT combination promoted adipogenesis and lipogenesis by upregulating the PPAR-γ-induced lipogenic proteins. In conclusion, this study identified PAE and TLT as the main BACs of WTD in alleviating the severity of RA, and also developed a novel combination of PAE and TLT as a promising candidate drug for RA therapy.


greenmedinfo--2020-06-18--Paeoniflorin alleviates lipopolysaccharide-induced disseminated intravascular coagulation.

Lipopolysaccharide ( LPS ) is a toxic component of the outer membrane of gram-negative bacteria that can activate the blood coagulation system , leading to disseminated intravascular coagulation ( DIC ) .
DIC is a syndrome characterized by thromboembolism and multiple organ failure .
Herein , the beneficial effect of paeoniflorin ( PF ) on the alleviation of LPS-induced DIC was investigated with an experimental DIC mouse model .
Briefly , mice were randomly divided into the following six groups : ( 1 ) control ; ( 2 ) LPS ; ( 3 ) heparin ; ( 4 ) low-PF @ @ @ @ @ @ @ ; and ( 6 ) high-PF treatment .
The histological morphology of the liver and kidney was observed , and the coagulation indicators ( such as prothrombin time ) , function indicators ( such as alanine transferase ) , and inflammatory factors ( such as TNF-α ) were detected .
Additionally , an in vitro cell inflammation model using RAW 264.7 murine macrophages was established .
Activation of the nuclear factor kappa B ( NF-κB ) signaling pathway and tumor necrosis factor-α ( TNF-α ) were determined by western blotting .
Based on @ @ @ @ @ @ @ the histological morphology of the liver and kidney , indicating that PF protects the liver and kidney against damage induced by LPS .
Additionally , PF improved the function and coagulation indicators and reduced the production of inflammatory factors .
In vitro , PF inhibited the expression of TNF-α by suppressing NF-κB signaling pathway activation .
Collectively , our findings support the hypothesis that PF has anti-inflammatory and anticoagulation effects for the alleviation of LPS-induced DIC .
PF is thus a potential co-treatment option for DIC .

Lipopolysaccharide (LPS) is a toxic component of the outer membrane of gram-negative bacteria that can activate the blood coagulation system, leading to disseminated intravascular coagulation (DIC). DIC is a syndrome characterized by thromboembolism and multiple organ failure. Herein, the beneficial effect of paeoniflorin (PF) on the alleviation of LPS-induced DIC was investigated with an experimental DIC mouse model. Briefly, mice were randomly divided into the following six groups: (1) control; (2) LPS; (3) heparin; (4) low-PF treatment; (5) medium-PF treatment; and (6) high-PF treatment. The histological morphology of the liver and kidney was observed, and the coagulation indicators (such as prothrombin time), function indicators (such as alanine transferase), and inflammatory factors (such as TNF-α) were detected. Additionally, an in vitro cell inflammation model using RAW 264.7 murine macrophages was established. Activation of the nuclear factor kappa B (NF-κB) signaling pathway and tumor necrosis factor-α (TNF-α) were determined by western blotting. Based on our findings, PF could significantly improve the histological morphology of the liver and kidney, indicating that PF protects the liver and kidney against damage induced by LPS. Additionally, PF improved the function and coagulation indicators and reduced the production of inflammatory factors. In vitro, PF inhibited the expression of TNF-α by suppressing NF-κB signaling pathway activation. Collectively, our findings support the hypothesis that PF has anti-inflammatory and anticoagulation effects for the alleviation of LPS-induced DIC. PF is thus a potential co-treatment option for DIC.


greenmedinfo--2020-06-18--Paeoniflorin relieves LPS-induced inflammatory pain in mice by inhibiting NLRP3 inflammasome activat

Paeoniflorin relieves LPS-induced inflammatory pain in mice by inhibiting NLRP3 inflammasome activation.

LPS has been widely used to induce inflammatory pain , attributing to production of inflammatory cytokines and sensitization of nociceptors .
Paeoniflorin ( PF ) possesses anti-nociceptive property , but its effect on LPS-induced inflammatory pain has not been investigated .
In this study , we aimed to investigate the analgesic effect of PF on an inflammatory pain mouse model and explore the underlying mechanisms .
LPS-induced inflammatory pain model was established in C57BL/6J mice after PF treatment .
Then , thermal hyperalgesia , neutrophil infiltration , inflammatory cytokine production , intracellular Calevels , PKC activity , transient receptor potential @ @ @ @ @ @ @ NF-κB transcription , and NLPR3 inflammasome activation were assessed by thermal withdrawal latency , histopathology , ELISA , intracellular Caconcentration , immunohistochemistry , and Western blot , separately .
PF significantly relieved inflammatory pain and paw edema in mice with LPS-induced inflammatory pain .
Additionally , PF inhibited neutrophil infiltration , inflammatory cytokine production ( IL-1β , TNF-α , and IL-6 ) , intracellular Calevels , and PKC activity as well as suppressed TRPV-1 expression , NF-κB transcription , and NLPR3 inflammasome activation in the footpad tissue samples .
Importantly , capsaicin ( @ @ @ @ @ @ @ effect of PF , suggesting the involvement of TRPV-1 in the analgesic activity of PF .
Our results indicated PF ameliorated LPS-induced inflammation and pain in mice by inhibiting TRPV-1-mediated NLRP3 inflammasome activation .
These findings suggest that PF can be as a potential pharmacological agent for inflammatory pain and thus deserves more attention and further investigation .

LPS has been widely used to induce inflammatory pain, attributing to production of inflammatory cytokines and sensitization of nociceptors. Paeoniflorin (PF) possesses anti-nociceptive property, but its effect on LPS-induced inflammatory pain has not been investigated. In this study, we aimed to investigate the analgesic effect of PF on an inflammatory pain mouse model and explore the underlying mechanisms. LPS-induced inflammatory pain model was established in C57BL/6J mice after PF treatment. Then, thermal hyperalgesia, neutrophil infiltration, inflammatory cytokine production, intracellular Calevels, PKC activity, transient receptor potential vanilloid 1 (TRPV-1) expression, NF-κB transcription, and NLPR3 inflammasome activation were assessed by thermal withdrawal latency, histopathology, ELISA, intracellular Caconcentration, immunohistochemistry, and Western blot, separately. PF significantly relieved inflammatory pain and paw edema in mice with LPS-induced inflammatory pain. Additionally, PF inhibited neutrophil infiltration, inflammatory cytokine production (IL-1β, TNF-α, and IL-6), intracellular Calevels, and PKC activity as well as suppressed TRPV-1 expression, NF-κB transcription, and NLPR3 inflammasome activation in the footpad tissue samples. Importantly, capsaicin (TRPV-1 agonists) obviously reversed the pain-relieving effect of PF, suggesting the involvement of TRPV-1 in the analgesic activity of PF. Our results indicated PF ameliorated LPS-induced inflammation and pain in mice by inhibiting TRPV-1-mediated NLRP3 inflammasome activation. These findings suggest that PF can be as a potential pharmacological agent for inflammatory pain and thus deserves more attention and further investigation.


greenmedinfo--2020-06-18--Paeoniflorin attenuates early brain injury through reducing oxidative stress and neuronal apoptosis

Paeoniflorin attenuates early brain injury through reducing oxidative stress and neuronal apoptosis after subarachnoid hemorrhage.

Paeoniflorin is a natural monoterpene glucoside from Paeoniae Radix with neuroprotective properties .
However , it is still unclear whether paeoniflorin has neuroprotective effects on subarachnoid hemorrhage ( SAH ) .
This study explores the effect of paeoniflorin on early brain injury ( EBI ) using rat SAH model .
We found that paeoniflorin significantly improves neurological deficits , attenuates brain water content and Evans blue extravasation at 72 h after SAH .
Paeoniflorin attenuates the oxidative stress following SAH as evidenced by decrease of reactive oxygen species ( ROS ) , malondialdehyde ( MDA ) , 3-Nitrotyrosine , and @ @ @ @ @ @ @ increase of superoxide dismutase ( SOD ) , glutathione peroxidase ( GSH-Px ) , and catalase activity , and up-regulates the nuclear factor erythroid‑related factor 2 ( Nrf2 ) /heme oxygenase‑1 ( HO-1 ) pathway .
Inhibition of microglia activation and neuro-inflammatory response both contributed to paeoniflorin 's protective effects .
Moreover , paeoniflorin treatment significantly reduces the ratio of Bax/Bcl-2 , active caspase-3/ neuronal nuclei ( NeuN ) and TUNEL/DAPI positive cells at 72 h following SAH .
Our results indicate that paeoniflorin may attenuate early brain injury after experimental SAH .

Paeoniflorin is a natural monoterpene glucoside from Paeoniae Radix with neuroprotective properties. However, it is still unclear whether paeoniflorin has neuroprotective effects on subarachnoid hemorrhage (SAH). This study explores the effect of paeoniflorin on early brain injury (EBI) using rat SAH model. We found that paeoniflorin significantly improves neurological deficits, attenuates brain water content and Evans blue extravasation at 72 h after SAH. Paeoniflorin attenuates the oxidative stress following SAH as evidenced by decrease of reactive oxygen species (ROS), malondialdehyde (MDA), 3-Nitrotyrosine, and 8-Hydroxy-2-deoxy guanosine (8-OHDG) level, increase of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase activity, and up-regulates the nuclear factor erythroid‑related factor 2 (Nrf2)/heme oxygenase‑1 (HO-1) pathway. Inhibition of microglia activation and neuro-inflammatory response both contributed to paeoniflorin's protective effects. Moreover, paeoniflorin treatment significantly reduces the ratio of Bax/Bcl-2, active caspase-3/ neuronal nuclei (NeuN) and TUNEL/DAPI positive cells at 72 h following SAH. Our results indicate that paeoniflorin may attenuate early brain injury after experimental SAH.