greenmedinfo--2020-07-23--Cucurbitacins extracted from Cucumis melo L. (CuEC) exert a hypotensive effect via regulating vascul

Cucurbitacins extracted from Cucumis melo L. (CuEC) exert a hypotensive effect via regulating vascular tone.

As an effective medicine for jaundice in traditional Chinese medicine , Cucumis melo L. has been widely used in China .
However , its effect on vascular function is still unclear .
In this study , we extracted the compounds of Cucumis melo L. , and the major ingredients were identified as cucurbitacins ( CuEC , cucurbitacins extracted from Cucumis melo L. ) , especially cucurbitacin B .
We replicated the toxicity in mice by intraperitoneal injection of a high dose of CuEC ( 2 mg/kg ) and demonstrated that the cause of death was CuEC-induced impairment of the endothelial @ @ @ @ @ @ @ permeability via decreasing VE-cadherin conjunction .
The administration of low doses of CuEC ( 1 mg/kg ) led to a decline in systolic blood pressure ( SBP ) without causing toxicity in mice .
More importantly , CuEC dramatically suppressed angiotensin II ( Ang II ) -induced SBP increase .
Further studies demonstrated that CuEC facilitated acetylcholine-mediated vasodilation in mesenteric arteries of mice .
In vitro studies showed that CuEC induced vasodilation in a dose-dependent manner in mesenteric arteries of both mice and rats .
Pretreatment with CuEC inhibited phenylephrine-mediated vasoconstriction .
In @ @ @ @ @ @ @ reduced SBP by improving blood vessel tension .
Therefore , our study provides new experimental evidence for developing new antihypertensive drugs .

As an effective medicine for jaundice in traditional Chinese medicine, Cucumis melo L. has been widely used in China. However, its effect on vascular function is still unclear. In this study, we extracted the compounds of Cucumis melo L., and the major ingredients were identified as cucurbitacins (CuEC, cucurbitacins extracted from Cucumis melo L.), especially cucurbitacin B. We replicated the toxicity in mice by intraperitoneal injection of a high dose of CuEC (2 mg/kg) and demonstrated that the cause of death was CuEC-induced impairment of the endothelial barrier and, thus, increased vascular permeability via decreasing VE-cadherin conjunction. The administration of low doses of CuEC (1 mg/kg) led to a decline in systolic blood pressure (SBP) without causing toxicity in mice. More importantly, CuEC dramatically suppressed angiotensin II (Ang II)-induced SBP increase. Further studies demonstrated that CuEC facilitated acetylcholine-mediated vasodilation in mesenteric arteries of mice. In vitro studies showed that CuEC induced vasodilation in a dose-dependent manner in mesenteric arteries of both mice and rats. Pretreatment with CuEC inhibited phenylephrine-mediated vasoconstriction. In summary, a moderate dose of CuEC reduced SBP by improving blood vessel tension. Therefore, our study provides new experimental evidence for developing new antihypertensive drugs.


greenmedinfo--2020-07-23--Cucumol B has cytotoxic effects toward ovarian and human breast adenocarcinoma.

Phytochemical investigation of the methanolic extract ofL .
( Cucurbitaceae ) seeds furnished a new triterpene benzoate derivative : cucumol @ @ @ @ @ known flavonoids : quercetin-3 -- -D-glucopyranosyl- ( 1→6 ) -- L-rhamnopyranoside ( ) , quercetin-3 @ @ @ @ @ quercetin ( ) , and luteolin ( ) .
Their structures were identified by UV @ @ @ @ @ C andH ) , 2D ( HSQC , H-H COSY , HMBC , and NOESY @ @ @ @ @ spectral as well as comparing with literature data .
Compoundhas been assessed for thecytotoxic effect @ @ @ @ @ and HCT-116 cell lines .
It had selective and potent effect toward SKOV-3 and MCF-7 @ @ @ @ @ and 0.41 μM , respectively , in comparison to doxorubicin ( ICs 0.32 and 0.05 @ @ @ @ @ it showed moderate activity toward HCT-116 cell line with IC8.27 μM .

Phytochemical investigation of the methanolic extract ofL. (Cucurbitaceae) seeds furnished a new triterpene benzoate derivative: cucumol B () and four known flavonoids: quercetin-3---D-glucopyranosyl-(1→6)--L-rhamnopyranoside (), quercetin-3---D-glucopyranoside (), quercetin (), and luteolin (). Their structures were identified by UV, IR, 1D (C andH), 2D (HSQC,H-H COSY, HMBC, and NOESY) NMR, and HRESIMS spectral as well as comparing with literature data. Compoundhas been assessed for thecytotoxic effect against SKOV-3, MCF-7, and HCT-116 cell lines. It had selective and potent effect toward SKOV-3 and MCF-7 cell lines with ICs 2.05 and 0.41 μM, respectively, in comparison to doxorubicin (ICs 0.32 and 0.05 μM). However, it showed moderate activity toward HCT-116 cell line with IC8.27 μM.


greenmedinfo--2020-07-23--Watermelon juice exhibits anti-diabetic potential.

Introduction : Watermelon is one of the commonly eaten fruit in most homes in Nigeria and has been used in the management of diabetes mellitus traditionally .
This study was carried out to explore the antidiabetic potential of watermelon ( ) juice in alloxan-induced diabetic rats .
Methods : Watermelon juice was used for the determination of in vitro parameters such as 1,1-diphenyl-2-picryl-hydrazil ( DPPH ) , nitric oxide and ferric reducing antioxidant potential ( FRAP ) as well as phytochemicals such as total phenol , total flavonoids .
In vitroα-glucosidase and α-amylase inhibitory activities were also accessed using standard @ @ @ @ @ @ @ rats by a single intraperitoneal ( I.P ) injection of freshly prepared alloxan ( 150 mg/kg body weight ) .
The animals were randomly grouped into five groups of normal control , untreated diabetic control , diabetic rats administered 200 mg/kg body weight of metformin , diabetic rats administered 500 mg/kg body weight of watermelon ( ) juice and diabetic rats administered 1000 mg/kg body weight of watermelon juice .
The rats were sacrificed on the 14th day of the experiment and various in vivo biochemical parameters were also evaluated in the serum @ @ @ @ @ @ @ Results : The watermelon juice exhibits anti-oxidant properties and inhibitory activities againstα-glucosidase and α-amylase in a dose-dependent manner .
Added to this , the administration of different doses of the watermelon juice significantly ( Conclusion : Taken together , this study demonstrates that watermelon ( ) juice exhibits its antidiabetic potential in experimental diabetic animal model via multiple pathways involving modulation of glucose transporters , anti-inflammatory activities as well as antioxidant defense system and inhibition ofα-glucosidase and α-amylase .
This suggests that the watermelon ( juice may have a useful clinical application in @ @ @ @ @ @ @ metabolic complications if developed as adjuvant therapy .

Introduction: Watermelon is one of the commonly eaten fruit in most homes in Nigeria and has been used in the management of diabetes mellitus traditionally. This study was carried out to explore the antidiabetic potential of watermelon () juice in alloxan-induced diabetic rats.
Methods: Watermelon juice was used for the determination of in vitro parameters such as 1,1-diphenyl-2-picryl-hydrazil (DPPH), nitric oxide and ferric reducing antioxidant potential (FRAP) as well as phytochemicals such as total phenol, total flavonoids. In vitroα-glucosidase and α-amylase inhibitory activities were also accessed using standard procedures. Diabetes was induced in the rats by a single intraperitoneal (I.P) injection of freshly prepared alloxan (150 mg/kg body weight). The animals were randomly grouped into five groups of normal control, untreated diabetic control, diabetic rats administered 200 mg/kg body weight of metformin, diabetic rats administered 500 mg/kg body weight of watermelon () juice and diabetic rats administered 1000 mg/kg body weight of watermelon juice. The rats were sacrificed on the 14th day of the experiment and various in vivo biochemical parameters were also evaluated in the serum and tissue homogenates of diabetic rats.
Results: The watermelon juice exhibits anti-oxidant properties and inhibitory activities againstα-glucosidase and α-amylase in a dose-dependent manner. Added to this, the administration of different doses of the watermelon juice significantly ( < 0.05) reduced the fasting blood glucose level, serum lipid profile, glucose-6-phosphatase, lipid peroxidation and anti-inflammatory activities in alloxan-induced diabetic rats. There was a significant ( < 0.05) increase in antioxidant enzyme activities, hexokinase activity as well as glucose transporters (GLUT 2 and GLUT 4) levels in diabetic rats administered different doses of
Conclusion: Taken together, this study demonstrates that watermelon () juice exhibits its antidiabetic potential in experimental diabetic animal model via multiple pathways involving modulation of glucose transporters, anti-inflammatory activities as well as antioxidant defense system and inhibition ofα-glucosidase and α-amylase. This suggests that the watermelon (juice may have a useful clinical application in the management of diabetes mellitus and its metabolic complications if developed as adjuvant therapy.


greenmedinfo--2020-07-23--In vivo anti-inflammatory activity of the peels and pulps of Cucumis melo.

ETHNOPHARMACOLOGICAL RELEVANCE : Cucumis melo var .
cantalupensis and Cucumis melo var .
reticulatus are the most famous varieties of netted muskmelon or cantaloupe in Egypt .
Cantaloupe has a great reputation as an anti-inflammatory drug for hot inflammation of liver , cough , eczema , and kidney disorders such as ulcers in the urinary tract , and our objective was to confirm this use scientifically .
MATERIALS AND METHODS : Inflammation was induced in adult male Sprague Dawley rats by subcutaneous injection of 0.05 ml of carrageenan ( 1 % solution in saline ) into the plantar surface of @ @ @ @ @ @ @ oral pretreatment of the rats with 95 % ethanolic extracts of Cucumis melo var .
cantalupensis peels ( CCP ) and pulps ( CCU ) and Cucumis melo var .
reticulatus peels ( CRP ) and pulps ( CRU ) at doses of 25 and 50 mg/kg .
Indomethacin ( 10 mg/kg ) was used as a standard drug .
The effect of the tested samples was measured on the oedema volume , as well as PGE-2 , TNF-α , IL-6 and IL-1β levels .
Metabolic profiling of the extracts was performed using @ @ @ @ @ @ @ rats with the ethanol extract of the pulps and peels of the two varieties at doses of 25 and 50 mg/kg significantly inhibited the carrageenan-induced increase in the oedema volume of the rat paws after 3 h , except for the low dose of the French cantaloupe pulp .
CRP at 50 mg/kg caused the most significant reductions in both TNF-α ( P CONCLUSION : This is the first report of the chemical and biological study of the peels of Cucumis melo var .
cantalupensis and Cucumis melo var .
reticulatus .

ETHNOPHARMACOLOGICAL RELEVANCE: Cucumis melo var. cantalupensis and Cucumis melo var. reticulatus are the most famous varieties of netted muskmelon or cantaloupe in Egypt. Cantaloupe has a great reputation as an anti-inflammatory drug for hot inflammation of liver, cough, eczema, and kidney disorders such as ulcers in the urinary tract, and our objective was to confirm this use scientifically.
MATERIALS AND METHODS: Inflammation was induced in adult male Sprague Dawley rats by subcutaneous injection of 0.05 ml of carrageenan (1% solution in saline) into the plantar surface of the right hind paw 30 min after oral pretreatment of the rats with 95% ethanolic extracts of Cucumis melo var. cantalupensis peels (CCP) and pulps (CCU) and Cucumis melo var. reticulatus peels (CRP) and pulps (CRU) at doses of 25 and 50 mg/kg. Indomethacin (10 mg/kg) was used as a standard drug. The effect of the tested samples was measured on the oedema volume, as well as PGE-2, TNF-α, IL-6 and IL-1β levels. Metabolic profiling of the extracts was performed using UPLC-MS/MS analysis.
RESULTS: Pretreatment of rats with the ethanol extract of the pulps and peels of the two varieties at doses of 25 and 50 mg/kg significantly inhibited the carrageenan-induced increase in the oedema volume of the rat paws after 3 h, except for the low dose of the French cantaloupe pulp. CRP at 50 mg/kg caused the most significant reductions in both TNF-α (P < 0.05) and IL-1β (P < 0.001) levels, while CCP caused the most significant reductions in PGE-2 and IL-6 (P < 0.05) levels. Increases in PGE-2, TNF-α, IL-6 and IL-1β levels were also significantly prevented by indomethacin (10 mg/kg). UPLC-MS/MS facilitated the identification of 44 phenolic compounds, including phenolic acids and flavonoids.
CONCLUSION: This is the first report of the chemical and biological study of the peels of Cucumis melo var. cantalupensis and Cucumis melo var. reticulatus.


greenmedinfo--2020-07-23--Administration of Cucumis improved insulin resistance by reducing inflammation.

Obesity results in the progression of metabolic disorders , especially type 2 diabetes ( T2DM ) .
Obesity-induced insulin resistance ( IR ) is a causative factor of T2DM morbidity in obese people .
It is generally held by clinicians that IR is caused by adiposity-related inflammation that is mediated by changes in composite ions in the gut microbiome .
This experimental study was designed to investigate the effects ofL .
( Cucumis ) on obesity-induced IR in genetically leptin-deficient Lep/Lepmice .
Specifically , we examined the anti-inflammatory effects of Cucumis and the effects of Cucumis on the gut microbiota @ @ @ @ @ @ @ FBS , performing the OGTT , quantifying serum IR , calculating the HOMA-IR , and determining the lipid profiles .
To see whether inflammation was reduced , we analyzed adipose tissue macrophages as well as monocytes in the blood .
We also profiled the gut microbiota to determine whether the ratios of microbial phyla changed .
We found that Cucumis improved IR in obese mice and relieved inflammation in adipose tissue and blood .
Simultaneously , the microbiota composition ratios changed .
In conclusion , administration of Cucumis improved IR by reducing inflammation @ @ @ @ @ @ @ .
Cucumis is thus a promising treatment for obesity-induced insulin resistance and the inflammatory state .

Obesity results in the progression of metabolic disorders, especially type 2 diabetes (T2DM). Obesity-induced insulin resistance (IR) is a causative factor of T2DM morbidity in obese people. It is generally held by clinicians that IR is caused by adiposity-related inflammation that is mediated by changes in composite ions in the gut microbiome. This experimental study was designed to investigate the effects ofL. (Cucumis) on obesity-induced IR in genetically leptin-deficient Lep/Lepmice. Specifically, we examined the anti-inflammatory effects of Cucumis and the effects of Cucumis on the gut microbiota. We evaluated glucose control by measuring FBS, performing the OGTT, quantifying serum IR, calculating the HOMA-IR, and determining the lipid profiles. To see whether inflammation was reduced, we analyzed adipose tissue macrophages as well as monocytes in the blood. We also profiled the gut microbiota to determine whether the ratios of microbial phyla changed. We found that Cucumis improved IR in obese mice and relieved inflammation in adipose tissue and blood. Simultaneously, the microbiota composition ratios changed. In conclusion, administration of Cucumis improved IR by reducing inflammation, thereby changing the gut microbiota composition. Cucumis is thus a promising treatment for obesity-induced insulin resistance and the inflammatory state.


greenmedinfo--2020-07-23--In vitro antioxidant activity of Ficus carica L. latex from 18 different cultivars.

As synthetic antioxidants that are widely used in foods are known to cause detrimental health effects , studies on natural additives as potential antioxidants are becoming increasingly important .
In this work , the total phenolic content ( TPC ) and antioxidant activity of Ficus carica Linn latex from 18 cultivars were investigated .
The TPC of latex was calculated using the Folin-Ciocalteu assay .
1,1-Diphenyl-2-picrylhydrazyl ( DPPH ) , 2,2'-azinobis- ( 3-ethylbenzothiazoline-6-sulfonic acid ) ( ABTS ) and ferric ion reducing antioxidant power ( FRAP ) were used for antioxidant activity assessment .
The bioactive compounds from F. carica @ @ @ @ @ @ @ extraction ( UAE ) with 75 % ethanol as solvent .
Under the same extraction conditions , the latex of cultivar 'White Genoa ' showed the highest antioxidant activity of 65.91 % ± 1.73 % and 61.07 % ± 1.65 % in DPPH , 98.96 % ± 1.06 % and 83.04 % ± 2.16 % in ABTS , and 27.08 ± 0.34 and 24.94 ± 0.84 mg TE/g latex in FRAP assay via maceration and UAE , respectively .
The TPC of 'White Genoa ' was 315.26 ± 6.14 and 298.52 ± 9.20 @ @ @ @ @ @ @ , respectively .
The overall results of this work showed that F. carica latex is a potential natural source of antioxidants .
This finding is useful for further advancements in the fields of food supplements , food additives and drug synthesis in the future .

As synthetic antioxidants that are widely used in foods are known to cause detrimental health effects, studies on natural additives as potential antioxidants are becoming increasingly important. In this work, the total phenolic content (TPC) and antioxidant activity of Ficus carica Linn latex from 18 cultivars were investigated. The TPC of latex was calculated using the Folin-Ciocalteu assay. 1,1-Diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and ferric ion reducing antioxidant power (FRAP) were used for antioxidant activity assessment. The bioactive compounds from F. carica latex were extracted via maceration and ultrasound-assisted extraction (UAE) with 75% ethanol as solvent. Under the same extraction conditions, the latex of cultivar 'White Genoa' showed the highest antioxidant activity of 65.91% ± 1.73% and 61.07% ± 1.65% in DPPH, 98.96% ± 1.06% and 83.04% ± 2.16% in ABTS, and 27.08 ± 0.34 and 24.94 ± 0.84 mg TE/g latex in FRAP assay via maceration and UAE, respectively. The TPC of 'White Genoa' was 315.26 ± 6.14 and 298.52 ± 9.20 µg GAE/mL via the two extraction methods, respectively. The overall results of this work showed that F. carica latex is a potential natural source of antioxidants. This finding is useful for further advancements in the fields of food supplements, food additives and drug synthesis in the future.


greenmedinfo--2020-07-23--Ficus carica polysaccharide attenuates DSS-induced ulcerative colitis in C57BL/6 mice.

The Ficus carica polysaccharide ( FCPS ) components of the common fig fruit have been demonstrated to exhibit antioxidant and immunity-enhancing activities .
However , it is unclear whether it could prevent the ulcerative colitis development .
Here , we reported that 5 week orally administered FCPS ( 150-300 mg per kg bw ) significantly prevented DSS-induced colitis in C57BL/6J mice by improving the colon length and suppressing the infiltration of inflammatory cells in the gut .
FCPS treatment protected the goblet cells , elevated the expression of tight junction protein claudin-1 , and suppressed the formation of cytokines including @ @ @ @ @ @ @ reformed the gut microbiome by enhancing the abundance of S24-7 , Bacteroides , and Coprococus , and suppressing the abundance of Escherichia and Clostridium at the genus level .
Consistently , the formation of beneficial microbial metabolites , short chain fatty acids , especially acetate and butyrate , were improved in FCPS-treated colitis mice .
The correlation analysis indicated that the protective effects of FCPS on ulcerative colitis might be highly correlated with the microbiota composition changes and the formation of SCFAs .
In conclusion , theseresults indicated that FCPS supplementation could be @ @ @ @ @ @ @ bowel disease and the gut microbes play essential roles in providing these beneficial effects .

The Ficus carica polysaccharide (FCPS) components of the common fig fruit have been demonstrated to exhibit antioxidant and immunity-enhancing activities. However, it is unclear whether it could prevent the ulcerative colitis development. Here, we reported that 5 week orally administered FCPS (150-300 mg per kg bw) significantly prevented DSS-induced colitis in C57BL/6J mice by improving the colon length and suppressing the infiltration of inflammatory cells in the gut. FCPS treatment protected the goblet cells, elevated the expression of tight junction protein claudin-1, and suppressed the formation of cytokines including TNF-α and IL-1β. FCPS supplementation significantly reformed the gut microbiome by enhancing the abundance of S24-7, Bacteroides, and Coprococus, and suppressing the abundance of Escherichia and Clostridium at the genus level. Consistently, the formation of beneficial microbial metabolites, short chain fatty acids, especially acetate and butyrate, were improved in FCPS-treated colitis mice. The correlation analysis indicated that the protective effects of FCPS on ulcerative colitis might be highly correlated with the microbiota composition changes and the formation of SCFAs. In conclusion, theseresults indicated that FCPS supplementation could be a promising nutritional strategy for reducing inflammatory bowel disease and the gut microbes play essential roles in providing these beneficial effects.


greenmedinfo--2020-07-23--Gold nanoparticles enhanced the anti-oxidative properties of the Fig extract in targeting kidney dam

Gold nanoparticles enhanced the anti-oxidative properties of the Fig extract in targeting kidney damage by cisplatin.

BACKGROUND : Cisplatin ( CisPt ) is one of the most widely used and highly effective drugs for the treatment of various solid tumors , unfortunately acute kidney injury ( AKI ) is considered one of its side effects through several mechanisms including production of reactive oxygen species ( ROS ) , pro-inflammatory and pro-fibrotic cytokines .
Due to the poor effect of AKI therapy , the use of nanoparticles loaded with natural extracts for delivering to the kidney molecules are desirable .
AIM : This study aims to investigate the effectiveness of different concentrations of gold nanoparticles ( Au-NPs @ @ @ @ @ @ @ L. ( Fig ) leaves extract against CisPt induced AKI .
METHODS : Seventy male albino rats were used and divided into seven groups .
After the experimental period , blood was withdrawn , serum was separated for determination of urea , creatinine , homocystein ( Hcy ) and folic acid while reduced glutathione ( GSH ) , nitric oxide ( NO ) , malondialdehyde ( MDA ) , total antioxidant capacity ( TAC ) and hydroxyproline content ( Hyp ) were evaluated in kidney tissue homogenate .
RESULTS : CisPt induced AKI @ @ @ @ @ @ @ increase in the levels of serum urea , creatinine , Hcy and kidney Hyp , lipid peroxidation along with a significant reduction of kidney GSH , NO and TAC compared to the control rats .
Treatment with Au-NPs and Fig extract particularly in a ratio of ( 3:2 ) respectively was shown to improve renal functions with efficient capacity in scavenging ROS and reduced AKI severity .
CONCLUSION : Au-NPs enhanced the anti-oxidative properties of the Fig extract in targeting kidney damaged tissue and reduced oxidative toxicity induced by CisPt .

BACKGROUND: Cisplatin (CisPt) is one of the most widely used and highly effective drugs for the treatment of various solid tumors, unfortunately acute kidney injury (AKI) is considered one of its side effects through several mechanisms including production of reactive oxygen species (ROS), pro-inflammatory and pro-fibrotic cytokines. Due to the poor effect of AKI therapy, the use of nanoparticles loaded with natural extracts for delivering to the kidney molecules are desirable.
AIM: This study aims to investigate the effectiveness of different concentrations of gold nanoparticles (Au-NPs) as a carrier for Ficus carica L. (Fig) leaves extract against CisPt induced AKI.
METHODS: Seventy male albino rats were used and divided into seven groups. After the experimental period, blood was withdrawn, serum was separated for determination of urea, creatinine, homocystein (Hcy) and folic acid while reduced glutathione (GSH), nitric oxide (NO), malondialdehyde (MDA), total antioxidant capacity (TAC) and hydroxyproline content (Hyp) were evaluated in kidney tissue homogenate.
RESULTS: CisPt induced AKI in rats and results in a significant increase in the levels of serum urea, creatinine, Hcy and kidney Hyp, lipid peroxidation along with a significant reduction of kidney GSH, NO and TAC compared to the control rats. Treatment with Au-NPs and Fig extract particularly in a ratio of (3:2) respectively was shown to improve renal functions with efficient capacity in scavenging ROS and reduced AKI severity.
CONCLUSION: Au-NPs enhanced the anti-oxidative properties of the Fig extract in targeting kidney damaged tissue and reduced oxidative toxicity induced by CisPt.


greenmedinfo--2020-07-23--Antioxidants and health-beneficial nutrients in fruits of eighteen Cucurbita cultivars.

Aging is accompanied by gradual accumulation of molecular damage within cells in response to oxidative stress resulting from adverse environmental factors , inappropriate lifestyle , and numerous diseases .
Adequate antioxidant intake is a key factor of proper diet .
The study aimed to assess the antioxidant/antiradical capacities offruits ( 18 cultivars of the species : Duch.
, Duch.
, L. , andBouché ) grown in central Europe .
The analyses were based on the FRAP ( ferric reducing antioxidant power ) , CUPRAC ( cupric ion reducing antioxidant capacity ) , and DPPH ( 2,2-diphenyl-1-picrylhydrazyl radical ) assays .
@ @ @ @ @ @ @ was evaluated with HPLC ( high performance liquid chromatography ) , while the main macro- and micronutrients by ICP-OES ( inductively coupled plasma mass spectrometry ) .
The results revealed high intraspecies variability within thegenus .
The Japanese 'Kogigu ' fruits were distinguished as extraordinary sources of phenolic compounds , including syringic and protocatechuic acids , catechin , and kaempferol .
Another popular cultivar 'Hokkaido ' exhibited the highest antioxidant and antiradical capacities .
Most of the fruits proved to be rich sources of zinc and copper .
The obtained data are discussed @ @ @ @ @ @ @ the elderly and suggest thatfruits should become daily components of their diet .

Aging is accompanied by gradual accumulation of molecular damage within cells in response to oxidative stress resulting from adverse environmental factors, inappropriate lifestyle, and numerous diseases. Adequate antioxidant intake is a key factor of proper diet. The study aimed to assess the antioxidant/antiradical capacities offruits (18 cultivars of the species:Duch.,Duch.,L., andBouché) grown in central Europe. The analyses were based on the FRAP (ferric reducing antioxidant power), CUPRAC (cupric ion reducing antioxidant capacity), and DPPH (2,2-diphenyl-1-picrylhydrazyl radical) assays. The content of phenolic compounds and β-carotene was evaluated with HPLC (high performance liquid chromatography), while the main macro- and micronutrients by ICP-OES (inductively coupled plasma mass spectrometry). The results revealed high intraspecies variability within thegenus. The Japanese 'Kogigu' fruits were distinguished as extraordinary sources of phenolic compounds, including syringic and protocatechuic acids, catechin, and kaempferol. Another popular cultivar 'Hokkaido' exhibited the highest antioxidant and antiradical capacities. Most of the fruits proved to be rich sources of zinc and copper. The obtained data are discussed in the context of optimized nutrition of the elderly and suggest thatfruits should become daily components of their diet.


greenmedinfo--2020-07-23--Cucurbita maxima seeds oil might ameliorate high fat diet-induced obesity.

In this study , we evaluated the ameliorative potential of Cucurbita maxima seeds oil ( CSO ( 100 mg/kg body @ @ @ @ @ high fat diet ( HFD ) -induced obese rats for 30 days on the changes @ @ @ @ @ of lipid metabolism such as LDL , HDL , triglycerides , total cholesterol , adiponectin @ @ @ @ @ and lipase .
We also investigated the effects of CSO on the changes of lipid @ @ @ @ @ synthase , acetyl CoA carboxylase , carnitine palmitoyl transferase-1 , HMG CoA reductase , and @ @ @ @ @ IL-6 ) .
Administration of CSO revealed significant diminution in body weight gain , altered @ @ @ @ @ lipid marker enzymes and inflammatory markers .
It demonstrated that CSO had considerably altered these @ @ @ @ @ control rats .
In conclusion , this study suggested that CSO might ameliorate the HFD-induced @ @ @ @ @ and mRNA expressions important to lipid metabolism .

In this study, we evaluated the ameliorative potential of Cucurbita maxima seeds oil (CSO (100 mg/kg body weight)) supplementation to high fat diet (HFD)-induced obese rats for 30 days on the changes in body weight, markers of lipid metabolism such as LDL, HDL, triglycerides, total cholesterol, adiponectin, leptin, amylase, and lipase. We also investigated the effects of CSO on the changes of lipid metabolic enzymes such as fatty-acid synthase, acetyl CoA carboxylase, carnitine palmitoyl transferase-1, HMG CoA reductase, and inflammatory markers (TNF-α and IL-6). Administration of CSO revealed significant diminution in body weight gain, altered the activity, expressions of lipid marker enzymes and inflammatory markers. It demonstrated that CSO had considerably altered these parameters when evaluated with HFD control rats. In conclusion, this study suggested that CSO might ameliorate the HFD-induced obesity by altering the enzymes and mRNA expressions important to lipid metabolism.


greenmedinfo--2020-07-24--Lycopene alleviates oxidative stress via the PI3K/Akt/Nrf2pathway in a cell model of Alzheimer's dis

Lycopene alleviates oxidative stress via the PI3K/Akt/Nrf2pathway in a cell model of Alzheimer's disease.

Background & Aims : Oxidative stress ( OS ) plays an important role in neurodegenerative diseases such as Alzheimer 's disease ( AD ) .
Lycopene is a pigment with potent antioxidant and anti-tumor effects .
However , its potential role in central nervous system is not well-defined .
The aim of this study was to investigate the effect of lycopene on the cell model of AD and determine its underlying mechanisms .
Methods : M146L cell is a double-transfected ( human APP gene and presenlin-1 gene ) Chinese hamster ovary ( CHO ) cell line that overexpressesβ -amyloid ( @ @ @ @ @ @ @ model for AD .
We treated cells with lycopene , and observed the effect of lycopene on M146L cells .
Results : Oxidative stress and apoptosis in M146L cells were significantly higher than those in CHO cells , suggesting that Aβ induced OS and apoptosis .
Lycopene alleviated OS and apoptosis , activated the PI3K/Akt/Nrf2 signaling pathway , upregulated antioxidant and antiapoptotic proteins and downregulated proapoptotic proteins .
Additionally , lycopene inhibited β -secretase ( BACE ) activity in M146L cells .
These results suggest that lycopene inhibits BACE activity and protects M146L @ @ @ @ @ @ @ activating the PI3K/Akt/Nrf2 pathway .
Conclusion : Lycopene possibly prevents Aβ-induced damage by activating the PI3K/Akt/Nrf2 signaling pathway and reducing the expression of BACE in M146L cells .

Background & Aims: Oxidative stress (OS) plays an important role in neurodegenerative diseases such as Alzheimer's disease (AD). Lycopene is a pigment with potent antioxidant and anti-tumor effects. However, its potential role in central nervous system is not well-defined. The aim of this study was to investigate the effect of lycopene on the cell model of AD and determine its underlying mechanisms.
Methods: M146L cell is a double-transfected (human APP gene and presenlin-1 gene) Chinese hamster ovary (CHO) cell line that overexpressesβ -amyloid (Aβ) and is an ideal cell model for AD. We treated cells with lycopene, and observed the effect of lycopene on M146L cells.
Results: Oxidative stress and apoptosis in M146L cells were significantly higher than those in CHO cells, suggesting that Aβ induced OS and apoptosis. Lycopene alleviated OS and apoptosis, activated the PI3K/Akt/Nrf2 signaling pathway, upregulated antioxidant and antiapoptotic proteins and downregulated proapoptotic proteins. Additionally, lycopene inhibited β -secretase (BACE) activity in M146L cells. These results suggest that lycopene inhibits BACE activity and protects M146L cells from oxidative stress and apoptosis by activating the PI3K/Akt/Nrf2 pathway.
Conclusion: Lycopene possibly prevents Aβ-induced damage by activating the PI3K/Akt/Nrf2 signaling pathway and reducing the expression of BACE in M146L cells.


greenmedinfo--2020-07-24--Lycopene ameliorates PTSD-like behaviors in mice.

Posttraumatic stress disorder ( PTSD ) is a mental disorder that can translate into severe economic problems .
Lycopene is an aliphatic hydrocarbon carotenoid extracted from plants , including papayas , tomatoes , and water melons .
Previous studies have shown that lycopene can produce antidepressant-like effects in rodent models of depression .
However , little is known about its anti-PTSD-like effect .
This was addressed in the present study by using the single prolonged stress ( SPS ) protocol to induce PTSD-like behavioral deficits in mice .
Our results showed that 12 days of lycopene treatment at the dose @ @ @ @ @ @ @ not at 5 mg/kg , ameliorated the PTSD-like phenotype induced by SPS , including the increase in freezing time in contextual fear paradigm , the decrease in time and entries in open arms in elevated plus maze test , and the decrease in distance and time in the central area of the open field test , without affecting the mouse locomotor activity .
Mechanistic studies revealed that lycopene treatment ( 20 mg/kg , 12 days ) could suppress the SPS-induced increase in levels of interleukin-6 ( IL-6 ) , IL-1β , tumor necrosis @ @ @ @ @ @ @ in the hippocampus and prefrontal cortex in mice , as well as the increased markers that indicate high levels of oxido-nitrosative stress in the hippocampus and prefrontal cortex in SPS mice .
Lycopene treatment ( 20 mg/kg , 12 days ) also suppressed theSPS-induced decrease in brain derived neurotrophic factor ( BDNF ) levels in the hippocampus and prefrontal cortex in mice .
Overall , the anti-PTSD-like effect of lycopene may be associated with its anti-neuroinflammation and anti-oxidative stress activities .

Posttraumatic stress disorder (PTSD) is a mental disorder that can translate into severe economic problems. Lycopene is an aliphatic hydrocarbon carotenoid extracted from plants, including papayas, tomatoes, and water melons. Previous studies have shown that lycopene can produce antidepressant-like effects in rodent models of depression. However, little is known about its anti-PTSD-like effect. This was addressed in the present study by using the single prolonged stress (SPS) protocol to induce PTSD-like behavioral deficits in mice. Our results showed that 12 days of lycopene treatment at the dose of 10 and 20 mg/kg, but not at 5 mg/kg, ameliorated the PTSD-like phenotype induced by SPS, including the increase in freezing time in contextual fear paradigm, the decrease in time and entries in open arms in elevated plus maze test, and the decrease in distance and time in the central area of the open field test, without affecting the mouse locomotor activity. Mechanistic studies revealed that lycopene treatment (20 mg/kg, 12 days) could suppress the SPS-induced increase in levels of interleukin-6 (IL-6), IL-1β, tumor necrosis factor-α (TNF-α), and nitrite in the hippocampus and prefrontal cortex in mice, as well as the increased markers that indicate high levels of oxido-nitrosative stress in the hippocampus and prefrontal cortex in SPS mice. Lycopene treatment (20 mg/kg, 12 days) also suppressed theSPS-induced decrease in brain derived neurotrophic factor (BDNF) levels in the hippocampus and prefrontal cortex in mice. Overall, the anti-PTSD-like effect of lycopene may be associated with its anti-neuroinflammation and anti-oxidative stress activities.


greenmedinfo--2020-07-24--Lycopene inhibits epithelial-mesenchymal transition and promotes apoptosis in oral cancer.

Background : Oral cancer ( OC ) is one of the most common cancers around the world .
Despite the progress in treatment , the prognosis of OC remains poor , especially for patients with advanced diseases .
It urges the development of novel therapeutic options against OC .
Lycopene ( LYC ) is an antioxidant with chemoprotective properties against cancer .
However , little is known about the mechanisms underlying the protective role of LYC in OC tumorigenesis .
Methods : In this study , we investigated the anti-cancer effect of LYC on the progression of OC in vitro @ @ @ @ @ @ @ mechanisms involved in this process .
Results : LYC inhibited OC cell proliferation , migration , invasion , apoptosis , and xenograft tumor growth in a dose-dependent manner .
Furthermore , we found that LYC might inhibit epithelial-mesenchymal transition and induce apoptosis in OC cells by deactivating the PI3K/AKT/m-TOR signaling through increasing the levels of E-cadherin and Bax and downregulating N-cadherin , p-PI3K , p-AKT , p-m-TOR , and bcl-2 .
Conclusion : We reported for the first time that LYC exhibited anti-cancer effects on OC development both in vitro and in vivo @ @ @ @ @ @ @ These findings provide support for the potential clinical use of LYC in OC treatment .

Background: Oral cancer (OC) is one of the most common cancers around the world. Despite the progress in treatment, the prognosis of OC remains poor, especially for patients with advanced diseases. It urges the development of novel therapeutic options against OC. Lycopene (LYC) is an antioxidant with chemoprotective properties against cancer. However, little is known about the mechanisms underlying the protective role of LYC in OC tumorigenesis.
Methods: In this study, we investigated the anti-cancer effect of LYC on the progression of OC in vitro and in vivo and explored the underlying mechanisms involved in this process.
Results: LYC inhibited OC cell proliferation, migration, invasion, apoptosis, and xenograft tumor growth in a dose-dependent manner. Furthermore, we found that LYC might inhibit epithelial-mesenchymal transition and induce apoptosis in OC cells by deactivating the PI3K/AKT/m-TOR signaling through increasing the levels of E-cadherin and Bax and downregulating N-cadherin, p-PI3K, p-AKT, p-m-TOR, and bcl-2.
Conclusion: We reported for the first time that LYC exhibited anti-cancer effects on OC development both in vitro and in vivo via regulating EMT process and apoptosis. These findings provide support for the potential clinical use of LYC in OC treatment.


greenmedinfo--2020-07-24--Following 3-month astaxanthin supplementation, suppressed oxidative stress and improved cardiac cont

Following 3-month astaxanthin supplementation, suppressed oxidative stress and improved cardiac contractility and exercise tolerance.

Astaxanthin has strong antioxidant properties .
We conducted a prospective pilot study on heart failure ( HF ) patients with left ventricular ( LV ) systolic dysfunction to investigate improvements in cardiac function and exercise tolerance in relation to suppression of oxidative stress by 3-month astaxanthin supplementation .
Oxidative stress markers-serum Diacron reactive oxygen metabolite ( dROM ) , biological antioxidant potential ( BAP ) , and urinary 8-hydroxy-2'-deoxyguanosine ( 8-OHdG ) concentrations , LV ejection fraction ( LVEF ) , and 6-min walk distance ( 6MWD ) were assessed before and after 3-month astaxanthin supplementation .
Finally , the @ @ @ @ @ @ @ .
Following 3-month astaxanthin supplementation , dROM level decreased from 385.6± 82.6 U.CARR to 346.5 ± 56.9 U.CARR ( = 0.041 ) despite no changes in BAP and urinary 8-OHdG levels .
LVEF increased from 34.1± 8.6 % to 38.0 ± 10.0 % ( = 0.031 ) and 6MWD increased from 393.4± 95.9 m to 432.8 ± 93.3 m ( = 0.023 ) .
Significant relationships were observed between percent changes in dROM level and those in LVEF .
In this study , following 3-month astaxanthin supplementation , suppressed oxidative stress and improved @ @ @ @ @ @ @ in HF patients with LV systolic dysfunction .
Correlation between suppression of oxidative stress and improvement of cardiac contractility suggests that suppression of oxidative stress by astaxanthin supplementation had therapeutic potential to improve cardiac functioning .

Astaxanthin has strong antioxidant properties. We conducted a prospective pilot study on heart failure (HF) patients with left ventricular (LV) systolic dysfunction to investigate improvements in cardiac function and exercise tolerance in relation to suppression of oxidative stress by 3-month astaxanthin supplementation. Oxidative stress markers-serum Diacron reactive oxygen metabolite (dROM), biological antioxidant potential (BAP), and urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) concentrations, LV ejection fraction (LVEF), and 6-min walk distance (6MWD) were assessed before and after 3-month astaxanthin supplementation. Finally, the data of 16 HF patients were analyzed. Following 3-month astaxanthin supplementation, dROM level decreased from 385.6± 82.6 U.CARR to 346.5 ± 56.9 U.CARR (= 0.041) despite no changes in BAP and urinary 8-OHdG levels. LVEF increased from 34.1± 8.6% to 38.0 ± 10.0% (= 0.031) and 6MWD increased from 393.4± 95.9 m to 432.8 ± 93.3 m (= 0.023). Significant relationships were observed between percent changes in dROM level and those in LVEF. In this study, following 3-month astaxanthin supplementation, suppressed oxidative stress and improved cardiac contractility and exercise tolerance were observed in HF patients with LV systolic dysfunction. Correlation between suppression of oxidative stress and improvement of cardiac contractility suggests that suppression of oxidative stress by astaxanthin supplementation had therapeutic potential to improve cardiac functioning.


greenmedinfo--2020-07-24--Astaxanthin in liver health and disease: a potential therapeutic agent.

Astaxanthin is a carotenoid derived from oxygen-containing non-vitamin A sources and is mainly obtained from marine organisms .
Studies have @ @ @ @ @ natural antioxidant product and it is widely used in the fields of medicine , health-care @ @ @ @ @ have shown that astaxanthin has important preventive and therapeutic effects on liver fibrosis , non-alcoholic @ @ @ @ @ , drug and ischemia-induced liver injury , and its mechanism is related to antioxidant and @ @ @ @ @ regulation of multiple signaling pathways .
In this review , we discuss the latest data @ @ @ @ @ and treatment of liver diseases .
An understanding of the structure , source and mechanism @ @ @ @ @ the body would not only provide a theoretical basis for its clinical application but could @ @ @ @ @ screening and improving related compounds for the treatment of liver diseases .

Astaxanthin is a carotenoid derived from oxygen-containing non-vitamin A sources and is mainly obtained from marine organisms. Studies have demonstrated that astaxanthin is a natural antioxidant product and it is widely used in the fields of medicine, health-care products and cosmetics. Studies have shown that astaxanthin has important preventive and therapeutic effects on liver fibrosis, non-alcoholic fatty liver, liver cancer, drug and ischemia-induced liver injury, and its mechanism is related to antioxidant and anti-inflammatory activities, and the regulation of multiple signaling pathways. In this review, we discuss the latest data on astaxanthin in the prevention and treatment of liver diseases. An understanding of the structure, source and mechanism of action of astaxanthin in the body would not only provide a theoretical basis for its clinical application but could also have important significance in screening and improving related compounds for the treatment of liver diseases.


greenmedinfo--2020-07-24--Astaxanthin as a putative geroprotector: molecular basis and focus on brain aging.

In recent years , the scientific interest in natural compounds with geroprotective activities has grown exponentially .
Among the various naturally derived molecules , astaxanthin ( ASX ) represents a highly promising candidate geroprotector .
By virtue of the central polyene chain , ASX acts as a scavenger of free radicals in the internal membrane layer and simultaneously controls oxidation on the membrane surface .
Moreover , several studies have highlighted ASX 's ability to modulate numerous biological mechanisms at the cellular level , including the modulation of transcription factors and genes directly linked to longevity-related pathways .
One of @ @ @ @ @ @ @ by astaxanthin is the forkhead box O3 gene ( FOXO3 ) , which has been recognized as a critical controller of cell fate and function .
Moreover , FOXO3 is one of only two genes shown to robustly affect human longevity .
Due to its tropism in the brain , ASX has recently been studied as a putative neuroprotective molecule capable of delaying or preventing brain aging in different experimental models of brain damage or neurodegenerative diseases .
Astaxanthin has been observed to slow down brain aging by increasing brain-derived neurotrophic factor ( @ @ @ @ @ @ @ attenuating oxidative damage to lipids , protein , and DNA and protecting mitochondrial functions .
Emerging data now suggest that ASX can modulate Nrf2 , FOXO3 , Sirt1 , and Klotho proteins that are linked to longevity .
Together , these mechanisms provide support for a role of ASX as a potential geroneuroprotector .

In recent years, the scientific interest in natural compounds with geroprotective activities has grown exponentially. Among the various naturally derived molecules, astaxanthin (ASX) represents a highly promising candidate geroprotector. By virtue of the central polyene chain, ASX acts as a scavenger of free radicals in the internal membrane layer and simultaneously controls oxidation on the membrane surface. Moreover, several studies have highlighted ASX's ability to modulate numerous biological mechanisms at the cellular level, including the modulation of transcription factors and genes directly linked to longevity-related pathways. One of the main relevant evolutionarily-conserved transcription factors modulated by astaxanthin is the forkhead box O3 gene (FOXO3), which has been recognized as a critical controller of cell fate and function. Moreover, FOXO3 is one of only two genes shown to robustly affect human longevity. Due to its tropism in the brain, ASX has recently been studied as a putative neuroprotective molecule capable of delaying or preventing brain aging in different experimental models of brain damage or neurodegenerative diseases. Astaxanthin has been observed to slow down brain aging by increasing brain-derived neurotrophic factor (BDNF) levels in the brain, attenuating oxidative damage to lipids, protein, and DNA and protecting mitochondrial functions. Emerging data now suggest that ASX can modulate Nrf2, FOXO3, Sirt1, and Klotho proteins that are linked to longevity. Together, these mechanisms provide support for a role of ASX as a potential geroneuroprotector.


greenmedinfo--2020-07-24--Impact of astaxanthin on diabetes pathogenesis and chronic complications.

Oxidative stress ( OS ) plays a pivotal role in diabetes mellitus ( DM ) onset , progression , and chronic complications .
Hyperglycemia-induced reactive oxygen species ( ROS ) have been shown to reduce insulin secretion from pancreaticβ-cells , to impair insulin sensitivity and signaling in insulin-responsive tissues , and to alter endothelial cells function in both type 1 and type 2 DM .
As a powerful antioxidant without side effects , astaxanthin ( ASX ) , a xanthophyll carotenoid , has been suggested to contribute to the prevention and treatment of DM-associated pathologies .
ASX reduces inflammation , @ @ @ @ @ @ @ OS pathways though the exact mechanism remains elusive .
Based on several studies conducted on type 1 and type 2 DM animal models , orally or parenterally administrated ASX improves insulin resistance and insulin secretion ; reduces hyperglycemia ; and exerts protective effects against retinopathy , nephropathy , and neuropathy .
However , more experimental support is needed to define conditions for its use .
Moreover , its efficacy in diabetic patients is poorly explored .
In the present review , we aimed to identify the up-to-date biological effects and underlying mechanisms of @ @ @ @ @ @ @ and subsequent complications .
The development of an in-depth research to better understand the biological mechanisms involved and to identify the most effective ASX dosage and route of administration is deemed necessary .

Oxidative stress (OS) plays a pivotal role in diabetes mellitus (DM) onset, progression, and chronic complications. Hyperglycemia-induced reactive oxygen species (ROS) have been shown to reduce insulin secretion from pancreaticβ-cells, to impair insulin sensitivity and signaling in insulin-responsive tissues, and to alter endothelial cells function in both type 1 and type 2 DM. As a powerful antioxidant without side effects, astaxanthin (ASX), a xanthophyll carotenoid, has been suggested to contribute to the prevention and treatment of DM-associated pathologies. ASX reduces inflammation, OS, and apoptosis by regulating different OS pathways though the exact mechanism remains elusive. Based on several studies conducted on type 1 and type 2 DM animal models, orally or parenterally administrated ASX improves insulin resistance and insulin secretion; reduces hyperglycemia; and exerts protective effects against retinopathy, nephropathy, and neuropathy. However, more experimental support is needed to define conditions for its use. Moreover, its efficacy in diabetic patients is poorly explored. In the present review, we aimed to identify the up-to-date biological effects and underlying mechanisms of ASX on the ROS-induced DM-associated metabolic disorders and subsequent complications. The development of an in-depth research to better understand the biological mechanisms involved and to identify the most effective ASX dosage and route of administration is deemed necessary.


greenmedinfo--2020-07-24--Astaxanthin attenuates joint inflammation induced by monosodium urate crystals.

Gouty arthritis is the one of the most painful arthritis and is caused by an inflammatory reaction .
This study investigated whether astaxanthin ( AXT ) , which has documented anti-inflammatory and antioxidant properties , exhibits protective effects against monosodium urate ( MSU ) crystal-induced inflammation .
Cell viability of J774A.1 murine macrophages was assessed by AXT dose-dependent incubation by MTT assays , and expression levels of iNOS and COX-2 proteins as well as secretion of IL-1β were also analyzed under MSU crystals stimulation with or without AXT treatment .
The production of inflammatory mediators was found to significantly decrease @ @ @ @ @ @ @ of the inflammasome complex was also attenuated when cells were co-stimulated with MSU crystals and AXT .
Furthermore , we found that expression of the MAPK pathway was downregulated in J774A.1 cells .
AXT also inhibited the induction of COX-2 and IL-6 in human chondrocytes and synovial fibroblasts by western blots .
Finally , an MSU crystal intra-articular injection rat model for gouty arthritis was utilized in which treatment groups received 5-daily intraperitoneal injections of AXT prior to MSU crystal stimulation , or once intra-articular injections of AXT following MSU crystal stimulation for @ @ @ @ @ @ @ analysis revealed that inflammation was significantly attenuated in the group which received intraperitoneal AXT injection prior to MSU crystal stimulation compared to the group which received MSU only .
These results indicate that AXT attenuates the effects of MSU crystal-induced inflammation by suppressing the production of pro-inflammatory cytokines and inflammatory mediators .
Our findings that the anti-inflammatory activities of AXT may be beneficial in the treatment of MSU crystal-induced arthritis .

Gouty arthritis is the one of the most painful arthritis and is caused by an inflammatory reaction. This study investigated whether astaxanthin (AXT), which has documented anti-inflammatory and antioxidant properties, exhibits protective effects against monosodium urate (MSU) crystal-induced inflammation. Cell viability of J774A.1 murine macrophages was assessed by AXT dose-dependent incubation by MTT assays, and expression levels of iNOS and COX-2 proteins as well as secretion of IL-1β were also analyzed under MSU crystals stimulation with or without AXT treatment. The production of inflammatory mediators was found to significantly decrease with AXT treatment, and the formation of the inflammasome complex was also attenuated when cells were co-stimulated with MSU crystals and AXT. Furthermore, we found that expression of the MAPK pathway was downregulated in J774A.1 cells. AXT also inhibited the induction of COX-2 and IL-6 in human chondrocytes and synovial fibroblasts by western blots. Finally, an MSU crystal intra-articular injection rat model for gouty arthritis was utilized in which treatment groups received 5-daily intraperitoneal injections of AXT prior to MSU crystal stimulation, or once intra-articular injections of AXT following MSU crystal stimulation for 6 hours. Results of synovitis score analysis revealed that inflammation was significantly attenuated in the group which received intraperitoneal AXT injection prior to MSU crystal stimulation compared to the group which received MSU only. These results indicate that AXT attenuates the effects of MSU crystal-induced inflammation by suppressing the production of pro-inflammatory cytokines and inflammatory mediators. Our findings that the anti-inflammatory activities of AXT may be beneficial in the treatment of MSU crystal-induced arthritis.


greenmedinfo--2020-07-24--The effect of astaxanthin supplementation on performance and fat oxidation during a 40 km cycling ti

The effect of astaxanthin supplementation on performance and fat oxidation during a 40 km cycling time trial

OBJECTIVES : This study aimed to investigate whether supplementation with 12 mg⋅dayastaxanthin for 7 days can improve exercise performance and metabolism during a 40 km cycling time trial .
METHODS : Twelve recreationally trained male cyclists ( VO : 56.5± 5.5 mL⋅kg⋅min , W : 346.8 ± 38.4 W ) were recruited .
Prior to each experimental trial , participants were supplemented with either 12 mg⋅dayastaxanthin or an appearance-matched placebo for 7 days ( separated by 14 days of washout ) .
On day 7 of supplementation , participants completed a 40 km cycling time trial on a cycle ergometer @ @ @ @ @ @ @ throughout .
RESULTS : Time to complete the 40 km cycling time trial was improved by 1.2± 1.7 % following astaxanthin supplementation , from 70.76 ± 3.93 min in the placebo condition to 69.90 ± 3.78 min in the astaxanthin condition ( mean improvement = 51 ± 71 s , p = 0.029 , g = 0.21 ) .
Whole-body fat oxidation rates were also greater ( +0.09 ± 0.13 g⋅min , p = 0.044 , g = 0.52 ) , and the respiratory exchange ratio lower ( -0.03± 0.04 , p = @ @ @ @ @ @ @ 39-40 km in the astaxanthin condition .
CONCLUSIONS : Supplementation with 12 mg⋅dayastaxanthin for 7 days provided an ergogenic benefit to 40 km cycling time trial performance in recreationally trained male cyclists and enhanced whole-body fat oxidation rates in the final stages of this endurance-type performance event .

OBJECTIVES: This study aimed to investigate whether supplementation with 12 mg⋅dayastaxanthin for 7 days can improve exercise performance and metabolism during a 40 km cycling time trial.
DESIGN: A randomised, double-blind, crossover design was employed.
METHODS: Twelve recreationally trained male cyclists (VO: 56.5± 5.5 mL⋅kg⋅min, W: 346.8 ± 38.4 W) were recruited. Prior to each experimental trial, participants were supplemented with either 12 mg⋅dayastaxanthin or an appearance-matched placebo for 7 days (separated by 14 days of washout). On day 7 of supplementation, participants completed a 40 km cycling time trial on a cycle ergometer, with indices of exercise metabolism measured throughout.
RESULTS: Time to complete the 40 km cycling time trial was improved by 1.2± 1.7% following astaxanthin supplementation, from 70.76 ± 3.93 min in the placebo condition to 69.90 ± 3.78 min in the astaxanthin condition (mean improvement = 51 ± 71 s, p = 0.029, g = 0.21). Whole-body fat oxidation rates were also greater (+0.09 ± 0.13 g⋅min, p = 0.044, g = 0.52), and the respiratory exchange ratio lower (-0.03± 0.04, p = 0.024, g = 0.60) between 39-40 km in the astaxanthin condition.
CONCLUSIONS: Supplementation with 12 mg⋅dayastaxanthin for 7 days provided an ergogenic benefit to 40 km cycling time trial performance in recreationally trained male cyclists and enhanced whole-body fat oxidation rates in the final stages of this endurance-type performance event.


greenmedinfo--2020-07-24--Astaxanthin promotes M2 macrophages and attenuates cardiac remodeling after myocardial infarction.

BACKGROUND : Cardiac remodeling after acute myocardial infarction ( AMI ) is an important process .
The present study aimed to assess the protective effects of astaxanthin ( ASX ) on cardiac remodeling after AMI .
METHODS : The study was conducted between April and September 2018 .
To create a rat AMI model , rats were anesthetized by intraperitoneal injection of 40 mg/kg pentobarbital sodium , and their left anterior descending coronary artery was ligated .
The rats in the ASX group received 10 mg·kg·day ASX by gavage for 28 days .
On the 1st day after AMI , @ @ @ @ @ @ @ from each group were sacrificed to evaluate changes in the heart function and peripheral blood ( PB ) levels of inflammatory factors .
On the 7th day after AMI , eight rats from each group were sacrificed to evaluate the PB levels of inflammatory factors and the M2 macrophage count using both immunofluorescence ( IF ) and flow cytometry ( FC ) .
The remaining rats wereobserved for 28 days .
Cardiac function was examined using echocardiography .
The inflammatory factors , namely , tumor necrosis factor-α ( TNF-α ) , interleukin-1β ( @ @ @ @ @ @ @ assessed using enzyme-linked immunosorbent assay .
The heart weight/body weight ( BW ) , and lung weight ( LW ) /BW ratios were calculated , and myocardial fibrosis in the form of collagen volume fraction was measured using Masson trichrome staining .
Hematoxylin and eosin ( H & E ) staining was used to determine the myocardial infarct size ( MIS ) , and TdT-mediated dUTP nick-end labeling staining was used to analyze the myocardial apoptosis index .
The levels of apoptosis-related protein , type I/III collagen , transforming growth factorβ1 ( TGF-β1 @ @ @ @ @ @ @ , and caspase 3 were assessed by western blotting .
Unpaired t-test , one-way analysis of variance , and non-parametric Mann-Whitney test were used to analyze the data .
RESULTS : On day 1 , cardiac function was worse in the ASX group than in the sham group ( left ventricular end-systolic diameter [ LVIDs ] : 0.72 ± 0.08 vs. 0.22 ± 0.06 cm , t = -11.38 ; left ventricular end-diastolic diameter [ LVIDd ] : 0.89 ± 0.09 vs. 0.48 ± 0.05 cm , t = -9.42 ; end-systolic volume @ @ @ @ @ @ @ , 0.94 ] vs. 0.04 [ 0.03 , 0.05 ] mL , Z = -2.89 ; end-diastolic volume [ EDV ] : 1.39 [ 1.03 , 1.49 ] vs. 0.28 [ 0.22 , 0.32 ] mL , Z = -2.88 ; ejection fraction [ EF ] : 0.40 ± 0.04 vs. 0.86 ± 0.05 , t = 10.00 ; left ventricular fractional shortening [ FS ] rate : 0.19 [ 0.18 , 0.20 ] % FS vs. 0.51 [ 0.44 , 0.58 ] % FS , Z = -2.88 , all P CONCLUSIONS @ @ @ @ @ @ @ M2 macrophages and effectively attenuate cardiac remodeling by inhibiting inflammation and reducing myocardial fibrosis .

BACKGROUND: Cardiac remodeling after acute myocardial infarction (AMI) is an important process. The present study aimed to assess the protective effects of astaxanthin (ASX) on cardiac remodeling after AMI.
METHODS: The study was conducted between April and September 2018. To create a rat AMI model, rats were anesthetized by intraperitoneal injection of 40 mg/kg pentobarbital sodium, and their left anterior descending coronary artery was ligated. The rats in the ASX group received 10 mg·kg·day ASX by gavage for 28 days. On the 1st day after AMI, but before ASX administration, six rats from each group were sacrificed to evaluate changes in the heart function and peripheral blood (PB) levels of inflammatory factors. On the 7th day after AMI, eight rats from each group were sacrificed to evaluate the PB levels of inflammatory factors and the M2 macrophage count using both immunofluorescence (IF) and flow cytometry (FC). The remaining rats wereobserved for 28 days. Cardiac function was examined using echocardiography. The inflammatory factors, namely, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-10, were assessed using enzyme-linked immunosorbent assay. The heart weight/body weight (BW), and lung weight (LW)/BW ratios were calculated, and myocardial fibrosis in the form of collagen volume fraction was measured using Masson trichrome staining. Hematoxylin and eosin (H&E) staining was used to determine the myocardial infarct size (MIS), and TdT-mediated dUTP nick-end labeling staining was used to analyze the myocardial apoptosis index. The levels of apoptosis-related protein, type I/III collagen, transforming growth factorβ1 (TGF-β1), metalloproteinase 9 (MMP9), and caspase 3 were assessed by western blotting. Unpaired t-test, one-way analysis of variance, and non-parametric Mann-Whitney test were used to analyze the data.
RESULTS: On day 1, cardiac function was worse in the ASX group than in the sham group (left ventricular end-systolic diameter [LVIDs]: 0.72 ± 0.08 vs. 0.22 ± 0.06 cm, t = -11.38; left ventricular end-diastolic diameter [LVIDd]: 0.89 ± 0.09 vs. 0.48 ± 0.05 cm, t = -9.42; end-systolic volume [ESV]: 0.80 [0.62, 0.94] vs. 0.04 [0.03, 0.05] mL, Z = -2.89; end-diastolic volume [EDV]: 1.39 [1.03, 1.49] vs. 0.28[0.22, 0.32] mL, Z = -2.88; ejection fraction [EF]: 0.40 ± 0.04 vs. 0.86 ± 0.05, t = 10.00; left ventricular fractional shortening [FS] rate: 0.19 [0.18, 0.20] %FS vs. 0.51 [0.44, 0.58] %FS, Z = -2.88, all P < 0.01; n = 6). The levels of inflammatory factors significantly increased (TNF-α: 197.60 [133.89, 237.94] vs. 50.48 [47.21 57.10] pg/mL, Z = -2.88; IL-1β: 175.23 [160.74, 215.09] vs. 17.78 [16.83, 19.56] pg/mL, Z = -2.88; IL-10: 67.64 [58.90, 71.46] vs. 12.33 [11.64, 13.98] pg/mL, Z = -2.88, all P < 0.01; n = 6). On day 7, the levels of TNF-α and IL-1β were markedly lower in the ASX group than in the AMI group (TNF-α: 71.70 [68.60, 76.00] vs. 118.07 [106.92, 169.08] pg/mL, F = 42.64; IL-1β: 59.90 [50.83, 73.78] vs. 151.60 [108.4, 4 198.36] pg/mL, F = 44.35, all P < 0.01, n = 8). Conversely, IL-10 levels significantly increased (141.84 [118.98, 158.36] vs. 52.96 [42.68, 74.52] pg/mL, F = 126.67, P < 0.01, n = 8). The M2 macrophage count significantly increased (2891.42 ± 211.29 vs. 1583.38 ± 162.22, F = 274.35, P < 0.01 by IF test; 0.96 ± 0.18 vs. 0.36 ± 0.05, F = 46.24, P < 0.05 by FC test). On day 28, cardiac function was better in the ASX group than in the AMI group (LVIDs: 0.50 [0.41, 0.56] vs. 0.64 [0.56, 0.74] cm, Z = -3.60; LVIDd: 0.70 [0.60, 0.76] vs. 0.80 [0.74 0.88] cm, Z = -2.96; ESV: 0.24 [0.18, 0.45] vs. 0.58 [0.44, 0.89] mL, Z = -3.62; EDV:0.76 [0.44, 1.04] vs. 1.25 [0.82, 1.46] mL, Z = -2.54; EF: 0.60 ± 0.08 vs. 0.50 ± 0.12, F = 160.48; %FS: 0.29 [0.24, 0.31] vs. 0.20 [0.17, 0.21], Z = -4.43, all P < 0.01; n = 16). The MIS and LW/BW ratio were markedly lower in the ASX group than in the AMI group (MIS: 32.50 ± 1.37 vs. 50.90 ± 1.73, t = 23.63, P < 0.01, n = 8; LW/BW: 1.81 ± 0.15 vs. 2.17 ± 0.37, t = 3.66, P = 0.01, n = 16). The CVF was significantly lower in the ASX group than in the AMI group: 12.88 ± 2.53 vs. 28.92 ± 3.31, t = 10.89, P < 0.01, n = 8. The expression of caspase 3, TGF-β1, MMP9, and type I/III collagen was lower in the ASX group than in the AMI group (caspase 3: 0.38 ± 0.06 vs. 0.66 ± 0.04, t = 8.28; TGF-β1: 0.37 ± 0.04 vs. 0.62 ± 0.07, t = 6.39; MMP9: 0.20 ± 0.06 vs. 0.40 ± 0.06, t = 4.62; type I collagen: 0.42 ± 0.09 vs. 0.74 ± 0.07, t = 5.73; type III collagen: 0.13 ± 0.02 vs. 0.74 ± 0.07, t = 4.32, all P < 0.01; n = 4).
CONCLUSIONS: ASX treatment after AMI can promote M2 macrophages and effectively attenuate cardiac remodeling by inhibiting inflammation and reducing myocardial fibrosis.


greenmedinfo--2020-07-24--A blackberry-dill extract combination synergistically increases skin elasticity.

The elastin fiber network in the dermis enables the skin to stretch and recoil .
Unlike other extracellular matrix ( @ @ @ @ @ collagen and hyaluronic acid , which are continually synthesized and assembled through life , elastic @ @ @ @ @ late gestation and early childhood , have a half-life of about 70 years , and @ @ @ @ @ through an individual 's lifespan .
However , due to common aging processes , accelerated @ @ @ @ @ fibers are enzymatically degraded through elastases and can not be repaired or replaced properly .
@ @ @ @ @ fibers can lead to a wide range of congenital and acquired skin elastic fiber disorders @ @ @ @ @ and cutis laxa .

The elastin fiber network in the dermis enables the skin to stretch and recoil. Unlike other extracellular matrix (ECM) components such as collagen and hyaluronic acid, which are continually synthesized and assembled through life, elastic fibers are primarily synthesized during late gestation and early childhood, have a half-life of about 70 years, and are therefore considered to persist through an individual's lifespan. However, due to common aging processes, accelerated by environmental factors, elastic fibers are enzymatically degraded through elastases and cannot be repaired or replaced properly. Severe enzymatic degradation of elastic fibers can lead to a wide range of congenital and acquired skin elastic fiber disorders, such as mid-dermal elastolysis and cutis laxa.


greenmedinfo--2020-07-24--Hypoglycemic effect of the fruit extracts of two varieties of Rubus rosifolius.

Oral glucose tolerance test on male Sprague-Dawley rats was done to determine the hypoglycemic effect of the n-hexane , ethyl acetate and methanol fruit extracts ( 50 mg/kg BW ; oral administration ) of two varieties of Rubus rosifolius .
Metformin was used as a positive control ( 15 mg/kg BW ; intravenous administration ) .
The n-hexane extract was most potent and was investigated phytochemically to yield compound 1 , a mixture of triacylglycerols .
In its oxidized state compound 1 produced a significant hypoglycemic effect which was more effective than metformin for the first 30 min of the @ @ @ @ @ @ @ not significantly different for up to 120 min .
Mechanisms through which the oxidized triacylglycerol species could form were explored and presented .
This is the first account of the hypoglycemic activity of R. rosifolius and it is also the first account of this activity being credited to compounds other than polyphenols and terpenes in Rubus plants .
PRACTICAL APPLICATIONS : A significant percentage of the world 's population is affected by diabetesand diabetes-related illnesses .
One of the most popular antidiabetic drug on the market is metformin which is used to lower @ @ @ @ @ @ @ this study indicate that an oxidized mixture of triacylglycerols is more fast-acting than metformin for the first 30 min of an oral glucose tolerance test .
This effect was also not significantly different from that of the popular drug up to 120 min .
These results demonstrate the hypoglycemic activity of an oxidized R. rosifolius fruit extract and indicate its potential use in applications such as functional food product development and drug discovery .
Therapeutic applications can also include the plant extract as a potential primary treatment or as adjunct therapy to conventional @ @

Oral glucose tolerance test on male Sprague-Dawley rats was done to determine the hypoglycemic effect of the n-hexane, ethyl acetate and methanol fruit extracts (50 mg/kg BW; oral administration) of two varieties of Rubus rosifolius. Metformin was used as a positive control (15 mg/kg BW; intravenous administration). The n-hexane extract was most potent and was investigated phytochemically to yield compound 1, a mixture of triacylglycerols. In its oxidized state compound 1 produced a significant hypoglycemic effect which was more effective than metformin for the first 30 min of the assay (p = .03) and not significantly different for up to 120 min. Mechanisms through which the oxidized triacylglycerol species could form were explored and presented. This is the first account of the hypoglycemic activity of R. rosifolius and it is also the first account of this activity being credited to compounds other than polyphenols and terpenes in Rubus plants. PRACTICAL APPLICATIONS: A significant percentage of the world's population is affected by diabetesand diabetes-related illnesses. One of the most popular antidiabetic drug on the market is metformin which is used to lower blood glucose concentrations. The findings of this study indicate that an oxidized mixture of triacylglycerols is more fast-acting than metformin for the first 30 min of an oral glucose tolerance test. This effect was also not significantly different from that of the popular drug up to 120 min. These results demonstrate the hypoglycemic activity of an oxidized R. rosifolius fruit extract and indicate its potential use in applications such as functional food product development and drug discovery. Therapeutic applications can also include the plant extract as a potential primary treatment or as adjunct therapy to conventional medications.


greenmedinfo--2020-07-24--Effects of bilberry supplementation on metabolic and cardiovascular disease risk.

Metabolic syndrome is a cluster of interrelated conditions that is associated with an increased risk of cardiovascular disease ( CVD ) and type 2 diabetes mellitus ( T2DM ) .
Oxidative stress may impair normal physiological functions , leading to various illnesses .
T2DM is considered to be associated with increased oxidative stress , inflammation , and dyslipidemia , which may play a significant role in the development of cardiovascular complications , cancer and vision loss through cataracts and retinopathy .
While conventional therapies are a cornerstone for the management of the major risk factors of metabolic syndrome , increasing @ @ @ @ @ @ @ foods may improve long term prospects in CVD , obesity and T2DM .
Bilberry ( ) is one of the richest natural sources of anthocyanins which give berries their red/purple/blue coloration .
Anthocyanins are powerful antioxidants and are reported to play an important role in the prevention of metabolic disease and CVD as well as cancer and other conditions .
This review focuses on the potential effects of bilberry supplementation on metabolic and cardiovascular risk factors .
Although there is evidence to support the use of bilberry supplementation as part of a healthy @ @ @ @ @ @ @ use of bilberry supplementation in patients with T2DM or CVD needs to be clarified in large clinical trials .

Metabolic syndrome is a cluster of interrelated conditions that is associated with an increased risk of cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM). Oxidative stress may impair normal physiological functions, leading to various illnesses. T2DM is considered to be associated with increased oxidative stress, inflammation, and dyslipidemia, which may play a significant role in the development of cardiovascular complications, cancer and vision loss through cataracts and retinopathy. While conventional therapies are a cornerstone for the management of the major risk factors of metabolic syndrome, increasing antioxidant defense by increasing intake of antioxidant-rich foods may improve long term prospects in CVD, obesity and T2DM. Bilberry () is one of the richest natural sources of anthocyanins which give berries their red/purple/blue coloration. Anthocyanins are powerful antioxidants and are reported to play an important role in the prevention of metabolic disease and CVD as well as cancer and other conditions. This review focuses on the potential effects of bilberry supplementation on metabolic and cardiovascular risk factors. Although there is evidence to support the use of bilberry supplementation as part of a healthy diet, the potential benefits from the use of bilberry supplementation in patients with T2DM or CVD needs to be clarified in large clinical trials.


greenmedinfo--2020-07-27--A pervasive scientific overview on mangiferin in the prevention and treatment of various diseases wi

A pervasive scientific overview on mangiferin in the prevention and treatment of various diseases with preclinical and clinical updates.

Natural products are increasing used in preventing and treating various diseases .
Mangiferin belongs to the xanthone family , and has potential antiangiogenic , anticancer , immunomodulatory and anti-inflammatory activity along with the antioxidant activity .
It is also used in the treatment of cardiac problem , diabetes and neurodegenerative disease .
Finding of various researchers proves that mangiferin has a broad spectrum therapeutic application .
Motive of this review is to describe the various studies performed on mangiferin for its different pharmacological activities .
It also discusses various challenges associated with mangiferin such as stability and bioavailability .
Strategies @ @ @ @ @ @ @ have also been discussed .
Both research and review articles were used to write the manuscript .
They were collected from various search engines like Pub Med , Science Direct and Google Scholar , using keywords like mangiferin , polyphenol , bioavailability enhancement , solubility enhancement , and antioxidant .
Mangiferin being a potent antioxidant is effective in the treatment of various diseases .
With novel drug delivery approaches we can overcome poor solubility and bioavailability problem which eventually can result to better utilisation of mangiferin in treating a variety of diseases and @ @ @ @ @ @

Natural products are increasing used in preventing and treating various diseases. Mangiferin belongs to the xanthone family, and has potential antiangiogenic, anticancer, immunomodulatory and anti-inflammatory activity along with the antioxidant activity. It is also used in the treatment of cardiac problem, diabetes and neurodegenerative disease. Finding of various researchers proves that mangiferin has a broad spectrum therapeutic application. Motive of this review is to describe the various studies performed on mangiferin for its different pharmacological activities. It also discusses various challenges associated with mangiferin such as stability and bioavailability. Strategies and approaches to improve bioavailability of mangiferin have also been discussed. Both research and review articles were used to write the manuscript. They were collected from various search engines like Pub Med, Science Direct and Google Scholar, using keywords like mangiferin, polyphenol, bioavailability enhancement, solubility enhancement, and antioxidant. Mangiferin being a potent antioxidant is effective in the treatment of various diseases. With novel drug delivery approaches we can overcome poor solubility and bioavailability problem which eventually can result to better utilisation of mangiferin in treating a variety of diseases and make mangiferin a revolutionary drug.


greenmedinfo--2020-07-27--Artesunate inhibited osteoclastogenesis and osteoclast functions in vitro.

Osteoporosis is a metabolic bone disease that is characterized by decreased bone density and strength due to excessive loss of bone protein and mineral content , which can be induced by increased osteoclast activity .
Developing agents targeting osteoclast activation is considered to be the most effective method to reverse bone destruction and alleviate the pain caused by osteoporosis .
MTT assay was conducted to detect the cell viability after artesunate treatment of RAW264.7 cells .
TRACP staining and pit formation assays were performed to examine the TRACP-positive cells and pit-forming activity of osteoclasts .
qRT-PCR and Western blot analysis @ @ @ @ @ @ @ protein expression levels of the osteoclastogenesis-related genes NFATc1 , TRAP , and cathepsin k. The protein levels of RANK , p-Akt , p-p38 , and p-ERK were examined by Western blotting .
Luciferase reporter assay was conducted to determine whether miR-503 targeted RANK directly .
Artesunate inhibited TRACP-positive cells and the pit-forming activity of osteoclasts .
However , artesunate increased the expression of miR-503 .
Artesunate suppressed osteoclastogenesis-related gene expression and RANKL-induced activation of MAPKs and the AKT pathway .
In addition , miR-503 inhibited RANK expression by directly targeting RANK during osteoclast @ @ @ @ @ @ @ functions in vitro by regulating the miR-503/RANK axis and suppressing the MAPK and AKT pathways , which resulted in decreased expression of osteoclastogenesis-related markers .

Osteoporosis is a metabolic bone disease that is characterized by decreased bone density and strength due to excessive loss of bone protein and mineral content, which can be induced by increased osteoclast activity. Developing agents targeting osteoclast activation is considered to be the most effective method to reverse bone destruction and alleviate the pain caused by osteoporosis. MTT assay was conducted to detect the cell viability after artesunate treatment of RAW264.7 cells. TRACP staining and pit formation assays were performed to examine the TRACP-positive cells and pit-forming activity of osteoclasts. qRT-PCR and Western blot analysis were performed to assess the mRNA and protein expression levels of the osteoclastogenesis-related genes NFATc1, TRAP, and cathepsin k. The protein levels of RANK, p-Akt, p-p38, and p-ERK were examined by Western blotting. Luciferase reporter assay was conducted to determine whether miR-503 targeted RANK directly. Artesunate inhibited TRACP-positive cells and the pit-forming activity of osteoclasts. However, artesunate increased the expression of miR-503. Artesunate suppressed osteoclastogenesis-related gene expression and RANKL-induced activation of MAPKs and the AKT pathway. In addition, miR-503 inhibited RANK expression by directly targeting RANK during osteoclast differentiation. Artesunate inhibited osteoclastogenesis and osteoclast functions in vitro by regulating the miR-503/RANK axis and suppressing the MAPK and AKT pathways, which resulted in decreased expression of osteoclastogenesis-related markers.


greenmedinfo--2020-07-27--This present study provides new insights into the mechanisms of Art’s anticancer potential in leukem

This present study provides new insights into the mechanisms of Art’s anticancer potential in leukemia.

Background : Leukemia is characterized by the presence of highly malignant tumors formed in the hematopoietic system .
Artesunate ( Art ) , a semi-synthetic derivative of artemisinin , is commonly used as an antimalarial drug and has been proven to possess anticancer potential .
Methods : In this study , the effect of Art on the proliferation and stemness of human acute promyelocyte leukemia HL-60 cells and acute myeloid leukemia KG1a cells was investigated .
Flow cytometry , colony formation assay , the protein expressive levels of survivin , P21 , cleaved caspase 3 , Bax , Bcl-2 , @ @ @ @ @ @ @ on HL-60 and KG1a cells proliferation and apoptosis .
At the same time , cell sphere formation assay and the protein expressive levels of CD44 , SOX2 , ALDH1 and OCT4 were used to analyze the effects of Art on cancer stem cell-like property .
The orthotopic xenograft mouse models were established by using KG1a cells in BALB/c athymic nude mice .
Tumor weigh was detected .
The protein levels of survivin and Ki67 were detected by immunohistochemistry assays .
Results : Art induced cell apoptosis and inhibited cell proliferation and stemness in @ @ @ @ @ @ @ , the results exhibited that Art inhibited the growth and stemness of transplanted tumors via the suppression of the MEK/ERK and PI3K/Akt pathway .
Conclusions : Our present study provides new insights into the mechanisms of Art 's anticancer potential in leukemia .

Background: Leukemia is characterized by the presence of highly malignant tumors formed in the hematopoietic system. Artesunate (Art), a semi-synthetic derivative of artemisinin, is commonly used as an antimalarial drug and has been proven to possess anticancer potential.
Methods: In this study, the effect of Art on the proliferation and stemness of human acute promyelocyte leukemia HL-60 cells and acute myeloid leukemia KG1a cells was investigated. Flow cytometry, colony formation assay, the protein expressive levels of survivin, P21, cleaved caspase 3, Bax, Bcl-2, Ki67 were detected the effect of Art on HL-60 and KG1a cells proliferation and apoptosis. At the same time, cell sphere formation assay and the protein expressive levels of CD44, SOX2, ALDH1 and OCT4 were used to analyze the effects of Art on cancer stem cell-like property. The orthotopic xenograft mouse models were established by using KG1a cells in BALB/c athymic nude mice. Tumor weigh was detected. The protein levels of survivin and Ki67 were detected by immunohistochemistry assays.
Results: Art induced cell apoptosis and inhibited cell proliferation and stemness in a dose-dependent manner. In the meantime, the results exhibited that Art inhibited the growth and stemness of transplanted tumors via the suppression of the MEK/ERK and PI3K/Akt pathway.
Conclusions: Our present study provides new insights into the mechanisms of Art's anticancer potential in leukemia.


greenmedinfo--2020-07-27--Artesunate ameliorates sepsis-induced acute lung injury.

Sepsis-induced acute lung injury ( ALI ) remains one of the most common disorders in hospitals .
The aim of this research was to explore the underlying characteristics and mechanisms of artesunate ( AS ) in protecting rat lungs from sepsis .
The sepsis-induced ALI model was generated in SD rats by the intratracheal administration of lipopolysaccharide ( LPS , 5 mg/kg ) for 24 h. The rats were randomly assigned into 4 groups : Sham , LPS , LPS + AS , and LPS + AS +LY294002 .
Pathological evaluation of the lungs was conducted by HE staining , @ @ @ @ @ @ @ the MPO activity and the W/D ratio of each group were evaluated .
The levels of inflammatory mediators ( TNF-α and IL-6 ) were measured by immunoblotting , immunofluorescence and real-time PCR .
Western blotting was used to determine the protein levels of PI3K , cleaved Caspase-3 , p-mTOR , mTOR , p-Akt , and Akt in the lungs .
The MPO activity , W/D ratio and lung injury score were obviously elevated after induction of ALI by LPS .
Nevertheless , these alterations could be inhibited by AS .
In addition , @ @ @ @ @ @ @ p-Akt , and PI3K and elevated the expression of cl-caspase-3 , TNF-α , and IL-6 in the lungs .
After AS administration , these alterations were obviously decreased , but treatment with the PI3K antagonist LY294002 inhibited the function of AS .
AS could partially protect against LPS-induced ALI by inhibiting apoptosis and inflammatory mediator production , and this function is perhaps associated with the regulation of the mTOR/AKT/PI3K axis .
Thesefindings suggest that AS may possess certain beneficial characteristics in protecting the lungs from sepsis .

Sepsis-induced acute lung injury (ALI) remains one of the most common disorders in hospitals. The aim of this research was to explore the underlying characteristics and mechanisms of artesunate (AS) in protecting rat lungs from sepsis. The sepsis-induced ALI model was generated in SD rats by the intratracheal administration of lipopolysaccharide (LPS, 5 mg/kg) for 24 h. The rats were randomly assigned into 4 groups: Sham, LPS, LPS + AS, and LPS + AS +LY294002. Pathological evaluation of the lungs was conducted by HE staining, immunofluorescence, and TUNEL assay, and the MPO activity and the W/D ratio of each group were evaluated. The levels of inflammatory mediators (TNF-α and IL-6) were measured by immunoblotting, immunofluorescence and real-time PCR. Western blotting was used to determine the protein levels of PI3K, cleaved Caspase-3, p-mTOR, mTOR, p-Akt, and Akt in the lungs. The MPO activity, W/D ratio and lung injury score were obviously elevated after induction of ALI by LPS. Nevertheless, these alterations could be inhibited by AS. In addition, sepsis decreased the levels of p-mTOR, p-Akt, and PI3K and elevated the expression of cl-caspase-3, TNF-α, and IL-6 in the lungs. After AS administration, these alterations were obviously decreased, but treatment with the PI3K antagonist LY294002 inhibited the function of AS. AS could partially protect against LPS-induced ALI by inhibiting apoptosis and inflammatory mediator production, and this function is perhaps associated with the regulation of the mTOR/AKT/PI3K axis. Thesefindings suggest that AS may possess certain beneficial characteristics in protecting the lungs from sepsis.


greenmedinfo--2020-07-27--Artesunate synergizes with sorafenib to induce ferroptosis in hepatocellular carcinoma.

Sorafenib is the first-line medication for advanced hepatocellular carcinoma ( HCC ) , but it can only extend limited survival .
It is imperative to find a combination strategy to increase sorafenib efficacy .
Artesunate is such a preferred candidate , because artesunate is clinically well-tolerated and more importantly both drugs can induce ferroptosis through different mechanisms .
In this study we investigated the combined effect of sorafenib and artesunate in inducing ferroptosis of HCC and elucidated the involved molecular mechanisms .
We showed that artesunate greatly enhanced the anticancer effects of low dose of sorafenib against Huh7 , SNU-449 @ @ @ @ @ @ @ vitro and against Huh7 cell xenograft model in Balb/c nude mice .
The combination index method confirmed that the combined effect of sorafenib and artesunate was synergistic .
Compared with the treatment with artesunate or sorafenib alone , combined treatment induced significantly exacerbated lipid peroxidation and ferroptosis , which was blocked by N-acetyl cysteine and ferroptosis inhibitors liproxstatin-1 and deferoxamine mesylate , but not by inhibitors of other types of cell death ( z-VAD , necrostatin-1 and belnacasan ) .
In Huh7 cells , we demonstrated that the combined treatment induced oxidative stress @ @ @ @ @ @ @ of ferroptosis .
Sorafenib at low dose mainly caused oxidative stress through mitochondrial impairments and SLC7A11-invovled glutathione depletion .
Artesunate-induced lysosome activation synergized with sorafenib-mediated pro-oxidative effects by promoting sequential reactions including lysosomal cathepsin B/L activation , ferritin degradation , lipid peroxidation , and consequent ferroptosis .
Taken together , artesunate could be repurposed to sensitize sorafenib in HCC treatment .
The combined treatment can be easily translated into clinical applications .

Sorafenib is the first-line medication for advanced hepatocellular carcinoma (HCC), but it can only extend limited survival. It is imperative to find a combination strategy to increase sorafenib efficacy. Artesunate is such a preferred candidate, because artesunate is clinically well-tolerated and more importantly both drugs can induce ferroptosis through different mechanisms. In this study we investigated the combined effect of sorafenib and artesunate in inducing ferroptosis of HCC and elucidated the involved molecular mechanisms. We showed that artesunate greatly enhanced the anticancer effects of low dose of sorafenib against Huh7, SNU-449, and SNU-182 HCC cell lines in vitro and against Huh7 cell xenograft model in Balb/c nude mice. The combination index method confirmed that the combined effect of sorafenib and artesunate was synergistic. Compared with the treatment with artesunate or sorafenib alone, combined treatment induced significantly exacerbated lipid peroxidation and ferroptosis, which was blocked by N-acetyl cysteine and ferroptosis inhibitors liproxstatin-1 and deferoxamine mesylate, but not by inhibitors of other types of cell death (z-VAD, necrostatin-1 and belnacasan). In Huh7 cells, we demonstrated that the combined treatment induced oxidative stress and lysosome-mediated ferritinophagy, two essential aspects of ferroptosis. Sorafenib at low dose mainly caused oxidative stress through mitochondrial impairments and SLC7A11-invovled glutathione depletion. Artesunate-induced lysosome activation synergized with sorafenib-mediated pro-oxidative effects by promoting sequential reactions including lysosomal cathepsin B/L activation, ferritin degradation, lipid peroxidation, and consequent ferroptosis. Taken together, artesunate could be repurposed to sensitize sorafenib in HCC treatment. The combined treatment can be easily translated into clinical applications.


greenmedinfo--2020-07-26--Enhanced lysosomal function is critical for paclitaxel resistance in cancer cells: reversed by artes

Enhanced lysosomal function is critical for paclitaxel resistance in cancer cells: reversed by artesunate.

The mechanism underlying the resistance of cancer cells to chemotherapeutic drug varies with different cancer cells .
Recent evidence shows that lysosomal function is associated with drug resistance of cancer cells .
Artesunate , a derivative of artemisinin , displays broad antitumor activity and direct cytotoxicity on various tumor cells .
Our previous study shows that artesunate increases autophagosome accumulation , while significantly decreases autolysosome number in cancer cells , suggesting that artesunate might impair the lysosomal function .
In this study , we investigated the effects of artesunate on lysosomal function and its relationship with chemotherapeutic drug resistance in @ @ @ @ @ @ @ lysosomal function was significantly enhanced in two drug-resistant ( A549/TAX and A549/DDP ) cells .
Furthermore , we showed that the enhanced lysosomal function by overexpression of transcription factor EB ( TFEB ) significantly increased MCF-7 cells resistance to doxorubicin ( DOX ) , whereas the decreased lysosomal function by TFEB-knockdown or lysosome inhibitor chloroquine increased MCF-7 cells sensitivity to DOX .
Treatment of A549/TAX cells with artesunate ( 2.5-50 μM ) dose-dependently inhibited lysosomal function and the clearance of dysfunctional mitochondria , and induced cell apoptosis .
Moreover , we demonstrated that @ @ @ @ @ @ @ resistant ( A549/TAX and MCF-7/ADR ) cells with higher activity of lysosomal function .
Ourresults suggest that artesunate or other inhibitors of lysosomal function would be potential in the treatment of cancer cells with drug resistance caused by the enhanced lysosomal function .

The mechanism underlying the resistance of cancer cells to chemotherapeutic drug varies with different cancer cells. Recent evidence shows that lysosomal function is associated with drug resistance of cancer cells. Artesunate, a derivative of artemisinin, displays broad antitumor activity and direct cytotoxicity on various tumor cells. Our previous study shows that artesunate increases autophagosome accumulation, while significantly decreases autolysosome number in cancer cells, suggesting that artesunate might impair the lysosomal function. In this study, we investigated the effects of artesunate on lysosomal function and its relationship with chemotherapeutic drug resistance in cancer cells. We found that the lysosomal function was significantly enhanced in two drug-resistant (A549/TAX and A549/DDP) cells. Furthermore, we showed that the enhanced lysosomal function by overexpression of transcription factor EB (TFEB) significantly increased MCF-7 cells resistance to doxorubicin (DOX), whereas the decreased lysosomal function by TFEB-knockdown or lysosome inhibitor chloroquine increased MCF-7 cells sensitivity to DOX. Treatment of A549/TAX cells with artesunate (2.5-50 μM) dose-dependently inhibited lysosomal function and the clearance of dysfunctional mitochondria, and induced cell apoptosis. Moreover, we demonstrated that artesunate exerted more potent inhibition on the resistant (A549/TAX and MCF-7/ADR) cells with higher activity of lysosomal function. Ourresults suggest that artesunate or other inhibitors of lysosomal function would be potential in the treatment of cancer cells with drug resistance caused by the enhanced lysosomal function.


greenmedinfo--2020-07-26--Artesunate inhibits intestinal tumorigenesis through Inhibiting Wnt signalling.

Artesunate ( ART ) is a clinically approved antimalarial drug and was revealed as a candidate of colorectal cancer chemopreventive @ @ @ @ @ system .
Here , we aimed to understand the suppressive effects of ART on intestinal @ @ @ @ @ ART reduced T-cell factor/lymphoid enhancer factor ( TCF/LEF ) promoter transcriptional activity .
In vivo @ @ @ @ @ development .
We found that ART reduces TCF1/TCF7 nuclear translocation by binding the Ras-related nuclear @ @ @ @ @ suggesting that ART inhibits TCF/LEF transcriptional factor nuclear translocation by binding to RAN , thereby @ @ @ @ @ results provide a novel mechanism through which artesunate inhibits intestinal tumorigenesis .

Artesunate (ART) is a clinically approved antimalarial drug and was revealed as a candidate of colorectal cancer chemopreventive agents in our drug screening system. Here, we aimed to understand the suppressive effects of ART on intestinal tumorigenesis. In vitro, ART reduced T-cell factor/lymphoid enhancer factor (TCF/LEF) promoter transcriptional activity. In vivo, ART inhibited intestinal polyp development. We found that ART reduces TCF1/TCF7 nuclear translocation by binding the Ras-related nuclear protein (RAN), suggesting that ART inhibits TCF/LEF transcriptional factor nuclear translocation by binding to RAN, thereby inhibiting Wnt signaling. Our results provide a novel mechanism through which artesunate inhibits intestinal tumorigenesis.


greenmedinfo--2020-07-26--Kaempferol addition increases the antimalarial activity of artesunate.

Kaempferol ( KMF ) is a member of flavonol widely found in tea , broccoli , apples , strawberries , and beans .
It has been demonstrated to present several pharmacological properties with potent antimalarial activity against-infected mice .
Hence , the search for a safe and new antimalarial compound with combinations to delay the development of resistance was the aim of this study .
Thus , the therapeutic effect of the combination of KMF and artesunate ( ART ) in-infected mice was evaluated .
Combination of KMF and ART inANKA- ( PbANKA- ) infected ICR mice in a fixed-ratio @ @ @ @ @ @ @ fractions of their median effective dose ( ED ) was also investigated using the standard 4-day suppressive test .
The EDlevels of KMF and ART in mice infected with PbANKA were 20.06 ± 2.65 and 6.06 ± 1.33 mg/kg , respectively .
Moreover , KMF showed promising synergistic combination with ART at the doses of their EDand fixed-ratio combination ( 1 : 1 ) of their EDof 1/2 with combination index ( CI ) values of 0.86 and 0.47 , respectively .
Additionally , KMF , ART , and its combination at the @ @ @ @ @ @ @ 1 : 1 ) of their EDof 1/2 also presented significantly ( < 0.001 ) prolonged mean survival time ( MST ) .
The findings of this study showed that a combination of KMF and ART enhanced the antimalarial activity of ART and prolonged MST .
This study supports the basis for the selection of KMF as a prospective compound for further consideration as a partner drug for ART .

Kaempferol (KMF) is a member of flavonol widely found in tea, broccoli, apples, strawberries, and beans. It has been demonstrated to present several pharmacological properties with potent antimalarial activity against-infected mice. Hence, the search for a safe and new antimalarial compound with combinations to delay the development of resistance was the aim of this study. Thus, the therapeutic effect of the combination of KMF and artesunate (ART) in-infected mice was evaluated. Combination of KMF and ART inANKA- (PbANKA-) infected ICR mice in a fixed-ratio combination (1 : 1) and fractions of their median effective dose (ED) was also investigated using the standard 4-day suppressive test. The EDlevels of KMF and ART in mice infected with PbANKA were 20.06 ± 2.65 and 6.06 ± 1.33 mg/kg, respectively. Moreover, KMF showed promising synergistic combination with ART at the doses of their EDand fixed-ratio combination (1 : 1) of their EDof 1/2 with combination index (CI) values of 0.86 and 0.47, respectively. Additionally, KMF, ART, and its combination at the doses of their EDand fixed-ratio combination (1 : 1) of their EDof 1/2 also presented significantly (<0.001) prolonged mean survival time (MST). The findings of this study showed that a combination of KMF and ART enhanced the antimalarial activity of ART and prolonged MST. This study supports the basis for the selection of KMF as a prospective compound for further consideration as a partner drug for ART.