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PMID: Tumour Biol. 2016 Mar 16. Epub 2016 Mar 16. PMID: 26984157 Abstract Title: Silibinin inhibits triple negative breast cancer cell motility by suppressing TGF-β2 expression. Abstract: Transforming growth factor-beta (TGF-β) is a multifunctional cytokine that regulates many biological events including cell motility and angiogenesis. Here, we investigated the role of elevated TGF-β2 level in triple negative breast cancer (TNBC) cells and the inhibitory effect of silibinin on TGF-β2 action in TNBC cells. Breast cancer patients with high TGF-β2 expression have a poor prognosis. The levels of TGF-β2 expression increased significantly in TNBC cells compared with those in non-TNBC cells. In addition, cell motility-related genes such as fibronectin (FN) and matrix metalloproteinase-2 (MMP-2) expression also increased in TNBC cells. Basal FN, MMP-2, and MMP-9 expression levels decreased in response to LY2109761, a dual TGF-β receptor I/II inhibitor, in TNBC cells. TNBC cell migration also decreased in response to LY2109761. Furthermore, we observed that TGF-β2 augmented the FN, MMP-2, and MMP-9 expressionlevels in a time- and dose-dependent manner. In contrast, TGF-β2-induced FN, MMP-2, and MMP-9 expression levels decreased significantly in response to LY2109761. Interestingly, we found that silibinin decreased TGF-β2 mRNA expression level but not that of TGF-β1 in TNBC cells. Cell migration as well as basal FN and MMP-2 expression levels decreased in response to silibinin. Furthermore, silibinin significantly decreased TGF-β2-induced FN, MMP-2, and MMP-9 expression levels and suppressed the lung metastasis of TNBC cells. Taken together, these results suggest that silibinin suppresses metastatic potential of TNBC cells by inhibiting TGF-β2 expression in TNBC cells. Thus, silibinin may be a promising therapeutic drug to treat TNBC.
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PMID: Genomics Insights. 2016 ;9:1-16. Epub 2016 Feb 16. PMID: 27006591 Abstract Title: Identification of Potential Anticancer Activities of Novel Ganoderma lucidum Extracts Using Gene Expression and Pathway Network Analysis. Abstract: Ganoderma lucidum (lingzhi) has been used for the general promotion of health in Asia for many centuries. The common method of consumption is to boil lingzhi in water and then drink the liquid. In this study, we examined the potential anticancer activities of G. lucidum submerged in two commonly consumed forms of alcohol in East Asia: malt whiskey and rice wine. The anticancer effect of G. lucidum, using whiskey and rice wine-based extraction methods, has not been previously reported. The growth inhibition of G. lucidum whiskey and rice wine extracts on the prostate cancer cell lines, PC3 and DU145, was determined. Using Affymetrix gene expression assays, several biologically active pathways associated with the anticancer activities of G. lucidum extracts were identified. Using gene expression analysis (real-time polymerase chain reaction [RT-PCR]) and protein analysis (Western blotting), we confirmed the expression of key genes and their associated proteins that were initially identified with Affymetrix gene expression analysis.
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PMID: Indian J Exp Biol. 2015 Dec ;53(12):794-802. PMID: 26742324 Abstract Title: Moringa oleifera Lam. seed extract prevents fat diet induced oxidative stress in mice and protects liver cell-nuclei from hydroxyl radical mediated damage. Abstract: High fat diet (HFD) prompts metabolic pattern inducing reactive oxygen species (ROS) production in mitochondria thereby triggering multitude of chronic disorders in human. Antioxidants from plant sources may be an imperative remedy against this disorder. However, it requires scientific validation. In this study, we explored if (i) Moringa oleifera seed extract (MoSE) can neutralize ROS generated in HFD fed mice; (ii) protect cell-nuclei damage developed by Fenton reaction in vitro. Swiss mice were fed with HFD to develop oxidative stress model (HFD group). Other groups were control, seed extract alone treated, and MoSE simultaneously (HS) treated. Treatment period was of 15 days. Antioxidant enzymes with tissue nitrite content (TNC) and lipid peroxidation (LPO) were estimated from liver homogenate. HS group showed significantly higher (P
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PMID: J Ayurveda Integr Med. 2015 Oct-Dec;6(4):273-9. PMID: 26834427 Abstract Title: Evaluation of the antidepressant activity of Moringa oleifera alone and in combination with fluoxetine. Abstract: BACKGROUND: The prevalence of mental depression has increased in recent years, and has become a serious health problem in most countries of the world, including India. Due to the high cost of antidepressant synthetic drugs and their accompanying side effects, the discovery of safer antidepressant herbal remedies is on the rise. Moringa oleifera (MO) (drumstick) has been used in traditional folk medicine, and in Ayurveda, it is considered as a valuable remedy for treating nervous system disorders as well as memory enhancing agent.OBJECTIVE: The present study was designed to evaluate the acute and chronic behavioral and antidepressant effects of alcoholic extracts of MO leaves in standardized mouse models of depression.MATERIALS AND METHODS: Alcoholic extracts of MO (MOE) leaves were prepared, and phytoconstituents were determined using appropriate chemical analytical methods. Following preliminary dose-finding toxicity studies, the biological activity of MOE was tested in Swiss albino mice. Animals were divided into six groups: Groups 1 and 2 served as vehicle control and fluoxetine (20 mg/kg) standard control, respectively. Groups 3 and 4 served as treatment groups and were orally administered ethanolic MOE at doses of 100 mg/kg and 200 mg/kg, respectively. Groups 5 and 6, respectively, received combination doses of MOE 100 mg/kg + 10 mg fluoxetine, and MOE 200 mg/kg + 10 mg/kg fluoxetine. Following acute and 14 days chronic treatments, all animals were tested using behavioral models of depression, such as forced swim test (FST), tail suspension test (TST), and locomotor activity test (LAT).RESULTS: Significant changes in all tested activities (FST, TST, LAT) of chronically dosed mice were observed, especially in animals given simultaneously combined doses of 200 mg/kg/day MOE + 10 mg/kg/day fluoxetine for 14 days. The antidepressant effect of MOE may have been invoked through the noradrenergic-serotonergic neurotransmission pathway, which is the hallmark of selective serotonin reuptake inhibitors (SSRI) class of drugs.CONCLUSION: The results obtained in this study suggest that combined administration of MOE with low doses of fluoxetine or other SSRI drugs seems to have promising potential.
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PMID: J Ethnopharmacol. 2016 Apr 22 ;182:101-9. Epub 2016 Feb 10. PMID: 26875643 Abstract Title: Ethanolic extract of Moringa oleifera Lam. leaves protect the pre-pubertal spermatogonial cells from cyclophosphamide-induced damage. Abstract: ETHNOPHARMACOLOGICAL RELEVANCE: Moringa oleifera Lam. is widely cultivated in Asian and African countries for its medicinal and dietary significance. The leaves are highly nutritious and are known to possess various biological activities.MATERIALS AND METHODS: Pre-pubertal Swiss albino male mice were injected with single dose of cyclophosphamide (CP, 200mg/kg body weight) or ethanolic extract of Moringa oleifera leaves (MOE, 100mg/kg body weight) intraperitoneally. In combination group, MOE was administered 24h prior to CP injection.RESULTS: CP induced a significant decrease in testicular weight (p
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PMID: Am J Hypertens. 2016 Feb 10. Epub 2016 Feb 10. PMID: 26864583 Abstract Title: Cardiac Protective Effects of Moringa oleifera Seeds in Spontaneous Hypertensive Rats. Abstract: BACKGROUND: Hypertension is characterized by a maintained high blood pressure leading to cardiac complications such as left ventricular hypertrophy and fibrosis and an increased risk of heart failure and myocardial infarction. This study investigated the cardiac effects of oral administration of Moringa oleifera (MOI) seed powder in spontaneous hypertensive rats (SHR).METHODS: SHR received food containing MOI seed powder (750mg/d, 8 weeks) or normal food. In vivo measurement of hemodynamic parameters by telemetry and cardiac structure and function analysis by echocardiography were performed. Histological studies were performed to determine fibrosis and protein expression.RESULTS: MOI treatment did not modify blood pressure in SHR but reduced nocturnal heart rate and improved cardiac diastolic function (reduction of isovolumetric relaxation time and deceleration time of the E wave, increase of ejection volume and cardiac output compared to nontreated SHR). Left ventricular anterior wall thickness, interseptal thickness on diastole, and relative wall thickness were reduced after MOI treatment. Furthermore, we found a significant reduction of fibrosis in the left ventricle of MOI-treated SHR. This antihypertrophic and antifibrotic effect of MOI was associated with increased expression of peroxisome proliferator-activated receptor (PPAR)-α and δ, reduced cardiac triglyceride level, and enhanced plasmatic prostacyclins.CONCLUSIONS: Our data show a beneficial effect of MOI on the cardiac structure and function in SHR associated with an upregulation of PPAR-α and δ signaling. This study thus provides scientific rational support for the empirical use of MOI in the traditional Malagasy medicine against cardiac diseases associated with blood pressure overload.
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PMID: Pharmacogn Mag. 2015 Oct ;11(Suppl 4):S556-63. PMID: 27013794 Abstract Title: Bioactive Extract from Moringa oleifera Inhibits the Pro-inflammatory Mediators in Lipopolysaccharide Stimulated Macrophages. Abstract: INTRODUCTION: Inflammation is a well-known physiological response to protect the body against infection and restore tissue injury. Nevertheless, the chronic inflammation can trigger various inflammatory associated diseases/disorder. Moringa oleifera is a widely grown plant in most tropical countries and it has been recognized traditionally for several medicinal benefits.OBJECTIVES: The objective of this study was to investigate the anti-inflammatory properties of M. oleifera extract on lipopolysaccharide (LPS) - stimulated macrophages.MATERIALS AND METHODS: The anti-inflammatory effect of M. oleifera hydroethanolic bioactive leaves extracts was evaluated by assessing the inhibition of nitric oxide (NO) production during Griess reaction and the expression of pro-inflammatory mediators in macrophages.RESULTS: Interestingly, we found that M. oleifera hydroethanolic bioactive leaves extract significantly inhibited the secretion of NO production and other inflammatory markers such as prostaglandin E2, tumor necrosis factor alpha, interleukin (IL)-6, and IL-1β. Meanwhile, the bioactive extract has induced the production of IL-10 in a dose-dependent manner. In addition, M. oleifera hydroethanolic bioactive leaves extract effectively suppressed the protein expression of inflammatory markers inducible NO synthase, cyclooxygenase-2, and nuclear factor kappa-light-chain-enhancer of activated B-cells p65 in LPS-induced RAW264.7 macrophages in a dose-dependent manner.CONCLUSION: These findings support the traditional use of M. oleifera plant as an effective treatment for inflammation associated diseases/disorders.SUMMARY: Hydroethanolic extracts of Moringa oleifera effectively inhibit the NO production in LPS induced inflammatory model.M. oleifera crude extracts successfully modulate the production of pro-inflammatory mediators in LPS stimulated macrophages.M. oleifera extracts suppressed the expression of inflammatory mediators in LPS stimulated macrophages.
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PMID: Environ Toxicol. 2016 Mar 7. Epub 2016 Mar 7. PMID: 26948951 Abstract Title: Melatonin attenuates (60) Coγ-ray-induced hematopoietic, immunological and gastrointestinal injuries in C57BL/6 male mice. Abstract: Protection of hematopoietic, immunological, and gastrointestinal injuries from deleterious effects of ionizing radiation is prime rational for developing radioprotector. The objective of this study, therefore, was to evaluate the radioprotective potential of melatonin against damaging effects of radiation-induced hematopoietic, immunological, and gastrointestinal injuries in mice. C57BL/6 male mice were intraperitoneally administered with melatonin (50-150 mg/kg) 30 min prior to whole-body radiation exposure of 5 and 7.5 Gy using (60) Co-teletherapy unit. Thirty-day survival against 7.5 Gy was monitored. Melatonin (100 mg/kg) pretreatment showed 100% survival against 7.5 Gy radiation dose. Melatonin pretreatment expanded femoral HPSCs, and inhibited spleenocyte DNA strands breaks and apoptosis in irradiated mice. At this time, it also protected radiation-induced loss of T cell sub-populations in spleen. In addition, melatonin pretreatment enhanced crypts regeneration and increased villi number and length in irradiated mice. Translocationof gut bacteria to spleen, liver and kidney were controlled in irradiated mice pretreated with melatonin. Radiation-induced gastrointestinal DNA strand breaks, lipid peroxidation, and expression of proapoptotic-p53, Bax, and antiapoptotic-Bcl-xL proteins were reversed in melatonin pretreated mice. This increase of Bcl-xL was associated with the decrease of Bax/Bcl-xL ratio. ABTS and DPPH radical assays revealed that melatonin treatment alleviated total antioxidant capacity in hematopoietic and gastrointestinal tissues. Present study demonstrated that melatonin pretreatment was able to preventhematopoietic, immunological, and gastrointestinal radiation-induced injury, therefore, overcoming lethality in mice. These results suggest potential of melatonin in developing radioprotector for protection of bone marrow, spleen, and gastrointestine in planned radiation exposure scenarios includingradiotherapy. © 2016 Wiley Periodicals, Inc. Environ Toxicol, 2016.
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PMID: Clin Nutr. 2016 Mar 15. Epub 2016 Mar 15. PMID: 27020528 Abstract Title: Effects of vitamin D on serum lipid profile in patients with type 2 diabetes: A meta-analysis of randomized controlled trials. Abstract: BACKGROUND & AIMS: The effect of vitamin D on lipid profile in type 2 diabetic patients is controversial. This meta-analysis aimed to assess the effect of vitamin D on serum total cholesterol (TC), triglycerides (TG), low-density lipoproteins (LDL), and high-density lipoproteins (HDL) of these patients to elucidate the subject.METHODS: Seven databases were searched and randomized controlled trials (RCTs) assessed the effect of vitamin D on lipid profile published until November 2015 were identified. Un-standardized mean difference and its corresponding 95% confidence interval (CI) was calculated from the effect sizes by using random effects model.RESULTS: We found 2220 articles in our systematic search, after exclusion of un-related studies we enrolled 17 studies comparing intervention group (received vitamin D) with control group (received placebo) in the meta-analysis. Vitamin D significantly reduced serum TC (-3.74 mg/dl, 95% CI: -7.13 to -0.34, P = 0.031), but serum TG did not show significant reduction (-4.90 mg/dl, 95% CI: -15.11-5.31, P = 0.347). Results confirmed the significant lowering effect of vitamin D on LDL in patients with T2D (-2.55 mg/dl, 95% CI: -4.83 to -0.26, P = 0.029), but change in serum HDL was negligible (-0.72 mg/dl, 95% CI: -1.27 to -0.17, P = 0.010). Subgroup analyses showed that the baseline serum 25-hydroxy vitamin D of patients, vitamin D dosage, intervention duration, and the method of vitamin D application influence the effect of vitamin D on lipid markers.CONCLUSION: This study demonstrated that vitamin D improved serum levels of TC, TG, and LDL in patients with T2D but changes of serum HDL was not satisfactory.
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PMID: Curr Oncol. 2016 Mar ;23(2):S15-22. Epub 2016 Mar 16. PMID: 27022310 Abstract Title: In vitro and in vivo efficacy of non-psychoactive cannabidiol in neuroblastoma. Abstract: BACKGROUND: Neuroblastoma (nbl) is one of the most common solid cancers in children. Prognosis in advanced nbl is still poor despite aggressive multimodality therapy. Furthermore, survivors experience severe long-term multi-organ sequelae. Hence, the identification of new therapeutic strategies is of utmost importance. Cannabinoids and their derivatives have been used for years in folk medicine and later in the field of palliative care. Recently, they were found to show pharmacologic activity in cancer, including cytostatic, apoptotic, and antiangiogenic effects.METHODS: We investigated, in vitro and in vivo, the anti-nbl effect of the most active compounds in Cannabis,Δ(9)-tetrahydrocannabinol (thc) and cannabidiol (cbd). We set out to experimentally determine the effects of those compounds on viability, invasiveness, cell cycle distribution, and programmed cell death in human nbl SK-N-SH cells.RESULTS: Both compounds have antitumourigenic activity in vitro and impeded the growth of tumour xenografts in vivo. Of the two cannabinoids tested, cbd was the more active. Treatment with cbd reduced the viability and invasiveness of treated tumour cells in vitro and induced apoptosis (as demonstrated by morphology changes, sub-G1 cell accumulation, and annexin V assay). Moreover, cbd elicited an increase in activated caspase 3 in treated cells and tumour xenografts.CONCLUSIONS: Our results demonstrate the antitumourigenic action of cbd on nbl cells. Because cbd is a nonpsychoactive cannabinoid that appears to be devoid of side effects, our results support its exploitation as an effective anticancer drug in the management of nbl.
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