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Antineoplastic activity of strawberry (Fragaria × ananassa Duch.) crude extracts on B16-F10 melanoma cells -

The antiproliferative and differentiation potential of anthocyanin-rich strawberry fruit crude extracts (SE) were investigated on B16-F10 murine melanoma cells. Treatment of melanoma cells with SE produced a remarkable reduction of cell proliferation, paralleled with both the lowering of the intracellular levels of polyamine, and the enhancement of tissue transglutaminase (TG2, EC 2.3.2.13) activity (used as a differentiation marker). To gain further insight into profiling altered protein expression as a potential biomarker of the SE action on melanoma cells, analysis of the proteomic profile was performed on the treated B16-F10 cells, compared to the control. Following SE treatment, 30 proteins resulted up-regulated, and 87 proteins were down-regulated. In particular proteins overexpressed in cancer cells, involved in tumor progression and metabolism, were down-regulated. The possibility that SE may affect the Warburg effect in B16-F10 melanoma cells is discussed.

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A Tale of Two Medicines
Natural Medicine, Pharmaceuticals and GMO’s, the Good, the Bad and the OMG! - (The information provided is not intended to be a substitute for professional medical advice, diagnosis or treatment.  Never disregard professional medical advice, or delay in seeking it, because of something you have read on this scoopit page.)
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High-dose of vitamin C supplementation reduces amyloid plaque burden and ameliorates pathological changes in the brain of 5XFAD mice

High-dose of vitamin C supplementation reduces amyloid plaque burden and ameliorates pathological changes in the brain of 5XFAD mice | A Tale of Two Medicines | Scoop.it
Blood–brain barrier (BBB) breakdown and mitochondrial dysfunction have been implicated in the pathogenesis of Alzheimer's disease (AD), a neurodegenerative disease characterized by cognitive deficits and neuronal loss. Besides vitamin C being as one of the important antioxidants, recently, it has also been reported as a modulator of BBB integrity and mitochondria morphology. Plasma levels of vitamin C are decreased in AD patients, which can affect disease progression. However, investigation using animal models on the role of vitamin C in the AD pathogenesis has been hampered because rodents produce with no dependence on external supply. Therefore, to identify the pathogenic importance of vitamin C in an AD mouse model, we cross-bred 5 familial Alzheimer's disease mutation (5XFAD) mice (AD mouse model) with ι-gulono-γ-lactone oxidase (Gulo) knockout (KO) mice, which are unable to synthesize their own vitamin C, and produced Gulo KO mice with 5XFAD mice background (KO-Tg). These mice were maintained on either low (0.66 g/l) or high (3.3 g/l) supplementation of vitamin C. We found that the higher supplementation of vitamin C had reduced amyloid plaque burden in the cortex and hippocampus in KO-Tg mice, resulting in amelioration of BBB disruption and mitochondrial alteration. These results suggest that intake of a larger amount of vitamin C could be protective against AD-like pathologies.
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The Remedial Efficacy of Spirulina platensis versus Chromium-Induced Nephrotoxicity in Male Sprague-Dawley Rats

The Remedial Efficacy of Spirulina platensis versus Chromium-Induced Nephrotoxicity in Male Sprague-Dawley Rats | A Tale of Two Medicines | Scoop.it
This study was conducted to investigate the possible protective effect of Spirulina platensis against chromium-induced nephrotoxicity. A total of 36 adult male Sprague-Dawley rats were divided into 4 equal groups (Gps). Gp1 served as control, rats of Gps 2, 3, and 4 were exposed to Spirulina platensis (300 mg/kg b.wt per os) and sodium dichromate dihydrate (SDD) via drinking water at concentration of 520 mg /l respectively. Chromium administration caused alterations in the renal function markers as evidenced by significant increase of blood urea and creatinine levels accompanied with significant increase in kidney’s chromium residues and MDA level as well as decreased catalase activity and glutathion content in kidney tissue. Histologically, Cr provoked deleterious changes including: vascular congestion, wide spread tubular epithelium necrobiotic changes, atrophy of glomerular tuft and proliferative hyperplasia. The latter was accompanied with positive PCNA expression in kidney tissues as well as DNA ploidy interpretation of major cellular population of degenerated cells, appearance of tetraploid cells, high proliferation index and high DNA index. Morphometrical measurements revealed marked glomerular and tubular lumen alterations. On contrary, spirulina co-treatment with Cr significantly restored the histopathological changes, antioxidants and renal function markers and all the previously mentioned changes as well.
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Whooping cough resurgence due to vaccinated people not knowing they're infectious?

Whooping cough resurgence due to vaccinated people not knowing they're infectious? | A Tale of Two Medicines | Scoop.it
Whooping cough has made an astonishing comeback, with 2012 seeing nearly 50,000 infections in the U.S. (the most since 1955), and a death rate in infants three times that of the rest of the population. The dramatic resurgence has puzzled public health officials, who have pointed to the waning effectiveness of the current vaccine and growing anti-vaccine sentiment as the most likely culprits.

But that might not be the whole story, suggests a new study published in BMC Medicine by Santa Fe Institute Omidyar Fellows Ben Althouse and Sam Scarpino. Their research points to a different, but related, source of the outbreak -- vaccinated people who are infectious but who do not display the symptoms of whooping cough, suggesting that the number of people transmitting without symptoms may be many times greater than those transmitting with symptoms.
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From Stress to Inflammation and Major Depressive Disorder: A Social Signal Transduction Theory of Depression

From Stress to Inflammation and Major Depressive Disorder: A Social Signal Transduction Theory of Depression | A Tale of Two Medicines | Scoop.it
Major life stressors, especially those involving interpersonal stress and social rejection, are among the strongest proximal risk factors for depression. In this review, we propose a biologically plausible, multilevel theory that describes neural, physiologic, molecular, and genomic mechanisms that link experiences of social-environmental stress with internal biological processes that drive depression pathogenesis. Central to this social signal transduction theory of depression is the hypothesis that experiences of social threat and adversity up-regulate components of the immune system involved in inflammation. The key mediators of this response, called proinflammatory cytokines, can in turn elicit profound changes in behavior, which include the initiation of depressive symptoms such as sad mood, anhedonia, fatigue, psychomotor retardation, and social-behavioral withdrawal. This highly conserved biological response to adversity is critical for survival during times of actual physical threat or injury. However, this response can also be activated by modern-day social, symbolic, or imagined threats, leading to an increasingly proinflammatory phenotype that may be a key phenomenon driving depression pathogenesis and recurrence, as well as the overlap of depression with several somatic conditions including asthma, rheumatoid arthritis, chronic pain, metabolic syndrome, cardiovascular disease, obesity, and neurodegeneration. Insights from this theory may thus shed light on several important questions including how depression develops, why it frequently recurs, why it is strongly predicted by early life stress, and why it often co-occurs with symptoms of anxiety and with certain physical disease conditions. This work may also suggest new opportunities for preventing and treating depression by targeting inflammation.
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Perioperative Systemic Magnesium to Minimize Postoperative Pain: A Meta-analysis of Randomized Controlled Trials

Perioperative Systemic Magnesium to Minimize Postoperative Pain: A Meta-analysis of Randomized Controlled Trials | A Tale of Two Medicines | Scoop.it
In summary, systemic magnesium reduces postoperative pain after surgical procedures following general anesthesia. In addition, the administration of systemic magnesium also reduced the postoperative consumption of opioids. Systemic levels associated with clinical toxicity were not reported in any of the examined studies. Perioperative magnesium administration should be considered as a strategy to reduce postoperative pain outcomes in patients undergoing surgical procedures.
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Metabolism: Dietary emulsifiers - sweepers of the gut lining?

Metabolism: Dietary emulsifiers - sweepers of the gut lining? | A Tale of Two Medicines | Scoop.it
Low doses of two commonly used dietary emulsifiers—carboxymethylcellulose and polysorbate-80—are reported to induce low-grade inflammation, metabolic disorders and increases in body weight in mice. These emulsifiers also promote colitis in mice that are susceptible to this disorder. Interestingly, changes in the gut microbiota were both necessary and sufficient to induce the metabolic alterations.
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Clinical efficacy on vertebrobasilar insufficiency treated with auricular acupuncture.

Clinical efficacy on vertebrobasilar insufficiency treated with auricular acupuncture. | A Tale of Two Medicines | Scoop.it

To compare the efficacy on vertebrobasilar insufficiency (VBI) between auricular acupuncture therapy and oral administration of medicine.

Sixty patients of VBI were randomized into an auricular acupuncture therapy group and a medicine group, 30 cases in each one. In the auricular acupuncture group, acupuncture was applied bilaterally to gan (CO12) and jiejie (HX8) on the ears and needles were retained for 15 min. After needle withdrawal, the vaccariae semen were fixed with plaster at naogan (AT3, 4i), zhen (AT3), jing (AH12), shen (CO10) and pi (CO13) on the ears. In the medicine group, flunarizine hydrochloride capsules (Sibelium), 5mg were prescribed for oral administration, once every night. The treatment lasted continuously for 2 weeks (14 days) in the two groups. In 2 weeks, the clinical efficacy was assessed and the transcranial doppler (TCD) examination was performed.

After treatment, the symptom scores were all apparently reduced in the patients of the two groups (P < 0.01, P < 0.05). Compared with the medicine group, the reduced score was much more obvious in the auricular acupuncture group (P < 0.05), indicating the significant difference. After treatment, with TCD examination, the blood velocity was increased to different degrees in the patients of low velocity type in the auricular acupuncture group and the medicine group; that was reduced to different degrees in the patients of high velocity type in the auricular acupuncture group and the medicine group. All of them were different significantly as compared with those before treatment (all P 0.05). In comparison of clinical efficacy between the two groups, the effective rate was 93.3% (28/30) in the acupuncture group and better than 76.7% (23/30) in the medicine group, indicating the significant difference in comparison (P < 0.05).

The auricular acupuncture therapy achieves the definite efficacy on VBI and the efficacy is better than flunarizine hydrochloride capsules.

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Tangeretin enhances radiosensitivity and inhibits the radiation-induced epithelial-mesenchymal transition of gastric cancer cells.

Tangeretin enhances radiosensitivity and inhibits the radiation-induced epithelial-mesenchymal transition of gastric cancer cells. | A Tale of Two Medicines | Scoop.it
Irradiation has been reported to increase radioresistance and epithelial-mesenchymal transition (EMT) in gastric cancer (GC) cells. The Notch pathway is critically implicated in cancer EMT and radioresistance. In the present study, we investigated the use of a Notch-1 inhibiting compound as a novel therapeutic candidate to regulate radiation-induced EMT in GC cells. According to previous screening, tangeretin, a polymethoxylated flavonoid from citrus fruits was selected as a Notch-1 inhibitor. Tangeretin enhanced the radiosensitivity of GC cells as demonstrated by MTT and colony formation assays. Tangeretin also attenuated radiation-induced EMT, invasion and migration in GC cells, accompanied by a decrease in Notch-1, Jagged1/2, Hey-1 and Hes-1 expressions. Tangeretin triggered the upregulation of miR-410, a tumor-suppressive microRNA. Furthermore, re-expression of miR-410 prevented radiation-induced EMT and cell invasion. An in vivo tumor xenograft model confirmed the antimetastasis effect of tangeretin as we observed in vitro. In nude mice, tumor size was considerably diminished by radiation plus tangeretin co-treatment. Tangeretin almost completely inhibited lung metastasis induced by irradiation. Tangeretin may be a novel antimetastatic agent for radiotherapy.
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Wound healing potential of antibacterial microneedles loaded with green tea extracts

Wound healing potential of antibacterial microneedles loaded with green tea extracts | A Tale of Two Medicines | Scoop.it
This study evaluates the utility of an antibacterial microneedle composed of green tea (GT) extract and hyaluronic acid (HA), for the efficient delivery of GT. These microneedles have the potential to be a patient-friendly method for the conventional sustained release of drugs. In this study, a fabrication method using a mold-based technique to produce GT/HA microneedles with a maximum area of ~ 50 mm2 with antibacterial properties was used to manufacture transdermal drug delivery systems. Fourier transform infrared (FTIR) spectrometry was carried out to observe the potential modifications in the microneedles, when incorporated with GT. The degradation rate of GT in GT/HA microneedles was controlled simply by adjusting the HA composition. The effects of different ratios of GT in the HA microneedles were determined by measuring the release properties. In HA microneedles loaded with 70% GT (GT70), a continuous higher release rate was sustained for 72 h. The in vitro cytotoxicity assays demonstrated that GT/HA microneedles were not generally cytotoxic to Chinese hamster ovary cells (CHO-K1), human embryonic kidney cells (293T), and mouse muscle cells (C2C12), which were treated for 12 and 24 h. Antimicrobial activity of the GT/HA microneedles was demonstrated by ~ 95% growth reduction of gram negative [Escherichia coli (E. coli), Pseudomonas putida (P. putida), and Salmonella typhimurium (S. typhimurium)] and gram positive bacteria [Staphylococcus aureus (S. Aureus) and Bacillus subtilis (B. subtilis)], with GT70. Furthermore, GT/HA microneedles reduced bacterial growth of infected wound sites in the skin and improved wound healing process of skin in rat model.
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Cancer chemoprevention by dietary chlorophylls: a 12,000-animal dose-dose matrix biomarker and tumor study.

Recent pilot studies found natural chlorophyll (Chl) to inhibit carcinogen uptake and tumorigenesis in rodent and fish models, and to alter uptake and biodistribution of trace (14)C-aflatoxin B1 in human volunteers. The present study extends these promising findings, using a dose-dose matrix design to examine Chl-mediated effects on dibenzo(def,p)chrysene (DBC)-induced DNA adduct formation, tumor incidence, tumor multiplicity, and changes in gene regulation in the trout. The dose-dose matrix design employed an initial 12,360 rainbow trout, which were treated with 0-4000ppm dietary Chl along with 0-225ppm DBC for up to 4weeks. Dietary DBC was found to induce dose-responsive changes in gene expression that were abolished by Chl co-treatment, whereas Chl alone had no effect on the same genes. Chl co-treatment provided a dose-responsive reduction in total DBC-DNA adducts without altering relative adduct intensities along the chromatographic profile. In animals receiving DBC alone, liver tumor incidence (as logit) and tumor multiplicity were linear in DBC dose (as log) up to their maximum-effect dose, and declined thereafter. Chl co-treatment substantially inhibited incidence and multiplicity at DBC doses up to their maximum-effect dose. These results show that Chl concentrations encountered in Chl-rich green vegetables can provide substantial cancer chemoprotection, and suggest that they do so by reducing carcinogen bioavailability. However, at DBC doses above the optima, Chl co-treatments failed to inhibit tumor incidence and significantly enhanced multiplicity. This finding questions the human relevance of chemoprevention studies carried out at high carcinogen doses that are not proven to lie within a linear, or at least monotonic, endpoint dose-response range.
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Pasquale Valente's curator insight, May 29, 7:08 AM

"These results show that Chl concentrations encountered in Chl-rich green vegetables can provide substantial cancer chemoprotection, and suggest that they do so by reducing carcinogen bioavailability"

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Beneficial Effects of Polyphenol-Rich Chokeberry Juice Consumption on Blood Pressure Level and Lipid Status in Hypertensive Subjects.

Beneficial Effects of Polyphenol-Rich Chokeberry Juice Consumption on Blood Pressure Level and Lipid Status in Hypertensive Subjects. | A Tale of Two Medicines | Scoop.it
Epidemiological studies have shown a positive association between intake of foods rich in antioxidants and lower incidence of cardiovascular disease development. Polyphenols are considered the most abundant and important dietary antioxidants. The aim of this study was to evaluate effects of polyphenol-rich chokeberry juice consumption on 24-h ambulatory monitored blood pressure (BP) level in subjects with no pharmacologically treated high normal BP or grade I hypertension. Twenty-three subjects (12 men and 11 women) aged 33-67 were enrolled and instructed to consume 200 mL of juice daily for 4 weeks. Participants were divided in two groups, based on prevalence of sympathetic or parasympathetic activity. Measurements of biochemical parameters and heart rate variability analysis were also applied. At the end of the intervention period, average 24-h and awake systolic and diastolic BP were significantly decreased (P<.05). This was more pronounced in the group with prevalence of sympathetic activity. Significant reduction in triglyceride level (P<.05) and a reducing effect on total and low-density lipoprotein cholesterol were also found. Obtained results indicate a positive impact of regular chokeberry juice consumption on BP and lipid status in pharmacologically untreated hypertensive subjects.
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Chemopreventive effects of wild carrot oil against 7,12-dimethyl benz(a)anthracene-induced squamous cell carcinoma in mice.

Chemopreventive effects of wild carrot oil against 7,12-dimethyl benz(a)anthracene-induced squamous cell carcinoma in mice. | A Tale of Two Medicines | Scoop.it

Daucus carota L. ssp. carota (Apiacea) is widely distributed throughout the world and has many uses in traditional medicine.

The present study investigates the chemopreventive effects of oil extract of D. carota umbels on 7,12-dimethyl benz(a)anthracene (DMBA)-induced skin cancer in mice.

D. carota oil extract (DCOE) was prepared by extracting the dried umbels with 50:50 acetone:methanol. Skin papilloma were initiated by DMBA and promoted by 12-O-tetradecanoyl phorobol-13-acetate (TPA). The extract was administered to animals via gavage (0.02 mL of 100% oil), intraperitoneal (0.3 mL of 2% oil), and topical (0.2 mL of 5, 50, and 100% oil) routes for 20 weeks. Tumor appearance, incidence, yield, and volume were compared with those of a non-treated control group.

Topical 100% treatment delayed tumor appearance, and inhibited tumor incidence and yield by 40 and 89%, respectively. Topical 50% treatment inhibited tumor incidence and yield by 30 and 83%, respectively, whereas the 5% treatment inhibited tumor yield by 36%. Tumor volume was decreased by 99, 91, and 70% following topical treatments with 100, 50, and 5% oil, respectively. Intraperitoneal treatment inhibited tumor yield by 43%, and decreased tumor volume by 85%, whereas gavage treatment showed minimal effects on both. Intraperitoneal and topical treatment decreased infiltration and hyperplasia with an increase in the level of hyperkeratosis.

These findings demonstrate that DCOE has remarkable antitumor activity against DMBA-induced skin cancer compared with non-treated animals paving the ground for further investigations.

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Green Tea Polyphenol (−)-Epigallocatechin-3-Gallate Restores Nrf2 Activity and Ameliorates Crescentic Glomerulonephritis

Green Tea Polyphenol (−)-Epigallocatechin-3-Gallate Restores Nrf2 Activity and Ameliorates Crescentic Glomerulonephritis | A Tale of Two Medicines | Scoop.it
Crescentic glomerulonephritis (GN) is the most severe form of GN and is associated with significant morbidity and mortality despite aggressive immunotherapy with steroids, cytotoxic drugs, and plasmapheresis. We examined the therapeutic efficacy of the green tea polyphenol (−)-epigallocatechin-3-gallate (EGCG, 50 mg/kg BW/day x3weeks), a potent anti-inflammatory and anti-oxidant agent, on experimental crescentic GN induced in 129/svJ mice by administration of rabbit anti-mouse glomerular basement membrane sera. Routine histology and key molecules involved in inflammatory and redox signaling were studied. EGCG treatment significantly reduced mortality, decreased proteinuria and serum creatinine, and markedly improved renal histology when compared with vehicle-treated mice. The improvements in renal function and histology were accompanied by the restoration of Nrf2 signaling (which was impaired in vehicle-treated mice) as shown by increased nuclear translocation of Nrf2 and cytoplasmic glutamate cysteine ligase catalytic subunit, glutamate cysteine ligase modifier subunit, and glutathione peroxidase. EGCG-treated mice also showed reduction in p-Akt, p-JNK, p-ERK1/2 and p-P38 as well as restoration of PPARγ and SIRT1 levels. Lower dose of EGCG (25 mg/kg BW/day x2 weeks) treatment also significantly decreased proteinuria and serum creatinine, and markedly improved renal histology when compared with vehicle-treated mice. Thus, our data illustrate the efficacy of EGCG in reversing the progression of crescentic GN in mice by targeting multiple signaling and inflammatory pathways as well as countering oxidative stress.
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Ascorbate supplementation inhibits growth and metastasis of B16FO melanoma and 4T1 breast cancer cells in vitamin C-deficient mice

Ascorbate supplementation inhibits growth and metastasis of B16FO melanoma and 4T1 breast cancer cells in vitamin C-deficient mice | A Tale of Two Medicines | Scoop.it
Degradation of the extracellular matrix (ECM) plays a critical role in the formation of tumors and metastasis and has been found to correlate with the aggressiveness of tumor growth and invasiveness of cancer. Ascorbic acid, which is known to be essential for the structural integrity of the intercellular matrix, is not produced by humans and must be obtained from the diet. Cancer patients have been shown to have very low reserves of ascorbic acid. Our main objective was to determine the effect of ascorbate supplementation on metastasis, tumor growth and tumor immunohistochemistry in mice unable to synthesize ascorbic acid [gulonolactone oxidase (gulo) knockout (KO)] when challenged with B16FO melanoma or 4T1 breast cancer cells. Gulo KO female mice 36-38 weeks of age were deprived of or maintained on ascorbate in food and water for 4 weeks prior to and 2 weeks post intraperitoneal (IP) injection of 5×105 B16FO murine melanoma cells or to injection of 5×105 4T1 breast cancer cells into the mammary pad of mice. Ascorbate-supplemented gulo KO mice injected with B16FO melanoma cells demonstrated significant reduction (by 71%, p=0.005) in tumor metastasis compared to gulo KO mice on the control diet. The mean tumor weight in ascorbate supplemented mice injected with 4T1 cells was reduced by 28% compared to tumor weight in scorbutic mice. Scorbutic tumors demonstrated large dark cores, associated with increased necrotic areas and breaches to the tumor surface, apoptosis and matrix metalloproteinase-9 (MMP-9), and weak, disorganized or missing collagen I tumor capsule. In contrast, the ascorbate-supplemented group tumors had smaller fainter colored cores and confined areas of necrosis/apoptosis with no breaches from the core to the outside of the tumor and a robust collagen I tumor capsule. In both studies, ascorbate supplementation of gulo KO mice resulted in profoundly decreased serum inflammatory cytokine interleukin (IL)-6 (99% decrease, p=0.01 in the B16F0 study and 85% decrease, p=0.08 in the 4T1 study) compared to the levels in gulo KO mice deprived of ascorbate. In the B16FO study, ascorbate supplementation of gulo KO mice resulted in profoundly decreased serum VEGF (98% decrease, p=0.019 than in the scorbutic gulo KO mice). As expected, mean serum ascorbate level in ascorbate-restricted mice was 2% (p<0.001) of the mean ascorbate levels in supplemented mice. In conclusion, ascorbate supplementation hinders metastasis, tumor growth and inflammatory cytokine secretion as well as enhanced encapsulation of tumors elicited by melanoma and breast cancer cell challenge in gulo KO mice.
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ABC Says Echinacea Preparation as Effective as Tamiflu® in Early Flu Cases in Large Clinical Trial

ABC Says Echinacea Preparation as Effective as Tamiflu® in Early Flu Cases in Large Clinical Trial | A Tale of Two Medicines | Scoop.it
New clinical research suggests that an herbal medicinal product containing a proprietary combination of a concentrated echinacea herb and root extract is as effective as the conventional antiviral medicine oseltamivir (Tamiflu®) in the early treatment of influenza. The results of the randomized, double-blind, controlled clinical trial were published online in April in the open-access journal Current Therapeutic Research. [1]

For the study, researchers recruited 473 patients who had exhibited flu symptoms for less than 48 hours from 29 primary care practices in the Czech Republic. The patients were randomly assigned to take Echinaforce® Hotdrink syrup, a beverage containing an alcoholic extract prepared from freshly harvested echinacea (Echinacea purpurea) herb and root (95% herb; 5% root) supplemented with European elderberry (Sambucus nigra), for 10 days, or oseltamivir for five days followed by placebo for five days. (Echinaforce Hotdrink is produced and marketed by A. Vogel Bioforce AG of Roggwil, Switzerland. It is not currently sold in the United States.)

The primary endpoint of the clinical trial was the percentage of patients with mild or no symptoms after one, five, and 10 days of treatment. At each time point, the researchers found that a similar number of patients had recovered in both groups. After day one, 1.5% of patients in the Echinaforce Hotdrink group and 4.1% of those in the oseltamivir group exhibited mild or no symptoms; recovery rates for days five and 10 were 50.2% and 48.8%, and 90.1% and 84.8%, respectively.
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Echinaforce Hotdrink versus Oseltamivir in Influenza: A randomized, double-blind, double dummy, multicenter, non-inferiority clinical trial.

Echinaforce Hotdrink versus Oseltamivir in Influenza: A randomized, double-blind, double dummy, multicenter, non-inferiority clinical trial. | A Tale of Two Medicines | Scoop.it

Echinacea has antiviral activity against influenza viruses in vitro. This randomized, double-blind, double-dummy, multicenter, controlled clinical trial compared a new Echinacea formulation with the neuraminidase inhibitor Oseltamivir, the gold standard treatment of influenza.

Following informed consent, 473 patients with early influenza symptoms (≤48h) were recruited in primary care in the Czech Republic and randomized to either 5 days Oseltamivir followed by 5 days placebo, or 10 days Echinaforce Hotdrink. The proportion of recovered patients (influenza symptoms rated as absent or mild in the evening) was analyzed for non-inferiority between treatment groups using a generalized Wilcoxon test with significance level α = 0.05 (two-sided) and using a confidence interval (CI) approach in the per protocol sample.

Recovery from illness was comparable in the two treatment groups at 1.5% vs. 4.1% after 1 day, 50.2% vs. 48.8% after 5 days and 90.1% vs. 84.8% after 10 days treatment with Echinaforce Hotdrink and Oseltamivir, respectively. Non-inferiority was demonstrated for each day and overall (95% CI [0.487 – 0.5265], generalized Wilcoxon test). Very similar results were obtained in the group with virologically confirmed influenza virus infections and in a retrospective analysis during the peak influenza period. The incidence of complications was lower with Echinaforce than with Oseltamivir (2.46% vs. 6.45%, p = 0.076) and fewer adverse events (particularly nausea and vomiting) were observed with Echinaforce Hotdrink.

Echinaforce Hotdrink is as effective as Oseltamivir in the early treatment of clinically diagnosed and virologically confirmed influenza virus infections with a reduced risk of complications and adverse events. It appears to be an attractive treatment option, particularly suitable for self care.

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Quercetin increased bioavailability and decreased methylation of green tea polyphenols in vitro and in vivo

Quercetin increased bioavailability and decreased methylation of green tea polyphenols in vitro and in vivo | A Tale of Two Medicines | Scoop.it
The extensive methylation of green tea polyphenols (GTPs) in vivo may limit their chemopreventive potential. We investigated whether quercetin, a natural inhibitor of catechol-O-methyltransferase (COMT) and multidrug resistance proteins (MRPs), will differentially increase the intracellular concentration and decrease the methylation of GTPs in different cancer cell lines. Intrinsic COMT activity was lowest in lung cancer A549 cells, intermediate in kidney 786-O cells and highest in liver HepG2 cells. Quercetin increased the cellular absorption of epigallocatechin gallate (EGCG) four-fold in A549 cells with a decreased methylation rate from 63% to 19%, 2-fold in 786-O cells with a decreased methylation from 97% to 56%, while no significant effect was observed in HepG2 cells. The combination significantly decreased the activity and protein expression of COMT and decreased the protein expression of MRP1 compared to individual treatments. The combination exhibited the strongest increase in antiproliferation in A549 cells, an intermediate effect in 786-O cells and lowest effect in HepG2 cells. The effect of quercetin on bioavailability and metabolism of GTPs was confirmed in vivo. SCID mice were administered brewed green tea (GT) and a diet supplemented with 0.4% quercetin alone or in combination for 2 weeks. We observed a 2 to 3-fold increase of total and non-methylated EGCG in lung and kidney and a trend to increase in liver. In summary, combining quercetin with GT provides a promising approach to enhance the chemoprevention of GT. Responses of different cancers to the combination may vary by tissue depending on the intrinsic COMT and MRP activity.
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Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome.

Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome. | A Tale of Two Medicines | Scoop.it
The intestinal tract is inhabited by a large and diverse community of microbes collectively referred to as the gut microbiota. While the gut microbiota provides important benefits to its host, especially in metabolism and immune development, disturbance of the microbiota–host relationship is associated with numerous chronic inflammatory diseases, including inflammatory bowel disease and the group of obesity-associated diseases collectively referred to as metabolic syndrome. A primary means by which the intestine is protected from its microbiota is via multi-layered mucus structures that cover the intestinal surface, thereby allowing the vast majority of gut bacteria to be kept at a safe distance from epithelial cells that line the intestine1. Thus, agents that disrupt mucus–bacterial interactions might have the potential to promote diseases associated with gut inflammation. Consequently, it has been hypothesized that emulsifiers, detergent-like molecules that are a ubiquitous component of processed foods and that can increase bacterial translocation across epithelia in vitro2, might be promoting the increase in inflammatory bowel disease observed since the mid-twentieth century3. Here we report that, in mice, relatively low concentrations of two commonly used emulsifiers, namely carboxymethylcellulose and polysorbate-80, induced low-grade inflammation and obesity/metabolic syndrome in wild-type hosts and promoted robust colitis in mice predisposed to this disorder. Emulsifier-induced metabolic syndrome was associated with microbiota encroachment, altered species composition and increased pro-inflammatory potential. Use of germ-free mice and faecal transplants indicated that such changes in microbiota were necessary and sufficient for both low-grade inflammation and metabolic syndrome. These results support the emerging concept that perturbed host–microbiota interactions resulting in low-grade inflammation can promote adiposity and its associated metabolic effects. Moreover, they suggest that the broad use of emulsifying agents might be contributing to an increased societal incidence of obesity/metabolic syndrome and other chronic inflammatory diseases.
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Clinical observasion of acupuncture in patients with depression and its impact on serum 5-HT.

Clinical observasion of acupuncture in patients with depression and its impact on serum 5-HT. | A Tale of Two Medicines | Scoop.it

To observe the clinical effect of acupuncture for depression and to discuss its impact on the content of 5-HT in patients with depression.

Eighty patients with depression were randomly divided into an acupuncture group and a western medication group,40 cases in each one. Acupuncture was applied in the acupuncture group,Siman(KI 14),Shenshu(BL 23),Guanyuan(CV 4),Dazhui(GV 14),Yinlingquan(SP 9), Zusanli(ST 36),Taichong(LR 3),Yanglingquan(GB 34) and Jingming(BL 1) were selected, the intensive moxibustion was applied at G(uanyuan(CV 4). Fluoxetine was treated with oral administration in the western medication group. The treatments of six weeks were required in each group. The Hamilton depression rating scale (HAMD) was applied to evaluate efficacy and serum 5-HT was detected before and after treatment in the two groups.

After treatment,the scores of HAMD were decreased obviously in the two groups compared with those before treatment (scores in the acupuncture group: 24. 48 ± 0. 28 vs 8. 95 ± 2. 24; scores in the western medication group: 24. 14±0. 24 vs 10. 29±1. 30),and the differences were statistically significant (both P<0. 05). Between the two groups,the scores of HAMD in the acupuncture group at the end of the lst,2nd,4th,6th weeks were superior to those in the western medication group (all P<0. 05). The content of serum 5-HT after treatment was increased markedly compared with that before treatment [the content in the acupuncture group: (26. 21 2. 36)pg/mL vs (52. 07 ± 0. 56)pg/mL, the content in the western medication group:(26. 26±2. 31)pg/mL vs (51. 70±0. 52)pg/ mL, both P0.05).

The efficacy of acupuncture for depression is superior to that of western medication with fluoxetine.

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Hesperidin, nobiletin, and tangeretin are collectively responsible for the anti-neuroinflammatory capacity of tangerine peel.

Hesperidin, nobiletin, and tangeretin are collectively responsible for the anti-neuroinflammatory capacity of tangerine peel. | A Tale of Two Medicines | Scoop.it
Inhibiting microglial activation-mediated neuroinflammation has become a convincing target for the development of functional foods to treat neurodegenerative diseases. Tangerine peel (Citri reticulatae pericarpium) has potent anti-inflammatory capacity; however, its anti-neuroinflammatory capacity and the corresponding active compounds remain unclear. To this end, the composition of a tangerine peel ethanolic extract was analysed by LC-MS, and the anti-neuroinflammatory ability was evaluated using a lipopolysaccharide (LPS)-activated BV2 microglia culture system. Hesperidin is the most predominant flavonoid in tangerine peel, followed by tangeretin and nobiletin. Among the eight tested flavanone glycosides and polymethoxy flavones, only nobiletin displayed a capacity of>50% to inhibit LPS-induced proinflammatory NO, TNF-α, IL-1β and IL-6 secretion at a concentration of 100 μM. At 2 mg/ml, tangerine peel extract attenuated LPS-induced NO, TNF-α, IL-1β and IL-6 secretion by 90.6%, 80.2%, 66.7%, and 86.8%, respectively. Hesperidin, nobiletin, and tangeretin individually (at concentrations of 135, 40, and 60 μM, respectively) in 2 mg/ml tangerine peel extract were only mildly inhibitory, whereas in combination, they significantly inhibited LPS-induced proinflammatory cytokine expression at levels equal to that of 2 mg/ml tangerine peel extract. Overall, tangerine peel possesses potent anti-neuroinflammatory capacity, which is attributed to the collective effect of hesperidin, nobiletin, and tangeretin.
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Influence of red wine polyphenols and ethanol on the gut microbiota ecology and biochemical biomarkers

Few studies have investigated the effect of dietary polyphenols on the complex human gut microbiota, and they focused mainly on single polyphenol molecules and select bacterial populations.

The objective was to evaluate the effect of a moderate intake of red wine polyphenols on select gut microbial groups implicated in host health benefits.

Ten healthy male volunteers underwent a randomized, crossover, controlled intervention study. After a washout period, all of the subjects received red wine, the equivalent amount of de-alcoholized red wine, or gin for 20 d each. Total fecal DNA was submitted to polymerase chain reaction(PCR)–denaturing gradient gel electrophoresis and real-time quantitative PCR to monitor and quantify changes in fecal microbiota. Several biochemical markers were measured.

The dominant bacterial composition did not remain constant over the different intake periods. Compared with baseline, the daily consumption of red wine polyphenol for 4 wk significantly increased the number of Enterococcus, Prevotella, Bacteroides, Bifidobacterium, Bacteroides uniformis, Eggerthella lenta, and Blautia coccoides–Eubacterium rectale groups (P < 0.05). In parallel, systolic and diastolic blood pressures and triglyceride, total cholesterol, HDL cholesterol, and C-reactive protein concentrations decreased significantly (P < 0.05). Moreover, changes in cholesterol and C-reactive protein concentrations were linked to changes in the bifidobacteria number.

This study showed that red wine consumption can significantly modulate the growth of select gut microbiota in humans, which suggests possible prebiotic benefits associated with the inclusion of red wine polyphenols in the diet.

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Comparison of the urinary excretion of quercetin glycosides from red onion and aglycone from dietary supplements in healthy subjects: a randomized, single-blinded, cross-over study.

Comparison of the urinary excretion of quercetin glycosides from red onion and aglycone from dietary supplements in healthy subjects: a randomized, single-blinded, cross-over study. | A Tale of Two Medicines | Scoop.it
Some intervention studies have shown that quercetin supplementation can regulate certain biomarkers, but it is not clear how the doses given relate to dietary quercetin (e.g. from onion). We conducted a two-period, two-sequence crossover study to compare the bioavailability of quercetin when administered in the form of a fresh red onion meal (naturally glycosylated quercetin) or dietary supplement (aglycone quercetin) under fasting conditions. Six healthy, non-smoking, adult males with BMI 22.7 ± 4.0 kg m(-2) and age 35.3 ± 12.3 y were grouped to take the two study meals in random order. In each of the 2 study periods, one serving of onion soup (made from 100 g fresh red onion, providing 156.3 ± 3.4 μmol (47 mg) quercetin) or a single dose of a quercetin dihydrate tablet (1800 ± 150 μmol (544 mg) of quercetin) were administered following 3 d washout. Urine samples were collected up to 24 h, and after enzyme deconjugation, quercetin was quantified by LC-MS. The 24 h urinary excretion of quercetin (1.69 ± 0.79 μmol) from red onion in soup was not significantly different to that (1.17 ± 0.44 μmol) for the quercetin supplement tablet (P = 0.065, paired t-test). This means that, in practice, 166 mg of quercetin supplement would be comparable to about 10 mg of quercetin aglycone equivalents from onion. These data allow intervention studies on quercetin giving either food or supplements to be more effectively compared.
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Dietary intake of flavonoids and oesophageal and gastric cancer: incidence and survival in the United States of America (USA).

Dietary intake of flavonoids and oesophageal and gastric cancer: incidence and survival in the United States of America (USA). | A Tale of Two Medicines | Scoop.it

Flavonoids, polyphenolic compounds concentrated in fruits and vegetables, have experimentally demonstrated chemopreventive effects against oesophageal and gastric cancer. Few epidemiologic studies have examined flavonoid intake and incidence of these cancers, and none have considered survival.

In this USA multicentre population-based study, case participants (diagnosed during 1993-1995 with oesophageal adenocarcinoma (OEA, n=274), gastric cardia adenocarcinoma (GCA, n=248), oesophageal squamous cell carcinoma (OES, n=191), and other gastric adenocarcinoma (OGA, n=341)) and frequency-matched controls (n=662) were interviewed. Food frequency questionnaire responses were linked with USDA Flavonoid Databases and available literature for six flavonoid classes and lignans. Case participants were followed until 2000 for vital status. Multivariable-adjusted odds ratios (ORs) and hazard ratios (HRs) (95% confidence intervals (CIs)) were estimated, comparing highest with lowest intake quartiles, using polytomous logistic and proportional hazards regressions, respectively.

Little or no consistent association was found for total flavonoid intake (main population sources: black tea, orange/grapefruit juice, and wine) and incidence or survival for any tumour type. Intake of anthocyanidins, common in wine and fruit juice, was associated with a 57% reduction in the risk of incident OEA (OR=0.43, 95% CI=0.29-0.66) and OES (OR=0.43, 95% CI=0.26-0.70). The ORs for isoflavones, for which coffee was the main source, were increased for all tumours, except OES. Anthocyanidins were associated with decreased risk of mortality for GCA (HR=0.63, 95% CI=0.42-0.95) and modestly for OEA (HR=0.87, 95% CI=0.60-1.26), but CIs were wide.

Our findings, if confirmed, suggest that increased dietary anthocyanidin intake may reduce incidence and improve survival for these cancers.

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Targeted delivery of 1,25-dihydroxyvitamin D3 to colon tissue and identification of a major 1,25-dihydroxyvitamin D3 glycoside from Solanumglaucophyllum plant leaves

Leaves of the Solanum glaucophyllum (Sg) plant, indigenous to South America, have long been known for their calcinogenic toxicity in ruminant animals. It was determined the leaves contained glycosidic derivatives of 1,25-dihydroxyvitamin D3 (1,25D3) and liberation of the free hormone by rumen bacterial populations elicited a hypercalcemic response. Our interest in the leaves is predicated on the concept that the glycoside forms of 1,25D3 would target release of the active hormone in the lower gut of non-ruminant mammals. This would provide a means of delivering 1,25D3 directly to the colon, where the hormone has been shown to have beneficial effects in models of inflammatory bowel disease (IBD) and colon cancer. We fed mice for 10 days with variable amounts of Sg leaf. Feeding 7–333 μg leaf/day produced no changes in plasma Ca2+ and 1,25D3 concentrations, and only at ≥1000 μg leaf/day did these values become significantly elevated compared to controls. Gene expression studies from colon tissue indicated a linear relationship between the amount of leaf consumed and expression of the Cyp24a1 gene. In contrast, Cyp24a1 gene expression in the duodenums and ileums of these mice was unchanged compared to controls. One of the major 1,25D3-glycosides was isolated from leaves following extraction and purification by Sep-Pak cartridges and HPLC fractionation. Ultraviolet absorbance was consistent with modification of the 1-hydroxyl group, and positive ion ESI mass spectrometry indicated a diglycoside of 1,25D3. 2-Dimensional NMR analyses were carried out and established the C1 proton of the A-ring was interacting with a C1′ sugar proton, while the C3 proton of the A-ring was linked with a second C1′ sugar proton. The structure of the isolated compound is therefore consistent with a β-linked 1,3-diglycoside of 1,25D3. Thus, Sg leaf administered to mice at up to 333 ug/day can elicit colon-specific enhancement of Cyp24a1 gene expression without inducing hypercalcemia, and the 1,3-diglycoside is one of the major forms of 1,25D3 found in the leaf.
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Wild carrot oil extract is selectively cytotoxic to human acute myeloid leukemia cells.

Wild carrot oil extract is selectively cytotoxic to human acute myeloid leukemia cells. | A Tale of Two Medicines | Scoop.it
In this study, we used Daucus carota oil extract (DCOE) to target acute myeloid leukemia (AML) cells. All the AML cell lines tested were sensitive to the extract while peripheral mononuclear cells were not. Analysis of mechanism of cell death showed an increase in cells positive for annexinV and for active caspases, indicating that DCOE induces apoptotic cell death in AML. Inhibition of the MAPK pathway decreased sensitivity of AML cells to DCOE, indicating that cytotoxicity may be dependent on its activity. In conclusion, DCOE induces selective apoptosis in AML cells, possibly through a MAPK-dependent mechanism.
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EmmanuelGrunenberger's curator insight, May 19, 10:34 AM

Always surprised that carrot can still be a #therapeutic resource! #cytotoxic #leukemia