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Fenugreek extract diosgenin and pure diosgenin inhibit the hTERT gene expression in A549 lung cancer cell line.

Fenugreek extract diosgenin and pure diosgenin inhibit the hTERT gene expression in A549 lung cancer cell line. | A Tale of Two Medicines | Scoop.it

rigonella foenum-graecum generally known as fenugreek, has been normally cultivated in Asia and Africa for the edible and medicinal values of its seeds. Fenugreek leaves and seeds have been used widely for therapeutic purposes. Fenugreek seed is recognized to show anti-diabetic and anti-nociceptive properties and other things such as hypocholesterolaemic, and anti-cancer. Diosgenin is a steroidal saponin from therapeutic herbs, fenugreek (T. foenum-graceum L.), has been well-known to have anticancer properties. Telomerase activity is not identified in usual healthy cells, while in carcinogenic cell telomerase expression is reactivated. Therefore telomerase illustrates a promising cancer therapeutic target. We deliberate the inhibitory effect of pure diosgenin and fenugreek extract diosgenin on human telomerase reverse transcriptase gene (hTERT) expression which is critical for telomerase activity. MTT-assay and qRT-PCR analysis were achieved to discover cytotoxicity effects and hTERT gene expression inhibition properties, separately. MTT results exhibited that IC50 for pure diosgenin were 47, 44 and 43 µM and for fenugreek extract diosgenin were 49, 48 and 47 µM for 24, 48 and 72 h after treatment. Culturing cells with pure diosgenin and fenugreek extract diosgenin treatment caused in down regulation of hTERT expression. These results indication that pure and impure diosgenin prevents telomerase activity by down regulation of the hTERT gene expression in A549 lung cancer cell line, with the difference that pure compound is more effective than another.

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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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Impact of aspartame and saccharin on the rat liver: Biochemical, molecular, and histological approach.

Impact of aspartame and saccharin on the rat liver: Biochemical, molecular, and histological approach. | A Tale of Two Medicines | Scoop.it

The current work was undertaken to settle the debate about the toxicity of artificial sweeteners (AS), particularly aspartame and saccharin. Twenty-five, 7-week-old male Wistar albino rats with an average body weight of 101 ± 4.8 g were divided into a control group and four experimental groups (n = 5 rats). The first and second experimental groups received daily doses equivalent to the acceptable daily intake (ADI) of aspartame (250 mg/Kg BW) and four-fold ADI of aspartame (1000 mg/Kg BW). The third and fourth experimental groups received daily doses equivalent to ADI of saccharin (25 mg/Kg BW) and four-fold ADI of saccharin (100 mg/Kg BW). The experimental groups received the corresponding sweetener dissolved in water by oral route for 8 weeks. The activities of enzymes relevant to liver functions and antioxidants were measured in the blood plasma. Histological studies were used for the evaluation of the changes in the hepatic tissues. The gene expression levels of the key oncogene (h-Ras) and the tumor suppressor gene (P27) were also evaluated. In addition to a significant reduction in the body weight, the AS-treated groups displayed elevated enzymes activities, lowered antioxidants values, and histological changes reflecting the hepatotoxic effect of aspartame and saccharin. Moreover, the overexpression of the key oncogene (h-Ras) and the downregulation of the tumor suppressor gene (P27) in all treated rat groups may indicate a potential risk of liver carcinogenesis, particularly on long-term exposure

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Higher plain water intake is associated with lower type 2 diabetes risk: a cross-sectional study in humans.

Higher plain water intake is associated with lower type 2 diabetes risk: a cross-sectional study in humans. | A Tale of Two Medicines | Scoop.it
The aim of this study was to investigate the relationship between plain water intake and type 2 diabetes (T2D) risk. It was hypothesized that higher plain water intake would be associated with a lower T2D risk score. One hundred thirty-eight adults from Southwest and Southeast England answered a cross-sectional online survey assessing T2D risk (using the Diabetes UK risk assessment); physical activity (using the short International Physical Activity Questionnaire); and consumption of fruits, vegetables, and beverages (using an adapted version of the Cambridge European Prospective Investigation into Cancer and Nutrition Food Frequency Questionnaire). There was a trend for differences in mean plain water intake between those stratified as having low, increased, moderate, or high risk of T2D; but these did not achieve significance (P = .084). However, plain water intake was significantly negatively correlated with T2D risk score (τ = -0°180, P = .005); and for every 240-mL cup of water consumed per day, T2D risk score was reduced by 0.72 point (range, 0-47) (B = -0.03, 95% confidence interval = -0.06 to -0.01, P = .014). The current study has provided preliminary results that are supported by theory; mechanisms need to be explored further to determine the true effect of plain water intake on disease risk. As increasing plain water intake is a simple and cost-effective dietary modification, its impact on T2D risk is important to investigate further in a randomized controlled trial. Overall, this study found that plain water intake had a significant negative correlation with T2D risk score; and regression analysis suggested that water may have a role in reducing T2D risk.
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Moringa oleifera as an Anti-Cancer Agent against Breast and Colorectal Cancer Cell Lines

Moringa oleifera  as an Anti-Cancer Agent against Breast and Colorectal Cancer Cell Lines | A Tale of Two Medicines | Scoop.it
In this study we investigated the anti-cancer effect of Moringa oleifera leaves, bark and seed extracts. When tested against MDA-MB-231 and HCT-8 cancer cell lines, the extracts of leaves and bark showed remarkable anti-cancer properties while surprisingly, seed extracts exhibited hardly any such properties. Cell survival was significantly low in both cells lines when treated with leaves and bark extracts. Furthermore, a striking reduction (about 70–90%) in colony formation as well as cell motility was observed upon treatment with leaves and bark. Additionally, apoptosis assay performed on these treated breast and colorectal cancer lines showed a remarkable increase in the number of apoptotic cells; with a 7 fold increase in MD-MB-231 to an increase of several fold in colorectal cancer cell lines. However, no significant apoptotic cells were detected upon seeds extract treatment. Moreover, the cell cycle distribution showed a G2/M enrichment (about 2–3 fold) indicating that these extracts effectively arrest the cell progression at the G2/M phase. The GC-MS analyses of these extracts revealed numerous known anti-cancer compounds, namely eugenol, isopropyl isothiocynate, D-allose, and hexadeconoic acid ethyl ester, all of which possess long chain hydrocarbons, sugar moiety and an aromatic ring. This suggests that the anti-cancer properties of Moringa oleifera could be attributed to the bioactive compounds present in the extracts from this plant. This is a novel study because no report has yet been cited on the effectiveness of Moringa extracts obtained in the locally grown environment as an anti-cancer agent against breast and colorectal cancers. Our study is the first of its kind to evaluate the anti-malignant properties of Moringa not only in leaves but also in bark. These findings suggest that both the leaf and bark extracts of Moringa collected from the Saudi Arabian region possess anti-cancer activity that can be used to develop new drugs for treatment of breast and colorectal cancers.
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Comparing the Therapeutic Effects of Garlic Tablet and Oral Metronidazole on Bacterial Vaginosis: A Randomized Controlled Clinical Trial

Comparing the Therapeutic Effects of Garlic Tablet and Oral Metronidazole on Bacterial Vaginosis: A Randomized Controlled Clinical Trial | A Tale of Two Medicines | Scoop.it

Bacterial vaginosis (BV) is one of the most common gynecological infections during reproductive age. Although metronidazole is one of the most effective medications recommended as the first-line treatment, it has various side effects. Because of the side effects and contraindications of some chemical medicines, using herbs has been investigated in treating BV.

The aim of this study was to compare the effect of garlic tablet (Garsin) and oral metronidazole in clinical treatment of the BV in women referred to Resalat Health Center, affiliated with Mazandaran University of Medical Sciences, in 2013.

This randomized clinical trial was conducted on 120 married women aged 18 to 44 years who were diagnosed with BV by Amsel’s clinical criteria and Gram staining. Enrolled women were randomly allocated to two groups of 60 patients and were treated with either garlic tablet or oral metronidazole for seven days. Amsel’s criteria and Gram stain were assessed seven to ten days after beginning the treatment period and side effects were registered.

Amsel’s criteria were significantly decreased after treatment with garlic or metronidazole (70% and 48.3%, respectively; P < 0.001). Therapeutic effects of garlic on BV were similar to that of metronidazole (63.3% and 48.3%, respectively; P = 0.141). There were significant differences between the two treatment groups in terms of side effects; metronidazole was associated with more complications (P = 0.032).

This study reveals that garlic could be a suitable alternative for metronidazole in treatment of BV in those interested in herbal medicines or those affected by side effects of metronidazole.

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Ascorbate depletion increases growth and metastasis of melanoma cells in vitamin C deficient mice.

Ascorbate depletion increases growth and metastasis of melanoma cells in vitamin C deficient mice. | A Tale of Two Medicines | Scoop.it
Our main objective was to determine the effect of ascorbate supplementation in mice unable to synthesize ascorbic acid (gulo KO) when challenged with murine B16FO cancer cells. Methods: Gulo KO female mice 36–40 weeks of age were deprived of or maintained on ascorbate in food and water for 4 weeks prior to subcutaneous injection of 2.5×106 B16FO murine melanoma cells in the right flank of mice. A control group of wild type mice were also injected with the melanoma cells and maintained on a regular murine diet. Mice were continued on their respective diets for another 2 weeks after injection. The mice were then sacrificed, blood was drawn and their tumors were measured, excised and processed for histology. Results: Mean weight of animals decreased significantly (30%, p < 0.0001) in the ascorbate-restricted group but increased slightly, but insignificantly, in the ascorbate-supplemented group. The mean tumor weight in ascorbate supplemented mice was significantly reduced (by 64%, p = 0.004) compared to tumor weight in ascorbate-deprived gulo mice. The mean tumor weight of wild type mice did not differ significantly from the ascorbate-supplemented mice. Gulo KO mice supplemented with ascorbate developed smaller tumors with more collagen encapsulation and fibrous capsule interdigitation, while gulo KO mice deprived of ascorbate hosted large tumors with poorly defined borders, showing more necrosis and mitosis. Ascorbate supplementation of gulo KO mice resulted in profoundly decreased serum inflammatory cytokine IL-6 (90% decrease, p = 0.04) and IL-1β (62% decrease) compared to the levels in gulo KO mice deprived of ascorbate. Conclusion: Ascorbate supplementation modulated tumor growth and inflammatory cytokine secretion as well as enhanced encapsulation of tumors in scorbutic mice.
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In vitro antioxidant, collagenase inhibition, and in vivo anti-wrinkle effects of combined formulation containing Punica granatum, Ginkgo biloba, Ficus carica, and Morus alba fruits extract

In vitro antioxidant, collagenase inhibition, and in vivo anti-wrinkle effects of combined formulation containing Punica granatum, Ginkgo biloba, Ficus carica, and Morus alba fruits extract | A Tale of Two Medicines | Scoop.it

In phytotherapy, the therapeutic potential is based on the combined action of different herbal drugs. Our objective was to evaluate the antioxidant, anti-collagenase (in vitro), and anti-wrinkle (in vivo) effect of combined formulation containing Ginkgo biloba, Punica granatum, Ficus carica, and Morus alba fruits extract.

Antioxidant evaluation was based on the scavenging activity of free radicals (1,1-diphenyl-2-picrylhydrazyl, H2O2, and O2−) and the anti-collagenase activity was based on the reduction of collagenase enzyme in vitro. In an in vivo study, 21 female subjects were examined in a placebo-controlled trail. Facial wrinkle, especially the crow’s feet region of eyes, was treated with topical formulated 2% cream for 56 days and compared with the placebo.

In the in vitro study, the combination of fruits extract showed a higher antioxidant activity which was comparable with the positive standard (ascorbic acid, butylated hydroxyanisole, and Trolox). The data also showed a dose-dependent inhibition of collagenase. In the in vivo study, treatment with 2% formulated cream for 56 days significantly reduced the percentage of wrinkle depth, length, and area with 11.5, 10.07, and 29.55, respectively.

The combined formulation of fruit extracts showed excellent antioxidative and anti-collagenase activity as well as a significant effect on anti-wrinkle activity on human skin.

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pH dependent antioxidant activity of lettuce (L. sativa) and synergism with added phenolic antioxidants.

pH dependent antioxidant activity of lettuce (L. sativa) and synergism with added phenolic antioxidants. | A Tale of Two Medicines | Scoop.it
Influence of pH on the antioxidant activities of combinations of lettuce extract (LE) with quercetin (QC), green tea extract (GTE) or grape seed extract (GSE) was investigated for both reduction of Fremy's salt in aqueous solution using direct electron spin resonance (ESR) spectroscopy and in l-α-phosphatidylcholine liposome peroxidation assay measured following formation of conjugated dienes. All examined phenolic antioxidants showed increasing radical scavenging effect with increasing pH values by using both methods. QC, GTE and GSE acted synergistically in combination with LE against oxidation of peroxidating liposomes and with QC showing the largest effect. The pH dependent increase of the antioxidant activity of the phenols is due to an increase of their electron-donating ability upon deprotonation and to their stabilization in alkaline solutions leading to polymerization reaction. Such polymerization reactions of polyphenolic antioxidants can form new oxidizable -OH moieties in their polymeric products resulting in a higher radical scavenging activity.
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Stability of the Ellagitannin Fraction and Antioxidant Capacity of Varietal Pomegranate Juices.

Stability of the Ellagitannin Fraction and Antioxidant Capacity of Varietal Pomegranate Juices. | A Tale of Two Medicines | Scoop.it
This work aimed to assess the effect of combining two pomegranate (Punica granatum L.) cultivars at different rates on the ellagitannin content, antioxidant capacity, and total phenolic content of varietal pomegranate juices. Widely distinct juices made from Mollar de Elche and Wonderful cultivars were used for the elaboration of blended juices. They were stored for 70 days at both room and refrigeration temperatures. This study revealed a significant cultivar effect on the stability of main pomegranate ellagitannins (punicalagins, punicalins, punicalagin-like compound, and ellagic acid derivatives) and on the antioxidant capacity measured by the ABTS+ and DPPH* in vitro assays. Blended juices enhanced and/or retained the initial ellagitannin content and antioxidant capacity of pure juices during storage. Thus, blending varietal juices could be suggested as a promising alternative to the development of fresh juices with a high, stable phytochemical load.
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Vitamin D3 potentiates myelination and recovery after facial nerve injury.

Vitamin D3 potentiates myelination and recovery after facial nerve injury. | A Tale of Two Medicines | Scoop.it
Roles of vitamin D on the immune and nervous systems are increasingly recognized. Two previous studies demonstrated that ergocalciferol (vitamin D2) or cholecalciferol (vitamin D3) induced functional recovery and increased myelination in a rat model of peroneal nerve transection. The current report assessed whether cholecalciferol was efficient in repairing transected rabbit facial nerves. Animals were randomized into two groups of rabbits with an unilateral facial nerve surgery: the vitamin D group included animals receiving a weekly oral bolus of vitamin D3 (200 IU/kg/day), from day 1 post-surgery; the control group included animals receiving a weekly oral bolus of vehicle (triglycerides). Contralateral unsectioned facial nerves from all experimental animals were used as controls for the histological study. The facial functional index was measured every week while the inner diameter of myelin sheath and the G ratio were quantified at the end of the 3 month experiment. The current report indicates that cholecalciferol significantly increases functional recovery and myelination, after 12 weeks of treatment. To the best of our knowledge, this is the first study investigating the therapeutic benefit of vitamin D supplementation in an animal model of facial paralysis. It paves further the way for clinical trials based on the administration of this steroid in individuals with injured facial nerves.
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Toxoplasma gondii seropositivity and cognitive functions in school-aged children.

Toxoplasma gondii seropositivity and cognitive functions in school-aged children. | A Tale of Two Medicines | Scoop.it
Toxoplasma gondii (T. gondii) infects one-third of the world population, but its association with cognitive functions in school-aged children is unclear. We examined the relationship between Toxoplasma seropositivity and neuropsychological tests scores (including math, reading, visuospatial reasoning and verbal memory) in 1755 school-aged children 12-16 years old who participated to the Third National Health and Nutrition Examination Survey, using multiple linear regressions adjusted for covariates. Toxoplasma seroprevalence was 7·7% and seropositivity to the parasite was associated with lower reading skills (regression coefficient [β] = -5·86, 95% confidence interval [CI]: -11·11, -0·61, P = 0·029) and memory capacities (β = -0·86, 95% CI: -1·58, -0·15, P = 0·017). The interaction between T. gondii seropositivity and vitamin E significantly correlated with memory scores. In subgroup analysis, Toxoplasma-associated memory impairment was worse in children with lower serum vitamin E concentrations (β = -1·61, 95% CI: -2·44, -0·77, P < 0·001) than in those with higher values (β = -0·12, 95% CI: -1·23, 0·99, P = 0·83). In conclusion, Toxoplasma seropositivity may be associated with reading and memory impairments in school-aged children. Serum vitamin E seems to modify the relationship between the parasitic infection and memory deficiency.
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Vitamin B2 sensitizes cancer cells to vitamin C-induced apoptosis via modulation of Akt and Bad phosphorylation.

Vitamin B2 sensitizes cancer cells to vitamin C-induced apoptosis via modulation of Akt and Bad phosphorylation. | A Tale of Two Medicines | Scoop.it
Vitamin C is an essential dietary nutrient that has a variety of biological functions. Recent studies have provided promising evidence for its additional health benefits including anti-cancer activity. Vitamin B2, another essential dietary nutrient, is often coexisted with vitamin C in some fruits, vegetables or dietary supplements. The objective of the present study is to determine whether combination of vitamin C and B2 can achieve a synergistic anti-cancer activity. MDA-MB-231, MCF-7 and A549 cells were employed to evaluate the combinatory effects of vitamin C and B2. We found that combination of vitamin C and vitamin B2 resulted in a synergistic cell death induction in all cell lines tested. Further mechanistic investigations revealed that vitamin B2 sensitized cancer cells to vitamin C through inhibition of Akt and Bad phosphorylation. Our findings identified vitamin B2 as a promising sensitizer for improving the efficacy of vitamin C-based cancer chemoprevention and chemotherapy.
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Enhanced absorption and pharmacokinetics of fresh turmeric (Curcuma Longa L) derived curcuminoids in comparison with the standard curcumin from dried rhizomes

Despite the various attempts to overcome the poor oral bioavailability of curcuminoids isolated from dried turmeric, no attempt has so far been reported on fresh turmeric derived curcuminoids. Herein, we report a novel preparation of curcuminoids from fresh turmeric rhizomes (FTC) as amorphous water soluble stable powder and its enhanced absorption and pharmacokinetics in comparison with 95% pure curcuminoids isolated from dried turmeric (DTC). While the oral administration of FTC at 250 mg/kg body weight was found to offer significant levels of plasma curcumin in Wistar rats for longer duration, an equivalent dose of curcuminoids as DTC failed to produce detectable plasma levels. Dose dependent human studies (100, 250 and 1000 mg doses of FTC) also showed significant (p < 0.001) absorption of total curcuminoids (46-fold) and free unconjugated curcuminoids from FTC with improved pharmacokinetics as compared to equivalent doses of curcuminoids as DTC.
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MR-guided focused ultrasound (MRgFUS) ablation for the treatment of nonspinal osteoid osteoma: a prospective multicenter evaluation.

MR-guided focused ultrasound (MRgFUS) ablation for the treatment of nonspinal osteoid osteoma: a prospective multicenter evaluation. | A Tale of Two Medicines | Scoop.it

Magnetic resonance-guided focused ultrasound (MRgFUS) is a novel imaging-guided surgical technique that allows the performance of noninvasive and radiation-free ablation. Presently, computed tomography (CT)-guided radiofrequency ablation, a minimally invasive percutaneous technique, is the standard for treating symptomatic osteoid osteomas. The purpose of this study was to evaluate the use of MRgFUS ablation for the treatment of nonspinal osteoid osteomas in terms of technical success, complications, and clinical success through one year of follow-up.

In this prospective multicenter study, thirty consecutive patients with a nonspinal osteoid osteoma were enrolled between May 2010 and April 2012 at three different university centers; twenty-nine of the patients were treated with use of MRgFUS. Lesions had been previously diagnosed on the basis of imaging, including dynamic contrast-enhanced MR. The mean number of sonications and energy deposition were determined. Technical success was evaluated through an assessment of complications immediately after treatment. Clinical success was determined on the basis of pain reduction as measured with a visual analog scale (VAS), recurrence, and long-term complications through twelve months.

Technical success of MRgFUS was observed for all twenty-nine patients. The mean number of sonications (and standard deviation) was 7 ± 3, and the mean delivered acoustic energy was 1180 ± 736 J. At the twelve-month follow-up, complete clinical success was observed in twenty-six (90%) of the twenty-nine patients (95% confidence interval [CI] = 84 to 95; mean VAS, 0 ± 0 points). Partial success was observed in three (10%) of the twenty-nine patients (95% CI = 5 to 16; mean VAS score, 5 ± 0 points); two of these patients subsequently underwent CT-guided radiofrequency ablation, and one underwent open surgery. Pain score values showed a significant reduction (p < 0.001) between baseline (mean VAS score, 8 ± 1 points) and post treatment (mean VAS score, 1 ± 2 points). No complications were observed.

MRgFUS may be an effective and safe alternative approach in the treatment of nonspinal osteoid osteoma. A complete clinical success rate of 90% was demonstrated without adverse events. MRgFUS is totally noninvasive and eliminates radiation exposure.

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LSD-assisted psychotherapy for anxiety associated with a life-threatening disease: a qualitative study of acute and sustained subjective effects.

LSD-assisted psychotherapy for anxiety associated with a life-threatening disease: a qualitative study of acute and sustained subjective effects. | A Tale of Two Medicines | Scoop.it

A recently published study showed the safety and efficacy of LSD-assisted psychotherapy in patients with anxiety associated with life-threatening diseases. Participants of this study were included in a prospective follow-up.

12 months after finishing LSD psychotherapy, 10 participants were tested for anxiety (STAI) and participated in a semi-structured interview. A Qualitative Content Analysis (QCA) was carried out on the interviews to elaborate about LSD effects and lasting psychological changes.

None of the participants reported lasting adverse reactions. The significant benefits as measured with the STAI were sustained over a 12-month period. In the QCA participants consistently reported insightful, cathartic and interpersonal experiences, accompanied by a reduction in anxiety (77.8%) and a rise in quality of life (66.7%). Evaluations of subjective experiences suggest facilitated access to emotions, confrontation of previously unknown anxieties, worries, resources and intense emotional peak experiences à la Maslow as major psychological working mechanisms. The experiences created led to a restructuring of the person's emotional trust, situational understanding, habits and world view.

LSD administered in a medically supervised psychotherapeutic setting can be safe and generate lasting benefits in patients with a life-threatening disease. Explanatory models for the therapeutic effects of LSD warrant further study.

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Methanolic extract of Moringa oleifera leaves improves glucose tolerance, glycogen synthesis and lipid metabolism in alloxan-induced diabetic rats.

Methanolic extract of Moringa oleifera leaves improves glucose tolerance, glycogen synthesis and lipid metabolism in alloxan-induced diabetic rats. | A Tale of Two Medicines | Scoop.it

Glucose-lowering effects of Moringa oleifera extracts have been reported. However, the mechanism for its hypoglycemic effects is not yet understood. This study investigated the effect of oral administration of methanolic extracts of M. oleifera (MOLE) on glucose tolerance, glycogen synthesis, and lipid metabolism in rats with alloxan-induced diabetes.

MOLE was screened for key phytochemicals and its total flavonoids and phenolic contents were quantified. Diabetes was induced by intraperitoneal injection of 120 mg/kg BW alloxan. Normal and diabetic control rats received saline, while rats in other groups received 300 or 600 mg/kg body weight of MOLE or metformin (100 mg/kg body weight of metformin) for 6 weeks. Food intake and body weight were monitored throughout the experiment. Intraperitoneal glucose tolerance was assessed and serum glucose, insulin, and lipids were measured at the end of the experiment. Liver and muscle glycogen synthase activities, glycogen content, and glucose uptake were determined.

Administration of MOLE did not affect food intake but inhibited weight loss, significantly (p<0.01) improved glucose tolerance, and increased serum insulin levels by 1.3-1.7-fold (p<0.01). MOLE treatment significantly (p<0.001) reduced serum concentrations of triglyceride, total cholesterol, and low-density lipoprotein (LDL)-cholesterol and enhanced serum level of high-density lipoprotein (HDL) by 2.4- to 3.2-fold (p<0.001). Glycogen synthase activities and glycogen contents were higher in MOLE-treated rats compared with rats receiving metformin or saline and the extract improved glucose uptake by 49%-59% (p<0.01).

These results showed that hypoglycemic effects of MOLE might be mediated through the stimulation of insulin release leading to enhanced glucose uptake and glycogen synthesis.

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The anti-inflammatory activity of curcumin protects the genital mucosal epithelial barrier from disruption and blocks replication of HIV-1 and HSV-2.

Inflammation is a known mechanism that facilitates HIV acquisition and the spread of infection. In this study, we evaluated whether curcumin, a potent and safe anti-inflammatory compound, could be used to abrogate inflammatory processes that facilitate HIV-1 acquisition in the female genital tract (FGT) and contribute to HIV amplification. Primary, human genital epithelial cells (GECs) were pretreated with curcumin and exposed to HIV-1 or HIV glycoprotein 120 (gp120), both of which have been shown to disrupt epithelial tight junction proteins, including ZO-1 and occludin. Pre-treatment with curcumin prevented disruption of the mucosal barrier by maintaining ZO-1 and occludin expression and maintained trans-epithelial electric resistance across the genital epithelium. Curcumin pre-treatment also abrogated the gp120-mediated upregulation of the proinflammatory cytokines tumor necrosis factor-α and interleukin (IL)-6, which mediate barrier disruption, as well as the chemokines IL-8, RANTES and interferon gamma-induced protein-10 (IP-10), which are capable of recruiting HIV target cells to the FGT. GECs treated with curcumin and exposed to the sexually transmitted co-infecting microbes HSV-1, HSV-2 and Neisseria gonorrhoeae were unable to elicit innate inflammatory responses that indirectly induced activation of the HIV promoter and curcumin blocked Toll-like receptor (TLR)-mediated induction of HIV replication in chronically infected T-cells. Finally, curcumin treatment resulted in significantly decreased HIV-1 and HSV-2 replication in chronically infected T-cells and primary GECs, respectively. All together, our results suggest that the use of anti-inflammatory compounds such as curcumin may offer a viable alternative for the prevention and/or control of HIV replication in the FGT.
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Drug exposure in a metastatic human lung adenocarcinoma cell line gives rise to cells with differing adhesion, proliferation, and gene expression: Implications for cancer chemotherapy

Drug exposure in a metastatic human lung adenocarcinoma cell line gives rise to cells with differing adhesion, proliferation, and gene expression: Implications for cancer chemotherapy | A Tale of Two Medicines | Scoop.it
The Am1010 cell line was previously established from a metastatic deposit in an arm muscle from a patient with lung adenocarcinoma who had undergone four cycles of chemotherapy with cisplatin and taxol. Am1010 cells were labeled with red fluorescent protein or green fluorescent protein. A total of eight sublines were isolated following in vitro exposure to cisplatin or taxol. The sublines differed with regard to their adhesion and proliferation properties, with certain sublines exhibiting an increased proliferation rate and/or decreased surface adhesion. Gene expression assays demonstrated that tenascin C; cyclin D1; collagen, type 1, α2; integrin α1; related RAS viral (r‑ras) oncogene homolog 2; platelet‑derived growth factor C; and Src homolog 2 domain containing in the focal adhesion pathway, and intercellular adhesion molecule 1, F11 receptor, claudin 7 and cadherin 1 in the cell adhesion pathway, varied in expression among the sublines. The results of the present study suggested that drug exposure may alter the aggressiveness and metastatic potential of cancer cells, which has important implications for cancer chemotherapy.
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Activation of the SIRT1/p66shc antiapoptosis pathway via carnosic acid-induced inhibition of miR-34a protects rats against nonalcoholic fatty liver disease

Activation of the SIRT1/p66shc antiapoptosis pathway via carnosic acid-induced inhibition of miR-34a protects rats against nonalcoholic fatty liver disease | A Tale of Two Medicines | Scoop.it
Recent studies have demonstrated that miR-34a expression is significantly upregulated and associated with apoptosis in nonalcoholic fatty liver disease (NAFLD). Carnosic acid (CA) is a novel antioxidant and a potential inhibitor of apoptosis in organ injury, including liver injury. This study aimed to investigate the signaling mechanisms underlying miR-34a expression and the antiapoptotic effect of CA in NAFLD. CA treatment significantly reduced the high-fat diet (HFD)-induced elevations in aminotransferase activity as well as in serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and malondialdehyde (MDA) levels but increased serum high-density lipoprotein cholesterol (HDL-C) and hepatic superoxide dismutase (SOD) levels. Moreover, CA treatment ameliorated the increase in cleaved caspase-3 caused by HFD exposure and completely reversed the HFD-induced decreases in manganese superoxide dismutase (MnSOD) and B-cell lymphoma-extra large expression. CA also counteracted the HFD- or palmitic acid (PA)-induced increases in caspase-3 and caspase-9 activity. Mechanistically, CA reversed the HFD- or PA-induced upregulation of miR-34a, which is the best-characterized regulator of SIRT1. Importantly, the decrease in miR-34a expression was closely associated with the activation of the SIRT1/p66shc pathway, which attenuates hepatocyte apoptosis in liver ischemia/reperfusion injury. A dual luciferase assay in L02 cells validated the modulation of SIRT1 by CA, which occurs at least partly via miR-34a. In addition, miR-34a overexpression was significantly counteracted by CA, which prevented the miR-34a-dependent repression of the SIRT1/p66shc pathway and apoptosis. Collectively, our results support a link between liver cell apoptosis and the miR-34a/SIRT1/p66shc pathway, which can be modulated by CA in NAFLD.
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Link between inflammation and cancer

Link between inflammation and cancer | A Tale of Two Medicines | Scoop.it
Each of us has a calculable risk of cancer, but beyond the misfortune of actually developing cancer, the precision of these estimates is very low. You may hear that you ‘have a 20 percent – 50 percent chance’ of developing a particular type of cancer in your lifetime based on your family history and lifestyle factors. Or you may hear a rather unhelpful statistic such as ‘you have about a 50 percent risk’ of developing [fill in the blank] cancer. So basically there is a coin flip’s chance (50/50) that you may develop this type of cancer. Or that you won’t. These are enormously broad population-scale likelihoods, and if applied to a group of say 10,000 people, it means that 5,000 (+/-) will develop that particular cancer. But also that 5,000 people (+/-) won’t.
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Stabilisation of Laryngeal AL Amyloidosis with Long Term Curcumin Therapy

Multiple myeloma (MM), smoldering myeloma (SMM), and monoclonal gammopathy of undetermined significance (MGUS) represent a spectrum of plasma cell dyscrasias (PCDs). Immunoglobulin light chain amyloidosis (AL) falls within the spectrum of these diseases and has a mortality rate of more than 80% within 2 years of diagnosis. Curcumin, derived from turmeric, has been shown to have a clinical benefit in some patients with PCDs. In addition to a clinical benefit in these patients, curcumin has been found to have a strong affinity for fibrillar amyloid proteins. We thus administered curcumin to a patient with laryngeal amyloidosis and smoldering myeloma and found that the patient has shown a lack of progression of his disease for a period of five years. This is in keeping with our previous findings of clinical benefits of curcumin in patients with plasma cell dyscrasias. We recommend further evaluation of curcumin in patients with primary AL amyloidosis.

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Dietary γ-Tocopherol Rich Mixture Inhibits Estrogen-Induced Mammary Tumorigenesis by Modulating Estrogen Metabolism, Antioxidant Response and PPARγ.

Dietary γ-Tocopherol Rich Mixture Inhibits Estrogen-Induced Mammary Tumorigenesis by Modulating Estrogen Metabolism, Antioxidant Response and PPARγ. | A Tale of Two Medicines | Scoop.it
This study evaluated the anti-cancer activity and mechanism of action of a γ-tocopherol rich tocopherol mixture, γ-TmT, in two different animal models of estrogen-induced breast cancer. The chemopreventive effect of γ-TmT at early (6 weeks), intermediate (18 weeks) and late (31 weeks) stages of mammary tumorigenesis was determined using the ACI rat model. Female rats receiving 17β-estradiol (E2) implants were administered with different doses (0, 0.05%, 0.1%, 0.3% and 0.5%) of γ-TmT diet. Treatment with 0.3% and 0.5% γ-TmT decreased tumor volume and multiplicity. At 31 weeks, serum concentrations of E2 were significantly decreased by γ-TmT. γ-TmT preferentially induced expression of the E2 metabolizing enzyme CYP1A1, over CYP1B1 in the rat mammary tissues. Nrf2-dependent antioxidant response was stimulated by γ-TmT, as evident from enhanced expression of its downstream targets, NQO1, GCLM and HMOX1. Serum concentrations of the oxidative stress marker, 8-isoprostane, were also decreased in the γ-TmT treated groups. Treatment with γ-TmT increased expression of PPARγ and its downstream genes, PTEN and p27, while the cell proliferation marker, PCNA, was significantly reduced in γ-TmT treated mammary tumors. In an orthotopic model in which human MCF-7 breast cancer cells were injected into the mammary fat pad of immunodeficient mice, γ-TmT inhibited E2-dependent tumor growth at all the doses tested. In conclusion, γ-TmT reduced mammary tumor development, in part through decreased E2 availability and reduced oxidative stress in mammary tissues; γ-TmT could thus be an effective agent for the prevention and treatment of E2-induced breast cancer.
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Curcumin reverses cisplatin resistance in cisplatin-resistant lung caner cells by inhibiting FA/BRCA pathway.

Curcumin reverses cisplatin resistance in cisplatin-resistant lung caner cells by inhibiting FA/BRCA pathway. | A Tale of Two Medicines | Scoop.it
Cisplatin (DDP) is the most widely used chemotherapy agent for treatment of malignancies including lung cancer. However, the effectiveness of DDP is often weakened by acquired resistance of tumor cells. DDP kills cancer cells primarily by creating intrastrand and interstrand DNA cross-links, which block DNA replication. The Fanconi anemia (FA)/BRCA pathway is a DNA cross-link damage repair pathway, which regulates cellular resistance to DNA cross-link agents, such as DDP. Some study has shown that natural compound curcumin sensitize human ovarian and breast cancer cells to DDP. However, whether curcumin may reverse resistance to DDP in DDP-resistant lung cancer cells has not been understood. In this study, we showed that curcumin enhanced the proliferation inhibitory effect of DDP and promote DDP-induced apoptosis in A549/DDP cells (DDP-resistant lung adenocarcinoma cells). Moreover, we observed that FA/BRCA pathway DNA damage repair processes, such as DDP-induced FANCD2 monoubiquitination and nuclear foci formation were downregulated in the presence of curcumin, suggesting that curcumin enhanced sensitivity to DDP in A549/DDP cells through the inhibition of FA/BRCA pathway. Furthermore, the calculation of q value and apoptosis analyses revealed that curcumin in combination with DDP could exert a synergistic cytotoxic effect in A549/DDP cells, further demonstrating that curcumin can reverse cisplatin resistance of A549/DDP cells. In conclusion, by suppressing the FA/BRCA pathway DNA repair, curcumin potentiates DDP-induced proliferation inhibitory effect and apoptosis in A549/DDP cell, indicating that curcumin may serve as a chemosensitizer to cross-link-inducing anticancer drugs DDP.
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Resveratrol and curcumin enhance pancreatic β-cell function by inhibiting phosphodiesterase activity

Resveratrol and curcumin enhance pancreatic β-cell function by inhibiting phosphodiesterase activity | A Tale of Two Medicines | Scoop.it
Resveratrol (RES) and curcumin (CUR) are polyphenols that are found in fruits and turmeric, and possess medicinal properties that are beneficial in various diseases, such as heart disease, cancer, and type 2 diabetes mellitus (T2DM). Results from recent studies have indicated that their therapeutic properties can be attributed to their anti-inflammatory effects. Owing to reports stating that they protect against β-cell dysfunction, we studied their mechanism(s) of action in β-cells. In T2DM, cAMP plays a critical role in glucose- and incretin-stimulated insulin secretion as well as overall pancreatic β-cell health. A potential therapeutic target in the management of T2DM lies in regulating the activity of phosphodiesterases (PDEs), which degrade cAMP. Both RES and CUR have been reported to act as PDE inhibitors in various cell types, but it remains unknown if they do so in pancreatic β-cells. In our current study, we found that both RES (0.1–10 μmol/l) and CUR (1–100 pmol/l)-regulated insulin secretion under glucose-stimulated conditions. Additionally, treating β-cell lines and human islets with these polyphenols led to increased intracellular cAMP levels in a manner similar to 3-isobutyl-1-methylxanthine, a classic PDE inhibitor. When we investigated the effects of RES and CUR on PDEs, we found that treatment significantly downregulated the mRNA expression of most of the 11 PDE isozymes, including PDE3B, PDE8A, and PDE10A, which have been linked previously to regulation of insulin secretion in islets. Furthermore, RES and CUR inhibited PDE activity in a dose-dependent manner in β-cell lines and human islets. Collectively, we demonstrate a novel role for natural-occurring polyphenols as PDE inhibitors that enhance pancreatic β-cell function.
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Effect of vitamin C on inflammation and metabolic markers in hypertensive and/or diabetic obese adults

Effect of vitamin C on inflammation and metabolic markers in hypertensive and/or diabetic obese adults | A Tale of Two Medicines | Scoop.it
At baseline of the randomization process, we proved the balance between the groups to be approximate equality in terms of patient demographics and clinical variables. None of the patients’ characteristics violated this, so equality was assumed in all aspects. The strength of our study lies in the comparison between the experimental and control groups at the end point of the study. As far as we are aware, no previous studies have been interested in evaluating comparisons of the clinical efficacy of vitamin C, while the majority have been interested in within-group before and after tests only. Our results indicate a clear effect of 1 g of vitamin C in alleviating inflammatory markers (hs-CRP and IL-6) among hypertensive and/or diabetic obese adults. Also, vitamin C strongly affected the level of FBG, significantly reducing it after 8 weeks of daily intake. For the lipid-profile variables TC and TG, our results are consistent with those of Afkhami-Ardekani and Shojaoddiny-Ardekani38 who found a positive effect of vitamin C on TG but no effect on TC.

We found that a moderate amount of vitamin C can significantly treat and reduce the inflammation, as measured by hs-CRP and IL-6, in hypertensive and/or diabetic adults and also helps to reduce FBG levels. Additional studies of different durations are needed to further explore the role of vitamin C in the lipid profile.
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Dose-response associations between cycling activity and risk of hypertension in regular cyclists: The UK Cycling for Health Study

Dose-response associations between cycling activity and risk of hypertension in regular cyclists: The UK Cycling for Health Study | A Tale of Two Medicines | Scoop.it
Most population studies on physical activity and health have involved largely inactive men and women, thus making it difficult to infer if health benefits occur at exercise levels above the current minimum guidelines. The aim was to examine associations between cycling volume and classical cardiovascular risk markers, including hypertension and hypercholesterolemia, in a population sample of habitual cyclists. A nationwide sample comprising 6949 men and women (aged 47.6 years on average) completed questions about their cycling levels, demographics and health. Nearly the entire sample (96.3%) achieved the current minimum physical activity recommendation through cycling alone. There was a dose–response association between cycling volume and risk of diagnosed hypertension (P-trend =0.001), with odds ratios of 0.98 (95% confidence interval (CI), 0.80–1.21), 0.86 (0.70, 1.06), 0.67 (95% CI, 0.53–0.83) across categories of 23–40, 40–61 and >61 metabolic equivalent hours/week (MET-h/week) compared with <23 MET-h/week. These associations persisted in models adjusted for age, sex, smoking, alcohol, body mass index (BMI) and other moderatevigorous physical activities. We also observed inverse associations between cycling volume and other risk factors including BMI and hypercholesterolemia. In summary, results from a population sample of cyclists suggest that additional cardiovascular health benefits can be achieved beyond the current minimum physical activity recommendation.
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