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Cannabis Extracts Rich In Cannabidiol (CBD) May Effectively Treat Colon Cancer.

Cannabis Extracts Rich In Cannabidiol (CBD) May Effectively Treat Colon Cancer. | A Tale of Two Medicines | Scoop.it

 

Cannabidiol (CBD) seems to carry less of a stigma than tetrahydrocannabinol (THC), a psychoactive cannabinoid that is credited with the “high” associated with cannabis, and shows promise as a way to treat a variety of cancers. In turn, CBD has received a great deal of attention in recent years.

 

Now, a team of researchers from Italy and the UK report that cannabis extracts high in cannabidiol (CBD) can help prevent the genesis and spread of colon cancer in mice. Their study was published in Phytomedicine December 27.

 

According to their results, a “botanical drug substance” (BDS) with high levels of cannabidiol (CBD) inhibited the growth of tumor cells, but not healthy ones. The researchers determined that this action was mediated by activation of the cells’ CB1 and CB2 receptors.

 

Also investigated in the study was the effect of pure cannabidiol (CBD) on colon cancer. According to the data collected, pure CBD inhibited tumor growth also. Interestingly, it did so through activation of the CB1 receptors only.

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Christian Yamashiba Kasongo's curator insight, January 18, 2014 4:09 PM

Cannabis Extracts Rich In Cannabidiol (CBD) May Effectively Treat Colon Cancer.

Christian Yamashiba Kasongo's curator insight, January 20, 2014 12:30 AM

Cannabis Extracts Rich In Cannabidiol (CBD) May Effectively Treat Colon Cancer.

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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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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 

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Heart palpitation relief with Melissa officinalis leaf extract: double blind, randomized, placebo controlled trial of efficacy and safety.

Heart palpitation relief with Melissa officinalis leaf extract: double blind, randomized, placebo controlled trial of efficacy and safety. | A Tale of Two Medicines | Scoop.it

In Traditional Iranian Medicine (TIM), Melissa officinalis L. is commonly regarded as an effective therapy for heart palpitations.

Heart palpitation is a common complaint that is often benign and associated with a marked distress that makes the condition difficult to treat. Herbal medicines provide an alternative to conventional drugs for treating various kinds of diseases. This study was done as a double blind randomized placebo-controlled clinical trial to evaluate the efficacy and safety of the dried extract of M. officinalis on adults suffering from benign palpitations.

Eligible volunteers were randomly assigned as outpatients to a 14 day treatment with 500 mg twice a day of lyophilized aqueous extract of M. officinalis leaves (or placebo). Participants in the tests, physicians and researchers were blind to group assignments. Both primary and secondary outcomes were patient-reported. Primary outcomes were obtained from two measures: mean frequency of palpitation episodes per week, derived from patients׳ diaries, and mean intensity of palpitation estimated through Visual Analogue Scale (VAS) in a self-report questionnaire. Psychiatric symptoms (somatization, anxiety and insomnia, social dysfunction and severe depression) were evaluated as secondary outcomes by General Health Questionnaire-28 (GHQ-28), before and after intervention.

Fifty-five volunteers out of 71 recruited study subjects completed the trial. Results showed that 14-day of treatment with lyophilized aqueous extract of M. officinalis leaves reduced frequency of palpitation episodes and significantly reduced the number of anxious patients in comparison to the placebo (P=0.0001, P=0.004 resp.). Also, M. officinalis extract showed no indication of any serious side effects.

Lyophilized aqueous extract of M. officinalis leaves may be a proper and safe herbal drug for the treatment of benign palpitations.

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Senile hair graying: H2O2-mediated oxidative stress affects human hair color by blunting methionine sulfoxide repair

Senile graying of human hair has been the subject of intense research since ancient times. Reactive oxygen species have been implicated in hair follicle melanocyte apoptosis and DNA damage. Here we show for the first time by FT-Raman spectroscopy in vivo that human gray/white scalp hair shafts accumulate hydrogen peroxide (H2O2) in millimolar concentrations. Moreover, we demonstrate almost absent catalase and methionine sulfoxide reductase A and B protein expression via immunofluorescence and Western blot in association with a functional loss of methionine sulfoxide (Met-S=O) repair in the entire gray hair follicle. Accordingly, Met-S=O formation of Met residues, including Met 374 in the active site of tyrosinase, the key enzyme in melanogenesis, limits enzyme functionality, as evidenced by FT-Raman spectroscopy, computer simulation, and enzyme kinetics, which leads to gradual loss of hair color. Notably, under in vitro conditions, Met oxidation can be prevented by l-methionine. In summary, our data feed the long-voiced, but insufficiently proven, concept of H2O2-induced oxidative damage in the entire human hair follicle, inclusive of the hair shaft, as a key element in senile hair graying, which does not exclusively affect follicle melanocytes. This new insight could open new strategies for intervention and reversal of the hair graying process.

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Antioxidant Vitamin C Prevents Decline in Endothelial Function during Sitting

Antioxidant Vitamin C Prevents Decline in Endothelial Function during Sitting | A Tale of Two Medicines | Scoop.it
Three hours of sitting leads to a significant decline in endothelial function, most likely through an oxidative stress mechanism. Sitting is a common activity of modern human beings. Repeated sitting sessions may lead to chronically altered shear patterns, oxidative stress, endothelial dysfunction, and a predisposition to atherosclerosis. With the prevalence of sedentary behavior increasing, vitamin C as a regular supplement taken during the seated sessions may play a role in maintaining vascular health in the inactive population.
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Stress Hormone Causes Epigenetic Changes.

Stress Hormone Causes Epigenetic Changes. | A Tale of Two Medicines | Scoop.it

Researchers found that chronic exposure to a stress hormone causes modifications to DNA in the brains of mice, prompting changes in gene expression. The new finding provides clues into how chronic stress might affect human behavior.

 

During stressful situations, we produce steroid hormones called glucocorticoids that affect many systems throughout the body. These effects are mediated by the hypothalamic-pituitary-adrenal (HPA) axis, a network involving the hypothalamus and pituitary gland in the brain and the adrenal glands near the kidneys

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EmmanuelGrunenberger's curator insight, May 19, 10:36 AM

Remember to relax. Mindfulness Stress reduction can be an option.

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An anthocyanin-rich extract from Kamchatka honeysuckle increases enzymatic activity within the gut and ameliorates abnormal lipid and glucose metabolism in rats.

An anthocyanin-rich extract from Kamchatka honeysuckle increases enzymatic activity within the gut and ameliorates abnormal lipid and glucose metabolism in rats. | A Tale of Two Medicines | Scoop.it

The berries of blue honeysuckle (Lonicera caerulea L.), including an edible Kamchatka variety (var. kamtschatica Sevast.), are a potential but relatively unknown source of anthocyanins, which are thought to have favorable effects on diabetes and cardiovascular disease (CVD). The aim of this study was to examine whether the dietary addition of a Kamchatka honeysuckle berry extract (KHBE, 327 mg anthocyanins/g) is able to limit the disorders related to these diseases induced by a high-fructose diet in rats.

 

The experiment was conducted using 24 adult male Wistar rats distributed into 3 groups of 8 animals each and fed semipurified casein diets differentiated by the carbohydrate source for 4 wk, as follows: a control cornstarch diet (681 g/kg) or a high-fructose diet (633 g/kg), with or without the addition of KHBE (2 g/kg).

 

The mucosal lactase activity in the small intestine was increased in the rats fed the KHBE-containing diet compared with the rats fed the control diet. In the cecal digesta, the dietary KHBE considerably increased bacterial α- and β-glucosidase activity. Furthermore, hyperlipidemia, hyperinsulinemia, insulin resistance, and impaired glucose tolerance were detected in the rats fed the high-fructose diet. The dietary KHBE normalized the plasma triglyceride concentration and atherogenicity, whereas plasma non-HDL cholesterol, insulin concentration, and insulin resistance were ameliorated to levels comparable with the rats fed the control diet.

 

An anthocyanin-rich Kamchatka honeysuckle berry extract supplemented to an unbalanced diet is able to ameliorate the disturbances in lipid and glucose metabolism that are the fundamental risk factors for CVD and diabetes. Moreover, the extract stimulates enzymatic activity within the gut that seems to be related to the metabolism of polyphenols.

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Reactive oxygen species-mediated therapeutic response and resistance in glioblastoma

Reactive oxygen species-mediated therapeutic response and resistance in glioblastoma | A Tale of Two Medicines | Scoop.it
Glioblastoma (GBM) resistance to therapy is the most common cause of tumor recurrence, which is ultimately fatal in 90% of the patients 5 years after initial diagnosis. A sub-population of tumor cells with stem-like properties, glioma stem cells (GSCs), is specifically endowed to resist or adapt to the standard therapies, leading to therapeutic resistance. Several anticancer agents, collectively termed redox therapeutics, act by increasing intracellular levels of reactive oxygen species (ROS). In this study, we investigated mechanisms underlying GSC response and resistance to cannabidiol (CBD), a non-toxic, non-psychoactive cannabinoid and redox modulator. Using primary GSCs, we showed that CBD induced a robust increase in ROS, which led to the inhibition of cell survival, phosphorylated (p)-AKT, self-renewal and a significant increase in the survival of GSC-bearing mice. Inhibition of self-renewal was mediated by the activation of the p-p38 pathway and downregulation of key stem cell regulators Sox2, Id1 and p-STAT3. Following CBD treatment, a subset of GSC successfully adapted, leading to tumor regrowth. Microarray, Taqman and functional assays revealed that therapeutic resistance was mediated by enhanced expression of the antioxidant response system Xc catalytic subunit xCT (SLC7A11 (solute carrier family 7 (anionic amino-acid transporter light chain), member 11)) and ROS-dependent upregulation of mesenchymal (MES) markers with concomitant downregulation of proneural (PN) markers, also known as PN–MES transition. This ‘reprogramming’ of GSCs occurred in culture and in vivo and was partially due to activation of the NFE2L2 (NRF2 (nuclear factor, erythroid 2-like)) transcriptional network. Using genetic knockdown and pharmacological inhibitors of SLC7A11, we demonstrated that combining CBD treatment with the inhibition of system Xc resulted in synergistic ROS increase leading to robust antitumor effects, that is, decreased GSC survival, self-renewal, and invasion. Our investigation provides novel mechanistic insights into the antitumor activity of redox therapeutics and suggests that combinatorial approaches using small molecule modulators of ROS offer therapeutic benefits in GBM.
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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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A dietary pattern rich in lignans, quercetin and resveratrol decreases the risk of oesophageal cancer.

A dietary pattern rich in lignans, quercetin and resveratrol decreases the risk of oesophageal cancer. | A Tale of Two Medicines | Scoop.it
Dietary lignans, quercetin and resveratrol have oestrogenic properties, and animal studies suggest that they synergistically decrease cancer risk. A protective effect of lignans on the development of oesophageal cancer in humans has recently been demonstrated, and the present study aimed to test whether these three phytochemicals synergistically decrease the risk of oesophageal cancer. Data from a Swedish nationwide population-based case-control study that recruited 181 cases of oesophageal adenocarcinoma (OAC), 158 cases of oesophageal squamous-cell carcinoma (OSCC), 255 cases of gastro-oesophageal junctional adenocarcinoma (JAC) and 806 controls were analysed. Exposure data were collected through face-to-face interviews and questionnaires. The intake of lignans, quercetin and resveratrol was assessed using a sixty-three-item FFQ. Reduced-rank regression was used to assess a dietary pattern, and a simplified dietary pattern score was categorised into quintiles on the basis of the distribution among the control subjects. Unconditional multivariable logistic regression provided OR with 95% CI, adjusted for all the potential risk factors. A dietary pattern rich in lignans, quercetin and resveratrol was mainly characterised by a high intake of tea, wine, lettuce, mixed vegetables, tomatoes, and whole-grain bread and a low intake of milk. There were dose-dependent associations between simplified dietary pattern scores and all types of oesophageal cancer (all P for trend < 0.05). On comparing the highest quintiles with the lowest, the adjusted OR were found to be 0.24 (95% CI 0.12, 0.49) for OAC, 0.31 (95% CI 0.15, 0.65) for OSCC, and 0.49 (95% CI 0.28, 0.84) for JAC. The results of the present study indicate that a dietary pattern characterised by the intake of lignans, quercetin and resveratrol may play a protective role in the development of oesophageal cancer in the Swedish population.
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Evidence of an Epigenetic Modification in Cell-cycle Arrest Caused by the Use of Ultra-highly-diluted Gonolobus Condurango Extract

Evidence of an Epigenetic Modification in Cell-cycle Arrest Caused by the Use of Ultra-highly-diluted Gonolobus Condurango Extract | A Tale of Two Medicines | Scoop.it

Our earlier works revealed quite clearly that certain ultra-highly-diluted homeopathy remedies were capable of altering gene expressions while the succussed alcohol (placebos) invariably failed to do so; however, the precise molecular mechanisms behind successful gene alterations caused by using potentized homeopathic remedies still remain largely unknown. Therefore, the present findings are quite significant because we have demonstrated for the first time that an ultra-highly-diluted remedy can have affect one of the key regulatory machineries of gene expression, namely, the acetylation/deacetylation mechanism of histone core protein. HeLa cells, known for their high level of HDAC activity, can actually serve as a model system for testing the ability of any drug in epigenetic modification because any agent that can alter the process of deacetylation can also be considered as having a significant and direct role in the regulation of the gene expression. In this study, ultra-highly-diluted Condurango 30C showed a potential for modulating the histone deacetylase enzyme. Correspondingly, another known fact is that when an agent is capable of suppressing deacetylation activity, it can also block the synthesis of nuclear DNA. In this study, low-dose Condurango 30C treatment lowered the cell population at the S-phase, thus indicating a reduced synthesis of DNA.

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Ingestion of coffee polyphenols increases postprandial release of the active glucagon-like peptide-1 (GLP-1(7–36)) amide in C...

Ingestion of coffee polyphenols increases postprandial release of the active glucagon-like peptide-1 (GLP-1(7–36)) amide in C... | A Tale of Two Medicines | Scoop.it
The widespread prevalence of diabetes, caused by impaired insulin secretion and insulin resistance, is now a worldwide health problem. Glucagon-like peptide 1 (GLP-1) is a major intestinal hormone that stimulates glucose-induced insulin secretion from β cells. Prolonged activation of the GLP-1 signal has been shown to attenuate diabetes in animals and human subjects. Therefore, GLP-1 secretagogues are attractive targets for the treatment of diabetes. Recent epidemiological studies have reported that an increase in daily coffee consumption lowers diabetes risk. The present study examined the hypothesis that the reduction in diabetes risk associated with coffee consumption may be mediated by the stimulation of GLP-1 release by coffee polyphenol extract (CPE). GLP-1 secretion by human enteroendocrine NCI-H716 cells was augmented in a dose-dependent manner by the addition of CPE, and was compatible with the increase in observed active GLP-1(7–36) amide levels in the portal blood after administration with CPE alone in mice. CPE increased intracellular cyclic AMP (cAMP) levels in a dose-dependent manner, but this was not mediated by G protein-coupled receptor 119 (GPR119). The oral administration of CPE increased diet (starch and glyceryl trioleate)-induced active GLP-1 secretion and decreased glucose-dependent insulinotropic polypeptide release. Although CPE administration did not affect diet-induced insulin secretion, it decreased postprandial hyperglycaemia, which indicates that higher GLP-1 levels after the ingestion of CPE may improve insulin sensitivity. We conclude that dietary coffee polyphenols augment gut-derived active GLP-1 secretion via the cAMP-dependent pathway, which may contribute to the reduced risk of type 2 diabetes associated with daily coffee consumption.
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EmmanuelGrunenberger's curator insight, May 19, 10:40 AM

Coffee is good for diabetic patints through action on glucagon-like peptide-1

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Dietary Supplementation of Walnut Partially Reverses 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine Induced Neurodegeneration in a Mouse Model of Parkinson's Disease.

Dietary Supplementation of Walnut Partially Reverses 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine Induced Neurodegeneration in a Mouse Model of Parkinson's Disease. | A Tale of Two Medicines | Scoop.it
Numerous studies indicating that natural plant sources and their active phytochemicals offer protection to the pathological processes related to the development of neurogenerative diseases including Parkinson's disease (PD). In the present study, the neuro protective efficacy of dietary supplementation of walnut (6 %) for 28 days was examined in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (i.p., 20 mg/kg body weight/day) for last four consecutive days. MPTP injection diminished the levels of GSH, dopamine and metabolites along with decreased activities of GPx and mitochondrial complex I. Further, the levels of TBARS and enzymatic antioxidants such as SOD and catalase, MAO-B activities were enhanced by MPTP treatment. Behavioral deficits and lowered TH expression are also proved MPTP induced neurotoxicity. Dietary supplementation of walnut attenuated MPTP-induced impairment in PD mice might be by its MAO-B inhibitory, antioxidant and mitochondrial protective actions. To find out the exact mechanism of action walnut on PD mice warrants further extensive studies.
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The Role of Grape Seed Extract in the Treatment of Chemo/Radiotherapy Induced Toxicity: A Systematic Review of Preclinical Studies.

The Role of Grape Seed Extract in the Treatment of Chemo/Radiotherapy Induced Toxicity: A Systematic Review of Preclinical Studies. | A Tale of Two Medicines | Scoop.it
Grapes are one of the most consumed fruits in the world and are rich in polyphenols. Grape seed proanthocyanidins (GSP) have demonstrated chemopreventive and/or chemotherapeutic effects in various cancer cell cultures and animal models. The clinical efficacy of chemotherapy is often limited by its adverse effects. Several studies show that reactive oxygen species mediate the cardiotoxicity and neurotoxicity induced by various cancer chemotherapeutic agents. This implies that concomitant administration of antioxidants may prevent these adverse effects. The review was carried out in accordance with the PRISMA guidelines. An electronic search strategy in Medline and Embase databases was conducted. Of the 41 studies reviewed, 27 studied GSP while the remainder (14) studied grape seed or skin extracts (GSE). All the studies were published in English, except 2 in Chinese. A significant percentage (34%) of the studies we reviewed assessed the effect of GSE or GSP on cardiotoxicity induced by chemotherapy. Doxorubicin was the most common chemotherapeutic drug studied followed by cisplatin. Research studies that assessed the effect of GSE or GSP on radiation treatment accounted for 22% of the articles reviewed. GSE/GSP ameliorates some of the cytotoxic effects on normal cells/tissues induced by chemo/radiotherapy.
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