A Tale of Two Medicines
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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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Effectiveness of Stevia Rebaudiana Whole Leaf Extract Against the Various Morphological Forms of Borrelia Burgdorferi in Vitro

Effectiveness of Stevia Rebaudiana Whole Leaf Extract Against the Various Morphological Forms of Borrelia Burgdorferi in Vitro | A Tale of Two Medicines | Scoop.it
Lyme disease is a tick-borne multisystemic disease caused by Borrelia burgdorferi. Administering antibiotics is the primary treatment for this disease; however, relapse often occurs when antibiotic treatment is discontinued. The reason for relapse remains unknown, but recent studies suggested the possibilities of the presence of antibiotic resistant Borrelia persister cells and biofilms.

In this study, we evaluated the effectiveness of whole leaf Stevia extract against B. burgdorferi spirochetes, persisters, and biofilm forms in vitro. The susceptibility of the different forms was evaluated by various quantitative techniques in addition to different microscopy methods. The effectiveness of Stevia was compared to doxycycline, cefoperazone, daptomycin, and their combinations. Our results demonstrated that Stevia had significant effect in eliminating B. burgdorferi spirochetes and persisters. Subculture experiments with Stevia and antibiotics treated cells were established for 7 and 14 days yielding, no and 10% viable cells, respectively compared to the above-mentioned antibiotics and antibiotic combination. When Stevia and the three antibiotics were tested against attached biofilms, Stevia significantly reduced B. burgdorferi forms. Results from this study suggest that a natural product such as Stevia leaf extract could be considered as an effective agent against B. burgdorferi.
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Removal of 16 pesticide residues from strawberries by washing with tap and ozone water, ultrasonic cleaning and boiling

Removal of 16 pesticide residues from strawberries by washing with tap and ozone water, ultrasonic cleaning and boiling | A Tale of Two Medicines | Scoop.it
The effects of washing with tap and ozone water, ultrasonic cleaning and boiling on 16 pesticide (ten fungicides and six insecticides) residue levels in raw strawberries were investigated at different processing times (1, 2 and 5 min). An analysis of these pesticides was conducted using gas chromatography with nitrogen-phosphorous and electron capture detection (GC-NPD/ECD). The processing factor (PF) for each pesticide in each processing technique was determined. Washing with ozonated water was demonstrated to be more effective (reduction from 36.1 to 75.1 %) than washing with tap water (reduction from 19.8 to 68.1 %). Boiling decreased the residues of the most compounds, with reductions ranging from 42.8 to 92.9 %. Ultrasonic cleaning lowered residues for all analysed pesticides with removal of up to 91.2 %. The data indicated that ultrasonic cleaning and boiling were the most effective treatments for the reduction of 16 pesticide residues in raw strawberries, resulting in a lower health risk exposure. Calculated PFs for alpha-cypermethrin were used to perform an acute risk assessment of dietary exposure. To investigate the relationship between the levels of 16 pesticides in strawberry samples and their physicochemical properties, a principal component analysis (PCA) was performed.
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Expression and/or activity of the SVCT2 ascorbate transporter may be decreased in many aggressive cancers, suggesting potential utility for sodium bicarbonate and dehydroascorbic acid in cancer the...

Expression and/or activity of the SVCT2 ascorbate transporter may be decreased in many aggressive cancers, suggesting potential utility for sodium bicarbonate and dehydroascorbic acid in cancer the... | A Tale of Two Medicines | Scoop.it
Hypoxia-inducible factor-1 (HIF-1) is a heterodimer transcription factor whose elevated activity in many cancers helps them to survive under hypoxic conditions and enhances their capacity to grow invasively, establish metastases, and survive chemo- or radiotherapy. Optimal intracellular levels of ascorbate suppress the level and transcriptional activity of HIF-1under normoxic or mildly hypoxic conditions by supporting the activity of proly and asparagyl hydroxylases that target HIF-1alpha. High intracellular ascorbate can also work in various ways to down-regulate activation of NF-kappaB which, like HIF-1 is constitutively active in many cancers and promotes aggressive behavior - in part by promoting transcription of HIF-1alpha. Yet recent evidence suggests that, even in the context of adequate ascorbate nutrition, the intracellular ascorbate content of many aggressive cancers may be supoptimal for effective HIF-1 control. This likely reflects low expression or activity of the SVCT2 ascorbate transporter. The expression of SVCT2 in cancers has so far received little study; but the extracellular acidity characteristic of many tumors would be expected to reduce the activity of this transporter, which has a mildly alkaline pH optimum. Unfortunately, since SVCT2 has a high affinity for ascorbate, and its activity is nearly saturated at normal healthy serum levels of this vitamin, increased oral administration of ascorbate would be unlikely to have much impact on the intracellular ascorbate content of tumors. However, cancers in which HIF-1 is active express high levels of glucose transporters such as GLUT-1, and these transporters can promote influx of dehydroascorbic acid (DHA) via facilitated diffusion; once inside the cell, DHA is rapidly reduced to ascorbate, which effectively is "trapped" within the cell. Hence, episodic intravenous infusions of modest doses of DHA may have potential for optimizing the intracellular ascorbate content of cancers, potentially rendering them less aggressive. Indeed, several published studies have concluded that parenteral DHA--sometimes in quite modest doses--can retard the growth of transplanted tumors in rodents. As an alternative or adjunctive strategy, oral administration of sodium bicarbonate, by normalizing the extracellular pH of tumors, has the potential to boost the activity of SCTV2 in tumor cells, thereby promoting increased ascorbate uptake. Indeed, the utility of oral sodium bicarbonate for suppressing metastasis formation in nude mice xenografted with a human breast cancer has been reported. Hence, oral sodium bicarbonate and intravenous DHA may have the potential to blunt the aggressiveness of certain cancers in which suboptimal intracellular ascorbate levels contribute to elevated HIF-1 activity.
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The possible roles of vitamin D and curcumin in treating gonorrhea.

The possible roles of vitamin D and curcumin in treating gonorrhea. | A Tale of Two Medicines | Scoop.it
Drug-resistant gonorrhea, Neisseria gonorrhoeae (N. gonorrhoeae), is an emerging concern, especially because the risk of bladder cancer is associated with this infection. N. gonorrhoeae suppresses T-helper 1(Th1) and Th2 responses and enhances Th17 responses via a mechanism involving transforming growth factor-beta (TGF-β) and regulatory T cells. Blockade of TGF-β alleviates the suppression of specific anti-gonococcal responses and allows Th1 and Th2 responses to emerge with concomitant boosting of immune memory and protective immunity. Gonorrhea activates nuclear factor kappaB (NF-kappaB), which plays a critical role in signal-transduction pathways involved in inflammation. The innate immune system can eventually clear gonorrhea. Vitamin D is emerging as a potential, powerful, anti-microbial agent with these effects: it supports the innate immune system in combating bacterial infections; it decreases levels of TGF-β and NF-kappaB activation; and it induces production of LL-37 (cathelicidin), which has antimicrobial and antiendotoxin properties. In addition, via an independent vitamin D receptor pathway, curcumin also induces LL-37 production, inhibiting N. gonorrhoeae-induced NF-kappaB signaling and inducing autophagy. Therefore, vitamin D and curcumin taken together may be useful in combating both normal and drug-resistant gonorrhea. Moreover, the possible synergy between these two agents in improving outcomes is worthy of additional investigation.
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The Transient Receptor Potential Melastatin 2 (TRPM2) Channel Contributes to β-Amyloid Oligomer-Related Neurotoxicity and Memory Impairment.

The Transient Receptor Potential Melastatin 2 (TRPM2) Channel Contributes to β-Amyloid Oligomer-Related Neurotoxicity and Memory Impairment. | A Tale of Two Medicines | Scoop.it
In Alzheimer's disease, accumulation of soluble oligomers of β-amyloid peptide is known to be highly toxic, causing disturbances in synaptic activity and neuronal death. Multiple studies relate these effects to increased oxidative stress and aberrant activity of calcium-permeable cation channels leading to calcium imbalance. The transient receptor potential melastatin 2 (TRPM2) channel, a Ca(2+)-permeable nonselective cation channel activated by oxidative stress, has been implicated in neurodegenerative diseases, and more recently in amyloid-induced toxicity. Here we show that the function of TRPM2 is augmented by treatment of cultured neurons with β-amyloid oligomers. Aged APP/PS1 Alzheimer's mouse model showed increased levels of endoplasmic reticulum stress markers, protein disulfide isomerase and phosphorylated eukaryotic initiation factor 2α, as well as decreased levels of the presynaptic marker synaptophysin. Elimination of TRPM2 in APP/PS1 mice corrected these abnormal responses without affecting plaque burden. These effects of TRPM2 seem to be selective for β-amyloid toxicity, as ER stress responses to thapsigargin or tunicamycin in TRPM2(-/-) neurons was identical to that of wild-type neurons. Moreover, reduced microglial activation was observed in TRPM2(-/-)/APP/PS1 hippocampus compared with APP/PS1 mice. In addition, age-dependent spatial memory deficits in APP/PS1 mice were reversed in TRPM2(-/-)/APP/PS1 mice. These results reveal the importance of TRPM2 for β-amyloid neuronal toxicity, suggesting that TRPM2 activity could be potentially targeted to improve outcomes in Alzheimer's disease.
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Protoscolecidal Effect of Berberis vulgaris Root Extract and Its Main Compound, Berberine in Cystic Echinococcosis.

Cystic echinococcosis (CE), a zoonotic parasitic infection caused by the metacestode (larvae) stage of dog tapeworm Echinococcus granulosus and recognized as a major economic and public health concern in the world. This study aimed to investigate the in vitro scolicidal effect of methanolic extract of Berberis vulgaris L. roots and its main compound, berberine against protoscoleces of hydatid cysts.

For this purpose, protoscoleces were aseptically aspirated from sheep livers having hydatid cysts. Various concentrations of the methanolic extract (0.25-2 mg/ml) and berberine (0.062- 0.5 mg/ml) were used for 5 to 30 min. Viability of protoscoleces was confirmed by eosin exclusive test.

In the present study, all of the various concentrations of the B. vulgaris methanolic extract (0.25, 0.5, 1 and 2 mg/ml) and berberine (0.062, 0.125, 0.25 and 0.5 mg/ml) revealed significant (P<0.05) scolicidal effects against protoscoleces of E. granulosus in a dose-dependent manner. Both berberine and methanolic extract exhibited 100% inhibition against protoscoleces of E. granulosus at the concentration of 2.0 and 0.5 mg/ml after 10 min incubation, respectively.

According to the results, both B. vulgaris methanolic extract and berberine alone demonstrated high scolicidal activities against protoscoleces of hydatid cysts in low concentration and short exposure time on in vitro model. However, in vivo efficacy of B. vulgaris and berberine also requires to be evaluated using an animal model with hydatid infection.

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Transdermal cannabidiol reduces inflammation and pain-related behaviours in a rat model of arthritis.

Transdermal cannabidiol reduces inflammation and pain-related behaviours in a rat model of arthritis. | A Tale of Two Medicines | Scoop.it

Current arthritis treatments often have side-effects attributable to active compounds as well as route of administration. Cannabidiol (CBD) attenuates inflammation and pain without side-effects, but CBD is hydrophobic and has poor oral bioavailability. Topical drug application avoids gastrointestinal administration, first pass metabolism, providing more constant plasma levels.

This study examined efficacy of transdermal CBD for reduction in inflammation and pain, assessing any adverse effects in a rat complete Freund's adjuvant-induced monoarthritic knee joint model. CBD gels (0.6, 3.1, 6.2 or 62.3 mg/day) were applied for 4 consecutive days after arthritis induction. Joint circumference and immune cell invasion in histological sections were measured to indicate level of inflammation. Paw withdrawal latency (PWL) in response to noxious heat stimulation determined nociceptive sensitization, and exploratory behaviour ascertained animal's activity level.

Measurement of plasma CBD concentration provided by transdermal absorption revealed linearity with 0.6-6.2 mg/day doses. Transdermal CBD gel significantly reduced joint swelling, limb posture scores as a rating of spontaneous pain, immune cell infiltration and thickening of the synovial membrane in a dose-dependent manner. PWL recovered to near baseline level. Immunohistochemical analysis of spinal cord (CGRP, OX42) and dorsal root ganglia (TNFα) revealed dose-dependent reductions of pro-inflammatory biomarkers. Results showed 6.2 and 62 mg/day were effective doses. Exploratory behaviour was not altered by CBD indicating limited effect on higher brain function.

These data indicate that topical CBD application has therapeutic potential for relief of arthritis pain-related behaviours and inflammation without evident side-effects.

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Inhibition effects of Chinese cabbage powder on aflatoxin B1-induced liver cancer

In this study, 0.25 μg/ml aflatoxin B1 was used to establish a liver cancer model for assessing the potential anticancer ability of Chinese cabbage powder, which is a complex water-soluble extract from Chinese cabbage by spray-drying at an outlet temperature of 130 °C. We found at least 11 potential anticancer substances in Chinese cabbage powder. A 90-d animal experiment demonstrated that 10% of Chinese cabbage powder in drinking water could improve the plasma micronutrient status, inhibit the formation of aflatoxin B1-DNA adducts in liver cells, and effectively reduce the incidence of liver tumor induced by aflatoxin B1 from 6.67% to 0%. The dose effect experiment revealed that 10% may be the minimal effective dose to prevent the occurrence of early liver tumors. This study will help elucidate the basis of epidemiological observations of dietary cancer prevention in humans, as well as explore related mechanisms.
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Protective Effects of Dietary Supplementation with a Combination of Nutrients in a Transgenic Mouse Model of Alzheimer’s Disease

Protective Effects of Dietary Supplementation with a Combination of Nutrients in a Transgenic Mouse Model of Alzheimer’s Disease | A Tale of Two Medicines | Scoop.it

This study investigated the effects of intervention with a combination of nutrients in the amyloid precursor protein-presenilin (APP-PSN) C57BL/6J double transgenic mouse model of Alzheimer’s disease (AD).

A total of 72 2-month-old APP-PSN mice were randomly assigned to three groups. The model group (MG) was fed regular, unsupplemented chow, while the low- and high-dose treatment groups (LG and HG, respectively) were given a combination of nutrients that included phosphatidylserine, blueberry extracts, docosahexaenoic acid, and eicosapentaenoic acid as part of their diet. An additional 24 wild-type littermates that were fed unsupplemented chow served as the negative control group (NG). After 3 and 7 months of treatment, the cognitive performance was assessed with the Morris water maze and the shuttle box escape/avoidance task, and the biochemical parameters and oxidative stress were evaluated in both the blood and brain.

An improvement in antioxidant capacity was observed in the treatment groups relative to the MG at 3 months, while superior behavioral test results were observed in the mice of the HG and NG groups. In the MG, pycnosis was detected in neuronal nuclei, and a loss of neurons was observed in the cerebral cortex and the hippocampus. At 7 months, the β-amyloid1–42 peptide accumulation was significantly elevated in the MG but was markedly lower in the mice fed the nutrient combination. The antioxidant capacity and behavioral test scores were also higher in these mice.

Early intervention with a combination of nutrients should be considered as a strategy for preventing cognitive decline and other symptoms associated with AD

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Comparison of human gut microbiota in control subjects and patients with colorectal carcinoma in adenoma: Terminal restriction fragment length polymorphism and next-generation sequencing analyses.

Comparison of human gut microbiota in control subjects and patients with colorectal carcinoma in adenoma: Terminal restriction fragment length polymorphism and next-generation sequencing analyses. | A Tale of Two Medicines | Scoop.it
Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in Japan. The etiology of CRC has been linked to numerous factors including genetic mutation, diet, life style, inflammation, and recently, the gut microbiota. However, CRC-associated gut microbiota is still largely unexamined. This study used terminal restriction fragment length polymorphism (T-RFLP) and next-generation sequencing (NGS) to analyze and compare gut microbiota of Japanese control subjects and Japanese patients with carcinoma in adenoma. Stool samples were collected from 49 control subjects, 50 patients with colon adenoma, and 9 patients with colorectal cancer (3/9 with invasive cancer and 6/9 with carcinoma in adenoma) immediately before colonoscopy; DNA was extracted from each stool sample. Based on T-RFLP analysis, 12 subjects (six control and six carcinoma in adenoma subjects) were selected; their samples were used for NGS and species-level analysis. T-RFLP analysis showed no significant differences in bacterial population between control, adenoma and cancer groups. However, NGS revealed that i), control and carcinoma in adenoma subjects had different gut microbiota compositions, ii), one bacterial genus (Slackia) was significantly associated with the control group and four bacterial genera (Actinomyces, Atopobium, Fusobacterium, and Haemophilus) were significantly associated with the carcinoma-in-adenoma group, and iii), several bacterial species were significantly associated with each type (control: Eubacterium coprostanoligens; carcinoma in adenoma: Actinomyces odontolyticus, Bacteroides fragiles, Clostridium nexile, Fusobacterium varium, Haemophilus parainfluenzae, Prevotella stercorea, Streptococcus gordonii, and Veillonella dispar). Gut microbial properties differ between control subjects and carcinoma-in-adenoma patients in this Japanese population, suggesting that gut microbiota is related to CRC prevention and development.
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Chilean Strawberry Consumption Protects against LPS-Induced Liver Injury by Anti-Inflammatory and Antioxidant Capability in Sprague-Dawley Rats

Chilean Strawberry Consumption Protects against LPS-Induced Liver Injury by Anti-Inflammatory and Antioxidant Capability in Sprague-Dawley Rats | A Tale of Two Medicines | Scoop.it
The Chilean strawberry fruit has high content of antioxidants and polyphenols. Previous studies evidenced antioxidant properties by in vitro methods. However, the antioxidant effect and its impact as functional food on animal health have not been evaluated. In this study, rats were fed with a Chilean strawberry aqueous extract (4 g/kg of animal per day) and then subjected to LPS-induced liver injury (5 mg/kg). Transaminases and histological studies revealed a reduction in liver injury in rats fed with strawberry aqueous extract compared with the control group. Additionally, white strawberry supplementation significantly reduced the serum levels and gene expression of TNF-α, IL-6, and IL-1β cytokines compared with nonsupplemented rats. The level of F2-isoprostanes and GSH/GSSG indicated a reduction in liver oxidative stress by the consumption of strawberry aqueous extract. Altogether, the evidence suggests that dietary supplementation of rats with a Chilean white strawberry aqueous extract favours the normalization of oxidative and inflammatory responses after a liver injury induced by LPS.
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Preventive and treatment effects of a hemp seed (Cannabis sativa L.) meal protein hydrolysate against high blood pressure in spontaneously hypertensive rats.

Preventive and treatment effects of a hemp seed (Cannabis sativa L.) meal protein hydrolysate against high blood pressure in spontaneously hypertensive rats. | A Tale of Two Medicines | Scoop.it

This work determined the ability of hemp seed meal protein hydrolysate (HMH)-containing diets to attenuate elevated blood pressure (hypertension) development in spontaneously hypertensive rats (SHRs). Effects of diets on plasma levels of renin and angiotensin I-converting enzyme (ACE) in the SHRs were also determined.

Defatted hemp seed protein meal was hydrolyzed using simulated gastrointestinal tract digestion with pepsin followed by pancreatin, and the resulting HMH used as a source of antihypertensive peptides. The HMH was substituted for casein at 0.5 and 1.0% levels and fed to young growing rats for 8 weeks (preventive phase) or adult rats for 4 weeks (treatment phase).

Feeding of young growing SHRs with HMH resulted in attenuation of the normal increases in systolic blood pressure (SBP) with an average value of ~120 mmHg when compared to the casein-only group of rats (control) with a maximum of 158 mm Hg (p < 0.05). Feeding adult rats (SBP ~145 mmHg) with same diets during a 4-week period led to significant (p < 0.05) reduction in SBP to ~119 mmHg in comparison with 150 mmHg for the control rats. Plasma ACE activity was significantly (p < 0.05) suppressed (0.047-0.059 U/mL) in HMH-fed rats when compared to control rats (0.123 U/mL). Plasma renin level was also decreased for HMH-fed rats (0.040-0.054 μg/mL) when compared to control rats that were fed only with casein (0.151 μg/mL).

The results suggest that HMH with strong hypotensive effects in SHRs could be used as a therapeutic agent for both the prevention and treatment of hypertension.

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NIH researchers find potential target for reducing obesity-related inflammation

Scientists at the National Institutes of Health have identified a potential molecular target for reducing obesity-related inflammation. Researchers have known that overeating (that is, excess calorie consumption) by individuals with obesity often triggers inflammation, which has been linked to such diseases as asthma and Type 2 diabetes. In their study, published recently in The Journal of Clinical Investigation (Nov. 3, 2015, online version (link is external)), the investigators found that a protein called SIRT3 provides resistance to this inflammatory response and could potentially prevent or reverse obesity-associated diseases of inflammation.

Lead researcher Michael N. Sack, M.D., Ph.D., a senior investigator at NIH’s National Heart, Lung, and Blood Institute, explained that he and his team identified the role of SIRT3 through an investigation involving 19 healthy volunteers who fasted for a 24-hour period.

“Previous research has shown that intermittent fasting or intermittent calorie restriction — by way of eating fewer calories for a few days a month — reduces inflammation,” said Dr. Sack. “We found through our study that this effect is mediated, in part, on a molecular level when SIRT3 blocks the activity of another molecule known as the NLRP3 inflammasome.” He explained that NLRP3 inflammasomes are components of an intracelluar immune response triggered when mitochondria undergo stress, such as from excess calorie intake.
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Bacterial infection and Alzheimer's disease: a meta-analysis.

Bacterial infection and Alzheimer's disease: a meta-analysis. | A Tale of Two Medicines | Scoop.it
The possibility of an infectious etiology for Alzheimer's disease (AD) has been repeatedly postulated over the past three decades. We provide the first meta-analysis to address the relationship between bacterial infection and AD. Studies examining the association between AD and spirochetal bacteria or Chlamydophila pneumoniae (Cpn) were identified through a systematic search of the databases MEDLINE, EMBASE, PubMed, and Google Scholar. Data combined from 25 relevant, primarily case-control studies demonstrated a statistically significant association between AD and detectable evidence of infection of either bacterial group. We found over a ten-fold increased occurrence of AD when there is detectable evidence of spirochetal infection (OR: 10.61; 95% CI: 3.38-33.29) and over a four-fold increased occurrence of AD in a conservative risk estimate (OR: 4.45; 95% CI: 2.33-8.52). We found over a five-fold increased occurrence of AD with Cpn infection (OR: 5.66; 95% CI: 1.83-17.51). This study shows a strongly positive association between bacterial infection and AD. Further detailed investigation of the role of bacterial infection is warranted.
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Dandelion Extracts Protect Human Skin Fibroblasts from UVB Damage and Cellular Senescence

Dandelion Extracts Protect Human Skin Fibroblasts from UVB Damage and Cellular Senescence | A Tale of Two Medicines | Scoop.it
Ultraviolet (UV) irradiation causes damage in skin by generating excessive reactive oxygen species (ROS) and induction of matrix metalloproteinases (MMPs), leading to skin photoageing. Dandelion extracts have long been used for traditional Chinese medicine and native American medicine to treat cancers, hepatitis, and digestive diseases; however, less is known on the effects of dandelion extracts in skin photoageing. Here we found that dandelion leaf and flower extracts significantly protect UVB irradiation-inhibited cell viability when added before UVB irradiation or promptly after irradiation. Dandelion leaf and flower extracts inhibited UVB irradiation-stimulated MMP activity and ROS generation. Dandelion root extracts showed less action on protecting HDFs from UVB irradiation-induced MMP activity, ROS generation, and cell death. Furthermore, dandelion leaf and flower but not root extracts stimulated glutathione generation and glutathione reductase mRNA expression in the presence or absence of UVB irradiation. We also found that dandelion leaf and flower extracts help absorb UVB irradiation. In addition, dandelion extracts significantly protected HDFs from H2O2-induced cellular senescence. In conclusion, dandelion extracts especially leaf and flower extracts are potent protective agents against UVB damage and H2O2-induced cellular senescence in HDFs by suppressing ROS generation and MMP activities and helping UVB absorption.
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Nutritional Supplementation with Chlorella pyrenoidosa Lowers Serum Methylmalonic Acid in Vegans and Vegetarians with a Suspected Vitamin B12 Deficiency.

Nutritional Supplementation with Chlorella pyrenoidosa Lowers Serum Methylmalonic Acid in Vegans and Vegetarians with a Suspected Vitamin B12 Deficiency. | A Tale of Two Medicines | Scoop.it
Since vitamin B12 occurs in substantial amounts only in foods derived from animals, vegetarians and particularly vegans are at risk of developing deficiencies of this essential vitamin. The chlorella used for this study is a commercially available whole-food supplement, which is believed to contain the physiologically active form of the vitamin. This exploratory open-label study was performed to determine if adding 9 g of Chlorella pyrenoidosa daily could help mitigate a vitamin B12 deficiency in vegetarians and vegans. Seventeen vegan or vegetarian adults (26-57 years of age) with a known vitamin B12 deficiency, as evidenced by a baseline serum methylmalonic acid (MMA) level above 270 nmol/L at screening, but who otherwise appeared healthy were enrolled in the study. Each participant added 9 g of C. pyrenoidosa to their daily diet for 60 ± 5 days and their serum MMA, vitamin B12, homocysteine (Hcy) levels as well as mean corpuscular volume (MCV), hemoglobin (Hgb), and hematocrit (Hct) were measured at 30 and 60 days from baseline. After 30 and 60 days, the serum MMA level fell significantly (P < .05) by an average ∼34%. Fifteen of the 17 (88%) subjects showed at least a 10% drop in MMA. At the same time, Hcy trended downward and serum vitamin B12 trended upward, while MCV, Hgb, and Hct appeared unchanged. The results of this work suggest that the vitamin B12 in chlorella is bioavailable and such dietary supplementation is a natural way for vegetarians and vegans to get the vitamin B12 they need.
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The Role of Curcumin Administration in Patients with Major Depressive Disorder: Mini Meta-Analysis of Clinical Trials.

The Role of Curcumin Administration in Patients with Major Depressive Disorder: Mini Meta-Analysis of Clinical Trials. | A Tale of Two Medicines | Scoop.it
Major depression is a common, recurrent, and chronic disease that negatively affects the quality of life and increases the risk of mortality. Several studies have demonstrated that curcumin, the yellow-pigmented substance of the turmeric, possesses antidepressant properties. The aim of this review is to meta-analytically assess the antidepressant effect of curcumin in patients with major depressive disorders. We extensively searched the literature until August 2015. The random-effect model was used to calculate the pooled standardized difference of means (SMD). Subgroup analyses were also performed to examine the effect of different study characteristics on the overall model. Six clinical trials met the inclusion criteria. Overall, curcumin administration showed a significantly higher reduction in depression symptoms [SMD = -0.34; 95% confidence interval (CI) = -0.56, -0.13; p = 0.002]. Subgroup analyses showed that curcumin had the highest effect when given to middle-aged patients (SMD = -0.36; 95% CI = -0.59; -0.13; p = 0.002), for longer duration of administration (SMD = -0.40; 95% CI = -0.64, -0.16; p = 0.001), and at higher doses (SMD = -0.36; 95% CI = -0.59, -0.13; p = 0.002). The administration of new formulation of curcumin (BCM-95) had non-significantly higher effect on depression as compared with the conventional curcumin-piperine formula. We conclude that there is supporting evidence that curcumin administration reduces depressive symptoms in patients with major depression.
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Curcumin inhibits activation of TRPM2 channels in rat hepatocytes.

Curcumin inhibits activation of TRPM2 channels in rat hepatocytes. | A Tale of Two Medicines | Scoop.it
Oxidative stress is a hallmark of many liver diseases including viral and drug-induced hepatitis, ischemia-reperfusion injury, and non-alcoholic steatohepatitis. One of the consequences of oxidative stress in the liver is deregulation of Ca2+ homeostasis, resulting in a sustained elevation of the free cytosolic Ca2+ concentration ([Ca2+]c) in hepatocytes, which leads to irreversible cellular damage. Recently it has been shown that liver damage induced by paracetamol and subsequent oxidative stress is, in large part, mediated by Ca2+ entry through Transient Receptor Potential Melastatin 2 (TRPM2) channels. Involvement of TRPM2 channels in hepatocellular damage induced by oxidative stress makes TRPM2 a potential therapeutic target for treatment of a range of oxidative stress-related liver diseases. We report here the identification of curcumin ((1E,6E)-1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione), a natural plant-derived polyphenol in turmeric spice, as a novel inhibitor of TRPM2 channel. Presence of 5µM curcumin in the incubation medium prevented the H2O2- and paracetamol-induced [Ca2+]c rise in rat hepatocytes. Furthermore, in patch clamping experiments incubation of hepatocytes with curcumin inhibited activation of TRPM2 current by intracellular ADPR with IC50 of approximately 50nM. These findings enhance understanding of the actions of curcumin and suggest that the known hepatoprotective properties of curcumin are, at least in part, mediated through inhibition of TRPM2 channels.
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Protective Effect of Ocimum basilicum Essential Oil Against Acetic Acid–Induced Colitis in Rats

Ocimum basilicum L has been traditionally used for the treatment of inflammatory bowel disease in Iran. This study investigates the ameliorative effect of Ocimum basilicum essential oil on an acetic acid–induced colitis model in rats. Ocimum basilicum essential oil with 2 doses (200 and 400 μL/kg) significantly ameliorated wet weight/length ratio of colonic tissue compared to the control group. Higher doses of essential oil (200 and 400 μL/kg) significantly reduced ulcer severity, ulcer area, and ulcer index. On the other hand, histological examination revealed the diminution of total colitis index as a marker for inflammatory cell infiltration in the colonic segments of rats treated with Ocimum basilicum essential oil (200 and 400 μL/kg). The increased level of myeloperoxidase was significantly decreased after the treatment with the essential oil (200 and 400 μL/kg). These results suggest that Ocimum basilicum exhibits protective effect against acetic acid–induced colitis.
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Cannabidiol lowers incidence of diabetes in non-obese diabetic mice

Cannabidiol lowers incidence of diabetes in non-obese diabetic mice | A Tale of Two Medicines | Scoop.it
Cannabidinoids are components of the Cannabis sativa (marijuana) plant that have been shown capable of suppressing inflammation and various aspects of cell-mediated immunity. Cannabidiol (CBD), a non-psychoactive cannabidinoid has been previously shown by us to suppress cell-mediated autoimmune joint destruction in an animal model of rheumatoid arthritis. We now report that CBD treatment significantly reduces the incidence of diabetes in NOD mice from an incidence of 86% in non-treated control mice to an incidence of 30% in CBD-treated mice. CBD treatment also resulted in the significant reduction of plasma levels of the pro-inflammatory cytokines, IFN-γ and TNF-α. Th1-associated cytokine production of in vitro activated T-cells and peritoneal macrophages was also significantly reduced in CBD-treated mice, whereas production of the Th2-associated cytokines, IL-4 and IL-10, was increased when compared to untreated control mice. Histological examination of the pancreatic islets of CBD-treated mice revealed significantly reduced insulitis. Our results indicate that CBD can inhibit and delay destructive insulitis and inflammatory Th1-associated cytokine production in NOD mice resulting in a decreased incidence of diabetes possibly through an immunomodulatory mechanism shifting the immune response from Th1 to Th2 dominance.
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New antiinflammatory sucrose esters in the natural sticky coating of tomatillo (Physalis philadelphica), an important culinary fruit.

New antiinflammatory sucrose esters in the natural sticky coating of tomatillo (Physalis philadelphica), an important culinary fruit. | A Tale of Two Medicines | Scoop.it
Tomatillo is a popular culinary fruit. The sticky material on its surface, consumed as part of the fruit, has never been investigated. Chemical characterization of sticky material on tomatillo fruits yielded five new sucrose esters, as confirmed by spectroscopic methods. The solvent extract of the sticky material from the whole fresh fruit and pure isolates showed antiinflammatory activity as confirmed by in vitro cyclooxygenase enzymes inhibitory assays. Five sucrose esters isolated at 100μg/mL (153.8, 138.8, 136.2, 141.6 and 138.8μM, respectively) inhibited cyclooxygenase-1 and -2 enzymes by 50%. The cyclooxygenase enzyme inhibitory activity of extract and isolates at 100μg/mL was similar to non-steroidal antiinflammatory drugs aspirin, ibuprofen and naproxen, used as positive controls in the assay at 108, 12 and 15μg/mL (600, 60 and 60μM), respectively.
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Antibacterial Cannabinoids from Cannabis sativa: A Structure−Activity Study

Antibacterial Cannabinoids from Cannabis sativa: A Structure−Activity Study | A Tale of Two Medicines | Scoop.it
Marijuana (Cannabis sativa) has long been known to contain antibacterial cannabinoids, whose potential to address antibiotic resistance has not yet been investigated. All five major cannabinoids (cannabidiol (1b), cannabichromene (2), cannabigerol (3b), Δ9-tetrahydrocannabinol (4b), and cannabinol (5)) showed potent activity against a variety of methicillin-resistant Staphylococcus aureus (MRSA) strains of current clinical relevance. Activity was remarkably tolerant to the nature of the prenyl moiety, to its relative position compared to the n-pentyl moiety (abnormal cannabinoids), and to carboxylation of the resorcinyl moiety (pre-cannabinoids). Conversely, methylation and acetylation of the phenolic hydroxyls, esterification of the carboxylic group of pre-cannabinoids, and introduction of a second prenyl moiety were all detrimental for antibacterial activity. Taken together, these observations suggest that the prenyl moiety of cannabinoids serves mainly as a modulator of lipid affinity for the olivetol core, a per se poorly active antibacterial pharmacophore, while their high potency definitely suggests a specific, but yet elusive, mechanism of activity.
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Curcumin improves the efficacy of cisplatin by targeting cancer stem-like cells through p21 and cyclin D1-mediated tumour cell inhibition in non-small cell lung cancer cell lines.

Curcumin improves the efficacy of cisplatin by targeting cancer stem-like cells through p21 and cyclin D1-mediated tumour cell inhibition in non-small cell lung cancer cell lines. | A Tale of Two Medicines | Scoop.it
Natural compounds such as curcumin have the ability to enhance the therapeutic effectiveness of common chemotherapy agents through cancer stem‑like cell (CSC) sensitisation. In the present study, we showed that curcumin enhanced the sensitivity of the double‑positive (CD166+/EpCAM+) CSC subpopulation in non‑small cell lung cancer (NSCLC) cell lines (A549 and H2170) to cisplatin‑induced apoptosis and inhibition of metastasis. Our results revealed that initial exposure of NSCLC cell lines to curcumin (10‑40 µM) markedly reduced the percentage of viability to an average of ~51 and ~54% compared to treatment with low dose cisplatin (3 µM) with only 94 and 86% in both the A549 and H2170 cells. Moreover, sensitisation of NSCLC cell lines to curcumin through combined treatment enhanced the single effect induced by low dose cisplatin on the apoptosis of the double‑positive CSC subpopulation by 18 and 20% in the A549 and H2170 cells, respectively. Furthermore, we found that curcumin enhanced the inhibitory effects of cisplatin on the highly migratory CD166+/EpCAM+ subpopulation, marked by a reduction in cell migration to 9 and 21% in the A549 and H2170 cells, respectively, indicating that curcumin may increase the sensitivity of CSCs to cisplatin‑induced migratory inhibition. We also observed that the mRNA expression of cyclin D1 was downregulated, while a substantial increased in p21 expression was noted, followed by Apaf1 and caspase‑9 activation in the double‑positive (CD166+/EpCAM+) CSC subpopulation of A549 cells, suggested that the combined treatments induced cell cycle arrest, therefore triggering CSC growth inhibition via the intrinsic apoptotic pathway. In conclusion, we provided novel evidence of the previously unknown therapeutic effects of curcumin, either alone or in combination with cisplatin on the inhibition of the CD166+/EpCAM+ subpopulation of NSCLC cell lines. This finding demonstrated the potential therapeutic approach of using curcumin that may enhance the effects of cisplatin by targeting the CSC subpopulation in NSCLC.
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Cannabisin B induces autophagic cell death by inhibiting the AKT/mTOR pathway and S phase cell cycle arrest in HepG2 cells

Cannabisin B induces autophagic cell death by inhibiting the AKT/mTOR pathway and S phase cell cycle arrest in HepG2 cells | A Tale of Two Medicines | Scoop.it
This study investigates the anticancer properties of cannabisin B, purified from hempseed hull, in HepG2 human hepatoblastoma cells. The results indicate that cannabisin B significantly inhibited cell proliferation by inducing autophagic cell death rather than typical apoptosis. Cell viability transiently increased upon the addition of a low concentration of cannabisin B but decreased upon the addition of high concentrations. Cannabisin B-induced changes in cell viability were completely inhibited by pre-treatment with 3-methyladenine (3-MA), indicating that the induction of autophagy by cannabisin B caused cell death. Additionally, cannabisin B induced S phase cell cycle arrest in a dose-dependent manner. Moreover, cannabisin B was found to inhibit survival signaling by blocking the activation of AKT and down-stream targets of the mammalian target of rapamycin (mTOR). These findings suggest that cannabisin B possesses considerable antiproliferative activity and that it may be utilised as a promising chemopreventive agent against hepatoblastoma disease.
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Trichosanthes kirilowii fruits inhibit non-small cell lung cancer cell growth through mitotic cell-cycle arrest.

Trichosanthes kirilowii fruits inhibit non-small cell lung cancer cell growth through mitotic cell-cycle arrest. | A Tale of Two Medicines | Scoop.it
Lung cancer is the leading cause of cancer-related death worldwide. Non-small cell lung cancer (NSCLC) accounts for 80% of lung cancer cases and the reported overall 5-year survival rate is less than 5%. Natural medicines have attracted much attention due to their lower toxicity and fewer side effects. Trichosanthes kirilowii Maxim (TKM) fruits are commonly used in cancer treatment in combination with other Chinese medicinal herbs. However, little is known about their biological functions and mechanisms in NSCLC cells. In this study, we investigated the efficacy of TKM fruits in NSCLC cells using cell proliferation, invasion, migration, and anchorage independent assays and a Xenograft NSCLC tumor model, and explored the possible biological mechanism by flow cytometric analysis, cDNA microarray and real-time PCR. Results showed that TKM fruits significantly suppressed NSCLC cell proliferation, migration, invasion, tumorigenicity and tumor growth, and significantly extended the survival time of NSCLC-bearing mice. Flow cytometric analysis showed that TKM fruits significantly induced G2-M arrest, necrosis and apoptosis in NSCLC cells. cDNA microarray analysis revealed that TKM fruits regulated the differential expression of 544 genes, and the differential expression of selected genes was also confirmed. Gene ontology (GO) analysis showed that 18 of first 20 biological processes were involved in cell cycle and mitosis. These results indicate that TKM fruits have certain inhibitory effect on NSCLC cells through cell-cycle and mitosis arrest, and suggest that TKM fruits may be an important resource for developing new antitumor drugs, and a potent natural product for treating patients with NSCLC.
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