PMID: 

Biomedicines. 2019 Dec 5 ;7(4). Epub 2019 Dec 5. PMID: 31817440

Abstract Title: 

Synergistic Action of Stilbenes in Muscadine Grape Berry Extract Shows Better Cytotoxic Potential Against Cancer Cells Than Resveratrol Alone.

Abstract: 

Muscadine grape is rich in stilbenes, which include resveratrol, piceid, viniferin, pterostilbene, etc. Resveratrol has been extensively studied for its biological activities; however, the synergistic effect of stilbene compounds in berry extracts is poorly understood. The aim of this study was to evaluate the anti-cancer activity of stilbene-rich muscadine berry extract and pure resveratrol. Stilbenes were extracted from ripened berries of muscadine grape cultivars, Pineapple, and Southern Home. HPLC analysis was performed to determine quantity of stilbenes. The extracts were tested for their cytotoxic activity against A549 (lung carcinoma cells), triple negative breast cancer (HCC-1806) and HepG2 (human liver cancer) cells. The stilbene-rich extracts of the muscadine berry extracts showed cytotoxic activity against all of the cells tested. The extracts at 1μg/mL induced death in 50-80% of cells by 72 h of treatment. About 50 μg/mL of resveratrol was required to induce a similar response in the cells. Further, modulation of genes involved in tumor progression and suppression was significantly (

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PMID: 

J Anim Sci. 2019 Dec 11. Epub 2019 Dec 11. PMID: 31822918

Abstract Title: 

Dietary pterostilbene supplementation attenuates intestinal damage and immunological stress of broiler chickens challenged with lipopolysaccharide1.

Abstract: 

The present study explored the potential effect of pterostilbene as a prophylactic treatment on the lipopolysaccharide (LPS)-induced intestinal injury of broiler chickens by monitoring changes in mucosal injury indicators, redox status, and inflammatory responses. In total, 192 one-day-old male Ross 308 broiler chicks were randomly divided into four groups. This trial consisted of a 2× 2 factorial design with a diet factor (supplemented with 0 or 400 mg/kg pterostilbene from 1 to 22 days of age) and a stress factor (intraperitoneally injected with saline or LPS at 5.0 mg/kg body weight at 21 days of age). The results showed that LPS challenge induced a decrease in body weight gain (P

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PMID: 

Exp Ther Med. 2020 Jan ;19(1):45-52. Epub 2019 Nov 18. PMID: 31853271

Abstract Title: 

Pterostilbene reduces endothelial cell injury in vascular arterial walls by regulating the Nrf2-mediated AMPK/STAT3 pathway in an atherosclerosis rat model.

Abstract: 

Endothelial cell injury in vascular arterial walls is a hallmark of atherosclerosis. Pterostilbene (Pts) has been shown to have an anti-oxidative and anti-apoptotic effect in numerous diseases via regulation of intracellular metabolism. The purpose of this study was to investigate the protective effect and possible mechanism of Pts against endothelial cell apoptosis in an atherosclerotic rat model. An atherosclerotic rat model was established using a high-fat, high glucose and high cholesterol diet. The effects of Pts on apoptosis and oxidative stress injury were measured using atherosclerotic lesion analysis, western blot analysis, hematoxylin and eosin straining, TUNEL assay and immunohistochemistry.results in an atherosclerosis rat model showed that Pts administration decreased the inflammatory response. Pts administration attenuated atherogenesis, reduced aortic plaque size, reduced macrophage infiltration, and suppressed oxidative stress and apoptosis of vascular arterial walls.assays using cultured human endothelial cells showed that Pts administration decreased hydrogen peroxide-induced cytotoxicity, oxidative stress injury and apoptosis via nuclear factor erythroid 2-related factor 2 (Nrf2) activation in endothelial cells. Additionally, Pts administration increased the expression level of Nrf2 and 5' adenosine monophosphate-activated protein kinase (AMPK), and the phosphorylation level of AMPK and decreased signal transducer and activator of transcription 3 (STAT3) expression in these cells. Furthermore, knockdown of Nrf2 prevented Pts-decrease oxidative stress injury and apoptosis. In conclusion, these data suggest that Pts can protect endothelial cells in the vascular arterial walls against atherosclerosis-induced injury through regulation of the Nrf2-mediated AMPK/STAT3 pathway.

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PMID: 

Front Pharmacol. 2019 ;10:1238. Epub 2019 Oct 22. PMID: 31695612

Abstract Title: 

Pterostilbene, An Active Constituent of Blueberries, Suppresses Proliferation Potential of Human CholangiocarcinomaEnhancing the Autophagic Flux.

Abstract: 

Human cholangiocarcinoma (CCA) is a highly lethal cancer that occurs in the biliary tract. It is characterized by early invasion, poor outcomes, and resistance to current chemotherapies. To date, an effective therapeutic strategy for this devastating and deadly disease is lacking. Pterostilbene, a natural compound found in the extracts of many plants including blueberries, kino tree, or dragon blood tree, has several health benefits. However, its effects on CCA have not been clarified. Here, we investigated the potential application of pterostilbene for the treatment of human CCAand.The effects of pterostilbene on CCA cells were determined by assessing cell viability (CCK), cell proliferation, and colony formation. Cell cycle arrest and apoptosis were measured by flow cytometric analysis, whereas proteins related to autophagy were detected by immunofluorescence and immunoblotting assays. A well-established xenograft mouse model was used to evaluate the effects of pterostilbene on tumor growth.Pterostilbene induced dose-dependent and time-dependent cytotoxic effects, inhibited proliferation and colony formation, and caused S phase cell cycle arrest in CCA cells. Instead of triggering apoptotic cell death in these cells, pterostilbene was found to exert potent autophagy-inducing effects, and this correlated with p62 downregulation, elevated expression of endogenous Beclin-1, ATG5, and LC3-II, and increases in LC3 puncta. Pretreating cancer cells with the autophagy inhibitor 3-MA suppressed the induction of autophagy and antitumor activity caused by pterostilbene. Finally, we confirmed that pterostilbene inhibited tumor growth in a CCA xenograft mouse model with minimal general toxicity.Taken together, our findings indicate that pterostilbene, through the induction of autophagic flux, acts as an anti-cancer agent against CCA cells.

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PMID: 

Food Funct. 2019 Dec 11 ;10(12):7621-7633. PMID: 31776541

Abstract Title: 

Blueberries and cardiovascular disease prevention.

Abstract: 

Blueberries are a rich source of (poly)phenols, particularly anthocyanins. Epidemiological studies indicate that anthocyanin-rich foods including blueberries are associated with a reduction in the risk of cardiovascular disease. These observational findings are supported by a number of randomized-controlled trials showing improvements in biomarkers of cardiovascular disease risk. The beneficial effects of blueberry (poly)phenols are particularly clear when measuring flow-mediated dilation over various timeframes and study populations. However, other outcomes are less clear, such as effects on blood pressure, arterial stiffness and blood lipid profile. This may be due to the heterogeneity existing in study designs, such as duration of the intervention, and the health status of participants. Longer-term RCTs using gold standard methods in relevant populations which can be translated to the general public are needed to clarify and strengthen the evidence available. While circulating phenolic blueberry metabolites have been linked with improvements in vascular function, the biological activities and mechanisms of action of individual metabolites and their interaction in vivo are still unknown. Evaluating the bioactivities of metabolites alone and together, and analysing their structure-activity relationship in well-designed and physiologically relevant experimental and human studies are needed to understand the mechanisms of how these metabolites affect vascular function.

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PMID: 

Phytother Res. 2019 Dec 17. Epub 2019 Dec 17. PMID: 31845444

Abstract Title: 

Bitter melon fruit extract has a hypoglycemic effect and reduces hepatic lipid accumulation in ob/ob mice.

Abstract: 

Bitter melon (Momordica charantia L.) is a vegetable and has been used as traditional medicine. Recently, we reported that bitter melon fruit extracts and its ethyl acetate (EtOAc)-soluble fraction markedly suppressed the expression of proinflammatory genes, including the inducible nitric oxide synthase gene. However, it is unclear whether bitter melon exhibits antidiabetic effects. In this study, we showed that cucurbitacin B, a cucurbitane-type triterpenoid, was present in an EtOAc-soluble fraction and suppressed nitric oxide production in hepatocytes. When the EtOAc-soluble fraction was administered for 7 days to ob/ob mice, a type 2 diabetes mellitus model, the mice fed with this fraction exhibited a significant decrease in body weight and blood glucose concentrations compared with the mice fed without the fraction. The administration of the fraction resulted in significant increases in serum insulin concentrations and the levels of both insulin receptor mRNA and protein in the ob/ob mouse liver. The EtOAc-soluble fraction decreased the interleukin-1β mRNA expression, as well as hepatic lipid accumulation in hepatocytes. Taken together, these results indicate that administration of an EtOAc-soluble fraction improved hyperglycemia and hepatic steatosis, suggesting that this fraction may be responsible for both the antidiabetic and anti-inflammatory effects of bitter melon fruit.

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PMID: 

Nat Prod Res. 2019 Jul 24:1-6. Epub 2019 Jul 24. PMID: 31339383

Abstract Title: 

Effect of the proportion of curcuminoids on the gastroprotective action ofL. in rats.

Abstract: 

The gastroprotective effect of a turmeric acetone extract (TAE) (L. [Zingiberaceae]) was evaluated and compared against its major curcuminoids; curcumin (CUR), demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC). Additionally, to demonstrate the importance of the metabolites' ratio in the extract on the synergistic effect, different mixtures were evaluated. An ethanol-induced gastric injury model was used to evaluate the gastroprotection activity in Wistar rats. The pharmacologic interaction analysis was performed using themethod. Thecalculated at 0.5 of affected fraction () for the TAE indicated a synergistic interaction between its components. However, when the proportion of curcuminoids changed from 3.7:1:10 in TAE to a 1:1:1 ratio, theimplied an antagonistic effect. The binary combinations of curcuminoids (1:1) also showed an antagonistic interaction. The results of this work suggest that the proportion of curcuminoids in the TAE is crucial for the gastroprotective effect against ethanol-induced damage.

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PMID: 

J Cancer Res Clin Oncol. 2019 Dec 16. Epub 2019 Dec 16. PMID: 31844979

Abstract Title: 

Combined treatment of AT101 and demethoxycurcumin yields an enhanced anti-proliferative effect in human primary glioblastoma cells.

Abstract: 

PURPOSE: Glioblastoma multiforme (GBM) is a poorly curable disease due to its profound chemoresistance. Despite recent advances in surgery, radiotherapy and chemotherapy, the efficient treatment of GBMs is still a clinical challenge. Beside others, AT101, the R-(-) enantiomer of gossypol, and demethoxycurcumin (DMC), a curcumin-related demethoxy compound derived from Curcuma longa, were considered as possible alternative drugs for GBM therapy.METHODS: Using different human primary GBM cell cultures in a long-term stimulation in vitro model, the cytotoxic and anti-proliferative effects of single and combined treatment with 5 µM AT101 and 5 µM or 10 µM DMC were investigated. Furthermore, western blots on pAkt and pp44/42 as well as JC-1 staining and real-time RT-PCR were performed to understand the influence of the treatment at the molecular and gene level.RESULTS: Due to enhanced anti-proliferative effects, we showed that combined therapy with both drugs was superior to a single treatment with AT101 or DMC. Here, by determination of the combination index, a synergism of the combined drugs was detectable. Phosphorylation and thereby activation of the kinases p44/42 and Akt, which are involved in proliferation and survival processes, were inhibited, the mitochondrial membrane potential of the GBM cells was altered, and genes involved in dormancy-associated processes were regulated by the combined treatment strategy.CONCLUSION: Combined treatment with different drugs might be an option to efficiently overcome chemoresistance of GBM cells in a long-term treatment strategy.

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PMID: 

J Ethnopharmacol. 2019 Jun 28 ;238:111882. Epub 2019 Apr 13. PMID: 30991137

Abstract Title: 

Curcuma longa L. ameliorates asthma control in children and adolescents: A randomized, double-blind, controlled trial.

Abstract: 

ETHNOPHARMACOLOGICAL RELEVANCE: Roots of Curcuma longa L. are used as medicine for millennia. They possess several pharmacological properties, including anti-inflammatory action, and can be suitable for asthma treatment.AIM OF THE STUDY: We aimed to test the hypothesis that, in children and adolescents with persistent asthma, the administration of powdered roots of C. longa for 6 months, in addition to standard treatment, compared to placebo, will result in better disease control.PATIENTS AND METHODS: We conducted a randomized, double-blind, placebo-controlled, phase II clinical trial. Patients were randomly assigned to receive 30 mg/kg/day of C. longa for 6 months, or placebo. Data were collected prospectively. All patients were categorized for asthma severity and control according to GINA-2016 and underwent pulmonary function tests.RESULTS: Overall, both groups experienced amelioration of their frequency of symptoms and interference with normal activity, but no differences were found between the two treatment groups. However, patients receiving C. longa experienced less frequent nighttime awakenings, less frequent use of short-actingβ-adrenergic agonists, and better disease control after 3 and 6 months.CONCLUSION: The powdered roots of C. longa led to less frequent nighttime awakenings, less frequent use of short-actingβ-adrenergic agonists, and better disease control after 3 and 6 months, when compared to placebo.

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PMID: 

J Exp Pharmacol. 2019 ;11:115-119. Epub 2019 Dec 10. PMID: 31849540

Abstract Title: 

Effect of Bitter Melon on Spatial Memory of Rats Receiving a High-Fat Diet.

Abstract: 

Introduction: Momordica charantia or bitter melon is a tropical vine of the family Cucurbitaceous widely grown in India. Its fruits have potent anti-oxidant properties due to the presence of tannins, vitamin C and flavonoids. There is much evidence it protects cognitive function and cholesterol level. In addition, there are reports of the effect of a high-fat diet (HFD)on memory. In this study, the effect of bitter melon on spatial memory in rats, following an HFD, in a water maze was examined.Material and methods: In this study, 28 male Wistar rats aged 10 weeks and weighing between 180 and 250 grams were divided into four groups (N=7). Control, High-fat, High-fat + bitter melon, and bitter melon. The control group was fed a standard rat diet, whereas the high-fat groups were fed the same standard diet containing 5% cholesterol for eight weeks, and the treated group received, in addition, 1 g/kg bitter melon fruit powder in their diet, Learning and spatial memory were evaluated by using a Morris Water Maze (MWM) for a six-day period, including five days of training, the last day was the test day (probe day).Results: The high-fat group was fed a high-fat diet for two months, this resulted in reduced learning ability;, this group took longer and travelled a longer distance compared to the control group. However, the administration of bitter melon improved memory function only in the high-fat group.Conclusion: The administration of bitter melon improves spatial-memory performance in rats receiving an HFD.

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