scholarly journals Bioavailability of Epigallocatechin Gallate Administered with Different Nutritional Strategies in Healthy Volunteers

Antioxidants ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 440 ◽  
Author(s):  
Vicente Andreu Fernández ◽  
Laura Almeida Toledano ◽  
Nieves Pizarro Lozano ◽  
Elisabet Navarro Tapia ◽  
María Dolores Gómez Roig ◽  
...  
Keyword(s):  
Experimental Design ◽  
Healthy Volunteers ◽  
Epigallocatechin Gallate ◽  
Pharmacokinetic Profile ◽  
The Body ◽  
Food Supplements ◽  
Interindividual Variation ◽  
Therapeutic Effects ◽  
Standard Breakfast ◽  
Clinical Experiments

The flavanol epigallocatechin gallate (EGCG) is being tested for the treatment of several diseases in humans. However, its bioavailability and pharmacokinetic profile needs a better understanding to enable its use in clinical trials. There is no consensus on the most appropriate concentration of EGCG in the body to obtain the maximum therapeutic effects. Therefore, the aim of this study is to analyze the bioavailability of EGCG orally administered alone or with different food supplements after overnight fasting in order to determine its optimal conditions (high concentrations in blood and the lowest interindividual variations) to be used as a pharmacological tool in human trials. Ten healthy volunteers (5 men and 5 women) aged 25 to 35 years were recruited prospectively. Three series of clinical experiments with a washout period of seven days among each were performed: (1) Teavigo® (EGCG extract) alone, (2) Teavigo® with a standard breakfast, and (3) FontUp® (Teavigo® commercially prepared with fats, carbohydrates, proteins, vitamins, and minerals). Blood samples were collected at 0, 30, 60, 90, 120, 180, 240, and 360 min after EGCG intake. Free EGCG in plasma was measured using a liquid chromatography and mass spectrometry UPLC-ESI-MS/MS analytical method. The pharmacokinetic variables analyzed statistically were area under the curve (AUC0–360), Cmax, Cav, Cmin, T1/2, and Tmax. EGCG (Teavigo®) alone was the group with higher AUC0–360, Cmax, and Cav both in men (3.86 ± 4.11 µg/mL/kg/6 h; 5.95 ng/mL/kg; 2.96 ng/mL/kg) and women (3.33 ± 1.08 µg/mL/kg/6 h; 6.66 ng/mL/kg; 3.66 ng/mL). Moreover, FontUp® was the group with the highest value of T1/2 both in men (192 ± 66 min) and women (133 ± 28 min). Teavigo® intake after fasting overnight revealed the highest concentration of EGCG in plasma according to its pharmacokinetic profile, indicating that this is an excellent alternative of administration if the experimental design requires good absorption in the gastrointestinal tract. Moreover, EGCG taken along with food supplements (FontUp®) improved the stability of the molecule in the body, being the best choice if the experimental design wants to reduce interindividual variation.

A Synthetic Peptide AWRK6 Combined with Epigallocatechin Gallate Alleviates Type 2 Diabetes in Mice

2020 ◽  
Vol 12 (5) ◽  
pp. 740-745
Author(s):  
Li Liu ◽  
Qiuyu Wang ◽  
Zhenni Chen ◽  
Beibei Duan ◽  
Lili Jin ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Epigallocatechin Gallate ◽  
The Body ◽  
Control Group ◽  
Therapeutic Effects ◽  
Diabetes In Mice ◽  
Combined Administration ◽  
Treatment Of Diabetes ◽  
Potential Strategy

The treatment of diabetes is facing severe challenges globally. Recent advances of peptide AWRK6 and epigallocatechin gallate (EGCG) indicated novel potential strategies against type 2 diabetes. Here, the combined administration of AWRK6 and EGCG was investigated in mice with type 2 diabetes. Compared with control group, the blood glucose was significant reduced and the body weight was inhibited. The dyslipidemia and damage of antioxidant capacity were found to be restored using biochemical analysis methods. For mechanisms, western blotting was applied and it was found that PI3K/AKT signaling pathway was involved in the therapeutic effects of AWRK6 and EGCG. In summary, AWRK6 combined with EGCG could alleviate type 2 diabetes in mice. It presented a novel potential strategy against type 2 diabetes.

scholarly journals Extracellular Vesicles of Mesenchymal Stem Cells: Therapeutic Properties Discovered with Extraordinary SuccessOK

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 667
Author(s):  
Gabriella Racchetti ◽  
Jacopo Meldolesi
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Immune Responses ◽  
Extracellular Vesicles ◽  
Immune Regulation ◽  
Great Increase ◽  
The Body ◽  
Cell Aging ◽  
Therapeutic Effects ◽  
Therapeutic Properties

Mesenchymal stem cells (MSCs), the cells distributed in the stromas of the body, are known for various properties including replication, the potential of various differentiations, the immune-related processes including inflammation. About two decades ago, these cells were shown to play relevant roles in the therapy of numerous diseases, dependent on their immune regulation and their release of cytokines and growth factors, with ensuing activation of favorable enzymes and processes. Such discovery induced great increase of their investigation. Soon thereafter, however, it became clear that therapeutic actions of MSCs are risky, accompanied by serious drawbacks and defects. MSC therapy has been therefore reduced to a few diseases, replaced for the others by their extracellular vesicles, the MSC-EVs. The latter vesicles recapitulate most therapeutic actions of MSCs, with equal or even better efficacies and without the serious drawbacks of the parent cells. In addition, MSC-EVs are characterized by many advantages, among which are their heterogeneities dependent on the stromas of origin, the alleviation of cell aging, the regulation of immune responses and inflammation. Here we illustrate the MSC-EV therapeutic effects, largely mediated by specific miRNAs, covering various diseases and pathological processes occurring in the bones, heart and vessels, kidney, and brain. MSC-EVs operate also on the development of cancers and on COVID-19, where they alleviate the organ lesions induced by the virus. Therapy by MSC-EVs can be improved by combination of their innate potential to engineering processes inducing precise targeting and transfer of drugs. The unique properties of MSC-EVs explain their intense studies, carried out with extraordinary success. Although not yet developed to clinical practice, the perspectives for proximal future are encouraging.

scholarly journals Dietary Curcumin: Correlation between Bioavailability and Health Potential

Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 2147 ◽  
Author(s):  
Michele Dei Cas ◽  
Riccardo Ghidoni
Keyword(s):  
Small Intestine ◽  
Cellular Uptake ◽  
Oral Delivery ◽  
Therapeutic Potential ◽  
Pharmacokinetic Profile ◽  
Yellow Pigment ◽  
The Body ◽  
Anti Cancer ◽  
Poor Absorption ◽  
Oral Delivery Systems

The yellow pigment curcumin, extracted from turmeric, is a renowned polyphenol with a broad spectrum of health properties such as antioxidant, anti-inflammatory, anti-cancer, antidiabetic, hepatoprotective, anti-allergic, anti-dermatophyte, and neuroprotective. However, these properties are followed by a poor pharmacokinetic profile which compromises its therapeutic potential. The association of low absorption by the small intestine and the extensive reductive and conjugative metabolism in the liver dramatically weakens the oral bioavailability. Several strategies such as inhibition of curcumin metabolism with adjuvants as well as novel solid and liquid oral delivery systems have been tried to counteract curcumin poor absorption and rapid elimination from the body. Some of these drug deliveries can successfully enhance the solubility, extending the residence in plasma, improving the pharmacokinetic profile and the cellular uptake.

scholarly journals Therapeutic Effects of Traditional Chinese Medicine on Spinal Cord Injury: A Promising Supplementary Treatment in Future

2016 ◽  
Vol 2016 ◽  
pp. 1-18 ◽  
Author(s):  
Qian Zhang ◽  
Hao Yang ◽  
Jing An ◽  
Rui Zhang ◽  
Bo Chen ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Epigallocatechin Gallate ◽  
Therapeutic Effects ◽  
Cord Injury ◽  
Supplementary Treatment ◽  
Natural Drugs ◽  
Doctoral Dissertations

Objective. Spinal cord injury (SCI) is a devastating neurological disorder caused by trauma. Pathophysiological events occurring after SCI include acute, subacute, and chronic phases, while complex mechanisms are comprised. As an abundant source of natural drugs, Traditional Chinese Medicine (TCM) attracts much attention in SCI treatment recently. Hence, this review provides an overview of pathophysiology of SCI and TCM application in its therapy.Methods. Information was collected from articles published in peer-reviewed journals via electronic search (PubMed, SciFinder, Google Scholar, Web of Science, and CNKI), as well as from master’s dissertations, doctoral dissertations, and Chinese Pharmacopoeia.Results. Both active ingredients and herbs could exert prevention and treatment against SCI, which is linked to antioxidant, anti-inflammatory, neuroprotective, or antiapoptosis effects. The detailed information of six active natural ingredients (i.e., curcumin, resveratrol, epigallocatechin gallate, ligustrazine, quercitrin, and puerarin) and five commonly used herbs (i.e., Danshen, Ginkgo, Ginseng, Notoginseng, and Astragali Radix) was elucidated and summarized.Conclusions. As an important supplementary treatment, TCM may provide benefits in repair of injured spinal cord. With a general consensus that future clinical approaches will be diversified and a combination of multiple strategies, TCM is likely to attract greater attention in SCI treatment.

scholarly journals Therapeutic nanomedicine surmounts the limitations of pharmacotherapy

Open Medicine ◽  
2017 ◽  
Vol 12 (1) ◽  
pp. 271-287 ◽  
Author(s):  
Arome Odiba ◽  
Victoria Ottah ◽  
Comfort Ottah ◽  
Ogechukwu Anunobi ◽  
Chimere Ukegbu ◽  
...  
Keyword(s):  
Cytotoxic Effect ◽  
Unique Property ◽  
The Body ◽  
Regulatory Agencies ◽  
Therapeutic Effects ◽  
Genetic Therapy ◽  
Target Drug Delivery ◽  
Target Drug ◽  
And Control ◽  
Manipulation And Control

AbstractScience always strives to find an improved way of doing things and nanoscience is one such approach. Nanomaterials are suitable for pharmaceutical applications mostly because of their size which facilitates absorption, distribution, metabolism and excretion of the nanoparticles. Whether labile or insoluble nanoparticles, their cytotoxic effect on malignant cells has moved the use of nanomedicine into focus. Since nanomedicine can be described as the science and technology of diagnosing, treating and preventing diseases towards ultimately improving human health, a lot of nanotechnology options have received approval by various regulatory agencies. Nanodrugs also have been discovered to be more precise in targeting the desired site, hence maximizing the therapeutic effects, while minimizing side-effects on the rest of the body. This unique property and more has made nanomedicine popular in therapeutic medicine employing nanotechnology in genetic therapy, drug encapsulation, enzyme manipulation and control, tissue engineering, target drug delivery, pharmacogenomics, stem cell and cloning, and even virus-based hybrids. This review highlights nanoproducts that are in development and have gained approval through one clinical trial stage or the other.

scholarly journals Olanzapine-high potency antipsychotic drug inducing significant weight gain: A case report

2008 ◽  
Vol 136 (5-6) ◽  
pp. 284-288 ◽  
Author(s):  
Nadja Maric ◽  
Dragana Josifovic-Kostic ◽  
Olivera Vukovic ◽  
Dubravka Britvic ◽  
Miroslava Jasovic-Gasic
Keyword(s):  
Weight Gain ◽  
Psychotic Disorders ◽  
Vascular Diseases ◽  
Initial Response ◽  
Young Female ◽  
The Body ◽  
Average Weight ◽  
Therapeutic Effects ◽  
Significant Weight Gain ◽  
High Level

INTRODUCTION Olanzapine is a second generation antipsychotic (SGA) with a high level of therapeutic effectiveness in schizophrenia and other psychotic disorders. Along with the positive therapeutic effects, an increase of the body weight frequently occurs. According to the literature, the average weight gain is about 6-7 kg during several months of treatment. This could be valued as a moderate weight increase. CASE OUTLINE This article presents a case of a young female with schizophrenia, without clinical improvement with several antipsychotics (clozapine, risperidone, haloperidol) and with the occurrence of significant neurological side effects. The treatment started with olanzapine (baseline) was associated with good initial response (PANSS reduction 20% in the first two weeks) and the improvement was maintained further on (PANSS reduction 50% after 16 weeks). Significant increase (20 kg, 40%) in weight appeared during the following 16 weeks (BMI at baseline 17.9 kg/m2; BMI 16 weeks later 25.1 kg/m2). CONCLUSION High effectiveness of olanzapine in schizophrenia symptoms reduction was accompanied by a significant weight gain. However, this drug leads to impaired glucoregulation, dyslipidaemia etc. It also increases the risk of diabetes and cardio-vascular diseases, i.e. the main causes of mortality in schizophrenia after a suicide. Therefore, clinicians are suggested to focus on possible predictors of weight gain during olanzapine therapy, and act accordingly in order to prevent serious health consequences.

scholarly journals The reconstitution of African women's spiritualities in the context of the Amazwi Abesifazane (Voices of Women) project in KwaZulu-Natal (1998-2005)

2006 ◽  
Author(s):  
◽  
Bernice Stott
Keyword(s):  
South Africa ◽  
Narrative Therapy ◽  
Well Being ◽  
National Archive ◽  
The Body ◽  
Government Support ◽  
African Women ◽  
Primary Data ◽  
Therapeutic Effects ◽  
Kwazulu Natal

This study will investigate and critically evaluate the reconstitution of African women’s spiritualities in the context of the Amazwi Abesifazane project. This project forms part of the endeavours of Create Africa South, a Non Governmental Organisation situated in Durban, KwaZulu-Natal, which was initiated by the artist Andries Botha. It encourages women, post trauma, to ‘re-member’ themselves by creating memory cloths of embroidery and appliqué reflecting on their experiences in pre- and post-apartheid South Africa. This interdisciplinary study theorises that it is an archive that speaks about African women resisting destructive forces and reconstituting their spiritualities through the therapeutic effects of creativity. The study will not include research into the many other activities undertaken by Create Africa South. Rupture is implied in the use of the word ‘reconstitution’. Reconstitution encompasses the act of constituting again the character of the body, mind and spirit as regards health, strength and well-being of the women (McIntosh, 1970:261). In this study, spirituality is defined as the way in which the women in the Amazwi Abesifazane project reflect upon and live out their belief in God. The power of storytelling is examined from the perspectives of narratology, narrative therapy, sewing and orality/literary studies as resources for the women’s reclamation of their lives. Defining feminisms in South Africa is problematised by issues of race, class and culture. In a context of poverty, everyday survivalist strategies are the diverse forms of resistance seen in the Amazwi Abesifazane project. The women’s stories, cloths and interviews are triangulated as primary data. They are examples of the rich art of resistance against despair and are located in a paradigm of hope. In conclusion, I strongly call for government support in declaring the project a national archive. The multidimensional mediums of the Amazwi Abesifazane/ UbuMama projects nurture the women’s creativity and revitalise their spiritualities towards personal and national transformation.

scholarly journals 380 GS-3583, a novel FLT3 agonist Fc fusion protein, expands conventional dendritic cells in healthy volunteers

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A413-A414
Author(s):  
Nishanthan Rajakumaraswamy ◽  
Anees Dauki ◽  
Michelle Kuhne ◽  
Torsten Trowe ◽  
Winnie Weng ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Fusion Protein ◽  
Healthy Volunteers ◽  
Phase 1 ◽  
Vital Role ◽  
Controlled Study ◽  
Therapeutic Effects ◽  
Fc Fusion Protein ◽  
Quantitative Changes ◽  
Dose Dependent

BackgroundConventional dendritic cells subtype 1 (cDC1) play a vital role in the priming and expansion of tumor specific CD8+ T cells and their recruitment to tumor microenvironment (TME). However, cDC1s are often underrepresented in the TME. Systemic administration of Fms-like tyrosine kinase 3 ligand (FLT3L), a hematopoietic growth factor that binds to FLT3 on myeloid and lymphoid progenitor cells, leads to expansion of cDC1s in the periphery which can then be recruited into the TME. FLT3 pathway stimulation using GS-3583, a novel FLT3 agonistic Fc fusion protein, has the potential to promote T cell mediated anti-tumor activity. We sought to evaluate the pharmacodynamic (PD) effect of a single dose of GS-3583 in healthy volunteers alongside its safety. Herein, we present the updated results of the study.MethodsThis was a first-in-human, placebo-controlled study of GS-3583 in healthy volunteers to evaluate the safety, pharmacokinetics (PK), and PD of escalating single doses (ranging from 75 micrograms to 2000 micrograms) of GS-3583. The study was blinded to the subjects and the investigator. Each dose cohort enrolled 8–12 healthy subjects who received GS-3583 or placebo as single IV infusion at 3:1 ratio. Subjects were observed in the phase 1 unit for 15 days and then for 12 weeks as outpatients. As part of the PD evaluation, we investigated the changes in the number of cDC1 and cDC2 cells.ResultsAs of 2nd July 2021, selected safety, PK and PD data from all 4 cohorts were available. GS-3583 was well tolerated and all subjects had been discharged. To date, there have been no serious or grade 3 or higher adverse events. Preliminary PK analysis suggested dose-dependent increase in GS-3583 exposure (AUC and Cmax). Preliminary PD analysis shows that administration of GS-3583 resulted in temporary, dose-dependent increases in cDC1/cDC2 cells that peaked between days 5–11 (higher doses resulted in later peaks) and returned to baseline within 3 weeks of drug administration (table 1, figure 1).Abstract 380 Table 1Selected subject characteristics and pharmacodynamic resultsAbstract 380 Figure 1A) Comparison of cDC1 cell quantitative changes in cohorts 1–4; B) Comparison of cDC2 cell quantitative changes in cohorts 1–4ConclusionsGS-3583 infusion was well tolerated and induced dose dependent expansion of dendritic cells in the periphery in healthy volunteers. In patients with cancer, this increase in dendritic cells can be utilized to enhance anti-tumor therapeutic effects of immuno-oncology therapies.AcknowledgementsFunding provided by Gilead Sciences, Inc.Ethics ApprovalThe study received study site IRB/Ethics Committee approval prior to enrollment of subjects.

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