Heteropterys tomentosa A. Juss: Toxicological and adaptogenic effects in experimental models

2017 ◽  
Vol 23 (4) ◽  
pp. 289-298 ◽  
Author(s):  
Géssica Alves Fraga ◽  
Sikiru Olaitan Balogun ◽  
Emilly Della Pascqua ◽  
Ruberlei Godinho de Oliveira ◽  
Guilherme Botelho ◽  
...  
Keyword(s):  
Oral Administration ◽  
High Performance ◽  
Scientific Evidence ◽  
Endurance Performance ◽  
Experimental Models ◽  
Time To Exhaustion ◽  
Oral Toxicity ◽  
Exercise Load

Background: The constant pursuit of improved athletic performance characterizes high-performance sport and the use of medicinal plants as dietary supplements is becoming widespread among athletes to enhance long-term endurance performance. Aim: The present study evaluated the toxicity of Heteropterys tomentosa (HEHt) and its acute adaptogenic effects. Methods: The in vitro safety profile was evaluated on CHO-k1 cells using the alamar Blue assay, at concentrations ranging from 3.125 to 200 µg/mL. In vivo acute oral toxicity was conducted in male and female mice with oral administration of graded doses of HEHt from 400 to 2000 mg/kg. A subchronic oral toxicity study was completed by oral administration of HEHt (50, 200 or 1000 mg/kg) and vehicle for 30 days in male Wistar rats. Clinical observations and toxicological related parameters were determined. Blood was collected for biochemical and hematological analyses, while histological examinations were performed on selected organs. Thereafter, an adaptogenic test consisting of progressive loads until exhaustion was conducted in rats ( n = 5/group) orally pre-treated with the vehicle and HEHt (25, 100 or 400 mg/kg). Results: HEHt exhibited no cytotoxic effects on the CHO-k1 cells and, apparently, no acute toxicity in mice and no subchronic toxicity in rats. An ergogenic effect was observed only at the dose of 25 mg/kg compared with the vehicle in relation to time to exhaustion and exercise load ( p = .011 and .019, respectively). HEHt is safe at up to 400 mg/kg, contains astilbin and taxifolin as the major phytochemical compounds, and exhibited a potential adaptogenic effect. Conclusions: These results justify its anecdotal usage as a tonic, show that the hydroethanolic maceration of the root does not cause toxicity, and provide scientific evidence of its potential as a source of new adaptogenic substance(s).

scholarly journals Pharmacokinetics of 1-(2-fluoro-5-methyl-beta-L-arabinofuranosyl)uracil in woodchucks.

1997 ◽  
Vol 41 (10) ◽  
pp. 2184-2187 ◽  
Author(s):  
J W Witcher ◽  
F D Boudinot ◽  
B H Baldwin ◽  
M A Ascenzi ◽  
B C Tennant ◽  
...  
Keyword(s):  
Animal Model ◽  
Oral Administration ◽  
Intravenous Administration ◽  
High Performance ◽  
Hepatitis Virus ◽  
Volume Of Distribution ◽  
Terminal Phase ◽  
Intravenous And Oral Administration

1-(2-Fluoro-5-methyl-beta-L-arabinofuranosyl)uracil (L-FMAU) is a nucleoside analog with potent in vitro activity against hepatitis B virus (HBV) and Epstein-Barr virus. The purpose of this study was to characterize the disposition of L-FMAU following oral and intravenous administration in the woodchuck animal model. The numerous similarities between woodchuck hepatitis virus and HBV infection justify the use of the woodchuck as an animal model for preclinical studies of anti-HBV agents in vivo. Woodchucks were given 25 mg of L-FMAU per kg of body weight intravenously and orally. Concentrations of L-FMAU in urine and plasma were determined by high-performance liquid chromatography. Following intravenous administration of 25 mg of L-FMAU per kg to woodchucks, total clearance was moderate, averaging 0.23 +/- 0.07 liter/h/kg. Renal clearance and nonrenal clearance averaged 0.13 +/- 0.08 and 0.10 +/- 0.06 liter/h/kg, respectively. The steady-state volume of distribution averaged 0.99 +/- 0.17 liter/kg, indicative of intracellular distribution of the nucleoside. The terminal-phase half-life of L-FMAU following intravenous administration averaged 6.2 +/- 2.0 h, and mean residence time averaged 4.5 +/- 0.8 h. Absorption of L-FMAU after oral administration was incomplete, and bioavailability was approximately 20%. Concentrations of L-FMAU in plasma remained above the in vitro 50% effective concentration of 0.026 microg/ml for HBV (C. K. Chu, T. Ma, K. Shanmuganathan, C. Wang, Y. Xiang, S. B. Pai, G.-Q. Yao, J.-P. Sommadossi, and Y.-C. Cheng, Antimicrob. Agents Chemother. 39:979-981, 1995) for 24 h after both intravenous and oral administration of 25 mg of L-FMAU per kg.

Anti-atherosclerotic effects of fruit bioactive compounds: A review of current scientific evidence

2012 ◽  
Vol 92 (3) ◽  
pp. 407-419 ◽  
Author(s):  
Surangi H. Thilakarathna ◽  
H. P. Vasantha Rupasinghe
Keyword(s):  
Bioactive Compounds ◽  
Antioxidant Activities ◽  
Scientific Evidence ◽  
Experimental Models ◽  
Lipid Lowering ◽  
Experimental Conditions ◽  
Beneficial Effects ◽  
Positive Effects

Thilakarathna, S. H. and Rupasinghe, H. P. V. 2012. Anti-atherosclerotic effects of fruit bioactive compounds: A review of current scientific evidence. Can. J. Plant Sci. 92: 407–419. Atherosclerosis is a condition which leads to a cascade of processes involved in thickening of arterial walls as a result of fatty deposition, which can increase the risk of cardiovascular diseases. Among numerous remedies, the consumption of fruits is believed to have beneficial effects on atherosclerosis development. Various bioactive compounds are present in fruits and they have been found to be responsible for exerting these beneficial effects. Fruit flavonoids and certain terpenoids are among the most efficacious fruit bioactive compounds that have shown positive effects on different in vitro as well as in vivo research models of atherosclerosis. The mechanisms of actions of these compounds vary from exerting antioxidant activities to anti-atherogenic and lipid lowering activities, based on different experimental models. This review article briefly explains how some of the fruit bioactive compounds have affected atherosclerosis under experimental conditions.

scholarly journals An Appraisal of Antidotes’ Effectiveness: Evidence of the Use of Phyto-Antidotes and Biotechnological Advancements

Molecules ◽  
2020 ◽  
Vol 25 (7) ◽  
pp. 1516
Author(s):  
Christiana Eleojo Aruwa ◽  
Yusuf Ola Mukaila ◽  
Abdulwakeel Ayokun-nun Ajao ◽  
Saheed Sabiu
Keyword(s):  
Rural Areas ◽  
Urban Areas ◽  
Scientific Evidence ◽  
Experimental Models ◽  
Proof Of Concept ◽  
Avoidable Death ◽  
Short And Long Term

Poisoning is the greatest source of avoidable death in the world and can result from industrial exhausts, incessant bush burning, drug overdose, accidental toxication or snake envenomation. Since the advent of Albert Calmette’s cobra venom antidote, efforts have been geared towards antidotes development for various poisons to date. While there are resources and facilities to tackle poisoning in urban areas, rural areas and developing countries are challenged with poisoning management due to either the absence of or inadequate facilities and this has paved the way for phyto-antidotes, some of which have been scientifically validated. This review presents the scope of antidotes’ effectiveness in different experimental models and biotechnological advancements in antidote research for future applications. While pockets of evidence of the effectiveness of antidotes exist in vitro and in vivo with ample biotechnological developments, the utilization of analytic assays on existing and newly developed antidotes that have surpassed the proof of concept stage, as well as the inclusion of antidote’s short and long-term risk assessment report, will help in providing the required scientific evidence(s) prior to regulatory authorities’ approval.

Neutralization of a Low Molecular Weight Heparin (LHN-1) and Conventional Heparin by Protamine Sulfate in Rats

1986 ◽  
Vol 56 (03) ◽  
pp. 318-322 ◽  
Author(s):  
V Diness ◽  
P B Østergaard
Keyword(s):  
Molecular Weight ◽  
Low Molecular Weight Heparin ◽  
Thrombus Formation ◽  
Experimental Models ◽  
Protamine Sulfate ◽  
Low Molecular Weight ◽  
Antithrombotic Effect ◽  
Higher Doses

SummaryThe neutralization of a low molecular weight heparin (LHN-1) and conventional heparin (CH) by protamine sulfate has been studied in vitro and in vivo. In vitro, the APTT activity of CH was completely neutralized in parallel with the anti-Xa activity. The APTT activity of LHN-1 was almost completely neutralized in a way similar to the APTT activity of CH, whereas the anti-Xa activity of LHN-1 was only partially neutralized.In vivo, CH 3 mg/kg and LHN-1 7.2 mg/kg was given intravenously in rats. The APTT and anti-Xa activities, after neutralization by protamine sulfate in vivo, were similar to the results in vitro. In CH treated rats no haemorrhagic effect in the rat tail bleeding test and no antithrombotic effect in the rat stasis model was found at a protamine sulfate to heparin ratio of about 1, which neutralized APTT and anti-Xa activities. In LHN-1 treated rats the haemorrhagic effect was neutralized when APTT was close to normal whereas higher doses of protamine sulfate were required for neutralization of the antithrombotic effect. This probably reflects the fact that in most experimental models higher doses of heparin are needed to induce bleeding than to prevent thrombus formation. Our results demonstrate that even if complete neutralization of APTT and anti-Xa activities were not seen in LHN-1 treated rats, the in vivo effects of LHN-1 could be neutralized as efficiently as those of conventional heparin. The large fall in blood pressure caused by high doses of protamine sulfate alone was prevented by the prior injection of LHN-1.

Antimicrobial peptides for the treatment of pulmonary tuberculosis, allies or foes?

2018 ◽  
Vol 24 (10) ◽  
pp. 1138-1147
Author(s):  
Bruno Rivas-Santiago ◽  
Flor Torres-Juarez
Keyword(s):  
Pulmonary Tuberculosis ◽  
Antimicrobial Peptides ◽  
Experimental Models ◽  
New Drugs ◽  
World Health ◽  
Public Health Issue ◽  
Health Organization ◽  
Drug Resistant Strains

Tuberculosis is an ancient disease that has become a serious public health issue in recent years, although increasing incidence has been controlled, deaths caused by Mycobacterium tuberculosis have been accentuated due to the emerging of multi-drug resistant strains and the comorbidity with diabetes mellitus and HIV. This situation is threatening the goals of World Health Organization (WHO) to eradicate tuberculosis in 2035. WHO has called for the creation of new drugs as an alternative for the treatment of pulmonary tuberculosis, among the plausible molecules that can be used are the Antimicrobial Peptides (AMPs). These peptides have demonstrated remarkable efficacy to kill mycobacteria in vitro and in vivo in experimental models, nevertheless, these peptides not only have antimicrobial activity but also have a wide variety of functions such as angiogenesis, wound healing, immunomodulation and other well-described roles into the human physiology. Therapeutic strategies for tuberculosis using AMPs must be well thought prior to their clinical use; evaluating comorbidities, family history and risk factors to other diseases, since the wide function of AMPs, they could lead to collateral undesirable effects.

Epithelial Organotypic Cultures: A Viable Model to Address Mechanisms of Carcinogenesis by Epitheliotropic Viruses

2018 ◽  
Vol 18 (4) ◽  
pp. 246-255 ◽  
Author(s):  
Lara Termini ◽  
Enrique Boccardo
Keyword(s):  
Three Dimensional ◽  
Cell Types ◽  
Experimental Models ◽  
Biological Research ◽  
Specific Gene ◽  
Specific Cell ◽  
Organotypic Cultures ◽  
Skin Physiology

In vitro culture of primary or established cell lines is one of the leading techniques in many areas of basic biological research. The use of pure or highly enriched cultures of specific cell types obtained from different tissues and genetics backgrounds has greatly contributed to our current understanding of normal and pathological cellular processes. Cells in culture are easily propagated generating an almost endless source of material for experimentation. Besides, they can be manipulated to achieve gene silencing, gene overexpression and genome editing turning possible the dissection of specific gene functions and signaling pathways. However, monolayer and suspension cultures of cells do not reproduce the cell type diversity, cell-cell contacts, cell-matrix interactions and differentiation pathways typical of the three-dimensional environment of tissues and organs from where they were originated. Therefore, different experimental animal models have been developed and applied to address these and other complex issues in vivo. However, these systems are costly and time consuming. Most importantly the use of animals in scientific research poses moral and ethical concerns facing a steadily increasing opposition from different sectors of the society. Therefore, there is an urgent need for the development of alternative in vitro experimental models that accurately reproduce the events observed in vivo to reduce the use of animals. Organotypic cultures combine the flexibility of traditional culture systems with the possibility of culturing different cell types in a 3D environment that reproduces both the structure and the physiology of the parental organ. Here we present a summarized description of the use of epithelial organotypic for the study of skin physiology, human papillomavirus biology and associated tumorigenesis.

Phytochemical, Analytical and Medicinal Studies of Holoptelea integrifolia Roxb. Planch - A Review

2019 ◽  
Vol 5 (4) ◽  
pp. 270-277 ◽  
Author(s):  
Vijay Kumar ◽  
Simranjeet Singh ◽  
Ragini Bhadouria ◽  
Ravindra Singh ◽  
Om Prakash
Keyword(s):  
Liquid Chromatography ◽  
Thin Layer ◽  
Thin Layer Chromatography ◽  
High Performance ◽  
Biologically Active ◽  
Toxicological Studies ◽  
Wide Range ◽  
Layer Chromatography

Holoptelea integrifolia Roxb. Planch (HI) has been used to treat various ailments including obesity, osteoarthritis, arthritis, inflammation, anemia, diabetes etc. To review the major phytochemicals and medicinal properties of HI, exhaustive bibliographic research was designed by means of various scientific search engines and databases. Only 12 phytochemicals have been reported including biologically active compounds like betulin, betulinic acid, epifriedlin, octacosanol, Friedlin, Holoptelin-A and Holoptelin-B. Analytical methods including the Thin Layer Chromatography (TLC), High-Performance Thin Layer Chromatography (HPTLC), High-Performance Liquid Chromatography (HPLC) and Liquid Chromatography With Mass Spectral (LC-MS) analysis have been used to analyze the HI. From medicinal potency point of view, these phytochemicals have a wide range of pharmacological activities such as antioxidant, antibacterial, anti-inflammatory, and anti-tumor. In the current review, it has been noticed that the mechanism of action of HI with biomolecules has not been fully explored. Pharmacology and toxicological studies are very few. This seems a huge literature gap to be fulfilled through the detailed in-vivo and in-vitro studies.

scholarly journals In-vitro and in-vivo metabolism of different aspirin formulations studied by a validated liquid chromatography tandem mass spectrometry method

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Michele Dei Cas ◽  
Jessica Rizzo ◽  
Mariangela Scavone ◽  
Eti Femia ◽  
Gian Marco Podda ◽  
...  
Keyword(s):  
Oral Administration ◽  
Whole Blood ◽  
Serum Levels ◽  
Reversed Phase ◽  
Weekly Treatment ◽  
Low Dose Aspirin ◽  
Liquid Chromatography Tandem Mass ◽  
Enteric Coated

AbstractLow-dose aspirin (ASA) is used to prevent cardiovascular events. The most commonly used formulation is enteric-coated ASA (EC-ASA) that may be absorbed more slowly and less efficiently in some patients. To uncover these “non-responders” patients, the availability of proper analytical methods is pivotal in order to study the pharmacodynamics, the pharmacokinetics and the metabolic fate of ASA. We validated a high-throughput, isocratic reversed-phase, negative MRM, LC–MS/MS method useful for measuring circulating ASA and salicylic acid (SA) in blood and plasma. ASA-d4 and SA-d4 were used as internal standards. The method was applied to evaluate: (a) the "in vitro" ASA degradation by esterases in whole blood and plasma, as a function of time and concentration; (b) the "in vivo" kinetics of ASA and SA after 7 days of oral administration of EC-ASA or plain-ASA (100 mg) in healthy volunteers (three men and three women, 37–63 years). Parameters of esterases activity were Vmax 6.5 ± 1.9 and Km 147.5 ± 64.4 in plasma, and Vmax 108.1 ± 20.8 and Km 803.2 ± 170.7 in whole blood. After oral administration of the two formulations, tmax varied between 3 and 6 h for EC-ASA and between 0.5 and 1.0 h for plain-ASA. Higher between-subjects variability was seen after EC-ASA, and one subject had a delayed absorption over eight hours. Plasma AUC was 725.5 (89.8–1222) for EC-ASA, and 823.1(624–1196) ng h/mL (median, 25–75% CI) for plain ASA. After the weekly treatment, serum levels of TxB2 were very low (< 10 ng/mL at 24 h from the drug intake) in all the studied subjects, regardless of the formulation or the tmax. This method proved to be suitable for studies on aspirin responsiveness.

scholarly journals A novel PET tracer 18F-deoxy-thiamine: synthesis, metabolic kinetics, and evaluation on cerebral thiamine metabolism status

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Changpeng Wang ◽  
Siwei Zhang ◽  
Yuefei Zou ◽  
Hongzhao Ma ◽  
Donglang Jiang ◽  
...  
Keyword(s):  
High Performance ◽  
Specific Activity ◽  
High Accumulation ◽  
Metabolic Kinetics ◽  
Thiamine Metabolism ◽  
Pet Tracer ◽  
The Status ◽  
The Brain

Abstract Background Some neuropsychological diseases are associated with abnormal thiamine metabolism, including Korsakoff–Wernicke syndrome and Alzheimer’s disease. However, in vivo detection of the status of brain thiamine metabolism is still unavailable and needs to be developed. Methods A novel PET tracer of 18F-deoxy-thiamine was synthesized using an automated module via a two-step route. The main quality control parameters, such as specific activity and radiochemical purity, were evaluated by high-performance liquid chromatography (HPLC). Radiochemical concentration was determined by radioactivity calibrator. Metabolic kinetics and the level of 18F-deoxy-thiamine in brains of mice and marmosets were studied by micro-positron emission tomography/computed tomography (PET/CT). In vivo stability, renal excretion rate, and biodistribution of 18F-deoxy-thiamine in the mice were assayed using HPLC and γ-counter, respectively. Also, the correlation between the retention of cerebral 18F-deoxy-thiamine in 60 min after injection as represented by the area under the curve (AUC) and blood thiamine levels was investigated. Results The 18F-deoxy-thiamine was stable both in vitro and in vivo. The uptake and clearance of 18F-deoxy-thiamine were quick in the mice. It reached the max standard uptake value (SUVmax) of 4.61 ± 0.53 in the liver within 1 min, 18.67 ± 7.04 in the kidney within half a minute. The SUV dropped to 0.72 ± 0.05 and 0.77 ± 0.35 after 60 min of injection in the liver and kidney, respectively. After injection, kidney, liver, and pancreas exhibited high accumulation level of 18F-deoxy-thiamine, while brain, muscle, fat, and gonad showed low accumulation concentration, consistent with previous reports on thiamine distribution in mice. Within 90 min after injection, the level of 18F-deoxy-thiamine in the brain of C57BL/6 mice with thiamine deficiency (TD) was 1.9 times higher than that in control mice, and was 3.1 times higher in ICR mice with TD than that in control mice. The AUC of the tracer in the brain of marmosets within 60 min was 29.33 ± 5.15 and negatively correlated with blood thiamine diphosphate levels (r = − 0.985, p = 0.015). Conclusion The 18F-deoxy-thiamine meets the requirements for ideal PET tracer for in vivo detecting the status of cerebral thiamine metabolism.

scholarly journals In Vitro Antibacterial Effect of the Methanolic Extract of the Korean Soybean Fermented Product Doenjang against Staphylococcus aureus

Animals ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 2319
Author(s):  
Klara Lalouckova ◽  
Lucie Mala ◽  
Petr Marsik ◽  
Eva Skrivanova
Keyword(s):  
Staphylococcus Aureus ◽  
High Performance ◽  
Methanolic Extract ◽  
Bioactive Substances ◽  
Microdilution Method ◽  
Antibacterial Compound ◽  
Fermented Product ◽  
Broth Microdilution Method

Ultra-high performance liquid chromatography/mass spectrometry showed soyasaponin I and the isoflavones daidzein, genistein, and glycitein to be the main components of the methanolic extract of the Korean soybean fermented product doenjang, which is known to be a rich source of naturally occurring bioactive substances, at average contents of 515.40, 236.30, 131.23, and 29.00 ng/mg, respectively. The antimicrobial activity of the methanolic extract of doenjang against nine Staphylococcusaureus strains was determined in vitro by the broth microdilution method to investigate its potential to serve as an alternative antibacterial compound. The results suggest that the extract is an effective antistaphylococcal agent at concentrations of 2048–4096 µg/mL. Moreover, the tested extract also showed the ability to inhibit the growth of both methicillin-sensitive and methicillin-resistant animal and clinical S. aureus isolates. The growth kinetics of the chosen strains of S. aureus at the minimum inhibitory concentration of the methanolic extract of doenjang support the idea that the tested extract acts as an antibacterial compound. To the best of our knowledge, this is the first report on the antistaphylococcal action of the methanolic extract of doenjang thus, additional studies including in vivo testing are necessary to confirm this hypothesis.

Sign in / Sign up

Export Citation Format

Share Document