scholarly journals Toxicological Evaluation of Piceatannol, Pterostilbene, and ε-Viniferin for Their Potential Use in the Food Industry: A Review

Foods ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 592
Author(s):  
Concepción Medrano-Padial ◽  
Ana Isabel Prieto ◽  
María Puerto ◽  
Silvia Pichardo
Keyword(s):  
Food Industry ◽  
Biological Activities ◽  
In Vitro Tests ◽  
Toxicological Evaluation ◽  
Cytotoxic Effects ◽  
Cancerous Cell ◽  
Toxicological Studies ◽  
Genotoxicity Testing

The application of stilbenes in the food industry is being considered because of their biological activities. Piceatannol, pterostilbene and ε-viniferin have awakened the industry’s interest. However, before they can be commercialized, we must first guarantee their safety for consumers. The present work reviews the toxicological studies performed with these stilbenes. A wide variety of studies has demonstrated their cytotoxic effects in both cancer and non-cancerous cell lines. In contrast, although DNA damage was detected by some authors, in vitro genotoxic studies on the effects of piceatannol, pterostilbene, and ε-viniferin remain scarce. None of the three reviewed substances have been evaluated using the in vitro tests required by the European Food Safety Authority (EFSA) as the first step in genotoxicity testing. We did not find any study on the toxic effects of these stilbenes in vivo. Thus, more studies are needed to confirm their safe use before they can be authorized as additive in the food industry.

scholarly journals Phytochemistry and Pharmacology of Thymus broussonetii Boiss

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Hanae Naceiri Mrabti ◽  
Latifa Doudach ◽  
Naoual El Menyiy ◽  
Mohammed Bourhia ◽  
Ahmad Mohammad Salamatullah ◽  
...  
Keyword(s):  
Secondary Metabolites ◽  
Essential Oils ◽  
Skin Diseases ◽  
Biological Activities ◽  
Aerial Parts ◽  
Toxicological Studies ◽  
Toxicological Investigation ◽  
Antioxidant Effects

Thymus broussonetii Boiss (T. broussonetii) is a rare medicinal and aromatic plant. It is widely used in traditional medicine to treat several diseases, including diarrhea, fever, cough, irritation, skin diseases, rheumatism, respiratory ailments, influenza, and digestion problems. In this review, we have critically summarized previous data on T. broussonetii about its phytochemistry, botanical and geographical distribution, toxicological investigation, and pharmacological properties. Using scientific research databases such as Wiley Online, SciFinder, ScienceDirect, PubMed, SpringerLink, Web of Science, Scopus Wiley Online, and Google Scholar, the data on T. broussonetii were collected and discussed. The presented data regrouped bioactive compounds and biological activities of T. broussonetii. The findings of this work showed that essential oils and extracts of T. broussonetii exhibited numerous pharmacological activities (in vitro and in vivo), particularly antibacterial, antifungal, antioxidant, anticancer, anti-inflammatory, insecticidal, antipyretic, antinociceptive, and immunological and behavioral effects. While toxicological studies of T. broussonetii essential oils and extracts are lacking, modern scientific tools revealed the presence of different classes of secondary metabolites such as terpenoids, alkaloids, flavonoids, tannins, coumarins, quinones, carotenoids, and steroids. T. broussonetii essential oils, especially from the aerial parts, exhibited potent antibacterial, antifungal, and antioxidant effects. An in-depth toxicological investigation is needed to validate the efficacy and safety of T. broussonetii extracts and essential oils and their secondary metabolites. However, further pharmacokinetic and pharmacodynamic studies should be performed to validate its bioavailability.

scholarly journals Scrophulariae Radix: An Overview of Its Biological Activities and Nutraceutical and Pharmaceutical Applications

Molecules ◽  
2021 ◽  
Vol 26 (17) ◽  
pp. 5250
Author(s):  
Hae-Jin Lee ◽  
Hae-Lim Kim ◽  
Dong-Ryung Lee ◽  
Bong-Keun Choi ◽  
Seung-Hwan Yang
Keyword(s):  
Biological Activities ◽  
Neuroprotective Effect ◽  
In Vivo Studies ◽  
Amnesic Effect ◽  
In Vivo Experiments ◽  
Toxicological Studies ◽  
Apoptotic Effect ◽  
Pharmaceutical Industries

Scrophulariae Radix (SR) has an important role as a medicinal plant, the roots of which are recorded used to cure fever, swelling, constipation, pharyngitis, laryngitis, neuritis, sore throat, rheumatism, and arthritis in Asia for more than two thousand years. In this paper, the studies published on Scrophularia buergeriana (SB) and Scrophularia ningpoensis (SN) in the latest 20 years were reviewed, and the biological activities of SB and SN were evaluated based on in vitro and in vivo studies. SB presented anti-inflammatory activities, immune-enhancing effects, bone disorder prevention activity, neuroprotective effect, anti-amnesic effect, and anti-allergic effect; SN showed a neuroprotective effect, anti-apoptotic effect, anti-amnesic effect, and anti-depressant effect; and SR exhibited an immune-enhancing effect and cardioprotective effects through in vitro and in vivo experiments. SB and SN are both known to exert neuroprotective and anti-amensice effects. This review investigated their applicability in the nutraceutical, functional foods, and pharmaceutical industries. Further studies, such as toxicological studies and clinical trials, on the efficacy and safety of SR, including SB and SN, need to be conducted.

Hypotensive effects of the triterpene oleanolic acid for cardiovascular prevention

2020 ◽  
Vol 13 ◽  
Author(s):  
A. Sureda ◽  
M. Monserrat-Mesquida ◽  
S. Pinya ◽  
P. Ferriol ◽  
S. Tejada
Keyword(s):  
Blood Pressure ◽  
Oleanolic Acid ◽  
Ex Vivo ◽  
Biological Activities ◽  
Cardiovascular Prevention ◽  
In Vivo Studies ◽  
Antihypertensive Activity ◽  
In Vitro Tests

Background:: Hypertension is a high prevalent chronic disease worldwide and a major cardiovascular risk factor. Oleanolic acid (3β-hydroxy-olea-12-en-28-oic acid) is a wide distributed bioactive pentacyclic triterpenoid with diverse biological activities such as anti-inflammatory, hepaprotective anti-diabetic or anti-hypertensive. Objective:: The aim of this study was to review and highlight the available data about antihypertensive activity of oleanolic acid and the described mechanisms of action. Method:: Extensive searches were made in the available literature on oleanolic acid and the data investigating its antihypertensive effects were analysed. Results:: Most of research has been performed on animal models of hypertension, ex vivo studies with aortic ring and some in vitro tests with cell cultures, whereas clinical trials are still lacking. Treatment of hypertensive animals with oleanolic acid significantly ameliorated the rise in the systolic blood pressure. In addition, the hypotensive effects of oleanolic acid are also related to a potent diuretic-natriuretic activity and nephroprotection. In vitro studies have characterized the participation of various signalling pathways that modulate the release of vasodilation mediators. Conclusion:: In vitro and in vivo studies suggest that oleanolic acid effectively reduce blood pressure and could be an interesting co-adjuvant to conventional treatment of hypertension.

scholarly journals Design, Synthesis and In-Vitro Biological Evaluation of Antofine and Tylophorine Prodrugs as Hypoxia-Targeted Anticancer Agents

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3327
Author(s):  
Ziad Omran ◽  
Chris P. Guise ◽  
Linwei Chen ◽  
Cyril Rauch ◽  
Ashraf N. Abdalla ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Biological Activities ◽  
Multidrug Resistant ◽  
Biological Evaluation ◽  
High Chemical ◽  
Design Synthesis ◽  
Hypoxic Conditions ◽  
Cancerous Cell

Phenanthroindolizidines, such as antofine and tylophorine, are a family of natural alkaloids isolated from different species of Asclepiadaceas. They are characterized by interesting biological activities, such as pronounced cytotoxicity against different human cancerous cell lines, including multidrug-resistant examples. Nonetheless, these derivatives are associated with severe neurotoxicity and loss of in vivo activity due to the highly lipophilic nature of the alkaloids. Here, we describe the development of highly polar prodrugs of antofine and tylophorine as hypoxia-targeted prodrugs. The developed quaternary ammonium salts of phenanthroindolizidines showed high chemical and metabolic stability and are predicted to have no penetration through the blood–brain barrier. The designed prodrugs displayed decreased cytotoxicity when tested under normoxic conditions. However, their cytotoxic activity considerably increased when tested under hypoxic conditions.

scholarly journals A Toxicological Evaluation of Germanium Sesquioxide (Organic Germanium)

2020 ◽  
Vol 2020 ◽  
pp. 1-17
Author(s):  
Robin A. Reddeman ◽  
Róbert Glávits ◽  
John R. Endres ◽  
Timothy S. Murbach ◽  
Gábor Hirka ◽  
...  
Keyword(s):  
Micronucleus Test ◽  
Germanium Dioxide ◽  
Oral Toxicity ◽  
Toxicological Evaluation ◽  
Toxicological Studies ◽  
Adverse Effect Level ◽  
Dose Oral ◽  
Chromosomal Aberration Test

A battery of OECD- and GLP-compliant toxicological studies was performed to assess the safety of a highly purified germanium sesquioxide, an organic form of the naturally occurring, nonessential trace element germanium. Germanium dioxide and germanium lactate citrate (inorganic germaniums) have been shown to induce renal toxicity, whereas germanium sesquioxide (an organic germanium) has been shown to have a more favorable safety profile. However, past toxicity studies on germanium sesquioxide compounds have not clearly stated the purity of the tested compounds. In the studies reported herein, there was no evidence of mutagenicity in a bacterial reverse mutation test or an in vitro mammalian chromosomal aberration test. There was no genotoxic activity observed in an in vivo mammalian micronucleus test at concentrations up to the limit dose of 2000 mg/kg bw/day. In a 90-day repeated-dose oral toxicity study in Han:WIST rats conducted at doses of 0, 500, 1000, and 2000 mg/kg bw/day by gavage, there were no mortalities, treatment-related adverse effects, or target organs identified. The no-observed-adverse-effect-level (NOAEL) was determined to be 2000 mg/kg bw/day.

Regulatory Genotoxicity Testing: A Critical Appraisal

1995 ◽  
Vol 23 (3) ◽  
pp. 352-379
Author(s):  
Robert D. Combes
Keyword(s):  
Data Interpretation ◽  
In Vitro Tests ◽  
Negative Results ◽  
Testing Strategies ◽  
Current Controversy ◽  
In Vivo Testing ◽  
Development And Validation ◽  
Genotoxicity Testing

This review considers current approaches to regulatory genotoxicity testing, focusing on how the use of animals can be further replaced, reduced and refined. The complementary roles of in vitro and in vivo testing, and the justification for using animals, are discussed in detail. Recommendations are made for improvements and further work, in the light of the considerable current controversy surrounding the composition and deployment of testing strategies, and the interpretation of the data generated, particularly for carcinogenicity prediction. The major problems are the oversensitivity of in vitro tests and the insensitivity of in vivo assays. On the basis of an analysis of some published databases, it is concluded that there is insufficient support for using in vivo genotoxicity assays for screening. Also, it is questionable whether the scientific benefits of using such assays always outweigh the costs to the animals involved. The considerable efforts being made to harmonise in vivo protocols and to develop improved methods for detecting genotoxicity are discussed. It is recommended that more emphasis be placed on characterising genotoxins in vitro, especially for mechanisms of activity, to optimise the benefits of any confirmatory animal tests.. Also, regulatory agencies are urged to require better-designed and more-scientifically sound protocols, in which animal numbers are minimised and data interpretation, particularly that of negative results, is facilitated. Lastly, in the development and validation of transgenic rodent systems, emphasis should be placed on developing protocols in which other acute toxicity and metabolism endpoints can be measured simultaneously with in vivo mutagenesis, while minimising animal numbers.

In vitro and in vivo toxicity evaluation of the freshwater cyanobacterium Heteroleiblenia kuetzingii

2013 ◽  
Vol 8 (12) ◽  
pp. 1216-1229
Author(s):  
Ivanka Teneva ◽  
Plamen Stoyanov ◽  
Rumen Mladenov ◽  
Balik Dzhambazov
Keyword(s):  
Mammalian Cells ◽  
Biological Activities ◽  
In Vitro Tests ◽  
Growth Media ◽  
Fish Cell ◽  
Potential Hazard ◽  
In Vivo Toxicity ◽  
Freshwater Cyanobacterium

AbstractCyanobacteria are prokaryotic organisms characterized by their ability to produce secondary metabolites with different biological activities. The aim of this work was to evaluate the in vitro and in vivo toxicity of the cosmopolitan freshwater cyanobacterium H. kuetzingii. An extract from H. kuetzingii and cyanobacterial growth media were assessed for presence of intracellular and extracellular toxins by in vitro tests using primary cell cultures from mouse kidney and fibroblasts, cell lines A549 and 3T3, a fish cell line RTgill-W1 as well as by a traditional in vivo mouse bioassay. The presence of toxicity was compared with the ELISA and HPLC data for corresponding cyanotoxins. In vitro tests showed pronounced cytotoxicity of the cyanobacterium extract and growth medium in which H. kuetzingii released potential extracellular toxic compounds as the mammalian cells were significantly more sensitive to exposure compared to the fish cells. Histopathological analyses of the liver and kidneys of treated mice showed pathological changes such as leukocyte infiltration and necrosis, changes in the proximal and distal convoluted tubules, lack of differentiation of Bowman’s space, enlarged Bowman’s capsules and massive hemorrhages. ELISA and HPLC analyses confirmed the presence of saxitoxins and microcystins at low concentrations. In addition, the histological analyses suggest that H. kuetzingii produces other, yet unknown toxic metabolites. Monitoring efforts are therefore required to evaluate the potential hazard for the freshwater aquatic systems and possible public health implications associated with this cyanobacterium.

scholarly journals Hyssopus Essential Oil: An Update of Its Phytochemistry, Biological Activities, and Safety Profile

2022 ◽  
Vol 2022 ◽  
pp. 1-10
Author(s):  
Javad Sharifi-Rad ◽  
Cristina Quispe ◽  
Manoj Kumar ◽  
Muhammad Akram ◽  
Mewish Amin ◽  
...  
Keyword(s):  
Essential Oils ◽  
Safety Profile ◽  
Food Industry ◽  
Biological Activities ◽  
Herbal Remedies ◽  
Household Products ◽  
Cosmetic Industry ◽  
Loss Of Appetite

The genus Hyssopus is widespread in central Asia, East Mediterranean, and Mongolian areas. It has six main species which are used as herbal remedies, such as Hyssopus officinalis which is used as a condiment and flavoring agent in food industry. The other five species are H. ambiguus, H. cuspidatus, H. latilabiatus, H. macranthus, and H. seravschanicus. Its species are used in the treatment of various ailments such as cold, cough, loss of appetite, fungal infection, and spasmodic condition. Its constituents especially essential oils are popularly used as an additive in beverages, foods, and cosmetics. The volatile constituents are used for aroma in the food industry, cosmetic industry, and household products. The important active constituents in its essential oils are β-pinene, pinocamphone, isopinocamphone, and other terpenoids. Hyssopus genus is also bundled with other secondary metabolites including flavonoids luteolin, quercetin, apigenin, and their glucosides, as well as phenolic compounds including ferulic, p-hydroxy-benzoic acid, protocatechuic acid, chlorogenic, and caffeic acid. Combinedly, the extracts of Hyssopus are reported to have potential antiviral and antifungal activities proven using in vitro studies, whereas in vivo investigations have reported the crucial role of Hyssopus extracts in plasma membrane relaxation, cytotoxic, and sedative effects. This plant is believed to be relatively safe at levels commonly used in foods; nevertheless, more studies are needed to determine the safety profile.

scholarly journals Cobaltabis(dicarbollide) ([o-COSAN]−) as Multifunctional Chemotherapeutics: A Prospective Application in Boron Neutron Capture Therapy (BNCT) for Glioblastoma

Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6367
Author(s):  
Miquel Nuez-Martinez ◽  
Catarina I. G. Pinto ◽  
Joana F. Guerreiro ◽  
Filipa Mendes ◽  
Fernanda Marques ◽  
...  
Keyword(s):  
Small Molecules ◽  
Biological Activities ◽  
3D Models ◽  
In Vitro Tests ◽  
C Elegans ◽  
Model Animal ◽  
Prospective Application ◽  
Small Model

Purpose: The aim of our study was to assess if the sodium salt of cobaltabis(dicarbollide) and its di-iodinated derivative (Na[o-COSAN] and Na[8,8′-I2-o-COSAN]) could be promising agents for dual anti-cancer treatment (chemotherapy + BNCT) for GBM. Methods: The biological activities of the small molecules were evaluated in vitro with glioblastoma cells lines U87 and T98G in 2D and 3D cell models and in vivo in the small model animal Caenorhabditis elegans (C. elegans) at the L4-stage and using the eggs. Results: Our studies indicated that only spheroids from the U87 cell line have impaired growth after treatment with both compounds, suggesting an increased resistance from T98G spheroids, contrary to what was observed in the monolayer culture, which highlights the need to employ 3D models for future GBM studies. In vitro tests in U87 and T98G cells conclude that the amount of 10B inside the cells is enough for BNCT irradiation. BNCT becomes more effective on T98G after their incubation with Na[8,8′-I2-o-COSAN], whereas no apparent cell-killing effect was observed for untreated cells. Conclusions: These small molecules, particularly [8,8′-I2-o-COSAN]−, are serious candidates for BNCT now that the facilities of accelerator-based neutron sources are more accessible, providing an alternative treatment for resistant glioblastoma.

scholarly journals A Toxicological Evaluation of Mango Leaf Extract (Mangifera indica) Containing 60% Mangiferin

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Robin A. Reddeman ◽  
Róbert Glávits ◽  
John R. Endres ◽  
Amy E. Clewell ◽  
Gábor Hirka ◽  
...  
Keyword(s):  
Leaf Extract ◽  
Micronucleus Test ◽  
Mangifera Indica ◽  
Female Rats ◽  
Oral Toxicity ◽  
Toxicological Evaluation ◽  
Male And Female Rats ◽  
Toxicological Studies

A battery of OECD- and GLP-compliant toxicological studies was performed on mango leaf extract (Mangifera indica) containing 60% mangiferin (MLE). No evidence of genotoxicity was found in a bacterial reverse mutation test (Ames). While evidence of clastogenic activity was noted in an in vitro chromosomal aberration test, an in vivo mammalian micronucleus test showed no findings up to the limit dose (2000 mg/kg bw). A 90-day repeated dose oral toxicity study was conducted in rats using doses of 0 (vehicle control), 500, 1000, and 2000 mg/kg bw/day. Based on the lack of mortality or toxic effects in the 90-day study, the NOAEL for MLE in Han:Wist male and female rats was determined to be 2000 mg/kg bw/day, the highest dose tested.

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