Phenolic Bioactives as Antiplatelet Aggregation Factors: The Pivotal Ingredients in Maintaining Cardiovascular Health

Cardiovascular diseases (CVD) are one of the main causes of mortality in the world. The development of these diseases has a specific factor—alteration in blood platelet activation. It has been shown that phenolic compounds have antiplatelet aggregation abilities and a positive impact in the management of CVD, exerting prominent antioxidant, anti-inflammatory, antitumor, cardioprotective, antihyperglycemic, and antimicrobial effects. Thus, this review is intended to address the antiplatelet activity of phenolic compounds with special emphasis in preventing CVD, along with the mechanisms of action through which they are able to prevent and treat CVD. In vitro and in vivo studies have shown beneficial effects of phenolic compound-rich plant extracts and isolated compounds against CVD, despite that the scientific literature available on the antiplatelet aggregation ability of phenolic compounds in vivo is scarce. Thus, despite the current advances, further studies are needed to confirm the cardioprotective potential of phenolic compounds towards their use alone or in combination with conventional drugs for effective therapeutic interventions.

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Isolation of hydroxytyrosol from olive leaves extract, radioiodination and investigation of bioaffinity using in vivo/in vitro methods

Radiochimica Acta ◽

10.1524/ract.2013.2068 ◽

2013 ◽

Vol 101 (9) ◽

pp. 585-593 ◽

Cited By ~ 1

Author(s):

M. Ozkan ◽

F. Z. Biber Muftuler ◽

A. Yurt Kilcar ◽

E. I. Medine ◽

P. Unak

Keyword(s):

Small Intestine ◽

Phenolic Compounds ◽

Biological Activities ◽

In Vivo Studies ◽

Flavonoid Content ◽

Olive Leaves ◽

In Vitro Methods ◽

Extraction And Purification

Summary It is known that medicinal plants like olive have biological activities due to their flavonoid content such as olueropein, tyrosol, hydroxytyrosol etc. In current study, hydroxytrosol (HT) which is one of the major phenolic compounds in olive, olive leaves and olive oil, was isolated after methanol extraction and purification of olive leaves which are grown in the northern Anatolia region of Turkey. The isolated HT was radiolabeled with 131I (131I-HT) and the bioaffinity of this radiolabeled component of olive leaves extract was investigated by using in vivo/in vitro methods. It was found that HT could be radiolabeled with 131I in yields of 95.6±4.4% (n = 8), and in vivo studies showed that 131I-HT is taken up by urinary bladder, stomach, small intestine, large intestine, breast and prostate. Significant incorporation of activity was observed in cell lines via in vitro studies.

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Activity profile of two 5-nitroindazole derivatives over the moderately drug-resistant Trypanosoma cruzi Y strain (DTU TcII): in vitro and in vivo studies

Parasitology ◽

10.1017/s0031182020000955 ◽

2020 ◽

Vol 147 (11) ◽

pp. 1216-1228

Author(s):

Cristina Fonseca-Berzal ◽

Cristiane França da Silva ◽

Denise da Gama Jaen Batista ◽

Gabriel Melo de Oliveira ◽

José Cumella ◽

...

Keyword(s):

Trypanosoma Cruzi ◽

Positive Impact ◽

Cardiac Cells ◽

In Vivo Studies ◽

Drug Resistant ◽

Activity Profile ◽

Reference Drug ◽

Novel Drugs

AbstractIn previous studies, we have identified several families of 5-nitroindazole derivatives as promising antichagasic prototypes. Among them, 1-(2-aminoethyl)-2-benzyl-5-nitro-1,2-dihydro-3H-indazol-3-one, (hydrochloride) and 1-(2-acetoxyethyl)-2-benzyl-5-nitro-1,2-dihydro-3H-indazol-3-one (compounds 16 and 24, respectively) have recently shown outstanding activity in vitro over the drug-sensitive Trypanosoma cruzi CL strain (DTU TcVI). Here, we explored the activity of these derivatives against the moderately drug-resistant Y strain (DTU TcII), in vitro and in vivo. The outcomes confirmed their activity over replicative forms, showing IC50 values of 0.49 (16) and 5.75 μm (24) towards epimastigotes, 0.41 (16) and 1.17 μm (24) against intracellular amastigotes. These results, supported by the lack of toxicity on cardiac cells, led to better selectivities than benznidazole (BZ). Otherwise, they were not as active as BZ in vitro against the non-replicative form of the parasite, i.e. bloodstream trypomastigotes. In vivo, acute toxicity assays revealed the absence of toxic events when administered to mice. Moreover, different therapeutic schemes pointed to their capability for decreasing the parasitaemia of T. cruzi Y acute infected mice, reaching up to 60% of reduction at the peak day as monotherapy (16), 79.24 and 91.11% when 16 and 24 were co-administered with BZ. These combined therapies had also a positive impact over the mortality, yielding survivals of 83.33 and 66.67%, respectively, while untreated animals reached a cumulative mortality of 100%. These findings confirm the 5-nitroindazole scaffold as a putative prototype for developing novel drugs potentially applicable to the treatment of Chagas disease and introduce their suitability to act in combination with the reference drug.

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Prosopis Plant Chemical Composition and Pharmacological Attributes: Targeting Clinical Studies from Preclinical Evidence

Biomolecules ◽

10.3390/biom9120777 ◽

2019 ◽

Vol 9 (12) ◽

pp. 777 ◽

Cited By ~ 1

Author(s):

Javad Sharifi-Rad ◽

Farzad Kobarfard ◽

Athar Ata ◽

Seyed Abdulmajid Ayatollahi ◽

Nafiseh Khosravi-Dehaghi ◽

...

Keyword(s):

Chemical Composition ◽

Clinical Studies ◽

Positive Impact ◽

Biological Effects ◽

Food Supplement ◽

In Vivo Studies ◽

Plant Chemical ◽

Food Applications

Members of the Prosopis genus are native to America, Africa and Asia, and have long been used in traditional medicine. The Prosopis species most commonly used for medicinal purposes are P. africana, P. alba, P. cineraria, P. farcta, P. glandulosa, P. juliflora, P. nigra, P. ruscifolia and P. spicigera, which are highly effective in asthma, birth/postpartum pains, callouses, conjunctivitis, diabetes, diarrhea, expectorant, fever, flu, lactation, liver infection, malaria, otitis, pains, pediculosis, rheumatism, scabies, skin inflammations, spasm, stomach ache, bladder and pancreas stone removal. Flour, syrup, and beverages from Prosopis pods have also been potentially used for foods and food supplement formulation in many regions of the world. In addition, various in vitro and in vivo studies have revealed interesting antiplasmodial, antipyretic, anti-inflammatory, antimicrobial, anticancer, antidiabetic and wound healing effects. The phytochemical composition of Prosopis plants, namely their content of C-glycosyl flavones (such as schaftoside, isoschaftoside, vicenin II, vitexin and isovitexin) has been increasingly correlated with the observed biological effects. Thus, given the literature reports, Prosopis plants have positive impact on the human diet and general health. In this sense, the present review provides an in-depth overview of the literature data regarding Prosopis plants’ chemical composition, pharmacological and food applications, covering from pre-clinical data to upcoming clinical studies.

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Pleiotropic Biological Effects of Dietary Phenolic Compounds and their Metabolites on Energy Metabolism, Inflammation and Aging

Molecules ◽

10.3390/molecules25030596 ◽

2020 ◽

Vol 25 (3) ◽

pp. 596 ◽

Cited By ~ 3

Author(s):

María del Carmen Villegas-Aguilar ◽

Álvaro Fernández-Ochoa ◽

María de la Luz Cádiz-Gurrea ◽

Sandra Pimentel-Moral ◽

Jesús Lozano-Sánchez ◽

...

Keyword(s):

Energy Metabolism ◽

Phenolic Compounds ◽

Molecular Mechanisms ◽

Biological Effects ◽

Biological Properties ◽

In Vivo Studies ◽

Wide Range ◽

High Prevalence

Dietary phenolic compounds are considered as bioactive compounds that have effects in different chronic disorders related to oxidative stress, inflammation process, or aging. These compounds, coming from a wide range of natural sources, have shown a pleiotropic behavior on key proteins that act as regulators. In this sense, this review aims to compile information on the effect exerted by the phenolic compounds and their metabolites on the main metabolic pathways involved in energy metabolism, inflammatory response, aging and their relationship with the biological properties reported in high prevalence chronic diseases. Numerous in vitro and in vivo studies have demonstrated their pleiotropic molecular mechanisms of action and these findings raise the possibility that phenolic compounds have a wide variety of roles in different targets.

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Insects as a source of phenolic compounds and potential health benefits

Journal of Insects as Food and Feed ◽

10.3920/jiff2020.0113 ◽

2021 ◽

pp. 1-12

Author(s):

M.C. Nino ◽

L. Reddivari ◽

C. Osorio ◽

I. Kaplan ◽

A.M. Liceaga

Keyword(s):

Phenolic Compounds ◽

De Novo ◽

Health Benefits ◽

Antimicrobial Activities ◽

In Vivo Studies ◽

Plant Phenolics ◽

Potential Health ◽

Bioactive Potential

The use of insects in traditional medicine and unveiling the chemical structure of the bright pigments in butterfly wings led to the discovery of bioactive phenolic compounds in the insect bodies. These metabolites have been found not only due to the insect absorption and metabolisation of the plant-derived phenolic present in their diet, but also from the ability of insects to synthesise phenolic compounds de novo through the sclerotisation process. Plant phenolics are secondary metabolites involved in the protection of tissues against UV radiation, herbivores, and pathogens, as well as pigmentation of fruits and flowers. These bioactive compounds exhibit antioxidant, anti-inflammatory, anticancer, and antimicrobial activities, demonstrated through in vitro and in vivo studies. This bioactive potential is thought to occur due to their chemical characteristics that allow them to stabilise reactive oxygen species (ROS), chelate prooxidant metal ions, interact with key enzymes and signal cascades involved in biological pathways. Bioactivity of plant phenolics and both in vitro, in vivo studies, suggest that the dietary compounds absorbed by the insect maintain their chemical and bioactive properties. Further characterisation of the phenolic composition in edible insects and evaluation of their bioactive capacity as well as their bioavailability, could result in discovering additional health benefits of entomophagy apart from macro-nutritional (e.g. protein) content.

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Hydroxytyrosol, Tyrosol and Derivatives and Their Potential Effects on Human Health

Molecules ◽

10.3390/molecules24102001 ◽

2019 ◽

Vol 24 (10) ◽

pp. 2001 ◽

Cited By ~ 67

Author(s):

Ana Karković Marković ◽

Jelena Torić ◽

Monika Barbarić ◽

Cvijeta Jakobušić Brala

Keyword(s):

Phenolic Compounds ◽

Olive Oil ◽

Biological Activities ◽

In Vivo Studies ◽

Therapeutic Effects ◽

Endocrine Effects ◽

Pharmacological Potential ◽

A Minor

The Mediterranean diet and olive oil as its quintessential part are almost synonymous with a healthy way of eating and living nowadays. This kind of diet has been highly appreciated and is widely recognized for being associated with many favorable effects, such as reduced incidence of different chronic diseases and prolonged longevity. Although olive oil polyphenols present a minor fraction in the composition of olive oil, they seem to be of great importance when it comes to the health benefits, and interest in their biological and potential therapeutic effects is huge. There is a growing body of in vitro and in vivo studies, as well as intervention-based clinical trials, revealing new aspects of already known and many new, previously unknown activities and health effects of these compounds. This review summarizes recent findings regarding biological activities, metabolism and bioavailability of the major olive oil phenolic compounds—hydroxytyrosol, tyrosol, oleuropein, oleocanthal and oleacein—the most important being their antiatherogenic, cardioprotective, anticancer, neuroprotective and endocrine effects. The evidence presented in the review concludes that these phenolic compounds have great pharmacological potential, however, further studies are still required.

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Phenolic Compounds in Prevention and Treatment of Skin Cancers: a review

Current Medicinal Chemistry ◽

10.2174/0929867328666210324160324 ◽

2021 ◽

Vol 28 ◽

Author(s):

Francesca Gado ◽

Maria Digiacomo ◽

Jasmine Esposito Salsano ◽

Marco Macchia ◽

Clementina Manera

Keyword(s):

Phenolic Compounds ◽

Skin Cancer ◽

Uv Radiation ◽

Therapeutic Potential ◽

In Vivo Studies ◽

Antitumor Action ◽

Negative Effects ◽

Non Melanoma Skin Cancer

: Several clinical studies have shown that exposure of skin to solar ultraviolet (UV) radiation causes adverse effects, such as inflammation, oxidative stress and DNA damage. As a result, different skin disorders can arise among which skin cancer, including non-melanoma skin cancer (NMSC) and melanoma (MM). Phenolic compounds are plant-derived secondary metabolites with a well-known antioxidant activity, able to counteract the negative effects of UV radiation. In this review we discuss the effects of some selected phenols on NMSC and MM, demonstrating that they can be useful in the prevention and in the treatment of these types of tumors. Moreover, we report the mechanisms by which these phenols carry out their antitumor action. In vitro and in vivo studies have highlighted that many phenols are capable of inducing photoprotection, apoptosis and autophagy. They can also reduce DNA methylation, tumorigenesis, tumor incidence and proliferation. Moreover, we describe some examples of plant extracts, whose anticancer activity appears to be better than that of single phenols. A great concordance of results emerged, despite the differences in experimental methods. Therefore, the knowledge compiled here could provide the basis for conducing some well-organized clinical trials to validate the chemopreventive and the therapeutic potential of some phenolic compounds in patients with NMSC and MM.

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Epicatechin Impact on Primary Hemostasis, Coagulation and Fibrinolysis

Blood ◽

10.1182/blood.v126.23.4677.4677 ◽

2015 ◽

Vol 126 (23) ◽

pp. 4677-4677

Author(s):

Thomas Sinegre ◽

André Mazur ◽

Marc G Berger ◽

Dragan Milenkovic ◽

Anne-Françoise Sapin ◽

...

Keyword(s):

Cardiovascular Health ◽

Conflicts Of Interest ◽

Clinical History ◽

Procoagulant Activity ◽

In Vivo Studies ◽

Clot Lysis ◽

The Impact ◽

Coagulation And Fibrinolysis

Abstract Introduction Cardiovascular diseases are the leading causes of death worldwide. Among cardiovascular risk factors, some are linked to the stages of hemostasis : primary haemostasis, coagulation and fibrinolysis. There is a growing interest on the potential beneficial effects of some nutritional components on cardiovascular health, in particular in the field of thrombosis. Dark chocolate is associated with a one-third reduction in the risk of cardiovascular disease. Cocoa is particularly rich in a flavonoid subclass called flavan-3-ol which includes epicatechin. Epicatechin is a micronutrient found mainly in chocolate, green tea and grape. It has already been proven that epicatechin impacts platelet functions but there are only poor data on the role of epicatechin on coagulation and fibrinolysis. The aim of this study was to evaluate the impact of epicatechin in vitro on the different stages of hemostasis. Patients and methods The study was performed on 10 major healthy subjects. Exclusion criteria were antiplatelet or anticoagulant therapy intake, clinical history of thrombosis or bleeding, thrombocytopenia (platelet count < 150 G/L) and abnormal coagulation profile (fibrinogen < 1.8 g/L, Prothrombin time > 13 s, and activated partial thromboplastin time > 39 s). Platelets agregometry were performed according the ISTH recommendations with (final concentrations) : ADP (2 µmol/L), epinephrin (5 mmol/L), collagen (2 µg/ml), arachidonic acid (1 mmol/L) (Helena Laboratories, Beaumont, USA), thromboxan A2 analog, U46619 (1 mmol/L) (Merck, Darmstadt, Germany), Thrombin Receptor Activating peptide (TRAP, 10 µmol/L) (Roche Rotkreuz, Switzerland). Area under curve at 4 minutes and maximal agregation were the main parametres analysed. Thrombin generation assays (TGA) were performed with PPP reagent low (phospholipids (4 µmol/L) and tissue factor (TF, 1 pmol/L); Stago, Asnières sur Seine, France) on platelet free plasma (PFP). The platelets procoagulant activity was evaluated with PRP reagent (TF 1 pmol/L) (Stago) on platelets rich plasma (PRP) and microparticles procoagulant activity with PRP reagent on plasma rich in microparticles (without platelets). After activation by Ca ionophore ?? Fibrinolysis was evaluated by a clot lysis assay determined by measurements of optical densitometry at 405 nm overtime. Coagulation was initiated by PPP reagent (Stago) sensibilised by an activator of plasminogen (t-PA, actylise®, Boehringer, France ; 200 ng/mL, final concentration). The plasma fibrinolytic potential was assessed by the clot lysis time (CTL), defined as the time from the midpoint of the baseline to maximum turbid transition, to the final plateau phase. In each of the experiments plasmas were used pure or supplemented with a range of (-)-epicatechin (Extrasynthese; Lyon, France) concentration (final concentrations of 0, 1, 10 and 100 mM). All ethical considerations were obtained. Results and discussion 5 women and 5 men were included in this study, with a median age of 33 years (Q1 - Q3) (28-38). Epicatechin 100 µmol/L inhibits platelet aggregation induced by ADP and collagen with maximal agregation of 45 % versus 73 % in control (p< 0.001) and 67 % versus 79 % in control (p < 0.05) respectively. Epicatechin 10 µmol/L impact coagulation and decrease the TGA parameters such as peak or endogenous thrombin potential with 1345 (1161 - 1563) nM.min versus 1503 (1262 - 1728) nM.min (p<0.05) in control. Epicatechin did not seem to interact significantly on the platelet procoagulant activity. No impact of epicatechin was found in microparticles procoagulant activity assessed by TGA. Epicatechin play a profibrinolytic role as evaluated by a clot lysis assay : the CLT with epicatechin 100 µmol/L was significantly lower than without epicatechin with 11,0 (8,0 - 16,0) min versus 15,0 (9,5 - 20,8) min in control (p < 0.01). Conclusion Epicatechin seems to play a role in each stage of haemostasis. The impact on platelets functions is highlighted by lower maximal agregation induced by ADP and collagen. The coagulation is slightly decreased as shown by TGA on PFP. Epicatechin also impairs fibrinolysis evaluated with a clot lysis assay. Further in vivo studies are needed to confirm these results. Disclosures No relevant conflicts of interest to declare.

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In vitro action of Mimosa caesalpinifolia ketone extract on Haemonchus contortus and Trichostrongylus colubriformis

Semina Ciências Agrárias ◽

10.5433/1679-0359.2017v38n4p1963 ◽

2017 ◽

Vol 38 (4) ◽

pp. 1963 ◽

Cited By ~ 1

Author(s):

Danilo Rodrigues Barros Brito ◽

Livio Martins Costa Júnior ◽

João Luis Garcia ◽

Suzana Gomes Lopes ◽

Giselle Cutrim de Oliveira Santos ◽

...

Keyword(s):

Phenolic Compounds ◽

Haemonchus Contortus ◽

Anthelmintic Activity ◽

In Vivo Studies ◽

In Vitro Assays ◽

Trichostrongylus Colubriformis ◽

Lower Efficiency ◽

Egg Hatchability

This study aimed to evaluate the in vitro anthelmintic activity of Mimosa caesalpinifolia (sabiá) ketone extract, which is rich in condensed tannins (CT), on Haemonchus contortus and Trichostrongylus colubriformis. The leaves and stems of M. caesalpinifolia were collected, dried in the shade, and ground to a dry powder from which ketone extracts were obtained for in vitro assays. The extracts were diluted in 5% acetone and PBS to concentrations in the range 0.25-2.80 mg mL-¹ and the inhibition of egg hatchability was assayed. Feces collected from goats naturally infected with H. contortus (55%) and T. colubriformis (45%) were macerated and the helminth eggs were collected to conduct in vitro egg hatchability tests. Nematode larvae collected from the feces were used for a larval exsheathment inhibition assay of M. caesalpinifolia leaf and M. caesalpinifolia leaf and stem ketone extracts at concentrations of 0.6 and 1.2 mg mL-¹; three replicates were performed for each concentration. PBS was used as a negative control. Polyvinylpolypyrrolidone (PVPP) was added to the extracts to assess the effect of phenolic compounds on anthelmintic activity. An inhibitory effect of 80.7% and 82.3% was observed on hatchability after treatment with 1.0 and 2.0 mg mL-¹ M. caesalpinifolia leaf ketone extract, respectively. An inhibition rate lower than 75% was observed for 1.0 mg mL-¹ M. caesalpinifolia leaf and stem ketone extract. The M. caesalpinifolia leaf ketone extract larval exsheathment assay resulted in inhibition of 97.3% and 99.8% at concentrations of 0.6 and 1.2 mg mL-¹, respectively. For the leaf and stem ketone extract, the larval exsheathment inhibition was 94.3% at 1.2 mg mL-¹. The leaf and leaf and stem extracts showed no inhibitory effects on larval exsheathment after the addition of PVPP. These results showed that cuticular loss was related to the action of the phenolic compounds in the M. caesalpinifolia extracts. M. caesalpinifolia leaf ketone extract inhibited egg hatchability, but the leaf and stem extract showed lower efficiency, which indicated a greater abundance of active compounds in the leaves. The M. caesalpinifolia ketone extracts were effective in the inhibition of larval exsheathment at the highest concentration tested. Based on these results, in vivo studies should be performed to demonstrate the anthelmintic activity of this plant in goats.

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Influence of different morphological parts of buckwheat (Fagopyrum esculentum) and its major secondary metabolite rutin on rumen fermentation in vitro

Czech Journal of Animal Science ◽

10.17221/5479-cjas ◽

2012 ◽

Vol 57 (No. 1) ◽

pp. 10-18 ◽

Cited By ~ 17

Author(s):

F. Leiber ◽

C. Kunz ◽

M. Kreuzer

Keyword(s):

Fatty Acids ◽

Phenolic Compounds ◽

Dietary Protein ◽

Dry Matter ◽

Volatile Fatty Acids ◽

In Vivo Studies ◽

Ruminal Fermentation ◽

Beneficial Effects

It was hypothesized that buckwheat, especially its flowers, influences foregut fermentation in ruminant animals because it is rich in phenolic compounds. The entire fresh aerial buckwheat herb, or its parts (leaves, stems, flowers and grain), were incubated for 24 h together with pure ryegrass (1:1, dry matter basis) in an in vitro ruminal fermentation system (Hohenheim Gas Test). Additionally ryegrass, supplemented with 0, 0.5, 5, or 50 mg rutin trihydrate/g dry matter, was incubated. Contents of extractable phenols (g/kg dry matter) were the highest in buckwheat flowers (88), followed by leaves (63), and the lowest in ryegrass (8). The levels of production of total gas and volatile fatty acids demonstrated that the nutritional value of buckwheat was slightly lower than that of ryegrass. Compared to ryegrass alone, ruminal transformation of dietary protein-N <br />into ammonia was lower with 50 mg rutin, buckwheat flowers and buckwheat leaves. Thus, these treatments appeared to have partly protected dietary protein from ruminal degradation. Rutin, at the highest level, buckwheat flowers and the total aerial fraction of the buckwheat plant suppressed methane per unit of total gas by > 10%, either at elevated (rutin) or reduced total gas volume. This indicates that the ways of the influence on the ruminal fermentation pattern differed between pure rutin and buckwheat. In vivo studies have to confirm these potentially beneficial effects of buckwheat if used as forage for ruminants and clarify the role of further phenolic compounds present in buckwheat. Abbreviations: DM = dry matter, HGT = Hohenheim Gas Test, NDF = neutral detergent fibre, TEP = total extractable phenols, VFA = volatile fatty acids

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