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Long-term intake of rosemary and common thyme herbs inhibits experimental thrombosis without prolongation of bleeding time
Abstract
Our earlier study demonstrated an inhibition of experimental thrombogenesis after acute administration of rosemary and common thyme. The present study aimed to investigate the effect of long-term intake of these herbs on platelets, thrombus formation and bleeding time.
Western-style high-fat diet containing 5% or 0.5% dried rosemary or common thyme was given to male 6 week old C57BL/6 mice for 12 weeks. Shear-induced platelet reactivity was measured in vitro by haemostatometry. The antithrombotic effect was assessed by the laser-induced thrombosis technique in the carotid artery of mice. Bleeding time was tested by the tail cut method. Endothelial function was assessed by the flow-mediated vasodilation test.
Rosemary (5% and 0.5%) significantly inhibited arterial thrombus formation. Only the higher concentration of common thyme (5%) had a significant antithrombotic effect. In 5% concentration, both rosemary and common thyme significantly inhibited platelet reactivity and enhanced the flow-mediated vasodilation.
Long-term daily intake of rosemary and common thyme has an antithrombotic effect, which is probably due to inhibition of platelets and stimulation of endothelial cells. The antithrombotic effect was not accompanied by prolongation of bleeding time.
... группа Т -получала диету с низким уровнем кальция и порошком тимьяна (5 мас. %) [16]; ...
... группа Р -получала диету с низким уровнем кальция и порошком розмарина (5 мас. %) [16]; ...
Millions of people around the world suffer from osteoporosis. We need highly effective, safe, and affordable therapeutic agents to help them. Medicinal plants offer a great potential for solving this problem, because they contain many bioactive substances in high concentrations. Of particular value are essen-tial-oil-bearing plants, such as rosemary (Rosmarinus officinalis L.) and thyme (Thymus vulgaris L.). In this research, these two plants were analyzed to identify their effects on the state and formation of the bone tissue in rats. With this aim, we extracted volatile compounds and studied their essential oils using the method of gas chromatography. The results obtained demonstrate that thyme and rosemary monoterpenes effectively inhibit bone resorption. The addition of thyme and rosemary to the diet of rats significantly increased the calcium concentration in their blood plasma and the bone mineral density as compared to the group of rats that were fed a calcium-deficient diet. Notably, thyme bioactive substances have a stronger effect on the bone tissue than rosemary.
... suggests that rosemary extract could inhibit LDL-C oxidation in a biologically relevant human cell culture system (254). Rosemary has shown antithrombotic activity and may improve endothelial function both in vitro and in vivo (255,256). At a 5% concentration, rosemary significantly improved vascular function by inhibiting platelet reactivity and arterial blood clot formation as well as enhancing flow-mediated vasodilation in animals (256). ...
... Rosemary has shown antithrombotic activity and may improve endothelial function both in vitro and in vivo (255,256). At a 5% concentration, rosemary significantly improved vascular function by inhibiting platelet reactivity and arterial blood clot formation as well as enhancing flow-mediated vasodilation in animals (256). Further, rosemary extract inhibited rabbit lung angiotensin I-converting enzyme (ACE) in vitro (257). ...
Spices and herbs have been in use for centuries both for culinary and medicinal purposes. Spices not only enhance the flavor, aroma, and color of food and beverages, but they can also protect from acute and chronic diseases. More Americans are considering the use of spices and herbs for medicinal and therapeutic/remedy use, especially for various chronic conditions. There is now ample evidence that spices and herbs possess antioxidant, anti-inflammatory, antitumorigenic, anticarcinogenic, and glucose- and cholesterol-lowering activities as well as properties that affect cognition and mood. Research over the past decade has reported on the diverse range of health properties that they possess via their bioactive constituents, including sulfur-containing compounds, tannins, alkaloids, phenolic diterpenes, and vitamins, especially flavonoids and polyphenols. Spices and herbs such as clove, rosemary, sage, oregano, and cinnamon are excellent sources of antioxidants with their high content of phenolic compounds. It is evident that frequent consumption of spicy foods was also linked to a lower risk of death from cancer and ischemic heart and respiratory system diseases. However, the actual role of spices and herbs in the maintenance of health, specifically with regards to protecting against the development of chronic, noncommunicable diseases, is currently unclear. This review highlights potential health benefits of commonly used spices and herbs such as chili pepper, cinnamon, ginger, black pepper, turmeric, fenugreek, rosemary, and garlic.
... Examples of plants foods that may possess antioxidant and hypolipidemic effects are tomato and carrots which are rich in carotenoids (Fuhrman et al., 1997), wheat germ and rice bran oil which are rich in tocopherols, phytosterols, unsaturated fatty acids and other oil soluble active constituents (Ardiansyah et al., 2006; khatoon and Gopalakrishna, 2004; Wang and Johnson, 2001; Rustan et al., 1993). Thyme and celery seed contain high levels of phenolic compounds (Naemura et al., 2008; Momin and Nair, 2002). If bioactive extracts from the abovementioned plant foods were mixed together, they may act synergistically as powerful anti atherogenic and hypocholesterolemic nutraceuticals. ...
... It was reported that long-term dietary intake of thyme in C57BL/6 mice impaired platelet functions in vitro and thrombus formations in vivo, while bleeding times were not affected. The mechanism of the antithrombotic effect may involve the suppression of platelet reactivity and the stimulation of the vascular endothelium (Naemura et al., 2008). Flavanoids were shown to markedly reduce platelet deposition, mural thrombi, and injury-induced vasoconstriction after deep arterial injury (Mruk et al., 2000). ...
The present study was postulated to prepare and evaluate the influence of two plant food extract mixtures on plasma lipid profile, oxidative stress and testosterone levels in rats fed a hypercholesterolemic diet. The safety of the studied extract mixtures was evaluated through the determination of liver and kidney functions. The total phenolic contents, tocopherols, fatty acids and unsaponifiable matter (UNSAP) in the extract mixtures were determined. Rats fed a hypercholesterolemic diet were given a daily oral dose (300 mg/kg rat body weight) of either mixture I or II for a month and compared with a control hypercholesterolemic group and a normal control group. Results showed that α-tocopherol was 0.750 and 4.017 mg, γ-tocopherol was 0.564 mg and 0 and δ-tocopherol was 15.23mg and 0.634mg/100g for mixtures I and II, respectively. The phenolic contents in mixtures I and II were 36.74 and 23.72 g gallic acid equivalent/100g mixture, respectively. The GLC investigation of UNSAP revealed that stigmasterol and b-sitosterol were the major phytosterols in mixtures I and II, respectively followed by campesterol in both. The GLC analysis of the fatty acids showed that oleic acid was the major fatty acid in both extract mixtures. Results from the animal experiment showed that feeding a hypercholesterolemic diet produced a significant increase in total lipids, total cholesterol (T-Ch), triglycerides (TGs), low density lipoprotein cholesterol (LDLCh), T-Ch/HDL-Ch, TGs/HDL-Ch and malondialdehyde (MDA) and a significant reduction in high density lipoprotein cholesterol (HDL-Ch), vitamin E, b-carotene and testosterone. Rats fed a hypercholesterolemic diet and given mixture I or II showed significant improvements in plasma lipid profile compared to the hypercholesterolemic control group. This improvement was associated with a significant reduction in oxidative stress reflected by an elevation in plasma levels of antioxidants (vitamin E and b-carotene) and a reduction in plasma MDA levels. The plasma level of testosterone increased significantly in the rats fed the hypercholesterolemic diet and given mixture I or II compared to the hypercholesterolemic control. Plasma testosterone showed a significant negative correlation with plasma TGs and TGs/HDL-Ch in the hypercholesterolemic control rats. The studied extract mixtures showed complete safety towards liver and kidney functions. In conclusion the tested extract mixtures showed an improvement in the plasma lipid profile, a significant increase in testosterone and a decrease in oxidative stress with promising prevention of atherosclerosis and cardiovascular diseases. The antiatherogenic effect of the extract mixtures may be due to the presence of phenolic compounds, phytosterols, tocopherols and unsaturated fatty acids.
El presente estudio fue dirigido a preparar y evaluar la influencia de dos mezclas de extractos de plantas comestibles sobre el perfil lipídico del plasma, estrés oxidativo y nivel de testosterona en ratas alimentadas con una dieta hipercolesterolemica. La salubridad de las mezclas de extractos estudiadas fue evaluada mediante la determinación de las funciones del hígado y del riñón. El contenido total de fenoles, tocoferoles, ácidos grasos, y materia insaponificable (UNSAP) fueron determinado en la mezclas de extractos. Las ratas fueron alimentadas con dietas hipercolesterolémica junto con una dosis oral diaria de (300 mg/kg de peso) cada mezcla I y II durante un mes y comparada con un control hipercolesterolémico y un control normal. Los resultados muestran que el contenido de α-tocopherol fue 0.750 y 4.017 mg, γ-tocopherol fue 0.564 mg y 0 y δ-tocopherol fue 15.23mg y 0.634mg/100g de mezcla I y II, respectivamente. El contenido de fenoles en las mezcla I and II fue 36.74 y 23.72 g equivalentes de ácido gálico/100g de mezcla, respectivamente. La investigación por GLC de UNSAP reveló que el estigmasterol y el b-sitosterol fueron los principales fitoesteroles de las mezclas I y II, respectivamente seguido por el campesterol en ambos casos. El análisis por GLC de los ácidos grasos mostró que el ácido oleico fue el ácido graso mayoritario en ambas mezclas de extractos. Los resultados con animales de experimentación mostraron que la alimentación con dietas hipercolesterolémicas produce un incremento significativo en los lípidos totales, colesterol total (T-Ch), triglicéridos (TGs), colesterol en lipoproteínas de baja densidad (LDL-Ch), en las relaciones T-Ch/ HDL-Ch y TGs/HDL-Ch y malondialdehido (MDA) y una significativa reducción en el colesterol de las lipoproteínas de alta densidad (HDL-Ch), vitamina E, b-caroteno and testosterona. Las ratas alimentadas con dietas hipercolesterolémicas junto con mezclas I y II mostraron una mejora significativa del perfil lipídico del plasma comparado con el grupo control hypercholesterolémico. Esta mejora estuvo asociada con una significativa reducción del estrés oxidativo reflejado por la elevación de los niveles de antioxidantes en el plasma (vitamin E y bcarotene) y reducción de los niveles de MDA en plasma. Los niveles de testosterona en plasma aumentaron significativamente en ratas alimentadas con dietas hipercolesterolémicas junto con mezclas I y II en comparación con el control hipercolesterolémico. La testosterona del plasma mostró una correlación negativa significativa con los TGs y TGs/HDL-Ch en ratas control hipercolesterolémicas. Las mezclas de los extractos estudiados mostraron una completa salubridad hacia las funciones del hígado y el riñón. En conclusión las mezclas mostraron una mejora del perfil lipídico del plasma, un significativo incremento en la testosterona, y un descenso del estrés oxidativo con una prometedora prevención de las enfermedades cardiovasculares y ateroesclerosis. El efecto anti-aterogénico de las mezclas de los extractos puede ser debida a la presencia de compuestos fenólicos, fitoesteroles, tocoferoles y ácidos grasos insaturados.
... In conclusion, it was revealed that long-term dietary intake containing 5% or 0.5% rosemary or 5% thyme remarkable suppressed the rate of thrombus formation in vivo, but the bleeding time did not prolong. The mechanism of the antithrombotic activity has been described as pressing of platelet reactivity and excitation of the vascular endothelium (Naemura et al. 2008). ...
Rosmarinus officinalis L. (Rosemary) is a medicinal and aromatic herb belonging to the Lamiaceae family. The geographical distribution of the plant covers especially the Mediterranean Region and regions with a Mediterranean climate. In addition, it has been cultured in many countries around the world so far. The aerial components of the plant, particularly the leaves, are rich in both volatile and nonvolatile phytochemicals: terpenes, flavonoids, phenolic compounds, alcohols, and esters. Phenolic compounds such as carnosol, carnosic acid, and rosmarinic acid in its content have been associated with the plant’s anticancer, anti-inflammatory, antihyperglycemic, antithrombotic, and antioxidant activities. The antimicrobial and antioxidant bioactivities of its essential oil have been utilized and accepted as a safe conservator in the food industry. While the bioactivity of the plant has been proven by in vivo and in vitro experiments, the results of clinical studies support the existence of these bioactivities. The potential of rosemary to be transformed into herbal medicine is considerable. In this chapter, we present an overview of the distribution, ethnobotany, bioactive and nutritional composition and available extraction techniques, scientific evidences, clinical and toxicological studies, available commercial formulations, and challenges and future recommendations as potential drug candidate of rosemary.KeywordsRosemaryPhenolic compoundsRosmarinic acidBiological activity
Toxicity
... This study will address this knowledge gap and will present the in vitro antimicrobial activity of an eco-friendly strategy based on R. officinalis plant extract, against deteriogenic fungal and bacterial strains. R. officinalis is known for its antibacterial, antifungal cytotoxic, anti-rheumatic, antimutagenic, antioxidant, inflammatory, analgesic, astringent carminative, antithrombotic and chemo-preventive properties, which are mediated by different bioactive compounds such as 1,8-cineol, camphor, α-pinene, limonene, camphene, linalool, borneol, rosmarinic acid, caffeic acid, ursolic acid, betulinic acid, carnosic acid and carnosol [22][23][24][25]. ...
Biodeterioration of cultural heritage is caused by different organisms capable of inducing complex alteration processes. The present study aimed to evaluate the efficiency of Rosmarinus officinalis hydro-alcoholic extract to inhibit the growth of deteriogenic microbial strains. For this, the physico-chemical characterization of the vegetal extract by UHPLC–MS/MS, its antimicrobial and antibiofilm activity on a representative number of biodeteriogenic microbial strains, as well as the antioxidant activity determined by DPPH, CUPRAC, FRAP, TEAC methods, were performed. The extract had a total phenol content of 15.62 ± 0.97 mg GAE/mL of which approximately 8.53% were flavonoids. The polyphenolic profile included carnosic acid, carnosol, rosmarinic acid and hesperidin as major components. The extract exhibited good and wide spectrum antimicrobial activity, with low MIC (minimal inhibitory concentration) values against fungal strains such as Aspergillus clavatus (MIC = 1.2 mg/mL) and bacterial strains such as Arthrobacter globiformis (MIC = 0.78 mg/mL) or Bacillus cereus (MIC = 1.56 mg/mL). The rosemary extract inhibited the adherence capacity to the inert substrate of Penicillium chrysogenum strains isolated from wooden objects or textiles and B. thuringiensis strains. A potential mechanism of R. officinalis antimicrobial activity could be represented by the release of nitric oxide (NO), a universal signalling molecule for stress management. Moreover, the treatment of microbial cultures with subinhibitory concentrations has modulated the production of microbial enzymes and organic acids involved in biodeterioration, with the effect depending on the studied microbial strain, isolation source and the tested soluble factor. This paper reports for the first time the potential of R. officinalis hydro-alcoholic extract for the development of eco-friendly solutions dedicated to the conservation/safeguarding of tangible cultural heritage.
... This anti-inflammatory response has been attributed to the low glycemic impact of cereal fibers (Manning et al., 2008). Celery and thyme in the studied mixtures showed previously antioxidant and antiinflammatory effects due to presence of phenolic compounds (Mohamed and Al-Okbi, 2008;Naemura et al., 2008). Also phenolic compounds may also directly reduce lipid accumulation in adipocytes and pre-adipocytes (Hsu and Yen, 2008). ...
Metabolic syndrome has become a major health problem which may lead to cardiovascular diseases. In a previous work we have proved the cardiovascular protective effect of two plant food mixtures in rats. So, the present work was established to study the cardiovascular protective effect of consumption of balady bread containing the two plant food mixtures beside dietary advice in type 2 diabetic patients having the main components of metabolic syndrome. Mixture I was thyme herb, wheat germ and dry carrot. Mixture II was celery seeds, rice bran and dry tomato. The dietary intervention study with the two types of balady bread in addition of dietary regimen continued for a month. Different biochemical parameters were assessed before and after bread consumption, these include plasma lipid profile, testosterone, adiponectin, malondialdehye and glucose. Nutritional status was evaluated through anthropometric measurements and dietary intake. Correlation study was carried out between biochemical and anthropometric parameters in the patients before dietary intervention. Proximate composition, rheological properties, sensory attributes and color quality of the balady bread were studied. Results clarified that basal line of patients showed elevation of plasmaT-Ch/HDL-Ch, TG/HDL-Ch and oxidative stresscompared to normal values which reflected risks of CVD. Also, plasma adiponectin and testosterone have significant negative correlation with total cholesterol (T-Ch), triglycerides (TGs), malondialdehyde (MDA), low density lipoprotein-cholesterol (LDL-Ch), body mass index and waist circumference, together with significant positive correlation with high density lipoprotein-cholesterol (HDL-Ch) level. Mean Dietary intake of patient in the beginning of the study revealed that all diabetic patients were normo-caloric. Mean Dietary intake of patient after a month of dietary intervention revealed that all diabetic patients reduced their caloric, saturated fat and cholesterol intake and increased their minerals and vitamins intake as a result of dietary advice. Consumption of the two types of balady bread resulted in significant decrease in fasting and postprandial plasma glucose and MDA level and significant improvement of plasma lipid profile together with significant increase in plasma testosterone and adiponectin. Kidney function tests showed non-significant change. Waist circumference and the ratio of waist circumference to height were reduced significantly. Physicochemical evaluation of bread revealed that addition of plant food mixture I or II to wheat flour elevated all the proximate composition parameters (except for carbohydrate), increased water absorption, arrival time, mixing tolerance index and weakening. Dough development time and dough stability were reduced on adding mixture I or II. Adding mixture I or II produced decrease in sensory scores of balady bread for crust colour, and taste. Conclusion: Dietary intervention with functional balady bread beside dietary advice produced increase in plasma adiponectin and testosterone in type 2 diabetic patients along with reduction of visceral obesity, dyslipidemia and oxidative stress. The observed elevation in plasma adiponectin and testosterone together with reduction of T-Ch/HDL-Ch and TG/HDL-Ch could be taken as good marker of the reduction of cardiovascular risk in diabetic patients.
... The activity of REO might be related to the stimulation or protection of bone marrow hematopoiesis and protecting stem cells from hematopoietic responsible for the regeneration and recovery of the system (Abd El-Aziz et al. 2014). Rosemary has shown significant antithrombotic activity in mice that may encompass a direct inhibitory effect on platelets, so protection or treatment with rosemary showed a considerable decline in platelets (Naemura et al. 2008). Also, rosemary extract has been found to exert hepatoprotective effect against Cr (VI) via attenuating the alterations in AST, ALT, and ALP activities in acute liver damage and liver cirrhosis of the animals due to its antioxidant properties (Gutiérrez et al. 2009;Botsoglou et al. 2010). ...
Hexavalent chromium (Cr VI) is widely known as a potential hepatotoxic in humans and animals and its toxicity is associated with oxidative stress. So, an in vivo study was outlined to assess the protective and therapeutic role of Rosmarinus officinalis essential oil (rosemary; REO) against Cr VI-induced hepatotoxicity. Male Wistar rats were assigned into five equal groups (1st group served as control; 2nd and 3rd groups received 0.5 ml/kg BW REO and 2 mg/kg BW Cr VI, respectively; 4th group pretreated with REO then injected with K2Cr2O7; and 5th group received Cr VI then treated with REO for 3 weeks). Results revealed that rats exposed to Cr VI showed a valuable changes in hematological parameters and an increase in oxidative stress markers (Protein carbonyl, TBARS, and H2O2) and a noteworthy decline in glutathione (GSH) content. Furthermore, a considerable decrease in enzymatic antioxidants (SOD, CAT, GPx, and GST), transaminases (AST and ALT), and alkaline phosphatase (ALP) activities, as well as total protein and albumin levels, was detected, while serum liver function biomarkers were increased significantly. In addition, the evaluation of histopathological and immunohistochemical PCNA expression showed significant variations in the liver that confirm the biochemical results. Administration of REO pre- or post-chromium treatment restored the parameters cited above near to the normal values. Otherwise, individual intake with REO slumped lipid peroxidation and gotten better antioxidant status significantly. Conclusively, REO proved to be an effective antioxidant in modulating Cr VI-induced hepatotoxicity, especially in the pretreated rats.
... Besides to the abovementioned remarkable effects of rosemary, some studies have also shown that it displays interesting antiviral (Aruoma et al., 1996;Nasr-Eldin et al., 2017), insecticidal (Isman, 2016), anthelmintic (Zoral, Futami, Endo, Maita, & Katagiri, 2017), (Dias et al., 2000) promotion (Attia et al., 2017;Heidari-Vala et al., 2013;Nusier, Bataineh, & Daradkah, 2007), radioprotective (Ghoneim & Arafat, 2016), bone protective (Putnam, Scutt, Bicknell, Priestley, & Williamson, 2007), myogenic (Şengül, Çeleb _ I, Gelen, & Çinar, 2017), antinociceptive (Gonzalez-Trujano et al., 2007;Martinez, Gonzalez-Trujano, Chavez, & Pellicer, 2012), antidepressant (Machado et al., 2009;Machado et al., 2012;Sasaki, El Omri, Kondo, Han, & Isoda, 2013), and antithrombotic (Naemura, Ura, Yamashita, Arai, & Yamamoto, 2008;Yamamoto, Yamada, Naemura, Yamashita, & Arai, 2005) effects (Table 14). ...
Rosmarinus species are aromatic plants that mainly grow in the Mediterranean region. They are widely used in folk medicine, food, and flavor industries and represent a valuable source of biologically active compounds (e.g., terpenoids, flavonoids, and phenolic acids). The extraction of rosemary essential oil is being done using three main methods: carbon dioxide supercritical extraction, steam distillation, and hydrodistillation. Furthermore, interesting antioxidant, antibacterial, antifungal, antileishmanial, anthelmintic, anticancer, anti‐inflammatory, antidepressant, and antiamnesic effects have also been broadly recognized for rosemary plant extracts. Thus the present review summarized data on economically important Rosmarinus officinalis species, including isolation, extraction techniques, chemical composition, pharmaceutical, and food applications. Rosmarinus species are aromatic plants that mainly grow in the Mediterranean region. They are widely used in folk medicine, food, and flavor industries and represent a valuable source of biologically active compounds (e.g., terpenoids, flavonoids, and phenolic acids). The extraction of rosemary essential oil is being done using three main methods: carbon dioxide supercritical extraction, steam distillation, and hydrodistillation.
... R. officinalis has shown substantial antithrombotic activity in various experimental animals (Naemura et al. 2008). R. officinalis has also shown antithrombotic activity in patients with coagulation disorders or receiving antiplatelet agents (Yamamoto et al. 2005). ...
Rosemary (Rosmarinus officinalis L.), the representative of Lamiaceae family is known for its various medicinal uses that are accompanied by their hallmark secondary metabolites, i.e., carnosol, carnosic acid and rosmarinic acid (mostly the polyphenolic diterpenes). In the age of medicines and methodologies, when we are floating through the advancements and achievements, we are being hijacked by various diseases leading to increased number of young deaths. Neurological disorders are one of them and characterized by any impairment in the nervous system, brain or spinal cord. The majority of young and aged people around the globe are manifested by neurological disorders, i.e., stroke, epilepsy, dementia, Alzheimer’s disease (AD), Parkinson’s disease (PD) and migraine. A large number of therapeutic approaches mend the symptoms in early stages of these disorders, but with the span of time, patients become progressively more disabled as they may suffer from drug-associated adverse effects. Emphasizing on the urgent need of alternative therapeutic regimens, natural products are encouraged worldwide in terms of safety and to minimize the aforesaid loss. In this order, the current chapter summarizes the protective role of R. officinalis L. and its bio-active metabolites against various neurological disorders via targeting amyloid-beta (A-β) aggregation, neuronal cell death, acetylcholinesterase (AChE), neuroinflammation, β-secretase (BACE-1) activity, mitochondrial redox status, etc. Based on the multifunctional nature due to effective bio-active secondary metabolites, R. officinalis can be a terrific alternative therapeutic source against many neurodegenerative diseases.
... e animals had ad libitum access to food and deionized water and were subdivided into five groups (7 rats each) as follows: group 1: control negative (C−) was fed standard balanced diet AIN-93G with normal calcium level (0.5% w/ w) according to formula described by Reeves et al. [22]; group 2: control positive (C+) was fed balanced diet with low calcium level (L Ca) (Ca 0.1% w/w) according to Shinoki and Hara [23]; group 3: thyme (T) was given L Ca diet and treated with thyme power (5% w/w) [24]; group 4: rosemary (R) was given L Ca diet and treated with rosemary power (5% w/w) [25]; group 5: oral calcium (O) was orally administered with CaCO3 (27 mg/kg b.w.) and fed L Ca diet [26]. ...
Osteoporosis poses an important public health problem which affects millions of people worldwide. There is a direct link between calcium deficiency in diet and induction of osteoporosis and bone loss. The current study was conducted to evaluate the protective effect of thyme ( Thymus vulgaris L.) and rosemary ( Rosmarinus officinalis L.) against osteoporosis in rats with low calcium intake. Essential oils of rosemary and thyme were analyzed. The experiment was carried out on growing male Sprague–Dawley rats; the experimental animals were divided into 5 groups: 1, control negative was fed standard balanced diet; 2, control positive was fed balanced diet with low calcium level (L Ca) (Ca 0.1% w/w); 3, (L Ca) + thyme powder (5% w/w); 4, (L Ca) + rosemary powder (5% w/w); 5, (L Ca) + orally administration with CaCO 3 (27 mg/kg body weight). Blood samples were collected for different biochemical analyses in plasma (calcium (Ca), phosphorus (P), magnesium (Mg), tumor necrosis factor-alpha (TNF- α ), C-reactive protein (CRP), malondialdehyde (MDA), parathyroid hormone (PTH), C-terminal telopeptide (CTX), and 1,25-(OH)2-vitamin D3). Femur mass, length, and bone mineral density (BMD) were recorded, and histopathological studies for femurs were examined. Low-calcium diet induced osteoporotic changes in positive control rats (decrease in Ca, vitamin D3, and BMD and increase in CTX, PTH, TNF- α , CRP, and MDA). Supplementation with thyme and rosemary inhibited significantly the development of bone loss, increased Ca and vitamin D3 in plasma, improved BMD, and also prevented the inflammation and oxidative stress (improved TNF- α , CRP and MDA) compared to the positive control. The histopathological examination of treated groups showed an improvement in bone histology and protection against bone loss. However, thyme powder showed more effective impact than rosemary. Our study demonstrates that thyme and rosemary effectively mitigated calcium deficiency-induced bone loss and maybe considered as promising candidates for preventing bone resorption and osteoporosis.
... Anticancer activity against different types of cancer; ovarian cancer cell lines [11], cervical cancer [12] prostate cancer cells [13] and antispasmodic [14]. Antidepressant-like effect in animal models [15], anti-thrombotic effect [16] and it is used for obesity, constipation, kidney stones, hypertension, common cold, abdominal pains, ulcer, flatulence, toothache and edema [17]. ...
Purpose: The aim of the current study was to investigate the invitro antiproliferative activity of methanolic extracts of six plants regardless of their claimed ethnopharmacological application. Methods: Methanol extracts of different parts of Glycyrrhizaglabra L. (Licorice),Matricariachamomilla L. (Chamomile), Salvia triloba L. (Sage), Rheum palmatum L. (Rhubarb), Trigonellafoenum-graecumL. (Fenugreek) and Sambucusebulus L. (Dwarf Elder) were prepared. The antiproliferative effects of the extracts were tested on two skin cancer melanoma cell lines namely A375.S2 (low tyrosinase expression) and WM 136.1A (high tyrosinase expression) using MTT assay. The IC50 values for the active extracts were determined against the two melanoma cell lines. Results: The methanolic extracts of G.glabra, M. chamomilla, S.triloba, R. palmatum inhibited the melanotic WM1361A proliferation in a dose-dependent manner revealing IC50 values of 35.2, 25.2, 20.6, 17.8, µg/ml, respectively but not A375.S2 cell line. However, the extracts of T. foenum-graecum and S. ebulus did not exhibit any significant cytotoxic activity on both melanoma cell lines. Conclusion: The results of these experiments show that methanol extracts of licorice, chamomile, sage and rhubarb have significant antiproliferative activity onWM1361A cell line; a representative human melanotic melanocyte tumor cell line. This renders these plants as potential sources of new lead compounds for the development of new drugs for melanoma cancer. © Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, 300001 Nigeria and 2018 The authors.
... In vitro and in vivo antithrombotic activity of rosemary has been shown significantly [40,41]. Carnosic acid the major phenolic compound of rosemary has been shown to possess antiplatelet activity via inhibition of cytosolic calcium mobilization [66]. ...
Thrombosis is one of the major causes of morbidity
and mortality in a wide range of vessels diseases.
Due to the high prevalence of thromboembolic disorders
investigations are being carried out on new antithrombotic
agents with limited adverse side effects in which herbal
medicines are considered as alternative remedies. Persian
medicine (PM) as a traditional medicine has a good potential
for pharmacotherapy based on its own principles and
development of drugs via investigating PM literature. In
PM manuscripts there are some concepts that express the
management of blood clots and antithrombotic properties.
This study reviewed the pharmacological effects of medicinal
plants mentioned in PM literature for blood clot management
in light of current knowledge. Plants mentioned in
PM for management of blood clot belong to 12 families in
which Apiaceae, Lamiaceae and Compositae were the most
repeated ones. Among the proposed plants Allium sativum,
Rosmarinus officinalis, Boswellia serrata, Sesamum indicum,
Matricaria chamomilla and Carthamus tinctorius have
been the most researched plants in modern antithrombotic
studies while for some plants such as Helichrysum stoechas,
Dracocephalum kotschi, Carum carvi, Bunium persicum and
Lagoecia cuminoides no evidence could be found. One of
the interesting notes in clot management in PM texts was introducing the target organ for some of the recommended
herbs like Carum carvi and Bunium persicum for dissolving
blood clot in stomach and Commiphora mukul for thrombosed
hemorrhoid. It seems review of PM recommendations
can help to design future researches for antithrombotic drugs
discovering with more effectiveness and safety.
... Anticancer activity against different types of cancer; ovarian cancer cell lines [11], cervical cancer [12] prostate cancer cells [13] and antispasmodic [14]. Antidepressant-like effect in animal models [15], anti-thrombotic effect [16] and it is used for obesity, constipation, kidney stones, hypertension, common cold, abdominal pains, ulcer, flatulence, toothache and edema [17]. ...
Two methanolic extracts of common medicinal plants; Rosmarinus officinalis (rosemary), Salvia triloba (sage), were tested for their antiviral activity against Measles (MV) virus in vitro with the aim of evaluation of the biological activity (cytotoxicity on measles virus) of these aromatic, traditionally used plants in Jordan. A colorimetric tetrazolium-based (MTT) assay as well as visual evaluation of cell morphology using inverted light microscopy has been applied to test cytotoxicity of the different plants concentrations. Antiviral properties of the plant extracts were determined by cytopathic effect inhibition assay using african monkey kidney (Vero) cells. Cytotoxicity results showed that rosemary and sage extracts were toxic at the concentrations 50 and 100 µg /ml to Vero cells. The % inhibition of the Measles virus infectivity was evaluated, Interestingly sage showed a dose dependant inhibition of Measles virus cytopathic effect (CPE) at all virus dilutions A good correlation at the second dilution of the virus was achieved with 50% effective concentration (EC50 =14.74 µg/ml) While rosemary extract exhibited dose-dependent inhibition of Measles virus cytopathic effect at the first dilution of the virus only with an EC50 of 23.96 µg /ml and a considerable inhibition of the viral infectivity with the lowest dilution of virus. Consequently rosemary and sage could be potentially promising for treatment of measles virus and could possess antiviral agents that may act against other viruses too.
... Rosemary, genus Rosmarinus, is comprised of three species, namely Rosmarinus eryocalix, Rosmarinus tomentosus, and Rosmarinus officinalis, which are cultivated as medicinal plants in different areas of the world, such as the Mediterranean, Asia, and Latin America (Hernández et al., 2016). Rosemary is a medicinal plant with a high content of aromatic phenolic compounds with nutraceutical and pharmaceutical properties, including antiobesity, antiinflammatory, antidiabetic, diuretic, antithrombotic, antimicrobial, anticancer, hepatoprotective, and antioxidant (Haloui et al., 2000;Sotelo-Félix et al., 2002;Bozin et al., 2007;Altinier et al., 2007;Naemura et al., 2008;Pérez-Fons et al., 2010;Jiang et al., 2011;Borrás Linares et al., 2011;Srancikova et al., 2013;Petiwala et al., 2013;Borrás-Linares et al., 2015;Sedighi et al., 2015;Fernández-Ochoa et al., 2017). ...
... Phenolic compounds from rosemary (e.g., carnosic acid, carnosol, rosmarinic acid, rosmanol, methyl carnosate, luteolin, betulinic acid, myrcene 7-methyl-epirosmanol, isorosmanol, rosmadial, caffeic acid, and flavonoids as cirsimartin and genkwain), protect against hyperglycemia and hypercholesterolemia-induced oxidative stress, increasing the activities of antioxidant enzymes. Rosemary can prevent the arterial thrombotic, inhibiting platelet reactivity and coagulation (Naemura et al., 2008). The rosmarinic acid has an antipertensive effect by inhibiting and/or modulating angiotensin converting enzyme, or activating NO pathways (which have vasodilator effects) endotheliumdependent hyperpolarizing factor, and prostacyclin (PGI2). ...
Since ancient times, herbs and spices have been used for culinary, medicinal, cosmetic, and spiritual purposes. Many traditional foods around the world are cooked with spices and herbs to enhance their flavor, color, and to improve conservation. Spices are derived from any part of a plant that is not a leaf, such as the root, stem, bulb, bark or seeds; instead, herbs come from the green, leafy part of the plant. In some cases, herbs and spices may come from the same plant. The American Spice Trade Association uses the term spice as an all-inclusive term that encompasses three categories: spices, herbs, and aromatic seeds. Both spices and herbs are rich sources of phytochemicals, many of which are biologically active with antioxidant and antiinflammatory effects; moreover, they may contain essential oils, antioxidants, minerals, and vitamins that are important for overall wellness. As a result, some herbs and spices may be classed as a functional food, with a range of health benefits beyond basic nutrition, such as reduction of the risks of heart diseases, diabetes, obesity, cancer, and Alzheimer's disease. In this chapter, we discuss how spices and herbs may be used for the prevention of deficiencies and against diseases.
... In vitro and in vivo antithrombotic activity of rosemary has been shown significantly [40,41]. Carnosic acid the major phenolic compound of rosemary has been shown to possess antiplatelet activity via inhibition of cytosolic calcium mobilization [66]. ...
Thrombosis is one of the major causes of morbidity and mortality in a wide range of vessels diseases. Due to the high prevalence of thromboembolic disorders investigations are being carried out on new antithrombotic agents with limited adverse side effects in which herbal medicines are considered as alternative remedies. Persian medicine (PM) as a traditional medicine has a good potential for pharmacotherapy based on its own principles and development of drugs via investigating PM literature. In PM manuscripts there are some concepts that express the management of blood clots and antithrombotic properties. This study reviewed the pharmacological effects of medicinal plants mentioned in PM literature for blood clot management in light of current knowledge. Plants mentioned in PM for management of blood clot belong to 12 families in which Apiaceae, Lamiaceae and Compositae were the most repeated ones. Among the proposed plants Allium sativum, Rosmarinus officinalis, Boswellia serrata, Sesamum indicum, Matricaria chamomilla and Carthamus tinctorius have been the most researched plants in modern antithrombotic studies while for some plants such as Helichrysum stoechas, Dracocephalum kotschi, Carum carvi, Bunium persicum and Lagoecia cuminoides no evidence could be found. One of the interesting notes in clot management in PM texts was introducing the target organ for some of the recommended herbs like Carum carvi and Bunium persicum for dissolving blood clot in stomach and Commiphora mukul for thrombosed hemorrhoid. It seems review of PM recommendations can help to design future researches for antithrombotic drugs discovering with more effectiveness and safety.
... Rosemary (Rosmarinus officinalis L., Lamiaceae) is a shrubby plant which has a high content in bioactive compounds with different pharmacological activities, especially antimicrobial (Bozin, Mimica-Dukic, Samojlik, & Jovin, 2007;Jiang et al., 2011), antithrombotic (Naemura, Ura, Yamashita, Arai, & Yamamoto, 2008), diuretic (Haloui, Louedec, Michel, & Lyoussi, 2000), anti-inflammatory (Altinier et al., 2007), hepatoprotective (Sotelo-Félix et al., 2002), anti-oxidant (Pérez-Fons, Garzón, & Micol, 2010), anticancer (Srancikova, Horvathova, & Kozics, 2013), anti-diabetic (Sedighi, Zhao, Yerke, & Sang, 2015) and anti-obesity . Numerous studies have highlighted that the majority of these biological activities are correlated with the phenolic composition (Borrás Linares et al., 2011). ...
Phenolic compounds in rosemary have shown antiproliferative/cytotoxic activity against colorectal cancer cells. The aim of this work was to study in depth the absorption and metabolism of the compounds present in a rosemary extract. An in-situ perfusion assay was performed in mice, for which samples of gastrointestinal liquid taken at different times and plasma obtained at the end of the experiment were analysed by HPLC-ESI-QTOF-MS. The absorption-rate coefficients showed that flavonoids and diterpenes were highly absorbed compared to triterpenes. Several diterpenes and their metabolites were also bioavailable in plasma, highlighting the higher concentrations of glucuronide metabolites compared to non-metabolised phenolic compounds. The antiproliferative/cytotoxic properties could be attributed to the absorbed diterpenes and metabolites, which could reach the colon through bloodstream. On the other hand, compounds poorly absorbed, such as triterpenes and some diterpenes, could exhibit their bioactivity in the large intestine by a mechanism of direct interaction with the microbiota.
... Besides being an aromatic herb, garden thyme has been described to have medicinal properties and a beneficial impact on health, e.g., digestive stimulation action, anti-inflammatory, antimicrobial, hypolipidemic, antimutagenic, and antithrombotic effects, and with anticarcinogenic potential. [11][12][13][14] Its extracts are also used orally to treat dyspepsia and other gastrointestinal disturbances, cough, bronchitis, and laryngitis, but it is also used in the treatment of minor wounds and in oral hygiene [15]. Furthermore, crude extracts of herbs and spices, and other plant materials rich in phenolic compounds (such as thyme), have drawn increasing interest in the food industry because they retard oxidative degradation of lipids and, thereby, improve the quality and nutritional value of food. ...
Thyme is used worldwide both as a spice and crude drug. In addition, nowadays in the food industry it has increasing significance as a natural antioxidant. Volatile aromatic compounds of thyme have been thoroughly characterized; however, the non-volatile compounds may also contribute to the organoleptic quality and antioxidant properties. The aim of this work is to determine the phenolic acids and to profile the flavonoid compounds in the aqueous extract of two chemotypes of Thymus vulgaris L. Experiments were carried out using high performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS). Predefined phenolic acids were quantified in untreated and alkaline hydrolyzed aqueous extracts. Flavonoid derivatives were qualitatively analyzed by a non-targeted screening method. Our results showed that among the phenolic acids rosmarinic acid was the main component (882-1677 μg g-1 fresh weight) and in the thymol-type samples the amount of syringic acid and rosmarinic acid was predominantly higher compared with the non-thymol type sample. Apigenin and luteolin were the major flavonoids in the extracts, which were present in the form of hexopyranuronic acid conjugates.
... Rosemary can prevent the arterial thrombotic disease based on inhibition platelet reactivity and inhibition coagulation tests in vivo and in vitro. The antithrombotic effect of rosemary is likely to be based on an inhibitory effect on platelets (Naemura, Ura, Yamashita, Arai, & Yamamoto, 2008;Yamamoto, Yamada, Naemura, Yamashita, & Arai, 2005). ...
Background: Rosemary (Rosmarinus officinalis L.) is a widely consumed aromatic plant that belongs to the
Lamiaceae family. Fresh and dried leaves are frequently used in traditional Mediterranean cuisine and in
folk medicine.
Scope and approach: For this study, an extensive bibliographic review on rosemary was carried out,
including its main uses, components (both nutrients and bioactive), biological activities, interactions
with drugs and potential applications.
Key findings and conclusions: The nutrient composition of rosemary reveals a great amount of vitamins
and minerals. The most well studied bioactive compounds are carnosic acid, carnosol, caffeic acid and its
derivative, rosmarinic acid. The levels on bioactive compounds depend on many factors, such as the
variety, plant part, edafoclimatic conditions, drying conditions (if applied) and extraction and analysis
methods. Numerous biological activities of rosemary are recognized including antioxidant, antibacterial
and antifungal, anti-cancer, anti-inflammatory, among others. Therefore it has a vast range of industrial
applications such as food and food packaging, pharmaceutical, perfumery and cosmetics industries.
... In the present study, following Rosemary consumption, a significant increase in RBF was observed in comparison with the I/R group ( Table 1). The study by Naemura et al. (2008) demonstrated the acute administration of Rosemary (nearly 5%) significantly inhibits the formation of arterial thrombosis that its mechanism of effect has been attributed to the inhibition of the plackets activity and endothelial stimulation in increased production of vasodilatory mediators because of the presence of flavonoid in it. William showed that Rosemary possesses vasodillatory properties of essential oils and anti-spasmodic properties of alpha-and beta-pinene which enhance blood flow ( Frishman et al., 2004;Taddei et al., 1988;Hosseinzadeh and Nourbakhsh, 1987). ...
... Rosmarinic acid showed significant antithrombotic activity, potentially due to direct inhibition of platelet activity and reduced stimulation of endothelial cells in vitro. 38 Additionally, antifibrotic activity has been demonstrated in vivo by the reduction of fibrin, leading to concerns that Rosmarinus officinalis may interact with antiplatelet and anticoagulant medications. 39 Dose-dependent levels of rosmarinic acid demonstrated angiotensin converting enzyme (ACE) inhibitory activity in vitro. ...
It is common to utilise herbal extracts such as Silybum marianum and Rosmarinus officinalis in naturopathic practice to support hepatic function and improve oestrogen clearance, but what pharmacodynamic evidence is there to support this hypothesis? This article explores the potential use of these two traditional hepatic herbs for the potential treatment of uterine fibroids via and their action on specific CYP450 enzymes. Uterine fibroids are benign smooth muscle overgrowths which occur in various locations in the myometrium and develop from an unknown cause. There is however a wide diversity of known promoters involved in the pathogenesis including steroid hormones, such as oestrogen. Excessive oestrogen synthesis from aromatase P450 can lead to an overexpression of alpha (ER-í µí»¼) and beta (ER-í µí»½) oestrogen receptors, which through binding activity, causes a cascade of growth factors contributing to fibroid development. Considering this increased oestrogen activity has been implicated in stimulating uterine tissue, a novel approach to treating uterine fibroids is by inducing CYP1A1 and inhibiting CYP3A4 to improve the ratio between 2:16 hydroxy catechol oestrogens. Silybum marianum has shown potential in inhibiting CYP3A4 activity in vitro, but evidence from two small clinical trials did not support this. Rosmarinus officinalis shows promise by improving 2:16 hydroxy catechol oestrogen ratio equilibrium in vivo by inducing CYP1A1 and inhibiting CYP3A4 activity. Rosmarinus officinalis may have a role in altering these pathways and therefore may help to reduce the excessive uterotropic action of oestrogen and its metabolites by shifting the metabolism of oestrogen to a less proliferative pathway, but further clinical research is required.
... In the present study, following Rosemary consumption, a significant increase in RBF was observed in comparison with the I/R group (Table 1). The study by Naemura et al. (2008) demonstrated the acute administration of Rosemary (nearly 5%) significantly inhibits the formation of arterial thrombosis that its mechanism of effect has been attributed to the inhibition of the plackets activity and endothelial stimulation in increased production of vasodilatory mediators because of the presence of flavonoid in it. William showed that Rosemary possesses vasodillatory properties of essential oils and anti-spasmodic properties of alpha-and beta-pinene which enhance blood flow (Frishman et al., 2004; Taddei et al., 1988; Hosseinzadeh and Nourbakhsh, 1987). ...
Ischemia/reperfusion (I/R) induced acute renal failure (ARF), causes renal functional and histological disorders. This study investigated the effect of oral Rosemary extract on ARF disorders in rat. Forty male Sprague-Dawley rats were used in 4 groups (n=10) as control, sham, I/R with gavage feeding normal saline, and I/R with gavage feeding of 8% aqueous extract of Rosemary (10 ml/kg/day). ARF was induced by bilateral renal artery and vein occlusion for 30 min. Reperfusion period was continued for 24 h. Blood pressure and renal blood flow of rats were measured using a power lab system (AD instruments). After placing the rats into metabolic cages, urine sampling was done. Plasma samples were obtained and after removing both kidneys and staining kidney sections, histological studies were performed. Data were analyzed using SPSS software version 11.5. The comparison between Rosemary and vehicle groups indicated significant reduction in [Cr]p (P< 0.001), [BUN]P (P < 0. 01), UNaV° (P < 0.001), and significant increase in UKV° (P< 0.001) in the Rosemary group. Oxidative stress studies indicated the ability of the aqueous extract of Rosemary to decrease malondialdehyde (MDA) and increase ferric reducing antioxidant power (FRAP) in comparison with the I/R group. Histopathological analyses indicated significant decreases in vessels congestion, tubules disorder, and space of Bowman's capsule in the Rosemary group in comparison with the vehicle groups. Post treatment with Rosemary aqueous extract protects the rats against histological injury and functional impairment induced by 24 h I/R.
... As medicinal plant rosemary belongs to the pool of herbs, which probably more than others, lies at the boundary between myth, superstition and traditional popular usages, but at the same, its efficacy is largely acknowledged, being, in fact, listed in the official Pharmacopoeia of several countries. Several biological activities have been ascribed to rosemary: as memory improving tool (Moss et al., 2003; Kennedy and Scholey, 2006.), against neurodegenerative diseases (Adams et al., 2007; Orhan et al., 2008; Youdim et al., 2004) and hypertension (Tahraoui et al., 2007), as antidepressant (Machado et al. 2009), anticancer (Aggarwal et al., 2008), anti-inflammatory (Altinier et al., 2007; Peng et al., 2007), antimicrobial (Askun et al., 2009; Celiktas et al., 2007;, Weckessera et al., 2007; Shan et al., 2007), antithrombotic (Naemura et al., 2008) and antioxidant (Botsoglou et al., 2009; Posadas et al., 2009; Etter, 2004; Suhaj, 2006; Yanishlieva et al., 2006). Concerning this last property it is so high that rosemary is the sole herb spice used as source of commercial antioxidant derivatives, marketed as oil and/or water miscible formulations in Europe and United States (Bozin et al., 2007). ...
The qualitative and quantitative composition of the essential oils obtained from wild Sicilian rosemary plants (Rosmarinus officinalis L.) has been investigated. Samples were collected in Sicily after an ideal division of the island into three large areas, namely Val Mazara (M), Val di Noto (N) and Val Demona (D), according to an ancient and historical territorial subdivision of the island. The essential oils were obtained by hydrodistillation and analyzed by GC-FID-MS, identifying 100 compounds representing more than 96% of the oils. Monoterpenes, both hydrocarbons and oxygenated, were the most highly represented components: the former with a range of 21–68% and the latter with a range of 29–79%. On the basis of the results of this study, comprising a cluster analysis, and on the commonly accepted subdivision of rosemary essential oils, namely cineoliferum, verbenoniferum and camphoriferum chemotypes, most of the wild Sicilian rosemary samples must be classified as cineoliferum chemotype.
Rosmarinus officinalis L. (family Lamiaceae; common name rosemary) is an aromatic, evergreen, medicinally important plant species. The species is widely used for cooking, consumed as an herbal tea, preparation of cosmetics, as well as traditional and modern medicine system (viz. cold, cough, rheumatism, etc). In addition, essential oil of the species has antibacterial and cytotoxic properties and reported good sources of 1,8-cineole, α-pinene, linalool, myrcenol, camphor, borneol, terpinen-4-ol, α-terpineol, verbinone, piperitone and β-pinene. Due to the presence of several secondary metabolites species showed antimutagenic properties, antiinflammatory, hypoglycemic, hypolipidemic, hypotensive, antiatherosclerotic, antithrombotic, hepatoprotective, and hypocholesterolemic effects. Numerous reports highlighted the importance of the species and suggested utilization for to treat depression, Parkinson disease, Alzheimer disease, etc. Besides this, further studies and clinical trials are needed for knowing the impact of rosemary on CNS-related diseases or disorders. Therefore, detailed investigation of pharmacological and clinical studies is essentially required for future utilization.
Culinary spices and herbs have been used in food and beverages to enhance aroma, flavor, and color. They are rich in phytochemicals that provide significant antioxidant and anti-inflammatory effects. There is growing interest in identifying compounds from spices and herbs responsible for modulating oxidative and inflammatory stress to prevent diet-related diseases. This contribution will provide an overview of culinary spices and herbs, their classification, their sources or origins and more importantly, their chemical composition, antioxidant activity and their impacts on human health based on important and recent studies.
The simultaneous intake of food and drugs can have a strong impact on drug release, absorption, distribution, metabolism and/or elimination and consequently, on the efficacy and safety of pharmacotherapy. As such, food-drug interactions are one of the main challenges in oral drug administration. Whereas pharmacokinetic (PK) food-drug interactions can have a variety of causes, pharmacodynamic (PD) food-drug interactions occur due to specific pharmacological interactions between a drug and particular drinks or food. In recent years, extensive efforts were made to elucidate the mechanisms that drive pharmacokinetic food-drug interactions. Their occurrence depends mainly on the properties of the drug substance, the formulation and a multitude of physiological factors. Every intake of food or drink changes the physiological conditions in the human gastrointestinal tract. Therefore, a precise understanding of how different foods and drinks affect the processes of drug absorption, distribution, metabolism and/or elimination as well as formulation performance is important in order to be able to predict and avoid such interactions. Furthermore, it must be considered that beverages such as milk, grapefruit juice and alcohol can also lead to specific food-drug interactions. In this regard, the growing use of food supplements and functional food requires urgent attention in oral pharmacotherapy. Recently, a new consortium in Understanding Gastrointestinal Absorption-related Processes (UNGAP) was established through COST, a funding organisation of the European Union supporting translational research across Europe. In this review of the UNGAP Working group “Food-Drug Interface”, the different mechanisms that can lead to pharmacokinetic food-drug interactions are discussed and summarised from different expert perspectives.
Essential oils from the aerial parts of 15 samples of Algerian Rosmarinus officinalis L. were analysed by gas chromatography (GC) and Gas chromatography/mass spectroscopy. Thirty eight components have been characterized; among the monoterpene hydrocarbons α-pinene, camphene and limonene were individuated as the main components; camphor, 1,8-cineole and borneol were the principal oxygenated compounds, caryophyllene, α-bisabolol and partly humulene were the most represented sesquiterpenes. The scavenging activity of the oils was determined by the DPPH model system. The SC 50 (Scavenging Concentration) values were in the range 120.4-326.1 μL/mL, representing a moderate antioxidant effectiveness. Essential oils were evaluated for their antimicrobial activity against Escherichia coli and Staphylococcus aureus; as well as against ten fungal strains belonging to Aspergillus, Alternaria, Candida, Fusarium, Penicillium and Saccharomyces genera. The results showed a moderate antimicrobial activity. The Algerian rosemary essential oils could be promising sources of biologically active compounds if they receive further studies on their biological properties.
This contribution presents the main constituents responsible for or contributing to the health-enhancing and therapeutic properties of medicinal plants in general, and of thyme (Thymus spp.), spearmint (Mentha spicata L.) and rosemary (Rosmarinus spp.) in particular. Special consideration is given to their phenolic constituents, also known as polyphenols.
Enzymes are of critical importance in maintaining a species and protecting it against various forms of environmental stresses. In particular, the formation of reactive oxygen species and ensuing oxidative stress is a constant menace for any organism. Plants are equipped with a battery of antioxidative stress enzymes, including peroxidases that fulfill a variety of functions while scavenging H2O2. In this study, peroxidase activities were identified in an extract obtained from Thymus citriodorus roots by monitoring spectrophotometrically the H2O2-mediated oxidation of either o-dianisidine (at 460 nm), guaiacol (at 470 nm) or ferulic acid (at 310 nm) (lignin peroxidase) in the presence of extract aliquots. Assays were performed at pH 4 for o-dianisidine, 6 for guaiacol and 5 for ferulic acid oxidation, using extinction coefficients of, respectively, 11.3, 26.6 and 8.68 mM-1.cm-1. With o-dianisidine as the reducing substrate, apparent Km, Vmax and catalytic efficiency were, respectively, 0.65 ±0.06 mM, 0.17 ±0.007 mM.min-1.mg prot-1 and 0.27 ±0.01 min-1.mg prot-1 for odianisidine and 0.5 ±0.05 mM, 0.255 ±0.005 mM.min -1.mg prot-1 and 0.5 min-1.mg prot-1 for H2O2; with guaiacol, the kinetics parameters were, respectively, 4.5 ±3 mM, 0.6 ±0.06 mM.min-1. mg prot-1 and 0.13 ±0.002 min-1.mg prot-1 for guaiacol and 0.9 ±0.2 mM, 0.52 ±0.04 mM.min-1.mg prot-1 and 0.58 ±0.04 min-1.mg prot-1 for H2O2; with ferulic acid, kinetics parameters were, respectively, 0.07 ±0.01 mM, 0.9 ±0.09 mM.min-1. mg prot-1 and 13 ±1 min-1.mg prot-1 for ferulic acid and 0.025 ±0.005 mM, 0.7 ±0.01 mM.min-1.mg prot-1 and 28 ±3 min-1.mg prot-1 for H2O2. The peroxidatic activities were sensitive to KCN, with IC50 of 0.12 ± 0.02 μM for o-dianisidine, 0.75 ±0.05 μM for guaiacol and 0.6 ± 0.05 μM for ferulic acid. Results point out the predominance of lignin peroxidase activity over o-dianisidine and guaiacol peroxidases.
Objective: This report was to investigate the effect of rosemary extract on blood, liver cholesterol level and gene expression of cholesterol-regulating enzymes in Golden Syrian hamsters maintained high fat-high cholesterol diet. Method: 40 hamsters were randomly divided into four groups, namely, high fat-high cholesterol group (HF-HC) and three experimental groups with 0.1%, 0.3% or 0.9% rosemary extract. Serum total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and triglyceride (TG) were measured. To determine the hypocholesterolic mechanism of rosemary extract, the content of cholesterol and mRNA expression of key enzymes related to cholesterol metabolism, such as LDL-receptor(LDL-R), Liver X receptor (LXR), cholesterol 7-alpha hydroxy-lase (CYP7A1), and 3-hydroxy-3-mathylglu-taryl-CoA reductase (HMG-CoA-R) in liver were detected. Results: Serum triglyceride (TG) was significantly decreased and high-density-lipoprotein-cholesterol (HDL-C) was significantly increased in the 0.3% and 0.9% groups but not in the 0.1% group compared with those in the control hamsters. The content of liver cholesterol in experimental groups were decreased compared with those in the control group (P<0.01). Real Time-PCR analysis showed that HMG-CoA reductase mRNA level in experimental groups significantly reduced (P<0.01) and CYP7A1 mRNA expression level significantly increased (P<0.01) compared with those in the control group, but not LDLR, LXR, SREBP-2. Conclusion: Cholesterol-lowering mechanism of rosemary extract probably by inhibiting HMG-CoA reductase mRNA expression and enhanced expression of CYP7A1 which promoting conversion of cholesterol to bile acids in liver. ©, 2015, Chinese Institute of Food Science and Technology. All right reserved.
To identify the best biotypes, an extensive survey of Sicilian wild rosemary was carried out by collecting 57 samples from various sites, followed by taxonomic characterization from an agronomic perspective. All the biotypes collected were classified as Rosmarinus officinalis L. A cluster analysis based on the morphological characteristics of the plants allowed the division of the biotypes into seven main groups, although the characteristics examined were found to be highly similar and not area-dependent. Moreover, all samples were analyzed for their phytochemical content, applying an extraction protocol to obtain the nonvolatile components and hydrodistillation to collect the essential oils for the volatile components. The extracts were characterized by LC-UV-DAD/ESI-MS, and the essential oils by GC-FID and GC/MS analyses. In the nonvolatile fractions, 18 components were identified, namely, 13 flavones, two organic acids, and three diterpenes. In the volatile fractions, a total of 82 components were found, with as predominant components α-pinene and camphene among the monoterpene hydrocarbons and 1,8-cineole, camphor, borneol, and verbenone among the oxygenated monoterpenes. Cluster analyses were carried out on both phytochemical profiles, allowing the separation of the rosemary samples into different chemical groups. Finally, the total phenol content and the antioxidant activity of the essential oils and extracts were determined with the Folin-Ciocalteu (FC) colorimetric assay, the UV radiation-induced peroxidation in liposomal membranes (UV-IP test), and the scavenging activity of the superoxide radical (O). The present study confirmed that the essential oils and organic extracts of the Sicilian rosemary samples analyzed showed a considerable antioxidant/free radical-scavenging activity.
Copyright © 2015 Verlag Helvetica Chimica Acta AG, Zürich.
Food industries generally use synthetic antioxidants to extend the shelf-life of meat products, preserving the organoleptic, nutritional and microbiological quality and food safety. During the last decades, the increasing concern for a healthier life led the consumers to demand for more 'natural' foods, consequently, researches aiming to substitute the synthetic additives increased, mainly on the use of spices and aromatic herbs as antioxidants. In this chapter, the effects of rosemary, a plant native from the Mediterranean region, will be review concerning its addition to meat products, as well as the compounds and the mechanisms behind the antioxidant activity. Moreover, new data will be presented on the potential of rosemary to inhibit lipid oxidation and color loss in pork and chicken patties during chill (5 °C for 10 days) and frozen (-18 °C for 90 days) storage in comparison to a mixture of butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT), both synthetic antioxidants. The efficiency of the antioxidants was assessed in raw and grilled patties by the analyses of thiobarbituric reactive substances (TBARS), cholesterol content, total lipids and color measurements (L*, a*, b*). The results showed that rosemary presented the same effects of BHA and BHT mixture in the protection of lipids against oxidation and loss of color. These results will be presented and discussed.
Treatment of mycotic infection is problematic if compared to the antibacterial ones, the number of antifungal drugs available at present is very little. Recently the excessive use of antibiotics and after the evolution of immuno-suppressive treatments, widespread of fungal diseases took place and highlighted the need to understand the fungal diseases and to develop means for their prevention and control. This evolution has been much slower in veterinary medicine; on many occasions the fungal diseases have been relegated to post-mortem discoveries. Untreated Systemic Candidiasis has a mortality rate approaching 100%. The present study aimed to study the abi-lity of some herbs that showed unmatched availability of chemical diversity and can provide unlimited opportunities for the isolation of new antifungal compounds used for treatment of mycotic endometritis induced by Candida albicans infection. By screening of the antimicrobial effect of different plants, Rosemarinus officinalis (RO) and Thymus vulgaris (TV) showed the highest antimycotic effect and were the plants of choice for the treatment trial. The plant extracts showed high antioxidant effect and radical scavenging activity and high amount of total phenolics. The study was conducted on female albino rats. After induction of the infection, animals received treatment with RO and TV as food additives representing 20%of the ration RO and TV. These groups of animals were matched with other treated with commercial drug, beside the control groups. Animals were followed up for recovery and the nutritional status was recorded. After complete recovery the animals were bred and conception rate was recorded in different groups. Serum samples were collected to perform some biochemical and immu-nological parameters. Results revealed that Rosemarinus officinalis and Thymus vulgaris have a good curative effect for Candida infection, immunostimulant,free radical scavenger, hepatoprotective and hypolipidimic effect. RO could work as growth promoter as it improved the food conversion efficiency. Further studies on different doses of these plants is recommended to determine the best therapeutic dose for man and animals.
The Mediterranean area has a particular geomorphologic and climatic environment in which the island of Sicily plays a predominant role due its central position and coastal extension. Sicilian weather, with its mild winter and warm to hot summer seasons, favours a large plant biodiversity. Here, numerous aromatic plants find their optimal habitat, notably characterizing large areas of the Sicilian territory. The traditional harvest and use of these plants by the population, the sensitivity towards the environment and the propensity to rediscover the culture and popular traditions, have prompted a number of farmers and investors to undertake the cultivation of local biotypes to create new opportunities of income. With this in mind, we have developed a systematic study, financially supported by the Regione Siciliana, aimed at the biomolecular characterization of Sicilian aromatic wild flora, over these recent years. Wild oregano, rosemary, thyme, sage and fennel have been collected during the years 2006-2007 throughout the whole Sicilian territory. The chemical volatile profile of the plant material was achieved by analyzing the essential oil obtained by hydrodistillation, by a combination of gas chromatography equipped with a flame ionization detector (FID) and a mass spectrometer (MS). The main goal of this study has thus been to establish the typical aromatic profile of these plants, verifying their transfer to controlled cultivation in order to achieve the best and standardized product, avoiding the indiscriminate harvesting of wild material which, among other negative aspects, does not guarantee a qualitative homogeneity over the long term. The phytochemical screening of the essential oils of aromatic Sicilian plants allows confirming that oregano is the preeminent Sicilian spice. It can be classified as Origanum vulgare ssp. hirtum (Link) Ietswaart (syn. O. heracleoticum L.) species, characterized as a thymol chemotype, distinct from the same species growing in Greece, which instead is a carvacrol chemotype species. For this reason, Sicilian oregano has a marked territorial specificity. The aromatic profile of wild thyme (Thymus capitatus L.) is fairly uniform, apart from the sampling localities. Indeed, all samples are characterized by a very high (> 70%) content of carvacrol. The chemical composition of the essential oils of sage (Salvia officinalis L.) and rosemary (Rosmarinus officinalis L.) is, instead, much more variegated. For these two species it is then difficult to establish a Sicilian typicalness. Finally, Sicilian fennel (Foeniculum vulgare var. vulgare) is characterised by having estragole as its main component, making the Sicilian fennel rather unique. The results of this study, together with some preliminary data on the cultivation of a number of these plants, by the introduction of alternative productions of high quality, points the way toward new occupational opportunities and new kinds of income, as well as the recovery of marginal and neglected lands.
An evidence-based systematic review of rosemary (Rosmarinus officinalis), including written and statistical analysis of scientific literature, expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing.
The prevention of arterial thrombotic disease has a high priority in developed countries. An inappropriate diet is known to enhance the risk for acute thrombotic events and a regular diet with proven antithrombotic effects might be a beneficial way to prevent disease. The present study was undertaken as a part of a series of investigations to examine vegetables and fruits for antithrombotic activity. A shear-induced in vitro platelet reactivity/thrombolysis method [Global Thrombosis Test, formerly Gorog Thrombosis Test] was used to screen 15 different varieties of carrot for antiplatelet and thrombolytic activities. Effective varieties were further investigated using an in vivo, laser-induced thrombosis model in mice. The different carrot varieties demonstrated a variable effect on thrombosis in vitro and in vivo. In particular, a variety designated SAKATA-0421 exerted an antithrombotic effect in vivo independent from heat treatment of the filtrate at 100 degrees C for 10 min. There was no significant correlation between antithrombotic activity and the levels of polyphenolics and any other biochemical parameter, including antioxidant activity, alpha-carotene and beta-carotene, alpha-tocopherol and ascorbic acid. Different varieties of carrot demonstrated a range of antithrombotic and prothrombotic activities. After oral intake, the particular heat resistant variety (SAKATA-0421) showed antithrombotic effect in vivo possibly due to antiplatelet reactivity and/or spontaneous thrombolytic activity. The present study added a new variety to the list of antithrombotic fruits and vegetables.
Previous investigations using an He-Ne laser-induced thrombosis method have shown that stroke-prone spontaneously hypertensive rats (SHRSP) have an enhanced thrombotic tendency in vivo compared to normotensive, Wistar Kyoto rats (WKY). In addition, studies in the presence of acetylcholine have suggested the presence of endothelial dysfunction in SHRSP. In contrast, shearinduced platelet reactivity in vitro appeared to be depressed in SHRSP. The aim of the present study was to investigate endothelial function in SHRSP using a new physiological in vivo model, and to determine the response of platelets to nitric oxide (NO) in non-anticoagulated blood using a shear-induced platelet function in vitro method (haemostatometry). Endothelial function was estimated by measuring flow-mediated vasodilation (FMV) of the femoral artery. Vessels were exposed and blood flow was arrested using a silicone-coated arterial clamp. Vasodilation was measured by computer-assisted image analysis 3 min after release of stasis. Arterial vasodilation was observed in the femoral artery of WKY, but not in SHRSP. Vasodilation was seen in both WKY and SHRSP; however, in response to the NO donor, 1-hydroxy-2-oxo-3-(3-aminopropyl)-3-isopropyl-1triazene (NOC 5). In contrast, 100 ÌM NOC 5 did not affect platelet reactivity in SHRSP. The NO scavenger, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide, sodium salt (carboxy-PTIO) and the NO synthase inhibitor, NG-nitro-L-arginine methyl ester, hydrochloride (L-NAME), did not affect shear-induced platelet reactivity. NOC 5 at 10 ÌM (final concentration) inhibited shear-induced platelet reactivity in WKY. These results confirm the presence of endothelial dysfunction in SHRSP and indicate that platelets are non-responsive to NO in this hypertensive model. The data suggest that defective endothelial reactions or disturbed thrombogenic mechanisms outweigh the platelet hyporeactivity and contribute to the prothrombotic status in SHRSP.
Prevention of arterial thrombotic disease has high priority in developed countries. As inappropriate diet predispose to acute thrombotic events, regular intake of an antithrombotic diet may be a convenient and effective way of prevention. The present study was performed to examine antithrombotic effect of mulberry varieties. A shear-induced in vitro platelet reactivity/thrombolysis test (Gorog Thrombosis Test) was used to screen for antiplatelet and thrombolytic activities. In case of effectiveness, it was followed by an in vivo test of laser-induced thrombosis in mice. Antioxidant capacity was assessed by superoxide anion and radical scavenging activities. Total polyphenolics, anthocyanin and citrate contents were also measured. The tested varieties showed different effect in vitro on platelet reactivity and endogenous thrombolytic activity. Varieties inhibiting platelet reactivity were antithrombotic in vivo regardless inhibition or enhancement of thrombolysis. Those mulberry varieties, which enhanced platelet reactivity in vitro, were prothrombotic only if inhibitory activity on endogenous thrombolysis coexisted with the platelet effect. Antioxidant activities and polyphenolics content did not affect platelets and the overall thrombotic status. However, antioxidant activities and polyphenolics content significantly correlated with the endogenous thrombolytic activity. These data showed that mulberry varieties can be grouped into subclasses with either anti- or prothrombotic activities. Antioxidant activities and polyphenolic contents do not affect platelets but may enhance endogenous thrombolysis, thus causing an overall antithrombotic effect.
The prevention of arterial thrombotic diseases has a high priority in developed countries. An inappropriate diet may be an important risk factor for thrombotic events. The daily intake of an anti-thrombotic diet may offer a convenient and effective way of prevention. The aim of the present study was to test tomato extracts for anti-thrombotic effects and to identify those varieties that have such an effect. A shear-induced platelet-function test (haemostatometry) was used to test anti-thrombotic potential in vitro. Extracts from those tomato varieties that showed a significant anti-thrombotic activity in vitro were further assessed in vivo, using a laser-induced thrombosis test in mice. One tomato variety (KG99-4) showed significant anti-thrombotic activity both in vitro and in vivo. KG99-4 inhibited not only platelet-rich thrombus formation but also had a thrombolytic effect. It is concluded that haemostatometry can detect and classify the anti-thrombotic potential of fruits and vegetables and offers a simple way of screening for such effects.
The effects of exercise and catecholamines on platelet reactivity or coagulation and fibrinolysis appear to be inconsistent. This may be partly due to the methods employed in previous studies. In the present study, we investigated the effects of acute aerobic exercise and catecholamines on the thrombotic status by a novel in vitro method, shear-induced hemostatic plug formation (hemostatometry), using nonanticoagulated (native) blood. Aerobic exercise (60% maximal O2 consumption) was performed by healthy male volunteers for 20 min, and the effect on platelet reactivity and coagulation was assessed by performing hemostatometry before and immediately after exercise. Exercise significantly increased shear-induced platelet reactivity, coagulation, and catecholamine levels. The effect of catecholamines on platelet reactivity and coagulation was assessed in vitro by adding catecholamines to blood collected in the resting state. The main findings of the present study are that elevation of circulating norepinephrine at levels that are attained during exercise causes platelet hyperreactivity and a platelet-mediated enhanced coagulation. This may be a mechanism of an association of aerobic exercise with thrombotic risk.
Platelet aggregation and spontaneous thrombolytic activity were assessed in patients with non-insulin dependent diabetes and stroke using a shear-induced and agonist-induced platelet aggregation test. The Thrombotic Status Analyser (TSA), induces platelet-rich thrombus formation solely by shear forces, while whole blood platelet aggregometry measures platelet reactivity to different agonists. These tests were employed in the present study because in earlier studies they both demonstrated that platelet aggregability in healthy volunteers was unchanged with age. On the other hand, it is known that thrombolytic activity decreases with age in males, but not in females. In diabetic patients shear-induced platelet aggregability varied according to the stage of nephropathy but platelet aggregation to collagen was suppressed at all stages. Platelet reaction to shear stress was enhanced in stroke patients with haemorrhagic episodes but not in patients with lacunar infarction. In contrast, platelet reactivity to collagen was suppressed and changes in ADP-induced platelet aggregability were inconsistent. Suppressed thrombolysis was observed only in diabetes with minor renal defect. Fibrinogen was increased in diabetes with stage III and IV nephropathy. Fibrinopeptide A (FPA) and D-dimer were increased in stroke. Thus, the observed increase in fibrinogen, FPA and D-dimer is inconsistent with changes in platelet aggregability. Our present findings suggest that a shear-induced platelet aggregation test is superior to other tests such as agonist-induced platelet aggregation and thrombotic markers such as fibrinogen, FPA and D-dimer in detecting a prothrombotic state. It is concluded that elderly males may have a prothrombotic state not because of platelet hyper-aggregability but because of suppressed thrombolytic activity. On the other hand, a prothrombotic state in patients with non-insulin dependent diabetes and after stroke may be due to changes in age-independent platelet aggregability.
Diabetes is associated with thrombotic disorders. Chemically induced and spontaneously induced diabetic animals and various in vitro tests have been used to reveal the prothrombotic state of diabetic patients. However, the results are not consistent. In the present study, platelet reactivity of spontaneously diabetic Goto-Kakizaki rats in vivo and in vitro was evaluated by laser-induced and shear-induced thrombosis models, which are physiologically relevant to thrombosis. Both results showed platelet hyperreactivity.
Prevention of arterial thrombotic diseases has high priority in developed countries. Because people who eat inappropriate food are prone to thrombotic events, regular intake of an antithrombotic diet may offer a convenient and effective way of prevention. The aim of the present study was to find herbs that have antithrombotic effects.
Herbs were crushed and centrifuged and the juice obtained was filtered. The effect of filtrate on platelet-rich thrombus formation was assessed by a shear-induced in vitro platelet function test (hemostatometry). Filtrates showing significant antithrombotic activity were further assessed by using a laser-induced in vivo thrombosis test in mice. The effect of orally administered herb filtrates on flow-mediated vasodilation was also measured.
Common thyme and rosemary showed significant antithrombotic activity in vitro and in vivo. Neither herb affected flow-mediated vasodilation.
Some herbs possess antithrombotic effects in experimental models of thrombosis. The mechanism of the antithrombotic effect of common thyme and rosemary may involve a direct inhibitory effect on platelets.
Because of the high mortality, prevention of arterial thrombotic disease has top priority in developed countries. As inappropriate diet is known to predispose to acute thrombotic events, regular intake of an anti-thrombotic diet may offer a convenient and effective method of prevention. As part of a systematic investigation into the anti-thrombotic effect of fruits and vegetables, strawberry varieties were tested in this study. An in vitro platelet function test (haemostatometry) was used for screening strawberry filtrates. Those that showed significant antiplatelet effect were further assessed with a laser-induced thrombosis test in mice. Measurement of flow-mediated vasodilation in the femoral artery of mice reflected the effect on the vascular endothelium. Correlation between the effects on platelet reactivity in vitro and the antioxidant activity (hypoxanthine/xanthine oxidase test) or phenolic compound content was assessed. Strawberry varieties KYSt-4 (Nohime), KYSt-11 (Kurume IH-1) and KYSt-17 (Kurume 58) showed significant antiplatelet activity both in vitro and, after oral administration, in vivo. Both KYSt-11 and KYSt-17, but not KYSt-4, significantly reduced flow-mediated vasodilation; that is, caused endothelial dysfunction. Antiplatelet activities were heat stable. Significant correlation was found between antiplatelet and antioxidant activities (P=0.049, R=0.23) or total phenolic compounds (P=0.0096, R=0.36). Of the tested strawberry varieties, KYSt-4, KYSt-11 and KYSt-17 showed significant anti-thrombotic effect. The dual mechanism of the effect may involve a direct inhibition of both platelet function and antioxidant activities.
Spontaneous thrombolysis is an endogenous protective mechanism against lasting arterial thrombotic occlusion, which is implicated in the pathogenesis of myocardial infarction and acute coronary events. Novel therapies for coronary heart disease (CHD) targeting atherosclerosis and thrombosis, together with cardiovascular prevention programs targeting risk-factors and lifestyle provide evidence that CHD is preventable. Although reduced fibrinolytic activity is a recognized risk-factor for ischemic cardiovascular events, it has so far been neglected. Our knowledge of the fibrinolytic effect of drugs commonly used for CHD such as antiplatelet agents (aspirin, ticlopidine, clopidogrel), anti-diabetic biguanides (phenformin, metformin) or anti-hypertensive drugs is scanty and conflicting. This is mainly due to the lack of a global test of spontaneous thrombolysis, as opposed to fibrinolysis of plasma or whole blood, i.e. the assessment of various activators and inhibitors of the fibrinolytic system. A recently described technique allows the measurement of spontaneous thrombolysis, that is, lysis of an autologous platelet-rich thrombus in the absence of added plasminogen activators. Early results suggest that this test may have significant clinical potential both in identifying those at risk of fatal cardiac events and in finding new therapeutic avenues or lifestyles to improve spontaneous thrombolytic activity.
Morphological features of haemostatic plugs formed in vitro under high shear forces were investigated. Electron microscopy confirmed the relevance of such haemostatic plug to a platelet-rich arterial thrombus, which is formed in vivo . In rat blood samples, the effects of anticoagulants and various antiplatelet agents on platelet reactivity (rate of haemostatic plug formation) and subsequent coagulation of the flowing blood were investigated. Haemostasis did not occur in citrated blood, and heparin greatly inhibited the shear-induced platelet reaction. Aspirin (1 mM), a thromboxane A(2) receptor antagonist (5 microM), a stable prostacyclin (0.55 nM), a stable prostaglandin E(1) (141 nM) and a phosphodiesterase inhibitor (100 microM) were tested. All these agents exerted significant inhibitory effect on shear-induced platelet reaction, including the inhibition of the very first phase of platelet plug formation, due to aggregation of shear-activated platelets. Except for the phosphodiesterase inhibitor, which prolonged clotting time, none of the above agents affected dynamic coagulation. These results suggest that the employed in vitro shear-induced thrombosis/haemostasis test can reveal in vivo the antithrombotic effect of various agents independently of their mechanism of action.
Substantial evidence suggests that spontaneous thrombolytic activity of blood is an effective mechanism for protection against tissue damage that is the consequence of lasting arterial occlusion. Despite the generally held belief that coronary artery disease and stroke are preventable, a promising avenue of prevention, namely the identification and prophylactic treatment of those at risk of inefficient spontaneous thrombolysis, has been neglected. This is mainly due to the lack of physiologically relevant test. A recently described technique allows the measurement of spontaneous thrombolysis, that is, lysis of an autologous platelet-rich thrombus in the absence of added plasminogen activators. Early results suggest that this test may have significant clinical potential both in identifying those at risk from fatal thrombotic event and in finding new therapeutic avenues of improving spontaneous thrombolytic activity.
Prevention of arterial thrombotic diseases is of high priority in developed countries. As inappropriate diet is regarded as an important risk factor of thrombotic events, daily intake of an antithrombotic diet may offer a convenient and effective way of prevention. Earlier we used animal models of thrombosis to find fruits and vegetables with potential antithrombotic activity. Among various strawberry varieties tested, a particular variety (KYSt-4, Nohime) showed a significant antithrombotic effect. The aim of the present investigation was to extend this study to humans, by testing the experimentally active KYSt-4 and inactive KYSt-10 variety for effectiveness in humans after oral intake. Filtrates of strawberries were prepared and administered orally. Thrombotic status was tested by a novel global test (Gorog Thrombosis Test). The strawberry variety (KYSt-4; Nohime) which earlier inhibited experimental thrombosis showed antithrombotic effects in humans, while the experimentally inactive variety (KYSt-10) as well as the relevant control (water) were ineffective.
This is the first laboratory evaluation of a new instrument, designed to test both platelet function and thrombolytic activity from a native blood sample, in vitro. The inventor assumed that the reduction and arrest of blood flow was due to activation, aggregation and stabilized thrombus formation by shear-activated platelets, and that re-establishment of flow was due to thrombolysis. Morphologic and functional studies presented here confirm these mechanisms. In vitro tests provided incontestable evidence for the principal role of platelets in the obstruction of flow (occlusion time) and for thrombolysis as the principal mechanism underlying the restoration of blood flow (lysis time). In addition to aggregation, it is the explosive generation of thrombin by shear-activated platelets that results in the formation of an occlusive haemostatic thrombus. Anticoagulation of blood completely prevented occlusion. Platelet-rich thrombus formation (occlusion time) was dose-dependently inhibited by monoclonal antibody against platelet glycoprotein (GP) Ib (6B4 and 12E4), aurin tricarboxylic acid, monoclonal antibody against platelet GPIIb/IIIa (MA-16N7C2 and abciximab), a synthetic GPIIb/IIIa antagonist (TAK-029), thrombin inhibitor (argatroban), and anti-von Willebrand factor, but not by anti-fibrinogen. Plasminogen activator streptokinase (Varidase) and tissue-type plasminogen activator (Monteplase) dose-dependently enhanced thrombolysis (lysis time) without affecting platelet function (occlusion time). The test is specific for thrombolysis. The plasmin inhibitor tranexamic acid prevented plasminogen activator-induced thrombolysis, while inhibition of clot retraction by cytochalasin B did not affect the lysis time. This rapid and sensitive global test of platelet function and thrombolytic activity could be of great value both in research and in clinical practice.
Because of the high mortality, prevention of arterial thrombotic disease has top priority in developed countries. As inappropriate diet is known to predispose to acute thrombotic events, regular intake of an anti-thrombotic diet may offer a convenient and effective method of prevention. As part of a systematic investigation into the anti-thrombotic effect of fruits and vegetables, strawberry varieties were tested in this study. An in vitro platelet function test (haemostatometry) was used for screening strawberry filtrates. Those that showed significant antiplatelet effect were further assessed with a laser-induced thrombosis test in mice. Measurement of flow-mediated vasodilation in the femoral artery of mice reflected the effect on the vascular endothelium. Correlation between the effects on platelet reactivity in vitro and the antioxidant activity (hypoxanthine/xanthine oxidase test) or phenolic compound content was assessed. Strawberry varieties KYSt-4 (Nohime), KYSt-11 (Kurume IH-1) and KYSt-17 (Kurume 58) showed significant antiplatelet activity both in vitro and, after oral administration, in vivo. Both KYSt-11 and KYSt-17, but not KYSt-4, significantly reduced flow-mediated vasodilation; that is, caused endothelial dysfunction. Antiplatelet activities were heat stable. Significant correlation was found between antiplatelet and antioxidant activities (P = 0.049, R-2 = 0.23) or total phenolic compounds (P = 0.0096, R-2 = 0.36). Of the tested strawberry varieties, KYSt-4, KYSt-11 and KYSt-17 showed significant anti-thrombotic effect. The dual mechanism of the effect may involve a direct inhibition of both platelet function and antioxidant activities.
Thrombus formation based on selective intraluminal lesion of the vessel wall can be induced by HeNe gas laser irradiation, provided an adequate energy-absorbing material has been previously introduced into the vascular bed. Evans blue has been found to be optimal for the purpose of laser-energy-absorbing material for: (1) absorption is maximal at the wavelength of HeNe laser; (2) in the 30 min after intravenous administration the plasma level of dye may be regarded as constant; (3) under acute conditions (30 min) the platelet count and platelet behavior (collagen-induced aggregation) are not influenced by the dye.Ultrastructural analysis of carotid artery of rat after irradiation with laser and microcirculatory thrombus in the mouse mesenteric arteries and hamster cheek pouch arterioles and venules confirmed the assumption, that in addition to the damage to red blood cells and platelets, the subendothelium became exposed after laser irradiation.
A unifying concept of explaining all pharmacological actions of aspirin by the irreversible blockage of the enzyme cyclooxygenase and therefore the inhibition of prostaglandin biosynthesis has left many unanswered questions.
Two hundred ninety-four patients taking 75 mg/day aspirin were tested 3 months after coronary artery bypass surgery. Platelet thromboxane formation (whole blood aggregation to arachidonate) was completely prevented in 80% of patients. Compared with matched healthy controls (n = 95), a significant platelet hyperreactivity was observed in patients (p less than 0.0001 versus less than 0.002). Ninety patients were advised to increase their daily dose of aspirin from 75 mg to 300 mg. Platelet reactivity retested 1 month after increasing the dose has significantly decreased (p = 0.0008; less than 0.0001), whereas it remained unchanged in those patients (n = 84) who continued with the same dose regimens. In normal subjects, ingestion of a single 600-mg aspirin significantly inhibited shear-induced platelet reaction.
It is concluded that aspirin does affect the platelet response to shear forces, but this requires higher dosage (greater than 300 mg/day), suggesting a mechanism probably different from that of interference with thromboxane formation.
A physiologically relevant global in vitro test is described which allows the overall assessment of both thrombotic and thrombolytic activities of blood. In principle, native blood is drawn in pulses through a capillary tube where haemodynamic forces induce a platelet reaction culminating in vessel occlusion. Dislodgement/disintegration of the stabilised thrombus under pressure is a reflection of thrombolysis. Evidence is presented for the platelet-rich nature of the occlusion and that disruption of the thrombus and re-established patency is the result of thrombolysis, that is fibrinolysis with significant contribution from platelets.
This test sensitively detects hypercoagulability (stasis); platelet hyperreactivity (coronary artery disease); anti-platelet effect (aspirin, prostacyclin) and the thrombolytic effect of, thrombin generation by, and resistance to streptokinase. Therefore, this overall assessment of thrombotic status could be of great diagnostic and therapeutic benefit in clinical practice.
Flavone-8-acetic acid (FAA; [Flavonoid]), an adjuvant antitumor drug, inhibits ristocetin-induced aggregation of human platelets. The effect of FAA on platelet-dependent thrombosis was studied in vivo in the porcine carotid artery after deep arterial injury by balloon angioplasty.
(111)In-labeled autologous platelet and (125)I-labeled porcine fibrin(ogen) deposition, and the incidence of macroscopic mural thrombosis onto deeply injured artery (tunica media) were compared in 20 pigs (40+/-1 kg [mean+/-SEM], body surface area=1.0+/-0.1 m(2)), randomized to FAA bolus (n=10) of 5.5g/m(2), followed by an infusion at 0.14g. m(-2). min(-1) or placebo (n=10). Vasoconstriction was measured immediately beyond the dilated segment using quantitative angiography. Platelet deposition (x10(6)/cm(2) of carotid artery) was reduced over 12-fold in pigs treated with FAA (13+/-3 versus 164+/-51, P=0.001) compared with placebo. Fibrin(ogen) deposition (x10(12) molecules/cm(2) of carotid artery) did not significantly differ in FAA-treated pigs versus placebo (40+/-8 versus 140+/-69, P=0.08). Large mural thrombi were present in 100% of placebo-treated pigs versus very small thrombi in 40% of FAA-treated pigs (P=0.005). Vasoconstriction was reduced from 46+/-6% in the placebo group to 15+/-3% in the FAA group (P<0.001). Plasma level of FAA before angioplasty was 515+/-23 microgram/mL. The activated partial thromboplastin time was unchanged. The bleeding time was >2SD above the normal mean in 4 of 5 treated pigs (increased from 157+/-29 to 522+/-123 s).
FAA markedly reduced platelet deposition, mural thrombi, and injury-induced vasoconstriction after deep arterial injury, suggesting that a major inhibition of platelet glycoprotein Ibalpha may be beneficial therapy.
Epidemiological studies suggest the high fat content of the Western diet to be responsible for atherosclerosis and its thrombotic complications. Despite such a prevailing view, few animal experiments have so far succeeded in demonstrating enhanced thrombogenicity due to a high fat diet. Even a high fat and a very high cholesterol (1%) diet has failed to demonstrate an enhanced thrombotic reaction in rodents and rabbits. The aim of the present study was twofold. First, we wanted to establish a new, sensitive and specific thrombosis model in mice, which can then be used to study the effect of diets. Second, we intended to employ such a thrombosis model in investigations into the effect of high or low fat diets on thrombosis. The technique described uses a laser to induce thrombus formation in the exposed carotid artery of apolipoprotein E-deficient and low-density lipoprotein receptor-deficient mice. Thrombus formation was recorded on video, analysed by computer, and the size of thrombus was calculated by image analysis software. Thrombotic status was evaluated by analysing a total of 61 individual images of the thrombotic reaction, which were taken over 600 s. The severity of atherosclerosis was assessed by image analysis of the stained elastic fibers. Two kinds of diets were used: the Western type, high fat diet contained 20% fat (w/w) and 0.05% cholesterol (w/w); the low fat diet contained 7% fat, without cholesterol. These diets were on the basis of AIN93G and were given to mice for 4 or 8 weeks. The high fat diet significantly enhanced both the thrombotic reaction and the development of atherosclerosis as compared with the low fat diet.
We used a new test (the Görög Thrombosis Test) for assessing the effect of aging, smoking and exercise habits on the overall thrombotic status including platelet reactivity and spontaneous thrombolytic activity of 30 healthy young males (mean, 21.1 +/- 0.4 years) and 34 elderly males (64.5 +/- 1.1 years). The occlusion time (OT) and the lysis time (LT) were measured from a single native blood sample. The OT is an index of platelet activation and subsequent occlusive thrombus formation by high shear stress, while the LT is an index of the resumption of blood flow due to thrombolysis. The LTs in the elderly group were significantly longer than in the young group (P < 0.001). The LTs of elderly smokers were significantly longer than those of non-smokers (P < 0.001). Exercise did not affect the LT significantly. Platelet reactivity to shear stress (OT) was not affected either by aging, smoking or exercise habits. Suppressed spontaneous thrombolytic activity in elderly males and smokers could be a mechanism of acute thrombotic events in these people.
The historical development of in-vitro bleeding time tests, using solely shear forces to initiate haemostatic plug formation, in the absence of the vessel wall or its components, is described. Techniques that have no potential for routine use in clinical practice, such as flow chambers and cone-and-plate viscometers, are excluded. The problems related to the use of citrated blood in platelet function tests are discussed. In light of the pivotal role of thrombin and platelet-dependent thrombin generation in haemostasis/thrombosis, the advantage and clinical benefits of testing unadulterated native blood is discussed.
This is the first laboratory evaluation of a new instrument, designed to test both platelet function and thrombolytic activity from a native blood sample, in vitro. The inventor assumed that the reduction and arrest of blood flow was due to activation, aggregation and stabilized thrombus formation by shear-activated platelets, and that re-establishment of flow was due to thrombolysis. Morphologic and functional studies presented here confirm these mechanisms. In vitro tests provided incontestable evidence for the principal role of platelets in the obstruction of flow (occlusion time) and for thrombolysis as the principal mechanism underlying the restoration of blood flow (lysis time). In addition to aggregation, it is the explosive generation of thrombin by shear-activated platelets that results in the formation of an occlusive haemostatic thrombus. Anticoagulation of blood completely prevented occlusion. Platelet-rich thrombus formation (occlusion time) was dose-dependently inhibited by monoclonal antibody against platelet glycoprotein (GP) Ib (6B4 and 12E4), aurin tricarboxylic acid, monoclonal antibody against platelet GPIIb/IIIa (MA-16N7C2 and abciximab), a synthetic GPIIb/IIIa antagonist (TAK-029), thrombin inhibitor (argatroban), and anti-von Willebrand factor, but not by anti-fibrinogen. Plasminogen activator streptokinase (Varidase) and tissue-type plasminogen activator (Monteplase) dose-dependently enhanced thrombolysis (lysis time) without affecting platelet function (occlusion time). The test is specific for thrombolysis. The plasmin inhibitor tranexamic acid prevented plasminogen activator-induced thrombolysis, while inhibition of clot retraction by cytochalasin B did not affect the lysis time. This rapid and sensitive global test of platelet function and thrombolytic activity could be of great value both in research and in clinical practice.
Prevention of arterial thrombotic diseases has a high priority in developed countries. As inappropriate diet has been shown to be an important risk factor for thrombotic events, regular antithrombotic diet may offer a convenient and effective way of prevention. The aim of the present study was to test onion extracts for antithrombotic effect and to identify the effective varieties in Allium cepa.
A shear-induced platelet function test (haemostatometry) was used to screen for antithrombotic potential. Onion extracts showing significant antithrombotic activity in vitro were further assessed in vivo by using a laser-induced thrombosis test in mice.
An onion variety, Toyohira, showed significant antithrombotic activity both in vitro and in vivo. Toyohira showed thrombolytic activity in addition to the antiplatelet effect. Superkitamomiji, 2935A, and K83211 showed only thrombolytic activity. Quercetin, the richest flavonoid in onion, was measured, but no correlation was found between quercetin content and antithrombotic activity. It is concluded that onion A. cepa can be classified into varieties with or without antithrombotic and thrombolytic effects. This should be taken into account in future population studies on the antithrombotic effects of vegetables.
Although incidence of arterial thrombotic events increases with advancing age, the mechanism of such increased risk is poorly understood. There is also a gender difference; coronary heart disease is more common in men than women. The aim of the present study was to investigate the possible contribution from platelet reactivity and spontaneous thrombolysis, determinants of arterial thrombosis, to the increased risk of thromboembolism in aging, but otherwise healthy subjects.
One hundred and forty-five normal subjects (61 men, 82 women) of age between 19 and 77 years were grouped into groups of young (<30 years); middle aged (31-50 years), and older (>51 years), according to their gender and body mass index (BMI). A new in vitro test [Gorog Thrombosis Test (GTT)] was used to measure in sequence both platelet reactivity [occlusion time (OT)] and spontaneous thrombolysis [lysis time (LT)] from one non-anticoagulated blood sample.
OT in all women was 315+/-9.2 s (mean+/-S.E.M.), in all men OT was 300+/-10.6 s. The mean LT in all women was 2557+/-201.5 s, and in all men LT was 2493+/-198.6 s. Advanced age did not enhance platelet reactivity (OT), but increased BMI did (P=0.039). Spontaneous thrombolysis (LT) was impaired in older men but not in women (difference between young vs. middle age: P=0.019; young vs. older: P=0.0002).
Our findings suggest that in men, spontaneous thrombolytic activity is reduced with age, and this may explain the increased frequency and severity of thromboembolic events. Interestingly, in women, spontaneous thrombolytic activity did not change after menopause.
Earlier we have demonstrated a prothrombotic state in spontaneously atherogenic rodents kept on Western-style high fat diet. The aim of the present study was to investigate the cellular mechanism of such prothrombotic state.
Two kinds of diets, Western-style high fat diet containing 20% fat (w/w) and 0.05% cholesterol (w/w) and low fat diet containing 7% fat without cholesterol based on AIN93G, were added to diet-sensitive apolipoprotein E and low-density lipoprotein receptor double deficient male mice for 12 or 18 weeks from 6 weeks of age. Atherosclerosis was assessed by morphometry of the aortic wall or lipid-stained lesions. Endothelial function was measured by flow-mediated vasodilation (FMV) of the femoral artery. Platelet reactivity was measured ex vivo by a shear-induced platelet aggregation test.
12 weeks feeding of mice with high fat diet significantly impaired FMV, as compared with mice fed with low fat diet (P<0.05). In contrast, there was no significant difference in the lipid-stained areas and in the reactivity of platelets between the two groups. 18 weeks feeding with high fat diet significantly impaired FMV (P<0.05) and enhanced both lipid-stained areas (P<0.05) and platelet reactivity (P<0.01). These findings show that in high fat diet-induced prothrombotic state, endothelial dysfunction precedes both the morphologically detectable lesions and the enhancement of platelet reactivity.
Comparison of platelet reactivity of three kinds of spontaneously diabetic rat models
- T Taka
- J Seki
- J Yamamoto
- Gk
- Wbn Oletf
- Kob
Taka T, Seki J, Yamamoto J. Comparison of platelet reactivity of three kinds of spontaneously diabetic rat models, GK, OLETF, WBN/Kob. Diabetes Front 1999;10:582—3.
A new endothelial function test using flow-mediated vasodilation and a mouse femoral artery
- Y Tamura
Tamura, Y. A new endothelial function test using flow-mediated vasodilation and a mouse femoral artery. Master's Thesis, 2006.
Review: Spontaneous thrombolysis: A forgotten determinant of life or death
- Kovacs Ib Yamamoto
Kovacs IB, Yamamoto J. Review: Spontaneous thrombolysis: A forgotten determinant of life or death. Clin Appl Thromb/ Hemost 2006;12:358—63.
Comparison of platelet reactivity of three kinds of spontaneously diabetic rat models, GK, OLETF, WBN/Kob.
- Taka T.
- Seki J.
- Yamamoto J.
Review: Shear-induced in vitro haemostasis/ thrombosis tests: the benefit of using native blood
- Yamamoto
A shear-induced in vitro platelet function test can assess clinically relevant anti-thrombotic effects
- Yamamoto
Comparison of platelet reactivity of three kinds of spontaneously diabetic rat models, GK, OLETF, WBN/Kob
- Taka
Impaired spontaneous thrombolytic activity in elderly and in habitual smokers, as measured by a new global thrombosis test
- Ikarugi