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Thrombosis Preventive Potential of Chicory Coffee Consumption: A Clinical Study
Abstract
The protective effects of plant polyphenol intake on cardiovascular morbidity and mortality are widely acknowledged. Caffeine-free chicory coffee is a rich source of plant phenolics, including caffeic acid, which inhibits in vitro platelet aggregation, and also phenylpyruvate tautomerase enzymatic activity of the proinflammatory cytokine, macrophage migration inhibitory factor (MIF). To assess whether chicory coffee consumption might confer cardiovascular benefits a clinical intervention study was performed with 27 healthy volunteers, who consumed 300 mL chicory coffee every day for 1 week. The dietary intervention produced variable effects on platelet aggregation, depending on the inducer used for the aggregation test. Whole blood and plasma viscosity were both significantly decreased, along with serum MIF levels, after 1 week of chicory coffee consumption. Moreover, significant improvements were seen in red blood cell deformability. No changes in hematocrit, fibrinogen level or red blood cell counts were detected. The full spectrum of these effects is unlikely to be attributable to a single compound present in chicory coffee, nevertheless, the phenolics, including caffeic acid, are expected to play a substantial role. In conclusion, our study offers an encouraging starting-point to delineate the antithrombotic and antiinflammatory effects of phenolic compounds found in chicory coffee.
... Two trials evaluated the safety of a combination of inulin and phytochemicals in chicory coffee. It should be noted that the composition of chicory coffee is different from raw chicory roots since inulin and phytochemicals are partly broken down during the roasting process forming new chemical compounds (117,118). The effect of chlorogenic acids on thrombosis prevention was tested in 27 subjects who consumed 20 g of chicory coffee in 300 mL for 1 wk. ...
... The effect of chlorogenic acids on thrombosis prevention was tested in 27 subjects who consumed 20 g of chicory coffee in 300 mL for 1 wk. They did not observe any negative side effects during this short time period and found some, but variable, effects on the measured thrombosis markers (118). Similarly, the effect of inulin on GI tolerance was tested in chicory coffee with a higher inulin content produced by a new method (117). ...
... A significant improvement of glycated hemoglobin (HbA1c) and stool frequency was found, however, no improvements in fasting glucose or insulin concentrations and lipid metabolism were observed. Chicory coffee was also used in relation to its phenolic acid content (chlorogenic acids), which was thought to beneficially affect thrombosis prevention, as was previously demonstrated in vitro and in vivo in mice using synthesized compounds (118). In the human intervention, it was found that the in vivo effects were far lower than expected and blood values remained unchanged. ...
Fibers are increasingly recognized as an indispensable part of our diet and vital for maintaining health. Notably, complex mixtures of fibers have been found to improve metabolic health. Following an analysis of the fiber content of plant-based products, we found the taproot of the chicory plant (Cichorium intybusL.) to be 1 of the vegetables with the highest fiber content, comprising nearly 90% of its dry weight. Chicory roots consist of a mixture of inulin, pectin, and (hemi-)cellulose and also contain complex phytochemicals, such as sesquiterpene lactones that have been characterized in detail. Nowaday, chicory roots are mainly applied as a source for the extraction of inulin, which is used as prebiotic fiber and food ingredient. Chicory roots, however, have long been consumed as a vegetable by humans. The whole root has been used for thousands of years for nutritional, medicinal, and other purposes, and it is still used in traditional dishes in various parts of the world. Here, we summarize the composition of chicory roots to explain their historic success in the human diet. We revisit the intake of chicory roots by humans and describe the different types of use along with their various methods of preparation. Hereby, we focus on the whole root in its complex, natural form, as well as in relation to its constituents, and discuss aspects regarding legal regulation and the safety of chicory root extracts for human consumption. Finally, we provide an overview of the current and future applications of chicory roots and their contribution to a fiber-rich diet.
... Recent studies have identified several medicinally active constituents in chicory; for example, caffeic acid, caffeoylquinic acid, quercetin, fructooligosaccharides, flavonoids, inulin, and polyphenols. It has been shown to have anti-diabetic [4,5], anti-inflammatory [6], antioxidant [7], and antihepatotoxic activities [8]. ...
... A human pilot study suggested that CRE could play a role in the management of osteoarthritis [46]. The chicory coffee consumption for 1 week significantly reduced whole blood and plasma viscosity, along with serum macrophage migration inhibitory factor (MIF) levels [6]. ...
... C. intybus is a coffee substitute and its leaves, flowers, seeds and roots are traditionally used as herbal medicines since ancient times. Pilot studies have shown that CRE is beneficial in osteoarthritis [46] has antithrombotic and anti-inflammatory effects [6] and is beneficial in non-alcoholic fatty liver disease [25]. Experimental studies on C. intybus seed extract in animal models showed hepatoprotective, antioxidative, antithrombotic, and antidiabetic properties. ...
The genus Cichorium (Asteraceae) is comprised six species, widely cultivated in Europe and Asia. Cichorium intybus (common name- chicory) is
used as a coffee substitute. However, its leaves, flowers, seeds, and roots have been customarily utilized as home grown solution for various ailments
since ancient times. Although commercialized as coffee substitute, C. intybus is also used in indigenous system of medicine to treat different ailments
from wounds to diabetes. Several numbers of chemical constituents of chicory have been identified, and a significant number of these constituents
have not been fully investigated for their pharmacological potential. Toxicological information on chicory is also limited. This review targets on the
socially imperative medicinal use of chicory in lifestyle disorders. The pharmacological activities of this plant in lifestyle disorders, phytochemical
composition (active compounds) isolated from chicory plant with medicinal importance and safety studies are discussed in detail.
... Schumacher et al. [34] analyzed the antiplatelet activity of coffee made from chicory, a preparation with high levels of caffeic acid, a polyphenol known to inhibit platelet aggregation. Briefly, 27 healthy volunteers drink 300 mL of 20 g ground chicory coffee each morning. ...
... The antiplatelet activity was measured with platelet aggregation in plateletrich plasma taken from the participants. It was found that the chicory coffee inhibited collagen-induced platelet aggregation after eight days of regular consumption [34] (Table 1). ...
Cardiovascular (CV) system dysfunction can result in the development of cardiovascular diseases (CVDs), a key cause of death around the world. For many people, the most common treatment choices are still based on various plants used in traditional and folk medicine. Interestingly, many of these plants demonstrate various biological activities and pro-health properties; as such, there has been growing scientific interest in their use as medicines, including treatments for CVDs. Due to their varied biological properties, including anti-inflammatory and anticancer potential, the members of the Asteraceae and Cucurbitaceae have long been used in traditional medicine. These properties are believed to derive from the chemical composition of the plants, which includes various flavonoids, phenolic acids, and terpenes. Although many of their pro-health properties have been well described, their effect on the cardiovascular system and CVDs remains unclear. The present work reviews the current literature about the effects of preparations of vegetables of the Asteraceae and Cucurbitaceae families on the cardiovascular system and CVDs. Various species from the two families demonstrate antioxidant and antiplatelet activities in vitro and in vivo, which play key roles in the prophylaxis and treatment of CVDs. Additionally, some species have been evaluated for their anticoagulant activity. This review also describes the biological properties of these vegetables and discusses their anti-hyperlipidemic action, and their potential for obesity prevention and body weight control.
... Several clinical trials were conducted to evaluate inulin or chicory coffee's effects on various human organ and system functions (e.g., lipid profile, bowel movement, and platelet Frontiers in Pharmacology | www.frontiersin.org November 2021 | Volume 12 | Article 738504 10 aggregation Schumacher et al., 2011;Grela et al., 2014;Buddington et al., 2017). One of these studies evaluated whether chicory coffee has any beneficial effects on the cardiovascular system (Schumacher et al., 2011). ...
... November 2021 | Volume 12 | Article 738504 10 aggregation Schumacher et al., 2011;Grela et al., 2014;Buddington et al., 2017). One of these studies evaluated whether chicory coffee has any beneficial effects on the cardiovascular system (Schumacher et al., 2011). The consumption of chicory coffee for 1 week resulted in a significant decrease in whole blood, red blood cell deformability, plasma viscosity, and macrophage migration inhibitory factors. ...
Humans used plants for thousand of years as food, drugs, or fuel to keep homes warm. People commonly used fruits and roots, and other parts of the plant were often wasted. This review aims to discuss the potential of rational stem-to-stern use of three highly versatile and valuable plants with hepatoprotective properties. Milk thistle ( Silybum marianum L. Gaertn.), artichoke ( Cynara cardunculus ), and chicory ( Cichorium intybus L.) have well-characterized hepatoprotective properties. These plants have been chosen since liver diseases are significant diseases of concern worldwide, and all parts of plants can be potentially utilized. Artichoke and chicory are commonly used as food or dietary supplements and less often as phytodrugs. Various dietary supplements and phytodrugs prepared from milk thistle (MT) fruits/seeds are well-known to consumers as remedies supporting liver functions. However, using these plants as functional food, farm animal feed, is not well-described in the literature. We also discuss bioactive constituents present in various parts of these plants, their pharmacological properties. Distinct parts of MT, artichoke, and chicory can be used to prepare remedies and food for humans and animals. Unused plant parts are potentially wasted. To achieve waste-free use of these and many other plants, the scientific community needs to analyze the complex use of plants and propose strategies for waste-free technologies. The government must stimulate companies to utilize by-products. Another problem associated with plant use as a food or source of phytodrug is the overharvesting of wild plants. Consequently, there is a need to use more active cultivation techniques for plants.
... In streptozotocin-induced diabetic rats, Schmatz et al. [103] also proved in an ex vivo study that moderate consumption of grape juice and red wine modulates the hydrolysis of the adenine nucleotides and decreases platelet aggregation. Schumacher et al. [104] studied the effect of 300 mL chicory coffee rich in caffeic acid given daily to 27 healthy volunteers for 1 week. They found that the whole blood and plasma viscosity were both significantly decreased. ...
... They found that the whole blood and plasma viscosity were both significantly decreased. In another study, 20 healthy subjects daily consumed 7 mL/kg of both red wine and purple grape juice for 14 days [104]. Platelet aggregation was inhibited and platelet-derived NO production increased, whereas the superoxide release decreased significantly [105]. ...
Cardiovascular diseases (CVD) are one of the main causes of mortality in the world. The development of these diseases has a specific factor-alteration in blood platelet activation. It has been shown that phenolic compounds have antiplatelet aggregation abilities and a positive impact in the management of CVD, exerting prominent antioxidant, anti-inflammatory, antitumor, cardioprotective, antihyperglycemic, and antimicrobial effects. Thus, this review is intended to address the antiplatelet activity of phenolic compounds with special emphasis in preventing CVD, along with the mechanisms of action through which they are able to prevent and treat CVD. In vitro and in vivo studies have shown beneficial effects of phenolic compound-rich plant extracts and isolated compounds against CVD, despite that the scientific literature available on the antiplatelet aggregation ability of phenolic compounds in vivo is scarce. Thus, despite the current advances, further studies are needed to confirm the cardioprotective potential of phenolic compounds towards their use alone or in combination with conventional drugs for effective therapeutic interventions.
... Previous studies showed that chicory roots have constituents such as caffe-oylquinic acid, quercedina, antidiabetic, antihepatotoxic, anti-inflammatory and antioxidant activities (Ahmad et al., 2002;Schumacher et al., 2011;Ghamarian et al., 2012;Jurgonski et al., 2012;Kaskos, 2012). On the other hand, chicory roots have been considered as coffee additives since ancient times. ...
... Chicory coffee which is caffeine-free is the source of plant phenolics, and phenolic content is correlated with antioxidant activity (Lavelli, 2008). Chicory coffee is a source of caffeic acid and a healthy person is recommended to consume 300 ml chicory coffee per week (Schumacher et al., 2011). Besides, the plant has anti-inflammatory, antiviral and anti-cancer characteristics. ...
In this study, roots of Turkish origin wild chicory (Cichorium intybus L.) genotypes were investigated for total flavonoid and phenolic contents, radical cation scavenging activity (ABTS), Free radical scavenging activity (DPPH), and radical, mineral content. These characteristics were also compared with other coffee varieties. The total flavonoid and phenolic contents ranged between 0.290-4.350 mg QE/g dry weight (DW) and 0.943-13.860 mg GAE/g DW. The DPPH was listed here from high to low value: raw coffee beans = roasted coffee beans > roasted fruits of turpentine tree > instant coffee = roots of chicory. The content of P, Ca, Mg, Zn, B, Cr, Co and Mo ranged between 0.71-2.78%, 0.25-0.46%, 7.29-20.66, 4.44-11.07, 0.40-1.67, 0.49-5.48 and 5.69-14.46 ppm, respectively. As a result, chicory roots exhibited low antioxidant activity, but higher mineral content compared to the other tested coffee varieties which indicates that chicory could be used a coffee additive.
... As a result, blood and plasma viscosity were substantially diminished. Major improvements were noticed in red blood cell deformability with an overall antithrombotic and anti-inflammatory action, which might be attributed to the chicory coffee's phenolics, including caffeic acid [139]. ...
... It was shown that chicory root extracts comprising inulin and inulin-type fructans are beneficial in the management of metabolic disorders such as CVD and diabetes [135]. Chicory root polysaccharides can exert hepatoprotective and preventive actions in NASH [137], can control hyperglycemia [131], and present antithrombotic and anti-inflammatory action due to the chicory root's phenolics like caffeic acid [139]. A few studies conducted on chicory leaves extracts suggest that chicory leaves are efficient in managing diabetes due to their ability to improve glucose metabolism and the serum insulin level [133,134]. ...
The current pharmacological agents advised for the management of diabetes as well as cardiovascular and hepatic diseases are subject to numerous studies for safety and efficacy. There-fore, it is worth looking into alternative therapeutic aids such as natural products of medicinal plants. By a broad review of in vitro and in vivo studies on the various dandelion, chicory, and mulberry extracts, this work highlights their bioactive compounds and therapeutic action when used as a prevention and management aid in public health such as diabetes, cardiovascular disease, and hepatic disorders like non-alcoholic steatohepatitis. Natural products of dandelion leaves and root extracts can suppress the development of liver cancer, decrease insulin resistance, and suppress total triglyceride and cholesterol levels. Recent studies on mulberry leaves extracts indicated that they could decrease palmitic acid-induced lipotoxicity, increase total cholesterol and bile acid ex-cretion, improve superoxide dismutase expression, and improve insulin resistance. Chicory root extracts boost satiety, reverse insulin resistance, and augment lipid metabolism thanks to their con-tents in chicoric acid, chlorogenic acid, and polysaccharides. Taraxacum officinale L., Morus nigra L., and Cichorium intybus L. present hepatoprotective, anti-inflammatory, antioxidant, hypolipidemic, and hypoglycemic activities and are shown to be advantageous in the management of obesity, dyslipidemia, Type 2 diabetes, and non-alcoholic fatty liver diseases. These plants are commonly available in the European spontaneous flora and more attention could be paid to their natural prod-ucts.
... In addition, chicory root also contains other bioactive compounds such as phenolic compounds, sesquiterpene lactones, monomeric flavonoids, alkaloids and pectin (Nwafor et al., 2017). These compounds reduce inflammation, modulate lipid metabolism, inhibit growth of certain pathogens and improve redox balance which increase immunocompetence that may result to improve growth performance (Ferioli and D'Antuono, 2012;Karioti, 2008;Kocsis, 2003;Schumacher et al., 2011). ...
... Inulin was observed to Downloaded from https://academic.oup.com/tas/advance-article-abstract/doi/10.1093/tas/txz129/5539702 by Uniwersytet Warminsko-Mazurski w Olsztynie user on 08 August 2019 M a n u s c r i p t boost LPS-induced secretion of IL-10 in mice (Capitán-Cañadas et al., 2014). Antiinflammatory effect of phenolic compounds from chicory have also been observed in humans (Schumacher et al., 2011). In the clinical study, humans given caffeine-free chicory coffee (20 g chicory/300 mL) had reduced phenylpyruvate tautomerase enzymatic activity and serum concentration of proinflammatory cytokine macrophage migration inhibitory factor (MIF). ...
The objective of the experiment was to investigate the effects of prebiotics in nursery pigs on growth performance and immune biomarkers. Sixty-four weaned pigs (31 ± 1 d; BW 8 ± 0.1 kg) of mixed gender were housed (4 pigs/pen) in an environmentally-controlled nursery with ad libitum access to feed and water over a 35-d study. Pigs were randomly assigned to 1 of 4 treatments: control (53% corn, 32% SBM, 7% fishmeal, 8% others), control + 2.5% GroBiotic-S (GS), control + 0.05% chicory (CL), or control + 0.5% chicory (CH). Feeders and pigs were weighed weekly. On d 21, blood samples were obtained from 3 pigs/treatment for collection of peripheral blood mononuclear cells (PBMC). Isolated PBMC were cultured and subsequently challenged with lipopolysaccharide (LPS; 20 ng/mL). Cell culture supernatants were collected for quantification of the pro- and anti-inflammatory cytokines, interleukin (IL)-8 and IL-10, respectively. Dietary treatment had no effect on BW. At d 28 to 35, pigs fed GS (790±15 g), CL (704±15 g), or CH (692±15 g) had greater (P < 0.05) ADG compared to control (643±15 g) pigs. In addition, overall (d 0 to 35), pigs fed GS (823±18 g), CL (783±18 g), or CH (782±18 g) had greater (P < 0.05) ADFI compared to control, and ADFI for GS-fed pigs was greater (P < 0.05) than either CL or CH. There was no difference in G:F among treatments. In vitro LPS challenge increased (P < 0.05) IL-8 secretion from PBMC isolated from CL (23,731±3221 pg/mL) pigs compared to control (10,061±3221 pg/mL) and CH (12,411±3221 pg/mL) pigs. Secretion of IL-10 from PBMC isolated from CL (63±9 pg/mL) pigs was greater (P < 0.05) compared to control (22±9 pg/mL) pigs and tended (P < 0.1) to be greater compared to CH (34±9 pg/mL) pigs. Results indicate that inclusion of prebiotics in nursery pig diets has positive effects on growth performance and may have immunomodulatory effects (in vitro) on cells isolated from prebiotic-fed pigs.
... Epidemiological studies suggest correlations between the intake of high levels of phenolics and the prevention of some diseases, 19 such as thrombose and inflammation. 20 It is generally believed that the health-promoting activities of the phenolics are due to the ability to scavenge free radicals, as shown by Kono et al. for chlorogenic acid and caffeic acid. 21 The roots and leaves of C. intybus plants are also rich in sesquiterpene lactones (STLs). ...
Belgian endive is grown in a two-step cultivation process that involves growing of the plants in the field, cold storage of the taproots, and a second growth period in dark conditions called forcing to yield the witloof heads. In this study, the changes in the carbohydrate content and the secondary metabolite composition were studied in different tissues of Belgian endive during the cultivation process. Belgian endive heads contain between 336–388 mg/g DW of total soluble carbohydrates, predominantly fructose and glucose. The heads also contain phenolic compounds and terpenoids that give Belgian endive its characteristic bitter taste. The terpenoid and phenolic compound composition of the heads was found to be constant during the cultivation season, regardless of the root storage time. In roots, the main storage carbohydrate, inulin, was degraded during storage and forcing processes; however, more than 70% of total soluble carbohydrates remained unused after forcing. Additionally, high amounts of phenolics and terpenoids were found in the Belgian endive taproots, predominantly chlorogenic acid, isochlorogenic acid A, and sesquiterpene lactones. As shown in this study, Belgian endive taproots, which are currently discarded after forcing, are rich in carbohydrates, terpenes, and phenolic compounds and therefore have the potential for further valorization. This systematic study contributes to the understanding of the carbohydrate and secondary metabolite metabolism during the cultivation process of Belgian endive
... Inulin, a prebiotic fiber produced from roots of chicory, is an important dietary element because of their altering properties which modify physiological and biochemical processes which ultimately results in overall betterment of human health and a lower possibility of a variety of disorders in humans (Kaur and Gupta, 2002). Root extract of chicory has been demonstrated in trials to be useful in the treatment of osteoarthritis (Olsen et al., 2010), to have antithrombotic and anti-inflammatory properties (Schumacher, 2011), and it is useful in the treatment of NAFLD (Abd El-Mageed, 2011). In vivo studies of C. intybus seed extract revealed the antidiabetic, antithrombotic, antioxidative and hepatoprotective activity. ...
... Similarly, cocoa flavonols intake (2 g/day) for 12 weeks was not linked to significant changes in platelet function (Ottaviani et al. 2015). In a recent study, the caffeic acid showed notable antiaggregation effects whereas a clinical intervention with caffeine-free chicory coffee (rich in caffeic acid) has not reported clear results (Hung et al. 2005;Schumacher et al. 2011). ...
Cardiovascular ailments are the number one cause of mortalities throughout the globe with 17.9 million deaths per year. Platelet activation and aggregation play a crucial role in the pathogenesis of arterial diseases, including acute coronary syndrome, acute myocardial infarction, cerebrovascular transient ischemia, unstable angina, among others. Flavonoids-rich plant extracts are gaining interest for treating the heart-related problems due to safe nature of these herbal extracts. Consumption of plant-food-derived bioactives, particularly flavonoids, has shown antithrombotic, and cardiovascular protective effects due to its anti-platelet activity. Preclinical and clinical trials have proven that flavonoid-rich plant extracts are protective against the cardiac ailments through anti-platelet aggregation activity. This review aims to highlight the anti-platelet aggregation potential of flavonoids with a key emphasis on the therapeutic efficacy in humans. The mechanism of flavonoids in preventing and treating cardiovascular diseases is also highlighted based on preclinical and clinical experimental trials. Further studies are the need of time for exploring the exact molecular mechanism of flavonoids as anti-platelet aggregation agents for treating heart-related problems.
... Moreover, these medicinal properties have widened the use of chicory in phytotherapy and give the insight to explore other medicinal values with a specific mechanism against the disease. Studies performed on chicory suggests that use of the plant is safe, and plenty of clinical trials depicted the potential of this herb for postponing in the commencement of diabetes (Nishimura et al., 2015), suppression of osteoarthritis (Olsen et al., 2010) and prevention of cardiovascular ailments (Schumacher et al., 2011). On the basis of applicability the chicory can be categorized in following types such as (a) 'industrial chicory' which can also be known as root chicory and employed for the huge production of inulin and further as a substitute of coffee, (b) 'Leaf chicory', for human consumption as a fresh salad or in cooked form and, (c) 'forage chicory' for animals/cattle feeding (Street et al., 2013;Peña-Espinoza et al., 2018). ...
In the modern era, the exploration of herbal plants is required to sustain a healthy
and disease-free lifestyle by following traditional medicine system and to develop novel
plant-based drugs for numerous therapeutic uses. Nature provides various therapeutic
agents in the form of this multipurpose and medicinal plant widely known as ‘Chicory’
(Cichorium intybus). It shows wide distribution (major geographically presence in
Asia, South Africa, and Europe) and has a rich history to use in folklore medicines. In
different ethnic-medication systems, folk healers use this herb to cure various ailments
such as diabetes, liver disorders, and others. Various parts of plants contain a range of
major phytochemicals (inulin, esculin, flavonoids, phenolics, sesquiterpene lactones,
caffeic acid, chicoric acid, terpenoids, and vitamins) have potentially be identified and
validated for some medicinal purposes. In pharmacological studies, this plant exhibited
wide-arrays of medicinal properties such as antimicrobial, anti-diabetic, hepatoprotective,
antioxidant, etc. This chapter focuses on the basic introduction of ethnic values of
Cichrium intybus and its possible remedial application for treating a vast number of
ailments.
... Caffeic acid also significantly reduces whole blood and plasma viscosity. The combined effect of caffeic acid with other phenolic compounds was suggested to have antithrombotic and antiinflammatory effects (Schumacher et al., 2011). rats. ...
The ancient world practically depended on herbal sources of medicines to treat common as well as chronic diseases. Till now, over 80% population in the developing and under developed countries depend on plant materials for the same. Many claims have been justified about the efficacy of modern medicines; it is interesting to know that most of them are derived from plants. The common herbs and spices are exploited by the existing herbal branches of medicines to prepare potential drugs. Occasionally, it also uses rare species of medicinal plants, native to specific climate or region. The screening of new and rare plant species is required to improve the scope of pharmacological alternatives. However, the common herbs and spices provide a more practical, productive as well as a feasible source of medicine. Hence, the current review describes the medicinal benefits of black cumin (Nigella sativa L.) and celery (Apium graveolens L.) seeds, and chicory (Cichorium intybus L.) roots. They are not only commonly available but are loaded with essential nutrients that promote overall health and boosts immunity.
... A human pilot study suggested that chicory root extract played a significant role in the management of osteoarthritis [89] . The chicory coffee consumption for 1 week significantly reduced whole blood and plasma viscosity, alongwith serum macrophage migration inhibitory factor (MIF) levels [90] . The leaves of chicory maintained calcium levels by heterologous expression of total RNA [91] . ...
Research on the bio-activities and chemical composition of roasted C. intybus roots from India is very little. In present studies GC-MS analysis of volatile components of roasted C. intybus roots, phenolics and flavonoid content estimation and antioxidant potential of roasted C. intybus roots was carried out. Antioxidant potential was also evaluated using FRAP, DPPH, hydroxyl radical, nitric oxide and superoxide free radical scavenging method. Extracts were prepared by sequential Soxhlet extraction. GC-MS analysis of volatile components of roasted C. intybus root extracts revealed that 5-hydroxymethyl furfural was major volatile component in dichloromethane and methanol extract whereas lupeol and its derivative compounds were major constituents of hexane extract. Quantitative estimation for total phenols and flavonoids showed that the methanol extract of C. intybus roots contained highest phenolic and flavonoid content as compared to other extracts and also showed strong radical scavenging activities which were comparable with ascorbic acid used as standard. All extracts showed IC50 values less than 0.6 mg/mL furthermore, extracts of roasted C. intybus showed the high total antioxidant potential for the reduction of Fe3+ to Fe2+. The C. intybus roots possess good antioxidant capacity even after roasting and all the extracts showed good activities.
... The number of completed cancer or tumor-related clinical trials of C. intybus whole plant or crude or purified extract is inadequate. A phase 1, placebo-controlled, double-blind, dose-escalating trial was performed in patients with osteoarthritis and showed the potential of C. intybus root extract in the management of osteoarthritis (137). A second clinical trial reported that daily consumption of chicory coffee reduced the risk of cardiovascular disorder by lowering whole blood and plasma viscosity as well as serum MIF level but had a variable effect on platelet aggregation (138). ...
Cichorium intybus L. (Chicory) is a widely distributed, edible, perennial, herbaceous member of the Asteraceae family. Besides its use in modern Chinese herbal medicine, its ethnomedicinal use is evident in the text from ancient Greece, Egypt and China. It is also used as a food and coffee substitute, which is mainly responsible for its extensive domestication. In recent decades, cytotoxic studies of C. intybus extracts have shown its antitumor potential. These studies also identified metabolite constituents including guaianolides, 6‑methoxyflavone, eudesmanolides, germacranolides, polyacetylene, sterol, anthocyanin, delphinidin, 3,4‑dihydroxyphenethyl and other novel compounds. Many of these phytometabolites have shown positive cytotoxic activities in vitro, and antitumor action in vivo and in clinical trials, demonstrating the potential of C. intybus metabolites as antitumor drugs. Structural activity relationship studies have further confirmed these bioactivities. In this review, we focused on the phytochemicals of C. intybus with reported cytotoxicity and potential antitumor properties. We also discuss their specificity towards tumor cells, structural activity relationship, the involved signaling pathways and molecular mechanism, with the expectation of the future development of efficient and targeted antitumor therapeutic strategies.
... A human pilot study suggested that chicory root extract played a significant role in the management of osteoarthritis [89] . The chicory coffee consumption for 1 week significantly reduced whole blood and plasma viscosity, alongwith serum macrophage migration inhibitory factor (MIF) levels [90] . The leaves of chicory maintained calcium levels by heterologous expression of total RNA [91] . ...
Cichorium intybus L. (chicory) is a Mediterranean plant species belonging to the Asteraceae family. The genus Cichorium consists of six species, widely cultivated in Europe and Asia, out of which C. intybus is utilized as home grown solution for various ailments since ancient times. C. intybus is also used in indigenous system of medicine to treat different ailments from wounds to diabetes. It has been implemented in Indian medicine to treat fever, diarrhea, spleen enlargement, jaundice, liver enlargement, gout, and rheumatism. The phytoconstituents reported in chicory are sucrose, cellulose, proteins, caffeic acid derivatives, flavonoids, polyphenols, carotenoids, anthocyanins, tannins, coumarins, sesquiterpene lactones, fatty acids, pectin, cholins, benzo-isochromenes, alkaloids, vitamins, amino acids, and minerals. C. intybus is known to exhibit various medicinal properties like antioxidant, antimicrobial, antihepatotoxic, antidiabetic, anti-inflammatory, prebiotic, cardioprotective, antihyperlipidemic, bulking agent and immunostimulatory properties. This review embraces phytochemistry and pharmacological uses of C. intybus L.
... The study showed varying effects on platelet aggregation, depending on the inducer used for the aggregation test, also, blood and plasma viscosity was decreased, as well as level of serum MIF. Moreover, significant improvements were seen in red blood cell deformability [2]. 65 % of produced chicories in the world comes from Belgium becoming an outstanding leader in the field in 2016 [3]. ...
Chicory coffee is the most used coffee substitute due to similar properties between original coffee – coffee Arabica – and chicory coffee itself that is made out of chicory root. To increase the use of locally produced products such as chicory coffee, it should be competitive in the market with similar products which at the moment are imported from foreign countries. At the moment, the price of locally produced chicory coffee is higher than similar products that are imported. In this paper chicory coffee’s production two main energy consuming processes – drying and roasting – were analysed in different production plants and countries (including Latvia) assuming that the energy that are consumed in these two processes mostly defines the price of the chicory coffee. The purpose of this paper is to obtain the information on how much energy is consumed for material drying and roasting in various chicory coffee production plants and to compare retrieved information between Latvian and other countries production plants.
... One study on patients suffering from osteoarthritis revealed that treatment with chicory is well-tolerated and only one patient was withdrawn from the study due to adverse reaction (in order to highest dose of extract) (38). Another clinical study was designed to assess the intake of chicory coffee as well as cardiovascular protection and showed a new insight for investigating the antiinflammatory, antithrombotic, and beneficial hemorheologic properties of chicory coffee phenolic compounds (39). ...
Background: Neonatal hyperbilirubinemia, a high-incidence disease, arises from an imbalance of bilirubin production and elimination. Neonatal jaundice requires medical attention in the clinic. Findingnewtherapeutic approaches, besides available strategies such as phototherapy, seems necessary. In traditional beliefs Cichorium intybus could exert hepatoprotective effects. Objectives: In this study we evaluated the effect of administration of hydroalcoholic Cichorium intybus extract to the lactating rats in δ-aminolaevulic acid-induced hyperbilirubinemia in rat neonates. Methods: We injected δ-aminolaevulic acid (i.p, 80 micromolar) three times at the intervals of 4 hours to rat newborns (7 to 10- day-old). Cichorium intybus extract (p.o, 25 and 50 mg/kg) was administered to lactating rats at the time of interval of 2 hours (0 - 10 hours). After neonatal feeding, we assessed the bilirubin plasma levels in 0, 8, 16, and 48 hours. Results: Injection of δ-aminolaevulic acid significantly enhanced the conjugated and total bilirubin concentration in rat newborns. Maternal administration of Cichorium intybus extract at the dose of 25 and 50 mg/kg led to significant reduction of bilirubin plasma levels in neonates after feeding. The dose of 50 mg/kg showed a more potent effect. Conclusions: Taken together, treatment of lactating rats with Cichorium intybus extract exerts protective effects in the δ- aminolaevulic acid-induced hyperbilirubinemia of rat neonates. © 2018, Jundishapur Journal of Natural Pharmaceutical Products.
... Seo et al. (2009) reported that the dominant bitter taste of chicory has been linked to the presence of sesquiterpene lactones (lactucin and lactucopicrin). Several studies have shown the health effects of chicory in relation to sesquiterpene lactones, such as liver-protective effects, antidiabetic properties, tumor inhibition, and thrombosis protection (Ahmed et al., 2003;Pushparaj et al., 2007;Rasmussen et al., 2011;Schumacher et al., 2011). However, Pirson et al. (2009) reported that sesquiterpene lactones are also well known as potential allergenics. ...
... Accordingly, a reduction in platelet aggregation was accepted by EFSA as a beneficial effect of food and dietary constituents, in the context of maintaining CV health enabling claims related to foods or substances affecting disturbed platelet function (EFSA Panel, 2011). It was shown both in human and animal studies, in vitro, in vivo and ex vivo that coffee extracts decrease platelet aggregation, induced by different agonists (adenosine diphosphate (ADP), arachidonic acid or collagen) (Silverio Ados et al., 2013;Schumacher et al., 2011;Bhaskar et al., 2010) and also induces a significant increase in phenolic acid platelet concentration (Natela et al., 2008). ...
Coffee is one of the most popular beverages (almost 9 million tons of coffee was consumed in 2014) and the second largest commodity traded worldwide. Coffee beans have long been used for human consumption, in the last centuries, producing coffee brews and instant coffee. About 50% of the coffee produced is directed for the production of soluble coffee generating spent coffee grounds (SCG) as a byproduct that is rich in carbohydrates, protein, lipids and bioactive molecules. SCG has found application as compost (soil conditioner), animal feed (poultry and ruminants), mushroom production, a substrate for fermentation (enzymes) and energy (biogas, liquid biofuel and bioelectricity). SCG composition and structure depends on the coffee beans used in the coffee production, as well as the industrial extraction process. The instant coffee manufacturing uses several hot water extraction steps with different temperature and its severity influences in the soluble solids extraction from the roasted beans and the characteristics of the generated SCG. The industrial process impacts on the amount of SCG generated and soluble compounds extraction, in average 4 kg of wet SCG per kilogram of instant coffee produced. Moreover, the structure of the remained polysaccharides in SCG, cellulose, galactomannan and arabinogalactan, can be more recalcitrant to further use. The SCG still contain extractable compounds (flavor and oil) in a lignocellulosic matrix formed by cellulose, hemicelluloses and lignin. These structural compounds are organized in the cell wall as a recalcitrant structure to the biological conversion process. Moreover, SCG is resistant to degradation and may need a pretreatment to make the material suitable for biotechnological conversion. The pretreatment disrupts the cellulose-hemicellulose-lignin structure, changing its properties and allowing a complex of cellulolytic and hemicellulolytic enzymes breaking down polysaccharides into fermentable sugars. The factors responsible for SCG recalcitrance is related to its chemical composition, structural and physicochemical properties that influence the pretreatment response end requires a complex pool of enzymes to its hydrolysis. This review will focus on discuss the recalcitrance properties of the SCG, based on its composition and structural organization, and the complex enzyme necessary for its conversion, highlighting its impact on biotechnology and bioenergy process.
... However, in many studies the in vivo antiplatelet effects of flavonoids are lower or without evident effects than expected from previous in vitro assays. In fact, caffeic acid has shown notable anti-aggregation effects whereas a clinical intervention with caffeine-free chicory coffee, rich in caffeic acid did not report clear results (Hung et al., 2005;Schumacher et al., 2011). A double-blind randomized intervention supplying with monomeric and oligomeric flavonoids from grape seeds (200 mg/day) to 28 male smokers did not find any effect on platelet aggregation (Weseler et al., 2011). ...
Platelets are small anucleated fragments derived from a megakaryocyte precursor. Platelets play a key role in many physiological functions especially in hemostasis and wound healing processes in order to maintain the integrity of the circulatory system. In addition, activated platelets release cytokines and chemokines which modulate the immune response and, in some cases of hyperactivation, they could be associated to the pathogenesis of inflammatory diseases. Flavonoids are polyphenolic compounds ubiquosly found in plants known to be potent antioxidants with positive effects against diverse diseases such as cancer, neurodegenerative or cardiovascular disease. It has been reported that some flavonoids possess anti-platelet aggregation effects though different pathways, being the inhibition of the arachidonic acid-based pathway the most representative mechanism of action. In the present review, the main sources of flavonoids, as well as their bioavailability and metabolism are summarized. Moreover, the available data about the anti-aggregation effects of flavonoids and the different mechanisms of action that has been proposed until now are also discussed.
... No changes in hematocrit, fibrinogen level or red blood cell counts were detected. The full spectrum of these effects is unlikely to be attributable to a single compound present in chicory coffee, nevertheless, the phenolics, including caffeic acid, are expected to play a substantial role (111) . ...
Phytochemical analysis showed that the different parts Cichorium intybus contained sesquiterpene lactones (especially lactucin, lactucopicrin, 8-desoxy lactucin,, wound healing and many other pharmacological effects. This review was designed to highlight the chemical constituents and medical importance of Cichorium intybus.
... No changes in hematocrit, fibrinogen level or red blood cell counts were detected. The full spectrum of these effects is unlikely to be attributable to a single compound present in chicory coffee, nevertheless, the phenolics, including caffeic acid, are expected to play a substantial role [48]. ...
... Accordingly, a reduction in platelet aggregation was accepted by EFSA as a beneficial effect of food and dietary constituents, in the context of maintaining CV health enabling claims related to foods or substances affecting disturbed platelet function (EFSA Panel, 2011). It was shown both in human and animal studies, in vitro, in vivo and ex vivo that coffee extracts decrease platelet aggregation, induced by different agonists (adenosine diphosphate (ADP), arachidonic acid or collagen) (Silverio Ados et al., 2013;Schumacher et al., 2011;Bhaskar et al., 2010) and also induces a significant increase in phenolic acid platelet concentration (Natela et al., 2008). ...
There is growing interest in the presence of OTA in coffee since it was detected in green coffee beans, roasted and infusions. Numerous studies show that the roasting process influences the destruction of OTA, although the results are quite contradictory, as some authors believe that no significant differences were detected below 12% in relation to OTA reduction roasting operation, while others have argued that OTA production around 80%, or even higher values is reduced. Species Allium cepa is an efficient test organism to study the genotoxic effects induced by mycotoxins such as OTA. A. cepa were studied for genotoxic properties of roasted coffee beans and artificially contaminated with OTA. Genotoxicity tests in meristem cells indicated that the roasting process was not efficient enough for the degradation of OTA as the mutagenic and clastogenic effects were not reduced. This demonstrates that the compounds of OTA degraded possibly combined with compounds of Coffee arabica form toxic compounds for plant cells.
... Accordingly, a reduction in platelet aggregation was accepted by EFSA as a beneficial effect of food and dietary constituents, in the context of maintaining CV health enabling claims related to foods or substances affecting disturbed platelet function (EFSA Panel, 2011). It was shown both in human and animal studies, in vitro, in vivo and ex vivo that coffee extracts decrease platelet aggregation, induced by different agonists (adenosine diphosphate (ADP), arachidonic acid or collagen) (Silverio Ados et al., 2013;Schumacher et al., 2011;Bhaskar et al., 2010) and also induces a significant increase in phenolic acid platelet concentration (Natela et al., 2008). ...
The quality control of coffee and related products needs to consider several factors that are known to play important roles in the final organoleptic characteristics perceived by the consumers. The aroma exhibited by a coffee is determined by variables such as climate, soil, coffee species/variety, post-havest processing and the quality of the beans, as well as by the storage and roasting conditions. For instance, different degrees of roasting give rise to drinks with varying aromatic profiles, ranging from coffees with aromas rich in volatile acids and furans (responsible for fresh and floral notes), to coffees with aromas rich in compounds like pyrazines and pyridine (responsible for characteristic roasted and earthy notes). The geographic provenance of the coffee is also associated with characteristic compositional compounds, which can be used as markers to confirm or disclose the origin of a given sample.
This chapter focuses on two of these factors, namely the geographic origin (associated with climate and soil) and the roasting procedure, and aims at providing a systematic assessment of the chemical compounds that are mainly responsible for the quality of coffee samples. In this respect, multivariate statistical analysis can be employed with advantage to build discriminant models able to differentiate coffee samples, as well asto identify the key chemical compounds suitable for such differentiation. Although more than 800 compounds have already been identified in coffee samples, the discriminant models can rely on only a few markers such as aldehydes, pyrazines, pyrroles, and furans. An evaluation is also made of the link between key compounds and the organoleptic characteristics perceived by the consumer. This approach provides reliable means of complementing typical quality control procedures that rely on sensorial evaluation (cup tests), because not all the odorant compounds present are useful for differentiating geographical origins and degrees of roasting, while some non-organoleptically active molecules are statistically decisive for an enhanced discrimination.
... Chicory coffee has repeatedly been assessed for resistance to thrombosis and inflammation due to its phenolics and caffeic acid content[31]. Chicory Capsule is consists of chicory, ramulusmori, tea polysaccharide, Juemingzi (seed of Cassia obtusifolia) and bee propolis; while the main functions are anti-diabetic, lipid lowering and hypouricemic effect etc.[32]. ...
Juju, a perennial herb in the family of Asteraceae is famous for its therapeutic and medicinal properties. It is used both in food, and traditional or modern medicine. Although there are 10–12 species of genus Cichorium in the world, only two of them, Cichorium intybus and Boiss. et Huet are familiar to us as medicine and edible food. Cichorium intybus L and Cichorium glandulosum Boiss. et Huet are major and legal sources recorded in The Pharmacopoeia of People’s Republic of China (Pharmacopoeia Committee of P. R. China in Pharmacopoeia of People’s Republic of China. Chemical Industry Publishers, Beijing, 2010), and many historical records of traditional Uyghur medical works.
... Mif is an inflammatory cytokine with chemokine-like functions, which has the capacity to induce apoptosis and cell dysfunction (16). Schumacher et al have reported that an increased level of Mif is associated with thrombosis (17), and that it plays a pivotal role in regulating platelet survival and thrombotic potential (18). CFL1 plays an important role in the regulation of cell morphology and cytoskeletal organization. ...
Endothelial injury has been implicated in the pathogenesis of many cardiovascular diseases, including thrombotic disorders. Hyperin (quercetin-3-O-galactoside), a flavonoid compound and major bioactive component of the medicinal herb Apocynum venetum L., is commonly used to prevent endothelium dysfunction. However, its mode of action remains unclear. To the best of our knowledge, we have for the first time investigated the protective effect hyperin exerts against H2O2-induced injury in human endothelium-derived EA.hy926 cells using isobaric tags for relative and absolute quantitation (iTRAQ)‑based quantitative proteomic analysis. The results showed that H2O2 exposure induced alterations in the expression of 250 proteins in the cells. We noted that the expression of 52 proteins associated with processes such as cell apoptosis, cell cycle and cytoskeleton organization, was restored by hyperin treatment. Of the proteins differentially regulated following H2O2 stress, the anti-apoptotic protein, myeloid cell leukemia-1 (Mcl-1), and the pro-apoptotic protein, BH3-interacting domain death agonist (Bid), exhibited marked changes in expression. Hyperin increased Mcl-1 expression and decreased that of Bid in a dose-dependent manner. In addition, flow cytometric analysis and western blot analysis of the apoptosis-related proteins, truncated BID (tBid), cleaved caspase-3, cleaved caspase-9, Fas, FasL and caspase-8, demonstrated that the rate of apoptosis and the pro-apoptotic protein levels were decreased by hyperin pre‑treatment. In the present study we demonstrate that hyperin effectively prevents H2O2‑induced cell injury by regulating the Mcl‑1‑ and Bid-mediated anti‑apoptotic mechanism, suggesting that hyperin is a potential candidate for use in the treatment of thrombotic diseases.
... These diverse biological effects result from an array of medicinally important compounds, such as alkaloids, inulin, sesquiterpene lactones, coumarins, vitamins, chlorophyll pigments, unsaturated sterols, flavonoids, saponins, tannins and polyphenols that are spread in all parts of the plant in different proportions [17]. Chicory, generally regarded as safe, has been implemented in several clinical trials with potential for delaying the onset of diabetes and management of osteoartheritis and cardiovascular disease [18][19][20]. ...
Background:
Inflammation is an early event in the development of diabetes type 2 (T2D). Cichorium intybus L. (chicory) possesses anti-inflammatory action. We compared the anti-inflammatory aspect of aqueous chicory seed extract (CSE) in early and late stage T2D in rats.
Methods:
Wistar albino rats were divided into nine final groups (n = 6). Three main groups consisted of non-diabetic (Control), early stage diabetes (ET2D; niacinamide/streptozotocin, i.e., NIA/STZ), and late stage diabetes (LT2D; STZ). Within each main group, a subgroup was treated with CSE (125 mg/kg; i.p.); within each diabetic group (STZ and NIA/STZ) a subgroup received metformin (100 mg/kg; i.p.); another subgroup in STZ group received aspirin (120 mg/kg; oral). After 21 days, fasting blood glucose (FBS), insulin, and TNF-α level were measured in serum; IKKβ and NF-κB (p65) mRNA and protein expression were evaluated by real time PCR and Western blotting; p65 DNA binding activity was determined by ELISA, in liver tissue.
Results:
The mRNA and protein expression levels of IKKβ, and P65 genes increased in both stages of T2D (p < 0.01); CSE decreased their expression (p < 0.001, mRNAs; p < 0.05, proteins). The increased DNA-binding capacity of NF-κB (p < 0.0001) in diabetes was lowered by CSE (p < 0.001). The effect of CSE was limited to ET2D requiring insulin.
Conclusions:
The anti-inflammatory action of CSE is due to a direct modulation of cytokine expression. The dependency of chicory action on the presence of insulin indicates its usefulness in the early stages of diabetes and for the purpose of preventing and delaying diabetes onset.
... CA derivatives have been reported to ameliorate oxidative stress in endothelial cells and protect endothelial cells from oxidative stress 24 . A clinic study showed that daily consumption of chicory coffee rich in anti-inflammatory phenols including CA for 1 week substantially decreased the serum macrophage migration inhibitory factor levels of healthy volunteers in parallel with the improved red blood cell deformability, suggesting the encouraging antithrombotic and anti-inflammatory effects of phenolic compounds, including CA 25 . These results, along with the findings of the present study that CA protected thrombus formation at the injury site of mouse cerebral arterioles and in cerebral venules, highly suggest CA as a potential multiple targeting option for antithrombotic therapy. ...
Caffeic acid (CA), one of the active constituents of Radix Salvia miltiorrhizae, exhibits antioxidant and anti-inflammatory activities. However, few studies have assessed the ability of CA to inhibit platelet mediated thrombus generation in vivo. In this study, we investigated the antithrombotic effect of CA in mouse cerebral arterioles and venules using intravital microscopy. The antiplatelet activity of CA in ADP stimulated mouse platelets in vitro was also examined in attempt to explore the underlying mechanism. Our results demonstrated that CA (1.25-5 mg/kg) significantly inhibited thrombus formation in vivo. In vitro, CA (25-100 μM) inhibited ADP-induced platelet aggregation, P-selectin expression, ATP release, Ca(2+) mobilization, and integrin αIIbβ3 activation. Additionally, CA attenuated p38, ERK, and JNK activation, and enhanced cAMP levels. Taken together, these data provide evidence for the inhibition of CA on platelet-mediated thrombosis in vivo, which is, at least partly, mediated by interference in phosphorylation of ERK, p38, and JNK leading to elevation of cAMP and down-regulation of P-selectin expression and αIIbβ3 activation. These results suggest that CA may have potential for the treatment of aberrant platelet activation-related diseases.
... Moreover, in a clinical trial, the safety and usefulness of a proprietary bioactive extract of its root in patients with osteoarthritis have been demonstrated [18]. A decrease observed in macrophage migration inhibitory factor (MIF) serum level in healthy volunteers consuming Chicory coffee [19] and an inhibition in the expression and activity of COX-2 by the ethyl acetate root extract in human colon carcinoma HT29 cells treated with the pro-inflammatory cytokine TNF-α are further evidences implying the effectiveness of this plant on modulation of immune mediators release [1]. As DCs have a critical role in inducing inflammation as well as immune responses, in the present study we ar- of MHC II antigen on DCs was not also significantly different with the control, however the intensity of expression of this molecule showed a significant decrease by increasing the concentration of the extract up to 100 μg/ml, indicating a dose-dependent trend to reduce the expression of this molecule on treated DCs as the extract concentration is increased. ...
Cichorium intybus is a medicinal plant commonly used in traditional medicine for its benefits in immune-madiated disorders. There are several evidences showing that C. intybus can modulate immune responses. In the present study we have investigated the effects of the ethanolic root extract of this plant on the immune system by targeting dendritic cells (DCs). For this purpose, phenotypic and functional maturity of murine DCs after treatment with the extract was analyzed by flow cytometry and mixed lymphocyte reaction (MLR) assay.
C. intybus did not change the expression of CD40, CD86 and MHC-II molecules as important co-stimulatory markers on DCs compared to the control, indicating that it could not promote DCs phenotypic maturation. Treatment of DCs with lower concentrations of the extract resulted in an increased production of IL-12 by these cells with no change in IL-10 release. The capacity of treated DCs to stimulate allogenic T cells proliferation and cytokines secretion was examined in the co-cuture of these cells with T cells in MLR. C. intybus at higher concentrations inhibited proliferation of allogenic T cells and in lower concentrations changed the level of cytokines such that IL-4 decreased and IFN-gamma increased.
These results indicated that C. intybus extract at higher concentrations can inhibit T cell stimulating activity of DCs, whereas at lower concentrations can modulate cytokine secretion toward a Th1 pattern. These data may in part explain the traditional use of this plant in treatment of immune-mediated disorders.
... The results of the pilot study suggested that a proprietary bioactive extract of chicory root has a potential role in the management of OA and merits further investigation. The second pilot study was conducted to assess whether chicory coffee consumption might confer cardiovascular benefits; thus, a clinical intervention was performed with 27 healthy volunteers, who consumed 300 mL chicory coffee daily for one week [63]. Depending on the inducer used for the aggregation test, the dietary intervention showed variable effects on platelet aggregation. ...
The genus Cichorium (Asteraceae) is made up of six species with major geographical presence in Europe and Asia. Cichorium intybus, commonly known as chicory, is well known as a coffee substitute but is also widely used medicinally to treat various ailments ranging from wounds to diabetes. Although this plant has a rich history of use in folklore, many of its constituents have not been explored for their pharmacological potential. Toxicological data on C. intybus is currently limited. This review focuses on the economic and culturally important medicinal uses of C. intybus. Traditional uses, scientific validation, and phytochemical composition are discussed in detail.
The pointed feature of the traditional Iranian medicinal system, Ayurveda, is its
emphasis on the maintenance of positive health effects of them. As per Ayurveda, Iranian
medicinal plants are rich sources of substances that have several therapeutic features including
cardiopro- tection. Globally, cardiovascular disorders are a leading cause of mortality. This
review deals with medicinal plants which possess cardiotonic, cardioprotective and antioxidant
or positive effects on heart. It also includes our studies on the antioxidant prop- erties of some
of these plants such as Agrimonia eupatoriaAllium sativum, Althaea rosea, Ammi visnaga
Anethum graveolens, Arachis hypogaea, Avena sativa, Bryophyllum calycinum, Caesalpinia
crista, Capparis spinose, Carthamus tinctorius, Cicer arietinum, Cichorium intybus Cistanche
tubulosa, Citrus species, Cordia myxa, Coriandrum sativum, Crocus sativus, Cuminum
cyminum, Cydonia oblonga, Daucus carota, Adonisa estivalis, Alhagi maurorum, Althaea
rosea, Ammi visnaga, Anchusa strigose, Apium graveolens, Asclepias curassavica, Bacopa
monnieri, Brassica nigra, Caesalpinia crista, Calendula officinalis, Calotropis procera,
Cheiranthus cheiri, Citrus species, Corchorus aestuans, Corchorus capsularis, Coriandrum
sativum, Coronilla scorpioides, Coronilla variaCrocus sativus, Cynodon dactylon, Cyperus
rotundus, Dalbergia sissoo, Daucus carota, Digitalis lanata and Arachis hypogaea,
Asparagus officinalis, Avena sativa, Bauhinia variegate, Bellis perennisCistanche
tubulosaCitrullus colocynthisAchillea santolina, Allium cepa and etc. possesses the highest
potential and inhibit whole effects in rats besides showing significant intestinal absorption or
reports in human. Other plants studied also exhibit radical scavenging effects as studied using
various biochemical assays. These effects may possibly be responsible for their known
beneficial remedies effects including their use in cardioprotection in Iran.
[Ebrahim Alinia-Ahandani, Ani Boghozian, Zahra Alizadeh-Terepoei, Zahra Musavizadeh, Habibollah Nazem,
Mohammad Fazilati,Mahdi Alinia-Ahandani. Role of Medicinal plants on Remedies and prevention
of cardiovascular disorders in Iran-A review. Life Sci J 2023;20(1):29-84]. ISSN 1097-8135 (print);
ISSN 2372-613X (online). http://www.lifesciencesite.com. 03. doi:10.7537/marslsj200123.03.
Background: Cichorium intybus Linn., belonging to Compositae family is a common drug found in India. It is traditionally used in the treatment of inflammation, cancer, viral, bacterial fungal infections and liver toxicity. This plant also has power to stimulate the immune system. Aim: Here in the paper an attempt has been made to determine the authenticity of C.intybus stem by means of Pharmacognostical and Phytochemical analysis. Methods: Macroscopy, microscopy, powder analysis, physicochemical properties, preliminary phytochemical analysis and TLC of different extracts of stem were done. Result: Microscopy of stem showed all typical features of the species Cichorium intybus Linn., The physicochemical study showed the highest extractive value with alcohol. Preliminary phytochemical confirmed the positive chemical test for Flavanoids, Alkaloids, Sterols, Carbohydrates, Resins, Phenolics and Glycosides in various extracts.
Objectives: Hot flashes are unpleasant long-term complications of breast cancer. This study aimed to evaluate the effects of a traditional Persian medicine containing extracts of Cichorium intybus L. (chicory) and Fumaria parviflora L. (Fumitory) extract syrup (CFS) compared with placebo when used as intended. Design: Randomized, double-blind, placebo-controlled clinical trial. Setting/Location: The Oncology Ward of Shahid Modarres Hospital (Tehran, Iran). Subjects: Breast cancer survivors undergoing hormone deprivation therapy. Interventions: Patients were randomly allocated to receive 5 mL CFS or placebo syrup three times a day, for 4 weeks. Outcome measures: The co-primary outcomes were self-reported daily hot flashes frequency and severity scores assessed using self-reported daily dairies, including 1 week of baseline data. Results: Of the 148 patients screened, 137 were eligible, and 96 were randomly allocated to receive either CFS (n = 48) or placebo (n = 48). All participants who returned their dairies were compliant and analyzed as randomized in the a priori per-protocol analysis. After 4 weeks of treatment, both the mean daily hot flashes frequency and severity score had reduced by 57% in the CFS group and 10% in the placebo group. The overall weekly mean daily hot flashes frequency (effect size ηp2 0.221, p < 0.001, n = 66) and severity scores (effect size ηp2 0.160, p = 0.001, n = 66) were significantly lower in the CFS group compared with the placebo group (one-within one-between repeated-measures analysis of variance adjusted for baseline). CFS was well tolerated, with similar proportions of serious and nonserious adverse events occurring in both groups. Conclusions: This is the first study to report the effects of chicory or fumitory for the treatment of hot flashes. The findings provide preliminary evidence that CFS can improve hot flashes in breast cancer survivors undergoing hormone deprivation therapy. More research is warranted to confirm its effectiveness, safety, and mechanisms of action. IRCT20210226050506N1.
Objective: Acute leukemia is a cancer of the blood and bone marrow. Due to chemotherapy drug side effect, the use of natural compound is important. The Cichorium intybus L is a natural compound which showed antitumor and antioxidant effects. The present study aimed to investigate the effect of the C. intybus extract, alone and in combination with Doxorubicin (DOX) on apoptosis induction in myeloid (NALM-6) and lymphoid (KG-1) cell lines. Materials and Methods: In this in vitro experimental study, the NALM-6 and KG-1 cell lines were treated with different doses of C. intybus and DOX, and their combination for 24, 48, 72, 96 hours, and cell viability were investigated with the MTT assay. The percentage of apoptotic cells was determined using caspase-3, and 9 genes expression. Results: C. intybus could induce cytotoxic effects in KG-1, Nalm-6 cell with IC50 values of 400±1.7 and 275±5.6 µg/ml. It has a significant apoptotic effect on Nalm-6 and KG-1 cell lines of ALL and AML in dose-and time-dependent manner (p<0.05). Gene expression of Bax and Caspase 3,and 9 increased and Bcl2 decreased (p<0.05). Conclusions: Cichorium upgraded cytotoxic effect of DOX on Nalm-6 and KG-1 cell lines, and could be suggested as a chemotherapy supplement in acute leukemia.
Introduction: This randomized controlled trial study aimed to find the benefits and possible side effects of brewed chicory leaf consumption in non-alcoholic fatty liver disease (NAFLD) patients.
Methods
Sixty NAFLD patients were randomly allocated into intervention and control groups and consumed brewed chicory leaf made from 15 g chicory leaf along with usual treatment or only the usual treatment, respectively. This study was planned for 12 weeks, but it was stopped in the sixth week due to unexpected side effects.
Results
After 6 weeks, total bilirubin, ALT and AST in the intervention group were significantly reduced compared to the control group (p < 0.05). In the intervention group compared to the control group we observed a significant increase in number of red blood cells (0.16 ± 0.33 vs. −0.01 ± 0.27, p = 0.026), platelets (34.00 ± 45.55 vs. 7.96 ± 25.30, p = 0.014), hemoglobin (0.37 ± 0.84 vs. −0.09 ± 0.59, p = 0.018), fasting blood sugar (5.85 ± 8.47 vs. 0.29 ± 6.67, p = 0.017), total cholesterol (14.08 ± 20.80 vs. −1.30 ± 4.42, p = 0.001), low-density lipoprotein (15.36 ± 20.02 vs. −0.17 ± 6.70, p < 0.0001), and a significant decrease in the mean platelet volume (−3.03 ± 1.79 vs. 0.01 ± 0.62, p < 0.0001).
Discussion
Consumption of brewed chicory leaf could have unexpected side effects on people with NAFLD. (IRCT20190819044565N2)
Statistical and international health organizations state that about 31% of all deaths worldwide are caused by cardiovascular disease (CVD), which represents the main cause of death associated with noncommunicable disease. Various researches performed in the last 10 years have shown the beneficial effects induced by polyphenolic compounds in reducing the risk factors for CVD, thus acting either as preventive factors and also, in some cases, as reparative ones, supporting the treatment of patients with chronic cardiovascular impairments. However, larger cohort of studies are still necessary in order to assess and integrate the potential beneficial effects along with data regarding the low bioavailability of the compounds and also with their potential to interfere with the chronic pharmacological treatment of the selected patients.KeywordsCardiovascular disease (CVD)BioavailabilityPolyphenolic compoundsPharmacological treatment
Chicory (Cichorium intybus L.) is a widely distributed plant which belongs to the family Asteraceae. It is used for the treatment of many diseases related to the heart, kidney, and liver. It is reported as an antioxidant and nutraceutical (forage and food). Chicory is known to produce a unique fiber inulin in roots, and the roots contain ∼15–20% inulin. The inulin fiber has received a lot of attention for it being the source of fiber in functional food and pharmaceutical industry. Inulin is used as a soluble dietary fiber, fat, sweetening agent, stabilizer, and an incipient. Inulin has building blocks of sugar (up to 90 monosaccharides), and the industrial oligofructan is produced from the chicory inulin. Inulin and oligofructans are the prebiotics which help in preventing digestive tract infections and also support the immune system. New uses for inulin are constantly being discovered, with recent research into its use for slow release during drug delivery. Given its increasing importance to industry, the present review will explain inulin’s unique properties which bestow it with many useful industrial and pharmaceutical applications.
Objective: Cardiovascular disease (CVD) including atherosclerosis is currently the most common cause of death in the world. Atherosclerosis can be treated by a vast variety of modalities: from lifestyle modification to invasive open surgical bypass procedures. Regarding the limitations of conventional medicine, worldwide attention to complementary and alternative medicines has increased because of their holistic approach, lower cost and better public access. In this move towards Integrative Medicine -besides other traditional schools of medicine-Persian Medicine (PM) with its long historical background should be considered as a suitable source for research. Method: In this study we investigated major traditional literature of PM, Avicenna’s “Al-Qanun fi al-Tibb” [The Canon of medicine], to find suitable treatment modalities of atherosclerosis in comparison to conventional methods. Result: In the quest for a concept close to atherosclerosis, “sodde” (meaning obstruction) seems to be equal to atherosclerosis and “Mofattehaat” as opener drugs with different types including “Mohallelaat” (dissolvers) and “Moghatteaat” (cutting agents) have been recommended to remove the obstructing materials. Recent studies indicate that many of the medicinal herbs which were introduced as opener drugs by Avicenna have potential pharmacological effects on managing atherosclerosis. Conclusion: Scientific evidence confirm the efficacy of traditional herbs for elimination of atheroma. Antiobstructive traditional medicines are similar to the conventional atherectomy in targeting atheroma by removing atherosclerotic plaque directly, but they are non-invasive, user-friendly, much cheaper and probably with less side effects.
Plants of Cichorium genus are famous for their therapeutic and medicinal properties. They are used as traditional medicine and edible food. Hitherto, a large amount of compounds, including coumarins, flavonoids, sesquiterpenoids, triterpenoids, steroids, organic acids and other chemical constituents, have been obtained. Pharmacological effects such as photo-protective effect, hepatoprotective effect, anti-diabetic and lipid lowering effects, antioxidant, anti-inflammation, antifungal effect, antimalarial activity, increased bone mineral density, vasorelaxant activity and antitumour activity were wildly reported. In this paper, Cichorium genus were summarized in botanical resources, ethanopharmacological application, chemical consistents and bioactivities, safety and toxicity evaluation, and clinical application, which may provide the basis for the further development and utilization of Cichorium resources.
Platelets and platelet microparticles (PMPs) play a key role in the pathophysiology of vascular disorders such as coronary artery disease and stroke. In atherosclerosis, for example, the disruption of the plaque exposes endogenous agonists such as collagen, which activates platelets. Platelet hyper-activation and the high levels of PMPs generated in such situations pose a thrombotic risk that can lead to strokes or myocardial infarctions. Interestingly, dietary polyphenols are gaining much attention due to their potential to mimic the antiplatelet activity of treatment drugs such as aspirin and clopidogrel that target the glycoprotein VI (GPVI)-collagen and cyclooxygenease-1 (COX-1)-thromboxane platelet activation pathways respectively. Platelet function tests such as aggregometry and flow cytometry used to monitor the efficacy of antiplatelet drugs can also be used to assess the antiplatelet potential of dietary polyphenols. Despite the low bioavailability of polyphenols, several in vitro and dietary intervention studies have reported antiplatelet effects of polyphenols. This review presents a summary of platelet function in terms of aggregation, secretion, activation marker expression, and PMP release. Furthermore, the review will critically evaluate studies demonstrating the impact of polyphenols on aggregation and PMP release.
Hemostasis is a process which encompasses the clotting, fibrinolysis, blood platelet activation and endothelial cell function. Certain dietary components may modulate some elements of hemostasis, particularly blood platelet function, and modify the progression of cardiovascular diseases. The aim of this review paper is to provide an overview of current knowledge of the role of coffee, energy drinks and their bioactive compounds in such modulation. It describes the effect of coffee, energy drinks and their selected components (e.g. caffeine) on hemostasis, especially blood platelets, and their underlying mechanisms. Like coffee, energy drinks may modify platelet reactivity by changing the activity of signaling enzymes, and by modifying cAMP and reactive oxygen species levels. However, the effects of coffee and energy drinks on platelet activation are dependent on a range of factors, including their bioactive components, platelet activators and the methods used for monitoring platelet activation. While some studies (in vivo models) indicate that energy drinks have pro-aggregatory affects, which may be associated with an elevated risk of thrombosis, others indicate that coffee in fact reduces platelet activation, which may be beneficial for prophylaxis of thrombosis.
Epidemiological studies have demonstrated that nutritional habits, like those based on high consumption of fruits and vegetables, have been associated with a longer life expectancy and a significant decrease in the incidence and prevalence of several chronic diseases with inflammatory basis, such as cardiovascular diseases (CVD). This beneficial activity has been related to the content of several bioactive compounds in fruit and vegetables, such as polyphenols. The cardioprotective effects of polyphenols have been linked mainly to its antioxidant properties; however, recent findings attribute its anti-atherosclerotic potential to modulate simultaneous signaling and mechanistic pathways. Emerging data suggest that polyphenols can regulate cellular lipid metabolism; vascular and endothelial function; haemostasis; as well as platelet function; which represent primary conditions for atherosclerotic plaque formation and development. This review presents the results of a selection of experimental studies and clinical trials regarding the atheroprotective effects of the most common dietary polyphenols.
There were substantial evidences that many medicinal plants decreased the risk of cardiovascular diseases. With the high prevalence of herbal medicine use worldwide, the information regarding the therapeutic use or safety of herbal remedies usually obtained from books and pamphlets, most of which base their information on traditional reputation rather than relying on existing scientific research. This review will cover the plants with vascular, hypotensive, cardiac, cardioprotective, antiarrhythmic, hypolipidemic, hemostatic, fibrinolytic and anticoagulant effects.
In the present study, curly endive (Cichorium endivia L. var. crispum) and escarole (Cichorium endivia L. var. latifolium) accessions were investigated for their sensory characters (bitterness, astringency and herbaceous flavour) and acceptance in relation to sesquiterpene lactone and phenolic content. Different facets of the perception of these sensory traits in relation to lactones and phenolics were brought out. Lactucopicrin and kaempferol malonyl glucoside were consistently related to bitterness, astringency and herbaceous flavour perceptions. Overall acceptance was significantly and inversely related mainly to bitterness. The generic statement that sesquiterpene lactones and phenolic compounds are determinants of bitterness and other related sensory characters does not seem to be fully consistent with our data, that indicated how the balance of different compounds affects these traits individually, in a rather complex manner, with a prevailing negative impact of phenolics.
Bitter, astringent, and herbaceous perceptions were significantly affected by variety, with curly endive showing on average higher scores in comparison to escarole, with particular respect to bitterness
Polyphenols are food constituents rich in a number of phenolic compounds. Polyphenols are commonly used in good health keeping and disease prevention. Recently, several food industries, fruit processing and nutrition formula companies have marketed polyphenol brands after careful government-sponsored pre-clinical and clinical trials at advanced university medical centers and government sponsored hospitals. This chapter is divided into eight sections. The first section introduces a brief description of the overall structures of polyphenols. The second section reflects on the emerging art of polyphenols as food, followed by the second section on polyphenol-rich diet sources, the role of polyphenols in the body, and the mechanism of polyphenol action. The third section discusses the nutritional value of polyphenols in fruits and foods and biochemical action. The fourth section deals with polyphenols in health practices and their health benefits, followed by the fifth section on evidence-based values. A database of polyphenols in health and disease for nurses, scientists, physicians and social workers, is given in the sixth section. The seventh section deals with hypes in polyphenol health benefits and future directions. A major focus is on the mechanism of polyphenol-induced metabolic changes as a basis of benefits in chronic diseases. In conclusion, polyphenols have potentials in health and disease prevention, evidenced by preclinical trials with a caution of incomplete available clinical data and no federal regulatory guidelines available on toxicity or public concerns.
Phenolic compounds are important components of many fruits, vegetables and beverages, contributing to their flavor, color and sensory properties. Besides, they are associated with prevention of diseases thought to be induced by oxidative stress, such as cardiovascular diseases, cancer and inflammation. Due to their bioactive functions, phenolic compounds have received particular attention in recent years. Amongst the different analytical methods reported to determine the polyphenol content and composition of food and beverages, liquid chromatography (LC) is the preferred option compared to gas chromatography (GC) since no derivatization is needed. UV detectors have been commonly used for the determination of phenolic compounds, but they lack of sensitivity and/or specificity. LC coupled with electrochemical detection (ECD) or coupled to mass spectrometry (MS) detectors are the most sensitive, selective and reproducible methods for quantifying phenolic compounds. This manuscript reviews the main applications of LC coupled to ECD or MS for the analysis of phenolic compounds in food and beverages.
Dietary sources of polyphenols, which are derivatives and/or isomers of flavones, isoflavones, flavonols, catechins and phenolic acids, possess antioxidant properties and therefore might be important in preventing oxidative‐stress‐induced platelet activation and attenuating adverse haemostatic function. Free radicals, including reactive oxygen and nitrogen species, promote oxidative stress, leading to platelet hyperactivation and the risk of thrombosis. The consumption of antioxidant/polyphenol rich foods might therefore impart anti‐thrombotic and cardiovascular protective effects via their inhibition of platelet hyperactivation or aggregation. Most commonly‐used anti‐platelet drugs such as aspirin block the cyclooxygenase (COX)‐1 pathway of platelet activation, similar to the action of antioxidants with respect to neutralising hydrogen peroxide (H2O2), with a similar effect on thromboxane production via the COX‐1 pathway. Polyphenols also target various additional platelet activation pathways (e.g. by blocking platelet‐ADP, collagen receptors); thus alleviating fibrinogen binding to platelet surface (GPIIb‐IIIa) receptors, reducing further platelet recruitment for aggregation and inhibiting platelet degranulation. As a result of the ability of polyphenols to target additional pathways of platelet activation, they may have the potential to substitute or complement currently used anti‐platelet drugs in sedentary, obese, pre‐diabetic or diabetic populations who can be resistant or sensitive to pharmacological anti‐platelet therapy.
The capacity of red blood cells to deform is of crucial importance for both macro and microcirculation. A satisfying technique for the measurement of this parameter is lacking so far. We have developed and tested in various studies an instrument for automatic measurement of red cell deformability by laser diffractometry. Recently, it appeared that the applicability of the instrument could be extended for measuring another structural hemorheological parameter, red blood cell aggregation. In this communication, a description of the Laser-assisted Optical Rotational Cell Analyser (LORCA) is followed by the general methodology for the measurement of both red blood cell deformability and aggregation, demonstrating the practical versatility of this instrument in the field of hemorheology.
The well known medicinal plant, Cichorium intybus L. (Asteraceae) contains dietary oligofructose compounds which have beneficial effect on carbohydrate and lipid metabolism, other compounds e.g. polyphenol type derivatives could be responsible for the antioxidant properties reported in several studies before. Male Fischer rats were kept on normal and lipid rich diet supplemented with chicory extract in this study. Our aim was to investigate the influence of this supplementation on pancreas status of rats, especially in dislipidemia. Polyphenols, flavonoids and caffeic acid derivatives were measured in chicory extract by spectrophotometric and chromatographic methods. Antioxidant property of the plant extract was determined in vitro and the biological activity of antioxidant compounds of chicory was investigated in vivo by a luminometric technique.The effects of bioactive molecules of chicory extract influenced the lipid metabolism and the redox balance of pancreatic tissue of rats in experimental dislipidemia. Acta Biol Szeged 47(1-4):143-146 (2003)
The effect of consumption of red or white wine (11% alcohol) with meals on the propensity of plasma and low-density lipoprotein (LDL) to undergo lipid peroxidation was studied in 17 healthy men who were divided into two groups: 8 received 400 mL red wine/d for 2 wk, and 9 received a similar amount of white wine. Red wine consumption for 2 wk resulted in a 20% reduction in the propensity of plasma to undergo lipid peroxidation (in the presence of a free-radical-generating system) as determined by the thiobarbituric acid reactive substances (TBARS) assay. In parallel, red wine consumption reduced the propensity of the volunteers' LDL to undergo lipid peroxidation (in response to copper ions) as determined by a 46%, 72%, and 54% decrease in the content of TBARS, lipid peroxides, and conjugated dienes in LDL, respectively, as well as by a substantial prolongation of the lag phase required for the initiation of LDL oxidation. On the contrary, dietary consumption of white wine for 2 wk resulted in a 34% increase in plasma's propensity to undergo lipid peroxidation and also in a 41% increased propensity of the LDL to undergo lipid peroxidation. The antioxidant effect of dietary red wine on plasma lipid peroxidation was not secondary to changes in the plasma vitamin E or beta-carotene content but could be related to the elevation of polyphenol concentration in plasma and LDL. Thus, some phenolic substances that exist in red wine, but not in white wine, are absorbed, bind to plasma LDL, and may be responsible for the antioxidant properties of red wine.
Chlorogenic acid, an ester of caffeic acid and quinic acid, is a major phenolic compound in coffee; daily intake in coffee drinkers is 0.5-1 g. Chlorogenic acid and caffeic acid are antioxidants in vitro and might therefore contribute to the prevention of cardiovascular disease. However, data on the absorption of chlorogenic acid and caffeic acid in humans are lacking. We determined the absorption of chlorogenic acid and caffeic acid in a cross-over study with 4 female and 3 male healthy ileostomy subjects. In such subjects, degradation by the colonic microflora is minimal and absorption can be calculated as the amount ingested minus the amount excreted in ileostomy effluent. The ileostomy subjects ingested 2.8 mmol chlorogenic acid and 2.8 mmol caffeic acid on separate days in random order and subsequently collected ileostomy fluid and urine for 24 h. Absorption of chlorogenic acid was 33 +/- 17% (mean +/- SD) and of caffeic acid 95 +/- 4%. Traces of the ingested chlorogenic acid and 11% of the ingested caffeic acid were excreted in urine. Thus, one third of chlorogenic acid and almost all of the caffeic acid were absorbed in the small intestine of humans. This implies that part of chlorogenic acid from foods will enter into the blood circulation, but most will reach the colon.
The cytokine macrophage migration inhibitory factor (MIF) has emerged to be an important regulator of the inflammatory response and is critically involved in the development of septic shock, arthritis, and glomerulonephritis. Although the biological activities of MIF are presumed to require a receptor-based mechanism of action, the protein is also a tautomerase and has a catalytically active N-terminal proline that is invariant in structurally homologous bacterial isomerases. This observation raises the possibility that MIF may exert its biological action via an enzymatic reaction. Physiologically relevant substrates for MIF have not been identified, nor have site-directed mutagenesis studies consistently supported the requirement for a functional catalytic site. Small molecule inhibitors of MIF's isomerase activity also have been developed, but none have been shown yet to inhibit MIF biological activity. We report herein that the iminoquinone metabolite of acetaminophen, N-acetyl-p-benzoquinone imine (NAPQI), inhibits both the isomerase and the biological activities of MIF. The reaction between NAPQI and MIF is covalent and produces a NAPQI-modified MIF species with diminished cell binding activity and decreased recognition by anti-MIF mAb. These data are consistent with a model by which the NAPQI reacts with the catalytic Pro-1 of MIF to disrupt the integrity of epitope(s) critical to MIF's biological activity and point to the importance of the catalytic domain, but not the catalytic activity per se, in MIF function. These results also point to a powerful approach for the design of small molecule inhibitors of MIF based on interaction with its catalytic site and constitute an example of a pharmacophore capable of irreversibly inhibiting the action of a proinflammatory cytokine.
Macrophage migration inhibitory factor (MIF) is an immunoregulatory protein that is a potential therapeutic target for a number of inflammatory diseases. Evidence exists that an unexpected catalytic active site of MIF may have a biological function. To gain further insight into the role of the catalytic active site, a series of mutational, structural, and biological activity studies were performed. The insertion of an alanine between Pro-1 and Met-2 (PAM) abolishes a non-physiological catalytic activity, and this mutant is defective in the in vitro glucocorticoid counter-regulatory activity of MIF. The crystal structure of MIF complexed to (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1), an inhibitor of MIF d-dopachrome tautomerase activity, reveals that ISO-1 binds to the same position of the active site as p-hydroxyphenylpyruvic acid, a substrate of MIF. ISO-1 inhibits several MIF biological activities, further establishing a role for the catalytic active site of MIF.
Cell adhesion molecules are critical in monocyte (MN) recruitment in immune-mediated and hematologic diseases. We investigated the novel role of recombinant human migration inhibitory factor (rhMIF) in up-regulating vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) and their signaling pathways in human MNs. rhMIF-induced expression of VCAM-1 and ICAM-1 was significantly higher compared with nonstimulated MNs. rhMIF induced MN VCAM-1 and ICAM-1 expression in a concentration-dependent manner (P < .05). Antisense oligodeoxynucleotides (ODNs) and inhibitors of Src, PI3K, p38, and NFkappaB significantly reduced rhMIF-induced MN VCAM-1 and ICAM-1 expression (P < .05). However, Erk1/2 and Jak2 were not involved. Silencing RNA directed against MIF, and inhibitors of Src, PI3K, NFkappaB, anti-VCAM-1, and anti-ICAM-1 significantly inhibited rhMIF-induced adhesion of HL-60 cells to human dermal microvascular endothelial cells (HMVECs) or an endothelial cell line, HMEC-1, in cell adhesion assays, suggesting the functional significance of MIF-induced adhesion molecules (P < .05). rhMIF also activated MN phospho-Src, -Akt, and -NFkappaB in a time-dependent manner. rhMIF induced VCAM-1 and ICAM-1 up-regulation in 12 hours via Src, PI3K, and NFkappaB as shown by Western blotting and immunofluorescence. MIF and MIF-dependent signaling pathways may be a potential target for treating diseases characterized by up-regulation of cell adhesion molecules.
Epidemiological studies indicate a J-shaped relationship linking coffee consumption and cardiovascular risk, suggesting that moderate coffee consumption can be beneficial. Platelet aggregation is of critical importance in thrombotic events, and platelets play a major role in the aetiology of several CVD. The aim of this study was to evaluate the effect of coffee drinking on platelet aggregation ex vivo, using caffeine as control. A crossover study was performed on ten healthy subjects. In two different sessions, subjects drank 200 ml coffee, containing 180 mg caffeine, or a capsule of caffeine (180 mg) with 200 ml water. Platelets were separated from plasma at baseline and 30 and 60 min after coffee drinking. Platelet aggregation was induced with three different agonists: collagen, arachidonic acid and ADP. Coffee drinking inhibited collagen (P < 0.05 from baseline at time 30 min) and arachidonic acid (P < 0.05 from baseline at time 60 min) induced platelet aggregation. Caffeine intake did not affect platelet aggregation induced by the three agonists. Coffee consumption induced a significant increase of platelet phenolic acids (likely present as glucuronate and sulphate derivatives), caffeic acid, the principal phenolic acid in coffee, raising from 0.3 (SEM 0.1) to 2.4 (SEM 0.6) ng/mg (P < 0.01). Caffeine was not detectable in platelets. Coffee drinking decreases platelet aggregation, and induces a significant increase in phenolic acid platelet concentration. The antiplatelet effect of coffee is independent from caffeine and could be a result of the interaction of coffee phenolic acids with the intracellular signalling network leading to platelet aggregation.
In the regulation of coronary circulation both hemodynamical and hemorheological factors play an important role. Recent studies emphasize the role of hemorheological parameters as primary risk factors in cardiovascular diseases. The data of 377 patients (pts) with ischemic heart disease (IHD) (mean age (ma): 55 yrs) and 59 healthy controls (HC) (ma: 35 yrs) at rest and 32 pts with IHO (ma: 51 yrs) and 20 HC (ma: 23 yrs) during exercise stress test were analysed. Hemodynamical parameters (cardiac output and cardiac index *CI*) by impedance-cardiographic and radio-cardiographic methods and hemorheological parameters (whole blood *WBV* and plasma viscosity and fibrinogen level) were determined, and a new index - the circulatory index (* CRI = CI/WBV *) - was introduced. The rheological parameters in IHD were in the pathological range and were significantly (p < 0.01) higher than in HC. The CRI both at rest and during exercise was significantly lower in IHD pts than in the controls (p < 0.01). Our data show that hemorheological factors are altered in IHD and CRI is significantly lower than in HC. These findings underline the pathophysiological role of these factors in cardiovascular diseases.
The capacity of red blood cells to deform is of crucial importance for both macro and microcirculation. A satisfying technique for the measurement of this parameter is lacking so far. We have developed and tested in various studies an instrument for automatic measurement of red cell deformability by laser diffractometry. Recently, it appeared that the applicability of the instrument could be extended for measuring another structural hemorheological parameter, red blood cell aggregation. In this communication, a description of the Laser-assisted Optical Rotational Cell Analyser (LORCA) is followed by the general methodology for the measurement of both red blood cell deform ability and aggregation, demonstrating the practical versatility ofthis instrument in the field of hemorheology.
The p-coumaric, ferulic, and caffeic acid contents of alfalfa, cabbage, and spinach were determined by gas chromatography after derivatization with N,N-bis(trimethylsilyl)trifluoroacetamide. Total phenolic acids were estimated by extraction with 1% NaOH containing 0.5% NaBH4. Free or nonesterified acids were extracted with 80% methanol. Alfalfa contained the highest concentration of total p-coumaric acid (1 mg/g) and of free caffeic acid (0.68 mg/g). Lower levels of free caffeic acid were found in cabbage and spinach but none in wheat bran. Wheat bran had the highest content of ferulic acid (4.4 mg/g). Only the free form of caffeic acid was found in alfalfa and cabbage, probably because the alkaline treatment destroyed all that was present.
Data on the association between coffee consumption and risk of stroke are sparse. We assessed the association between coffee consumption and the risk of stroke over 24 years of follow-up in women.
We analyzed data from a prospective cohort of 83,076 women in the Nurses' Health Study without history of stroke, coronary heart disease, diabetes, or cancer at baseline. Coffee consumption was assessed first in 1980 and then repeatedly every 2 to 4 years, with follow-up through 2004. We documented 2280 strokes, of which 426 were hemorrhagic, 1224 were ischemic, and 630 were undetermined. In multivariable Cox regression models with adjustment for age, smoking status, body mass index, physical activity, alcohol intake, menopausal status, hormone replacement therapy, aspirin use, and dietary factors, the relative risks (RRs) of stroke across categories of coffee consumption (<1 cup per month, 1 per month to 4 per week, 5 to 7 per week, 2 to 3 per day, and >or=4 per day) were 1, 0.98 (95% CI, 0.84 to 1.15), 0.88 (95% CI, 0.77 to 1.02), 0.81 (95% CI, 0.70 to 0.95), and 0.80 (95% CI, 0.64 to 0.98) (P for trend=0.003). After further adjustment for high blood pressure, hypercholesterolemia, and type 2 diabetes, the inverse association remained significant. The association was stronger among never and past smokers (RR for >or=4 cups a day versus <1 cup a month, 0.57; 95% CI, 0.39 to 0.84) than among current smokers (RR for >or=4 cups a day versus <1 cup a month, 0.97; 95% CI, 0.63 to 1.48). Other drinks containing caffeine such as tea and caffeinated soft drinks were not associated with stroke. Decaffeinated coffee was associated with a trend toward lower risk of stroke after adjustment for caffeinated coffee consumption (RR for >or=2 cups a day versus <1 cup a month, 0.89; 95% CI, 0.73 to 1.08; P for trend=0.05).
Long-term coffee consumption was not associated with an increased risk of stroke in women. In contrast, our data suggest that coffee consumption may modestly reduce risk of stroke.
The caffeine content of a number of non-alcoholic beverages was determined using HPLC. It was found that Diet Coke had a greater caffeine content than Coke (4.15 compared with 3.13 mg/fl oz), Tab is virtually caffeine free, and Lucozade, sold as a tonic, contains more caffeine than any of the other carbonated beverages tested (5.17 mg/fl oz). The pure instant coffee tested contained much more caffeine than the coffee/chicory mixtures (12.61 compared with 3.18 mg/fl oz). The caffeine content of Ceylon tea blends increases with the time the tea is allowed to draw (from about 8 mg/fl oz after 1 min to about 12 mg/fl oz after 20 min). Tea that has been allowed to draw for 20 min has a caffeine content similar to that of pure coffee.
Presentation d'un rheoscope, l'ektacytometre, permettant de mesurer le comportement rheologique des globules rouges face a des forces de cisaillement. Le principe de la mesure, ses avantages et inconvenients sont exposes. Le schema de l'appareillage et ses eventuelles modifications permettant des mesures dans des conditions particulieres, sont decrites, l'analyse des resultats se faisant par un systeme d'exploitation par traitement d'images
The cell type responsible for inhibition by antigen of migration in vitro of peritoneal exudate cells obtained from tuberculin-hypersensitive guinea pigs was studied. Exudate populations were separated into component cell types, the lymphocyte and the macrophage. Peritoneal lymphocytes from sensitive donors were the immunologically active cells in this system, the macrophages, being merely indicator cells which migrate. Sensitized peritoneal lymphocyte populations, upon interaction with specific antigen in vitro, elaborated into the medium a soluble material capable of inhibiting migration of normal exudate cells.
Cytokines are critical in the often fatal cascade of events that cause septic shock. One regulatory system that is likely to be important in controlling inflammatory responses is the neuroendocrine axis. The pituitary, for example, is ideally situated to integrate central and peripheral stimuli, and initiates the increase in systemic glucocorticoids that accompanies host stress responses. To assess further the contribution of the pituitary to systemic inflammatory processes, we examined the secretory profile of cultured pituitary cells and whole pituitaries in vivo after stimulation with bacterial lipopolysaccharide (LPS). Here we identify macrophage migration inhibitory factor (MIF) as a major secreted protein release by anterior pituitary cells in response to LPS stimulation. Serum analysis of control, hypophysectomized and T-cell-deficient (nude) mice suggests that pituitary-derived MIF contributes to circulating MIF present in the post-acute phase of endotoxaemia. Recombinant murine MIF greatly enhances lethality when co-injected with LPS and anti-MIF antibody confers full protection against lethal endotoxaemia. We conclude that MIF plays a central role in the toxic response to endotoxaemia and possibly septic shock.
Background:
Recent studies of melanin biosynthesis have uncovered an unusual enzymatic activity which converts the non-naturally occurring D-isomer of 2-carboxy-2,3-dihydroindole-5,6-quinone (dopachrome) into 5,6-dihydroxyindole-2-carboxylic acid (DHICA). The aim of the present investigation was to isolate and characterize the enzyme catalyzing this tautomerization reaction.
Materials and methods:
After we performed a tissue survey of D-dopachrome tautomerase activity, 10 bovine lenses were homogenized and used as a source of enzyme. A soluble fraction was obtained by high-speed centrifugation and subjected to successive FPLC chromatography on Phenyl-sepharose, Mono S cation-exchange, and Superdex gel-filtration. The isolated enzyme was electrophoresed, blotted onto PVDF membrane, and the N terminus analyzed by gas phase micro-sequencing.
Results:
The protein catalyzing the conversion of D-dopachrome to DHICA was purified to homogeneity in 14% yield and showed a molecular weight of 12 kD when analyzed by SDS-PAGE. The first 27 amino acid residues of this protein were sequenced and found to be identical with those of bovine macrophage migration inhibitory factor (MIF). The catalytic activity of native MIF was confirmed by studies of purified recombinant human MIF, which showed the same tautomerase activity. While L-dopachrome was not a substrate for this reaction, the methyl esters of the L- and D-isomers were found to be better substrates for MIF than D-dopachrome.
Conclusions:
MIF has been described recently to be an anterior pituitary hormone and to be released from immune cells stimulated by low concentrations of glucocorticoids. Once secreted, MIF acts to control, or counter-regulate, the immunosuppressive effects of glucocorticoids on the immune system. Although the tested substrate, D-dopachrome, does not occur naturally, the observation that MIF has tautomerase activity suggests that MIF may mediate its biological effects by an enzymatic reaction. These data also offer a potential approach for the design of small molecule pharmacological inhibitors of MIF that may modulate its potent immunoregulatory effects in vivo.
This chapter discusses the conceptual development of the macrophage migration inhibitory factor (MIF)/glucocorticoid regulatory system and reviews the implications of MIF action in the overall control of host inflammatory and immune responses. MIF protein exists preformed in macrophages, T cells, and the corticotrophic cells of the anterior pituitary gland. MIF acts as a physiological counter-regulator of glucocorticoid action within the immune system. It has the unique property of being released from macrophages and T cells in response to glucocorticoids. Once MIF are released, MIF overrides or counter-regulates the inhibitory effect of glucocorticoids on immune and inflammatory responses. Both MIF and glucocorticoids circulate at concentrations that have regulatory activity, indicating that the baseline state of the MIF/glucocorticoid diad is an active balance between pro- and anti-inflammatory effects. The chapter also discusses the potential role of MIF in various inflammatory disease states, such as septic shock, delayed-type hyperserisitivity, and arthritis.
A macrophage migration inhibitory factor (MIF), originally described as a product of activated lymphocytes, has been defined as a 12 kDa protein, expressed in a wide variety of tissues. Here MIP is identified as a phenylpyruvate tautomerase (EC 5.3.2.1) having p-hydroxyphenylpyruvate and phenylpyruvate as its natural substrates. The definition of MIF as an enzyme may yield insight into the mechanism of action of this proinflammatory and immunomodulating cytokine. (C) 1997 Federation of European Biochemical Societies.
The microcirculatory disturbances in sepsis have prompted micropore bulk-filtration studies of red blood cell (RBC) mechanical behavior (i.e., deformability). However, these prior reports may not solely reflect RBC behavior because of possible white blood cell (WBC) occlusion of the filter pores. The present study was designed to examine RBC mechanical alterations in human and experimental sepsis using techniques that are not affected by WBC artifacts. RBC were obtained from adult patients with sepsis and from healthy control donors. RBC were also obtained from Swiss-albino rats in which experimental sepsis was induced via cecal ligation-puncture. Red cell mechanical behavior was tested using a computerized micropore filtration system (CTA) and a laser-diffraction shearing device (LORCA); the latter provides the extent of RBC deformation at various stresses and the time constant for RBC shape recovery. Salient findings include: (1) for human RBC, significantly decreased deformability at fluid shear stresses < 5 Pa (LORCA) yet no differences from control with the CTA; (2) for rat RBC in experimental sepsis, significant decreases of deformability and shape-recovery time constant (LORCA) but no differences with the CTA. We conclude that RBC deformability is reduced in sepsis but that micropore bulk-filtration methods may not be appropriate for detecting these changes.
The molecular mechanism of action of macrophage migration inhibitory factor (MIF), a cytokine with a critical role in the immune and inflammatory response, has not yet been identified. Here we report that MIF can function as an enzyme exhibiting thiol-protein oxidoreductase activity. Using a decapeptide fragment of MIF (MF1) spanning the conserved cysteine sequence motif Cys57-Ala-Leu-Cys60 (CALC), Cys-->Ser mutants (C57S MIF, C60S MIF, and C57S/C60S MIF) of human MIF (wtMIF), and alkylated wtMIF, we show that this activity is mediated by the CALC region and is important for the macrophage-activating properties of MIF. Both wtMIF and MF1 were demonstrated to form an intramolecular disulfide bridge. Using two common oxidoreductase assays, MIF was shown to enzymatically catalyze the reduction of insulin and 2-hydroxyethyldisulfide (HED). Examination of wtMIF and the mutants by far-UV circular dichroism spectroscopy (CD) together with denaturation studies showed that substituting or reducing the cysteine residues of CALC led to a reduced conformational stability of MIF but did not significantly change its overall conformation. A functional role for the CALC region was revealed by subjecting the mutants and alkylated wtMIF to the enzymatic assays. Mutant C60S did not have any enzymatic activity while mutant C57S had a reduced activity. Thiol-modified wtMIF that was alkylated under oxidizing conditions was found to have full enzymatic activity, whereas alkylation of wtMIF under reducing conditions completely eliminated MIF-mediated redox activity. Importantly, further physiological relevance of the disulfide motif was obtained by examining the mutants and alkylated MIF in an immunological assay that involved the macrophage-activating properties of MIF. In this test, mutant C60S was essentially inactive and mutant C57S was partly active, indicating together that at least some of the cytokine-like biological activities of MIF are dependent on the presence of cysteine 57 and 60. Again, use of the alkylated MIF species confirmed the role of the cysteine motif for this MIF activity. In conclusion, our results argue (a) that MIF exhibits enzymatic oxidoreductase activity, (b) that this activity is dependent on the presence of the catalytic center that is formed by cysteine residues 57 and 60, and (c) that certain MIF-mediated immune processes are due to the cysteine-mediated redox mechanism.
Macrophage migration inhibitory factor (MIF) plays an important role in inflammation and immunity via autocrine/paracrine and endocrine routes. We examined the presence of MIF in the synovial fluids of rheumatoid arthritis (RA) patients. The content of MIF in the synovial fluid was quantitated by enzyme-linked immunosorbent assay which revealed that the concentration of MIF for RA patients was 85. 7+/-35.2 ng/ml (mean+/-SD) (n=25). In comparison, the concentrations for osteoarthritis patients and normal volunteers were 19.5+/-5.3 ng/ml (n=12) and 10.4+/-1.1 ng/ml (n=5), respectively. The expression of MIF mRNA and presence of MIF protein in the synovial tissues of RA were demonstrated by Northern blot and Western blot analyses, respectively. Immunohistochemical analysis revealed that positive staining was largely observed in the cytoplasm of infiltrating T lymphocytes, which might be the major source of MIF detected in the synovial fluids. The pathophysiological role of MIF in RA remains to be elucidated; however, the present results for the first time suggest the possibility that MIF is involved in the potentiation of inflammatory and immunological responses in rheumatoid joints.
Despite extensive literature describing the biological effects of polyphenols, little is known about their absorption from diet, one major unresolved point consisting of the absorption of the bound forms of polyphenols. In this view, in the present work we studied the absorption in humans of phenolic acids from coffee, a common beverage particularly rich in bound phenolic acids, such as caffeic acid, ferulic acid, and p-coumaric acid. Coffee brew was analyzed for free and total (free + bound) phenolic acids. Chlorogenic acid (5'-caffeoylquinic acid), a bound form of caffeic acid, was present in coffee at high levels, while free phenolic acids were undetectable. After alkaline hydrolysis, which released bound phenolic acids, ferulic acid, p-coumaric acid, and high levels of caffeic acid were detected. Plasma samples were collected before and 1 and 2 h after coffee administration and analyzed for free and total phenolic acid content. Two different procedures were applied to release bound phenolic acids in plasma: beta-glucuronidase treatment and alkaline hydrolysis. Coffee administration resulted in increased total plasma caffeic acid concentration, with an absorption peak at 1 h. Caffeic acid was the only phenolic acid found in plasma samples after coffee administration, while chlorogenic acid was undetectable. Most of caffeic acid was present in plasma in bound form, mainly in the glucuronate/sulfate forms. Due to the absence of free caffeic acid in coffee, plasma caffeic acid is likely to be derived from hydrolysis of chlorogenic acid in the gastrointestinal tract.
"Bioactive compounds" are extranutritional constituents that typically occur in small quantities in foods. They are being intensively studied to evaluate their effects on health. The impetus sparking this scientific inquiry was the result of many epidemiologic studies that have shown protective effects of plant-based diets on cardiovascular disease (CVD) and cancer. Many bioactive compounds have been discovered. These compounds vary widely in chemical structure and function and are grouped accordingly. Phenolic compounds, including their subcategory, flavonoids, are present in all plants and have been studied extensively in cereals, legumes, nuts, olive oil, vegetables, fruits, tea, and red wine. Many phenolic compounds have antioxidant properties, and some studies have demonstrated favorable effects on thrombosis and tumorogenesis and promotion. Although some epidemiologic studies have reported protective associations between flavonoids or other phenolics and CVD and cancer, other studies have not found these associations. Various phytoestrogens are present in soy, but also in flaxseed oil, whole grains, fruits, and vegetables. They have antioxidant properties, and some studies demonstrated favorable effects on other CVD risk factors, and in animal and cell culture models of cancer. However, because phytoestrogens act both as partial estrogen agonists and antagonists, their effects on cancer are likely complex. Hydroxytyrosol, one of many phenolics in olives and olive oil, is a potent antioxidant. Resveratrol, found in nuts and red wine, has antioxidant, antithrombotic, and anti-inflammatory properties, and inhibits carcinogenesis. Lycopene, a potent antioxidant carotenoid in tomatoes and other fruits, is thought to protect against prostate and other cancers, and inhibits tumor cell growth in animals. Organosulfur compounds in garlic and onions, isothiocyanates in cruciferous vegetables, and monoterpenes in citrus fruits, cherries, and herbs have anticarcinogenic actions in experimental models, as well as cardioprotective effects. In summary, numerous bioactive compounds appear to have beneficial health effects. Much scientific research needs to be conducted before we can begin to make science-based dietary recommendations. Despite this, there is sufficient evidence to recommend consuming food sources rich in bioactive compounds. From a practical perspective, this translates to recommending a diet rich in a variety of fruits, vegetables, whole grains, legumes, oils, and nuts.
A series of amides of caffeic acid were synthesized and evaluated for their anti-platelet and anti-oxidative activities. N-(2-Bromo-phenyl)-3-(3,4-dihydroxy-phenyl)-acrylamide (12) and N-(3-Bromo-phenyl)-3-(3,4-dihydroxy-phenyl)-acrylamide (13) exhibited potent inhibitory activity (IC(50)=5.8 and 6.7 microM, respectively) against arachidonic acid-induced (AA) platelet aggregation, comparable with invalid caffeic acid. Most of the synthesized caffeic acid anilides exhibited the promising anti-platelet aggregation in AA-induced assay and anti-oxidative activities. This study also exhibited that caffeic anilides displayed more potent anti-oxidative activity in the radical scavenging activity assay than trolox and vitamin E.
The cytokine macrophage migration inhibitory factor (MIF) has recently emerged as a crucial factor in the pathogenesis of rheumatoid arthritis (RA). It is debated whether the MIF mediated tautomeric conversion of either phenylpyruvate or of its other phenolic substrates is implicated in the pro-inflammatory action of this cytokine. Traditional herbal remedies have been used for centuries to alleviate inflammatory ailments of many kinds including arthritis. Several of their active ingredients identified are mono- or poly-phenol derivatives. In the present study the effect of some anti-inflammatory plant phenols on MIF mediated tautomerism of phenylpyruvate was investigated. Curcumin and caffeic acid were found to be the most potent inhibitors, exhibiting IC(50) values in the submicromolar range in the ketonase assay. Resveratrol and umbelliferon were almost as potent inhibitors as the antipyretic-analgetic drug acetaminophen. Our results reveal MIF as a possible target for the herbal anti-rheumatic agents.
Caffeic acid phenethyl ester (CAPE), which is derived from the propolis of honeybee hives, has been demonstrated to possess multiple pharmacological activities. In the present study, CAPE (6-25 microM) specifically inhibited collagen-induced platelet aggregation and the ATP release reaction in platelet suspensions.
Platelet aggregation, flow cytometric analysis, immunoblotting, and electron spin resonance (ESR) were used to assess the anti-platelet activity of CAPE. Fluorescein sodium-induced platelet thrombi in mesenteric microvessels of mice were used for an in vivo study.
CAPE (15-100 microM) produced a concentration-related rightward displacement of the collagen concentration-response curve, and the Schild plot gave pA(2) and pA(10) values of 4.28+/-0.07 and 3.14+/-0.73, respectively, with a slope of -0.83+/-0.16, indicating specific antagonism. CAPE (25 microM) also inhibited platelet aggregation stimulated by the glycoprotein VI agonist, convulxin, and the alpha(2)beta(1) integrin agonist, aggretin. CAPE (25 microM) also markedly interfered with FITC-collagen binding to platelet membranes. CAPE (15 and 25 microM) concentration-dependently inhibited collagen-induced platelet activation accompanied by [Ca(+2)](i) mobilization, phosphoinositide breakdown, activation of protein kinase C and mitogen-activated protein kinases (i.e., ERK2, JNK, and p38 MAPK), Akt phosphorylation, and thromboxane A(2) formation. In the ESR study, CAPE (15 and 25 microM) markedly reduced hydroxyl radical (OH) formation in collagen-activated platelets. In an in vivo study, CAPE (5 mg/kg) significantly prolonged the latency in inducing platelet plug formation in mesenteric venules of mice.
The most important findings of this study suggest that CAPE specifically inhibits collagen-induced platelet activation. Thus, CAPE treatment may represent a novel approach to lowering the risk of or improving function in thromboembolism-related disorders.
The effect of coffee consumption on cardiovascular disease has been debated for many years. In this work, we evaluated the association between coffee consumption and the risk of developing acute coronary syndromes, based on a random sample of 848 patients with their first coronary heart disease event and 1078 frequency-matched controls with no cardiovascular disease in their medical history, from the entire country. The multivariate analysis raises a J-shaped association between the risk of developing acute coronary syndromes and the quantity of coffee consumed per day. In particular, the odds ratios for moderate (<300 mL/d), heavy (300-600 mL/d), and very heavy (>600 mL/d), consumption, relative to no consumption, were 0.69 (95% CI, 0.50-0.86), 1.56 (95% CI, 1.10-2.34) and 3.10 (95% CI, 1.82-5.26), respectively, after controlling for the presence of hypertension, hypercholesterolemia, diabetes mellitus, family history of premature coronary heart disease, physical activity status, smoking habits, BMI, alcohol consumption, triglycerides, consumption of several food items, depression scale score and education status. The suggested J-shaped association between coffee consumption and the risk of developing acute coronary syndromes may partially explain the conflicting results from other studies in the past.
Potato peels are waste by-product of the potato processing industry. They are reportedly rich in polyphenols. Our earlier studies have shown that extracts derived from potato peel (PPE) possess strong antioxidant activity in chemical and biological model systems in vitro, attributable to its polyphenolic content. The main objective of this study was to investigate the ability of PPE to protect erythrocytes against oxidative damage, in vitro. The protection rendered by PPE in erythrocytes was studied in terms of resistance to oxidative damage, morphological alterations as well as membrane structural alterations. The total polyphenolic content in PPE was found to be 3.93 mg/g powder. The major phenolic acids present in PPE were predominantly: gallic acid, caffeic acid, chlorogenic acid and protocatechuic acid. We chose the experimental prooxidant system: FeSO(4) and ascorbic acid to induce lipid peroxidation in rat RBCs and human RBC membranes. PPE was found to inhibit lipid peroxidation with similar effectiveness in both the systems (about 80-85% inhibition by PPE at 2.5 mg/ml). While PPE per se did not cause any morphological alteration in the erythrocytes, under the experimental conditions, PPE significantly inhibited the H(2)O(2)-induced morphological alterations in rat RBCs as revealed by scanning electron microscopy. Further, PPE was found to offer significant protection to human erythrocyte membrane proteins from oxidative damage induced by ferrous-ascorbate. In conclusion, our results indicate that PPE is capable of protecting erythrocytes against oxidative damage probably by acting as a strong antioxidant.
Coffee consumption has been linked to various beneficial and detrimental health effects, but data on its relation with mortality are sparse.
To assess the association between coffee consumption and mortality from cardiovascular disease (CVD), cancer, and all causes during 18 years of follow-up in men and 24 years of follow-up in women.
Sex-specific Cox proportional hazard models were used to investigate the association between coffee consumption and incidence of all-cause and disease-specific mortality in a prospective cohort study.
Health Professionals Follow-up Study and Nurses' Health Study.
41,736 men and 86,214 women with no history of CVD or cancer at baseline.
Coffee consumption was assessed first in 1986 for men and in 1980 for women and then every 2 to 4 years through 2004. Investigators documented 6888 deaths (2049 due to CVD and 2491 due to cancer) among men and 11,095 deaths (2368 due to CVD and 5011 due to cancer) among women.
After adjustment for age, smoking, and other CVD and cancer risk factors, the relative risks for all-cause mortality in men across categories of coffee consumption (<1 cup per month, 1 cup per month to 4 cups per week, 5 to 7 cups per week, 2 to 3 cups per day, 4 to 5 cups per day, and >or=6 cups per day) were 1.0, 1.07 (95% CI, 0.99 to 1.16), 1.02 (CI, 0.95 to 1.11), 0.97 (CI, 0.89 to 1.05), 0.93 (CI, 0.81 to 1.07), and 0.80 (CI, 0.62 to 1.04), respectively (P for trend = 0.008). For women, the relative risks were 1.0, 0.98 (CI, 0.91 to 1.05), 0.93 (CI, 0.87 to 0.98), 0.82 (CI, 0.77 to 0.87), 0.74 (CI, 0.68 to 0.81), and 0.83 (CI, 0.73 to 0.95), respectively (P for trend < 0.001). This inverse association was mainly due to a moderately reduced risk for CVD mortality and was independent of caffeine intake. By contrast, coffee consumption was not statistically significantly associated with risk for cancer death after adjustment for potential confounders. Decaffeinated coffee consumption was associated with a small reduction in all-cause and CVD mortality.
Coffee consumption was estimated from self-report; thus, some measurement error is inevitable.
Regular coffee consumption was not associated with an increased mortality rate in either men or women. The possibility of a modest benefit of coffee consumption on all-cause and CVD mortality needs to be further investigated.
Phenolic acid content of food plants and Hung CC Evaluation of caffeic acid amide analogues as anti-platelet aggregation and anti-oxidative agents
- Hm Huang
- O Gl Johanning
- Bl Dell
- Wj Tsai
- Lm Kuo
- Kuo
Huang HM, Johanning GL, O’Dell BL. 1986. Phenolic acid content of food plants and Hung CC, Tsai WJ, Kuo LM, Kuo YH. 2005. Evaluation of caffeic acid amide analogues as anti-platelet aggregation and anti-oxidative agents. Bioorg Med Chem 13: 1791–1797