The Cardioprotective Power of Leaves
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State of the art paper The cardioprotective power of leaves Dominika Dudzińska, Magdalena Boncler, Cezary Watala Department of Haemostasis and Haemostatic Disorders, Medical University of Lodz, Corresponding author: Lodz, Poland Dominika Dudzińska Department of Haemostasis Submitted: 9 May 2013 and Haemostatic Disorders Accepted: 21 August 2013 Chair of Biomedical Sciences Medical University of Lodz Arch Med Sci 2015; 11, 4: 819–839 6/8 Mazowiecka St DOI: 10.5114/aoms.2015.53303 92-215 Lodz, Poland Copyright © 2015 Termedia & Banach Phone/fax: +48 42 272 57 20/ +48 42 272 57 30 E-mail: Abstract [email protected] Lack of physical activity, smoking and/or inappropriate diet can contribute to the increase of oxidative stress, in turn affecting the pathophysiology of cardiovascular diseases. Strong anti-oxidant properties of plant polyphe- nolic compounds might underlie their cardioprotective activity. This paper reviews recent findings on the anti-oxidant activity of plant leaf extracts and emphasizes their effects on blood platelets, leukocytes and endothelial cells – the targets orchestrating the development and progression of cardiovas- cular diseases. We also review the evidence linking supplementation with plant leaf extracts and the risk factors defining the metabolic syndrome. The data point to the importance of leaves as an alternative source of poly- phenolic compounds in the human diet and their role in the prevention of cardiovascular diseases. Key words: anti-oxidants, cardiovascular diseases, leaf extracts, polyphenols. Introduction Cardiovascular disease (CVD) is one of the leading causes of mortality in developed countries. Cardiovascular disease may be a result of heart and/or blood vessels abnormalities, such as atherosclerosis, coronary heart disease, cerebrovascular disease, peripheral artery disease, con- genital heart disease, rheumatic heart disease, pulmonary embolism and deep vein thrombosis. The main cause of CVD is inappropriate lifestyle, such as unhealthy diet, smoking, and the lack of physical activity. These factors contribute to the development of oxidative stress, atherosclero- sis, chronic inflammation and metabolic syndrome (MS) [1]. Epidemiolog- ical studies indicate that a diet rich in polyphenols may reduce the risk of CVD without changes in lifestyle [2, 3]. Among patients with established CVD, polyphenols can diminish the effects of risk factors and improve parameters disturbed by the development of disease [4]. In vitro studies suggest that the mechanism of action of phenolic compounds is a re- sult of their anti-oxidative properties and their ability to interfere with blood platelets, the immune system and endothelial cell signalling [5–7]. Polyphenols are secondary metabolites distributed in edible as well as inedible parts of plants. Leaves, flowers and woody parts, such as stems or bark, are a rich source of flavonoids, phenolic acids, stilbenes, tan- nins and lignans. Fruits, especially berries, are the most popular source of polyphenols beneficial to the vascular system, including anthocyanins, Dominika Dudzińska, Magdalena Boncler, Cezary Watala proanthocyanidins, flavonols, catechins and hydro- of its conversion, such as hydroxyl radical (HO–), hy- – xylated derivates of benzoic and cinnamic acid drogen peroxide (H2O2), and peroxynitrite (ONOO ) [8]. However, there is evidence that extracts from [17, 18]. In small quantities, ROS are important for other parts of plants, e.g. leaves, are also a rich physiological processes, but they become toxic for source of phenolic compounds, which may have cells and lead to their death at higher concentra- cardioprotective potential due to their strong tions [19]. This pathogenic effect of ROS on cells free-radical scavenging, anti-oxidant and/or anti- is a result of changes in cellular compounds, i.e. peroxidative properties towards lipids. Leaves protein oxidation, lipid peroxidation and nucle- from strawberry, red and black raspberry, as well ic acid damage. Changes in amino acid residues, as thornless blackberry, appeared to have even splitting of the polypeptide chain, creation of pro- higher total polyphenol content and exhibit high- tein dimers and aggregates are some consequenc- er antioxidant capacity than their fruits [9]. Also, es of protein oxidation. These processes lead to blackcurrant and apple leaves have higher content inactivation of membrane transporters, enzymes of polyphenols than their fruits and demonstrate and regulatory proteins [20, 21]. Major damage to – elevated antioxidant activity [10, 11]. Leaves have proteins is caused by O2 , but the action of H2O2 been widely used in traditional medicine, e.g. oxidizes –SH residues and ONOO– decreases the Rubus spp. (Rosaceae) leaves have been used as activity of some enzymes [22, 23]. Hydroxyl rad- antimicrobial, anticonvulsant and muscle-relaxing ical and singlet oxygen are the main factors re- agents. Morus alba (Moraceae) leaves have been sponsible for strand breaks in DNA and RNA, as applied in Chinese medicine as a remedy for fever, they destabilize phosphodiester and hydrogen as a hepatoprotective agent and as an agent low- bonds and damage nitrogenous bases [24]. Lipid ering blood pressure [12]. These examples clearly peroxidation is initiated by anion superoxide and demonstrate that leaves can be at least equally the hydroxyl radical, resulting in disintegration of interesting as fruits or other parts of plants. Im- polyunsaturated fatty acids and inactivation of portantly, they are also a much more accessible membrane enzymes and transporting proteins source of polyphenols than fruits. [25]. Compounds with anti-oxidative activity, in- cluding natural plant extracts, have the ability to Literature search strategy eliminate free radicals, protect cells from ROS, pre- vent lipid and protein oxidation, and reduce DNA We searched for the papers cited in this review damage. in May to November 2013, using the electronic databases PubMed, Google Scholar and Research Methods for the detection of anti-oxidant Gate. The main search keyword phrases were: capacity “leaves” AND “polyphenols”, “leaves” AND “plate- let”, “leaves” AND “metabolic syndrome”, “leaves” Anti-oxidative activity of various compounds AND “inflammation”, “leaves” AND “endothelium”, in vitro can generally be measured using 2 ap- “leaves” AND “atherosclerosis”, “leaves” AND “car- proaches, as a hydrogen atom transfer (HAT) and diovascular disease”, “leaves” AND “anti-oxidant”. a single electron transfer (SET). When the essential pieces of information were Oxygen radical absorbance capacity (ORAC) is cited in the relevant papers (e.g. in the Discus- a commonly applied HAT method based on the sion) found according to the keywords mentioned monitoring of linearly decreased fluorescence above, we additionally used the particular Latin of a molecular probe (usually β-phycoerythrin or names of the eligible plants as search keywords. fluorescein), caused by free radicals, and referred to as the Trolox equivalent anti-oxidant capac- Anti-oxidative properties of leaf extracts ity (TEAC) [26]. Trolox is a synthetic, water solu- ble, vitamin E derivative with strong anti-oxidant Consequences of radical production in vivo properties, commonly applied as a standard in The imbalance between free-radical production anti-oxidant activity assays [27]. Most frequently, during metabolic reactions and their removal from the applied SET method measures the ability of cells by anti-oxidative systems causes oxidative anti-oxidant to scavenge the stable synthetic rad- stress, which underlies the pathogenesis of nu- ical 1,1-diphenyl-2-picrylhydrazyl radical (DPPH). merous chronic disease, including atherosclerosis, Upon reduction, DPPH changes colour from purple diabetes, Alzheimer disease, carcinogenesis and to yellow, which can be measured spectrophoto- inflammation [13–15]. Excessive reactive oxygen metrically. The interpretation of results is based species (ROS) are released during activation of on the calculation of EC50 (the concentration of membrane NADPH oxidase, arachidonic acid me- anti-oxidative agent that decreases the initial tabolism, cyclooxygenase and lipoxygenase path- DPPH concentration by 50%). The main disadvan- ways [16]. The most significant oxygen radical is tage is that DPPH as a hydrophobic agent cannot – the anion superoxide (O2 ) and derivative products be used to examine water soluble anti-oxidants 820 Arch Med Sci 4, August / 2015 The cardioprotective power of leaves [28]. The alternative method that allows for ex- (catechin, naringenin, kaempferol), and 2 in root amining not only hydrophobic substances, but extract (catechin, benzoic acid). Better anti-oxida- also those dissolved in water, involves the ABTS tive properties of leaf extract were explained by (2, 2’-azino-bis(3-ethylbenzothiazoline-6-sulpho- a higher content of polyphenols and stronger abil- nic acid)) radical. The ABTS assay depends on ity to inhibit the DPPH radical [33, 34]. reaction time, anti-oxidant concentration and its The leaves and seeds of Abelmoschus moscha- activity. Its reduction in a solution is observed as tus belonging to the Malvaceae family have been the fading of a blue-green colour proportionally applied in traditional medicine for the treatment to anti-oxidant concentration. Anti-oxidant con- of digestive system disorders or skin diseases. tent is often expressed as TEAC per capacity or Seeds are also used as antispasmodic and car- weight unit [29]. The FRAP (ferric reducing ability diotonic agents. Gul et