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Natural Products as the Integral Part of the Therapy?
Current Pharmaceutical Design, 2017, Vol. 23, No. 17
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Editorial Natural Products as the Integral Part of the Therapy? Maciej Banach1,2, Dimitri P. Mikhailidis3, Maria-Corina Serban4 and Amirhossein Sahebkar5,6 1 Department of Hypertension, Chair of Nephrology and Hypertension, Medical University of Lodz, Lodz, Poland; 2Polish Mother’s Memorial Hospital Research Institute (PMMHRI), Lodz, Poland; 3Department of Clinical Biochemistry, Royal Free Campus, University College London Medical School, University College London (UCL), London, UK; 4Department of Functional Sciences, Discipline of Pathophysiology, “Victor Babes” University of Medicine and Pharmacy, Timisoara, Romania; 5Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; 6Metabolic Research Centre, Royal Perth Hospital, School of Medicine and Pharmacology, University of Western Australia, Perth, Australia.
In spite of significant advances in the fields of prevention, diagnosis and treatment, cardiovascular disease (CVD) remains the number one cause of morbidity and mortality worldwide [1]. In the past decade, the interest towards the use of natural products for the treatment of human diseases has boomed due to evidence from studies reporting robust associations between consumption of fruits, vegetables, and certain phytochemicals, as well as nutraceuticals and functional food and CVD [2-4]. In parallel, there has been a surge of interest for drug discovery and high-throughput screening approaches to isolate, purify and pharmacologically evaluate small molecules with potential antiatherosclerotic activities derived from dietary natural products [5-7]. Natural products have several advantages over synthetic and biological agents – they are safe (particularly those isolated from dietary sources), and possess a multi-mechanistic mode of action owing to their capacity to interact with several key molecular regulators of cellular function [2,8]. Moreover, compound herbal products are generally known to exert potent effects because of synergistic actions that exist among phytochemicals [8,9]. With respect to the underlying mechanisms, natural products can counterbalance many culprit processes involved in atherogenesis including dyslipidaemia, oxidative stress, inflammation, endothelial dysfunction, vasoconstriction, immune dysregulation and vascular calcification [8,9]. Many of these beneficial effects have been confirmed by different levels of evidence, and proof-ofconcept in vitro, in vivo and clinical studies [8-10]. Their effectiveness has been confirmed as a part of lipid-lowering or hypoglycaemic and antihypertensive combination therapy (both in primary and secondary prevention) and in improving adherence to treatment [1,10]. Moreover, the cardioprotective action of selected medicinal plants is supported by the findings of traditional medicine, which shows the antiquity of herbal medicine and its safety owing to repeated use over centuries [9]. Taking all the above evidence into account we prepared this special issue of Current Pharmaceutical Design in order to present the current state of knowledge on the usefulness and application of natural products in health and disease (mainly CVD). The 10 reviews included in this issue present the most recent knowledge in this field. Antal et al. review nanoscale delivery systems and their role in the natural products industry [11]. Nanomedicine facilitates the efficient delivery of natural products, in terms of increased bioavailability, targeting, and controlled release while protecting active constituents against physico-chemical alterations. Most of the plants with well documented therapeutic properties and registered in pharmacopoeias are waiting to benefit from advances in nanotechnology. As the authors emphasize, for some of them, adequate nanoformulation will contribute to their removal from the group of dietary supplements and pharmaceutical preparations with suboptimal bioavailability and efficacy [11]. Cicero and colleagues, focus on the effect of carotenoids on health [12]. Carotenoids have antioxidant properties, due to their ability to quench singlet oxygen and to scavenge free radicals that may prevent and treat a wide range of chronic diseases [12]. The authors described the beneficial effects of carotenoids on human health, in particular skin, eye, hepatic diseases as well as CVD and some types of cancer. However, they also emphasize that some studies did not evaluate the intake of carotenoids alone and sometimes the results are discordant. Therefore, they conclude, that it is necessary to test carotenoids alone and to evaluate their safety in long-term clinical trials in large and heterogeneous populations [12]. This issue also includes a review by Sobhani et al. [13], where the authors discuss the cardioprotective properties of medicinal plants in relation to the work of Avicenna, a famous Persian physician who lived in the 11th century and who mentioned 50 active plants and described their effects in the treatment of CVD [13]. The polyphenolic compounds found in berries, grapes, coffee, dark chocolate, and tea have generated a considerable level of interest based on their cardioprotective effects against inflammation, endothelial function, oxidative stress and the activity of enzymes involved in the renin-angiotensin-aldosterone system, resulting in improved blood pressure (BP) [2,14-16]. In the review by Murillo & Fernandez, the authors presented some of the evidence derived from epidemiological studies, clinical interventions as well as animal and cell studies supporting the cardioprotective effects of dietary polyphenols [16]. Besides polyphenol supplementation, current strategies to lower BP involve caffeine, alcohol and stress reduction, smoking cessation, balanced diet enriched with herbs, decreased sodium intake, potassium supplementation and regular physical activity [17-19]. These natural products and non-pharmacological management might be an important part of antihypertensive and hypoglycaemic treatment, as Rysz et al. [19] and Schultz et al. [20], present in detail in their reviews [21]. The role of curcumin in the protection of the endothelium is discussed in the review by Karimian and colleagues [22]. More and more studies are describing the important role of this nutraceutical in different conditions [23,24]. Curcumin, a yellow pigment of the spice turmeric obtained from the Curcuma longa Linn plant exerts beneficial anti-inflammatory, anti-hypertensive, antioxidant, antiviral, antiinfective, anticancer and wound-healing properties. Curcumin supplementation might also reverse oxidative stress and inflammation, which can adversely affect endothelial function [22].
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2412 Current Pharmaceutical Design, 2017, Vol. 23, No. 17
Natural Products as the Integral Part of the Therapy?
Tea and coffee consumption, the most intensively studied beverages after water, has been shown to be potentially beneficial against CVD in various clinical trials [4,7,8]. Di Lorenzo et al. [25] update the scientific data obtained from clinical trials published in the last 5 years on the role of tea and coffee consumption against CVDs and risk factors such as hypertension, hyperglycaemia and hyperlipidaemia. The literature supports that tea consumption might reduce CV risk factors in healthy, overweight and obese subjects. Regarding coffee, the available data is not clear [25]. Nevertheless, some recent investigations reported that moderate coffee consumption has no effect or even protective effects against CVD risk factors. However, further research is needed before definitive recommendations for tea and coffee consumption against CVD development can be made. Combination therapy for dyslipidaemia is discussed in this issue. While waiting for new drugs, there is almost no effective lipid lowering combination therapy, which would reduce residual CV risk effectively [26-28]. Therefore, the combination of statins with effective natural products might be an important option [29]. Some studies showed that sterols and stanols might be effective in decreasing low-density lipoprotein cholesterol (LDL-C) levels and CV risk [30]. Patti et al. [31] emphasize that nutraceutical supplements were tested in a large number of hyperlipidaemic patients, allowing the determination of their effectiveness and safety. However, most of the cholesterol-lowering effects with nutraceutical preparations available on the market had not been tested in the long-term or in large numbers of subjects. Therefore, further clinical trials are necessary to identify the best combination of nutraceuticals for each patient in terms of cost/benefit and risk/benefit and to demonstrate long-term safety and tolerability before extensive clinical use [31]. There have been significant advances in the identification of natural products that could effectively improve CVD. While the current volume of findings is impressive, several issues still remain to be addressed in order for the natural products to become part of lipid, hypertension, diabetes treatment or preventive guidelines. First, most of the clinical evidence comes from observational studies and randomized controlled trials assessing the long-term effects of natural products on CV events and outcomes are lacking. Second, some of the encouraging experimental findings regarding natural products might be difficult to replicate in human studies. Whether the application of pharmaceutical methods to enhance the systemic bioavailability of phytochemicals and nutraceuticals can improve the pharmacological effects of these agents is another controversial issue that is yet to be clarified. Finally, potential pharmacokinetic interactions between phytochemicals and drugs used in CV patients need to be further assessed. Despite these limitations, natural products, nutraceuticals, functional food, lifestyle changes should be considered as a part of therapy, especially for high and very high risk patients, because it might help to reduce residual risk, achieve treatment goals, improve adherence (especially in case of polypills), and might be important in cases of drug-related side effects or drug intolerance [32-35]. We hope that these 10 comprehensive reviews covering different aspects of the use of natural products for the prevention and treatment of CVD are a valuable source of recent knowledge. We would like to thank all the authors for their valuable contributions, as well as the journal’s Editor-in-Chief, Editorial Board and production team for their kind assistance in preparing this issue. DECLARATION OF INTEREST MB - speakers bureau: Abbott/Mylan, Abbott Vascular, Actavis, Akcea, Amgen, KRKA, MSD, Sanofi-Aventis; consultant to Abbott Vascular, Amgen, Daichii Sankyo, Esperion, Lilly, MSD, Resverlogix, Sanofi-Aventis; DPM has given talks and attended conferences sponsored by MSD, AstraZeneca and Libytec. MCS and AS have noting to declare. REFERENCES [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20]
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Maciej Banach Department of Hypertension WAM University Hospital in Lodz Medical University of Lodz Zeromskiego 113; 90-549 Lodz Poland
