Current Pharmaceutical Design - Volume 23, Issue 7, 2017

Nonalcoholic fatty liver disease (NAFLD) is the most common type of liver disease. NAFLD is considered a multifactorial disease and a clinically relevant hepatic manifestation of metabolic syndrome. NAFLD is often accompanied by a constellation of metabolic and non-metabolic alterations, like dyslipidemia, insulin resistance in the liver and peripheral tissues, inflammation and oxidative stress; therefore, treatment of NAFLD should be directed at correcting all of these disturbances. The natural polyphenol curcumin has been the subject of increasing research for the treatment of NAFLD due to its lipid-modifying, antioxidant, anti-inflammatory, insulinsensitizing, anti-steatotic, and anti-fibrotic properties. The therapeutic efficacy of curcumin has been demonstrated in several experimental models of NAFLD, however, clinical evidence is still scarce. The present review summarizes the current knowledge on the impact of curcumin supplementation on different biochemical and histopathological features of NAFLD.

Some epidemiological studies suggest that increased consumption of anthocyanins is associated with lower risk of cardiovascular disease (CVD) and hypertension. Also, high consumption of anthocyanin-rich fruit, such as berries, is associated with a lower risk of developing type 2 diabetes (T2D). In this review, we briefly yet critically assess the available evidence in support of an anti-diabetic role of anthocyanins derived from berries, especially bilberry (Vaccinium myrtillus L., also known as European blueberry, whortleberry, huckleberry and blaeberry) and blueberry (Vaccinium corymbosum, native to the United States). Further, cellular and molecular mechanisms are discussed and the “pharma-nutrition” use of anthocyanin-based preparations for the prevention and treatment of T2D is examined. We conclude that animal and in vitro studies strongly indicate that bilberry and blueberry have the potential to ameliorate T2D and its cardio-metabolic outcomes. However, appropriate clinical trials are lacking and will eventually clarify whether these foods (either as such or formulated as nutraceuticals) might be added to the current pharma-nutritional armamentarium.

Background: Dietary factors play a key role in the development as well as prevention of certain human diseases, including cardiovascular diseases. Currently there has been an increase in global interest to identify medicinal plants that are pharmacologically effective and have low or no side effects for use in preventive medicine. Culinary herbs and spices are an important part of human nutrition in all the cultures of the world. There is a growing amount of literature concerning the potential benefits of these herbs and spices from a health perspective especially in conferring protection against cardiovascular diseases. Objective: The objective of this review is to provide information on the recent scientific findings on some common spices that have a distinct place in folk medicine in several of the Asian countries as well as on their traditional uses for the role they can play in the management of heart diseases and which may be useful in defining cost effective and inexpensive interventions for the prevention and control of CVDs. Method: Systematic literature searches were carried out and the available information on various medicinal plants traditionally used for cardiovascular disorders was collected via electronic search (using Pubmed, SciFinder, Scirus, GoogleScholar, JCCC@INSTIRC and Web of Science) and a library search for articles published in peerreviewed journals. No restrictions regarding the language of publication were imposed. Results: This article highlights the recent scientific findings on four common spices viz. Greater cardamom (Amomum subulatum Roxb.), Coriander (Coriandrum sativum L.), Turmeric (Curcuma longa L.) and Ginger (Zingiber officinale Roscoe), for the role they can play in the management of heart diseases. Although they have been used by many cultures since ancient times and have been known to exhibit several medicinal properties, current research shows that they can also be effectively used for the prevention and control of CVDs. Conclusion: Although scientific evidences supporting the benefits of spices in maintaining a healthy heart are available, more complete information is needed about the actual exposures to these dietary components that are required to bring about a response. The innumerable actions of spices that have been shown in in vitro experiments need to be demonstrated in more systematic, well-designed animal model studies. More rigorous clinical trials at the normally consumed levels are needed to determine long-term benefits as well as to assess adverse effects if any at higher concentrations, especially if consumed over longer periods. Once these extensive studies are carried out, it will be easy to define the appropriate intervention strategies utilizing these commonly used spices for achieving the maximum benefits on cardiovascular health without producing any ill-effects.

Introduction: Hyperlipidemia, obesity, hypertension, and diabetes are the most important risk factors for cardiovascular diseases. The aim of this systematic review article is to introduce the medicinal plants that exert significant clinical effects on hypertension, hyperlipidemia, obesity, and diabetes. Methods: In this review article, the international research databases including MEDLINE, Google scholar, EBSCO, Academic Search, Web of Science, SciVerse, Scopus (SCOPUS), EBSCO, Academic Search, Cochrane, Central Register of Controlled Trials (CENTRAL) and a Chinese database (China Network Knowledge Infrastructure [CNKI]) were searched using the key words hyperlipidemia, hypertension, diabetes, herbal, obesity, and phytomedicine, matched by MESH, from their respective inceptions up to March, 2016. The plants that were effective on one, two, three, or all of four diseases were determined. The doses, side effects, the most important pharmaceutically effective compounds, the used organs, and important points regarding usage were separately recorded. Also known clinically significant interactions were presented. Results: 1023 articles were found to be about medicinal plants and hypertension, 1912 articles about medicinal plants and hyperlipidemia, 810 articles about medicinal plants and obesity, 1174 articles about medicinal plants and diabetes. Of 144 plants included in the analysis, 83 were found to be effective on hyperlipidemia, 100 on hypertension, 66 on obesity, and 72 on diabetes. 43 plants were found to be effective on two diseases, 14 on three diseases, and 34 on all four diseases. Three plants (Tomato, Cranberry and Pomegranate), in food and therapeutic doses, were found to be used to treat cardiovascular diseases especially in pre-eclampsia and hyperlipidemia in pregnancy. Conclusion: Regarding the findings of this study, we can argue that the medicinal plants, other than monotherapy, can be used as poly-therapy, to treat cardiovascular diseases.

Background: Nuts have been an indispensable component of the human diet for hundreds because of their unique nutrient composition and are thought to play a beneficial part in the prevention of cardiovascular diseases. Objective: To evaluate the extent, validity and presence of evidence for studies investigating the impact of nuts intake on biomarkers of cardiovascular disease and cardiovascular events, we performed an umbrella review of all published meta-analyses synthesizing data from both observational studies and randomized controlled trials. Method: PubMed (between 1966 and April 2016) was searched for systematic reviews and meta-analyses. Methodological quality was assessed by applying the AMSTAR score (0-11 points), and the meta-evidence by applying NutriGrade, our recently developed scoring system (0-10 points). Results: In total, 14 meta-analyses were included in the umbrella review. Only 4 out of 14 reported an AMSTAR score ≥8 (high methodological quality), whereas NutriGrade meta-evidence score varied between 2 (very low meta-evidence) and 7.9 (moderate meta-evidence). There is consistent evidence from intervention trials, reporting significant reductions for total cholesterol, and from observational studies that higher intakes of nuts were associated with reduced risk of cardiovascular disease and hypertension. On the other side no effect could be observed for stroke, HDL-cholesterol, and blood pressure in the normal range. Conclusion: In summary, the present umbrella review showed that nuts intake was associated with reduced risk of cardiovascular disease and hypertension, and lower levels of total cholesterol. The observed evidence is limited by the moderate methodological quality and very low to moderate quality of evidence.

Cardiovascular disease (CVD) is the leading cause of global mortality with a substantial economic impact. The annual deaths are expected to increase in the next decade. An array of dietary supplements is being used by people worldwide to ameliorate cardiovascular risk factors. Garlic (Allium sativum L.), a top-selling herbal dietary supplement, is renowned for its wide range beneficial effects, particularly in the treatment and prevention of CVD. This review aims to present a thorough discussion of the available evidence-based data which support the use of garlic in the treatment or prevention of cardiovascular diseases, including atherosclerosis, hypertension, and hyperlipidemia. The molecular mechanisms underlying these effects are dissected as well. This review supports the notion that garlic has the potential to treat mild hypertension, to decrease hypercholesterolemia, and to prevent atherosclerosis. More clinical studies are essential to unequivocally understand the mechanisms underlying treatment or prevention of these cardiovascular conditions.

Background: Pomegranate (Punica granatum L.) is a polyphenol-rich fruit with diverse medicinal properties. Several lines of experimental and clinical evidence have shown that pomegranate intake helps lowering blood pressure (BP) through different mechanisms. Aims: This study aimed to present a narrative review on the anti-hypertensive properties of different parts of pomegranate such as pomegranate juice (PJ), pomegranate peels (PP), pomegranate seed oil (PSO), pomegranate fruit extract (PFE) and the mechanisms and phytochemicals responsible for these effects. Methods: A review on the efficacy of consuming different parts of pomegranate (juice, peels, fruit extract and seed oil) in lowering BP has been performed. To find relevant studies, a search in PubMed, Science Direct and Scopus up from inception to May 4, 2015 was performed. Human, animals and in vitro studies investigating the anti-hypertensive effects of pomegranate were included in the search. Results: Findings arising from animal and clinical studies have shown pomegranate juice can reduce BP in both short-term and long-term course. These effects are accompanied by antioxidant and anti-atherosclerotic actions that collectively improve cardiovascular health. The anti-hypertensive effects have been reported for both pomegranate juice and seed oil. Both systolic and diastolic pressures are affected. Conclusion: Pomegranate juice possesses antioxidant, anti-hypertensive and anti-atherosclerotic properties.

Plants have been always a fruitful source of active metabolites against many human disorders, where cardiovascular (CV) diseases have been one of the major health problems all over the world. There are some clinically proved medicinal plants with cardioprotective effects such as Crataegus monogyna and C. oxyacantha (hawthorn) from Rosaceae. On the other hand, cardiac glycosides, present in a number of plant species, are wellknown for their cardiotonic activity. However, we encountered such a fact that very less number of studies are available on the source plants; e.g. Adonis vernalis, Convallaria majalis, Strophanthus kombe, Thevetia peruviana, Leonurus cardiaca, etc. Consequently, we herein aimed to cover all available data consisting of in vitro, in vivo, and human studies (if any) on cardiotonic effects of the aforementioned species through a wide literature search using Scopus, Web of Science as well as Pubmed.

Autophagy, a highly conserved starvation response mechanism with both defensive and protective effects in eukaryotic cells, is a lysosome-mediated degradation process for non-essential or damaged cellular constituents. It plays an important role in the cell survival, differentiation and development to maintain homeostasis. Autophagy is involved in cardiovascular diseases, cerebrovascular diseases, and neurodegenerative diseases, as well as tumours. Thus, modulating autophagy may provide potential therapeutic strategies. Recently, many active components of Chinese herbal medicines (CHM) have been found to modulate autophagy in myocardial cells, cerebral vascular cells, endothelial cells and tumour cells. This paper reviews the advances in studies on the active components of CHM that modulating autophagy in treating cardiovascular diseases and other chronic diseases over the past five years.

Cardiovascular disorders are the most common diseases all over the world, which have limitations in the current treatment stratergies. As two subtypes of potassium channel, KCa and KATP ion channels are playing important roles in the occurrence and development of cardiovascular diseases. KCa by activating the signal pathway of c-Src/PI3-kinase/Akt-dependent or eNOS-NO-cGMP effects the function of vascular endothelial cell, while KATP acting as a medium combines the cell electrical activity and energy metabolism. Thus, through acting on KCa or/and KATP, some drugs can play roles in these cardiovascular diseases. Nevertheless, specific and effective western medicines selectively working on these two channels are not identified at present. Some Chinese herbal medicines or bioactive ingredients in contrast have been discovered to be safe and effective in the regulation of the two recently. Therefore, this review article summarized some single herbs and bioactive ingredients targeting KCa or/and KATP ion channels in the management of cardiovascular diseases, with the purpose of demonstrating the alternative treatment of these diseases in perspective of Traditional Chinese medicine.

Salvia miltiorrhiza Bunge, also known as Danshen in Chinese, has been widely used to treat cardiovascular diseases (CVD) in China and other Asia countries. Here, we summarize literatures of the historical traditional Chinese medicine (TCM) interpretation of the action of Salvia miltiorrhiza, its use in current clinical trials, its main phytochemical constituents and its pharmacological findings by consulting Pubmed, China Knowledge Resource Integrated, China Science and Technology Journal, and the Web of Science Databases. Since 2000, 39 clinical trials have been identified that used S. miltiorrhiza in TCM prescriptions alone or with other herbs for the treatment of patients with CVD. More than 200 individual compounds have been isolated and characterized from S. miltiorrhiza, which exhibited various pharmacological activities targeting different pathways for the treatment of CVD in various animal and cell models. The isolated compounds may provide new perspectives in alternative treatment regimes and reveal novel chemical scaffolds for the development of anti-CVD drugs. Meanwhile, there are also some rising concerns of the potential side effects and drug-drug interactions of this plant. The insights gained from this study will help us to better understanding of the actions of this herb for management of cardiovascular disorders. As an herb of red root, S. miltiorrhiza will act as a potential red light to prevent the development of CVD.

Refractory angina (RFA) is an unfavourable condition that is characterized with persistent angina due to reversible myocardial ischemia in patients with coronary artery disease that remains uncontrollable despite an optimal combination of pharmacological agents and revascularization. Despite significant advances in revascularization techniques and agents used in pharmacological therapy, there is still a significant population suffering from RFA and the global prevalence is even increasing. Anti- anginal treatment and secondary risk-factor modification are the traditional approaches for this group of patients. Furthermore, now there is still a large number of alternative treatment options. In order to review traditional and alternative treatment strategies in patients with RFA, we searched Pubmed for articles in English using the search terms “pharmacological therapy, refractory angina”, “alternative therapy, refractory angina” between inception to June 2016. We also went through separately for each alternative treatment modality on Pubmed. To identify further articles, we handsearched related citations in review articles and commentaries. We also included data from the European Society of Cardiology (2013), and the Canadian Society of Cardiology/ Canadian Pain Society (2012) guidelines. Data show that besides traditional pharmacological agents, such as nitrates, beta- blockers or calcium channel blockers, novel antiischemic drugs and if symptoms persist, several non- invasive and/ or invasive alternative strategies may be considered. Impact of some pharmacological agents, such as rho- kinase inhibitors, and novel alternative treatment modalities, such as coronary sinus reducers, stem cell therapy, gene and protein therapy, on outcomes are still under investigation.

Cardiovascular diseases (CVD) are of major causes of death worldwide. Complementary and alternative medicines (CAM) are considered as new sources to find preventive and treatment approaches with mostly a historical perspective. Chinese medicine (CM), Persian medicine (PM), Ayurveda and homeopathy are as most popular traditional systems of medicine among various CAM methods. In this survey, we aimed to review most relevant and approved treatment by current investigations on these CAM systems in the field of CVD to present best traditional remedies and treatment approaches. To this, a search within databases including PubMed, Scopus and Google scholar was performed to find and select traditional approaches for CVD with the help of four CAM systems: CM, PM, Ayurveda and homeopathy. There are numerous cardiovascular and allied complications. Based on the type and group of disorder, the aforementioned complementary and alternative systems of medicine offer convenient and practical treatment approaches which can be considered along with the conventional interventions. Many mono and multi-ingredient preparations have been introduced by those popular systems of medicine. In addition, non-pharmacological treatments such as acupuncture and cupping are reported in some circumstances. Apart from various compound formulations, most of the human studies are limited to the single medicinal plants from modern phytotherapy. Accordingly, more comprehensive assessments are to be performed to distinguish those traditional remedies from popular holistic medical systems.

Peroxisome proliferation-activated receptors (PPARs) are ligand-activated transcription factors that mainly regulate genes responsible for fatty acid (FA) and energy metabolism. There are three members of the PPAR family, PPAR-α, PPAR- β/δ and PPAR-γ. All three isoforms have therapeutic potential for treatment of cardiovascular disorders, and PPAR agonists are currently being actively studied in pre-clinical and clinical trials. PPAR γ agonists, main tissue expressing isoform, have potential to influence on inflammation processes, reduce oxidative stress, improve endothelial function and plays an important role in lipid metabolism. PPAR-γ agonists are used as insulin sensitizers for treatment of diabetes; however, there is accumulating evidence that their clinical application can be broadened. The wide spectrum of PPAR-γ activation effects may be beneficial for treatment of various cardiovascular conditions as atherosclerosis, hypertension and aortic aneurysm, including surgical interventions. In this Review we will discuss the implication of PPAR-γ in the cardiovascular system and potential role of PPAR-γ agonists in treatment of conditions associated with high cardiovascular risks.

In the absence of definite guidelines in the area, we have carried a systemic review to provide a thorough overview concerning the efficacy and safety of recombinant activated factor VII (rFVIIa, NovoSeven®, Novo Nordisk A/S, Bagsværd, Denmark) in patients with Glanzmann’s thrombasthenia (GT) and FVII deficiency, undergoing surgical procedures. PubMed, Web of Science, Scopus and EMBASE databases was employed for the search. Three multicenter registries were identified: the Glanzmann’s Thrombasthenia Registry (GTR), the Seven Treatment Evaluation Registry (STER), and a German post-marketing surveillance registry (the WIRK study). In addition, data from 10 case-series and/or single-center experiences have been summarized. We have found that the following; perioperatively, the hemostatic effectiveness of rFVIIa was high in GT patients and in those with FVII deficiency undergoing both minor and major surgical procedures. Moreover, in all studies, rFVIIa was well tolerated. Thus, the current evidence shows an optimal perioperative safety/efficacy profile of rFVIIa in the setting of these rare bleeding disorders, and provides the rationale for further studies aimed at evaluating the optimal perioperative anti-hemorrhagic prophylaxis with rFVIIa in GT and in FVII deficient patients.