Cardioprotective Natural Products

Promises and Hopes

Goutam Brahmachari

• Publisher: WSPC
• Year: 2017
• ISBN:
  9789813231177
• Topic: Medicine
• Subtopic: Cardiology

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Cardioprotective Natural Products: Promises and Hopes focuses on the recent advances in the research of bioactive natural products with cardioprotective potential against various cardiovascular diseases/disorders. The aim of this book is to underline the promise and future hope in bioactive natural molecules, herbal formulations, natural dietary supplements and related materials in the prevention and cure of cardiovascular diseases in a scientific way.

This book, which comprises a variety of about 9 chapters written by active researchers and leading experts, brings together an overview of current discoveries and trends in this field. This volume is also an outstanding source of information with regard to the industrial application of natural products for medicinal purposes. The broad interdisciplinary approach adopted in this book ensures that it is much more interesting to scientists deeply engaged in the research and/or use of bioactive natural products. It will serve not only as a valuable resource for researchers in their own fields to predict promising leads for developing pharmaceuticals to prevent and treat disease manifestations, but will hopefully also motivate young scientists to engage in the dynamic field of natural products research.

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--> Contents:

• Cardioprotective Natural Products: Promises and Hopes — An Overview (Goutam Brahmachari)
• Naturally Occurring Matrix Metalloproteinase Inhibitors: A Group of Promising Cardioprotective Agents (Tayebeh Anajafi, Abbas Sedigh and Sanku Mallik )
• Promising Natural Cardioprotective Agents in Drug- and Toxin-Induced Pathophysiology (Semantee Bhattacharya and Parames C Sil)
• Natural Products Against Drug-Induced Cardiotoxicity (Meghana Koneru, Nasiruddin Nalban, Bidya Dhar Sahu and Ramakrishna Sistla )
• Cardioprotective Potential of Medicinal Plants in Attenuating Doxorubicin-Induced Cardiotoxicity (Sameer N Goyal, C R Patil, Nimisha Mishra, Rajesh Mohanraj and Shreesh Ojha)
• The Role of Dietary Supplements in Cardiovascular Diseases (Essam Abdel-Sattar, Soheir M El Zalabani and Manal M Sabry)
• Beneficial Role of Antioxidant Molecules with Therapeutic Potential in Cardiac Disease (Jyotirmoy Ghosh, Krishnendu Sinha and Parames C Sil)
• Small Molecule Phytocompounds as Promoters of LDL-Receptor and PCSK9 Inhibition: Potential Role as Non-Statin Based Cardio-Protective Agents (Ajoy Basak, Paul O'Reilly, Bethel Ozed Williams and Sarmistha Basak)
• 7,8-Dihydroxy-3-methylisochroman-4-one: A Promising Anti-Hypertensive Lead-Molecule from Banana ( Musa sapientun L) Peel (Goutam Brahmachari)

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--> Readership: Phytochemists; combinatorial chemists; pharmacologists; institutes for drug research (drug discovery and development); industrial research groups developing drugs from medicinal plants; pharmaceutical companies; manufacturers of herbal and ayurvedic medicines and cosmetic products; manufacturers of natural products; advanced and research students. -->
Keywords:Cardioprotective Natural Products;Cardiovascular Diseases and Related Symphtoms;Protection and Therapies;Ayurvedic/Herbal Formulations;Medicinal Compounds of Natural Origins;Therapeutic Targets;Mode of Actions;Pharmacokinetics;Drug Discovery and DevelopmentsReview: Key Features:

• Contains a variety of 10-12 chapters with written by active researchers and leading experts deeply engaged in the research field with medicinal natural products and herbal formulations
• Recent cutting-edge advances on medicinal natural products as the preventives and therapies against deadly cardiovascular diseases in a single volume
• Exhaustive and authoritative presentations of research outcomes on medicinal natural products, their mode of action, chemistries, pharmacokinetics, etc. in the treatment of cardiovascular diseases and related symptoms in a single volume
• An outstanding source of information with regard to the industrial application of natural products for medicinal purposes
• This Volume is of first-time appearance in the market

1

Cardioprotective Natural Products: Promises and Hopes — An Overview

Goutam Brahmachari^∗,†

Abstract

This chapter is aimed to offer an overview of the present book, and summarizes the contents and subject matter of each chapter with an intention to highlight on certain glimpses of the coverage to the readers before they go in-depth.

1.Introduction

This book titled Cardioprotective Natural Products: Promises and Hopes is an endeavor to access the on-going developments and recent cutting-edge research advances in the field of cardioprotective natural products having regard to their identification, isolation, clinical aspects and underlying mechanisms of actions, as well as to underline how natural product research continues to make significant contributions in the domain of discovery and development of new medicinal entities. The reference is meant for phytochemists, synthetic chemists, combinatorial chemists, biologists, pharmacologists, clinicians as well as other practitioners and advanced students in related fields. This book comprising eight technical chapters, offers recent update on these areas of natural product research with an intention to unravel their pharmaceutical applicability in modern drug discovery processes in the field of cardiovascular diseases.

Cardiovascular diseases (CVDs) are today the leading cause of death around the globe. According to the American Heart Association, cardio-vascular diseases are responsible for nearly 17.5 million deaths per year worldwide or 31% in 2012. This figure is expected to grow to 23.5 million by 2030. CVDs mainly include those that compromise the pumping ability of the heart, cause failure of the valves, or result in narrowing or hardening of the arteries. In modern times, the ischemic heart diseases including acute myocardial infarction, caused due to lack of blood flow to the heart, are the most alarming. The contributing factors for the growing burden of CVDs involve increase in the prevalence of cardiovascular risk factors, especially hypertension, dyslipidemia, diabetes, obesity, physical inactivity and use of tobacco. In addition, many toxins, infectious agents as well as some drugs, especially anthracyclines may damage the heart and blood vessels.

One obvious treatment of CVDs involves the administration of LDL-cholesterol reducing drugs. Among these, the most commons are the “statins” which inhibit Hydroxy-Methyl Glutaryl Coenzyme A (HMG-CoA) reductase — an enzyme associated with cholesterol synthesis in the liver and these drugs have been shown to effectively lower LDL-C. Though well tolerated, they are limited in their ability for lowering LDL-C. In recent years, various side effects of statin drugs have also been reported. As the currently used ‘statin’ drugs are facing new challenges and can have adverse effects, the search for small molecule, non-statin drugs for reducing cholesterol is warranted. Thus, researchers have been motivated in identifying new targets for the development of novel cholesterol-lowering drugs as alternatives to statins. It has been evidenced that natural products play a vital role in the cardio-protection and improving related health problems in the recent past. Cardio-protection usually refers to the prevention of coronary heart disease and the clinical improvement in patients suffering from cardiovascular problems. Cardio-protection includes “all mechanisms and means that contribute to the preservation of the heart by reducing or even preventing myocardial damage”. There is now a considerable interest in bioactive compounds present in edible plants and thus in “letting your food be your medicine”, as recommended by Hippocrates. Beyond individual natural molecules, the recent expansion and the growing popularity of functional foods and nutraceuticals aimed to promote cardiac health are of promise.

Chapter-1 presents an overview of the book, and summarizes the contents and subject matter of each chapter to offer certain glimpses of the coverage of discussion to the readers before they go for detailed study.

2.An Overview of the Book

The present book contains a total of eight technical chapters — Chapter-2 to 9; this section summarizes the contents and subject matter of each of these chapters.

2.1.Chapter 2

In Chapter 2, Mallik and his group have offered a comprehensive overview on naturally occurring matrix metalloproteinase (MMPs) inhibitors with potent cardioprotective promise. MMPs are a large group of enzymes extensively investigated for their physiological and pathological functions, and their overexpression is demonstrated in many inflammatory conditions, including heart diseases, Alzheimer’s, cancers, and arthritis. Endogenous, exogenous, and synthetic MMP inhibitors are suggested as one of the treatment options for these diseases. The authors have, herein, summarized the recent research outcomes suggesting that the consumption of natural exogenous MMP inhibitors (especially ω-3 fatty acids and flavonoids) leads to cardio-protection. This illuminating review on the benefits of natural product MMP inhibitors would obviously enrich the researchers with a motivation in undertaking in-depth further research.

2.2.Chapter 3

Bhattacharya and Sil have furnished a thorough discussion on promising natural cardio-protective agents in drug- and toxin-induced pathophysiology in Chapter 3. Natural products have been found wide applications as medical treatments for cardiovascular diseases since ancient times. Extracts of several medicinal plants have been evaluated to ameliorate cardiotoxicity induced by a variety of agents like arsenic, cadmium, aflatoxin, and so on. Extracts of Urtica parviflora, Curcumis trigonus, Premna serratifolia, Mangifera indica, Olea europaea and so forth are found to have cardioprotective effect against isoproterenol-induced myocardial infarction. Extracts of plants like Terminalia arjuna, Stachys schimperi Vatke and so forth can effectively suppress doxorubicin- and cyclophosphamide-induced oxidative stress and cardiotoxicity. Many phytochemicals with cardioprotective activity have also been isolated from different parts of various plants. In their presentation, the authors have screened some of the well-known natural compounds with cardioprotective potential isolated from various plants or algae explicating their prophylactic role in drug- and toxin-induced pathophysiological conditions. The role of these molecules in drugs- and toxins-induced pathophysiology, their extraction processes from natural sources, therapeutic application and mode of action by regulating different signaling pathways have been discussed in detail. This illustrative review, thus, unravels the potential use of some naturally occurring compounds as novel promising therapeutic strategies for cardiovascular diseases.

2.3.Chapter 4

Chapter 4 by Sistla and his group is dedicated to natural products against drug-induced cardiotoxicity. Certain drug candidates, especially anthracyclines are involved in the incidence of cardiotoxicity. Although anthracyclines find useful applications in the treatment of cancer, the complications associated with these drugs such as cardiomyopathy, congestive heart failure and alterations in the electrocardiogram limit their use as effective chemotherapeutic agents. Cardiac tissues are usually highly prone to oxidative damage, and anthracyclines were known to cause cardiac damage by increasing the production of reactive oxygen species (ROS). These drug candidates are also known to cause mitochondrial and inflammatory damages. It has been documented that phytochemical constituents belonging to various classes such as polyphenols, alkaloids, terpenoids, carotenoids, essential oils and so forth exhibit their beneficial effects against various cardiac disorders. In the present chapter, the authors offer an account of some promising phytochemicals found effective against cardiotoxicity along with elucidating their underlying mechanisms of action. This informative review would act as a stimulus in this direction.

2.4.Chapter 5

In Chapter 5, Ojha and co-authors describes cardioprotective potential of medicinal plants in attenuating doxorubicin (DOX)-induced cardiotoxicity. Doxorubicin is a potent and widely used anthracycline anti-biotic as anti-cancer drug; however, it also causes dose-dependent organ toxicity, mainly cardiotoxicity. The occurrence of fatal cardiotoxicity characterized by an irreversible cardiomyopathy often compromised the clinical usage of DOX. The appearance of association between significant burden of cancer and chemotherapy-induced cardiotoxicity brings enthusiasm among researchers for search of targeted strategies that can simultaneously provide long-term cardio-protection from DOX-associated cardiotoxicity without compromising the efficacy of DOX. Numerous preclinical and human studies reveal that oxidative stress, inflammation and subsequent cardiomyocytes apoptosis are the primary pathogenic mechanisms leading to cardiomyopathy. The authors of this chapter have presented an exhaustive overview on the cardioprotective efficacy of various naturally occurring plants belonging to different families and genera reported to exhibit cardioprotective properties against DOX-induced cardiotoxicity in different types of in vitro and in vivo animal models employing the biochemical, morphological, hemodynamic, histopathological, ultrastructural and molecular biology approaches. This illuminating review would surely offer huge relevant information to both the natural and medicinal chemists at large.

2.5.Chapter 6

Abdel-Sattar and co-authors have offered a good deal of thorough discussion on the role of dietary supplements in cardiovascular diseases (CVDs) in Chapter 6. Certain functional foods and dietary supplements are reported to contain diverse physiologically active components with established potential in management and/or prevention of CVDs, especially those acquired. The authors have surveyed the beneficial role of these products and their individual ingredients with special emphasis on their chemical composition and mode/mechanism of action. The role of dietary plant metabolites, viz. polyphenols, phytosterols and phytostanols, terpenoids and saponins as cardio-protective, are separately overviewed in this chapter. In addition, examples of commonly used herbs and herbal products, claimed to reduce CVD-risk incidence and suggested for incorporation in daily diets, are also mentioned. This illustrative review on the role of dietary supplements in cardiovascular diseases should truly create an enthusiasm among the readers.

2.6.Chapter 7

Cardiovascular diseases are the major cause of morbidity and mortality worldwide due to their complex pathogenesis. Cardiovascular diseases include hypertension, coronary heart disease (heart attack), cerebrovascular disease (stroke), heart failure and peripheral vascular disease. Recent years have witnessed a steady increase in the incidence of cardiovascular disorders throughout the world. Oxidative stress plays an important role in various types of cardiac pathophysiology. In Chapter 7, Sil and his group have reviewed on the beneficial role of some natural antioxidant molecules as promising therapeutics against cardiac diseases along with their detailed molecular mechanism of cardiac protection. This illuminating review would provide detailed information on the subject to the readers with a motivation to take up further research to bring natural product-based drug discovery programs back to the forefront of drug discovery in the relevant field.

2.7.Chapter 8

Chapter 8 by Basak and his group deals with small molecule phytochemicals as promoters of Low Density Lipoprotein (LDL)-receptor and Proprotein Convertase Subtilisin Kexin9 (PCSK9) inhibition with a focus on non-statin based cardio-protective agents. Cardiovascular Disease (CVD) or Coronary Artery Disease (CAD) which involves disorder of the heart and blood vessels continues to be the leading cause of death among the global population. Currently, “statins” are administered as LDL-cholesterol reducing drugs; however, these drugs are associated with various side effects. Hence, the search for small molecule, non-statin drugs for reducing cholesterol becomes more urgent, practical and relevant. Under this purview, PCSK9 has at present become the most widely studied PCSK because of its crucial role in cholesterol metabolism. This soluble protein is expressed predominantly in the liver and can also be produced in the cerebellum, small intestine, and kidney. Extensive research during the past decade confirms that PCSK9 plays a key role in maintaining a correct balance of Low Density Lipoprotein (LDL)-cholesterol via its action in degrading the LDL-Receptor (LDL-R). Thus, higher level of circulating PCSK9 coincides with lower levels of the LDL-R leading to reduced clearance of LDL-cholesterol from the blood — a condition known as “Hypercholesterolemia” considered as a risk factor for cardiovascular diseases. Thus, functional PCSK9 inhibitors would exhibit cholesterol-reducing effects by blocking LDL-R degrading activity of PCSK9, which thus became a high target for the development of new non-statin cholesterol lowering drugs. In recent years, attention has been devoted to medicinal plant kingdom as a new source for the discovery of small molecule PCSK9 inhibiting compounds. In their chapter, the authors have presented their recent findings with some promising naturally occurring small molecules in this direction. The promising outcome of their research findings should boost the on-going endeavor in the cardiovascular drug discovery program.

2.8.Chapter 9

Chapter 9 by Brahmachari offers a recent update on the anti-hypertensive small molecule, 7,8-dihydroxy-3-methylisochroman-4-one, an iso-chromanone derivative isolated from water soluble fraction of banana (Musa sapientum L.) peels. Banana and other parts of the plant are traditionally used to treat hypertension, depression, anemia, heartburn and ulcers, bacterial infections, and gastrointestinal tract disorders including other vascular diseases; banana peel also finds similar kinds of applications as well. The present chapter offers a vivid description on the isolation from its natural source, purification, spectral properties, chiral resolution into individual enantiomers, total syntheses and evaluation of anti-hypertensive activity of this natural molecule. It is anticipated that the present chapter would attract the researchers with this beneficial molecule for its further exploration in the field of designing cardiovascular drugs!

3.Concluding Remarks

This introductory chapter summarizes each technical chapter of the book for which representation of facts and their discussions are exhaustive, authoritative and deeply informative. The readers would find interest in each of the chapters, which practically cover a wide area of cardioprotective natural product research, particularly on their identification, pharmacology, clinical aspects and modes of action. The reference encourages interdisciplinary works among chemists, pharmacologists, clinici...

Table of contents

• Cover
• Half
• Title
• Copy
• Dedication
• Contents
• Foreword
• Preface
• Editor Biography
• List of Contributors
• Chapter 1 Cardioprotective Natural Products: Promises and Hopes — An Overview
• Chapter 2 Naturally Occurring Matrix Metalloproteinase Inhibitors: A Group of Promising Cardioprotective Agents
• Chapter 3 Promising Natural Cardioprotective Agents in Drug- and Toxin-Induced Pathophysiology
• Chapter 4 Natural Products against Drug-Induced Cardiotoxicity
• Chapter 5 Cardioprotective Potential of Medicinal Plants in Attenuating Doxorubicin-Induced Cardiotoxicity
• Chapter 6 Role of Dietary Supplements in Cardiovascular Diseases
• Chapter 7 Beneficial Role of Antioxidant Molecules with Therapeutic Potential in Cardiac Disease
• Chapter 8 Small Molecule Phytocompounds as Promoters of LDL-receptor and PCSK9 Inhibition: Potential Role as Non-statin Based Cardio-protective Agents
• Chapter 9 7,8-Dihydroxy-3-methylisochroman-4-one: A Promising Anti-hypertensive Lead-Molecule from Banana (Musa sapientun L.) Peel
• Index