Discovery and Development of Anti-inflammatory Agents from Natural Products

Goutam Brahmachari

• Publisher: Elsevier
• Year: 2019
• Print ISBN: 9780128169926
• eBook ISBN: 9780128169933
• Topic: Physical Sciences
• Subtopic: Chemistry
• Index: Chemistry

Discovery and Development of Anti-inflammatory Agents from Natural Products, the latest volume in the Natural Product Drug Discovery series, presents cutting-edge research advances in the field of bioactive natural products and natural drug formulations, with this volume focusing on molecules of natural origin and their synthetic analogues that have the potential to act against the pathogens responsible for inflammatory diseases. All aspects of each are covered, including isolations and structure elucidations, in vitro and in vivo biological activity, synthetic optimization, investigations of pharmacodynamics and kinetics, and the structure-activity relationships of anti-inflammatory natural products. Written by active researchers and leading experts, this book brings together an overview of current discoveries and trends in this field. It will be a valuable resource for researchers working to discover promising leads for the development of pharmaceuticals in the prevention and treatment of anti-inflammatory diseases. - Features contributions from active researchers and leading experts working in medicinal natural products and herbal formulations - Includes recent, cutting-edge advances on medicinal natural products, along with preventative therapies for different kinds of inflammation-directed diseases - Offers an authoritative source of information on the industrial application of natural products for medicinal purposes

Chapter 1

Discovery and development of anti-inflammatory agents from natural products

An overview

Goutam Brahmachari Laboratory of Natural Products and Organic Synthesis, Department of Chemistry, Visva-Bharati (A Central University), Santiniketan, India

Abstract

This chapter offers an overview of the current book and summarizes the contents and subject matter of each chapter with the intention of highlighting certain glimpses of the content for readers before they proceed more deeply.

Keywords

Biosynthesis; Chemical and pharmacological aspects; Clinical aspects; Inflammation; Modes of action; Natural products with anti-inflammatory potential; Natural sources and isolation; Overview; Structure–activity relationships; Total synthesis

1. Introduction

This volume, entitled Discovery and Development of Anti-inflammatory Agents From Natural Products, within the book series Natural Product Drug Discovery, endeavors to access ongoing developments and cutting-edge advances in research in the field of natural products against inflammation-related diseases with regard to their identification, isolation, and overall chemistry and pharmacology. It also underlines how natural product research continues to make significant contributions to the domain of discovery and development of new medicinal entities. This reference book is meant for phytochemists, synthetic chemists, combinatorial chemists, biologists, pharmacologists, and clinicians as well as other practitioners and advanced students in related fields. This book is composed of nine technical chapters offering updates in these areas of natural product research with the intent of characterizing their pharmaceutical applicability in anti-inflammatory drug discovery processes.

Inflammation involving the innate and adaptive immune system is a normal body response to infection and offers protection to the body. The resulting inflammation, which is characterized by redness, swelling, heat, and pain, serves as a physical barrier against the spread of infection or further injury. Chemical factors released during inflammation sensitize pain signals, creating a more suitable environment for healing. Sometimes, however, the body becomes hyperactive and launches an offensive to healthy tissue. A major underlying factor in the different ways in which people are affected by inflammation is an imbalance in their acquired immune system, which may result in inflammatory diseases such as arthritis or joint disease, atherosclerosis, neurodegenerative diseases, diabetes, or cancer. Thus, uncontrolled inflammation requires treatment with substances that can reduce inflammation in the body. These chemical substances, called anti-inflammatory agents, block certain profiles in the body that cause inflammation. A variety of anti-inflammatory agents are currently in use, including aspirin and other nonsteroidal anti-inflammatories, with many more drugs under development. Nevertheless, safer, cost-effective, and more effective anti-inflammatory drugs are needed for a better future for inflammation-affected people, because inflammation is the cause of several deadly diseases in mankind.

Natural products once served humanity as the source of all drugs, and higher plants provided most of these therapeutic agents. Natural products continue to supply useful drugs in themselves but they are also templates for the development of other compounds. A major advantage of the natural product approach to drug delivery is that it can provide complex molecules inaccessible by other routes. Among natural sources for new bioactive chemicals, terrestrial plants, bacteria, and fungi have traditionally had major roles; however, increasingly over the past few decades, many interesting active molecules have been found in marine life-forms. Secondary metabolites from an immense diversity of living organisms thus represent a huge repository of chemical structures that have been and will continue to be a source of new drugs directly in their native form or after optimization by synthetic medicinal chemistry.

This introductory chapter (Chapter 1) presents an overview of the book and summarizes the contents and subject matter of each chapter. It offers a glimpse of the upcoming discussion for readers before they proceed to the detailed study.

2. Overview of the book

This book contains nine technical chapters: Chapters 2–10. This section summarizes the content and subject matter of each chapter.

2.1. Chapter 2

In Chapter 2, Pilar Gómez-Serranillos and coauthors offer a comprehensive overview of curcumin, highlighting its therapeutic potential as a lead candidate for anti-inflammatory drugs. No doubt, curcumin is a magical biomolecule from turmeric (Curcuma longa); it exhibits promising pharmacological efficacy against a diverse range of diseases. Here, the authors present a detailed discussion on general aspects related to the origin, pharmacokinetics/pharmacodynamics, and chemical synthesis of curcumin and its semisynthetic derivatives, together with an exhaustive review of the latest results from preclinical and clinical research on these compounds as anti-inflammatory agents. This illuminating review boosts ongoing research on curcumin and its analogues to understand their current status as promising lead molecules for the development of potential anti-inflammatory drugs.

2.2. Chapter 3

Chapter 3 by Sil and associates categorically offers an overview of the anti-inflammatory efficacy of some potentially bioactive natural products against rheumatoid arthritis. Among several kinds of arthritis, rheumatoid arthritis is the most likely fatal kind of inflammatory joint disease affecting people worldwide. It is a painful autoimmune disease that leads to synovial fibroblast hyperproliferation and massive infiltration of inflammatory immune cells, including CD4⁺ T cells and innate immune cells such as macrophages in the joints. Major anti-inflammatory drugs (such as nonsteroidal anti-inflammatory drugs and corticosteroids) suppress this inflammation-induced pain by inhibiting the activation and production of various enzymes (such as cyclooxygenase 1 and 2), cytokines (such as tumor necrosis factor-α and interleukin-1β), and transcription factors (such as nuclear factor-κB, c-Jun N-terminal kinase, and p38 kinases); however, their use is associated with several adverse effects as well. Hence, researchers have been searching for alternative therapies, particularly those originating from traditional medicines and natural products, which via their ameliorative activity and minimal side effects offer great hope as promising therapeutic candidates. The authors have carefully screened many natural products of various skeletons (phenolics, flavonoids, terpenoids, alkaloids, etc.) and discussed their anti-inflammatory potential along with their limitations so as to direct ongoing research to resolve issues for better efficacy and safety. This chapter is anticipated to be highly useful to chemists and pharmacologists working in the area of anti-inflammatory drug discovery research.

2.3. Chapter 4

Ali and his group offer a thorough account of natural anti-inflammatory agents for managing osteoarthritis (OA), a progressive degenerative joint disease affecting the mobility of individuals and their quality of life, in Chapter 4. Current treatments employed for managing OA aim for symptomatic relief and are unable to block or reverse the degradation of cartilage and destruction of joints. Besides, these anti-inflammatory drugs are reported to exhibit undesirable side effects including gastric ulceration, renal and hepatic failure, myocardial infarction, and stroke. This has led to growing interest in identifying natural compounds that have a remarkable safety profile with minimal side effects and that are known to provide health benefits. Within this purview, in the current chapter, the authors provide a vivid discussion about a handful of potential natural products that may prove to be useful in managing OA. In addition, scientific evidence supporting the efficacy of these natural products is discussed. This illustrative review of such potentially important natural products will create enthusiasm among readers.

2.4. Chapter 5

Chapter 5, by Saeed and coauthors, portrays the total synthetic routes of a good number of potent anti-inflammatory natural products. Synthetic chemists have been working continuously on new and efficient procedures for the total synthesis of bioactive natural products and their derivatives. This field is important because it allows medicinal chemists and biologists to have enough bioactive natural products of interest to perform detailed in-depth studies. In this chapter, the authors summarize the synthetic methodologies of most common and potent anti-inflammatory natural products and their derivatives to point out current developments in the area of total synthesis of anti-inflammatory natural products and their derivatives, and to encourage the medical and synthetic community to construct more potent biologically active analogues of natural products and modify their structure(s) to enhance their anti-inflammatory affinity or reduce their side effects. This exhaustive review offers a tremendous amount of relevant information to both natural and synthetic chemists.

2.5. Chapter 6

Chaturvedi offers a thorough overview of the developments in the anti-inflammatory potential of sesquiterpene lactones and their semisynthetic analogues in Chapter 6. The wide structural diversity and potential biological activities reported for this class of compounds against various diseases have attracted a great deal of attention from medicinal chemists. A considerable number of structurally diverse sesquiterpene lactones have emerged as potential anti-inflammatory agents. This chapter presents a comprehensive account of sesquiterpene lactones as anti-inflammatory agents. This thorough and illuminating review of a specific class of natural products against the manifestation of disease will be helpful to readers for an understanding of their potential role as lead candidates in drug discovery pipelines.

2.6. Chapter 7

In Chapter 7, Nakajima and coauthors present a focused discussion on two potentially bioactive flavanones, hesperetin and naringenin, delineating their protective roles against metabolic syndrome-associated inflammation. In their review, the authors highlight various inflammatory pathways (indicating the target genes) with which the flavanones interfere. They also offer a comparison of the benefits of these compounds with drugs already available in the market. In addition, the main natural sources of hesperetin and naringenin for extraction and identification are presented, as well as the forms of processing (fermentative and enzymatic biotransformation) for higher yield. This informative review acts as a stimulus to the field of flavonoid research.

2.7. Chapter 8

Alzheimer disease is the most common progressive neurodegenerative disorder. It is characterized by the formation of extraneuronal amyloid plaques and intraneuronal hyperphosphorylated tau proteins, which cause neuronal dysfunction and death. Hyperactivated astrocytes and microglia, referred to as neuroinflammation, have been documented as the prima facie mechanisms of neurodegeneration in Alzheimer disease. Chapter 8, by Borah and associates, offer an excellent overview of the therapeutic implications of anti-inflammatory natural products in controlling Alzheimer disease. The authors cover major scientific work carried out to unveil the mechanisms of their action and an understanding of their safety profiles. This illuminating review will help the readers to update their knowle...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• Dedication
• Contributors
• Editor Biography
• Foreword
• Preface
• Chapter 1. Discovery and development of anti-inflammatory agents from natural products: An overview
• Chapter 2. Curcumin: Current evidence of its therapeutic potential as a lead candidate for anti-inflammatory drugs—an overview
• Chapter 3. Anti-inflammatory efficacy of some potentially bioactive natural products against rheumatoid arthritis
• Chapter 4. Natural anti-inflammatory agents for the management of osteoarthritis
• Chapter 5. Portrait of the synthesis of some potent anti-inflammatory natural products
• Chapter 6. Recent developments in the anti-inflammatory potential of sesquiterpene lactones and their semisynthetic analogs
• Chapter 7. Hesperetin and naringenin: Protective effects against metabolic syndrome–associated inflammation
• Chapter 8. Therapeutic implications of anti-inflammatory natural products in Alzheimer’s disease
• Chapter 9. Anti-inflammatory effects of probiotics
• Chapter 10. 6-Gingerol: A therapeutically potent lead candidate in anti-inflammatory drug discovery
• Index