Herbal Medicine for Autoimmune Diseases E-Book
46,39 €
Mehr erfahren.
- Herausgeber: Bentham Science Publishers
- Kategorie: Fachliteratur
- Sprache: Englisch
Herbal Medicine for Autoimmune Diseases addresses the immune system's role in autoimmune conditions and introduces evidence-based herbal therapies for diseases like lupus, diabetes, rheumatoid arthritis, and more. Chapters highlight innovative approaches such as phyto-nanotechnology for enhanced drug delivery and the therapeutic benefits of berry fruits. Readers will gain insights into bioactive compounds, their efficacy in clinical settings, and the integration of traditional wisdom with contemporary research. Ideal for students, researchers, and pharmaceutical professionals, this book bridges the gap between ancient remedies and cutting-edge healthcare solutions, offering a valuable resource for understanding and managing autoimmune disorders.
Key Features:
- Detailed exploration of herbal treatments for specific autoimmune diseases.
- Integration of phyto-nanotechnology for advanced drug delivery systems.
- Evidence-based insights supported by preclinical and clinical research.
- Practical implications for academia, pharmaceutical research, and clinical practice.
Readership: Undergraduate and graduate students and researchers.
Das E-Book können Sie in Legimi-Apps oder einer beliebigen App lesen, die das folgende Format unterstützen:
Seitenzahl: 440
Veröffentlichungsjahr: 2024
Ähnliche
BENTHAM SCIENCE PUBLISHERS LTD.
End User License Agreement (for non-institutional, personal use)
This is an agreement between you and Bentham Science Publishers Ltd. Please read this License Agreement carefully before using the book/echapter/ejournal (“Work”). Your use of the Work constitutes your agreement to the terms and conditions set forth in this License Agreement. If you do not agree to these terms and conditions then you should not use the Work.
Bentham Science Publishers agrees to grant you a non-exclusive, non-transferable limited license to use the Work subject to and in accordance with the following terms and conditions. This License Agreement is for non-library, personal use only. For a library / institutional / multi user license in respect of the Work, please contact: [email protected].
Usage Rules:
All rights reserved: The Work is the subject of copyright and Bentham Science Publishers either owns the Work (and the copyright in it) or is licensed to distribute the Work. You shall not copy, reproduce, modify, remove, delete, augment, add to, publish, transmit, sell, resell, create derivative works from, or in any way exploit the Work or make the Work available for others to do any of the same, in any form or by any means, in whole or in part, in each case without the prior written permission of Bentham Science Publishers, unless stated otherwise in this License Agreement.You may download a copy of the Work on one occasion to one personal computer (including tablet, laptop, desktop, or other such devices). You may make one back-up copy of the Work to avoid losing it.The unauthorised use or distribution of copyrighted or other proprietary content is illegal and could subject you to liability for substantial money damages. You will be liable for any damage resulting from your misuse of the Work or any violation of this License Agreement, including any infringement by you of copyrights or proprietary rights.Disclaimer:
Bentham Science Publishers does not guarantee that the information in the Work is error-free, or warrant that it will meet your requirements or that access to the Work will be uninterrupted or error-free. The Work is provided "as is" without warranty of any kind, either express or implied or statutory, including, without limitation, implied warranties of merchantability and fitness for a particular purpose. The entire risk as to the results and performance of the Work is assumed by you. No responsibility is assumed by Bentham Science Publishers, its staff, editors and/or authors for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products instruction, advertisements or ideas contained in the Work.
Limitation of Liability:
In no event will Bentham Science Publishers, its staff, editors and/or authors, be liable for any damages, including, without limitation, special, incidental and/or consequential damages and/or damages for lost data and/or profits arising out of (whether directly or indirectly) the use or inability to use the Work. The entire liability of Bentham Science Publishers shall be limited to the amount actually paid by you for the Work.
General:
Any dispute or claim arising out of or in connection with this License Agreement or the Work (including non-contractual disputes or claims) will be governed by and construed in accordance with the laws of Singapore. Each party agrees that the courts of the state of Singapore shall have exclusive jurisdiction to settle any dispute or claim arising out of or in connection with this License Agreement or the Work (including non-contractual disputes or claims).Your rights under this License Agreement will automatically terminate without notice and without the need for a court order if at any point you breach any terms of this License Agreement. In no event will any delay or failure by Bentham Science Publishers in enforcing your compliance with this License Agreement constitute a waiver of any of its rights.You acknowledge that you have read this License Agreement, and agree to be bound by its terms and conditions. To the extent that any other terms and conditions presented on any website of Bentham Science Publishers conflict with, or are inconsistent with, the terms and conditions set out in this License Agreement, you acknowledge that the terms and conditions set out in this License Agreement shall prevail.Bentham Science Publishers Pte. Ltd. 80 Robinson Road #02-00 Singapore 068898 Singapore Email: [email protected]
FOREWORD
Autoimmunity is defined by the presence of self-reactive immune components, while autoimmune diseases result from the combination of autoimmunity and pathology. Both phenomena are significantly increasing worldwide, likely due to changes in our exposure to environmental factors. Significant changes in our diet, exposure to xenobiotics, air quality, infection rates, personal habits, stress levels, and the effects of climate change are all associated with this increase. These factors have significant consequences not only for the individuals and families affected but also for our society and healthcare expenditures. Projections suggest that autoimmune diseases may soon become the most common medical conditions, underscoring the urgency of addressing these complex health challenges.
Autoimmune diseases represent a family of around 100 disorders that share a common pathogenesis, namely an immune-mediated attack on the body's organs. Although immunosuppressive and immunomodulatory drugs represent the fundamental basis for the treatment of autoimmune diseases, there is currently no known radical treatment for these diseases. The use of medicinal plant extracts or secondary plant substances in herbal remedies is currently being investigated as a possible therapeutic approach for autoimmune diseases. Bringing together many studies on autoimmune diseases and herbal remedies in one book titled "Herbal Medicine for Autoimmune Diseases" with great dedication, this will be an excellent resource for researchers studying this topic.
The editors have strived to highlight the potential effectiveness of herbal treatments for autoimmune diseases, while bringing a broad viewpoint from various disciplines, such as pharmacy, medicine, nutrition, and basic sciences. Also, I would like to compliment the authors of all the chapters and acknowledge their efforts in publishing this comprehensive book.
PREFACE
Autoimmune diseases are common conditions in which impaired immune activation leads to pathological immune responses directed against either cellular or organ-specific self-antigens. The exact cause of autoimmune diseases is generally unknown, but stress, genetics, and environmental factors have been suggested as possible triggers. However, the connection between these proposed factors and autoimmune diseases is very complex. They are generally undertreated and there is currently no cure for these diseases. Immunosuppressive and immunomodulatory drugs are used in the treatment of autoimmune diseases, but they cannot cure these diseases, only slow down their progression. These medications are also associated with significant adverse effects. Given that the global increase in autoimmune diseases is leading to increased individual and societal suffering as well as higher private and public healthcare costs, the development of appropriate treatments for patients with autoimmune diseases is of great importance.
Therefore, various studies have been carried out to find an effective treatment. Due to their anti-oxidant and anti-inflammatory properties, herbal medicines and their phytochemicals appear to be a promising therapy. Hence, the main purpose of this book is to draw attention to herbal medicines for autoimmune diseases. Data on the therapeutic potential of related medicinal plants for autoimmune diseases can now be accessed from a single source. The book begins with an introductory chapter that serves as a framework for understanding autoimmunity and autoimmune diseases, as well as key principles and components of the immune system. The following chapters of the book, introduce potential medicinal plants and their phytochemicals that can be used in the management of autoimmune diseases such as multiple sclerosis, type 1 diabetes, rheumatoid arthritis, celiac disease, inflammatory bowel disease, Graves’ disease, Hashimoto thyroiditis, and systemic lupus erythematosus, which are among the most common autoimmune diseases in the society mentioned with evidence-based data from preclinical and clinical studies. It is known that traditional knowledge about the use of medicinal plants in therapy is an important resource for the discovery of new treatment options and drug targets. One chapter of the book focuses on phyto-nano drug delivery systems that can enhance the efficacy of medicinal plants in the treatment of rheumatoid arthritis. Another chapter provides a comprehensive overview of berry fruits related to autoimmune diseases.
As editors, we would like to express our special thanks to all the contributing authors for making their invaluable chapter contributions in a timely manner, thereby enabling us to publish this book on time. We would also like to express our heartfelt thanks to the team at Bentham Science Publishers for their invaluable help and kind support throughout the editorial process of this book.
Finally, we would like to thank our family members, all the esteemed teachers, friends, colleagues, and students for their constant encouragement, inspiration, and support during the preparation of this book. Together with our contributing authors and publishers, we hope that our efforts will meet the needs of students, academics, researchers, and professionals in the pharmaceutical industry.
DEDICATION
We would like to dedicate this book to our beloved fathers, Nurettin and Munir, who passed away in recent years. Our fathers gave us the greatest gift a human being can give another human being: They believed in us. Thanks to them, we could try to touch people's lives through science. Their memories will inspire us every day of our lives.
They will remain forever in our hearts and our prayers.
List of Contributors
Autoimmune Diseases, Immune System and Herbal Medicine
Cennet Ozay1,*,Sengul Uysal2,3,Gokhan Zengin4Abstract
The immune system is a defense mechanism against infections and illnesses caused by various agents, including bacteria, viruses, and other causative factors. Any disruption in the functioning of the immune system, which is highly organized and precisely regulated, can result in the emergence of immune deficiencies, hypersensitivity reactions, or autoimmune diseases (AIDs). Under certain circumstances, the immune system generates autoantibodies that target their cells, giving rise to AIDs, including multiple sclerosis, type I diabetes, rheumatoid arthritis, inflammatory bowel disease, hashimoto thyroiditis, systemic lupus erythematosus, psoriasis, etc. In such cases, the immune system cannot differentiate between foreign substances and the body's own cells. Different factors, such as genetic, epigenetic, and environmental factors, trigger autoimmunity. Currently, autoimmune diseases of various origins are managed using glucocorticoids, non-steroidal anti-inflammatory drugs, immunosuppressive agents, and biological treatments. Nevertheless, a comprehensive cure for these conditions continues to remain beyond our reach. Numerous herbal natural products have been investigated as potential alternative approaches for the management of autoimmune disorders. In this introductory chapter, we summarized the essential concepts of the immune system, the formation, stages, and types of autoimmune diseases, and the role of herbal medicines in the management of AIDs.
INTRODUCTION
Immunity represents a harmonious equilibrium in which the body possesses effective biological defenses to combat infections, diseases, or unwanted biological intrusions, all while maintaining tolerance to prevent allergies and autoimmune diseases (AIDs). Immune responses result from effective interactions between innate (natural/non-specific) and acquired (adaptive/specific) immune system components. The interaction between phagocytes and micro-organisms in the immune system is a protective pathway, but if inappropriately or improperly organized, it can damage the body and contribute to the development of various long-term inflammatory conditions such as allergies, carcinomas, and AIDs [1].
There are over 80 AIDs known to date, ranging from relatively common to rare conditions. The determination of which AIDs are the most common can vary based on a variety of factors, including patient-reported data, clinical experience, hospital records, and research studies. As of the current information available, some of the more prevalent AIDs include rheumatoid arthritis, multiple sclerosis, type 1 diabetes mellitus, inflammatory bowel disease, hashimoto thyroiditis, Alopecia areata, Graves’ disease, celiac disease, systemic lupus erythematosus, and psoriasis, among others. However, the prevalence and ranking of AIDs may change as new research and data emerge [2].
AIDs, arising from the immune system's misalignment targeting the body itself, presents a notable and escalating unmet demand within clinical healthcare. Generally, due to their wide-ranging action rather than being tailored to specific diseases, current treatments are linked to a multitude of side effects. Hence, there is a rising need for the usage of herbal drugs that lead to suppressive effects on the immune system.
The aim of this introductory chapter is (1) to establish a fundamental understanding of the key principles and constituents of the immune system, serving as a framework for comprehending autoimmunity and autoimmune diseases, (2) to provide information about the formation, stages and types of autoimmune diseases, and (3) the role of herbal medicines in the management of autoimmune diseases.
AUTOIMMUNE DISEASES
Autoimmune diseases are a wide range of disorders characterized by chronic inflammation and tissue damage [1, 2]. Autoimmune diseases range from Psoriatic arthritis to Type 1 diabetes mellitus (T1DM), Crohn’s disease, Rheumatoid arthritis (RA), Grave’s disease (GD), Psoriasis, and Multiple sclerosis (MS). Most of these are incurable, but the symptoms can be managed [3]. Recently, autoimmune diseases have emerged as a significant health concern with increasing incidence. Autoimmune diseases affect approximately 10% of the population worldwide. These diseases are associated with tremendous economic burden [4, 5]. According to Conrad and Misra [3], autoimmune diseases affect almost one in ten individuals in the UK. In 2019, an estimated 18 million people worldwide were diagnosed with Rheumatoid arthritis [6]. In 2020, the data showed that 2.8 million people were diagnosed with MS worldwide [7]. Crohn’s disease has emerged as a global disease and affects over 3.5 million people [8]. There were approximately 8.4 million people worldwide with T1DM in 2021. An estimated number of people with T1DM is expected to reach 13.5-17.4 million by 2040 [9] (Table 1) (Fig. 1).
Causes of Autoimmune Diseases
Autoimmune diseases are multifactorial diseases. The development of AIDs is affected by many factors, including viral infections, genetic predisposition and environmental factors [18, 19]. A large number of autoimmune diseases are more prevalent in women than men [20, 21]. The abnormal activation of chemokine signaling pathways is implicated in the development of several autoimmune diseases including RA and SLE and systemic sclerosis [22]. Tumor necrosis factor-alpha (TNF-α) plays an important role in many AIDs, including RA, MS, PsA, CD, and AS [23].
Fig. (1)) A: Number of people with MS - prevalence per 100,000 people [7]. B: Map of T1DM in children aged under 15 years [15].Some Common Factors
Gender
About 78% of people affected by autoimmune diseases are women [24]. Systemic lupus erythematosus (SLE) affects women more commonly than men, with both genetic and hormonal factors. X-chromosome-linked genetic factors have been strongly implicated in the pathogenesis of SLE [25]. MS is more prevalent in women of reproductive years [26]. More than 70% of MS patients are women [27]. Men aged 20-30 years have a higher prevalence of Ankylosing spondylitis (AS) [28]. Graves’ disease (GD) is 5-10 times more frequent in women between the ages of 30 and 60 [29].
Genetics
Many genes can contribute to autoimmune diseases. More than 100 genetic loci may confer risk for autoimmune diseases, including SLE and RA [30]. The PTPN22 gene has been demonstrated to be associated with a variety of different autoimmune diseases, including T1DM, RA, and SLE [31]. Rheumatoid arthritis is associated with HLA-DRw4. Furthermore, systemic lupus erythematosus (SLE) has been found to be associated with HLA-DR3 and HLA-B8 [32]. Several studies reported an association between some SNPs in the IFIH1 gene and the risk of various autoimmune diseases, including psoriatic arthritis (PA) and SLE, GD [33]. The NOD2, IL23R and ATG16L1 genes are strongly linked to CD [34, 35]. In T1DM, genetic and familial factors play a significant role in disease susceptibility [36].
External Triggers
In this category, sunlight, diet, stress, drugs, chemicals, viruses, and bacteria can be counted in general. Microorganisms are considered a direct trigger of autoimmune diseases. The pathogenesis of Crohn’s disease (CD) is influenced by the gut microbiome [37]. Smoking is a risk factor for the development of RA. This is one example of gene-environment interactions [38]. Furthermore, lifestyle factors including stress, diet, and lack of exercise pose an increased the risk of developing RA [39]. External triggers like smoking, vitamin D, sunlight or infective agents (including Epstein Barr virus) have been implicated in MS pathogenesis [40]. Several viruses have been linked to the development of T1DM, including enteroviruses, such as Coxsackie virus B (CVB), mumps virus, and rotavirus [41]. Obesity has been linked with increased risk of RA, SLE, MS, T1DM [39].
Stages of Autoimmune Diseases
Autoimmune diseases result from the failure of tolerance to self-antigens [42]. Immune tolerance includes central tolerance and peripheral tolerance. Thus, the main problem in the development of autoimmune diseases is the breakdown of some or all of these mechanisms. Currently, autoimmune diseases are triggered by interactions between environmental and genetic factors [43-45]. Most autoimmune diseases are long-term diseases. There are three major stage of autoimmune diseases: initiation, propagation, and resolution.
Stage 1 - The Initiation of Autoimmunity
In general, the exact factors responsible for the initiation of autoimmune diseases are not known. Autoimmune diseases are caused by a combination of environmental and genetic factors. Cytokine gene polymorphisms have been linked with a number of autoimmune diseases [46]. The human leukocyte antigen (HLA) is the major genetic factor in autoimmune diseases [47]. IL23R polymorphisms have been determined in ankylosing spondylitis, Crohn’s disease, and psoriasis [48].
Stage 2 - The Propagation of Autoimmune Reactions
Propagation phase is defined by tissue damage and progressive inflammation and most patients present with clinical disease in this phase. TNF-α inhibitors play a significant role in the propagation of inflammation in rheumatoid arthritis and psoriatic arthritis. The propagation of autoimmunity can be linked to the progressively growing ratio of effector to regulatory cells [46].
Stage 3 - The Resolution of Autoimmunity
There is generally no care for an autoimmune disease, but the symptoms can be managed by immunosuppression and hormone replacement [49]. The control of autoimmune reactions is probably associated with the induction and activation of regulatory mechanisms. T cells (Tregs) play a significant role in these mechanisms [46].
Types of Autoimmune Diseases
There are 80-100 known autoimmune diseases. Some common autoimmune disorders include Psoriatic arthritis (PsA), Type 1 diabetes mellitus (T1DM), Multiple sclerosis (MS), Crohn’s disease (CD), Rheumatoid arthritis (RA), Psoriasis, Graves’ disease (GD), Ankylosing spondylitis (AS), Systemic lupus erythematosus (SLE), Celiac disease (CD), Hashimoto thyroiditis (HT) and Inflammatory bowel disease (IBD) [50, 51] (Fig. 2).
Psoriatic arthritis (PsA) is a chronic inflammatory arthritis and it is characterized as bone proliferation and osteolysis [52, 53]. About 0.5-0.8% of the general population has been infected [10]. The pathogenesis of Psoriatic arthritis is multi-factorial, with demographic, genetic, lifestyle, and clinical [54]. Primarily, psoriatic arthritis is considered to be driven by the IL-23/IL-17 axis and related cytokines [55].
Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes joint inflammation [56]. RA significantly affects their physical function, life quality and emotional state [57]. A total of 18 million people worldwide were living with rheumatoid arthritis in the year 2019 [6]. This disease affects 0.5% to 1% of the global population aged between 25 and 60 years [11]. Rheumatoid arthritis is increasing in the world. The pathogenesis of RA is affected by genetic, immune system and environmental factors (smoking, air pollution, and infections) [58-60]. More than 100 have been associated with the RA, and the main influence is associated with HLA-DR (HLA DR1 and HLA DR4) [61]. RA is more common in women than men [62].
Fig. (2)) Some common autoimmune diseases (Drawn in BioRender.com).Systemic lupus erythematosus (SLE) is a prevalent autoimmune disease related to genetic as well as environmental factors [63]. Women are most affected by Systemic lupus erythematosus [64]. For the past 50 years, the 5-year survival rate of patients with SLE has improved from 50% in the 1950s [65] to 95% in more recent years [66].
Ankylosing spondylitis (AS) is a chronic inflammatory disease [67, 68]. It is characterized by prolonged inflammation of the spine and various joints [69, 70]. The worldwide prevalence of AS ranges from 0.07% to 0.32% [12]. AS occurs more frequently in young adults, most commonly in men aged 20-30 years [28]. AS is strongly linked to human leukocyte antigen (HLA-B27) [71].
Multiple sclerosis (MS) is defined as a chronic inflammatory autoimmune disease of the central nervous system and is associated with gliosis, inflammation, myelin loss, demyelination, and variable degrees of axonal loss [72-74]. About 2.8 million people live with MS worldwide [7]. The etiology of MS is not entirely understood. However, genetic and environmental factors (like smoking, vitamin D deficiency, viral infections, sun exposure, gender, and age) may contribute to MS development [75-78]. Cytokines are key players during the immunopathogenic process of MS [79].
Crohn’s disease (CD) is a chronic inflammatory gastrointestinal disease. This disease is typically characterized by abdominal pain, transmural inflammation, diarrhea, weight loss, and blood in the stool [80, 81]. More than 3.5 million people are affected by Crohn’s disease (CD) globally. The prevalence of CD ranged from 3 to 20 cases per 100.000 people [8]. CD is much more common in young people and is a multifactorial disorder caused by genetic, environmental, immunological, and microbial factors [82-87].
Graves’ disease (GD), the most common cause of hyperthyroidism, is considered a typical autoimmune disease characterized by excessive production of stimulatory antibodies (TSAb) against the TSH receptor [13]. GD is diagnosed in around 1%-1.5% of the global population [13, 14]. Environmental and genetic factors are associated with GD development, such as smoking and stress [14, 88].
Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disorder defined by the destruction of insulin producing β-cells in the pancreas [89]. T1DM in childhood and adolescence is rising and continuously increasing in the world [90]. It is estimated that about 98.200 children under 15 years develop T1DM worldwide in 2019 [15]. T1DM is caused by a combination of environmental, immunological, metabolic, and genetic factors [91].
Psoriasis is a chronic systemic inflammatory skin disorder characterized by vascularization of the skin, erythematous and scaly papules, excessive proliferation of keratinocytes, and plaques [92-94]. Psoriasis affects about 1.5-3% of the population globally. This disease occurs equally in women and men [16]. The pathogenesis of psoriasis is complex and still unclear and is determined by a combination of environmental and genetic factors [95].
Systemic sclerosis (SSc), also known as scleroderma, is a complex autoimmune disease characterized by multiple organ involvement, immune system abnormalities, and vasculopathy [96, 97]. Scleroderma predominantly affects women [98]. The prevalence of SSc ranges from 30-300 cases per million individuals [17]. The leading cause of death in scleroderma is pulmonary arterial hypertension (PAH) [99].
Hashimoto's thyroiditis (HT), alternatively referred to as chronic lymphocytic thyroiditis and Hashimoto's disease, is as an autoimmune disorder characterized by the progressive destruction of the thyroid gland. Usually initiating between the ages of 30 and 50, this condition is notably more prevalent in women compared to men [100].
Celiac disease (CD) is an immune reaction to eating gluten, a protein found in wheat, barley and rye, and is sometimes called celiac sprue or gluten-sensitive enteropathy. In celiac disease, the ingestion of gluten begins an immune reaction within the small intestine. As time progresses, this immune response harms the lining of the small intestine, impeding the absorption of certain nutrients (malabsorption). The resultant damage to the intestine frequently gives rise to symptoms like diarrhea, fatigue, weight loss, bloating, and anemia, and it has the potential to give rise to severe complications [101].
Inflammatory bowel disease (IBD) is a group of inflammatory diseases of the colon and small intestine, the most common of which are Crohn's disease and ulcerative colitis. The average incidence of IBD in 2016-2021 was 18 per 100,000 population/year, an increase of 169% compared to 2001-2006 [102].
OVERVIEW OF THE IMMUNE SYSTEM
In principle, the immune system is designed to mount rapid, specific and protective responses against harmful pathogens or their biological products. The mechanisms of immunity operate in a wide range of clinical conditions, ranging from the resolution of infectious diseases, the recognition and rejection of tumors, and the tolerance or rejection of transplanted tissues or organs to autoimmunity and allergy. The immune system consists of two arms, the innate (non-specific) and the adaptive (specific), which are made up of specialized cell types that carry out different effector functions. However, the two arms of the immune system do not operate completely independently. For example, the innate system elicits antigen-specific responses, recruiting cells to the site of infection or injury and delivering antigen to the lymphoid tissue, leading to the activation of adaptive effector cell types [103].
There are two types of adaptive immune response - the primary and the secondary immune response. When a foreign antigen interacts with and activates antigen-specific lymphocytes, a primary immune response is initiated. In general, primary responses are quite effective in resolving infection in combination with innate mechanisms. Immunological memory, which protects against secondary challenges, is also initiated by this first antigenic encounter. Immunological memory is the basis of vaccine strategies and leads to rapid, highly specific clearance of the infectious agent by high-affinity antibody molecules [103].
Innate Immune System
The innate immune system consists of a variety of different mechanisms that perform different functions in host defense. These include, but are not limited to: (i) the phagocytic system; (ii) the acute phase response and complement; (iii) natural killer (NK) cells; and (iv) dendritic cells (DCs) [104]. Speed is a distinguishing feature of the innate immune system, as it swiftly initiates a protective inflammatory response within minutes of encountering a pathogen. Additionally, innate immunity holds a pivotal role in triggering the subsequent adaptive immune response. The innate immune system is emerging as a critical regulator of human inflammatory diseases, although it is critical for host defense against infectious challenges. In fact, the innate immune system is involved in the development of asthma, atopy and several autoimmune diseases, including inflammatory bowel disease, type 1 diabetes and systemic lupus erythematosus [105].
Cells of both haematopoietic and non-haematopoietic origin provide innate immune protection. Mast cells, macrophages, neutrophils, eosinophils, dendritic cells, NK cells and NK T cells are haematopoietic cells involved in the innate immune response. To complement these cellular defensive mechanisms, innate immunity also has a humoral component, including well-characterized components such as complement proteins, C-reactive protein, LPS binding protein, and other collectins, pentraxins, and antimicrobial peptides, including defensins [105].
Adaptive Immune System
In adaptive (acquired/specific) immunity, white blood cells called lymphocytes (B cells and T cells) come across an invader, learn how to attack it, and remember the specific invader so that they can attack it even more efficiently the next time they encounter it. The establishment of acquired immunity requires a period of time following the initial encounter with a novel invader, as lymphocytes need to undergo adaptation to effectively respond to it. But after that, the response is quick. B and T cells work together to kill the invaders. To recognize invaders, T cells need to be helped by cells called antigen-presenting cells, including dendritic cells. These cells ingest an invader and break it into fragments [106].
The adaptive immune system, so called because it is shaped by exposure to antigens, is made up of T and B lymphocytes. Unlike the innate immune system, which relies on a restricted set of pathogen receptors, the adaptive immune system boasts an exceptionally wide-ranging and randomly generated collection of receptors [107]. The advantage of this diversity of receptors is that the adaptive immune system is able to recognize virtually any antigen, but there is a price to pay for this diversity. Firstly, there is the AIDs risk. Receptors designed to recognize self-proteins, such as insulin and myelin, emerge through the stochastic mechanism of gene rearrangement, responsible for producing the receptors expressed by T and B cells. As a result, sophisticated tolerance mechanisms have evolved for the elimination or regulation of self-reactive cells. Secondly, after initial exposure to a pathogen, there is a delay in the generation of a protective adaptive immune response [106].
Cytokines: The Language of Immunity
Cytokines, small soluble proteins, emerge in reaction to antigens, serving as molecular messengers that govern the orchestration of both the innate and adaptive immune systems. These proteins are generated by nearly all cells participating in innate and adaptive immunity, but especially by T- helper (Th) lymphocytes. Activation of cytokine-producing cells triggers their synthesis and secretion of cytokines. The cytokines are then able to bind to specific cytokine receptors on other cells of the immune system and influence their activity in some way [108].
Cytokines display pleiotropy, redundancy, and multifunctionality. Pleiotropy signifies that a given cytokine can influence numerous cell types rather than just one. Redundancy pertains to multiple cytokines having the capability to perform the same role. Multifunctionality denotes that a single cytokine is capable of overseeing various functions [109]. Certain cytokines exhibit antagonistic behavior, where one cytokine triggers a specific defensive action while another cytokine inhibits that same action. On the other hand, some cytokines display synergy, where the combined effect of two different cytokines surpasses the impact of each individual cytokine. Cytokines can be categorized into three functional groups: (i) Cytokines that govern innate immune reactions, (ii) cytokines that regulate adaptive immune reactions, and (iii) cytokines that induce hematopoiesis [110].
Cytokines assume vital roles in the context of innate immunity against various categories of microorganisms. They are discharged during infections caused by pyogenic (pus-forming) extracellular bacteria. These encompass TNF-α, IL-1, IL-10, IL-12, IL-6, IL-18, interferons, as well as chemokines. In addition, the cytokines required for the development and activity of the adaptive immune system are IL-2, IL-4, IL-5, TGFβ, IL-10 and IFN-γ [111].
Immune System and Autoimmune Diseases
Autoimmune disease is regulated by a combination of host genes and environmental factors. Both of these components can enhance vulnerability to autoimmunity by influencing the general responsiveness and characteristics of immune system cells. They also control which antigens, and therefore which organs, are targeted by the immune system. The specificity of antigens and target organs is influenced by factors such as antigen presentation and recognition, antigen expression, and the condition and response of the targeted organs [112].
The immune system is a delicate and active process that balances antimicrobial effector functions with adequate mechanisms for the resolution of inflammation and prevention of self-damage. Certainly, when immune responses become dysregulated, and the equilibrium among these mechanisms is disrupted, it can result in tissue damage, inflammation, and the emergence of autoimmune conditions. The term ‘autoimmunity’ encompasses a diverse array of conditions where the immune system generates or fails to eliminate antibodies and immune cells that exhibit reactivity against self-antigens (also referred to as autoantigens). This process leads to harm inflicted upon targeted tissues and the development of distinct diseases. The path leading to autoimmunity is intricate and multifaceted and involves numerous presumed stages that entail intricate interactions among diverse immune and stromal cells. This process is affected by external exposures, genetic and epigenetic elements, and unpredictable stochastic incidents that are not yet fully comprehended [113, 114].
The treatment of autoimmune diseases can be seen as a jigsaw puzzle in progress. Current treatments for autoimmune diseases include physiotherapy, non-steroidal anti-inflammatory drugs (NSAIDs), disease-modifying anti-inflammatory drugs (DMARDs), corticosteroids, anti-cytokine therapies, biological inhibitors of T-cell function, inhibition of intracellular signaling pathways, regulatory T cells, B-cell anergy and depletion, stem cell transplantation [115].
Although there is no permanent cure for AIDs, standard treatments aim to reduce the signs and symptoms of the disease and limit the autoimmune processes. The development of more effective medicines to treat and prevent these diseases is therefore urgently needed.
HERBAL MEDICINE WITH THE POTENTIAL ROLE IN THE MANAGEMENT OF AUTOIMMUNE DISEASES
Typical and widely used therapeutic approaches for AIDs encompass the use of analgesics, NSAIDs, and glucocorticoids. In recent years, however, therapeutic immunosuppression and biological agents have also been demonstrated to be beneficial in the treatment of AIDs [116]. Indeed, even as these treatments can alleviate the inflammatory symptoms or slow down disease progression, a complete and definitive cure for AIDs continues to be out of reach. Dietary and herbal natural products are also widely studied as potential strategies for treating AIDs [117, 118].
Herbal medicines and the metabolites extracted from them have a rich historical background in the treatment of immune system disorders. The theory and application of herbal medicines have demonstrated that many of them exhibit immune-regulating properties and are commonly employed to address immune-related ailments [119]. Most of the active constituents of herbal medicines are being investigated for their immunosuppressive properties. These medicinal plants are useful in several immune-mediated diseases, such as autoimmune diseases. Various plants, such as Curcuma longa, Artemisia annua, Camellia sinensis, Andrographis paniculata, Salvia miltiorrhiza, and Tripterygium wilfordii, etc. exert their suppressive effects on the immune system [120].
Artemisia annua has been widely used in traditional Chinese medicine to treat autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. In a study evaluating the immunosuppressive effect of ethanol extract of A. annua on specific antibodies and cellular responses of mice against ovalbumin, a single dose of 0.25, 0.5 and 1.0 mg of the extract significantly reduced the ovalbumin-specific serum lgG, lgG1 and lgG2b antibody levels and suppressed the splenocyte proliferation [121]. Green tea, derived from the dried leaves of Camellia sinensis, is employed in the management of autoimmune arthritis. This is attributed to the anti-inflammatory properties of the polyphenolic compound catechin found in green tea [122]. A study has identified Cornus officinalis and Paeonia lactiflora as potential therapeutic candidates for treating Rheumatoid arthritis. This is based on their main active compounds, ursolic acid and paeoniflorin, which have been shown to decrease synovial hyperplasia and inflammatory infiltration of joint tissues while promoting synovial apoptosis in a rat model of collagen-induced arthritis [123].
Withania somnifera is extensively utilized in the treatment of Rheumatoid arthritis and Psoriasis. This plant contains various chemical constituents, including alkaloids (such as isopelletierine and anaferine), steroidal lactones (including withanolides and withaferins), saponins (like sitoindoside VII and VIII), and withanolides. These phytochemicals are responsible for exerting immunosuppressive effects by modulating the activity of B and T cells in hyperimmune states [124]. Quercetin is a natural flavonoid found in many fruits, herbs and vegetables. It has been shown to have a wide range of beneficial effects and biological activities, including anti-inflammatory, antioxidant and neuroprotective properties. In several recent studies, quercetin has been reported to attenuate multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, and inflammatory bowel disease in human or animal models [125]. As a result, numerous medicinal plants have been used for the treatment of diverse autoimmune disorders. Substantial research has been conducted to elucidate how the constituents of these plants function as immunosuppressive agents. Therefore, their pharmacological properties provide a strong foundation for further confirmatory studies and the potential expansion of their applications in various immunosuppressive therapies.
CONCLUDING REMARKS
Autoimmune diseases represent a global health concern, with increasing rates of morbidity. They are marked by the malfunction and dysregulation of the immune system. The development and pathogenesis of autoimmune diseases involve multiple associations and interacting factors. Many potent conventionally used drugs are available for these diseases, but severe adverse effects besides a high cost accompany their prolonged use. Therefore, there is an unmet need for effective but less expensive medications for AIDs.
Natural plant products belonging to the traditional systems of medicine offer a vast and promising resource in this regard. Several ongoing scientific studies are investigating the use of natural plant products to develop drugs for the treatment of autoimmune diseases. The herbal medicines due to their antioxidant and anti-inflammatory properties have an important role in the management of AIDs. Nonetheless, the scientific evidence for herbal medicines' effects on diseases linked to immune responses and inflammatory processes remains limited. The evidence regarding their clinical effectiveness and safety is even scarcer, often hindered by inadequate characterization/description of the substances being studied.
